Albarel Frédérique, Perrin Jeanne, Jegaden Margaux, Roucher-Boulez Florence, Reynaud Rachel, Brue Thierry, Courbiere Blandine
Aix-Marseille Université, CNRS, CRN2M UMR 7286, 13344 cedex 15, Marseille, France.
APHM, Hôpital Conception, Service d'Endocrinologie, Diabète et Maladies Métaboliques, Centre de Référence des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 cedex 15, Marseille, France.
Hum Reprod. 2016 Nov;31(11):2609-2612. doi: 10.1093/humrep/dew239. Epub 2016 Oct 3.
Steroidogenic acute regulatory protein (StAR) mutations are the most frequent aetiologies of congenital lipoid adrenal hyperplasia (CLAH). Phenotypes may vary, and puberty may be absent in affected individuals. To date, only two pregnancies have been described in 46,XX CLAH patients with StAR mutations; these patients exhibited ovarian steroidogenesis along with spontaneous puberty and menarche and normal menses. The patient described here presented with CLAH caused by the homozygous (unreported, 1 bp) deletion c.719del in the StAR gene, which was diagnosed after acute adrenal insufficiency when the patient was 10 days old. The patient did not undergo spontaneous puberty, so puberty was induced by HRT when the patient was 13 years old. At the age of 25 years, the patient was referred to our reproductive unit because she desired to conceive. An initial cycle of clomiphene, stimulation produced follicular growth with two mature follicles measuring 18 and 15 mm, respectively, but the plasma oestradiol levels remained low (18 pg/ml) and the endometrium was thin (3 mm). Pregnancy was finally achieved after ovarian stimulation, IVF and transfer of frozen-thawed embryos after endometrial preparation with HRT. A normal female child was delivered following a 40 weeks' uneventful pregnancy. We therefore report the first IVF pregnancy achieved in a 46,XX CLAH patient homozygous for a StAR mutation, with inadequate ovarian steroidogenesis and no spontaneous puberty.
类固醇生成急性调节蛋白（StAR）突变是先天性类脂性肾上腺增生（CLAH）最常见的病因。其表型可能各不相同，受影响个体可能没有青春期发育。迄今为止，在携带StAR突变的46,XX型CLAH患者中仅报道过两例妊娠情况；这些患者表现出卵巢类固醇生成，伴有自然青春期发育、月经初潮和正常月经。本文所述患者因StAR基因纯合（未报道的1个碱基对）缺失c.719del导致CLAH，在10日龄时因急性肾上腺功能不全被诊断出来。该患者没有自然青春期发育，因此在13岁时通过激素替代疗法（HRT）诱导青春期发育。25岁时，该患者因希望怀孕而转诊至我们的生殖科。首次使用克罗米芬刺激周期产生了卵泡生长，有两个成熟卵泡，直径分别为18毫米和15毫米，但血浆雌二醇水平仍然很低（18皮克/毫升），子宫内膜很薄（3毫米）。在经过卵巢刺激、体外受精以及用HRT进行子宫内膜准备后移植冻融胚胎，最终成功怀孕。经过40周的顺利妊娠后，产下一名正常女婴。因此，我们报告了首例在携带StAR突变的纯合46,XX型CLAH患者中实现的体外受精妊娠，该患者卵巢类固醇生成不足且无自然青春期发育。
