The Male Biological Clock

Delaying parenthood has serious medical risks for both men and women, study warns

2012-01-17T15:18:00.000-08:00

Delaying parenthood has serious medical risks for both men and women, study warns

Postmedia News Jan 17, 2012 – 9:48 AM ET

Fotolia

Babies born to fathers of “advanced paternal age” — defined as 40 and older at the time of conception — are at increased risk of genetic disorders, as well as schizophrenia, autism and some forms of cancer, according to the authors

By Sharon Kirkey
Men, and not just women, need to be aware of the “reproductive consequences” of postponing parenthood, new national guidelines on the risks of delayed child-bearing warn.
Though women especially should recognize that their “fecundity and fertility” starts to decline precipitously after 32, a man’s semen quality and fertility also worsens with age, according to guidelines endorsed by the Society of Obstetricians and Gynaecologists of Canada.
In addition, babies born to fathers of “advanced paternal age” — defined as 40 and older at the time of conception — are at increased risk of genetic disorders, as well as schizophrenia, autism and some forms of cancer, according to the authors.
The new guideline to doctors comes amid growing concerns about the number of women delaying childbearing. In Canada, 11 per cent of first births now occur in women aged 35 and older, up from five per cent in 1987.

If the trend holds, society can expect to spend more on intensive care, special care nurseries and community services for children born to older parents who may have developmental, hearing, speech or language problems, the authors say.
It could also affect the future growth of the country; women who postpone their first births tend to have fewer babies, if they become pregnant at all.
“Widespread pre-conception counselling and education are needed and must be implemented so that the 95 per cent of Canadians who anticipate parenting at some point can make informed decisions,” the authors write in this month’s issue of the Journal of Obstetrics and Gynaecology Canada.
But while the popular belief is that women are deferring motherhood for their careers, a related survey of more than 1,000 women in Calgary and Edmonton who gave birth to their first child between 2002 and 2003 found that the top three factors influencing timing of pregnancy — regardless of a woman’s age — are relationship security, feeling in control of their life and feeling prepared to be a mother.
Less than a third of women cited career goals, though women more than 35 were more likely than younger women to say they felt their biological clock was ticking.
“We were really surprised, because that was the colloquial dogma — ‘Oh, I need to get my career underway,’ ” said Suzanne Tough, a professor in pediatrics and community health sciences at the University of Calgary and a co-author of the study, as well as the guideline on delayed child-bearing.
“Once women hit 25 . . . it was really the relationship that was the key factor in influencing when they chose to become a parent.”
The concern is that women may not realize what they’re risking while they’re waiting.
For females, the biologically optimum period for having a baby is between 20 and 35. By age 32, a woman’s fecundity — the probability of getting pregnant in a menstrual cycle — starts an irreversible slide.

Postponing parenthood could have serious consequences, warns new study

2012-01-17T09:44:00.000-08:00

consequences, warns new study

By Sharon Kirkey, Postmedia News January 17, 2012 10:13 AM

The new guideline to doctors comes amid growing concerns about the number of women delaying childbearing. In Canada, 11 per cent of first births now occur in women aged 35 and older, up from five per cent in 1987.

Photograph by: Thinkstock, canada.com

Men, and not just women, need to be aware of the "reproductive consequences" of postponing parenthood, new national guidelines on the risks of delayed child-bearing warn.

Though women especially should recognize that their "fecundity and fertility" starts to decline precipitously after 32, a man's semen quality and fertility also worsens with age, according to guidelines endorsed by the Society of Obstetricians and Gynaecologists of Canada.

In addition, babies born to fathers of "advanced paternal age" — defined as 40 and older at the time of conception — are at increased risk of genetic disorders, as well as schizophrenia, autism and some forms of cancer, according to the authors.

The new guideline to doctors comes amid growing concerns about the number of women delaying childbearing. In Canada, 11 per cent of first births now occur in women aged 35 and older, up from five per cent in 1987.

Read more: http://www.canada.com/health/Postponing+parenthood+could+have+serious+consequences+warns+study/6007363/story.html#ixzz1jjqxZIxQ

James F. Crow, 1916-2012

2012-01-11T10:41:00.000-08:00

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James F. Crow, 1916-2012
.

Wed, 2012-01-04 23:23 -- John Hawks

I received today the sad news that my friend and colleague James F. Crow has died, at the age of 95. Jim was a legend in the field of population genetics, who remained active until his final year.

Jim was always extraordinarily gracious and generous with his time, and was kind to me throughout the ten years I have known him. At our last meeting, before I went to Siberia last summer, Jim told me the story of his meeting Dmitry Belyaev, early in the days of his famous fox experiment. I was eager to see the foxes and I conveyed Jim's greetings and reminiscences to the researchers in Novosibirisk. Again and again during the years, I found Jim to be a rich source of information about topics in population genetics. Even as my work brought me to consider fundamentals often outside the current mainstream, Jim invariably had encountered similar problems and given them deep thought long before I arrived on the scene.

During the last 25 years, Jim took on a role as unofficial historian for the field of genetics. He coedited the Perspectives feature in the journal Genetics, and for many of those years wrote the lion's share of them. He was proud to note that his birth coincided with the first issue of the journal (January,1916), but although he arrived on schedule, the first issue of the journal was mailed two months late! Reviewing the major figures in the history of genetics, Jim gave a narrative history of the science often from his own memories.

During the next few months, the journal Genetics will be running a series of perspectives in Jim's honor, reviewing aspects of his extraordinary career. I recommend the introduction to the series, printed in the December 2011 issue [1], and the first entry written by Daniel Hartl about Jim as a teacher and advisor [2]. From the editorial introduction by Michael Turelli and Charles Langley:

Jim Crow is a living link between our generations and the founders of population genetics. Jim was Sewall Wright's colleague at the University of Wisconsin, Madison, for decades (1955–1988); Jim initiated a friendship with Ronald Fisher over an impromptu champagne tête-à-tête in the 1940s; and he hosted J. B. S. Haldane for a memorable lecture visit to Madison in the early 1960s (after learning from the New York Times that North Carolina had just canceled a public lecture by this famous Communist). There are few population geneticists who do not owe Jim a significant intellectual debt; none are unaware of his mastery of our field and of human interactions. For many of us, Crow and Kimura (1970) was an inspiring and elegant introduction to the mathematical models that form the foundation of population genetics theory. Crow instantiates the ideal of a cherished era when manners and dress were a sign of gentility. And no one who meets Jim is surprised to learn that he is an accomplished violist.

And from Hartl's contribution:

Professor Crow ran his laboratory on the principles of bringing smart people together to pursue their passions and encouraging interaction, mutual respect and support, constructive criticism, and the free sharing of ideas and resources. There were no formal group meetings or reports, as there was so much daily interaction that group meetings would have been superfluous. He would advise, suggest, and encourage, but never direct or cajole. The standard of mutual respect was set by Professor Crow himself and extended not only to members of the lab but also to everyone in the field. I never heard him utter an unkind word about anyone. He also treated everyone in the lab as a colleague. One day he came to me and said, “Dan, there’s a matter on which I’d like your advice.” He must have seen how flattered I was at being asked because he quickly added, “That doesn’t mean I’ll take it. It only means I want to hear it.”

Hartl gives some of the flavor of Crow's laboratory in the 1960's, when he was already one of the most prominent geneticists in the world, and was a frequent host to the field's legends and advisor to some of the brightest students. I can only wish that someday I will be so lucky.

Several years ago, colleagues from several departments here at the University of Wisconsin-Madison succeeded in a long-time ambition of Jim's to found an Institute for the Study of Evolution. He had envisioned that the institute should be named for Sewall Wright, who had been important to Jim himself and forms a major part of the legacy of genetics and evolution. But the future institute's members insisted instead to name the new entity in honor of Jim. It is a fitting legacy for a great evolutionary geneticist.

--------------------------------------------------------------------------------

References

1.Turelli M, and Langley C. 2011. Honoring our colleague James F. Crow, an outstanding gentleman, citizen, and scientist. Genetics 189:1127.
2.Hartl DL. 2011. James F. Crow and the art of teaching and mentoring. Genetics 189:1129-33.

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In memory of a friend and colleague, one of the most prominent figures in the history of genetics
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James F. Crow, Population Genetics Pioneer, Dies at 95

2012-01-11T10:21:00.000-08:00

James F. Crow, Population Genetics Pioneer, Dies at 95

James Crow Dies

2012-01-11T10:16:00.000-08:00

James Crow Dies

January 11, 2012

James Crow, who was a population geneticist at the University of Wisconsin-Madison, has died, reports The New York Times. He was 95. Crow studied mutational load, and was part of on a National Academy of Sciences committee that assessed mutational damage to the populations of Hiroshima and Nagasaki following the use of atomic bombs there. He also was on a committee that paved the way for using DNA forensics in court. The Times notes that when Crow began teaching in the 1940s and 1950s, the field of genetics underwent rapid changes. "When anxious students asked Dr. Crow what would be in the exams, he would tell them that the questions were the same every year but that the answers were different," the Times says.

High Frequencies of De Novo CNVs in Bipolar Disorder and Schizophrenia.

2012-01-07T09:38:00.001-08:00

Neuron. 2011 Dec 22;72(6):951-63.

High Frequencies of De Novo CNVs in Bipolar Disorder and Schizophrenia.

Malhotra D, McCarthy S, Michaelson JJ, Vacic V, Burdick KE, Yoon S, Cichon S, Corvin A, Gary S, Gershon ES, Gill M, Karayiorgou M, Kelsoe JR, Krastoshevsky O, Krause V, Leibenluft E, Levy DL, Makarov V, Bhandari A, Malhotra AK, McMahon FJ, Nöthen MM, Potash JB, Rietschel M, Schulze TG, Sebat J.

Source

Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 12824, USA.

Abstract

While it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n = 185), schizophrenia (n = 177), and healthy controls (n = 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR = 4.8 [1.4,16.0], p = 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR = 6.3 [1.7,22.6], p = 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR = 5.0 [1.5,16.8], p = 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID: 22196331 [PubMed - in process]

The results of these different studies are confirmed by two recent meta-analyses which found an increased risk of schizophrenia in offspring of fathers older than 35 years.

2012-01-04T08:50:00.001-08:00

Encephale. 2011 Jun;37(3):199-206. Epub 2011 Apr 2.

[Influence of paternal age in schizophrenia].

[Article in French]

Hubert A, Szöke A, Leboyer M, Schürhoff F.

Source

Pôle de psychiatrie du CHU de Créteil, groupe hospitalier Henri-Mondor-Albert-Chenevier, AP-HP, 40, rue Mesly, 94000 Créteil, France.

Abstract

BACKGROUND:

Schizophrenia is an aetiologically heterogeneous syndrome, with a strong genetic component. Despite a reduced fertility in this disorder, its prevalence is maintained and could be explained by de novo genetic mutations. Advanced paternal age (APA) is a major source of new mutations in human beings and could thus be associated with an increased risk of developing schizophrenia in offspring. New mutations related to APA have been implicated as a cause of sporadic cases in several autosomal dominant diseases and also in neurodevelopmental diseases, autism, intellectual disabilities, and social functioning. The aim of the present study was to summarize the results of studies investigating the role of APA, and to discuss some interpretations.

METHODS:

All relevant studies were identified through the National Library of Medicine (PubMed(®) database). Keywords used for research were "age" and "schizophrenia" linked to "paternal or father". We have identified and analysed eight cohort studies, five case-control studies, two meta-analyses, and one review concerning different father's mutations potentially transmitted, two studies comparing paternal age at conception between sporadic versus familial cases of schizophrenia. All studies selected have been published between 2000 and 2009.

RESULTS:

After controlling for several confounding factors including maternal age, the relative risk of schizophrenia increased from 1.84 to 4.62 in offspring of fathers with an older age of fatherhood. Mother's age showed no significant effects after adjusting for paternal age. There was a significant association between paternal age and risk of developing schizophrenia, there was a weaker association with psychosis.

DISCUSSION:

The results of these different studies are confirmed by two recent meta-analyses which found an increased risk of schizophrenia in offspring of fathers older than 35 years. Two main hypotheses could explain these results. The first one is based on the presence of new mutations in the spermatogonia, possibly because of accumulating replication errors in spermatogonial cell lines. This hypothesis is confirmed by Malaspina et al. (2002) [19], who found that patients without a family history of schizophrenia had significantly older fathers than probands with a positive family history of schizophrenia. However, this result has not been confirmed by other studies, and paternal age effect could be also explained by a mechanism called imprinting, which is a form of gene regulation. The second hypothesis is based on the fact that fathers with schizophrenia spectrum personality disorder, known to be genetically related to schizophrenia, could have an advanced age at conception. However, regarding this hypothesis, advanced maternal age at conception should be a risk factor for schizophrenia, and this is not the case. Thus, the first hypothesis seems more plausible than the second. APA has been identified as a risk factor for other psychiatric disorders such as autism, bipolar disorder, obsessive-compulsive disorder, and phobia, and thus seems to be a non-specific risk factor. Furthermore, its association with impaired neurocognitive outcomes during infancy and childhood in normal populations raises the question of the phenotype linked to APA.

CONCLUSION:

APA at conception appears to be a risk factor for schizophrenia. This risk factor probably interacts with genetic factors in a gene-environment interaction. To date, there is no validated cut-off at which the risk is significantly increased in offspring. In the future, studies could benefit from analyzing the phenotype related to APA.

Copyright © 2010 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

PMID: 21703435 [PubMed - indexed for MEDLINE]

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Advancing paternal age and simplex autism.

2011-12-20T08:40:00.000-08:00

Autism. 2011 Dec 16. [Epub ahead of print]

Advancing paternal age and simplex autism.

Puleo CM, Schmeidler J, Reichenberg A, Kolevzon A, Soorya LV, Buxbaum JD, Silverman JM.

Source

Temple University, Philadelphia, PA, USA.

Abstract

De novo events appear more common in female and simplex autism spectrum disorder (ASD) cases and may underlie greater ASD risk in older fathers' offspring. This study examined whether advancing paternal age predicts an increase in simplex (n = 90) versus multiplex ASD cases (n = 587) in 677 participants (340 families). Whether or not controlling for maternal age, results support a significant interaction of linear paternal age and sex of the child on simplex family type. Female ASD cases were significantly more likely to be simplex as paternal age increased, but the increase for males was not significant. Findings suggest that ASD arising from non-familial, de novo events may be far less prominent in males than in females, even if more prevalent in males, due to the substantially larger number of male cases attributable to other, more strongly male-biased risk factors

Advanced paternal age appears to be associated with an increased risk of spontaneous abortion and increased frequency of some autosomal dominant conditions, autism spectrum disorders, and schizophrenia.

2011-11-16T08:37:00.000-08:00

J Obstet Gynaecol Can. 2011 Nov;33(11):1165-75.
Advanced reproductive age and fertility.
Liu K, Case A.
SourceToronto ON.

Abstract
Objective: To improve awareness of the natural age-related decline in female and male fertility with respect to natural fertility and assisted reproductive technologies (ART) and provide recommendations for their management, and to review investigations in the assessment of ovarian aging. Options: This guideline reviews options for the assessment of ovarian reserve and fertility treatments using ART with women of advanced reproductive age presenting with infertility. Outcomes: The outcomes measured are the predictive value of ovarian reserve testing and pregnancy rates with natural and assisted fertility. Evidence: Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in June 2010, using appropriate key words (ovarian aging, ovarian reserve, advanced maternal age, advanced paternal age, ART). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated into the guideline to December 2010. Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table). Benefits, harms, and costs: Primary and specialist health care providers and women will be better informed about ovarian aging and the age-related decline in natural fertility and about options for assisted reproductive technology. Recommendations 1. Women in their 20s and 30s should be counselled about the age-related risk of infertility when other reproductive health issues, such as sexual health or contraception, are addressed as part of their primary well-woman care. Reproductive-age women should be aware that natural fertility and assisted reproductive technology success (except with egg donation) is significantly lower for women in their late 30s and 40s. (II-2A) 2. Because of the decline in fertility and the increased time to conception that occurs after the age of 35, women > 35 years of age should be referred for infertility work-up after 6 months of trying to conceive. (III-B) 3. Ovarian reserve testing may be considered for women ≥ 35 years of age or for women < 35 years of age with risk factors for decreased ovarian reserve, such as a single ovary, previous ovarian surgery, poor response to follicle-stimulating hormone, previous exposure to chemotherapy or radiation, or unexplained infertility. (III-B) 4. Ovarian reserve testing prior to assisted reproductive technology treatment may be used for counselling but has a poor predictive value for non-pregnancy and should be used to exclude women from treatment only if levels are significantly abnormal. (II-2A) 5. Pregnancy rates for controlled ovarian hyperstimulation are low for women > 40 years of age. Women > 40 years should consider IVF if they do not conceive within 1 to 2 cycles of controlled ovarian hyperstimulation. (II-2B) 6. The only effective treatment for ovarian aging is oocyte donation. A woman with decreased ovarian reserve should be offered oocyte donation as an option, as pregnancy rates associated with this treatment are significantly higher than those associated with controlled ovarian hyperstimulation or in vitro fertilization with a woman's own eggs. (II-2B) 7. Women should be informed that the risk of spontaneous pregnancy loss and chromosomal abnormalities increases with age. Women should be counselled about and offered appropriate prenatal screening once pregnancy is established. (II-2A) 8. Pre-conception counselling regarding the risks of pregnancy with advanced maternal age, promotion of optimal health and weight, and screening for concurrent medical conditions such as hypertension and diabetes should be considered for women > age 40. (III-B) 9. Advanced paternal age appears to be associated with an increased risk of spontaneous abortion and increased frequency of some autosomal dominant conditions, autism spectrum disorders, and schizophrenia. Men > age 40 and their partners should be counselled about these potential risks when they are seeking pregnancy, although the risks remain small. (II-2C).

Poor sperm quality and advancing age are associated with increased sperm DNA damage in infertile men.

2011-11-02T14:53:00.000-07:00

Andrologia. 2011 Nov 1. doi: 10.1111/j.1439-0272.2011.01243.x. [Epub ahead of print]
Poor sperm quality and advancing age are associated with increased sperm DNA damage in infertile men.
Varshini J, Srinag BS, Kalthur G, Krishnamurthy H, Kumar P, Rao SB, Adiga SK.
Source Clinical Embryology, Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal, India National Centre for Biological Sciences, Tata Institute for Fundamental Research UAS-GKVK Campus, Bangalore, India Department of Radiation Biology and Toxicology, Manipal Life Science Centre, Manipal University, Manipal, India.

Abstract
With increasing evidence for faulty paternal contribution to reproduction, there has been a steady increase in studies highlighting an association between sperm DNA damage, failed/delayed fertilisation and aberrant embryo development. Owing to prevailing ambiguity, the aims of the study were to analyse the genetic integrity of the male gamete and then to understand its association with age, standard semen parameters, lifestyle and occupational factors. The study included 504 subjects, attending university infertility clinic for fertility evaluation and treatment. Semen characteristics were analysed by standard criteria; terminal deoxynucelotidyl transferase-mediated nick end-labelling assay was employed for DNA damage assessment. The average incidence of sperm DNA damage in patients with normozoospermic semen parameters was <10%. Patients with oligozoospermia, severe oligozoospermia, oligoasthenoteratospermia, asthenoteratozoospermia and necrozoospermia had significantly higher level of sperm DNA damage (P < 0.001). Patients above 40 years of age had significantly high levels of DNA damage (P < 0.001) compared with their counterparts. Patients with varicocele and a history of alcohol consumption had higher incidence of spermatozoa with DNA damage (P < 0.01). Poor sperm characteristics in the ejaculate are associated with increased sperm DNA damage. Age-related increase in sperm DNA damage and association of the same with varicocele and alcohol consumption are also demonstrated.

© 2011 Blackwell Verlag GmbH.

PMID:22040161[PubMed - as supplied by publisher]

The male biological clock

2011-10-24T15:23:00.000-07:00

The male biological clock
Friday, October 21, 2011
After 41 your chances of becoming a father ‘decline rapidly’, warn researchers

LONDON: It is not just women that have to worry about their biological clock. Male fertility declines with age – with even a year making a difference, researchers have warned. They say that after the age of 41, a man’s odds of fathering a child decline rapidly.

And after 45, those who haven’t started a family and want one should start doing something about it.

But with the likes of Des O’Connor having his fifth child at 72, and Rod Stewart becoming father for the eighth time at the age of 66, other experts said the finding should be taken with a pinch of salt.

The warning comes from a study of IVF patients in which the man’s sperm fertilised an egg from a donor.

In the context of the study, the use of donor eggs allowed the researchers to separate out the effect of the man’s age from that of the woman’s. The donor eggs all came from young, healthy women and so any differences in pregnancy rate must be due to the sperm.

And the difference was clear, with fertility declining by up to seven per cent with each extra year on a man’s age between 41 and 45. After that, it declined even more rapidly.

The average age of the men whose partners got treatment through IVF was 41.

In the context of the study, the use of donor eggs allowed the researchers to separate out the effect of the man’s age from that of the woman’s.

The donor eggs all came from young, healthy women and so any differences in pregnancy rate must be due to the sperm. And the difference was clear, with fertility declining by up to seven per cent with each extra year on a man’s age between 41 and 45. After that, it declined even more rapidly.
The average age of the men whose partners got treatment through IVF was 41.

But the average age of those in which the IVF was unsuccessful was 45, the American Society for Reproductive Medicine’s annual conference heard.

The chances of pregnancy fell from 60 per cent at the age of 41 to just 35 per cent for the 45-year-olds.

Researcher Paula Fettback, of the Huntington Medicina Reproductiva clinic in Brazil, said: “Age counts.

“Men have a biological clock too. It is not the same as for women but they can’ t wait forever to have children.

“They have to think about having children, especially after 45.”

A second study presented at the conference backed up the warning.

There, fertility plummeted in male mice from a year old – equivalent to middle-age in people.

Fewer eggs were fertilised and fewer embryos grew long enough to be used in IVF.

Pregnancies took longer to occur and when they did, the miscarriage rate rocketed from zero using sperm from young animals, to over 60 per cent.

The researchers, from the Colorado Center for Reproductive Medicine, said they believed there would be ‘some parallel’ with men.

“We found an abrupt reproductive deterioration in mid-life, equivalent to humans in their 40s.”

Other studies have found that children of older fathers also run an increased risk of heart defects, autism, schizophrenia and epilepsy, and are almost twice as likely to die before adulthood.

.Male fertility showed a 21-23% annual decrease starting at the age of 39.

2011-10-18T08:41:00.000-07:00

Gynecol Obstet Invest. 2011;71(4):229-35. Epub 2010 Dec 15.
Decline in human fertility rates with male age: a consequence of a decrease in male fecundity with aging?
Matorras R, Matorras F, Expósito A, Martinez L, Crisol L.
SourceHuman Reproduction Unit, Department of Obstetrics and Gynecology, Hospital de Cruces, Basque Country University, Baracaldo, Spain. roberto.matorras @ osakidetza.net

Abstract
BACKGROUND: The objective of this study is to investigate the influence of male age on human fertility, defined as the birth rate for a given population.

METHODS: Data from the Spanish National Statistics Institute (INE) for the year 2004 from a total of 454,753 newborn infants and sorted by male and female age groups were evaluated. In order to correct the influence of female age-related fertility, a different analysis was performed considering only women under 30 years of age.

RESULTS: From a demographic point of view, male fertility started to decline at 35-39 years of age. This decline is constant and follows an exponential pattern (slope -0.11 to -0.12). The trend persisted when the data were adjusted for every 1,000 men in the age group, as well as when only women under the age of 30 were considered. Male fertility showed a 21-23% annual decrease starting at the age of 39.

CONCLUSION: An exponential decrease in human fertility which is independent of the woman's age was observed with male aging. This decay is probably due to a downfall in male fecundity, closely related to a decline in sperm quality. However, social or behavioral causes for this trend cannot be excluded.

Copyright © 2010 S. Karger AG, Basel.

Advanced paternal and grandpaternal age and schizophrenia: A three-generation perspective.

2011-10-18T08:18:00.000-07:00

Schizophr Res. 2011 Oct 13. [Epub ahead of print]
Advanced paternal and grandpaternal age and schizophrenia: A three-generation perspective.
Frans EM, McGrath JJ, Sandin S, Lichtenstein P, Reichenberg A, Långström N, Hultman CM.
SourceDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Abstract
BACKGROUND: Advanced paternal age has been linked with an increased risk of schizophrenia in the offspring. If age-related de novo mutations in the male germ line underlie this association, grandpaternal and paternal age would both be expected to influence the risk of schizophrenia. The aim of the current study was to explore the links between both paternal and grandpaternal age with respect to the risk of schizophrenia in a large, national register-based cohort.

METHOD: We linked the Swedish Multi-Generation and Hospital Discharge Registers and compared parents' ages at offspring birth for 20,582 schizophrenia-affected and 100,176 non-affected individuals. Grandparents' ages at the birth of the parent were compared between 2511 affected and 15,619 non-affected individuals. The risk of schizophrenia was examined with logistic regression when the predictor variable (parent or grandparent age) varied across age strata.

RESULTS: After adjusting for maternal age, birth year and proband sex, we confirmed that offspring of older fathers had an increased risk of schizophrenia. Compared to those with paternal age 20-24years, those with fathers >55years had a two-fold increased risk of schizophrenia. With respect to grandparent age, older maternal (but not paternal) grandfather age was associated with an increased risk of schizophrenia. Compared to maternal grandfather age 20-24years, those with maternal grandfathers >55years had a significantly increased risk of schizophrenia (adjusted odds ratio and 95% confidence intervals; 2.79, 1.71-4.56). The pattern of results was essentially unchanged when we examined male and female probands separately.

CONCLUSION: This is the first study to report an association between grandpaternal age and risk of schizophrenia. The selective effect of advanced maternal grandfather age suggests that the biological mechanisms involving the X-chromosome may differentially contribute to the association between paternal age and offspring risk of schizophrenia.

Copyright © 2011. Published by Elsevier B.V.

De novo copy number variants associated with intellectual disability have a paternal origin and age bias.

2011-10-05T08:52:00.000-07:00

J Med Genet. 2011 Oct 3. [Epub ahead of print]
De novo copy number variants associated with intellectual disability have a paternal origin and age bias.
Hehir-Kwa JY, Rodríguez-Santiago B, Vissers LE, de Leeuw N, Pfundt R, Buitelaar JK, Pérez-Jurado LA, Veltman JA.
Source1Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences and Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Abstract
BackgroundDe novo mutations and structural rearrangements are a common cause of intellectual disability (ID) and other disorders with reduced or null reproductive fitness. Insight into the genomic and environmental factors predisposing to the generation of these de novo events is therefore of significant clinical importance.MethodsThis study used information from single nucleotide polymorphism microarrays to determine the parent-of-origin of 118 rare de novo copy number variations (CNVs) detected in a cohort of 3443 patients with ID.ResultsThe large majority of these CNVs (76%, p=1.14×10(-8)) originated on the paternal allele. This paternal bias was independent of CNV length and CNV type. Interestingly, the paternal bias was less pronounced for CNVs flanked by segmental duplications (64%), suggesting that molecular mechanisms involved in the formation of rare de novo CNVs may be dependent on the parent-of-origin. In addition, a significantly increased paternal age was only observed for those CNVs which were not flanked by segmental duplications (p=0.02).ConclusionThis indicates that rare de novo CNVs are increasingly being generated with advanced paternal age by replication based mechanisms during spermatogenesis.

The prevalence of spontaneous mutations increases with age in the male germline; consequently, older men have an increased risk of siring children with genetic disease due to de novo mutations.

2011-09-16T13:18:00.001-07:00

Mol Reprod Dev. 2011 Aug 5. doi: 10.1002/mrd.21374. [Epub ahead of print]
Age-related instability in spermatogenic cell nuclear and mitochondrial DNA obtained from Apex1 heterozygous mice.
Vogel KS, Perez M, Momand JR, Acevedo-Torres K, Hildreth K, Garcia RA, Torres-Ramos CA, Ayala-Torres S, Prihoda TJ, McMahan CA, Walter CA.
SourceDepartment of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.

