July 9, 2008 Researchers have shown for the first time that it is possible to stimulate a woman's ovaries to produce eggs for collection during the final phase of the menstrual cycle. The finding offers the chance for more women who have been diagnosed with cancer to restore their fertility following chemotherapy or radiotherapy -- cancer treatments that can seriously damage the ovaries, often permanently. The findings were presented at the 24th annual meeting of the European Society of Human Reproduction and Embryology in Barcelona July 7.
At present, women who have been diagnosed with cancer may want to have some of their eggs collected and frozen in order to give them an opportunity of having children once their cancer treatment has finished. However, conventional protocols involve starting ovarian stimulation only at the beginning of a woman's menstrual cycle (the day that menstruation starts). Therefore, if the cancer diagnosis is made at any other time in the cycle, a woman could wait up to six weeks before it would be possible to collect eggs (or oocytes) after ovarian stimulation. For many women, six weeks is too long to wait before starting cancer treatment.
Dr Michael von Wolff, vice-director of the Department of Gynaecological Endocrinology and Reproduction Medicine at the University of Heidelberg, Germany, told a conference news briefing: "Depending on what phase of her menstrual cycle a woman is in when she receives a cancer diagnosis, it can take between two and six weeks to start ovarian stimulation and collect oocytes. Two weeks is an acceptable amount of time in many diseases to wait before starting a cancer treatment such as chemotherapy, but three to six weeks is far too long."
The researchers conducted a pilot study in 40 women in 2007 to see whether it would be possible to initiate ovarian stimulation during the luteal phase (the phase in the menstrual cycle from ovulation to the start of the next menstruation), without first having to give drugs to stop the luteal phase.
"Although other research has looked at giving medication to stop the luteal phase and then starting regular IVF treatment a few days later, to my knowledge, nobody has ever started ovarian stimulation immediately, without delay, in the luteal phase, either for IVF or for cancer patients," said Dr von Wolff. "This is because, in traditional IVF, ovarian stimulation has to be started at the beginning of the menstrual cycle, otherwise the endometrium is inadequately developed and a fertilised oocyte would be unable to implant successfully."
The researchers started ovarian stimulation in 28 patients in the proliferative phase of their cycle (the time from the start of menstruation to ovulation) using standard stimulation medications (GnRH-analogues and human menopausal gonadtropin, HMG, or follicle stimulation hormone, FSH). In a second group of 12 women they started stimulation during the luteal phase, using GnRH-antagonists and recombinant FSH (a synthetic form of FSH) in order to hasten the end of the luteal phase (luteolysis) and promote the development of new follicles containing oocytes.
The average time of ovarian stimulation was 10.3 days in the first group and 11.4 days in the second group. A mean average of 13 oocytes were collected from the first group and 10 from the second group. Nearly 77% and 73% of the oocytes were mature in the respective groups, and after intracytoplasmic sperm injection (ICSI), 70% and 75% of the oocytes were fertilised respectively.
The researchers found that if ovarian stimulation was started in the second group during ovulation, then the luteal phase stopped after five days, and if stimulation was started in the mid-luteal phase, then it stopped within two days, enabling new follicles to start maturing.
Dr von Wolff said: "We found that the ovarian stimulation regime for patients in the luteal phase was successful in triggering the end of the luteal phase and the recruitment of a new cohort of follicles. The number of oocytes obtained after stimulation in the luteal phase was slightly but not significantly lower than those obtained after stimulation in the proliferative phase. However the oocyte quality was the same in both groups. This pilot study demonstrates for the first time that mature oocytes can be obtained before cancer therapy within a time frame of two weeks.
"This new protocol would enable patients with cancers such as breast cancer and Hodgkin lymphoma to have ovarian stimulation and oocyte collection. Waiting for two weeks before they start cancer treatment is acceptable for most patients while this process happens. For breast cancer patients, this technique can be combined with the anti-oestrogen drug letrozole. Furthermore, this protocol allows the combination of freezing and storing both ovarian tissue and oocytes, which results in the women having a higher chance of achieving pregnancy if their cancer treatment causes ovarian failure."
Dr von Wolff said information about these new techniques needed to be disseminated to oncologists so that they were aware of the options available to their patients to help them preserve their fertility. National networks of specialised centres capable of carrying out these techniques should be established, he concluded.
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