Aerobe Cycling Training in Women With Unexplained Recurrent Pregnancy Loss

N/AActive Not RecruitingNCT06007560

Radboud University Medical Center30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Recurrent Pregnancy Loss

Interventions

Eligibility

Sex: FEMALEMax age: 40 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

CD56 endometrial NK cell frequency

Change in CD56 eNK cell frequency measured as percentage of total lymphocyte or total CD56 population by flowcytometry.

Time frame: 3 months

CD56 endometrial NK cell function

Change in CD56 eNK cell function measured as percentage of CD56 degranulation by flowcytometry.

Time frame: 3 months

Secondary Outcomes

CD56 endometrial NK cell phenotype

Change in CD56 eNK cell phenotype measured as percentage of (sub)population or mean fluorescent intensity respectively by flowcytometry.

Time frame: 3 months

CD56 peripheral NK cell frequency

Change in CD56 pNK cell frequency measured as percentage of total lymphocyte or CD56 population by flowcytometry.

Time frame: 3 months

CD56 peripheral NK cell function

Change in CD56 pNK cell function measured as percentage of CD56 degranulation by flowcytometry.

Time frame: 3 months

CD56 peripheral NK cell phenotype

Change in CD56 pNK cell phenotype measured as percentage of (sub)population or mean fluorescent intensity respectively by flowcytometry.

Time frame: 3 months

Vaginal microbiome

Change in taxonomic classification of vaginal microbiota of different subtypes but also classified in clustering of different subtypes.

Time frame: 3 months

Metabolic syndrome parameters I

Change in cm waist circumference.

Time frame: 3 months

Metabolic syndrome parameters II

Chance in mmHg blood pressure, both systolic as diastolic.

Time frame: 3 months

Metabolic syndrome parameters III

Change in concentration (mg/dL) triglyceride.

Time frame: 3 months

Metabolic syndrome parameters IV

Change in concentration (mg/dL) cholesterol levels.

Time frame: 3 months

Metabolic syndrome parameters V

Change in concentration (mg/dL) blood sugar levels.

Time frame: 3 months

Sympathetic activity

Change in baroreceptor sensitivity in ms/mmHg.

Time frame: 3 months

Uterine blood flow

Change in pulsatility index, lower indicates better outcome.

Time frame: 3 months

Physical fitness

Change in VO2max.

Time frame: 3 months

Pregnancy rate and live birth rate after one year of intervention, higher rater indicate better outcome.

Questionnaire.

Time frame: 3 months

Aerobe Cycling Training in Women With Unexplained Recurrent Pregnancy Loss

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes