Efficacy Study of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) for Use in Human IVF (GM-CSF)

April 28, 2015 updated by: Origio A/S

The Effect of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) During in Vitro Culture of Human Embryos on Subsequent Implantation Rates.

This study is to assess whether addition of 2 ng/ml GM-CSF into a specific culture medium will increase the chance of a pregnancy after in vitro fertilisation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Throughout its development, the embryo is naturally exposed to a large number of cytokines and growth factors that are present in the woman's reproductive organs. A growing body of evidence indicates that these factors play a physiological role in the regulation of normal development of the pre-implanted embryo and that these factors therefore help to increase the implantation of the embryo and subsequently ensure optimal development of both foetus and placenta. The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to be present in the female reproductive organs during early pregnancy in mice, sheep, cows and humans.

2 ng/ml GM-CSF has been proven safe in a previous study presented at the European Society of Human Reproduction and Embrylogy (ESHRE) congress 2007 (A. Loft et al. 2007).

The present investigation (DK001) is to our knowledge the first large prospective randomised in vivo study in humans. Previous publications counting one Korean pilotstudy of 154 women prospectively randomised between culture medium with and without GM-CSF 2 ng/ml (Kim et al., 2001), showing a significant effect of GM-CSF on embryo implantation rate.

Based on this knowledge we hypothesize that culture of human embryos in the presence of GM-CSF will significantly increase the implantation rate also in a larger population.

This hypothesis is being tested by conducting a multicentre, randomised, parallel group, double-blind, placebo-controlled study with adaptive design, performed at 14 study centres. Each patient will participate in the study from retrieval of oocytes following standard hormonal treatment and until the 12th gestational week. Further a follow-up will be performed on pregnancies and children born.

The test group will include a standard culture medium with 2 ng/ml GM-CSF added from the time of insemination, and the control group will be the exact same medium but without any additions.

All procedures are according to standards of the clinic, with applied standard media except for the patient randomised study medium which is used for oocyte insemination, embryo culture and transfer. Embryo transfer will be performed Day 3.

An interim analysis has been performed for final sample size calculation.

Study Type

Interventional

Enrollment (Actual)

1332

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus, Denmark, 8270
        • Ciconia Aarhus Privathospital, Fertilitetsklinikken
      • Brædstrup, Denmark, 8740
        • Brædstrup Sygehus; IVF-Klinikken
      • Copenhagen, Denmark, 2100
        • Rigshospitalet, Fertilitetsklinikken afd. 4071
      • Dronninglund, Denmark, 9330
        • Fertilitetsklinikken Dronninglund
      • Fredericia, Denmark, 7000
        • IVF-SYD
      • Herlev, Denmark, 2730
        • Herlev Hospital, Fertilitetsklinikken G114F
      • Holbæk, Denmark, 4300
        • Holbæk Sygehus, Fertilitetsklinikken
      • Hvidovre, Denmark, 2650
        • Hvidovre Hospital; Fertilitetsklinikken afd. 455
      • Odense, Denmark, 5000
        • Odense Universitets Hospital, Fertilitetsklinikken
      • Skive, Denmark, 7800
        • Regionshospitalet Skive, Fertilitetsklinikken
      • Århus, Denmark, 8200
        • Maigaard Fertilitetsklinik
  • Sweden
      • Malmö, Sweden, 205 12
        • IVF Kliniken Öresund
      • Stockholm, Sweden, 14186
        • Karolinska Universitetssjukhuset Huddinge, Fertilitetsenheten K59
      • Uppsala, Sweden, 751 85
        • Reproduktionscentrum

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 39 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • The couple or single woman has signed an informed consent form before any trial-related activities.
  • In Vitro Fertilization (IVF) or IntraCytoplasmic Sperm Injection (ICSI) treatment indicated
  • 25-39 years of age (both inclusive)
  • Regular menstrual cycle: 21-35 days (both inclusive)
  • Women treated with a standard Gonadotropin-Releasing Hormone (GnRH) agonist or antagonist protocol and a Follicle Stimulating Hormone (FSH) / human Menopausal Gonadotropin (hMG) starting dose between 100 and 300 IU daily.
  • human Chorionic Gonadotropin (hCG) administration when the leading follicle has a calculated diameter of minimum 17 mm, or the day after.
  • At least 3 follicles with a calculated diameter of ≥ 14 mm at the day of hCG.

Exclusion Criteria:

  • The woman has previously participated in the DK001 study.
  • Use of assisted hatching.
  • Indication for Testicular Sperm Aspiration (TESA) or Percutaneous Epididymal Sperm Aspiration (PESA)
  • Any medical conditions or genetic disorders prohibiting IVF/ICSI or interfering with the interpretation of results of the study (including pre-implantation genetic diagnostics).
  • Use of any investigational drug within 30 days before oocyte retrieval
  • Any severe chronic disease of relevance for reproductive function.
  • Oocyte donation patients (donor or recipient).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Test culture
Culture with GM-CSF
Device: Test culture
A standard culture medium with added GM-CSF (ready-to-use)
Other Names:
  • EmbryoGen
Placebo Comparator: Control culture
Culture without GM-CSF
Device: Control culture
The same standard culture medium, but without any additions (ready-to-use)
Other Names:
  • EmbryoAssist

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ongoing Implantation Rate Week 7
Time Frame: Approximately 5 weeks from oocyte pick-up (corresponding to 7 weeks from ovulation)
Defined as number of gestational sacs with fetal heart beat, shown by ultrasound in gestational week 7 in percentage of number of embryo transferred.
Approximately 5 weeks from oocyte pick-up (corresponding to 7 weeks from ovulation)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Top Quality Embryos (TQE´s)
Time Frame: 3 days from oocyte pick-up
Number of 4-5 cell embryo at 44 hours,at least 7 cell embryo at 68 hours, maximum 20% fragmentation, equally large blastomeres (less than 25% difference in size),No signs of multinucleation. Calculated in percentage of number of 2 pronuclei (2PN) oocytes.
3 days from oocyte pick-up
Live Birth
Time Frame: Until 7 days after birth
Subject having at least one live birth. Including a foetus which breathes or shows any other evidence of life after expulsion/extraction from its mother. The definition is independent of the duration of the pregnancy (ICMART/WHO criteria).
Until 7 days after birth

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Origio A/S

Investigators

  • Principal Investigator: Søren Ziebe, M.Sc., Rigshospitalet, Fertilitetsklinikken afd. 4071

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2007

Primary Completion (Actual)

November 1, 2010

Study Completion (Actual)

September 1, 2011

Study Registration Dates

First Submitted

November 28, 2007

First Submitted That Met QC Criteria

November 28, 2007

First Posted (Estimate)

November 30, 2007

Study Record Updates

Last Update Posted (Estimate)

May 15, 2015

Last Update Submitted That Met QC Criteria

April 28, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DK001
  • Journal no. 8313-24 (Other Identifier: Danish Medicines Agency)
  • Journal no. 461:2007/78029 (Other Identifier: Medical Products Agency - Sweden)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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