At High-risk for Pre-eclampsia After Assisted Reproductive Technology

NCT05746793 | Recruiting

• 1 other identifier: 22271HEART
• Study Type: observational
• Target: 1,050
• Locations: 1 country
• Sites: 1

Brief Summary

The overarching goal of the project is to unravel PE etiopathogenesis in high-risk patients (PCOS patients and oocyte acceptors) after assisted reproductive technology (ART) to individualize prenatal care following ART and to determine potential targets for new PE prevention options decreasing the morbidity/mortality caused by this pathology. More specifically, the following objectives/work packages (WPs) are put forward:

• WP1 - PRECONCEPTION: Identify preconceptional maternal characteristics associated with in-creased risk of PE in ART patients (1a) and investigate the potential role of the endometrium prior to pregnancy (1b).
• WP2 - DURING PREGNANCY: Evaluate the Fetal Medicine Foundation's (FMF) first trimester PE screening in selected high-risk groups post ART to explore the clinical benefit in this specific context (2a) and investigate the association between parameters during the pregnancy and PE development post-ART.
• WP3 - AT DELIVERY: Identifying placental molecular pathways associated with PE post-ART.

Conditions

Pre-Eclampsia

Outcome Measures

Primary Outcomes (51)

• BMI (kg/m2)

  measurement of height en weight. Work package 1: preconceptional, metabolic analysis Work package 2: during pregnancy, metabolic analysis

  1 year

• Total energy expenditure (kcal/day)

  Work package 1: preconceptional, metabolic analysis Work package 2: during pregnancy, metabolic analysis

  1 year

• number of laps of 6MWT (number)

  6 minute walking test Work package 1: preconceptional, metabolic analysis Work package 2: during pregnancy, metabolic analysis

  1 year

• Saturation beginning and end of 6MWT (%)

  6 minute walking test Work package 1: preconceptional, metabolic analysis Work package 2: during pregnancy, metabolic analysis

  1 year

• pulse beginning and end of 6MWT

  6 minute walking test Work package 1: preconceptional, metabolic analysis Work package 2: during pregnancy, metabolic analysis

  1 year

• Effective maximal handgrip strength (KPa)

  Hangrip strenght Work package 1: preconceptional, metabolic analysis Work package 2: during pregnancy, metabolic analysis

  1 year

• Time until 50% of effective handgrip strenght (s)

  Hangrip strenght Work package 1: preconceptional, metabolic analysis Work package 2: during pregnancy, metabolic analysis

  1 year

• IVSd (mm)

  Transthoracic ultrasound Evaluation of left ventricle and left ventricle systolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• PWTd (mm)

  Transthoracic ultrasound Evaluation of left ventricle and left ventricle systolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• LVEDD (mm)

  Transthoracic ultrasound Evaluation of left ventricle and left ventricle systolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• IVSs (mm)

  Transthoracic ultrasound Evaluation of left ventricle and left ventricle systolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• PWTs (mm)

  Transthoracic ultrasound Evaluation of left ventricle and left ventricle systolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• LVESD (mm)

  Transthoracic ultrasound Evaluation of left ventricle and left ventricle systolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• LV mass (indexed) mg/m2

  Transthoracic ultrasound Evaluation of left ventricle and left ventricle systolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• LVEF (visual, manual modified Simpson's biplane, auto-EF) (%)

  Transthoracic ultrasound Evaluation of left ventricle and left ventricle systolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• LV GLS (LV MW) (-%)

  Transthoracic ultrasound Evaluation of left ventricle and left ventricle systolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• E-wave velocity (cm/s)

  Transthoracic ultrasound Evaluation of left ventricle diastolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• A-wave velocity (cm/s)

  Transthoracic ultrasound Evaluation of left ventricle diastolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• Deceleration time (ms)

  Transthoracic ultrasound Evaluation of left ventricle diastolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• E/A ratio

  Transthoracic ultrasound Evaluation of left ventricle diastolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• Septal wall e' (cm/s)

  Transthoracic ultrasound Evaluation of left ventricle diastolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• Lateral wall e' (cm/s)

  Transthoracic ultrasound Evaluation of left ventricle diastolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• E/e' ratio

  Transthoracic ultrasound Evaluation of left ventricle diastolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• Septal e'/lateral e' ratio

  Transthoracic ultrasound Evaluation of left ventricle diastolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• LA AP diameters (mm)

  Transthoracic ultrasound Evaluation of left atrium Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• LAESVi (mL/M2)

  Transthoracic ultrasound Evaluation of left atrium Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• La strain (-%)

  Transthoracic ultrasound Evaluation of left atrium Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• TAPSE (mm)

  Transthoracic ultrasound Evaluation of right ventricle and RV systolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• RV s' (cm)

  Transthoracic ultrasound Evaluation of right ventricle and RV systolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• RV GLS (RV MW) (-%)

  Transthoracic ultrasound Evaluation of right ventricle and RV systolic function Work package 1: preconceptional, Work package 2: during pregnancy, cardiac evaluation

