Study Says Male Fertility Falls After 35

Human fertility starts to decline earlier than previously believed, new research suggests, providing the most precise insight yet into when biological clocks start ticking loudly ? at age 27 for women and 35 for men.

Until now, it was thought that women's fertility starts to drop significantly in the early 30s, with a big plunge after 35. But the new study indicates that, on average, female fertility begins its meaningful slide at age 27.

And while the decline in human fertility tied to aging had traditionally been attributed to the female factor, the study, published Tuesday in the journal Human Reproduction, showed that men's fertility starts dwindling after 35.

and

A recent report from the Journal of the American Medical Association looks at past research to examine why aging men experience declining fertility.

It appears that men older than 35 are twice as likely to be infertile as men younger than 25.


As men age, both the number and quality of their sperm decline — so older men become less likely to father a child and more likely to father a child with schizophrenia, Down syndrome, or other problems.

A recent study suggests that autism, an increasing problem with no known cause, may also be linked to paternal age because men 40 years or older are almost six times more likely to have a child with an autism disorder than men younger than 30.

Miscarriages also are more common as dad gets older.


It's not unusual for a woman to get her hormones, ovulatory function and fallopian tubes tested months before her husband has even had a basic semen analysis.

Given that 20 percent of couples are infertile because of abnormal or absent sperm and that 27 percent of infertile couples have a combination of male and female factors, it makes sense to evaluate a man's equipment, so to speak, sooner rather than later.

Prevent Infertility and Paternal Age Related Autism and Schizophrenia etc. in Offspring

NEW DELHI: Call it innovative insurance. More and more young men in Delhi who are busy chasing fast-track careers, but are not yet ready to start a family, are choosing to freeze their sperms — to be used when they are ready.

More than 50% of the long-term frozen samples in Delhi's sole commercial sperm banking organisation, Cryogenie, are of healthy young men who are not ready for procreation and do not want to rely on donor sperms either.

Says Dr Iqbal Mehdi, head of cryobanking services at Cryogenie, "The long-term banking facility was initially started with malignancy patients in mind. People who undergo chemo or radiotherapy often suffer from low sperm counts so they store semen before the treatment starts. It was much later that we realised that freezing of sperms gave healthy individuals the option of starting a family when they want to, no matter what their age."


and also this article from Mumbai





“Many who are working in the US or Dubai for long periods of time are freezing their sperms so that their wives can be impregnated here at home,” says Dr Gautam Allahbadi, scientific director, Rotunda.

The growing awareness has also seen a rise in the number of cancer patients opting to save their sperm. Cancer treatment is known to reduce sperm count drastically. “Many oncologists are sending such patients to us to help them freeze their sperm and assure them a family,” says Malpani.

Add to this the changing attitude among women. With an increasing number putting marriage and children on a standby mode the average conceiving age of women is now early-30s, up from mid-20s a couple of years back.

This trend, however, has left women in urban India with an average of just 5-6 ‘good years’ to get pregnant. “Women are unwilling to wait. They would rather use the intrauterine insemination technique that involves injecting sperm in the uterus,” says Anjali Malpani.

Anirudha and Anjali Malpani have been running their infertility clinic for the last 15 years, and have noticed a sea-change in attitude towards assisted pregnancy and sperm banking. But there is still a long way to go.

LIONEL PENROSE, THE PATERNAL AGE EFFECT ON GENETIC HEALTH OF OFFSPRING

"Male-mediated anomalies of pregnancy outcomes are currently well known in both humans and animals."

In 1955 Lionel Penrose wrote "Parental Age and Mutations" which was published in Lancet,ii,312-313.

Will the scientists assay the spermatagonia of the fathers of the children with copy number variations?




The effects of parental age upon the occurrence of abnormalities in offspring never ceased to intrigue Penrose. It was Weinberg who first noted the phenomenon in 1912, and there were others who suggested that it was the father's not the mother's age that played a significant role in the occurrence of infants with, for example, achondroplasia. However, it was Penrose who, again using the partial correlation method employed by Wright, provided the data to prove the hypothesis. His results were a mirror image of those found in families with Down syndrome. In other words, if the maternal age was kept constant, a significantly positive correlation (+0.273) was found between the paternal age and the incidence of achondroplasia, whereas the maternal age effect disappeared completely if the paternal age was regressed out. Furthermore, Penrose noted that the statistical significance of the paternal age effect increased considerably when nonsurviving infants with achondroplasia were excluded from the calculations (PENROSE 1955 , PENROSE 1957 ). It is possible, although no proof exists from the old data, that the infants with "achondroplasia" who died neonatally or shortly thereafter had different diagnoses of more severe, perhaps lethal, short-limbed dwarfing disorders. The survivors represented true instances of new (paternally derived) mutations of the gene.

