The clinical impact of oligozoospermia in oocyte donation ICSI cycles using preimplantation genetic test for aneuploidy

Abstract STUDY QUESTION Do severely impaired sperm concentrations (oligozoospemia) in male factor infertility affect embryo aneuploidy rates and clinical results after IVF oocyte donation cycles? SUMMARY ANSWER Severe oligozoospermia (SO) in IVF cycles utilizing donor oocytes does not significantly affect embryo euploidy rates or IVF outcomes or cumulative live birth rates (CLBRs). WHAT IS KNOWN ALREADY SO has previously been linked to elevated rates of chromosomal abnormalities in spermatozoa and altered rates of embryo development with poorer reproductive outcomes. Nonetheless, the precise impacts of severe male factor infertility on embryonic aneuploidy rates and the success of IVF, in the context of controlled female ages in oocyte donation cycles with preimplantation genetic testing for aneuploidy (PGT-A), are still not fully understood. STUDY DESIGN, SIZE, DURATION This retrospective observational cohort study involved 690 IVF oocyte donation cycles undergoing PGT-A from multiple clinics across Europe between January 2017 and December 2023. The study population was divided into three groups based on sperm concentration: SO (<5 million sperm/ml), moderate oligozoospermia (MO, 5–16 million sperm/ml), and a normozoospermia control group (≥16 million sperm/ml) for outcome analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS The IVF outcomes and variables for couples undergoing oocyte donor cycles were investigated. ICSI was performed in all cycles using fresh sperm samples that were assessed for standard semen parameters with fresh or frozen donated oocytes. All of the resulting embryos were biopsied at the blastocyst stage for PGT-A, and all transfers were of single embryos performed in subsequent cycles after vitrification and warming. Statistical analysis was performed using multivariate regression models to identify correlations between rates of oligozoospermia and clinical, embryological and genetic outcomes. MAIN RESULTS AND THE ROLE OF CHANCE The study included 690 couples, in the SO (N = 202), MO (N = 102), and the control normozoospermia (N = 386) groups. The SO group had significantly lower sperm motility (P < 0.0001) and significantly reduced fertilization rates compared to the MO and control groups (P < 0.01). However, no statistical difference was observed for the blastocyst formation rate (per fertilized oocyte). Mostly due to the reduced fertilization rates, the number of euploid blastocysts obtained was significantly lower in the SO group (P = 0.007), however, this did not affect the pregnancy, biochemical or clinical miscarriage (P = 0.37, P = 0.22, and P = 0.86), or CLBRs (P = 0.26) after single blastocyst transfers. The multivariate analysis showed no effect of SO or MO on aneuploidy, miscarriage, or live birth rates. Interestingly, the PGT laboratory strategy (<0.001) was associated with the rate of euploid blastocysts but had no significant effect on pregnancy outcomes. LIMITATIONS, REASONS FOR CAUTION This is a retrospective observational study focusing on outcomes associated with reduced sperm concentration. Other elements of severe male factor infertility may have different associations with outcomes. Also, potential confounding factors including male lifestyle factors that can influence sperm quality were not considered. WIDER IMPLICATIONS OF THE FINDINGS In this oocyte donation setting, we demonstrated that SO is unlikely to significantly affect IVF outcomes following blastocyst development, which contradicts previous findings in less controlled settings. This suggests that male factor infertility in the setting of oocyte donation is not an indication per se to perform PGT-A. These results provide reassurance for couples when undergoing treatment with oocyte donation that any related male factor infertility will not significantly impact treatment outcomes. Further research should use similar controlled oocyte donation settings to investigate other severely impaired sperm parameters to better understand associations with paternal embryonic aneuploidy and IVF outcomes, guiding a more informed path for male factor infertility treatment. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used and the authors have no conflicting interests. TRIAL REGISTRATION NUMBER N/A.