Embryo ploidy rates following PPOS or GnRH antagonist protocol. A prospective study with repeated ovarian stimulation

Abstract Study question Is there any difference in embryo ploidy rates following progesterone primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist protocol? Summary answer Pituitary downregulation with a PPOS protocol with micronized progesterone results in a comparable number of euploid blastocysts with a GnRH antagonist protocol. What is known already Although the GnRH antagonist is consider by most the gold standard protocol for controlling the LH surge during ovarian stimulation for IVF/ICSI, progesterone-primed ovarian stimulation protocols (PPOS) are being increasing used in freeze-all protocols. Still, despite the promising results of PPOS protocols, an early randomized trial reported potentially lower live births in recipients of oocytes resulting following downregulation with medroxyprogesterone acetate as compared with a GnRH antagonist protocol. The scope of the current prospective study was to investigate whether PPOS with micronized progesterone results in equivalent blastocyst euploidy rates as compared with a GnRH antagonist protocol. Study design, size, duration In this prospective study, performed between September 2019 to January 2022, 44 women underwent two consecutive ovarian stimulation (OS) protocols within a period of 6 months in a GnRH antagonist protocol or in a PPOS protocol with oral micronized progesterone. Participants/materials, setting, methods Overall, 44 women underwent two OS cycles with identical fixed dose of rFSH (225 or 300 IU) in both cycles. Downregulation in the 1st cycles was performed with the use of a flexible GnRH antagonist protocol and consecutively, after a washout period of one month, control of LH surge was performed with oral micronized progesterone from stimulation day 1. After the completion of both cycles, all generated blastocysts underwent genetic analysis for aneuploidy screening (PGT-A). Main results and the role of chance Comparisons between cycles did not reveal differences between the duration of OS neither in the gonadotrophins dose. Hormonal profile on the day of trigger revealed statistically significant differences between cycles in all the tested hormones except for FSH: with significantly higher serum E2 levels, more elevated LH levels and higher Progesterone levels in PPOS cycles as compared with antagonist cycles, respectively. PPOS protocol resulted in a significantly higher number of oocytes (10.27± 5.84 versus 12.68± 8.09), (DBM -2.4 [95% CI -4.1; -0.73]), MIIs (7.34±4.15 versus 9.09± 6.12), (DBM -1.8 [95% CI -3.1; -0.43]), and 2PNs (5.66±3.35 versus 7.14± 4.99), (DBM -1.5 [95% CI -2.6.1; -0.32]) as compared with the GnRH antagonist protocol. Nevertheless, no differences were observed regarding the mean number of blastocysts (2.84±2.12 versus 2.91±2.11), (DBM -0.07 [95% CI -0.67; 0.53]) and the mean number of biopsied blastocysts (2.86±2.15 versus 2.93±2.16), (DBM -0.07 [95% CI -0.70; 0.56]). Finally, no difference was observed for the primary outcome, with a mean number of euploid embryos of 0.86 ± 0.90 vs. 1.00 ± 1.12 for the comparison of PPOS vs. GnRh antagonist. Limitations, reasons for caution The study was powered to detect differences in the mean number of euploid embryos and not in terms of pregnancy outcomes. Additionally, per protocol there was no randomisation, the first cycle was always a GnRH antagonist cycle and the 2nd a PPOS with one month of washout period in between. Wider implications of the findings The current study provides evidence that the PPOS may result in equivalent blastocyst euploidy rates compared with antagonist protocol. This may imply that in case of a freeze-all protocol, clinicians may safely consider PPOS to control the LH surge and patients could benefit from the advantages (cost and oral administration). Trial registration number NCT04108039