ESPE Abstracts

Background: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder among women of reproductive age and is characterised by chronic low-grade inflammation, ovulatory dysfunction and hyperandrogenism, and often by insulin resistance. The IGF system is involved in glucose metabolism regulation and is altered in chronic inflammation where both IGF-I and –II can be reduced. We previously described increased HMGB1 content in follicular fluid (FF) in PCOS. HMGB1 is related with both inflammation and insulin resistance, and the IGF system regulates ovarian function; specifically, IGF-II promotes follicular maturation. The aim of this study was to investigate changes in the IGF system in FF from PCOS with respect to controls and to evaluate possible relationships with HMGB1.

Methods: 72 women with PCOS [CA:34.1±4.7yr; BMI:25.6±5.5kg/m²] diagnosed following the Rotterdam criteria, and 72 healthy controls [CA:36.9±3.6yr; BMI 23.1±4.2kg/m²] were included. Induction of multiple follicular development for IVF was conducted according to a specific long luteal GnRH agonist protocol. FF were collected from dominant follicles during oocyte retrieval and centrifuged to remove red blood cells and debris. IGF-I, IGF-II, IGFBP-1, IGFBP-2 and HMGB1 were measured in FF using specific ELISA kits. Student’s T-test was used for comparison between PCOS and controls. Data are mean±SD.

Results: IGF-II levels in FF were lower in PCOS women with respect to controls (386.2±208.4vs518.6±152.0ng/ml, respectively;P<0.0001) whereas IGF-I (104.4±36.3vs 107.1±36.0ng/ml, IGFBP-1 (9.1±4.0vs 9.3±4.5ng/ml) and IGFBP-2 levels (673.9±199.9vs 647.7±211.0ng/ml) were similar in both groups. Interestingly, the stratification of the PCOS population based on BMI showed that obese women (BMI>30Kg/m²;n=19)had a lower content of both IGF-I (80.7±18.8vs107.1±36.0ng/ml; P=0.01) and IGF-II (368.9±173.9vs518.6±152.0ng/ml; P=0.003), while IGFBP-1 and -2 were unchanged with respect to controls. IGF-1 levels were negatively correlated with BMI both in PCOS and controls. HMGB1 FF levels were confirmed to be higher in PCOS patients compared to controls (40.6±22.0vs28.9±19.7ng/ml; P=0.001), and were not associated with any IGF system peptide.

Conclusions: FF IGF-II content was reduced in PCOS and could contribute to explain reduced follicle development. As both IGF-I and -II content was reduced in the obese PCOS women this could reflect both increased insulin resistance, and effects of body weight/adipose tissue on changes in the ovary. Being HMGB1 an indirect measurement of both inflammation and glucose metabolism this could explain the lack of any correlation with the IGF system in the ovary.