Effect of Colony Stimulating Factor on Implantation and Pregnancy Rates Following IVF (in Vitro Fertilization)

Study Overview
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Brief Summary
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This a trial designed to test whether granulocyte colony stimulating factor (G-CSF, Neupogen) can increase the rate of embryo implantation following IVF and embryo transfer. Preliminary data at the Center for Human Reproduction(CHR) and elsewhere suggest that intrauterine infusion of G-CSF can improve endometrial development and can increase implantation rates of embryos.

Detailed Description
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Objective: To investigate the effect of treatment with CSF on pregnancy rates in routine in vitro fertilization (IVF). Design: Double blinded crossover randomized controlled clinical trial Setting: Academically affiliated private infertility centers Subjects: Normal female IVF patients 18-38 years old, and above age 38 years, who are willing to be randomized to treatment. Interventions: Subjects receive transvaginally, utilizing an insemination catheter, a slow uterine lavage with G-CSF (Neupogen), 300ug (in 1 ml); controls receive saline. Patients who do not conceive will, after one month washout time, continue treatment in the opposite study arm. Main Outcome Measures: Implantation rate(IR) and pregnancy rates. Second Outcome Measures: Live birth rates and miscarriage rates. Statistical and Power considerations: Analysis will be by regression with IR as dependent and treatment as independent. Results will be adjusted by age and indices of ovarian reserve, such as antiMulerian Hormone (AMH). Presuming an implantation rate of 10% and anticipating a 10% increase to 20% with treatment, 120 women, producing about 200 embryos in each study arm, will have to be recruited for 80% power and alpha of 0.05.

Official Title
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G-CSF(Granulocyte Colony Stimulating Factor) and Embryo Implantation and Pregnancy Following IVF (in Vitro Fertilization)

Conditions
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Infertility, Female

Intervention / Treatment
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* Drug: G-CSF
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women already enrolled in an IVF cycle at one of the participating institutions Exclusion Criteria: Sickle Cell disease Renal insufficiency Upper respiratory infection or Pneumonia Chronic Neutropenia Known Past or present malignancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G-CSF then Saline<br>G-CSF (Granulocyte colony stimulating factor) | Drug: G-CSF<br>* One infusion of G-CSF 300 units administered by intrauterine infusion<br>* Other names: Neupogen (Filgrastim);Drug: Saline<br>* intrauterine saline infusion 1 cc<br>* Other names: 0.91% w/v of NaCl, about 300 mOsm/L;|
| Placebo Comparator: Saline then G-CSF<br>Normal Saline | Drug: G-CSF<br>* One infusion of G-CSF 300 units administered by intrauterine infusion<br>* Other names: Neupogen (Filgrastim);Drug: Saline<br>* intrauterine saline infusion 1 cc<br>* Other names: 0.91% w/v of NaCl, about 300 mOsm/L;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Embryo Implantation and Clinical Pregnancy Rates | Implantation rate: The number of gestational sacs noted in the endometrial cavity 26 to 30 days after embryo transfer divided by the number of embryos transferred Clinical pregnancy: Gestational sac with evidence of a viable pregnancy at least 28 days after embryo transfer | 26 to 30 days after embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live Birth Rates | Live birth rates among normal infertile couples undergoing IVF | Within nine months of embryo transfer | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fertility Agents, Female, In vitro fertilization