Abstract

Abstract Study question Does Progesterone Primed Ovarian Stimulation (PPOS) demonstrate comparable efficiency to the GnRH-antagonist protocol in terms of laboratory/reproductive outcomes in PGT-A cycles with donated oocytes? Summary answer PPOS demonstrates efficiency in PGT-A cycles with donated oocytes, comparable to the GnRH-antagonist protocol, providing cost-effectiveness and enhanced donor comfort. What is known already The demand for TRA cycles with donated oocytes steadily rises each year. This treatment instills high hopes for success. Ongoing advancements in donor stimulation protocols prioritize safety and comfort. The shift from LH agonist to antagonist suppresses LH peaks, and recently, PPOS has joined, offering a more comfortable, cost-effective, and equally safe alternative with fewer ultrasound checks, mitigating ovarian hyperstimulation syndrome. Study design, size, duration Retrospective assessment of an oocyte donor cohort undergoing ovarian stimulation: 182 cycles with the GnRH-antagonist protocol (Group 1: G1) and 120 with PPOS (Group 2: G2), conducted between July 2017 and June 2023. Ovarian stimulation involved 225 IU/d of FSHr or FSHu, triggering with a GnRH agonist, and subsequent biopsy of evolutionarily robust embryos after extended culture. Both fresh and vitrified oocytes, inseminated with either self or donor sperm, were included. Participants/materials, setting, methods We analyzed 1188 embryos (G1: 676; G2: 512). Trophoectoderm biopsies from D5/D6 blastocysts underwent NGS using the Illumina platform (VeriSeq Illumina®, San Diego, CA, USA). Comparison included total and MII oocyte numbers, fertilization rates, viable embryos, euploid/aneuploid embryos, mosaic embryos, and clinical outcomes: biochemical pregnancy (BPR), biochemical pregnancy loss (BPLR), clinical pregnancy (CPR), early pregnancy loss (EPLR), ongoing pregnancy (OPR), and live birth (LBR) rates. Statistical analyses were carried out using R statistical software (v.4.3.1). Main results and the role of chance The mean ages of donors (25.57±4.05) and recipients (41.82±4.06) were comparable in both groups. The male partner’s age differed (G1: 40.47±7.87; G2: 42.34±7.65) (p = 0.019). Results were adjusted for confounding factors, including recipient and donor ages, oocyte and seminal origin, and male factor variables. Ovarian stimulation duration (9.26 days), total gonadotropin dose (2015.64 IU), and oocyte origin (fresh G1: 69.8 %; G2: 62.5 %; vitrified G1: 30.2 %; G2: 37.5 %) showed equivalence. Statistical significance emerged in total oocytes retrieved (G1: 17.92±7.64; G2: 20.23±7.89) (p = 0.008), mean microinjected MII (G1: 10.25±1.79; G2: 10.07±1.36) (p = 0.040) and fertilization rate (G1: 73.98 %; G2: 79.44 %) (p = 0.001). The usable embryo rate was similar (G1: 54.78 %; G2: 54.47 %). Significant differences arose in mean biopsied embryos/cycle (G1: 3.71; G2: 4.27) (p = 0.016), but not for aneuploid embryos (G1: 29.71 %; G2: 29.49 %) (p = 0,998). Biochemical pregnancy rates were significant (G1: 48.8 %, G2: 60.4 %) (p = 0.022). Other clinical parameters showed no differences, with LBR at 35.5 % in G1 and 37.8 % in G2 (p = 0.752). Limitations, reasons for caution The study is retrospective, where we addressed potential biases by incorporating confounding variables. However, to confirm our initial findings, randomized prospective studies with an appropriate sample size are essential. Wider implications of the findings In egg donation cycles, PPOS shows optimal embryonic performance resulting in a live birth rate comparable to the GnRH antagonist protocol. Additionally, it offers cost-effectiveness and enhanced comfort for donors. Trial registration number Not applicable

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