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

NCT ID: NCT06334003

Last Updated: 2024-11-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

600 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-05-17

Study Completion Date

2027-01-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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ART IVF Children, Only Cardiovascular Disease Other

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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FET-group

Children conceived by frozen embryo transfer

No interventions assigned to this group

Fresh ET-group

Children conceived by fresh embryo transfer

No interventions assigned to this group

NC group

Naturally conceived children

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Herlev Hospital

OTHER

Sponsor Role collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role lead

Responsible Party

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Anja Bisgaard Pinborg

Clinical Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Anja B. Pinborg, Prof., MD

Role: PRINCIPAL_INVESTIGATOR

Fertility Department, Rigshospitalet

Rikke B. Jensen, MD, Ass. prof

Role: STUDY_CHAIR

Dept. of Paediatric and Adolescent Medicine, Herlev Hospital

Locations

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Fertility Clinic, Rigshospitalet, Copenhagen University Hospital

Copenhagen, , Denmark

Site Status RECRUITING

Department of Fetalmedicin, Herlev Hospital

Copenhagen, , Denmark

Site Status RECRUITING

Dept. of Paediatric and Adolescent Medicine, Herlev Hospital

Copenhagen, , Denmark

Site Status NOT_YET_RECRUITING

Countries

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Denmark

Central Contacts

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Maria L Vestager, MD

Role: CONTACT

+4528306039

Anna Sophie Lebech Kjær, MD

Role: CONTACT

Facility Contacts

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Anja B. Pinborg, Prof., MD

Role: primary

Anna Sophie Lebech Kjær, MD, PhD-student

Role: backup

Maria Linander Vestager

Role: primary

Rikke B. Jensen, MD, Ass. Prof

Role: primary

Maria L. Vestager, MD, PhD-student

Role: backup

References

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Kjaer ASL, Vestager ML, Blixenkrone-Moller E, Asserhoj LL, Kloppenborg JT, Lossl K, Ekelund CK, Rode L, Hjort L, Hoffmann ER, Lyng Forman J, Beck Jensen R, Pinborg A. Cardiometabolic function in Offspring, Mother and Placenta after Assisted Reproductive Technology (COMPART): a prospective cohort study. BMJ Open. 2025 Sep 16;15(9):e105754. doi: 10.1136/bmjopen-2025-105754.

Reference Type DERIVED
PMID: 40957860 (View on PubMed)

Other Identifiers

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H-23071266

Identifier Type: -

Identifier Source: org_study_id

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