P-709 A retrospective cohort study of the stability of ovarian reserve in women with Turner Syndrome (TS) and spontaneous menstruation
Authors: Pinches E , Nash Z , Petrie A , Davies M 
Published: July 2024

Abstract

Study question
What is the stability of ovarian reserve, as measured by anti-Müllerian hormone (AMH), over time in women with TS and spontaneous menstruation beyond age 16?

Summary answer
Ovarian reserve, as measured by AMH, is stable over time in adult (&gt;16 years) women with TS and spontaneous menstruation.

What is known already
TS is associated with gonadal dysgenesis and premature ovarian insufficiency (POI). In a minority of TS women, ovarian function is maintained with ongoing menstruation and the possibility of achieving spontaneous pregnancy. There is uncertainty as to the role of fertility preservation in this population. The 2016 Clinical practice guidelines for the care of girls and women with TS recommend counselling women with TS that their probability to conceive spontaneously decreases rapidly with age. However, the natural history of AMH over time in this sub-population has not been reported.

Study design, size, duration
Retrospective cohort study of patients attending the TS clinic at University College London Hospital between December 2020 and December 2022. This time interval was chosen to ensure that the entire UCLH TS cohort was screened, even if one year of annual follow-up was missed during COVID-19. Clinical records were reviewed to identify adult patients (&gt;16years old) with spontaneous menstruation at any time and at least one measurement of AMH.

Participants/materials, setting, methods
To assess the stability of the AMH values, the rate of change was calculated using the formula: ratechangeAMH = (lastAMH-baselineAMH)/(time in months between readings). The distribution of the rate of change in the PCOS and non-PCOS groups was then compared using a non-parametric Mann-Whitney test: a regression analysis was performed with the outcome as the ratechangeAMH and the explanatory variables being baseline AMH and age at baseline AMH.

Main results and the role of chance
55 patients were identified, median age 25.9 (range 16 to 41).Their karyotypes were 45X (n = 2) 45X/46XX mosaic (n = 28), 45X/47XXX mosaic (n = 11), and other (n = 14). The number of AMH measurements varied from 1-10 and the longest duration of AMH follow-up was 11 years. A subgroup of 9 patients met diagnostic criteria for PCOS.
Median AMH for the 45X/46XX group was 21.25pmol/L (range 0.45-59.36), for the 45X group the median was 1.39pmol/L (range 0.20-2.57), in the 47XXX mosaic group the median was 5.05pmol/L (range 0.70-13.97) and in the other group the median was 9.35pmol/L (0.20-54.40).
There was a significantly higher mean AMH, adjusted for age and baseline AMH, in the PCOS group than non PCOS group, mean 26.83 vs 16.23 pmol/L (p &lt; 0.01).
Overall, the mean rate of change of AMH was +0.0386pmol/L per month 95%CI [-0.0454, +0.1227] and the median was 0.0000pmol/L per month. In the PCOS group, the mean rate of change was +0.0034 pmol/L per month, median 0.0000pmol/L per month. Regression analyses determined that neither age or baseline AMH had a significant impact on the rate of change.
Only one patient in the cohort went onto develop POI during the period of follow up.

Limitations, reasons for caution
The average age of this cohort at the end of the reported follow up period is 25.9. Ongoing prospective follow up is needed to assess the stability of ovarian reserve into the later part of the typical reproductive window to confirm ongoing stability and assess age reated decline.

Wider implications of the findings
These findings question the necessity and efficacy of fertility preservation in this subset of TS patients as ovarian reserve is stable over time. Until further data is available, we advocate offering observation with annual AMH masurement rather than immediate recourse to fertility preservation.

Trial registration number
Not applicable