P-357 Downregulation (DR) with combined gonadotropin-releasing hormone agonist (GnRHa) and aromatase inhibitor (AI) optimizes the frozen-thawed embryo transfer (FET) results in women with adenomyosis
Authors: Salkar J , Hegde V , Agarwal A , Vytla D , Singh S , Bommakanti L , Mogili I 
Published: June 2023

Abstract

Study question
Does combined GnRHa & AI therapy for downregulation in women with adenomyosis optimize the FET success rates / outcomes on par with women without adenomyosis?

Summary answer
GnRHa combined with AI used for downregulation in women with adenomyosis optimized the outcomes of frozen–thawed embryo transfer cycle on par with women without adenomyosis.

What is known already
Women with adenomyosis have lower rates of successful implantation via altered molecular expressions in the endometrium due to local hyperestrogenism & also an increased risk of early pregnancy loss (Munro et al 2019). DR improves the clinical pregnancy rate by reducing the endometrial inflammatory reaction and/or myometrial contractility and their impact on uterine receptivity in women with adenomyosis undergoing FET (Sania Latif et al 2021). Combined treatment for uterine adenomyosis with Anastrazole plus GnRHa showed better results than dienogest treatment with a higher reduction of symptoms & higher pregnancy rates (M Sbracia & F Scarpellini, 2018).

Study design, size, duration
A Retrospective cohort study conducted at a tertiary care fertility unit. Data for 326 women with/without adenomyosis undergoing frozen–thawed embryo transfer after IVF was was retrieved from the hospital's database and analyzed for a period between September 2021 to November 2022.

Participants/materials, setting, methods
Women with adenomyosis (n = 107) received Anastrozole 1mg/day for 2months plus 3doses of Inj. Goserelin 3.6mg subcutaneously at 28days interval between 2successive doses. Hormone replacement therapy (HRT) was started 2weeks after the 3rddose of Inj. Goserelin & FET was performed after an optimum endometrial thickness (EMT) was achieved. For women without adenomyosis (n = 219) HRT was started on cycle Day-2 & FET was performed after achieving an optimum EMT. Serum beta-hCG was performed on Day15 after FET.

Main results and the role of chance
Statistical analysis was performed using SPSS20version. Normally distributed continuous variables were compared using a student t-test, and categorical variables were compared by χ2 and Fisher's exact test, where appropriate. To reduce selection bias, propensity score matching was used, and propensity matching yielded 99 pairs.
Baseline characters like age (p-value=0.36), BMI (p-value=0.12), duration (p-value=0.28), type (p-value=1) & cause (p-value=0.3) of infertility, endometrial thickness (p-value=0.37), day of embryo transfer (p-value=0.57) were comparable for the two groups. FET results in terms of positive pregnancy test (Serum beta-hCG &gt; 50mIU/ml) were found to be 68.21% for the DR- FET group and 67.71% for the HRT group which were comparable(p-value=0.17). This suggests that downregulation in women with adenomyosis helps achieve success rates similar to women without the disease.
Pregnancy outcomes like miscarriage (15 vs 13.13 %, p-value=1.00), biochemical pregnancy (3.03 vs 2.02 %, p-value=1.00) and ectopic pregnancy (1.01 vs 0 %, p-value=0.49) rates analyzed between the DR FET and HRT groups showed no statistically significant difference. Clinical pregnancy rates were almost similar for the 2 groups (55.71 Vs 57.46%, p-value=0.65).
Thus, we conclude that downregulation with combined GnRHa and AI optimizes the frozen-thawed embryo transfer results in women with adenomyosis on par with women without adenomyosis.

Limitations, reasons for caution
This is a retrospective study and hence randomized comparison was not possible. Women were followed up for 12 weeks of pregnancy, hence live birth rates were not analyzed in our study.

Wider implications of the findings
Combining the two treatment modalities (GnRHa + AI) which work at different sites optimizes IVF success rates & pregnancy outcomes. Hence we suggest that well-designed prospective randomized studies are needed to further analyze the synergistic role of this drug combination for downregulation in women with varied severity of adenomyosis.

Trial registration number
Not applicable