Successful fertility outcome in a woman with 17ɑ‐hydroxylase deficiency

Falhammar, Henrik

doi:10.1111/cen.13549

Cited by 18 publications

(9 citation statements)

References 5 publications

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“…However, there are still some reports of successful live birth of this kind of patient through IVF-ET. Based on a comprehensive consultation of literature associated with IVF-ET treatments on 17-OHD women, we listed the following cases in chronological order ( Table 5 ): a 33-year-old woman with 17-OHD and IVF-donated oocytes resulted in a live birth in 2003 ( 17 ); in the same year, an infertile 17-OHD woman achieved pregnancy and delivered three healthy babies with the help of IVF using her own oocytes ( 14 ); a successful live birth in a 26-year-old woman with IVF was documented in 2016 ( 20 ); two consecutive live births of a 24-year-old 17OHD woman followed ( 19 ); another successful live birth in a 26-year-old woman with IVF using was recorded in 2018 ( 18 ); Blumenfeld et al. described the achievement of the first successful pregnancy and delivery in a patient with 17,20-lyase deficiency ( 16 ); the first two Chinese cases of partial 17-OHD conceived and had a live birth through PPOS protocol ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

Reproductive endocrine characteristics and in vitro fertilization treatment of female patients with partial 17α-hydroxylase deficiency: Two pedigree investigations and a literature review

Jiang

Xu²,

Qiao³

et al. 2022

Front. Endocrinol.

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Background17α-hydroxylase/17, 20-lyase deficiency (17-OHD) is caused by the mutations of the CYP17A1 gene. The classical phenotype of 17-OHD includes hypertension, hypokalemia, and abnormal sexual development, with partial 17-OHD typically less severe than the complete deficiency. Infertility is always one of the main clinical manifestations of partial 17-OHD. However, to date, the pregnancy potentials of partial 17-OHD female patients have rarely been investigated, and few live-birth cases have been reported among them. Moreover, the reproductive endocrine characteristics of partial 17-OHD female patients have not been completely clarified and the treatment skills of in vitro fertilization and embryo transfer (IVF-ET) have not been well summarized yet.MethodsTwo Chinese infertile female patients clinically diagnosed as partial 17-OHD were enrolled and their pedigree investigations were performed. Hormones were determined to depict the endocrine conditions of partial 17-OHD female patients. The adrenocorticotropic hormone (ACTH) stimulation test was performed to evaluate the functions of the adrenal cortex. Genotype analysis was conducted by next-generation sequencing (NGS) and Sanger sequencing was used to verify the results. IVF-ET was performed for the treatment of their infertility. Specifically, the progestin-primed ovarian stimulation (PPOS) protocol was chosen for the controlled ovarian hyperstimulation (COH) cycles, and the hormone replacement treatment (HRT) protocol was adopted for the endometrial preparation in frozen–thawed embryo transfer (FET) cycles.ResultsHormone assays revealed a reduced estradiol (E2) and testosterone (T) level, and an elevated progesterone (P4) level. The classic ACTH stimulating test evidenced a suboptimal response of cortisol to ACTH. Genotype analysis demonstrated that the proband1 carried two variants: c.1459_1467del (p.Asp487_Phe489del)het and c.995T>C (p.lle332Thr)het. The proband2 was found to be a homozygote with the mutation of c.1358T>A (p.Phe453Ser)hom. The two female patients both succeeded in pregnancy and delivery of healthy babies through IVF-ET, with the usage of PPOS, HRT, and low-dose glucocorticoids.ConclusionsPartial 17-OHD female patients manifested menstrual cycle disorders and infertility clinically; displayed high P4 and low E2 and T; showed sparse pubic hair in physical examinations; and revealed multiple ovarian cysts in ultrasonic visualization. Moreover, the pregnancy potentials of infertile partial 17-OHD women seemed to increase with the adoption of IVF-ET. Considering the sustained elevated P4 level, PPOS is a feasible protocol for them in COH.

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Section: Discussionmentioning

confidence: 99%

Reproductive endocrine characteristics and in vitro fertilization treatment of female patients with partial 17α-hydroxylase deficiency: Two pedigree investigations and a literature review

Jiang

Xu²,

Qiao³

et al. 2022

Front. Endocrinol.

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“…In 17OHD cases, elevated progesterone is very common in controlled ovarian stimulation, despite the use of dexamethasone ( 8 , 9 , 11 , 20 ). This may be due to the deficiency of 17OH in the developing ovarian follicles.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone application for in vitro fertilisation in non-classic 17-hydroxylase/17,20-lyase-deficient women

Yang

Zhang²,

Shang³

et al. 2022

Front. Endocrinol.

