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Completed

NCT Number: NCT02761772

Early Pregnancy Cohort and Preimplantation Factor

Miscarriage is a common event associated with severe psychological and social morbidity, further tormenting in women suffering recurrent pregnancy loss (RPL) by at least three consecutive losses.

Ultrasonography and biomarkers have yet to precisely predict viability in pregnancies with symptoms of threatening miscarriage.

A novel biomarker Preimplantation Factor (PIF) derived by the developing embryo might be the key factor for this prediction ameliorating the implantation process by promoting a favorable local immune system in the uterus.

The investigators aim to establish a prospective early pregnancy cohort (PEP-cohort) that includes women throughout the first trimester by both assisted reproductive technology (ART) and spontaneous conceptions. By a combination of consecutive ultrasonographys and blood samples of known predictors of implantation PIF as a predictor of viability will be evaluated.

These data are finally compared to the same data in a retrospective cohort of RPL patients emphasizing the role of PIF.

All collected data will be stored in a Research Biobank for the current studies outlined as well as potential future studies of reproductive medicine in the first trimester.

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Key information

About this study

The investigators aim to evaluate Preimplantation Factor (PIF) throughout the first trimester we need to employ two settings of recruitment.

Early part:

The PEP in ART (PEP-A) will enroll participants referred for fertility treatment at Rigshospitalet and North Zealand Hospital. Participants all have cryopreserved embryos suitable for frozen embryo transfer in a natural menstrual cycle. No type of ovulation trigger will be employed, as the LH peak is monitored via home urine-LH test.

For a thorough examination of the luteal phase, participants are recalled for blood samples on day 7, 11, 14 and 16 after positive urine-LH test. Hereafter positive serum human chorionic gonadotropin (hCG) denotes a pregnancy and these participants are offered to continue in the later part of the PEP-cohort.

Late part:

PEP in Spontaneous conceptions (PEP-S) represents the sampling of expected normal pregnancies from the local community. Enrolled at the time of the first positive pregnancy test, participants are expected to be included from approximately 5 weeks of gestation. Hereafter participants are recalled every two weeks for blood sampling and transvaginal ultrasonographys of endometrial thickness until a gestational sac and yolk sac are visible for mean sac diameter measuring and eventually the crown-rump-length.

Research biobank All collected data: questionnaires of medical history before enrollment, ultrasonographys and blood samples of progesterone, 17-OH-progesterone, estradiol, alpha-feto-protein (AFP), pregnancy associated placental protein A (PAPP-A), hCG and PIF are stored in a research biobank.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

PEP-A

Inclusion criteria

  • Women in ART treatment by natural cycle frozen embryo transfer only monitored by urine LH.
  • Age above 18 years.
  • Ability to understand read and write Danish for the informed consent.
  • Planned delivery at the hospitals involved in the project.

Exclusion criteria

  • Abnormal uterine anatomy or function already known or estimated at first transvaginal ultrasonography.
  • History of recurrent pregnancy loss.
  • Ongoing or former (at least 12 months of no use) narcotics or alcohol abuse (above 14 units of alcohol per week).
  • Contraindication for pregnancy.

PEP-S

Inclusion criteria

  • Spontaneous pregnancy in women above 18 years of age.
  • Gestational age of singleton pregnancy below full eight weeks by first transvaginal ultrasound.
  • Ability to understand read and write Danish for the informed consent.
  • Planned delivery at the hospitals involved in the project.

Exclusion criteria

  • All types of ART treatment in the actual pregnancy.
  • Abnormal uterine anatomy or function already known or estimated at first transvaginal ultrasonography.
  • History of recurrent pregnancy loss.
  • Ongoing or former (at least 12 months of no use) narcotics or alcohol abuse (above 14 units of alcohol per week).
  • Contraindication for pregnancy.

Treatment and study plan

Primary outcomes

  1. PIF in PEP-A

    Time frame: During 2018

    Serum PIF by gestational age in the luteal phase

  2. Prediction model for the risk of spontaneous abortion

    Time frame: During 2018

    The ability of serum PIF to predict viability of natural pregnancies with and without other biomarkers, ultrasonographys and medical history data.

  3. PIF and recurrent pregnancy loss (RPL)

    Time frame: Late 2018

    Serum PIF levels in a unique retrospective cohort of RPL patients

Secondary outcomes

  1. Hormonal development in the luteal phase

    Time frame: During 2018

    Descriptive overview of natural hormones in the luteal phase and their ability to predict pregnancy and live birth rates

Other outcomes

  1. Research biobank for future use

    Time frame: During 2017

    Establishment of a robust research biobank for future studies in blood derived conditions in the first trimester of pregnancy

Sponsors and collaborators

Lead sponsor

Nordsjaellands Hospital

Other

Collaborators

  • BioIncept LLC
  • Rigshospitalet, Denmark
  • Yale University

Registry information

Official study title

Prospective Early Pregnancy Cohort and Preimplantation Factor: Factors Related to Successful Implantation, Risk of Miscarriage and Recurrent Pregnancy Loss in the First Trimester

Acronym: PEP-cohort

Important dates

Study start
2016
Primary completion
2017
Study completion
2018
First posted
May 4, 2016
Registry last updated
Mar 27, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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