Ask a woman of reproductive age when her fertility becomes an issue, and she will likely answer: 35. As an OB-GYN in private practice, I see patients who are, for the most part, either pregnant or in some orbit thereof—trying to get pregnant, having trouble getting pregnant, actively trying to prevent pregnancy—and they seem to think there is a threshold midway through one’s 30s that matters very, very much. This may partially result from the fact that women on average are having their first child later in life, so they’re more aware of fertility declining with age. And now, thanks to COVID-19, single and partnered women alike are grappling with delay and uncertainty about whatever timelines they previously held.
Being 35 or older is labeled by the medical community as “advanced maternal age.” In diagnosis code speak, these patients are “elderly,” or in some parts of the world, “geriatric.” In addition to being offensive to most, these terms—so jarringly at odds with what is otherwise considered a young age—instill a sense that one’s reproductive identity is predominantly negative as soon as one reaches age 35. But the number 35 itself, not to mention the conclusions we draw from it, has spun out of our collective control.
Where exactly did the focus on 35 come from? The number was derived decades ago, during a very different reproductive era. Birth control options were limited. Most first pregnancies occurred in women’s 20s. In vitro fertilization was in its infancy.
Most people assume we use age 35 because studies show that things get worse for women at that point. Indeed, early population studies do demonstrate that certain risks, namely the risks of infertility, miscarriage, and chromosomal abnormalities, increase more significantly at age 35. (To be clear, these risks are age-dependent and increase steadily with age generally, but at some point their rate of increase increases, and that inflection point has been pinpointed by some studies at age 35.)
But using age 35 in this way is not as clear cut as it seems. One problem is that it’s an incredibly subjective way of defining what should be objective. The age-related risks of these issues are derived from several large studies, and to look at the tables or graphs of the reported risks is a bit like being administered a Rorschach test: Some will see worrisome numbers starting at age 35, some at 40, some maybe even at younger ages. Moreover, comparing these studies is complicated by their design. For example, when looking at studies regarding Down syndrome risk, some report risk as a function of all live births, while others report it based on amniocentesis results; the amnio risk will appear higher, since some subset of the abnormal pregnancies will miscarry or be electively terminated before the end of the pregnancy could be reached. Put more simply, if you were to ask a dozen professionals to interpret the data and pick one age cutoff whereby to distinguish low-risk from high-risk women, you may very well get a dozen different answers.
The bigger problem is that the real origin of the number 35 comes from a very specific—and essentially outdated—line of clinical reasoning. It was borne out of the desire to counsel women clearly on their options regarding testing for aneuploidy (an abnormal number of chromosomes in the fetus). In the mid-’70s, the only option for genetic testing during a pregnancy was amniocentesis, an invasive procedure in which a needle is placed through the mother’s abdomen in order to sample amniotic fluid containing shed fetal skin cells. Doctors struggled with how to tell women whether it was worth it to have one, whether the benefit outweighed the risk. In the case of an amnio, the benefit is knowledge in advance of birth, but since it is an invasive procedure, there is a risk of losing the pregnancy as a result of the amnio. Taking into account the known procedure-related risk rate at the time (1 in 200 chance of miscarriage) and the likelihood of a genetic abnormality (specifically Down syndrome) based on a woman’s age, the numbers seemed to come out in favor of an amnio—that is, the likelihood of Down syndrome was higher than the risk of procedure-related pregnancy loss—around age 35.
But as I said, even this calculation is outdated. With increased experience since those foundational studies, the risks of having an amniocentesis are lower, which calls into question that calculation; if you were to rerun that risk-benefit calculation by comparing today’s quoted risk (around 1 in 500) to the age-related risk of Down syndrome, we would define advanced maternal age as 32.5 years—younger than before. Additionally, the high detection rate of noninvasive screening methods, particularly cell-free DNA testing, means women are more commonly seeking amnio (or a related earlier procedure, chorionic villus sampling) as a follow-up to an abnormal screening test, further complicating the effort to define advanced maternal age based on the risk of any testing options. Finally, different patients perceive risk, benefit, and necessity in different ways, which means some women that the medical community labels “low-risk” would pursue an amnio, while some “high-risk” women would not.
For all the above reasons, the definition of age 35 has gone from arbitrary and rigid in its beginning to essentially obsolete. Yet, in the interim, it has become codified, largely out of convenience, as being reflective of the changing risk of all reproductive issues, not simply the chance of Down syndrome. Knowing what we know now, it would be best if we could go back in time and reframe the conversation, hopefully doing away with a single age cutoff that drives our perception of reproductive risk. But as things stand, age 35 has stuck in our minds, mostly for the worse.
The 35-year-old threshold is not only known by patients, it is embraced by doctors as a tool that guides the care of their patients. It’s used bimodally: If you’re under 35, you’re fine; if you’re 35 or older, you have a new host of problems. This interpretation treats the issue at hand as what is known as a “threshold effect.” Cross the threshold of age 35, it implies, and the intrinsic nature of a woman’s body has changed; she falls off a cliff from one category into another. (Indeed, many of my patients speak of crossing age 35 as exactly this kind of fall, with their fertility “plummeting” suddenly.) As I’ve already stated, though, the age-related concerns are gradual and exist along a continuum. Even if the rate of those risks accelerates at a certain point, it’s still not a quantum leap from one risk category to another.
