How Researchers Are Making 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. Patients age more slowly and have lower success rates.

Researchers around the globe have been working hard to increase the effectiveness of IVF due to the financial, emotional and physical consequences that can be incurred from failed IVF cycles. “In medicine, nobody can guarantee success,” says Dr. Zev Williams, chief of reproductive endocrinology and infertility at Columbia University Irving Medical Center. “The question is, how close can we get?”

Little steps to better testing

There are many ways to increase the chances that IVF patients will have a healthy child. Preimplantation genetic testing (PGT) is one of the most popular tests. Clinicians take biopsies after eggs have been fertilized in order to identify aneuploidies or other chromosomal abnormalities which may raise the chance of IVF failure or miscarriage or genetic disorders at childbirth. PGT is argued to increase the chance of success as it helps identify embryos more likely to produce a healthy baby.

However, these tests can be 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. The already costly process of genetic testing is further complicated by additional costs.

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.

Gleicher, along with colleagues at Rockefeller University, demonstrated that certain embryos have the ability to self-correct after pregnancy. This was evident in a tiny study 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.

Lital Gilad Shaoulian, a Californian resident who was 39 when she tried to have her fourth child, is still haunted. Surprised to discover that all her embryos were abnormally classified by the test, even though her other three children had been conceived via IVF, she was not surprised. “I remember telling myself, ‘[The results] are wrong,’” she says.

Over the years she went through the emotionally draining process of fertilizing eggs. However, most of her embryos were deemed to be 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.

Gilad-Shaoulian recalled being surprised when Gilad-Shaoulian became pregnant. A further chromosomal test at 10 weeks was normal. About 18 months later, her daughter was born. 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.”

Williams and other experts support the value of preimplantation testing. Williams says that while some embryos may be viable, others might not. However, preimplantation testing is able to identify these babies and provide significant benefits for the 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.

Researchers are working to modify PGT–A in order to increase its effectiveness. 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 has recently published a paper in which she co-authored. It describes a new method of taking molecular photographs of embryos to evaluate fetal cell activity, not just those that make the placenta. This will help to identify non-viable embryos. “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 causes the mother’s womb to become slippery. This could prevent the attachment of embryos. If PCX levels are low and embryos are transferred at the appropriate time, this could increase your chances of getting pregnant.

Guiying Nie is a co-author on the study and a reproductive biologist. Unfortunately, no test of this nature is available for patients at present. It is difficult to find a quick, non-invasive method of testing 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.

Beyond the tests

Williams said that any testing can only do so much. Therefore, his laboratory is looking at other options to increase success rates. His clinic, for example, uses a robot arm to make the small trays that embryos are grown in to reduce human error.

Some tasks are being outsourced to robotics by other companies. Startup TMRW developed automated storage tanks that can store frozen eggs and embryos. It eliminates potential mishaps such as freezer failures. The tanks have sensors that detect any changes in storage conditions and alert staff to fix them before they turn into critical.

Artificial intelligence is also promising 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.

Fertility care made easier

Also, it is crucial to optimize the logistics for fertility care. New York-based New Hope Fertility offers a program called “At Home IVF,” which makes the process as remote-friendly as possible. An online consultation can be completed by a patient, who then receives fertility medication at their doorstep if necessary. Only major appointments, such as embryo transfers and egg harvesting, require patients to go into the clinic.

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. The new method allows for men to create sperm at home. They can then take them to the clinic to be frozen and made available to the couple. 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.

When it comes to fertility treatment, every improvement is important. “We really fight for every percent improvement in success rates,” Williams says, because each one can be life-changing for families.

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