Ovarian transplant reverses fertility loss in cancer survivors

A new robot-assisted ovarian transplant could extend organ viability by an additional 14 months, culminating in multiple healthy pregnancies in previously infertile patients.

Valentina Simon 12:18 pm, November 30, 2021

Contributing reporter

Cecilia Lee

Yale researchers designed a robot-assisted ovarian transplant procedure that extends the life of the implanted organ by more than a year compared to previous methods. The technology has been used to facilitate multiple healthy pregnancies.

Some cancer treatments, such as certain chemotherapy, can sterilize women. For patients for whom the traditional method of fertility preservation through egg harvesting is not an option, freezing ovarian tissue can be a source of hope. Kutluk Oktay, Professor of Obstetrics and Gynecology and Director of Laboratory of Molecular Reproduction and Fertility Preservation, pioneered the first ovarian transplant in 1999 and has since improved the technique by leading a successful robotic-assisted surgical method. His results were published Nov. 17 in the journal Fertility and Sterility.

“We found that we could extend the function of the graft by 14 months, and every patient who wanted to have a baby had one or two children or had embryos frozen,” Oktay said. “Compared to the 25 percent global success rate, our technique appears very successful.”

One of the biggest challenges of ovarian transplants is revascularization or restoration of blood flow. Once implanted, it takes about 10 days for blood flow to be restored to the ovarian tissue and the eggs it contains. During that time, some eggs die from lack of oxygen. Due to previous methods of transplantation, the ovarian tissue only functions for 29 months compared to the 43 to 47 month tissue function achieved by the new robot-assisted technology.

The new technique uses robotic surgery to improve the precision and speed of the procedure. In addition, Oktay used a revascularizing human extracellular matrix membrane as the base for the transplant. He also gives patients pharmacologic drugs that are known to improve revascularization. The new procedure, which allows grafts to survive an additional 14 months, is a combination of these three modifications.

“[Robotic surgery is] less invasive than open surgery, but offers much more of the ability to quickly place tissue in the right part of the ovary and suture it nicely, which you can’t really do easily or quickly with a traditional laparoscopy,” said Hugh Taylor , chair of Obstetrics, Gynecology, and Reproductive Sciences at the School of Medicine and chief of obstetrics and gynecology at Yale New Haven Hospital. “Robots have revolutionized many of the surgeries we do.”

Because previous ovarian tissue transplants had a shorter lifespan, it was recommended that patients become pregnant through in vitro fertilization (IVF). The timeframe of the new technique for tissue revascularization and viability now makes natural conception an option for patients undergoing ovarian tissue transplantation, Taylor said.

The preliminary clinical trial of robotic-assisted ovarian tissue transplantation included only seven patients. In the future, Oktay is recruiting additional people for future studies to confirm the benefits of the new approach.

“Dr. Oktay pioneered it all – the freezing of ovarian tissue, the transplant, and now the robotic transplant. He really is the pioneer who initiated the whole field and we are very lucky to have him here at Yale,” said Taylor.

Ovarian tissue freezing fulfills a critical need for those who find egg freezing impractical. For some women, cancer treatment must begin immediately and cannot wait for the two-week egg harvesting period. In contrast, freezing of ovarian tissue can be completed in one day and may be performed in conjunction with another surgery. The tissue can then be stored indefinitely.

According to Taylor, one of the biggest obstacles to fertility for cancer survivors is that they don’t think about fertility before treatment and are often advised about their options too late, preventing them from having children. The ovarian tissue harvesting process takes less than an hour, making it an attractive option for patients.

“It’s no longer experimental,” said Fernanda Pacheco, a fellow under Oktay and co-author of the paper. “It is a standard technique for fertility preservation. We have born about 200 babies. In Germany they store more ovarian tissue than eggs.”

According to Taylor, the hormones needed to stimulate ovulation for egg collection are expensive and can potentially stimulate even more tumor growth. In addition, it is not possible for prepubescent girls to harvest eggs because the ovulatory cycle has not yet started.

Frozen eggs cannot be used after menopause, which can be caused by serious cancer treatments. Transplating ovarian tissue can reverse menopause as the body starts producing necessary hormones again.

“There are patients who were 12 years into menopause, we do a transplant and they are functioning perfectly,” Oktay said. “That’s the magic of this procedure. Even though I developed it, every time I see it I still shake my head.”

Cryopreservation of ovarian tissue is offered as a method of fertility preservation at Yale New Haven Hospital.

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