Female Infertility, Anovulatory Infertility, Unexplained Infertility
Conditions
Keywords
Clomiphene citrate, Ovulation induction, Vaginal estradiol, Guaifenesin, Endometrial thickness, Cervical mucus, Infertility treatment
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
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. ''
Interventions
Clomiphene citrate administered orally for ovulation induction according to standard clinical protocols.
DRUGGuaifenesin
Oral guaifenesin administered during the follicular phase to improve cervical mucus characteristics.
DRUGEstradiol (E2)
Vaginal estradiol administered during the follicular phase to improve endometrial development.
Sponsors
Yuzuncu Yil University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Outcome assessors were blinded to treatment allocation.
Intervention model description
Participants were randomized into three parallel treatment arms and followed prospectively for outcome assessment.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical pregnancy rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endometrial thickness | On the day of ovulation trigger administration (cycle day-specific). | Endometrial thickness was measured by transvaginal ultrasonography. |
| Cervical mucus score | 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. |
| Spinnbarkeit | 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. |
| Miscarriage rate | Up to 12 weeks of gestation | Miscarriage was defined as pregnancy loss before 12 weeks of gestation. |
| Cycle cancellation rate | By the end of the treatment cycle (one cycle, approximately 28 days). | Cycle cancellation was recorded when ovulation induction could not be completed. |
Countries
Turkey (Türkiye)
Contacts
STUDY_DIRECTORGamze K Karababa
VAN YUZUNCU YİL UNİVERCITY
Outcome results
None listed