Traditional Clomiphene Citrate Administration vs. Stair-step Approach (Clomid)

Traditional Clomiphene Citrate Administration Versus a Stair-Step Approach: A Randomized Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Anovulation; Ovulation Induction; Ovulatory Dysfunction
• Intervention / Treatment: Drug: clomiphene citrate; Drug: clomiphene citrate

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73013
      • University of Oklahoma Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Traditional Administration; 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.	Drug: clomiphene 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.; Other Names: Clomid; Drug: clomiphene 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, a blood draw (to test progesterone level) will be done. Increased dose of clomiphene citrate for 5 days starting that day. A repeat transvaginal ultrasound in one week to determine if there is a dominant follicle. This process will be repeated at increased doses of clomiphene citrate (100 mg and 150 mg) until a dominant follicle(s) is present.; Other Names: Clomid
Experimental: Stair-Step Administration; 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.	Drug: clomiphene 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.; Other Names: Clomid; Drug: clomiphene 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, a blood draw (to test progesterone level) will be done. Increased dose of clomiphene citrate for 5 days starting that day. A repeat transvaginal ultrasound in one week to determine if there is a dominant follicle. This process will be repeated at increased doses of clomiphene citrate (100 mg and 150 mg) until a dominant follicle(s) is present.; Other Names: Clomid

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Ovulation	Rate of ovulation with each dose of clomid within each protocol	5 years
Delivery Outcomes	Proportion of participants that delivered a baby based on which protocol they were randomized to.	5 years

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Investigators: Principal Investigator: LaTasha Craig, MD, University of Oklahoma

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: November 3, 2009
• First Submitted That Met QC Criteria: November 3, 2009
• First Posted (Estimate): November 5, 2009

Study Record Updates

• Last Update Posted (Actual): January 8, 2018
• Last Update Submitted That Met QC Criteria: January 5, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Anovulation; Ovulation induction
• Additional Relevant MeSH Terms: Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Anovulation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Anticoagulants; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Chelating Agents; Sequestering Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Calcium Chelating Agents; Citric Acid; Sodium Citrate; Clomiphene; Enclomiphene; Zuclomiphene
• Other Study ID Numbers: 2078