“Ovarian reserve” refers to egg quantity and quality–or reproductive potential–and it impacts a woman’s ability to conceive. Age plays a significant factor in fertility and is directly linked to reproductive aging.
The concept of reproductive aging is based on the principle that eggs peak in number during fetal life, undergo degeneration, and do not regenerate. Remarkably, the most eggs women will have are when she is a 20-week-old fetus with approximately 6-7 million eggs. At birth, the number of eggs falls to 1-2 million, and at puberty, she has only 300,000-500,000 remaining eggs. From puberty though menopause, it is estimated women will ovulate about 400-500 total eggs.
Although female fertility declines with advancing age, it is difficult to predict the overall rate of reproductive decline. The quality of a woman’s eggs is highest in her mid 20s through her early 30s, representing the most fertile period in her life. After the early 30s, both the quality and quantity of eggs begin to decline, resulting in a decline of fertility potential, with the most significant declines occurring in the mid 30s and early 40s.
The decline in both egg quantity and quality may manifest in a longer time to conception. As a result, fecundability–the probability of achieving a pregnancy in one menstrual cycle– begins to decline significantly in the early 30s, with a more rapid decline after the age 37.
Chromosomal Abnormalities and Miscarriage
As women age, the risk of ovulating a chromosomally abnormal egg increases, resulting in lower fertility and increased risk of miscarriage. If a poor-quality egg is fertilized, either the embryo is unable to implant, or the embryo initially implants, but is unable to develop properly, resulting in a subsequent miscarriage. Though older women are more likely to have poor quality eggs, younger women, too, can have poor quality eggs.
A common misconception is having regular periods indicated normal ovarian reserve and therefore means you will be able to conceive. This is not always the case, as many women who have regular periods can still have challenges conceiving if there is poor ovarian reserve (egg quality and quantity).
A few screening tests for ovarian reserve exist, but no single test is highly reliable for predicting pregnancy potential. So, the results of these tests also need to take a woman’s age into account age, and are best interpreted by a fertility specialist.
Common ovarian reserve screening tests include an assessment on day 2 or 3 of the menstrual cycle of serum FSH (follicle-stimulating hormone) and estradiol level, AMH (anti-Müllerian hormone), and antral follicle count (AFC).
FSH is a hormone produced by the anterior pituitary gland in the brain and stimulates a dominant follicle in the ovary to grow and secrete estradiol (estrogen). A high level of FSH may indicate the brain is trying to compensate for ovaries that are behaving older. In general, FSH levels can be variable from month to month.
A high basal estradiol level is generally caused by advanced follicular recruitment that can occur in women of advanced age or poor ovarian reserve. High estradiol levels can inhibit pituitary FSH secretion thus causing a falsely low FSH level. As a result, simultaneous measurement of both FSH and estradiol levels is required to avoid misinterpretation of falsely low FSH level.
As FSH levels vary from cycle to cycle, serum AMH is more of a reliable indicator, with minimal variability during and between menstrual cycles, and so can be checked at any point throughout the menstrual cycle. The AMH level reflects how many potential eggs there are in the follicle; this gradually declines with age, and can be an early indicator of declining ovarian function, making it one of the best indicators of ovarian function. During an in vitro fertilization (IVF) cycle, AMH is one of the best markers for predicting both poor and excessive ovarian response to stimulation, and also correlates with the number of eggs retrieved.
The antral follicle count (AFC) is the total number of small follicles in the ovaries seen with transvaginal sonography, and can be evaluated anytime throughout the menstrual cycle. The AFC can vary from month to month and also correlates with the number of eggs retrieved following an IVF cycle.
Diminished Ovarian Reserve
Diminished Ovarian Reserve (DOR) refers to diminished egg quality, egg quantity, reproductive potential, and can therefore cause infertility. A high day 2 or 3 FSH level, a low AMH level, a low antral follicle count (AFC), and a history of a poor response during stimulation in an IVF cycle are indicative of DOR (diminished ovarian reserve). It is important to note that evidence of DOR does not necessarily translate to inability to conceive.
In most cases, the causes of DOR is unknown, with reproductive aging being the primary cause. Other factors that can affect ovarian reserve include:
- tobacco use
- underlying medical conditions
- prior ovarian surgery
- systemic chemotherapy
- pelvic radiation
- certain genetic abnormalities.
There is no universally agreed-on criteria for diagnosing DOR. So, it can be difficult to provide prognosis to those with DOR, since it may predict a diminished response to ovarian stimulation in an IVF cycle, but not necessarily overall pregnancy rate.
Assisted Reproductive Technology (ART) and Reproductive Aging
No treatment or supplement has been shown to halt the process of reproductive aging, but women with infertility as a result of DOR can use assisted reproductive technologies to increase their chances of conceiving. Identifying if you have DOR is an important component of a fertility evaluation, especially as more and more women seek fertility treatment later in their reproductive years.
Dr. Matthew Lederman is a board-certified Reproductive Endocrinologist and Infertility Specialist, and is often acknowledged for his compassionate care, devotion to patients and his clinical expertise. Prior to joining RMA of NY in 2014, Dr. Lederman treated patients at the Continuum Reproductive Center at St. Luke’s Roosevelt Hospital Center. Dr. Lederman has published scientific abstracts and articles in peer-reviewed journals in the fields of endocrinology and infertility, and has presented his research at national conferences. He has extensive clinical experience in all areas of fertility, including unexplained infertility, recurrent pregnancy loss, in vitro fertilization, egg freezing, pre-implantation genetic screening and fertility preservation for patients recently diagnosed with cancer (oncofertility) and those who are pre-disposed to hereditary cancer syndromes (ie. BRCA).