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LONDON, Mar 29 (Reuters Health) - Women who become pregnant soon after taking a chemotherapy drug may be at higher risk for miscarriage or fetal malformations, according to a study in mice released Thursday.
The finding could have implications for cancer patients who undergo egg retrieval and in vitro fertilization (IVF) during a break in treatment, the researchers said.
The research on mice suggests that eggs collected from women within 6 to 12 months of treatment could be particularly vulnerable to malformations.
The study, published in the journal Human Reproduction, was carried out by Dr. Dror Meirow at the Rabin Medical Centre and Schneider Children Medical Centre in Israel and colleagues at the Hadassah Medical Centre in Jerusalem, the University of Leeds in the UK, and the Royal Victoria Hospital in Montreal.
The chemotherapy drug cyclophosphamide is known to increase the risk of fetal malformations and miscarriages, and at higher doses it may cause premature menopause and infertility.
However, the outcome in cancer patients who have gotten pregnant have been reassuring, although in some cases, women became pregnant a long time after treatment stopped.
Women with cancer can have their eggs retrieved, fertilized and the resulting embryos frozen before treatment in case their fertility is damaged. But because this takes time--and may lead to a delay in cancer treatment--some women undergo egg retrieval and embryo freezing during a break in treatment or when patients go into remission. For example, they may undergo the procedure following initial non-sterilizing chemotherapy and before a bone marrow transplant.
"Eggs retrieved at these points have suffered very recent exposure to chemotherapy and may therefore have been at growth stages rather than the dormant primordial stage," Meirow said in a statement issued by the European Society for Human Reproduction and Embryology. "So we are in a new situation and it has become essential to determine if there are greater risks associated with eggs exposed to chemotherapy during or immediately before growth stages."
In the study, the researchers looked at pregnancy outcomes in mice 1 and 4 weeks after treatment with cyclophosphamide. Human eggs take from 6 to 12 months to go from the dormant stage to a pre-ovulatory stage, which corresponds to about 3 weeks in mice.
The researchers found fewer pregnancies in mice whose eggs were at a mature stage when they received chemotherapy. The miscarriage rate was increased and the malformation rate was 10 times that seen in untreated mice.
However, the malformation rate declined over time and was similar to that seen in untreated mice if the pregnancies occurred 12 weeks or more after treatment.
More research is needed to know whether the same applies in humans.
"If it does, it will become vital to define a 'safety period' between treatment stopping and egg retrieval," Meirow said. "Until we know more, it would seem advisable to monitor the pregnancy outcome of all cancer patients who undergo IVF and embryo cryopreservation after chemotherapy, and possibly to screen fetuses and babies for chromosomal aberrations and birth defects."
SOURCE: Human Reproduction 2001;16:632-637.
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