Abstract
The prevalence of spontaneous mutations increases with age in the male germline; consequently, older men have an increased risk of siring children with genetic disease due to de novo mutations. The lacI transgenic mouse can be used to study paternal age effects, and in this system, the prevalence of de novo mutations increases in the male germline at old ages. Mutagenesis is linked with DNA repair capacity, and base excision repair (BER), which can ameliorate spontaneous DNA damage, decreases in nuclear extracts of spermatogenic cells from old mice. Mice heterozygous for a null allele of the Apex1 gene, which encodes apurinic/apyrimidinic endonuclease I (APEN), an essential BER enzyme, display an accelerated increase in spontaneous germline mutagenesis early in life. Here, the consequences of lifelong reduction of APEN on genetic instability in the male germline were examined, for the first time, at middle and old ages. Mutant frequency increased earlier in spermatogenic cells from Apex1(+/-) mice (by 6 months of age). Nuclear DNA damage increased with age in the spermatogenic lineage for both wild-type and Apex1(+/-) mice. By old age, mutant frequencies were similar for wild-type and APEN-deficient mice. Mitochondrial genome repair also depends on APEN, and novel analysis of mitochondrial DNA (mtDNA) damage revealed an increase in the Apex1(+/-) spermatogenic cells by middle age. Thus, Apex1 heterozygosity results in accelerated damage to mtDNA and spontaneous mutagenesis, consistent with an essential role for APEN in maintaining nuclear and mtDNA integrity in spermatogenic cells throughout life. Mol. Reprod. Dev. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

Published 2011 Wiley-Liss, Inc. This article is a U.S. Government work and is in the public domain in the USA.

Urology. 2011 Sep;78(3):496-9.

2011-09-03T09:33:00.000-07:00

Urology. 2011 Sep;78(3):496-9.
Fertility concerns for the aging male.
Stewart AF, Kim ED.
SourceDivision of Urology, Department of Surgery, University of Tennessee, Graduate School of Medicine, Knoxville, TN.

Abstract
Because of many societal factors, the number of men over the age of 35 desiring to conceive children has increased over the past 40 years. The purpose of this review is to identify the mechanisms of aging on male fertility, to evaluate the genetic risk for the offspring, and to provide counseling for the older male. Most evidence suggests trends that increased paternal age has negative effects on fertility and some genetic risk for offspring, but the age at which the risk develops and the magnitude of risk are poorly defined.

Copyright © 2011 Elsevier Inc. All rights reserved.

Father Time: Children with Older Dads at Greater Risk for Mental Illness

2011-08-29T18:03:00.001-07:00

Father Time: Children with Older Dads at Greater Risk for Mental Illness

The present trend of increasing paternal age is accompanied by concerns for the development of complex multi-gene diseases, e.g. autism and schizophrenia

2011-08-26T09:43:00.000-07:00

Biol Reprod. 2011 Aug 24. [Epub ahead of print]
Aging Results in Differential Regulation of DNA Repair Pathways in Pachytene Spermatocytes in the Brown Norway Rat.
Paul C, Nagano M, Robaire B.
Abstract
The present trend of increasing paternal age is accompanied by concerns for the development of complex multi-gene diseases, e.g. autism and schizophrenia, in progeny. Recent studies have established strong correlations between male age, increased oxidative stress, decreased sperm quality and structural aberrations of chromatin and DNA in spermatozoa. We tested the hypothesis that increasing age would result in altered gene expression relating to oxidative stress and DNA damage/repair in germ cells. To test this hypothesis, pachytene spermatocytes and round spermatids were isolated from Brown Norway (BN) rats at 4 (young) and 18 (aged) months of age. Microarray analysis was used to compare gene expression between the groups. The probe sets with significantly altered expression were linked to DNA damage/repair and oxidative stress in pachytene spermatocytes but not in round spermatids. Further analysis of pachytene spermatocytes demonstrated that genes involved in the base excision repair (BER) and nucleotide excision repair (NER) pathways were specifically altered. Quantitative RT-PCR confirmed that NER genes were upregulated (>1.5 fold) whereas BER genes were downregulated (>1.5 fold). At the protein level the members of the BER pathway were also altered by up to 2.3 fold; levels of NER proteins remained unchanged. Furthermore there was an increase in 8-oxo-2'-deoxyguanosine (8-oxodG) immunoreactivity in testes from aged males and in the number of spermatozoa positive for 8-oxodG. In conclusion, aging is associated with differential regulation of DNA repair pathways with a decrease in the BER pathway leading to deficient repair of 8-oxo-dG lesions in germ cells and spermatozoa.

Parental Age Effects on Cortical Morphology in Offspring.

2011-08-06T10:20:00.000-07:00

Parental Age Effects on Cortical Morphology in Offspring.
Cereb Cortex. 2011 Aug 4. [Epub ahead of print]
Parental Age Effects on Cortical Morphology in Offspring.
Shaw P, Gilliam M, Malek M, Rodriguez N, Greenstein D, Clasen L, Evans A, Rapoport J, Giedd J.
SourceChild Psychiatry Branch, Intramural Program of the National Institute of Mental Health.

Abstract
The age at which a parent has a child impacts the child's cognition and risk for mental illness. It appears that this risk is curvilinear, with both age extremes associated with lower intelligence and increased prevalence of some neuropsychiatric disorders. Little is known of the neural mechanisms underpinning this phenomenon. We extracted lobar volumes, surface areas, and cortical thickness from 489 neuroanatomic magnetic resonance images acquired on 171 youth. Using linear mixed model regression, we determined the association between parental age and offspring's neuroanatomy, adjusting for offspring's age, sex, intelligence, and parental socioeconomic class. For gray matter volumes, quadratic paternal and maternal age terms contributed significantly (maternal quadratic age effect: t = -2.2, P = 0.03; paternal quadratic age effect: t = -2.4, P = 0.02) delineating an inverted "U" relationship between parental age and gray matter volume. Cortical volume increased with both advancing paternal and maternal age until around the early 30s after which it fell. Paternal age effects were more pronounced on cortical surface area, whereas maternal age impacted more on cortical thickness. There were no significant effects of parental age on white matter volumes. These parental age effects on cerebral morphology may form part of the link between parental age extremes and suboptimal neurocognitive outcomes.

PMID:21817090[PubMed - as supplied by publisher]

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia.

2011-06-30T08:47:00.000-07:00

J Vis Exp. 2011 Jun 15;(52). pii: 2534. doi: 10.3791/2534.
A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia.
Julie G, Hamdan FF, Rouleau GA.
SourceCentre of Excellence in Neuromics, CHUM Research Center and the Department of Medicine, Universite de Montreal.

Abstract
There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, the de novo mutation rate in humans is relatively high, so new mutations are generated at a high frequency in the population. However, de novo mutations have not been reported in most common diseases. Mutations in genes leading to severe diseases where there is a strong negative selection against the phenotype, such as lethality in embryonic stages or reduced reproductive fitness, will not be transmitted to multiple family members, and therefore will not be detected by linkage gene mapping or association studies. The observation of very high concordance in monozygotic twins and very low concordance in dizygotic twins also strongly supports the hypothesis that a significant fraction of cases may result from new mutations. Such is the case for diseases such as autism and schizophrenia. Second, despite reduced reproductive fitness(1) and extremely variable environmental factors, the incidence of some diseases is maintained worldwide at a relatively high and constant rate. This is the case for autism and schizophrenia, with an incidence of approximately 1% worldwide. Mutational load can be thought of as a balance between selection for or against a deleterious mutation and its production by de novo mutation. Lower rates of reproduction constitute a negative selection factor that should reduce the number of mutant alleles in the population, ultimately leading to decreased disease prevalence. These selective pressures tend to be of different intensity in different environments. Nonetheless, these severe mental disorders have been maintained at a constant relatively high prevalence in the worldwide population across a wide range of cultures and countries despite a strong negative selection against them(2). This is not what one would predict in diseases with reduced reproductive fitness, unless there was a high new mutation rate. Finally, the effects of paternal age: there is a significantly increased risk of the disease with increasing paternal age, which could result from the age related increase in paternal de novo mutations. This is the case for autism and schizophrenia(3). The male-to-female ratio of mutation rate is estimated at about 4-6:1, presumably due to a higher number of germ-cell divisions with age in males. Therefore, one would predict that de novo mutations would more frequently come from males, particularly older males(4). A high rate of new mutations may in part explain why genetic studies have so far failed to identify many genes predisposing to complexes diseases genes, such as autism and schizophrenia, and why diseases have been identified for a mere 3% of genes in the human genome. Identification for de novo mutations as a cause of a disease requires a targeted molecular approach, which includes studying parents and affected subjects. The process for determining if the genetic basis of a disease may result in part from de novo mutations and the molecular approach to establish this link will be illustrated, using autism and schizophrenia as examples.

PMID:21712793[PubMed - in process]

Influence of paternal age in schizophrenia

2011-06-28T09:03:00.001-07:00

Encephale. 2011 Jun;37(3):199-206. Epub 2011 Apr 2.
[Influence of paternal age in schizophrenia.]
[Article in French]
Hubert A, Szöke A, Leboyer M, Schürhoff F.
SourcePôle de psychiatrie du CHU de Créteil, groupe hospitalier Henri-Mondor-Albert-Chenevier, AP-HP, 40, rue Mesly, 94000 Créteil, France; Inserm unité 955, IMRB, département de génétique, équipe 15, 94000 Créteil, France; Faculté de médecine, université Paris-Est Créteil, IFR10, 94000 Créteil, France; Fondation Fondamental, fondation de coopération scientifique, hôpital Chenevier, 40, rue Mesly, 94000 Créteil, France.

Abstract
BACKGROUND: Schizophrenia is an aetiologically heterogeneous syndrome, with a strong genetic component. Despite a reduced fertility in this disorder, its prevalence is maintained and could be explained by de novo genetic mutations. Advanced paternal age (APA) is a major source of new mutations in human beings and could thus be associated with an increased risk of developing schizophrenia in offspring. New mutations related to APA have been implicated as a cause of sporadic cases in several autosomal dominant diseases and also in neurodevelopmental diseases, autism, intellectual disabilities, and social functioning. The aim of the present study was to summarize the results of studies investigating the role of APA, and to discuss some interpretations.

METHODS: All relevant studies were identified through the National Library of Medicine (PubMed(®) database). Keywords used for research were "age" and "schizophrenia" linked to "paternal or father". We have identified and analysed eight cohort studies, five case-control studies, two meta-analyses, and one review concerning different father's mutations potentially transmitted, two studies comparing paternal age at conception between sporadic versus familial cases of schizophrenia. All studies selected have been published between 2000 and 2009.

RESULTS: After controlling for several confounding factors including maternal age, the relative risk of schizophrenia increased from 1.84 to 4.62 in offspring of fathers with an older age of fatherhood. Mother's age showed no significant effects after adjusting for paternal age. There was a significant association between paternal age and risk of developing schizophrenia, there was a weaker association with psychosis.

DISCUSSION: The results of these different studies are confirmed by two recent meta-analyses which found an increased risk of schizophrenia in offspring of fathers older than 35 years. Two main hypotheses could explain these results. The first one is based on the presence of new mutations in the spermatogonia, possibly because of accumulating replication errors in spermatogonial cell lines. This hypothesis is confirmed by Malaspina et al. (2002) [19], who found that patients without a family history of schizophrenia had significantly older fathers than probands with a positive family history of schizophrenia. However, this result has not been confirmed by other studies, and paternal age effect could be also explained by a mechanism called imprinting, which is a form of gene regulation. The second hypothesis is based on the fact that fathers with schizophrenia spectrum personality disorder, known to be genetically related to schizophrenia, could have an advanced age at conception. However, regarding this hypothesis, advanced maternal age at conception should be a risk factor for schizophrenia, and this is not the case. Thus, the first hypothesis seems more plausible than the second. APA has been identified as a risk factor for other psychiatric disorders such as autism, bipolar disorder, obsessive-compulsive disorder, and phobia, and thus seems to be a non-specific risk factor. Furthermore, its association with impaired neurocognitive outcomes during infancy and childhood in normal populations raises the question of the phenotype linked to APA.

CONCLUSION: APA at conception appears to be a risk factor for schizophrenia. This risk factor probably interacts with genetic factors in a gene-environment interaction. To date, there is no validated cut-off at which the risk is significantly increased in offspring. In the future, studies could benefit from analyzing the phenotype related to APA.

Copyright © 2010 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Advanced paternal age is a risk factor for schizophrenia in Iranians.

2011-04-26T08:08:00.000-07:00

Ann Gen Psychiatry. 2011 Apr 24;10(1):15. [Epub ahead of print]
Advanced paternal age is a risk factor for schizophrenia in Iranians.
Naserbakht M, Ahmadkhaniha HR, Mokri B, Smith CL.
Abstract
ABSTRACT:

BACKGROUND: Since 1958 many, but not all studies have demonstrated that paternal age is a risk factor for schizophrenia. There may be many different explanations for differences between studies, including study design, sample size, collection criteria, heterogeneity and the confounding effects of environmental factors that can for example perturb epigenetic programming and lead to an increase in disease risk. The small number of children in Western families makes risk comparisons between siblings born at different paternal ages difficult. In contrast, more Eastern families have children both at early and later periods of life. In the present study, a cross-sectional population study in an Iranian population was performed to compare frequency of schizophrenia in younger offspring (that is, older paternal age) versus older offspring.

METHODS: A total of 220 patients with the diagnosis of schizophrenia (cases) from both psychiatric hospitals and private clinics and 220 individuals from other hospital wards (controls), matched for sex and age were recruited for this study. Patients with neurological problem, substance abuse, mental retardation and mood disorder were excluded from both groups.

RESULTS: Birth rank comparisons revealed that 35% vs 24% of the cases vs the controls were in the third or upper birth rank (P = 0.01). Also, the mean age of fathers at birth in case group (30 +/- 6.26 years) was significantly more than the control group (26.45 +/- 5.64 years; P = 0.0001). The age of 76 fathers at birth in case group was over 32 versus 33 fathers in control group. Individuals whose fathers' age was more than 32 (at birth) were at higher risk (2.77 times) for schizophrenia versus others (P <0.0001, 95% CI 1.80 to 4.27). The maternal age at parturition of the case versus controls groups was 26.1 +/- 5.41 vs 25.07 +/- 4.47 (P = 0.02). Logistic regression analysis suggests that maternal age is less likely to be involved in the higher risk of schizophrenia than advanced parental age.

DISCUSSION: This study demonstrates a relationship between paternal age and schizophrenia in large families of an Iranian population. Arguments have been put forth that DNA bases changes or epigenetic changes in sperm account for the increased risk associated with older fathers. However, it would not be surprising that both de novo germline mutations and epigenetic changes contribute to disease occurrence because DNA replication and DNA methylation are closely linked at both the macromolecular level (that is, methylation closely follows replication), and at the metabolic level (both processes require folate), and susceptible to modulation by the environment. Further research on samples such as those collected here are needed to sort out the contributions of de novo mutations versus epigenetic changes to schizophrenia.

PMID:21513574[PubMed - as supplied by publisher]

Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis.

2011-03-01T08:56:00.000-08:00

Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis.

Lee H, Malaspina D, Ahn H, Perrin M, Opler MG, Kleinhaus K, Harlap S, Goetz R, Antonius D.

Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA.

Abstract
BACKGROUND: Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia.

METHODS: We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers' age at birth ≥35years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale-Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS.

RESULTS: Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early.

CONCLUSIONS: These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment.

Copyright © 2011 Elsevier B.V. All rights reserved.
PMID: 21353765 [PubMed - as supplied by publisher]

Are Advanced Paternal Age and Point Mutation at Chromosome 4 Associated With Schizophrenia?

2011-01-30T17:43:00.000-08:00

Prim Care Companion J Clin Psychiatry. 2010;12(5). pii: PCC.10l00952.

Are Advanced Paternal Age and Point Mutation at Chromosome 4 Associated With Schizophrenia?
Phutane VH, Loganathan S, Jhirwal OP, Varghese M, Jain S, Girimaji SC.

Department of Psychiatry, Yale University, School of Medicine, Connecticut Mental Health Center, New Haven ; Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri ; Department of Psychiatry, National Institute of Human Behavior and Allied Science, Delhi, India ; and Department of Psychiatry, Institute of Mental Health and Neurosciences, Bangalore, India.

PMID: 21274353 [PubMed - as supplied by publisher]

The Male Biological Clock

2011-01-13T15:11:00.000-08:00

According to Nebraska Medical Center, ideally, fathers should finish their family by 40. It is quite risky for fathers over forty to have a child with an autosomal dominant mutation. Fathers over fifty were found to have a twenty percent greater incidence of producing a baby born with serious defects.

A research scientist has been looking into male infertility and remains unconvinced by the American findings on sperm quality.

They get men over sixty coming in for semen analysis and their sperm is no different from that of 20-year-old added the scientist. After 55, sperm numbers significantly reduce. Furthermore he takes the traditional view, maintaining that sperm quality is influenced by factors other than age. Alcohol, smoking, stress, diet, and large levels of cadmium and lead can affect sperm, Heavy alcoholics and cocaine users experience the severest drop in sperm production added research scientist.

According to studies, men are productivity better built than women, sperm are produced every minute of the day, each sperm taking 72 days to evolve. A man produces 200-400 million sperm a day- and it only needs one to fertilize an egg. This goes some way to explained why traditionally it has been more socially acceptable for men to "spread their seed"; it’s all in the name of procreation.

Author of the Rites of Man: love, sex and death in the making of the male, believes that encountering paternal death sooner rather than later makes a great deal of difference to a child. So, if the father is approaching that age, it’s likely that parental loss will occur just when the child is supposed to having the best time of her or his life. This can lead to awful emotional difficulties, apart from the understandable grief. It can result in terrible feelings of guilt and anger.

Nowadays, economic factors like money, jobs, maternity leave and child care play as even greater part in determining when is the right time to reproduce.

The older father will often become "Big Daddy", showering gifts on the daughter and spoiling her. Treating her as "his baby". The relationship will either be intensely paternalistic or lover-like. The more the older father invests in his daughter, the more difficult it will be for her daughter to become independent.

An older father only grows older and, as his daughter’s life is expanding, he is contracting. When he is post-menopausal, she is becoming a woman.

Beating the clock

Nowadays, economic factors like jobs, maternity leave, money and child care play an even greater part in determining when it is right time to reproduce. As women, it can be galling to feel there is a further pressing factor: the biological clock. The facts that biology may not be so favorable to men either is one that, curiously, has been all but ignored up to now. According to psychology adviser, as long as women are conscious of their biological clock, while men regard themselves as immune, this will remain a potential source of conflict and of women’s resentment. But if men start to become more conscious of their own internal ticking the two sexes will gain understanding of each other.

Delayed fathering and risk of mental disorders in adult offspring.

2011-01-12T08:07:00.000-08:00

Early Hum Dev. 2011 Jan 8. [Epub ahead of print]

Delayed fathering and risk of mental disorders in adult offspring.
Krishnaswamy S, Subramaniam K, Ramachandran P, Indran T, Abdul Aziz J.

University of New England, Locked bag 4, NSW 2351, Australia.

Abstract
INTRODUCTION: Delayed parenting and child bearing at a very young age impose various risks to development of the offspring.

OBJECTIVE: This study aims to investigate the association between disparities in parental age and increased risk factor for common mental disorders in the progenies during adulthood.

METHODOLOGY: The Malaysian Mental Health Survey (MMHS) was analysed for this study. Respondents were asked to estimate the age of their parents at their birth. Presence of common mental disorders (CMD) was determined by referring to the diagnosis given by the Clinical Interview Schedule-Revised (CIS-R) instrument in the Programmed Questionnaire System (PROQSY) format. The association between parental age disparities and CMD was studied using logistic regression.

RESULT: Fifty three percent (n=1972) of the MMHS respondents (N=3666) knew the age of both parents and were included in the study. Three percent (n=53) had significant disparity in parental age, or a difference of 11years or more. Respondents born to parents with significant age disparity had a prevalence rate of 24% (95% CI=22.12-25.89) for CMD in comparison to 6% (95% CI=5.99-6.11) in their counterparts and 3.4 times higher risk for CMD, after adjusting for demographic factors, paternal age at birth and presence of family history of mental disorders. Amongst those born to older fathers aged 50 and above, the presence of disparity increased the rate for CMD to 42% (95% CI=39.82-44.18).

DISCUSSION: Disparity in parental age was significantly associated with increased risk for CMD. Various psychosocial factors contributing to age disparity in both the father and the mother could predispose to stress and mental health problems.

Copyright Â© 2010 Elsevier Ltd. All rights reserved.

Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies.

2010-12-01T11:17:00.000-08:00

Mol Psychiatry. 2010 Nov 30. [Epub ahead of print]

Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies.
Hultman CM, Sandin S, Levine SZ, Lichtenstein P, Reichenberg A.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Abstract
Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort (N=1 075 588) was established. Linkage to the National Patient Register ascertained all autism cases (N=883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged 50 years were 2.2 times (95% confidence interval: 1.26-3.88: P=0.006) more likely to have autism than offspring of men aged 29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity (P<0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de novo aberration and mutations or epigenetic alterations associated with aging.Molecular Psychiatry advance online publication, 30 November 2010; doi:10.1038/mp.2010.121.

looked into the relationship between a father’s age and his adult offspring’s likelihood of developing certain cancers.

2010-11-12T14:51:00.001-08:00

Study could change the way doctors understand certain cancers

Dr. Yani Lu’s latest research discovery at City of Hope could change the way doctors understand and treat certain cancers.

Lu, a postdoctoral fellow in the Division of Cancer Etiology, looked into the relationship between a father’s age and his adult offspring’s likelihood of developing certain cancers.

Dr. Yani Lu discovered a connection between a father’s age and his children’s chances to develop certain cancers.
Dr. Lu concluded that the children of older fathers face an increased risk of non-Hodgkin’s lymphoma later in life.

“As a man, you may think you can have a baby at 50 or 60” with no real repercussions, Lu says. “But there may be other risks for your child down the line.”

The idea of a “biological clock” is commonly associated with women alone, but Lu’s research challenges that double standard. In the study, Lu points out that older parents are prone to passing on undesirable genetic traits.

Lu believes the male biological clock might relate to mutations that can accumulate in a man’s reproductive cells over the course of a lifetime. Such cells divide more rapidly than a woman’s reproductive cells. More divisions lead to more chances for abnormalities.

But because many non-Hodgkin’s lymphoma patients are well into their 60s or 70s at the time of diagnosis, most research on the disease has failed to consider genetic effects at all.

Lu and her research team recognized that being born to older parents can have consequences extending well into adulthood.

“For adult-onset malignancies, people seldom think back to factors early in life,” Lu says.

Lu plans to continue her research on the male biological clock by focusing on other, similar cancers

2010-10-18T15:07:00.001-07:00

Nicholas Murdoch
October 18, 2010
The Male Biological Clock: The Startling News About Aging, Sexuality, and Fertility in Men
Filed under: Braun Clocks — Tags: Aging, Biological, Clock, Fertility, Sexuality, Startling — duboring @ 11:50 am

: – The Male Biological Clock: The Startling News About Aging, Sexuality, and Fertility in Men

The Male Biological Clock: The Startling News About Aging, Sexuality, and Fertility in Men

Part fertility guide, part owner’s manual to the male reproductive system, The Male Biological Clock attempts to ditch some of the numerous existing myths about men’s roles in pregnancy while introducing up-to-date medical research on hormones and health. In modern culture, the words “male” and “biological clock” aren’t typically seen together, but Dr. Harry Fisch has news: after the age of 35, men have increased rates of infertility, can contribute to the likelihood of a miscarriage, and are more likely to father a child with Down syndrome.

These results support the claim that increased paternal age is associated with a birth of a child with autism spectrum disorder

2010-09-15T08:09:00.001-07:00

Pediatr Neurol. 2010 Oct;43(4):300-302.

Paternal Age in Autism Spectrum Disorders and ADHD.
Gabis L, Raz R, Kesner-Baruch Y.

Weinberg Child Development Center, Safra Children's Hospital, Sheba Medical Center (affiliated with the Sackler School of Medicine, Tel-Aviv University, Israel), Tel Hashomer, Israel.

Abstract
Increased paternal age has been associated with an increased risk for autism spectrum disorders. The present study compared the paternal age distribution in autism spectrum disorders children with that of the general population and among children with attention deficit hyperactivity disorder. Study participants were drawn from the records of children diagnosed with one of these conditions in the years 1998-2006 at the Weinberg Child Development Center, Israel. Data regarding paternal age distribution in the general Israeli population were drawn from the yearly official publications of the Central Bureau of Statistics, Israel. Paternal age at the child's birth was found for autism spectrum disorders children (n = 268) and attention deficit hyperactivity disorders children (n = 320). Paternal age distribution of the attention deficit hyperactivity disorder children was similar to that of the general population in Israel, whereas autism spectrum disorders children were born to older fathers, compared with either the general population (P < 0.001) or children with attention deficit hyperactivity disorder (P = 0.04). These results support the claim that increased paternal age is associated with a birth of a child with autism spectrum disorders, but indicate that this finding cannot be generalized to attention deficit hyperactivity disorder.

In cases of sporadic achondroplasia as well as in fibrodysplasia ossificans progressiva, there is a strong association with paternal age,

2010-09-09T08:25:00.000-07:00

Adv Exp Med Biol. 2010;686:335-48.

Osteochondral diseases and fibrodysplasia ossificans progressiva.
Morales-Piga A, Kaplan FS.

Jefe de Servicio de Proyectos Clínicos del Instituto de Investigación de Enfermedades Raras, Instituto de Salud Carlos III, Sinesio Delgado, 6, 28029, Madrid, Spain, amorales@isciii.es.

Abstract
Osteochondrodysplasias like thanatophoric dysplasia, osteogenesis imperfecta, achondroplasia, and other genetic skeletal disorders like fibrodysplasia ossificans progressiva are infrequently seen in clinical practice. In cases of sporadic achondroplasia as well as in fibrodysplasia ossificans progressiva, there is a strong association with paternal age, a relationship that is less evident in other genetic osteochondral diseases. No other constitutional or environmental factor has proven to be associated with these disorders. The use of prenatal ultrasonography as a routine component of prenatal care is crucial in the early suspicion of osteochondrodysplasias whereas definitive diagnosis is usually obtained by pre-natal molecular analysis. In the case of fibrodysplasia ossificans progressiva, recognition of congenital great toe malformations associated with rapidly-appearing soft tissue swelling is sufficient to make the proper clinical diagnosis, which can be confirmed by genetic testing. Large regional centres will improve diagnosis performance, provide accurate genetic counselling, and ensure an integral assistance for these often severe and incapacitating conditions.

Older paternal age strongly increases the morbidity for schizophrenia in sisters of affected females.

2010-08-19T08:07:00.000-07:00

Am J Med Genet B Neuropsychiatr Genet. 2010 Aug 17. [Epub ahead of print]

Older paternal age strongly increases the morbidity for schizophrenia in sisters of affected females.
Perrin M, Harlap S, Kleinhaus K, Lichtenberg P, Manor O, Draiman B, Fennig S, Malaspina D.

Department of Psychiatry, New York University School of Medicine, New York, New York.

Abstract
The effect of a family history of schizophrenia on the risk for this disorder in the offspring has rarely been examined in a prospective population cohort accounting for the sex of the proband and the first-degree relatives, and certainly not with respect to later paternal age. The influence of affected relatives on offspring risk of schizophrenia was estimated using Cox proportional hazards regression in models that accounted for sex, relation of affected first degree relatives and paternal age in the prospective population-based cohort of the Jerusalem Perinatal Schizophrenia Study. Of all first-degree relatives, an affected mother conferred the highest risk to male and female offspring among the cases with paternal age <35 years, however, female offspring of fathers >/=35 years with an affected sister had the highest risk (RR = 8.8; 95% CI = 3.9-19.8). The risk seen between sisters of older fathers was fourfold greater than the risk to sisters of affected females of younger fathers (RR = 2.2, 95% CI 0.7-6.7). The test for interaction was significant (P = 0.03). By contrast, the risk of schizophrenia to brothers of affected males was only doubled between older (RR = 3.3, 95% 1.6-6.6) and younger fathers (RR = 1.6, 95% CI 0.7-3.5). The most striking finding from this study was the very large increase in risk of schizophrenia to sisters of affected females born to older fathers. The authors speculate that the hypothesized paternally expressed genes on the X chromosome might play some role in these observations. (c) 2010 Wiley-Liss, Inc.

PMID: 20718003 [PubMed - as supplied by publisher]

Paternal age increases the risk for autism in an Iranian population sample.

2010-08-04T09:37:00.001-07:00

http://www.ncbi.nlm.nih.gov/pubmed/20678245

Mol Autism. 2010 Feb 22;1(1):2.

Paternal age increases the risk for autism in an Iranian population sample.
Sasanfar R, Haddad SA, Tolouei A, Ghadami M, Yu D, Santangelo SL.

Department of Psychiatry, Harvard Medical School, Boston, MA, USA. ssantangelo@pngu.mgh.harvard.edu.

