Fertility preservation in Turner syndrome: Karyotype does not predict ovarian response to stimulation

Abstract

Objective Turner syndrome (TS) is responsible for gonadal dysgenesis with high risk of premature ovarian insufficiency. Little is known about fertility preservation (FP) strategies is this population. Design Data from women with TS consulting with a fertility specialist in our FP centre from 2014 to 2018 were retrospectively collected. Measurement Total number of mature oocytes cryopreserved using vitrification. Patients Nine women with TS were referred. Three women with different karyotypes underwent controlled ovarian stimulation (COS) for oocyte vitrification. Mean age at TS diagnosis was 13.7 years [9‐20]. Mean referral delay between TS diagnosis and fertility consultation was 9.7 years [7‐14]. First counselling for FP was provided at 23.7 years [18‐28]. Mean AMH serum level prior to COS was 53.8 pmol/L [3.6‐95]. Results All three women succeeded in obtaining cryopreserved oocytes with a mean number of 15.3 per woman [9‐20] and 9.2 per COS cycle [2‐20]. Ovarian response to COS was unexpectedly remarkable for the woman with a complete 45,X monosomy. Procedure was well tolerated for all women. None of them have used oocytes for in vitro fertilization yet. Conclusions Independently of karyotype, antral follicular count, AMH and FSH levels seemed to be reliable predictive markers of oocyte cryopreservation success. In a monosomic TS woman, cryptic ovarian mosaicism could explain a successful ovarian response to stimulation with a high number of retrieved oocytes. In case of spontaneous menarche, TS adolescents should be referred during transition to adulthood for FP counselling to avoid referral delay and limit time‐related diminished ovarian reserve.

Why are some patients with 45,X Turner syndrome fertile? A young girl with classical 45,X Turner syndrome and a cryptic mosaicism in the ovary

“…Over the past few years, several studies reported that follicles were found in girls with a 45,X karyotype (13,19). In addition, pregnancies were described in women with a complete monosomy of the X chromosome in extraovarian cells (20,21).…”

The indication for fertility preservation in women with Turner syndrome should not only be based on the ovarian reserve but also on the genotype and expected future health status

“…Experience with this method in Turner syndrome is already available. 8,[20][21][22] It should be noted, however, that the anatomical conditions for cryopreservation of oocytes (vaginal sonography) must be F I G U R E 1 Recommendation for fertility protection in women with Turner syndrome, based on genotype, ovarian reserve, and health of the woman. AMH, anti-Müllerian hormone [Color figure can be viewed at wileyonlinelibrary.com]…”

“…Experience with this method in Turner syndrome is already available 8,20‐22 . It should be noted, however, that the anatomical conditions for cryopreservation of oocytes (vaginal sonography) must be given for the mostly still young women.…”

“…The question of predicting the number of oocytes retrieved cannot yet be clearly answered. However, it appears that, in addition to the presence of a Turner syndrome mosaicism or structural aberration of the X chromosome, the predictive factors AMH, antral follicle count, and spontaneous menarche are of particular importance 8,20‐22 . As a result of the low ovarian reserve in women with Turner syndrome, repeated stimulation cycles might be required.…”

Adolescent Fertility Preservation: Where Do We Stand Now

“…52 However, spontaneous puberty and menarche has been reported in children with monosomy 45,X. 53,54 Oocyte cryopreservation has become an established component of assisted reproductive technology, allowing women of reproductive age to preserve their oocytes for future use. There have been a handful of published case reports and studies documenting successful oocyte cryopreservation in TS individuals.…”