Clinical Research Directory

Genomic Predictors of Recurrent Pregnancy Loss

The overall goals of this proposal are to determine the genetic architecture of recurrent pregnancy loss (RPL) and to discover genomic predictors of RPL.

Study of Endometrial Immune and Microbiological Modifications in Cases of Recurrent Implantation Failure and/or Recurrent Pregnancy Loss

The IMERR study aims to improve understanding of certain causes of infertility related to recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL), conditions that affect many women undergoing assisted reproductive technology (ART). Despite medical advances, some patients repeatedly fail to achieve pregnancy, or experience repeated miscarriages. These situations may be linked to subtle immune or microbial disturbances in the uterus. This study seeks to identify immune and microbiological profiles in the endometrium during the implantation window-a crucial period when the embryo attaches to the uterine wall. We will compare women who have experienced RIF and/or RPL with women who have had no such history. Blood and uterine samples will be analyzed to investigate whether certain immune or microbial features are associated with these reproductive failures. The ultimate goal is to uncover predictive factors that may explain why some women experience implantation failure or pregnancy loss, and to lay the foundation for future personalized treatments to improve reproductive outcomes.

Cardiac Autonomic and Anxiety Regulation Via Closed-loop nEurofeedback in Recurrent Pregnancy Loss

The goal of this clinical trial is to learn whether right dorsolateral prefrontal cortex (right DLPFC)-targeted fNIRS-BCI online closed-loop neurofeedback, delivered with slow-wave acoustic cueing, can reduce anxiety symptoms and improve cardiac autonomic regulation in women with recurrent pregnancy loss (RPL) and comorbid anxiety (women aged 18-45 years, right-handed, currently not pregnant or in a missed miscarriage state). The main questions it aims to answer are: Does real neurofeedback increase the proportion of participants who achieve an anxiety treatment response (defined as ≥50% reduction in Hamilton Anxiety Rating Scale \[HAMA\] total score from baseline) compared with sham feedback, at end of treatment and at 3-month follow-up? Is the intervention safe and well tolerated, as reflected by between-group differences in adverse events during the training period? Do brain and autonomic measures show between-group differences during the first formal session, including right DLPFC HbO downregulation, interhemispheric DLPFC synchronisation, heart rate (HR), and heart rate variability (HRV) indices? Researchers will compare real right DLPFC neurofeedback to sham feedback (identical procedures and displays but weakened coupling to real-time neural activity) to see if real neurofeedback improves anxiety outcomes and brain-heart autonomic regulation. Participants will: Complete screening, baseline clinical assessments, and physical examination Be randomly assigned (1:1) to real neurofeedback or sham feedback Complete 3 days of adaptation training followed by 3 weeks of training (15 sessions; one weekday session per day; \~20 minutes each) using a block design with slow-wave acoustic cueing (1 Hz amplitude-modulated tone; 20 s rest + 40 s cueing per block; 20 blocks/session) Undergo fNIRS recording in all sessions, with ECG recorded in session 1 only (for HR/HRV analyses) Receive matched, guideline-informed cognitive-behavioural therapy (CBT) during the intervention period Complete anxiety-related assessments at baseline, \~1 hour after the final session, and 3 months after treatment, with adverse events monitored throughout the intervention period

Association Between Plasma Level of Mannose Binding Lectin and Human Reproduction

A low plasma level of mannose binding lectin (p-MBL) is associated with unexplained recurrent pregnancy loss (RPL), but it is not investigated if it is associated with unexplained reproductive failure in general, including recurrent implantation failure (RIF) after assisted reproductive technology (ART) (including IVF, ICSI and FET), recurrent pregnancy loss (RPL) after spontaneous conception, and RPL after ART.

Effect of HCQ Combined With LT4 on LBR in Euthyroid Women With URPL and TPO-Ab

The goal of this clinical trial is to learn if combined treatment of levothyroxine and hydroxychloroquine would improve the live birth of euthyroid women with thyroid peroxidase antibodies and unexplained recurrent pregnancy loss. Researchers will compare combined treatment of levothyroxine and hydroxychloroquine to a treatment of levothyroxine alone to see if combined treatment works to improve live birth of euthyroid participants with thyroid peroxidase antibodies and unexplained recurrent pregnancy loss. Participants will: * Receive combined treatment of levothyroxine and hydroxychloroquine or treatment of levothyroxine alone every day at least 8 weeks before pregnancy, and continue their treatment till the end of pregnancy. * Visit the clinic 4 weeks and 8 weeks after their treatments, and every 12 weeks before they get pregnant for checkups and tests. During their pregnancy, they will visit the clinic before gestation of 12 weeks, and will be followed up with phone call in the second trimester and after parturition.

Effects of High-Intensity, Low-Frequency Periodic rTMS Over the Right Dorsolateral Prefrontal Cortex on Cardiac Autonomic Regulation in Women With Recurrent Pregnancy Loss and Anxiety: A Proof-of-Concept rTMS-ECG Clinical Trial ( NEURO-CARD)

This proof-of-concept trial investigates whether high-intensity, low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the right dorsolateral prefrontal cortex (DLPFC) can improve autonomic cardiac regulation in women with recurrent pregnancy loss (RPL) and anxiety. The study explores the lateralised function of the DLPFC in emotional and autonomic control and tests a novel neuromodulation-based strategy to relieve anxiety and sympathetic overactivation.

