People with Ovaries Age Faster. What If We Could Reverse That?

Ovarian tissue transplants could extend women’s health by delaying menopause, and even restore fertility.

By Ananya Dash

On average, women in the United States spend a greater number of years in poor health, despite having a life expectancy five years longer than men. The decline in quality of life stems from menopause, a point that marks the end of a woman’s reproductive years as her ovaries run out of eggs. Intervening to halt ovarian aging could be a game-changer to prevent deteriorating health in menopausal women. 

An approach from the early 2000s is now being re-examined to extend the lifespan of ovaries: freezing a strip of healthy cells from the ovary and planting them back into the body when the need arises. This method has successfully restored fertility in cancer patients, who often lose ovarian function early in life after undergoing chemotherapy. New research shows that this technique – ovarian tissue transplant –  can reverse accelerated aging in people with ovaries including cisgender women, trans men, non-binary, and intersex individuals. 

The Need to Treat Menopause

“A woman is not just her reproductive organs, but her whole body,” says Sarah R. Ocañas, assistant professor in the Genes and Human Disease Research Program at the Oklahoma Medical Research Foundation. “Delaying reproductive aging could potentially delay the onset of chronic diseases that are associated with aging.”

Ovarian tissue transplant relies on returning the ebb and flow of hormones to premenopausal levels. The technique places eggs back into the body while also returning the cells surrounding the eggs — the makers of a cocktail of hormones — in order to pause a cascade of negative health effects on the brain, bones, and heart.

The need to replenish ovarian tissue stems from the continuous decline in egg counts throughout life. Female babies are born with a million eggs, but by puberty, only about 300,000 remain. By the time women reach menopause, typically around the age of 50, almost no eggs are left to mature. The dwindling egg counts have led researchers to study ovaries primarily through the lens of reproduction. 

“They are worried about the quantity and quality of eggs and the ability for the ovaries to produce a successful pregnancy,” says Ocañas. “But the reality is that ovaries are beneficial for overall systemic health.”

Neither menopause nor female aging is necessarily a disease. Without any eggs present, however, the cells surrounding them stop producing hormones. This halt brings hot flashes, mood changes, and sleep disruptions. Then comes the long-term cost: fractures and heart diseases become more common, risk of dementia rises, and memories become blurrier. Vaginal dryness and urinary tract infections also become increasingly common and persistent. Women live for decades with ‘out-of-service’ ovaries with an overall negative impact on health. 

Ocañas studies the effect of estrogen, which protects the brain, as its levels decline. She also researches understanding ovarian aging, the cause of estrogen depletion. A recent study published in the Nature Aging, where Ocañas is a second author, found a particular type of immune cell doubled in number in ovaries of mice that mimic women’s late-30s compared to mice modeling women’s 20s. Further, cells lining the eggs in aged ovaries were inflamed. This inflammation and it accompany immune activation can further worsen both egg maturation and hormonal balance in women approaching menopause. 

Ovarian Tissue Transplant Can Alleviate Menopausal Symptoms

There has been a lack of understanding of ovarian aging and innovation in treatment options, until now. 

A recent modeling study published in the American Journal of Obstetrics and Gynecology predicts that ovarian tissue transplant could extend the life of ovaries by about 12 years. This estimate assumes a woman would choose to remove ovarian tissue in her 20s and place them back by her early 40s. The timing of freezing the ovarian strips and replanting them back affects these estimates.

Dr. Kutluk Oktay, reproductive biologist at Yale University and the corresponding author of the modeling study, envisions this procedure being available to healthy women to delay or even eliminate menopause. Since ovaries mature only about 500 eggs during a woman’s lifetime, 99.9% of eggs die without reaching their potential. The procedure taps into an ideal strip of ovary — a rich reserve of healthy eggs — before it is lost, making it available for future use. 

“Women are undergoing menopause at the same age, yet we’re living so much longer, and we want to be active so much longer,” says Monica M. Laronda, director of Basic and Translational Research, Fertility and Hormone Preservation and Restoration Program at Ann & Robert H. Lurie’s Children’s Hospital and assistant professor at the Feinberg School of Medicine, Northwestern University. “That’s where the restoration of these hormones can be really beneficial for quality of life,” she adds.

