Ovarian Hyperstimulation and Fibrin Clot Properties.

Study Overview
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Brief Summary
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The impact evaluation of ovarian hyperstimulation on coagulation and fibrinolysis in infertile women. Comparative analysis between different ovarian stimulation protocols on thrombin formation and efficiency of fibrinolysis in women diagnosed with infertility.

Detailed Description
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Infertility is a common problem. Assisted reproductive techniques (ART) increases the chance of getting pregnant by couples undergoing such treatment. Unfortunately, the numer of live births after ART remains still low. Over the past three decades, physicians have tried to improve infertility diagnosis and increase its successful treatment. An effort aimed at increasing effectivenes of diagnosis resulted in hypothesis that one of probable reasons of infertility may be the occurrence of microclots, which worsen implantation and embryos development. There are currently no published studies describing the effects of different ovarian hyperstimulation protocols on hemostasis (coagulation and fibrinolysis). The parameters of thrombin generation and efficiency of fibrinolysis will be evaluated in women qualified for ovarian hyperstimulation. The study may improve the effectiveness of ART.

Official Title
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The Impact of Different Ovarian Hyperstimulation Protocols on Coagulation and Fibrinolysis.

Conditions
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Fibrin Blood Clot, Infertility, Female, Endometriosis

Intervention / Treatment
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* Diagnostic Test: fibrin clot properties


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: infertility defined based on the WHO 2010 criteria Exclusion Criteria: ovarian involvement oral contraceptives use within previous 3 months dienogest therapy within 3 months until ART thrombotic events in the medical history severe hypertension diabetes mellitus the presence of known VTE risk factors, including obesity, recent major surgery with prolonged immobilization or trauma, deficiency of antithrombin, protein C or protein S, antiphospholipid syndrome, known malignancy, any chronic inflammatory diseases (e.g. rheumatoid arthritis) advanced chronic renal disease (estimated glomerular filtration rate [eGFR] <30 ml/min), international normalized ratio (INR) more than 1.2 at the day of blood draw pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Long protocol<br>Ovarian hyperstimulation started on day 2 or 3 of the cycle with daily subcutaneous injections of recombinant human FSH (follitropin α, Gonal F®, Merck Serono) and/or urinary human menopausal gonadotropin (menotropin, Menopur®, Ferring GmbH) or mixed recombinant human FSH/LH (Pergoveris®, Merck Serono) with a starting dose of 87.5-250 IE/day | Diagnostic Test: fibrin clot properties<br>* Assessment of thrombin generation and efficiency of fibrinolysis.<br>|
| Active Comparator: Short protocol<br>Ovarian hyperstimulation with a GnRH-antagonist consisted of the use of ganirelix (Orgalutran®, MSD) from the 6th day of stimulation until it's end at the daily dose of 0.25 mg | Diagnostic Test: fibrin clot properties<br>* Assessment of thrombin generation and efficiency of fibrinolysis.<br>|
| Active Comparator: Clomiphene citrate<br>Ovarian stimulation with clomiphene citrate (Clostilbegyt®, EGIS) 50 mg daily per os form 3rd to 7th day of the cycle | Diagnostic Test: fibrin clot properties<br>* Assessment of thrombin generation and efficiency of fibrinolysis.<br>|
| Active Comparator: Letrozole<br>Ovarian stimulation with letrozole (Lametta®, Vipharm) 2.5 mg daily per os form 3rd to 7th day of the cycle | Diagnostic Test: fibrin clot properties<br>* Assessment of thrombin generation and efficiency of fibrinolysis.<br>|
| Active Comparator: Gonadotropins<br>Ovarian hyperstimulation started on day 2 or 3 of the cycle with daily subcutaneous injections of recombinant human FSH (follitropin α, Gonal F®, Merck Serono). | Diagnostic Test: fibrin clot properties<br>* Assessment of thrombin generation and efficiency of fibrinolysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fibrin clot properties before and after the ovarian hyperstimulation. | Coagulation (endogenous thrombin potential) and fibrinolysis (F1+2, clot lysis time)parameters assessment. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometriosis and fibrin clot properties. | Changes of fibrin clot properties before and after ovarian hyperstimulation in women with endometriosis - Coagulation (endogenous thrombin potential) and fibrinolysis (F1+2, clot lysis time)parameters assessment. | 1 cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coagulation, fibrinolysis, ovarian hyperstimulation, infertility