The Biological Reason Why Older Moms Are More Likely To Get Pregnant With Multiples

 
Photo Source: Quaz Amir

Photo Source: Quaz Amir

 

You may have heard that more U.S. births are multiples than ever before. Juxtapose that with the fact that many women in the U.S. are delaying motherhood well into their 30s and 40s at a historic rate. Please allow this article to establish the causal relationship between those last two sentences.

If you are a woman who is 35 and older and plan to have a baby (I gave birth at age 37), I have some news that you can put into your crap pile along with getting the scarlet letters “AMA” (Advanced Maternal Age) branded onto your medical files. You are biologically more prone to have multiple babies (twins, triplets, or more) than younger women. If you have heard about this biological phenomenon and, like me, shrugged it off thinking “Oh, but that’s because older women do IVF and IVF makes one more prone to birth twins”, THINK AGAIN.

I recently spoke with Dr. Kelly Acharya, Fellow (soon-to-be Assistant Professor) in Reproductive Endocrinology and Infertility at Duke Medicine because I needed to understand WHY older mothers are more prone to multiple baby births. I found out that it has nothing to do with IVF . . .

Is it true that older mothers are more likely to get pregnant with multiples?

Dr. Kelly Acharya

Dr. Kelly Acharya

First, women may assume that they are less likely to get pregnant in their late 30s/early 40s, and this may make them less careful about using birth control consistently, resulting in unplanned pregnancies in the later reproductive years.***

And yes. Women ARE more likely to get pregnant with multiples (twins, triplets, etc…) during their late 30s and 40s. There is a biological reason for this. As our egg supply goes down with age, our follicle stimulating hormone (FSH), a brain hormone, goes up. You can think of this like the brain having to yell more loudly at the ovaries to get them to produce eggs. When the FSH level goes up, it may stimulate a woman’s ovaries to make more than one mature egg that month, which could result in twins (or more!).

Can you describe the actual mechanics of the FSH cycle?

The hypothalamus (brain region) releases a hormone called gonadotropin releasing hormone (GnRH), which stimulates the pituitary (another brain region) to release follicle stimulating hormone (FSH). We call this the "HPG" (hypothalamus, pituitary, gonadal) axis.

Anyways, FSH stimulates the ovaries to make an egg each month, and the ovaries (with maturing egg(s)) in turn release estrogen. Estrogen feeds back to the brain and tells it that your ovaries are making a mature egg, so the brain can calm down and decrease the release of FSH (a negative feedback loop).

In a young, healthy woman, it takes just a little bit of FSH released from the pituitary to stimulate her young, healthy ovaries to make an egg and estrogen. So in a woman with good "egg reserve", we would expect her FSH to be low (less than about 10).

In a woman that is closer to menopause, her ovaries are not as responsive to FSH as they once were, so the brain has to release more FSH to get her to make an egg. If I were to check the FSH level in a 45-year-old, I would expect it to be significantly higher than in a 30-year-old. In perimenopausal women, we often see FSH levels of 20 or higher. This is where it is almost like the brain is having to "yell more loudly" at the ovaries to get them to make an egg (or eggs).

Sometimes this increased FSH is enough to make the ovaries mature multiple eggs that month, and if both eggs fertilize, you could end up with (fraternal) twins. This is why the twin rate is slightly higher in older patients, because they are more likely to release multiple eggs due to their high FSH.

I know this is a very endocrine-heavy topic that is hard to state succinctly.

So basically, younger women have FSH levels of about 10 and older women have FSH level of about 20. FSH stimulates the ovaries to make eggs and due to their higher FSH levels, older women are more prone to mature and carry multiple eggs?

Yes, basically.

Does In Vitro Fertilization (IVF) fit into this?

I'm so glad that talking about fertility and IVF is becoming more mainstream.

When it comes to the risk of twins and triplets, the risk is actually greater with intrauterine insemination than with IVF, since we can control the number of embryos more exactly in IVF.

