Impact of Serum Progesterone in Modified Natural Cycles and Stimulated Cycles on Ongoing Pregnancy Rate (CORPUS-LUTEUM)

Impact of Serum Progesterone Concentration on the Day of Embryo Transfer in Modified Natural Cycles and Stimulated Cycles on Ongoing Pregnancy Rate

Prospective cohort unicentric study including infertile patients undergoing an embryo transfer in the context of natural or stimulated cycles and receiving luteal phase support with vaginal natural progesterone following the clinical practice in our clinic in IVIRMA Valencia, Spain.

Study Overview

Detailed Description

Progesterone as a promoter of endometrial maturation is essential for the process of embryo implantation. The transformation of the endometrium from a proliferative state to a receptive state depends on the adequate progesterone exposure of the endometrium. Therefore, in any assisted reproduction technique (ART) the management of the luteal phase with exogenous administered progesterone, aiming to achieve a receptive endometrial state, is an essential part of the therapy. This important part of infertility-treatment is called luteal phase support (LPS).

Currently, there is a scientific debate and research regarding the timing, the dose and route of administration of exogenous progesterone in ART cycles. For years, the administration of progesterone was based on a "one fits all"- concept, mainly driven from the doctors and patients' preference regarding dose, timing and route of administration of the exogenous progesterone. Due to the lack of solid and evidence-based knowledge, the LPS improving investigating LPS is of outmost importance.

Therefore, improving the LPS is continuously in the focus of research and investigation. Main objectives of those efforts are to clarify the optimal timing, dosage and route of administration of progesterone for every possible ART procedure, in order to improve therapy outcomes. Of special interest in this wide field is the management of LPS in embryo-transfer-cycles such as substituted cycles and modified natural cycles for frozen-thawed cycles, and in fresh embryo-transfers after stimulated cycles.

Measuring serum progesterone levels in the luteal phase of a transfer cycle seems to be a promising approach in resolving the former mentioned doubts. Now, research focuses on luteal-phase serum progesterone levels as a predictor of outcomes. The discovery of certain thresholds of progesterone levels in the serum would give us a handy tool for individualizing the LPS with the main objective to improve outcomes.

Previous studies could show that there exist certain thresholds of serum progesterone in substituted cycles that could be used as a predictor. Furthermore, the same group could show that modifying the dose and the route of administration in the sense of individualizing LPS can improve outcomes.

Considering those results, it remains to clarify if there also exist thresholds of serum progesterone in modified natural cycles and stimulated cycles and if it's possible to improve the results through individualization of LPS the same way as it has been shown for substituted cycles.

The intention of the present study is to carry out the determination of serum progesterone on the day of the embryo transfer to all those patients who are going to be subjected in IVIRMA Valencia to an embryo transfer in a modified natural cycle or a stimulated cycle.

Study Type

Observational

Enrollment (Actual)

488

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

Study Contact Backup

Study Locations

      • Valencia, Spain, 46015
        • Instituto Valenciano de Infertilidad Spain

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

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

All infertile patients undergoing a fresh or frozen blastocyst transfer (two blastocysts transferred as maximum) from own or donated oocytes; in the context of a modified natural cycle (group A) or a stimulated cycle (group B). As usually performed in our daily clinical practice, all patients will receive hCG to trigger ovulation and maintain the corpus luteum to produce endogenous progesterone. Luteal phase support will be given as usual according to the routine in our center.

Description

Inclusion Criteria:

  • The subject must provide written informed consent prior to any study related procedures
  • Women ≤50 years old
  • BMI ≤ 40 kg/m2
  • Adequate endometrial thickness (>6.5mm) and pattern (Triple A structure) in the proliferative phase
  • Regular menstrual cycles

Exclusion Criteria:

  • Uterine Pathology, adnexal pathology
  • Systemic diseases

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
MODIFIED NATURAL CYCLE

The term 'modified natural cycle' refers to a natural cycle in which ovulation is triggered by exogenous hCG administration in order to provide optimal timing scheduling embryo transfer. In contrast to the natural cycle, the applied hCG may lead to a different luteal phase profile. Luteal phase support is common clinical practice in those cycles.

On the day of embryo transfer (ET), eligible patients being transferred one or two good quality embryos on day 5 of development according to the Spanish ASEBIR classification will be informed about the nature of the study, read the informed consent (IC) form and decide if entering into the study. After signing the IC form, a blood test will be performed in a time frame between 1 and 2 hours before the ET.

The only intervention will be a single determination of serum P and E2 levels immediately before the embryo transfer.

The only intervention will be a single determination of serum P and E2 levels immediately before the embryo transfer.
STIMULATED CYCLE

On the day of embryo transfer (ET), eligible patients being transferred one or two good quality embryos on day 5 of development according to the Spanish ASEBIR classification will be informed about the nature of the study, read the informed consent (IC) form and decide if entering into the study. After signing the IC form, a blood test will be performed in a time frame between 1 and 2 hours before the ET.

The only intervention will be a single determination of serum P and E2 levels immediately before the embryo transfer.

The only intervention will be a single determination of serum P and E2 levels immediately before the embryo transfer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ongoing pregnancy rate
Time Frame: 12 months
Presence or absence of ongoing pregnancy
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Implantation rate
Time Frame: 12 months
Presence or absence of implantation
12 months
Live Birth
Time Frame: 12 months
Presence or absence of Live Birth
12 months
Pregnancy Loss
Time Frame: 12 months
Presence or absence of pregnancy loss
12 months

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Elena Labarta, MD, IVIRMA VALENCIA

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 (Actual)

February 19, 2020

Primary Completion (Actual)

July 25, 2022

Study Completion (Actual)

July 1, 2023

Study Registration Dates

First Submitted

February 5, 2020

First Submitted That Met QC Criteria

February 5, 2020

First Posted (Actual)

February 7, 2020

Study Record Updates

Last Update Posted (Actual)

October 24, 2023

Last Update Submitted That Met QC Criteria

October 23, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

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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