Medicine (Baltimore). 2026 Sep 4;105(36):e50581. doi: 10.1097/MD.0000000000050581.
ABSTRACT
RATIONALE: Cytochrome P450 oxidoreductase deficiency (PORD) is a rare autosomal recessive disorder caused by mutations in the POR gene, leading to impaired steroid hormone synthesis and a wide range of multisystem abnormalities. The condition is often associated with reproductive malformations and endocrine disorders, presenting clinically with symptoms such as infertility, menstrual irregularities, and adrenal dysfunction, and may be accompanied by skeletal malformations. Only a very limited number of patients have achieved successful pregnancies through assisted reproductive technology, and there is currently no standardized treatment strategy.
PATIENT CONCERNS: A 29-year-old woman presented with “7 years of infertility without contraception.”
DIAGNOSES: Genetic analysis identified compound heterozygous POR mutations (c.1820A>G/c.1474G>A), confirming PORD. Pelvic imaging revealed uterus didelphys. Endocrine evaluation demonstrated insulin resistance and adrenal dysfunction, and the patient fulfilled the diagnostic criteria for polycystic ovary syndrome.
INTERVENTIONS: Following unsuccessful long-protocol ovulation induction, a modified gonadotropin-releasing hormone antagonist protocol was implemented with metformin co-treatment for insulin sensitization. Stepwise glucocorticoid therapy (oral prednisone 5 mg/day → dexamethasone 0.5 mg/day → transition to hydrocortisone 20 mg/day during pregnancy) was administered for adrenal progesterone regulation. All embryos underwent vitrification, with subsequent single frozen-thawed blastocyst transfer.
OUTCOMES: Ovarian stimulation yielded 24 oocytes, resulting in 7 blastocysts. Successful singleton implantation was achieved. The pregnancy progressed without maternal metabolic or fetal complications, culminating in term delivery (39 weeks and 4 days) of a healthy male neonate (birth weight 3250 g, Apgar scores 9/10).
LESSONS: This case demonstrates that pregnancy attainment in complex PORD requires protocol individualization using gonadotropin-releasing hormone antagonists to mitigate premature luteinization, dynamic glucocorticoid titration to control adrenal steroid excess, and metabolic optimization addressing insulin resistance. The co-occurrence of POR mutations should be investigated in assisted reproductive technology failures with polycystic ovary syndrome-like presentations, particularly when accompanied by skeletal or genital tract anomalies.
PMID:42700033 | DOI:10.1097/MD.0000000000050581
