Age, genetics, and birth control: the root causes of infertility

Steven Loeb · June 12, 2024 · Short URL:

At Invent Health, healthcare execs and investors discuss why infertility rates are so high

Recently, VatorNews held its latest Invent Health event: these are salon-styled tech talks and mixers where valuable lessons and insights are shared by investors, tech pioneers and adopters. It is designed to take a 360-degree view of one particular topic. We conduct events in-person and online.

For this event, we looked at women’s health, specifically fertility and menopause.

The salon was hosted by Dr. Archana Dubey, Chief Medical Officer at UnitedHealthcare and Bambi Francisco Roizen, Founder of Vator. Panelists included: Dr. Jean Gekas (CEO, Genoscience); La Keisha Landrum Pierre (Partner, Emmeline Ventures); Dr. Tammy Mahaney (Venture Partner, Suncoast Ventures); Dr. Jillian Lopiano, Chief Health Officer (Wisp, part of Well Health Technologies); Dr. Tendai Chiware (Director of Third Party Reproductive Programs, GENESIS Fertility and Reproductive Medicine)

One of the first topics brought up in the chat were the root causes of infertility, which is a growing problem: about 11% of women and 9% of men of childbearing age having infertility issues in the United States and the total fertility rate worldwide has dropped by nearly 1% per year from 1960 to 2018, which is more than 10% per decade and more than 50% over 50 years. There are a number of reasons why this might be happening, chief among them is that women are having children later, with the median age at which women gave birth in the United States increasing from 27 in 1990 to 30 in 2019.

The problem with later pregnancies is that women are less fertile. In their 30s, women are about half as fertile as they are in their early 20s. 

(source: CDC)

Dubey began by bringing up all of the “P's” and the “M's” that happen to women throughout their life: puberty, pre-partum, pregnancy, post-partum, pre-menopausal syndrome, and then menopause.

"One of the areas that is highly impactful for women is infertility because that has the longest footprint in their reproductive age with a lot of it wrapped around trauma, sadness, hormones, all of the treatment pathways, new technology, all of this," she said, directing her question to Dr. Chiware.

"What are you seeing, especially working in the fertility clinic? What are the root causes of infertility that you encounter most commonly in women who come to see you?" Dubey asked, to which Dr. Chiware responded that infertility is "someone who is under 35, and is trying with regular intercourse over a 12-month period, and somebody over 35 for a six month period, without any success in terms of getting pregnant."

"As a fertility specialist, I see two sides of the coin, where it may be caused by the woman, whereby it could be a disorder like polycystic ovarian syndrome, endometriosis, things like that. It could be something structural, like fibroids, or blocked tubes, either from a prior infection or from prior sterilization for contraception reasons," she said.

"Also, we see quite a lot of women who are over the age of 35, or even over the age of 40, who are then seeking to start their families at that time and sometimes will have difficulties trying to conceive. And then there are some genetic conditions that also cause infertility, as well as medical disorders where, sometimes, women are taking medications that may result in infertility, particularly things like chemotherapy, radiation therapy to treat cancers."

Dubey then brought up that women take a longer time to ask the right question around fertility, because they feel like they're alone in their entire journey.

"There is a hesitancy, and I've seen this again and again in my practice: when they cannot get pregnant, they feel the blame is on them. But you're enlightening our viewers and audience that 35% can be as a result of the male side. And so, we need to have both individuals be evaluated and asking that first question becomes almost like the most necessary step in getting care from the provider," she said.

Voluntary infertility or actual condition

While most women who are infertile are in their later years, the percent of women who are infertile due to genetic or other conditions are extremely small in numbers. For example, ovarian or gynecological conditions, such as POI (primary ovarian insufficiency), affects .1% of women under 30 and 1-2% of women under 40.  

So Dubey then asked what Dr. Chiware is seeing at her clinic. In other words, what is the breakdown is between voluntary deferral of fertility, which can lead to older women potentially having issues, and what percentage are medical conditions.

Dr. Chiware responded that it's split down the middle between those two. "Being in New York, it's quite a fast-paced lifestyle, so a lot of women are in the midst of their career, so they are not thinking of starting families at this time. So, they do fall back on fertility preservation. The good thing is that a lot of organizations and companies are now starting to recognize this, and are actually starting to cover it in terms of covering the actual cycles and the payments for it but we still have quite a long way to go in terms of insurance coverage, which I'm sure you're going to delve into too," she said.

