Endocrine profiles and cycle characteristics of infertile 17α-hydroxylase/17,20-lyase Deficiency Patients undergoing assisted Reproduction Treatment: a retrospective cohort study

BACKGROUND: 17α-hydroxylase/17,20-lyase deficiency (17-OHD) is a rare form of congenital adrenal hyperplasia caused by CYP17A1 gene variants. Female patients with 17-OHD demonstrate a broad clinical spectrum, including oligomenorrhea or amenorrhea and infertility, often as the sole manifestation. However, no spontaneous pregnancies in affected women have been reported. OBJECTIVE: This retrospective cohort study aimed to explore the endocrine characteristics and assisted reproductive technique (ART) performance in women with 17-OHD. METHODS: Five women were referred for primary infertility in a university-affiliated hospital over an eight-year period. The endocrine profiles and cycle characteristics during a total of nine cycles of ovarian stimulation and eight cycles of frozen-thawed embryo transfer (FET) were described in details. RESULTS: Three cases had homozygous variants and two cases had compound heterozygous variants, including one novel missense variant (p.Leu433Ser) in the CYP17A1 gene. Despite dual-suppression of progesterone (P) production by glucocorticoid and gonadotropin releasing hormone agonist, gradually increased P level, relatively low estradiol concentrations and thin endometrium were observed, negating fresh embryo transfer. During FET cycles, appropriate treatment resulted in low serum P levels and adequate endometrial thickness, leading to four live births. CONCLUSIONS: Our findings demonstrate that continuous elevation of serum P during follicular growth impairs endometrial receptivity, the likely cause of female infertility in 17-OHD. Therefore, female infertility caused by 17-OHD is suggested as an indication for freeze-all strategy, with promising reproductive prognoses following segmented ovarian stimulation and FET treatment.