This issue comes up frequently in science and medicine. In order to categorize things that fall along a continuum, things that nature itself doesn’t necessarily distinguish as being separable into discrete groups, we have to create cutoffs. Those work very well when comparing large groups of patients, because that’s what the studies were designed to do, but to apply those to individual patients is more difficult. To a degree, they can be useful. For example, when we are operating far from those cutoffs—counseling a 25-year-old versus a 45-year-old—the conclusions to draw from that cutoff are more applicable. But operate close to it—counseling a 34-year-old trying to imagine her future 36-year-old self—and the distinction is so subtle as to be almost superfluous.
Still, age-related fertility decline is one of the main topics of conversation I have with my patients. The dread of age 35 is so pervasive that its effect bleeds backward in time, with women in their early 30s—and yes, sometimes even in their late 20s—already feeling as if they are behind in the race against their “biological clock.” Doctors have an obligation to put this to an end. While it is true that there exists a relative decline in fertility over time, the truth is that, in absolute terms, women 35 and over are still very likely to conceive without difficulty, and at about the same rate as women under 35. Although strong data on this subject are hard to come by, because studies like this are hard to design and execute for numerous reasons, one of the largest studies found that 78 percent of women aged 35 to 40 will conceive within a year, compared with 84 percent of women aged 20 to 34. That is a small difference, especially compared with how one’s fertility decline is so commonly perceived. Other studies are similarly reassuring. And while there are exceptions to every rule—there are some women who will experience difficulty conceiving at an earlier age than otherwise expected—it’s important to emphasize that the rule is less bleak than most people think. The message doctors should be giving their patients is: You are more likely than not to get pregnant of your own efforts, and with about the same success as when you were younger.
A similar failure of threshold effect thinking is how obstetricians treat pregnant patients of “advanced maternal age.” In many settings, patients 35 and older are automatically consigned to extra testing and treatment: low-dose aspirin to prevent preeclampsia, extra ultrasounds, extra testing of their baby’s well-being as they approach their due date. This approach treats age 35 as more different from age 34 than age 40 is from 35. Aside from being simplistic, this monolithic thinking creates stress and a stigma—it’s almost automatic that my patients age 35 and above ask if their age makes them “high-risk”—unnecessary for women to feel. It also creates a very real risk of changing the course of a pregnancy based on the results of extra tests—what is known as a “care cascade,” a domino effect of each test prompting another new test or treatment—in ways that are not always necessary and can sometimes be harmful. Consider, for example, a patient who has an early 16-week fetal anatomy ultrasound (in addition to the standard 20-week one). If that ultrasound shows a possible abnormality, it could really be something abnormal, or it could be an artifact of doing the scan so early and would clear up by the time of the 20-week scan. But, in the interim, in order to rule out any genetic abnormalities, the patient might be offered an amniocentesis, which runs the risk of causing a miscarriage. These extra risks are why, instead of reflexive thinking based on age, obstetricians should be thinking about all of the factors that influence the health of a patient’s pregnancy and choosing what is right for their patient.
I have three suggestions of how to combat this phenomenon. First, do no harm. We physicians often forget about psychological harm. Thanks to the messaging out in the world—from friends and family, the media, and, yes, the medical community—women are more likely to approach the issues associated with being over age 35 with trepidation rather than confidence. Recognizing that an increasing proportion of women will be approaching or have reached age 35 when they start trying to conceive for the first time—by one measure, this proportion has increased 23 percent since the year 2000—we should be trying to normalize what up until now had been considered a marginal experience. Especially now, in circumstances as extreme and uncontrollable as the COVID-19 epidemic—and all the social, romantic, and reproductive disruptions it entails—we should be pushing back on what creates undue stress for our patients. We should be focusing more thoughtfully on which parts of the 35-year cutoff matter, and how much so, while emphasizing the honest good news about age-related reproductive issues.
Second, we should be more flexible in our thinking. While I’m not one for rebranding just for appearance’s sake, the term “advancing reproductive age” is probably more useful than “advanced maternal age,” because it reminds us that this is a continuum, not a threshold. When my patient who is 34 and healthy and had an uncomplicated first pregnancy worries about being over 35 with her second pregnancy, I reassure her that changes are likely to be minimal and that the most important thing is the confidence she should have based on her first pregnancy.
Third, we must treat the patient, not a number. The number is meant for populations, and even at that, we should not be monolithic in our decisions of how we provide care. Not all 33-year-old women wondering about their fertility prospects are the same. Neither are all 38-year-old women on their first pregnancy. Patients deserve—and appreciate—individualized care. Such care will treat age as one of many factors that matter, but by no means the only, or most important, one.