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ContextHigh progesterone levels in the follicular stage interfere with the implantation window, causing infertility in women with 17-hydroxylase/17,20-lyase deficiency (17OHD). Dexamethasone can restore cortisol deficiency and suppress inappropriate mineralocorticoid secretion to control hypertension in 17OHD patients, but poses risks to the foetus if administered during pregnancy.ObjectiveWe prospectively explored a rational glucocorticoid use protocol for assistive reproduction in a woman with non-classic 17OHD that reduced glucocorticoid side effects.MethodIn this study, the treatment protocol for this 17OHD patient included the following steps. First, the appropriate type and dose of glucocorticoid for endogenous progesterone suppression was determined. Then, glucocorticoid was discontinued to increase endogenous progesterone levels for ovarian stimulation. Next, dexamethasone plus GnRHa were used to reduce progesterone levels in frozen embryos for transfer. Once pregnancy was confirmed, dexamethasone was discontinued until delivery.ResultsDexamethasone, but not hydrocortisone, reduced progesterone levels in the 17OHD woman. After endogenous progesterone-primed ovarian stimulation, 11 oocytes were retrieved. Seven oocytes were 2PN fertilised and four day-3 and two day-5 embryos were cryopreserved. After administering dexamethasone plus gonadotropin-releasing hormone agonist (GnRHa) to reduce progesterone levels to normal, hormone replacement therapy was administered until the endometrial width reached 9 mm. Exogenous progesterone (60 mg/day) was used for endometrial preparation. Two thawed embryos were transferred on day 4. Dexamethasone was continued until pregnancy confirmation on the 13th day post-transfer. Two healthy boys, weighing 2100 and 2000 g, were delivered at 36 weeks’ gestation.ConclusionRational use of dexamethasone synchronised embryonic development with the endometrial implantation window, while not using in post-implantation avoided its side effects and promoted healthy live births in women non-classic 17OHD undergoing in vitro fertilisation.

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“…Nevertheless, correct diagnosis and management may improve the poor reproductive prognosis of 46,XX 17OHD patients, which can be due to anovulation, big ovarian cysts, uterine hypoplasia, and high progesterone and low estrogen levels [35, 36]. Besides P10 in our study, there are a few successful pregnancy reports of 46,XX 17OHD following an appropriate glucocorticoid replacement, induction of menstrual cycles and ovulation, and IVF frozen-thawed embryo transfer [37-39].…”

Section: Discussionmentioning

confidence: 99%

Genotypic Sex and Severity of the Disease Determine the Time of Clinical Presentation in Steroid 17α-Hydroxylase/17,20-Lyase Deficiency

Kurnaz¹,

Baykan²,

Türkyılmaz³

et al. 2020

Horm Res Paediatr

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Context: Steroid 17α-hydroxylase/17,20-lyase deficiency (17OHD) is characterized by decreased sex steroids and cortisol, and excessive mineralocorticoid action. The clinical symptoms of hypocortisolemia are subtle. Aim: The clinical, biochemical, and molecular characteristics of patients with 17OHD were evaluated to determine the factors influencing the time of diagnosis and the management. Patients and Methods: Clinical data, steroid profiles by liquid chromatography-tandem mass spectrometry, and Sanger sequencing of the CYP17A1 gene was evaluated in 12 patients with 17OHD diagnosed between 2004 and 2020. Results: Median age of diagnosis was 13.9 (range: 0.04–29.5) years. Ten of 12 patients had 46,XY karyotype. Except for one boy with partial 17OHD, all patients had female external genitalia hence raised as females. The clinical presentation of 17OHD was earlier (median age: 7 years) in patients, who presented with severe hypertension, atypical genitalia, or positive family history (n = 6, 50%) than those without (median age: 15.3 years; p = 0.0005). The latter group presented with amenorrhea (n = 6, 50%). Steroid profile of patients uniformly showed a typical pattern of 17OHD regardless of the age at diagnosis. Serum gonadotropin concentrations were elevated in patients >12 years (n = 7), normal in pre-adolescents (n = 4), and low in a patient, who had a digenic inheritance of homozygous CYP17A1 and KISS1R mutations. Conclusions: Early clinical presentation and diagnosis in 17OHD are associated with symptomatic hypertension in both 46,XX and 46,XY patients or inadequate virilization of external genitalia in 46,XY partial 17OHD. In the absence of these, the clinical presentation is at late pubertal ages at which time amenorrhea and elevated gonadotropins are the hints for diagnosis.

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Successful fertility outcome in a woman with 17ɑ‐hydroxylase deficiency

Cited by 18 publications

References 5 publications

Reproductive endocrine characteristics and in vitro fertilization treatment of female patients with partial 17α-hydroxylase deficiency: Two pedigree investigations and a literature review

Reproductive endocrine characteristics and in vitro fertilization treatment of female patients with partial 17α-hydroxylase deficiency: Two pedigree investigations and a literature review

Dexamethasone application for in vitro fertilisation in non-classic 17-hydroxylase/17,20-lyase-deficient women

Genotypic Sex and Severity of the Disease Determine the Time of Clinical Presentation in Steroid 17α-Hydroxylase/17,20-Lyase Deficiency

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