Infertility
Conditions
Keywords
Frozen-thawed embryo transfer, Infertility, Crinone, Duphaston, Chinese population
Brief summary
The study to compare to the efficacy and safety of Crinone versus combination medication in infertile women receive frozen-thawed embryo transfer (FET) in artificial cycles (AC).
Interventions
DRUGCrinone
Participants received Crinone 8% (90 milligrams \[mg\] an intravaginal progesterone gel contained in a single use, one piece applicator) once daily in morning from the day of endometrial transformation (Day -5) until ongoing pregnancy was confirmed up to Day 63.
DRUGDuphaston
Participants received 10 mg of Duphaston tablet orally twice a day from the day of endometrial transformation (Day -5) until ongoign pregnancy was confirmed up to Day 63.
Sponsors
Merck Sharp & Dohme LLC
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 38 Years
Healthy volunteers
No
Inclusion criteria
Participants are eligible to be included in the study only if all the following criteria apply: * Participants who will receive artificial frozen-thawed embryo transfer (FET) cycle study interventions * Participants who have no more than two Day 5 embryos are planned to be transferred (follow the clinical practice of the study site) * Participants have received estradiol valerate for no more than 20 days * Participants have a transitional-endometrium of greater than or equal to 8 millimeter * Participants have normal uterine cavity * Participants can give signed informed consent * Participants are willing to follow the study protocol and able to complete the study
Exclusion criteria
* Participants are willing to follow the study protocol and able to complete the study * Participants with greater than or equal to three previously failed cycles of ET * Participants with diseases that cannot tolerate pregnancy * Hydrosalpinx * Severe endometriosis (Endometriosis American Society for Reproductive Medicine (ASRM) criteria from 1996) * Known hypersensitivity to progesterone, the excipients of Crinone and Duphaston Vaginal bleeding of unknown origin * History of recurrent miscarriages * Vaginitis * Thromboembolic diseases (thrombophlebitis, thromboembolic disorder, or cerebral apoplexy) or participants with a history of these conditions * Known or suspected progestogen-dependent neoplasm * Participation in another clinical trial within the past 30 days * Contraindications of both Crinone and Duphaston
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ongoing Pregnancy Rate | 8 to 10 weeks after embryo transfer | Ongoing pregnancy was assessed by the presence of viable intra uterine fetus detected by ultrasound examination in 10-12 weeks of pregnancy (8 to 10 weeks after embryo transfer). Ongoing pregnancy rate is defined as the number of participants with ongoing pregnancy divided by the number of participants with embryo transfer (ET) multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Implantation Rate | 4-6 weeks after embryo transfer | Implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred (ET) multiplied by 100. |
| Clinical Pregnancy Rate | 4-6 weeks after embryo transfer | Clinical Pregnancy was defined as the pregnancy diagnosed by ultrasound of one or more gestational sacs or definitive clinical signs of pregnancy. Clinical pregnancy rate was measured as the number of participants with clinical pregnancy divided by number of participants with embryo transfer (ET) multiplied by 100. |
| Beta Human Chorionic Gonadotrophin (Beta-hCG) Positive Rate | 2 weeks after embryo transfer | Beta-hCG positive rate defined as number of participants with positive beta-hCG divided by the number of participants with embryo transfer (ET) multiplied by 100. |
| Luteal Phase Bleeding Rate | 2, 5 and 9 weeks after embryo transfer | Luteal Phase Bleeding defined as the onset of any bleeding after embryo transfer and prior to the pregnancy test. Luteal phase bleeding rate defined as the number of participants with Luteal phase bleeding divided by number of participants with embryo transfer (ET) multiplied by 100. |
| Vaginal Bleeding Rate | 5 and 9 weeks after embryo transfer | Vaginal bleeding is defined as any bleeding recorded after a pregnancy test via serum Beta-Human Chorionic Gonadotrophin. Vaginal bleeding rate defined as the number of participants with vaginal bleeding divided by number of participants with embryo transfer (ET) multiplied by 100. |
| Early Abortion Rate | Time from embryo transfer to 12 weeks of pregnancy | Early abortion defined as the spontaneous loss of an intra-uterine pregnancy prior to 12 completed weeks of gestational age. Early abortion rate defined as the number of participants with early abortion divided by number of participants with clinical pregnancy multiplied by 100. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Crinone Participants received Crinone 8% (90 milligrams \[mg\] an intravaginal progesterone gel contained in a single use, one piece applicator) once daily in morning from the day of endometrial transformation (Day -5) until ongoing pregnancy was confirmed up to Day 63. | 86 |
| Crinone® Plus Duphaston Participants received Crinone 8% (90 mg an intravaginal progesterone gel contained in a single use, one piece applicator) once daily in morning followed by 10 mg of Duphaston tablet orally twice a day from the day of endometrial transformation (Day -5) until ongoing pregnancy was confirmed up to Day 63. | 86 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 16 | 9 |
| Overall Study | Other | 1 | 1 |
Baseline characteristics
| Characteristic | Crinone® Plus Duphaston | Total | Crinone |
|---|---|---|---|
| Age, Continuous | 30.74 Years STANDARD_DEVIATION 3.163 | 30.79 Years STANDARD_DEVIATION 3.034 | 30.84 Years STANDARD_DEVIATION 2.918 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 86 Participants | 172 Participants | 86 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 86 Participants | 172 Participants | 86 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 / 86 | 0 / 86 |
| other Total, other adverse events | 17 / 86 | 14 / 86 |
| serious Total, serious adverse events | 4 / 86 | 4 / 86 |
Outcome results
Primary
Ongoing Pregnancy Rate
Ongoing pregnancy was assessed by the presence of viable intra uterine fetus detected by ultrasound examination in 10-12 weeks of pregnancy (8 to 10 weeks after embryo transfer). Ongoing pregnancy rate is defined as the number of participants with ongoing pregnancy divided by the number of participants with embryo transfer (ET) multiplied by 100.
