Ovovid trial: the effect of a probiotic micronutrients supplement on oocyte retrieval and quality in oocyte donors. A double blind, randomized controlled trial

Purpose: To evaluate whether a micronutrients supplement combined with probiotics improves oocyte retrieval outcomes in normoresponder women undergoing controlled ovarian hyperstimulation for oocyte donation. Methods: A multicenter, prospective, randomized, double-blind, controlled clinical trial was conducted between July 2022 and July 2024 with 196 normoresponder oocyte donors at three fertility centers in Spain. Participants received either study supplement or a placebo for at least 30 days before and during controlled ovarian hyperstimulation. Results: The intention-to-treat analysis showed a significant increase in the total number of follicles (28.01 ± 10.4 vs. 24.7 ± 7.1; p = 0.0314) and follicles ≥ 16 mm (19.3 ± 8.6 vs. 15.8 ± 6.1; p = 0.0065) in the study group compared to the placebo group. Regarding the quality of MII oocytes, the mean number of good-quality oocytes showed no differences between groups (17.0 ± 7.7 (84.1%) vs. 15.4 ± 8.2 (81.4%); p = 0.2187). The per-protocol analysis (participants who completed the study and adhered fully to the supplement regimen, n = 79) revealed significantly higher total oocytes retrieved (27.7 ± 10.4 vs. 21.2 ± 7.9; p = 0.0045), MII oocytes (22.5 ± 8.89 vs. 17.3 ± 7.25; p = 0.0092), and good-quality MII oocytes (18.97 ± 7.7 vs. 13.42 ± 6.5; p = 0.0019) in the study group. Conclusions: Probiotic micronutrients supplementation improved follicular development and oocyte yield, in normoresponder oocyte donors, especially when administered according to the recommended protocol. These findings suggest potential benefits for oocyte donation programs; however, further research is needed to establish definitive recommendations. The study protocol was registered at ClinicalTrials.gov (TRN: NCT05473039) on June 27, 2022. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.