US doctors have created a human embryo from a woman's ovarian tissue after it was frozen for six years and then grafted on to her stomach.
The technique is a step towards helping female cancer patients bypass infertility caused by harsh chemotherapy and radiotherapy, and may help delay natural menopause in other women, says lead researcher Kutluk Oktay of the Center for Reproductive Medicine and Infertility, part of the Weill Medical College of Cornell University and New York-Presbyterian Hospital.
The team cut an ovary out of a 30-year-old breast cancer patient about to undergo chemotherapy and froze it at -196° C. Six years later, they thawed 15 fingernail-long strips and grafted them under the woman's abdominal skin using a local anaesthetic. They "feel like beads under the skin," says Oktay.
Three months later, the woman's hormones prompted the tissue to start making eggs, which the doctors boosted with fertility drugs. Over eight months they collected 20 mature eggs with a needle and mixed eight of them with sperm for in vitro fertilization (IVF).
Two eggs went on to form embryos in culture, the team report in The Lancet1. One was implanted in the woman, but it did not lead to pregnancy. This is not surprising in IVF treatment, where the chances of successful implantation are 20-30% at best. Oktay is trying once more to produce a pregnancy in the same woman and he is about to start the procedure on others.
Once the technique is improved, doctors say it may offer hope to cancer patients or others whose ovaries are affected by disease or drugs. Some of these patients have already banked their ovarian tissue.
But there are some caveats. The technique may not be appropriate for women suffering leukaemia, breast cancer or other cancers in which tumour cells can lodge in the ovary and might be reintroduced with the graft. "We cannot present it to patients as routinely possible now," says Johan Smitz who studies reproductive medicine at the Free University of Brussels, Belgium.
There are also concerns that any children born from the technique might be somehow different, although animal experiments suggest that offspring should be normal.
Success story
Over the last few years, Oktay's group have grafted pieces of thawed ovarian tissue on to women's ovaries or arms, and showed that the tissue resumes making eggs. "What is really new is that they got live embryos," says Smitz.
If the technique proves safe, then other women might bank ovarian tissue when they are young in order to bypass the natural decline in fertility that occurs with age. Women are born with a limited supply of immature eggs in their ovaries that either die or are ovulated throughout life and are exhausted at menopause.
Reproductive biologists have created 30-40 babies from frozen, mature eggs that were collected using fertility drugs. But only a handful of eggs can be harvested this way and many cancer patients do not have time for the procedure before their treatment.
Freezing ovaries appears one of the most promising techniques because the tissue contains a big store of immature eggs. Some scientists have tried grafting ovarian tissue on to mice or other animals to keep it alive, but this raises concerns about contamination with animal viruses.
Researchers are studying other ways to bypass age-related infertility or menopause, searching for molecules that might stall the natural decline in the number and quality of eggs. "If we can understand this then perhaps we can design a drug to stop it," says Smitz.
References
Oktay, K. et al. The Lancet, published online, (2004). |Article|
Park SP, Lee YJ, Lee KS, Shin HA, Cho HY, Chung KS, Kim EY, Lim JH.Establishment of human embryonic stem cell lines from frozen-thawed blastocysts using STO cell feeder layers. Hum Reprod. 2004 Mar;19(3):676-84. Epub 2004 Jan 29.
