Endometrial Preparation Strategies for Frozen Embryo Transfer in Women with Adenomyosis: A Systematic Review of Hormone Replacement Therapy, Gonadotropin-Releasing Hormone Agonist, and Oxytocin Antagonists

Ni Luh Lany Christina, Dian Tjahyadi, Ruswana Anwar, Anita RachmawatiDepartment of Obstetrics and Gynecology, Hasan Sadikin General Teaching Hospital, Faculty of Medicine, Padjadjaran University, Bandung, West Java, IndonesiaCorrespondence: Ni Luh Lany Christina, Department of Obstetrics and Gynecology, Hasan Sadikin General Teaching Hospital, Faculty of Medicine, Padjadjaran University, Pasteur No. 38 Street, Pasteur, Bandung, West Java, 40161, Indonesia, Tel +6281353455466, Email [email protected]: Adenomyosis is associated with impaired reproductive outcomes, including reduced implantation potential, lower pregnancy rates, and increased miscarriage risk. Despite the widespread use of frozen embryo transfer (FET), the optimal endometrial preparation strategy for women with adenomyosis remains uncertain.Purpose: This systematic review aimed to evaluate the effectiveness of different endometrial preparation strategies, including hormone replacement therapy (HRT), gonadotropin-releasing hormone agonist (GnRHa)-based protocols, and oxytocin receptor antagonist therapy, in women with adenomyosis undergoing FET.Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Cochrane, Oxford, Scopus, and Wiley databases were searched until November 2024. Randomized controlled trials and comparative observational studies evaluating endometrial preparation strategies in women with adenomyosis undergoing FET were included. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool for randomized controlled trials and ROBINS-I for observational studies.Results: Seven studies were included, consisting of one randomized controlled trial and six observational cohort studies. The randomized trial found no significant differences in clinical pregnancy, chemical pregnancy, miscarriage, or live birth rates between HRT with GnRHa pretreatment and HRT alone. In contrast, several observational studies suggested that long-term GnRHa down-regulation combined with HRT may improve implantation, clinical pregnancy, ongoing pregnancy, and live birth outcomes, particularly in selected patients with more severe adenomyosis characteristics. Oxytocin receptor antagonist administration was associated with a lower early miscarriage rate.Conclusion: GnRHa-based endometrial preparation, particularly long-term down-regulation, may provide potential benefits for selected women with adenomyosis undergoing FET, although randomized evidence remains inconclusive. Oxytocin receptor antagonist therapy may reduce early miscarriage risk, but further studies are required. Additional randomized controlled trials are needed to establish optimal GnRHa duration, patient selection criteria, and standardized treatment strategies.Keywords: adenomyosis, HRT, GNRH agonist down-regulation, GNRH agonist, oxytocin antagonist