JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):76
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263655

P-64. Does prior GnRH agonist suppression improve live birth rates in women with moderate to severe endometriosis undergoing IVF, compared to IVF without hormonal suppression?

Aline Borlenghi De Freitas¹, Isabella Alves Tambosi¹, Daniela Luongo Siqueira Lopes De Castro¹, Maria Monica Pereira¹

¹ Centro Universitário São Camilo - São Paulo - SP - Brasil

Objective: This study aimed to assess whether prior suppression with GnRH agonists improves live birth rates in women with moderate to severe endometriosis undergoing in vitro fertilization (IVF), compared to IVF without hormonal suppression. Additionally, it sought to identify the most effective GnRH agonist protocols regarding duration and administration route for optimizing live birth outcomes in this patient population.
Methods: A systematic literature review was conducted in accordance with PRISMA guidelines (simplified format), using the databases Medline (via PubMed), LILACS (via BVS), and Scopus. Search strategies were adapted for each database using the same descriptors and Boolean operators. The descriptors used were: Endometriosis, Fertilization in Vitro, and Gonadotropin-Releasing Hormone. The search was performed between June 30 and July 10, 2025. Studies were eligible if they included women diagnosed with moderate to severe endometriosis (stage III or IV according to ASRM classification or equivalent), undergoing IVF with or without prior GnRH agonist suppression. Only randomized controlled trials, prospective and retrospective cohort studies, and clinical studies published in the last 20 years were included. Exclusion criteria comprised studies involving minimal/mild endometriosis (stage I or II), absence of a comparator group, systematic reviews, editorials, letters, in vitro studies, animal models, or studies focused on infertility due to causes other than endometriosis. A total of 201 articles were identified (PubMed: 17; Scopus: 124; BVS: 60) and screened by three independent reviewers. After the removal of 66 duplicates, 135 articles remained. Articles selected by at least two reviewers were included in the final analysis. Based on title and abstract screening, 122 articles were excluded for not meeting inclusion criteria.
Results: The majority of included studies demonstrated improved reproductive outcomes associated with prior GnRH agonist suppression, particularly with long or ultra-long protocols lasting approximately 2 to 3 months. These regimens were linked to increased implantation rates, higher clinical pregnancy rates, and improvements in live birth rates among women with stage III or IV endometriosis. Some studies showed statistically significant enhancements in live birth rates with ultra-long protocols compared to standard IVF or antagonist regimens. Others observed favorable trends in implantation and clinical pregnancy without reaching statistical significance. Conversely, a subset of studies reported no significant benefit of GnRH agonist suppression, particularly when comparing different GnRH analogues or shorter durations of suppression. Regarding the administration route, all included studies utilized injectable GnRH agonists; no current evidence from comparative clinical trials evaluates oral GnRH agonists in this context. Thus, the impact of an oral GnRH analogue formulation, such as those under development by pharmaceutical companies (e.g., AbbVie), remains unknown and warrants future investigation. Concerning treatment duration, while long (2–3 months) and ultra-long protocols appear more effective in improving clinical outcomes, no definitive evidence clarifies the optimal length of suppression universally. Some data suggest that shorter or modified regimens may produce similar live birth rates with reduced gonadotropin consumption and treatment burden. Hence, no firm conclusion regarding the best duration of GnRH agonist pre-treatment can yet be drawn.
Conclusion: Current evidence suggests that prior suppression with GnRH agonists, especially using long or ultra-long injectable protocols, may improve live birth rates in women with moderate to severe endometriosis undergoing IVF. However, not all studies report statistically significant differences. Protocol duration and patient selection appear to be key factors influencing effectiveness, while the route of administration remains exclusively injectable in clinical practice to date. More high-quality randomized controlled trials are necessary to confirm these findings, elucidate the optimal protocol duration, and evaluate emerging oral GnRH agonists. Treatment individualization, considering disease severity, ovarian reserve, patient preferences, and resource availability, remains essential.