Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses.

Sandeep Kumar Bansal,Satya Narayan Sankhwar,Rima Dada,Deepika Jaiswal,Kiran Singh,Gopal Gupta,Nishi Gupta,Singh Rajender

doi:10.1038/srep19798

Abstract

We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.20% of the cases. Among partial deletions, the frequency of gr/gr deletions was the highest (5.84%). The comparison of partial deletion data between cases and controls suggested a significant association of the gr/gr deletions with infertility (P = 0.0004); however, the other partial deletions did not correlate with infertility. In cohort analysis, men with gr/gr deletions had a relatively poor sperm count (54.20 ± 57.45 million/ml) in comparison to those without deletions (72.49 ± 60.06), though the difference was not statistically significant (p = 0.071). Meta-analysis also suggested that gr/gr deletions are significantly associated with male infertility risk (OR = 1.821, 95% CI = 1.39–2.37, p = 0.000). We also performed trial sequential analyses that strengthened the evidence for an overall significant association of gr/gr deletions with the risk of male infertility. Another meta-analysis suggested a significant association of the gr/gr deletions with low sperm count. In conclusion, the gr/gr deletions show a strong correlation with male infertility risk and low sperm count, particularly in the Caucasian populations.

Highlights

We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions in 822 infertile and 225 proven fertile men
Given the fact that b2/b4 is already established as a causative factor for infertility[43,44] and that we did not find its occurrence in the control group, statistical comparison for the complete AZFc deletions was not undertaken
The present study was conducted on an untested Indian population with clearly defined cases and controls to analyze the frequencies of complete and partial deletions in the AZFc region of the Y-chromosome

Summary

Introduction

We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. 25–55% of the patients with severe testicular pathologies (hypospermatogenesis, sperm maturation arrest and Sertoli cell only syndrome) and 5–25% of the patients with severe oligozoospermia or azoospermia harbor these deletions, making them the most common known genetic cause of spermatogenic failure[2,3,4,5,6,7,8] These deletions occur in three non-overlapping regions (AZFb and AZFc are partially overlapped) mapped to the proximal (AZFa), middle (AZFb), and distal (AZFc) portions of the Y-chromosome[9]. We designed the present study to find the frequency of complete (b2/b4) and partial (gr/gr/, b1/b3, b2/b3) AZFc deletions in Indian populations for their association with spermatogenic failure/male infertility. We performed meta-analyses and trial sequential analyses to estimate the impact of the gr/gr deletions on sperm count and male fertility

Methods

Results

Conclusion