Effect of Colony Stimulating Factor on Poor Endometrial Development During IVF
The purpose of this study is to investigate the effect of G-CSF on endometrial thickness in women who have failed reaching minimal endometrial thickness by standard treatments, to assess how many reach embryo transfer and what implantation and pregnancy rates are in comparison to control patients. The study will be conducted in women undergoing transfer of previously cryopreserved embryos or undergoing transfer of embryos from donor eggs.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||G-CSF and Endometrial Growth, Embryo Implantation and Pregnancy Following FET or Donor ET|
- Endometrial thickness [ Time Frame: Five days after first dose of G-CSF ] [ Designated as safety issue: No ]Number of participants reaching an Endometrial thickness of 7 mm or more on the 5th day after the first dose of G-CSF
- Clinical Pregnancy [ Time Frame: 4 weeks and 5 days after first dose of G-CSF ] [ Designated as safety issue: No ]Patients with evidence of a gestational sac on sonogram
|Study Start Date:||September 2010|
|Estimated Study Completion Date:||January 2013|
|Estimated Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
G-CSF 300 units
two infusions of G-CSF 300 units administered by intrauterine infusion on two occasions 48 hours apart
Other Name: NEUPOGEN (Filgrastim)
|Placebo Comparator: Saline||
two intrauterine saline infusions of 1 cc 48 hours apart
Objective: To investigate the effect of treatment with CSF : A placebo controlled double blinded crossover study.
Design: Crossover Randomized Control Trial
Setting: Academically affiliated private infertility centers
Subjects: Female IVF patients of all ages who are willing to be randomized to treatment and, in either IVF treatment, frozen embryo cycles (FET) or donor IVF cycles (D-IVF), 5 days before ET, have inadequate endometrial thickness.
Interventions: Subjects receive transvaginally, utilizing an insemination catheter, 2 slow intrauterine lavages with CSF-1 (Neupogen or generic, 300ug in 1 ml) 5 and 3 days, respectively, before embryo transfer and controls receive 1 ml of saline instead. Patients who do not become pregnant will after one month washout times continue treatment in the opposite study arm if they so choose and if they have remaining embryos.
Main Outcome Measures: Number of patients reaching embryo transfer with adequate endometrial thickness of at least 7mm.
Second Outcome Measures: Implantation and pregnancy rates..
Statistical and Power considerations: This is a Randomized Controlled Trial (RCT) with two study arms and panned crossover. Patients will be randomly assigned to Study group A or B according to a computer generated randomization table with 50:50 distributions. The study will test the null hypothesis that there is no difference in the transfer rates between the two groups. Transfer is only possible if the endometrial thickness reaches 7 mm or more. Order of treatment ab v ba will be added to the models as a separate factor and each phase will be analyzed as separate treatment strata.
The investigators are planning a study of independent cases and controls with 1 control per case. Prior data indicate that the transfer rate among controls is < 1%. If the true transfer rate for experimental subjects is 25%, the investigators will need to study 38 experimental subjects and 38 control subjects to be able to reject the null hypothesis that the transfer rates for experimental and control subjects are equal with probability (power) 0.8. The Type I error probability associated with this test of this null hypothesis is 0.05. We will use a continuity-corrected chi-squared statistic or Fisher's exact test to evaluate this null hypothesis.
There will be a planned interim analysis after 20 participants have completed the trial and if significant effects are observed the trial may be terminated at that time. The power to detect a difference in this interim analysis is only 42.6%.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01202643
|United States, New York|
|Center for Human Reproduction|
|New York, New York, United States, 10021|
|American Fertility Services|
|New York, New York, United States, 10022|
|Principal Investigator:||David H Barad, MD, MS||Center for Human Reproduction|
|Study Chair:||Norbert Gleicher, MD||Center for Human Reproduction|