The transplant begins with a minimally invasive keyhole surgery, during which about one-third of the ovarian tissue is removed through a small incision in the abdomen. “Ovaries are like oranges,” says Dr. Luciana Cacciottola, a gynecologist and postdoctoral researcher in the Department of Histology at Saint Camillus University in Rome, Italy, who has performed ovarian tissue transplants on patients. She explains that the peel is where the eggs are, and the center contains the blood vessels. The extracted tissue is sliced into thin sections, preserved in a substance that prevents formation of ice crystals, and stored in liquid nitrogen. The tissue can be recovered and placed back on the same spot on the ovaries when needed. 

Ovarian tissue can remain functional even after 17 years of preservation, making this procedure a promising long-term solution for both menopause and infertility.

Currently, hormone replacement therapy, or HRT, is the only way to treat symptoms of menopause. HRT involves the release of estrogen and progesterone from pills, patches, gels, or creams in the body. The treatment is highly effective to treat hot flashes and sleep irregularities. The rise of estrogen through HRT also helps to reduce the risk of osteoporosis – breaking of bones – in menopausal women. 

Concerns about HRT, however, arose after the Women’s Health Initiative in the early 2000s indicated that the treatment increases the risk for heart diseases, as well as breast and uterine cancers for post-menopausal women. Experts, such as Laronda, argue that the study had significant limitations. “The women enrolled in the study were far from menopause”, says Laronda. “The ovarian environment was not conducive to being restorative”, she adds. HRT can only be administered to women who have recently reached menopause.

HRT comes with drawbacks, despite being safe to use in women. It delivers a constant dose of both estrogen and progesterone that cannot mimic the hormonal oscillations produced naturally by ovaries. “There are no better sources of hormones than the ones coming from your ovaries”, says Ocañas. As such, the transplant, if made widely available, shows the potential to prevent negative effects of menopause by restoring this dynamic hormonal levels of the body. Repeated transplants of ovarian strips might even delay menopause by several decades.

Whether it is worth it for healthy people to get an ovarian tissue transplant to reap its benefits years later is not yet explored. There is minimal bleeding during surgery, which makes the procedure an approachable choice for healthy people, especially younger women. “It is like a conservative surgery”, says Dr. Cacciottola, referring to the transplant as more of a non-invasive surgery since the vessels remain untouched at the center. 

But some scientists believe that there are too many unknowns with the procedure to recommend it to patients. “When transplanting tissue back into ovary, you have to think of the impact of taking healthy tissue and putting it back onto an aged environment”, says Francesca Elizabeth Duncan, Thomas J. Watkins Memorial Professor of Reproductive Science in the Department of Obstetrics and Gynecology at Feinberg School of Medicine, Northwestern University. “The eggs are within a nest, and if the nest is not good, those eggs will not be good”, she explains. Duncan’s research examines ways to fix that nest to maintain the healthy state of the ovaries to ensure both hormonal and fertility restoration.

Ovarian Tissue Transplant to Treat Fertility in Cancer Patients

The first successful ovarian tissue transplant was performed by Dr. Oktay in 1999. His patient, a 28-year-old woman, underwent surgery to remove her ovaries due to severe bleeding. She experienced menopausal symptoms at just 29 years old. Her ovarian tissue was placed back into her body with the hope to restore ovarian function. The success of the transplant led doctors to use this method to treat infertility in cancer patients. 

The earliest live birth from transplanted ovarian tissue occurred in 2004. At first, a strip of ovarian cells was collected from a 25-year-old patient with an aggressive form of cancer. The strip was placed back into the ovaries after seven years, leading to the birth. Now, about 130 live births have been made possible because of the transplant. 

“The technology works well, and it gives hope to so many people,” says Dr. Cacciottola. A meta-analysis published in Fertility and Sterility in 2021, co-authored by Dr. Cacciottola, analyzed data from 285 women treated at five European centers. It reported a success rate of 26% for live births and 90% for hormonal balance. Another meta-analysis, published in Human Reproduction Update in 2022, examined data from around seven hundred cancer survivors and revealed a 28% success rate for live births. More recently, a 2024 study published in Obstetrics and Gynecology echoed similar success rates for pregnancy in women with reproductive cancers.

