In Vitro Fertilization (IVF) and Prenatal Effects Independent of Genetics

NCT07296107 | Recruiting

• 2 other identifiers: AAAV41231R01HD118949-01
• Study Type: observational
• Target: 360
• Locations: 1 country
• Sites: 1

Brief Summary

This study examines how maternal stress during pregnancy affects infant brain and behavioral development, focusing on whether these effects are due to the prenatal environment or shared genes. By comparing IVF pregnancies using donor eggs/embryos (no shared genetics) with non-donor IVF pregnancies, the investigators aim to understand how stress influences the baby's development independent of genetic factors. Participants will complete questionnaires, provide blood samples, and take part in placenta and cord blood collection, fetal monitoring, and newborn brain activity assessments. Aim 1: The influence of maternal distress on perinatal neurobehavioral development. Hypotheses: Independent of IVF group status, higher maternal AL will be associated with higher 3rd trimester FHR reactivity, lower FHR variability, AND lower FHR-movement coupling Aim 2: Maternal distress affecting placenta gene methylation. Hypotheses: Independent of IVF group status, maternal AL will be associated with placenta differential DNA methylation in glucocorticoid-regulating genes (FKBP5 and HSD11B2), Aim 3: Maternal experiences associated with unique placenta transcriptomic profiles. Hypotheses: Independent of IVF group status, maternal AL and well-being each will be associated with unique placenta gene expression in pro-inflammatory genes

Conditions

Maternal Distress; Child Development

Keywords

Developmental Origins of Health and Disease (DOHaD); Maternal Health; Child development; IVF

Outcome Measures

Primary Outcomes (6)

• Change in fetal heart rate (FHR)

  This is to measure 3rd trimester fetal heart rate (FHR) reactivity. Change in FHR in response to maternal response to the Stroop task, indicating greater fetal autonomic response associated with maternal distress. Units: Beats per minute (bpm). Greater FHR indicates higher stress.

  At Pregnancy Session 2 (approximately 34-36 weeks of pregnancy)

• Standard deviation of fetal heart rate

  This is to measure fetal heart rate (FHR) variability, reflecting less vagal modulation of the heart associated with maternal distress. Units: Standard deviation of beats per minute. Lesser standard deviation (SD) indicates lower stress.

  At Pregnancy Session 2 (approximately 34-36 weeks of pregnancy)

• Cross correlation of fetal movement and heart rate change

  This is to measure fetal heart rate (FHR)-movement coupling, reflecting central nervous system regulation. Units: Cross correlation value. Lower value indicates lower coupling.

  At Pregnancy Session 2 (approximately 34-36 weeks of pregnancy)

• Average percent DNA methylation of the FKBP5 gene in placental tissue

  This is to measure FKBP5 DNA Methylation. Units: proportion of methylated vs unmethylated. Greater percent indicates higher methylation.

  At delivery (approximately 37-40 weeks)

• Average percent DNA methylation of the HSD11B2 gene in placental tissue

  This is to measure HSD11B2 DNA Methylation. Units: proportion of methylated vs unmethylated. Greater percent indicates higher methylation.

  At delivery (approximately 37-40 weeks)

• Relative expression of key pro-inflammatory markers in placental tissue

  This is to measure expression of Pro-Inflammatory Placental Genes. Units: Gene expression. Greater value indicates greater expression.

  At delivery (approximately 37-40 weeks)

Study Arms (2)

Donor Oocyte/Embryo IVF Pregnancies

This cohort includes pregnant individuals who conceived through in vitro fertilization (IVF) using donor oocytes or embryos, and are therefore not genetically related to the fetus. Participants follow the same study protocol as the non donor oocyte cohort, with enrollment in the second trimester and data collection through delivery and early postpartum. The purpose of including this cohort is to evaluate the effects of maternal prenatal distress and well-being on perinatal development independent of shared maternal-child genetics. Data collection includes psychosocial questionnaires, maternal physiological monitoring, blood draws for immune and transcriptomic analyses, placental and cord blood collection at delivery, newborn physiological monitoring during the postpartum hospital stay, and birth outcomes obtained from the electronic health record (EHR).

