Making IVF relevant for the 85 percent

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In vitro fer­til­iza­tion of a human egg cell. Photo via Thinkstock.

At any given moment, about 7 mil­lion US cou­ples want to get preg­nant but can’t. Of these, just 60 thou­sand or so go through in vitro fer­til­iza­tion. What hap­pened to the other 85 per­cent? Well, con­sid­ering each round of IVF costs on average $9K, and it takes, on average, 6 rounds to be suc­cessful, there’s cer­tainly an issue of cost.

But the majority of those 6.5 mil­lion infer­tile cou­ples that don’t go through IVF aren’t being thrifty, they’re simply not can­di­dates for the therapy. “You have to have a recep­tive ovary to hor­mone stim­u­la­tion so that the endocri­nol­o­gist can go in and har­vest eggs from it,” said Jon Tilly, pro­fessor and chair of the Depart­ment of Biology. “If you can’t make an egg, IVF as it’s prac­ticed today is irrelevant.”

In the late 1990s, a man named Jacques Cohen  achieved the unachiev­able. Founder and lab director of a fer­tility clinic in New Jersey called Repro­g­e­netics, Cohen brought the IVF suc­cess rates of 27 infer­tile cou­ples from zero to 43 per­cent. “That’s the best you can hope for in any IVF clinic under the best con­di­tions,” said Tilly.

So how did Cohen do it? He rea­soned that the eggs of these women were simply “tired” (most of them were in their mid to late 30s), and that with a little help from a younger egg, they would be able to mature to a stage where they could be suc­cess­fully fer­til­ized. He sucked a bit of cyto­plasm (that’s the gel-​​like mate­rial swim­ming around the inside of every one of our cells) from younger women’s eggs and trans­ferred it to the older women’s eggs.

It turns out the thing that’s respon­sible for “tired­ness” in our cells is an organelle called the mito­chon­drion, which con­tains ATP — the cel­lular vehicle for energy. Although mito­chon­dria are nowhere near our cells’ nuclei, which con­tain our DNA, they do have their own minia­ture genomes, called mitochondrial-​​DNA.

Despite its soaring suc­cess rates, Cohen’s pro­ce­dure was shut down almost as quickly as it began because the FDA takes a harsh stand against human “genetic engi­neering” of any kind (under­stand­ably: would the next step not be toying around with things like hair color, eye color, or intelligence?).

So one of the poten­tially biggest changes in the field of human assisted repro­duc­tion was put on the shelf,” said Tilly. But what if you could do the same exact thing without trans­fer­ring genetic infor­ma­tion from one person to another? What if you could do it with a woman’s own ovarian “Red Bull,” as Tilly put it?

In 2012, Tilly’s lab dis­cov­ered the nat­ural pre­cursor cells to human eggs. These cells are just as ener­gized as a young woman’s mature egg, from which Cohen was cap­turing cyto­plasm back in the 1990s. Tilly’s dis­covery could open the doors for Cohen’s work to recom­mence without the issue of genetic het­ero­plasmy (more than two genetic par­ents) coming into the pic­ture at all.

There’s another more obvious impact of Tilly’s dis­covery. In normal IVF, patients have to be stim­u­lated with a slew of hor­mones to release a few more eggs than normal (one a month). Then clin­i­cians go in and har­vest those eggs (maybe a couple dozen if you’re really lucky), then try to fer­tilize them in the lab. With a single egg pre­cursor cell, Tilly’s team has the oppor­tu­nity to stim­u­late the dif­fer­en­ti­a­tion of mil­lions of egg cells again and again and again. What cur­rently costs $9,000 (for the luck­iest of the infer­tile cou­ples out there), could be sig­nif­i­cantly reduced by such a development.