ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2022) 19 9.6 | DOI: 10.1530/ey.19.9.6

ESPEYB19 9. Oncology and Chronic Disease Fertility issues and reproductive outcomes in childhood cancer survivors (9 abstracts)

9.6. Serum anti-mullerian hormone levels and risk of premature ovarian insufficiency in female childhood cancer survivors: systematic review and network meta-analysis

M. Torella , G. Riemma , P. De Franciscis , M. L Verde & N. Colacurci Cancers 2021, 13, 6331. PMID: 34944951.

Brief Summary: This systematic review and meta-analysis examined the value of anti-Müllerian hormone (AMH) to predict premature ovarian failure (POI) in childhood cancer survivors (CCSs), compared to the general population.

The potential toxic effect of alkylating agents and body irradiation on female reproductive function is well known. To date, antral follicle count (AFC) by transvaginal ultrasound is considered the most reliable measurement to predict ovarian reserve. AFG is not applicable in young children and is often refused by adolescents due to discomfort. Several studies aimed to identify a specific biochemical marker to predict POI. AMH is secreted by granulosa cells of growing pre- and early antral ovarian follicles. The serum level of AMH is low during childhood, increases during puberty reaching a plateau during the mid-twenties; thereafter it decreases until the menopause. Age-related reference ranges are available. AMH is representative of ovarian reserve in all ages and its level is not dependent on the menstrual cycle phase.

The Authors identified 251 studies, but selected only the 8 studies which had an appropriate age-matched control group (1303 participants: 663 CCSs and 640 healthy controls). A forest plot and a prediction interval plot were constructed to compare the impact of the different cancers on women’s fertility (AMH levels) and to rank them using a ranking plot (Surface Under the Cumulative Ranking curve Area (SUCRA). The SUCRA is a numeric representation of each treatment effect by a percentage, ranging from 0 to 100%. The closer the SUCRA is to 100%, the higher is the likelihood that a therapy ranks as the most influential.

Women treated for a neuroblastoma during infancy ranked first for impaired AMH levels (SUCRA 65.4%), followed by mixed CCSs (29.6%). Neuroblastoma survivors showed the highest rates of POI (42.5%), followed by acute lymphoid leukaemia (26.3%) or any other neoplasia (20.5%), and rare chances were reported in patients with thyroid cancer (1.9%) or no cancer (1.6%).

The Authors concluded that AMH levels represent a reliable indirect tool to predict POI. The major strength of this meta-analysis is that all the 8 selected studies included a matched control group. On the other hand, the selected studies had been performed between 1964 and 2017, on patients affected by different neoplasms treated with various therapeutic regimens, some of which are now outdated.

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