Northeastern University

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.


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