Trial Information

G-CSF and Endometrial Growth, Embryo Implantation and Pregnancy Following FET or Donor ET

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%.