Effect of Colony Stimulating Factor on Implantation and Pregnancy Rates Following IVF (in Vitro Fertilization)

• ClinicalTrials.gov Identifier: NCT01202656
• Recruitment Status: Completed
• First Posted: September 16, 2010
• Results First Posted: December 2, 2014
• Last Update Posted: December 2, 2014
• Sponsor: Center for Human Reproduction
• Collaborator: Foundation for Reproductive Medicine
• Information provided by (Responsible Party): David H. Barad, Center for Human Reproduction

Study Description

Brief Summary:

This a trial designed to test whether granulocyte colony stimulating factor (G-CSF, Neupogen) can increase the rate of embryo implantation following IVF and embryo transfer. Preliminary data at the Center for Human Reproduction(CHR) and elsewhere suggest that intrauterine infusion of G-CSF can improve endometrial development and can increase implantation rates of embryos.

Condition or disease	Intervention/treatment	Phase
Infertility, Female	Drug: G-CSF; Drug: Saline	Phase 1; Phase 2

Detailed Description:

Objective: To investigate the effect of treatment with CSF on pregnancy rates in routine in vitro fertilization (IVF).

Design: Double blinded crossover randomized controlled clinical trial

Setting: Academically affiliated private infertility centers

Subjects: Normal female IVF patients 18-38 years old, and above age 38 years, who are willing to be randomized to treatment.

Interventions: Subjects receive transvaginally, utilizing an insemination catheter, a slow uterine lavage with G-CSF (Neupogen), 300ug (in 1 ml); controls receive saline. Patients who do not conceive will, after one month washout time, continue treatment in the opposite study arm.

Main Outcome Measures: Implantation rate(IR) and pregnancy rates.

Second Outcome Measures: Live birth rates and miscarriage rates.

Statistical and Power considerations: Analysis will be by regression with IR as dependent and treatment as independent. Results will be adjusted by age and indices of ovarian reserve, such as antiMulerian Hormone (AMH). Presuming an implantation rate of 10% and anticipating a 10% increase to 20% with treatment, 120 women, producing about 200 embryos in each study arm, will have to be recruited for 80% power and alpha of 0.05.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: G-CSF(Granulocyte Colony Stimulating Factor) and Embryo Implantation and Pregnancy Following IVF (in Vitro Fertilization)
• Study Start Date: September 2010
• Actual Primary Completion Date: December 2012
• Actual Study Completion Date: June 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: G-CSF then Saline; G-CSF (Granulocyte colony stimulating factor)	Drug: G-CSF; One infusion of G-CSF 300 units administered by intrauterine infusion; Other Name: Neupogen (Filgrastim); Drug: Saline; intrauterine saline infusion 1 cc; Other Names: Normal Saline; 0.91% w/v of NaCl, about 300 mOsm/L
Placebo Comparator: Saline then G-CSF; Normal Saline	Drug: G-CSF; One infusion of G-CSF 300 units administered by intrauterine infusion; Other Name: Neupogen (Filgrastim); Drug: Saline; intrauterine saline infusion 1 cc; Other Names: Normal Saline; 0.91% w/v of NaCl, about 300 mOsm/L

Outcome Measures

Primary Outcome Measures :

1. Embryo Implantation and Clinical Pregnancy Rates [ Time Frame: 26 to 30 days after embryo transfer ]

   Implantation rate: The number of gestational sacs noted in the endometrial cavity 26 to 30 days after embryo transfer divided by the number of embryos transferred

   Clinical pregnancy:

   Gestational sac with evidence of a viable pregnancy at least 28 days after embryo transfer

Secondary Outcome Measures :

1. Live Birth Rates [ Time Frame: Within nine months of embryo transfer ]
   Live birth rates among normal infertile couples undergoing IVF

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Women already enrolled in an IVF cycle at one of the participating institutions

Exclusion Criteria:

• Sickle Cell disease
• Renal insufficiency
• Upper respiratory infection or Pneumonia
• Chronic Neutropenia
• Known Past or present malignancy

Contacts and Locations

Locations

United States, New York

Center for Human Reproduction

New York, New York, United States, 10021

Sponsors and Collaborators

Center for Human Reproduction

Foundation for Reproductive Medicine

Investigators

• Principal Investigator: David H Barad, MD, MS; Center for Human Reproduction
• Study Chair: Norbert Gleicher, MD; Center for Human Reproduction

More Information

Publications of Results:

Barad DH, Yu Y, Kushnir VA, Shohat-Tal A, Lazzaroni E, Lee HJ, Gleicher N. A randomized clinical trial of endometrial perfusion with granulocyte colony-stimulating factor in in vitro fertilization cycles: impact on endometrial thickness and clinical pregnancy rates. Fertil Steril. 2014 Mar;101(3):710-5. doi: 10.1016/j.fertnstert.2013.12.016. Epub 2014 Jan 11.

• Responsible Party: David H. Barad, Director of Clinical Research, Center for Human Reproduction
• ClinicalTrials.gov Identifier: NCT01202656
• Other Study ID Numbers: 09012010-02
• First Posted: September 16, 2010
• Results First Posted: December 2, 2014
• Last Update Posted: December 2, 2014
• Last Verified: November 2014

Keywords provided by David H. Barad, Center for Human Reproduction:

Fertility Agents, Female; In vitro fertilization

Additional relevant MeSH terms:

Infertility; Infertility, Female; Lenograstim; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs