Successful IVF pregnancy despite inadequate ovarian steroidogenesis due to congenital lipoid adrenal hyperplasia (CLAH): a case report

Abstract

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.

Successful Live Birth in a Chinese Woman with P450 Oxidoreductase Deficiency through Frozen-thawed Embryo Transfer

“…In the successful pregnancies in CAH women caused by 17-hydroxylase de ciency and steroidogenic acute regulatory protein (StAR) mutations, the patients presented with primary amenorrhea and absent or incomplete sexual maturation [18,26]. The authors both reported that during their IVF treatment, endogenous estrogen level was very low but follicles grew normally after ovarian stimulation and normal embryos and pregnancies were obtained [18,26], just as our case reported. So we suggest that the disorders of gonadal steroidogenesis caused by rare forms of CAH may have little effect on the follicular growth and the developmental capacity of the oocytes.…”

“…As for low estradiol, previous reports showed estrogen may not play a key role in folliculogenesis and follicular development in vivo and in vitro [23,24], but gonadotrophins play a vital role in the growth and maturation of follicles [25]. In the successful pregnancies in CAH women caused by 17-hydroxylase de ciency and steroidogenic acute regulatory protein (StAR) mutations, the patients presented with primary amenorrhea and absent or incomplete sexual maturation [18,26]. The authors both reported that during their IVF treatment, endogenous estrogen level was very low but follicles grew normally after ovarian stimulation and normal embryos and pregnancies were obtained [18,26], just as our case reported.…”

Congenital adrenal hyperplasia

“…100 In vitro fertilization and transfer of cryopreserved embryos has successfully resulted in a live birth in lipoid CAH and 17OH deficiency. 101,102 Patients with POR, StAR, and CYP17A1 mutations may also have ovarian cysts and ovarian cyst torsion. [103][104][105] In the virilizing forms of CAH, excess adrenal sex steroids can lead to hypogonadotropic hypogonadism 106,107 and increased progesterone can interfere with endometrial implantation.…”

Disorders of Sex Development—Novel Regulators, Impacts on Fertility, and Options for Fertility Preservation

“…In non-classical forms of CAH due to partial enzyme deficiencies, live-birth rates are higher (63-90%) than classical CAH and are similar to age-matched controls [24]. In more rare forms of 46,XX CAH that may also affect gonadal steroid production, fertility is rarely described, other than in few case reports of a spontaneous pregnancy, e.g., in an individual with 3β-hydroxysteroid dehydrogenase deficiency [148], and successful in vitro fertilization (IVF) in individuals with 17α-hydroxylase deficiency [149][150][151], and another with congenital lipoid adrenal hyperplasia [152]. In CAH, infertility may occur as a result of anovulation, menstrual irregularities, thickening of cervical mucus, and anatomical factors [132].…”