Sperm Donation: An Alternative to Improve Post-ICSI Live Birth Rates in Advanced Maternal Age Patients

M. Mignini Renzini; M. Dal Canto; M.C. Guglielmo; D. Garcia; E. De Ponti; A. La Marca; R. Vassena; J. Buratini


Hum Reprod. 2021;36(8):2148-2156. 

In This Article

Abstract and Introduction


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.


Sperm donation is a growing practice in reproductive medicine, accounting for up to one in five of all IVF/ICSI cycles performed in the world with donated gametes. In the United States, it represents around 17% of all gamete donation IVF/ICSI cycles (Kushnir et al., 2017; Gerkowicz et al., 2018) and, in Europe, although combined data from all countries are not available, the Italian National Registry of Medically Assisted Procreation (13th Report, 2017) and the National Registry of the Spanish Fertility Society (2018) indicate a percentage of donor sperm IVF/ICSI cycles comparable to that of the United States.

Sperm donation has been predominantly applied to overcome male infertility in couples with maternal age below 35 years (Kushnir et al., 2017). However, sperm quality is important in ICSI/IVF practice also when there is no diagnosis of male infertility. Increased oxidative stress can cause DNA damage in both sperm and oocyte, and has been pointed to as a major driver of age-related infertility (Mihalas et al., 2017; Stringer et al., 2018; Aitken, 2020; Drevet and Aitken, 2020). As the woman ages, oocyte DNA repair capacity gradually fades, and sperm DNA integrity becomes particularly important to prevent the transfer of gene truncations and de novo mutations to the zygote. These genetic defects constitute, in turn, an important threat to embryonic development, pregnancy completion, and post-natal health (Bisht et al., 2017; Mihalas et al., 2017). Interestingly, however, sperm quality may be important not only in preventing the inheritance of damaged paternal DNA but also in ensuring adequate DNA repair capacity in the zygote. This is suggested by the observation that optimal DNA repair activity following fertilization involves paternal inheritance of 8-oxoguanine DNA glycosylase (OGG1), a rate-limiting enzyme in the base excision repair (BER) pathway (Smith et al., 2013; Martin et al., 2019).

In the face of social changes leading to maternity delay, advanced maternal age (AMA) has become one of the main challenges in current reproductive medicine practice. A number of approaches including adaptation of hormonal protocols, embryo selection strategies, oocyte cryopreservation, and, ultimately, oocyte donation have been proposed to overcome this challenge (Ubaldi et al., 2019). While these approaches have specifically focused on oocyte quality (Cimadomo et al., 2018), the contribution of simultaneous paternal aging and decreased sperm quality in AMA cycles has been neglected. Given this knowledge gap, the objective of this study was to assess the ability of high-quality sperm to improve ICSI outcomes in AMA and non-AMA patients. More specifically, we tested the hypothesis that, in AMA patients, sperm donation provides higher live birth rates than those achieved in homologous normozoospermic cycles.