The goal of the patient who is experiencing infertility is to achieve a healthy live birth at term. Prior to embarking on treatment directed towards that outcome, it is invaluable to be able to provide the patient (-s) with prognostic information on their proposed treatments. Towards that aim, ovarian reserve test has been developed, with the goal of being able to predict the probability of fertility treatment success.
However, in spite of the limited value of many of such tests in predicting the gold standard of fertility treatment success (i.e., live birth), they are routinely performed without a clear understanding by the physician or patient as to the clinical utility of the result. Furthermore, some of this ovarian reserve test has now been advocated for mass screening as a predictor of fertility potential in women not currently trying to conceive.
Such widespread testing of fertility potential by ovarian reserve test without meeting the requisite principles of a valid screening test can lead to unnecessary interventions for individuals who may be advised to consider fertility treatments when scant evidence demonstrates they are needed.
Ovarian Reserve Test: What Is It Measured and Why?
While the literature has described a multitude of ovarian reserve test, there are a select number that is most commonly utilized. Currently, the most common ovarian reserve test consists of female age, day 3/basal FSH, antral follicle count (AFC), and anti-Müllerian hormone (AMH). To further understand their utility in the context of fertility, it is important to understand their predictive value for spontaneous conception in the fertile population, predictive value of live birth in the context of fertility treatment, and the value of ovarian reserve test in predicting ovarian response in IVF. When ordering and interpreting an ovarian reserve test, it is important that the test is interpreted in the context of one of these specific scenarios.
Below we will talk about the patient’s age. The rest of the ovarian reserve tests we will discuss in the following blog posts.
Age as an Ovarian Reserve Test
In the literal and figurative sense, female age is the oldest and most widely accepted ovarian reserve test. Spontaneous and treatment-related reproductive senescence has no greater influence than chronologic age. At age 20, the inability for a live birth is approximately 2.4%, with significant reduction in fertility in the fourth and fifth decades, with 35% of women unable to achieve a live birth at age 40, 50% of women unable to achieve a live birth at age 41, and 90% at age 45.
Nothing has greater impact in reducing the risk of unwanted childlessness or the inability to achieve the desired number of children than attempting conception at a younger female age. However, the effect of primary interventions to achieve the aim of decreasing the age at attempted conception (i.e., through the implementation of fertility assessment clinics) remains unknown.
Advancing female reproductive age is immutable and is associated with increasing disease prevalence. As a result, a larger cohort of older patients will subsequently experience infertility and pursue assisted reproductive technologies (ART) or medically assisted reproduction (MAR) in an effort to compensate for the loss in natural fertility. The probability of achieving the desired family size can be improved through the use of MAR. If a female patient is willing to accept a 90% probability of having either a one-, two-, or three-child family, she can delay childbearing by 3–5 years, if she is willing to undergo IVF treatment to achieve the desired family size. However, this prediction model assumes that the patient is willing to undergo up to three full IVF cycles.
However, on a per IVF cycle using non-donor eggs, the chance of a live birth per fresh IVF cycle which started e.g., in the USA in 2014 was 37% for female age under 35 years, 30% for ages 35–37, 19% for ages 38–40, 10% for ages 41–42, 4% for ages 43–44, and 1% for age 45 and greater. While the reduction in pregnancy rates is partially explained due to an increase in cycle cancellations and embryo transfer cancellations due to an increasing prevalence of poor ovarian response with advancing female age, the predominant factor for failure to achieve live birth is due to failed ongoing embryo implantation.
Comprehensive chromosomal screening data has demonstrated that while the blastocyst development yield is attenuated with age, the greatest factor is the high prevalence of embryonic aneuploidy with advancing female age.
While live birth remains the most important IVF outcome, poor ovarian response (POR) is an important surrogate outcome, as POR is related to low probability of live birth with IVF. Using conventional ovarian stimulation protocols, cycle cancellation, or retrieval of three or fewer oocytes occurs in approximately 15% of females under age 30 undergoing IVF and increases to 50% after age 40. Such prognostic information, in the absence of the addition of other ORTs, provides an initial crude estimate of the probability of cycle cancellation or suboptimal oocyte yield, leading to decreased likelihood of IVF treatment success.