Effect of Colony Stimulating Factor on Poor Endometrial Development During IVF

Sponsor
Center for Human Reproduction (Other)
Overall Status
Terminated
CT.gov ID
NCT01202643
Collaborator
Foundation for Reproductive Medicine (Other)
12
1
2
29
0.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
12 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
G-CSF and Endometrial Growth, Embryo Implantation and Pregnancy Following FET or Donor ET
Study Start Date :
Sep 1, 2010
Actual Primary Completion Date :
Feb 1, 2013
Actual Study Completion Date :
Feb 1, 2013

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. Endometrial Thickness [Day of embryo transfer]

      Thickness of the endometrium on the day of embryo transfer

    Secondary Outcome Measures

    1. Implantation Rate [28 days after embryo transfer]

      Number of gestational sacs per number of embryos transferred in each treatment group

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years to 45 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Center for Human Reproduction New York New York United States 10021

    Sponsors and Collaborators

    • Center for Human Reproduction
    • 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 Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    David H. Barad, Director of Clinical Research, Center for Human Reproduction
    ClinicalTrials.gov Identifier:
    NCT01202643
    Other Study ID Numbers:
    • 09012010-01
    First Posted:
    Sep 16, 2010
    Last Update Posted:
    Jul 26, 2019
    Last Verified:
    Jul 1, 2019
    Keywords provided by David H. Barad, Director of Clinical Research, Center for Human Reproduction
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details All patients presenting for embryos transfer between October 3, 2010, and January 1, 2013, were offered participation in the trial. A total of 419 eligible patients were offered participation: Only 12 patients consented to participate in this study,(129 addtional patient participated in the NCT01202656 study) and 278 declined.
    Pre-assignment Detail The principal reasons for refusal to participate were ''lack of interest'' and technical difficulties in presenting in timely fashion for the treatment to the center. Women with renal disease, sickle cell disease, or a history of malignancy were considered ineligible. No consenting patient was excluded from participation for medical reasons.
    Arm/Group Title G-CSF Then Saline Saline Then G-CSF
    Arm/Group Description G-CSF 300 units administered by trans-cervical infusion one time on day of hCG trigger for Ovulation then Saline administered by trans-cervical infusion one time on day of hCG trigger for ovulation Saline administered by trans-cervical infusion one time on day of hCG trigger for ovulation then G-CSF 300 units administered by trans-cervical infusion one time on day of hCG trigger for Ovulation
    Period Title: Period 1
    STARTED 6 6
    COMPLETED 6 6
    NOT COMPLETED 0 0
    Period Title: Period 1
    STARTED 1 2
    COMPLETED 1 2
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title G-CSF Then Saline Saline Then G-CSF Total
    Arm/Group Description G-CSF 300 units administered by trans-cervical infusion one time on day of hCG trigger for Ovulation then Saline administered by trans-cervical infusion one time on day of hCG trigger for ovulation Saline administered by trans-cervical infusion one time on day of hCG trigger for ovulation then G-CSF 300 units administered by trans-cervical infusion one time on day of hCG trigger for Ovulation Total of all reporting groups
    Overall Participants 6 6 12
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    6
    100%
    6
    100%
    12
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    39.79
    (5.13)
    39.38
    (6.03)
    39.59
    (5.56)
    Sex: Female, Male (Count of Participants)
    Female
    6
    100%
    6
    100%
    12
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    16.7%
    0
    0%
    1
    8.3%
    White
    5
    83.3%
    6
    100%
    11
    91.7%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    FSH (mIU/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mIU/mL]
    8.64
    (3.92)
    8.27
    (4.01)
    8.46
    (3.95)
    Endometrial Thickness (mm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mm]
    5.6
    (0.22)
    6.2
    (0.69)
    5.8
    (0.46)

    Outcome Measures

    1. Primary Outcome
    Title Endometrial Thickness
    Description Thickness of the endometrium on the day of embryo transfer
    Time Frame Day of embryo transfer

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title G-CSF Saline
    Arm/Group Description G-CSF 300 units administered by trans-cervical infusion one time on day of hCG trigger for Ovulation Saline administered by trans-cervical infusion one time on day of hCG trigger for ovulation
    Measure Participants 8 7
    Mean (Standard Deviation) [mm]
    11.3
    (3.1)
    7.8
    (0.8)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection G-CSF, Saline
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.67
    Comments
    Method ANCOVA
    Comments
    2. Secondary Outcome
    Title Implantation Rate
    Description Number of gestational sacs per number of embryos transferred in each treatment group
    Time Frame 28 days after embryo transfer

    Outcome Measure Data

    Analysis Population Description
    Presuming an implantation rate of 10% and anticipating a 10% increase to 20% with treatment, about 200 embryos transferred in each study arm would be needed for 80% power and alpha of 0.05.
    Arm/Group Title G-CSF Saline
    Arm/Group Description G-CSF 300 units administered by trans-cervical infusion one time on day of hCG trigger for Ovulation Saline administered by trans-cervical infusion one time on day of hCG trigger for ovulation
    Measure Participants 8 7
    Measure embryos transferred 14 18
    Number [Gestational sacs]
    1
    2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection G-CSF, Saline
    Comments Study was closed due to insufficient recruitment
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.74
    Comments
    Method Chi-squared, Corrected
    Comments

    Adverse Events

    Time Frame 1 year
    Adverse Event Reporting Description
    Arm/Group Title G-CSF Saline
    Arm/Group Description G-CSF 300 units administered by trans-cervical infusion one time on day of hCG trigger for Ovulation Saline administered by trans-cervical infusion one time on day of hCG trigger for ovulation
    All Cause Mortality
    G-CSF Saline
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    G-CSF Saline
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/8 (0%) 0/7 (0%)
    Other (Not Including Serious) Adverse Events
    G-CSF Saline
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/8 (0%) 0/7 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. David Barad
    Organization Center for Human Reproduction
    Phone 212 994-4400
    Email dbarad@theCHR.com
    Responsible Party:
    David H. Barad, Director of Clinical Research, Center for Human Reproduction
    ClinicalTrials.gov Identifier:
    NCT01202643
    Other Study ID Numbers:
    • 09012010-01
    First Posted:
    Sep 16, 2010
    Last Update Posted:
    Jul 26, 2019
    Last Verified:
    Jul 1, 2019