A Randomized controlled trial of combination letrozole plus clomiphene citrate and letrozole alone for ovulation induction in infertile women with polycystic ovary syndrome.

Infertility is a common reproductive health problem, with polycystic ovary syndrome being the leading cause of anovulatory infertility in women of reproductive age. Ovulation induction remains the cornerstone of infertility management in polycystic ovary syndrome. Letrozole is currently recommended as the first line agent for ovulation induction, while clomiphene citrate, previously the standard therapy, is now used as a second line or adjunctive agent. Although both drugs act by reducing estrogen mediated negative feedback on the hypothalamic pituitary axis, they differ in their mechanisms of action and effects on the endometrium and follicular development.

Several studies suggest that combining letrozole and clomiphene citrate may improve ovulation rates compared to letrozole alone, however, existing evidence is limited and inconsistent. This randomized controlled study is designed to compare the effectiveness of combination therapy (letrozole plus clomiphene citrate) versus letrozole alone for ovulation induction in infertile women with polycystic ovary syndrome.

Eligible women aged 18 to 40 years diagnosed with polycystic ovary syndrome according to Rotterdam criteria and with at least one patent fallopian tube and normal partner semen parameters will be randomized into two groups. Group I will receive letrozole 2.5 mg plus clomiphene citrate 50 mg daily from cycle day 3 to day 7, while Group 2 will receive letrozole 2.5 mg alone for the same duration. Participants will be monitored with serial transvaginal ultrasonography for follicular development and endometrial thickness. Ovulation will be confirmed by mid luteal serum progesterone levels more than 3 ng per mL. Pregnancy will be assessed by serum or urine B hCG testing.

The primary outcome is ovulation rate. Secondary outcomes include number and size of dominant follicles, endometrial thickness, pregnancy rate, and incidence of adverse events such as ovarian hyperstimulation syndrome.

This study aims to determine whether combination therapy offers superior ovulation outcomes compared to letrozole alone, while maintaining safety and cost effectiveness, potentially providing an alternative to more invasive and expensive second line treatments.