EARLY-PREG COHORT
EARLY-PREG is an open, preconception, longitudinal, bidirectional, and counterfactual cohort designed to investigate maternal–embryonic molecular communication during the first weeks after conception.
To date, this pioneering research has collected multiple types of biological samples—including cervicovaginal fluid (CVF), urine, blood, saliva, and cervicovaginal brushing—from healthy women in Chile who were trying to conceive, as well as samples during pregnancy and at delivery. The main strength of the study lies in its innovative design, which allows comparison of conception and non-conception cycles within the same woman, thus reducing interindividual variability. Currently, high-resolution proteomic techniques are being used to identify biomarkers in the earliest stages of pregnancy.
The aim of the EARLY-PREG cohort is to investigate the molecular crosstalk between the embryo and the mother during the first two weeks after conception. The primary objective is to characterize how the embryo and the maternal environment communicate at the molecular level before implantation—a fundamental process for successful pregnancy that remains poorly understood due to technical and ethical limitations in human studies.
This study seeks to identify changes in the proteome of biological fluids—particularly cervicovaginal fluid (CVF)—that may serve as biomarkers for the ultra-early stages of pregnancy.
COHORT Design
The EARLY-PREG open cohort adopted a preconception, longitudinal, bidirectional, and counterfactual cohort design. Between 2017 and 2024, three waves of recruitment were carried out, involving healthy women aged 18–40 who were trying to conceive, alongside a control group consisting of abstinent and sterilized women. Sociodemographic, clinical, and biological data were collected for up to six menstrual cycles, and during pregnancy for those who conceived.
Ovulation has been monitored using:
Ultrasound
LH test strips
Fertility monitors
During the menstrual cycle, the following biological samples are systematically collected:
Blood
Urine
Saliva
Cervicovaginal fluid (CVF)
Cervicovaginal brushing
Samples are stored in a biorepository for proteomic analysis via mass spectrometry, enabling daily molecular monitoring based on cycle outcomes.
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A fourth recruitment wave is scheduled to begin in 2025. This wave will focus on characterizing changes in maternal immunophenotypes in peripheral blood mononuclear cells during ultra-early pregnancy.
Significance
The importance of this research lies in the fact that, while many studies examine pregnancy from the eighth week onward, the ultra-early stages of conception and implantation remain a "black box" for scientists. This knowledge gap hinders the development of early diagnostic tools and effective treatments for reproductive challenges such as infertility or recurrent pregnancy loss.
Moreover, the counterfactual design of the cohort—where each woman serves as her own control between conception and non-conception cycles—represents a significant methodological advancement. This approach enhances the validity of findings by minimizing interindividual variability, which is particularly valuable in human reproductive biology research.
Recruitment to date
223 participants recruited
129 completed at least one fertile cycle under the protocol
407 menstrual cycles documented
55 conception cycles
35 full-term pregnancies
20 early pregnancy losses
Samples Collected and Stored
6400 cervicovaginal fluid (CVF) samples
5100 urine samples
1400 saliva samples
1000 blood samples
293 cervicovaginal brushing samples