P-453 No major changes in ovarian function after unilateral ovariectomy in the context of ovarian tissue cryopreservation in girls with Turner syndrome
Authors: Van der Coelen S , Nadesapillai S , Peek R , Schleedoorn M , Braat D , Fleischer K , Van der Velden J 
Published: June 2022

Abstract

Study question
What is the impact of unilateral ovariectomy on the ovarian function in girls with Turner syndrome (TS) undergoing ovarian tissue cryopreservation (OTC)?

Summary answer
In most girls with TS, ovarian markers remained stable up to three years after unilateral ovariectomy.

What is known already
Girls with TS have a complete or partial loss of one of the sex-chromosomes causing premature ovarian insufficiency which reduces the chances of a spontaneous pregnancy. OTC may be an option to preserve fertility at an early age to increase the chance on genetic offspring. However, this requires a unilateral ovariectomy for young girls with TS who are already subjected to an accelerated loss of ovarian reserve. Previous research in women without TS undergoing a unilateral ovariectomy has shown that the remaining ovary compensate for the function of the removed ovary with no effect on pubertal development and fertility outcome.

Study design, size, duration
This is a descriptive study of 28 girls with TS (age 5-19 years). Girls were monitored for up to three years after unilateral ovariectomy on pubertal development, and level of follicle stimulating hormone (FSH), luteinizing hormone (LH), oestrogen, Anti-Mullerian hormone (AMH) and inhibin B.

Participants/materials, setting, methods
The cohort was recruited from girls with TS undergoing OTC as part of the ongoing TurnerFertility study at a university medical centre. Follicles were found in the ovarian cortex fragments in 28 of the 86 cases. These cases were considered to have functional ovaries and were included in the study.

Main results and the role of chance
Follow-up data are not yet available for three girls because they had surgery only three months ago. Of the other 25 girls, two girls had a monosomic karyotype (45,X), fourteen were mosaic (45,X/46,XX), four had a mosaic with triple X-chromosome (45,X/47,XXX) and five girls had structural aberrations of the X chromosome. Ten girls were prepubertal at time of unilateral ovariectomy, twelve girls had a spontaneous thelarche and three girl had induced puberty. After unilateral ovariectomy, one of the 10 prepubertal girls entered puberty spontaneously and one of the prepubertal girls needed puberty induction. It is still unknown what the impact of a unilateral ovariectomy will be on the pubertal development of the other girls, due to their young age but AMH levels remained stable. 8/12 girls with spontaneous thelarche maintained a measurable AMH and FSH &lt;20 IE/L during the median follow-up of 20 months (IQR 13-30). 4/12 girls with spontaneous thelarche before OTC needed hormone supplementation because of signs of premature ovarian insufficiency, e.g. irregular menstruations (n = 2), flushes (n = 1) and high FSH (84 IE/L; n = 1). However, these girls had unfavourable hormonal parameters before unilateral ovariectomy (e.g. AMH &lt; 0.5 ug/L or FSH &gt; 20 IE/L).

Limitations, reasons for caution
These results should be interpreted with caution because of the highly heterogeneous population of girls with TS. Moreover, the results should ideally be compared with age- and karyotype-matched controls to determine the natural course of ovarian function of girls with TS.

Wider implications of the findings
This cohort will be monitored for a longer period of time to observe the consequences on pubertal development, need for hormone supplementation, and eventually fertility outcome. If OTC becomes part of routine care for girls with TS, our results will be of great value in the counselling for future parenthood.

Trial registration number
NCT03381300