Abstract
ABSTRACT: BACKGROUND: Autism is a neurodevelopmental disorder which is known to have a strong genetic component and is most likely oligogenic. However, the necessary role of environmental factors has been well documented. Prior research suggests that parental characteristics, such as age and level of education, may be associated with a risk of autism. Parental age has been shown to be associated with many disorders, such as schizophrenia, childhood cancer and fetal death. However, results from studies of parental age and autism are inconsistent. METHODS: In the present study, we investigated the association of autism with parental age in 179 autism cases and 1611 matched cohort children from Iran. Each case was matched with nine cohort controls on parental education, sex, order of birth, consanguineous marriage, urbanism and province of residence. The Cox regression model was used to carry out conditional logistic regression on the matched data. RESULTS: There was a significant association between higher paternal age, but not maternal age, and an increasing risk of autism. An analysis of the combined effect of parental age and education also revealed that parents with higher education had an increased risk of having autistic children, with a dose-response effect of parental age. CONCLUSIONS: This study, which is

In females but not in males, increasing paternal age was associated with a linear increased risk of suicide

2010-06-10T10:50:00.000-07:00

J Nerv Ment Dis. 2010 Jun;198(6):404-411.

Advanced Paternal Age, Mortality, and Suicide in the General Population.
Miller B, Alaräisänen A, Miettunen J, Järvelin MR, Koponen H, Räsänen P, Isohanni M, Kirkpatrick B.

*Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta, Georgia; daggerDepartment of Psychiatry, University of Oulu, Oulu, Finland; double daggerDivision of Epidemiology, Public Health, and Primary Care, Imperial College, London, United Kingdom; section signDepartment of Public Health and General Practice, University of Oulu, Oulu, Finland; and paragraph signDepartment of Psychiatry, University of Kuopio, Kuopio, Finland.

Abstract
Advanced paternal age is a risk factor for adverse health outcomes in the offspring. In a population-based birth cohort from Finland, 10,965 singleton offspring born in 1966 and alive at age 1 were followed to age 39. Hazard ratios were calculated, adjusting for maternal age, gender, paternal social class, and maternal parity. In females but not in males, increasing paternal age was associated with a linear increased risk of suicide (hazard ratio [HR] = 1.13, 95% confidence interval [CI] = 1.04-1.24, p < 0.01) and all-causes mortality (HR = 1.06, 95% CI = 1.01-1.10, p = 0.02). Increasing maternal age was associated with a significantly decreased risk of suicide (HR = 0.93, 95% CI = 0.86-1.00, p = 0.04) and all-causes mortality (HR = 0.96, 95% CI = 0.93-1, p = 0.02) in the entire cohort. For paternal age >/=30, the population attributable risk percentage was 13.7% for all deaths and 7.5% for suicides. Parental age at birth may affect suicide and all-causes mortality risk in the offspring in the general population. The causal pathways and specific disorders associated with this increased mortality are largely unknown.

PMID: 20531118 [PubMed - as supplied by publisher]

Advanced paternal age may play a role in non-Hodgkin lymphoma etiology.

2010-05-29T06:49:00.000-07:00

Am J Epidemiol. 2010 May 27. [Epub ahead of print]

Parents' Ages at Birth and Risk of Adult-onset Hematologic Malignancies Among Female Teachers in California.
Lu Y, Ma H, Sullivan-Halley J, Henderson KD, Chang ET, Clarke CA, Neuhausen SL, West DW, Bernstein L, Wang SS.

Abstract
Although advanced parental age at one's birth has been associated with increased risk of breast and prostate cancers, few studies have examined its effect on adult-onset sporadic hematologic malignancies. The authors examined the association of parents' ages at women's births with risk of hematologic malignancies among 110,999 eligible women aged 22-84 years recruited into the prospective California Teachers Study. Between 1995 and 2007, 819 women without a family history of hematologic malignancies were diagnosed with incident lymphoma, leukemia (primarily acute myeloid leukemia), or multiple myeloma. Multivariable-adjusted Cox proportional hazards models provided estimates of relative risks and 95% confidence intervals. Paternal age was positively associated with non-Hodgkin lymphoma after adjustment for race and birth order (relative risk for age >/=40 vs. <25 years = 1.51, 95% confidence interval: 1.08, 2.13; P-trend = 0.01). Further adjustment for maternal age did not materially alter the association. By contrast, the elevated non-Hodgkin lymphoma risk associated with advanced maternal age (>/=40 years) became null when paternal age was included in the statistical model. No association was observed for acute myeloid leukemia or multiple myeloma. Advanced paternal age may play a role in non-Hodgkin lymphoma etiology. Potential etiologic mechanisms include de novo gene mutations, aberrant paternal gene imprinting, or telomere/telomerase biology.

PMID: 20507900 [PubMed - as supplied by publisher]

Men’s Biological Clock

2010-05-28T07:06:00.000-07:00

Naked Fatherhood

Men’s Biological Clock
by justin on May 24, 2010

There were rumours a while back that Hugh Hefner, the octogenarian founder of the Playboy empire was planning to father a child with Holly Madison (53 years his junior), the alpha female of his three live-in girlfriends. Of course that was before the jam hit the fan and all three moved out of the mansion.

But, apropos the baby – why not? Charlie Chaplin and Picasso both fathered children well into their 70s, with no ill-effects. There are even anecdotal reports in the medical press of men in their 90s becoming fathers. Everyone knows that we men can just carry on having children until very late in life, (although it’s possible that having kids just makes you feel 100 hundred years old).

Photo by: judepics
But is it all true? It seems that medical evidence is mounting that men are not immune from the ticking of the biological clock (although we often battle to hear it quite as loudly as our partners).

The first part of the problem lies with the decline in fertility of men as they age. Testosterone levels fall over time which not only makes it harder for men to hold their tummies in at the beach, but also affects sexual performance. There is also a decline in sperm count and sperm quality which means that it takes men over 45 significantly longer to produce a pregnancy than men under 25 – up to 5 times longer according to some research.

Still, it was thought that even with a decline in fertility, any genetic issues with the pregnancy or resulting child lay with the mother. This was because while a woman is born with her full quota of eggs, men manufacture sperm continually without even having to think about it, so conception between an older couple might be the meeting of a forty-year-old egg with a three-month-old sperm (the time taken to manufacture mature spermatozoa).

However, it now seems that there’s also a deterioration in the quality of the genetic material that each sperm carries. This is first seen in an increase in the number of miscarriages – three times greater where fathers are older than 35 compared to those younger than 25. The incidence of pre-eclampsia also rises with increasing paternal age.

This deterioration of genetic material is thought to arise from a number of causes. The cells which divide to produce sperm cells replicate around 23 times per year starting from puberty, so by the time a man hits 50, those cells have divided about 800 times, increasing the risk of errors.

With age, the frequency of sporadic single-gene mutations also increases four to five times for a person over 45. On top of that, the enzymes that repair faulty DNA decrease in efficiency as one gets older.

All of which means an increase in a list of medical problems now totalling about 20.

A study of data from a huge Israeli health database showed that, for example, schizophrenia is twice as likely to occur in the children of men over forty as in those in their twenties. Men over fifty lead to a three-time increase in risk.

A further study on the same database showed that autism too is six times more frequent where fathers are over forty than those under 30.

An earlier study by Dr Harry Fisch (author of the book The Male Biological Clock) concluded that parents over 40 have a six-times higher risk of having a child affected by Down Syndrome than where both are under 35. And where a woman over forty has a child affected by Down Syndrome, the genetic blame is now thought to lie 50% with the father.

And the list goes on, with various studies linking advanced paternal age to disorders such as dwarfism, progeria (an extremely rare accelerated aging disease), skeletal disorders, congenital heart defects, certain types of cancer and even reduced scores in nonverbal IQ tests.

All of which helps explain why the cutoff age for sperm donors in The States is set at 40. So that’s another paying hobby limited to the youth – smacks of ageism, doesn’t it?

And yet more and more couples are leaving it later to have children for any number of reasons. Many want to feel like they’ve experienced something of a life and a career before the little tyrants arrive. Some prefer to wait until they’re in a more financially stable phase of their lives before committing. Maybe its just that there are more frogs to kiss nowadays in search of princes. Or even that the kiss-per-frog ratio has risen.

And really, what’s the downside? You may be more likely to spend time in casualty with a back problem from flinging your toddler around and there’s the danger of injuring yourself by tripping over your Zimmer frame when playing cricket with the young ‘uns.

Having kids later probably means that you’re going to have a bit less energy for them, but then again, that depends on how well you’ve looked after yourself in getting to where you are. Also, a decrease in the time available to spend with children can be offset to a certain degree by an increase in the quality of the time spent.

Many parents are finding that they’re having children later without even planning it that way – life often gets in the way of our plans. Then when one’s finally ready to make this life-altering commitment it takes a little while to get everything ready to even start trying (especially when you discover that the whole house has to be remodelled before you can even start).

And then it doesn’t just happen right away, and where there are miscarriages, recovery, both physical and emotional, takes time before you can start again.

All of which means an upswing in the number of parents who battle to remember where they left the children a few minutes before.

Then again, children of older parents should be more independent when they grow up, if only because they’re used to being able to easily outpace their pursuers.

From a selfish point of view, having kids later means that you’ll have someone around who is able to intuitively figure out how to use the new DVD player that has been standing unused because you can’t work out what the instruction manual is trying to tell you.

Also, you don’t resent the loss of your social life to the same degree as those that have their children while they are young (the parents, not the children) – you’re giving up a whole lot less when your idea of a good time is staying in with a good book and listening to Smooth Classics.

And when you’re lucky enough to have your mid-life crisis with small children you’re much less likely to embarrass yourself by running off and buying a convertible or any motorcycle that comes with tassles hanging from the handlebars.

The bottom line? Don’t leave it too late. While it is physiologically possible for a man to produce heirs at a very late stage of life, the risks do rise along the way.

And Hef? I think that at his age, he’s just perfected the art of saying ‘Yes Dear’ without really listening to what anyone is actually saying.

Paternal age and assisted reproductive technology outcome in ovum recipients

2010-04-27T07:42:00.000-07:00

Fertility and Sterility
Volume 92, Issue 5, November 2009, Pages 1772-1775
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doi:10.1016/j.fertnstert.2009.05.036 | How to Cite or Link Using DOI
Copyright © 2009 Published by Elsevier Inc. Cited By in Scopus (0)
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Correspondence
Paternal age and assisted reproductive technology outcome in ovum recipients

References and further reading may be available for this article. To view references and further reading you must purchase this article.

Martha Luna M.D.a, Elissa Finkler B.S.a, Jason Barritt Ph.D.a, Natan Bar-Chama M.D.a, Benjamin Sandler M.D.a, Alan B. Copperman M.D., a, and Lawrence Grunfeld M.D.a

aMount Sinai School of Medicine, Department of Obstetrics and Gynecology, Department of Reproductive Endocrinology and Infertility and Reproductive Medicine Associates of New York, New York, New York

Received 26 February 2009; revised 13 May 2009; accepted 13 May 2009. Available online 21 June 2009.

This study suggests that paternal age may be inversely associated with reproductive outcome, as demonstrated by a decline in fertilization, blastocyst formation, implantation and cryopreservation rates with advancing age.

Article Outline

Ask Mr. Dad: That clock you hear ticking may not be hers

2010-04-13T22:18:00.000-07:00

Ask Mr. Dad: That clock you hear ticking may not be hers
Comments (0) Recommend
By ARMIN BROTT - McClatchy-Tribune News Service
Dear Mr. Dad: I'm 45 and my wife is 35. We've been together for more than 10 years and have finally decided to have a family. I know that it may be harder for my wife to conceive than it would have been if she was a little younger. But someone recently told her that my age could be a factor too. Is that true? Sounds crazy.

A: I hate to take sides, but your wife wins this round. Like most people, you know about the difficulties that women older than 35 have getting pregnant. That's only the beginning. As women age, the risk of miscarriage, preterm birth, and birth defects increases. But we rarely hear anything how the father's age affects fertility and beyond. Here's a quick overview.

-Researchers at Bristol University in the UK found that men's fertility begins to decrease starting at about age 24. The odds of conceiving within six months of trying go down 2 percent per year over that age.

-Sperm count decreases with age, and the little guys gradually lose their speed and accuracy, meaning fewer of them will make it all the way to the egg, and those that do will take a lot longer to get there.

-Sperm quality also decreases, starting when the man is about 35. That means that the ones that reach the egg are less able to fertilize it. And even if they do, the resulting pregnancies have an increased risk of ending in miscarriage.

-A small number of very rare health risks and genetic conditions are associated with older dads. For example, compared do men younger than 30, dads older than 40 have a higher risk of fathering children with autism, schizophrenia, dwarfism, heart defects, facial abnormalities, epilepsy, and some childhood cancers. Advanced paternal age may also be associated with children's lower IQ scores, increased risk of developing breast cancer and shortened lifespan (for women born to dads 45 and over). This may be why the American Society for Reproductive Medicine has set 40 as the upper limit for sperm donations. Some clinics have even lower limits.

-As your kids get older, you may not like it very much when people assume you're the grandfather instead of the dad.

-As you age, it may be a bit harder for you to do some of the physical things young dads do, such as skateboarding, giving piggy-back rides, and just crawling around on the floor.

On the other hand, being an older dad has its advantages. And in many people's eyes, those advantages far outweigh the disadvantages.

-Older dads are generally more financially secure, less worried about saving up for a down payment or making partner, and they're better able to provide for their family.

-Research indicates that older dads are more likely to share responsibility for taking care of their children and tend to be more actively involved with them.

-Older dads may also be warmer, more nurturing, and focus more on their children than younger dads.

-Older dads rate themselves as being more patient, more mature, and calmer than the young bucks.

-There is some indication that children of older dads do better in school. That's probably at least partly due to some of the factors above.

-Being an older dad keeps you thinking and feeling young. You're up on the latest culture, you hang out with younger couples, get to throw baseballs and go to school plays, and you'll know who Lady Gaga and Jay-Z are.

(Contact Armin Brott, armin@askmrdad.com, or visit his Web site, www.mrdad.com.)

Read more: http://www.newsobserver.com/2010/04/13/435224/ask-mr-dad-that-clock-you-hear.html#ixzz0l35GT1IH

2010-04-03T16:43:00.001-07:00

The Male Biological Clock: Speaking of Biological Clocks

2010-03-31T17:58:00.001-07:00

Marfan Syndrome
The Male Biological Clock: Speaking of Biological Clocks - http://themalebiologicalclock....
yesterday from blog "Marfan" - Google Blog... - Comment - Like - Share
... medical conditions: The longer you wait, the more likely it is that your kid will be affected by schizophrenia, dwarfism, bipolar disorder, autism, Marfan syndrome, certain childhood cancers, or even, later in life, Alzheimer's. ...

Speaking of Biological Clocks

2010-03-30T17:26:00.000-07:00

Speaking of Biological Clocks
Women aren’t the only ones who should pay attention to their biological clocks…

While men can still have kids at 50, it turns out there are increased health and psychological risks to the child:

Is Your Sperm Too Old?

Are you still bearing healthy fruit? Turns out that it’s not just women who have a biological clock—your sperm may be going to seed a lot faster than you think.

By Kevin Conley,
Photographs by Christian Weber

While you’ve never been against the idea of a serious relationship, you are in no particular rush to become a schlub. The attendant trappings of new fatherhood—the preschool viewings, the sleepless nights, the humiliation of carrying a diaper bag—aren’t exactly calling out to you the way, say, another night slinging Pisco sours would. The ever-intensifying din of the proverbial biological clock? That’s for the opposite sex to worry about—you know, like periods, frizz, and whether Mr. Big will dump Carrie in the Sex and the City sequel. As far as you know, your little swim team of DNA carriers will be competing at Olympic level into Letterman age. So what’s the rush?

“I always thought my biological clock was the 36 hours I had left after I took my Cialis pill,” says Zack, a 30-year-old producer in Los Angeles. “That’s the only clock I’ve ever felt ticking.” Turns out, Zack might want to consider the unsung glories of fatherhood.

According to a study released last March in the Public Library of Science Medicine, children born to fathers who were 20 scored an average of 2 points higher on an IQ test than children born to 50-year-old fathers. And that’s not all. Recent studies from Israel, California, and Sweden have connected “late paternal age” with any number of serious medical conditions: The longer you wait, the more likely it is that your kid will be affected by schizophrenia, dwarfism, bipolar disorder, autism, Marfan syndrome, certain childhood cancers, or even, later in life, Alzheimer’s. In some cases, the risk factors skyrocket. A 2005 study conducted by the University of California, Los Angeles, found a fourfold rise in Down syndrome among babies born to men 50 and older. Worse still, those risk factors aren’t limited to your tweed-sporting years: Statistically, “late paternal age” starts at 30, as in Zack’s age. A 2006 study conducted by Mount Sinai School of Medicine found that fathers in their thirties have children with about 1.5 times the risk of developing autism compared with fathers in their teens and twenties. That factor jumps to five times for dads in their forties. The cherry on the cake? The American Society for Reproductive Medicine recommends that sperm banks do not accept specimens from men over 40.

“The biological clock for men and women is really the same,” says Dr. Dolores Malaspina of Bellevue Hospital Center in New York City and New York University, who conducted one of the first studies. “It’s just that men can keep having babies.”

The biology behind this isn’t hard to grasp: Starting in puberty, spermatogonia, the master copies for sperm production, replicate themselves every couple of weeks. After 300 to 500 copies—somewhere in your thirties—a meaningful number of small copy errors, or point mutations, start to emerge, which accumulate over time.

Yet, despite the alarming new science, most men greet parenthood with a sense of urgency that’s more in line with Zack’s than Angelina Jolie’s. The reason is simple: While women are inculcated with the risks of late-age motherhood in sixth-grade sex ed, men remain blissfully ignorant. Since the recent studies have been published, the bad news still doesn’t seem to be making it to the doctor’s office. Scott, a 32-year-old schoolteacher from Babylon, New York, decided to start a family when he was Zack’s age, strictly because he wanted to raise his child while he was young. “For me the doctors were like, ‘Hey, this is going to be good. You’re still active,’” Scott says. “Nobody ever told me about the medical risks of being an older dad.”

That’s because men don’t usually get this news flash until they’re looking through a microscope at a batch of fugly sperm with no sense of direction. Swain, a 37-year-old IT professional in Dallas, wishes he had heard sooner. “Who cares if the baby is born with six fingers we can’t get that far,” he says. “I’d be thrilled to have that problem.” His wife is four years younger than he is, and they decided to wait. “What I did was let her clock be the one in control,” Swain says. “I would have been happy having kids five, six years ago, but she just wasn’t ready. The female clock seems to dominate the conversation.”

But don’t expect sweeping social change anytime soon. “Tell a man he’s got a chance of having kids with genetic abnormalities, and it’s like he’s going through the stages of the acceptance of death,” says Dr. Harry Fisch, a professor of urology and the author of The Male Biological Clock. “They’ll say, ‘I’m losing my manliness, my sexual ability.’ To them it all comes under the same umbrella.”

The good news is that no one, not even Malaspina, is suggesting that older men eschew the joys of fatherhood. But if you’re a younger guy who hasn’t thought twice about postponing it, be forewarned: The female of the species is about to get her just rewards. That bell tolling? It’s for you.

______________________________________________________________

Oh my goodness! Late paternal age starts at 30? I think most men don’t even consider babies until then..

Tick Tock or When Your Biologic Clock Slows Down

2010-03-26T19:15:00.000-07:00

--------------------------------------------------------------------------------

Archive for the ‘male infertility’ Category
Tick Tock or When Your Biologic Clock Slows Down
March 10, 2010
When the phrase “biologic clock” is mentioned, most think this is in reference to women who experience a loss of hormone production at the time of menopause. But men also have a clock that starts to slow down around age 35. It is at this time that men experience decreasing hormone production, decrease in fertility potential, as well as an increase risk of genetic problems in children born to men who are older.

The theory that men go through a change in life, similar to what women experience, could be taking hold. We know for certain that the cause of the slowing of the biologic clock in women is due to a decrease in the production of estrogen. If less estrogen in women leads to the end of menstruation, moodiness, hot flashes, loss of sexual interest and osteoporosis, couldn’t male versions of these symptoms be caused by less testosterone?

How common is male hormone deficiency? Currently in the U.S., at least 6 to 10 million men suffer from the effects of extremely low testosterone levels in their bloodstream. Sadly, only 1 out of 6 of these men will ever receive treatment to resolve this problem.

Infertility and aging

It has been noted that more men, and women, are deferring parenting until they are older, finished their education, and are more financially stable. As a result the number of children born to fathers older than 35 years has increased considerably in the past few decades. This creates a problem as there is a decrease in fertility in men with increasing age. Since it takes longer to achieve a pregnancy in older men, they should be counseled and may consider starting their family sooner before their clock completely winds down.

Since there is evidence of the existence of a male “biological clock,” the likelihood of taking more than a year to conceive doubles when the man is over 35. The implication is that a man’s age should be another factor that is taken into account when looking at the chances of conception in couples who are having difficulty conceiving.

In addition, as men age, the genetic quality of their sperm declines significantly. According to the Centers for Disease Control and Prevention, the number of babies born to parents older than age 35 more than doubled from 1970 to 1999, from 6 percent to 13 percent. This trend has led to the rise in the rates of infertility in the past decade, and to increased miscarriage rates and the possibility of a baby born with Down Syndrome (in addition to other genetic abnormalities).

When testosterone levels drop

In women, menopause generally marks the end of youth, hence the idea of a “mid-life crisis.” Some women get hot flashes, are moody, irritable and/or depressed. Male menopause, or andropause, is not as clearly defined for men as it is for women. There probably is a syndrome of testosterone deficiency in aging men, and that testosterone deficiency is manifested by a diminished sexual drive, difficulty in getting or maintaining an erection, lack of energy, even irritability and grumpiness. There are even changes in a man’s height, caused by bone loss and osteoporosis.

If a man is experiencing any of the symptoms of testosterone deficiency, they need to see their physician and undergo an evaluation which includes a blood test to measure the testosterone level. Not all male mid-life crises are a result of testosterone deficiency. First, the doctor must be sure that the symptoms are not due to depression. Many of the issues in testosterone levels could be confused with the effects of depression. If you’ve got symptoms that may be suspicious, the first thing is to have a thorough physical and laboratory work and make sure you rule out other medical conditions such as diabetes, which also affect testosterone levels. Treat those conditions first, before you consider looking at testosterone.

There is also a useful questionnaire, ADAM-Androgen Deficiency in the Aging Male, that is helpful for men to identify testosterone deficiency.

The ADAM questionnaire asks you to check for the following symptoms:

1.Decrease in sex drive
1.Lack of energy
1.Decrease in strength and/or endurance
1.Lost height
1.Decreased “enjoyment of life”
1.Sad and/or grumpy feelings
1.Erections less strong
1.Deterioration in sports ability
1.Falling asleep after dinner
1.Decreased work performance
Men experiencing Loss of morning erections depression, tiredness, memory loss, decreased muscle mass and increased weight, more fragile bones, or a diminished sex drive might be candidates for testosterone replacement therapy. Treatment of testosterone deficiency is easily accomplished with injections of testosterone, patches placed on the skin that transmit the medication from the skin to the blood stream, or topical gels applied to the upper arm or lower abdomen can quickly restore a man’s libido and sex drive.

So if you are over 35 and are feeling less than your best, you should talk with your doctor about your symptoms. A complete medical examination that includes laboratory tests can help show whether testosterone supplements might help you feel better. If treatment is suggested, then I encourage men to try it for a period of a few months while keeping track of the changes. If low testosterone is the cause of their symptoms, men will not have to wait long to see the effects of treatment. Bottom line…men, you may not be able to turn back the clock of time but you certainly can reset your biologic clock with hormone replacement therapy.

Dr. Neil Baum is a urologist at Touro Infirmary. For more information, contact Dr. Neil Baum at (504) 891-8454 or go to his Website, www.neilbaum.com

2010-03-19T15:24:00.001-07:00

2010-03-18T20:03:00.001-07:00

Sat Mar 13, 2010 10:11 AM CST : Why do most women want to date men older than them?
Older men five times more likely to father children with birth defects
Last updated at 8:45 AM on 27th October 2009
It is not just women who need to keep an eye on the biological clock when it comes to having children.
Older men are up to five times more likely to father children with birth defects, according to some studies.
Experts claim that after 35, the risk of chromosomal abnormalities such as Down's Syndrome increases in proportion with the father's age.
Men are being warned not to have children too late in life
Children born to older fathers also appear to run an increased risk of autism, say researchers.
The problem is caused by mutations in cells which increase in men and women as they age and can cause congenital malformations.
A study of more than 70,000 births using records in Denmark of mothers under 29 and men of any age found the risk of a number of syndromes went up with increasing paternal age.
A 45-year old man is almost three times more likely to father a Down's child than a man under 30, while for men over 50 the risk is almost fivefold.
The risk of having a child with a cleft lip doubles for a man aged over 50.
The results show the risk of some congenital conditions starts to rise when the father is between 35 and 40.
French research suggested over-40s are three times more likely than younger men to father a baby with Down's.
Miscarriages and stillbirths increase with advancing age of the father, which suggests rates of genetic damage could be even higher but many pregnancies do not progress.
Studies have shown that men's fertility declines with age - in much the same way as women have less chance of conceiving as they get older.
Older men's sperm is also less likely to undergo a self-destruct mechanism called apoptosis, which is meant to get rid of damaged cells.
It might not be only chronological age which affects sperm quality, but also the environmental damage that comes with age.
The organs involved in sperm production can be affected by smoking, chemicals, sunlight and lifestyle.
http://www.dailymail.co.uk/health/article-1223230/Older-men-likely-father-children-birth-defects.html

Read more:
http://www.bionews.org.uk/page_12440.asp
http://www.ivf.net/ivf/older_father_link_to_birth_defects-o1559.html
http://www.mothers35plus.co.uk/older-fathers.htm
http://www.theage.com.au/lifestyle/wellbeing/bipolar-link-to-older-fathers-20090407-9y6t.html
http://www.dailymail.co.uk/health/article-1015164/Children-older-fathers-likely-die-early.html
http://www.slate.com/id/2140494/

Do men have a biological clock?

2010-02-28T13:38:00.000-08:00

Do men have a biological clock?
Michael
Is Your Sperm Too Old?Turns out that it’s not just women who have a biological clock.While you've never been against the idea of a serious relationship, you are in no particular rush to become a schlub. The attendant trappings of new fatherhood—the preschool viewings, the sleepless nights, the humiliation of carrying a diaper bag—aren't exactly calling out to you the way, say, another night slinging Pisco sours would. The ever-intensifying din of the proverbial biological clock? That's for the opposite sex to worry about—you know, like periods, frizz and whether Mr. Big will dump "Carrie in the Sex and the City" sequel. As far as you know, your little swim team of DNA carriers will be competing at Olympic level into Letterman age. So what's the rush?"I always thought my biological clock was the 36 hours I had left after I took my Cialis pill," says Zack, a 30-year-old producer in Los Angeles. "That's the only clock I've ever felt ticking." Turns out, Zack might want to consider the unsung glories of fatherhood.According to a study released last March in the Public Library of Science Medicine, children born to fathers who were 20 scored an average of 2 points higher on an IQ test than children born to 50-year-old fathers. And that's not all. Recent studies from Israel, California and Sweden have connected "late paternal age" with any number of serious medical conditions: The longer you wait, the more likely it is that your kid will be affected by schizophrenia, dwarfism, bipolar disorder, autism, Marfan syndrome, certain childhood cancers, or even, later in life, Alzheimer's. In some cases, the risk factors skyrocket. A 2005 study conducted by the University of California, Los Angeles, found a fourfold rise in Down syndrome among babies born to men 50 and older. Worse still, those risk factors aren't limited to your tweed-sporting years: Statistically, "late paternal age" starts at 30, as in Zack's age. A 2006 study conducted by Mount Sinai School of Medicine found that fathers in their 30s have children with about 1.5 times the risk of developing autism compared with fathers in their teens and 20s. That factor jumps to five times for dads in their 40s. The cherry on the cake? The American Society for Reproductive
Juan
The 'andropause' idea is probably just a way for private doctors to make a quick buck out of prescribing testosterone to middle aged men. But yeah everything wears out as you get older, including sperm quality.
soundsandimages
Having children is best left up to young adults. Not 40 somethings. I always laugh when I hear about the corporate douchebag worrying about her biological clock ticking away. But my priorities differ, I chose a family instead of a cubicle or irrelevant business.
aGes_mD
NO.Men have been known to father into their 70's.Easily.Funny thing is, we really do not need more babies on planet earth.We're pushing 7 billion." Be fruitful and multiply"But, come on.Enough's enough.Mother earth is screaming bloody rape
dariodh
no, women have it thats why they want to grubb as much money from men before they become ugly and saggy and wrinkley.
lisa_oo0
Yes and no. Men are not born with a limited number of a few hundred thousand sperm that they must use up before the age of 45 like women do with their eggs. Men are constantly making new sperm and they have an endless supply of it too. The problem with men's fertility is that as they age, the quality of their sperm decreases, as every cell in your body ages, so do your sperm. A significant number of men have such a low sperm count as they age that they become nearly sterile or completely sterile. And it's not like 70 year old men can easily get women pregnant, their sperm is very slow and weak and the DNA is damaged. Even a 40 year old man has more damaged DNA in his sperm than a 30 year old man, and a 20 year old man has the highest quality sperm of all. By age 50 men have a high risk of fathering children with autism, schizophrenia, bipolar disorder and other disorders/conditions.There is also a problem with pollutants and chemicals in our enviornment that is causing record levels of infertility in otherwise healthy young people of childbearing age. Pollutants are causing a feminizing effect on men, and scientists are predicting that many baby boys born today will be sterile as adults. Many species of animals are also predicted to go extinct in the coming years due to the feminizing of the males, and the low birth rates of males.

