PRIOR Study (Pre-eclampsia Risk In Oocyte Recipients) (PRIOR)

April 7, 2026 updated by: Pernille Fog Svendsen, Copenhagen University Hospital, Hvidovre

PRIOR Study (Pre-eclampsia Risk In Oocyte Recipients) - Investigating Matching, Biomarkers and Outcomes.

The aim of this prospective observational cohort study is to investigate the pathophysiological mechanisms behind and risk of pre-eclampsia in women pregnant after fertility treatment with oocyte donation. The participants are included in of of two cohorts. One includes women pregnant after oocyte donation whereas the other includes women pregnant after IVF treatment with autologous oocytes.

Participants will be followed throughout pregnancy with blood samples, blood pressure, clinical controls and ultrasound examinations. Clinical outcomes will be registered post-partum.

Study Overview

Status

Recruiting

Conditions

Detailed Description

INTRODUCTION AND BACKGROUND Maternal age at conception has increased globally, leading to a higher proportion of pregnancies among women aged ≥35 years. In Denmark, the average maternal age at first birth has risen from 24 years in 1970 to 30 years in 2021. As female fecundity declines markedly after age 35, the need for assisted reproductive technology (ART) is increasing.

The success rate of ART using autologous oocytes decreases significantly after age 40, making oocyte donation (OD) a relevant option for women with diminished ovarian reserve or poor oocyte quality. OD was first introduced in 1984 to treat infertility due to premature ovarian failure and is now used for various indications including Turner syndrome, previous oophorectomy, gonadotoxic therapy, and certain genetic disorders.

OD has been legal in Denmark since 2007 and double gamete donation since 2018. Healthy women under 36 years can donate oocytes anonymously or non-anonymously. The number of OD procedures in Denmark has increased from 124 in 2011 to 2,782 in 2022, resulting in 756 deliveries in 2021. The rise is attributed to delayed motherhood, legal changes, and increased donor compensation.

Several studies have demonstrated that pregnancies following OD are associated with a higher risk of obstetric complications, including pre-eclampsia (PE), intrauterine growth restriction, preterm birth, cesarean section, placental abruption, and postpartum hemorrhage. The risk appears to be even higher in double gamete donation pregnancies. The mechanisms behind these associations remain unclear but are thought to involve immune maladaptation due to exposure to non-self paternal and donor antigens.

PE complicates approximately 3-8% of pregnancies and is defined as new-onset hypertension (≥140/90 mmHg) with proteinuria (≥300 mg/24 h) and/or signs of organ dysfunction after 20 weeks of gestation. Risk factors include prior PE, chronic hypertension, renal disease, diabetes, autoimmune disease, multifetal gestation, nulliparity, advanced maternal age, high BMI, long interpregnancy interval, and family history of PE.

PE and related disorders share a common pathophysiology involving abnormal placentation, impaired trophoblast invasion, and endothelial dysfunction. The etiology is multifactorial and may include genetic, immunological, and vascular components. Recent data indicate that fetal-maternal HLA mismatches, particularly HLA-DR incompatibility, are associated with increased PE risk.

This study hypothesizes that OD pregnancies, known to have elevated risk of PE, provide a relevant model to investigate the pathophysiological mechanisms of the disease.

STUDY OBJECTIVE The aim of this prospective observational cohort study is to investigate the pathophysiological mechanisms and the risk of pre-eclampsia in women who become pregnant following fertility treatment with oocyte donation.

The study population comprises two cohorts. These are a cohort of women pregnant after oocyte donation compared with a cohort of women pregnant after IVF with autologous gametes.

PRIMARY RESEARCH QUESTIONS

  • To assess the risk of pre-eclampsia in pregnancies conceived after single or double gamete donation compared with pregnancies achieved using autologous gametes.
  • To investigate immunological and angiogenic biomarkers, as well as HLA tissue-type markers, involved in the pathogenesis of pre-eclampsia.
  • To evaluate obstetric and neonatal outcomes, including pre-eclampsia, gestational diabetes, preterm birth, placental abruption, intrauterine growth restriction, asphyxia, neonatal morbidity, and mortality among women pregnant after oocyte or double donation in Denmark.
  • To establish a comprehensive database and biobank to facilitate future research, including long-term follow-up studies of children born following oocyte donation.