Other: Prenatal maternal psychosocial and biological assessment protocol

Non-Donor Oocyte IVF Pregnancies

This cohort includes pregnant individuals who conceived through IVF using their own oocytes, and are therefore genetically related to the fetus. Participants follow the same study protocol as the donor oocyte cohort, with enrollment in the second trimester and data collection through delivery and early postpartum. This group serves as a comparison to assess whether observed associations between maternal prenatal distress, biological markers, and infant neurodevelopment are attributable to intrauterine (environmental) influences or shared genetic factors. Data collection includes psychosocial questionnaires, maternal physiological monitoring, blood draws for immune and transcriptomic analyses, placental and cord blood collection at delivery, newborn physiological monitoring during the postpartum hospital stay, and birth outcomes obtained from the electronic health record (EHR)

Other: Prenatal maternal psychosocial and biological assessment protocol

Interventions

Prenatal maternal psychosocial and biological assessment protocol OTHER

This is not a therapeutic or experimental intervention. The data-collection protocol includes structured psychosocial questionnaires, physiological monitoring, maternal blood draws, placental and cord blood collection, and newborn physiological monitoring. These procedures are used to observe associations between maternal prenatal distress and infant outcomes. All participants undergo the same assessments; no clinical treatment or behavioral manipulation is delivered.

Donor Oocyte/Embryo IVF Pregnancies; Non-Donor Oocyte IVF Pregnancies

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

This five-year study will recruit and enroll approximately 200 pregnant individuals, ages 18-50 years, using IVF (120 homologous, 60 donor oocyte/embryo) and their offspring to achieve a post-attrition sample size of n=180. While based in Washington Heights, the sample reflects individuals undergoing IVF, not the general neighborhood. Based on Columbia Fertility Center data and national IVF trends, the investigators expect participants to be mostly Non-Hispanic/Latinx. While the investigators aim for inclusivity and diversity, non-English speakers will not be enrolled due to study team language constraints.

You may qualify if:

• Individuals at 22-26 gestational weeks with donor and homologous IVF pregnancies, ages 18-50.
• Participants must be patients receiving their perinatal health care through Columbia University Irving Medical Center's Department of OB/GYN and delivering at New York-Presbyterian Morgan Stanley Children's Hospital.
• Participants will include the offspring of patients receiving care at the above institutions.
• Enrollment Location(s): Columbia University Irving Medical Center's Department of OB/GYN, delivering at New York-Presbyterian Morgan Stanley Children's Hospital.

You may not qualify if:

• Current cigarette smoking
• Active drug use
• Unstable psychiatric condition
• Multiple fetal pregnancy
• Known chromosomal, genetic, or major fetal malformations (unlikely due to routine preimplantation genetic testing)
• Inflammatory conditions including rheumatoid arthritis, lupus, and multiple sclerosis
• Current use of synthetic glucocorticoids
• Not planning to deliver at a CUIMC-affiliated hospital

Sponsors & Collaborators

• Columbia University: lead
• University of California, Los Angeles: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Columbia University Irving Medical Center/New York Presbyterian Hospital

New York, New York, 10032, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Cord blood, placenta, maternal blood

MeSH Terms

Conditions

Developmental Origins of Health and Disease

Condition Hierarchy (Ancestors)

Prenatal Exposure Delayed Effects; Prenatal Injuries; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Catherine Monk, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catherine Monk, PhD

CONTACT

917-543-6031; cem31@cumc.columbia.edu

Khadija Jones, MPH

CONTACT

917-817-1490; kj2660@cumc.columbia.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Diana Vagelos Professor of Women's Mental Health

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: December 22, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2030
• Last Updated: February 13, 2026

Record last verified: 2026-02

Locations

US (1)