Paternal age and mortality in nonaffective psychosis.

2010-02-19T07:15:00.000-08:00

Schizophr Res. 2010 Feb 16. [Epub ahead of print]

Paternal age and mortality in nonaffective psychosis.
Miller B, Pihlajamaa J, Haukka J, Cannon M, Henriksson M, Heilä H, Huttunen M, Tanskanen A, Lönnqvist J, Suvisaari J, Kirkpatrick B.

Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta, Georgia, United States; Department of Psychiatry, University of Oulu, Oulu, Finland.

INTRODUCTION: Advanced paternal age (APA) is associated with an increased mortality in the general population, and is a risk factor for schizophrenia. We aimed to test if APA is associated with increased mortality in people with nonaffective psychosis. METHODS: Subjects with nonaffective psychosis who were born in Helsinki, Finland, between 1951 and 1960 (n=529) were followed until June 2006 (age 46 to 55). Hazard ratios were calculated, adjusting for subject age, age of the other parent, and gender. RESULTS: In females but not males, there was a significant increase in all-causes mortality (HR=7.04, 95% CI 1.60-31.04, p=0.01) and natural deaths (HR=7.64, 95% CI 1.20-48.66, p=0.03) in offspring of fathers age >/=40, after adjustment for potential confounders. In males but not females, there was a significant decrease in suicides (HR=0.89, 95% CI 0.81-0.97, p=0.01) with increasing maternal age (as a continuous variable). In the entire sample, there was also a trend for decreased all-cause mortality (HR=0.96, 95% CI 0.92-1.01, p=0.08) with increasing maternal age (as a continuous variable). DISCUSSION: Both paternal and maternal age may affect mortality risk in offspring with psychosis. The specific disorders and pathway(s) associated with the increase in natural cause mortality remain to be determined. Copyright © 2010 Elsevier B.V. All rights reserved.

PMID: 20163936 [PubMed - as supplied by publisher]

Tick tock goes the male biological clock

2010-02-18T17:34:00.000-08:00

Tick tock goes the male biological clock
by Raquel on February 18, 2010 · 0 comments

in INFERTILITY

Tick tock tick tock. As soon we women reach the age of 30, we hear the biological ticking away as we try to hold on to our fertility just for another while. But what about men? Don’t they have a biological clock to listen to?

I mean, look at the following oldies celebrity dads who fathered kids beyond their 60th birthday:

David Letterman, at age 61
Donald Trump, 62
Sylvester Stallone, 62
Rod Stewart, 63
Michael Douglas, 64
Mick Jagger, 65
Hugh Hefner, 65
Paul McCartney, 66
Clint Eastwood 66.
Sir Michael John Gambon, 68
Woody Allen, 73
Charlie Chaplin, 73
Larry King, 75
Anthony Quinn, 81
Surely for men, age doesn’t matter for fertility.

However, there is increasing evidence that this is not the case, and that men too, should listen to the ticking clock starting at midlife. Researchers report that the sperm quality of men decreases with age, and that fertility starts to wane when they reach the 30s, and plummets when they reach their 40s. During the time, the overall chance of fathering a child drastically decreases. And if a pregnancy is ever achieved, the likelihood of miscarriage is increased. In addition, the resulting offspring would have a higher likelihood to suffer from genetically related disorders such as autism, schizophrenia, autism and low IQ. This is according to a study by researchers at the Eylau Centre for Assisted Reproduction in Paris, France who looked at more than 1,200 couples.

So what’s reason behind the male biological clock?

Researchers think it is due to some kind of “sperm decay” which is characterized by DNA damage and abnormalities. Men start producing sperms at puberty at a rate of 100 million new sperms per day. During the process, DNA is copied and duplication from one sperm to another. During the countless sperm-copying processes, mistakes occur and DNA mutations happen. These errors accumulate with age, leading to decreasing sperm quality.

According to fertility specialist Dr. Carl Herbert

“These subtle copying defects cause a long list of diseases in the children of older fathers. Lesch Nyhan syndrome, polycystic kidney disease and hemophilia A are among the most well known. For fathers over age 40, the risk of having a child with a disease-causing mutation is similar to the risk the mother has for a child with Down syndrome.”

Aside from age, other health factors, including body weight and diabetes, can also adversely affect sperm quality.

According to Dr. Harry Fisch, urologist at Columbia University, and author of the book The Male Biological Clock

“…couples are waiting longer to have children, and advances in reproductive technology are allowing older men and women to consider having children. The lack of appreciation among both medical professionals and the lay public for the reality of a male biological clock makes these trends worrisome.”

He further advises older dads to “have a thorough history and physical examination focused on their sexual and reproductive capacity. Such examination should entail disclosure of any sexual dysfunction and the use of medications, drugs, or lifestyle factors that might impair fertility or sexual response.”

Read more: http://battlingforhealth.com/2010/02/tick-tock-goes-the-male-biological-clock/#ixzz0fwQkd6fu

Men: Your Biological Clocks are Ticking

2010-01-30T21:56:00.000-08:00

Men: Your Biological Clocks are Ticking!
by Whitney Rhodes on January 30, 2010

For many years, it was tacitly assumed that while women have a “Sell By” date when it comes to fertility, men become fertile at puberty and remain so until a ripe old age.

Actually, although there is some truth in that myth, to the extent that males do not have a hormonal menopause as women do; the fact is that fertility in men does begin to decline after a certain age.

Men don’t completely stop being fertile at any age.

However, older fathers are prone to problems that younger fathers usually don’t experience.

What are Some of the Problems Experienced by Older Fathers?

A study that was conducted recently at the University of California, Berkeley, on a test group of men aged 22 to 80 showed that the sperm of older men are fewer in number with less mobility, as well as being less able to move in a straight line.

This research also showed an increased risk of achondroplasia, a genetic mutation that produces a kind of dwarfism.

Nor was this the only risk.

Older fathers were shown to have an increased risk of siring children with autism, or who were mentally retarded, or have behavioral problems with conditions such as schizophrenia.

Downs Syndrome, although associated with older mothers, doesn’t seem so far to be one of the risks of older fathers, but testing is still in progress.

It is believed that many times, male fertility problems caused by age and/or a medical condition might be mistaken as a potency issue, and mistakenly treated with a prescription for Viagra or a similar medication.

Investigating male infertility, and research of male sperm is gaining much new ground these days, as specialists recognize that infertility is not any more likely to rest with the female half of a couple than the male.

Today, more than ever, men and women alike are waiting longer to start families. This has given rise to an increasing frequency of fertility problems encountered with older parents.

So, although men are never completely infertile due to age, research has shown that the quality and quantity of sperm decrease with age.

Advanced paternal age is associated with alterations in discrete behavioural domains and cortical neuroanatomy of C57BL/6J mice.

2010-01-29T08:18:00.000-08:00

Eur J Neurosci. 2010 Jan 25. [Epub ahead of print]

Advanced paternal age is associated with alterations in discrete behavioural domains and cortical neuroanatomy of C57BL/6J mice.
Foldi CJ, Eyles DW, McGrath JJ, Burne TH.

Queensland Brain Institute, The University of Queensland, St Lucia, Qld 4072, Australia.

Abstract Advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and schizophrenia. A previous study in mice suggested that the offspring of aged sires have altered locomotion and avoidance learning. The aim of the current study was to conduct a comprehensive behavioural screen in adult offspring of mice of APA. We also examined brain morphology in neonate and adult mice. The adult offspring of 12- to18-month-old (APA) and 4-month-old (control) male C57BL/6J mice underwent a behavioural test battery comprising tests for locomotion, anxiety, exploration, social behaviour, learned helplessness and sensorimotor gating. The brains of these mice were collected at 3 months and imaged ex vivo using a 16.4T MRI scanner to assess gross neuroanatomy. Neuroanatomy was also examined at birth in a separate cohort of animals. Overall, the APA mouse model was associated with subtle behavioural changes and altered cortical morphology. The behavioural phenotype of female APA mice included increased anxiety-related behaviour, increased exploration and decreased learned helplessness compared to control females. Male APA mice had thinner cortices at birth and increased cortical volume as adults. This animal model may assist in exploring the mechanism of action linking APA with disorders such as schizophrenia and autism.

PMID: 20105239 [PubMed - as supplied by publisher]

Paternal Age and Schizophrenia

2010-01-08T07:24:00.000-08:00

Paternal Age and Schizophrenia
Research Date:
03/23/2006
An Expert Interview with Dolores Malaspina, M.D., M.P.H.

Great Neck, NY - March 23, 2006) — Scientists have linked paternal age to genetic diseases since the 1950s, and some have suggested an association between the age of the father and the risk for schizophrenia. In 2001, Dolores Malaspina, M.D., M.P.H., and her colleagues reported their research identifying a relationship between paternal age and the occurrence of schizophrenia. On behalf of Medscape* Jessica Gould interviewed Dr. Malaspina, Professor of Clinical Psychiatry at Columbia University and Research Psychiatrist at New York State Psychiatric Institute in New York City. Dr. Malaspina elaborates on her research and speaks about new directions in genetic research on schizophrenia. (NARSAD NOTE: Dr. Malaspina was a NARSAD 1993 and 1995 Young Investigator and a 2001 Independent Investigator.)

Medscape: Tell me about your research on paternal age and schizophrenia.

Dolores Malaspina: I have been compelled by the idea that schizophrenia is not a single disease. The consensus in the field is that schizophrenia is a syndrome, and a syndrome is a collection of different disorders. Yet there is still some controversy over whether or not there are variants of schizophrenia that might have separate causes and respond differently to various medications.

Since beginning my research in the late 1980s, I have focused on this heterogeneity, and one way that I've done that is by examining aspects of the disease in people who come from densely affected families, where two or more relatives have schizophrenia, and comparing them with cases of schizophrenia that have no family history of any chronic psychosis.

Now, in genetic research, it's known that for human genetic diseases, when a new case presents itself in a family, the mutation almost always arises during spermatogenesis. We have known for almost 100 years that the late born children in a family have more new genetic diseases. In the 1950s, a scientist named Penrose showed that only the age of the father predicts these genetic diseases. Over the last decade, it was shown that the risk for many complex genetic diseases was also correlated with paternal age. I thought that if schizophrenia cases with no family history were due to new genetic events, maybe they would also be correlated with the father's age.

I have the good fortune to be funded by the National Institutes of Health to study a very special birth cohort in Israel of about 100,000 pregnancies. We have a rich amount of demographic and clinical data on the parents, including the age of the father. The analysis showed what we considered to be a striking effect of the age of the father on the risk for schizophrenia.

Medscape: Could you tell me more about this group of research subjects from Israel?

Dr. Malaspina: The offspring were born between 1964 and 1976, and the original birth cohort was designed to examine the health of women during pregnancy as well as fetal outcomes. Israel maintains a high-quality psychiatric case registry. Working with the people at the Ministry of Health in Israel, my colleagues linked the birth cohort data to the psychiatric case registry data. The results showed that the risk of schizophrenia was tripled for the offspring of the oldest group of fathers.

We found that paternal age explained over a quarter of the risk for schizophrenia in the population. At the time, people were skeptical. But the findings have been replicated many times now, and not a single study has failed to find this strong relationship between father's age and the risk for schizophrenia. And at this point, other explanations for the relationship have been ruled out, including social factors in the family, prenatal care, and parental psychiatric ailments. There simply seems to be a relationship between paternal age and schizophrenia risk.

Medscape: Can you explain why the relationship between paternal age and schizophrenia exists?

Dr. Malaspina: When Penrose found that paternal age predicted new human genetic diseases, he proposed the Copy Error Theory. He said that each time the spermatozoa are copied there's an opportunity for a new mutation. Sperm cells divide every 16 days after puberty, so the DNA in the sperm of a 20-year-old father has been copied 100 times, but sperm DNA from a 50-year-old father has been copied more than 800 times. By comparison, egg cells from the mother only undergo a few dozen cell divisions all together. It is clear that there are many more opportunities for mutations to occur during spermatogenesis and that these increase with the age of the father. That is why new mutations are introduced in mammals in proportion to paternal age.

To further establish that paternal age is associated with schizophrenia risk, we went back to examine if paternal age is related to other factors associated with schizophrenia risk. We looked at intellectual functioning at age 17 in our birth cohort. Those data were available because adolescents in Israel are screened for military service. Working with personnel at the Israeli Defense Force, we examined whether intelligence was related to paternal age. And what we found was a very strong specific effect of paternal age on performance IQ. Very young mothers and very old mothers had offspring with impairments in verbal and performance intelligence. While there was no effect of late fathers' age on verbal IQ, there was a strong effect on performance intelligence, or nonverbal intelligence, which we have published.

In a parallel study, we examined the effect of late paternal age in a mouse model. Working with my colleague, Jay Gingrich, we studied several cohorts of inbred mice to compare offspring with younger and older fathers. The mouse model demonstrated striking effects of paternal age on the behavior of mice.

Those three lines of evidence provide converging data that paternal age does influence neural functioning and that paternal age is a plausible risk factor for schizophrenia.

Medscape: Could you describe what is meant by sporadic schizophrenia and how that relates to paternal age?

Dr. Malaspina: This goes along with the issue of whether schizophrenia is one single disease or several different variants, several different diseases. If it is several diseases, we could make much more progress if we knew how to separate individuals who have one variant of the disease from individuals who have the other variant, such as for treatment studies.

So, we have this finding that father's age predicts schizophrenia, but we don't know if the genetic changes are in the same genes that cause familial schizophrenia or if they occur at a different place. Some of the birth cohorts have actually looked to see how the risk of schizophrenia with paternal age is related to the family history of schizophrenia. The finding is that father's age is not connected to the risk of schizophrenia when it runs in families, but only for cases with no family history. That is called sporadic schizophrenia.

We have also looked at patients, with the help of funding from the National Alliance for Research on Schizophrenia and Depression, and we have examined whether or not cases with late paternal age and no family history have different symptoms and brain abnormalities from those of other cases. That work is under way.

Medscape: You also looked at the duration of the parents' marriage.

Dr. Malaspina: Yes, and we found that the duration of marriage was protective against the risk for schizophrenia. This goes in the opposite direction of paternal age, but it's an independent factor. Couples that have a very long marriage are less likely to have offspring with schizophrenia. One possibility is that parents who have mental disorders themselves may have shorter marriages. Another possibility is that there is an increased risk of schizophrenia when there is a marital separation.

Medscape: A variety of environmental factors can influence the development of schizophrenia. How do you control for that?

Dr. Malaspina: On the one hand, there may be scores of different intrauterine exposures that increase the risk for schizophrenia through different pathways. Another possibility, though, is that there are only a few final common pathways through which various intrauterine adversities are linked to the risk for schizophrenia.

The Barker hypothesis deals with the area of fetal programming. Research shows that the risk for many adult-onset chronic diseases, such as cardiovascular disease, obesity, diabetes, and hypertension, is related to fetal development. The mechanism may be that an adverse fetal environment compromises the development of organs and tissues and changes lifelong gene expression. The fetus survives, but its health is compromised. Effects on the developing nervous system could contribute to schizophrenia risk. So that's a possible pathway for the risk for schizophrenia, through a variety of prenatal exposures.

The benefit of our study in Israel is that we had such a wealth of obstetric data. The birth cohort involved early pregnancy interviews with the mom. It also involved evaluations of the progress of the pregnancy and records of the delivery. Our study was able to show that other prenatal exposures did not explain the linkage of paternal age to the risk of schizophrenia. Also, there have been many excellent studies after ours was conducted that have looked at numerous fetal exposures and found that those also do not explain the risk of paternal age for schizophrenia.

I do, however, believe that many fetal exposures can increase the risk of schizophrenia. I would suggest that the mechanism of these events may be via changes in lifelong gene expression.

Medscape: What about the influence of environmental factors after birth, during childhood and adolescence?

Dr. Malaspina: I think three of the interesting factors that have been linked to the risk of schizophrenia are severe stress in a stress-sensitive person who has underlying genes for schizophrenia, traumatic brain injury in those with underlying genes for schizophrenia, and, very importantly, cannabis exposure in early adolescence.

Medscape: Your research about paternal age became public in 2001. Do you think fewer men over a certain age might choose to have children as a result?

Dr. Malaspina: I haven't heard that. I would personally not discourage anyone from having a child at any age. People weigh their own risks. For the offspring of older fathers, the risk of schizophrenia is about 3 percent. That means that 97percent of the offspring do not have schizophrenia. Other cognitive diseases linked to paternal age include mental retardation of unknown etiology and Alzheimer's disease, and there is a strong relationship between paternal age and autism.

Medscape: What do you expect to be the future of your research in this area?

Dr. Malaspina: The genes for schizophrenia that we have identified lately are very interesting; they explain a large degree of the risk of the disease. Attention probably should turn toward factors that affect the expression of these genes and other genes. This is the area of epigenetics, the code that determines whether or not genes will be expressed.

We're pursuing a gene expression hypothesis for paternal age and schizophrenia. Humans have dozens or hundreds of genes that are expressed, not on the basis of being dominant or recessive, but on the basis of which parent we have inherited them from. So genes that control the growth of the fetus tend to be expressed on the basis of inheritance from the father. Other genes are expressed only on the basis of inheritance from the mother. These are called "parent of origin genes" or "parentally-imprinted genes." In these genes, the father's copy is expressed and the mother's is silenced, or vice versa. We are interested in this mechanism of gene-silencing. For the male parent, the silencing, or the activation/expression of genes from dad, takes place late in spermatogenesis. So our hypothesis and model right now for how paternal age affects the risk for schizophrenia is that it has altered the expression of genes inherited from the father.

Even exposures that interact with genetic susceptibility may act by changing gene expression, such as traumatic brain injury, cannabis, and stress. Maybe we can integrate our understanding of the many exposures tied to schizophrenia and the many genes tied to schizophrenia with the understanding that certain exposures may act by changing gene expression.

Meanwhile, some individuals who develop schizophrenia have a good outcome and stability without much deterioration -- but not as many as we would like. If we can't prevent the disease, perhaps we can learn the risk factors for deterioration and how to prevent it.

Although I see schizophrenia as a syndrome of separate illness variants, I think the field has benefited from considering it as a single disease. From here forwards, we may be diluting our ability to find risk factors and optimize outcome by considering the disease as a whole. To go forward in schizophrenia, we need to better understand how similar symptoms may arise from abnormalities in different neural circuits; that the set of symptoms we call schizophrenia could reflect a common pathway, but that the underlying biology may differ for groups of people, and that those differences may explain which medications they should receive, or which factors are more adverse for them. I think the field needs to move toward a finer understanding of the variants that exist. The identified genes may be clearly explanatory for some cases but not for others.

Funding Information

This interview is published in collaboration with NARSAD: The Mental Health Research Association, and is supported by an educational grant from Pfizer.

Dolores Malaspina, M.D., Professor of Clinical Psychiatry, Columbia University, New York, NY;
Director of Clinical Neurobiology, New York State Psychiatric Institute and Columbia University Medical Center, New York, N.Y.

Disclosure: Jessica Gould has disclosed no relevant financial relationships.

Disclosure: Dolores Malaspina, MD, has disclosed no relevant financial relationships.

*Reprinted with permission from Medscape Psychiatry & Mental Health 2006:11(1) http://www.medscape.com/viewarticle/520009 © 2006, Medscape. Please be advised that Medscape requires free registration to view articles.

News flash: Men have a biological clock and it ticks pretty damn loudly.

2010-01-05T14:34:00.000-08:00

News flash: Men have a biological clock and it ticks pretty damn loudly.

Not so fast - women under 30 beware. Research has shown that for women under 30, a male partner aged 40 or over reduced their chances of conceiving by a quarter; for women between 35 and 37, a partner over 40 reduced conception to a one-in-three possibility.[3] Studies also show that men over 35 are twice as likely to be infertile.[4]

Other research shows that there is an increased risk for autism in instances of men in their 30s fathering children and the risk of having an autistic child is five times higher when the father is in his 40s.[5] For men having children over 40, studies show there is also a dramatic increase in the risk that the child will be affected by schizophrenia, dwarfism, bipolar disorder, certain childhood cancers, or even, later in life, Alzheimer's.[6] In fact, the American Society for Reproductive Medicine "has set an upper age limit of 40 years old for semen donors because of the increased risk of genetic abnormalities in the offspring of older fathers." .[7]

Thus, these men who are so quick to point to the women’s biological clock as a deal breaker are truly an example of the pot calling the kettle black. Sure Tony Randall could have a baby at 77 (whereas a septuagenarian women has long passed menopause), but that does not mean the male’s biological clock does not exist. For some reason it is just never discussed. News flash: Men have a biological clock and it ticks pretty damn loudly.

Advancing Paternal Age Is Associated with Deficits in Social and Exploratory Behaviors in the Offspring: A Mouse Model

2009-12-30T08:11:00.000-08:00

Advancing Paternal Age Is Associated with Deficits in Social and Exploratory Behaviors in the Offspring: A Mouse Model

http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0008456

Accumulating evidence from epidemiological research has demonstrated an association between advanced paternal age and risk for several psychiatric disorders including autism, schizophrenia and early-onset bipolar disorder. In order to establish causality, this study used an animal model to investigate the effects of advanced paternal age on behavioural deficits in the offspring.

C57BL/6J offspring (n = 12 per group) were bred from fathers of two different ages, 2 months (young) and 10 months (old), and mothers aged 2 months (n = 6 breeding pairs per group). Social and exploratory behaviors were examined in the offspring.

The offspring of older fathers were found to engage in significantly less social (p = 0.02) and exploratory (p = 0.02) behaviors than the offspring of younger fathers. There were no significant differences in measures of motor activity.

Given the well-controlled nature of this study, this provides the strongest evidence for deleterious effects of advancing paternal age on social and exploratory behavior. De-novo chromosomal changes and/or inherited epigenetic changes are the most plausible explanatory factors.

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Abstract
Introduction
Results
Discussion
Methods
Author Contributions
References
Rebecca G. Smith1#, Rachel L. Kember1#, Jonathan Mill1, Cathy Fernandes2*, Leonard C. Schalkwyk1, Joseph D. Buxbaum3,4, Abraham Reichenberg1,3

1 Medical Research Council Social Genetic and Developmental Psychiatry Centre, King's College London, London, United Kingdom, 2 Department of Psychological Medicine and Psychiatry, King's College London, London, United Kingdom, 3 Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, United States of America, 4 Laboratory of Molecular Neuropsychiatry, and the Seaver Autism Center for Research and Treatment, Mount Sinai School of Medicine, New York, New York, United States of America

Abstract Top
Background
Accumulating evidence from epidemiological research has demonstrated an association between advanced paternal age and risk for several psychiatric disorders including autism, schizophrenia and early-onset bipolar disorder. In order to establish causality, this study used an animal model to investigate the effects of advanced paternal age on behavioural deficits in the offspring.

Methods
C57BL/6J offspring (n = 12 per group) were bred from fathers of two different ages, 2 months (young) and 10 months (old), and mothers aged 2 months (n = 6 breeding pairs per group). Social and exploratory behaviors were examined in the offspring.

Principal Findings
The offspring of older fathers were found to engage in significantly less social (p = 0.02) and exploratory (p = 0.02) behaviors than the offspring of younger fathers. There were no significant differences in measures of motor activity.

Conclusions
Given the well-controlled nature of this study, this provides the strongest evidence for deleterious effects of advancing paternal age on social and exploratory behavior. De-novo chromosomal changes and/or inherited epigenetic changes are the most plausible explanatory factors.

Citation: Smith RG, Kember RL, Mill J, Fernandes C, Schalkwyk LC, et al. (2009) Advancing Paternal Age Is Associated with Deficits in Social and Exploratory Behaviors in the Offspring: A Mouse Model. PLoS ONE 4(12): e8456. doi:10.1371/journal.pone.0008456

Editor: Kenji Hashimoto, Chiba University Center for Forensic Mental Health, Japan

Received: October 28, 2009; Accepted: December 2, 2009; Published: December 30, 2009

Copyright: © 2009 Smith et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This study was supported by the Beatrice and Samuel A. Seaver Foundation, by a British Medical Association Margaret Temple Award, and National Institute of Health Research (NIHR) Biomedical Research Centre (BRC) for Mental Health at the South London and Maudsley National Health Service (NHS) Foundation Trust and Institute of Psychiatry, King's College London (KCL) Pilot Award to Drs. Jonathan Mill and Abraham (Avi) Reichenberg. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: cathy.fernandes@kcl.ac.uk

# These authors contributed equally to this work.

Introduction Top
Accumulating evidence from epidemiological research has demonstrated an association between advanced paternal age and risk for several psychiatric disorders including autism [1], schizophrenia [2] and early-onset bipolar disorder [3]. Despite the methodological advantages of epidemiological research, a major limitation is that techniques are limited to observation. In order to establish causality, experimental evidence in the form of randomized-controlled trials or the development of animal models is required [4]. Animal models are particularly important as they allow environmental and genetic confounds to be controlled.

The lack of complete specificity in the association between advancing paternal age and psychiatric disorders may suggest that advancing paternal age is related to phenotypes shared across disorders. One phenotype in-common to schizophrenia, autism and bipolar disorder is abnormalities in social cognition broadly defined severe social deficit [5], [6], [7], [8]. A recent epidemiological study found an association between advancing paternal age and impaired social functioning in male offspring in the general population [9].

In this study we examined the effect of older paternal age on social and non-social behavior in mice. To the best of our knowledge this is the first fully-controlled animal study of the effects of paternal age on these behaviors.

Results Top
Social Behavior
Offspring of old fathers engaged in less social activity than the offspring of young fathers, spending less time socially-interacting with the conspecific mice (t = 2.23, d.f. = 22, p = 0.02, one-tailed test, Figure 1). This result was consistently observed across all measures of social behavior. There were no significant differences in overall locomotor activity.

Figure 1. Results of social behavioral data from male offspring of young fathers (n = 12) and old fathers (n = 12).

* shows a p-value of less than 0.05, † shows p-value of 0.06. A. Mean time (±SEM) displaying all social behaviors toward a conspecific mouse (broken down into components in B, C and D). B. Mean time (±SEM) displaying allogrooming behavior towards a conspecific mouse. C. Mean time (±SEM) displaying anogenital sniffing behavior towards a conspecific mouse. D. Mean time (±SEM) displaying sniffing behavior towards a conspecific mouse.

doi:10.1371/journal.pone.0008456.g001
Exploration in the Holeboard
Offspring of old fathers demonstrated reduced exploration in the holeboard, making fewer nose pokes and spending less time nose poking than offspring of young fathers (t = −2.21, d.f. = 22, p = 0.02; Figure 2A). No significant differences were evident in distance moved or time spent in the centre of the Holeboard arena.

Figure 2. Results of holeboard and open field data from male offspring of young fathers (n = 12) and old fathers (n = 12).

* shows a p-value of less than 0.05. A. Mean number of nose pokes (±SEM) into holes in the holeboard trial. B. Mean time spent in each area of arena (±SEM) in the open field task.

doi:10.1371/journal.pone.0008456.g002
Exploration in the Open Field
Offspring of old fathers were less exploratory in the Open Field, taking longer to enter the central zone of the arena (t = 1.7837, d.f. = 22, p = 0.04). However, there were no significant differences inthe time spent in the middle (t = −0.9548, d.f. = 22, p = 0.1785) or central zones (t = −1.3166, d.f. = 22, p = 0.1056) (Figure 2B) or in overall locomotor activity between offspring of old fathers and offspring of young fathers in the open field.

To further explore these findings we examined the same set of behaviors in a small group of mice that were the offspring of very old fathers (aged >12 months, n = 9 male offspring generated from 7 breeding pairs). The behavioral results of reduced social behavior and exploration were seen in the offspring of very old fathers, but the numbers are too small to allow for a reliable statistical test (data not shown).

Discussion Top
Using a mouse model we documented deleterious effects of advancing paternal age on offspring behavior. Male offspring of older fathers engaged in less social behavior and exhibited less exploration in a novel environment. These effects were not confounded by differences in overall locomotor activity. Abnormalities in social behavior characterize psychiatric disorders previously linked to advancing paternal age, suggesting a common phenotype affected by paternal age.

