Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation

Abstract

Background: Polycystic ovarian syndrome (PCOS) is characterized by increased ovarian angiogenesis and vascularity. Accumulating evidence indicates that vascular endothelial growth factor (VEGF) is increased in PCOS and may play an important role in these vascular changes and the pathogenesis of this disease. Placental growth factor (PlGF), a VEGF family member, has not been previously characterized in PCOS women. We investigated levels and temporal expression patterns of PlGF and its soluble receptor sFlt-1 (soluble Fms-like tyrosine kinase) in serum and follicular fluid (FF) of women with PCOS during controlled ovarian stimulation.

Methods: This was a prospective cohort study of 14 PCOS women (Rotterdam criteria) and 14 matched controls undergoing controlled ovarian stimulation. Serum was collected on day 3, day of hCG and day of oocyte retrieval. FF was collected on retrieval day. PlGF, sFlt-1 and anti-mullerian hormone (AMH) protein concentrations were measured using ELISA. Since sFlt-1 binds free PlGF, preventing its signal transduction, we calculated PlGF bioavailability as PlGF/sFlt-1 ratio.

Results: Serum PlGF and sFlt-1 levels were constant throughout controlled ovarian stimulation, and no significant differences were observed in either factor in PCOS women compared with non-PCOS controls at all three measured time points. However, FF PlGF levels were increased 1.5-fold in PCOS women compared with controls (p < 0.01). Moreover, FF PlGF correlated positively with number of oocytes retrieved and the ovarian reserve marker anti-mullerian hormone (AMH) and negatively with age. In addition, FF sFlt-1 levels were decreased 1.4-fold in PCOS women compared to controls (p = 0.04). PlGF bioavailability in FF was significantly greater (2-fold) in PCOS women compared with non-PCOS controls (p < 0.01).

Conclusions: These data provide evidence that FF PlGF correlates with ovarian stimulation and that its bioavailability is increased in women with PCOS undergoing controlled ovarian stimulation. This suggests that PlGF may play a role in PCOS pathogenesis and its angiogenic dysregulation.

Figure 1

Follicular fluid PlGF and sFlt-1 concentrations. Follicular fluid concentration of PlGF (pg/ml) (A) and sFlt-1 (ng/ml) (B) in PCOS (polycystic ovarian syndrome) and non-PCOS women undergoing controlled ovarian stimulation. Data are presented as mean ± standard deviation. *p < 0.05 for PCOS vs. non-PCOS women.

Figure 2

Follicular fluid PlGF bioavailability is increased in PCOS. PlGF bioavailability (PlGF/sFlt-1 ratio) in follicular fluid (ng/ml) of PCOS (polycystic ovarian syndrome) and non-PCOS women undergoing controlled ovarian stimulation. Data are presented as mean ± standard deviation. *p < 0.01 for PCOS vs. non-PCOS women.

Figure 3

Follicular fluid PlGF correlates with oocyte yield, AMH and age. Correlations between follicular fluid levels of PlGF and (A) number of oocytes retrieved, (B) AMH or (C) age in women with polycystic ovarian syndrome or controls. Positive correlations were found between PlGF and number of oocytes retrieved (r = 0.41, p = 0.03) and between PlGF and AMH (r = 0.60, p = 0.001). PlGF and age correlated inversely (r = −0.38, p = 0.04).