Vaginal Estradiol and Oral Guaifenesin in Clomiphene Ovulation Induction (CC-OVI)

February 9, 2026 updated by: Gamze Karababa, Yuzuncu Yil University

Comparison of Vaginal Estradiol and Oral Guaifenesin Interventions in Patients Undergoing Ovulation Induction With Clomiphene Citrate

Clomiphene citrate is commonly used for ovulation induction; however, it may negatively affect endometrial development and cervical mucus quality, which can reduce pregnancy rates. Various adjunctive treatments have been proposed to overcome these antiestrogenic effects.

This randomized clinical trial aimed to compare the effects of vaginal estradiol and oral guaifenesin, alone or in combination, on endometrial thickness, cervical mucus characteristics, and clinical pregnancy rates in women undergoing ovulation induction with clomiphene citrate.

A total of 90 women with infertility undergoing ovulation induction were randomly assigned to one of three treatment groups: clomiphene citrate plus guaifenesin, clomiphene citrate plus vaginal estradiol, or clomiphene citrate combined with both guaife

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study was designed as a single-center, randomized, parallel-group interventional clinical trial conducted at a university-affiliated tertiary care hospital. Women diagnosed with infertility and scheduled for ovulation induction with clomiphene citrate were eligible for inclusion.

Participants were randomly assigned to one of three treatment arms: clomiphene citrate plus oral guaifenesin, clomiphene citrate plus vaginal estradiol, or clomiphene citrate combined with both oral guaifenesin and vaginal estradiol. Clomiphene citrate was administered according to standard ovulation induction protocols. Adjunctive treatments were initiated during the follicular phase.

Baseline demographic and clinical characteristics were recorded. Follicular development and endometrial thickness were assessed by transvaginal ultrasonography. Cervical mucus characteristics, including spinnbarkeit and cervical mucus score, were evaluated during the periovulatory period. Ovulation was triggered when appropriate follicular criteria were met.

The primary outcome of the study was the clinical pregnancy rate. Secondary outcomes included endometrial thickness, cervical mucus quality, ovulation response, cycle cancellation, and miscarriage rate. Statistical analyses were performed to compare outcomes between treatment groups.

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Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Turkey (Türkiye)
    • Di̇yarbakir
      • Van, Di̇yarbakir, Turkey (Türkiye), 21640
        • Van Yuzuncu Yil University Dursun Odabasi Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • - Women aged 18 to 40 years
  • Diagnosis of infertility
  • Indication for ovulation induction with clomiphene citrate
  • Regular or irregular menstrual cycles suitable for ovulation induction
  • At least one patent fallopian tube
  • Normal uterine cavity on ultrasonography
  • Male partner with normal or mildly abnormal semen parameters
  • Willingness to participate and provide informed consent

Exclusion Criteria:

  • - Known hypersensitivity to clomiphene citrate, guaifenesin, or estradiol
  • Severe male factor infertility
  • Presence of uterine anomalies or intrauterine pathology
  • Endocrine disorders affecting ovulation (e.g., uncontrolled thyroid disease, hyperprolactinemia)
  • Polycystic ovary syndrome requiring alternative stimulation protocols
  • History of recurrent pregnancy loss
  • Use of hormonal treatment within the last 3 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Clomiphene Citrate + Guaifenesin
Participants received clomiphene citrate for ovulation induction combined with oral guaifenesin during the follicular phase.
Drug: Clomiphene Citrate.
Clomiphene citrate administered orally for ovulation induction according to standard clinical protocols.
Other Names:
  • Clomifene Citrate
Drug: Guaifenesin
Oral guaifenesin administered during the follicular phase to improve cervical mucus characteristics.
Other Names:
  • Glyceryl guaiacolate
Experimental: Clomiphene Citrate + Vaginal Estradiol
Participants received clomiphene citrate for ovulation induction combined with vaginal estradiol during the follicular phase.
Drug: Clomiphene Citrate.
Clomiphene citrate administered orally for ovulation induction according to standard clinical protocols.
Other Names:
  • Clomifene Citrate
Drug: Estradiol (E2)
Vaginal estradiol administered during the follicular phase to improve endometrial development.
Other Names:
  • Vaginal Estradiol
Experimental: Clomiphene Citrate + Guaifenesin + Vaginal Estradiol
Participants received clomiphene citrate combined with both oral guaifenesin and vaginal estradiol during the follicular phase.
Drug: Clomiphene Citrate.
Clomiphene citrate administered orally for ovulation induction according to standard clinical protocols.
Other Names:
  • Clomifene Citrate
Drug: Guaifenesin
Oral guaifenesin administered during the follicular phase to improve cervical mucus characteristics.
Other Names:
  • Glyceryl guaiacolate
Drug: Estradiol (E2)
Vaginal estradiol administered during the follicular phase to improve endometrial development.
Other Names:
  • Vaginal Estradiol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical pregnancy rate
Time Frame: From ovulation trigger administration to confirmation of clinical pregnancy by transvaginal ultrasonography within the same treatment cycle (approximately 4-6 weeks).
Clinical pregnancy was defined as the presence of an intrauterine gestational sac detected by transvaginal ultrasonography.
From ovulation trigger administration to confirmation of clinical pregnancy by transvaginal ultrasonography within the same treatment cycle (approximately 4-6 weeks).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endometrial thickness
Time Frame: On the day of ovulation trigger administration (cycle day-specific).
Endometrial thickness was measured by transvaginal ultrasonography.
On the day of ovulation trigger administration (cycle day-specific).
Cervical mucus score
Time Frame: During the peri-ovulatory period, from the day before ovulation trigger to the day after ovulation trigger (approximately 2-3 days).
Cervical mucus quality was evaluated using cervical mucus scoring.
During the peri-ovulatory period, from the day before ovulation trigger to the day after ovulation trigger (approximately 2-3 days).
Spinnbarkeit
Time Frame: During the peri-ovulatory period, from the day before ovulation trigger to the day after ovulation trigger (approximately 2-3 days).
Spinnbarkeit was assessed as an indicator of cervical mucus stretchability.
During the peri-ovulatory period, from the day before ovulation trigger to the day after ovulation trigger (approximately 2-3 days).
Miscarriage rate
Time Frame: Up to 12 weeks of gestation
Miscarriage was defined as pregnancy loss before 12 weeks of gestation.
Up to 12 weeks of gestation
Cycle cancellation rate
Time Frame: By the end of the treatment cycle (one cycle, approximately 28 days).
Cycle cancellation was recorded when ovulation induction could not be completed.
By the end of the treatment cycle (one cycle, approximately 28 days).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yuzuncu Yil University

Investigators

  • Study Director: Gamze K Karababa, VAN YUZUNCU YİL UNİVERCITY

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 6, 2022

Primary Completion (Actual)

June 6, 2023

Study Completion (Actual)

June 23, 2023

Study Registration Dates

First Submitted

January 26, 2026

First Submitted That Met QC Criteria

February 9, 2026

First Posted (Actual)

February 10, 2026

Study Record Updates

Last Update Posted (Actual)

February 10, 2026

Last Update Submitted That Met QC Criteria

February 9, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • YYU-CC-OVI-2022
  • YYU-ETH-2021 (Other Identifier: Yuzuncu Yil University Ethics Committee Approval)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared due to ethical and privacy considerations.

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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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