Traditional Clomiphene Citrate Administration vs. Stair-step Approach

Phase 3

Completed

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Traditional Administration	clomiphene citrate	The traditional approach to ovulation induction with clomiphene citrate involves administration of 50mg/day for five days (starting on cycle day 3, 4, or 5). If ovulation does not occur then a progestin is prescribed to induce menses (which occurs within one week of stopping the progestin) and then a higher dose of medication is used in the next cycle.
Stair-Step Administration	clomiphene citrate	The stair-step protocol the dose of clomiphene citrate would be increased without administering progestin and inducing a period. This would eliminate the days of progestin (10 days) and the waiting for the period (usually 3 to 7 days) and finally waiting to start clomiphene citrate on cycle day 3 at the earliest (3 more days) for a total of up to 20 days difference for the 100 mg dose of clomid. If they did not ovulate on 100mg, then the process repeats and another 20 days before they start 150mg. Therefore, the time to ovulation and pregnancy may be reduced, and hopefully pregnancy, by using the stair-step protocol. This method utilizes ultrasound monitoring for follicle development before increasing the dose of clomiphene citrate.

Primary Outcome Measures

Name	Time	Method
Time to Ovulation With Each Protocol	5 years	We hypothesized that time to ovulation would be shorter with stair-step protocol vs. traditional.

Secondary Outcome Measures

Name	Time	Method
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.