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 »

Presence of M540 bodies in human semen: techniques to detect them require attention

20 06 2013

To the Editor:

We read with interest the paper by Gomez-Lopez et al., published in Fertility and Sterility (1), in which the authors investigated the presence of merocyanine 540 bodies (M540 bodies) and their impact on the detection of sperm apoptotic markers, including sperm DNA fragmentation.
In this paper the authors report that the incidence of M540 bodies in the semen of infertile men is very low (about 1%) and that their occurrence does not affect the determination of sperm DNA Fragmentation (sDF) by TUNEL coupled to flow cytometry.

These results contrast with previous data by our group that first described M540 bodies (2) and later on demonstrated that they are apoptotic bodies of testicular origin (3). Indeed, we found that M540 bodies can be present in high amount in semen of sub/infertile men (2, 3) and that they heavily flaw the determination of TUNEL positive sperm by flow cytometry (4). We believe that the cause of such discrepancies is the technique that the authors used to reveal M540 bodies in TUNEL processed samples. They first stained by merocyanine 540 and then washed and processed samples by TUNEL assay. By this procedure, merocyanine labeling is washed away from the bodies, since M540 does not bind in a stable (covalent) manner to bodies. As a consequence, they failed to detect M540+ elements, not because of their absence but because of the loss of merocyanine staining. 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


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 »

Acridine orange binding to RNA interferes DFI calculation in SCSA

18 03 2010

To the Editor:

In the era of assisted reproductive technique (ART), it is very important to assess DNA fragmentation index (DFI) and establish threshold levels beyond which there is poor ART outcome, pre- or post-implantation failure or recurrent spontaneous abortions. The study by Smit et al. (1) is very informative and of immense clinical significance. Read the rest of this entry »