Corpus Luteum Function and Cardiovascular Adaptation in a Natural MOCK Cycle. (CLEAR)

In infertility treatment, embryos are created in vitro after eggs have been fertilised by sperm using in vitro fertilisation or intracytoplasmic sperm injection techniques. These embryos, resulting from hormonal ovarian stimulation, can be transferred shortly after egg retrieval (fresh transfer) or frozen for later use. Both natural menstrual cycles and artificial cycles (using hormones to mimic a normal cycle) can prepare the uterus for embryo transfer. Patients with regular menstrual cycles often prefer the non-medicated approach. However, these cycles offer less flexibility in timing because they rely on ovulation. As the number of FET cycles increases worldwide, scientists are exploring the possibility of inducing ovulation in smaller follicles to increase the flexibility of natural cycles. However, the safety for future pregnancies is unknown. This study aims to better understand the function of the corpus luteum, the follicle remnant in the ovary after ovulation, by measuring several factors that change throughout the cycle due to substances produced by the corpus luteum. The results of the study will have a direct impact on clinical practice by increasing the flexibility of frozen transfer cycles.

Study Overview

• Status: Not yet recruiting
• Conditions: Menstrual Cycle; Luteal Phase Progesterone Levels; Luteal Phase Adaptation; MOCK Cycle
• Intervention / Treatment: Diagnostic test: Blood samples for the analysis of biomarkers.; Diagnostic test: Transvaginal ultrasound for follicle and endometrium measurements.; Diagnostic test: Mean Arterial Pressure measurement.; Drug: Ovitrelle injection for ovulation induction

• Study Type: Observational
• Enrollment (Estimated): 118

Contacts and Locations

• Study Contact: Name: Caroline Roelens; Phone Number: 0032 2 477 9887; Email: caroline.roelens@uzbrussel.be

Study Locations

• Belgium
  • Jette, Belgium, 1090
    • UZ Brussel
    • Contact: Caroline Roelens; Phone Number: 0032 2 477 9887; Email: caroline.roelens@uzbrussel.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Our study population pertains to female patients and volunteers, of the age between 18 years old and 40 years old, with a regular menstrual cycle (25-35 days) and a normal BMI (18.5-35). You are eligible if you have not used any form of hormonal contraception or copper IUD throughout the last 3 months, have not had an ovarian stimulation during this time period, and are not known with renal or cardiac disease, diabetes or hypertension.

Description

Inclusion Criteria:

• Age below 40 years
• Regular menstrual cycles (between 25-35 days)
• Normal BMI between 18.5 and 35

Exclusion Criteria:

• Underlying renal or cardiac disease
• Hypertension
• Diabetes mellitus
• Contraceptive use less than 3 months before MOCK cycle, including: IUD (hormonal and copper), hormonal patch, contraceptive pill (combination and mini), hormonal intravaginal ring, contraceptive implant, contraceptive injection.
• Ovarian stimulation during the previous three months
• History of recurrent pregnancy loss (defined as 2 or more previous pregnancy losses before 24 weeks gestation).

Study Plan

How is the study designed?

