The Role of Granulocyte Colony Stimulating Factor in Embryo Transfer Outcomes

Study Overview
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Brief Summary
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The goal of this clinical trial is to test the effect of granulocyte colony-stimulating factor (G-CSF, A.K.A. Filgrastim) in infertility patients undergoing in vitro fertilization (IVF) treatment. The main question it aims to answer is: Can in vitro fertilization-embryo transfer (IVF-ET) outcomes be improved by supplementing the transfer media with Granulocyte colony-stimulating factor (GCSF)? Participants will undergo their embryo transfer as per the normal clinic protocol but will be randomized to either receive the standard embryo transfer media or the GCSG-supplemented transfer media. Researchers will compare the GCSF and standard transfer media groups to see if clinical outcomes are improved (i.e., implantation rate, pregnancy, clinical pregnancy rate, live birth rate).

Detailed Description
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Please see uploaded study protocol.

Official Title
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The Role of Granulocyte Colony Stimulating Factor in Embryo Transfer Outcomes

Conditions
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Infertility, Infertility,Female, Infertility; Female, Nonimplantation, Infertility Unexplained, Infertility of Uterine Origin

Intervention / Treatment
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* Drug: Granulocyte Colony-Stimulating Factor (Filgrastim)
* Other: Standard Embryo Transfer Media


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recruited subjects will either be undergoing a fresh IVF-ET cycle in which the embryo(s) generated from the initial treatment cycle are transferred during that same cycle (i.e., on day 5 or 6 post-egg retrieval) or an FET cycle in which the embryo(s) transferred were generated in a previous IVF cycle and were cryopreserved for subsequent warming and transfer. Exclusion Criteria: Patients with uterine factor or severe male factor infertility will be excluded. Patients who have had previous IVF failures will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GCSF-Supplemented Embryo Transfer Media<br>Intervention Group Frozen Embryo Transfers: Cryopreserved embryos will be thawed according to the Kitazato thawing protocol and will be subsequently transferred to a center-well dish containing 1 mL of embryo transfer media supplemented with GCSF. The embryos will be cultured in this medium for approximately 3 hours before the embryo transfer (ET) procedure. During the ET procedure, the same media will be used to fill the ET syringe and catheter that will be used to deposit the embryos into the uterus by the physician. Fresh Embryo Transfers: On day 5 or 6 of culture, viable embryos will be transferred into a center-well dish containing 1 mL of embryo transfer media supplemented with GCSF. The embryos will be cultured in this medium for approximately 3 hours before the ET procedure. During the ET procedure, the same media will be used to fill the ET syringe and catheter that will be used to deposit the embryos into the uterus by the physician. | Drug: Granulocyte Colony-Stimulating Factor (Filgrastim)<br>* Intervention Group Fresh Embryo Transfers: On day 5 or 6 of culture, viable embryos will be transferred into a center-well dish containing 1 mL of embryo transfer media supplemented with GCSF. The embryos will be cultured in this medium for approximately 3 hours before the embryo transfer (ET) procedure. During the ET procedure, the same media will be used to fill the ET syringe and catheter that will be used to deposit the embryos into the uterus by the physician. Intervention Group Frozen Embryo Transfers: Cryopreserved embryos will be thawed according to the Kitazato thawing protocol and will be subsequently transferred to a center-well dish containing 1 mL of embryo transfer media supplemented with GCSF. The embryos will be cultured in this medium for approximately 3 hours before the ET procedure. During the ET procedure, the same media will be used to fill the ET syringe and catheter that will be used to deposit the embryos into the uterus by the physician.<br>* Other names: Filgrastim;|
| Placebo Comparator: Standard Embryo Transfer Media<br>Control Group Fresh Embryo Transfers: On day 5 or 6 of culture, viable embryos will be transferred into a center-well dish containing 1 mL of standard embryo transfer media. The embryos will be cultured in this medium for approximately 3 hours before the embryo transfer (ET) procedure. During the ET procedure, the same media will be used to fill the ET syringe and catheter that will be used to deposit the embryos into the uterus by the physician. Control Group Frozen Embryo Transfers: Cryopreserved embryos will be thawed according to the Kitazato thawing protocol and will be subsequently transferred to a center-well dish containing 1 mL of standard embryo transfer media. The embryos will be cultured in this medium for approximately 3 hours before the ET procedure. During the ET procedure, the same media will be used to fill the ET syringe and catheter that will be used to deposit the embryos into the uterus by the physician. | Other: Standard Embryo Transfer Media<br>* Control Group Fresh Embryo Transfers: On day 5 or 6 of culture, viable embryos will be transferred into a center-well dish containing 1 mL of embryo transfer media. The embryos will be cultured in this medium for approximately 3 hours before the embryo transfer (ET) procedure. During the ET procedure, the same media will be used to fill the ET syringe and catheter that will be used to deposit the embryos into the uterus by the physician. Control Group Frozen Embryo Transfers: Cryopreserved embryos will be thawed according to the Kitazato thawing protocol and will be subsequently transferred to a center-well dish containing 1 mL of embryo transfer media. The embryos will be cultured in this medium for approximately 3 hours before the ET procedure. During the ET procedure, the same media will be used to fill the ET syringe and catheter that will be used to deposit the embryos into the uterus by the physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implantation Rate | Number of embryos implanted (i.e. number of gestational sacs observed under ultrasound guidance) divided by total number of embryos transferred | From enrollment to the time of 6-week ultrasound. | 
| Clinical Pregnancy Rate | Number of patients with fetal heartbeats detected at time of 6-week ultrasound divided by the total number of patients in that group. | From enrollment to the time of 6-week ultrasound. | 
| Pregnancy Rate | Number of patients with a positive beta-human chorionic gonadotropin (bhCG) pregnancy blood test at 10 days post-ET divided by the total number of patients in that group. | From enrollment to the time of blood test at 10 days post-ET. | 
| Live Birth Rate | Total Number of infants born divided by the total number of embryo transfers performed (i.e., patients) in that group. | From enrollment to the time of birth (up to 9-months post-ET). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical Pregnancy Rate | Number of patients who had a positive beta-human chorionic gonadotropin (bhCG) pregnancy blood test at 10 days post-ET but that did not display a gestational sac/fetal heartbeat at 6-week ultrasound, divided by the total number of patients in that group. | From enrollment to the time of 6-week ultrasound. | 
| Spontaneous Abortion Rate | Number of patients with a confirmed clinical pregnancy who lost their pregnancy before 20 weeks of gestation divided by the total number of patients with confirmed clinical pregnancies. | From enrollment to the time of pregnancy loss (up to 20 weeks post-ET). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infertility, Embryo Transfer, GCSF, Granulocyte Colony-Stimulating Factor, Filgrastim, Neupogen, Implantation