There are several advantages for the mouse model used in this study. First, given the tractable nature of animal work, the environment was tightly controlled, minimizing any environmental confounds. Second, the age of all the mothers of the offspring was standard such that differences observed in the offspring cannot be accounted for by maternal age.

Finally, the most common reference inbred strain of mouse was used (C57BL/6J), reducing genetic variation.

In men, it is thought that the spermatogonial stem cell divisions occurring over the life-course of males result in higher mutational rates and cytogenetic abnormalities in the sperm of older men [10], [11]. Numerous neurological and psychiatric disorders have been related to genomic alterations [12]. A number of studies have uncovered an increased prevalence of de-novo copy-number variants (CNVs), and other forms of genomic alterations in autistic and in schizophrenia cases [13], [14].

An alternative explanation is that epigenetic dysfunction underlies some paternal age effects. Epigenetic dysfunction has been associated with several neuropsychiatric disorders, including schizophrenia and bipolar disorder [15]. A study by Flanagan and colleagues [16] reported intra- and inter-individual epigenetic variability in the male germline, and found a number of genes that demonstrated age-related DNA-methylation changes. Epigenetic signals are generally reprogrammed in the germline, although it appears that such reprogramming may not be fully complete across all regions of the genome [17]. In particular, repetitive and transposable elements in the genome, which are generally hypermethylated, are often not efficiently reprogrammed [18]. It is thus plausible that de novo structural mutations, which are often associated with repetitive DNA sequence motifs, may also be subjected to differential epigenetic reprogramming implicating both mutagenic and epigenetic processes in the phenotypic manifestation of increased paternal age.

Despite the advantages of this model, the results of this study should be interpreted in light of some limitations. We only examined one strain of male mice. This was a-priori decided in order to follow common practice in animal research aimed at limiting variation caused by sex differences in behaviors. Hence, findings should not be generalized across sexes. In addition, behavior was assessed at one developmental stage (12 weeks, young adulthood). Thus, the developmental nature of these differences could not be determined.

In conclusion, this study provides the strongest evidence to date for the behavioral effects of advancing paternal age on the offspring. Studies are ongoing to investigate the role of molecular changes in mediating the effects of advancing paternal age on social and exploratory behaviors in offspring, by assessing de-novo CNV events and alterations in DNA methylation.

Methods Top
Breeding Strategy
C57BL/6J mice were bred and maintained in the Biological Services Unit at the Institute of Psychiatry, Kings College London using stocks purchased from Charles River Laboratories. All housing and experimental procedures were performed in accordance with the UK Home Office Animals (Scientific Procedures) Act 1986. Typical breeding age for mice starts at 2 months. Male breeders are generally retired after 7–8 months. Therefore, females aged 2 months were bred with males of two different ages; young males of 2 months (n = 6 breeding pairs), and old males of 10 months (n = 6 breeding pairs). The average litter size within each age group was 7 (male to female ratio 1:1) and total progeny generated was 40 mice in the young fathers group and 44 mice in the old fathers group. Two males were randomly selected from each litter (n = 12 males per group) and weaned aged 4–5 weeks and pair housed with their siblings and then individually housed for two weeks prior to testing. Mice were housed in standard cages measuring 30.5×13×11 cm, with food and water available ad libitum. The housing room was maintained on a standard light/dark cycle with white lights on from 08:00 to 20:00. Ambient temperature in all rooms was maintained at 21±2°C with 45% humidity.

Offspring Behavioral Testing
Offspring were aged 12 weeks at the start of testing and all testing took place during the light phase with a light level <30 lux in the test room. Each apparatus was wiped clean with 1% Trigene® between subjects to avoid olfactory cueing behaviors. Behaviors for all tests were recorded on videotapes for further detailed analysis. Mice were returned to their home cage at the end of each test.

Social Behavior
The social behavior of the test mice towards a juvenile conspecific was assessed in a 5 minute trial [19]. The test mouse is habituated in an arena (36×20×14 cm) for 5 minutes, after which a male juvenile conspecific of the same strain (aged 4 weeks) was introduced for a further 5 minutes. During this trial, social behavior (including social sniffing, anogenital sniffing and allogrooming) by the test mouse towards the conspecific were scored from videotape by an observer blind to the group factor of paternal age.

Holeboard
The holeboard test is used to measure activity and exploration in a novel arena [20]. The Truscan Photo Beam Activity System (Coulbourn Instruments, Whitehall, PA) was used, which consists of an arena (25.4 cm square) and a nose poke floor with 16 holes (4×4 array) with sensor rings to track movement. The beams are spaced 1.52 cm apart providing a 0.76 cm spatial resolution. Animals were placed in the arena and the movement, the number of nose pokes and the time spent nose poking were recorded automatically by beam breaks for 5 minutes using the Truscan program.

Open Field
The open field [21] used a square white acrylic box with dimensions 72×72×33 cm. The animal was placed in the outer part of the arena facing an outer wall and allowed to freely explore the arena for 5 minutes. A video camera placed above the arena allowed movement to be tracked using an automated tracking system (Ethovision, Noldus Information Technologies). The number of faecal boli and urination were recorded at the end of the test. A square of equal distance from the periphery (36×36 cm) was defined in Ethovision as the ‘outer’, ‘middle’ and ‘central’ zones in order to determine the number of entries into, and time spent in, these zones in the arena. In addition, the latency to enter the inner zones as well as locomotor activity in all three zones of the arena were measured by the tracking system.

Statistical Analysis
Behavioral performances of offspring of young fathers and offspring of old fathers in the social interaction task, holeboard and open field were compared using unpaired, one-tailed Students t-tests. Significance level was set at 0.05.

Author Contributions Top
Conceived and designed the experiments: JM CF LCS AR. Performed the experiments: RGS RLK. Analyzed the data: RGS RLK CF. Contributed reagents/materials/analysis tools: JDB. Wrote the paper: RGS RLK JM CF LCS AR.

References Top
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Frans EM, Sandin S, Reichenberg A, Lichtenstein P, Langstrom N, et al. (2008) Advancing paternal age and bipolar disorder. Arch Gen Psychiatry 65: 1034–1040. Find this article online
Rothman KJ, Greenland S (1997) Modern Epidemiology: Lippincott Williams and Wilkins.
Geschwind DH (2009) Advances in autism. Annu Rev Med 60: 367–380. Find this article online
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Green MF (2006) Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry 67: e12. Find this article online
Brotman MA, Skup M, Rich BA, Blair KS, Pine DS, et al. (2008) Risk for bipolar disorder is associated with face-processing deficits across emotions. J Am Acad Child Adolesc Psychiatry 47: 1455–1461. Find this article online
Weiser M, Reichenberg A, Werbeloff N, Kleinhaus K, Lubin G, et al. (2008) Advanced parental age at birth is associated with poorer social functioning in adolescent males: shedding light on a core symptom of schizophrenia and autism. Schizophr Bull 34: 1042–1046. Find this article online
Crow JF (2000) The origins, patterns and implications of human spontaneous mutation. Nat Rev Genet 1: 40–47. Find this article online
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Flanagan JM, Popendikyte V, Pozdniakovaite N, Sobolev M, Assadzadeh A, et al. (2006) Intra- and interindividual epigenetic variation in human germ cells. Am J Hum Genet 79: 67–84. Find this article online
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"However, birth defects and genetic diseases have been associated with advanced paternal age, especially for fathers above the age of 50,"

2009-12-27T12:21:00.000-08:00

Baby bonus

Sat, Dec 26, 2009
Mind Your Body, The Straits Times

Put 50 couples in a room and chances are that seven or eight of them have a fertility problem.

That is assuming they all want to start a family. In a society which reveres the family, however, childless couples have it tough. "For many couples, having a baby is often an easy, uncomplicated and joyous time. But the effects can be devastating for those experiencing infertility," said Dr Suresh Nair.

Related:
» Common causes of infertility(women)
» Common causes of infertility(men)
» Help to usher in the stork
» Happy Mum 1
» Happy Mum 2
The obstetrician, gynaecologist and medical director of Parkway Fertility Centre at Mount Elizabeth Hospital added: "It is a life crisis that can be extremely frustrating and depressing."

It affects a couple's hopes, dreams and future plans and can lead to shock, disbelief, anger, sadness, blame and even marital discord and loss of self-esteem, Dr Nair said.

Infertility is the inability to conceive after a couple has actively tried to do so over the past 12 months, said Dr Ann Tan, a consultant obstetrician and gynaecologist at Women and Fetal Centre.

A Ministry of Health spokesman said it is estimated that 15 per cent of couples here are affected by infertility. When a normal, healthy young couple have sexual intercourse, the chance of the woman getting pregnant is about 25 per cent.

After sex, sperm released by the male partner into the woman's vagina needs to travel up her fallopian tubes to fertilise the egg. When fertilisation occurs, an embryo is formed, which then moves down into the woman's womb or uterus for implantation.

Most fertile when young

Women reach peak fertility in their 20s. They are most fertile in the middle of their 28- to 30-day cycle.

Dr Stephen Chew, a senior consultant at the department of obstetrics and gynaecology at National University Hospital, said: "The woman's age is the most important factor determining fertility outcome."

Fertility in women falls by 4 to 8 per cent when they are between 25 and 29 years old; 15 to 19 per cent between 30 and 34 years old; 26 to 46 per cent between 35 and 39 years old; and 95 per cent by the time they hit 45 years of age.

Women stop producing eggs once they reach menopause and the average age when this occurs is 48 years. Natural spontaneous conception is not possible after menopause.

Age no barrier for men

In contrast, men are fertile from puberty until their 70s, although their testosterone levels decline at a rate of about 1 per cent each year after the age of 30.

Sperm quality, quantity and sexual performance also go downhill as men get older. Dr Jazlan Joosoph, a specialist in obstetrics & gynaecology at Raffles Hospital, said: "For men, the biological clock never stops. It only slows down.

"However, birth defects and genetic diseases have been associated with advanced paternal age, especially for fathers above the age of 50," Dr Jazlan said.

This is due to poorer sperm quality. "Men, like women, are advised to start procreation at an early age," he added.

Other health factors

Various other factors can cause infertility. In women, it can arise from one of three sites: the eggs, the fallopian tubes and the uterus. Dr Nair said: "Fallopian tube problems include endometriosis, pelvic inflammatory disease and ectopic pregnancies which damage the tubes.

"A woman may also suffer from a misshapen or scarred womb, one that is physically unable to either have the embryo take seed or to nurture the developing foetus."

Dr Jazlan added: "Ovulatory problems are common causes of female infertility. Successful fertilisation or conception cannot occur if there is absence of egg production or if there are eggs of poor quality."

In men, infertility can be due to defects in sperm quality, its quantity or a sexual dysfunction such as premature ejaculation. Dr Loh Seong Feei, the head and senior consultant at the department of reproductive medicine at KK Women's and Children's Hospital, said: "Many factors can cause the quality or quantity of sperm in the ejaculate to be low.

"Some common causes include genital tract infection and varicocele (widening of the veins along the cord that holds up a man's testicles).

"These factors can result in abnormally shaped sperm, which may not fertilise the egg, poor sperm motility such that sperm is unable to swim through the cervix to meet the egg, and low or zero sperm count."

Illnesses like mumps or cancer also affect fertility in men.

Lifestyle choices

Professor P.C. Wong, the head and senior consultant at the reproductive endocrinology and infertility division in the obstetrics and gynaecology department at National University Hospital, said smoking affects sperm production, causing sperm quality and quantity to drop.

Dr Nair said that sperm concentration and motility fall by 19 per cent and 29 per cent respectively in men who smoke 10 to 20 cigarettes a day.

Besides smoking, other lifestyle factors also play a part in fertility.

Heavy drinking, over-exercise, anorexia and obesity contribute to infertility in men and women.

Of course, infertility is never just one partner's problem.

Dr Nair said: "Knowing that you are less fertile and having to perform the sexual act can be demanding.

"This can affect spontaneity and lead to sexual difficulties or psychological stress that can strain the marriage or relationship."

junec@sph.com.sg

'Effect of advanced paternal age on fertility and pregnancy'

2009-12-26T09:48:00.000-08:00

Medline ® Abstracts for References

--------------------------------------------------------------------------------

7
TI Changes with age in the level and duration of fertility in the menstrual cycle.
AU Dunson DB; Colombo B; Baird DD
SO Hum Reprod 2002 May;17(5):1399-403.

BACKGROUND: Most analyses of age-related changes in fertility cannot separate effects due to reduced frequency of sexual intercourse from effects directly related to ageing. Information on intercourse collected daily through each menstrual cycle provides the data for estimating day-specific probabilities of pregnancy for specific days relative to ovulation, and these estimates allow unconfounded analysis of ageing effects. METHODS: A total of 782 healthy couples using natural family planning methods contributed prospective data on 5860 menstrual cycles. Day of ovulation was based on basal body temperature measurements. Estimates of day-specific probabilities of pregnancy and the length of the fertile window were compared across age groups. RESULTS: Nearly all pregnancies occurred within a 6 day fertile window. There was no evidence for a shorter fertile window in older men or women. On average, the day-specific probabilities of pregnancy declined with age for women from the late 20s onward, with probabilities of pregnancy twice as high for women aged 19-26 years compared with women aged 35-39 years. Controlling for age of the woman, fertility was significantly reduced for men aged>35 years. CONCLUSIONS: Women's fertility begins to decline in the late 20s with substantial decreases by the late 30s. Fertility for men is less affected by age, but shows significant decline by the late 30s.

AD Biostatistics Branch, MD A3-03, National Institute of Environmental Health Sciences, National Institutes of Health, P.O.Box 12233, Research Triangle Park, NC 27709, USA. dunson1@niehs.nih.gov
PMID 11980771

--------------------------------------------------------------------------------

8
TI Effect of male age on fertility: evidence for the decline in male fertility with increasing age.
AU Hassan MA; Killick SR
SO Fertil Steril 2003 Jun;79 Suppl 3:1520-7.

OBJECTIVE: To evaluate the effect of men's age on time to pregnancy (TTP) using age at the onset of pregnancy attempts, adjusting for the confounding effects of women's age, coital frequency, and life-style characteristics. DESIGN: Observational study. SETTINGS: Teaching hospital in Hull, United Kingdom. PATIENT(S): Two thousand one hundred twelve consecutive pregnant women. INTERVENTION(S): A questionnaire inquiring about TTP, contraceptive use, pregnancy planning, previous subfertility, previous pregnancies, age, and individual life-style characteristics of both partners. MAIN OUTCOME MEASURE(S): Time to pregnancy, conception rates, and relative risk of subfecundity for men and women's age groups. RESULTS: As with women's age, increasing men's age was associated with significantly rising TTP and declining conception rates. A fivefold increase in TTP occurred with men's age>45 years. Relative to men<25 years old, those>45 years were 4.6-fold and 12.5-fold more likely to have had TTP of>1 or>2 years. Restricting the analysis to partners of young women revealed similar effects of increasing men's age. Women>35 years were 2.2-fold more likely to be subfertile than women<25 years. The results were comparable, whether age at conception or at the onset of pregnancy attempts was analyzed, and they remained unchanged after adjustment for the confounding factors. CONCLUSION(S): Evidence for and quantification of the decline in men's fertility with increasing age is provided.

AD The University of Hull, Post Graduate Medical Institute and Hull&York Medical School, Hull, United Kingdom. manhassan@yahoo.com
PMID 12801554

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9
TI The effect of advancing paternal age on pregnancy and live birth rates in couples undergoing in vitro fertilization or gamete intrafallopian transfer.
AU Klonoff-Cohen HS; Natarajan L
SO Am J Obstet Gynecol 2004 Aug;191(2):507-14.

OBJECTIVE: This study was undertaken to determine effects of male aging on sperm parameters, fertilization, pregnancy, and live birth rates among in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) couples. The impact of female age was also investigated. STUDY DESIGN: Prospective study was made up of 221 IVF and GIFT couples. RESULTS: Pregnancy rates declined as the male subjects aged. Each additional year of paternal age was associated with 11% increased odds (P=.007) of not achieving a pregnancy, and 12% odds (P=.01) of not having a successful live birth. For first-time IVF/GIFT recipients, each additional year of paternal age was associated with a 5% increased odds of not achieving a pregnancy, whereas for repeaters it was 40% (P=.01). Advancing maternal age was associated with decreased numbers of oocytes retrieved or fertilized. Women 40 years or older compared with younger than 35 years had greater than 4-fold risk of not becoming pregnant, and greater than 20-fold risk of not achieving a live birth. CONCLUSION: Advancing paternal (and maternal) age had a deleterious effect on IVF and GIFT outcomes.

AD Department of Family and Preventive Medicine, University of California, San Diego, CA, USA.
PMID 15343228

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10
TI Paternal age>or=40 years: an important risk factor for infertility.
AU de La Rochebrochard E; Thonneau P
SO Am J Obstet Gynecol 2003 Oct;189(4):901-5.

OBJECTIVE: The purpose of this study was to examine the risk of infertility that is associated with paternal age, because this factor rarely has been investigated, whereas maternal age of>or=35 years is a well-known risk factor. STUDY DESIGN: This large, retrospective, population-based sample included 6188 European women (from Denmark, Italy, Spain, Germany) aged 25 to 44 years who were selected randomly from census registers in 1991 through 1993. RESULTS: Among couples composed of a woman aged 35 to 39 years, risks were significantly higher when paternal age was>or=40 years than when paternal age was<40 years, with an adjusted odds ratio of 2.21 (95% CI, 1.13, 4.33) for delay in pregnancy onset (failure to conceive within 12 months) and of 3.02 (95% CI, 1.56, 5.85) for difficulties in having a baby (failure to conceive within 12 months or pregnancy not resulting in a live birth). CONCLUSION: Like maternal age of>or=35 years, paternal age of>or=40 years should be considered to be a key risk factor for infertility.

AD Institut National de la Sante et de la Recherche Medicale, Le Kremlin-Bicetre, France.
PMID 14586322

--------------------------------------------------------------------------------

11
TI Fathers over 40 and increased failure to conceive: the lessons of in vitro fertilization in France.
AU de La Rochebrochard E; de Mouzon J; Thepot F; Thonneau P
SO Fertil Steril. 2006 May;85(5):1420-4. Epub 2006 Apr 17.

OBJECTIVE: To investigate paternal age effect mediated by biological modifications with use of data from assisted reproductive technologies. DESIGN: National IVF registry. SETTING: Fifty nine French IVF centers. PATIENT(S): A total of 1,938 men whose partners were totally sterile, with bilateral tubal obstruction or absence of both tubes (to avoid bias sampling in analysis of paternal age) and treated by conventional IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Risk of failure to conceive defined as absence of intrauterine pregnancy. RESULT(S): The odds ratio of failure to conceive for paternal age>or =40 years was 2.00 (95% confidence interval [CI]: 1.10-3.61) when the woman was 35-37 years old, 2.03 (95% CI: 1.12-3.68) for age 38-40 years, and 5.74 (95% CI: 2.16, 15.23) for age 41 years and over. CONCLUSION(S): As an increasing number of couples choose to postpone childbearing, they should be informed that paternal age over 40 years is an important risk factor for failure to conceive.

AD INED, Le Kremlin-Bicetre, F-94276, France. roche@ined.fr
PMID 16616749

2009-12-23T14:13:00.000-08:00

The Male Biological Clock

Aging, Mitochondria and Male Reproductive Function.

2009-12-22T05:41:00.000-08:00

Curr Aging Sci. 2009 Dec;2(3):165-173.

Aging, Mitochondria and Male Reproductive Function.
Amaral S, Ramalho-Santos J.

Center for Neuroscience and Cell Biology, Department of Zoology, School of Science and Technology, University of Coimbra, 3004-517 Coimbra, Portugal. jramalho@ci.uc.pt.

The rise in life expectancy over the last century, together with higher maternal and paternal ages and have highlighted the issue of reduced fertility with advancing age. Aging of the male reproductive system is incited by multi-factorial changes at molecular, cellular and regulatory levels, and individual characteristics are highly variable, although strongly influenced by lifestyle and environmental factors. Damage accumulated with age leads to progressive deregulation of the hypothalamic-pituitary-gonadal axis and of local auto/paracrine interactions, thereby inducing changes in target organs such as the testis, penis and prostate. Elderly human males produce less testosterone, have fewer motile sperm and a higher incidence of erectile dysfunction and prostate disorders, all of which contribute to lower fertility. Cellular aging can manifest itself at several levels. Aging cells progressively accumulate "waste" products, resulting in a decreased functionally. Changes to mitochondria are among the most remarkable features observed in aging cells and several theories place mitochondria at the hub of cellular events related to aging, namely in terms of the accumulation of oxidative damage to cells and tissues, a process in which these organelles may play a prominent role, although alternative theories have also emerged. Furthermore, mitochondrial energy metabolism is also crucial for male reproductive function and mitochondria may therefore constitute a common link between aging and fertility loss.

Man’s Age Affects Pregnancy Success And Miscarriage Rate In Couples With Fertility Problems

2009-12-18T07:37:00.000-08:00

Man’s Age Affects Pregnancy Success And Miscarriage Rate In Couples With Fertility Problems
Filed under News
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Researchers in France studying over 12,000 couples with fertility problems found that when the man was over 35 pregnancy rates fell and
perhaps more surprisingly, miscarriage rates rose, leading them to conclude that the age of the father was just as important as the age of the mother
in reaching a successful pregnancy.

The findings are being presented today, Monday 7th July, at the 24th annual conference of the European Society of Human Reproduction and
Embryology (ESHRE) in Barcelona, Spain, by lead investigator Dr Stephanie Belloc, of the Eylau Centre for Assisted Reproduction in Paris,
France.

This is the first time such a strong effect from the father on reproductive success rates has been found from research, said Belloc in a press
statement.

Belloc and her team studied 12,236 couples who underwent 21,239 intrauterine inseminations (IUIs) at the Eylau Centre between January 2002 and
December 2006 and used the male partner’s sperm (as opposed to donated sperm) in all cases. Most couples were being treated because of the
man’s infertility.

In IUI, the sperm is spun in a centrifuge to remove the seminal fluid and then inserted directly into the uterus while the woman is ovulating. This
technique is less invasive than IVF and is used when the woman’s fertility is not a problem.

If the sperm is not “washed” in the centrifuge to remove the seminal fluid, the prostaglandins in the seminal fluid can cause cramps in the uterus which
expels the semen.

For each IUI, the sperm was examined for a number of characteristics, such as sperm count, motility (how agile they are) and morphology or shape,
and the clinical pregnancy, miscarriage and delivery rates were noted. The researchers then analyzed the results, distinguishing between male and
female factors in influencing outcomes for each IUI case.

The results showed that maternal age was closely linked to decreased pregnancy rate, which was 8.9 per cent in women over 35 compared to 14.5
per cent in younger women.

But the scientists also found that the father’s age was also important, not only on pregnancy rates, but perhaps more surprisingly, on the rate of
miscarriage, with a pronounced negative effect once the father was over 35 years of age.

The effect of the mother’s age on conception and miscarriage rates is already well known to scientists, but the effect of the father has not been very
clear; studies have shown that sperm count and quality declines as men get older, but until now there has been no clinical evidence of the impact of
the age of the man on a couple’s ability to have a successful pregnancy.

As Belloc explained, it was a question that needed to be answered once and for all:

“We already believed that couples where the man was older took longer to conceive, but a number of reasons had been put forward for
this.”

“Neither was there any definite evidence that miscarriage rates increased when the man was older,” she said.

Speculating on the reasons why the age of the man should impact fertility, Belloc said a number of recent studies have shown a ink between IUI
success and DNA damage, which is linked to the man’s age.

The researchers are hoping to gather more evidence as they add more couples to the study in the coming years.

Belloc said this research will yield important information for couples wanting to start a family, and the larger the pool of couples from which the
evidence is drawn the more helpful the information will be.

The study is clinical evidence to support the notion that DNA damage in older men reflects in fertility, Belloc said:

“Our research proves for the first time that there is a strong paternal age-related effect on IUI outcomes, and this information should be considered
by both doctors and patients in assisted reproduction programmes.”

She said that perhaps this will support the recommendation that IVF or ICSI should be the preferred treatment when either of the partners is over 35.
In IVF the outer membrane of the egg (the zona pellucida) appears to stop the entry of sperm with DNA damage, and in ICSI, the best quality sperm
is selected out.

“These methods, although not in themselves a guarantee of success, may help couples where the man is older to achieve a pregnancy more quickly,
and also reduce the risk of miscarriage,” said Belloc.

A representative of the Eylau Centre also said on an interview with the BBC aired early this morning that the likely cause of the decrease in male
fertility after 35 was DNA fragmentation. He said that DNA fragmentation was not unusual in male sperm and often this is repaired “by the woman”,
but when it is too fragmented it is beyond repair, leading to pregnancy failure and miscarriage, he said.

Egg and sperm donation rules to be reviewed

2009-12-09T21:45:00.000-08:00

Egg and sperm donation rules to be reviewed

By John von Radowitz, Press Association

Wednesday, 9 December 2009

A major review of the rules regarding sperm, egg and embryo donation will take place over the course of next year.

The most controversial area to be discussed concerns expenses payments made to donors.

Also on the agenda will be age limits for male and female donors, and restrictions on how many families a man can donate his sperm to.

Currently in the UK payments for sperm and egg donations can only be made to reimburse travel costs and loss of earnings.

Some other European countries interpret the rules more liberally to include compensation for "inconvenience".

Under EU law donors cannot be paid directly for their eggs and sperm, as happens in the US where people earn large sums of money helping infertile couples. An EU directive limits compensation to "making good expenses and inconveniences related to the donation".

In the UK expenses payments for donors are broadly in line with those given to jurors. There is an overall limit of £250 for each course of sperm or egg donation.

Four years ago the Human Fertilisation and Embryology Authority (HFEA), which regulates fertility services and research, decided not to allow compensation for "inconvenience". It was felt that paying "inconvenience" money might encourage people to make donations without thinking enough of the consequences.

Since then there have been calls for more flexibility to better reflect the sacrifices made by many donors.

Members of the HFEA agreed to hold the review at a meeting today.

Professor Lisa Jardine, who chairs the authority, said: "The authority had a rewarding and well informed debate across a wide range of important issues and arrived at some significant decisions. I welcome the fact that we are now beyond the implementation of the new legislation and can address issues which have implications for all of our stakeholders.

"There was a general view that the HFEA's policy with regard to reimbursement for donors, which has now been in place for two years since the introduction of the European Tissue and Cell Directive, was one that could usefully be revisited in light of what we have learned over those two years. We will not prejudge the outcome of the review that will now take place."

Other issues to be addressed include whether to change the current lower age limit for egg donation, which currently stands at 18, to take account of potential health risks.

The authority will also look at whether its upper age limit of sperm donors should be brought in line with professional guidelines. The official age limit is now 45, while the professional guidance recommends 40 or younger.

Also under discussion is the 10-family limit for sperm donors. This prevents a man donating his sperm to more than 10 families, irrespective of the number of babies that result.

Egg sharing, donations between family members, and the possibility of allowing people only to donate to certain patient groups will also be considered.

Man's age has a direct effect on fertility

2009-12-07T06:23:00.000-08:00

Man's age has a direct effect on fertility: reportMatthew CouttsThe age of the potential father - not just the mother - can seriously limit the chances of having a baby later in life, according to a study released today.

While it has long been documented would-be mothers in their mid-30s or older face reduced pregnancy rates and increased miscarriages, researchers say this is the strongest proof to date that similar problems are caused by the age of the would-be father in couples that face difficulty conceiving.

Researchers at France's Eylau Centre for Assisted Reproduction monitored 21, 239 cases of intrauterine inseminations (IUI), an effective type of artificial insemination, in more than 12,000 couples between 2002 and 2006.

They found maternal age was closely associated with a decrease in the pregnancy rate - 8.9 per cent in women over 35 years, compared with 14.5 per cent in younger women - as well as a higher miscarriage rate.

"But we also demonstrated that the age of the father was important in the rate of pregnancy, with a negative effect for men over 40,'' said Stephanie Belloc, lead author of the study.

"And even more surprising, the proportion of miscarriages went up as well, '' she added.

The study, to be presented at the European Society of Human Reproduction and Embryology conference in Barcelona, showed paternal age led to decreases in the pregnancy rate, from 12.3 per cent with fathers 30 years of age or younger, to 9.3 per cent in fathers older than 45 years of age. The rate of miscarriage more than doubled over the same periods, from 13.7 per cent to 32.4 per cent.

In most cases the couples were being treated at the clinic because the husband had infertility issues, but researchers say the findings relate to men without such problems. "There is no doubt that we can extrapolate from the study to men in general,'' said co-author Yves Menezo, also a researcher at the Eylau Centre.

In IUI the sperm is "washed'' in order to separate them from the seminal fluid, and then inserted directly into the uterus. The goal is to increase the chances of fertilization and remove any chemicals in the semen that may cause discomfort for the woman.

