Pregnancy in patient with Swyer syndrome.

Fertil Steril. 2011 Apr;95(5):1789.e1-2. doi: 10.1016/j.fertnstert.2010.12.012. Epub 2010 Dec 31.

Pregnancy in patient with Swyer syndrome.

Tulic I1, Tulic L, Micic J.

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To report a case of successful pregnancy and delivery after IVF and ET in a patient with Swyer syndrome.

Case report.

Unit of Assisted Reproduction, Gynecology and Obstetrics Institute, University of Belgrade.

A 30-year-old patient with 46,XY gonadal dysgenesis.

Chromosomal analysis, diagnostic laparoscopy, IVF using donor oocytes, ET, and cesarean delivery.

Successful pregnancy and live birth.

Successful treatment, pregnancy, and delivery.

A patient with 46,XY gonadal dysgenesis in a donor oocyte program, can maintain a normal pregnancy and delivery.

Swyer was the first one to describe 46 gonadal dysgenesis, and the syndrome may be expressed either in a complete or incomplete form. Characteristics of a fully expressed syndrome are as follows: female phenotype, either normal or tall stature, bilateral gonadal dysgenesis, and sexual infantilism with primary amenorrhea and eunuchoid habitus. The phenotype is completely female, with existing tubes, vagina, and various grades of uterus hypoplasia ranging from severe to mild underdevelopment.

Dysgenesis-related streak gonads appear in 30%–40% cases of patients with primary amenorrhea. The prevalence of ovarian insufficiency in women with primary amenorrhea varies between 10% and 28% (1).
Case report

The report refers to a female patient, age 30, who was diagnosed with Swyer syndrome at the age of 19; the diagnosis was made by an endocrinologist. The patient underwent detailed examination for the cause of primary amenorrhea. She was of a female phenotype, of eumetabolic state, tall stature, and eunochoid proportion: lower trunk: 111 cm, extended arm distance 190 cm, undeveloped breasts, and grade 2 axillary hair. Thyroid gland was within physiological limits. She had female external genitalia and female body hair (grade II–III) and no evidence of clitoromegaly. Psychologically, the patient was clearly defined as a female. Pelvic ultrasound revealed an extremely hypoplastic uterus with the largest sagittal diameter of 30 mm. Ovaries were unavailable for exploration. Ultrasound examination of breasts revealed bilaterally a rather deficient fibroglandular component. Gynecological examination confirmed female genitalia with normal characteristics and normal vagina. The uterus was not differentiated, and the adnexa were not palpable. Pelvis computed tomography showed a hypoplastic uterus of 30 mm in diameter. No soft tissue mass of ovarian origin was detected in the bilateral adnexal area. Laparoscopic examination revealed a 30 mm diameter uterus out of which extended hypoplastic tubes of preserved ampulla-infundibulum segments of distinct fimbrials. Whitish fibrotic changes were noticed at the site of the missing ovaries.

Her karyotype was 46,XY. Genetic analyses of the SRY and ATL1 genes were performed, and SRY I ATL1 gene expression was confirmed by multiplex polymerase chain reaction in genomic DNA. Direct sequencing on genomic DNA in both directions did not reveal a mutation in the SRY gene.

Hormone levels were as follows: low-normal cortisol level (220 nmol/L), high levels of gonadotropin (FSH, 176.4 mIU/L; LH, 26.9 mIU/L), nonmeasurable E2 (0.02 pmol/L), T within normal limits (1/72 nmol/L), and PRL within normal limits (184.2 mIU/L). Tumor markers and alfa-fetoprotein (1.36 ng/mL) and β-hCG (<1.0 mIU/mL) were within normal limits.

The patient has been undergoing replacement therapy since the age of 19. Among other things, the growth and development of the uterus itself were monitored. When the patient was at the age of 29, vaginal ultrasound examination showed uterine dimensions as follows: uterine longitudinal diameter 60 mm, anteroposterior diameter 25 mm, and transversal diameter 35 mm. The patient was introduced to the oocyte donation program. Her cousin was the oocyte donor. The donor underwent the controlled ovarian stimulation through a long protocol. Recipient treatment consisted of stimulation of GnRH and estrogen as per the scheme of Styne-Gross et al. (2). Five donated oocytes were inseminated with processed sperm of the recipient’s husband. On the second day, three embryos of the four-blastomere stage were returned using the ultrasound control. The level of serum β-hCG was 230 mIU/mL on the 14th day after ET. Four weeks after ET, during ultrasound examination, intrauterine presence of a gestational sac was noted; 2 weeks later, there was a fetus with registered heart action. The pregnancy was continuously monitored. A healthy baby with an Apgar score of 9 was delivered by cesarean section at the 39th week of gestation. The cesarean delivery was performed owing to breech presentation and reduced amniotic fluid.

Swyer syndrome was originally described in 1955 in two women with primary amenorrhea, with normal appearance of external genitalia and normal vagina but with hypoplastic uterus and gonads localized at the place where ovaries are commonly positioned. These women were of tall stature, minimally developed breasts, normal pubic and axillary hair, normal vagina and cervix, small uterus, and no palpable adnexal structures. Swyer syndrome implies no match between genotype-phenotype correlations. Phenotype is female and genotype is male (3). It is commonly detected at the age of 18–23 owing to primary amenorrhea (4, 5). Risks of gonadal dysgenesis include prolonged hypoestrogenemia with osteoporosis, virilization and a high risk of gonadal neoplasia; therefore, early prophylactic removal of the dysgenetic gonads is recommended. For hypoestrogenemia, cycle regulation, and beneficial psychological effect, hormone replacement therapy is essential. The presence of the XY genotype and H-Y antigen does not affect normal uterine and endometrial response, and the possibility of maintaining a normal pregnancy and delivery confirms the physiological ability of the uterus to accommodate and maintain a successful pregnancy in patients with XY dysgenesis (6). However, the literature reports fewer than 12 full-term pregnancies in patients with Swyer syndrome (7, 8, 9, 10, 11, 12, 13, 14). It is quite clear that we need reports on pregnancy outcomes in patients with Swyer syndrome to expand our knowledge and define better any specific risks in this unique patient population. As in our case, most pregnancies in patients with Swyer syndrome necessitated cesarean section owing to a number of indications. Despite some opinions that androgenic pelvic shape in Swyer syndrome patients may indicate a possible abnormal delivery, causes of the high prevalence of cesarean sections is still unclear.