Cardiometabolic Function in Offspring, Mother and Placenta After Assisted Reproductive Technology (COMPART)

March 20, 2024 updated by: Anja Bisgaard Pinborg, Rigshospitalet, Denmark
The overall objective is to establish the first-of-its-kind longitudinal cohort of pregnant women, biological fathers/partners and offspring from pregnancies achieved by frozen embryo transfer (FET), fresh-embryo transfer (fresh ET) and naturally conceived (NC) to investigate maternal cardiometabolic profiles, fetal growth patterns and placental function during pregnancy as well as metabolic and endocrine health in the offspring. Additionally, the aim is to explore genetic and epigenetic patterns in placenta, fetus and parents. As secondary objectives, the investigator group will examine telomere length and minipuberty hormones in children born after FET, fresh-ET and NC.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Background and research gap: Increasing use of assisted reproductive technology (ART) necessitates vigilance on the health of the offspring. The use of frozen embryo transfer (FET) in ART increases the risk of the children being born large-for-gestational-age (LGA) compared to conventional fresh embryo transfer (fresh ET) and naturally conceived children (NC). In general, children born LGA are predisposed to childhood obesity and later metabolic syndrome, thus FET may increase the societal burden of this. The mechanism between FET and LGA is unclear and its impact on neonatal body composition and metabolic health is unknown.

Hypothesis and objectives: The growth hormone (GH) - insulin-like growth factor (IGF) axis plays an essential role in fetal growth and is also linked to metabolic disease due to its interactions with insulin. Thus, the investigator group hypothesize that FET imposes epigenetic alterations towards the GH-IGF-axis leading to enhanced fetal growth and a potential persisting phenotype of metabolic dysfunction. The objective is to determine the effect of endocrine growth factors, maternal metabolic profile, and placental function on intrauterine growth patterns as well as early postnatal body composition and metabolic profile in children born after ART with FET compared to children born after fresh ET and NC children.

Methods and outcomes: The investigator group will conduct a prospective cohort study including women pregnant by FET (N=200), fresh ET (N=200) and NC children (N=200). The women will undergo three examinations during pregnancy with blood sampling (analyzed for GH-IGF-related growth factors and metabolic biomarkers), fetal biometry and doppler ultrasound. For a subpopulation the placenta will be collected at delivery. The expression of placental growth factors will be determined using western blot and qPCR and epigenetic alterations assessed by DNA methylation using targeted CpG arrays. The newborns will be examined within two weeks of birth with blood samples (analyzed for growth factors, glucose-metabolism markers, lipids, and cytokines) and a DEXA-scan to evaluate body composition. Information on ART-procedure, obstetric adverse events, birth weight and neonatal complications will be available from electronic health records. The outcomes are grouped in three work packages comparing the differences between FET, fresh ET, and NC in 1) maternal growth factors and metabolic profile and the relationship with fetal growth trajectories, 2) expression and DNA methylation of GH-IGF-axis components in placental tissue, 3) body composition, metabolic profile and DNA methylation of regions related to the GH-IGF axis in neonates.

Significance: It is crucial to understand the mechanism between FET and LGA and its impact on metabolic health in children in order to determine the safest ART technique. The investigator group expect that the results will identify the role of the GH-IGF axis in the pathogenesis of FET-induced LGA and its associated metabolic risk which may highlight potential biomarkers of abnormal fetal growth and therapeutic targets for prevention of obesity and metabolic diseases.

Study Type

Observational

Enrollment (Estimated)

600

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2100
        • Fertility Clinic, Rigshospitalet, Copenhagen University Hospital
      • Copenhagen, Denmark
        • Dept. of Paediatric and Adolescent Medicine, Herlev Hospital
        • Contact:
          • Rikke B. Jensen, MD, Ass. Prof
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The study population will be recruited from the Capital Region of Denmark.

Description

Inclusion Criteria:

Pregnant women who have either had fertility treatment at Rigshospitalet or Herlev Hospital (FET and fresh ET groups) or are scheduled for prenatal ultrasounds at Rigshospitalet or Herlev Hospital (NC group) will be screened for eligibility. Inclusion must happen before their routine ultrasound scan in 1. trimester.

Exclusion Criteria:

  • Maternal pregestational diabetes type 1 or 2
  • Non-singleton pregnancies
  • Maternal pregestational BMI > 35 kg/m2
  • Severe maternal co-morbidity
  • Oocyte donation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
FET-group
Children conceived by frozen embryo transfer
Fresh ET-group
Children conceived by fresh embryo transfer
NC group
Naturally conceived children

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Offspring body composition
Time Frame: Assessed at 2,5 months of age
Total fat mass (in gram) assessed by air displacement plethysmography (PEA POD).
Assessed at 2,5 months of age
Maternal cardiometabolic profile
Time Frame: One times during each trimester
Fetal growth patterns determined by ultrasound
One times during each trimester

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Epigenetic in placenta and cord blood
Time Frame: 2 years
Differences between ovulatory FET, programmed FET, fresh ET and NC
2 years
Early markers of reproductive function in FET, fresh-ET and NC children: LH, FSH, SHBG, AMH, androgens, estrogens (SDS)
Time Frame: 3 years
Bloodsamples: Differences between ovulatory FET, programmed FET, fresh ET and NC
3 years
Telomere length in children born after FET, fresh-ET and NC children
Time Frame: 3 years
Differences between ovulatory FET, programmed FET, fresh ET and NC in 1) LTL in newborns and 2) parental LTL
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rigshospitalet, Denmark

Collaborators

Herlev Hospital

Investigators

  • Principal Investigator: Anja B. Pinborg, Prof., MD, Fertility Department, Rigshospitalet
  • Study Chair: Rikke B. Jensen, MD, Ass. prof, Dept. of Paediatric and Adolescent Medicine, Herlev Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2024

Primary Completion (Estimated)

April 30, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

February 26, 2024

First Submitted That Met QC Criteria

March 20, 2024

First Posted (Actual)

March 27, 2024

Study Record Updates

Last Update Posted (Actual)

March 27, 2024

Last Update Submitted That Met QC Criteria

March 20, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-23071266

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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