Researchers have proposed that leptin, a peptide secreted by fat cells in adipose tissue, may play a role in the pathophysiology of PCOS (Hum Reprod 2002;17(12): 3016-3025). Leptin has also been proposed as a marker for response to metformin in PCOS patients. As ovulation induction is one of the most difficult aspects of PCOS to treat, the purpose of our study was to investigate leptin levels during controlled ovarian hyperstimulation (COH) for IVF in PCOS patients and determine if leptin levels are a marker for ovarian response to ovulation induction. Here we review RESULTS with the commonly employed protocol incorporating oral contraceptive pill (OCP)/GnRH-agonist dual suppression followed by low-dose gonadotropin therapy (≤3 ampules/day). Prospective analysis of serum leptin levels of PCOS patients undergoing IVF We conducted a study of patients with PCOS undergoing 77 IVF cycles with the dual suppression /low dose gonadotropin protocol during a two year period. Twenty patients (29.0%) were concurrently treated with metformin. Serum was prospectively collected and cryopreserved for analysis at a later date. Serum leptin levels were measured by ELISA (R&D Systems, MN) on day 3 of GnRH-agonist withdrawal bleed and on the day of hCG administration. Patient statistics and cycle parameters were compared using non-parametric and Chi-Square tests and correlation coefficients. The mean age of patients was 30.6±2.9 years, and the mean BMI was 24.1±4.7. Peak mean estradiol (E2) levels were 1578 ± 912 pg/mL on day of hCG. Almost all patients completed the cycle with oocyte retrieval (94.6%) and embryo transfer (96.2%). An average of 13.3±3 oocytes with 9.7±4.9 mature oocytes were retrieved per cycle, with 6.9±3.8 normally fertilized oocytes per cycle. Total, clinical and ongoing pregnancy rates were 62.3%, 58.5%, and 50.9%, respectively. Day 3 and day of hCG leptin levels correlated with BMI (Day 3, r=0.4, Fisher’s exact value P<.005; Day of hCG, r=0.83, Fisher’s exact p<.0001). Mean serum leptin levels increased during stimulation: 8825.0±9944.3 pg/mL vs. 22971.9±20027.7, p<.0001 (Day 3 vs. day of hCG). The magnitude of the increase in leptin was not associated with a higher number of oocytes or mature oocytes. Furthermore, there was no association with the likelihood of becoming pregnant, even when BMI was controlled for as a confounder. Neither leptin levels nor the rise in leptin levels correlated with serum E2 levels during stimulation. Metformin usage was not associated with any changes in leptin level increase during stimulation. Although leptin levels consistently rose during hormonal stimulation, they do not appear to be predictive of ovarian response to stimulation or clinical outcome. The fact that leptin levels at least double in the majority of PCOS patients undergoing stimulation suggests that leptin may play a significant role in multifollicular recruitment during COH in PCOS patients. However, the exact modality and significance of its role have yet to be elucidated.