Dr Robert Gilchrist

Reproductive Medicine Unit, University of Adelaide

The current options for preserving or extending fertility for women are limited.  Advances in cryobiology (the science of deep freezing cells and tissues) mean that the freezing of early embryos and sperm is now routine in IVF labs, however the freezing of female eggs or pieces of ovary is far more difficult.  It is not clear why this is, but there is something about the physical structure of the egg that makes it difficult to freeze.  So the technique is still largely experimental, and in Australian ART clinics, successful freezing of eggs or ovarian tissue is not widely available to patients. 

For young women who are diagnosed with cancer this is an added blow to an already disastrous situation.  Radiotherapy and chemotherapy cause destruction of the developing eggs in the ovary leading to sterility.  Women undergoing surgery to remove tumours immediately prior to chemotherapy could safely have an ovary or pieces of ovary removed and frozen.  If we knew how to protect the eggs from freezing damage and how to grow the small follicles from this tissue, then we could use this tissue to restore fertility to these women.  Sadly limitations in the technology mean this is still not a clinical reality.

A breakthrough in freezing ovaries

This possibility came one step closer in January this year with the announcement that researchers in Montreal, Canada, have recently achieved a pregnancy in rats after freezing the whole ovary¹.  The experiment involved removing a whole rat ovary, the fallopian tubes and part of the uterus, infusing these organs with cryoprotectant (a type of anti-freeze), freezing them in liquid nitrogen, then later thawing and transplanting the organs back into recipient rats.  Hormone levels were restored to close to normal levels in the recipient animals, and four out of the seven rats that received a frozen-thawed ovary transplant ovulated. The recipients were mated with males and one pregnancy was established.  This is a promising breakthrough because it demonstrates for the first time that a whole ovary and part of the reproductive tract can remain functional after freezing, thawing and transplantation. 

Up until now, researchers have focused on using small pieces of ovary and either trying to grow the ovarian follicles in the laboratory, or transplanting the tissue back to the patient.  In fact in 1999 the same group in Montreal transplanted ovary pieces to the pelvic wall in a young woman who had had both her ovaries removed for other medical reasons, and in so doing they were able to restore her menstrual cycle for a short period.  There are a number of difficulties associated with this approach; the transplanted ovary pieces generally have a poor blood supply and in the time it takes for a capillary network to develop many of the eggs die, there is only a limited supply of eggs in a small piece of ovary which is quickly exhausted, and finally, because the tissue is not in its natural place at the end of the fallopian tube, further intervention would be required to collect the eggs and transfer them to the tube or to fertilise them in vitro. 

The current finding circumvents these drawbacks because a whole ovary is transplanted back into its correct place in the body, with a blood supply more or less intact.  However the technical difficulties of infusing a whole rat ovary with cryoprotectant are substantial.  The possibility of doing it with a human ovary that is about 100 times larger is some way off.  Many more years of research are required to substantiate the results in rats and to extend the technique to larger animals, before a clinical trial could be initiated in women.  Furthermore it needs to be proven that cancer patients that have been through treatment are not at risk of receiving cancerous cells again in their transplanted ovary.

Slowing the biological clock ?

This type of technology could be used for other applications as well – for the preservation of endangered animals and, far more controversially, to slow the biological clock in women.  Young women who for non-medical reasons want to post-pone their child-bearing years, could theoretically have one ovary removed, for example in their late 20s, and frozen indefinitely.  The remaining ovary would compensate so that normal hormone levels are retained, and the woman could then have her ovary transplanted back to her in her forties, or even later, without biological ageing of the eggs. 

If such a technique was successful, this would effectively setback menopause 20 years, and eliminate the chromosomal and congenital problems associated with conceiving late in a woman’s reproductive life.  There are however many hurdles to overcome before such a technology could be offered to patients.  Apart from conquering the technical challenges and proving in animals that the technology is safe, society will have to grapple with the moral issues of ART clinics having the means to extend women’s fertility well into later life, and with the use of public money to fund non-medical fertility manipulation.

¹Wang X., et al  (2002) Fertility after intact ovary transplantation.  Nature 415:385.