Progesterone Levels During Ovulation and Luteal Phase

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Infertility, Female

Intervention / Treatment
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* Drug: human chorionic gonadotropin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pure Natural Cycle<br>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<br>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<br>* once the dominant follicle reaches 17mm or above, a bolus of 6500 rhCG (Ovitrelle, Merck-Serono) will be administered subcutaneously<br>* Other names: Ovitrelle;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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luteal phase, natural cycle, human chorionic gonadotropin, progesterone, progesterone rise, ovulation