P-347 Pituitary suppression plus aromatase inhibitors improve the ongoing pregnancy rate in women with adenomyosis

Abstract Study question Does pretreatment with GnRHa plus aromatase inhibitor improve the ongoing pregnancy rate in women with severe adenomyosis? Summary answer The pretreatment with GnRH agonist (GnRHa) plus aromatase inhibitor (AI) may increase the ongoing pregnancy rate in patients with adenomyosis undergoing FET,offering a new strategy What is known already Adenomyosis is driven by excess estrogen due to high tissue aromatase activity, which leads to chronic inflammation, progesterone resistance, and impaired fertility in affected women. Adenomyosis reduced the live birth rates and increased miscarriage rates, especially in assisted reproductive technology (ART) cycles. GnRHa downregulation may help improve uterine receptivity by reducing inflammation, decreasing myometrial contractility, and lowering estrogen levels, which are known to impair implantation in patients with adenomyosis. Small case series have explored IVF outcomes using a GnRH agonist/Aromatase Inhibitor for patients with adenomyosis. Study design, size, duration Retrospective single-center study at IVI Roma to compare frozen embryo transfer (FET) success rates in patients with adenomyosis, with and without a pretreatment protocol. A total of 147 blastocyst-stage single embryo transfers (SETs) were analyzed: 105 SETs in the non-pretreatment FET (no-PT-FET) group, which included hormonal or natural cycles, and 42 SETs in the pretreatment FET (PT-FET) group. The ongoing pregnancy rate was the main outcome. Secondary outcomes were clinical pregnancy and miscarriage rates. Participants/materials, setting, methods Women aged 30-49 who underwent blastocyst SET were included in the study. Adenomyosis was diagnosed according to the MUSA criteria, with at least one direct sign of the disease. The pretreatment protocol consisted of GnRHa 3.75 mg for two months and AI (5 mg) for 21 days.FETs with natural or artificial cycles were included in the control group.Statistical analyses included chi-square and Student’s t-tests for group comparisons.Logistic regression adjusting for confounders was used for LBR. Main results and the role of chance There were no significant differences in mean age, BMI, donor age, sperm characteristics, number of embryos transferred, endometrial thickness and days of endometrial preparation before FET between aGnRH/AI cycles and other cycles. No statistical differences were found in the day of embryo transfer or embryo morphology/quality. Women with adenomyosis receiving PT-FET had higher ongoing pregnancy rate (47.06%, 95%CI 29.78-64.87) than those in the no-PT-FET (25.96%, 95% CI 17.86-35.48), p = 0.03. The pregnancy rate was also higher in PT-FET (73.17%, 95% CI 57.06-85.78) compared to no-PT-FET (43.27%, 95% CI 33.59-53.35), p = 0.002. The PT-FET had a higher clinical pregnancy rate (65.85%, 95% CI 49.41-79.92) than no-PT-FET (32.69%, 95% CI 23.81-42.59), p < 0.001. The miscarriage rate was lower in the PT-FET without reaching statistical significance (27.27%, 95% CI 10.73-50.22) versus no-PT-FET (37.78%, 95% CI 23.77-53.46), p = 0.56. Multivariate analysis adjusted for confounders (patients and oocyte age, BMI, sperm parameters, endometrial thickness, blastocyst stage/grade) showed a higher ongoing pregnancy rate in the adenomyosis patients receiving PT-FET compared to no-PT-FET (OR 2.52, 95% CI 1.13-5.85; p = 0.02). The miscarriage rate, after the multivariate analysis adjusted for confounders, showed no differences in PT-FET vs no-PT-FET (OR 1.21, 95% CI 0.40-2.61; p = 0.72). Limitations, reasons for caution The study’s small sample size, single-center design, and lack of randomization limit generalizability and introduce potential bias. Larger multicenter studies are needed to validate these findings, refine treatments, and establish standardized protocols. Collaboration with IVF centers is crucial to assess the impact of this new strategy for adenomyosis before ET. Wider implications of the findings The pretreatment with GnRHa/AI decreased the hyperestrogenism, improving the LBR in women with adenomyosis. Further research should explore the molecular mechanisms of uterine factor infertility related to estrogen suppression in adenomyosis to improve outcomes. The AI may increase the integrin expression in the endometrium, improving endometrial receptivity. Trial registration number No