Could We Delay Menopause? The Science of Ovarian Tissue Freezing | Dr. Kutluk Oktay, PhD

How Ovarian Aging Works

• Women are born with a finite supply of eggs, held in immature primordial follicles. Current evidence does not support the idea that adult ovaries routinely make new eggs.
• Egg numbers peak during fetal development—around six months into pregnancy, according to Dr. Oktay—and decline substantially before birth and throughout life. Only a small fraction are ever ovulated.
• Ovarian aging involves both:
  • Declining quantity: Follicle loss accelerates for many women around ages 37–38.
  • Declining quality: Eggs become more prone to DNA damage and errors during cell division, which can make embryos nonviable. Oktay said these changes also accelerate in the late 30s.
• Menopause occurs as the follicle reserve becomes very low. A few follicles may sometimes be detectable afterward, but Oktay said they are generally too damaged or dysfunctional to develop normally.

What May Affect Ovarian Aging

• Genetics is a major influence. A woman’s menopause timing is correlated with that of her mother and other relatives.
• Smoking and chemotherapy are recognized factors associated with earlier ovarian aging or loss of ovarian function. Ovarian surgery can also reduce reserve.
• The link between endometriosis and earlier menopause may relate partly to ovarian surgery and tissue loss, rather than to a clearly established direct aging mechanism.
• Some people with PCOS have an unusually large follicle reserve and may, in some cases, have a longer reproductive lifespan. This is not guaranteed, and PCOS can also cause fertility and metabolic problems.
• Oktay said evidence that lifestyle changes or particular antioxidants slow ovarian aging remains insufficient. He discussed oxidative stress as a plausible contributor to DNA damage, but did not present a proven prevention strategy.

Measuring Ovarian Reserve

• AMH is produced by small, growing follicles; it does not directly measure the dormant primordial follicles that make up most of the reserve.
• AMH can vary, including with cycle timing, and may be harder to interpret in conditions such as PCOS. Oktay advised against relying on a single AMH result.
• He described assessing reserve with repeated AMH tests, often alongside early-cycle estradiol and FSH tests, and an ultrasound antral follicle count. These measures can provide complementary information, but none is a perfect measure of the underlying reserve.

PCOS and Fertility

• Oktay said the main fertility issue in PCOS is usually irregular or absent ovulation, rather than egg quality alone.
• Obesity and insulin resistance may also affect egg quality, whether or not they occur alongside PCOS.
• Historically, some PCOS patients underwent ovarian wedge resection. That approach was largely abandoned because of scarring and fertility risks.
• For some patients who do not respond to medication that stimulates ovulation, ovarian drilling—making small holes in the ovary using laser or electrocautery—may help restore response. Oktay described it as a treatment for selected, medication-resistant cases, not a general solution.

Ovarian Tissue Freezing and the Possibility of Delaying Menopause

• Ovarian tissue cryopreservation was developed to preserve fertility for people facing treatments such as chemotherapy. Oktay described the procedure as established for medical fertility preservation, following years of research and successful transplants.
• The procedure removes and freezes ovarian tissue, which may later be transplanted back. The tissue can resume hormone production and, in some cases, fertility.
• Oktay’s group is studying whether tissue frozen at a younger age could later be transplanted to extend ovarian function and delay menopause. The rationale is that younger tissue has more follicles and eggs that may be better able to survive.
• A model on the group’s website estimates possible delays based on factors such as age, the amount of tissue removed, and how much survives transplantation. The interview described predictions of delays of many years—and, in some theoretical scenarios, much longer—especially when tissue is preserved early.
• Important distinction: The proposed use for healthy people specifically to delay menopause is investigational. The estimates discussed are model-based predictions, not established outcomes from long-term trials in healthy women.
• Oktay said the potential benefit is greatest before age 35. Ages 35–40 may still be worthwhile for someone with average reserve, while the team is more cautious after 40. Individual reserve and transplant effectiveness also matter.
• A major technical challenge is that transplanted tissue needs to establish a blood supply. Oktay estimated current transplant effectiveness at roughly 60%, compared with about 40% for earlier approaches, and said robotic techniques, scaffolds, and other methods may improve survival.

Claims About “Waking Up” Dormant Eggs

• Oktay rejected the idea that dormant eggs can generally be awakened to restore fertility after menopause. In his account, menopause reflects a severely depleted reserve, and the few remaining follicles are usually too damaged to develop.
• Some people with premature ovarian insufficiency may still have intermittent follicular activity. He said pregnancies in these cases can occur spontaneously, so results reported after experimental “activation” procedures need to be compared with the underlying spontaneous pregnancy rate.
• He cautioned that hormone treatment choices matter: birth-control pills used for hormone replacement can suppress ovulation, whereas other hormone-replacement approaches may not. He described monitoring follicles in some patients who hope to conceive.

DNA Repair and Future Treatments

• Oktay’s research links age-related decline in egg quality to reduced ability to repair DNA damage. He discussed genes involved in DNA repair, including BRCA1, BRCA2, ATM, and MRE11, and said the decline becomes more pronounced after about age 37.
• His group is exploring ways to improve DNA repair or prevent its decline. These are research directions, not established clinical treatments.
• He also described research on growing follicles outside the body. His team can bring eggs to an advanced stage in the laboratory and is working on final maturation. He presented in-vitro growth as a possible future route to obtaining eggs without conventional ovarian stimulation and retrieval, while emphasizing that further work is needed.
• The interview also mentioned planned research and a proposed company called NoPause, including work on drugs that might slow follicle loss.

Endometriosis

• Oktay characterized endometriosis as complex and understudied, with no complete explanation for why it develops or why severity varies.
• Treatments discussed included hormonal suppression, surgery, and—in selected difficult cases—letrozole, which inhibits estrogen production. He noted potential bone effects from long-term estrogen suppression.
• He said he was not aware of a targeted, non-surgical treatment for endometriotic lesions or a reliable prevention approach. Some companies are working on diagnostic markers.

Speakers and Sources Featured

• Kayla Barnes-Lentz — host and interviewer.
• Dr. Kutluk Oktay, MD, PhD — guest; reproductive endocrinologist and researcher in ovarian aging and fertility preservation.
• Researchers named during the discussion: Jim Nelson, Roger Gosden, and Jonathan Tilly. They were mentioned in the context of earlier research on ovarian aging, ovarian reserve, tissue freezing, and claims about egg regeneration.
• Institutions and research groups mentioned: Yale School of Medicine; the University of Leeds; the University of Texas at San Antonio; the NIH; and colleagues at the University of Colorado at Denver.
• Sponsor segments read by the host: Eight Sleep and WHOOP.