Ovarian transplants appear to be safe and effective

Women who have ovarian tissue removed, stored and then transplanted back to them at a later date have a good chance of successfully becoming pregnant, according to a review of the largest series of ovarian transplants performed worldwide.

Treatment for cancer is usually the reason why ovarian tissue is removed prior to chemotherapy and radiation in the hope that ovaries can be transplanted back into the patient at a later date to preserve her fertility. However, there have been concerns that transplanted tissue might contain cancer cells that could prompt a recurrence of the cancer.

The study, published in Human Reproduction - one of the world's leading reproductive medicine journals, reveals that while in some patients, transplanted ovarian tissue can last at least ten years to produce eggs, the procedure appears to carry little risk of causing a return of the disease that had prompted the removal of the tissue in the first place.

Dr Annette Jensen, a doctor and PhD student in Laboratory of Reproductive Biology in the Rigshospitalet, Copenhagen, Denmark, and colleagues from the Rigshospitalet, the Odense University Hospital and the Aarhus University Hospital in Denmark, reviewed the outcomes of 41 Danish women who had had a total of 53 transplantations of thawed ovarian tissue. Each woman had been followed for 10 years to assess ovarian function, fertility and the safety of the procedure.

"Many girls and young women who have been diagnosed with a disease such as cancer now have a realistic hope of recovery and living a normal life, but treatment of their disease can cause infertility by damaging the functioning of their ovaries.

"As awareness of quality of life after cancer treatment has increased and techniques for removing, freezing, storing and then transplanting ovarian tissue have developed, fertility preservation is increasingly becoming an integral part of treatment. However, as ovarian transplantation is still in its early days, its efficacy and safety needs to be investigated."

Annette Jensen MD, and PhD student, Laboratory of Reproductive Biology, Rigshospitalet, Copenhagen, Denmark.

The ovarian transplantation program started in Denmark in 2000. Since then nearly 800 women have had tissue frozen. For this study, the researchers studied the outcomes of women who had received transplantations between 2003 and June 2014.

The average age of women at the time their tissue was frozen was 29.8 years, the average age when the first transplant was performed — 33. Out of the 41 women, 32 wished to become pregnant. Ten (31%) were successful and had at least one child (14 children in total), including one woman who is in her third trimester of pregnancy. In addition, there were two legal abortions, one because the woman was separating from her partner; the other because of a recurrence of breast cancer. A third woman experienced a miscarriage in her 19th week of gestation.

Eight children were conceived naturally following the ovarian transplant and six children were conceived with the help of in vitro fertilisation (IVF).

For three women, it has been over ten years since they had the tissue transplanted; for six patients it has been more than eight years, and for 15 patients it has been more than five years. The remaining patients have had transplanted tissue for between six months and five years. "The full functional lifespan of grafts is still being evaluated, as many of these women have ovaries that are continuing to function," adds Dr Jensen.

Three of the 41 women who received an ovarian transplant had a relapse of their cancer: two with recurrence of their breast cancer at their original tumor site, and one Ewing's sarcoma patient had a relapse. Researchers say that none of these relapses appeared to be related to the transplantation of ovarian tissue, and no cancer has developed in the transplanted tissue.

"As far as we know this is the largest series of ovarian tissue transplantation performed worldwide, and these findings show that grafted ovarian tissue is effective in restoring ovarian function in a safe manner. In this series of women the pregnancy rate was about 30%. The fact that cancer survivors are now able to have a child of their own is an immense, quality-of-life boost tor them.

"However, it's important that women who have received transplanted ovarian tissue continue to be followed-up. In particular, we have not performed transplants in patients who have suffered from leukaemia, since the ovarian tissue may harbour malignant cells in this group of patients."

Annette Jensen MD

In addition to enabling women to become pregnant, the restoration of ovarian function is also important for restoring normal levels of circulating sex hormones, which serve many other functions in the body, such as preventing menopausal symptoms.

Dr Jensen and her colleagues continue to follow-up the Danish women.

Dr Jensen: "We hope that our results will enable this procedure to be regarded as an established method in other parts of the world, which has an important implication on how it is funded and reimbursed."

Abstract
Modern effective treatment regimens often pose a considerable risk of causing infertility, either directly or later on as premature ovarian insufficiency (POI). Therefore, fertility preservation is increasing- ly becoming an integral part of treating young cancer patients. Freezing of ovarian tissue can be performed on short notice and is often the preferred fertility preservation technique due to an urgent need to commence treatment. Cryopreservation of ovarian tissue includes surgical removal and freezing of tissue prior to commencing treatment. If the cancer treatment renders the patient infertile, transplantation of cryo-preserved ovarian tissue may restore fertility. However, because fertility preservation is still in its early days and counseling may not be offered to 30 – 50% of young women diagnosed with cancer, a greater awareness of these new possibilities is still required.
The program of ovarian cryopreservation started in the year 2000 in Denmark following governmental approval, which made the treatment free of costs for patients. Since then, almost 800 patients have had tissue frozen, with a steady annual activity of about 13–14 cases per million inhabitants per year. Patients are counseled and tissue can be excised at four different centers, three in Denmark and, more recently, one centre in southern Sweden. The tissue is transported (for up to 5 h) to one central laboratory, where preparation and storage of tissue takes places. If the patient requests transplantation, tissue is transported to the local hospital. This model has been termed the Danish model (‘the woman stays—the tissue moves’) and has now been introduced in different countries around the world.
Our program has performed 53 transplantations to 41 patients during the last 10 years and here we report our collective experience from this 1 centre.

[1] "Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in Denmark", by A.K. Jensen et al. Human Reproduction journal. doi:10.1093/humrep/dev230

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Oct 9, 2015   Fetal Timeline   Maternal Timeline     News     News Archive   

Stinne Holm Bergholdt holding her two daughters, Aviaja (left) and Lucca, who were
conceived after an ovarian transplant.  Science Daily
Image Credit: Flemming Holm Bergholdt (Stinne's husband)