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

NCT ID: NCT00565747

Last Updated: 2015-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1332 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2011-09-30

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Test culture

Culture with GM-CSF

Group Type: EXPERIMENTAL

Test culture

Intervention Type: DEVICE

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

Control culture

Culture without GM-CSF

Group Type: PLACEBO_COMPARATOR

Control culture

Intervention Type: DEVICE

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

Interventions

Test culture

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

Intervention Type: DEVICE

Control culture

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

Intervention Type: DEVICE

Other Intervention Names

EmbryoGen; EmbryoAssist

Eligibility 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).

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Origio A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Søren Ziebe, M.Sc.

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Fertilitetsklinikken afd. 4071

Locations

Maigaard Fertilitetsklinik

Aarhus, , Denmark

Ciconia Aarhus Privathospital, Fertilitetsklinikken

Aarhus, , Denmark

Brædstrup Sygehus; IVF-Klinikken

Brædstrup, , Denmark

Rigshospitalet, Fertilitetsklinikken afd. 4071

Copenhagen, , Denmark

Fertilitetsklinikken Dronninglund

Dronninglund, , Denmark

IVF-SYD

Fredericia, , Denmark

Herlev Hospital, Fertilitetsklinikken G114F

Herlev, , Denmark

Holbæk Sygehus, Fertilitetsklinikken

Holbæk, , Denmark

Hvidovre Hospital; Fertilitetsklinikken afd. 455

Hvidovre, , Denmark

Odense Universitets Hospital, Fertilitetsklinikken

Odense, , Denmark

Regionshospitalet Skive, Fertilitetsklinikken

Skive, , Denmark

IVF Kliniken Öresund

Malmo, , Sweden

Karolinska Universitetssjukhuset Huddinge, Fertilitetsenheten K59

Stockholm, , Sweden

Reproduktionscentrum

Uppsala, , Sweden

Countries

Denmark; Sweden

References

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.

Reference Type: DERIVED

PMID: 32274634 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23380186 (View on PubMed)

Other Identifiers

Journal no. 8313-24

Identifier Type: OTHER

Identifier Source: secondary_id

Journal no. 461:2007/78029

Identifier Type: OTHER

Identifier Source: secondary_id

DK001

Identifier Type: -

Identifier Source: org_study_id