Progesterone Levels During Ovulation and Luteal Phase

Progesterone Levels During Ovulation and Luteal Phase in Spontaneous Natural Ovulatory Cycles vs Modified Natural Cycle. A Prospective Study

Natural cycles are evaluated during fertility treatments for different therapeutic options, like insemination (IUI), time intercourse (TI) or frozen-thawed embryo transfers (FET). Two possible protocols can be used for natural cycles, with or without hCG trigger. Usually, studies including natural cycles consider both options as equivalent, not considering the possible bias that the exogenous hCG (human chorionic gonadotrophin) might have. In this prospective study, Investigators aim to evaluate the differences in the hormonal profile during the ovulation when it occurs spontaneously vs triggered with a bolus of hCG.

Study Overview

• Status: Completed
• Conditions: Infertility, Female
• Intervention / Treatment: Drug: human chorionic gonadotropin

Detailed Description

For the pure natural cycle (PNC), ovulation will be detected by a combination of ultrasound monitoring the follicular growth and serial measurement of luteinizing hormone (LH), estradiol (E2) and progesterone (P4) levels, which is recognised to be the most accurate method of correctly identifying ovulation.

For the modified natural cycle (MNC), a bolus of rhCG 6500 IU subcutaneous (sc) will be administered when 1 dominant follicle reaches 17mm or above, after excluding previous LH surge. This is the first prospective study where the differences on the hormonal profile for ovulation will be studied.

HYPOTHESIS:

H0: The hormonal profile is not different between the PNC and the MNC H1: The hormonal profile is different between the PNC and MNC

Administration of hCG is a popular method for triggering ovulation since it may avoid the need to perform IUI or FET at weekends. However, it is an intervention compared with the detection of the spontaneous LH rise. Moreover, due to the presence of hCG receptors in the human endometrium, administration of hCG might interfere with endometrial receptivity. Previous publications evaluating pregnancy rates demonstrated that the use of hCG injection during the natural cycle reduces the pregnancy rates, in FET and IUI. It remains unclear what might be the mechanism to explain the lower pregnancy rates: a possible direct effect of hCG on the hCG receptors of the endometrium or a modification of the hormonal profile after the administration of the hCG, affecting the window of implantation (WOI).

• Study Type: Observational
• Enrollment (Actual): 6

Contacts and Locations

Study Locations

• United Arab Emirates
  • Abu Dhabi, United Arab Emirates, 60202
    • ART Fertility Clinics LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

healthy women with spontaneous ovulation

Description

Inclusion Criteria:

• Healthy women below 40 years
• Regular and Ovulatory cycles

Exclusion Criteria:

• Previous adnexal surgery
• Endometriosis
• PCOs
• Using hormonal contraception during the previous 2 months: OCP, progesterone IUD

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pure Natural Cycle; Transvaginal ultrasound (TVUS) on day 2/3 of cycle + hormones FSH, LH, E2, P4 (IVF1); TVUS day 9-10 of cycle to identify dominant follicle.; Blood test for IVF1 every 24h until identification of the LH surge.; The LH surge will be diagnosed when the concentration rises by 180% above the latest serum value available in that patient and continued to rise thereafter (Fatemi et al, 2010).; Once the LH rise is detected, blood test for IVF1 to be performed after 2h, and then every 12h after LH rise for 2 days.; During luteal phase, IVF1 day 7 after LH rise and day 14 after LH rise.
Modified Natural Cycle; Transvaginal ultrasound (TVUS) on day 2/3 of cycle + hormones FSH, LH, E2, P4 (IVF1); TVUS day 9-10 of cycle to identify dominant follicle.; Once the dominant follicle reaches 17mm or above, a bolus of 6500 rhCG (Ovitrelle, Merck-Serono) will be administered subcutaneously. IVF1 to be performed just before the rhCG-administration.; IVF1 2h after rhCG.; IVF1 every 12h for 2 days after rhCG.; During luteal phase, IVF1 day 7 after rhCG and day 14 after rhCG.	Drug: human chorionic gonadotropin; once the dominant follicle reaches 17mm or above, a bolus of 6500 rhCG (Ovitrelle, Merck-Serono) will be administered subcutaneously; Other Names: Ovitrelle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in hormone levels	Small sample data will be analyzed with the use of non-parametric test like Wilcoxon test to a paired a test of difference in hormones levels of the patients represented in both cycles (PNC and MNC) (dependent samples). This test will be preferred due to non-independent interval or ratio data in addition not to meet the normality or homogeneity of variances assumptions as paired t-test. Hormonal pattern over the days (measured for some days during cycle 1 and cycle 2) will be analyzed using trend analysis (line fit).	35 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of visits in luteal phase	Number of visits will be analyzed. The differences will be analyzed across PNC and MNC with CI. Fisher's exact test.	17 days
Luteal phase length	Luteal phase length will be analyzed. The differences will be analyzed across PNC and MNC with CI. Fisher's exact test.	17 days

Collaborators and Investigators

• Sponsor: ART Fertility Clinics LLC
• Investigators: Principal Investigator: Laura Melado, PhD, ART Fertility Clinics LLC

Publications and helpful links

General Publications

• Hertzog MA. Considerations in determining sample size for pilot studies. Res Nurs Health. 2008 Apr;31(2):180-91. doi: 10.1002/nur.20247.
• Fatemi HM, Kyrou D, Bourgain C, Van den Abbeel E, Griesinger G, Devroey P. Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle. Fertil Steril. 2010 Nov;94(6):2054-8. doi: 10.1016/j.fertnstert.2009.11.036. Epub 2010 Jan 25.
• Licht P, Fluhr H, Neuwinger J, Wallwiener D, Wildt L. Is human chorionic gonadotropin directly involved in the regulation of human implantation? Mol Cell Endocrinol. 2007 Apr 15;269(1-2):85-92. doi: 10.1016/j.mce.2006.09.016. Epub 2007 Feb 14.
• Connelly LM. Pilot studies. Medsurg Nurs. 2008 Dec;17(6):411-2. No abstract available.
• Kyrou D, Kolibianakis EM, Fatemi HM, Grimbizis GF, Theodoridis TD, Camus M, Tournaye H, Tarlatzis BC, Devroey P. Spontaneous triggering of ovulation versus HCG administration in patients undergoing IUI: a prospective randomized study. Reprod Biomed Online. 2012 Sep;25(3):278-83. doi: 10.1016/j.rbmo.2012.05.005. Epub 2012 May 23.

Helpful Links

• van Belle, G. (2002). Statistical rules of thumb. New York: John Wiley

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2021
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): December 30, 2021

Study Registration Dates

• First Submitted: September 20, 2021
• First Submitted That Met QC Criteria: October 10, 2021
• First Posted (Actual): October 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: progesterone; human chorionic gonadotropin; luteal phase; natural cycle; ovulation; progesterone rise
• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Physiological Effects of Drugs; Reproductive Control Agents; Chorionic Gonadotropin
• Other Study ID Numbers: 2107-ABU-009-LM

Drug and device information, study documents

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