Series of overviews on miscarriage and recurrent miscarriage

Miscarriage is a relatively common occurrence with many knowns and unknowns and a profound psychological impact on individuals and couples. The editors felt it was time to publish a series of overviews for Views and Reviews on both sporadic miscarriage and recurrent miscarriage. The series starts with the prevalence of miscarriage and recurrent miscarriage and subsequently describes the psychological impact, what we know of the genetics, whether uterine natural killer cells may play a role, the association with infections, and potential interventions. Miscarriage is a relatively common occurrence with many knowns and unknowns and a profound psychological impact on individuals and couples. The editors felt it was time to publish a series of overviews for Views and Reviews on both sporadic miscarriage and recurrent miscarriage. The series starts with the prevalence of miscarriage and recurrent miscarriage and subsequently describes the psychological impact, what we know of the genetics, whether uterine natural killer cells may play a role, the association with infections, and potential interventions. The present series of overviews for Views and Reviews aims to provide an overview of the six most relevant aspects on both sporadic miscarriage and recurrent miscarriage. As introduction for this series, I provide a short overview of what you can expect as reader. I believe you will enjoy reading these manuscripts as much as I did. Haley Genovese and Dada McQueen start reporting on the prevalence of early pregnancy loss, including "biochemical pregnancy, ectopic pregnancy, first trimester miscarriage, and pregnancy loss early in the second trimester, which is typically defined as before 20- or 24-week gestation." They argue that there is a rise in both miscarriage as a one-time event and recurrent miscarriage. This is not only caused by improved measurements and registration but also has a true effect because of the increasing maternal age at conception and the obesity pandemic. Jade Bilardi and Meredith Temple-Smith go beyond reporting on the well-known psychological impact of miscarriage. They highlight the inadequate support women and partners receive. Although available care is directed at recovering, there is often no consideration for the enormous mental impact miscarriage can have. The investigators provide low-cost opportunities to improve care and conclude by stating that "miscarriage and recurrent miscarriage affect a significant proportion of every population, and there are many ways to ameliorate the impact of these losses that are not difficult, expensive, or time-consuming." It is indeed surprising that this has not been implemented yet in most countries. Pedro Melo, Rima Dhillon-Smith, Asiful Islam, Adam Devall, and Arri Coomarasamy wrote a thought-provoking piece on the genetic causes of miscarriage. Most miscarriages are because of random chromosomal abnormalities that are, at least at present, beyond anyone's control. The investigators report on the impact of parental age, genetic causes of recurrent miscarriage, and diagnosis. The question is raised whether genetic factors can be eliminated, what the future could bring, and what ethical considerations to take into account. The investigators end by stating that "there remains an urgent need for additional research into gene-disease associations, which may pave the way for targeted interventions in the future." Yentl Béquet, Lisa Lashley, Mariette Goddijn, and Marie-Louise van der Hoorn were asked to write about immunological aspects. In view of the recent rise in knowledge about uterine natural killer (uNK) cells, the investigators decided to focus their piece on the role of uNK cells in recurrent pregnancy loss. This article reports in detail what we know and do not know about the role of uNK early in pregnancy. The investigators note that "despite the lack of a well-known pathophysiological mechanism, several therapeutical interventions targeting the maternal immune system to influence pregnancy outcome have been studied." One such intervention is providing a low dose of a corticosteroid like prednisolone early in pregnancy. Previous studies showed treatment results in a reduced number of uNK cells, but it is unclear whether it could have an effect on pregnancy outcomes. The results of four registered trials are eagerly awaited. The article on infections as causes of miscarriage I wrote together with Elena Kostova and Jelmer Prins. Infections seem to come next in line after genetic abnormalities and have been estimated to contribute up to 15% to first trimester miscarriages and more than half to second trimester miscarriages. In this article, transmission, evidence that infection results in an increased risk of miscarriage, and whether the infectious disease could be prevented or treated by an infectious agent are described for a selection of infections that have been reported to increase the chance of a miscarriage. In contrast to genetic abnormalities, many of these miscarriages are preventable by vaccines, taking hygienic measurements, and the use of condoms. It is concluded that prevention "is only feasible in the presence of adequate knowledge, education, and access to care." An update on interventions to prevent miscarriage was provided by the team of Rima Dhillon-Smith, Pedro Melo, Rosinder Kaur, Emily Fox, Adam Devall, Natalie Woodhead, and Arri Coomarasamy. This last article of the series starts off with what a couple can do to prevent a miscarriage. This is followed by possible interventions, of which some have proven to have an impact, although this is unclear for others. The investigators conclude that to prevent miscarriage, the lifestyle of the couple plays an essential role. Concerning medical intervention, the investigators state that effectiveness has been only adequately proven for first trimester progesterone administration, levothyroxine in women with subclinical hypothyroidism, and the combination of aspirin and heparin in women with antiphospholipid antibodies." The investigators call for further research into new interventions to prevent miscarriage. M.v.W. has nothing to disclose. The author thanks all the investigators of this series for their enthusiasm and wonderful contributions.