Infertility, Female
Conditions
Keywords
Fertility Agents, Female, In vitro fertilization
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.
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.
Interventions
DRUGG-CSF
One infusion of G-CSF 300 units administered by intrauterine infusion
DRUGSaline
intrauterine saline infusion 1 cc
Sponsors
Foundation for Reproductive Medicine
Center for Human Reproduction
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Embryo Implantation and Clinical Pregnancy Rates | 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
| Measure | Time frame | Description |
|---|---|---|
| Live Birth Rates | Within nine months of embryo transfer | Live birth rates among normal infertile couples undergoing IVF |
Countries
United States
Participant flow
Recruitment details
All patients presenting for embryos transfer between October 3, 2010, and January 1, 2013, were offered participation in the trial. A total of 419 eligible patients were offered participation: Only 129 patients consented to participate in this study,(12 addtional patient participated in the thin endometrium study) and 278 declined
Pre-assignment details
The principal reasons for refusal to participate were ''lack of interest'' and technical difficulties in presenting in timely fashion for the treatment to the center. Women with renal disease, sickle cell disease, or a history of malignancy were considered ineligible. No consenting patient was excluded from participation for medical reasons.
Participants by arm
| Arm | Count |
|---|---|
| G-CSF Then Saline G-CSF (Granulocyte colony stimulating factor)
G-CSF 300 units administered by trans-cervical infusion one time on day of hCG trigger for Ovulation
then
Normal Saline
Saline administered by trans-cervical infusion one time on day of hCG trigger for ovulation | 67 |
| Saline Then G-CSF Normal Saline
Saline administered by trans-cervical infusion one time on day of hCG trigger for ovulation
then
G-CSF (Granulocyte colony stimulating factor)
G-CSF 300 units administered by trans-cervical infusion one time on day of hCG trigger for Ovulation | 62 |
| Total | 129 |
Baseline characteristics
| Characteristic | G-CSF Then Saline | Saline Then G-CSF | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 67 Participants | 62 Participants | 129 Participants |
| AntiMulerian Hormone (AMH) | 2.07 ng/mL STANDARD_DEVIATION 2.17 | 1.99 ng/mL STANDARD_DEVIATION 2.38 | 2.03 ng/mL STANDARD_DEVIATION 2.26 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 12 Participants | 23 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 8 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 44 Participants | 42 Participants | 86 Participants |
| Region of Enrollment Germany | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United Kingdom | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 66 participants | 61 participants | 127 participants |
| Sex: Female, Male Female | 67 Participants | 62 Participants | 129 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 81 | 0 / 80 |
| serious Total, serious adverse events | 0 / 81 | 0 / 80 |
Outcome results
Primary
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
Time frame: 26 to 30 days after embryo transfer
Population: Presuming an implantation rate of 10% and anticipating a 10% increase to 20% with treatment, about 200 embryos transferred in each study arm would be needed for 80% power and alpha of 0.05.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| G-CSF | Embryo Implantation and Clinical Pregnancy Rates | 32 Gestational sacs |
| Saline | Embryo Implantation and Clinical Pregnancy Rates | 33 Gestational sacs |
p-value: 0.72Cochran-Mantel-Haenszel
Secondary
Live Birth Rates
Live birth rates among normal infertile couples undergoing IVF
Time frame: Within nine months of embryo transfer
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| G-CSF | Live Birth Rates | 22 Live Birth |
| Saline | Live Birth Rates | 19 Live Birth |