Effect of Rapamycin in Ovarian Aging

One of the earliest and most profound changes associated with human aging is the rapid decline in ovarian follicular activity and reproductive capacity. Beginning around age 35, fertility rates decline as the number and quality of oocytes fall, culminating in the onset of menopause around age 51. The onset of menopause has profound socioeconomic, quality of life, and health implications, including increasing the risks of cardiovascular disease, osteoporosis, cognitive decline and dementia. While human lifespan has increased, the age of menopause has remained largely unchanged, leaving more women living an ever-larger proportion of their lives in a postmenopausal state. The narrow reproductive window adds socioeconomic pressure on women to complete childbearing within a limited timeframe, or preserve their fertility with egg or embryo freezing. The investigators and others have demonstrated that rapamycin can delay ovarian aging in mice.

The purpose of this pilot study is to determine whether the same may be true in humans. Extending the reproductive lifespan will reduce the time pressure on women to complete childbearing and will allow more women to spend more of their lives in the premenopausal status and delay the negative healthy consequences of menopause.

Inclusion criteria

• Women aged 35-45 years
• In the menopausal transition stage -3a
• Have been unable to conceive based on diminished ovarian reserve and who have failed to develop any euploid embryos with IVF or who do not desire to conceive within the next 1.5 years
• Have regular menstrual periods (with less than 7 days of variability)
• Early follicular phase follicle stimulating hormone (FSH) levels ] < 20 mIU/mL
• Anti-müllerian hormone (AMH) levels of >0.1 ng/mL
• Antral Follicle Counts (AFC) of >3

Exclusion criteria

• Women with irregular menstrual cycles
• Severe ovarian deficiency, or with no evidence of remaining follicles
• Kidney or liver disease
• Any significant medical disease, including cancer
• Contraindications to receiving rapamycin