Childbirth, Early Pregnancy, Early Pregnancy Loss, Healthy, Pregnancy
Conditions
Keywords
longitudinal study, counterfactual design, embryo-mother crosstalk, biorepository, maternal fluids, menstrual cycle, preconception open cohort
Brief summary
EARLY-PREG is an open-cohort clinical study with a preconception, longitudinal, bidirectional and counterfactual design. The aim of this cohort is to investigate the proteomic signatures of maternal-embryonic communication by interrogating a growing biorepository of maternal fluids and tissues collected during the first two weeks after fertilisation. Participants in the EARLY-PREG cohort consist of healthy couples seeking pregnancy, as well as women who are not seeking to conceive. The three main outcomes in the cohort are defined according to menstrual cycles in which conception is achieved and those in which conception is not achieved. Their clinical definitions are as follows: * Pregnancy with a full-term live birth refers to the cycle in which the ovum is fertilised, leading to pregnancy, with beta-hCG levels above the clinical threshold for a positive pregnancy test. * Early pregnancy loss refers to a miscarriage up to 12 6/7 weeks. * Non-pregnancy refers to a menstrual cycle in which conception does not occur, confirmed by a clinically negative beta-hCG test. When referring to the same individual, this is, by definition, considered the counterfactual to the corresponding conception cycle.
Detailed description
Successful pregnancy depends on a coordinated exchange of signals between the early embryo and the mother. This complex process begins immediately after fertilisation, during the pre-implantation period. Although it plays a critical role in preparing the maternal environment for pregnancy, the mechanisms behind this communication remain incompletely understood. The unique 'dialogue' between the embryo and the mother is a bidirectional exchange known as embryo-maternal crosstalk. Evidence indicates that this interaction, mediated by molecular signals present in uterine fluid, supports appropriate embryo implantation and modulates the maternal immune system to facilitate tolerance of the developing embryo. To date, the majority of knowledge in this field has been derived from animal models and in vitro studies, which may not fully represent the physiology of spontaneous human conception. The EARLY-PREG preconception open cohort has been established to address this gap by characterising embryo-maternal crosstalk in vivo. This study follows healthy women who are trying to become pregnant, following them from before conception through the first two weeks of a natural conception, with continued follow-up into pregnancy and childbirth. Daily collection of a range of biological samples - including saliva, urine, blood, cervicovaginal fluid and cervicovaginal brushings - is undertaken during key phases of the menstrual cycle. These samples are processed, preserved and stored in a dedicated biorepository for subsequent analysis using omics-based approaches.
Interventions
OTHEREMBRYO EXPOSURE
The counterfactual design of EARLY-PREG enables the comparison of the systemic and localised physiological effects associated with embryo appearance and implantation in an individual (the factual) against the physiological state of the same individual without experiencing pregnancy (the counterfactual).
Sponsors
MELISA Institute Genomics & Proteomics Research SpA
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* being between 18 and 40 years of age * not being pregnant * normal colposcopy * body mass index (BMI) between 18 and 29 * regular menstrual cycles (21-35 days) * absence of chronic diseases (hypertension, diabetes mellitus, cancer, depression, personality disorder, thyroid pathology, polycystic ovary syndrome, or hyperprolactinemia). * If seeking pregnancy, they were included if their partners were males between 18 and 40 years old, without pathologies (diabetes mellitus, depression, personality disorder, or cancer), were not taking chronic medication, without erectile disorders, BMI between 18 and 29.9, moderate alcohol use, and with no recreational drug use.
Exclusion criteria
* pregnant women * history of alcoholism * infertility treatment * endometriosis * pelvic inflammatory disease * pelvic surgery * allergy to latex or silicone * If seeking pregnancy, they were excluded if their partners were working in contact with pesticides, or with history of erectile dysfunction, or history of mumps in adulthood, or with chronic diseases, or with psychological problems.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of menstrual cycles leading to full-term pregnancies | From enrollment for up to six menstrual cycles (each cycle ranges from 21-35 days) or until pregnancy resulting in live birth, whichever occurs first. | This outcome refers to the menstrual cycle in which the ovum is fertilised, leading to pregnancy with a full term live birth. The conception cycle requires beta-hCG levels above the clinical threshold for a positive pregnancy test, which is determined in peripheral venous blood on the 14th day post-ovulation. |
| Number of menstrual cycles not leading to pregnancy | From enrollment for up to six menstrual cycles (each cycle ranges from 21-35 days) or until pregnancy occurs, whichever occurs first. | This outcome refers to a menstrual cycle in which pregnancy does not occur. When referring to the same individual, it is, by definition, considered the counterfactual to the conception cycle described above. A non-conception cycle is confirmed by a clinically negative beta-hCG test, which is determined in peripheral venous blood on the 14th day post-ovulation. This cycle is characterised by the absence of a clinical pregnancy. |
| Number of menstrual cycles leading to early pregnancy loss | From the time beta-hCG levels rise above the clinical threshold for a positive pregnancy test until a miscarriage occurring up to 12 6/7 weeks. | This outcome refers to the menstrual cycle in which the ovum is fertilised, leading to a miscarriage until 12 6/7 weeks. The conception cycle requires beta-hCG levels above the clinical threshold for a positive pregnancy test, which is determined in peripheral venous blood on the 14th day post-ovulation. |
Countries
Chile
Contacts
CONTACTElard S Koch
CONTACTPatricio A Alcaino
STUDY_DIRECTORElard S Koch
MELISA Institute Genomics & Proteomics Research SpA
Outcome results
None listed