To the Editor:
Women experience a notable decrease in oocyte production in their late thirties; however, the effect of age on spermatogenesis is less well described. Indeed, while there are no known limits to the age at which men can father children, the effects of advanced paternal age are incompletely understood. Reproductive concerns related to advanced paternal age are less well defined (1) with a recent whole-genome sequencing study suggesting an increased risk for rare de novo mutations for older fathers (2). Whether the risk for major birth defects from de novo mutations is greater than the risk from assisted reproduction remains unknown (3).
Our retrospective study showed that sperm retrieval rates in men undergoing microdissection testicular sperm extraction (TESE) was not negatively affected by age (4). Despite the limited number of men in this study as pointed out by Kim (5), it remains the largest study to evaluate the effect of male age on sperm retrieval in nonobstructive azoospermia (NOA). The sperm retrieval rates were similar in men <30 years of age, 30 to 50 years of age, and older than 50 years of age (~50 – 60%). We identified that most men over 50 years of age who had successful sperm retrieval had hypospermatogenesis histology on previous diagnostic biopsy. It is possible that some older men with NOA may have secondary azoospermia with sperm detectable in the ejaculate at an earlier age. Therefore, it is likely that older men may be more likely to have acquired NOA (i.e., secondary infertility), whereas younger men may be more likely to have congenital NOA.
The clinical message is important; increased male age should not be a contraindication for microdissection TESE. The risk of de novo mutations in elderly fathers is increased but remains numerically very small. Similar mutations are also present in sperm from younger individuals and should not deter men from undergoing sperm retrieval.
Ranjith Ramasamy, M.D. and Peter N. Schlegel, M.D.
Department of Urology, New York – Presbyterian Hospital, Weill Cornell Medical College, New York, New York
1. Thacker PD. Biological clock ticks for men, too: genetic defects linked to sperm of older fathers. JAMA : the journal of the American Medical Association 2004;291:1683-5.
2. Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P, Magnusson G et al. Rate of de novo mutations and the importance of father’s age to disease risk. Nature 2012;488:471-5.
3. Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. The New England journal of medicine 2002;346:725-30.
4. Ramasamy R, Trivedi NN, Reifsnyder JE, Palermo GD, Rosenwaks Z, Schlegel PN. Age does not adversely affect sperm retrieval in men undergoing microdissection testicular sperm extraction. Fertil Steril 201x (in press).
5. Kim E. Using contemporary microdissection testicular sperm extraction techniques, older men with nonobstructive azoospermia should not be deterred from becoming fathers. Fertil Steril 201x (in press).
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.12.018