O-011 Is there a need for LH surge inhibition by GnRH-antagonists in luteal phase stimulation in poor ovarian responders undergoing Duostim? Efficacy of natural progesterone
Authors: Abdennebi I , Géraldine P B , Nicolas C , Elodie D , Seydou G , Camille J , Maud P , Hélène B , Nathalie M 
Published: July 2024

Abstract

Study question
Is there a need for LH surge inhibition by GnRH-antagonists in luteal phase stimulation in poor ovarian responders undergoing Duostim?

Summary answer
Inhibition of the LH surge by progesterone during the luteal phase of duostim protocols in POR appears to be effective, safe and makes GnRH-antagonists unnecessary.

What is known already
High levels of progesterone have long been shown to reversibly block the LH surge associated with increased estradiol levels, by reducing GnRH’s pulsatility from the hypothalamus. This inhibition is the basis of progestin-only contraceptives and has been shown to be completely reversible by discontinuing the progestin, and even seems to have a potentiating effect on the surge which occurs in the subsequent few days

Study design, size, duration
This is a secondary analysis of the BISTIM study, a multicentre, open-labelled randomized controlled trial, performed in 4 french IVF centers from 2018 to 2021, designed to compare Duostim protocol versus two follicular stimulations. We here present a paired-controlled study including patients randomized in the Duostim group, who underwent 2 consecutive stimulations in the same menstrual cycle, we compare the follicular phase stimulation with GnRH-antagonist versus the luteal phase stimulation with progesterone.

Participants/materials, setting, methods
The BISTIM study recruited poor ovarian reserve women defined with Bologna criteria who enrolled in an IVF or ICSI program, aged from 20 to 41, with BMI from 19 to 32, with no more than 2 previous IVF cycles. Women with amenorrhea, FSH &gt;20 UI/L or CFA &lt;1 were not included. 32 of them underwent two stimulations, consecutively.

Main results and the role of chance
For the same group of 32 women, stimulation parameters were similar between 1st and 2nd stimulations (stimulation duration, gonadotropin doses, number of retrieved oocytes). As expected, progesterone levels were significantly higher at D5 in the study group compared to controls (mean 34.8 ng/ml, Q1-Q3 [18.4 – 51.6])) and were still significantly higher at HCG-day (10.7 ng/ml, Q1-Q3 [2.7 – 14.3])), despite the addition of natural exogenous progesterone. LH levels were significantly lower in the progesterone group, regardless of the day of stimulation: at HCG day mean LH was 1,7 UI/L in the study group versus 6.8 UI/L in the control group, p &lt; 0.001. In the Duostim group no premature LH surge/ovulation was observed, however, 2 cancellations for premature ovulation were reported with antagonist protocol in the control group of the BISTIM study.

Limitations, reasons for caution
This study was carried out on a limited number of subjects (n = 32), all of whom were poor responders.

Wider implications of the findings
This study shows the effectiveness of LH surge inhibition by progestins, which represent a less expensive and more patient-friendly treatment than traditional protocols. Further studies are needed to determine the best protocol (type and doses of progestins) to effectively inhibit the LH surge, and on larger and different cohorts.

Trial registration number
2017-A00498-45