Yale biologist: Ovarian tissue freezing could prevent menopause, possibly forever

Most women agree that menopause – which usually arrives when they reach their early 50s, has its advantages and disadvantages. Some welcome the end of menstruation and concerns about unplanned pregnancies, while others dread the possibility of hot flashes, moodiness, and other unpleasant symptoms. What some women consider a brief and barely noticeable phase in their lives can evolve into lasting changes and discomfort for others.

Now, a new paradigm around the biological processes of menopause is capturing the attention of a small group of scientists around the country. The primary question is whether menopause can be delayed in healthy women, allowing them to extend their child-bearing years and perhaps even forestall some of the health risks and uncomfortable symptoms linked to plummeting estrogen levels.

These questions can be controversial – some people believe that such research could lead to life-changing benefits for women, while others consider menopause to be a biologically driven stage of life that should not be pathologized by medical science.

Ovarian biologist Dr. Kutluk Oktay, who is director of the molecular reproduction and fertility preservation lab at the Yale School of Medicine, recently added a new chapter to this conversation by publishing research on various possible outcomes when menopause is delayed in healthy women via ovarian tissue freezing. 

Oktay, who developed and performed 25 years ago the world’s first ovarian transplant procedure with cryopreserved tissue for a patient with a medical indication, predicts a future in which healthy women could use this process of freezing tens of thousands of eggs within the ovarian tissue to stave off menopause for as long as several decades or even prevent its onset altogether.

“For the first time in medical history, we have the ability to potentially delay or eliminate menopause,” said Oktay, who is also an adjunct professor of obstetrics, gynecology, and reproductive sciences at Yale.

Using data from hundreds of previous ovarian cryopreservation and transplantation procedures and molecular studies of how ovarian follicles behave in ovarian tissue, Oktay and his colleagues built a new mathematical model to predict how long the surgery could potentially delay menopause under a range of circumstances in healthy women.

Process of the study 

Their study has just been published in the American Journal of Obstetrics and Gynecology under the title “Modeling delay of age at natural menopause with planned tissue cryopreservation and autologous transplantation.” Since Oktay performed the first successful transplantation with cryopreserved tissue, ovarian tissue cryopreservation has been used successfully in cancer patients to preserve their fertility before their treatments, which can often permanently damage the egg reserve in the ovaries and trigger menopause.

During this outpatient procedure, a surgeon removes laparoscopically (keyhole surgery) the whole ovary or layers of the outer portion that contains hundreds of thousands of dormant, immature eggs known as primordial follicles.

These tissues are then stored in sealed containers after being frozen with a specialized process and kept as low as -195 Celsius. Freezing ovarian tissue with this specialized process preserves it for later use. At some point – typically years – in the future, the surgeon reimplants the thawed tissue into the patient either laparoscopically or with a simple procedure using methods developed by Oktay that places the tissue under the patient’s skin while intravenous sedation is administered. Three to 10 days after that, this transplanted tissue regains connections with the surrounding blood vessels and restores ovarian function in about three months.

The recently published mathematical model focusing on healthy women undergoing ovarian tissue cryopreservation considers multiple factors, including the age at which a patient gets the procedure, which plays a significant role in how long menopause can potentially be delayed.

“The younger the person, the larger the number of eggs she has, as well as the higher the quality of those eggs,” Oktay said. The model accounts for women between the ages of 21 and 40. Beyond age 40, data show that the procedure is unlikely to delay menopause for a woman with an average egg reserve, but this can change with the development of more efficient freezing and transplantation methods in the future.

The model also offers insight into the ideal amount of ovarian tissue to collect. The more tissue a surgeon removes, the longer the procedure can potentially delay menopause – but the removal of too much tissue can lead to early menopause. “This model gives us the optimum amount of tissue to harvest for a person of a given age,” Oktay noted.

The model also takes into account the healing process after a surgeon returns the harvested ovarian tissue to the patient. During this healing process, some of the primordial follicles are lost. Studies on animal models show that up to 60% of primordial follicles don’t survive post-transplantation, leaving 40% that are viable. With newer technologies, Oktay said that he believes surgeons can attain a survival rate of up to 80%. As the procedure continues to improve, he hopes to achieve a 100% survival rate eventually. Thus, the model accounts for survival rates ranging from 40% to 100%.

Additionally, through transplanting portions of the harvested tissues over several procedures, the research indicates that menopause can be delayed even longer. For example, the team’s model shows that returning a third of the outer portion of the ovary over each of three procedures delayed menopause longer than returning all of the tissue through one surgery.

Based on the model, Oktay predicts that for most women under 40, ovarian cryopreservation can significantly delay menopause. And for women under 30, the procedure may be able to prevent menopause altogether.

Delaying menopause with ovarian cryopreservation also may confer certain health benefits associated with a later menopausal age. Based on new research by Oktay and his colleagues, around 11% of women experience late-onset natural menopause – menopause after age 55. Studies show that women who experience menopause later may live longer and have a lower risk for a range of conditions, including cardiovascular disease, dementia, retinal disease, depression, and bone loss. However, uncertainty remains over whether later menopause actually reduces those health risks. 

Oktay suggests that those risks could also be reduced in healthy women who delay menopause via ovarian tissue cryopreservation. If the risk for such chronic diseases is reduced in healthy women who undergo this procedure, it could be a significant benefit, but additional research is needed to determine long-term benefits as well as risks.