Participants will be monitored throughout pregnancy with serial blood sampling, blood pressure measurements, clinical assessments, and ultrasound examinations. Clinical outcomes will be recorded postpartum.

INCLUSION OF PATIENTS STUDY POPULATION

The study will include two cohorts:

  1. Women who achieve pregnancy following oocyte or double gamete donation (OD cohort).
  2. Women who achieve pregnancy following IVF treatment with their own (autologous) frozen-thawed blastocysts (IVF control cohort).

Recruitment and Identification of Participants

Participants will be identified early in pregnancy through two recruitment pathways:

  1. Fertility Clinic Recruitment (Gestational Week 7-8)

    o Women attending an early pregnancy ultrasound after ART will breifly be informed about the study by fertility clinic staff.

    • If the woman expresses interest, her contact details (name, CPR number, and phone/email) will be forwarded to the principal investigator (PI).
    • The study team will contact the woman with detailed verbal and written information.
    • For women who are patients at Herlev Hospital, information will be provided in person, and a printed information sheet will be handed out.
    • For women treated at collaborating clinics (Rigshospitalet, Sellmer Fertility, Aleris Hamlet, Copenhagen Fertility Center, Trianglen), patient information will be provided via telephone, and written information will be either handed out or sent through secure digital mail (e-Boks).

  2. Referral from General Practitioner (Gestational Week 8-10)

    o When women are referred from their general practitioner to the obstetric department, the visitation office will notify the PI of potential participants.

    • Written study information will be sent via secure e-mail (e-Boks), including notification that the woman will receive a phone call from study staff within a few days.
    • The woman will receive verbal information and may schedule an inclusion visit if interested.

    INFORMED CONSENT All participants will receive both verbal and written information about the study. Women will be encouraged to bring a companion or assessor to the inclusion visit. The inclusion visit includes repeated verbal information, opportunity for questions, and a minimum 24-hour reflection period before signing the consent form. Consent covers study participation, access to relevant clinical records, and collection of biological samples as specified in the protocol.

    ELIGIBILITY CRITERIA

    • Inclusion Criteria:

    o Pregnant women who conceived through oocyte donation, double gamete donation, or IVF treatment using their own (autologous) oocytes.

    o Ability to understand study information and provide written informed consent.

    o Willingness to participate in follow-up visits throughout pregnancy.

    • Exclusion Criteria:

    • Withdrawal of consent at any time during the study period.
    • Known multiple pregnancy at the time of inclusion.
    • Chronic medical conditions such as hypertension,

    INCLUSION Inclusion Visit (Gestational Week 10-12) (Visit 1) At the inclusion visit, informed consent will be obtained by the principal investigator or a trained study nurse. Eligibility criteria will be verified, and baseline data will be collected, including demographic information (age, ethnicity, family status), medical and fertility history, hereditary diseases, and current medication. Lifestyle factors such as smoking and alcohol use will be recorded.

    A physical examination will be performed, including height, weight, blood pressure, and heart rate. Routine fertility screening (smear, TSH, TPO, AMH, HIV, hepatitis, syphilis, rubella) will extracted from the patient files. Blood samples for study-specific analyses, including pre-eclampsia biomarkers, will be collected.

    Follow-up Visits (Visit 2-6 and telemedicine)

    Participants will undergo structured follow-up visits throughout pregnancy:

    • Gestational Week 12-14: Nuchal translucency ultrasound and blood sampling for pre-eclampsia markers.

    • Gestational Week 18-20: Malformation ultrasound and blood sampling for pre-eclampsia markers.

    • Gestational Week 28: Initiation of weekly blood pressure measurements sent electronically to the hospital untill delivery. Bloodsampling for pre-eclampsia markers.
    • Gestational Week 34: Clinical visit with ultrasound, obstetric examination, and blood sampling for pre-eclampsia markers.
    • Gestational Week 38: Clinical visit with ultrasound and blood sampling for pre-eclampsia markers.

