Effect of Colony Stimulating Factor on Poor Endometrial Development During IVF

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

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 Overview

• Status: Terminated
• Conditions: Infertility, Female
• Intervention / Treatment: Drug: G-CSF; Drug: Saline

Detailed Description

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%.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Center For Human Reproduction

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patient's preparing for invitro fertilization and embryo transfer with endometrial growth of less than 7 mm, unresponsive to standard treatment

Exclusion Criteria:

• Sickle Cell disease
• Renal insufficiency
• Upper respiratory infection or Pneumonia
• Chronic Neutropenia
• Known Past or present malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: G-CSF; G-CSF 300 units administered by trans-cervical infusion one time on day of hCG trigger for Ovulation	Drug: G-CSF; One infusion of G-CSF 300 units administered by intrauterine infusion; Other Names: NEUPOGEN (Filgrastim)
Placebo Comparator: Saline; Saline administered by trans-cervical infusion one time on day of hCG trigger for ovulation	Drug: Saline; One intrauterine saline infusions of 1 cc; Other Names: Normal Saline (Salt water); 0.91% w/v of NaCl, about 300 mOsm/L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endometrial Thickness	Thickness of the endometrium on the day of embryo transfer	Day of embryo transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation Rate	Number of gestational sacs per number of embryos transferred in each treatment group	28 days after embryo transfer

Collaborators and Investigators

• Sponsor: Center for Human Reproduction
• Collaborators: Foundation for Reproductive Medicine
• Investigators: Principal Investigator: David H Barad, MD, MS, Center For Human Reproduction; Study Chair: Norbert Gleicher, MD, Center For Human Reproduction

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: September 14, 2010
• First Submitted That Met QC Criteria: September 15, 2010
• First Posted (Estimate): September 16, 2010

Study Record Updates

• Last Update Posted (Actual): July 26, 2019
• Last Update Submitted That Met QC Criteria: July 13, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Thin Endometrium; Asherman's Syndrome; Endometrial Scarring
• Additional Relevant MeSH Terms: Infertility; Infertility, Female
• Other Study ID Numbers: 09012010-01