Reply of the Authors (2006)

We appreciate the comments by Michiel J. Noordam, M.Sc., Fulco van der Veen, M.D. Ph.D., and Sjoerd Repping, Ph.D., regarding our manuscript (1Dewan S. Puscheck E.E. Coulam C.B. Wilcox A.J. Jeyendran R.S. Y-chromosome microdeletions and recurrent pregnancy loss.Fertil Steril. 2006; 85: 441-445Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar). The article that we published is a preliminary study verifying the association of genetic markers that have been reported by previous investigators in severe oligo/azoospermic men, among men whose spouses have been diagnosed with recurrent pregnancy loss (RPL). Thus, the data presented is qualitative (presence or absence) of the genetic entity that has been published. Second, AZFd has been studied (2Xio X.S. Liu X.Y. Wang Y.Q. Zhou Y. Ouyang L. Zhang X. et al.Using multiplex PCR to analyze the breakpoint of a severe Y-chromosome deletion.Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2005; 22: 560-562PubMed Google Scholar, 3Kent-First M. Muallem A. Shultz J. Pryor J. Roberts K. Nolten W. et al.Defining regions of the Y chromosome responsible for male infertility and identification of a fourth AZF region (AZFd) by Y-chromosome microdeletion detection.Mol Reprod Dev. 1999; 53: 27-41Crossref PubMed Scopus (237) Google Scholar, 4Yao G. Chen G. Pan T. Study of microdeletions in the Y Chromosome of infertile men with idiopathic oligo- or azoospermia.J Assist Reprod Genet. 2001; 18: 612-616Crossref PubMed Scopus (19) Google Scholar) and recognized by commercial sectors (Promega, Madison, WI). The original Promega kit referred to this region of the Y-chromosome as the AZFd region. The newer Promega kit notes that these genetic markers are more correctly located at the proximal portion of the AZFc region. Third, identity of the markers we used is in public domain GenBank (National Institutes of Health, Bethesda, Maryland). The markers in question, namely DYS262, which are also known as SHGC-5461 sY67 coordinates, are as follows: chromosome Y position 72777936-7278053 bp Gen Bank accession G40970 U01317 . Fourth, this region of the Y chromosome is noted for palindromes and duplications (5Fukushima M. Koh E. Choi J. Maeda Y. Namiki M. Yoshida A. Reevaluation of azoospermic factor c microdeletions using sequence-tagged site markers with confirmed physical positions from the GenBank database.Fertil Steril. 2006; 85: 965-971Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar). It is also the area of highest mutation rate of the AZF regions (6McElreavey K. Ravel C. Chantot-Bastaraud S. Siffroi J.P. Y chromosome variants and male reproductive function.Int J Androl. 2006; 29: 298-303Crossref PubMed Scopus (38) Google Scholar). Some of these deletions or duplications can be the result of polymorphisms and not actual mutations. To clarify this difference, further study would be required. This particular article describes a pilot study that looks for associations with Y-chromosome microdeletions and RPL. These findings are statistically significant, and further evaluation is needed to determine if these microdeletions are truly mutations or polymorphisms. Polymorphisms associated with a disorder can be informative whether or not it is causative (7Vogt P.H. AZF deletions and Y-chromosomal haplogroups: history and update based on sequence.Hum Reprod Update. 2005; 11: 319-336Crossref PubMed Scopus (110) Google Scholar). In either case, it is an associated finding, and it may become clinically important whether or not it is causative or just an associated finding. At this point in time, this article reports the findings of our research and it is not currently meant to change clinical practice. After re-reviewing our manuscript, we noted that there were a few inadvertent spelling errors in the STS names. DYF8551 should actually read DYF85S1, and DYF8651 should read DYF86S1. Y-chromosome microdeletions and recurrent pregnancy lossFertility and SterilityVol. 85Issue 2PreviewTo determine the prevalence of Y-chromosome microdeletions in recurrent pregnancy loss (RPL) couples as compared with couples with male factor infertility and fertile couples. Full-Text PDF Techniques and reasons to remain interested in the Y chromosomeFertility and SterilityVol. 86Issue 6PreviewWe have read with interest the paper by Müslümanoğlu et al. (1) in the August 2005 issue and the paper of Dewan et al. (2) in the February 2006 issue of Fertility and Sterility that describe the possible involvement of the AZFd region on the human Y chromosome in spermatogenesis and recurrent pregnancy loss (RPL), respectively. We want to comment on two technical flaws that make us question the validity of the results obtained in both studies and discuss more generally the pitfalls of Y-chromosome deletion screening. Full-Text PDF