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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Origio A/S
ClinicalTrials.gov Identifier:
NCT00565747
First received: November 28, 2007
Last updated: November 20, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Infertility
Device: Test culture
Device: Control culture
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) During in Vitro Culture of Human Embryos on Subsequent Implantation Rates.

Resource links provided by NLM:


Further study details as provided by Origio A/S:

Primary Outcome Measures:
  • Ongoing Implantation Rate Week 7 [ Time Frame: Approximately 5 weeks from oocyte pick-up (corresponding to 7 weeks from ovulation) ] [ Designated as safety issue: No ]
    Defined as number of gestational sacs with fetal heart beat, shown by ultrasound in gestational week 7 in percentage of number of embryo transferred.


Secondary Outcome Measures:
  • Number of Top Quality Embryos (TQE´s) [ Time Frame: 3 days from oocyte pick-up ] [ Designated as safety issue: No ]
    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.

  • Live Birth [ Time Frame: Until 7 days after birth ] [ Designated as safety issue: Yes ]
    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).


Enrollment: 1332
Study Start Date: November 2007
Study Completion Date: September 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Test culture
Culture with GM-CSF
Device: Test culture
A standard culture medium with added GM-CSF (ready-to-use)
Other Name: 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 Name: EmbryoAssist

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.

  Eligibility

Ages Eligible for Study:   25 Years to 39 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00565747

Locations
Denmark
Ciconia Aarhus Privathospital, Fertilitetsklinikken
Aarhus, Denmark, 8270
Brædstrup Sygehus; IVF-Klinikken
Brædstrup, Denmark, 8740
Rigshospitalet, Fertilitetsklinikken afd. 4071
Copenhagen, Denmark, 2100
Fertilitetsklinikken Dronninglund
Dronninglund, Denmark, 9330
IVF-SYD
Fredericia, Denmark, 7000
Herlev Hospital, Fertilitetsklinikken G114F
Herlev, Denmark, 2730
Holbæk Sygehus, Fertilitetsklinikken
Holbæk, Denmark, 4300
Hvidovre Hospital; Fertilitetsklinikken afd. 455
Hvidovre, Denmark, 2650
Odense Universitets Hospital, Fertilitetsklinikken
Odense, Denmark, 5000
Regionshospitalet Skive, Fertilitetsklinikken
Skive, Denmark, 7800
Maigaard Fertilitetsklinik
Århus, Denmark, 8200
Sweden
IVF Kliniken Öresund
Malmö, Sweden, 205 12
Karolinska Universitetssjukhuset Huddinge, Fertilitetsenheten K59
Stockholm, Sweden, 14186
Reproduktionscentrum
Uppsala, Sweden, 751 85
Sponsors and Collaborators
Origio A/S
Investigators
Principal Investigator: Søren Ziebe, M.Sc. Rigshospitalet, Fertilitetsklinikken afd. 4071
  More Information

No publications provided by Origio A/S

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Origio A/S
ClinicalTrials.gov Identifier: NCT00565747     History of Changes
Other Study ID Numbers: DK001, Journal no. 8313-24, Journal no. 461:2007/78029
Study First Received: November 28, 2007
Results First Received: May 7, 2013
Last Updated: November 20, 2013
Health Authority: Denmark: Danish Medicines Agency
Sweden: Medical Products Agency

Keywords provided by Origio A/S:
GM-CSF
infertility

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female

ClinicalTrials.gov processed this record on April 16, 2014