Could a bone marrow transplant be the answer?

In mice

Sometimes even the best embryo cannot implant in the uterus. Sometimes an apparently healthy woman cannot sustain a pregnancy. Science has trouble explaining it and medicine has trouble treating it. New research suggests stem cells from a healthy bone marrow might help.

In April this year, a new Twitter account appeared — @justsaysinmice. It retweets examples of where research in rodents has been portrayed as automatically relevant to humans. The account now has almost 69K followers, an indication of how exasperated people feel. So let me start by saying: this research was done in mice. 

Still ... a lot of good research starts in mice. 

This research looks at the largely untreatable conditions of recurrent pregnancy loss and recurrent implantation failure. Recurrent pregnancy loss is when you lose three consecutive pregnancies before the 20-week point. Recurrent implantation failure is when you are unable to establish a pregnancy after at least three IVF cycles using good embryos. They are devastating conditions.

Here's a short summary of one potential way forward. 

Proceed with caution. 

Bone marrow as reproductive tissue

New research suggests that a female's bone marrow plays a key role in building a high quality uterine lining. Implantation and early gestation appear to induce stem cells to migrate from the bone marrow to the uterus, and some of those cells are then transformed into structural, non-blood cells of the "decidua" — the lining that is so critical to launching and sustaining a pregnancy.

In mice where genetic defects would prevent the formation of a good lining, transplants of healthy bone marrow were able to improve lining quality or even lead to live birth.

Reshef Tal, an assistant professor of obstetrics, gynecology and reproductive sciences at Yale, and his colleagues, studied two groups of mice with genetic defects in their Homeobox a11 gene. Defects in this gene have been associated with problems with uterine development and female infertility, in both mice and humans.

One group of mice had no functioning copy of the gene. These mice are infertile: their uteri are small, they are not able to grow a good lining and their embryos cannot implant. The other group had one bad copy and one functioning copy. They have a high rate of pregnancy loss, resulting in small litters.

The researchers wanted to know if transplanting healthy bone marrow from mice that had two good copies of the gene would improve outcomes. To transplant new bone marrow, they first had to eradicate the old defective bone marrow, and they did so using drugs that would avoid damaging the ovaries. 

The researchers found that in the mice that had no functioning copies of the gene, transplants dramatically improved the quality of the uterine lining, although that did not lead to any pups being born. In the mice that had only one bad copy, though, transplants improved the quality of the lining so much that litter size was normal and excess pregnancy loss was averted.

The findings, they write in the paper, published last week in the journal PLoS Biology, raise the possibility that bone marrow stem cell dysfunction may be what underlies recurrent implantation failure or recurrent pregnancy loss, or both. Bone marrow can now be considered a critical reproductive organ, the team says.

But while this work helps elucidate the process — stem cells from the bone marrow are instrumental in transforming the lining into one that can sustain a pregnancy — and while it points the way to a possible treatment, it does not provide a clear roadmap for that treatment. For one thing, women will not be undergoing chemotherapy the way the mice did, says Tal. 

Understanding the types of bone marrow cells that have a hand in human implantation and pregnancy, however, will now help guide new therapies for women, he says. These therapies could be around, at least experimentally, in just a few years.

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Reshef Tal et al. "Adult bone marrow progenitors become decidual cells and contribute to embryo implantation and pregnancy." PLoS Biology

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Email me at alison.motluk@gmail.com. 

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