Belloc said sperm with DNA damage, common in older men, was still able to enter the egg during IUI, but the weakened sperm could result in failure to conceive. While previous reports show a decline in sperm count and quality in older men, this is the first clinical proof that a man's age has a direct effect on fertility.

National Post, with files from AFP

Limb malformations with associated congenital constriction rings

2009-11-27T06:18:00.000-08:00

Clin Dysmorphol. 2009 Nov 24. [Epub ahead of print]

Limb malformations with associated congenital constriction rings in two unrelated Egyptian males, one with a disorganization-like spectrum and the other with a probable distinct type of septo-optic dysplasia.
Temtamy SA, Aglan MS, Ashour AM, El-Badry TH.

Departments of aClinical Genetics bOrodental Genetics, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt.

In this report, we describe two unrelated Egyptian male infants with limb malformations and constriction rings. The first case is developing normally but has severe limb anomalies, congenital constriction rings, scoliosis because of vertebral anomalies, a left accessory nipple, a small tumor-like swelling on his lower back with tiny skin tubular appendages, a hypoplastic scrotum, and an anchored penis. The second case is developmentally delayed with limb malformations, congenital constriction rings, a lumbar myelomeningeocele, hemangioma, and tiny tubular skin appendages on the back. The patient also had bilateral optic atrophy. The constellation of features in our patients cannot be fully explained by the amniotic disruption complex. The first patient may represent an additional case of the human homolog of the mouse disorganization mutant. The presence of bilateral optic atrophy in the second case, although without an absent septum pellucidum nor other brain anomalies resembles the infrequently reported disorder of septo-optic dysplasia with limb anomalies. Both cases were sporadic and could be caused by a new dominant mutation because of the high paternal age of case 1 and the history of paternal occupational exposure to heat for both fathers. We draw attention to the phenotypic overlap between the disorganization-like syndrome and septo-optic dysplasia with limb anomalies.

PMID: 19940763 [PubMed - as supplied by publisher]

Turns out that it’s not just women who have a biological clock.

2009-11-22T18:32:00.000-08:00

Is Your Sperm Too Old?
Turns out that it’s not just women who have a biological clock.
By Kevin Conley,
While you've never been against the idea of a serious relationship, you are in no particular rush to become a schlub. The attendant trappings of new fatherhood—the preschool viewings, the sleepless nights, the humiliation of carrying a diaper bag—aren't exactly calling out to you the way, say, another night slinging Pisco sours would. The ever-intensifying din of the proverbial biological clock? That's for the opposite sex to worry about—you know, like periods, frizz and whether Mr. Big will dump "Carrie in the Sex and the City" sequel. As far as you know, your little swim team of DNA carriers will be competing at Olympic level into Letterman age. So what's the rush?

"I always thought my biological clock was the 36 hours I had left after I took my Cialis pill," says Zack, a 30-year-old producer in Los Angeles. "That's the only clock I've ever felt ticking." Turns out, Zack might want to consider the unsung glories of fatherhood.

According to a study released last March in the Public Library of Science Medicine, children born to fathers who were 20 scored an average of 2 points higher on an IQ test than children born to 50-year-old fathers. And that's not all. Recent studies from Israel, California and Sweden have connected "late paternal age" with any number of serious medical conditions: The longer you wait, the more likely it is that your kid will be affected by schizophrenia, dwarfism, bipolar disorder, autism, Marfan syndrome, certain childhood cancers, or even, later in life, Alzheimer's. In some cases, the risk factors skyrocket. A 2005 study conducted by the University of California, Los Angeles, found a fourfold rise in Down syndrome among babies born to men 50 and older. Worse still, those risk factors aren't limited to your tweed-sporting years: Statistically, "late paternal age" starts at 30, as in Zack's age. A 2006 study conducted by Mount Sinai School of Medicine found that fathers in their 30s have children with about 1.5 times the risk of developing autism compared with fathers in their teens and 20s. That factor jumps to five times for dads in their 40s. The cherry on the cake? The American Society for Reproductive Medicine recommends that sperm banks do not accept specimens from men over 40.

"The biological clock for men and women is really the same," says Dr. Dolores Malaspina of Bellevue Hospital Center in New York City and New York University, who conducted one of the first studies. "It's just that men can keep having babies."

The biology behind this isn't hard to grasp: Starting in puberty, spermatogonia, the master copies for sperm production, replicate themselves every couple of weeks. After 300 to 500 copies—somewhere in your 30s—a meaningful number of small copy errors, or point mutations, start to emerge, which accumulate over time.

Yet, despite the alarming new science, most men greet parenthood with a sense of urgency that's more in line with Zack's than Angelina Jolie's. The reason is simple: While women are inculcated with the risks of late-age motherhood in sixth-grade sex ed, men remain blissfully ignorant. Since the recent studies have been published, the bad news still doesn't seem to be making it to the doctor's office. Scott, a 32-year-old schoolteacher from Babylon, N.Y., decided to start a family when he was Zack's age, strictly because he wanted to raise his child while he was young. "For me the doctors were like, 'Hey, this is going to be good. You're still active,'" Scott says. "Nobody ever told me about the medical risks of being an older dad."

That's because men don't usually get this news flash until they're looking through a microscope at a batch of fugly sperm with no sense of direction. Swain, a 37-year-old IT professional in Dallas, wishes he had heard sooner. His wife is four years younger than he is, and they decided to wait. "What I did was let her clock be the one in control," Swain says. "I would have been happy having kids five, six years ago, but she just wasn't ready. The female clock seems to dominate the conversation."

But don't expect sweeping social change anytime soon. "Tell a man he's got a chance of having kids with genetic abnormalities, and it's like he's going through the stages of the acceptance of death," says Dr. Harry Fisch, a professor of urology and the author of The Male Biological Clock. "They'll say, 'I'm losing my manliness, my sexual ability.' To them it all comes under the same umbrella."

The good news is that no one, not even Malaspina, is suggesting that older men eschew the joys of fatherhood. But if you're a younger guy who hasn't thought twice about postponing it, be forewarned: The female of the species is about to get her just rewards. That bell tolling? It's for you.

Later Paternal Age and Sex Differences in Schizophrenia Symptoms.

2009-11-21T06:46:00.000-08:00

Later Paternal Age and Sex Difference in Schizophrenia

The effects of male age on semen parameters: analysis of 1364 men attending an andrology center.

2009-11-04T08:20:00.001-08:00

Aging Male. 2009 Nov 3. [Epub ahead of print]

The effects of male age on semen parameters: analysis of 1364 men attending an andrology center.
Maya WC, Berdugo J, Cadavid Jaramillo A.

Reproduction Group, University of Antioquia, Medellín, Colombia.

Although the effect of maternal age on fertility is well known, it is unclear whether paternal age also affects fertility. The aim of this retrospective study was to establish an association between the age of the individuals from Medellin, Colombia with semen volume, rapid progressive motility (a), total progressive motility (a + b) and concentration. We evaluated semen volume using a graduated tube, progressive motility using light microscopy (40x) and sperm concentration using a Makler Chamber. Semen samples were grouped according to age into three arbitrary groups (/= to 40 years). The semen volume, rapid progressive motility (a) and total progressive motility (a + b), concentration and total sperm count were found to be inversely related to age (p < 0.05). The reduction in semen parameters of 1364 men attending an andrology center was associated with increasing age of the individuals.

PMID: 19883297 [PubMed - as supplied by publisher]

Scientists discover link between older dads and genetic diseases

2009-10-26T07:37:00.000-07:00

October 26, 2009
Scientists discover link between older dads and genetic diseases
Mark Henderson

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Scientists have moved a step closer to understanding why older fathers are more likely to have children with certain genetic diseases.
They have discovered a surprising genetic link between the formation of benign testicular tumours called spermocytic seminomas and several rare growth disorders, which are more common among the children of older fathers.
The abnormal testicular cells that form these rare tumours also produce sperm carrying mutant genes that cause serious inherited diseases, research at the University of Oxford and Copenhagen University Hospital in Denmark has shown.
The findings offer important new insights into the origin of several rare genetic disorders, including a cause of dwarfism called achondroplasia, and also promise to illuminate more common conditions such as autism, schizophrenia and breast cancer.

All three of these are known to be affected by genetics, and to be more prevalent among the children of older fathers, but few of the DNA mutations responsible have yet been identified. Scientists behind the research believe that abnormal testicular cells of the sort that develop into tumours could be partially responsible.
Professor Andrew Wilkie, of the University of Oxford, who led the research, said: “What we have seen so far may just be the tip of a large iceberg of mildly harmful mutations being introduced into our genome. These mutations would be too weak and too rare to be picked up by our current technology, but their sheer number would have a cumulative effect, leading to disease.
“It may be that process we have identified might contribute to part of the excess risk for older fathers to have children with higher risks of, for example, breast cancer, schizophrenia, or autism. We have no direct evidence for this as yet.”
Details of the research are published in the journal Nature Genetics . Professor Wilkie’s team, which is funded by the Wellcome Trust, is now planning further research to investigate whether testicular abnormalities might be linked to conditions such as autism and schizophrenia.
Spermatocytic seminomas are rare tumours of the testes, almost always benign, which affect about one in 100,000 men. They are caused by the accumulation of genetic mutations in testicular cells, which can sometimes then divide to trigger tumours.
“We think most men develop these tiny clumps of mutant cells in their testicles as they age,” Professor Wilkie said. “They are rather like moles in the skin, usually harmless in themselves. But by being located in the testicle, they also make sperm - causing children to be born with a variety of serious conditions.”
The new study, has identified genetic mutations of the sort that cause achondroplasia and other rare inherited conditions in cells from spermatocytic seminomas. It appears that these mutations help the tumour cells to divide, but cause abnormal growth when transmitted to the offspring via sperm. “We call them ‘selfish’ because the mutations benefit the germ cell but are harmful to offspring,” Professor Wilkie said.
As the mutations cause the tumour cells to profilerate in the testes, they also increase the chances that a sperm that fertilises an egg will be abnormal.
The results will help doctors to explain to parents why children have developed these disorders, and to advise them about the risks of having further children. In most cases, these families will not have a high risk of having another affected child, though it will be higher than in the general population.
“The major implication is for older fathers,” Professor Wilkie said. “We already knew that men in their 50s have a risk of having children with various individually rare genetic disorders — achondroplasia is a well known one — about tenfold higher than men in their early 20s.
“Adding all these risks together, the total additional risk is still only a fraction of 1 per cent because each of these disorders is rare

Overcome Infertilty 03 –Understand Male Biological Clock

2009-10-13T15:02:00.000-07:00

Overcome Infertilty 03 –Understand Male Biological Clock

Infertility is defined as the inability of a couple to conceive after 12 months of unprotected sexual intercourse or the cannot carry the pregnancy full term. It effects over 5 million couples alone in the U. S. and many times more in the world. Because of an unawareness of treatments, only 10% seek help from professional specialists. In fact, about 35% of infertility is caused by the male’s inability to fertilize. 35% is caused by the female’s inability to conceive, 10% attributes to both, and 10 % is considered a failure with an unknown cause.

Even though the sperm in the male reproductive organ do not change much, the quality and quantity of sperm may be reduced by low levels of testosterone due to ageing. Therefore, you can see why a couple in their late 20’s is easier to conceive than a couple with a wife in her 20’s and a husband at the age of 40 and more. Study shows that the odds of male fertility rate decreases at an alarming rate of 11% every year and the chance for his partner to conceive declines even further.

According to the study of European Society of Human Reproduction and Embryology, the rate of miscarriage also increases substantially when the father was over the age of 35.
1. Nearly 17 percent if the father was over 34 years old.
2. Around 20 percent if the father was between the ages of 35 and 39.
3. Over 32 percent if the father was older than 44.

Most couple delay unwanted conception by having the female partner take contraceptive pill or by using condoms, or other methods. Unfortunately, by the time they think that they are ready to have children, they are in their mid thirties and according to the above statistics, the rate of fertility is low and the risk of miscarriage is increased substantially, not counting the risk of giving birth to a child with a defection, including chromosomal abnormalities. Like an old car, no matter how much money which you spend each year to fix it, it will never work like when it was new.

It is wise for a couple to conceive no later then the age of late 20’s and early 30’s to prevent any unnecessary stress caused by infertility within 12 months after they decide to have a baby.

For the best pregnancy self help program review, please visit
http://bestfertility.blogspot.com/
For series of Infertility Articles, please visit
http://fertility-infertility.blogspot.com/

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http://medicaladvisorjournals.blogspot.com

Advanced paternal age: How old is too old?

2009-10-11T07:42:00.000-07:00

:
Bray, I.
Gunnell, D. J Epidemiol Community Health. 2006 October; 60(10): 851–853.
doi: 10.1136/jech.2005.045179. PMCID: PMC2566050

Copyright ©2006 BMJ Publishing Group Ltd.
Advanced paternal age: How old is too old?
Isabelle Bray and David Gunnell, George Davey Smith
I Bray, D Gunnell, G Davey Smith, Department of Social Medicine, University of Bristol, UK
Correspondence to: Dr I Bray
Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK; Issy.Bray@bristol.ac.uk
Accepted March 25, 2006.
This article has been cited by other articles in PMC.
Top
Abstract
Time trends in paternal age
All births
Reasons for increasing age at parenthood
Risks associated with advanced paternal age
Conclusions
References AbstractAverage paternal age in the UK is increasing. The public health implications of this trend have not been widely anticipated or debated. This commentary aims to contribute to such a debate. Accumulated chromosomal aberrations and mutations occurring during the maturation of male germ cells are thought to be responsible for the increased risk of certain conditions with older fathers. Growing evidence shows that the offspring of older fathers have reduced fertility and an increased risk of birth defects, some cancers, and schizophrenia. Adverse health outcomes should be weighed up against advantages for children born to older parents, mindful that these societal advantages are likely to change over time.
Keywords: paternal age, DNA damage, fertility, abnormalities, schizophrenia
Top
Abstract
Time trends in paternal age
All births
Reasons for increasing age at parenthood
Risks associated with advanced paternal age
Conclusions
References Changing patterns of education, employment, and marriage mean that the average age of childbearing for women is increasing, resulting in higher risks of adverse reproductive outcomes.1,2 It has recently been suggested that the decade 25–35 years is the optimal age for women in Westernised societies to have their children balancing education, career, and family.3 In England and Wales, the mean age at childbearing increased from 26.4 years in 1974 to 29.3 years in 2002.1 Healthcare systems have responded to the increased risk associated with delaying maternity by offering screening for congenital abnormalities and treatment for infertility.4,5 Meanwhile, the average paternal age is also increasing. The mean age of fathers in England and Wales increased from 29.2 years in 1980 to 32.1 in 2002.6 The public health implications of this trend have not been widely anticipated or debated.
Top
Abstract
Time trends in paternal age
All births
Reasons for increasing age at parenthood
Risks associated with advanced paternal age
Conclusions
References Time trends in paternal ageBirths within marriage
In 1993, fathers aged <35 years accounted for 74% of live births within marriage in England and Wales, while only 25% of such births were to fathers aged 35–54 years. Ten years later, these percentages were 60% and 40%. Figure 1 1 illustrates these trends. If this trend continues, the proportion of fathers >35 years will further increase.
Figure 1Trends in paternal age for live births within marriage in England and Wales, 1993–2003: (A) decreasing trends <35 years, (B) increasing trends 35–54 years. Source: Series FM1 no 32 (ONS, 2003). (Births to fathers (more ...)

Top
Abstract
Time trends in paternal age
All births
Reasons for increasing age at parenthood
Risks associated with advanced paternal age
Conclusions
References All birthsData on time trends in paternal ages for all births in England and Wales are not available, and it could be argued that the increasing proportion of births occurring outside marriage will lead to declining paternal ages as the fathers of such children are younger than those for children born to married couples. Figure 2 2 shows the age distribution of fathers for all births in England and Wales in 2003, which reaches a maximum at age 32. While this approximately normal distribution is mirrored closely for the 60% of births that occurred within marriage, the paternal ages for births outside marriage is more uniform between the ages of 22 and 33 years, with a lower mean age at fatherhood. Between 1993 and 2003 the percentage of births occurring outside marriage increased steadily from 32% to 41%. However, the demographic composition of the group having children outside marriage is changing.
Figure 2Distribution of paternal age for births in England and Wales in 2003: total births* and live births within and outside marriage to fathers aged 13–49. Source: Series FM1 no 32 (ONS, 2003). *All births within marriage, (more ...)

Maternal age data are available for all births (within and outside marriage) in England and Wales6 and they show that the proportion and number of births to women of 30 and over are increasing.
Top
Abstract
Time trends in paternal age
All births
Reasons for increasing age at parenthood
Risks associated with advanced paternal age
Conclusions
References Reasons for increasing age at parenthoodChanges in the population structure (different sizes of birth cohorts across the span of reproductive ages) explain the trend towards older parents to some extent,1 but there is no doubt that societal changes have led to both men and women beginning families later. Advances in reproductive technologies are also contributing to this trend.7 Some 3%–6% of births in most developed countries are now the result of assisted reproduction.8 While the UK government directs substantial efforts towards reducing teenage pregnancy rates, little guidance is given on the risks of delaying childbearing until advanced maternal age, and less still on the risks of advanced paternal age. In the USA, the American Society for Reproductive Medicine has begun to publicise the risks of delaying childbearing, although their Patient Guide on Age and Fertility9 focuses mainly on the mechanisms and risks of maternal, rather than paternal, aging.
Top
Abstract
Time trends in paternal age
All births
Reasons for increasing age at parenthood
Risks associated with advanced paternal age
Conclusions
References Risks associated with advanced paternal ageIt is thought that accumulation of chromosomal aberrations and mutations during the maturation of male germ cells are responsible for increasing risks of certain conditions with advancing paternal age. The amount of DNA damage in sperm of men aged 36–57 is three times that of men <35 years.8 There is a recent body of literature discussing the possible effects on reproductive outcomes, which has been summarised by Kühnert and Nieschlag.10
Fertility and birth
Regarding fertility, Kühnert and Nieschlag10 conclude that men start to contribute to the reduced fertility of a couple in their late 30s, and to a reduced fecundity in their early 40s. For example, a descriptive study of birth rates in married couples in Ireland before the widespread use of contraception found that the probability of birth decreased for men from 42–43 years of age.11 A more recent prospective cohort study of 5121 pregnant women in California concluded that the risk of spontaneous abortion increased with increasing paternal age, and found that the association was stronger for first trimester losses,12 while another prospective cohort study of 23821 pregnant women (based on the Danish national birth cohort) reported that the paternal age related risk of late fetal death was higher than the risk of early fetal death, and started to increase from age 45 years.13 It has been suggested that advanced paternal age (>50 years) increases the risk of preterm delivery and low birth weight,14 although others have found no such effect.15 Although aneuploidy is the leading genetic cause of pregnancy loss, there is no substantial evidence for an effect of paternal age on the presence of extra or missing chromosomes10 and the proportion of fetal deaths attributable to advanced paternal age is currently probably small.13
Birth defects, developmental illnesses, and childhood cancer
A Danish population based study of 1920 affected births of 1489014 live births concluded that paternal age is associated with cleft lip and cleft palate, independently of maternal age.16 Single gene mutations are the suggested mechanism. Many autosomal dominant diseases (for example, achondroplasia) have been shown to be associated with increasing paternal age.10 A population based study of childhood brain cancers reported to the Swedish Cancer Registry between 1960 and 1994 concluded that there is a paternal age affect, estimated to confer about 25% excess risk in fathers >35 years of age.17 A case‐control study of 10162 matched pairs reported a threefold increase in risk of retinoblastoma for fathers 45 years18 and a 50% increased risk of childhood acute lymphoblastic leukaemia for fathers aged 35 years or more was found in a historical cohort of 434933 live births.19 There is conflicting evidence regarding congenital heart defects, although it has been estimated that among offspring of men aged >35 years, about 5% of cases may be attributable to advanced paternal age.10
What is already known on the topic
The average paternal age in the UK in increasing, and the public health implications of this trend have not been widely anticipated or debated
Accumulation of chromosomal aberrations and mutations during the maturation of male germ cells are thought to be responsible for increasing risks of certain conditions with advancing paternal age
There is a growing literature on the effects for offspring of advanced paternal age. Risks include reduced fertility and increased risk of birth defects, schizophrenia, and cancer

Policy implications
Adverse health outcomes should be weighed up against potential social advantages and disadvantages for children born to older parents, mindful that these societal effects are likely to change over time

Illnesses in adulthood
Some diseases of complex aetiology such as schizophrenia are associated with advanced paternal age.10 This may be because of an increase in mutations arising in paternal germ cells, although the possibility of confounding (for example, by schizoid personality traits) cannot be ruled out.16 To illustrate the possible scale of the effects, results from a Swedish population based cohort study have been used to estimate that the increase in paternal age since 1980 could account for about 10% of new cases of schizophrenia diagnosed in the UK in 2002.20 Advanced paternal age is associated with increased risk of cancers in offspring (for example, breast, prostate, nervous system).10 There is less conclusive data regarding Alzheimer's disease.10
Top
Abstract
Time trends in paternal age
All births
Reasons for increasing age at parenthood
Risks associated with advanced paternal age
Conclusions
References ConclusionsA recent report concluded that “even if the genetic risk for progeny from older fathers is slightly increased, the risk to the individual is low”.9 But as our appreciation of the genetic contribution to disease risk develops it seems probable that, if the current trends in timing of fatherhood continue, the consequences at a population level may nevertheless be worth considering further. The adverse health outcomes discussed here should be weighed up against potential social advantages for children born to older fathers who are more likely to have progressed in their career and to have achieved financial security. For example, data from the national child development study show that young fathers are more likely to come from economically disadvantaged families and to have lower educational attainment21; the labour force survey22 found increasing income with age for men up to their early 40s. Socioeconomic factors such as educational level and occupation are currently associated with many health outcomes. For example people from less affluent backgrounds are less likely to use prenatal care services23 but more likely to give birth to premature or low birthweight infants.24 However, potential social disadvantages of increased paternal age should also be considered, such as less energetic parents and decreased likelihood of the child benefiting from long term relationships with grandparents. Furthermore, as it becomes more common for men to become parents in later adulthood, the current (relatively affluent) socioeconomic composition of older fathers will change, and therefore the relative socioeconomic advantages of having an older father are likely to diminish. An evaluation of various scenarios may help to determine an optimal period of fatherhood balancing the social and economic advantages for the offspring of delayed paternity against the corresponding small, but increasingly well reported, genetic disadvantages. Such an evaluation would inform policy. Possible interventions might include health promotion advising people about the risk of delaying childbearing or changes at a societal level (for example, family benefits, flexible working) that encourage couples to have children earlier rather than later.
Contributors and sourcesAll authors contributed to the conception of the article. IB wrote the initial draft of the paper and subsequent drafts including comments from DG and GDS. All authors have seen and approved the final version. The article arises from a review of the literature and analysis of data available from the Office for National Statistics. All authors are epidemiologists with an interest in public health applications. DG and GDS are members of the Faculty of Public Health.
FootnotesCompeting interests: none.
Ethical approval: not needed.
Top
Abstract
Time trends in paternal age
All births
Reasons for increasing age at parenthood
Risks associated with advanced paternal age
Conclusions
References References1. Chamberlain J, Corbin T. Trends in reproductive epidemiology and women's health. In: Moody J, ed. Why mothers die 2000–2002—report on confidential enquiries into maternal deaths in the United Kingdom. London: RCOG Press at the Royal College of Obstetricians and Gynaecologists, 2004.
2. Bewley S, Davies M, Braude P. Which career first? BMJ 2005. 331589.
3. Heffner L J. Advanced maternal age—how old is too old? N Engl J Med 2005. 3511927–1929. [PubMed]
4. National Collaborating Centre for Women's and Children's Health. Fertility: assessment and treatment for people with fertility problems. London: NICE, 2004.
5. Nicolaides K H, Azar G, Byrne D. et al Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy. BMJ 1992. 304867–869. [PubMed]
6. Office for National Statistics. Birth statistics: review of the registrar general on births and family building patterns in England and Wales. London: Stationery Office, 2002.
7. Blickstein I. Motherhood at or beyond the edge of reproductive age. International Journal Fertlilty and Womens Medicine 2003. 4817–24.
8. Aitken R J, Koopman P, Lewis S E M. Seeds of concern. Nature 2004. 43248–52. [PubMed]
9. American Society for Reproductive Medicine. Age and fertility: a guide for patients. Birmingham, AL: American Society for Reproductive Medicine 2003.
10. Kühnert B, Nieschlag E. Reproductive functions of the ageing male. Human Reproduction Update 2004. 10327–339. [PubMed]
11. Anderson B A. Male age and infertility. Result from Ireland prior to 1911. Population Index 1975. 41561–567.
12. Slama R, Bouyer J, Windham G. et al Influence of paternal age on the risk of spontaneous abortion. Am J Epidemiol 2005. 161816–823. [PubMed]
13. Anderson A‐M N, Hansen K D, Anderson P K. et al Advanced paternal age and risk of fetal death: a cohort study. Am J Epidemiol 2004. 1601214–1222. [PubMed]
14. Tough S C, Faber A J, Svenson L W. et al Is paternal age associated with an increased risk of low birthweight, preterm delivery, and multiple birth? Can J Public Health 2003. 9488–92. [PubMed]
15. Nahum G G, Stainslow H. Relationship of paternal factors to birth weight. J Rerod Med 2003. 48963–968.
16. Bille C, Skytthe A, Vach W. et al Parent's age and the risk of oral clefts. Epidemiology 2005. 16311–316. [PubMed]
17. Hemminki K, Kyyronen P, Vaittinen P. Parental age as a risk factor of childhood leukaemia and brain cancer in offspring. Epidemiology 1999. 10271–275. [PubMed]
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Dr. Harry Fisch On the Male Biological Clock

2009-09-25T18:33:00.000-07:00

Fertility: women aren't to blame any more

Posted:
wnRenderDate('Friday, September 25, 2009 6:51 PM EST', '', true);
Sep 25, 2009 3:51 PM PDT Updated:

CHARLESTON, SC (WCSC) - When it comes to getting pregnant, many times fertility problems are blamed on the woman, but medical experts say 40 percent of the time the problem is with the man.
"Men are in denial, denial, denial, when it comes to fertility and sexual function," Dr. Harry Fisch said. Fisch says that denial often results in couples blaming the woman's body and prematurely trying extreme measures.
"If In Vitro Fertilization was a drug it probably would not be approved by the FDA because there's no long term data," Fisch said.
In fact, Fisch says more than 40 percent of fertility problems are caused by the man -- namely a low sperm count.
But there are ways you can increase that count, like increasing l-arginine, an amino-acid in your diet. "Soy, oats, blueberries, salmon, and tuna are high in l-arginine," Fisch said.
And keep in mind, biological clocks aren't just for women. "There is a male biological clock and after 30 that clock starts ticking," he said.
And while we've all heard of men in their later years reproducing, Fisch doesn't recommend it. "Turns out sperm from older men have a much larger chance of having babies with genetic problems. We know autism, downs syndrome, schizophrenia increases with the paternal father's age," Fisch said.
So how can you slow down your biological clock? Slow down your drinking.
"Two drinks a day is the max I recommend, if you're trying to have a child I don't recommend that much," Fisch said.
And when it comes to your belly, size does matter. "If you've got a beer gut, you're out acting like you're macho but when no one's looking you're tired, and fatigued," Fisch said.
And your sperm count is lower. Fisch also recommends couples coupling every other day. The longer sperm stays in a man's system the lower the sperm's mobility.
Even if you're not trying to get pregnant, you still need to pay attention. "The penis is the dipstick of the body's health so anything you do to increase vascular health will go to helping your penis," Fisch said.
Since sexual dysfunction can show up 3-5 years before heart disease, it's like the canary in the coal mine for a man's body.
Dr. Fisch is the only male fertility expert in the state and he doesn't even live here. He flies down from New York once a month. He says that's because the focus has been on the female factor, but MUSC wants to change that, so Fisch is teaching students about the role the man plays.

