Two consecutive successful live birth in woman with 17α hydroxylase deficiency by frozen–thaw embryo transfer under hormone replacement endometrium preparation

Abstract

17α-Hydroxylase deficiency is rare autosomal recessive disorder that manifested by hypertension, hypokalemia, delayed sexual development, primary amenorrhea and infertility. The information regarding infertility care and conception in women with this disorder are extremely limited. We report a 24-year-old Japanese woman with primary amenorrhea who was diagnosed as partial 17α-hydroxylase deficiency caused by homozygous 3 bp deletion in exon 1 of 17α-hydroxylase gene. In vitro fertilization with controlled ovarian stimulation was carried out and all viable embryo were frozen. During ovarian stimulation, serum progesterone levels were markedly elevated, and endometrial growth was impaired. Utilizing frozen-thaw embryo transfer under hormonal replacement (glucocorticoid, estradiol and progesterone), she had successfully given two consecutive live birth. Women with 17α-hydroxylase deficiency with residual ovarian reserve can afford reproductive success by appropriate diagnosis and treatment by assisted reproductive technology.

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

“…The second noticeable reproductive endocrine characteristic of partial 17-OHD women was decreased E2. In the previous cases, very low estradiol had also been noticed (19,20). Centered on this abnormal sexual hormone, the following problems may arise for the reproductive system and COH process.…”

“…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 ).…”

“…Since ovarian surgery might cause injury to the ovarian function, the ovarian reserve of our patient (proband 1) was relatively low with an AMH value of 1.43 ng/ml and an AFC of 3. However, the case reported in 2016 documented an AFC of 32, despite the limited number of dominant follicles ( 20 ); the women recorded in 2018 presented with hyper-response with 21 oocytes retrieved ( 19 ), although both of the cases had a lack of ovarian surgery histories. It reminded clinical physicians that when confronted with ovarian cysts in partial 17-OHD women, which seems to be a sticky condition requiring sophisticated and accurate treatment, they need to take a comprehensive diagnosis, strictly obey operation indications, and prudently manipulate, to avoid further damage to fertility.…”

Low estradiol responses in oocyte donors undergoing gonadotropin stimulation do not influence clinical outcomes

“…This can occur with letrozole use in women with hormone-sensitive cancer, without significantly reducing oocyte yield [24]. Similarly, case reports of patients with congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency have described successful in vitro fertilization cycles with subsequent conception and live births despite markedly low serum estradiol during controlled ovarian stimulation [25,26]. These examples, in addition to our cohort of oocyte donors with low estradiol response, suggest that in select populations, a low estradiol response may not portend a poor outcome.…”

Pregnancy and Prenatal Management of Congenital Adrenal Hyperplasia

“…46,XX 17-OHD patients have reduced fertility rates because of reduced estrogens and increased progesterone, with anovulatory cycles, primary amenorrhea, a high incidence of ovarian cysts, and a reduced uterine volume. Pregnancies have been described in patients treated with dexamethasone, GnRH analogues, and/or hCG and hMG, to reduce progesterone levels, prior to ovarian stimulation [ 39 , 40 , 41 , 42 ]. Female patients affected by StAR deficiency show normal pubertal development because of normal ovarian hormone secretion, but ovulation and embryo implant may be impaired, causing infertility.…”