Male factor & mosaicism: assessing the contribution of abnormal semen parameters to rate of mosaicism in next generation sequencing (NGS) preimplantation genetic screening (PGS) intracytoplasmic sperm injection (ICSI) cycles

Abstract

Advances in preimplantation genetic screening (PGS) have led to practices changes in assisted reproductive technology (ART), enabling fertility centers to transfer single embryos while maintaining excellent ongoing pregnancy rates, reducing miscarriage rates, and dramatically reducing ART-associated multiple pregnancies [1,2]. The introduction of next generation sequencing (NGS) has allowed PGS laboratories to assess for embryo mosaicism – although the true incidence and reproductive potential of mosaic embryos is controversial. Severe male factor is known to increase risk of aneuploidy [3]. However, the influence of male factor infertility on mosaicism is unknown at this time. While aneuploidy is mostly due to maternal meiotic errors, mosaicism is likely caused by post-fertilization mitotic errors [4] and abnormal sperm may contribute to an embryo's risk of being mosaic. We sought to examine the influence of abnormal semen parameters on mosaicism in NGS PGS-tested embryos. The purpose of this study was to evaluate rate of mosaic embryo formation in NGS PGS cycles according to semen abnormality. Secondary aims were to assess sex ratio and subtypes of mosaicism in NGS PGS cycles according to semen abnormality. We performed a retrospective review of women undergoing PGS at a single academic fertility center from July 1, 2015 to September 1, 2017. Only intracytoplasmic sperm injection (ICSI) PGS cycles were included. In all cycles, PGS was performed via trophectoderm biopsy on day 5 or 6 and analyzed using NGS at a single reference lab. Patient demographics, fertility testing, cycle characteristics and PGS outcomes were collected. PGS outcomes were compared between oligospermic and non-oligospermic cohorts, between asthenospermic and non-asthenospermic cohorts, and between oligoasthenospermic and normospermic cohorts. 228 ART-ICSI cycles with PGS testing were included for analysis: 130 normospermic, 32 oligospermic, 47 asthenospermic, and 12 oligoasthenospermic cycles, resulting in 374 normospermic, 106 oligospermic, 162 asthenospermic, and 38 oligoasthenospermic biopsied embryos. Baseline characteristics were similar between cohorts with the exception of semen parameters (Tables 1-3). PGS cycles with oligospermia demonstrated a higher proportion of mosaic embryos (36/100, 34%) versus PGS cycles without oligospermia (115/617, 18.6%), p<0.001. PGS cycles with oligoasethenospermia demonstrated a higher proportion of mosaic embryos (15/38, 39.5% versus 88/384, 23.5%, p<0.001) compared to PGS cycles without oligoasthenospermia. Additional PGS outcomes were similar between cohorts (Tables 1-3). Oligoasthenospermia and oligospermia, but not asthenospermia, may increase the risk of mosaic embryos following ART-ICSI cycles with NGS PGS.