The effectiveness of prolonged downregulation with gonadotrophin-releasing hormone analogue (GnRHa) treatment in women with adenomyosis undergoing IVF/ICSI: A systematic review and meta-analysis

Importance: Adenomyosis can reduce the chance of clinical pregnancy in women undergoing assisted conception. Treatment with prolonged gonadotrophin-releasing hormone analogue (GnRHa) downregulation prior to IVF/ICSI has been postulated to improve pregnancy outcomes.

Objective: We aimed to evaluate the effectiveness and safety of prolonged GnRHa treatment (minimum one month) versus no pre-treatment in women with adenomyosis undergoing IVF/ICSI using a systematic review and meta-analysis.

Data sources: We searched electronic databases: Embase (OVID), MEDLINE® (OVID), APA PsycInfo (OVID), Maternity & Infant Care Database (MIDIRS (OVID), HMIC Health Management Information Consortium (OVID) and ClinicalTrials.gov from inception until 27th of March 2023.

Study selection and synthesis: We included studies that reported on women with adenomyosis receiving GnRHa to down-regulate the hypothalamic-pituitary-ovarian axis for one to six months before IVF/ICSI. We pooled data using the Haensel-Mantel method and reported using Odds Ratio (OR) with 95 % confidence intervals (CI). We assessed the quality of included studies using the Newcastle-Ottowa Scale and confidence in evidence using the GRADE criteria. Bias analysis was conducted via the Cochrane recommended tool (RevMan Web, Academic License).

Main outcomes and results: We screened 365 citations and eight retrospective studies were included in the meta-analysis (n = 2422 women). The median age was 34 years [IQR 31.95-35.05], median BMI 21.30 kg/m² [IQR 21.05-23.55] and median duration of GnRHa downregulation was 2.5 months [Range 1-4; IQR 1.37-3]. Women with adenomyosis receiving prolonged GnRHa treatment had a higher implantation rate 1/OR 1.69 [95 % CI 1.09, 2.56], I² = 81 %, (P = 0.02) and clinical pregnancy rate 1/OR 1.42 [95 % CI 1.03, 2.0], I² 70 %, P = 0.03. There was no overall difference in live birth rate 1/OR 1.12 [95 % CI 0.70, 1.79], I² = 78 %, p = 0.63), miscarriage rate 1/OR 0.92 [95 % CI 0.63, 1.28, P = 0.61, I² 0 % or mean number of oocytes retrieved (10 oocytes [IQR 8.95; 11.15] vs. 9.28 [IQR 8; 10.20], p = 0.22) between groups.

Conclusions and relevance: The benefit of prolonged GnRHa treatment in women with adenomyosis undergoing assisted conception treatment is uncertain based on existing retrospective studies. Implantation and clinical pregnancy rates were higher following prolonged downregulation in this population, though there was no statistically significant difference in live birth and miscarriage rates. Given the limited, low-quality existing data, there is a need for a well-designed, prospective randomised controlled trial to precisely evaluate the effectiveness of prolonged GnRHa treatment in this population.