BackgroundThe egg donation model offers an opportunity to isolate the male factor and evaluate its impact on IVF–intracytoplasmic sperm injection and pregnancy outcomes.ObjectiveTo study the effect of non‐obstructive azoospermia on intracytoplasmic sperm injection and pregnancy outcomes compared with severe oligozoospermia and mild‐to‐moderate oligozoospermia in egg recipient cycles.Materials and methodsThis is a retrospective longitudinal cohort study, including 1594 patients who underwent intracytoplasmic sperm injection in egg recipient cycles with preimplantation genetic testing for aneuploidies. The cohort was divided into three groups: couples with non‐obstructive azoospermia accounting for 479 patients (30%); couples with severe oligozoospermia (sperm number <5 × 106/mL), accounting for 442 patients (27.8%); couples with mild‐to‐moderate oligozoospermia, with sperm number >5 × 106and <15 × 106/mL, accounting for 673 patients (42.2%).ResultsThe fertilisation rate was significantly reduced in the non‐obstructive azoospermia group as compared with the severe oligozoospermia and the mild‐to‐moderate oligozoospermia group: 30.3% versus 63% and 77.3% (p < 0.05). Logistic regression analysis adjusted for confounders highlighted non‐obstructive azoospermia as a negative predictor of obtaining a euploid blastocyst both per injected oocyte and per obtained blastocyst. The miscarriage rate in the non‐obstructive azoospermia group was 11.8%; higher than the severe oligozoospermia and mild‐to‐moderate oligozoospermia groups (7% and 2.7%) (p < 0.05). The live birth rate per embryo transfer (ET) was significantly lower in the non‐obstructive azoospermia group compared with the severe oligozoospermia and the mild‐to‐moderate oligozoospermia group (20.4% vs. 30.3% and 35.4%, p < 0.05). The risk of preterm labour was significantly higher in the non‐obstructive azoospermia group, compared with the severe oligozoospermia and mild‐to‐moderate oligozoospermia group (55.1% vs. 46.8% and 16.1%, p < 0.001), and this difference was observed in both singleton and twin pregnancies.Discussion and conclusionIn our retrospective comparative study, non‐obstructive azoospermia significantly affects early embryonic potential and live birth rates per cycle and per embryo transfer. It is also associated with higher risk of preterm birth. Future prospective multi‐centre studies are needed to highlight the effect of sperm quality on ART and pregnancy outcomes.

Study question To assess the effect of male factor on ICSI and pregnancy outcomes in egg recipient cycles combined with preimplantation aneuploidy testing Summary answer In egg donor cycles where sperm was obtained from azoospermic men there was a significant effect on ART and clinical outcomes. What is known already The increased incidence of chromosomal problems in men with azoospermia and its correlation with chromosomally abnormal embryos and with adverse pregnancy outcomes has been shown by multiple studies. Nevertheless, few studies in the literature outline the impact of non-obstructive azoospermia in the subgroup of couples who opt to use donated eggs. The egg donation model offers an opportunity to isolate the male factor and evaluate its impact on IVF-ICSI and pregnancy outcomes. The aim of our study was to study the effect of non-obstructive azoospermia(NOA) on ICSI outcomes compared with oligoasthenozoospermia(OATS) and moderate male factor(MMF) infertility, from ART parameters to clinical outcomes. Study design, size, duration This is a retrospective longitudinal cohort study involving 1,594 ICSI cycles using donor eggs performed between January 2016 and May 2020. The cohort was divided into three groups according to the male partner’s sperm parameters: couples with NOA accounting for 479 cycles (30%); couples with OAT-S (sperm number &lt;5 x 106/ml), accounting for 442 cycles (27.8%); couples with moderate male factor, with sperm number &gt;_5 x 106/ml and &lt;15 x 106/ml, accounting for 673 cycles (42.2%). Participants/materials, setting, methods Participants: Subfertile couples who opted to use donor eggs. Donor eggs were utilized, due to history of severe female infertility, including low ovarian reserve, poor response to ovarian stimulation, repeated IVF failures or premature ovarian failure. Setting: Private IVF Unit Intervention: ICSI with ejaculated/surgically retrieved sperm, blastocyst culture, PGT-A and frozen-thawed euploid embryo transfer. Outcomes: The primary outcomes were live birth, fertilization, blastocyst development and euploidy rates; the secondary outcomes were clinical pregnancy, miscarriage rates, preterm labour and SGA. Main results and the role of chance The fertilization rate was significantly reduced in the NOA group as compared to the OATS and the MMF group: 30.3% versus 63% and 77.3%. Logistic regression analysis adjusted for confounders highlighted NOA as a negative predictor of obtaining an euploid blastocyst per inseminated oocyte. When the analysis was performed per obtained blastocyst, no correlation between male factor and euploidy rate was observed. The clinical pregnancy rates were similar in the MMF and OATS group, but significantly lower in the NOA group (38.2% versus 36.3% and 29.5% respectively). The miscarriage rate in the NOA group was 11.8%; higher than the OATS and MMF group (7% and 2.7%). The live birth rate per ET was significantly lower in the NOA group compared to the OATS and the MMF group (20.4% vs 30.3% and 35.4%,p&lt;0.05). The live birth rate was significantly lower in the OATS group compared to the MMF group(p &lt; 0.05). The risk of preterm labour was significantly higher in the NOA group, compared to the OATS and MMF group (55.1% versus 46.8 and 16.1%,p&lt;0.001) and a higher number of babies born with a birth weight &lt;2.5kg came from the NOA group, compared to the OATS and MMF group (34% versus 19.8% and 12.2%, p &lt; 0.001). Limitations, reasons for caution The present study is limited by its retrospective design and the fact that the confounding factors of advanced maternal age, endometrial ageing and uterine factors cannot be fully evaluated. However, the study was controlled for female and male partner's age. Neonatal outcomes were not available. Wider implications of the findings Non-obstructive azoospermia can impair early embryonic potential and reduce live birth rates. Our study also shows an association between NOA and preterm birth. Future research should focus on prospective collection of data and long-term follow up of babies born by fathers with non-obstructive azoospermia. Trial registration number Not applicable