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

NCT06877429 | Not Yet Recruiting

• 1 other identifier: 2502-ABU-005-BL
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

ovarian stimulation; cortisol; cortisone

Outcome Measures

Primary Outcomes (1)

• Evaluate the concentration of cortisol and cortisone in serum and follicular fluid samples collected at 8 am versus collection at 8 p.m.

  From enrollment to the end of treatment at 8 weeks

Secondary Outcomes (1)

• Evaluate the concentration of sex-steroids and cortisol metabolites in follicular fluid samples collected at 8 am versus collection at 8 p.m.

  From enrollment to the end of treatment at 8 weeks

Study Arms (2)

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

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

Interventions

Time of OPU PROCEDURE

OPU procedure either at 8 am or 8 pm

Group A: will have oocyte retrieval at 8.00 a.m.; Group B: will have oocyte retrieval at 8.00 p.m.

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Women who undergo ovarian stimulation for IVF/ICSI at ART Fertility Clinic Abu Dhabi
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Healthy women

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• ART Fertility Clinics LLC: lead

Study Sites (1)

ART Fertility Clinics LLC

Abu Dhabi, United Arab Emirates

Location

Related Publications (5)

• Yong PY, Thong KJ, Andrew R, Walker BR, Hillier SG. Development-related increase in cortisol biosynthesis by human granulosa cells. J Clin Endocrinol Metab. 2000 Dec;85(12):4728-33. doi: 10.1210/jcem.85.12.7005.

  PMID: 11134135 BACKGROUND

• Tetsuka M, Thomas FJ, Thomas MJ, Anderson RA, Mason JI, Hillier SG. Differential expression of messenger ribonucleic acids encoding 11beta-hydroxysteroid dehydrogenase types 1 and 2 in human granulosa cells. J Clin Endocrinol Metab. 1997 Jun;82(6):2006-9.

  PMID: 9177422 BACKGROUND

• Yding Andersen C, Morineau G, Fukuda M, Westergaard LG, Ingerslev HJ, Fiet J, Byskov AG. Assessment of the follicular cortisol:cortisone ratio. Hum Reprod. 1999 Jun;14(6):1562-8.

  PMID: 10357976 BACKGROUND

• Shebl O, Ebner T, Sir A, Schreier-Lechner E, Mayer RB, Tews G, Sommergruber M. Age-related distribution of basal serum AMH level in women of reproductive age and a presumably healthy cohort. Fertil Steril. 2011 Feb;95(2):832-4. doi: 10.1016/j.fertnstert.2010.09.012.

  PMID: 20970126 BACKGROUND

• Hamdine O, Eijkemans MJ, Lentjes EW, Torrance HL, Macklon NS, Fauser BC, Broekmans FJ. Ovarian response prediction in GnRH antagonist treatment for IVF using anti-Mullerian hormone. Hum Reprod. 2015 Jan;30(1):170-8. doi: 10.1093/humrep/deu266. Epub 2014 Oct 29.

  PMID: 25355590 BACKGROUND

Central Study Contacts

Jonalyn Edades, EMBA

CONTACT

+97126528000; jonalyn.edades@artfertilityclinics.com

Barbara Lawrenz, PhD

CONTACT

+97126528000; barbara.lawrenz@artfertilityclinics.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Weeks
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Director

Study Record Dates

• First Submitted: March 10, 2025
• First Posted: March 14, 2025
• Study Start: December 30, 2025
• Primary Completion: April 30, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 2, 2025

Record last verified: 2025-06

Locations

AE (1)