Effects of AZFc (b2/b4, b1/b3, b2/b3, and gr/gr) deletions and primary duplications on the outcomes of the first intracytoplasmic sperm injection treatment cycle: A single-center retrospective cohort study.

Background: Current advances in high-throughput sequencing technology enable the precise identification of Y chromosome microdeletion and primary duplication in infertile couples, but the mechanism and clinical significance of these mutations in assisted reproductive techniques remain unclear.

Objectives: To investigate the effects of AZFc (b2/b4, b1/b3, b2/b3, and gr/gr) deletions and primary duplications on the outcomes of the first intracytoplasmic sperm injection (ICSI) treatment cycle.

Methods: Y chromosome microdeletions and primary duplications in infertile men were detected using next-generation sequencing (NGS) technology. A total of 813 patients undergoing their first ICSI treatment were divided into six groups: b2/b4 deletion group (n = 28), three partial AZFc subdeletion groups (b1/b3, n = 13; b2/b3, n = 72; gr/gr, n = 71), primary AZFc duplication group (n = 54), and control group with a normal Y chromosome (n = 575). The multivariate logistic regression analyses were conducted to assess and compare the embryologic and cumulative reproductive outcomes of ICSI treatment across these groups.

Results: Compared with the control group, the b2/b4 deletion group showed a poor ICSI embryologic outcome after ICSI treatment, with a significantly lower fertilization rate per oocytes retrieval (72.22% vs.79.89%; adjusted odds ratio [OR], 0.63; 95% confidence interval [CI], 0.45-0.88, p < 0.01) and 2 pronuclear (2PN) fertilization rate (66.37% vs. 74.80%; adjusted OR, 0.65; 95% CI, 0.47-0.89, p < 0.01) either before or after adjustment for confounding factors. Nevertheless, three partial AZFc deletion groups showed no effect on the ICSI fertilization rate after ICSI treatment. The primary AZFc duplication group had a significantly lower clinical pregnancy rate per transferred embryo (56.25% vs. 65.97%; adjusted OR, 0.64; 95% CI, 0.41-0.99, p < 0.05), and the semen characteristics varied from azoospermia to normozoospermia. In addition, all indicators related to embryo quality, clinical pregnancy, and live birth outcomes in the primary duplication group were inferior to those in the control group.

Conclusion: This study indicates that b2/b4 deletion has a negative effect on ICSI outcomes, particularly the fertilization rates. Partial AZFc deletions have no significant effect on the fertilization rate after ICSI treatment. Primary AZFc duplication can lead to varying seminal phenotypes and has a negative effect on ICSI embryologic and pregnancy outcomes, particularly showing a significant association with low birth weight in newborns after ICSI treatment.