# Ovarian Responses and Outcomes of In Vitro Fertilization Following Progesterone-Primed Ovarian Stimulation and Gonadotropin-Releasing Hormone (GnRH) Antagonist Protocols Using Follitropin Delta

## TL;DR

This study compared two ovarian stimulation protocols in Japanese women undergoing IVF and found similar pregnancy rates but trends toward better oocyte and blastocyst outcomes with the newer progesterone-primed method.

## Contribution

The study evaluates the clinical outcomes of progesterone-primed ovarian stimulation versus GnRH antagonist protocols in Japanese women using follitropin delta.

## Key findings

- No significant difference in oocyte retrieval between the two protocols.
- PPOS showed a higher trend in blastocyst formation, though not statistically significant.
- Comparable pregnancy rates were observed across all age groups for both protocols.

## Abstract

Aim: This study aimed to examine the effects on oocyte retrieval, culture results, and pregnancy rates in Japanese women who underwent ovarian stimulation for assisted reproductive technology using two different protocols with follitropin delta. Specifically, it compared ovarian responses between a gonadotropin-releasing hormone (GnRH) antagonist protocol, used as a conventional controlled ovarian stimulation method, and a progesterone-primed ovarian stimulation (PPOS) protocol, considered a relatively new method.

Materials and methods: This retrospective, observational study was conducted at a single in vitro fertilization clinic in Tokyo, Japan, from April 2022 to March 2024. The study population included infertile patients who were scheduled for treatment and met the inclusion criteria. Eligible participants were Japanese women aged 20-45 years with preserved ovarian function, indicated by an anti-Müllerian hormone level of ≥0.8 ng/mL. Exclusion criteria included contraindications for follitropin delta, previous oocyte stimulation for egg donation or fertility preservation, follicle-stimulating hormone levels ≥35 mIU/mL, uncontrolled malignant disease, stage III/IV endometriosis, and the use of hormone preparations (excluding thyroid medication) during the last menstrual cycle prior to study entry. The primary endpoint was the pregnancy rate per transfer in GnRH antagonist and PPOS cycles. Secondary endpoints included the number of oocytes retrieved and the blastocyst formation rate. Ongoing pregnancy was defined as a pregnancy in which a fetal heart rate was confirmed by 10 weeks of gestation. Accumulated data from GnRH antagonist cycles and PPOS cycles at the institution were combined to compare oocyte retrieval outcomes and pregnancy rates per transfer. Additionally, a stratified analysis by age (<35, 35-39, and ≥40 years) was performed.

Results: Accumulated data included 149 GnRH antagonist cycles and 147 PPOS cycles. Oocyte retrieval outcomes and pregnancy rates per transfer were compared between the two protocols. There was no significant difference in the number of oocytes retrieved. However, the number of blastocysts showed a higher trend in the PPOS group compared to the GnRH antagonist group (p = 0.065). Across all age groups, the PPOS cycle tended to yield higher numbers of retrieved oocytes and blastocysts. Nonetheless, no significant difference was observed in the pregnancy rate per transfer between the two protocols.

Conclusions: Both the GnRH antagonist and PPOS protocols demonstrated trends toward higher numbers of retrieved oocytes and blastocysts, with comparable pregnancy rates across all age groups, suggesting similar clinical outcomes. A key limitation of this study is its retrospective design at a single institution; therefore, future prospective, large-scale studies are warranted.