Sitagliptin and metformin alone or in combination in patients with polycystic ovarian syndrome (PCOS): a pilot study

Abstract

OBJECTIVE: To identify the relationship between diabetes associated peptide hormones (DAPH) and inflammatory markers in follicular fluid and serum of obese and lean polycystic ovary syndrome (PCOS) patients with in vitro fertilization (IVF) cycle parameters and pregnancy outcomes. DESIGN: Prospective Descriptive Study. MATERIALS AND METHODS: An IRB approved study of three groups of IVF patients 30 kg/m2; n1⁄48), lean PCOS (BMI<25 kg/m2; n1⁄412), and donor or tubal factor controls (n1⁄411). PCOS was diagnosed by Rotterdam criteria. Serumwas collected prior to IVF cycle initiation. Follicular fluid was collected at retrieval. A Human Diabetes 10plex Assay was used to quantify DAPH. A Human Cytokine 27-plex Assay was used to quantify inflammatory markers. Results were analyzed using one-way ANOVA with Tukey post hoc analysis using SPSS v 21. Significance was defined as p<0.05. RESULTS: Of the 10 DAPH assessed, C-peptide, insulin, and leptin had significant associations. Obese PCOS patients had higher levels of C-peptide (194.4 163.5 pg/mL), insulin (172.6 113.6 pg/mL), and leptin (10,046.1 4920.2pg/mL) in follicular fluid compared to lean PCOS and controls. A difference in C-peptide (p<0.03), insulin (p<0.01), and leptin (p1⁄40.04) was noted between obese and lean PCOS follicular fluid. A difference in C-peptide (p<0.03) and insulin (p<0.01) was noted between obese PCOS and control follicular fluid. Obese PCOS had higher levels of serum leptin (5575.5 1650.2pg/mL), with a difference in leptin concentrations noted between obese PCOS and controls (p1⁄40.01), and obese and lean PCOS (p<0.01). Higher levels of C-peptide (p<0.04) and leptin (p1⁄40.01) in the follicular fluid were associated with increased gonadotropin usage. A trend toward fewer oocytes retrieved (p1⁄40.06), and significantly lower number of normally fertilized zygotes (p<0.04) was seen with higher C-peptide levels. A trend toward an increased clinical pregnancy rate was noted with lower serum leptin levels (p1⁄40.08). There was no significant difference in inflammatory marker concentration or pregnancy outcomes between the groups. CONCLUSION: Elevated levels DAPH, which are highly correlated with adverse long-term health outcomes, are present in young obese PCOS patients undergoing IVF. DAPHs may play a role in the need for higher gonadotropin dosing in IVF cycles and suboptimal oocyte fertilization in this patient population. Supported by: Funding provided through a Merck Investigator Studies Program Grant.