Sperm donation: an alternative to improve post-ICSI live birth rates in advanced maternal age patients.

STUDY QUESTION: Can sperm donation increase live birth rates following ICSI in advanced maternal age (AMA) patients? SUMMARY ANSWER: Sperm donation increases the live birth rate in AMA ICSI cycles. WHAT IS KNOWN ALREADY: In ICSI practice, sperm donation has been predominantly applied to overcome male infertility. The involvement of paternal age and lower sperm quality in the severe reduction in fertility observed in AMA patients remains to be clarified. STUDY DESIGN, SIZE, DURATION: Retrospective multicenter cohort study including data generated between 2015 and 2019 from 755 ICSI cycles achieving a fresh embryo transfer, of which 337 were first homologous cycles (normozoospermic partner sperm and homologous oocytes) and 418 were first sperm donation cycles (donor sperm and homologous oocytes). The association of sperm origin (partner vs donor) with live birth was assessed by multivariate analysis in non-AMA (<37 years, n = 278) and AMA (≥37 years, n = 477) patients, separately, including in the model all variables previously found to be associated with live birth in a univariate analysis (number of MII oocytes recovered, number of embryos transferred, and maternal age). ICSI outcomes were compared between sperm donation and homologous cycles in overall, non-AMA and AMA patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted in three fertility clinics and included 755 Caucasian patients aged 24-42 years undergoing their first homologous or sperm donation ICSI cycle achieving a fresh embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE: The multivariate analysis revealed that sperm donation was positively associated with the likelihood of a live birth independently of all other variables tested in AMA (P = 0.02), but not in non-AMA patients. Live birth, delivery, and miscarriage rates differed substantially between sperm donation and homologous AMA cycles; live birth and delivery rates were 70-75% higher (25.4% vs 14.5% and 22.5% vs 13.5%, respectively; P < 0.01), while miscarriage occurrence was less than half (18.0% vs 39.5%; P < 0.01) in sperm donation compared to homologous AMA cycles. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective nature, differences in patients profiles between sperm donation and homologous-control groups and varying proportion of donor cycles between fertility centers, although these variations have been controlled for in the statistical analysis. WIDER IMPLICATIONS OF THE FINDINGS: The findings suggest that sperm donation increases live birth rates while reducing miscarriage occurrence in AMA patients, and thus may be a valid strategy to improve ICSI outcomes in this growing and challenging patient group. STUDY FUNDING/COMPETING INTEREST(S): N/A. TRIAL REGISTRATION NUMBER: N/A.

The effect of hepatocyte growth factor on the initial stages of mouse follicle development.

Interactions between theca and granulosa cells of the follicle are critical for the coordination of ovarian follicle development. The cell-cell interactions are mediated through the local production and actions of a variety of factors. The current study is designed to investigate the expression of Hgf and its receptor, c-Met, in the mouse ovary during in vivo folliculogenesis. We found that Hgf and c-Met mRNAs were already expressed in 2-day-old ovaries, and that, while c-Met levels remained constant until 22-day-old, Hgf levels slightly but not significantly increased with age. The expression of Hgf mRNA in theca/interstitial cells was higher than in granulosa cells in 22-day-old ovaries. Immunohistochemistry analysis confirmed the expression pattern demonstrated by RT-PCR. We investigated the role of hepatocyte growth factor (HGF) at the beginning of mouse folliculogenesis and its possible interaction with kit ligand (KL). Interestingly, both KL and HGF were able to increase the expression of each other, creating a positive feedback loop. In the presence of HGF, we observed an increase of granulosa cell proliferation and an increase in the number of pre-antral and early antral follicles in ovary organ cultures. We also observed a significant increase in the diameters of follicles in individual follicle cultures. Moreover, HGF stimulated the expression of the FSH receptors, both in the whole ovary and in isolated pre-antral follicle cultures. Based on the data presented, we concluded that HGF exerts multiple levels of control over follicular cell functions, which collectively enable the progression of follicular development.