ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 9.8 | DOI: 10.1530/ey.16.9.8


Hum Reprod. 2018 Jul 6. [Epub ahead of print]. doi: 10.1093/humrep/dey229

Childhood cancer treatment may compromise ovarian function in female childhood cancer survivors (CCSs), leading to delayed or arrested puberty, infertility, subfertility and adverse pregnancy outcomes. This Dutch nationwide retrospective cohort study collected measurements performed between 2008 and 2014. In total, 1749 female 5-year CCSs, diagnosed before age 18 years between 1963 and 2002 and 1201 controls were invited to participate. Ovarian reserve was assessed by anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B levels, and antral follicle counts (AFC). In total, 564 CCSs and 390 controls participated in the clinical part of the study.

The proportion of CCSs with abnormal ovarian reserve markers was remarkably low, even after treatment with alkylating agents (6.5–13.0%). Above age 35 years, a higher proportion of CCSs showed abnormalities of ovarian reserve markers compared to controls (AMH: 26% vs. 4%; AFC: 20% vs. 3%; inhibin B: 42% vs. 16%); while AMH and FSH levels showed differences also below age 35. Combined treatment with alkylating agents and gonadotoxic radiotherapy resulted in the lowest AMH, AFC, and inhibin B levels, and the highest FSH levels in all age groups. Clear dose–effect relationships were seen for procarbazine and abdominal/pelvic radiotherapy. Treatment with busulfan, melphalan, chlorambucil or lomustine also increased the risk of reduced ovarian reserve. Abdominal/pelvic RT affected all ovarian reserve markers at almost any dose, a finding consistent with previous studies and a clear dose–effect relationship was established for AFC and inhibin B.

This study surprisingly shows that the majority of CCSs do not show signs of a reduced ovarian reserve. Moreover, the results are important on order to design future childhood oncology protocols in which the curative effect of the treatment is balanced with the risk of gonadotoxicity. Specific subgroups of CCSs (in particular those treated with alkylating agents and radiotherapy) appear to have a higher risk of early gonadal failure. These CCSs should be counselled adequately and new patients receiving such treatments should be referred early to a reproductive specialist for parenthood and fertility preservation counselling.

Article tools

My recent searches

No recent searches.

Authors