Older Men with Tired Sperm: Health Blog Jon Barron

2009-09-06T16:50:00.000-07:00

Older Men with Tired Sperm: Health Blog
For a while now, scientists have known that men lose fertility as they age just as fast as women do — even faster, in fact. Women start heading “over the hill” reproductively at around age 30, but men begin the decline a full six years earlier, by age 24. Plus, studies have shown that older men stand a higher chance of fathering babies with autism, dwarfism, and schizophrenia. So much for the stereotype of the virile codger being a suitable match for the fertile young coed. In fact, several Israeli studies found that the likelihood of autism increases by almost 600 percent when the father is over 40 (immunization shots aside), while the risk of schizophrenia doubles.
And now, in a further blow to the macho dream, a new study of 80,000 people by researchers at Karolinska Institute in Sweden has found that once men reach age 29, their chances of fathering a bipolar child increase by 11 percent. That risk climbs by 37 percent by the time men reach age 55, when compared to men still in their 20s. And bipolar illness tends to have an earlier onset in children of older fathers: those born to dads over age 55 are twice as likely to develop manic-depressive illness before their 20th birthday. In contrast, maternal age doesn’t seem to be much of a factor in the development of the disease.
Historically, scientists have pointed to the correlation between maternal age and birth defects, while men have been comparatively left “off the hook.” The role of women in contributing to fertility and fetal problems seems more obvious. Women carry their eggs around for a long time before they conceive — they have all their eggs at birth (no new eggs are ever created again in their lifetime), and those eggs degrade over time due to biological stresses and environmental factors. But men keep producing new sperm throughout their lives. Until recently, the assumption has been that new sperm is fresh and healthy because it is new, even if it comes from an older man. Not so, the evidence shows because sperm production involves duplicating DNA, and as men age, their ability to accurately replicate DNA declines. This results in DNA copy errors, and the mutated DNA can lead to a host of complications.
One of the most surprising of the complications is that older sperm contributes to miscarriages. A study out of the University of California, Berkeley, found that the sperm of men aged 40-49 was twice as likely to have DNA fragmentation as the sperm of men in their 20s — possibly leading to spontaneous abortion. Given that it’s almost a universal assumption that “something is wrong with the woman” when she suffers multiple miscarriages, this fact comes as a revelation that may take some of the pressure off of prospective moms.
Commenting on the bipolar study, Dr. Harry Fisch, author of The Male Biological Clock, said, “The message here for men is: don’t wait too long. [The male biological clock] starts ticking after the age of 30….We are seeing problems in men over the age of 40, and there is an increase in disorders when the father is over the age of 45.”
In spite of all this gloomy news for men at midlife and beyond, it’s obvious that some older men do, in fact, father healthy children. In other words, there are things men can do to minimize the likelihood of having hormonal imbalances and genetic abnormalities that affect their sperm. For instance, the aforementioned Dr. Fisch suggests that men quit smoking, stay out of jacuzzis (which heat testicles and lower fertility), and rid the body of infections.
The biological clock does indeed keep ticking (for both men and women), but you can slow its beat by following a healthy lifestyle. Heck, you might as well just follow the Baseline of Health Program as outlined Lessons from the Miracle Doctors. For specific recommendations on supplements, check out Supplements from Preconception on Up.
Oh, and I almost forgot — apparently marijuana decreases male fertility (it’s directly sperm toxic). Man, that’s such a bummer! And so does Viagra, as it causes sperm to ejaculate its enzyme load too soon to penetrate the egg. And that’s just too darn poetic!

Mens' biological clocks are ticking, too

2009-09-03T10:08:00.000-07:00

Mens' biological clocks are ticking, too

By Dr. Tom Keenan, For The Calgary Herald

What will reduce the amount of autism and schizophrenia in the population?

2009-08-23T08:57:00.000-07:00

What will reduce the amount of autism and schizophrenia in the population?
August 22, 2009 | By admin In Autism |
Alex

90 % of autism and and 85 -90 % of schizophrenia is de novo, sporadic, non-familial
Is paternal age and risk of autism plausable biologically?

RESULTS: There was a significant monotonic association between advancing paternal age and risk of ASD. Offspring of men 40 years or older were 5.75 times (95% confidence interval, 2.65-12.46; P<.001) more likely to have ASD compared with offspring of men younger than 30 years, after controlling for year of birth, socioeconomic status, and maternal age. Advancing maternal age showed no association with ASD after adjusting for paternal age. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on maternal age. CONCLUSIONS: Advanced paternal age was associated with increased risk of ASD. Possible biological mechanisms include de novo mutations associated with advancing age or alterations in genetic imprinting.

Paternal age and reproduction.

2009-08-22T14:37:00.000-07:00

1: Hum Reprod Update. 2009 Aug 20. [Epub ahead of print]
Paternal age and reproduction.Sartorius GA, Nieschlag E.
Centre of Reproductive Medicine and Andrology of the University, Domagkstrasse 11, D-48149 Muenster, Germany.

BACKGROUND Due to various sociological factors, couples in developed countries are increasingly delaying childbearing. Besides ethical, economical and sociological issues, this trend presents us with several complex problems in reproduction. Although it is well-known that maternal age has a negative effect on fertility and increases the risk of adverse outcome during pregnancy and in offspring, the paternal influence on these outcomes is less well researched and not well-known. METHODS We performed a systematic search of PubMed, and retrieved original articles and review articles to update our previous survey in this journal. RESULTS This review highlights the link between male age and genetic abnormalities in the germ line and summarizes the knowledge about the effects of paternal age on reproductive function and outcome. Increasing paternal age can be associated with decreasing androgen levels, decreased sexual activity, alterations of testicular morphology and a deterioration of semen quality (volume, motility, morphology). Increased paternal age has an influence on DNA integrity of sperm, increases telomere length in spermatozoa and is suggested to have epigenetic effects. These changes may, at least in part, be responsible for the association of paternal age over 40 years with reduced fertility, an increase in pregnancy-associated complications and adverse outcome in the offspring. CONCLUSION Although higher maternal age can be an indication for intensive prenatal diagnosis, including invasive diagnostics, consideration of the available evidence suggests that paternal age itself, however, provides no rationale for invasive procedures.

PMID: 19696093 [PubMed - as supplied by publisher]

older men's sperm contributing to increases in autism, schizophrenia and Alzheimer's.

2009-08-19T17:40:00.000-07:00

The Pros and Cons of Being a Grandpa-Daddy

Wednesday, August 19, 2009
filed under: pregnancy & baby logic
There are physical and emotional consequences to having kids at such a late stage of life.
Michelle Golland, Psy.D.: With the wonderful news that Celine Dion, 41, is pregnant with her second child with her husband Rene, who is 67 years old, I wanted to share the pros and cons of being a Grandpa-Daddy. I choose that title because most of the men who are conceiving children beyond their 60s are most likely on their second wife and have older kids from their first marriage who have kids of their own as well.

There are physical and emotional consequences to having children at such a late stage of life. Because Celine Dion is a relatively young woman, she will be around to raise the children if anything were to happen to Rene. Let's be honest -- another positive is the fact that these children will not be concerned for their financial future in any way, which is usually a concern when becoming a parent at the age of 67. So when this child is 18, Rene will be 85.

Cons
Old sperm: Researchers are finding that it is not just our eggs that get old and cause all the problems, but old sperm may be contributing to increases in autism, schizophrenia and Alzheimer's.

Death/lost role model: Your children won't get to see you in your middle ages and you certainly won't see them in their 30's and having children. Your kids will most likely bury you.

Social stigma: You will be mistaken for the grandpa. Your kids' friends and their parents will assume that you are grandpa due to your age -- plain and simple. This will be embarrassing for your children -- and it will be a topic they will continue to explain their whole life.

Pros
Older dads are more involved in parenting, and are typically more nurturing, affectionate and gentle. Studies have shown that this may be caused by the drop in testosterone as men age.

Older dads are three times more likely to show equality in parenting. They change diapers, feed and bathe their children more often than younger dads.

Kids of older dads usually have higher self-esteem, more confidence, greater sense of security, better ability to handle stress and are more empathic.

Paternal age as a risk factor for schizophrenia: How important is it?

2009-08-18T14:03:00.000-07:00

Schizophr Res. 2009 Aug 13. [Epub ahead of print]
Paternal age as a risk factor for schizophrenia: How important is it?
Torrey EF, Buka S, Cannon TD, Goldstein JM, Seidman LJ, Liu T, Hadley T, Rosso IM, Bearden C, Yolken RH.
The Stanley Medical Research Institute, 8401 Connecticut Ave., Suite 200, Chevy Chase, MD 20815, USA.

Advanced paternal age has been widely cited as a risk factor for schizophrenia among offspring and even claimed to account for one-quarter of all cases. We carried out a new study on 25,025 offspring from the Collaborative Perinatal Project (CPP), including 168 diagnosed with psychosis and 88 with narrowly defined schizophrenia. We also conducted a meta-analysis of this and nine other studies for which comparable age-cohort data were available. The mean paternal age for the CPP cases was slightly, but not significantly, higher than the matched controls (p=0.28). Meta-analyses including these new results were conducted to determine the relative risk associated with alternative definitions of advanced paternal age (35, 45 or 55years and older). These yielded pooled odds ratios and 95% confidence intervals of 1.28 (1.10, 1.48), 1.38 (0.95, 2.01) and 2.22 (1.46, 3.37), respectively. Thus, increased paternal age appears to be a risk factor for schizophrenia primarily among offspring of fathers ages 55 and over. In these 10 studies, such fathers accounted for only 0.6% of all births. Compared with other known risk factors for schizophrenia, advanced paternal age appears to be intermediate in magnitude. Advanced paternal age is also known to be a risk factor for some chromosomal and neoplastic diseases in the offspring where the cause is thought to be chromosomal aberrations and mutations of the aging germline. Similar mechanisms may account for the relationship between advanced paternal age and schizophrenia risk.

De novo apparently balanced translocations in man are predominantly paternal in origin and associated with a significant increase in paternal age

2009-07-30T14:58:00.000-07:00

: J Med Genet. 2009 Jul 27. [Epub ahead of print]
De novo apparently balanced translocations in man are predominantly paternal in origin and associated with a significant increase in paternal age.Thomas NS, Morris JK, Baptista J, Ng BL, Crolla JA, Jacobs PA.
Salisbury District Hospital, United Kingdom.

BACKGROUND: Congenital chromosome abnormalities are relatively common in our species and among structural abnormalities the most common class is balanced reciprocal translocations. Determining the parental origin of de novo balanced translocations may provide insights into how and when they arise. While there is a general paternal bias in the origin of non-recurrent unbalanced rearrangements, there are few data on parental origin of non-recurrent balanced rearrangements. METHODS: The parental origin of a series of de novo balanced reciprocal translocations was determined using DNA from flow sorted derivative chromosomes and linkage analysis. RESULTS: Of 27 translocations, we found 26 to be of paternal origin and only one of maternal origin. We also found the paternally derived translocations to be associated with a significantly increased paternal age (p<0.008). CONCLUSION: Our results suggest there is a very marked paternal bias in the origin of all non-recurrent reciprocal translocations and that they may arise during one of the numerous mitotic divisions that occur in the spermatogonial germ cells prior to meiosis.

PMID: 19638350 [PubMed - as supplied by publisher]

Data Converges About Older Fathers

2009-07-14T15:06:00.000-07:00

Tuesday, July 14, 2009
Data Converges About Older Fathers
A recent post in the New York Times presents some evidence that men who become fathers at a later age have unhealthier children. It is well recognized that men retain their reproductive potential longer, and lose it in a more gradual manner, than do women. Whereas women's fertility declines sharply after age 35 or so, men retain their ability to father children, albeit to a diminished degree, for several decades longer. Recently, some evidence has been presented in the scientific literature that suggests that children conceived with sperm from an older male may have cognitive or psychological challenges compared to those fathered by younger males. A recent study performed by Australian scientists concluded that older dads have children with slightly lower IQs. Others have shown increased rates of schizophrenia, bipolar disorder, and autism in children fathered by older vs. younger men. This evidence suggests that men are susceptible to age-related effects on reproductive ability. This should not surprise anyone. However, the effects of reproductive ageing appear to be expressed differently in males than in females. Dr. Dolores Malaspina, a professor of psychiatry at New York University Medical Center, puts it this way: “It turns out the optimal age for being a mother is the same as the optimal age for being a father.”
posted by Kathleen, Contributing Editor at 1:00 PM

2009-07-14T14:08:00.000-07:00

PLoS Genet. 2009 Jul;5(7):e1000558. Epub 2009 Jul 10.
The ups and downs of mutation frequencies during aging can account for the apert syndrome paternal age effect.Yoon SR, Qin J, Glaser RL, Wang Jabs E, Wexler NS, Sokol R, Arnheim N, Calabrese P.
Molecular and Computational Biology Program, University of Southern California, Los Angeles, California, United States of America.

Apert syndrome is almost always caused by a spontaneous mutation of paternal origin in one of two nucleotides in the fibroblast growth factor receptor 2 gene (FGFR2). The incidence of this disease increases with the age of the father (paternal age effect), and this increase is greater than what would be expected based on the greater number of germ-line divisions in older men. We use a highly sensitive PCR assay to measure the frequencies of the two causal mutations in the sperm of over 300 normal donors with a wide range of ages. The mutation frequencies increase with the age of the sperm donors, and this increase is consistent with the increase in the incidence rate. In both the sperm data and the birth data, the increase is non-monotonic. Further, after normalizing for age, the two Apert syndrome mutation frequencies are correlated within individual sperm donors. We consider a mathematical model for germ-line mutation which reproduces many of the attributes of the data. This model, with other evidence, suggests that part of the increase in both the sperm data and the birth data is due to selection for mutated premeiotic cells. It is likely that a number of other genetic diseases have similar features.

Effect of maternal and paternal age on pregnancy and miscarriage rates after intrauterine insemination

2009-07-12T08:06:00.000-07:00

Effect of maternal and paternal age on pregnancy and miscarriage rates after intrauterine insemination
Authors: Belloc, Stéphanie1; Cohen-Bacrie, Paul1; Benkhalifa, Moncef2; Cohen-Bacrie, Martine2; De Mouzon, Jacques3; Hazout, André4; Ménézo, Yves1

Source: Reproductive BioMedicine Online, Volume 17, Number 3, September 2008 , pp. 392-397(6)

Publisher: Reproductive Healthcare Ltd

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Key: - Free Content - New Content - Subscribed Content - Free Trial Content

Abstract:

More than 17,000 intrauterine insemination (lUI) cycles were analysed retrospectively with respect to outcome according to differing aetiologies of infertility. The quantity and motility of spermatozoa in the final preparation used for insemination had a positive effect on the outcome, as classically observed in the past. It was found that advanced maternal age had a negative effect on the pregnancy rate and was associated with increased miscarriage rate. More interestingly, an exactly parallel effect was found for paternal age. The impact of increased age on necrospermia and sperm DNA structure is discussed as a probable direct cause of this paternal effect.
Keywords: IUI; MATERNAL AGE; MISCARRIAGE; PATERNAL AGE

Document Type: Research article

Affiliations: 1: Laboratoire d'Eylau, 55 rue Saint Didier, 75116 Paris, France; Unité AMP Eylau La Muette, 46-48 rue Nicolo 75116, Paris, France; Unité AMP Eylau Cherest, 5 Rue Pierre Cherest 92200 Neuilly sur Seine, France 2: Laboratoire d'Eylau, 55 rue Saint Didier, 75116 Paris, France 3: Unité INSERM 822, 82 rue General Leclerc, 94276 Le Kremlin Bicetre, France 4: Unité AMP Eylau La Muette, 46-48 rue Nicolo 75116, Paris, France

Tick-Tock Goes the Male Biological Clock

2009-07-09T15:08:00.000-07:00

Tick-Tock Goes the Male Biological Clock
By: Will Harrison (View Profile)

Scientists Warn That Biological Clock Affects Male Fertility

2009-07-09T11:17:00.000-07:00

Wednesday, July 8, 2009

Scientists Warn That Biological Clock Affects Male Fertility
The biological clock ticks for men as well as women, doctors warn today, after research found that male fertility begins to decline when they reach their mid-30s. Doctors said men who wait until their 40s before starting a family face a greater chance of their partner having a miscarriage, because of the poorer quality of their sperm. Researchers examined patient records of more than 12,000 couples treated at a fertility clinic in Paris, and separated out the influence of male and female ages on the couples' chances of having a baby. They found that women whose partners were 35 or older had more miscarriages than those who were with younger men, regardless of their own age. The men's ages also affected pregnancy rates, which were lower in the over-40s. Doctors have long known that a woman's fertility drops sharply in her mid to late 30s, but the effect of age on male fertility is less well understood. Among women, miscarriage rates typically double to 40% between the ages of 20 and 40. The findings are a concern, researchers say, because of the trend for men to delay fatherhood. The latest figures from the Office for National Statistics show the typical age of married fathers rose from 29.1 in 1971 to 34.1 in 2003. The age of men having children outside marriage has remained stable at about 30. And, for the first time, more women in Britain are giving birth in their early 30s than in their late 20s. Yves Ménézo, an embryologist at the Eylau Center for Assisted Reproduction, said older men become less fertile because genetic defects build up in their sperm. In younger men, the damage is minor and can be repaired inside the fertilised egg. But in older men the amount of DNA damage can overwhelm the body's natural repair mechanisms. "We think there's a critical threshold of DNA damage and above that, the damage can no longer be repaired. When that happens, genetic mistakes get through to the embryo and you get an increase in miscarriages," Ménézo said. The findings should cause fertility clinics to reconsider how they treat couples, Ménézo added. Those who fail to conceive after mild forms of fertility treatment, such as intrauterine insemination (IUI), in which sperm is washed and transferred directly into the uterus, should move quickly to more advanced treatments, such as ICSI, where the best quality sperm are picked out and injected directly into the woman's egg. The study looked at pregnancies and miscarriages recorded for couples having IUI treatment at the clinic between 2002 and 2006. It found the risk of miscarriage was on average 16.7% when men were aged 30-34. That rate rose to 19.5% when men were 35-39 and 33% in men aged 40 or over. Stéphanie Belloc, lead author of the study, which is due to be published in the journal RBM Online, said: "Until now, gynaecologists only focus on maternal age, and the message was to get pregnant before the age of 35 or 38 because afterwards it would be difficult. But now the gynaecologists must also focus on paternal age and give this information to the couple." She is to discuss her findings at the annual European Society of Human Reproduction and Embryology meeting in Barcelona today. Jacques de Mouzon, a co-author at the French National Institute for Medical Research, said: "People say men are fertile into old age, 90 even. That may be true sometimes, but the product is different and there are more semen abnormalities as age advances. There is a decrease [in male fertility] and an increase in the spontaneous abortion rate after the age of 40 and especially after 45. It is necessary for men to try to have children before the ages of 40 to 45." Previous research has pointed to a slight increase in birth defects in babies born to older men. A 2005 study of 70,000 couples by epidemiologist Jorn Olsen at the University of California, Los Angeles, found a fourfold rise in Down's syndrome among babies born to men aged 50 and older. They were also more likely to have limb deformities. The chances of having a baby with Down's syndrome increase rapidly with a woman's age. About one in 1,000 babies born to mothers under 30 have it, a figure that rises to one in 400 by the age of 35 and one in 105 by the age of 40. "There is growing evidence from a number of studies to show that men are not totally immune from reproductive aging," said Allan Pacey, an expert in male fertility at Sheffield University. "Previous studies of couples trying to conceive naturally or undergoing IVF have shown that men over the age of about 40 are less fertile than younger men."
Posted by TEEBOB at 6:10 PM

Overcome Infertility - Understanding the Male Biological Clock

2009-06-25T15:12:00.000-07:00

Overcome Infertility - Understanding the Male Biological Clock
By Kyle J Norton

Infertility is defined as the inability of a couple to conceive after 12 months of unprotected sexual intercourse or the cannot carry the pregnancy full term. It effects over 5 million couples alone in the U. S. and many times more in the world. Because of an unawareness of treatments, only 10% seek help from professional specialists. In fact, about 35% of infertility is caused by the male's inability to fertilize. 35% is caused by the female's inability to conceive, 10% attributes to both, and 10 % is considered a failure with an unknown cause.

Even though the sperm in the male reproductive organ do not change much, the quality and quantity of sperm may be reduced by low levels of testosterone due to ageing. Therefore, you can see why a couple in their late 20's is easier to conceive than a couple with a wife in her 20's and a husband at the age of 40 and more. Study shows that the odds of male fertility rate decreases at an alarming rate of 11% every year and the chance for his partner to conceive declines even further.

According to the study of European Society of Human Reproduction and Embryology, the rate of miscarriage also increases substantially when the father was over the age of 35.
1. Nearly 17 percent if the father was over 34 years old.
2. Around 20 percent if the father was between the ages of 35 and 39.
3. Over 32 percent if the father was older than 44.

Most couple delay unwanted conception by having the female partner take contraceptive pill or by using condoms, or other methods. Unfortunately, by the time they think that they are ready to have children, they are in their mid thirties and according to the above statistics, the rate of fertility is low and the risk of miscarriage is increased substantially, not counting the risk of giving birth to a child with a defection, including chromosomal abnormalities. Like an old car, no matter how much money which you spend each year to fix it, it will never work like when it was new.

It is wise for a couple to conceive no later then the age of late 20's and early 30's to prevent any unnecessary stress caused by infertility within 12 months after they decide to have a baby.

For the best pregnancy self help program review, please visit http://bestfertility.blogspot.com/
For series of Infertility Articles, please visit http://fertility-infertility.blogspot.com/

All rights reserved. Any reproducing of this article must have the author name and all the links intact.
"Let Take Care Your Health, Your Health Will Take Care You" Kyle J. Norton
I have been studying natural remedies for disease prevention for over 20 years and working as a financial consultant since 1990. Master degree in Mathematics, teaching and tutoring math at colleges and universities before joining insurance industries. Part time Health and entertainment Article Writer.

Article Source: http://EzineArticles.com/?expert=Kyle_J_Norton

Paternal age and assisted reproductive technology outcome in ovum recipients.

2009-06-23T13:52:00.000-07:00

Fertil Steril. 2009 Jun 17. [Epub ahead of print]
Paternal age and assisted reproductive technology outcome in ovum recipients.Luna M, Finkler E, Barritt J, Bar-Chama N, Sandler B, Copperman AB, Grunfeld L.
Mount Sinai School of Medicine, Department of Obstetrics and Gynecology, Department of Reproductive Endocrinology and Infertility and Reproductive Medicine Associates of New York, New York, New York.

This study suggests that paternal age may be inversely associated with reproductive outcome, as demonstrated by a decline in fertilization, blastocyst formation, implantation and cryopreservation rates with advancing age.

PMID: 19539905 [PubMed - as supplied by publisher]

Older Fathers: Increased risk of having children with autism, schizophrenia

2009-06-21T08:13:00.000-07:00

Older Fathers: Increased risk of having children with autism, schizophrenia
Older fathers: link to autism, schizophrenia.
By Paul Raeburn on January 28, 2009 - 1:52pm in About Fathers

Just after my two-year-old son, Henry, was born, I was surprised and disturbed to learn that he was at increased risk of autism, schizophrenia, bipolar disorder and other ills-because of my age.

My wife, Elizabeth, and I knew about the risks associated with the children of older mothers, with Down syndrome being the most widely recognized. She was tested for whatever was testable while she was pregnant with Henry, and he seemed to be healthy in every respect.

There is, however, no pre-natal test for autism or schizophrenia. And yet the risks are substantial: A 40-year-old man has the same chance of fathering a child with schizophrenia as does a 40-year-old woman of giving birth to a child with Down syndrome.

Why do we know so much about the genetic ailments associated with older mothers, but almost nothing about the diseases associated with older fathers?

In an article I've just written for Scientific American Mind, I note that the number of older fathers is on the rise, meaning the number of children at increased risk for autism and schizophrenia is also on the rise.

Nobody understand why this should be true. A woman's eggs are constructed and stored before she is born. It's reasonable to think that as they age, they might acquire genetic errors that could lead to disease. But sperm are freshly manufactured whenever they're needed; they are not stored. So what could be going on there?

The speculation is that something is going wrong with the so-called spermatogonial cells, the factories that make sperm. It's unclear what is happening, but the situation clearly deserves further research.

And why are older fathers not told of the risks?

That seems wrong to me. Some time ago, I called Charles J. Epstein, past president of the college of medical genetics, and Marilyn C. Jones, the current president, and asked them if they could explain why this don't ask-don't tell policy made sense, especially considering the new findings. "To put it out there every time somebody comes to you for counseling probably engenders more fear than light," Epstein said.

Jones agreed. "Paternal age is usually not addressed in counseling couples of advanced age because there is no simple test to address the risk," she said. "If there is nothing to offer a couple but increasing anxiety, many counselors and physicians do not bring the issue up."

Why then all the fuss about Down syndrome in the children of older women, when the risks for the children of older fathers are about the same? "You bring up Down syndrome, because you get sued if you don't," Epstein said. "And there are options. You can go through prenatal diagnosis, you have the option to terminate."

Epstein points out that the general rate of abnormalities of all kinds in newborns is about 2-4%. So even a 3% risk of schizophrenia in the children of men over 50 is not out of line with other risks. And it sounds less frightening when put this way: A 50-year-old man has a 97% chance of having a child without schizophrenia.

Still, I wish I had known what the risks were before we decided to have children. Would we have gone ahead anyway? That's difficult to say. But at least we would have had all the information we needed to make an intelligent decision.

Fathers'Sperm Delivers Much More Complex Material Than Previously Thought

2009-06-15T08:05:00.000-07:00

Fathers'Sperm Delivers Much More Complex Material Than Previously Thought
ScienceDaily (June 15, 2009) — It was long believed that conception does not involve a meeting of equals. The egg is a relatively large, impressive biological factory compared with the tiny sperm, which delivers to the egg one copy of the father's genes. However, a new study from Huntsman Cancer Institute (HCI) at the University of Utah reveals that the father's sperm delivers much more complex genetic material than previously thought. The findings could lead to a diagnostic test to help couples deal with infertility.

Researchers discovered particular genes packaged in a special way within the sperm, and that may promote the development of the fetus.

"Our findings show that the father plays an active role in packaging his genome to help ensure a healthy baby," says study co-leader Brad Cairns, Ph.D., investigator with HCI and the Howard Hughes Medical Institute, and professor of oncological sciences at the University of Utah. "However, they also raise the possibility that a man's aging, health and lifestyle may alter this packaging and negatively affect fertility and embryo development."

During fetal development, certain genes make decisions about organ and tissue development. The new research shows that in sperm, these genes are wrapped in special packaging materials called 'modified histones.' These modified histones appear to be key factors in ensuring genes are activated or repressed at the right level, place and time, which helps the fertilized egg develop properly.

Chromosomes are long strands of DNA containing thousands of genes, and their packaging helps determine which genes turn on and off. Understanding how these genes are activated or repressed leads to a better understanding of how disorders like birth defects and cancer develop.

"Genes have on-and-off switches, and understanding them allows us to target them, leading to possible treatments, cures or prevention strategies," says Cairns. "That's the good news."

The study is set for publication June 14 – a week before Father's Day – in the online edition of the journal Nature. The research involved collaboration between Cairns' lab at HCI and the University of Utah's in vitro fertilization (IVF) and andrology lab led by Doug Carrell – along with their joint graduate student, Sue Hammoud.

An implication of this study is that factors such as genetic mutations, age or lifestyle may affect sperm chromosome packaging, leading to infertility. "We are hopeful that this work will soon lead to a clinical diagnostic test that will help couples with infertility problems make better informed decisions regarding their prospects for a healthy child. We will also be testing if aspects of a man's lifestyle – such as age, diet or health – affect proper packaging and fertility," says Cairns. Other future work includes how decision-making genes are packaged in eggs, which remains a major mystery.

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Adapted from materials provided by University of Utah Health Sciences.
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6 Fold Increase in Autism for Offspring of Men Over 40

2009-06-03T16:45:00.000-07:00

2009-05-26T17:36:00.001-07:00

M:F ratio is reduced with increasing paternal age consistent with de novo genetic or genomic anomalies arising more frequently as men age

2009-05-20T16:43:00.000-07:00

Autism Dev Disord. 2009 May 19. [Epub ahead of print] Links
Brief Report: Parental Age and the Sex Ratio in Autism.Anello A, Reichenberg A, Luo X, Schmeidler J, Hollander E, Smith CJ, Puleo CM, Kryzak LA, Silverman JM.
Harvard University, Cambridge, MA, USA.

The male-to-female (M:F) ratio for autism spectrum disorders (ASD), typically about 4:1, appears to decrease with increasing paternal age, but this relationship has not been systematically tested. With 393 ASD cases from families with two or more ASD cases, we categorized paternal age into five age groups (<30, 30-34, 35-39, 40-44, 45+) and found that the M:F ratio was significantly decreased with increasing paternal age groups and remained so after also adjusting for maternal age. No significant relationship between maternal age group and the M:F ratio was observed. This study suggests that the M:F ratio is reduced with increasing paternal age consistent with de novo genetic or genomic anomalies arising more frequently as men age and then conceive children.

PMID: 19452267 [PubMed - as supplied by publisher]

According to Miller, the risk of schizophrenia in the offspring of fathers older than 30 is a significant public health concern

2009-05-18T13:34:00.000-07:00

According to Miller, the risk of schizophrenia in the offspring of fathers older than 30 is a significant public health concern, because average paternal ages are increasing
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May 18, 2009

APA 2009
Schizophrenia Risk May Be Higher in Male Offspring of Young Fathers
Myra Partridge

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For almost 10 years, studies have shown that advanced paternal age may be a risk factor for schizophrenia in offspring. However, the risk of schizophrenia may also be higher in male offspring of fathers who are younger than 25 years, according to the results of a study presented at the 2009 American Psychiatric Association annual meeting.

