Study gives new hope for women suffering from recurrent miscarriage

A team of researchers, led by the University of Warwick and University Hospitals Coventry & Warwickshire NHS Trust (UHCW), have published new data that could prove vital for advances in care for women who suffer from recurrent miscarriage.

The recurrent loss of pregnancy through miscarriage causes significant distress to couples, often exacerbated by there being so few treatments available to clinicians.

It has been estimated that one in three of all implanting embryos are lost before six weeks of pregnancy. In addition, more than 10% of more advanced pregnancies end in miscarriage. Most distressing, a significant number of couples find history repeats itself and they have three or more repeated miscarriages. In addition to the physical trauma, miscarriage, and especially recurrent miscarriage, is a major cause of psychological stress, with a third of women suffering from clinical depression or severe anxiety. Moreover, a history of recurrent miscarriages increases the risk of a variety of problems in a subsequent pregnancy, including preterm delivery, low birth weight, physical handicap and even death of a baby.

The search for an effective treatment has been the cause of significant controversy in the field of medical research, centering on the role of natural killer cells (or NK cells) and the ability of steroids to prevent miscarriage.

Scientists have been uncertain about how these NK cells could contribute to a miscarriage and this has raised doubt over their importance in causing pregnancy loss.

Led by Professor Jan Brosens of Warwick Medical School, the team found that elevated uterine NK cells in the lining of the womb indicate deficient production of steroids. Deficient steroid production in turn leads to reduced formation of fats and vitamins that are essential for pregnancy nutrition.

This study, published in The Journal of Clinical Endocrinology & Metabolism, is the first of its kind to provide an explanation for why high levels of NK cells can cause miscarriage.

Lead author Siobhan Quenby, Professor of Obstetrics at Warwick Medical School, explained, “This work is really exciting because after years of controversy and doubt we have a crucial breakthrough. This means, quite simply, that we have excellent scientific justification for steroid based treatment to prevent miscarriage.”
However, more work now needs to be done to identify which women would be suitable for such treatment.

A new model for recurrent miscarriage.

This research is linked to new findings in how recurrent miscarriage occurs.

Miscarriage can be caused by chromosomal abnormalities in the embryo or because the mother has some problem. Although numerous anatomical, endocrine, immunological, clotting and genetic abnormalities have been associated with recurrent miscarriages, none of these are specific or particularly common. Moreover, for most of these conditions, the mechanisms that would account for this persistent loss of life are either entirely speculative or simply unknown.

UK Researchers have now discovered an entirely novel mechanism that accounts for miscarriages, irrespective of whether the embryo is chromosomally normal or not.

Professor Brosen’s group has established that the lining of the womb is capable of recognising and responding to abnormal embryos but only when adequately prepared for pregnancy. This process is termed ‘decidualization’.  Furthermore, the ability of the lining of the womb to decidualize (to prepare itself for pregnancy) is defective in women suffering from recurrent miscarriages. Combined these observations indicate that impaired decidualization and lack of embryo quality control at the time of implantation is the primary cause of miscarriage.

These findings explain why many women suffering from recurrent miscarriages report that they become pregnant very easily yet are unable to carry the pregnancy. As decidualization is essential for the formation of a functional placenta in the first trimester of pregnancy, the model also explains why the likelihood of miscarriage drops markedly after the first 12 weeks. Finally, abnormal decidualization and lack of embryo quality control predict that many patients will experience a mixture of chromosomally normal and abnormal pregnancy losses, which turns out to be exactly the case.  The research may lead to testing to identify women at risk who would respond well to steroid based treatment.