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

G-CSF(Granulocyte Colony Stimulating Factor) and Embryo Implantation and Pregnancy Following IVF (in Vitro Fertilization)

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.

Study Overview

• Status: Completed
• Conditions: Infertility, Female
• Intervention / Treatment: Drug: G-CSF; Drug: Saline

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 Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Center for Human Reproduction

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: Neupogen (Filgrastim); Drug: Saline; intrauterine saline infusion 1 cc; Other Names: Normal Saline; 0.91% w/v of NaCl, about 300 mOsm/L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Embryo Implantation and Clinical Pregnancy Rates	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	26 to 30 days after embryo transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live Birth Rates	Live birth rates among normal infertile couples undergoing IVF	Within nine months of embryo transfer

Collaborators and Investigators

• Sponsor: Center for Human Reproduction
• Collaborators: 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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: September 14, 2010
• First Submitted That Met QC Criteria: September 14, 2010
• First Posted (Estimate): September 16, 2010

Study Record Updates

• Last Update Posted (Estimate): December 2, 2014
• Last Update Submitted That Met QC Criteria: November 24, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: In vitro fertilization; Fertility Agents, Female
• Additional Relevant MeSH Terms: Infertility; Infertility, Female
• Other Study ID Numbers: 09012010-02