Oocyte cryopreservation after controlled ovarian hyperstimulation in mosaic Turner syndrome: another fertility preservation option in a dedicated UK clinic

Abstract

A 22-year-old woman with mosaic Turner syndrome (TS) (45,X 86%, 47,XXX 11%, 46,XX 3%) had been attending our well-established and dedicated tertiary-level TS clinic annually since the age of 5 years. She was initially referred with short stature, and was subsequently diagnosed with mosaic TS, and received growth hormone treatment until the age of 15 years. Her final height was 150 cm with a body mass index of 21. Puberty developed spontaneously and she reached menarche at 13 years; she had a regular menstrual cycle every 28 days. She was normotensive, and had normal thyroid and kidney function tests, bone densitometry scan and echocardiography. She was not yet in a stable relationship, but hoped to have a family in the future, and wanted to discuss the option of fertility preservation owing to the risk of premature menopause. The possibility of controlled ovarian hyperstimulation (COH), followed by transvaginal oocyte retrieval and cryopreservation, was raised. After she had been fully counselled about the risks of pregnancy in TS, the genetic risks and the risks related to COH, such as poor response and cycle cancellation, she was keen to proceed. She therefore had an ovarian reserve assessment as part of the investigations, and was found to have a follicle-stimulating hormone level of 4.6 iu/ml, anti-mullerian hormone (AMH) level of 8.52 pmol/l and estradiol level of <44 pmol/l. Pelvic ultrasound revealed a normal uterus and the ovaries had an antral follicular count of seven. Controlled ovarian hyperstimulation was started using a short stimulation protocol from day 3 of menstruation, initially with 375 iu of human menopausal gonadotrophins (Menopur, Ferring, Berkshire, UK), which was then increased to 450 iu on day 5 of stimulation when the estradiol level was 651 pmol/l. After 11 days of COH and serial ultrasound monitoring, 10 000 units of human chorionic gonadotrophin were administered with an estradiol level of 5956 pmol/l. Eight oocytes were collected under transvaginal ultrasound-guidance 36 h later, and all the oocytes obtained were subsequently vitrified for future use, as described previously. 1 DiscussionFertility in women with TS is a rare phenomenon, as most suffer from gonadal dysgenesis, with only 2% of pregnancies a result of spontaneous conception, 2 and the remaining pregnancies resulting from oocyte donation which, to date, has been the only reproductive option. The accelerated loss of ovarian primordial follicles from the 18th week of fetal life characterises classical TS. However, in women with mosaic TS, follicular development can persist beyond puberty, leading to spontaneous pubertal development, regular menses and pregnancy before the onset of premature menopause.3 Indeed, even spontaneous monozygotic monochorionic twin pregnancy has been reported in such patients. 4 The possibility of fertility preservation in young women with mosaic TS was first raised by Abir et al. 5 Novel methods of fertility preservation in these women have been reported recently, including ovarian tissue cryopr...

Fertility preservation in Turner syndrome

“…However, it is important to notice that the reliability of these criteria may be questioned since some patients failed to show any follicles within their ovarian tissue (42,43). On the contrary, missing these criteria does not prevent the possibility of natural pregnancy (44,45). If the option of ovarian tissue cryopreservation is chosen, it may be interesting to consider its association with ex vivo IVM from cumulo-oocyte-complexes recovered in the laboratory, even though poor yield is expected.…”

TRANSITION IN ENDOCRINOLOGY: Induction of puberty

“…An increasing number are likely to turn to ovarian cryopreservation techniques, subject to financial constraints and local availability (66). Long-term outcome data for this in terms of live births will obviously take many years to accumulate.…”

Nonmalignant Diseases and Treatments Associated with Primary Ovarian Failure: An Expanded Role for Fertility Preservation

“…74 Recent literature from Europe supports the use of oocyte cryopreservation after ovarian stimulation in these patients, although no pregnancies have been reported. [75][76][77] Two of these initial reports included women with mosaic Turner syndrome in their early 20s who underwent conventional ovarian stimulation and oocyte retrieval to cryopreserve oocytes. 75,76 After ovarian reserve testing, it was thought that the patients had a good chance of responding to gonadotropin stimulation.…”

“…One additional report describes a patient who had previously undergone ovarian tissue cryopreservation at the age of 17 and then subsequently underwent oocyte cryopreservation in her mid-20s. 77 For adult Turner syndrome patients, oocyte cryopreservation performed on a case-by-case basis has been advocated and is relatively straightforward. Ovarian tissue cryopreservation for adolescent patients with Turner syndrome may be more challenging.…”