  1 year

• systolic, diastolic bloodpressure and mean arterial pressure (mmHg)

  Blood pressure measurement device. Work package 1: preconception Work package 2: during pregnancy

  1 year

• Pulsatility index of the uterine artery

  ultrasound Work package 1: preconception Work package 2: during pregnancy

  1 year

• (sub)endometrial flow (1,2,3)

  ultrasound Work package 1: preconception Work package 2: during pregnancy

  1 year

• PRL mRNA expression

  RNA sequencing Work package 1: preconception

  3 months

• PRL production (ng/ml)

  ELISA Work package 1: preconception

  3 months

• IGFBP1 mRNA expression

  RNA sequencing Endometrial tissue Work package 1: preconception

  3 months

• IGFBP1 (pg/ml)

  ELISA Endometrial tissue Work package 1: preconception

  3 months

• PlGF (pg/ml)

  blood sample Work package 1: preconception Work package 2: during pregnancy

  3 months

• sFLT1 (pg/ml)

  blood sample Work package 1: preconception Work package 2: during pregnancy

  3 months

• sENG (ng/ml)

  blood sample Work package 1: preconception Work package 2: during pregnancy

  3 months

• Incidence of positive PE screening (%)

  Fetal medicine foundation screening algorithm. Work package 2: during pregnancy

  6 months

• Estimated fetal weight (g)

  ultrasound Work package 2: during pregnancy

  1 year

• PI umbilical artery

  ultrasound Work package 2: during pregnancy

  1 year

• PI uterine artery

  ultrasound Work package 2: during pregnancy

  1 year

• gestational age at diagnoses PE (weeks)

  work package 2: during pregnancy

  1 year

• incidence of PE (%)

  work package 2: during pregnancy

  1 year

• severity of PE (mild/severe)

  work package 2: during pregnancy

  1 year

• gestational age at delivery (weeks)

  work package 3: at delivery

  1 year

• birth weight (grams)

  work package 3: at delivery

  1 year

• APGAR scores of baby after 1, 5 and 10 minutes (1-10)

  work package 3: at delivery

  1 year

• different expressed genes (DEGs) of placenta's

  work package 3: at delivery RNA sequencing

  1 year

Study Arms (2)

Subfertile polycystic ovarian syndrome (PCOS) patients undergoing ART treatment

Peripheral blood collection. MOCK frozen embryo preparative cycle. Endometrial pipelle biopsy. Collection of menstrual blood. Questionnaire. Nutritional/metabolic evaluation. Cardiac work-up. Preconceptional and prenatal ultrasound. Blood pressure measurements. Urine analysis.

Procedure: endometrium biopsy; Diagnostic Test: Transabdominal ultrasound; Diagnostic Test: Peripheral phlebotomy; Diagnostic Test: Urine collection; Other: MOCK frozen embryo transfer preparative cycle.; Diagnostic Test: Baseline questionnaire; Other: collection of menstrual blood; Diagnostic Test: nutritional and metabolic work-up; Diagnostic Test: cardiac work-up; Diagnostic Test: Blood pressure measurement

Oocyte acceptors

Peripheral blood collection. MOCK frozen embryo preparative cycle. Endometrial pipelle biopsy. Collection of menstrual blood. Questionnaire. Nutritional/metabolic evaluation. Cardiac work-up. Preconceptional and prenatal ultrasound. Blood pressure measurements. Urine analysis.

Procedure: endometrium biopsy; Diagnostic Test: Transabdominal ultrasound; Diagnostic Test: Peripheral phlebotomy; Diagnostic Test: Urine collection; Other: MOCK frozen embryo transfer preparative cycle.; Diagnostic Test: Baseline questionnaire; Other: collection of menstrual blood; Diagnostic Test: nutritional and metabolic work-up; Diagnostic Test: cardiac work-up; Diagnostic Test: Blood pressure measurement

Interventions

endometrium biopsy PROCEDURE

The procedure is performed without any anesthesia and takes approximately 5 minutes. A small plastic pipelle is put through the cervix into the uterine cavity. The endometrial tissue is aspirated into the pipelle.

Oocyte acceptors; Subfertile polycystic ovarian syndrome (PCOS) patients undergoing ART treatment

Transabdominal ultrasound DIAGNOSTIC_TEST

Evaluation of fetal biometry and doppler flow study using ultrasound.

Oocyte acceptors; Subfertile polycystic ovarian syndrome (PCOS) patients undergoing ART treatment

Peripheral phlebotomy DIAGNOSTIC_TEST

single puncture collection of peripheral venous blood.

Oocyte acceptors; Subfertile polycystic ovarian syndrome (PCOS) patients undergoing ART treatment

Urine collection DIAGNOSTIC_TEST

Collection of urine in a plastic cup.

