Seeing double: The science behind (natural) hyperovulation

Seeing double: The science behind (natural) hyperovulation

The past 30 years have been filled with significant changes in fertility patterns across the United States. We’ve seen changes in when we have kids, how many kids we have, and even how many kids we have at a time (i.e., the prevalence of twins and higher-order births). The highest rate of twinning (33.9 per 1,000 live births) ever recorded was in 2014, while the highest rate of triplets and higher-order births (a whopping 193.5 per 100,000 live births!) was recorded in 1998. Based on the most recent demographic data, both of these rates have since decreased (32.6 per 1,000 live births for twins, and 93 per 100,000 live births for triplets and higher-order births).

Though most of us (correctly) think that things like in-vitro fertilization (IVF) are the main reason why multiple births are as common as they are, there’s another naturally occurring factor that deserves some time in the spotlight as well: hyperovulation, aka multiple ovulation.

In this post, we’ll go over what hyperovulation is, the science behind it (spoiler alert: hormones are involved), and the factors that affect its prevalence.

What is hyperovulation?

Though menstrual cycles don’t look the same from person to person — and don’t even look the same across different cycles in the same person — the general pattern goes something like this:

  • Your follicle-stimulating hormone (FSH) encourages a few follicles that contain eggs to develop.
  • A follicular battle royale of sorts plays out, in which just one follicle (usually the most developed and largest one) survives, and all other follicles that were developing alongside it die off.
  • The dominant follicle continues to grow and develop.
  • An egg is released from the follicle during ovulation.
  • If the egg is fertilized and a pregnancy begins, follicle development is halted. Otherwise, the cycle of primordial follicle development starts again.

Given that things like twins and triplets exist, we know that there must be alterations to this general schema. In the case of identical twins, a single egg gets released and once it is fertilized by sperm (we call this egg + sperm combo a zygote), it splits into two, and the result is two completely identical zygotes. Because these two originate from the same zygote, we’d call them monozygotic. The result? Identical twins.  

In the case of fraternal twins though, there’s a different process at play, and that’s hyperovulation. Remember how we said that in the follicular battle royale, there’s only one winner? Well, that’s not always true.

It’s also possible for there to be more than one follicle that emerges as the dominant one, and more than one egg released during ovulation (i.e., hyperovulation). If these two genetically distinct eggs get fertilized, they’ll form two genetically distinct zygotes. Because these sorts of twins were always two separate zygotes from the start, we’d call them dizygotic (and in less sciencey terms, fraternal).

What’s the science behind hyperovulation?

Because hormones play a role in a million different bodily processes (not quite an exact count, but probably close!), you won’t be surprised to hear that they’re closely tied to whether you ovulate in a given cycle, and how many eggs you ovulate. Though several hormones play a role here, the star of this show is FSH.

Starting around menstruation, your body begins to produce more FSH to stimulate the development of follicles (clearly, whoever thought of the name “follicle-stimulating hormone” was feeling particularly creative that day). After about a week, FSH levels naturally begin to drop. Only the follicle that was largest and most developed is able to survive despite this FSH drop. This dominant follicle begins producing estradiol, which then triggers the production of luteinizing hormone (LH), and it’s a surge in LH that ultimately makes ovulation happen.

But what happens if FSH levels are just naturally higher, or if they don’t drop after about a week? According to some studies, those are precisely the scenarios in which multiple ovulation could occur. Mothers of naturally occurring fraternal twins (i.e., women who naturally had hyperovulation) have been shown to have higher FSH than mothers who did not have fraternal twins in several studies, though not all do. Mothers of fraternal twins might also release FSH more frequently early on in the cycle when follicles are developing. And while some studies have pointed to differences in how sensitive someone’s body is to the effects of FSH as an explanation for multiple ovulation, others haven’t found data that back this up.

There are two important things to keep in mind in drawing conclusions from these studies’ findings. First, they don’t give us any clinically applicable cutoffs — what we mean by that is there’s no single FSH level at which we can tell someone they’re definitely going to experience hyperovulation. Second, even though FSH may be associated with fraternal twinning (which is a surefire sign of multiple ovulation), that doesn’t necessarily mean that it causes it.

There are other lines of evidence that point to high FSH causing hyperovulation. For people who are having difficulty achieving pregnancy, it’s common to be prescribed a hormone-based medication, like Letrozole or Clomid, that puts follicle development in overdrive. Though there are slight differences in the way these medications work, their end result is the same: They cause higher levels of FSH, and this higher FSH results in a higher-than-normal number of follicles reaching the developed stage.

How often does hyperovulation happen?

It’s tricky to nail down exact prevalence rates, especially when studying the prevalence of things that aren’t accompanied by observable signs, as is the case with hyperovulation. Most of the time, hyperovulation goes undetected. While ovulation predictor kits (OPKs) can measure LH to tell you if you’re likely ovulating soon, those LH concentrations don’t tell you how many eggs you’ll be ovulating.

We also can’t just look at the rate of fraternal twinning and assume that it’s representative of the prevalence of hyperovulation. This is because of something that sounds like it’s straight out of a sci-fi movie, but is a real thing: vanishing twin syndrome.

This is when there are two fertilized eggs that implant into the uterine lining, with one “naturally disappearing” early on in the pregnancy. Though this phenomenon isn’t anything new, with advances in ultrasound technology and accessibility, our ability to detect so-called vanishing twins has improved. That being said, it’s likely that some women ovulate more than one egg and then multiple fertilized eggs implant in the uterine lining, but one of them “disappears” before they get their first ultrasound. Because of this, the fraternal twinning rate likely underestimates the true prevalence of hyperovulation.

