Clinical trial NCT06877429: Is the Diurnal Variation in Circulating Levels of Cortisol Reflected in Follicular Fluid of Preovulatory Follicles Close to Ovulation?
Official title: Is the Diurnal Variation in Circulating Levels of Cortisol Reflected in Follicular Fluid of Preovulatory Follicles Close to Ovulation?
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Healthy
Keywords: ovarian stimulation
cortisol
cortisone
Lead sponsor: ART Fertility Clinics LLC
Sponsor class: OTHER
First posted: 2025-03-14
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Healthy women

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.


Eligibility criteria: 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

Primary outcomes:
measure: Evaluate the concentration of cortisol and cortisone in serum and follicular fluid samples collected at 8 am versus collection at 8 p.m.
timeFrame: From enrollment to the end of treatment at 8 weeks
Secondary outcomes:
measure: Evaluate the concentration of sex-steroids and cortisol metabolites in follicular fluid samples collected at 8 am versus collection at 8 p.m.
timeFrame: From enrollment to the end of treatment at 8 weeks
Other outcomes:
Locations:
city: Abu Dhabi
country: United Arab Emirates
facility: ART Fertility Clinics LLC
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.