Gonadotropin-Releasing Hormone Agonist Applications in Luteal Phase Support

The luteal phase follows ovulation and is characterised by progesterone secretion from the corpus luteum to prepare the endometrium for embryo implantation. In assisted reproductive technology (ART), luteal phase deficiency may compromise implantation and early pregnancy maintenance. Gonadotropin-releasing hormone agonists (GnRH-a) have been introduced as an adjunctive luteal support strategy, acting both centrally to induce endogenous luteinising hormone pulses and peripherally via endometrial GnRH receptors. Clinical interest has centred on their use in fresh IVF/ICSI cycles, hormone replacement therapy frozen-thawed embryo transfer (HRT-FET) cycles and GnRH antagonist-triggered protocols. Pilot trials and meta-analyses suggest that single- or multiple-dose regimens of GnRH-a can increase implantation, clinical pregnancy and live birth rates without substantially increasing ovarian hyperstimulation syndrome risk. However, heterogeneity in stimulation protocols, timing of administration and patient characteristics has led to variability in reported outcomes. Current research aims to define optimal dosing schedules, elucidate mechanisms of endometrial receptivity enhancement and establish safety profiles across diverse populations. The integration of GnRH-a into personalised luteal support regimens holds promise for improving global ART success rates and reducing the burden of repeated treatment cycles.

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Gonadotropin-Releasing Hormone Agonist Applications in Luteal Phase Support publication trend

The graph below shows the total number of articles in gonadotropin-releasing hormone agonist applications in luteal phase support across all publications each year (not limited to Nature Index journals).

Technical terms

Gonadotropin-releasing hormone agonist: A synthetic analogue of GnRH that initially stimulates and then downregulates pituitary gonadotropin release.

Luteal phase: The post-ovulation segment of the menstrual cycle when progesterone from the corpus luteum prepares the endometrium for implantation.

Luteal phase support: Administration of hormones or agents to enhance endometrial receptivity and maintain early pregnancy in ART.

Frozen-thawed embryo transfer (FET): Transfer of embryos cryopreserved in a prior cycle after controlled endometrial preparation.

Hormone replacement therapy cycle (HRT-FET): A regimen using exogenous oestrogen and progesterone to mimic the natural cycle for endometrial development without ovarian stimulation.

References

1. Effect of luteal-phase GnRH agonist on frozen-thawed embryo transfer during artificial cycles: a randomised clinical pilot study. Frontiers in Endocrinology (2023).
2. Additional single dose GnRH agonist during luteal phase support may improve live birth rate in GnRHa-HRT frozen–thawed embryo transfer cycle: a retrospective cohort study. BMC Pregnancy and Childbirth (2023).
3. Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis. Reproductive Biology and Endocrinology (2010).
4. Single-Dose Versus Multiple-Dose GnRH Agonist for Luteal-Phase Support in Women Undergoing IVF/ICSI Cycles: A Network Meta-Analysis of Randomized Controlled Trials. Frontiers in Endocrinology (2022).
5. GnRH agonist as a luteal support in IVF cycle: mini-review—is there a role?. Middle East Fertility Society Journal (2022).
6. GnRH agonists to sustain the luteal phase in antagonist IVF cycles: a randomized prospective trial. Reproductive Biology and Endocrinology (2019).