O-010 Luteal estradiol versus follicular GnRH antagonist for ovarian follicular synchronization in POSEIDON poor responders: a multicentric randomized controlled trial
Authors: Goel K , Mantravadi K C , Gedela D R 
Published: July 2024

Abstract

Study question
In order to improve follicular synchronization, is pre-treatment with Luteal Estradiol (LE) more efficacious than Follicular GnRH Antagonist (FA) among poor responders?

Summary answer
Luteal Estradiol is better than Follicular GnRH Antagonist to improve maturation rates in Poor Ovarian Responders (POR)

What is known already
In poor responders, follicular asynchrony is a major obstacle in optimizing the pregnancy rates and leads to more cycle cancellations and increases the requirement of additional pool up cycles. It imposes significant financial burden on patients. ESHRE recommendations on FA and LE are conditional and require better quality studies.
Several studies have evaluated the individual role of pre-treatment with LE or FA in synchronising the number of mature oocytes retrieved. There have been no studies comparing the efficacy of luteal estradiol versus follicular antagonist

Study design, size, duration
A randomised controlled trial was conducted at multiple centres of a private fertility clinic over 1year. Block randomization was performed using a Web-based randomization system.Allocation concealment was done using envelopes.
196 POR patients were randomized and 145 successfully completed the study. 80 patients(55.17%) received LE while 65 patients (44.83%) received FA. A per-protocol analysis was conducted. A subgroup analyses was done after excluding endometriosis and male-factor infertility as they could have been significant confounding factors.

Participants/materials, setting, methods
We randomised POR patients(POSEIDON criteria) into 2 arms, in their previous menstrual cycle. LE arm received oral Estradiol valerate 4 mg/day from 7days before expected menses to Day1 of menses. FA arm received Inj.Cetrorelix 0.25mg S.C from Day1 to Day5 of menses. The primary outcomes analysed were oocytes retrieved ,Follicular Output Rate(FORT), Follicle-to-Oocyte Index(FOI), Ovarian Sensitivity Index(OSI), maturation rate and MII /AFC. Secondary outcomes were cycle cancellation rates, fertilization rate, cleavage rate and blastulation rate.

Main results and the role of chance
There was a significant improvement in maturation rates with luteal phase pre-treatment using estradiol (LE) compared to follicular GnRH antagonist (FA) (0.72 ± 0.03 vs. 0.63 ± 0.03, p-value = 0.045). However, there were no statistically significant differences observed in the oocytes retrieved, Follicle-to-Oocyte Index (FOI), Follicular Output Rate (FORT), or Ovarian Sensitivity Index (OSI) between the two pre-treatment groups. These non-significant differences remained consistent among both expected (poseidon category 3 and 4) and unexpected (posiedon group 1 and 2) poor responders.
Secondary outcomes, including cycle cancellation rates, fertilization rate, cleavage rate, and blastulation rate, did not show significant variations between the luteal estradiol (LE) and follicular GnRH antagonist (FA) pre-treatment groups.
Subgroup analyses without endometriosis (N = 136) and severe male factor infertility (N = 122), revealed no significant differences between the two study groups in these specific subpopulations.

Limitations, reasons for caution
Limited generalizability due to small sample size, potential bias from lack of blinding, restricted insight into long-term outcomes, and patient heterogeneity are notable limitations in this study.

Wider implications of the findings
Among poor responders, luteal estradiol demonstrated a significant improvement in maturation rates, probably due to better follicle synchronicity at trigger, compared to follicular antagonist. It’s also more cost-effective and patient-friendly.
However, further research with larger sample size and long-term clinical endpoints are needed to validate these findings and optimise clinical strategies.

Trial registration number
CTRI registration no. CTRI/2023/06/053760