When people are worried about having twins or the safety of IVF, it's important to know that it is generally a very safe procedure, and that we can now minimize the twin risk significantly by putting in only one embryo. Still, the process can be daunting.

It sounds like the science behind IVF is constantly changing. What’s something hot in this field right now based on your research?

The "fresh versus frozen” topic is hot right now.

So first, a distinction: There are people who decide between doing a fresh embryo transfer vs freezing embryos (not eggs) and then putting them back relatively soon. In other words, these are not women who were banking their eggs for "social egg freezing” or fertility preservation (which I encourage). Some clinics now extend the IVF process for everyone, meaning that you go through the two weeks of injections to stimulate your ovaries, you do the egg retrieval procedure, you fertilize the eggs with sperm, freeze the embryos, and then put one (or more) back the next month or shortly thereafter. This is referred to as a "freeze all” cycle followed by a frozen embryo transfer. We did a study that found that you probably don't need to go through all of that for women who get less than 15 eggs, as those women are just as likely to have a pregnancy and birth if you put the embryos in right away (in the same cycle as the egg retrieval). We are not saying one is better than the other; instead, we are saying that it may be best to take an individualized approach rather than saying "freeze all” is best all of the time for all patients.

You just said you encourage social egg freezing. Why?

A wonderful clinical psychologist that I work with describes this in a perfect way: with egg freezing, many women feel that it is like taking out an insurance policy on their fertility. In reality, nothing is 100% in the world of fertility. A better way to look at this would be like buying a lottery ticket, albeit one with a much higher chance of winning than the actual lottery. In general, women who freeze their eggs are happy that they did it, feeling that this gave them the sense of taking charge of their fertility, even if they later decided not to use those frozen eggs. I do think it's important to understand that, because of the natural inefficiencies in reproduction, a large number of eggs is needed to give a good chance of live birth. For someone in their mid-to-late 30s, we usually counsel that they'd need about 25 eggs frozen to have about a 70% chance of having a baby from those banked eggs. Sometimes this takes multiple rounds of IVF to bank this many eggs. As long as someone is up for this, I think egg freezing is a great idea.

What are aspects of your specialty that are not often discussed publicly, but should be?

I think that when people hear about Reproductive Endocrinology and Fertility, they immediately think of an IVF doctor. While that is a huge part of what we do, there are other aspects to the specialty, including management of pediatric reproductive endocrine disorders (like a young teenager with polycystic ovary syndrome, PCOS), premature ovarian failure in young women and girls, women or girls with congenital anomalies, perimenopausal medicine, and (a particular passion of mine) fertility preservation for cancer patients.

Dr. Acharya with one of her sons

Dr. Acharya with one of her sons

Where do you find joy in your profession?

Our patients. I know I'm biased, but I think fertility patients are some of the absolutely best people in the world. I love working with women all day, and I love working toward the goal of helping people become parents.

What is your self-care regimen? How do you sustain yourself in such a high-stakes line of work?

I don't have a set regimen, although I know I would probably benefit from being more intentional about self care! My outside-of-work life is all about my family. I have two young sons (three years and four months old), and coming home to them is the best part of my day. Plus, I'm lucky enough to have a husband that takes care of lots of the "life stuff” (taking the dogs to the vet, fixing the kitchen sink, day care drop-off).


***Evidence = my mother. My older sister was born in 1976. I was born in 1980. My parents really wanted a third child, but it was hard for them. So my mom went on fertility drugs for eight years. Finally, she was told that she was “infertile” and could not bear more children. The good news is that my parents were still doing it in their mid-40s. The other good news is that they (surprisingly) had their third child, in 1991, when my little sister was born. My mom was 44 when she gave birth to my little sister and 45 when she started menopause. The first moral of this paragraph: If you have not gone through menopause and you think you can’t get pregnant, you can. The second moral of this paragraph: My mom was really lucky because she had a singleton third child, even though, biologically, the chances of her having twins or more was likely.

At 38 years old, I was 99% sure that we were a #oneanddone family. Knowing that I have a higher probability of having twins or more now makes me 100% sure. Are you as surprised about this as I was?