Still, challenges remain in offering this treatment to all cancer patients who might benefit from it. A report published in the Journal of the American Medical Association in 2024 revealed that about half of cancer patients do not remember having a conversation about infertility upon undergoing cancer treatments and/or methods to preserve their eggs with their physician. “It is a failure of our healthcare system”, says Laronda. She addresses this challenge by educating and counselling pediatric cancer patients and their parents through her clinical work. “We want to make sure that people understand where they are on the predicted spectrum of reproductive failure and have autonomy to make decisions now for their future”, she adds.

The lack of dialogue about ovarian tissue transplants with cancer patients is not the only hurdle. The freezing of ovarian strips requires specific equipment that may not always be available at hospitals. The process of freezing also lasts about half a day after its removal. A fast-freezing method does exist but there is not enough data to support its success as compared to slow freezing. Dr. Cacciottola, nevertheless, advocates for an urgent need to increase counselling of cancer patients for ovarian tissue transplant despite its limited availability. “The conversation can empower them to think about life after cancer,” she says. The availability and accessibility of the transplant needs to improve if it is to become a plausible treatment option for both cancer patients and healthy people in the long term. 

The Need to Study Ovarian Tissue Transplant in Healthy People

Understandings of ovarian tissue transplant for healthy individuals largely builds on findings from studies conducted in cancer patients. These studies provide insights into the timing of tissue collection and transplantation, procedural success, and the restoration of hormonal oscillations. 

Cancer patients typically collect ovarian strips just before undergoing chemotherapy. The ovarian strips are transplanted after the patients recover and plan to conceive. Fertility preservation experts usually measure success based on live births following transplantation. The long-term restoration of hormonal function and its impact on delaying menopause, however, remains unexplored. 

Available studies do report hormonal balance related to attempts at pregnancy. Estimates range from 80 to 90% for attaining regular hormonal balance after undergoing the transplant. A recent meta-analysis published in the Frontiers of Endocrinology in 2024 shows nearly all patients who underwent ovarian tissue transplant at the Bologna University restored their natural ebb and flow of hormones. These patients were followed-up for six months only after the transplant, still estimates revealed ovarian function could last for about three years in patients. 

Oktay’s modeling study, based on previous studies, suggests the lowest age for ovarian tissue collection could be as low as 21 but only clinical trials can determine whether such models fit with real life outcomes. 

Placing ovarian strips on the surface of the ovary is also unlike a typical transplant. A kidney transplant, for example, connects the kidney to the vessels. There are no blood vessels to attach to the ovarian strips since the whole ovary is not transplanted. The transplanted tissue, then, awaits blood vessels to be recreated at the site of transplantation, which takes about a week. About 60% of eggs are lost during this time. Dr. Cacciottola’s work suggests preparing the transplant site with stem cells, as demonstrated in mice, to prevent this loss of eggs 

Predicting how long transplanted ovarian tissue will remain functional after the transplant is challenging. Some ovaries resume function for about one to two years, while others can turn back time for up to a decade. That would mean that people might need repeated transplants. Dr. Cacciottola cautions that one cannot change their ovarian tissue every few months. The transplant needs to be a long-term solution.

The experience of cancer patients undergoing this transplantation cannot provide all the answers needed. Many cancer patients may choose to preserve bits of their ovaries before undergoing chemotherapy, but only a limited number of patients, however, choose to get the tissue placed back. 

Additionally, not all cancers may lead to loss in ovarian health. There are also cancer patients who are too young to consider pregnancy and might be waiting for the right time. Finally, some suffer from severe spread of cancers impossible to recover from. Scientists and clinicians would need to run large-scale clinical trials to test the benefits of the process in healthy people.

“We take Tylenol, when we have a headache,” says Laronda. “Why wouldn’t we try to treat menopausal symptoms when we can do that safely?” 

Only time will tell whether ovarian tissue transplant will become a potential treatment option for menopausal symptoms. Dr. Oktay and Dr. Cacciotola’s work will continue to improve this technique both in healthy people and cancer patients in the coming decades. Meanwhile, basic research from labs such as those of Ocañas, Laronda, and Duncan will address the basic mechanisms that drive ovarian aging in women. “There is an exciting opportunity with the ovary to look at if we can sustain the function of this organ much longer,” Duncan says.