Time frame: 8 to 10 weeks after embryo transfer
Population: ITT Population included all participants who received at least one dose of randomized study intervention. Here, Number of participants analyzed signified those participants who had embryo transferred.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Crinone | Ongoing Pregnancy Rate | 18.8 Percentage of participants |
| Crinone® Plus Duphaston | Ongoing Pregnancy Rate | 29.1 Percentage of participants |
Secondary
Beta Human Chorionic Gonadotrophin (Beta-hCG) Positive Rate
Beta-hCG positive rate defined as number of participants with positive beta-hCG divided by the number of participants with embryo transfer (ET) multiplied by 100.
Time frame: 2 weeks after embryo transfer
Population: ITT Population included all participants who received at least one dose of randomized study intervention. Here, Number of participants analyzed signified those participants who had embryo transferred.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Crinone | Beta Human Chorionic Gonadotrophin (Beta-hCG) Positive Rate | 37.6 Percentage of participants |
| Crinone® Plus Duphaston | Beta Human Chorionic Gonadotrophin (Beta-hCG) Positive Rate | 43.0 Percentage of participants |
Secondary
Clinical Pregnancy Rate
Clinical Pregnancy was defined as the pregnancy diagnosed by ultrasound of one or more gestational sacs or definitive clinical signs of pregnancy. Clinical pregnancy rate was measured as the number of participants with clinical pregnancy divided by number of participants with embryo transfer (ET) multiplied by 100.
Time frame: 4-6 weeks after embryo transfer
Population: ITT Population included all participants who received at least one dose of randomized study intervention. Here, Number of participants analyzed signified those participants who had embryo transferred.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Crinone | Clinical Pregnancy Rate | 21.2 Percentage of participants |
| Crinone® Plus Duphaston | Clinical Pregnancy Rate | 33.7 Percentage of participants |
Secondary
Early Abortion Rate
Early abortion defined as the spontaneous loss of an intra-uterine pregnancy prior to 12 completed weeks of gestational age. Early abortion rate defined as the number of participants with early abortion divided by number of participants with clinical pregnancy multiplied by 100.
Time frame: Time from embryo transfer to 12 weeks of pregnancy
Population: ITT Population included all participants who received at least one dose of randomized study intervention. Here, Number of participants analyzed signified those participants with clinical pregnancy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Crinone | Early Abortion Rate | 11.1 Percentage of participants |
| Crinone® Plus Duphaston | Early Abortion Rate | 13.8 Percentage of participants |
Secondary
Implantation Rate
Implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred (ET) multiplied by 100.
Time frame: 4-6 weeks after embryo transfer
Population: ITT Population included all participants who received at least one dose of randomized study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Crinone | Implantation Rate | 20.9 percentage of gestational sacs per ET |
| Crinone® Plus Duphaston | Implantation Rate | 33.7 percentage of gestational sacs per ET |
Secondary
Luteal Phase Bleeding Rate
Luteal Phase Bleeding defined as the onset of any bleeding after embryo transfer and prior to the pregnancy test. Luteal phase bleeding rate defined as the number of participants with Luteal phase bleeding divided by number of participants with embryo transfer (ET) multiplied by 100.
Time frame: 2, 5 and 9 weeks after embryo transfer
Population: Safety analysis set included all participants who have received at least one dose of study intervention. Here, Number of participants analyzed signified those participants who had embryo transferred.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Crinone | Luteal Phase Bleeding Rate | 1.2 Percentage of participants |
| Crinone® Plus Duphaston | Luteal Phase Bleeding Rate | 3.5 Percentage of participants |
Secondary
Vaginal Bleeding Rate
Vaginal bleeding is defined as any bleeding recorded after a pregnancy test via serum Beta-Human Chorionic Gonadotrophin. Vaginal bleeding rate defined as the number of participants with vaginal bleeding divided by number of participants with embryo transfer (ET) multiplied by 100.
Time frame: 5 and 9 weeks after embryo transfer
Population: Safety analysis set included all participants who have received at least one dose of study intervention. Here, Number of participants analyzed signified those participants who had embryo transferred.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Crinone | Vaginal Bleeding Rate | 7.1 Percentage of participants |
| Crinone® Plus Duphaston | Vaginal Bleeding Rate | 10.5 Percentage of participants |