Assisted Reproduction Technology Treatment Outcomes in Female Carriers of 21-Hydroxylase Deficiency

Abstract

Context: Carriers of a CYP21A2 pathogenic variant exhibit distinct hormonal differences, yet their impact on assisted reproductive technology outcomes remains unknown.

Objective: To evaluate whether carriers of a CYP21A2 pathogenic variant exhibit differences in ovarian stimulation response and in vitro fertilization outcomes compared with noncarriers.

Design: A retrospective cohort study at a single, private, academic center.

Subjects: A total of 1284 subjects undergoing 1556 in vitro fertilization cycles were ultimately included in the analysis, comprising 244 carriers and 1040 noncarrier controls.

Exposure: Female monoallelic CYP21A2 mutation carrier status.

Main outcome measures: Live birth rates following frozen single euploid embryo transfer. Secondary outcomes included ovarian stimulation parameters, embryological development (fertilization and euploidy rates), and posttransfer outcomes (implantation, clinical pregnancy, and pregnancy loss rates).

Results: Baseline characteristics and ovarian stimulation parameters were similar between pathogenic CYP21A2 variant carriers and noncarriers. No significant differences were observed in live birth (50.7% vs 51.1%, P = .87), implantation (75.4% vs 73.4%, P = .99), or clinical pregnancy (63.3% vs 62.7%, P = .73) rates between carriers and noncarriers, respectively. Although a univariate analysis of fertilization rates (81.7% vs 83.3%, P = .008) showed a significance difference, this difference was not observed after adjusting for confounding variables in a multivariate analysis (adjusted odds ratio of 1.05; 95% CI, 0.93-1.18).

Conclusion: Female patients who carry a pathogenic CYP21A2 variant achieve in vitro fertilization outcomes comparable to noncarriers. These findings support maintaining standard assisted reproductive treatment protocols for carriers and help provide personalized counseling for carriers identified through genetic screening.

Keywords: ART; aOR; adjusted odds ratio; assisted reproductive technology; congenital adrenal hyperplasia; female infertility; fertilization in vitro; genetic carrier screening; heterozygote; ovarian function.