Clomiphene Citrate Treatment Cycle Outcomes of Polycystic Ovary Syndrome Patients Based on Basal High Sensitive C-Reactive Protein Levels: A Cross-Sectional Study

Abstract

Background: Polycystic ovary syndrome (PCOS) is highly associated with an ovulatory infertility, features of the metabolic syndrome, including obesity, insulin resistance and dyslipidemia. Serum concentrations of high sensitive C-reactive protein (hs-CRP) were significantly higher in obese than in non-obese PCOS patients at baseline, suggesting a relationship between elevated hs-CRP levels and obesity. The aim of this study was to evaluate whether cycle day 3 hs-CRP levels before clomiphene citrate (CC) treatment would predict cycle outcomes in women with PCOS.

Materials and methods: This cross-sectional study was conducted among 84 infertile women with PCOS who were treated with CC at Zekai Tahir Burak Women's Health Education and Research Hospital, Ankara, Turkey, between January 2014 and January 2015. Based on the exclusion criteria, cycle outcomes of remaining 66 infertile women with PCOS treated with CC were analyzed. The hs-CRP levels and insulin resistance indexes were evaluated on day 3 of the CC treatment cycle. The primary outcome measures were number of preovulatory follicles measuring≥17 mm and pregnancy rates.

Results: The mean ± SD age of the patients was 24.0 ± 3.8 years (range 18-36). The mean ± SD body mass index (BMI) of the patients was 25.7 ± 4.9 (range 17-43). Fifty patients developed dominant follicle (75%) and 5 patients established clinical pregnancy during the study (clinical pregnancy rate: 7%). The mean ± SD baseline hs-CRP, fasting insulin and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) values of the patients with and without dominant follicle generation during treatment cycle were 6.42 ± 7.05 and 4.41 ± 2.95 (P=0.27), 11.61 ± 6.94 and 10.95 ± 5.65 (P=0.73), 2.68 ± 1.79 and 2.41 ± 1.30 (P=0.58), respectively. The mean ± SD baseline hs-CRP, fasting insulin and HOMA-IR values of the patients with and without clinical pregnancy establishment following treatment cycle were 6.30 ± 2.56 and 5.90 ± 6.57 (P=0.89), 11.60 ± 7.54 and 11.44 ± 6.61 (P=0.95), 2.42 ± 1.51 and 2.63 ± 1.70 (P=0.79), respectively.

Conclusion: In this study, we did not observe a predictive value of cycle day 3 hs-CRP levels on preovulatory follicle development and pregnancy rates among infertile PCOS patients treated with CC. Also, no relationship between HOMA-IR values and dominant follicle generation or clinical pregnancy establishment was demonstrated in our study, confirming the previous studies emphasizing the neutral effect of metformin utilization before and/or during ovulation induction to pregnancy rates.

Keywords: CReactive Protein; Clomiphene; Ovulation Induction; Polycystic Ovary Syndrome.

Fig.1

ROC analysis of cycle day 3 hs-CRP levels and dominant follicle establishment following 5 days CC treatment for ovulation induction (AUC=0.44, 95% CI=0.29-0.59, P=0.52). ROC; Receiver operating curve, hs-CRP; High sensitive C-reactive protein, CC; Clomiphene citrate, AUC; Area under the curve, and CI; Confidence interval.

Fig.2

ROC analysis of ovulation triggering day by hCG and clinical pregnancy achievement (AUC=0.86, 95% CI=0.74-0.99, P=0.018). Cut-off value for predicting clinical pregnancy establishment by ovulation triggering day is 16.5 days with sensitivity and specificity of 75 and 85%, respectively. ROC; Receiver operating curve, hCG; human chorionic gonadotropin, AUC; Area under the curve, and CI; Confidence interval.