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AzTrials

InfertilityPhase 3GM-CSFNCT00565747

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

A Phase 3 study testing Test culture in people with Infertility, run by Origio A/S at 14 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 25 to 39 years, women only
Conditions the study is for
Infertility
What is being tested?
Test culture
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,332 participants
Where
14 sitesin 2 countries
Study dates
Nov 2007to Sep 2011
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 to 39 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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).

Trial locations and contacts

14 sites in 2 countries.

14 sites in 2 countries

Denmark11 sites

  • Maigaard Fertilitetsklinik

    Aarhus, 8200

  • Ciconia Aarhus Privathospital, Fertilitetsklinikken

    Aarhus, 8270

  • Brædstrup Sygehus; IVF-Klinikken

    Brædstrup, 8740

  • Rigshospitalet, Fertilitetsklinikken afd. 4071

    Copenhagen, 2100

  • Fertilitetsklinikken Dronninglund

    Dronninglund, 9330

  • IVF-SYD

    Fredericia, 7000

  • Herlev Hospital, Fertilitetsklinikken G114F

    Herlev, 2730

  • Holbæk Sygehus, Fertilitetsklinikken

    Holbæk, 4300

  • Hvidovre Hospital; Fertilitetsklinikken afd. 455

    Hvidovre, 2650

  • Odense Universitets Hospital, Fertilitetsklinikken

    Odense, 5000

  • Regionshospitalet Skive, Fertilitetsklinikken

    Skive, 7800

Other trials in Denmark

Sweden3 sites

  • IVF Kliniken Öresund

    Malmö, 205 12

  • Karolinska Universitetssjukhuset Huddinge, Fertilitetsenheten K59

    Stockholm, 14186

  • Reproduktionscentrum

    Uppsala, 751 85

Other trials in Sweden

About this study

Official title: 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.

Read the 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.

Conditions
Infertility
Being tested
Test culture, Control culture
Keywords
GM-CSF, infertility
Medical subject headings
Infertility

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Test cultureDevice

    Also called EmbryoGen

    A standard culture medium with added GM-CSF (ready-to-use)

  • Control cultureDevice

    Also called EmbryoAssist

    The same standard culture medium, but without any additions (ready-to-use)

Study groups in NCT00565747
Study groupRoleWhat they receive
Test cultureExperimentalCulture with GM-CSF
Receives: Device: Test culture
Control culturePlacebo comparatorCulture without GM-CSF
Receives: Device: Control culture

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ongoing Implantation Rate Week 7

    Defined as number of gestational sacs with fetal heart beat, shown by ultrasound in gestational week 7 in percentage of number of embryo transferred.

    Measured: Approximately 5 weeks from oocyte pick-up (corresponding to 7 weeks from ovulation)

Secondary outcomes (2)

  1. Number of Top Quality Embryos (TQE´s)

    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.

    Measured: 3 days from oocyte pick-up

  2. Live 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).

    Measured: Until 7 days after birth

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2007 (estimated)
  2. Study startNov 2007
  3. Primary completionNov 2010
  4. Study completionSep 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,332 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00565747
Sponsor's protocol ID
DK001
Other IDs
Journal no. 8313-24, Journal no. 461:2007/78029
Acronym
GM-CSF
Status last verified
Apr 2015
First submitted
28 Nov 2007
Last updated
15 May 2015
Data monitoring committee
No

Publications

  • Rodriguez-Wallberg KA, Munding B, Ziebe S, Robertson SA. GM-CSF does not rescue poor-quality embryos: secondary analysis of a randomized controlled trial. Arch Gynecol Obstet. 2020 May;301(5):1341-1346. doi: 10.1007/s00404-020-05532-3. Epub 2020 Apr 9.

    PubMed 32274634

  • Ziebe S, Loft A, Povlsen BB, Erb K, Agerholm I, Aasted M, Gabrielsen A, Hnida C, Zobel DP, Munding B, Bendz SH, Robertson SA. A randomized clinical trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium for in vitro fertilization. Fertil Steril. 2013 May;99(6):1600-9. doi: 10.1016/j.fertnstert.2012.12.043. Epub 2013 Feb 4.

    PubMed 23380186

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Test culture in people with Infertility, run by Origio A/S at 14 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Denmark, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ongoing Implantation Rate Week 7 (time frame: Approximately 5 weeks from oocyte pick-up (corresponding to 7 weeks from ovulation)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00565747, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2015.

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