Abstract

Abstract Study question Does paternal body mass index (BMI) affect preimplantation development and clinical outcomes in oocyte donation cycles? Summary answer High paternal BMI was associated with delays in early development and poorer embryo quality on day 3, but this did not adversely affect pregnancy outcomes. What is known already Maternal obesity is known to negatively affect preimplantation development and clinical outcomes. While oocyte competence plays a major role in early embryogenesis, male obesity has been linked to poorer semen parameters and epigenetic alterations in sperm. Such characteristics may inherently compromise preimplantation development and ultimately impair reproductive success. Only a few reports have assessed the effects of male BMI on the progression of cell divisions and embryo morphokinetic patterns. However, current findings remain contradictory, while the effects of male obesity on fertility continue to be understudied. Study design, size, duration This retrospective study included 7,656 embryos from 1,342 oocyte donation ICSI cycles, performed between April 2018 and December 2021 across two fertility centres. Sperm originated from the partner (n = 1087) or donor (n = 255) and was either fresh (n = 460) or frozen (n = 835). Only the first fresh (n = 1,140) or frozen (n = 202) embryo transfer (ET) was considered. Our database included 1,089 single and 238 double ETs performed at either the cleavage (n = 424) or blastocyst stage (n = 903) of development. Participants/materials, setting, methods Males were stratified according to BMI, based on WHO guidelines, defined as: normal weight (BMI<24.9, n = 677); pre-obese, (BMI=25.0–29.9, n = 533); and obese (BMI>30, n = 132). Patients with severe male factor and preimplantation genetic testing cycles were excluded. Univariate analyses and logistic regression were used to evaluate associations between BMI, embryo morphokinetics and clinical outcomes. Analyses were adjusted for various confounders pertaining to patient demographics, sperm and cycle parameters. A p-value of < 0.05 was considered significant. Main results and the role of chance Overall, obese men displayed poorer sperm motility and underwent more day 2-4 embryo transfers and freeze-all cycles, compared to pre-obese and normal weight men (p < 0,05). Fertilization rates were not affected by male BMI (77.0% ± 18.9 normal weight; 77.4% ± 18.1 pre-obese; 75.3% ± 19.9 obese; p = 0.62), also in our adjusted analysis. Several morphokinetic parameters were delayed in embryos from pre-obese and obese patients, including pronuclei fading (tPNf, p = 0.0064) and division timings from the 2 to 5-cell stage (t2-t3-t4-t5, p < 0,05). Successively, the number of good quality cleavage embryos decreased significantly with higher BMI (normal weight, 62%; pre-obese, 59%; obese, 50.8%; p = 0.02). In contrast, developmental events past the 5-cell stage, including time to 8-cells (t8), blastulation (tSB) and expanded blastocyst (tB) were comparable amongst the groups (p > 0.05). Similarly, we observed no effect of male BMI on blastocyst quality (normal weight, 70.2%; pre-obese, 73.4%; obese, 75.5%; p = 0.06). Despite early developmental delays, we observed no significant effects on biochemical pregnancy (normal weight, 64.7%; pre-obese 64.1%; obese, 58.7%; p = 0.45), ongoing pregnancy (normal weight, 60.0%; pre-obese, 58.8%; obese, 52.9%; p = 0.35) and live birth rate (normal weight, 41.9%; pre-obese, 42.0%; obese, 34.9%; p = 0.27). Our adjusted analysis corroborated these findings. Limitations, reasons for caution The main limitation of this study is its retrospective design, which may not account for all confounders. Moreover, lifestyle factors, such as smoking or alcohol consumption were not considered. As such, results cannot be generalized to all patient populations. Wider implications of the findings Obese males show lower motile sperm counts and delayed cleavage development. While these changes impaired day 3 embryo quality, they did not affect blastocyst development and quality. That translates into comparable clinical outcomes, suggesting that specific counselling is not required in obese patients. Trial registration number not applicable

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