Number of groups / cohorts

8

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Follicle size 11mm; Patients with a follicle of 11mm when measured through transvaginal ultrasound in 2D, at time of ovulation induction.	Diagnostic test: Blood samples for the analysis of biomarkers.; We will collect several blood samples: One at day 8 of the cycle: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; One for cycle follow up between day 8 and ovulation: measurement of P, E2, LH; One at day 7 after ovulation induction: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; Diagnostic test: Transvaginal ultrasound for follicle and endometrium measurements.; A transvaginal ultrasound will be performed after day 8 of the cycle to evaluate a 2D measurement of the growing follicle, as well as a measurement of the endometrial thickness to evaluate readiness for ovulation induction.; Diagnostic test: Mean Arterial Pressure measurement.; The MAP will be measured at cycle day 7 and 7 days post-ovulation induction to follow cardiovascular adaptations.; Drug: Ovitrelle injection for ovulation induction; When patient is deemed ready for ovulation based on follicle size, blood results and endometrium, she will be asked to inject Ovitrelle 250 micrograms to induce ovulation in a controlled and timed manner.
Follicle size 12 mm; Patients with a follicle of 12mm when measured through transvaginal ultrasound in 2D, at time of ovulation induction.	Diagnostic test: Blood samples for the analysis of biomarkers.; We will collect several blood samples: One at day 8 of the cycle: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; One for cycle follow up between day 8 and ovulation: measurement of P, E2, LH; One at day 7 after ovulation induction: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; Diagnostic test: Transvaginal ultrasound for follicle and endometrium measurements.; A transvaginal ultrasound will be performed after day 8 of the cycle to evaluate a 2D measurement of the growing follicle, as well as a measurement of the endometrial thickness to evaluate readiness for ovulation induction.; Diagnostic test: Mean Arterial Pressure measurement.; The MAP will be measured at cycle day 7 and 7 days post-ovulation induction to follow cardiovascular adaptations.; Drug: Ovitrelle injection for ovulation induction; When patient is deemed ready for ovulation based on follicle size, blood results and endometrium, she will be asked to inject Ovitrelle 250 micrograms to induce ovulation in a controlled and timed manner.
Follicle size 13 mm; Patients with a follicle of 13mm when measured through transvaginal ultrasound in 2D, at time of ovulation induction.	Diagnostic test: Blood samples for the analysis of biomarkers.; We will collect several blood samples: One at day 8 of the cycle: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; One for cycle follow up between day 8 and ovulation: measurement of P, E2, LH; One at day 7 after ovulation induction: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; Diagnostic test: Transvaginal ultrasound for follicle and endometrium measurements.; A transvaginal ultrasound will be performed after day 8 of the cycle to evaluate a 2D measurement of the growing follicle, as well as a measurement of the endometrial thickness to evaluate readiness for ovulation induction.; Diagnostic test: Mean Arterial Pressure measurement.; The MAP will be measured at cycle day 7 and 7 days post-ovulation induction to follow cardiovascular adaptations.; Drug: Ovitrelle injection for ovulation induction; When patient is deemed ready for ovulation based on follicle size, blood results and endometrium, she will be asked to inject Ovitrelle 250 micrograms to induce ovulation in a controlled and timed manner.
Follicle size 14 mm; Patients with a follicle of 14mm when measured through transvaginal ultrasound in 2D, at time of ovulation induction.	Diagnostic test: Blood samples for the analysis of biomarkers.; We will collect several blood samples: One at day 8 of the cycle: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; One for cycle follow up between day 8 and ovulation: measurement of P, E2, LH; One at day 7 after ovulation induction: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; Diagnostic test: Transvaginal ultrasound for follicle and endometrium measurements.; A transvaginal ultrasound will be performed after day 8 of the cycle to evaluate a 2D measurement of the growing follicle, as well as a measurement of the endometrial thickness to evaluate readiness for ovulation induction.; Diagnostic test: Mean Arterial Pressure measurement.; The MAP will be measured at cycle day 7 and 7 days post-ovulation induction to follow cardiovascular adaptations.; Drug: Ovitrelle injection for ovulation induction; When patient is deemed ready for ovulation based on follicle size, blood results and endometrium, she will be asked to inject Ovitrelle 250 micrograms to induce ovulation in a controlled and timed manner.
Follicle size 15 mm; Patients with a follicle of 15mm when measured through transvaginal ultrasound in 2D, at time of ovulation induction.	Diagnostic test: Blood samples for the analysis of biomarkers.; We will collect several blood samples: One at day 8 of the cycle: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; One for cycle follow up between day 8 and ovulation: measurement of P, E2, LH; One at day 7 after ovulation induction: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; Diagnostic test: Transvaginal ultrasound for follicle and endometrium measurements.; A transvaginal ultrasound will be performed after day 8 of the cycle to evaluate a 2D measurement of the growing follicle, as well as a measurement of the endometrial thickness to evaluate readiness for ovulation induction.; Diagnostic test: Mean Arterial Pressure measurement.; The MAP will be measured at cycle day 7 and 7 days post-ovulation induction to follow cardiovascular adaptations.; Drug: Ovitrelle injection for ovulation induction; When patient is deemed ready for ovulation based on follicle size, blood results and endometrium, she will be asked to inject Ovitrelle 250 micrograms to induce ovulation in a controlled and timed manner.