Those are the women over 35. But then there are those under 35 who are actively wanting to get pregnant and are having difficulty. This begs the question, what's going on? 

Birth control consequences

Enter birth control, which could be part of the problem women are struggling with infertility. Dr. Mahaney practices in women's health clinics while also doing medical missions in underdeveloped countries, who responded that she agrees with Dr. Chiware about the physiological causes, but that she is also noticing a lot of women, especially in her primary care clinic, wanting to get off birth control and wanting more of a natural approach for fertility awareness.

"As we know, there are certain types of hormonal birth control that can stop ovulation like the Depo-Provera and certain hormonal IUDs and it can affect women. I mean, think about it, if some of these girls started on birth control at 14 or 15 years old, and they wait until they're 35 before they want to start having babies and families, there's been a lot of just changes and side effects that have happened to their natural cycle," said Mahaney

For example, sometimes birth control can basically trick the body into thinking that the body's pregnant, so it keeps the endometrial lining very thin, which is not the natural cycle, because the endometrium, as we know, gets thick and thick, and then sheds the lining, which is the natural process. So, those types of things can affect fertility.

Mahaney also brought up environmental factors, such as food, estrogenic chemical exposure, hormone disruptors, which we're starting to finally see and look into and research is talking about that are affecting fertility as well, something that she does not in see in developing countries.

"Something that's very unique about America is even though we are a very wealthy nation, we're also a very sick nation, we have a lot of obesity, and insulin resistance is another root cause and factor for infertility. So, when we have a morbid obesity situation, I know even for fertility clinics you have to be a certain BMI before we can even start any intervention," said Mahaney.

"So, things like that are other root causes that we need to tap into and think about, as well as doing hormonal balance for hormone restorative endocrinology, just balancing those hormones; some women might be deficient in progesterone or low in estrogen and there's things that we can do to tap into to help empower the body to do better."

Dubey then brought up stress as directly contributing towards problem with women and their hormones.

"One thing that we do is ACEs training, which is adverse childhood experience training. That typically carries through a woman's life through the whole entire piece that we talked about: it impacts puberty, it impacts PMS, it impacts  pregnancy or fertility, and then also the menopausal experience," said Dubey.

"That would be a really, really good consideration for people to screen their patients or themselves for an advanced childhood experience that can impact all of the hormones that could be playing out in the body."

Francisco turned to Lopiano to see how Wisp creates awareness about what their users need to know about fertility and infertility.

"Tammy mentioned there's downside effects of birth control. There's environmental factors as well, but there's obesity concerns, there's a lot of different things that can affect your fertility," she said.

"Do you create awareness to your group about really what you need to know about fertility and infertility? Not just, 'here's your ovulation packet down the road when you want to consider fertility,' but the things that you need to consider through your lifetime and these are the downside effects of the things that you're taking," she asked.

Lopiano's answer was that contraception and preventing unintended pregnancy is also a really important component of women's health.

"50% of pregnancies are unplanned and a lot of those are undesired. And we have really good data on UCSF just did a beautiful study called the Turn Away Study, looking at the social, emotional, physical impacts of women that had an unplanned pregnancy and those that wanted to continue the pregnancy and those that did not, and what the consequences of that were," she said.

"We're talking about infertility but, ultimately, if we're talking about women and taking care of women, we're talking about control over your fertility and being able to plan your life, whether you want zero children or 10." 

As such, one of the things that Wisp does is talk about contraception in the sense of preventing pregnancy and being able to become pregnant when you want to is super important. And that includes side effects from birth control, which will depend on what that specific woman wants.

"One of the things that is a really important educational piece when you're talking about contraception is there is not a one size fits all approach. When you're talking about contraception, part of that clinical context should be, 'do you think you want to become pregnant? When do you think you want to become pregnant?' Because the return to fertility and ovulation is different for different types of contraception. Depo-Provera takes a little bit longer, IUD a little bit quicker. The side effects and return to fertility in the immediate sense is a really important component of contraception prescribing, and then management," Lopiano said. 

Watch the entire panel below:

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