Clinical Research Directory

Efficacy of Progesterone and Low Molecular Weight Heparin in Recurrent Pregnancy Loss

This prospective, single-centre, open-label, randomized Phase III superiority trial will enroll approximately 268 women aged 18-40 years with at least two consecutive unexplained miscarriages and a singleton intrauterine pregnancy confirmed by ultrasound at 5-7 weeks of gestation. Participants will be randomly assigned in a 1:1 ratio to standard antenatal care without active pharmacological treatment for recurrent pregnancy loss or to vaginal micronized progesterone plus subcutaneous enoxaparin. The primary outcome is live birth at or beyond 24+0 weeks of gestation. Study follow-up continues through six weeks postpartum. Delivery and postpartum outcomes will be obtained remotely using a structured participant-completed questionnaire. An optional exploratory translational sub-study involving one maternal blood sample at 10-12 weeks requires separate informed consent.

Effect of Participating in a Study of Causes of Pregnancy Loss on Mental Health Outcomes: A Target Trial Emulation Using the COPL Cohort and Danish National Registries

Pregnancy loss is the most common severe pregnancy complication and is associated with significant mental health sequelae, including depression and anxiety. Standard care in Denmark does not include systematic follow-up or aetiological investigation after pregnancy loss. The Copenhagen Odense Pregnancy Loss (COPL) Cohort offered extensive aetiological investigations, and a dedicated clinical follow-up visit 4-10 weeks post-loss. This is a target trial emulation (TTE) designed to estimate the causal effect of COPL participation on women's mental health outcomes one year after pregnancy loss. We will emulate a target trial comparing (1) enrolment into COPL versus (2) standard pregnancy loss care. The study population comprises women aged ≥18 years with a confirmed intrauterine pregnancy loss (ICD-10: DO020, DO021, DO030-DO034) before 22 weeks' gestation treated at Danish public hospitals between November 2020 and April 2025. The primary outcome is new-onset affective disorder (ICD-10: F32\*-F39\*), neurotic/stress-related disorder (F41\*, F43\*, F48\*), or dispensing of antidepressant (N06A\*), anxiolytic (N05B\*), or sedating (N05C\*) medication within 12 months of pregnancy loss diagnosis. All data will be sourced from Danish National Registries. The difference-in-differences estimator will serve as the primary analytical approach, complemented by instrumental variable analysis (hospital of treatment as instrument) and regression discontinuity design. Inverse probability of treatment weighting will be used to control for measured confounders. Results will be reported as risk ratios and risk differences with 95% confidence intervals. Sensitivity analyses will include per-protocol estimation and exclusion of women with treatable findings identified in COPL.

Microbiome and Metabolome Profiles in Couples Undergoing IVF and Reproductive Outcomes

This prospective observational cohort study investigates the role of the microbiome and metabolome in couples undergoing in vitro fertilization. Biological samples will be collected from both female and male partners, including semen, vaginal, and blood samples, to characterize microbial composition and metabolic profiles. The study aims to examine how these biological profiles are associated with reproductive outcomes such as fertilization, pregnancy, miscarriage, and live birth. Participants will be followed longitudinally, and reproductive and obstetric outcomes will be obtained through linkage with national health registers.

Comparison of Surgical Management of Early Pregnancy Loss by Suction Curettage Versus Hysteroscopy in Patients Undergoing In-vitro Fertilization (IVF)

Early pregnancy loss occurs in \~15% of pregnancies. The treatment options include surgical uterine evacuation by suction curettage, medical management with misoprostol, or conservative management without interventions. The advantages of surgical management include quick resolution of the pregnancy and avoidance of heavy vaginal bleeding, while the disadvantages include retained products of conception and intrauterine adhesion formation which could affect future fertility. With the aim of reducing the complications of suction curettage, uterine evacuation using operative hysteroscopy has been suggested. In a previous study, the investigators compared suction curettage with operative hysteroscopy for the surgical management of early pregnancy loss up to 10 weeks of gestation. The results showed significantly reduced adhesions rate (4.2% in the hysteroscopy group vs. 45.2% in the suction group, p \< 0.01), although the operative time was significantly longer for the hysteroscopy. In this follow-up study, the investigators will compare the outcomes of hysteroscopy and suction curettage in a select group of patients with early pregnancy loss following conception by in-vitro fertilization. These patients are at risk for adhesions and therefore candidates for the hysteroscopic intervention. The study will include 50 patients randomized to 2 intervention arms - hysteroscopy using a tissue removal device versus the standard suction curettage. Post-operative adhesions will be assessed by office hysteroscopy after 6-8 weeks.