Administration of dehydroepiandrosterone improves endometrial thickness in women undergoing IVF/ICSI: a systematic review and meta-analysis.

Background: The positive effects of dehydroepiandrosterone (DHEA) on oocyte and embryo quality improvement are often concerned. While the results on DHEA-induced endometrial improvement are controversial.

Objective: To evaluate whether DHEA intervention improved endometrial function and reproductive outcomes during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles and to thus provide clinical recommendations.

Data sources: PubMed, Cochrane Library, EMBASE and Web of Science from database inception to 31 July 2024, without language restrictions. The references of conference proceedings and websites on clinical trials were manually checked.

Study design: Systematic review and meta-analysis.

Study eligibility criteria: Parallel-controlled randomized controlled trials (RCTs) design; women underwent IVF/ICSI, patients in the experimental group received adminstration with DHEA, whereas the control group received with or without placebo; and the outcomes included reproductive or endometrial function.

Study appraisal and synthesis methods: RCTs evaluating the effects of DHEA on IVF/ICSI outcomes were included. Risk of bias and quality of evidence (QoE) were assessed according to the Cochrane Collaboration's tool and the Grading of Recommendations Assessment, Development and Evaluation system. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were assessed by random-effects or fixed-effects models. Subgroup and meta-regression analyses were used to find sources of heterogeneity. Trial sequential analysis was used to judge the stability of the outcomes. Trial sequential analysis was used in order to control for random errors.

Results: A total of 16 trials included 1973 women. DHEA treatment significantly increased endometrial thickness (MD = 0.93, CI: 0.27 to 1.60; low QoE), which helped improve clinical pregnancy rate (CPR) (OR = 1.34, 95% CI: 1.08 to 1.67; low QoE). DHEA administration also increased the quality of oocyte and embryo [including the number of oocytes retrieved (MD = 0.73, CI: 0.36 to 1.10; low QoE), oocytes fertilized (MD = 0.48, CI: 0.10 to 0.87; low QoE), transferred embryos (MD = 0.27, CI: 0.09 to 0.46; very low QoE), and high-quality embryos (MD = 0.65, CI: 0.27 to 1.03; low QoE)]. Subgroup and meta-regression analyses revealed that heterogeneity might be related to disease type, ovarian stimulation protocol, and addition time of DHEA treatment. There was insufficient evidence to reach a conclusion regarding the live birth rate/ongoing pregnancy rate, miscarriage rate, and MII oocyte number of DHEA. And no severe adverse effects were observed with DHEA administration. Due to the apparent improvemen in the CPR, women with thin endometrium might benefit from DHEA cotreament.

Conclusions: Due to the limited sample size and methodological problems, the QoE was low to very low; hence, the results should be interpreted with caution. The effectiveness of DHEA requires more research before it can be considered for clinical practice.

Prospero registration: CRD42023428885.