Comparison of Blood Flow in the Arteriae Uterinae in Ovarian Stimulation Cycles

Study Overview
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Brief Summary
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This study will measure the blood flow in the aa. uterinae in women, undergoing firstly ovarian stimulation for In-Vitro Fertilization (IVF) / Intracytoplasmic sperm injection (ICSI), in Hormonal Replacement cycles (HRT) and Natural cycles (NC) for Frozen Embryo Transfer (FET)

Detailed Description
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To evaluate the influence of ovarian stimulation on the blood flow in the arteriae uterinae as well as whether there is an influence of the type of endometrial preparation for FET with either hormonal replacement therapy or natural cycle on the blood flow of the arteria uterina left / right

Official Title
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Comparison of Blood Flow in the Arteriae Uterinae in Ovarian Stimulation Cycles for IVF/ICSI, in Hormonal Replacement Cycles and Natural Cycles for Frozen Embryo Transfer

Conditions
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Endometrial Receptivity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who undergo ovarian stimulation in a Gonadotropin-Releasing-Hormone (GnRH)-antagonist protocol for IVF / ICSI Patients who have vitrified embryo(s) Preparation for FET either in HRT or NC cycle Exclusion Criteria: Poor responder according to Bologna criteria (Ferraretti et al.) as follows: At least two of the following three features must be present: (i) Advanced maternal age (≥40 years) or any other risk factor for poor ovarian reserve (POR); (ii) A previous POR (≤3 oocytes with a conventional stimulation protocol); (iii) An abnormal ovarian reserve test (i.e. antral follicle count (AFC) 5-7 follicles or anti-mullerian hormone (AMH) 0.5 -1.1 ng/ml). Uterine surgery for removal of fibroids (hysteroscopic, laparoscopic) or removal of uterine septum Endometriosis Asherman-Syndrome Previous cytotoxic treatment Previous radiation of the uterus / adnexal region Known hypertension Intake of Aspirin or similar medication which might influence the blood flow Status after tubal ligation Status after surgery in the adnexal region on 1 side
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 |
| --- | --- |
| Artificial (HRT) Cycles<br>Commence estradiol tablets (E2) 4mg from day 2 or 3 of period for 3 days Increase E2 to 6mg on day 4 of E2 treatment, according to clinician discretion based on endometrial thickness. Transvaginal scan throughout the HRT cycle to not only monitor endometrial development but to also exclude the presence of a dominant follicle on the ovaries. Serial measurements of serum LH (luteinizing hormone), estradiol and progesterone levels. Initial progesterone dose of 100mg at 22hrs (vaginal suppository) after ≥ 10 days and ≤ 16 days of estradiol administration when the minimal endometrial thickness achieved is 6mm with a trilaminar appearance. Subsequently increase progesterone administration to 100mg vaginally three times daily. Continue E2 administration 6mg (3 tablets daily). Embryo transfer is scheduled 5 days following the initial initiation of progesterone | |
| Spontaneous natural cycles<br>Day 2 of menses and throughout patients' natural cycle scans to monitor follicular growth. Measurements of serum LH, estradiol and progesterone levels to determine ovulation. The LH surge will be considered to have begun when the concentration rises by 180% above the most recent serum value and continues to rise thereafter (Irani et al. 2017, Fatemi et al., 2010). Day 1 after the LH rise, a decrease in estradiol concentration is identified. Twenty four hours later progesterone concentrations rise with a level of greater than or equal to 1.5nmol /L confirming ovulation (day 0) (Irani et al., 2017; Speroff et al.). This is considered as day 0 with initiation of vaginal progesterone 100mg at 22hrs that night. The following day (day 1) the patient increases progesterone administration to 100mg vaginally 8 hourly and continues until 7 weeks gestation as per clinic protocol. Embryo transfer is scheduled 5 days (day 5) following confirmation of ovulation (day 0). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the blood flow, calculated as Pulsatility Index (PI) and Resistance Index (RI), between the HRT- and the NC-FET cycles | On the day of progesterone administration / progesterone rise. Quantitative continuous variable | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous quantitative variable measured as the differences between average PI value | On the day of cycle start and the day of ovulation induction. Continuous quantitative variable measured in millimeters (mm) | 1 day | 
| Continuous quantitative variable measured as the differences between average RI value | On the day of cycle start and the day of ovulation induction | 2 days | 
| Thickness of the lining | Continuous quantitative variable measured in millimeters (mm) | 1 day | 
| Number of days of estradiol exposure | Before the embryo transfer | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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progesterone, endometrium, blood flow, estradiol