Aerobe Cycling Training in Women With Unexplained Recurrent Pregnancy Loss

In 50% of women with recurrent pregnancy loss (RPL) miscarriages are unexplained, therefore no therapeutic intervention is possible. In a pilot study, women with unexplained RPL showed less endometrial NK cells (eNK) compared to women with a previously uncomplicated pregnancy. It is known that eNK cells are important for embryo implantation during early pregnancy. Investigators presume that high sympathetic activity in these women is related to eNK cell number, function and phenotype and that exercise is an effective intervention to lower sympathetic activity and to influence the immune system, as especially peripheral NK cells have been assumed to be responsive to physical training. The investigators hypothesize that moderate exercise can lower the adrenergic tone of the sympathetic nervous system hereby influencing endometrial NK cells in women with RPL and eventually pregnancy outcome.

Prospective Recurrent Pregnancy Loss Registry

The purpose of this Registry is to prospectively collect data of Recurrent Pregnancy Loss (RPL) patients attending the specialized care centre at the BC Women's Hospital, in order to evaluate investigation practices, treatment options, and outcomes for this patient population over time.

Prednisolone Administration in Patients With Unexplained REcurrent MIscarriages

Recurrent miscarriages (RM) affects 3% of all fertile couples, but remains unexplained in most cases, limiting therapeutic options. Possibly the maternal immune system plays a role in recurrent miscarriage. Prednisolone suppresses the immune system and might enable development of normal pregnancy. In this randomized controlled clinical trial the investigators will study the effect of prednisolone on the live birth rate in patients with RM. Secondary, the tolerability and safety for mother and child and the cost-effectiveness is investigated. In the study one group of pregnant women with RM and gestational age \<7 weeks will receive prednisolone, the other group will receive a placebo. Total use of the medicine during this study is 8 weeks, further care during the study is routinely antenatal care. Subjects will be asked to fill in 4 short questionnaires and will have contact with a research nurse at different time points to gain information on the course of the pregnancy and possible side effects. Results of the study will be implemented in (inter) national guidelines, to effect everyday practice.

Tender Loving Care for Recurrent Pregnancy Loss

The goal of this investigational study is to evaluate participation in a weekly, interactive, tender loving care messaging platform impact on pregnancy outcomes in patients with recurrent pregnancy loss. The main questions it aims to answer are: (1) does participation in weekly, interactive tender loving care messages increase live birth rates in patients with recurrent pregnancy loss? (2) Does participation in weekly, interactive tender loving care messages increase patients' quality of life? Does participation in weekly, interactive tender loving care messages decrease patients' depressive symptoms? Participants will be asked to interact with weekly messages providing prenatal counseling and support. Additionally, patients will be asked to complete the fertility quality of life survey several times over the course of the pregnancy.

Microfluidics Versus Gradient Centrifugation Effect on Euploidy Rates

This research is being done to determine if using a microfluidics chamber, a device used to process sperm, will be effective in improving the rates of embryos with normal chromosomes (structures that carry genetic information) during in vitro fertilization (IVF) treatment. The investigators hypothesize that this device is effective at improving rates of normal chromosomes among embryos.

On Pregnancy After Losses - OPAL Study

Rationale: Recurrent pregnancy loss (RPL) is defined as the loss of two or more conceptions before the fetus reaches viability. It affects 1-3% of all fertile couples and despite extensive diagnostic work-up, in only around 30% an underlying cause is identified. Several factors may increase the risk for miscarriage, but the chance of a normal, successful pregnancy is still high. So, in supporting couples with RPL, an important part of the clinical management of these couples is to provide couples with accurate prognoses for their next pregnancy. The main limitation in current prediction models is the lack of a sufficiently large cohort, adjustment for relevant risk factors such that prognoses are individualized, and separating between the cumulative live birth rate and the chance that the next conception will lead to a live birth. In this project therefore we aim to make an individualized prognosis regarding the future chance of live birth and the chance of a healthy child. This could then lead to improved wellbeing and the ability of making future reproductive choices. Objectives: Primary objective: to predict the chance of a live birth within three years after intake in couples with unexplained RPL Secondary objectives: * to predict the chance of an ongoing pregnancy (\>12 weeks) in the next pregnancy in couples with unexplained RPL. * to predict the chance of a complicated pregnancy in couples with unexplained RPL * to predict the chance dynamically of a live birth given the outcome of a pregnancy after intake * to predict the chance of above outcomes in couples with a known cause for RPL Study design: A multicenter retrospective and prospective cohort study. Study population: Couples with females aged ≤42 years in both prospective and retrospective inclusion. Retrospective inclusion: Couples with RPL who visited the RPL outpatient clinic in participating centers from 2006 until the start of this study. Prospective inclusion: new couples with RPL who will visit the clinic from 2021 onwards. Main study parameters/endpoints: * Pregnancy outcomes since intake * Time to pregnancy since intake * Time between pregnancies since intake * Pregnancy complications since intake * All outcomes will be obtained up to a maximum of five years after intake * Patient characteristics: cause for RPL, female age, male age, previous live birth, duration of RPL (since diagnosis) Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participating in this study does not yield any risks. There could be a burden in case of retrospectively collecting data. Participating does not yield direct benefits for the subjects, however it may lead to future improvements of care for couples with RPL.