How Researchers Are Working to Make IVF More Effective

Each year, tens of thousands of people in the U.S. try to conceive using in vitro fertilization (IVF), a process through which eggs are fertilized in a lab, then transferred to the patient’s uterus. Even though IVF has become relatively common, it’s not a sure bet: About 70% of people younger than 35 who were first-time IVF patients in 2019 and used their own eggs had a baby within two years, according to a fertility industry report. Success rates decline as patients get older.

Given the physical, financial, and emotional tolls of failed cycles, researchers around the world are working to make IVF more effective. “In medicine, nobody can guarantee success,” says Dr. Zev Williams, director of the Columbia University Fertility Center. “The question is, how close can we get?”

Baby steps toward better tests

Some of those efforts focus on how to improve screening tests meant to help patients optimize their chances of having a healthy baby through IVF. One of the most common tests is called preimplantation genetic testing for aneuploidies (PGT-A). After eggs are fertilized to create embryos, clinicians take biopsies to look for aneuploidies, or chromosomal abnormalities that may increase the risk of IVF failure, miscarriage, or genetic disorders at birth. Proponents of PGT-A argue that it increases the odds of success by identifying embryos most likely to result in a healthy pregnancy.

But these tests are controversial. Some studies suggest PGT-A does not increase the likelihood of giving birth and results in enough false positives that viable embryos are routinely discarded—potentially making it harder for people to get pregnant because they have fewer embryos to work with. Genetic tests also add even more fees to an already pricey process.

Almost 10 years ago, Dr. Norbert Gleicher, founder of the Center for Human Reproduction in New York City, became so disenchanted with PGT-A that he began getting patients’ permission to implant embryos the test had flagged as having a high chance of failure. “Lo and behold, we started seeing healthy, chromosomally normal pregnancies,” he says.

Some embryos with certain chromosomal abnormalities self-correct during pregnancy, Gleicher and colleagues from Rockefeller University demonstrated in a small study published last year. Of 32 women in the study, only five gave birth—but the results demonstrate that at least some imperfect embryos can lead to normal pregnancies, Gleicher says. That’s especially important for older IVF patients, who typically have fewer embryos to start and thus need as many as possible to maximize their chances of conceiving. “Imagine how many embryos are out there that are currently not being transferred,” Gleicher says.

That question haunts California resident Lital Gilad-Shaoulian, who went through PGT-A testing when she decided to try for a fourth child at age 39. She was surprised to learn that the test classified all of her embryos as abnormal, especially since her three older children were all conceived through IVF. “I remember telling myself, ‘[The results] are wrong,’” she says.

For years, she repeated the emotional and costly process of harvesting and fertilizing eggs, only for most of the resulting embryos to be deemed abnormal. Finally, after consulting with clinicians at the Center for Human Reproduction, she convinced her local doctor to move ahead with one of her highest-graded but abnormal frozen embryos—a scary decision, but one she felt was worth a try.

She got pregnant, which Gilad-Shaoulian remembers shocked her doctor. Additional chromosomal testing at 10 weeks of pregnancy came back normal. And about 18 months ago, she gave birth to a baby girl. Her daughter had some unrelated health issues following a delivery complication, but Gilad-Shaoulian says she is developing normally and is “perfect” and “so smart.”

While genetic testing may be right for some people, Gilad-Shaoulian wishes she’d never done it. “There’s possibly tens of thousands of good embryos that are thrown away from people who are working so hard and are so eager to have a baby,” she says. “I’ve been there. I know.”

Experts like Williams, however, stand by the utility of testing. While some embryos in the gray area between viable and nonviable may result in a healthy baby, he says preimplantation testing can identify those that are very unlikely to succeed, which can come with significant benefits for patients.

In 2022, Williams’ team at Columbia developed new technology to deliver genetic test results in hours rather than days or weeks, potentially allowing viable embryos to be transferred on the same day they’re tested. While the test can’t fix any problems it detects, Williams says quickly identifying a patient’s best embryos can help them get pregnant faster, with fewer expensive failed cycles and emotionally difficult miscarriages. “The big difference will be how long does it take to get pregnant, and how many losses does she have to go through before she gets pregnant?” Williams says.

Other researchers are also trying to tweak PGT-A to make it more effective. Currently, clinicians take biopsies from what becomes the placenta, so “you really don’t know what goes on inside the cells that go on to form the baby,” says Kylie Dunning, a reproductive biologist at the University of Adelaide in Australia. Dunning recently co-authored a paper describing a new approach: taking a molecular photograph of the embryo to assess fetal cells, rather than those that form the placenta. She believes that will clarify which embryos are truly nonviable. “Hopefully, that will result in more patients taking home a baby,” she says.

Another research team, this one led by scientists from Australia’s RMIT University and Monash IVF, published a pair of studies in 2021 describing another possible target for pre-IVF testing. They described a “golden window” for treatment: the several-day period in a woman’s natural reproductive cycle when levels of a molecule called PCX are lowest. PCX makes the surface of the womb slippery, potentially preventing embryos from attaching. Theoretically, if clinicians can determine when PCX levels are lowest and transfer embryos then, it could improve the chances of pregnancy.

Study co-author Guiying Nie, a reproductive biologist, says her team is still working to validate its findings, so no such test is currently available to patients. The challenge is finding a fast, non-invasive way to test PCX levels. Some kind of imaging test could work, she says, but it’s too soon to say.

A similar screening technique, called endometrial receptivity analysis, analyzes tissue from a uterine biopsy to try to determine the best time for an IVF cycle, but some research suggests it’s not as accurate as promised.

Looking beyond tests

There is a limit to what any test can do, Williams says, so his lab is trying to find other ways of boosting success rates. For example, his clinic uses a robotic arm to prepare the tiny trays where embryos grow to eliminate human error.

Other companies are also turning some tasks over to robots. Startup TMRW created automated tanks for storing frozen eggs and embryos, ideally eliminating mishaps like freezer failures. Sensors in the tanks detect changes in storage conditions, then alert staff so they can fix problems before they become critical.

Artificial intelligence also holds promise for fertility. Research teams are trying to teach AI systems to select the best embryos for transplantation by analyzing images of them, and various consumer apps use AI to help women pinpoint when they’re most likely to conceive based on fluctuations in hormone levels and other factors.

Making fertility care more convenient

Improving the logistics of fertility care is also important. New York-based New Hope Fertility offers a program called “At Home IVF,” which makes the process as remote-friendly as possible. A patient starts with an online consultation, then, when appropriate, gets fertility medication delivered to their door. Patients only need to come into the clinic for major appointments like egg harvesting and embryo transfers.

Some clinics, including New Hope, also offer what’s known as “mini” IVF, a process that is similar to traditional IVF but uses fewer or lower-dose fertility drugs to keep costs down. Because patients receive fewer stimulating drugs, they may produce fewer eggs that can be fertilized—but mini IVF can be the right choice for patients with budgetary constraints or certain health conditions, according to the Cleveland Clinic.

Williams’ lab has also been working to make IVF more convenient for couples. They developed a new transport technique, using a substance that keeps sperm samples warm and viable for several hours, to allow men to produce samples at home and then drop them off at the clinic, rather than going through the process in a medical office. It may seem like a small shift, but Williams says sperm samples tend to be higher quality when they’re collected at home, potentially because men feel more at ease.

Every refinement counts when it comes to fertility care. “We really fight for every percent improvement in success rates,” Williams says, because each one can be life-changing for families.