Those caveats aside, there are some studies that include ultrasounds performed across the cycle to directly observe how common it is to ovulate more than one egg. A 2006 study performed ultrasounds around ovulation in one to three cycles for 105 women, and found that 21% of women had at least one cycle where hyperovulation occurred. Other studies that are a bit more dated put the prevalence of hyperovulation at closer to 10%. The wide range in reported prevalences from ultrasound-based studies means, unfortunately, we can’t be super confident about what the true population prevalence is.

Factors associated with multiple ovulation

Though we can’t be positive about how often hyperovulation itself occurs, we can look at factors associated with FSH and fraternal twinning to roughly guess:

Age

There’s one factor that has been shown time and time again to be associated with FSH levels and the prevalence of naturally occurring fraternal twinning: age. The first reports of a link between age and twinning can be traced back to as early as the 1970s in a book called “The Biology of Twinning in Man,” (apparently women didn’t deserve a shout out there…) in which the author reports a 300% increase in twinning between the ages of 15 and 37.

At first glance this seems to contradict the fact that fertility decreases with age in women, so let’s take a closer look. Typically, developing follicles respond to increases in FSH by releasing hormones like E2 to inhibit FSH production, making hormones like E2 the brake pedal on FSH. As the number of developing follicles (and anti-Mullerian hormone, or AMH, levels) decreases with age, so does the ability to act as that brake pedal and inhibit that FSH production. More FSH production is associated with a higher likelihood of more than one follicle reaching the dominant follicle stage and voila! Hyperovulation. Clinical ultrasound data confirms this pattern. But keep in mind that egg quality decreases with age, meaning that though older women are significantly more likely to ovulate more than one egg at a time, it doesn’t necessarily mean that those two eggs will both be viable.

Genes

Second, genes likely play a role in hyperovulation and twinning. Unlike some animals, where there have been single genes identified that strongly affect the likelihood of fraternal twinning, the genetics of fraternal twinning and hyperovulation in humans are a little messier. Some recent studies have found that genes linked to FSH production influence fraternal twinning rates, though like many complex traits, it’s likely that any one gene will only explain a small part of your risk.

Stopping birth control

Because other factors potentially contributing to hyperovulation aren’t as strongly backed by data, we’ll go over them briefly. First up is recent birth control cessation. Hormonal birth control methods like the pill and the ring work by suppressing your brain’s centers that signal the production of hormones like FSH, and suppressed FSH → suppressed follicular development → no ovulation. After stopping these birth control methods, your brain has to get back into its regular hormone-producing groove, and there’s a chance that in this process it’ll overshoot its FSH production, thus making hyperovulation more likely.

Other factors

Interesting studies are constantly popping up, linking fraternal twinning to things like height, BMI, seasonality, and even smoking. We won’t discuss them here because these associations need to be poked and prodded a bit more before we can be confident that they’re legitimate, but a summary of some of these associations can be found here.

Is hyperovulation “good”?

While there are many situations in which more is better than less, that’s not necessarily the case when it comes to ovulation and developing embryos. Don’t get us wrong — hyperovulation and having twins can be natural, exciting, and, frankly, more efficient for those who want to expand their families quickly!

Multiple births, however, are also considered high-risk pregnancies because each additional baby is associated with a higher risk of preterm birth, gestational diabetes, and low birth weight, among other potential complications. Because of these increased risks, it’s not as simple as “more = better” when it comes to how many eggs you release during ovulation each month.

The more reproductive health research we do on people with ovaries, the more we learn that things don’t always follow the textbook patterns we’re taught. Hyperovulation is seen across species, populations, and across the reproductive lifespan in humans, and is associated with things like higher FSH and increasing age. Though there aren’t any tests that can tell you for sure whether hyperovulation is something you will experience, getting insight into your hormone levels (like FSH and AMH) may provide some initial clues about what your chances of hyperovulation may be like.

P.S. Just for fun… a note on animal twinning rates:

We came across this in our research and had to share: As rates of both identical and fraternal twinning are low in humans, you might be tempted to think that that’s normal across mammals and primates, our close genetic relatives. Turns out, the animal kingdom is an ever-surprising place, and there are fascinating patterns of twinning and multiple ovulation everywhere you look.

For example, armadillos always have four identical offspring — meaning that one fertilized egg splits and splits and splits until there are identical quadruplets. And marmosets, which are monkeys found in South America (some of which weigh less than half a pound!!), always have fraternal twins. Interestingly, twinning rates in captivity for our closest living genetic relatives, chimpanzees, are around 1.7%, which is eerily similar to the rate of 1.9% observed in the United States in 1980, before the popularization of procedures like IVF.

This article was medically reviewed by Dr. Eva Marie Luo, an OB-GYN at Beth Israel Deaconess Medical Center and a Health Policy and Management Fellow at Harvard Medical Faculty Physicians, the physicians organization affiliated with the Beth Israel-Lahey Health System.OvulationConceptionHormonesIVF

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Talia Shirazi

Talia is a biological anthropology PhD candidate at Penn State, passionate about women’s reproductive health and behavioral neuroendocrinology.Join our community on Slack

This is a space for us to talk about health, fertility, careers, and more. All people with ovaries are welcome (including trans and non-binary folks!).

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