Birth breakthrough offers hope for girls needing chemotherapy

More than a decade ago, a 14-year-old Belgian girl was left infertile after going through a bone marrow transplant to treat sickle-cell anaemia, a condition she was diagnosed with at age five.

In November last year, at 27 years old, the woman gave birth to a healthy baby boy after receiving a different kind of transplant: the reimplantation of her ovarian tissue that was extracted and frozen before she embarked on the cancer treatment.

What is so significant about this case is that the patient had not begun ovulating when her immature ovary was removed in her early teens.

Previously, cryopreserved ovarian tissue was used only to produce healthy pregnancies in women who had the tissue removed in adulthood. In 2004, another Belgian woman became the first to give birth to a healthy baby, seven years after banking her frozen ovarian tissue before starting chemotherapy.

"This is an important breakthrough in the field because children are the patients who are most likely to benefit from the procedure in the future," says Dr Isabelle Demeestere, a gynaecologist at Erasme Hospital in Brussels who led the medical team that restored the patient's fertility.

"When they are diagnosed with diseases that require treatment that can destroy ovarian function, freezing ovarian tissue is the only available option for preserving their fertility."

Young female cancer patients who have begun ovulating can freeze their eggs instead before treatment. "But the main advantage of ovarian tissue transplant over egg freezing is the large number of eggs that can be frozen in one procedure, without the need to delay cancer treatment because of multiple ovarian stimulation cycles needed to retrieve eggs," says Professor Dominic Stoop, director of the Centre for Reproductive Medicine at UZ Brussels in Belgium, in an unrelated report published in The Lancet last October.

Surgery to replace ovarian tissue is also a straightforward and uneventful procedure, according to fertility experts.

So far, such a procedure has not been done for girls or women in Hong Kong, according to Dr Ernest Ng Hung-yu, a clinical professor at the University of Hong Kong's department of obstetrics and gynaecology.

"The transplant is not as straightforward as it looks, and its success depends on a number of factors, such as expertise and resources, and damage of the ovarian tissue on freezing," he says.

"Plus, it is not just about whether the patient can ovulate after the transplant, but for how long, as some transplants only last a few months, while others can last for a few years."

Still, Ng believes that fertility preservation should be offered to girls or women who are at risk of ovarian failure after chemotherapy.

In a report published last month in the medical journal Human Reproduction, Demeestere and team detailed their breakthrough.

The Belgian teen had to undergo chemotherapy in order to "disable" her immune system to prevent rejection of the donor's bone marrow. While chemotherapy helps in the safety and success of such transplants, the procedure is known to result in permanent infertility in most patients.

So, prior to her chemotherapy, the doctors removed one of her ovaries and cryopreserved the tissue. At the time of the procedure, she had not yet begun menstruating.

After the transplant, the patient developed graft-versus-host disease and had to take immune-suppressive drugs for 18 months. At the age of 15, her remaining ovary failed and doctors had to give her hormone replacement therapy to induce her periods.

A decade later, the patient expressed a desire to have a baby, and Demeestere's team worked to restore her fertility.

First, they stopped her hormone replacement therapy. They then removed fragments of her frozen immature ovary and implanted them onto her remaining, non-viable ovary. Tissue fragments were also grafted onto other sites in her body.

The transplant was a success; the grafted ovarian tissue responded positively to her hormones and started developing follicles that contained mature eggs.

Five months later the patient began menstruating naturally and regularly, and, two years after the transplantation, she became pregnant.

More research into this invasive procedure is still needed, however, because of the many questions and issues that surround it.

"We think, at present, that cryopreserved ovarian tissue should be used only for fertility restoration in patients at high risk of ovarian failure, and not for puberty induction or for restoring menstrual cycles in adults," Demeestre adds.

Dr Alexander Doo, director of The IVF Clinic and The Women's Clinic, agrees that the transplant procedure is complicated, but he believes that technology is advancing so quickly that it is only a matter of time before it is available to patients in Hong Kong - subject to the rules and regulations of the council governing human fertility and embryology, of course.

"Preservation of ovarian tissue is an extension of the technology used to preserve eggs, and it is potentially more useful and effective since we only have one cycle to harvest the patient's eggs," he says.

"With this new advancement, fertility can be restored not only in patients who have to undergo chemotherapy or radiotherapy, but also in women who for some reason want to delay pregnancy. Ultimately, it can even delay menopause in women, although this is more controversial."