Clinical Features of an Unrecognized 21-hydroxylase Deficiency Woman During Controlled Ovarian Hyperstimulation

Correspondence To the Editor: Nonclassic congenital adrenal hyperplasia (NCAH) due to 21‑hydroxylase deficiency (21‑OHD) is one of the most common autosomal recessive disorders. Affected individuals typically present signs and symptoms related to excessive androgens. In the process of assisted reproductive technique (ART), the clinical features of NCAH may evade our attention and, therefore, be left untreated. Here, we present a case of NCAH, who underwent controlled ovarian hyperstimulation (COH). A 26‑year‑old woman with a 4‑year history of primary infertility was referred to our hospital on August 9, 2013. She had a regular menstrual cycle (3–4/29–30 days) without hirsutism or acne. Hysterosalpingography showed patent fallopian tubes with abnormal shapes. Semen analysis of her husband was normal. The patient was found to have thin endometrium at any time during menstrual cycles (3–6 mm) and hysteroscopy revealed a normal uterine cavity. Her basal hormonal levels on day 2 of menstrual cycle were as follows – follicle stimulation hormone (FSH): 6.0 IU/L, luteinizing hormone (LH): 3.1 IU/L, estradiol (E2): 231 pmol/L, prolactin: 7.9 ng/ml, testosterone (T): 3.7 nmol/L (range: 0–2.53 nmol/L), and androstanedione (A): >35 nmol/L (range: 1.4–14.3 nmol/L). Her thyroid hormones, serum cortisol levels, plasma renin, angiotensin II, aldosterone, and serum electrolytes levels were normal. Computed tomography of adrenals did not find an abnormality. The patient was given compound cyproterone acetate (Diane‑35, Bayer) for 3 cycles. Three months later, her androgen levels were still very high with T level of 4.0 nmol/L and A level more than 35 nmol/L. From then on, prednisone, 5 mg/d orally, was prescribed to her. The patient underwent in vitro fertilization cycle because of a tubal factor. On the first day of menstrual cycle, she was given 3.75 mg of leuprorelin (Beiyi, Livzon pharmaceutical, China) for pituitary down‑regulation. Twenty‑eight days after leuprorelin injection, hormone measurement showed FSH: 2. The thickness of endometrium was 3 mm. Two days later, the P level dropped to 1.5 nmol/L, but A level was still >35 nmol/L. She was given 1.8 mg of leuprorelin again. Meanwhile, prednisone, 10 mg/d, was administered. Fourteen days after second injection of leuprorelin, her P level decreased to 0.7 nmol/L and A level was <1.05 nmol/L. Recombinant FSH (Puregen, Organon) 50 IU/d + HMG (Livzon pharmaceutical) 75 IU/d was started to stimulate follicle growth. At the same time, prednisone was reduced to 5 mg/d. During COH, serum levels of P and A elevated again (P 5.6–8.1 nmol/L; A …