Randomized Controlled Trial Comparing Embryonic Quality in rFSH Versus hMG in IVF Protocol With GnRH Antagonist

Study Overview
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Brief Summary
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rFSH and HMG are both used to controlled ovarian stimulation for patients submitted to IVF. However, there is a debate in the literature which one is better to induce ovulation in patients receiving GnRH antagonist to block premature Luteinizing Hormone (LH) secretion. The investigators propose a Randomized Clinical Trial (RCT) to investigate the differences among recombinant FSH and HMG in patients submitted to IVF using GnRH antagonists.

Detailed Description
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To compare embryonic quality and other clinical outcomes when using human menopause gonadotropin (hMG) or recombinant follicle stimulating hormone (rFSH) to the ovarian stimulation in IVF cycles with the GnRH antagonist protocol. Design: open randomized single center study with infertile patients submitted to IVF comparing IVF outcomes between hMG and rFSH when controlled with GnRH antagonist. Setting: A single private center of reproductive medicine in association with Universidade Federal do Rio Grande do Sul. Patients: Infertile women with normal ovarian reserve with IVF indication. Intervention: The patients were randomized in two groups, 85 received rFSH and 83 received hMG to ovulation induction, both groups used GnRH antagonist to prevent ovulation. Main Outcome Measure: Total embryonic score and best embryonic score. Secondary outcomes: Total dose of gonadotropins, number and size of follicles in the end of the stimulation, number of mature oocytes, number of embryos, pregnancy rates.

Official Title
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Phase 4 Study Comparing Recombinant Follicle Stimulating Hormone (rFSH) or Ultra-pure to HMG in Patients Submitted to IVF Using Gnrh Antagonist

Conditions
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Infertility

Intervention / Treatment
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* Drug: rFSH
* Drug: HMG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 25 to 40 y infertile submitted to IVF no hormonal disease normal FSH (< 10) anti-mullerian hormone (AMH) > 1 ng and < 10 ng both ovaries only first or second IVF Exclusion Criteria: thyroid-stimulating hormone (TSH), prolactin (PRL) altered endometrioma ovarian tumor or cysts previous Ovarian Hyperstimulation Syndrome (OHSS) severe male factor

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 40 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: drug to ovulation induction: rFSH<br>Patients submitted to IVF that will use rFSH (Puregon®, Organon Ltd., Ireland) for ovarian stimulation | Drug: rFSH<br>* the patients will be asked to schedule an ultrasound in the first three days of the menstrual cycle and starts the ovarian stimulation with the previous randomized selected gonadotropin (rFSH or hMG) using a dose between 150 - 300 IU according with their AMH and antral follicle count (AFC). This dose will be maintained until day 6 of stimulation, when a second ultrasound will be performed and the GnRH antagonist will be initiated and continued until the end of the cycle. Seriated ultrasounds will be performed each two days<br>* Other names: Puregon®, Organon Ltd., Irlanda;|
| Other: drug to ovulation induction :HMG<br>Patients submitted to IVF that will use hMG (Menopur®, Ferring Pharmaceuticals, Denmark) for ovarian stimulation | Drug: HMG<br>* the patients will be asked to schedule an ultrasound in the first three days of the menstrual cycle and starts the ovarian stimulation with the previous randomized selected gonadotropin (rFSH or hMG) using a dose between 150 - 300 IU according with their AMH and AFC. This dose will be maintained until day 6 of stimulation, when a second ultrasound will be performed and the GnRH antagonist will be initiated and continued until the end of the cycle. Seriated ultrasounds will be performed each two days<br>* Other names: Menopur;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Embryo quality - score of embryo quality in the model od the Graduated Embryo Score (GES) | The embryo evaluation will be performed on day three after fertilization based on the Graduated Embryo Score (GES). It will be performed three evaluations occurring at 16 - 18 hours, 25 - 27 hours and 64 - 67 hours post insemination, by the same embryologist (DS) The score is composed by the following criteria: nucleolar alignment along pronuclear axis, regular cleavage and degree of fragmentation at the first cell division, and cell number and morphology on day 3 after fertilization. The score ranges from 20 to 100 per embryo. | 3 to 5 days after the ovarian punction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of follicles graduated by size in groups of 13-14mm; 15-16mm and more than 17mm |  | 10 to 13 days after the IVF protocol starts | 
| total number of units of gonadotrophins used to ovarian stimulation |  | 10 to 13 days after the IVF protocol starts | 
| number of oocytes retrieved (MII) |  | 10 to 13 days after the IVF protocol starts | 
| number of embryos |  | 3 to 5 days after the ovarian punction | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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follicular stimulating hormone, human menopausal gonadotrophin, Recombinant follicular stimulating hormone (rFSH), Gonadotrophin releasing hormone (GnRH) antagonists, GnRH agonist, in vitro fertilization, controled ovarian stimulation, number of mature oocytes