How uterus checks embryo reveals why some do not implant

Date: Sep-19-2013Fertility experts have discovered how the uterus performs quality control on a new embryo before determining
whether to accept it. They hope the discovery will help develop new techniques to improve the success rate of
IVF.

The team, from the UK Universities of Southampton and Warwick, and the University of Utrecht in the Netherlands,
found if the endometrium - the lining of the uterus - fails to sense chemical signals from the fertilized egg, it
silences many of the genes involved in allowing it to embed in the uterus.

One of the chemical signals the endometrium looks for is the amount of trypsin, a common enzyme, the embryo gives
off.

If this is not detected, the embryo is not accepted and is left to disintegrate, resetting the cycle.

One of the study leaders, Nick Macklon, professor of Gynecology and Obstetrics at the University of Southampton,
notes:

"The lack of trypsin signals appear to indicate to the endometrium that the embryo's quality is not very high and
initiates a reduction in receptivity to implantation."

Prof. Macklon presented the findings earlier this week at the University of Southampton's 2013 Institute for Life Sciences
Conference. He also gave a talk about the work recently at the Society for the Study of
Reproduction meeting in Montréal, Canada.

Prof. Macklon, who is also director of the Complete Fertility Centre at Southampton, says:

"One in six couples will experience some sort of infertility, which can be both frustrating and daunting, and many
will turn to IVF."

Discovering how the endometrium chooses an embryo could help improve treatments, like helping embryos in IVF successfully implant.

But one of the big problems in IVF is getting embryos to implant successfully.

By revealing new clues as to how the endometrium chooses an embryo, the findings should help improve treatments, he
adds.

For their study, the team incubated fluid in which embryos had been cultured with cells from the connective tissue
of the endometrium (stromal cells).

There was a huge reaction from endometrial genes when the fluid had contained poor quality embryos but almost no
reaction when the fluid had contained quality ones.

The down-regulated genes are ones known to be important in allowing new embryos to implant in the uterus.

The team then found the same happened in live animals. Again, they took fluid that had contained good and poor
quality embryos, except this time they placed it in the uterus of a live mouse and found the results were the same.

The other study leader was Professor Jan Brosens of Warwick Medical School, who also led another study that offers
new hope for women suffering from recurrent
miscarriage.

That study was the first of its kind to offer an explanation for why high levels of natural killer (NK) cells in the
uterus can cause miscarriage.

The team found high levels of NK cells in the endometrium are a sign of insufficient
production of steroids, which in turn leads to reduced formation of fats and vitamins that are essential for pregnancy
nutrition.

Written by Catharine Paddock PhD

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