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Your Fertility Crystal Ball

When I was in my mid 30s, I really wanted to have a baby, but I wasn’t quite ready. I talked to my OBGYN about freezing my eggs. It was 2009 and the procedure was still labeled “experimental” by the American Society for Reproductive Medicine, but my fertility doctor told me the technique was rapidly improving. We began by testing my fertility to see whether I was a good candidate. She evaluated my pool of healthy eggs with a pelvic ultrasound, and pointed to a video screen showing eight Antral Follicles, a good reserve for my age. She told me that at 37, I was biologically young and therefore a good candidate for freezing.

Genetic insight will help women who are struggling with infertility now, and it will also empower women in their 20s and 30s to make proactive decisions before they even start trying to become pregnant.

The information was my magic bullet, but I also wondered if it had been bad news. What if I had learned that my fertility was in rapid decline or that it was too late? I thought about all the stories I’d heard of friends who had faced infertility and miscarriages because so many of us are putting our economic power ahead of procreative power and starting our families older. I wished we could have a crystal ball that we could look into in our 20s that would tell us what our fertility timeline might look like. This information could prevent a lot of the difficult fertility stories and also help us to make proactive choices such as freezing our eggs or reconfiguring the balance of our careers and family life, so we can have a baby when the time is right.

The Dawn of Personalized Reproductive Medicine Little did I know that at the time I was wishing for a fertility crystal ball, Piraye Beim was toiling away at her PhD at Cornell’s Medical Center in New York in molecular biology, focusing on pharmacogenomics in Oncology. Instead of generically treating a tumor as breast cancer or lung cancer, she studied how doctors were using gene sequencing to learn about a tumor on a molecular and genetic level and then personalizing a drug treatment plan based on the tumor’s specific gene sequence. Later, Beim pivoted in her graduate thesis work and became one of a handful of experts in the molecular genetics of egg quality in early development in mammals.

In the midst of her post-doctoral work at Cambridge, Beim attended a symposium on the 40th anniversary of the first successful In Vitro Fertilization experiment in humans. She learned about infertility patients who were going through multiple rounds of IVF to become pregnant. Sometimes it worked and other times, it didn’t, but there was no understanding of these outcomes. One day, she raised her hand and said, “Wait a minute! There’s this genetics revolution happening in oncology, but who’s doing this for reproduction?” The answer she heard: “We don’t know anybody who’s doing anything like that.”

Predicting Fertility

What happened next is what she describes as “her flight of insanity.” She left her post-doctoral academic post and moved back to New York to start what would become Celmatix, the first personalized reproductive medicine company. (See Beim’s paper on personalized reproductive medicine). “I saw the price for genetic sequencing plummeting and also that no one was taking a big swing to apply this technology to fertility and women’s health,” she says. “With that, I saw this as the perfect opportunity to take that leap. Though in retrospect, it was a little crazy.” With meager funding, she started collecting data on why some women and couples succeed and why some fail at IVF. Seven years later, Beim and her colleagues have collected the largest data set for infertility, and have developed an analytics platform that allows clinicians to leverage the power of statistics.

Imagine a couple. Amy is 41 and Sam is 40. They’ve been trying to conceive for a year, and Amy has had two miscarriages. They’re emotionally worn out and wishing for a clearer picture of their chances to have a baby. By looking at their age, Amy’s Body Mass Index and hormone levels, and Sam’s sperm count, their doctor can give them a rough estimate based on standard outcomes that their chances getting pregnant naturally are 2 percent and 24 percent chance if they consider in vitro fertilization. Their insurance only covers three rounds of IVF, and they can’t afford to pay out of pocket.

Dr. Beim explains that she and her team have developed an analytics tool called Polaris that can take this prediction a step further to offer much more precise statistics. It can compare Amy and Sam’s personal fertility metrics to a database of hundreds of thousands of other patients. Their doctor can then use predictive analytics to calculate their most likely outcomes by comparing them to patients with a similar profile. Polaris can predict Amy’s likelihood of getting pregnant, how that likelihood will change over time, and other outcomes. Armed with this information, the couple will have more clarity and can make choices that could save them time trying to conceive, money and emotional energy.

A Proactive Fertility Test We still rely on general statistics that tell us a generic story about our reproductive potential. The American Society for Reproductive Medicine says that each month a healthy, fertile 30-year-old woman tries to get pregnant, she has a 20% chance of succeeding. By age 40, that percentage drops to just a 5% success rate. But the real truth is these are just statistics. Every woman has her own distinct biology and the variations among us are massive. After thirty-five, we enter what the writer Liza Mundy has called “a period of extreme variability.” Some of us stay fertile into our 40s and others undergo a precipitous drop in our ability to conceive. I told Beim that I’ve always thought that basing fertility outcomes on age is not enough, and she excitedly explains that this is her next project. She and her team will use their data set to gain genetic insights into a woman’s fertility potential and genetic risk factors for reproductive conditions like Polycystic Ovarian Syndrome, Primary Ovarian Insufficiency, recurring pregnancy loss and Endometriosis. “We might show a 25-year- old woman with a genetic signature that she’s not going to have a straightforward fertility journey,” she explains. The hope of this fertility test, which is now available through a prescription for you OB-GYN, will be for women to make better choices for their future. The test, called Fertilome, screens for genetic alterations in 32 genes that are associated with reproductive health. The test costs $1900 and is not yet covered by insurance.

But it could be vital preventive. If Amy, before she had her met her husband, had known that she had genetic markers that pointed to a fertility challenge in the future, she may have frozen her eggs when she was younger or gone straight to IVF.

The science is still new and as we’ve seen with genetic tests for the BRCA gene for breast cancer, having or not having the gene, doesn’t mean a woman will develop breast cancer. “This will be a similar sort of paradigm,” says Beim. “There will be a subset of women who will test positive for risk factors and just like women with the BRCA gene, there will be proactive steps that they can take if they want to mitigate that risk.”

Genetic insight could help women who are struggling with infertility now, and it could also empower women in their 20s and 30s to make proactive decisions before they even start trying to become pregnant. This information could make women feel that we can control our personal biological clock rather than have it control us.

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