北京大学学报(医学版) ›› 2022, Vol. 54 ›› Issue (4): 751-755. doi: 10.19723/j.issn.1671-167X.2022.04.027

• 疑难/罕见病例分析 • 上一篇    下一篇

46XX-17α-羟化酶缺乏症助孕成功1例

张春梅1,杨蕊1,李蓉1,乔杰1,王海宁2,王颖1,*()   

  1. 1. 北京大学第三医院妇产科,生殖医学中心,北京 100191
    2. 北京大学第三医院内分泌科,北京 100191
  • 收稿日期:2020-11-03 出版日期:2022-08-18 发布日期:2022-08-11
  • 通讯作者: 王颖 E-mail:wangying02114@bjmu.edu.cn
  • 基金资助:
    国家自然科学基金(81601243);国家自然科学基金(81670701);国家自然科学基金(81550022);国家自然科学基金(81873833)

Successful assisted reproductive technology treatment for a woman with 46XX-17α-hydroxylase deficiency: A case report

Chun-mei ZHANG1,Rui YANG1,Rong LI1,Jie QIAO1,Hai-ning WANG2,Ying WANG1,*()   

  1. 1. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
    2. Department of Endocrinology, Peking University Third Hospital, Beijing 100191, China
  • Received:2020-11-03 Online:2022-08-18 Published:2022-08-11
  • Contact: Ying WANG E-mail:wangying02114@bjmu.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(81601243);the National Natural Science Foundation of China(81670701);the National Natural Science Foundation of China(81550022);the National Natural Science Foundation of China(81873833)

摘要:

先天性肾上腺皮质增生症(congenital adrenal hyperplasia,CAH)是一类常染色体隐性遗传病,其中17α-羟化酶缺乏症(17α-hydroxylase deficiency,17α-OHD)为CAH少见类型。17α-OHD为CYP17基因突变所致,导致17α-羟化酶部分或完全缺乏,体内不能生成足够的皮质醇及性激素,表现为促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)分泌过多,雌二醇(estradiol,E2)和雄激素降低,孕酮(progesterone,P)、促卵泡生成素(follicle stimulating hormone,FSH)和黄体生成素(luteinizing hormone,LH)升高。患者社会性别多为女性,按照染色体核型可分为46XX和46XY,其中46XX型更少见。临床表现为低血钾和高血压,46XX型患者可出现月经不规律、闭经和不孕。患者症状轻重可因17α-羟化酶缺乏程度不同而异,部分性17α-OHD患者因症状不典型,易漏诊或误诊。染色体核型为46XX的部分性17α-OHD患者可有不同程度内外生殖器官的发育和月经来潮,具备潜在排卵和生育机会,但由于体内高P水平对子宫内膜的不良影响,患者存在不孕的问题。目前关于46XX-17α-OHD助孕治疗的报道国外仅见4例,国内曾有文献报道2例,但未提及其助孕过程。北京大学第三医院生殖医学中心1例46XX-17α-羟化酶缺乏症患者经过体外受精-胚胎移植技术(in vitro fertilization-embryo transfer,IVF-ET)治疗后成功受孕并分娩。首先给予患者糖皮质激素治疗降低P水平,随后采用超长方案促排卵,获卵10枚,冻存胚胎6枚。促性腺激素释放激素激动剂(gonadotropin releasing hormone agonist,GnRH-a)降调节人工周期解冻移植后,患者成功妊娠并于妊娠37周剖宫产分娩1名健康男婴。本例患者的诊治过程提示,46XX-17α-OHD患者可以有良好的卵母细胞和胚胎,IVF联合人工周期解冻移植可以是此类患者助孕的有效方法。

关键词: 17α-羟化酶缺乏症, 不孕症, 体外受精-胚胎移植

Abstract:

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder, and 17α-hydroxylase deficiency (17α-OHD) is a rare type of CAH. 17α-OHD is caused by CYP17 gene mutation, resulting in partial or complete deficiency of 17α-hydroxylase, which in turn leads to the lack of cortisol and sex hormone production. The disease is manifested by excessive secretion of adrenocorticotropic hormone (ACTH), decreased levels of estradiol (E2) and androgen, elevated levels of proges-terone (P), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Most of the patients are female in gender. According to the chromosome karyotype, 17α-OHD can be divided into 46XX and 46XY, of which 46XX is rarer. The clinical manifestations are hypokalemia and hypertension. Patients with 46XX-karyotype may have irregular menstruation, amenorrhea, and infertility. The severity of symptoms varies according to the degree of 17α-hydroxylase deficiency. Due to its untypical manifestation, the patients with partial 17α-OHD are more likely to be missed or misdiagnosed. Some 17α-OHD patients with 46, XX karyotypes have different degrees of development of internal and external reproductive organ and spontaneous menstrual cycle, so they may have the potential ovulation and fertility opportunities. However, due to the adverse effects of high serum P level on the endometrium, the patients would have infertility problems. To date, four cases from foreign countries have been reported about the infertility treatments among 46XX-17α-OHD patients, and two cases were mentioned in China without describing the process of treatments. Here, one case with partial 46XX-17α-OHD was diagnosed and successfully conceived and delivered after in vitro fertilization-embryo transfer (IVF-ET) in the Center for Reproductive Medicine, Peking University Third Hospital. Controlled ovarian stimulation with ultra-long protocol was initiated after glucocorticoid therapy was given to reduce P level. Ten oocytes were obtained and 6 embryos were cryopreserved. Frozen-thawed embryo transfer under hormonal replacement after gonadotropin releasing hormone agonist (GnRH-a) was carried out in an artificial cycle, and then the patient was successfully pregnant and delivered a healthy boy after 37 weeks of gestation by cesarean section. The treatment of this case suggests that patients with partial 46XX-17α-OHD can obtain oocytes and embryos with good quality. IVF combined with frozen-thawed embryo transfer under artificial cycle is an effective method for patients with partial 46XX-17α-OHD with infertility.

Key words: 17α-hydroxylase deficiency, Infertility, In vitro fertilization-embryo transfer

中图分类号: 

  • R711.6

图1

病例CYP17A1基因突变位点"

表1

患者的性激素变化"

Date Day of menstruation FSH/(IU/L) LH/(IU/L) E2/(pmol/L) P/(nmol/L)
2016-03-12 M3 8.67 3.63 165 16
2018-11-14 M13 - - - 12.5
2019-02-14 M2 7.07 8.23 141 5.15
2019-03-13 M3 11.6 6.85 227 4.29
2019-04-10 28 days later after GnRH-a 5.73 0.56 < 73.4 < 0.64
2019-04-25 HCG trigger day - 0.36 602 12
2019-05-08 M2 8.87 1.19 148 2.47
2019-06-04 28 days later after GnRH-a - - < 73.4 < 0.64
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