PB0454 - Women who achieved pregnancy after ovarian stimulation show prothrombotic fibrin clot phenotype compared to non-pregnant women: associations with neurohormones

Background: Infertility affects 10-16% of couples and is considered a civilization-related disease. Enhanced thrombin generation, higher factor VIII and fibrinogen in association with estradiol and progesterone levels were reported within the first few weeks of pregnancy. Recently, neurohormone concentrations, such as elevated phoenixin (PNX-14), nesfatin-1 (NES-1), dopamine (DA), and decreased oxytocin (OT) were associated with positive pregnancy outcome after ovarian stimulation (OS).

Aims: This study was aimed to evaluate potential associations between fibrin clot permeability (Ks) and/or clot lysis time (CLT) along with thrombin generation with relation to neurohormone levels.

Methods: In this prospective study we enrolled 56 infertile women aged 32±5 years, BMI 24.5±5 kg/m2, treated with letrozole at the Department of Gynecological Endocrinology. Ks, CLT, and thrombin generation capacity were performed at baseline and after OS, along with serum levels of PNX-14, NES-1, DA and OT measured using ELISAs. Pregnancy rates after OS were noted. All participants provided written informed consent in accordance with the Declaration of Helsinki.

Results: At baseline, women who achieved pregnancy (n=18, 32.1%) compared to non-pregnant showed 26.6% higher Ks (p=0.0006), with no differences in peak thrombin, ETP or CLT (all p>0.05). However, in pregnant women ETP correlated negatively with PNX-14 (r=-0.56, p=0.061) and positively with NES-1 (r=0.45, p=0.06) and OT (r=0.77, p=0.0002), while peak thrombin was solely associated with OT (r=0.50, p=0.033). No similar associations were observed for Ks and CLT.
After COS, pregnant women showed prolonged CLT (+11.8%, Fig. 1A) and higher ETP (+8%, Fig. 1B), along with a tendency to reduced Ks (-17.6%, Fig. 1C). Importantly, ETP was correlated with CLT (Fig. 2A) and tended to correlate with Ks (r=-0.43, p=0.075). Hypofibrinolysis and enhanced thrombin generation parameters were positively associated with PNX-14 levels (Fig. 2B-D).

Conclusion(s): Positive pregnancy outcome after OS is associated with hypofibrinolysis and enhanced thrombin generation in relation to elevated PNX-14 levels.