Next generation of fertility treatments

From genetic testing to attempts to grow viable eggs from stems cells, researchers are trying to improve the success rate of fertility treatments and cut their cost.

Why it matters: About 9% of men and 11% of women of reproductive age in the U.S. experience fertility problems, resulting in a multibillion dollar industry. The next-generation of fertility treatments has the potential to change who can have children and when but they are still in the early stages of development and have high hurdles to clear.

IVF

This year the first baby born using in vitro fertilization (IVF) will turn 40 years old. "The traditional IVF approach was essentially a beauty contest" in which embryos for implantation were assessed based on their morphology, says Barry Behr, director of the IVF Laboratory at Stanford University.

Today, genetic screening of embryos allows clinicians to check whether chromosomes are normal.

• "The biggest paradigm shift over the last 3–5 years has been the application of embryo screening using next-gen sequencing," Behr says.
• But he says pre-implantation genetic screening (PGS) is overused, especially among young people, because of a yearning for information. "We do double the amount of PGS that we think is necessary."

Another issue: There is only about a 50-50 chance an embryo will attach to the lining of the uterus.

• "The field has realized all the attention is on how many eggs there are without recognizing fully the role of the endometrium lining the uterus. But if you try to plant an apple seed in the sand, it's not going to grow," Behr says.
• Now, clinicians can use an endometrium receptivity assay (ERA) to look for molecular signatures that suggest the timing is right for the uterus. That currently requires a biopsy but researchers are working on less- or non-invasive methods.

What's next for IVF: Researchers have been tinkering with IVF methods in hopes of making the treatment less expensive. One of those is the vaginal incubation of embryos, which was approved by the FDA several years ago and is roughly half as expensive as standard IVF.

Genetic risk

Others are looking to genetics for insights into how likely a fertility treatment is to succeed. Celmatix's $950 Fertilome test is used to screen for 49 "genetic markers that show highest degree of association with a different reproductive condition in a moment in time," the company's CEO Piraye Yurttas Beim tells Axios. "It's not diagnostic. It lets you know if you are at risk."

• The big question is whether that actually helps women get pregnant, STAT's Rebecca Robbins points out. Beim tells Axios, "I can’t tell you if you take this test you will have a x% likelihood of getting pregnant. But we do hear from physicians of stories of women who were refractory to treatment and are now having viable pregnancies."
• What's next: Beim says they are looking to use AI — "artificial intelligence not artificial insemination" — to augment physicians decision-making about courses of treatment for people who have repeatedly failed IVF cycles.
• Carol Lynn Curchoe, an embryologist at San Diego Fertility Center and founder of 32ATPs, agrees that AI can play an important roll, adding that it could help determine "end-to-end care [of the patient] and not just for embryo selection."

IVG

Scientists are attempting to take adult human cells and turn them into artificial eggs or sperm in a process called in vitro gametogenesis (IVG):

• In 2016, Katsuhiko Hayashi from Kyushu University and Mitinori Saitou from Kyoto University created artificial eggs from skin cells taken from a mouse's tail, fertilized and implanted them in mice, which then gave birth to pups.
• Now, Saitou is studying whether human gametes can be developed similarly. But Hayashi tells Axios there are major obstacles in developing a human system. For one, the time required for immature eggs to mature is at least 1 year in humans vs. 5 weeks in mice.
• "It is interesting work from a scientific point of view but to take it and translate it into humans is a huge leap," says Evelyn Telfer from the University of Edinburgh.
• Hayashi agrees. Even in mice, he points out, there are "many miscarriages and [little] evidence that the mice from iPSCs are really healthy, although they are apparently normal and fertile." He said to adapt the tech to humans, the quality of gametes and the resultant embryo needs to be tested before transferring them into the mother.
• Curchoe says if this is ever able to happen in humans, "this would be a game-changer" and could allow LGBTQ families and infertile men and women to be able to have their own genetic offspring.
• Go deeper: Read Jason Pontin's piece in Wired about IVG.

Instead of starting with stem cells, Telfer recently reported isolating immature eggs from the primordial follicles in women's ovaries and activating them to grow into mature eggs in a dish. Theoretically, these would be ready to be fertilized.

• Eventually these approaches may be merged to take a stem cell all the way through to a fully mature egg in a dish.
• The bottom line: "There is a big gap between basic research and clinical applications. It will narrow as [we learn more] but basically we are in the dark," Telfer says.

Editor's note: This piece has been updated with more information about Curchoe.