Together with Haldane, Penrose also studied the paternal age effect upon mutations of genes located on the X chromosome. Haldane had accurately postulated an increased occurrence of hemophilia in the grandsons of older maternal grandfathers, implying another example of a higher mutation rate in males. Four decades later, it was Crow who finally completed the story by summarizing data showing that, at the molecular level, the rate for base substitutions (the cause of the achondroplasia mutation) is indeed higher in males than in females; he also showed that the phenomenon can be attributed partially to the larger number of cell divisions, estimated to be about 430 at age 30 in the male, as contrasted with the female germ line, in whom there are only about 24 divisions from zygote to egg (CROW 1997A , CROW 1997B ). More specifically, the mutation in achondroplasia, in the fibroblast growth factor receptor 3 gene (FGFR3) on 4p16.3, consists of a single substitution of the normal glycine residue by an arginine residue at codon 380. This same Gly380Arg mutation is, surprisingly, present in almost all of the hundreds of patients with achondroplasia who have had mutational analysis to date, and it is of paternal origin in those in which the parental origin could be determined (HORTON 1997 ). Thus, we owe our understanding of the paternal age factor, its causes as well as underlying mechanisms, to the imaginatively creative minds of three generations of genetics heroes.

Alzheimer's and Paternal Age & Myelin

George Bartzokis,M.D.


Visiting Professor

Laboratory of Neuro Imaging,
Department of Neurology, UCLA School of Medicine
635 Charles Young Drive South, Suite 225
Los Angeles, CA 90095-7332



Education

1975-1979, BA Harvard University, Cambridge, MA
1979-1983, MD Yale Medical School, New Haven, CT
1983-1984, Internship, UCLA/WLA VA, Los Angeles, CA
1984-1987, Psychiatry Residency, UCLA NPI, Los Angeles, CA
1987-1990, Schizophrenia Research Fellow, UCLA Dept of Psychology, Los Angeles, CA


Research

Development of brain imaging biomarkers for use in diagnosis of neuropsychiatric disorders and medication development
Assessing brain maturation and degeneration trajectories over the life-span in normal populations and how neuropsychiatric disorders interact with these processes


Projects

Myelin breakdown in aging and Alzheimer's disease
In vivo quantification of age-related increases in brain iron levels
Evaluation of brain maturational trajectories in normal adults and patientss with neuropsychiatrc diseases


Skills

Quantification of brain iron levels
Quantification of limbic structures volumes
Quantification of brain myelination
Quantification of myelin integrity
Clinical trials
Administration of multidisciplinary teams


Honors

U.S. Patent, Method for Quantitatively Measuring Stored Iron in Tissue Using MRI










This quote is not from a published paper.
I had asked Dr. Bartzokis why risk of non-familial autism, schizophrenia, MS, and Alzheimer's risk increases with the age of the father at a person's birth.



"The issue is that the older man will have sperm that has undergone more divisions and therefore had more chances to have mutations.
The COMPLEXITY of the myelination process makes it more vulnerable to mutations. I am not talking of one specific mutation. Many things could MANIFEST in the myelination or myelin breakdown process because it is so vulnerable - something going slightly wrong will impact it while it will not impact bone growth or the heart. A good example is ApoE4 - whatever else it may affect, it manifests in the reduced capacity of myelin repair and earlier onset of AD."

Increasing Paternal Age is a Risk Factor For Alzheimer's Disease

Neurogenetics. 1998 Aug;1(4):277-80. Links
Paternal age is a risk factor for Alzheimer disease in the absence of a major gene.Bertram L, Busch R, Spiegl M, Lautenschlager NT, Muller U, Kurz A.
Department of Psychiatry, Technical University Munich, Germany.

We compared the parental age at birth of patients with Alzheimer disease (AD) with that of cognitively healthy control subjects. Within 206 carefully diagnosed AD patients, two groups were distinguished according to the likelihood of carrying a major gene for AD (MGAD). This likelihood was calculated by applying a Bayesian approach which incorporates data on aggregation of the disease, age at onset, and "censoring" ages within the family. All AD patients were ranked by MGAD probability. According to the sample's quartiles, two subgroups were defined representing the 52 individuals with the lowest and the 52 with the highest MGAD probability. Age at onset of dementia, education, and apolipoprotein E epsilon4 allele frequencies were not statistically different between the two groups. Fathers of patients with a low MGAD probability were significantly older (35.7+/-8.1 years) than fathers of both other groups (high MGAD probability 31.3+/-6.9 years, P=0.004; controls 32.6+/-6.8 years, P=0.04, n=50). The differences for mothers were less pronounced and not statistically significant. These findings suggest that increased paternal age is a risk factor for AD in the absence of a major gene, whereas increased maternal age and AD are associated only weakly and independently of genetic disposition.

PMID: 10732803 [PubMed - indexed for MEDLINE]