O-132 Comparison of pregnancy rates in antagonist cycles after luteal support with GnRH-agonist versus progesterone – prospective randomized study
Authors: Buhbut E , Ben-Ami I , Nabulsi R , Avigdor G 
Published: June 2023

Study question

Are pregnancy rates in GnRH-antagonist cycles triggered with hCG and luteal phase support (LPS) with intranasal GnRH-agonist or vaginal progesterone comparable?

Summary answer

Nasal GnRH-agonist for LPS is associated with higher pregnancy rates compared with standard progesterone support in antagonist-based cycles triggered with hCG

What is known already

Regardless of its mechanism of action, the use of GnRH-a during the luteal phase in addition to progesterone, either in a single or multiple doses, has become a common practice as a part of ART protocols, based on its association with higher pregnancy and live birth rates . Its use as a sole agent for LPS has not gained the same popularity although studies supporting non-inferiority and even higher live birth rates with GnRH-a as a sole LPS agent have been published.

Study design, size, duration

A single-center, prospective, randomized study. A total of 150 patients underwent 164 GnRH-antagonist-based IVF cycles triggered with hCG and fresh embryo transfer. The study was conducted between June 9th, 2020, and May 5th, 2022.

Participants/materials, setting, methods

The study was conducted in the IVF clinic at University-affiliated tertiary medical center. Patients meeting the inclusion criteria who underwent antagonist-based IVF cycles and hCG triggering were enrolled. Computer-based randomization (1:1 ratio) was performed on the day of oocyte pickup (OPU). In both groups LPS was initiated on the evening of the OPU day with either GnRH-agonist nasal spray (Nafareline, nasal spray 200 mcg twice daily)or vaginal micronized progesterone (Utrogestan 300 mg, 3 times daily).

Main results and the role of chance

A total of 150 patients underwent 164 cycles, 127 cycles of which were included in the study cohort. Of them, 64 (50.4%) and 63 (49.6%) cycles were treated with GnRH-agonist or progesterone respectively as sole luteal phase support. A significantly higher pregnancy rate was found in the GnRH-a group compared with the progesterone group (43.8% versus 25.4% respectively; P = 0.030). After adjustment of several potential confounders such as age, body mass index (BMI), past obstetric history, number of IVF cycles, oocytes retrieved and embryos transferred, GnRH-agonist was still associated with a higher pregnancy rate (odds ratio 3.4, 95% confidence interval 1.4-8.3). Ovarian hyperstimulation syndrome (OHSS) rates were similar between the groups. Significantly higher progesterone levels were measured at β-hCG testing day in the GnRH-a group, both for the cleavage stage embryos (129.1±23.7 nmol/L vs. 97.7±48.9 nmol/L, P = 0.024) and for the blastocysts (127.2±0.1 nmol/L vs. 75.3±49.1 nmol/L, P = 0.034).

Limitations, reasons for caution

This study is not powered for analysis of clinical pregnancy rates, live birth rates and pregnancy outcomes. Larger studies are needed for research of these outcomes.

All patients participating were at low risk for OHSS, therefore the study is underpowered to find significant differences in early or late OHSS.Wider implications of the findings

Our findings suggest that intranasal GnRH-agonist administration as a sole luteal support in antagonist-based IVF cycles triggered with hCG results in higher pregnancy rates in comparison with traditional irritating vaginal preparations while not mandating additional support in the first weeks of pregnancy.

Trial registration number

Clinicaltrials.gov - NCT05484193