    Postpartum Data Collection After delivery, clinical outcome data will be obtained from electronic medical records. This includes gestational age at delivery, mode of delivery, birth weight, congenital malformations, and obstetric complications such as pre-eclampsia, gestational diabetes, intrauterine growth restriction, and postpartum hemorrhage.

    OUTCOME MEASURES

    Primary Outcome Measure:

    • Incidence of pre-eclampsia [Time Frame: From gestational week 20 until delivery]

      • Pre-eclampsia is defined as new-onset hypertension (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg) and proteinuria (≥300 mg/24h) and/or signs of organ dysfunction after 20 weeks of gestation. The primary outcome compares the incidence in pregnancies after oocyte or double gamete donation versus pregnancies after IVF with autologous oocytes.

    Secondary Outcome Measures:

  1. Immunological and angiogenic biomarkers [Time Frame: From inclusion until delivery] o Levels of specific biomarkers measured in maternal blood at multiple time points throughout pregnancy. Below are examples.

    o These are growth markers involved in early pregnancy (PAPP-A, IGF, PlGF, PGF and VEGFR), pro- and inflammatory cytokines (Interleukins, TNF-α and Interferon-γ), complement and thrombocyte activation markers (Selectin and BF-4), and markers for coagulation and fibrinolysis (Thrombin/anti-thrombin complexes and ex vivo fibrinogenesis/fibrinolysis).

  2. HLA tissue type markers

    o Analysis of HLA mismatches between fetus and mother and their association with pre-eclampsia risk.

  3. Obstetric complications [Time Frame: From inclusion until delivery]

    o Incidence of pre-eclampsia, postpartum hemorrhage, caesarean section, gestational diabetes, preterm birth (<37 weeks), IUGR, and placental abruption.

  4. Neonatal outcomes [Time Frame: Birth until hospital discharge]

    o Incidence of intrauterine growth restriction, birth asphyxia, neonatal morbidity, and neonatal mortality.

  5. Establishment of a database and biobank o Collection of clinical data and biological samples to enable future research, including potential long-term follow-up of children born after oocyte donation.

DATA COLLECTION AND HANDLING Signed informed consent allows access to relevant maternal and neonatal medical records for study purposes. All participant data will be collected in a secure electronic data capture system (REDCAP) compliant with local data protection regulations. Each participant will be assigned a unique study ID to ensure confidentiality. Source data will include electronic medical records, laboratory results, ultrasound reports, and telemedicine monitoring data. Only authorized study personnel will have access to identifiable data.

All study data will be recorded in case report forms (CRFs) and reviewed for completeness and accuracy. Queries will be resolved promptly with the study sites. Data will be backed up regularly, and audit trails will be maintained to track any changes to the dataset.

DATA STORAGE AND CONFIDENTIALITY Study data will be stored on secure servers with encryption. Access to identifiable information will be restricted to the principal investigator and designated study staff. Data will be retained for a minimum of 15 years following the end of the study, in accordance with institutional and national guidelines.

STATISTICAL ANALYSIS Data analysis will be performed according to a predefined statistical analysis plan. Descriptive statistics will be used to summarize baseline characteristics and clinical outcomes. Continuous variables will be expressed as means with standard deviations or medians with interquartile ranges, depending on distribution. Categorical variables will be presented as counts and percentages.

Comparisons between groups (e.g., oocyte donation vs. IVF pregnancies) will be conducted using appropriate statistical tests, such as t-tests or Mann-Whitney U tests for continuous variables and chi-square or Fisher's exact tests for categorical variables. Multivariable regression models will be applied to adjust for potential confounders.

All statistical tests will be two-sided, and a p-value <0.05 will be considered statistically significant. Interim analyses may be conducted if approved by the study steering committee, but final analyses will include all enrolled participants.

RISK MINIMIZATION The study involves minimal additional risk beyond standard clinical care for pregnant women. Blood draws will be performed by experienced personnel to minimize discomfort. Telemedicine monitoring will ensure timely detection of early signs of pre-eclampsia or other complications. Any participant developing severe complications will be referred for immediate clinical management according to standard obstetric protocols.

