Women who have survived having leukaemia as children should receive fertility counselling because their reproductive life may be shortened even though they have an apparently normal menstrual cycle after treatment, according to Danish researchers.

Dr Elisabeth Larsen, a research assistant from the Fertility Clinic at Copenhagen University Hospital, Denmark, has studied 26 long-term survivors of acute lymphoblastic leukaemia (ALL) and found that they tended to have smaller ovaries with fewer follicles (the group of cells containing the female egg) available in each menstrual cycle. However, the good news was that their ovaries appeared to be functioning normally in all other respects, she told the annual conference of the European Society of Human Reproduction and Embryology.

She said: "Multi-agent chemotherapy has radically increased long-term survival of children with acute lymphoblastic leukaemia, but the treatment can induce late effects. It is well known that a proportion of the patients experience ovarian failure and infertility. The new finding is that female childhood cancer survivors with an apparently normal menstrual cycle might have a shortened reproductive span."

Dr Larsen and her team took menstrual and pregnancy histories from 26 women* who had received standard chemotherapy for ALL contracted between the ages of six months and fourteen and a half years, and compared them with a control group of 20 women with no history of childhood cancer. Eight of the women in the ALL group had become pregnant naturally, resulting in 12 babies, one abortion and two ongoing pregnancies. One woman, aged 33, had tried to become pregnant without success for five years, but many of the women were young and 17 of the 26 had not even tried to conceive yet. All the women had regular menstrual cycles and normal hormonal levels, although the length of the cycle in the ALL group was significantly shorter than in the control group (28.9 versus 30.7 days).

The researchers used transvaginal ultrasounds, taken at the beginning of the menstrual cycle, to measure the volume of the women's ovaries and to count the number of antral follicles (follicles that may mature and subsequently ovulate). They found that women in the ALL group had ovaries which were significantly smaller than the control group (12.3 ml in total volume compared with 13.7ml), and the total number of antral follicles per ovary was significantly lower in the ALL women, with an average of eight per ovary compared with 11 in the control group.

Dr Larsen said: "Although these long-term survivors of childhood leukaemia have an apparently normal ovarian function, our results suggest that the chemotherapy has reduced the numbers of follicles in the ovaries. Therefore it is important that women who have survived childhood leukaemia should receive careful and individual fertility counselling as their reproductive life may be shortened."

She said that it was not possible to give a precise estimate of how much shorter the women's reproductive life might be. "At present, in our hospital, we recommend to all female survivors of childhood cancer with normal ovarian function that they should try to have their first child before they are 30. However this recommendation is not made on the basis of any scientific findings. The majority of long-term survivors attend regular follow-up check-ups at our outpatient clinic and we are considering offering fertility counselling to them between the ages of 18 and 20.

"The important message to come from this research is women who have survived ALL can become pregnant and have babies and they are doing so. However they should not postpone childbearing, and it might be that they should consider becoming mothers before pursuing a career," concluded Dr Larsen.

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Abstract no: 0-228 (Wednesday 11.00hrs CET Hall E2) URL: http://conf.eshre.com/PDF/O-228.pdf

* Childhood cancer is relatively rare with approximately 150 new cases diagnosed each year in Denmark. Fifty per cent are treated at Dr Larsen's hospital, and of these 35 will be girls and about 25-35% of these girls will have ALL.

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