Aerobe Cycling Training in Women With Unexplained Recurrent Pregnancy Loss

Not Applicable

Active, not recruiting

• Conditions: Recurrent Pregnancy Loss
• Interventions: Other: Exercise

• Registration Number: NCT06007560
• Lead Sponsor: Radboud University Medical Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-03-21
• Study First Submitted: 2022-11-29
• Study First Submitted QC: 2023-08-22
• Study First Posted: 2023-08-23
• Primary Completion: 2024-12-01
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-03
• Last Update Posted: 2025-04-06
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

• RPL defined as 2 or more unexplained pregnancy losses from the time of conception until 24 weeks of gestation, known cause for the miscarriages are the presence of thyroid abnormalities, anti-phospholipid syndrome, uterine malformation, and abnormal parental karyotype according to international guideline.
• Couples should not be aiming to conceive during the time course of the exercise intervention.

Exclusion Criteria

• Age above 40 years
• BMI above 40
• Current use of immunosuppressive or biological drugs
• Current use of hormone conceptive
• HIV positivity
• Current or recent (<2 weeks) symptomatic genital infection such as chlamydia, gonorroa, or pelvic inflammatory disease
• Pre-existent diabetes mellitus, autoimmune disease or overt cardiovascular disease
• Vaccination (i.e Covid) within 1 month prior to or during sampling and intervention
• New pregnancy at time of measurements, breastfeeding
• Current or recent (<2-3 months ago) pregnancy
• (Physical) inabilities to follow moderate aerobe cycling training
• Participants who are not capable of signing the informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
<80% eNK	Exercise	Women with low eNK bright cell numbers, defined as \<80% of the total endometrial NK cell population

Primary Outcome Measures

Name	Time	Method
CD56 endometrial NK cell function	3 months	Change in CD56 eNK cell function measured as percentage of CD56 degranulation by flowcytometry.
CD56 endometrial NK cell frequency	3 months	Change in CD56 eNK cell frequency measured as percentage of total lymphocyte or total CD56 population by flowcytometry.

Secondary Outcome Measures

Name	Time	Method
Metabolic syndrome parameters I	3 months	Change in cm waist circumference.
Physical fitness	3 months	Change in VO2max.
CD56 peripheral NK cell frequency	3 months	Change in CD56 pNK cell frequency measured as percentage of total lymphocyte or CD56 population by flowcytometry.
CD56 endometrial NK cell phenotype	3 months	Change in CD56 eNK cell phenotype measured as percentage of (sub)population or mean fluorescent intensity respectively by flowcytometry.
CD56 peripheral NK cell function	3 months	Change in CD56 pNK cell function measured as percentage of CD56 degranulation by flowcytometry.
CD56 peripheral NK cell phenotype	3 months	Change in CD56 pNK cell phenotype measured as percentage of (sub)population or mean fluorescent intensity respectively by flowcytometry.
Metabolic syndrome parameters III	3 months	Change in concentration (mg/dL) triglyceride.
Pregnancy rate and live birth rate after one year of intervention, higher rater indicate better outcome.	3 months	Questionnaire.
Vaginal microbiome	3 months	Change in taxonomic classification of vaginal microbiota of different subtypes but also classified in clustering of different subtypes.
Metabolic syndrome parameters II	3 months	Chance in mmHg blood pressure, both systolic as diastolic.
Metabolic syndrome parameters IV	3 months	Change in concentration (mg/dL) cholesterol levels.
Metabolic syndrome parameters V	3 months	Change in concentration (mg/dL) blood sugar levels.
Sympathetic activity	3 months	Change in baroreceptor sensitivity in ms/mmHg.
Uterine blood flow	3 months	Change in pulsatility index, lower indicates better outcome.

Trial Locations

Locations (2)

Maastricht UMC+; 🇳🇱 Maastricht, Netherlands

Radboud UMC; 🇳🇱 Nijmegen, Netherlands