Reproductive endocrine characteristics and in vitro fertilization treatment of female patients with partial 17α-hydroxylase deficiency: Two pedigree investigations and a literature review

BACKGROUND: 17α-hydroxylase/17, 20-lyase deficiency (17-OHD) is caused by the mutations of the CYP17A1 gene. The classical phenotype of 17-OHD includes hypertension, hypokalemia, and abnormal sexual development, with partial 17-OHD typically less severe than the complete deficiency. Infertility is always one of the main clinical manifestations of partial 17-OHD. However, to date, the pregnancy potentials of partial 17-OHD female patients have rarely been investigated, and few live-birth cases have been reported among them. Moreover, the reproductive endocrine characteristics of partial 17-OHD female patients have not been completely clarified and the treatment skills of in vitro fertilization and embryo transfer (IVF-ET) have not been well summarized yet. METHODS: Two Chinese infertile female patients clinically diagnosed as partial 17-OHD were enrolled and their pedigree investigations were performed. Hormones were determined to depict the endocrine conditions of partial 17-OHD female patients. The adrenocorticotropic hormone (ACTH) stimulation test was performed to evaluate the functions of the adrenal cortex. Genotype analysis was conducted by next-generation sequencing (NGS) and Sanger sequencing was used to verify the results. IVF-ET was performed for the treatment of their infertility. Specifically, the progestin-primed ovarian stimulation (PPOS) protocol was chosen for the controlled ovarian hyperstimulation (COH) cycles, and the hormone replacement treatment (HRT) protocol was adopted for the endometrial preparation in frozen–thawed embryo transfer (FET) cycles. RESULTS: Hormone assays revealed a reduced estradiol (E2) and testosterone (T) level, and an elevated progesterone (P4) level. The classic ACTH stimulating test evidenced a suboptimal response of cortisol to ACTH. Genotype analysis demonstrated that the proband1 carried two variants: c.1459_1467del (p.Asp487_Phe489del)(het) and c.995T>C (p.lle332Thr)(het). The proband2 was found to be a homozygote with the mutation of c.1358T>A (p.Phe453Ser)(hom). The two female patients both succeeded in pregnancy and delivery of healthy babies through IVF-ET, with the usage of PPOS, HRT, and low-dose glucocorticoids. CONCLUSIONS: Partial 17-OHD female patients manifested menstrual cycle disorders and infertility clinically; displayed high P4 and low E2 and T; showed sparse pubic hair in physical examinations; and revealed multiple ovarian cysts in ultrasonic visualization. Moreover, the pregnancy potentials of infertile partial 17-OHD women seemed to increase with the adoption of IVF-ET. Considering the sustained elevated P4 level, PPOS is a feasible protocol for them in COH.