Whole-ovary transplant successful in sheep

Whole, frozen and then thawed ovaries have been successfully transplanted in sheep, resulting in viable embryos. The technique offers the hope of motherhood to young women about to undergo cancer therapies known to cause infertility. Aggressive radiation or chemotherapy treatments for cancer can destroy ovaries. Unfortunately just 2% of human eggs, or oocytes, survive the freezing and thawing process necessary to preserve them for future use. Fertilised eggs have a much better track record, but for that, a woman must already have chosen the father.

The best treatment so far is frozen and thawed ovarian grafts. These small sections of tissue are harvested before cancer treatment and then transplanted back into the body – into the ovaries, arm or abdomen – when treatment is finished. Two direct grafts back onto ovaries have resulted in successful, natural pregnancies in humans. But without built-in blood vessels, up to half of the surviving follicles –sacs of cells in the ovary, each containing a maturing ovum – die immediately after transplantation due to lack of blood supply. Grafts also tend to be short lived. “The benefit of transplanting the whole ovary, the organ and blood vessels, is that you have immediately renewed blood flow. There is a much better chance of survival for the follicles,” says co-author Yehudit Nathan at IMT Ltd in Ness Ziona, Israel, a research company specialising in cryobiology.

Nathan and her colleagues removed both ovaries from eight sheep, being careful to take the delicate blood vessels attached to the right ovary, too. They then slowly froze the right ovaries at a steady rate to control ice crystal growth – if crystals grow too large, they can damage and kill fragile cells. Two weeks later, they thawed and implanted the ovaries back into the sheep, into the place previously occupied by the left ovary. Five of the eight ovaries showed immediate blood flow and were considered a success. One month later, the team successfully retrieved egg cells from two of the sheep. At four months, one of these two ewes produced another four egg cells. The team used chemicals to mimic fertilisation – to avoid the complications of varying sperm quality – and found that all eggs grew into viable embryos. Three years on, and MRI imaging and hormone tests showed that the ovaries were still functioning normally.

The feat, previously only accomplished in rats, is a “significant step forward”, says ovarian cryopreservation expert Kutluk Oktay at Weill Medical College at Cornell University, US. But he warns that the benefits of whole-ovary transplant must be weighed against the risks: it is literally putting half a woman’s eggs in one vulnerable basket. Human ovaries are three to four times larger than sheep ovaries and may not survive freezing and thawing so well, as size is a crucial variable to success – the bigger they are, the more difficult to safely freeze. Preserving grafts may end up being safer and more effective in the end. “One would need a head-to-head comparison of those two techniques. But if the survival rate after freezing is similar then the [whole-ovary] technique would be superior,” Oktay told New Scientist.

Source: journal Human Reproduction

New Scientist
September 27, 2005

Original web page at New Scientist