Y-Chromosome Microdeletions: A Review of Prevalence, Screening, and Clinical Considerations

Abstract

Deletions within the male-specific region of the Y-chromosome, known as Y-Chromosome Microdeletions (YCMs), are present in as many as 5% and 10% of severe oligospermic and azoospermic men, respectively. These microdeletions are distinguished by which segment of the Y chromosome is absent, identified as AZFa (the most proximal segment), AZFb (middle), and AZFc (distal). The reported prevalence of YCMs within the world’s populations of infertile men displays vast heterogeneity, ranging from less than 2% to over 24% based on region and ethnicity. AZFc is the most commonly identified YCM, and its phenotypic presentation provides for the highest chance for fertility through artificial reproductive techniques. Conversely, deletions identified in the subregions of AZFa, AZFb, or any combination of regions containing these segments, are associated with low probabilities of achieving pregnancy. A putative mechanism explaining this discrepancy lies within the expression of autosomal, DAZ-like genes which could serve to “rescue” wild type AZFc gene expression and hence spermatogenesis. Nevertheless, recent reports challenge this dogma and stress the importance of further analysis when an AZFb deletion is detected. The screening thresholds to determine which oligospermic and azoospermic men are tested for potential YCMs has been recently contested. More recent literature supports lowering the threshold from 5 million sperm/mL of ejaculate to 1 million/mL as the frequency of YCMs in men with sperm concentrations between 1 and 5 million sperm/mL is very low (~0.8%). As such, subsequent guidelines should recommend a lower screening threshold. While YCMs are extremely common globally, the understanding of their clinical significance in the field remains scattered and without consensus. Furthermore, very little is currently known about partial deletions within the AZFc region, such as b1/b3, b2/b3, and gr/gr. Hence, this review aimed to summarize and discuss modern trends in the epidemiology, screening guidelines, and clinical considerations pertaining to YCMs.

Frequency of Deletion of AZF Region of the Y Chromosome in Chhattishgarh, India

“…AZFbc deletion leads to impaired spermatogenesis and reduced probability of retrieval [4]. Based on the Poor outcome sperm retrieval procedure are not suggested for AZFbc deletion [18]. These patients should be offered the option of donor semen.…”

Commentary on Non-obstructive Azoospermia (NOA); From Past to the Present

“…All genes belonged to the azoospermia factor (AZF) proximal (a), middle (b), or distal (c) Yq 11 subregions and regulate cell cycle and germ cell survival. To our knowledge, microdeletions of the AZF c region is the most prevalent microdeletion of Yq, which have been detected in more than 80% of NOA patients (16).…”

Molecular Diagnosis of Y-Chromosome Microdeletions in Some Kurdish Infertile Males: EAA/EMQN PCR Protocol Optimization.

“…The current study was approved by the Research Ethics Committee at College of Science, Salahaddin University-Erbil (SUE), Iraq and informed consent was obtained from each subject (participants). This current study was conducted on 296 Iraqi Kurdish infertile males in Erbil province during December 2019 and December (Rabinowitz et al, 2021) 2020. The selection of patients who participated in this study was based on their medical histories that have been recorded in public and private hospitals and infertility centers.…”

“…Worldwide up to 15% of couples are affected by infertility, which is defined as the inability of sexually active couple to carry a pregnancy to delivery, after one year of unprotected intercourse. Generally, male factors are responsible for about 50% of all infertility cases (Rowe et al, 2000, Organization, 2010, Jungwirth et al, 2019 .…”