The transplantation of ovarian tissue is often performed to extend fertility among women and adolescents with cancer. But some reproductive specialists believe the procedure may have another role to play with much wider application: delaying, or even preventing, menopause in healthy women.
Kutluk Oktay, MD, director of the Laboratory of Molecular Reproduction and Fertility Preservation at the Yale School of Medicine in New Haven, Connecticut, has used ovarian tissue transplantation (OTT) in his own practice — Innovation Fertility Preservation & IVF — for several years. He said the approach can reduce health risks associated with menopause, such as the loss of bone density and cardiovascular disease.
Kutluk Oktay, MD”We have started offering [ovarian tissue transplantation] in carefully selected candidates, but the pace will accelerate now that we have a way to better inform the candidates on the potential of the procedure,” Oktay said. To date, he said he has performed the procedure on approximately 20 patients.
But Oktay’s vision of the future for OTT remains on the fringe of reproductive medicine.
“I think there are ethical considerations to take into account here,” said Stephanie Faubion, MD, medical director for the North American Menopause Society. “You’re taking a perfectly healthy 25- to 30-year-old woman and putting her through surgery to take out a healthy organ. Let’s just think about that.”
Stephanie Faubion, MDThe Promise and Risks of OTTOTT involves removing part of the ovarian tissue, cryopreservation, and then transplanting it back into the body. The procedure has reversed early menopause in women who underwent cancer treatment and resulted in over 140 live births worldwide.
Oktay recently published a nonclinical study in the American Journal of Obstetrics & Gynecology using a mathematical model based on decades of clinical research on cancer patients and ovarian follicle counts in cadaver to forecast how OTT can delay the onset of menopause through restored ovarian function and hormonal shifts.
The model forecasts a delay in menopause of up to 47 years, depending on factors such as the age of tissue removal, a woman’s ovarian reserve, and an estimated number of primordial follicles — where tens to hundreds of thousands of undeveloped eggs can live — that survive the process of removal, freezing, and reimplantation.
OTT is currently associated with a survival rate of 40% for follicles, Oktay said. But technological advancements, including revascularization drugs and robotic surgery, are likely to extend the survival rate to 80% by the time reimplantation occurs, potentially 15-20 years after tissue removal, he said.
Prospective patients at Oktay’s practice can use an interactive tool to receive an estimate of their potential menopausal delay. Patients receive a clinical assessment, including tests for ovarian reserve markers, to determine their potential for the procedure.
The model predicted that harvesting tissue before age 30 could delay menopause significantly. A 25-year-old woman with an average ovarian reserve who preserved a quarter of one ovary would have a delay in menopause of 11.8 years if 40% of the follicles survived. Women around age 40, and especially those with a low ovarian reserve, would need a follicle survival rate of close to 100% to result in a delay significant enough to justify the procedure.
The procedure also comes with risks. Removing ovarian tissue can bring on early menopause, Oktay said. Removing part or all of the ovarian cortex — the outer part of the ovary that contains the follicles — can start menopause about 1.5 years earlier. But as long as the tissue is transplanted, a woman would gain many more years of fertility before menopause.
While potentially promising, some obstetrics and gynecology experts question the procedure, with no proven benefits.
“While theoretically possible, my biggest question is, how is this better than egg freezing in your 20s or 30s combined with hormone replacement for the aging benefits, given the risks associated with potentially multiple surgeries?” said Paula Amato, MD, professor of obstetrics and gynecology at Oregon Health & Science University in Portland, Oregon.
Paula Amato, MDAny risks associated with receiving hormone therapy through OTT rather than traditional hormone replacement therapy are also unknown, Amato said.
A UK clinic, ProFam, based in Birmingham, also offered the procedure but faced criticism in 2020 for being unnecessary and experimental. Medscape Medical News could not confirm if the clinic is still in operation.
Why Delay Menopause?While the procedure may extend fertility, the goal of the procedure is not to enable patients to become pregnant at ages that are not safe, Oktay said. Rather, he said postponing menopause is medically beneficial.
Some research shows that women who have late menopause have a lower risk for all-cause mortality and cardiovascular disease but a higher risk for breast, endometrial, and ovarian cancers.
Oktay said that delaying menopause could improve the quality of life for women by reducing menopausal symptoms like anxiety and depression. Clinicians could also use the procedure as preventive care for those who are at high risk for conditions associated with menopause, such as osteoporosis and dementia.
But Faubion is unconvinced that delaying menopause through OTT carries health benefits.
“Just because we can do this, should we?” she said. “And will it do the things that we think it will? Does preventing or delaying menopause delay the aging process? I think that’s what they’re trying to imply, and we don’t have evidence that that’s true.”
The study was funded by the National Science Foundation, U-Anschutz Department of Obstetrics and Gynecology Research Funds, SF Faculty Early Career Development Program, and the National Institutes of Health awards. The authors reported no disclosures.
Brittany Vargas is a medicine, mental health, and wellness journalist.
Source : Medscape