Successful live birth in women with partial 17α hydroxylase deficiency: report of two cases

Abstract Background: The condition 17αhydroxylase deficiency (17-OHD) is a rare kind of congenital adrenal hyperplasia (CAH) manifested by delayed sexual development, infertility, failure to synthetize cortisol, adrenal androgens and elevated progesterone (P4). Partial deficiency is much rarer, presenting with subtler symptoms. It can inhibit folliculogenesis, and affect endometrial receptivity.The information regarding infertility care and conception in women with this disorder are extremely limited，and so far，to the best of our knowledge，there have been no reports of their natural pregnancy. Case Description: The first one was a 27-year-old Chinese woman with partial 17-OHD due to the compound heterozygote mutation (c.887T>C(p.I296T) / c.1304T>C(p.F435S) )in the CYP17A1 gene who had suffered from recurrent cysts and infertility. In the course of treatment, we observed inadequate endometric development associated with prematurely elevated series P4。Subsequently, oral prednisone was used to lower ovarian and adrenal P4 overproduction. Finally the patient resumed spontaneous ovulation, conceived naturally and lived birth a female. The second case was a 32-year-old Chinese woman with partial 17-OHD due to the compound heterozygote mutation (c.1396G>A(p.E466K) / c.1459-1467del (p.Asp487-Phe489del ) ) in the CYP17A1 gene. Among them, c.1396G>A(p.E466K) was novel missense mutations. In vitro fertilization (IVF) was recommended due to the complexity of the disorder. Ultimately, 17 oocytes were retrieved and 2 cleavage embryos and 5 blastocysts were cryopreserved due to thin endometrium associated with decreased estrogen(E2) and prematurely elevated P4 after ovarian stimulation. Then oral prednisone was used to control adrenal P4 overproduction, then artificial endometrial preparation and frozen embryo transfer(FET) were performed, resulting in a singleton pregnancy. After the literature search in 17OHD women, no spontaneous pregnancy has been reported and only few case reports of successful pregnancies through IVF were summarized. Conclusion: This report shows successful pregnancy was achieved in two partial 17-OHD women. It seemed that disorders of steroidogenesis caused by CYP17A1 didn't impair the developmental potential of oocytes. Women with partial 17-OHD can afford reproductive success by adequate hormonal control and endometrial preparation, and to our best knowledge, this is the first report on natural pregnancy in these women.