Anovulation, Ovulation Induction, Ovulatory Dysfunction
Conditions
Keywords
Anovulation, Ovulation induction
Brief summary
The purpose of this study is to compare the length of time to achieve ovulation and pregnancy with a traditional protocol administration of clomiphene citrate versus a stair step administration. Our hypothesis is by using a stair-step approach in which a period is not induced between administrations of escalating doses of clomiphene citrate, the time to ovulation and pregnancy may be reduced.
Detailed description
The traditional administration of clomiphene citrate for ovulation induction involves taking clomiphene citrate for 5 days. If ovulation does not occur within 14 days, a progestin pill (such as Provera) is prescribed for 10 days to induce a period (which normally occurs within 1 week of stopping the pill). Then a higher dose of clomiphene citrate will be prescribed. The stair-step administration of clomiphene citrate for ovulation induction also involves taking clomiphene citrate for 5 days. In contrast, if ovulation does not occur within 7-9 days, a progestin pill (such as Provera) would NOT be taken to induce a period. The dose of clomiphene will then be increased. Therefore, this would do away with the 10 days of taking the progestin pill, and also do away with waiting for a period (usually 3 to 7 days) for a total of up to a 20 day difference between clomiphene citrate dosing cycles.
Interventions
DRUGclomiphene citrate
Clomiphene citrate 50 mg for 5 days starting on cycle day 5. Transvaginal ultrasound between cycle days 11 to 14 to determine if there is a dominant follicle. If NO dominant follicle present, another ultrasound and blood draw (to test progesterone level) will be done one week later to confirm no response to the medication dose. Medroxyprogesterone acetate (Provera) 10 mg per day for 10 days. Increased dose of clomiphene citrate for 5 days starting on cycle day 5. This process will be repeated at increased doses of clomiphene citrate (100 mg and 150 mg) until a dominant follicle(s) is present.
Sponsors
University of Oklahoma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Ovulatory dysfunction as evidenced by mid-luteal progesterone less then 3ng/dL, non-biphasic basal body temperature charting, or menstrual history of cycles \> 35 days. * Female patients 18 to 45 years old * Six months or greater of unprotected intercourse without pregnancy. * Normal TSH and prolactin serum levels * Semen analysis of male partner with \> 15 million motile sperm on semen analysis. * NOTE: Must be willing to travel to the Oklahoma City area for treatment.
Exclusion criteria
* Failure to spontaneously menstruate or to menstruate following progestin administration * Allergy or intolerance to the side effects of clomiphene citrate, hCG (human chorionic gonadotropins), or medroxyprogesterone acetate (Provera). * Known anatomical defect affecting the uterine cavity including submucosal fibroids or endometrial polyps. * Know tubal hydrosalpinx or risk factors for tubal obstruction * Known liver dysfunction * Known or suspected androgen secreting tumor, cushings disease, or adrenal hyperplasia (congenital or adult onset) * Ovarian cyst \> 20mm or endometrial lining \>6 mm on trans-vaginal baseline ultrasound. * Stage III or IV endometriosis * Decreased ovarian reserve as evidenced by antral follicle count less than 6 by Transvaginal ultrasound or a cycle-day-3 serum FSH of \> 10 uIU/ml. * Positive HIV in either the female patient or her partner.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Ovulation With Each Protocol | 5 years | We hypothesized that time to ovulation would be shorter with stair-step protocol vs. traditional. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Ovulation | 5 years | Rate of ovulation with each dose of clomid within each protocol |
| Delivery Outcomes | 5 years | Proportion of participants that delivered a baby based on which protocol they were randomized to. |
Countries
United States
Participant flow
Recruitment details
Recruitment was in the infertility clinic.
Participants by arm
| Arm | Count |
|---|---|
| Traditional Administration | 60 |
| Stair-Step Administration | 60 |
| Total | 120 |
Baseline characteristics
| Characteristic | Stair-Step Administration | Total | Traditional Administration |
|---|---|---|---|
| Age, Continuous | 29.37 years STANDARD_DEVIATION 3.96 | 28.65 years STANDARD_DEVIATION 4.45 | 27.88 years STANDARD_DEVIATION 4.95 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 9 Participants | 6 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 | 55 Participants | 101 Participants | 46 Participants |
| Sex: Female, Male Female | 60 Participants | 120 Participants | 60 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 | 60 / 60 | 60 / 60 |
| serious Total, serious adverse events | 2 / 60 | 3 / 60 |
Outcome results
Primary
Time to Ovulation With Each Protocol
We hypothesized that time to ovulation would be shorter with stair-step protocol vs. traditional.
Time frame: 5 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Traditional Administration | Time to Ovulation With Each Protocol | 31.1 days | Standard Error 3.5 |
| Stair-Step Administration | Time to Ovulation With Each Protocol | 21.5 days | Standard Error 0.9 |
Secondary
Delivery Outcomes
Proportion of participants that delivered a baby based on which protocol they were randomized to.
Time frame: 5 years
Population: Number of participants randomized to each arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Traditional Administration | Delivery Outcomes | 21 Participants |
| Stair-Step Administration | Delivery Outcomes | 21 Participants |
Secondary
Rate of Ovulation
Rate of ovulation with each dose of clomid within each protocol
Time frame: 5 years
Population: Proportion of subjects that ovulated at each dose of Clomid based on which protocol they were randomized to.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Traditional Administration | Rate of Ovulation | Clomid 50mg | 45 Participants |
| Traditional Administration | Rate of Ovulation | Clomid 100mg | 7 Participants |
| Traditional Administration | Rate of Ovulation | Clomid 150mg | 1 Participants |
| Traditional Administration | Rate of Ovulation | Clomid No Response | 7 Participants |
| Stair-Step Administration | Rate of Ovulation | Clomid No Response | 6 Participants |
| Stair-Step Administration | Rate of Ovulation | Clomid 50mg | 26 Participants |
| Stair-Step Administration | Rate of Ovulation | Clomid 150mg | 10 Participants |
| Stair-Step Administration | Rate of Ovulation | Clomid 100mg | 18 Participants |