Efficacy Study of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) for Use in Human IVF
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 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.|
- 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.
- 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 2PN's.
- 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).
|Study Start Date:||November 2007|
|Study Completion Date:||September 2011|
|Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
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
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 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.
|Ciconia Aarhus Privathospital, Fertilitetsklinikken|
|Aarhus, Denmark, 8270|
|Brædstrup Sygehus; IVF-Klinikken|
|Brædstrup, Denmark, 8740|
|Rigshospitalet, Fertilitetsklinikken afd. 4071|
|Copenhagen, Denmark, 2100|
|Dronninglund, Denmark, 9330|
|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|
|Århus, Denmark, 8200|
|IVF Kliniken Öresund|
|Malmö, Sweden, 205 12|
|Karolinska Universitetssjukhuset Huddinge, Fertilitetsenheten K59|
|Stockholm, Sweden, 14186|
|Uppsala, Sweden, 751 85|
|Principal Investigator:||Søren Ziebe, M.Sc.||Rigshospitalet, Fertilitetsklinikken afd. 4071|