Ovarian Aging

Emre Seli, MD

The life expectancy of a 15-year-old girl who was lucky enough to survive infancy and early childhood in the 16th century United Kingdom was only 48 years. For the same girl, life expectancy would be 56 in the 18th century, 65 in the 19th century, and 75 by mid-20th century.[1] As a result of the significant reduction in infant and teen mortality, as well as improvements in access to health care over the course of the 20th century, life expectancy at birth for females in the United States reached 81.2 years in 2012.

Parallel with the increase in life expectancy, and promoted by the social changes that followed industrialization, many contemporary women choose to delay parenthood. Indeed, as summarized by Cil et al in this issue of Seminars in Reproductive Medicine, the average age of first-time mothers increased from 21.4 in 1970 to 25.0 in 2006 in the United States, where the number of women delivering their first child after the age of 35 increased from 1/100 to 1/12 in the same time period.[2]

However, despite the significant increase in longevity, studies show that the median age of menopause is currently around 50 in Western industrialized societies, with little apparent change over the past century.[3] [4] Consequently, today, at a time when women live longer and delay parenthood without a tangible change in the timing of their reproductive aging, assisted reproduction has become a beacon of reproductive hope.

Within the context of assisted reproduction, ovarian aging is often used to refer to the declining potential of ovaries to produce oocytes in adequate number or quality in response to controlled ovarian stimulation. Patients who present with ovarian aging are commonly diagnosed with diminished ovarian reserve (DOR), and offered in vitro fertilization (IVF) using either their own eggs or donated eggs or embryos. The number of women undergoing IVF for DOR has steadily increased over the past decade in the United States, where DOR accounted for 10% of assisted reproductive technology (ART) cycles in 2003, 14% in 2008, and 18% in 2013, and the number of fresh IVF cycles using nondonor oocytes performed for women with DOR increased from 6,947 in 2003 to 13,219 in 2013. Similarly, the number of women undergoing oocyte donation in the United States increased from 11,627 in 2003 to 19,320 in 2013. These numbers and many other analyses support the view that ovarian aging is an increasingly important reproductive health issue.

As science makes strides toward treating cardiovascular and metabolic disorders, infections, and malignancies, almost doubling life expectancy over a period of 200 years, understanding the mechanisms of aging and developing strategies to prevent or delay aging attract an increasing amount of attention from the scientists and lay people alike. However, despite the recent focus in aging research, many interesting questions on ovarian aging remain to be answered: What is the mechanism of ovarian aging? Is it the same or different from mechanism(s) that regulate aging in other tissues? Can ovarian aging be stopped or delayed? Can it be reversed? What can we offer women afflicted with ovarian aging while we wait for miraculous solutions?

In this issue of Seminars in Reproductive Medicine, we aimed to present cutting edge information on the mechanisms of reproductive senescence as well as currently available strategies to assist women affected by ovarian aging. Four articles by leading scientists address the potential molecular mechanisms (genetic [Dr. Laven], impaired DNA repair [Dr. Oktay], telomere-related [Dr. Keefe], and metabolic/energetic [Dr. Moley]) that mediate or contribute to ovarian aging, followed by reviews of emerging strategies to help women with ovarian aging in the clinical setting. Within this context, Drs. Fragouli and Wells discuss the use of mitochondrial DNA copy number as a diagnostic measure for embryo viability, while Dr. Tilly presents autologous germline mitochondrial transfer as a potential intervention in ART to improve embryo development and treatment outcome. These are followed by articles that discuss more established approaches aimed at decreasing ovarian loss in women with endometriosis (Dr. Uncu), cryopreserving oocytes as a preventive measure for age-related fertility loss (Dr. Cil), and providing evidence-based management protocols for controlled ovarian stimulation in women with DOR (Dr. Ata).

I hope that the current issue of Seminars in Reproductive Medicine will provide a helpful resource for the readers as they navigate through the increasingly complex data on molecular mechanisms of ovarian aging and existing and emerging diagnostic and therapeutic modalities.

• References

• 1 Hollingsworth TH. Demographic study of the British Ducal Families. In: Drake M, ed. Population in Industrialisation. London: Methuen & Co; 1969: 73-102
• 2 Matthews TJ, Hamilton BE. Delayed childbearing: more women are having their first child later in life. NCHS Data Brief 2009; (21) 1-8
• 3 Ginsberg J. What determines the age at the menopause?. BMJ 1991; 302 (6788) 1288-1289
• 4 Bengtsson C, Lindquist O, Redvall L. Is the menopausal age rapidly changing?. Maturitas 1979; 1 (3) 159-164