Over the past 40 years, medical science has gone from nascent experiments with in vitro fertilization (IVF) to being able to help millions of fertility-challenged couples and individuals conceive.

“Two hundred million years ago when Mother Nature designed the system, age didn’t matter — we were eaten by a tiger at age 26. But now everything has changed,” says James Grifo, MD, Ph.D., the program director at NYU Langone Prelude Fertility Center.

Women are born with about one million eggs and reach puberty withparent 400,000. By the time a woman is 40, the supply has dwindled to between 10,000 and 15,000. Yet last year, the only group of women with increased birth rates in the United States were those aged 37 and older.

“It’s pretty clear that if we are going to be smart about reproduction and understanding the biology, we need to do some things to help with what evolution can’t,” says Grifo.

These are the innovations, technologies and treatments top physicians consider to be the current cutting edge, and the breakthroughs they are working toward.

Refining IVF tech

Louise Joy Brown was the world’s first “test tube baby,” conceived via IVF and born in the UK in 1978. The procedure improved by leaps and bounds in the ‘80s and ‘90s, rising from a 1 to 2 percent success rate to contemporary heights of 60 to 70 percent.

“On a year to year basis, the safety and effectiveness of fertility treatments is just getting better,” says S. Zev Williams, MD, Ph.D., chief of the division of reproductive endocrinology and infertility at Columbia University Irving Medical Center.

Dr. Zev Williams
Dr. Zev WilliamsStefano Giovannini

Some of the advancements paving the way make a major difference. In March 2018, up to 4,000 eggs and embryos were lost when a Cleveland fertility clinic experienced a freezer tank malfunction at its storage facility, devastating those affected. Since then, experts at Columbia have tackled that issue by troubleshooting their tank alert system, starting with the development of a custom scale that sits underneath each one to monitor the weight and detect issues with the liquid nitrogen. “It’s the definition of early intervention,” says Williams.

Earlier this month, Columbia released another tank-focused tool, this time digital and accessible to clients anywhere with a Wi-Fi signal: the PreBaby Monitor. This online platform allows users to access the real-time temperature status of the cryogenic tanks where their eggs or frozen embryos are stored.

“It’s taking an [existing] technology and applying it to help bring some reassurance to patients who would otherwise be anxious about it,” Williams says.

Another aim is cost-cutting. For decades, the standard protocol for IVF egg retrieval has included women injecting themselves with synthetic hormones. The Columbia Oral, or Coral-IVF, program pioneered a substitution for shots, swapping them for a combination of pills that stimulate the production of a similar number of better quality eggs. The switch also brought the cost of treatment down, from $5,000 to $50, according to Williams, who adds that it’s been effective even among women for whom IVF has been unsuccessful in the past.

Precision medicine

Blastocysts at the Columbia University Fertility Center.
Stefano Giovannini

“Reproductive medicine is now really the leading edge of precision medicine,” says Williams. At Columbia, the Program for Preventing Genetic Diseases (PPGD) brings together a multidisciplinary mix of experts in the fields of genetics, genetic disease, genetic counselors and fertility doctors. “Now we’ve evolved to help couples who don’t have infertility at all but may be carriers for catastrophic genetic diseases and ensure they have healthy children. “

Josh Klein, MD, co-founder and chief medical officer of Extend Fertility, also points out that advances in genetic studies lead to better outcomes overall, using preimplantation genetic testing (PGT). “We’re leaning heavily on improvements in genetic technology to be able to say, with a higher degree of confidence, that this embryo is a good one. Or, we can say with confidence that this is one we should not be transferring because we don’t think it’s going to implant.”

However, according to Klein, we’re still some distance from being able to correct every genetic defect. It would be a huge step forward, he says, though “we’re not there,” and concerns about the ethics of modifying genes and embryos abound. “But there’s almost no doubt that [it’s] going to filter its way down to reality soon-ish.”

Data-driven

Dr. Zev Williams demonstrating a phone app that can monitor critical temperatures.
Dr. Zev Williams demonstrating a phone app that can monitor critical temperatures.Stefano Giovannini

The Extend Fertility team developed an algorithm that helps counsel women about when to freeze their eggs by monitoring certain biomarkers during an ovary ultrasound, which helps give women a concrete prediction of how many eggs they’ll make. It’s these kinds of innovations that make improvements on older medicine.

“Not everything is about the technological leaps: some of it is about doing it smarter, doing it better, doing it in the right ways, and the right times,” says Klein.

Wearables like the Ava Fertility Tracker, for which Williams is an advisor, function as more sophisticated versions of ovulation predictor kits, giving women more information about their cycles, like “an intelligent calendar.” Where we run into problems is when the marketing gets ahead of the science, Williams says, citing at-home genetic sequencing kits as an example.

“They’ll run tests for thousands of genes, but what that means at a practical level isn’t even clear to clinicians.”

Preservation dialog

Klein views the recent innovations around storage and cryo-bank technology as part of a fundamental shift into a proactive approach to fertility in general. It’s not a new thing to make a baby with a frozen egg, but it is a new thing for a 32-year-old to freeze her eggs and use them when she’s 42. Thousands of women freezing embryos and eggs is a reflection of advancements in the technology, increased accessibility and younger women seeing a “proactive investment in preventative medicine being something worthwhile to pursue,” says Klein.

‘You don’t know your outcome until you know your outcome.’

Grifo does have concerns about people understanding the facts: Even if you’ve frozen a batch of eggs, it doesn’t necessarily mean that you’ll definitely be able to have a baby with them. “You don’t know your outcome until you know your outcome,” says Grifo. “It’s more complicated than just plan and everything will be fine.”

Williams expressed similar concerns, highlighting the track record of some new clinics.

“They’re offering egg freezing and promising people this future when they haven’t, in many cases, been able to show that they can freeze an egg and have it survive,” he says.

The next big thing

Grifo’s assessment is frank: “We’ve gotten all the low hanging fruit—now it’s just incremental baby steps to do better.” He sees the future of reproductive medicine in the continued pursuit of fertility preservation that prioritizes efficiency and improvements in the areas of culturing embryos, freezing eggs and optimizing retrieval.

Williams identifies an area currently playing catch-up: Combining forces with chemical engineers and molecular biologists to improve outcomes. When chromosomally normal eggs are unavailable, medicine strains to help. Being able to take any cell and turn it into an egg would be a game changer, though it’s not yet clear if that will ever be possible. “If it [is],” he says, “it’s going to be in the far, far future.”