Fertility clue for recurring miscarriage

Behind the Headlines

Friday August 24 2012

Could recurring miscarriages be caused by 'super-fertility'?

‘Super-fertility’ may explain some miscarriages, BBC News has reported. It says that the wombs of some women are ‘too good at letting embryos implant’, even those that are of poor quality and so which should be rejected.

The story, also covered by The Daily Telegraph, is based on a small laboratory study. In the study, researchers examined the theory that in some women who have suffered unexplained recurrent miscarriages (the loss of three of more consecutive pregnancies) the lining of their womb (uterus) is not able to discriminate between “high-quality” embryos and “low-quality” embryos. These low-quality embryos would have little chance of developing normally.

The researchers looked at samples from the womb linings of six women with recurrent miscarriages and six control women who had had healthy pregnancies and babies. They looked at what happened to the womb cells when they were exposed to high-quality or low-quality early stage embryos. They found that the cells from the control women grew towards and took up the high-quality embryos only, while the cells from the women with recurrent miscarriages took up both embryos and did not seem to differentiate between the two.

The most important thing to realise is that this is an extremely small study, and while it is of value, it does not explain the reason for all miscarriages or recurrent miscarriages. Much more research would be needed to give this theory true credibility.

The reasons why some pregnancies miscarry are still poorly understood, and there may be a number of possible causes. There is no one treatment to prevent miscarriages from occurring. The most important thing is to ensure that women who have suffered miscarriages receive the full care and support that they need.

 

Where did the story come from?

The study was carried out by researchers from University Medical Center Utrecht, The Netherlands, Endokrinologikum Hamburg, Germany, and the University of Warwick and University of Southampton in the UK. The study was funded by the Foundation ‘De Drie Lichten’ in the Netherlands. The study was published in the peer-reviewed journal, PLOS One.

The media is representative of this research. The reference to women who have suffered from recurrent miscarriages being ‘super-fertile’ is based on the fact that the cells from their womb seemed to take up both higher and lower quality embryos that would not have much chance of developing normally.

 

What kind of research was this?

This was laboratory research aiming to investigate the researchers’ theory that in women who have suffered recurrent miscarriages, the lining of the womb (the endometrium) is not able to discriminate between high-quality embryos and low-quality embryos that would have little chance of developing normally, therefore allowing either to implant.

Over 10% of pregnancies are reported to end in miscarriage. Recurrent miscarriage is defined as the loss of three of more pregnancies in a row, and is reported to affect 1-2% of couples. The researchers speculated that experiencing recurrent miscarriages is more than would be expected by probability alone, and suggests that there is some specific cause, such as allowing embryos with genetic abnormalities to implant instead of just rejecting them from the start whereby the woman would simply not have become pregnant.  

To test the theory, the researchers aimed to see in the laboratory how endometrial cells responded to high-quality embryos and low-quality embryos, with the expectation that the cells from women with recurrent miscarriages would not be able to differentiate between them so well.

 

What did the research involve?

The researchers recruited six women who had experienced recurrent miscarriages and six fertile, control women. The control women had experienced on average two pregnancies and had two children, the women who had recurrent miscarriages had experienced six pregnancies, but had no children. Other than this, there were no differences between the women in weight, age or menstrual cycle.

Samples of the women’s endometrium were obtained during biopsies of women with recurrent miscarriages, and procedures for other indications for the control women (the paper reports that six women had received a hysterectomy for reasons including fibroids and painful or heavy menstrual bleeding). In the laboratory, the researchers observed how the endometrial cells of the women migrated towards and took up 5-day-old high-quality embryos and low-quality embryos after incubation for 18 hours. They also conducted additional tests looking at how the endometrial cells migrated towards ‘trophoblast’ cells (the cells that surround the embryo and go on to form the placenta).

 

What were the basic results?

Before the start of the study, the migration zone (how far the cells would travel) around the endometrial cells (which line the womb) from the women with recurrent miscarriages and the control women were comparable. There was some degree of baseline migration of endometrial cells in the absence of an embryo.

In the presence of a high-quality embryo they found no difference in the migration towards the embryo of endometrial cells from the women with recurrent miscarriages and from the control women. This rate of migration was the same as when no embryo was present.

Conversely, in the presence of a low-quality embryo there was a clear difference in the response of cells from the women with recurrent miscarriages and the control women. Compared to the migration zone around endometrial cells from the control women at the start of the study, in the presence of a low-quality embryo the migration zone significantly shrank back, suggesting that it was inhibiting the embryo from implanting. In contrast, in women with recurrent miscarriages, migration of endometrial cells towards the low-quality embryo was not reduced, and was comparable to the migration towards the high-quality embryo.

The migration of endometrial cells from women with recurrent miscarriages towards the trophoblast cells was significantly greater than that in the controls, suggesting that the women with recurrent miscarriages more readily took up the cells that attached the placenta.

 

How did the researchers interpret the results?

The researchers conclude that cells from the lining of the womb from women with recurrent miscarriages fail to discriminate between high- and low-quality embryos.

 

Conclusion

This is valuable research which furthers understanding of how implantation of the embryo may differ in women who have experienced recurrent miscarriages. It suggests that the cells which line their wombs may not be able to differentiate so well between high- and low-quality embryos, and so prevent a low-quality embryo (which has poor chance of developing normally) from implanting.

While this is valuable research, the most important thing to remember is that this is an extremely small study, and it does not explain the reason for all miscarriages or recurrent miscarriages. Much more research into this theory would be needed to give it credibility. It still needs to be determined how the womb cells can tell if an embryo is low quality, for example if it has a genetic abnormality.

The reasons why some pregnancies miscarry are still poorly understood, and there may be a number of possible reasons, such as developmental problems with the embryo, infections, or a problem with the womb or cervix.

The most important thing is to ensure that women who have suffered miscarriages receive the full care and support that they need. Women who have suffered recurrent miscarriages, or the loss of a baby in the later stages of pregnancy, are likely to need additional antenatal care in subsequent pregnancies, and may also receive investigations to try and find out whether they could be at risk of another miscarriage.

 

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.







Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Recurrent miscarriage 'caused by super-fertility'. The Daily Telegraph, August 24 2012

Super-fertility offers clue to recurrent miscarriage. BBC News, August 24 2012

Links to the science

Weimar CHE, Kavelaars A, Brosens JJ, et al. Endometrial Stromal Cells of Women with Recurrent Miscarriage Fail to Discriminate between High- and Low-Quality Human Embryos. PLoS One. Published online July 25 2012

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