Short Versus Long Protocol for IVF and IVF+ICSI

Study Overview
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Brief Summary
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Purpose: Comparing a GnRH agonist and an antagonist protocol for IVF/ICSI with regard to frequency of ovarian hyperstimulation syndrome (OHSS) (1. outcome measure) quality of life (2. outcome measure) live birth rate (2. outcome measure) gene expression profiles of granulosa and cumulus cells, and concentrations of estradiol and vascular endothelial growth factor in follicular fluid(not only compared between GnRH agonist and antagonist protocol, but also between patients with OHSS and no OHSS and patients becoming pregnant and not becoming pregnant (2. outcome measure), and number of oocytes removed per treatment, number of embryo transfers per treatment and number of spontaneous abortions per treatment (these three parameters are tertiary outcome measures). In addition to the above mentioned efficacy outcome measures the safety outcome measure frequency of known side-effects will be compared between the two protocols.

Detailed Description
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Patients: 1100 patients are randomized prospectively to either treatment. Stratification: =<36 y/>36 y, IVF/ICSI, and treatment centre. Methods: OHSS is quantified by consecutive measurements of weight, abdominal diameter, ultrasound measurements of ascites and ovarian volume, paraclinical parameters, and by a systematic patient questionnaire. Furthermore it is registered if the patients have been hospitalized and/or have had ascites drainage performed due to OHSS. Data from the first 100 patients are used together with Golans OHSS-classification, to make a more precise definition of OHSS. This definition is applied prospectively on data from the remaining patients. Quality of life is gauged by a questionnaire. Child birth rate is ascertained by a pregnancy response questionnaire and by obtaining data from the Danish National Birth Registry. Statistics: The study is designed to be able to show a 50% reduction of OHSS comparing short to long protocol.

Official Title
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Short Versus Long IVF-treatment. A Prospective, Consecutive and Randomized Comparative Study

Conditions
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Infertility, Ovarian Hyperstimulation Syndrome, Quality of Life, Live Birth

Intervention / Treatment
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* Drug: Patients receiving short protocol IVF/ICSI-treatment.
* Drug: Long protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients referred for infertility receiving their first IVF or IVF+ICSI treatment Exclusion Criteria: Previous IVF or IVF+ICSI-treatment Uterine anomalies It is necessary to perform direct sperm aspiration from husband's/partner's testicles Allergy to one of the intervention products Patient is 40 years or above

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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No

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 |
| --- | --- |
| Experimental: 1<br>Patients receiving short protocol IVF/ICSI-treatment. Intervention pharmacon: GnRH-antagonist (Orgalutran®: Ganirelix) | Drug: Patients receiving short protocol IVF/ICSI-treatment.<br>* Injection s.c. Orgalutran® (Ganirelix)0.25 mg once daily from day 5 of FSH-stimulation until HCG-day<br>|
| Active Comparator: 2<br>Patients receiving long protocol IVF/ICSI-treatment. Intervention pharmacon: GnRH-agonist (Synarela®: Nafarelin) | Drug: Long protocol<br>* Patients receiving long protocol IVF/ICSI-treatment. Intervention pharmacon: GnRH-agonist (Synarela®:Nafarelin)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Ovarian Hyperstimulation Syndrome (OHSS) |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life during treatment |  | 3 years | 
| Live births |  | 3 years | 
| Gene expression profiles of granulosa and cumulus cells |  | 3 years | 
| Estradiol and vascular endothelial growth factor concentrations in follicular fluid. |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OHSS, quality of life, IVF, ICSI, GnRH-agonist, GnRH-antagonist