Fetal, Obstetrics and Reproduction Genomics (FORgenomics)

September 13, 2023 updated by: Fundación Ginemed
The purpose of this study is to determine the impact of a clinical screening strategy and genomic analysis of the factors involved in Placental Dysfunction (Preeclampsia and IUGR) in women of advanced maternal age undergoing assisted reproduction techniques (ART), specifically, in vitro fertilization (IVF) and oocyte donation.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Given society's shift towards later childbearing, partly related to increased career development, women are increasingly delaying childbearing and, as a result, face declining biological fertility and increased maternal morbidity and adverse perinatal pregnancy outcomes, as well as increased use of ART. Preeclampsia (PE) complicates 2% of pregnancies and is a leading cause of severe maternal and perinatal complications. There is no curative treatment, and the only recognized beneficial primary prevention is low-dose aspirin. Finding an effective method of predicting and preventing placental dysfunction (PD) in women of advanced maternal age undergoing ART remains a challenge.

The investigators believe that maternal and perinatal complications in this group of pregnant women could be detected preclinically and allow early preventive actions.

On the other hand, establishing a differentiated genomic pattern in this group of patients would allow preventive actions both pregestational and during gestation. Furthermore, FORgenomics can be used to externally validate a prediction model for the development of PE and IUGR in pregnancy after IVF/ovodon. Our results could be applicable in most healthcare settings and have important implications for maternal-fetal health.

The justification and hypothesis of this proposal is: (1) maternal and perinatal complications in this group of pregnant women could be detected preclinically and allow preventive actions by systematic screening based on Doppler ultrasound of uterine arteries and anti-angiogenic factors (sFlt-1/PlGF ratio) at 13, 16, 20 and 26 weeks to identify pregnant women at high risk for developing PE; (2) morphological ultrasound at 13, 16 and 20 weeks would help to establish a standardized procedure for early detection of congenital anomalies and (3) establishing a differentiated genomic pattern in this group of patients would allow preventive actions both pregestational and during gestation.

Study Type

Observational

Enrollment (Estimated)

400

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

  • Name: Guillermo Antiñolo Gil, PhD, MD
  • Phone Number: 0034955012772
  • Email: gantinolo@us.es

Study Contact Backup

  • Name: Lutgardo García-Díaz, PhD, MD
  • Phone Number: 0034955012772
  • Email: lgarcia14@us.es

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

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Sample

  1. Virgen del Rocío Hospital Area: according to the data obtained from the pregnant women who start the pregnancy process in the Andalusian Congenital Anomalies Screening Program (PACAC) in 2021, we expect a total population of 165 pregnant women per year with age at the start of pregnancy equal to or greater than 40 years, and whose pregnancy was obtained through IVF or ovodonation.
  2. Clínicas Ginemed: according to the data obtained from the report of Ginemed Clinics for the year 2021, we expect a total population of 150 pregnant women per year with an age at the onset of pregnancy equal to or greater than 40 years old, and whose gestation was obtained through IVF or ovodonation.

Description

Inclusion Criteria:

  • Singleton pregnancy
  • Age ≥40 years
  • Signed informed consent
  • Gestation obtained by IVF or ovodonation

Exclusion Criteria:

  • Non-ongoing pregnancy
  • Gestation obtained by artificial insemination
  • Naturally obtained gestation, without ART
  • Multiple pregnancy
  • Pregnancies complicated by major fetal abnormality identified at the first-trimester ultrasound
  • Age <18 years
  • Poor understanding of the Spanish or English languages
  • Refusal in informed consent to participate in the study
  • Participation in another intervention study that could modify follow-up

