INSERM: Researchers from the Paris Public Hospitals (AP-HP), Inserm,
the Gustave Roussy and Curie Institutes, and Oscar Lambret Cancer
Centre, coordinated by Dr Cécile Thomas-Teinturier of the Paediatric
Endocrinology Service at Bicêtre Hospital, have studied the impact of
certain therapeutic agents on the fertility of women who have been cured
of a paediatric cancer. This research, carried out with support from
the French National Cancer League, is published in the journal Human Reproduction on 23 March 2015.
Now that survival is increasing, the impact of therapeutic agents on the future fertility of girls cured of cancer in childhood can affect their quality of life.
In all women, the length of reproductive life is related to the number
of follicles present in their ovaries, a reserve that cannot be renewed,
and that declines over time. Menopause occurs when this number declines below a certain threshold, 5-10 years after the end of fertility.
In this study, the researchers proposed the hypothesis that women who
have undergone chemotherapy with a class of drugs known as alkylating
agents—cyclophosphamide, ifosfamide, procarbazine—to treat a childhood
cancer can have reduced follicular reserve, even though their apparent ovarian function may still be intact (regular cycles).
They evaluated the ovarian reserve in 105 women cured of cancer
during childhood, who had received alkylating agents during their
childhood, but no radiation therapy in the pelvic area. Investigations
included measurement of hormone levels, particularly anti-Müllerian
hormone (a reliable marker of ovarian reserve), ultrasound measurement
of ovarian size, and follicle count. Results were compared to those for
20 women of the same age who had not received chemotherapy.
The team observed that the 105 women cured of paediatric cancer had smaller ovaries
than the untreated women, and a significantly lower level of
anti-Müllerian hormone. This reduction was more marked in patients who
had received procarbazine for Hodgkin’s lymphoma, or chemotherapy with
high doses of alkylating agents prior to a bone marrow transplant.
Neither the cyclophosphamide nor ifosfamide dose seemed to be associated
with reduced ovarian reserve.
“These results seem to confirm our hypothesis,” explains Dr Thomas-Teinturier. “From
a theoretical point of view, the end of fertility is likely to occur
earlier in these women who have been cured of a paediatric cancer. This
fact, when combined with increasing age at first pregnancy, is likely to
increase problems with reproduction.”
However, although assessment of ovarian reserve seems to be a good
predictor of the pregnancy rate in infertile women undergoing medically
assisted reproduction techniques, there are few data regarding its real
use when advising young women cured of paediatric cancer about the
potential effects on their fertility, and their risk of early menopause.
“It therefore seems necessary to monitor these markers in this
patient cohort in order to define the thresholds that may make it
possible to predict the window of fertility and onset of menopause in
the following years,” continues Dr Thomas-Teinturier. “The
ultimate objective of our study is to be able, in future, to advise
these young women individually on their potential for reproduction in
the following five years, based on the results of their review at a
given moment.”