OVARIAN TRANSPANTATION FOR FERTILITY PRESERVATION

February 25, 2010 — A former cancer patient in Denmark who had an ovarian transplant and gave birth to a daughter after IVF has had another child who was conceived naturally.

Doctors in Denmark are hailing the case as a medical first.

''We performed IVF [in vitro fertilization] initially, and expected to do that for the second child also," says Claus Yding Andersen, MD, a professor in human reproductive physiology at the University Hospital of Copenhagen, who reports the case in the journal Human Reproduction. ''However, this wasn't necessary and it turns out that maybe we do not need to do assisted reproduction in many of the cases," he tells WebMD in an email interview.

The news did not surprise a U.S fertility expert, who tells WebMD most of his transplant patients have conceived naturally. ''They just get pregnant naturally with intercourse," says Sherman Silber, MD, director of the Infertility Center of St. Louis, at St. Luke's Hospital.

Still, Andersen says that "we are surprised [at] how robust the procedure turns out and how long the transplants actually remain functional. We have other women who have had functional tissue for more than five years, having been transplanted with somewhat more tissue."

Although the numbers of transplants, pregnancies, and births resulting from ovarian transplants are in constant flux, Silber estimates about 50 ovarian transplant attempts have been made worldwide, with 13 at his center. Andersen says 15 women have received transplants with frozen or thawed tissue at his center.

In his paper, Andersen says before the Danish woman's second delivery, eight children worldwide had been born as a result of transplanted frozen or thawed ovarian tissue. Silber says the number is now higher. "We have 10 children [from his center] already,'' he says.

Timeline of a Medical First

The mother, Stinne Holm Bergholdt, now 32, was diagnosed with Ewing's sarcoma, a cancer of the bone or soft tissue, at age 27 in 2004. Before undergoing toxic cancer treatments, doctors retrieved part of her right ovary and preserved it by freezing. Her left ovary had been removed previously because of a cyst.

Her treatment included multiple sessions of chemotherapy and then surgical removal of the rest of the tumor. The chemo put her into early menopause.

In December 2005, doctors transplanted six thin strips of ovarian tissue from what remained of her right ovary. The ovary began working again. She underwent mild ovarian stimulation in Andersen's fertility clinic and became pregnant, giving birth to her first daughter Aviaja in February 2007.

In January 2008, Bergholdt, who is a doctor and a co-author of the paper, went back to Andersen's clinic, thinking she would need more IVF treatment to achieve a second pregnancy. But she found out she was already pregnant -- having conceived naturally -- and gave birth to her daughter Lucca in September 2008.

In an email interview, Bergholdt recalled the transplant experience. "Of course it is not pain free, but when you have cancer and are facing chemotherapy and much bigger and more invasive surgery this [transplant] was not a big deal," she writes. "At least not for me! The benefits and hope of having a child of my own did compensate for that pain and discomfort."

While both pregnancies were initially ''hard to believe," Bergholdt says eventually "as I grew bigger and bigger I became less skeptical and began to enjoy the pregnancies and all the great expectations about the babies, and me becoming a mother!"

How Ovarian Transplants Work

The freezing or cryopreservation of ovarian tissue is a relatively new medical method, Andersen reports in his paper, developed initially to help cancer patients with the hope of reproducing once their treatment is finished.

Although the transplant is still viewed as experimental, Andersen writes, it is slowly becoming accepted as an alternative to other fertility-preserving methods such as egg freezing.

Ovarian transplants might also help women whose fertility is impaired by treatments for other diseases such as autoimmune diseases, Andersen tells WebMD. More controversial than a transplant after treatment for a disease, Andersen says, is freezing ovarian tissue for transplantation in women who have delayed childbearing or who have entered menopause but then want to conceive.

Silber says that the transplant ''sounds like a lot of surgery, but actually it is just a simple outpatient procedure, and not very invasive, compared to months of hormonal stimulation and multiple cycles of treatment required for IVF or egg freezing.''

In response to the Human Reproduction paper, William Gibbons, MD, president of the American Society for Reproductive Medicine, said in a prepared statement: "There is no question that the science behind ovarian tissue preservation and transplantation continues to advance. It is an exciting and rapidly advancing field of research. While this work is exciting, we still have much to learn before these treatments can be put into broad clinical use."