Comparison of medroxyprogesterone acetate and gonadotropin releasing hormone antagonists in the prevention of premature luteinizing hormone surge during controlled ovarian hyperstimulation in in vitro fertilization treatment: Effects on developing embryos and pregnancy outcomes

Objective: The aim of this study was to evaluate the effects of Medroxyprogesterone Acetate (MPA) treatment in comparison to Gonadotropin Releasing Hormone (GnRH) antagonists for the prevention of premature luteinizing hormone (LH) surge during controlled ovarian hyperstimulation (KOH) in in vitro fertilization (İVF) treatment, and their impact on developing embryos and pregnancy outcomes. Material and Methods: Data from 757 cycles using GnRH antagonists and 756 cycles using MPA were evaluated at Akdeniz University Faculty of Medicine Assisted Reproductive Treatment Center between October 2018 and April 2022. Results: Patients using MPA were found to be significantly older (33.9±5.6 vs. 32.6±5.6, p<0.001) and had longer infertility periods (4.1±3.5 vs. 3.4±3.0 years, p<0.001) with a lower number of antral follicles (AFC) (10.7±8.6 vs. 11.9±10.8, p=0.007) than those using GnRH antagonists. Despite higher daily starting follicle stimulating hormone (FSH) doses in the MPA group (276.5±44.9 vs. 208.6±61.0 IU, p<0.001), the total gonadotropin dose used was lower (2685.8±852.7 vs. 3009.6±1356.6 IU, p<0.001) due to shorter stimulation periods (9.1±2.0 vs. 9.5±2.2 days, p<0.001). Both MPA (2.9%) and GnRH antagonists (2.2%) had similar effectiveness in preventing premature ovulation (p=0.415). The average Estradiol (E2) level on trigger day in the MPA group (2516.1±2069.2 pg/ml) was significantly higher than the GnRH antagonist group (2183.5±5592.3 pg/ml), (p<0.001). The total number of oocytes retrieved in the MPA group (9.3±8.1) was lower than that in the GnRH antagonist group (10.2±7.9), with a statistically significant difference (p=0.004). However, there was no significant difference between the two groups in terms of the number of MII oocytes (6.9±6.2 vs. 7.1±6.0, p=0.218), fertilization rates (3.2±3.2 vs. 3.5±3.5, p=0.289), or the number of total developed embryos (1.3±1.3 vs. 1.2±1.2, p=0.765). In contrast, the oocyte maturation rate (0.7±0.2 vs. 0.6±0.2, p<0.001) and the percentage of high-quality embryos developed per MII oocyte (%39.5 vs. %32.4, p<0.001) were higher in patients treated with MPA. The clinical pregnancy rates per embryo transfer (ET) were similar in the first transfers of patients using MPA and GnRH antagonists (%35.4 vs. %30.1, p=0.074). There was no statistically significant difference between the cumulative clinical pregnancy rates per total transfer of the MPA and GnRH antagonist groups (35.3% vs. 30.1%, p=0.077). Similarly, no significant difference was observed in the cumulative clinical pregnancy rates per patient treated after all ETs (24.1% vs. 23.2%, p=0.269). Furthermore, potential confounding factors such as age, duration of infertility, AFC, single or double ET, and the developmental stage of the transferred embryo were also evaluated using logistic regression analysis. The results revealed that the cumulative clinical pregnancy rate per patient initiated on KOH treatment was higher in patients using MPA (p<0,05, Exp(B)=1,704, %95 confidence interval: [1,286; 2,256]). Conclusion: MPA was found to be effective in preventing premature ovulation during KOH treatment, and the developing embryo and pregnancy outcomes of patients using MPA were similar to those using GnRH antagonists. Therefore, the use of MPA instead of GnRH antagonists during KOH may be a viable alternative for patients not scheduled for fresh ET. Keywords: ovarian stimulation, premature LH surge, medroxyprogesterone acetate, clinical pregnancy rates