Cecilia Lee

Yale researchers designed a robot-assisted ovarian transplant procedure that increases the lifespan of the implanted organ by more than a year in comparison to previous methods. The technology has been employed to facilitate multiple healthy pregnancies.

Some cancer treatments, such as certain chemotherapies, can sterilize women. For patients for whom the traditional fertility preservation method of harvesting eggs is not an option, ovarian tissue freezing can provide 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 upon the technique by spearheading a successful robot-assisted surgical method. His results were published in the journal Fertility and Sterility on Nov. 17.

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

One of the major challenges of ovarian transplants is revascularization, or blood flow restoration. Once implanted, it takes about 10 days for blood flow to be restored to the ovarian tissue, as well as the eggs it contains. During that time, some eggs die due to the lack of oxygen. Through previous transplant methods, the ovarian tissue only functions for 29 months in comparison to the 43 to 47 months of tissue function that the novel robot-assisted technology achieves.

The new technique uses robotic surgery to improve the precision and speed of the procedure. Additionally, Oktay used a revascularizing human extracellular matrix membrane as a scaffold for the transplant. He also gives patients pharmacological drugs known to improve revascularization. The new procedure, which results in grafts surviving an additional 14 months, is a combination of these three modifications.

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

Since previous ovarian tissue transplants had shorter life spans, it was recommended that patients conceive through in-vitro fertilization (IVF). The new technique’s time frame for revascularization and tissue viability now allows natural conception to be an option for patients who undergo ovarian tissue transplantation, according to Taylor.

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

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

Ovarian tissue freezing fulfills a crucial need for those who find egg freezing impractical. For some women, cancer treatment must begin immediately and they are unable to wait the two-week egg harvesting period. Ovarian tissue freezing, on the other hand, can be completed in a single day and can be performed in combination 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 do not think about fertility before treatment and are often counseled about their options too late, leaving them unable to have children. The ovarian tissue harvesting process takes less than an hour, making it an appealing option for patients.

“It’s not experimental anymore,” said Fernanda Pacheco, who was a fellow under Oktay and is a co-author on the paper. “It’s a standard technique for fertility preservation. We have about 200 babies born. In Germany they are cryopreserving more ovarian tissue than eggs.”

According to Taylor, the hormones required to stimulate ovulation for egg collection are expensive and can potentially spur even more tumor growth. Furthermore, for prepubescent girls, harvesting eggs is not possible as the ovulation cycle has not started yet. 

Frozen eggs cannot be used after menopause, which can be induced by severe cancer treatments. The transplating of ovarian tissue can reverse menopause, as the body begins producing necessary hormones again.

“There are patients that were in menopause for 12 years, we do a transplant, and they function perfectly,” Oktay said. “That’s the magic of this procedure. Even though I developed it, every time I see it I am still shaking my head.”

Ovarian tissue cryopreservation is offered as a fertility preservation method at Yale New Haven Hospital.