Conception Possible Even After Loss-of-Fertility Associated with Chemotherapy
Jan 9, 2003
One Breast Cancer Survivor Gives Birth to Twins
The Center for Reproductive Medicine and Infertility at NewYork Weill Cornell Medical Center has discovered that the wonder drug tamoxifen can help breast cancer patients have babies even after they experience fertility loss associated with chemotherapy. A preliminary study published in the current issue of Human Reproduction is the first to describe how an in vitro fertilization (IVF) pregnancy resulted from the use of tamoxifen as an ovarian stimulant.
In the study co-authored by Dr. Kutluk Oktay and Dr. Zev Rosenwaks, Director of the Center for Reproductive Medicine and Infertility research found that a short, carefully timed course of tamoxifen boosted patients' ability to produce eggs. Every woman participating in the study produced one or more embryos, which were then either frozen or immediately implanted in their womb. One patient who had two fresh embryos transferred has already given birth to twins.
Women with breast cancer no longer have to give up on having children, said Drs. Oktay and Rosenwaks. This treatment allows women to connect with their future and underlines that because they have breast cancer, it does not mean they have a terminal illness. It would be especially fitting if a drug that has saved so many women's lives should also preserve their fertility.
Dr. Oktay said that the experiment arose from a desire to find a safe way to preserve fertility among the 15 percent of breast cancer patients around 27,000 annually in the U.S. who are still of reproductive age when they are diagnosed.
Chemotherapy causes ovarian failure in many patients nearly as many as four out of five women in the case of those given cyclophosphamide. Even women who remain fertile or do not have chemotherapy face the problem of needing a recurrence-free period of two to five years before trying to conceive, bringing them up against the barrier of infertility due to aging and diminishing ovarian reserves.
These women can try natural cycle IVF without ovarian stimulation, but typically, no more than a single embryo can be achieved for immediate use or freezing. It turns out that tamoxifen is a safe way of increasing the number of embryos to give these women a better chance of having a baby," said Dr. Oktay.
Tamoxifen was developed in the U.K. in 1966 as a contraceptive, but was later found to stimulate ovarian follicle growth and became used in Europe as an ovarian stimulant. (A related compound, clomiphene, is commonly used in the U.S.) It wasn't until 1976 that tamoxifen's suppressive, anti-estrogenic effect on breast cancer was discovered. Since then, it has become the world's most successful anti-cancer drug, saving the lives of thousands of breast cancer patients every year worldwide.
Sometimes the best ideas are the obvious ones, and tamoxifen seemed the best drug to test, although, to my knowledge, no one has tried it before in breast cancer patients, said Dr. Oktay. We hypothesized that tamoxifen stimulation would result in higher numbers of embryos compared with natural cycle IVF, while theoretically shielding breast cancer cells against estrogen.
A retrospective group of five breast cancer patients who had undergone nine natural cycles of IVF was used as a control for the 12 study patients. The tamoxifen patients produced a greater number of mature eggs (1.6 versus 0.7) and embryos (1.6 versus 0.6) than the controls. All tamoxifen patients generated embryos compared with three out of five controls. After a mean follow up of around 15 months, none of the study patients has had a recurrence of cancer.
The authors caution that the study is a preliminary one, and larger numbers are needed to verify and confirm the results. Moreover, because most patients in the tamoxifen group froze their embryos while most in the control group had fresh embryo transfer, it has not been possible yet to compare pregnancy rates between the two protocols or to provide long-term data on the effects of tamoxifen on pregnancy. However, long-term experience of the drug in ovulation induction does not suggest an embryo-damaging effect.
Drs. Rosenwaks and Oktay urge all breast cancer physicians to be aware of the effect of chemotherapy on women of reproductive age, and to refer them to an appropriate assisted reproduction center as soon as a diagnosis is made so that options for preserving fertility can be discussed.
Dr. Zev Rosenwaks is also Revlon Distinguished Professor of Reproductive Medicine in Obstetrics and Gynecology at Weill Cornell Medical College, Co-Director of the Institute for Reproductive Medicine at Weill Cornell, and Attending Obstetrician and Gynecologist at NewYork-Presbyterian Hospital Weill Cornell Medical Center. Dr. Kutluk Oktay is Assistant Professor of Obstetrics and Gynecology at Weill Cornell Medical College and Assistant Attending Obstetrician and Gynecologist at NewYork-Presbyterian Weill Cornell.
Other contributing authors to the study all at Weill Cornell include Dr. Erkan Buyuk, Dr. Owen Davis, Dr. Lucinda Veeck, and I. Yermakova.