Infertility
Conditions
Brief summary
The purpose of this study is to evaluate implantation rate with intra-vaginal culture (IVC) with the INVOcell device versus traditional In-Vitro Fertilization (IVF) while using minimal stimulation protocols
Detailed description
This is a Phase IV, single center randomized controlled trial evaluating intra-vaginal culture (IVC) using INVOcell versus traditional In-Vitro Fertilization (IVF) using oral stimulation or minimal gonadotropin stimulation protocols. The pilot aims to includes 40 women who will be randomized to either the intra-vaginal culture group (N=20) using INVOcell or to the traditional IVF group (N=20). Primary aim is implantation rate, which is defined by number gestational sacs seen on early pregnancy ultrasound divided by number of embryos transferred. Secondary aims are: * Embryo quality, which is measured by system similar to the Gardner grading system at cleavage stage. Reported quality will be converted to the simplified SART embryo scoring system which provides an overall categorical embryo grade of Good, Fair or Poor. * Fertilization rate, which is defined by the total number of fertilized oocytes divided by total number of mature oocytes retrieved. This comparison will take place on day-3, as that is when the IVC embryos will be assessed. * Clinical pregnancy rate, which is defined by the number of fetal poles with heartbeat seen on ultrasound divided by the number of embryos transferred. * Live birth rate, which is defined by the number of living babies delivered divided by the number of transfers
Interventions
DEVICEINVOcell device
intra-vaginal culture of embryos using INVOcell device
OTHERTraditional IVF
traditional culture of embryos in-vitro
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Arm 1: intra-vaginal culture using INVOcell device. Arm 2: Traditional In-Vitro Fertilization (IVF) culture in an embryology laboratory
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 37 Years
Healthy volunteers
Yes
Inclusion criteria
* Normal uterine cavity * One or more years of infertility * Normal male partner semen analysis
Exclusion criteria
* Age \<18 years old or \>37 years old * Antral Follicle Count (AFC) \<8 * Abnormal male partner semen analysis or use of donor sperm * Vaginal inflammation or genital (vaginal, uterine, tubal) infection * Uncontrolled chronic disease (such as uncontrolled diabetes or hypertension) * Uterine anatomic abnormalities * Allergy to plastics or inability to use diaphragm retention device * Untreated hydrosalpinx * Current alcohol abuse (defined by \>14 drinks/week) * Prior history of IVF cycle where fertilization did not occur * History of recurrent pregnancy loss
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Implantation Rate | approximately 4 weeks following randomization. Clinically this is typically done around 6 weeks of gestational age | defined by number gestational sacs seen on early pregnancy ultrasound typically done at 6 weeks of gestational age divided by number of embryos transferred |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Embryo Quality | measured after 3 days of incubation | -Embryo quality, which is measured by system similar to the Gardner grading system at cleavage stage. Reported quality will be converted to the simplified SART embryo scoring system which provides an overall categorical embryo grade of Good, Fair or Poor. |
| Fertilization Rate | measured after 3 days of incubation | defined by the total number of fertilized oocytes divided by total number of mature oocytes retrieved |
| Clinical Pregnancy Rate | approximately 4 weeks following randomization. Clinically this is typically done around 6 weeks of gestational age | which is defined by the number of fetal poles with heartbeat seen on early pregnancy ultrasound typically done at 6 weeks of gestational age divided by the number of embryos transferred |
| Live Birth Rate | 9 months after embryo transfer | which is defined by the number of living babies delivered divided by the number of transfers |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred between October 2016 to February 2022, apart from a two year period of the COVID-19 Pandemic. Potential subjects were recruited from patient populations of the UCSF Center for Reproductive Health, the Zuckerberg San Francisco General Hospital and the general public.