Follicle size 16 mm; Patients with a follicle of 16mm when measured through transvaginal ultrasound in 2D, at time of ovulation induction.	Diagnostic test: Blood samples for the analysis of biomarkers.; We will collect several blood samples: One at day 8 of the cycle: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; One for cycle follow up between day 8 and ovulation: measurement of P, E2, LH; One at day 7 after ovulation induction: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; Diagnostic test: Transvaginal ultrasound for follicle and endometrium measurements.; A transvaginal ultrasound will be performed after day 8 of the cycle to evaluate a 2D measurement of the growing follicle, as well as a measurement of the endometrial thickness to evaluate readiness for ovulation induction.; Diagnostic test: Mean Arterial Pressure measurement.; The MAP will be measured at cycle day 7 and 7 days post-ovulation induction to follow cardiovascular adaptations.; Drug: Ovitrelle injection for ovulation induction; When patient is deemed ready for ovulation based on follicle size, blood results and endometrium, she will be asked to inject Ovitrelle 250 micrograms to induce ovulation in a controlled and timed manner.
Follicle size 17 mm; Patients with a follicle of 17mm when measured through transvaginal ultrasound in 2D, at time of ovulation induction.	Diagnostic test: Blood samples for the analysis of biomarkers.; We will collect several blood samples: One at day 8 of the cycle: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; One for cycle follow up between day 8 and ovulation: measurement of P, E2, LH; One at day 7 after ovulation induction: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; Diagnostic test: Transvaginal ultrasound for follicle and endometrium measurements.; A transvaginal ultrasound will be performed after day 8 of the cycle to evaluate a 2D measurement of the growing follicle, as well as a measurement of the endometrial thickness to evaluate readiness for ovulation induction.; Diagnostic test: Mean Arterial Pressure measurement.; The MAP will be measured at cycle day 7 and 7 days post-ovulation induction to follow cardiovascular adaptations.; Drug: Ovitrelle injection for ovulation induction; When patient is deemed ready for ovulation based on follicle size, blood results and endometrium, she will be asked to inject Ovitrelle 250 micrograms to induce ovulation in a controlled and timed manner.
Follicle size 18 mm; Patients with a follicle of 18mm when measured through transvaginal ultrasound in 2D, at time of ovulation induction.	Diagnostic test: Blood samples for the analysis of biomarkers.; We will collect several blood samples: One at day 8 of the cycle: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; One for cycle follow up between day 8 and ovulation: measurement of P, E2, LH; One at day 7 after ovulation induction: measurements of P, E2, Na, K, CL, CO2, Osmolality, PRL, direct renin, PAC, Nt-proBNP, Relaxin-2 and VEGF.; Diagnostic test: Transvaginal ultrasound for follicle and endometrium measurements.; A transvaginal ultrasound will be performed after day 8 of the cycle to evaluate a 2D measurement of the growing follicle, as well as a measurement of the endometrial thickness to evaluate readiness for ovulation induction.; Diagnostic test: Mean Arterial Pressure measurement.; The MAP will be measured at cycle day 7 and 7 days post-ovulation induction to follow cardiovascular adaptations.; Drug: Ovitrelle injection for ovulation induction; When patient is deemed ready for ovulation based on follicle size, blood results and endometrium, she will be asked to inject Ovitrelle 250 micrograms to induce ovulation in a controlled and timed manner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The relationship between progesterone levels and different follicular sizes on day 7 post ovulation induction.	Progesterone levels will be measured 7 days after ovulation induction to relate them to different follicular sizes.	From the start of the menstrual cycle until 7 days after ovulation induction.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estradiol evolution throughout the cycle and its relation to luteal progesterone levels.	We will measure the estradiol on different moments throught the menstural cycle, and see how these levels correspond to later (luteal) progesterone levels.	From the start of a menstrual cycle until 7 days post-ovulation induction.
Indirect factors reflecting cardiovascular and renal adaptation in the luteal phase	We will measure these factors (MAP, progesterone, estradiol, serum sodium, chloride, carbon dioxide and osmolality, prolactin, direct renin, plasma aldosterone, NT-proBNP, relaxin-2 and VEGF) at day 8 of the cycle, as well as 7 days after ovulation-induction. All these factors form a reflection of the body's cardiovascular and renal adaptation, and will be studied to estimate these adaptation at different follicular sizes.	From the start of the menstrual cycle until 7 days after ovulation induction.

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 15, 2026

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Investigative Techniques; Therapeutics; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Reproductive Techniques, Assisted; Reproductive Techniques; Gonadotropins; Placental Hormones; Pregnancy Proteins; Chorionic Gonadotropin; Blood Specimen Collection; Ovulation Induction
• Other Study ID Numbers: EC-2025-445

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No