“An increased risk associated with younger fathers raises the possibility of different causal mechanisms for schizophrenia between this group and for offspring of older fathers,” said Brian Miller,1 lead study author and a fellow in the department of psychiatry at the Medical College of Georgia in Atlanta.

Miller and colleagues from universities in Finland and London conducted a meta-analysis of both published and unpublished data on paternal age and schizophrenia in offspring. “We performed a meta-analysis in order to better estimate the effect size of this association, considering the effects of gender and study design,” said Miller.

Incidence of schizophrenia was lowest in offspring of fathers aged 25 to 30 years. Compared with this group, the population attributable risk was found to be 10% higher for paternal age of 30 years or older and 4% higher for paternal age younger than 25 years.

Results confirmed that there is a significantly higher increase in risk of schizophrenia in the offspring of fathers older than 30 years, and there was no evidence of sexual dimorphism. According to Miller, the risk of schizophrenia in the offspring of fathers older than 30 is a significant public health concern, because average paternal ages are increasing.

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Reference
1. Miller BJ, Messias E, Miettunen J, et al. Meta-analysis of paternal age and schizophrenia risk in the offspring [NR3-023]. Poster presented May 18, 2009.

Paternal Age May Also Affect ICSI Outcome in Oligozoospermic Patients

2009-05-16T13:45:00.000-07:00

Paternal Age May Also Affect ICSI Outcome in Oligozoospermic Patients
May 15, 2009
Maternal age has been identified as a key determining factor in the success rates of IVF/ICSI procedures; however, relatively few studies have investigated the effect of advanced paternal age on ICSI outcome. Now, a recent retrospective observational study, published in the journal, Fertility and Sterility, suggests the negative effect of increased paternal age of oligozoospermic patients on implantation rate after ICSI. The study reports a 5% decrease in the chances of pregnancy for such couples with each year of increase in paternal age.

Negative influence of paternal age on clinical intracytoplasmic sperm injection cycle outcomes in oligozoospermic patients.

2009-05-05T13:48:00.000-07:00

1: Fertil Steril. 2009 Apr 29. [Epub ahead of print]
Negative influence of paternal age on clinical intracytoplasmic sperm injection cycle outcomes in oligozoospermic patients.

Ferreira RC, Braga DP, Bonetti TC, Pasqualotto FF, Iaconelli A Jr, Borges E Jr.
Sapientiae Institute, Educational and Research Center in Assisted Reproduction, São Paulo, Brazil; Fertility, Assisted Fertilization Center, São Paulo, Brazil.

OBJECTIVE: To evaluate the effect of male age on clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles, according to sperm concentration. DESIGN: Retrospective, observational study. SETTING: Assisted reproduction center. PATIENT(S): The study included 1,024 couples undergoing ICSI cycles with fresh spermatozoa. INTERVENTION(S): The influence of paternal age on ICSI outcomes of oligozoospermic and normozoospermic patients was evaluated. MAIN OUTCOME MEASURE(S): Rates of high-quality embryos, pregnancy, implantation, and miscarriage were evaluated through linear logistic regression analyses. RESULT(S): When the sperm concentration was abnormal, paternal age influenced implantation (regression coefficient value = -0.7009) and pregnancy rates (odds ratio = 0.95, 95% confidence interval 0.91-0.99). However, in normozoospermic patients, no influence of paternal age was observed on implantation (regression coefficient value = 0.0566) or pregnancy rates (odds ratio = 1.00, 95% confidence interval 0.97-1.03). CONCLUSION(S): For couples in which the men are oligozoospermic, the implantation rate could be impaired by increased paternal age. In these couples, the chance of pregnancy decreased 5% for each year of paternal age. When men are normozoospermic, this effect is not observed

Men’s Biological Clocks. Will the Risks of Fathering a Baby After Age 35 Start A New Dating Trend?

2009-05-04T18:16:00.000-07:00

MAy 4

Men’s Biological Clocks. Will the Risks of Fathering a Baby After Age 35 Start A New Dating Trend?

Posted by admin in POW WOW SHOW Topic, Your Guide To Healthy Relationships Today’s 50 may be yesterday’s 30 in some aspects of men’s aging, but medical studies reveal this isn’t true for a 50 year old’s sperm. Men are learning about about the genetic risks of fathering a baby after age 35. Will their newly-found biological clocks start a new dating trend?

What is a biological clock?

It commonly refers to the declining fertility, increasing risk for fetal birth defects, and altered hormone levels experienced by women as they age. Abundant scientific evidence now suggests that men also have a biological clock.

What are some risks of fathering a child after age 40?

A team of UK and US researchers recently reported that children born to men over 40 had a six times higher risk of autism than those born to men under 30.

Other studies have linked older fathers to an increased risk of miscarriages, and to children with bipolar disorder and the rare birth disorders like dwarfism.

Researchers at Columbia University College of Physicians and Surgeons found that men older than 40 were more than twice as likely to have a child who develops schizophrenia as men in their 20’s.

Why is older fatherhood a new cause for concern?

The theory linking paternal age with an offspring’s health rests on spontaneous mutations in the genes of a man’s sperm cells as he ages. New studies refute the earlier theory that men could father children into their old age with no ill effects.

What is the ideal age for men to father children?

To minimize genetic abnormalities, the American Society for Reproductive Medicine has set an upper age limit of 40 years old for semen donors, while UK fertility clinics only accept sperm donations from men aged 39 and under.

Studies suggest that to minimize the risk of autism, the paternal age should be under 32.

Could a man’s biological clock start a new dating trend?

A young man’s biological clock may encourage him seek a serious relationship with a young woman who is ready and willing to have children before he reaches the age of 35 or 40. These young men will have fewer years to date cougars.

A young woman who desires children may be less likely to date a father figure, unless he agrees to use a sperm donor if they decide to have children after his 50th birthday. Or she may simply prefer to date men under age 35 to increase the odds of having healthy babies with a mate closer to her age.

If more men and women over 40 spend less time dating younger, will they find unexpected delights in dating each other? Let us know if you notice these new trends in your dating life.

Dedicated to your relationship happiness,

Hadley

Biological clock ticks for men as well

2009-04-24T17:28:00.000-07:00

Biological clock ticks for men as well
By Jenifer Goodwin (Contact) Union-Tribune Staff Writer
8:00 a.m. April 24, 2009
Ever since women began putting off childbearing to go to college and build careers, they've had to face a cold, hard truth. A growing body of research is showing that men have a biological clock, too. - JupiterimagesEver since women began putting off childbearing, they've had to face the harsh truth that there are only so many years they can have babies.
If a woman dares wait until age 35, she's declared “advanced maternal age” and told about the increased risk of having a baby with certain genetic conditions.
As it turns out, a growing body of research is showing that men have a biological clock, too.
The children of older fathers scored lower than the offspring of younger fathers on IQ tests and other cognitive measures at 8 months old, 4 years old and 7 years old, according to results of a study released in March.
Men who becomes fathers in their 40s or older are more than 1.5 times more likely to father children who are autistic, according to a 2006 study.
Other research has shown increased risk of schizophrenia and bipolar disorder in the children of older fathers, and that the risk of miscarriage rises with the father's age.
“Men are in denial,” said Dr. Harry Fisch, an expert on male infertility and author of the 2005 book “The Male Biological Clock.” “Men think as they age, they get better or more distinguished. As men get older, they get older.”
Scientists knew for years before the highly publicized autism and IQ studies that the children of older fathers were at higher risk of certain rare genetic conditions, such as dwarfism, Fisch said.
Yet outside of the science realm, few paid much attention.
Men were operating under the mistaken belief that since they generated new sperm every day, they could have children well into old age with no added risk.
What was missing from the equation was that even new sperm made by an older man is more prone to genetic defects. “As the body ages, there is no reason to think why these sperm cells wouldn't age too,” Fisch said.
So what should men do with the information?
Plenty of older dads father healthy, intelligent children. Still, men should consider the potential consequences of putting off childbearing, Fisch said.
The older both spouses are, the greater the chance they will have fertility problems, he said. “People need to know this information for family planning.”

Jenifer Goodwin: (760) 476-8210; (Contact)

For Whom The Clock Ticks Newsweek

2009-04-22T16:28:00.000-07:00

For Whom The Clock Ticks
A growing body of research supports the idea that there are biological disadvantages to late-in-life fatherhood. But will society's view of male fertility ever change?

By Daniel Heimpel | Newsweek Web Exclusive
Apr 22, 2009

In season two of Bravo's wildly popular television series "Millionaire Matchmaker," host Patti Stanger rants against older men who perpetually search for 20-somethings to date. What Stanger knows intuitively and what researchers are illustrating empirically, is that men 50 and older, no matter their financial stability, aren't always the greatest catch.

Even if they can theoretically father children till the day they die, a growing compendium of knowledge points to a male "biological clock" largely driven by the replication of sperm with damaged DNA. According to a number of recent studies, offspring of older men have increased chances of a wide range of problems from autism to psychiatric disorders such as schizophrenia. Unlike women, who are equipped with their life's supply of eggs at birth, men replicate sperm from their bar mitzvah to their funeral. It's like a Xerox copy of a Xerox copy millions of times over. The damage can be caused by glitches in the process of replicating DNA millions of times over, reduced efficiency of the DNA repair mechanism, or attributed to environmental factors like stress, smoking or heavy drinking.

But the bottom line is: as men age, the percentage of damaged sperm they carry in their testes tends to increase. "Men are making millions of sperm all the time, and the chance for a copy error is much higher," says Dr. Ethylin Jabs, director of the Center for Craniofacial Development and Disorders at Johns Hopkins, who has conducted extensive research on paternal age and mutations within sperm. Where older women may be concerned about the viability of their remaining eggs, the problem for men, says Jabs, is "quantity not quality."

Semen samples of men over 45 showed impairment to sperm in three categories: their motility (swimming capability), vitality and DNA integrity, according to Dr. Sergey Moskovtsev of Mount Sinai Hospital's Department of Pathology and Laboratory Medicine in New York. Moskovtsev's research shows that men older than 45 have twice as much damage to their sperm as men under 30. Researchers believe that an increase in the percentage of damaged sperm can have a number of consequences.

A report released in PLoS Medicine last month establishes a link between reduced intelligence and children who were fathered by older men. Using a sample of 33,000 children tested at the ages of 8 months, 4 years and 7 years, John McGrath of Australia's Queensland Centre for Mental Health Research and colleagues found that children of older fathers ranked consistently lower in cognitive ability tests than the offspring of younger fathers. For example, 7-year-old children born to 50-year-old dads performed two IQ points lower than peers born to 20-year-old fathers. This difference in IQ is of course subtle, and McGrath says that the results of his study shouldn't be cause for individual men to stop having children.

But he cautions that the mounting studies pointing to a male biological clock are worth considering on a macro level. "As a researcher, I am concerned that we have neglected the issue of paternal age," McGrath says. "Worryingly, the mutations associated with advanced paternal age can be passed on to the next generation. As the population delays parenthood, these mutations could, theoretically, accumulate. Other researchers—not me—have called this process a 'mutational time-bomb'."

Normally, individual sperm with impaired DNA would perform a kind of cell hara-kiri, killing themselves in a process called apoptosis. But research out of the University of Washington has shown that the sperm of men over 35 are less likely to go through that process. Coupled with higher amounts of semen bearing damaged DNA, the likelihood of a child born with an abnormality increases. In a study of hundreds of thousands of psychiatric records conducted by the Israeli draft board in the 1980s, Dr. Abraham Reichenberg of the Mount Sinai School of Medicine, New York, and the Institute of Psychiatry, King's College London, and colleagues showed a six-time increase in autism spectrum disorders for children of fathers over 40, compared with those 29 years and younger.

Since that report came out in 2006, Reichenberg says that efforts to link autism and other psychological disorders to older dads have been bolstered by similar results among sample groups from different countries. Another psychological disorder that has been linked to damaged sperm is schizophrenia. Men over 50 are 3 times as likely to have offspring with the debilitating mental disorder than fathers under the age of 25....
...

The Coming of the Daddy Wars

2009-04-06T11:17:00.000-07:00

The Coming of the Daddy Wars
My favorite item from this week's Sunday papers was Lisa Belkin's Times Magazine piece on men's biological clocks. Belkin looks at new research showing that as men age beyond about 30, their chance of fathering a child with an autism-spectrum disorder or schizophrenia increases. Simultaneously, men's overall fertility decreases after age 35. Put simply, in the words of NYU psychiatry researcher Dr. Dolores Malaspina: “It turns out the optimal age for being a mother is the same as the optimal age for being a father.”

If these preliminary findings are upheld over time, their cultural significance -- especially for college-educated, type A, planner types -- could be huge. It isn't surprising that it has taken science this long to seriously question men's biological role in producing healthy children; we are all conditioned to see women as the folks primarily responsible for children, from conception through pregnancy, childbirth, and child-rearing. Young women know they are facing menopause down the road, and have often been warned by mothers and other older women about the difficulties of conception. As a consequence, it isn't uncommon to talk to women in their twenties who are aware of the latest trends on prenatal testing or fertility, but whose male partners have never bothered to inform themselves on such issues, even though they fully intend on having children "someday." As Belkin writes:

The push and pull between timetables and dreams, between our bodies and our babies, is at the core of many women’s worldview, which also means it is at the core of relationships between the sexes. This tension feeds the stereotype of woman as eager to settle down and men as reluctant, and it’s the crux of why we see women as “old” and men as “distinguished.”

Imagine a world in which the stereotype of women rushing men to the alter, biological clocks on overdrive, simply disappeared, as men took full 50 percent ownership over the reproductive process. Or in which wealthy 50- year old divorced men ceased to be such catches for 30-year old women, because of weakened sperm. I wouldn't want to return to a society in which both men and women are pressured into settling down and having babies at an unduly young age. But I do like the idea of rejiggering our notions about the intersection of gender and aging. It isn't just women who have a lot to fit into their lives in terms of career, romance, and parenthood. Science is beginning to tell us that men are facing the same pressures.

cross-posted at TAPPED

Lisa Belkin Audio on the Male Genetic Biological Clock

2009-04-01T16:50:00.000-07:00

Lisa Belkin

Your Old Man

2009-04-01T08:36:00.000-07:00

The Way We Live Now
Your Old Man
by LISA BELKIN
Published: April 1, 2009
Read between the lines of a recent study out of Australia and you can see hints of a coming shift in the gender conversation. Researchers at the University of Queensland found that children born to older fathers have, on average, lower scores on tests of intelligence than those born to younger dads. Data they analyzed from more than 33,000 American children showed that the older the man when a child is conceived, the lower a child’s score is likely to be on tests of concentration, memory, reasoning and reading skills, at least through age 7.

It was a small difference — just a few I.Q. points separated a child born to a 20-year-old and a child born to a 50-year-old. But it adds weight to a new consensus-in-the-making: there is no fountain of youth for sperm, no “get out of aging free” card. The little swimmers, scientists are finding, one study at a time, get older and less dependable along with every other cell in the male body.

And men don’t have to be all that old to be “too old.” French researchers reported last year that the chance of a couple’s conceiving begins to fall when the man is older than 35 and falls sharply if he is older than 40. British and Swedish researchers, in turn, have calculated that the risk of schizophrenia begins to rise for those whose fathers were over 30 when their babies were born. And another Swedish study has found that the risk of bipolar disorder in children begins to increase when fathers are older than 29 and is highest if they are older than 55. British and American researchers found that babies born to men over the age of 40 have significantly greater risk of autism than do those born to men under 30. (The age of the mother, in most of these studies, showed little or no correlation.)

Lay this latest I.Q. news atop the pile, and you find yourself reaching the same conclusion as Dr. Dolores Malaspina, a professor of psychiatry at New York University Medical Center, who has done some of the schizophrenia research: “It turns out the optimal age for being a mother is the same as the optimal age for being a father.”...

Paternal Age Past 44 is Particularly Dangerous For Female Offspring

2009-03-26T14:43:00.000-07:00

Science 4 July 1997:
Vol. 277. no. 5322, pp. 17 - 21
DOI: 10.1126/science.277.5322.17b
Prev | Table of Contents | Next

Letters
When Fatherhood Should Stop?
Constance Holden's piece "The perils of late-age procreation" (Random Samples, 6 June, p. 1503), about our recent finding that daughters of older fathers live shorter lives, has stimulated us to return to this problem and to reanalyze the data for different ranges of paternal ages at reproduction.

Our previous analysis, based on a multiple linear regression model, has demonstrated that in the range of paternal ages of 35 to 55 years, the mean loss in daughters' life span is 0.16 ± 0.06 years per each additional year of paternal age (sample size, n = 2159; Student's test, t = 2.43; P = 0.02). It turned out, however, that for the subgroup of younger fathers (35 to 45 years) the mean loss of daughters' life span is small (0.02 ± 0.12 years per each additional year of paternal age) and statistically insignificant (n = 1651; t = 0.16; P = 0.87), while for older fathers (45 to 55 years) this loss is particularly high (0.48 ± 0.21 years per each additional year of paternal age) and significant (n = 598; t = 2.34; P = 0.02).

These results are consistent with the general conclusion of James Crow on the nonlinear accelerating increase of mutation rates with paternal age (1) and could decrease the anxiety among the majority of fathers who reproduce before 45 years.

Leonid A. Gavrilov
A. N. Belozersky Institute,
Moscow State University,
Moscow 119899, Russia,
E-mail: leonid@gavrilov.genebee.msu.su
Natalia S. Gavrilova
Institute for Systems Analysis,
Russian Academy of Sciences,
Moscow 117312, Russia

REFERENCES
J. Crow, J. Environ. Mol. Mutagenesis 21, 122 (1993); J. Exp. Clin. Immunogenet. 12, 121 (1995).

That said, the perfect compromise would be to try to complete your family before both partners reach the age of 35.

2009-03-23T08:31:00.000-07:00

March 23, 2009

Do older men have less intelligent children?
New research suggests the older your father is when you are born, the lower your IQ, so how late is too late?Dr Mark Porter
New research suggesting that the age of your father influences your IQ - the older he was when you were born, the worse you are likely to fare when tested - is the latest addition to growing evidence that it is not just maternal age that matters when it comes to starting a family. The longer a couple delay, the poorer the outcome for all concerned. But how late is too late?

Back in the early Nineties, about a quarter of children were fathered by men over the age of 35; today it is closer to half, at least for married couples, who still account for the majority (just) of children born in the UK, with the average first-time mother and father now being aged 30 and 32 respectively.

There are lots of reasons why couples are waiting longer, but career and financial pressures feature highly - a trend likely to have been exacerbated by the current economic climate. But while there are obvious benefits to having more mature parents, these have to be offset against the medical implications - and there are many.

For women the main hurdle is declining fertility. While it is technically possible to conceive naturally right up until your last period, female fertility wanes dramatically after the age of 35, and by the time most women reach their late forties they are technically infertile.

Related Links
Biological clock strikes for men too - at 35
Children of older fathers at risk of autism
The problems of being an older mum
A healthy couple in their twenties have a 25 to 30 per cent chance of conceiving each month. This falls to between 10 and 25 per cent when the woman is in her mid-thirties, and has plummeted to less than 5 per cent by the time she is in her early forties. What's more, nearly half of those who do manage to conceive at this age will miscarry within the first three months.

Much of this decline is due to genetic damage inflicted on a woman's eggs by a combination of environmental factors, such as toxins in the diet and natural background radiation. Women are born with a finite supply of eggs, and a 40-year-old egg is harder to fertilise and nurture than a 20-year-old one.

Tradition has it that advancing years do not have such a detrimental effect on men, who, unlike women, manufacture fresh sperm throughout their lives. But they are not actually manufactured from scratch, and the basic template that matures into a fully grown sperm is, like a woman's eggs, as old as the man - so male fertility wanes, too.

The fall starts to become significant when a man reaches his early forties, meaning that it takes longer to conceive, irrespective of the age of the would-be mother. When they are successful, the woman is also more likely to miscarry if her partner is over 40.

The effect of age on the risk of congenital abnormalities appears to be shared between the parents, too. The best known example in women is the link with Down's syndrome. If a woman is in her late twenties, the risk of her child having Down's is about 1 in 1,000. By the age of 35 it increases to 1 in 270, and by 40 it is closer to 1 in 100.

But less marked genetic mutations are thought to be a problem in older fathers as well, and the implications can be just as serious. Children born to men aged over 35 are more likely to have a cleft lip or palate, congenital heart defects, and to develop some forms of cancer, including leukaemia (a 50 per cent increase) and brain tumours (25 per cent increase).

There is also evidence of a link between paternal age and the chances of a child going on to develop autism, dyslexia or schizophrenia - the link with the last of these being particularly strong. Experts estimate that the trend towards delayed fatherhood could account for as many as 10 per cent of new cases of schizophrenia diagnosed each year.

But let's not be overly pessimistic. Torture statistics enough and they will tell you anything. In fact, the vast majority of older mums and dads will have trouble-free pregnancies and perfectly healthy children. Leaving it later may increase the risk of a range of complications - but a 50 per cent increase on a tiny risk is still only a tiny risk. And the medical implications need to be offset against the social and emotional benefits of bringing up a child in a more stable environment.

That said, the perfect compromise would be to try to complete your family before both partners reach the age of 35. It's a feat that my parents managed with ease - they were just 20 and 21 when they had me, which, statistically, means that I will probably live for ever.

The offspring of older fathers show subtle impairments on tests of neurocognitive ability during infancy and childhood

2009-03-19T09:25:00.000-07:00

Offspring of Older Fathers May Have Subtle Neurocognitive Impairments

Laurie Barclay, MD

March 18, 2009 — The offspring of older fathers show subtle impairments on tests of neurocognitive ability during infancy and childhood, according to the results of a study reported in the March 10 issue of PLoS Medicine.

"Advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and schizophrenia, as well as with dyslexia and reduced intelligence," write Sukanta Saha, from Queensland Centre for Mental Health Research, The Park Centre for Mental Health, in Richlands, Australia, and colleagues. "The aim of this study was to examine the relationship between paternal age and performance on neurocognitive measures during infancy and childhood."

The study sample consisted of 33,437 singleton children enrolled in the US Collaborative Perinatal Project. At ages 8 months, 4 years, and 7 years, these children underwent testing with the Bayley scales, Stanford Binet Intelligence Scale, Graham-Ernhart Block Sort Test, Wechsler Intelligence Scale for Children (WISC), and Wide Range Achievement Test. The primary analyses evaluated the association between neurocognitive measures and paternal or maternal age, after adjustment for potential confounding factors.

On all the neurocognitive measures, except for the Bayley Motor score, advanced paternal age correlated significantly with poorer scores. At all 3 ages tested, the findings were broadly consistent in direction and effect size. In contrast, there was an association between advanced maternal age and generally better scores on these same tests.

"The offspring of older fathers show subtle impairments on tests of neurocognitive ability during infancy and childhood," the study authors write. "In light of secular trends related to delayed fatherhood, the clinical implications and the mechanisms underlying these findings warrant closer scrutiny."

Limitations of this study include nonrandom sample attrition and missing data that could affect the generalizability of the results; cohort members born in the United States during the 1960s, limiting generalizability to more contemporary cohorts; and neurocognitive outcomes only determined until age 7 years.

"While most of the neurocognitive differences were small at the individual level, these could have important implications from a public health perspective," the study authors conclude.

The study authors have disclosed no relevant financial relationships.

PLoS Med. 2009;6:e40.

“It turns out the optimal age for being a mother is the same as the optimal age for being a father. The fact that men can stay fertile longer is a dif

2009-03-09T12:36:00.000-07:00

Vital Signs
Lower I.Q. Scores Among Children of Older Fathers

By RONI CARYN RABIN
Published: March 9, 2009
Children of older fathers scored lower than offspring of younger dads on I.Q. tests and a range of other cognitive measures at eight months, four years and seven years of age, according to a new study that adds to a growing body of evidence suggesting there are risks to postponing fatherhood.
The study is the first to show that children of older fathers don’t perform as well on cognitive tests at very young ages. Although the differences in scores were slight and usually just off by a few points on average, researchers called the findings “unexpectedly startling."
“The older the dads were, the slightly worse the children were doing,” said Dr. John J. McGrath, the paper’s senior author and a professor of psychiatry at the Queensland Brain Institute in Brisbane, Australia. “The findings fit in a straight line, suggesting there may be some steady beat of mutations happening in the dad’s sperm.”
Earlier studies have found a higher incidence of schizophrenia and autism among offspring of men who were in their mid- to late 40s or older when they had children. A study published in 2005 reported that 16- and 17-year-olds with older fathers scored lower on non-verbal I.Q. tests, as did the offspring of teenage fathers.
The new study, published on Monday in the journal PLoS Medicine, re-analyzed data from the Collaborative Perinatal Project, which gathered information from pregnant women seen at 12 university clinics in the United States between 1959 and 1965.
The researchers analyzed the scores of 33,437 babies resulting from these pregnancies. They had been tested at regular intervals on a variety of measurements of cognitive skills, including thinking and reasoning, concentration, memory, understanding, speaking and reading, as well as on motor skills.
Regardless of their mothers’ ages, children whose fathers were 50 years old had lower scores on all of the measures, except for those assessing physical coordination, than those whose fathers were 20, the researchers found. And the older the fathers, the more likely the children were to have lower scores, they found.
By contrast, children with older mothers generally performed higher on the cognitive measures, a finding that is in line with most other studies, suggesting these children may benefit from more nurturing home environments associated with the generally higher income and education levels of older mothers, researchers said.
“I think there has been a bit of a cultural bias against even looking at this issue, but finally people are willing to entertain this,” said Dr. Dolores Malaspina, professor of psychiatry at New York University Medical Center, who authored the studies finding an increased risk for schizophrenia among children of older fathers, as well as studies that found lower non-verbal I.Q. scores among teens with older dads.
“It turns out the optimal age for being a mother is the same as the optimal age for being a father. The fact that men can stay fertile longer is a different issue."

2009-03-09T10:49:00.000-07:00

Children of older fathers perform less well in intelligence tests during infancy
Press release from PLoS Medicine
Children of older fathers perform less well in a range of cognitive tests during infancy and early childhood, according to a study published this week in the open-access journal PLoS Medicine. In contrast, the study finds that children with older mothers gain higher scores in the same tests – designed to measure the ability to think and reason, including concentration, learning, memory, speaking and reading skills.
The age at which men and women are having children is increasing in the developed world, but whilst the "biological clock" – the effect of increasing maternal age on reduced fertility – is widely-discussed, the consequences of increased paternal age are not as well known. Recent evidence demonstrates a link between older fathers and specific health problems in their children, including birth deformities and cancer, as well as neuropsychiatric conditions such as autism and schizophrenia. This new study by John McGrath, of the Queensland Brain Institute, University of Queensland in Australia, and colleagues, investigates the link between a father's age and their child's general cognitive ability, by reanalyzing an existing dataset of 33,437 children born between 1959 and 1965 in the United States. This data formed part of the US Collaborative Perinatal Project (CPP), which tested each child in the dataset at 8 months, 4 years and 7 years of age with a number of widely-used intelligence scales – including assessments of sensory discrimination and hand-eye coordination, conceptual and physical coordination, and at 7 years reading, spelling and arithmetic ability.
Crucially in their reanalysis of this dataset, McGrath and colleagues adjusted their study to take into account socio-economic factors. They used two models: one that focused on physical factors including the parents' age, and a second that indexed social factors such as maternal and paternal education and family income. They found that the older the father, the more likely the child was to have lower scores on the various tests used by the CPP – with the exception of one measure of physical coordination. The researchers also grouped the children by their mother's age and found that in contrast, the older the mother the higher the scores of the child in the cognitive tests.
Previous researchers have suggested that the children of older mothers may perform better because they experience a more nurturing home environment; if this is the case, this study suggests that children of older fathers do not necessarily experience the same benefit. The researchers advance several hypotheses as possibilities to explain the association between advanced paternal age and children's cognitive ability, including genetic and social arguments. Unlike a woman's eggs – which are formed when she herself is in the womb – a man's sperm accumulates over his lifetime, which previous studies have suggested can mean increased incidence of mutations in the sperm at an older age. However, as emphasized in an expert commentary on the findings by Mary Cannon (Royal College of Surgeons in Ireland) – who was uninvolved with the study – genetic and social factors can operate in conjunction. "New explanatory models are needed that can encompass socio-cultural and interpersonal factors as well as biological variables", she argues. Given the trend towards older maternal and paternal ages in the developing world, policy-makers may want to consider promoting an awareness of the risks to children that this study associates with delayed fatherhood.