Impact of Y-chromosome Microdeletions From Infertile Men on the Chromosomal Constitution of Their Spermatozoa and Embryos. Combined IntraCytoplasmatic Sperm Injection (ICSI) and Preimplantation Genetic Screening (PGS) as Treatment Strategy.

Nowadays, Y-chromosome microdeletions are one of the most common causes of male infertility. With a frequency of 8-20% in non-obstructive azoospermic men and 3-14% in severe oligozoospermic men, is the most usual chromosome anomaly associated with failure in sperm production, although the frequency seems to change due to differences in the experimental designs, the ethnic differences, the genetic background, or even environmental influences.

The absence of some genes located on certain regions in the long arm of the human Y chromosome, known as the azoospermia factor region (AZF), causes spermatogenic failure, while spermatozoa has been found in either the ejaculate or the testicle of most patients. Detection of deletions is crucial for the medical treatment of these patients, since it has a prognostic value in predicting potential success of testicular sperm retrieval in azoospermic patients with certain microdeletions, and allows avoiding invasive techniques in oligozoospermic patients whose sperm production could result in progressive worsening.

The development of assisted reproduction techniques, such as intracytoplasmatic sperm injection (ICSI), together with testicular or epididymis sperm retrieval for azoospermic men has allowed these patients to become fathers using their own gametes. Although the effect of Y-chromosome microdeletions on ICSI outcome is controversial, the ability to vertically transmit that genetic defect, and so the infertility, to the offspring has been accepted. Until recently, no clinical consequences other than infertility were supposed in the ICSI-conceived sons of fathers with deletions. However, different studies in the last years, suggest other potentially risks transmitted to the offspring, such as the development of sexual dysfunction due to sex chromosome abnormalities (Turner or Klinefelter syndromes, etc.) or other somatic disorders with worse health implications caused by chromosome aberrations outside the AZF regions or in autosomes that has been associated to Y-chromosome microdeletions. No major clinical complications than infertility has been described in the offspring born from fathers with deletions to date, but it is important to remember that the first generation of those babies, mainly obtained by ICSI, has just reached maturity. Moreover, the mentioned chromosome anomalies, could stop embryo development or increase miscarriage rate. Few studies focused in the incidence of miscarriages in these couples but microdeletions have been detected more frequents in men from couples with recurrent pregnancy loss.

In order to offer fully genetic counseling to these couples, further studies focusing on the relationship between Y-chromosome microdeletions and other chromosomal abnormalities, which also provide information about their consequences in their embryos, are required. Thus, the actual risk of transmitting different anomalies associated to microdeletions to those embryos will be clarified, increasing the chances of a successful pregnancy and live birth.

In this study, investigators assess, using Fluorescence in situ Hybridization (FISH) and Comparative Genomic Hybridization (CGH) arrays for Preimplantation Genetic Screening (PGS), the incidence of aneuploidies in spermatozoa and embryos from infertile men with and without microdeletions who undergo assisted reproduction in their clinics.