LAUSR

Can the use of donor sperm improve post-ICSI live birth rate in advanced maternal age (AMA) patients? The use of donor sperm increases post-ICSI live birth rate while substantially reducing abortion occurrence in AMA patients. Oocyte DNA repair capacity decreases with maternal age, when sperm DNA integrity is particularly important to avoid the transfer of gene truncations and de novo mutations to the zygote. Optimal DNA repair activity in the zygote requires paternal inheritance of 8-oxoguanine DNA glycosylase (OGG1), a rate-limiting enzyme in the base excision repair pathway. However, the involvement of paternal aging and sperm quality in the severe drop in fertility observed in AMA patients has not been addressed. While strategies to mitigate the impact of AMA on fertility have exclusively targeted oocyte quality, the sperm contribution in this scenario remains somehow neglected. Retrospective, multicentric, international study including 755 first ICSI cycles with patients’ own oocytes achieving a fresh ET between 2015 and 2019, 337 of which using normozoospermic partner semen and 418 using donor sperm. The association of sperm origin (partner vs. donor) with live birth was assessed by univariate/multivariate analysis in non-AMA (<37 years, n = 278) and AMA (≥37 years, n = 477) patients. ICSI outcomes were compared between partner and donor sperm in non-AMA and AMA patients. The study was conducted in 3 fertility clinics including 755 Caucasian patients aged 24 to 42 years. Univariate/multivariate analyses were performed to test the association of sperm origin with live birth; infertility factor, maternal age, oocyte yield and number of embryos transferred were included in the model as confounding variables. In addition, ICSI outcomes were compared between donor and partner sperm groups with the Chi-square (percentages) or with the Wilcoxon sum rank (continuous variables) tests. The multivariate analysis revealed that the use of donor sperm was positively and independently associated with live birth occurrence in AMA [1.82 OR (1.08–3.07) 95% IC; p = 0.024], but not in non-AMA patients [1.53 (0.94–2.51); p = 0.090]. Maternal age [0.75 (0.64–0.87); p < 0.001], number of MII oocytes recovered [1.14 (1.05–1.23); p = 0.001] and number of embryos transferred [1.90 (1.27–2.86); p = 0.002] were also independently associated with live birth in AMA patients. Live birth and delivery rates were 70–75% higher, while miscarriage rate was less than half in donor sperm compared to partner sperm AMA cycles (LBR: 25.4% vs. 14.5%, p = 0.003; DR: 22.5% vs. 13.5%, p = 0.008; MR: 18.0% vs. 39.5%; p = 0.009). Implantation (17.4% vs. 13.5%; p = 0.075) and clinical pregnancy rates (27.5% vs. 22.3%; p = 0.121) did not significantly differ between sperm donation and partner sperm AMA cycles. Male age was substantially lower (23.6 ± 5.2 vs. 41.4 ± 5.0; p < 0.0001) and oocyte yield was higher (5.1 ± 3.1 vs. 4.3 ± 2.6; p < 0.0001) in sperm donation compared to partner sperm AMA cycles, while maternal age did not vary (39.8 ± 1.6 vs. 39.6 ± 1.7; p = 0.348). This study is limited by its retrospective nature and by differences in patients’ profiles between sperm donation and homologous cycles, although this variation has been controlled for in the statistical analysis. Wider implications of the findings: The findings suggest that donor sperm can improve live birth rates by drastically reducing miscarriage occurrence in AMA patients. Therefore, the present results may influence AMA treatment decisions and, above all, contribute for AMA patients to achieve a healthy birth. Not applicable