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with preeclampsia (PE) during pregnancy
Time Frame: ≥20 weeks to <37 weeks of gestation
Defined as systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90mmHg with an interval of at least 4 h after 20 weeks' gestation plus any of the following: (i) proteinuria (>300 mg/24 h) or a urine protein/creatinine ratio > 0.3 mg/mmol); (ii) end-organ dysfunction: systolic blood pressure > 160 mmHg, diastolic blood pressure >110 mmHg, platelet count <100x109/L, blood alanine and aspartate transaminases >70 IU/L, serum creatinine >1. 1 mg/dL, lactate dehydrogenase >700 IU/L, right upper quadrant or epigastric pain, dyspnea and/or cerebral/visual disturbances. Or (iii) utero-placental dysfunction (estimated fetal weight <3rd centile or <10th centile with abnormal uterine or umbilical Doppler [pulsatility index >95th centile]) as defined by the International Society for the Study of Hypertension in Pregnancy (ISSHP) with minor adaptations for study purposes.
≥20 weeks to <37 weeks of gestation
Number of fetuses diagnosed with intrauterine growth restriction (IUGR) during pregnancy
Time Frame: ≥20 weeks to <37 weeks of gestation
IUGR will be defined by the following criteria: Estimated fetal weight (EFW) between percentile (p) 3 and p 10 with Doppler alteration (uterine arteries > p 95 or cerebroplacental index < p 5, or middle cerebral artery < p 5, or umbilical artery > p 95). PFE < p 3 independently of feto-maternal Doppler.
≥20 weeks to <37 weeks of gestation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of fetuses and newborns with severe perinatal morbidity
Time Frame: From birth up to 7 days of life
Defined by a composite including any of the following: premature placental abruption, severe fetal growth restriction (birth weight <3rd centile), perinatal mortality, an Apgar score at 5'< 7.0, arterial pH less than 7.10, need for respiratory support within 72 hours of birth, neonatal intraventricular hemorrhage grade III/IV, necrotizing, periventricular leukomalacia, sepsis, bronchopulmonary dysplasia or encephalopathy due to hypoxic ischemic enterocolitis. Days of admission to ICU.
From birth up to 7 days of life
Cesarean section rate
Time Frame: During birth
Type of delivery and cesarean section rate will be recorded.
During birth
Number of Participants with pregnancy-related maternal morbidity
Time Frame: From conception up to 4 days after birth
defined by a composite including any of the following: (i) HELLP syndrome (lactate dehydrogenase [LDH] >700 IU/L, AST at twice normal values, and platelet count <100x109/L); (ii) central nervous system dysfunction (eclampsia, Glasgow Coma Score <13, stroke, reversible ischemic neurologic deficit, or cortical blindness); (iii) hepatic dysfunction (INR >1. 2 in the absence of disseminated intravascular coagulation, MELD score >10, or hepatic hematoma or rupture); (iv) renal dysfunction (dialysis, serum creatinine concentration greater than 150 μmol/L, or diuresis <0.5 mL/kg/h for 12 hours, according to renal failure by RIFLE criteria; or need for furosemide treatment to maintain diuresis >0. 5 mL/kg/h for 3 hours); (v) respiratory dysfunction (pulmonary edema, need for invasive or noninvasive mechanical ventilation, need for oxygen concentration greater than 50% for more than 1 hour, or severe respiratory distress [without pulmonary edema criteria but with presence of dyspnea,
From conception up to 4 days after birth
Maternal experience and psychological impact
Time Frame: From conception up to 4 days after birth

It will be assessed by:

- WHO Five Well-Being Index (WHO), Spanish version of 1998, applied at week 26. A brief self-assessment questionnaire on a person's perception of well-being over a specific period of time.
From conception up to 4 days after birth
Maternal anxiety and psychological impact
Time Frame: From conception up to 4 days after birth

It will be assessed by:

- Spielberger State-Trait Anxiety Questionnaire (STAI), in its Spanish adaptation applied in the 26th week of gestation. One of the first instruments validated in Spain and one of the most widely used by many researchers, it comprises two differentiated self-assessment scales: State Anxiety (SA), referring to a transitory anxious state that a person may feel in specific situations; and Trait Anxiety (RA), which characterizes a more or less stable anxious tendency that distinguishes people in their tendency to perceive situations as threatening.
From conception up to 4 days after birth

Collaborators and Investigators

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

Sponsor

Fundación Ginemed

Collaborators

University of Seville
Hospitales Universitarios Virgen del Rocío
Clínicas Ginemed
FIRST - Fetal, IVF and Reproduction Simulation Training Center

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

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)

October 1, 2023

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

January 29, 2023

First Submitted That Met QC Criteria

February 7, 2023

First Posted (Actual)

February 9, 2023

Study Record Updates

Last Update Posted (Actual)

September 14, 2023

Last Update Submitted That Met QC Criteria

September 13, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0001 (Cancer Research Institute)

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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