Is the Diurnal Variation in Circulating Levels of Cortisol Reflected in Follicular Fluid of Preovulatory Follicles Close to Ovulation?

May 6, 2026 updated by: Barbara Lawrenz, ART Fertility Clinics LLC

Glucocorticoids and especially cortisol exhibit a pronounced diurnal variation. Levels peak around 8 am and may decrease around two to three times during the day reaching a nadir during the evening and early in the night.

Ovulation has been described as a controlled inflammatory event. Following release of the oocyte, termination of the inflammatory reaction needs to take place in order for the follicle and the developing corpus luteum to avoid further damage. It has been suggested, that locally enhanced cortisol availability may play a role in limiting tissue damage and by acting as anti-inflammatory agents mediating repair and remodeling. The aim of the present study is evaluate the concentration of cortisol and cortisone in sets of serum and follicular fluid samples collected simultaneous and at different times of the day (8.00 a.m. and 8.00 p.m.) and compare the levels with the time of the day at which they are collected.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Healthy women

Description

Inclusion Criteria:

  • Indication for IVF / ICSI - treatment

    • Age ≥ 18 years and ≤ 35 years
    • Body weight: 19 - 29 kg/m2
    • Ovarian reserve parameters in the adequate age - range, determined by Anti-Muellerian-Hormone (AMH) and Antral Follicle Count (AFC) (Shebl 2011, Hamdine 2015)
    • Regular cycle (25-35 days)

Exclusion Criteria:

  • Age < 18 years and > 35 years

    • Body weight < 60 kg and > 90 kg
    • Ovarian reserve parameters outside the adequate age - range, determined by Anti-Muellerian-Hormone (AMH) and Antral Follicle Count (AFC) (Shebl 2011, Hamdine 2015)

    • Proven poor responder in preceding IVF-treatment-cycle, according to the Bologna criteria: at least two of the following three features must be present:

      (i) Advanced maternal age (≥40 years) or any other risk factor for POR (poor ovarian response) (ii) A previous POR (≤3 oocytes with a conventional stimulation protocol) (iii) An abnormal ovarian reserve test (i.e. AFC < 5-7 follicles or AMH < 0.5 -1.1 ng/ml)

    • Two episodes of POR after maximal stimulation are sufficient to define a patient as a poor responder in the absence of advanced maternal age or abnormal ORT
    • Diagnosis of polycystic ovarian syndrome (PCOS), according to Rotterdam criteria
    • Endometriosis stage 3 or 4 AFS (American Fertility Society)
    • Irregular cycle (< 25 days and > 35 days)
    • Treatment with GnRH-analogues during the previous 6 months
    • Intake of contraceptive pill (OCP) or any hormonal treatment during the last 3 months

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

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Group A: will have oocyte retrieval at 8.00 a.m.

Ovarian stimulation for both groups (Group A and B): 150 mcg Corifollitropin-Alpha (Elonva®, MSD) will be started in the afternoon of day 2/3 of the cycle. To inhibit premature LH surge, daily GnRH - antagonist (Orgalutran® 0,25mg, NV Organon) will be administered from the morning of day 6 of stimulation. From day 8 onwards, recFSH (Puregon, NV, The Netherlands) will be started and the dosage will be adjusted to the patients response. Final oocyte maturation will be achieved by administration of a dual trigger (5.000 IU of HCG (Pregnyl®,NV Organon) plus 0.3 mg of GnRH-agonist) as soon as ≥ 3 follicles ≥ 17 mm are present.

In case that patients are at risk of ovarian hyperstimulation (OHSS), defined as more than 20 follicles above 12 mm, patients will NOT receive hCG but only GnRH-agonist as trigger medication.

Oocyte retrieval will be carried out 36 hours after HCG administration. Previous studies have described ICSI and IVF procedures in detail (Van Steirteghem et al, 1993; Devroey
Procedure: Time of OPU
OPU procedure either at 8 am or 8 pm
Group B: will have oocyte retrieval at 8.00 p.m.

Ovarian stimulation for both groups (Group A and B): 150 mcg Corifollitropin-Alpha (Elonva®, MSD) will be started in the afternoon of day 2/3 of the cycle. To inhibit premature LH surge, daily GnRH - antagonist (Orgalutran® 0,25mg, NV Organon) will be administered from the morning of day 6 of stimulation. From day 8 onwards, recFSH (Puregon, NV, The Netherlands) will be started and the dosage will be adjusted to the patients response. Final oocyte maturation will be achieved by administration of a dual trigger (5.000 IU of HCG (Pregnyl®,NV Organon) plus 0.3 mg of GnRH-agonist) as soon as ≥ 3 follicles ≥ 17 mm are present.

In case that patients are at risk of ovarian hyperstimulation (OHSS), defined as more than 20 follicles above 12 mm, patients will NOT receive hCG but only GnRH-agonist as trigger medication.

Oocyte retrieval will be carried out 36 hours after HCG administration. Previous studies have described ICSI and IVF procedures in detail (Van Steirteghem et al, 1993; Devroey
Procedure: Time of OPU
OPU procedure either at 8 am or 8 pm

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Evaluate the concentration of cortisol and cortisone in serum and follicular fluid samples collected at 8 am versus collection at 8 p.m.
Time Frame: From enrollment to the end of treatment at 8 weeks
From enrollment to the end of treatment at 8 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Evaluate the concentration of sex-steroids and cortisol metabolites in follicular fluid samples collected at 8 am versus collection at 8 p.m.
Time Frame: From enrollment to the end of treatment at 8 weeks
From enrollment to the end of treatment at 8 weeks

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ART Fertility Clinics LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 30, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 10, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 14, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 7, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 6, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2025

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2502-ABU-005-BL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

upon request

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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