Speaker Ines Abdennebi

A French study was conducted across four fertility centers on progesterone inhibiting Luteinizing Hormone (LH) surge in duostim stimulation. The study is a part of the Biological and Immunological Studies on Translational Medicine (BISTM) study. The BISTM study, published in 2023, is a multicentre randomized controlled trial comparing the duostim protocol with two conventional stimulation cycles in poor ovarian responders. The duostim protocol involves two stimulations within the same cycle: the first in the follicular phase and the second immediately after the first oocyte pickup in the luteal phase. Approaches to inhibiting the LH surge vary by region, with Italians and Spaniards using antagonists and Chinese teams using progesterone. Ovulation is triggered differently as well, with some using Human Chorionic Gonadotropin (HCG) and others antagonists. The timing between stimulations also differs, with some starting immediately and others, like the Italians, waiting five days. The study offers insights into optimizing fertility treatments for poor ovarian responders.

A study was presented investigating progesterone's role in inhibiting the LH surge during the Duostim protocol. Progesterone's anti-gonadotropic properties, akin to combined hormonal contraception, were explored in the context of hormonal dynamics in women undergoing stimulation. The study, a multicentre randomized trial conducted between 2018 and 2021 in four French centers, aimed to assess the necessity and efficacy of LH surge inhibition by both endogenous and exogenous progesterone compared to a traditional antagonist protocol. Results aimed to optimize fertility treatment protocols, highlighting progesterone's reversible LH-suppressive effects upon cessation.

The study included women aged 20-41 meeting Bologna criteria for poor ovarian response, with up to two prior In Vitro Fertilization (IVF) attempts. Exclusions were applied to those with amenorrhea, Follicle-Stimulating Hormone (FSH) > 20 or less than one follicle. In the duostim group of the BISTM study, 44 women were randomized, with 32 receiving two stimulations within one cycle. One group was stimulated during the follicular phase, the other during the luteal phase. Treatment involved 300IU FSH daily starting day 3, with HCG triggering after each cycle. Monitoring occurred on days 5-6, 7-8, and day of administration. 

The study included relatively young, poor ovarian responders (mean age 35.3 years, Antral follicle count 5.1). Stimulation parameters were similar between groups, but the progesterone group showed significantly higher progesterone levels (10.7 vs. 0.8), lower LH levels (1.7 vs. 6.8), and no premature LH surges. Progesterone effectively inhibited LH surges without premature ovulation, highlighting its safety and cost-effectiveness compared to antagonists.

During the engaging discussion, the panel delved into several critical aspects of the duostim protocol. The most effective progesterone levels are required to reliably inhibit LH surges, emphasizing the importance of precise timing when introducing progesterone during the luteal phase. Considering the varied responses observed among participants, insights were shared on which patient profiles might derive maximal benefit from luteal phase supplementation. The debate extended to the choice between HCG and antagonist triggers across different phases of the duostim protocol. Consensus leaned towards the practical advantages of using HCG triggers, citing logistical ease and established clinical outcomes. Ethical considerations regarding embryo handling in fertility studies were briefly discussed, highlighting the moral responsibilities and complexities faced by researchers. The discussion also addressed the methodological challenges inherent in conducting randomized studies, underscoring the need for careful planning and ethical oversight in fertility studies.

European Society of Human Reproduction and Embryology, July 7-10, Amsterdam, The Netherlands