July 2, 2007 The first baby to be created from an egg that had been matured in the laboratory, frozen, thawed and then fertilised, has been born in Canada. Three other women are pregnant by the same process. The research was presented to the 23rd annual meeting of the European Society of Human Reproduction and Embryology today (Monday 2 July).
The baby girl was born to one of 20 patients with polycystic ovarian syndrome (PCOS) or with ovaries that had been detected to be polycystic by ultrasound (U/S), who took part in the trial at McGill Reproductive Center, Montreal, Canada. The baby is progressing well.
Dr Hananel Holzer, who led the team, is an assistant professor at the Center and coordinates the fertility preservation programme there . He said: "Freezing a woman's eggs (or oocytes) has become an important and integral part of fertility treatment, and the introduction of new freezing techniques such as oocyte vitrification has increased significantly both oocyte survival and resulting pregnancy rates. However, to date, the pregnancies reported have been the result of fertilisation of frozen or vitrified and then thawed oocytes that had been collected after ovarian stimulation. Unfortunately, some patients seeking fertility preservation may not have enough time to undergo ovarian simulation, or may suffer from a medical condition deemed by some oncologists as a relative contraindication to hormonal stimulation, such as oestrogen-receptor-positive breast cancer.
"In these circumstances, oocytes can be collected from the ovaries without hormonal stimulation, and the immature oocytes can be matured in the laboratory before being frozen or vitrified. But, until now, it was not known whether oocytes collected from unstimulated ovaries, matured in vitro and then vitrified, could survive thawing, be fertilised successfully and result in a viable pregnancy after embryo transfer.
"We have demonstrated for the first time that it is possible to do this and, so far, we have achieved four successful pregnancies, one of which has resulted in a live birth. The other three pregnancies are ongoing. These results are preliminary and the pregnancy rate is probably associated with a learning curve; indeed three of the pregnancies were achieved in the last five patients."
Dr Holzer warned that the research was still in its early stages and that it had not yet been proven in cancer patients. "It has the potential to become one of the main options for fertility preservation, especially for patients who cannot have ovarian stimulation and all patients who do not have enough time to undergo ovarian stimulation," he said. "However, we have to remember that these are only preliminary results from a small number of patients who were not cancer patients themselves. As for all methods for fertility preservation, they should be looked at as preliminary and experimental. We need to inform the patients about the early stage of these treatments without giving any false hopes."
Women who have been diagnosed with cancer face the prospect that the treatment they receive for their disease might make them infertile by destroying their ovarian reserve of oocytes. At present, there is the still experimental option of having the ovarian tissue removed, frozen and then transplanted back at a later date; however, there is the theoretical risk that this could re-introduce metastatic cancer into the woman. For women who are infertile due to PCOS, the administration of hormones to stimulate their ovaries to produce eggs can have the dangerous side-effect of over-stimulating their ovaries, resulting in the potentially life-threatening ovarian hyperstimulation syndrome (OHSS). Therefore, being able to obtain successful pregnancies after retrieving immature eggs from unstimulated ovaries is an important step forward for women in these situations.
The researchers selected 20 patients, with an average age of about 30, who were infertile, had polycystic ovaries and had agreed to have their eggs frozen as part of their in vitro maturation (IVM) treatment. A total of 296 oocytes were collected from the patients, of which 290 were immature. The oocytes were matured in the laboratory for 24-48 hours and then 215 were frozen using the Cryoleaf oocyte vitrification kit developed at McGill. They remained frozen for no longer than a few months, and then were thawed. From these, 148 oocytes survived the thawing process and were fertilised via ICSI (intra-cytoplasmic sperm injection); 64 embryos were transferred to the women. More than one embryo was transferred to each patient because IVM is known to have lower rates of implantation. The resulting pregnancies were singleton pregnancies, with the exception of one, which started as twins but became a singleton pregnancy due to spontaneous reduction.
Dr Holzer said he believed that adjusting the media in which the immature oocytes were matured in the laboratory was probably responsible for the improved success rate as the trial progressed.
"Fertility preservation is of the utmost importance to patients undergoing treatments that have the potential of making them infertile. Our research shows that it is possible to collect immature oocytes from unstimulated ovaries, mature them in vitro, freeze and thaw them and then achieve pregnancies and live births, without the risk of aggravating the patients' hormone-sensitive disease, delaying their treatment for cancer or re-instituting a metastatic malignant disease," he concluded.
The McGill Reproductive Center is led by Professor Seang Lin Tan and the scientific director is Professor Ri-Cheng Chian. They are both pioneers in the in vitro maturation of human oocytes and have developed the "McGill oocyte and embryo vitrification method" using the Cryoleaf system, which is now licensed to Medicult.
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