APPROVALS AND REGISTRATION The study is approved by the National Committee on Health Research Ethics (Approval no. H-22068878). This study was registered retrospectively on clinicaltrials.gov due to an administrative oversight in interpreting the prospective registration requirement. No changes were made to the protocol after study initiation. The research team has implemented revised internal procedures to ensure prospective registration for all future studies.

Study Type

Observational

Enrollment (Estimated)

462

Contacts and Locations

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

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2400
        • Recruiting
        • Copenhagen Fertility Center
        • Contact:
      • Hellerup, Denmark, 2900
        • Recruiting
        • Trianglen Fertility Clinic
        • Contact:
      • Herlev, Denmark, 2730
        • Recruiting
        • Fertility Clinic, Herlev / Gentofte Hospital
        • Contact:
      • København S, Denmark, 2300
        • Recruiting
        • Sellmer Klinik
        • Contact:
      • København Ø, Denmark, 2100
      • Søborg, Denmark, 2860
        • Recruiting
        • Aleris Fertility
        • 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
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Study population consists of women undergoing fertility treatment with IVF with either donated oocytes (Preg OD cohort) or autologous oocytes (Preg IVF cohort)

Description

Inclusion Criteria:

  • Age > 18 years
  • BMI < 35 kg/m2
  • Normal wet smear within the past three years
  • Both nulli- and multiparous
  • Singletons and multiple gestations

Exclusion Criteria:

  • Age < 18 years
  • BMI > 35 kg/m2
  • HIV/ hepatitis
  • Essential hypertension
  • Chronic kidney disease
  • Undiagnosed vaginal bleeding
  • Uterine malformations
  • Persisting ovarian cysts
  • Tumors in hypothalamus, pituitary, thyroid, or adrenal glands.
  • Previous breast cancer
  • Known BRCA 1 or 2 gene
  • Unregulated thyroid disease
  • Cardiovascular disease
  • Breast feeding
  • Present or previous chemotherapy/radiation therapy
  • Present or previous malignant disease
  • Smoking
  • Alcohol/drug abuse

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
Preg OD
Women pregnant after treatment with oocyte donation
Preg IVF
Women pregnant after IVF treatment with autologous oocytes

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pre-eclampsia
Time Frame: During pregnancy and in the following two weeks post-partum
Development of pre-eclampsia
During pregnancy and in the following two weeks post-partum
Biochemical markers for pre-eclampsia
Time Frame: From early pregnancy untill delivery
Analysis of bloodtests for biochemical markers of pre-eclampsia
From early pregnancy untill delivery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Post-partum hemorrhage
Time Frame: From delivery to 24 hours post-partum (Primary post-partum hemorrhage)
Excessive bleeding (above 1000 mL) post-partum
From delivery to 24 hours post-partum (Primary post-partum hemorrhage)
Gestational diabetes
Time Frame: During pregnancy untill delivery.
During pregnancy untill delivery.
Preterm delivery
Time Frame: Early delivery before gestational week 37
Delivery before gestational week 37.
Early delivery before gestational week 37
Placental abruption
Time Frame: During pregnancy and delivery
Abruption of placenta
During pregnancy and delivery
Intrauterine growth retardation (IUGR)
Time Frame: From pregnancy is obtained untill delivery
Fetal growth restriction
From pregnancy is obtained untill delivery
Asphyxia
Time Frame: During delivery or in the first 24 hours post-partum
Birth asphyxia
During delivery or in the first 24 hours post-partum
Neonatal morbidity
Time Frame: From delivery untill 28 days post-partum
Presence of health complications or adverse outcomes in newborn during the first 28 days of life.
From delivery untill 28 days post-partum
Neonatal mortality
Time Frame: From delivery untill 28 days post-partum
Death of a live-born infant within 28 days of life
From delivery untill 28 days post-partum

Collaborators and Investigators

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

Sponsor

Copenhagen University Hospital, Hvidovre

Collaborators

Ferring Pharmaceuticals
Gedeon Richter Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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 (Actual)

October 21, 2024

Primary Completion (Estimated)

October 31, 2027

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

November 18, 2025

First Submitted That Met QC Criteria

December 1, 2025

First Posted (Actual)

December 4, 2025

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 7, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-22068878
  • p-2024-17237 (Registry Identifier: Privacy.legal)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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