Reduced Protein C Global Assay Levels in Infertile Women with in vitro Fertilization Failure: A Pilot Study

Abstract

Protein C global is a global dotting assay that evaluates abnormalities in the protein C anticoagulant pathway. A few studies have examined this assay in relation to assisted reproductive technology (ART), but its role in infertile women with in vitro fertilization (IVF) failure remains unclear. In this study, we assessed protein C in infertile women with a history of IVF failure who were undergoing ART. We examined 45 healthy fertile women who conceived naturally, and 45 infertile women with 2 or more implantation failures undergoing ART. Both protein C and activated protein C resistance (APC-R) were evaluated. The results showed that mean protein C expressed as a normalized ratio (PCAT-NR) was significantly lower in the study group compared to the control group (0.76 ± 0.15 vs. 0.91 ± 0.14, respectively; p = 0.0001). Follow-up on ART outcomes showed that women who failed ART had significantly lower PCAT-NR compared to successful cases. PCAT-NR did not correlate with APC-R levels in the study (r = 0.125, p < 0.5) or failed ART subgroups. Using logistic regression analysis, patients with lower PCAT-NR levels showed an elevated risk of implantation failure (p = 0.04, OR 0.50, 95% CI 0.26-0.84). In conclusion, protein C global assay may play a role in the etiology of IVF failure, which might be independent of APC-R. Larger studies are encouraged to validate these findings and explore the underlying pathophysiological mechanisms.

The protein C deficiency and its effects on in-vitro fertilization outcome and recurrent pregnancy loss: a Syrian cohort study

“…Some studies indicate that the levels of protein C were low in infertile women who underwent IVF cycles. [11][12][13]17 When comparing the prevalence of protein C deficiency among women with history of abortions in other studies, we found that the prevalence in our study is higher than some previous studies, and it is also lower than others. 11,12,17,18 This disparity in the prevalence of protein C deficiency may be due to differences in the sample size, the inclusions' criteria of the patients or the types of protein C assay.…”

“…Although the test of protein C has been evaluated in different samples of women with RPL, and women with recurrent IVF failure, very few studies has evaluated protein C levels in relation to the success or failure of IVF. [11][12][13]19 Another significant finding in this study showed that the level of protein C affects the results of IVF cycles' outcomes. This is compatible with the findings of El Masry el al.…”

“…This is compatible with the findings of El Masry el al. 13 There are many contradictions and differences in the medical literature about the association between IVF failure and thrombophilia, and especially regarding protein C. Some studies have documented this association, while others did not find any association. [20][21][22][23][24][25] Furthermore, other studies did not find any protein C deficiency in women with recurrent IVF failure.…”

An enhanced clot growth rate before in vitro fertilization decreases the probability of pregnancy

“…However, in their study, the results of the thrombin generation assay and TEG before the start of IVF were not associated with IVF outcomes [42]. In another paper by El Masry and colleagues [4], it was shown that women who had a negative outcome have a more pronounced decrease in protein C activity than women who became pregnant, which also points to the connection between the initially present procoagulant disorder and a negative IVF outcome.…”

“…Infertility in women is often accompanied by a hypercoagulable state. The rates of thrombophilia [1,2] and circulating microvesicle concentrations [3] are higher and protein C activity is lower [4] in women with conception problems. In vitro fertilization (IVF) can enhance these procoagulant changes in infertile women mostly as a result of high-dose hormonal therapy.…”