EARLY-PREG: A Preconception Cohort Study Based on Counterfactuals to Study Maternal-Embryonic Molecular Interactions

MELISA Institute Genomics & Proteomics Research

Status: Enrolling

Conditions: Healthy; Early Pregnancy Loss; Early Pregnancy; Childbirth; Pregnancy

Treatments: Other: EMBRYO EXPOSURE

Study type: Observational

Funder types: Industry

Identifiers

NCT07358026

MEL109112011, MEL109112011R4 (Other Grant/Funding Number)

MEL109112011R5, MEL131032017R1 (Other Grant/Funding Number)

17-03-06

MEL205062018, REH042024-01 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 223 estimated patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

223 participants in 2 patient groups

CONCEPTION CYCLE

Description:

Conception cycle refers to the menstrual cycle in which the ovum is fertilised, leading to pregnancy. Confirmation of a 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.

Treatment:

Other: EMBRYO EXPOSURE

NON-CONCEPTION CYCLE

Description:

Non-conception cycle 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. Confirmation of a non-conception cycle requires a clinically negative beta-hCG test, determined in peripheral venous blood on the 14th day post-ovulation. This cycle is characterised by the absence of a clinical pregnancy.