A Comparative study of efficacy of Letrozole Versus Clomiphene Citrate in Ovulation Induction in patients with Polycystic Ovarian syndrome

The Ovarian cortex at puberty contains hundreds of thousands of primordial follicles. Initially independent of gonadotropins, a cohort (hundreds) of primordial follicles is recruited to grow. During the early follicle development, the oocyte enlarge and the granulosa cells proliferate to form a preantral follicle. Over 3 – 6 months, the follicle develops FSH receptors in the granulosa cells and LH receptors in the theca cells. At this stage, antral follicles become acutely dependent on FSH for further development. Just before menses, falling estrogen levels result in with drawal of negative feed back centrally leading to increased gonadotropin levels. FSH stimulates granulosacell proliferation and differentiation, with the development of more FSH receptors and the production of aromatase. LH stimulates androstenedione production by theca cells that diffuses in to the granulosa cell providing substrate for estrogen secretion. This step is catalysed by the aromatase enzyme, which is induced by FSH. The so called two – cell, two – gonadotropin theory postulated that FSH concentrations must exceed a certain level (FSH) threshold) before follicular development will proceed. AIM OF STUDY: To study about the comparative efficacy of Letrozole Vs clomiphene citrate in ovulation Induction in patients with polycystic ovarian syndrome. MATERIALS AND METHODS: 100 women belonging to eligible criteria of age (21 – 35 yrs) after obtaining informed consent from each participant. Study Design: Cohort study. A prospective, randomized, parallel, multicentric comparative trial. Period of Study: 2008 – 2009. Place of Study: Department of fertility research clinic, IOG, Egmore, Chennai. Inclusion Criteria: 1. Age : 21 – 35 yrs. 2. Period of Infertility. 3. PCOS with at least 2 of Diagnostic criteria • Oligomenorrhea / Amenorrhea. • Clinical evidence of Acne / hirsutism. • USG evidence of PCOS. 4. Normal semen analysis. 5. Normal pelvic USG. 6. Normal bilateral tubal patency. 7. No recent treatment for OI (with in 6 months). 8. Willingness and giving written informed consent. Exclusion Criteria: 1. Women with uterine /adnexal pathology (Eg) fibroid, ovarian cyst are excluded from the study. 2. Women with clinical features of hyperthyroidism, hypothyroidism are excluded. 3. Those with previous history of any surgeries related to genital tract as per history were excluded. 4. Those with impaired hepatic / renal function were excluded. 5. Women with RBS> 140 mg/d/ were excluded from the study. 6. Age > 35 yrs and obese patients were excluded from this study. 7. Lack of willingness. The participants in this study were subjected to history, clinical and biochemical evaluation. SUMMARY: In the patients recruited in this study, 1. The mean age in L group was 24.8 yrs and in CC group 25.1. years. 2. The mean duration of infertility in L group was 2.43 years and in CC group 2.44 years. 3. In Letrozole group, the ovulation rate was 67% and in CC group 52%. 4. In Letrozole group, 52% of the cases developed single dominant follicle and 15% of the cases had developed two dominant follicles. 5. In CC group only, 6% of the cases had monofollicular ovulation and 23% of the cases developed two follicles. 6. The mean diameter of largest follicle in L group is 21.15 mm and in CC group 18.76 mm. 7. The mean endometrial thickness is L group is 8.6 mm and in CC group 7.1 mm. 8. The serum progesterone level in L group is 13.41 ng/ml and CC group is 12.27 ng/ml. CONCLUSION: Letrozole is more effective in inducing ovulation in patients with an ovulatory cycles than clomiphene citrate in terms of monofollicular ovulation and a better endometrial thickness than when compared with clomiphene citrate. The mean diameter of the largest follicle and the serum progesterone level studied showed letrozole was superior than clomiphene citrate in inducing ovulation. Hence Letrozole can be recommended as the first line drug for ovulation induction in anovulatory patients with polycystic ovarian syndrome.