Letrozole vs. Clomiphene Citrate Plus Tamoxifen for Ovulation Induction and Pregnancy Outcomes.

Infertility affects a significant proportion of women worldwide and is often associated with ovulatory dysfunction. While letrozole and clomiphene citrate are standard treatments for ovulation induction, their comparative effectiveness alongside tamoxifen as adjunct therapy remains under investigation.

Infertility affects a significant proportion of women worldwide and is often associated with ovulatory dysfunction. While letrozole and clomiphene citrate are standard treatments for ovulation induction, their comparative effectiveness alongside tamoxifen as adjunct therapy remains under investigation.

This study is a randomized clinical trial enrolling women with anovulatory infertility. Participants will be assigned to receive either letrozole alone or clomiphene citrate combined with tamoxifen. Ovulation will be monitored using ultrasound and hormonal assays. Pregnancy outcomes will be recorded and analyzed to compare efficacy between the two treatment groups.

Endometrial thickness and follicular development will be evaluated throughout the treatment cycles. All participants provide informed consent before enrollment, and the study is conducted under the approval of the Sana'a University Ethics Committee at Al-Thawra Hospital, Sana'a, Yemen.

• Letrozole (Drug): Letrozole was administered for ovulation induction in infertile women according to the study protocol.
• Clomiphene Citrate + Tamoxifen (Drug): Clomiphene citrate combined with tamoxifen was administered for ovulation induction in infertile women according to the study protocol.

Primary outcomes

• Ovulation rate [During three treatment cycles, from days 10 to 16 of each cycle, adjustments will be made based on individual variations in menstrual cycle length (cycle length: 21-35 days).]: The primary outcome is the rate of ovulation among participants, assessed by ultrasound monitoring of follicular development and serum hormone levels.

Secondary outcomes

• clinical pregnancy rate . [Pregnancy was confirmed in three treatment cycles (cycle length 21-35 days) through serum beta-hCG testing two weeks post-ovulation, followed by a transvaginal ultrasound showing a gestational sac four to six weeks later.]: presence of a clinical pregnancy confirmed by transvaginal ultrasound visualization of a gestational sac with fetal heartbeat after ovulation induction treatment.
• Endometrial thickness [During each of the three treatment cycles, from cycle day 10 until the administration of the ovulation trigger, adjustments were made based on individual variations in menstrual cycle length(21-35 days).]: Measurement of Endometrial thickness in millimeters using transvaginal ultrasound on the day of ovulation trigger during ovulation induction treatment cycles.
• Adverse Events/ Side effect [From day 2 of the menstrual cycle (initiation of ovulation induction treatment) through up to 3 treatment cycles (cycle length: 21-35 days), until 2 weeks after the ovulation trigger.]: Incidence of adverse events (CTCAE v5.0 grades 1-3 ), including nausea, headache, hot flushes, and ovarian hyperstimulation syndrome ( OHSS), was assessed by patient questionnaire per ovulation induction cycles.

Sex: Female, ages: 18 Years to 40 Years

Inclusion Criteria:

* Women aged between 18 and 40 years.
* Patients with anovulatory polycystic ovaries.
* Presence of a normal uterus and patent fallopian tubes, as confirmed by hysterosalpingography (HSG).
* Husband's semen analysis within normal parameters.
* Normal serum prolactin and thyroid-stimulating hormone (TSH) levels.

Exclusion Criteria:

* Spontaneous pregnancy.
* Women with hyperprolactinemia or thyroid dysfunction.
* Active liver disease or renal disease.
* Documented pelvic diseases such as endometriosis, ovarian pathology, hydro- or pyosalpinx, or uterine fibroids.
* Previous history of ovarian drilling.
* Contraindications to letrozole, clomiphene citrate, or tamoxifen.
* History of hypersensitivity reactions to study medications.

• Ghada Abdullatef Al-Rajami, MD, Principal investigator, Sana'a University