In vitro fertilization-frozen embryo transfer in a patient with cytochrome P450 oxidoreductase deficiency: a case report

Abstract

Cytochrome P450 enzymes are required for the synthesis of cholesterol and steroid hormones. Cytochrome P450 oxidoreductase (POR) donates electrons to microsomal cytochrome P450 enzymes. POR deficiency (PORD) is a rare autosomal recessive disease. In patients with PORD, steroid hormone synthesis is disrupted, which can cause infertility. The objective of this study was to report on a case of in vitro fertilization–frozen embryo transfer (IVF–FET) in a patient with PORD. The patient’s hormone (i.e. 17α-hydroxyprogesterone) and electrolyte levels were within normal ranges ordinarily. Upon controlled ovarian stimulation, follicle growth was normal, but serum estrogen and progesterone levels were low and high, respectively. The serum progesterone level was elevated after long-acting gonadotropin-releasing hormone agonist treatment, and an endometrial biopsy showed a change in the proliferative phase. Genetic tests detected homozygous mutations (c.976 T > G, p.Y326D) in exon 10 of the POR gene. The frozen embryo was transferred during the administration of hormone replacement therapy. No significant morphological or metabolic abnormalities were observed in the neonate. Our findings suggest that infertile women with normal hormone levels may have metabolic diseases such as PORD. Further studies are needed to determine the cause of these diseases and to assist pregnancy in such women.

Chinese abstract

细胞色素P 450是合成胆固醇和类固醇激素所必需的酶。细胞色素P 450氧化还原酶(POR)向微粒体细胞色素P 450酶提供电子。POR缺乏症(PORD)是一种罕见的常染色体隐性遗传病。在PORD患者中, 类固醇激素的合成受到干扰, 从而导致不孕。本研究报道一例PORD患者接受体外受精-冷冻胚胎移植(IVF-FET)。患者的激素(即17a-羟基孕酮)和电解质水平通常在正常范围内。在控制性卵巢刺激下, 卵泡正常生长, 但血清雌激素水平较低, 孕酮水平较高。长效促性腺激素激动剂治疗后血清孕酮水平升高, 子宫内膜活检显示为增殖期改变。基因检测POR基因外显子10有纯合子突变(C.976 T > G, p.Y326D)。在激素替代治疗期间行冷冻胚胎移植。新生儿无明显的形态学或代谢异常。我们的研究表明, 激素水平正常的不孕女性可能患有代谢疾病, 如PORD。这些女性仍需要进一步研究以确定疾病的病因来助其怀孕。

Keywords:

• P450 oxidoreductase deficiency
• in vitro fertilization
• hormone synthesis disorder
• progesterone
• pregnancy

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This work was supported by The National Natural Science Foundation of China (grant number 81200410).