Incremental Clomiphene Citrate Doses in Successive Cycles and FSH, LH and Steroid Hormone Levels

The Effect of Incremental Clomiphene Citrate(CC) Doses in Successive Induction Cycles on the Endogenous Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and Steroid Hormone Responses to Treatment

This study was planned to assess the initial and endogenous FSH, LH and steroid responses to incremental CC doses in successive ovulation induction cycles to treat anovulation in patients with unexplained infertility.

Study Overview

• Status: Completed
• Conditions: Unexplained Infertility; Ovulation Disorder
• Intervention / Treatment: Drug: Clomiphene Citrate

Detailed Description

In the Bagcilar Research and Training Hospital Obstetrics and Gynecology department outpatient clinic for infertility, the basal gonadotropin and androgen levels are routinely measured. In unexplained infertility couples with normal ovarian reserves the first line drug used for ovulation induction is CC. The starting dose is 50mg/day and the treatment is started within the 2nd to the 5th days of the menstrual cycle and continued for 5 days. Starting on the 2nd-3rd day following the last dose of the drug, the follicular growth was monitored with the transvaginal ultrasound and blood levels of hormones including FSH, LH, estradiol, progesterone, androstenedione, testosterone, and dehydroepiandrosterone sulphate were measured every 2-3 days. In this follow-up, if no follicular growth was observed day21 of the cycle, the CC dose was increased to CC 100mg/day (2X1, 50mg). If follicular growth and ovulation is achieved with no concluding conception, the same dose of CC is used in the following 2-3 cycles. When a maximum number of 2 dominant follicles are obtained ovulation is triggered with recombinant human chorionic gonadotropin (rhCG) and timed coit or intrauterine insemination is conducted.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Turkey
  • Bagcilar
    • Istanbul, Bagcilar, Turkey, 34200
      • Bagcilar Teaching and Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 31 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 20-35 years of age
• unexplained infertility
• first-line treatment
• Normal or increased ovarian reserve
• lack of ovulatory response to CC 50mg for 5 days

Exclusion Criteria:

• Male factor
• Tubal Factor
• Severe endometriosis
• Previous ovarian surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clomiphene citrate group 1; Clomiphene citrate dose 50mg/day for 5 days starting on cycle day (2-4).	Drug: Clomiphene Citrate; Clomiphene citrate used in incremental doses in nonresponsive cases.; Other Names: CC
Active Comparator: Clomiphene citrate group 2; Non-responsive to ovulation induction with Clomiphene Citrate with dose:50mg/day; and treated with dose:100mg/day in the succeeding cycle for 5 days, starting on cycle day (2-4).	Drug: Clomiphene Citrate; Clomiphene citrate used in incremental doses in nonresponsive cases.; Other Names: CC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the endogenous blood levels of FSH, LH in successive cycles	FSH (mIU/ml), LH (mIU/ml) blood levels measured with Enzyme-Linked ImmunoSorbent Assay (ELISA) tests.	Menstrual cycle at day 3 and day 9 and the trigger day respectively (each cycle is 28 days
Changes in the endogenous blood levels of steroids (including Androstenedione, Progesterone, Testosterone, estradiol) in successive cycles	Blood levels of steroids: Androstenedione (ng/ml), Progesterone (ng/ml), Testosterone (ng/ml), estradiol (pg/ml) measured with ELISA tests.	Menstrual cycle at day 3 and day 9 and the trigger day respectively (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
conception rate	beta-hCG (IU/L)measured with ELISA.	15-20 days following intrauterine insemination.

Collaborators and Investigators

• Sponsor: Bagcilar Training and Research Hospital
• Investigators: Principal Investigator: Evrim E Kovalak, MD, Bagcilar Training and Research Hospital

Publications and helpful links

General Publications

• Ozyurek ES, Yoldemir T, Artar G. Androstenedione response to recombinant human FSH is the most valid predictor of the number of selected follicles in polycystic ovarian syndrome: (a case-control study). J Ovarian Res. 2017 May 12;10(1):34. doi: 10.1186/s13048-017-0330-7.
• Hager M, Horath S, Frigo P, Koch M, Marculescu R, Ott J. Changes in serum markers of patients with PCOS during consecutive clomiphene stimulation cycles: a retrospective study. J Ovarian Res. 2019 Oct 4;12(1):91. doi: 10.1186/s13048-019-0564-7.

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2019
• Primary Completion (Actual): May 20, 2020
• Study Completion (Actual): May 25, 2020

Study Registration Dates

• First Submitted: December 13, 2019
• First Submitted That Met QC Criteria: December 24, 2019
• First Posted (Actual): December 26, 2019

Study Record Updates

• Last Update Posted (Actual): February 3, 2021
• Last Update Submitted That Met QC Criteria: February 2, 2021
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: infertility; clomiphene citrate; ovulation induction; unexplained infertility
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Clomiphene; Enclomiphene; Zuclomiphene
• Other Study ID Numbers: 2019.08.1.04.061

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Study Data/Documents

1. Individual Participant Data Set
   Information comments: unfinished

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No