O-236 Why one is not enough when studying pregnancy loss - a European perspective
Authors: Schlaikjær Hartwig T , Bliddal Mortensen A  S P , Gruhn J , Westergaard D , Hoffmann E , Svarre Nielsen H 
Published: July 2024

Abstract
Pregnancy loss is a distressing but still poorly understood condition, ending one in four pregnancies.
With more than 30 million losses worldwide yearly, it is posing significant challenges to individuals, families, and healthcare systems. This presentation delves into the imperative for a multifaceted approach to studying pregnancy loss. By examining pregnancy loss through multiple lenses including fetal and parental genetics, male and female physiology, and psychosocial, lifestyle and political dimensions, we can achieve an improved understanding of the causes, impact, prevention, and treatment of pregnancy loss.
Historically, pregnancy loss has been considered a part of the reproductive journey – a course of nature. And until a couple has suffered from recurrent pregnancy loss, the physiological and mental impact has been neglected. This is an outdated approach that prevents a full understanding of the consequences and underlying etiologies hindering the potential of prevention and treatment, and thereby contributes to maintaining the women’s health gap. Moreover, current practice ignores the association of euploid pregnancy loss with an increased risk of future losses and later maternal health consequences such as diabetes and cardiovascular disease.
In Copenhagen, we are currently running a large-scale pregnancy loss study (Copenhagen Pregnancy Loss, COPL) involving 3000 pregnancy losses. By including the full trio (fetus, female, and male) we are gaining new insight to the mechanisms causing pregnancy loss and the consequences hereof, both in men and women. We know from previous cytogenetic investigation of lost pregnancies, that about 60% are caused by fetal aneuploidy. But the remaining part is still not well understood and leaves the opportunity of treatments and preventions if we knew the underlying mechanism. That we aim to cover by building the largest database and biobank in the field. Moreover, collected data from the COPL study will be linked to nationwide Danish registries including comprehensive information on medical history, social economic status, educational status, medication, and ancestry.
We have validated the use of cell-free fetal DNA in maternal blood to separate the losses caused by fetal genetics or not. This differentiation is essential to address the heterogeneous nature of pregnancy loss, but also to provide an individual answer to the couples. In 1000 consecutive pregnancy losses between gestational age 5 and 22 weeks, we were able to provide a cffDNA based result of the fetal ploidy status in 89% of cases. When comparing the method to direct sequencing of the pregnancy tissue, the cffDNA-based testing had a higher success-rate and identified 85% of the aneuplodies (sensitivity) with a 93% specificity. These results show the potential and feasibility of the method to distinguish euploid and aneuploid pregnancy loss for improved clinical management and benefit of future research.
From our close collaboration with couples that are experiencing a devastating event as pregnancy loss, we have seen the huge unmet need for better handling, but also a deep commitment and motivation from the men and women involved. We have investigated the conflicting feelings emerging in a next pregnancy and a need for closer support and care. We belief, that it takes a trio to improve the understanding and handling of pregnancy loss.