Vaginal Estradiol and Oral Guaifenesin in Clomiphene Ovulation Induction

NCT07398924 | Completed

• 2 other identifiers: YYU-CC-OVI-2022YYU-ETH-2021
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Female Infertility; Anovulatory Infertility; Unexplained Infertility

Keywords

Clomiphene citrate, Ovulation induction, Vaginal estradiol, Guaifenesin, Endometrial thickness, Cervical mucus, Infertility treatment

Outcome Measures

Primary Outcomes (1)

• Clinical pregnancy rate

  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 Outcomes (5)

• Endometrial thickness

  On the day of ovulation trigger administration (cycle day-specific).

• Cervical mucus score

  During the peri-ovulatory period, from the day before ovulation trigger to the day after ovulation trigger (approximately 2-3 days).

• Spinnbarkeit

  During the peri-ovulatory period, from the day before ovulation trigger to the day after ovulation trigger (approximately 2-3 days).

• Miscarriage rate

  Up to 12 weeks of gestation

• Cycle cancellation rate

  By the end of the treatment cycle (one cycle, approximately 28 days).

Study Arms (3)

Clomiphene Citrate + Guaifenesin

EXPERIMENTAL

Participants received clomiphene citrate for ovulation induction combined with oral guaifenesin during the follicular phase.

Drug: Clomiphene Citrate.; Drug: Guaifenesin

Clomiphene Citrate + Vaginal Estradiol

EXPERIMENTAL

Participants received clomiphene citrate for ovulation induction combined with vaginal estradiol during the follicular phase.

Drug: Clomiphene Citrate.; Drug: Estradiol (E2)

Clomiphene Citrate + Guaifenesin + Vaginal Estradiol

EXPERIMENTAL

Participants received clomiphene citrate combined with both oral guaifenesin and vaginal estradiol during the follicular phase.

Drug: Clomiphene Citrate.; Drug: Guaifenesin; Drug: Estradiol (E2)

Interventions

Clomiphene Citrate. DRUG

Clomiphene citrate administered orally for ovulation induction according to standard clinical protocols.

Also known as: Clomifene Citrate

Clomiphene Citrate + Guaifenesin; Clomiphene Citrate + Guaifenesin + Vaginal Estradiol; Clomiphene Citrate + Vaginal Estradiol

Guaifenesin DRUG

Oral guaifenesin administered during the follicular phase to improve cervical mucus characteristics.

Also known as: Glyceryl guaiacolate

Clomiphene Citrate + Guaifenesin; Clomiphene Citrate + Guaifenesin + Vaginal Estradiol

Estradiol (E2) DRUG

Vaginal estradiol administered during the follicular phase to improve endometrial development.

Also known as: Vaginal Estradiol

Clomiphene Citrate + Guaifenesin + Vaginal Estradiol; Clomiphene Citrate + Vaginal Estradiol

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \- 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

You may not qualify if:

• \- 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

Sponsors & Collaborators

• Yuzuncu Yil University: lead

Study Sites (1)

Van Yuzuncu Yil University Dursun Odabasi Medical Center

Van, Di̇yarbakir, 21640, Turkey (Türkiye)

Location

Related Links

• Related Info

MeSH Terms

Conditions

Infertility, Female

Interventions

Clomiphene; Guaifenesin; Acetylcysteine; Estradiol; segesterone acetate and ethinyl estradiol vaginal system

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Guaiacol; Methyl Ethers; Ethers; Phenyl Ethers; Catechols; Phenols; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Amino Acids; Amino Acids, Peptides, and Proteins; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Gamze K Karababa

  VAN YUZUNCU YİL UNİVERCITY

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assessors were blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Model Details: Participants were randomized into three parallel treatment arms and followed prospectively for outcome assessment.

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: February 10, 2026
• Study Start: January 6, 2022
• Primary Completion: June 6, 2023
• Study Completion: June 23, 2023
• Last Updated: February 10, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)