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

Tal R, Seifer DB, Grazi RV, Malter HE - Reprod. Biol. Endocrinol. (2014)

Bottom Line: Since sFlt-1 binds free PlGF, preventing its signal transduction, we calculated PlGF bioavailability as PlGF/sFlt-1 ratio.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).

View Article: PubMed Central - PubMed

Affiliation: Division of Reproductive Endocrinology and Infertility, Genesis Fertility & Reproductive Medicine, Maimonides Medical Center, Brooklyn, NY, USA. resheft@gmail.com.

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.

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Related in: MedlinePlus

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.
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Fig2: 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.

Mentions: Follicular fluid concentration of sFlt-1 was decreased 1.4-fold in PCOS compared with non-PCOS women (2.7 ± 0.6 vs. 3.7 ± 0.5 ng/ml, respectively, p = 0.04) (Figure 1B). Similarly, no differences were noted between PCOS and non-PCOS women in sFlt-1 serum levels at all three measured time points throughout controlled ovarian stimulation (Table 3). Since sFlt-1 binds PlGF, reducing its free levels and preventing its signal transduction, we calculated PlGF bioavailability as a ratio of PlGF to sFlt-1 (PlGF/sFlt-1). PlGF bioavailability in follicular fluid was significantly greater (2-fold) in PCOS women compared with non-PCOS controls (0.022 vs. 0.01, respectively, p < 0.01) (Figure 2).Pearson correlation analysis was performed to evaluate for correlations between PlGF or sFlt-1 concentration and various stimulation cycle parameters. Follicular fluid PlGF correlated positively with number of oocytes retrieved (r = 0.41, p = 0.03) and AMH (r = 0.60, p = 0.001), and inversely with age (r = −0.38, p = 0.04) (Figure 3). Follicular fluid PlGF was not found to correlate with total gonadotropin dose administered (r = −0.29, p = 0.15), peak estrogen level (r = 0.16, p = 0.43) or day 3 FSH (r = 0.09, p = 0.66). With regards to stimulation cycle outcomes, no correlation was found between follicular fluid PlGF and fertilization rate (r = −0.20, p = 0.34). Moreover, no difference was noted in follicular fluid PlGF level between pregnant and non-pregnant women (49.8 vs. 43.8 pg/ml, p = NS). No correlations were found between follicular fluid sFlt-1 and either age, AMH, day 3 FSH, total gonadotropin dose, peak estrogen level, number of oocytes retrieved, fertilization rate or clinical pregnancy rate (data not shown).Table 3


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

Tal R, Seifer DB, Grazi RV, Malter HE - Reprod. Biol. Endocrinol. (2014)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4150963&req=5

Fig2: 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.
Mentions: Follicular fluid concentration of sFlt-1 was decreased 1.4-fold in PCOS compared with non-PCOS women (2.7 ± 0.6 vs. 3.7 ± 0.5 ng/ml, respectively, p = 0.04) (Figure 1B). Similarly, no differences were noted between PCOS and non-PCOS women in sFlt-1 serum levels at all three measured time points throughout controlled ovarian stimulation (Table 3). Since sFlt-1 binds PlGF, reducing its free levels and preventing its signal transduction, we calculated PlGF bioavailability as a ratio of PlGF to sFlt-1 (PlGF/sFlt-1). PlGF bioavailability in follicular fluid was significantly greater (2-fold) in PCOS women compared with non-PCOS controls (0.022 vs. 0.01, respectively, p < 0.01) (Figure 2).Pearson correlation analysis was performed to evaluate for correlations between PlGF or sFlt-1 concentration and various stimulation cycle parameters. Follicular fluid PlGF correlated positively with number of oocytes retrieved (r = 0.41, p = 0.03) and AMH (r = 0.60, p = 0.001), and inversely with age (r = −0.38, p = 0.04) (Figure 3). Follicular fluid PlGF was not found to correlate with total gonadotropin dose administered (r = −0.29, p = 0.15), peak estrogen level (r = 0.16, p = 0.43) or day 3 FSH (r = 0.09, p = 0.66). With regards to stimulation cycle outcomes, no correlation was found between follicular fluid PlGF and fertilization rate (r = −0.20, p = 0.34). Moreover, no difference was noted in follicular fluid PlGF level between pregnant and non-pregnant women (49.8 vs. 43.8 pg/ml, p = NS). No correlations were found between follicular fluid sFlt-1 and either age, AMH, day 3 FSH, total gonadotropin dose, peak estrogen level, number of oocytes retrieved, fertilization rate or clinical pregnancy rate (data not shown).Table 3

Bottom Line: Since sFlt-1 binds free PlGF, preventing its signal transduction, we calculated PlGF bioavailability as PlGF/sFlt-1 ratio.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).

View Article: PubMed Central - PubMed

Affiliation: Division of Reproductive Endocrinology and Infertility, Genesis Fertility & Reproductive Medicine, Maimonides Medical Center, Brooklyn, NY, USA. resheft@gmail.com.

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.

Show MeSH
Related in: MedlinePlus