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New methods to preserve fertility

Yale Medicine Magazine, 2006 - Autumn

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Besides oocyte cryopreservation, researchers are exploring other methods to preserve female fertility. For women with early-stage cervical cancer, a more conservative, but technically challenging surgery called radical vaginal trachelectomy has been found to preserve fertility in some patients. A recent study found that of 319 women who had the surgery, 147 pregnancies were recorded, including 99 live births (67 percent). Charles J. Lockwood, M.D., the Anita O’Keefe Young Professor of Women’s Health and chief of obstetrics and gynecology at Yale-New Haven Hospital, says this procedure still needs improvement. It is used only for the “absolutely desperate,” because of the high rate of subsequent preterm deliveries associated with it.

Younger patients diagnosed with some borderline ovarian tumors can undergo a more conservative surgery, in which the surgeon removes only the affected ovary, leaving the unaffected ovary and uterus intact. So far, data show that the outcome after this surgery is comparable to that of the more radical approach of removing both ovaries and the uterus.

And patients with early-stage endometrial cancer can opt for progesterone therapy instead of an immediate hysterectomy. After the cancer has been diagnosed, the patient begins hormone therapy, which temporarily suppresses the cancer. The aim is to buy the patient enough time to conceive and carry the pregnancy to term. Once the baby is born, the patient stops taking the hormones and has a hysterectomy.

“This is a reasonable course of action for many early-stage endometrial cancers, but it requires careful monitoring,” says Lockwood. “We’ve cared for three patients using this approach, and they’ve all done fabulously well.”

A woman’s fertility can be compromised by any treatment for cancer that interferes with the functioning of the ovaries, fallopian tubes, uterus or cervix, or that causes a hormonal imbalance. Surgery is the most obvious way in which fertility can be lost, but other causes include the patient’s response to the chemotherapy or radiation, the method of administration (oral or intravenous), the dose intensity and the size and location of the radiation field.

For patients who need pelvic radiation, a surgical technique called ovarian transposition is sometimes used to reposition the ovaries at a safe distance from the radiation field. This approach, which is relatively simple and minimally invasive, is most commonly used in patients with Hodgkin’s disease, cervical and vaginal cancers and pelvic sarcomas.

Other therapies being explored include administration of gonadotropin-releasing hormone. This hormone temporarily puts the body in a menopausal state, which is believed to result in less damage to reproductive organs during chemotherapy. Another technique, still experimental, is ovarian tissue cryopreservation. Ovarian tissue is removed from the cancer patient prior to treatment, and frozen if it is found to be free of metastatic disease. Once the patient is cured and wants to get pregnant, the cryopreserved ovarian tissue is thawed and placed back in the ovary or another body part that is more easily accessible, such as the subcutaneous tissue of the abdomen, and that can accommodate the tissue and allow it to function. It has been shown that ovarian tissue removed prior to the initiation of cancer treatment is functional following the thawing process, but only for a short time. Worldwide, two babies, in Belgium and in Israel, have been born using this option when the ovarian tissue was placed back in the pelvis where the ovary is normally located. This fall Pasquale Patrizio, M.D., M.B.E., professor of obstetrics and gynecology, the director of the Yale Fertility Center and the oncofertility program, is starting a new project to perfect the method of ovarian preservation. Instead of freezing sliced tissue, he plans to freeze the entire ovary, which he believes will better survive the freezing and thawing process.

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