Human oocyte-freezing techniques are improving so rapidly that this procedure may soon be incorporated into routine in vitro fertilization cycles, experts predicted recently at the WARM meeting in Mexico last month. Currently, most oocyte freezing is done for cancer patients and other women who face potentially sterilizing chemotherapy treatments. And it is beginning to be offered for fertility preservation in young, healthy women worried about their biological clock.
But extending its application to the general in vitro fertilization (IVF) population could increase the flexibility of IVF; oocytes could be frozen rather than discarded in cycles that have to be canceled because of ovarian hyperstimulation syndrome or the absence of a sperm sample. Oocyte cryopreservation could also overcome some legal and ethical dilemmas posed by embryo freezing.
Until now, oocyte freezing has not been a satisfactory alternative to embryo freezing, because oocytes are more fragile than embryos and thus less likely to survive after being thawed. But recent technological improvements have made oocyte freezing a much more viable option, though there is still much debate over the merits of various freezing and thawing methods and of cryoprotective and culture solutions.
"Oocyte freezing will become a standard part of IVF within 5 years worldwide," predicted Giovanni Battista La Sala, M.D., whose clinic at Santa Maria Nuova Hospital in Reggio Emilia, Italy, is the first in the world to use the procedure in all standard IVF cycles. Under the protocol, patients have three of their oocytes fertilized, and the resulting embryos are transferred to the uterus. The remaining oocytes that have been retrieved are frozen and stored for future use, he told this newspaper.
Italy has always been at the forefront of oocyte-freezing research, and its efforts in this field have intensified in the last year after the introduction of new Italian legislation that bans embryo freezing and restricts standard IVF to the creation of no more than three embryos.
The Italian efforts to make oocyte freezing a viable alternative to embryo freezing may end up setting new standards even in less restricted countries, such as the United States, suggested Thomas L. Toth, M.D., director of the in vitro fertilization unit at Massachusetts General Hospital, Boston.
"This alternative approach may be more ideal for providing IVF therapies to our patients. I think the Italians have done very well, and the rest of the world should be watching carefully," he said in an interview.
Dr. La Sala's experience of incorporating oocyte freezing into his standard IVF protocol has produced only 8 ongoing pregnancies out of 324 thaw attempts in the last 14 months. However, worldwide data on oocyte freezing are more encouraging, suggested Eleonora Porcu, M.D., director of the fertility and IVF center at the University of Bologna and a pioneer in the field.
Although the world's first frozen oocyte birth was announced in 1986, followed by two more--one from her own patient and another in 1987 in the United States--there were no more such births in the ensuing decade. Since then, only about 150 babies have been produced using frozen oocytes because of specific technical difficulties, some of which can now be overcome.
"I am convinced that the previously poor results leading the majority of researchers to conclude that oocyte freezing was unreliable, inefficient, and unsafe were due to the fact that they were generally restricted to using excess oocytes," which were few, of inadequate quality, and often old, Dr. Porcu said.
In a study attempting to overcome these limitations, her team froze all oocytes of IVF patients with tubal infertility who were under age 38. They then performed oocyte thawing, fertilization, and embryo transfer in the subsequent cycle.
After more than 500 transfers, the team reported a pregnancy rate per embryo transfer of 17% and a pregnancy rate per patient of almost 24% (sometimes over more than one thaw cycle). There was a high spontaneous-abortion rate (25%), however, which has been noted by other oocyte-freezing experts.
The most extensive U.S. experience with oocyte freezing is from the IVF program at Community Hospital North in Indianapolis, where there have been 13 births reported from frozen oocytes since 1999. This brings the pregnancy rate per embryo transfer to 34% said Donald Cline, M.D., medical director of the clinic.
When comparing frozen-oocyte with frozen-embryo pregnancies, his group noted similar success rates--between 34% and 36% per transfer. "We were pleasantly surprised. It will take more numbers to determine if these data are accurate. But if they are, and we have the same pregnancy rates with frozen oocytes as we do with frozen embryos, this will be the way a number of our patients will want to go," he said.
