Male infertility biomarkers and genomic aberrations in azoospermia

17 02 2014

To the Editor:

Estimates indicate that 15-30% (or more) of male infertility is due to whole-organism genetic abnormalities with large numbers of genes already discovered to play important roles (1, 2). Numerous methods have yielded new genetic discoveries with the karyotype, fluorescent in situ hybridization, comparative genomic hybridization and microarrays all contributing (1). All identified genetic aberrations are further complicated by epigenetic modifications (i.e., methylation and protamination), as well as individual differences and environmental influences that make diagnosis and treatment frustrating (1). Unfortunately, in many men, the result of multiple investigations often yields inconclusive, or slightly abnormal results, with a subsequent diagnosis of idiopathic infertility. Read the rest of this entry »

Advertisements




Microdissection testicular sperm extraction in older men

10 12 2013

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. Read the rest of this entry »





Reply to editorial regarding Increased risk of cancer among azoospermic men

13 06 2013

To the Editor:

We thank the distinguished author for bringing attention to our work.

As Dr. Schlegel points out, a natural conclusion to draw from the manuscript is that a male factor evaluation is of critical importance for a man’s reproductive and overall health (1). Indeed, it is estimated that 20% of infertile couples do not receive a male evaluation in the U.S.(2) As is noted, the current estimates may be an underestimate of a man’s lifetime risk. The current analysis followed men for a relatively short period of time (up to 15 years) compared with a man’s complete lifespan (76.3 years) (3, 4). Thus, it is possible that his lifetime risk of cancer would continue to rise as he ages.

Dr. Schlegel does point out some limitations related to the granularity of information on each man. As is noted, infertile men are generally of higher socioeconomic status compared with the general population (5). However, access to care should be independent of semen parameters. Thus it is unlikely that the elevated cancer risk seen in azoospermic men could be entirely explained by socioeconomic factors. We look forward to seeing other groups substantiate our findings.

Michael Louis Eisenberg, M.D. , Stanford University School of Medicine, Stanford, California
Paul Betts, M.S., Cancer Epidemiology and Surveillance Branch, Texas Cancer
Registry, Texas Department of State Health Services, Austin, Texas
Danielle Herder, M.D., Baylor College of Medicine, Houston, Texas
Dolores Lamb, Ph.D., Baylor College of Medicine, Houston, Texas
Larry Lipshultz, M.D., Baylor College of Medicine, Houston, Texas

References

1. Schlegel PN. The relevance of increased cancer risk in infertile men. Fertil Steril 2013.

2. Eisenberg ML, Lathi RB, Baker VL, Westphal LM, Milki AA, Nangia AK. Frequency of the male infertility evaluation: data from the national survey of family growth. J Urol 2013;189:1030-4.

3. Murphy SL, Xu J, Kochanek KD. Deaths: final data for 2010. Natl Vital Stat Rep 2013;61:1-167.

4. Eisenberg ML, Betts P, Herder D, Lamb DJ, Lipshultz LI. Increased risk of cancer among azoospermic men. Fertil Steril 2013.

5. Hotaling JM, Davenport MT, Eisenberg ML, VanDenEeden SK, Walsh TJ. Men who seek infertility care may not represent the general U.S. population: data from the National Survey of Family Growth. Urology 2012;79:123-7.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.06.025





Genetic screening in the ASRM’s new guidelines on diagnostic evaluation of the infertile male

18 12 2012

To the Editor:

I read with interest the new ASRM Practice Committee opinion report on diagnostic evaluation of the infertile male (1). Considering the importance of these guidelines for clinical practice, I should draw attention to inaccuracies and outdated information in the section related to genetic screening.

In the section on Y-chromosome microdeletions (YMD), the report states:  “Microdeletions of clinically relevant regions of the Y chromosome have been found in 7% of infertile men with severely impaired spermatogenesis compared with 2% of normal men. However, the percentage of men with Y-chromosome microdeletions increases to 16% in men with azoospermia or severe oligospermia.” This statement referring to Y-chromosome microdeletions in normal men is new in relation to previous ASRM opinions on male infertility and azoospemic males (2). Another section states that “… some Y-chromosome microdeletions are rarely found in fertile or subfertile males who have fathered children.”

The section regarding the normal male references an article in The New England Journal of Medicine (4) that found “Y-chromosome microdeletions” in 4 of 200 (2%) “normal men” (without screening sperm quality in them), but only in 2 Y-chromosome markers; 2 had deletions in  sY207, and 2 had deletions in sY272. The section referring to males with YMD who fathered children references the same article (3) and another (4), the “AZFd” article, which only reported the absence of single markers in 4 of 320 controls in sY269 and in 2 other individuals in sY207 and sY272. The existence of AZFd region in Y chromosome was not confirmed. In addition, these supposed “partial deletions” are not supported by the known mechanism of production of YMD (5) and the practice guidelines for YMD testing (6). Read the rest of this entry »