Pre-assignment details
9 of 39 enrolled participants screen failed out of the study prior to randomization assignment. 6 never moved forward with starting clinical fertility treatment, 1 responded poorly to the minimal stimulation medication protocol that was part of the study design and couldn't proceed with the egg retrieval procedure, 1 was at risk for mild Ovarian Hyperstimulatory Syndrome and 1 voluntarily dropped out of the study prior to randomization due to financial and insurance coverage reasons.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Intra-vaginal Culture - INVOcell Device 3 day intra-vaginal incubation of embryos using INVOcell device | 14 |
| Active Comparator: Traditional IVF Culture 3 day traditional In Vitro Fertilization embryo incubation | 16 |
| Total | 30 |
Baseline characteristics
| Characteristic | Active Comparator: Traditional IVF Culture | Total | Experimental: Intra-vaginal Culture - INVOcell Device |
|---|---|---|---|
| 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 | 16 Participants | 30 Participants | 14 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 16 participants | 30 participants | 14 participants |
| Sex: Female, Male Female | 16 Participants | 30 Participants | 14 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 | 0 / 14 | 0 / 16 |
| other Total, other adverse events | 0 / 14 | 0 / 16 |
| serious Total, serious adverse events | 0 / 14 | 0 / 16 |
Outcome results
Primary
Implantation Rate
defined by number gestational sacs seen on early pregnancy ultrasound typically done at 6 weeks of gestational age divided by number of embryos transferred
Time frame: approximately 4 weeks following randomization. Clinically this is typically done around 6 weeks of gestational age
Population: 3 participants in the Traditional IVF culture arm and 2 participants in the intra-vaginal culture arm were excluded from analysis as they did not undergo embryo transfers.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-vaginal Culture - INVOcell Device | Implantation Rate | 12.50 percentage of embryo transfers | Standard Deviation 0.2976 |
| Traditional IVF Culture | Implantation Rate | 42.31 percentage of embryo transfers | Standard Deviation 43.17 |
Secondary
Clinical Pregnancy Rate
which is defined by the number of fetal poles with heartbeat seen on early pregnancy ultrasound typically done at 6 weeks of gestational age divided by the number of embryos transferred
Time frame: approximately 4 weeks following randomization. Clinically this is typically done around 6 weeks of gestational age
Population: 3 participants in the Traditional IVF culture arm and 2 participants in the intra-vaginal culture arm were excluded from analysis as they did not undergo embryo transfers.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-vaginal Culture - INVOcell Device | Clinical Pregnancy Rate | 12.5 percentage of embryo transfers | Standard Deviation 29.76 |
| Traditional IVF Culture | Clinical Pregnancy Rate | 46.15 percentage of embryo transfers | Standard Deviation 45.83 |
Secondary
Embryo Quality
-Embryo quality, which is measured by system similar to the Gardner grading system at cleavage stage. Reported quality will be converted to the simplified SART embryo scoring system which provides an overall categorical embryo grade of Good, Fair or Poor.
Time frame: measured after 3 days of incubation
Population: 1 participant from the intra-vaginal culture arm and 2 participants from the traditional IVF culture arm were excluded from the analysis due fertilization failures and no embryos on culture day 3 to grade.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Intra-vaginal Culture - INVOcell Device | Embryo Quality | Good | 34 Culture day 3 cleavage-stage embryos |
| Intra-vaginal Culture - INVOcell Device | Embryo Quality | Fair | 4 Culture day 3 cleavage-stage embryos |
| Intra-vaginal Culture - INVOcell Device | Embryo Quality | Poor | 7 Culture day 3 cleavage-stage embryos |
| Traditional IVF Culture | Embryo Quality | Good | 48 Culture day 3 cleavage-stage embryos |
| Traditional IVF Culture | Embryo Quality | Fair | 4 Culture day 3 cleavage-stage embryos |
| Traditional IVF Culture | Embryo Quality | Poor | 6 Culture day 3 cleavage-stage embryos |
Secondary
Fertilization Rate
defined by the total number of fertilized oocytes divided by total number of mature oocytes retrieved
Time frame: measured after 3 days of incubation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-vaginal Culture - INVOcell Device | Fertilization Rate | 61.75 percentage of oocytes fertilized | Standard Deviation 25.19 |
| Traditional IVF Culture | Fertilization Rate | 63.4 percentage of oocytes fertilized | Standard Deviation 30.55 |
Secondary
Live Birth Rate
which is defined by the number of living babies delivered divided by the number of transfers
Time frame: 9 months after embryo transfer
Population: 3 participants in the Traditional IVF culture arm and 2 participants in the intra-vaginal culture arm were excluded from analysis as they did not undergo embryo transfers.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intra-vaginal Culture - INVOcell Device | Live Birth Rate | 12.5 percentage of embryo transfers | Standard Deviation 29.76 |
| Traditional IVF Culture | Live Birth Rate | 38.46 percentage of embryo transfers | Standard Deviation 44.52 |