Oocyte acceptors; Subfertile polycystic ovarian syndrome (PCOS) patients undergoing ART treatment

MOCK frozen embryo transfer preparative cycle. OTHER

Start with daily estradiol (progynova, oestrogel) administration at hormonal baseline (day 2 of the cycle or with confirmation using endocrine evaluation). When adequate thickness (≥6.5 mm) of the endometrium is achieved (usually after 10-14 days), progesterone is administered daily. 6 days after progesterone administration, the pipelle biopsy will be performed. When this test cycle has ended and menstruation starts, patients will be asked to collect their menstrual flow, during the first night of heavy/red flow, in a menstrual cup. The next day patients will be asked to bring their collected menstrual blood to our center and they will undergo a blood analysis needed for the start of their ART treatment.

Oocyte acceptors; Subfertile polycystic ovarian syndrome (PCOS) patients undergoing ART treatment

Baseline questionnaire DIAGNOSTIC_TEST

questionnaire the patient has to fill in

Oocyte acceptors; Subfertile polycystic ovarian syndrome (PCOS) patients undergoing ART treatment

collection of menstrual blood OTHER

collection of menstrual blood during the first day of heavy menstrual flow for at least 6 hours

Oocyte acceptors; Subfertile polycystic ovarian syndrome (PCOS) patients undergoing ART treatment

nutritional and metabolic work-up DIAGNOSTIC_TEST

Including body composition analysis by BIA/whole body MRI and analysis of resting energy expenditure (REE).

Oocyte acceptors; Subfertile polycystic ovarian syndrome (PCOS) patients undergoing ART treatment

cardiac work-up DIAGNOSTIC_TEST

Using transthoracic ultrasound.

Oocyte acceptors; Subfertile polycystic ovarian syndrome (PCOS) patients undergoing ART treatment

Blood pressure measurement DIAGNOSTIC_TEST

Blood pressure measurement

Oocyte acceptors; Subfertile polycystic ovarian syndrome (PCOS) patients undergoing ART treatment

Eligibility Criteria

• Age: 18 Years - 48 Years
• Gender Eligibility Details: Patients with a womb, who want to get pregnant and present themselves at our fertility clinic.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients at high-risk of developing PE and planned to undergo ART: * Oocyte recipients: patients are planned to undergo a transfer of an embryo conceived with a donor oocyte * PCOS patients: patients diagnosed with polycystic ovary syndrome (Rotterdam criteria) and planned to undergo a IVF/ICSI or IVM treatment

You may qualify if:

• First time oocyte acceptors Or Nulliparous PCOS patients undergoing ART (IVF/ICSI)
• Criteria for PCOS: two out of the three following criteria must be present:
• Oligo-or anovulation: a menstrual cycle \>35 days
• Hyperandrogenism:
• Clinically: the presence of hirsutism and/ or severe acne in combination with alopecia confirmed hyperandrogenism Or
• Biochemically: serum total testosterone \>52 ng/dl or calculated free testosterone \>0,64 ng/dl
• Polycystic ovaries:
• Follicle number per ovary (FNPO) ≥ 12 on both ovaries Or
• Ovarian volume ≥ 10 ml in both ovaries Or
• One ovary with ≥ 20 follicles (Using endovaginal US transducers with a frequency bandwidth that includes 8 MHz) Or
• AMH ≥ 4,9 ng/ml

You may not qualify if:

• Known essential hypertension or development of a new-onset hypertension before 20 weeks' gestation
• Hypertension is defined as a systolic blood pressure ≥ 140 or a diastolic blood pressure ≥ 90 on two separate measurements with at least 20 minutes in between, taken when the patients is in a seated position Or
• The patient is known with hypertension, diagnosed by a certified doctor
• Known diabetes type 1 or 2 before pregnancy
• Diagnosis of diabetes is confirmed when one of the following is present:
• Fasting glucose ≥ 126 mg/dl
• A 2-hour plasma glucose level ≥ 200 mg/dL during a 75-g oral glucose tolerance test Or
• The patient is known with diabetes (type 1 or 2), diagnosed by a certified doctor
• Thyroid dysfunction not under control with medication:
• Hyperthyroidism, the diagnoses is made when:
• Peripheral blood TSH \<0,5 mIU/L and fT4 \>1,9 ng/dl Or
• When the patient is known with hyperthyroidism diagnosed by a certified physician
• Hypothyroidism, the diagnosis is made when:
• Peripheral blood TSH \>5 mIU/L and fT4 \<0,7 ng/dl Or
• When the patient is known with hypothyroidism diagnosed by a certified physician

Sponsors & Collaborators

• CRG UZ Brussel: lead

Study Sites (1)

Brussels IVF

Brussels, 1090, Belgium

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

endometrial biopsy; menstrual blood

MeSH Terms

Conditions

Pre-Eclampsia

Interventions

Urine Specimen Collection; Blood Pressure Determination

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Diagnostic Techniques, Cardiovascular; Physical Examination

Study Officials

• Shari Mackens, PhD, MD

  Medical director Brussels IVF

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study nurses Brussels IVF

CONTACT

+32 2 477 66 99; studieverpleegkundigen_crg@uzbrussel.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: February 28, 2023
• Study Start: February 15, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: March 28, 2023

Record last verified: 2023-03

Locations

BE (1)