In Vitro Fertilization
Conditions
Keywords
Luteal support in IVF
Brief summary
Prospective, open, randomized, parallel, multicenter, two-arm trial to evaluate the efficacy and tolerability of a new progesterone formulation to be used for luteal support in IVF (Progesterone-IBSA) administered subcutaneously at a daily dose of 25 mg versus Progesterone tablets administered intravaginally at 100 mg twice daily for a total dose of 200 mg.
Interventions
DRUGProgesterone
25 mg, once a day, SC
Sponsors
IBSA Institut Biochimique SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 42 Years
Healthy volunteers
No
Inclusion criteria
* Patient has given written informed consent; * BMI \< 30 kg/m2; * Age 18 - 42 (upon starting COH); * \<3 prior ART cycles (IVF, ICSI and related procedures); * Baseline (day 2-3 of cycling) FSH \<15 IU/L and E2 \<80 pg/mL; * Normal uterine cavity as per recent hysterosalpingogram, sonohysterogram or hysteroscopic exam (i.e. no polyps or protruding submucosal fibroids); * Patients must have at least three retrieved oocytes.
Exclusion criteria
* Intramural uterine fibroids that distort the uterine cavity or polyps \>1 cm; * Stage III or IV endometriosis (no endometriomas); * Hydrosalpinges; * History of past poor response to COH resulting in canceling ART; * Use of thawed/donated oocytes; * Use of thawed/donated embryos; * Gestational carrier; * Patients affected by pathologies associated with any contraindication of being pregnant; * Hypersensitivity to study medication; * Uncontrolled adrenal or thyroid dysfunction; * History of conditions (i.e. toxic shock syndrome) that would contraindicate use of a vaginal progesterone product; * History of arterial disease; * Patients with hepatic impairment (liver function tests \> 2x upper limits of normal); * Patients with dermatologic disease; * Patients with renal impairment (estimated creatinine clearance \<60 mL/min/1.73 m2); * Neoplasias (current) or history of neoplasia that may be responsive to progesterone; * High grade cervical dysplasia; * History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages, wherein pregnancy developed to a minimum of a gestational sac on TVUS; * Participation in a concurrent clinical trial or in another trial within the past 2 months; * Use of concomitant medications that might interfere with the study evaluation; * Pre-implantation genetic diagnosis/screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ongoing Pregnancy Rate | 10 weeks after treatment start |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Implantation Rate | 4-5 weeks after treatment start | Implantation rate was defined as the number of gestational sacs divided by the number of embryos transferred (%). This value was calculated for all the patients who had at least one embryo transferred. |
| Delivery Rate | nearly 9 months after treatment start | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Progesterone SC Progesterone SC given at a daily dose of 25 mg. | 400 |
| Progesterone Tablets Progesterone vaginal tables 100 mg given twice à day. | 400 |
| Total | 800 |
Baseline characteristics
| Characteristic | Progesterone Tablets | Progesterone SC | 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 | 400 Participants | 400 Participants | 800 Participants |
| Age Continuous | 34.3 years STANDARD_DEVIATION 4.5 | 34.3 years STANDARD_DEVIATION 4.4 | 34.3 years STANDARD_DEVIATION 4.4 |
| Region of Enrollment United States | 400 participants | 400 participants | 800 participants |
| Sex: Female, Male Female | 400 Participants | 400 Participants | 800 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 | 156 / 400 | 161 / 400 |
| serious Total, serious adverse events | 0 / 400 | 0 / 400 |
Outcome results
Primary
Ongoing Pregnancy Rate
Time frame: 10 weeks after treatment start
Population: All randomized patients were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone SC | Ongoing Pregnancy Rate | 40.8 percentage of randomized patients |
| Progesterone Tablets | Ongoing Pregnancy Rate | 43.3 percentage of randomized patients |
Comparison: The non -inferiority hypothesis to be tested for the primary endpoint was that the ongoing pregnancy rate (oPR) in the test group (Pe)was lower than the oPR in the control group (Pc)against the alternative one that the oPR in the test group was equal to or higher than the oPR in the control group.~H0 : Pc\>= Pe + d(-10%) H1 : Pc\< Pe + d(-10%)p-value: 0.5295% CI: [-9.4, 4.4]Fisher Exact
Secondary
Delivery Rate
Time frame: nearly 9 months after treatment start
Population: All randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone SC | Delivery Rate | 40.5 percentage of randomized patients |
| Progesterone Tablets | Delivery Rate | 42.5 percentage of randomized patients |
p-value: 0.6295% CI: [-8.8, 4.8]Fisher Exact
Secondary
Implantation Rate
Implantation rate was defined as the number of gestational sacs divided by the number of embryos transferred (%). This value was calculated for all the patients who had at least one embryo transferred.
Time frame: 4-5 weeks after treatment start
Population: Patient who had at least one embryo transferred.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Progesterone SC | Implantation Rate | 33.2 percentage of embryos transferred | Standard Deviation 42 |
| Progesterone Tablets | Implantation Rate | 35.1 percentage of embryos transferred | Standard Deviation 40.9 |
p-value: 0.5495% CI: [-7.6, 4]ANOVA