Protein C Activity in Women With Unexplained Infertility
Objectives: The relation between thrombophilia and infertility has drawn the attention in last few years. Most studies investigating the effect of inherited thrombophilia on infertility studied the relationship between thrombophilia and implantation failure. It was found to be a possible cause of impaired implantation in some subgroups of infertile women. Still thrombophilia screening in general infertile population is unjustified and in fact may lead to increased patient anxiety after a positive test result together with the increased cost. Due to the poor information available concerning the relationship between inherited thrombophilia and infertility, we performed a case–control study in order to evaluate the prevalence of protein C activity in women with unexplained infertility.
Materials & Methods: This is a case–control study conducted to evaluate the prevalence of protein C activity in women with unexplained infertility conducted at Ain-Shams University Maternity Hospital. 48 women with unexplained primary infertility and another 48 fertile women of matched age group as their control were recruited from July 2011 to January 2013. Using the BIOPHEN Protein C 2.5 assay, protein C was measured following a specific activation with Protac, an enzyme extracted from snake venom. Activated protein C (APC) then specifically cleaves the specific substrate SaPC-21, releasing para-Nitroaniline (pNA), and its color is measured at 405 nm. 2(4.2%) cases of protein C deficiency were encountered in the unexplained infertility group while none found in the control group.
Results: This study failed to find relationship between protein C activity and unexplained infertility compared to normal fertile population. In spite of finding 2 cases with protein C deficiency in the unexplained infertility sample population and none in the control group, this difference failed to reach significance (P=0.495 and P=0.076 respectively).
Conclusion: In conclusion, this study failed to find any association between protein C activity and unexplained infertility.
Jose-Miller AB, Boyden JW, Frey KA. Infertility. American Family Physician. 2007; 75:849-856.
Aboulghar M, Mansour R, Serour G, Abdrazek A, Amin Y, Rhodes C. Controlled ovarian hyperstimulation and intrauterine insemination for treatment of unexplained infertility should be limited to a maximum of three trials. Fertility and Sterility. 2001; 75(1):88–91. doi: 10.1016/s0015-0282(00)01641-1
Siristatidis C, Bhattacharya S. Unexplained infertility: does it really exist? Does it matter? Human Reproduction. 2007; 22(8):2084–7. doi: 10.1093/humrep/dem117
Steures P, van der Steeg JW, Hompes PG, Habbema JDF, Eijkemans MJ, Broekmans FJ, et al. Intrauterine insemination with controlled ovarian hyperstimulation versus expectant management for couples with unexplained subfertility and an intermediate prognosis: A randomised clinical trial. The Lancet. 2006; 368(9531):216–21. doi: 10.1016/s0140-6736(06)69042-9
Casadei L, Puca F, Privitera L, Zamaro V, Emidi E. Inherited thrombophilia in infertile women: Implication in unexplained infertility. Fertility and Sterility. 2010; 94(2):755–7. doi: 10.1016/j.fertnstert.2009.10.014
Coulam CB, Jeyendran RS. Thrombophilic gene polymorphisms are risk factors for unexplained infertility. Fertility and Sterility. 2009; 91(4):1516–7. doi: 10.1016/j.fertnstert.2008.07.1782
Coulam CB, Jeyendran R, Fishel LA, Roussev R. Multiple thrombophilic gene mutations are risk factors for implantation failure. Reproductive BioMedicine Online. 2006; 12(3):322–7. doi: 10.1016/s1472-6483(10)61004-8
Grandone E, Colaizzo D, Lo Bue A, Checola MG, Cittadini E, Margaglione M. Inherited thrombophilia and in vitro fertilization implantation failure. Fertility and Sterility. 2001; 76(1):201–2. doi: 10.1016/s0015-0282(01)01832-5
Bellver J, Soares SR, Alvarez C, Munoz E, Ramirez A, Rubio C, et al. The role of thrombophilia and thyroid autoimmunity in unexplained infertility, implantation failure and recurrent spontaneous abortion. Human Reproduction. 2007; 23(2):278–84. doi: 10.1093/humrep/dem383
Brenner B, Kupferminc MJ. Inherited thrombophilia and poor pregnancy outcome. Best Practice & Research Clinical Obstetrics & Gynaecology. 2003; 17(3):427–39. doi: 10.1016/s1521-6934(03)00006-3
Younis JS, Shukha M, Ben-Ami M, Izhaki I, Blumenfeld Z, Brenner B, et al. Evaluation of the Protein C Global Assay During Normal Pregnancy and After Assisted Reproduction. Obstetrics & Gynecology. 2010; 115(5):969–74. doi: 10.1097/aog.0b013e3181db67f3
Biron C, Galtier-Dereure F, Rabesandratana H, Bernard I, Aguilar-Martinez P, Schved J-F, et al. Hemostasis parameters during ovarian stimulation for in vitro fertilization: Results of a prospective study. Fertility and Sterility. 1997; 67(1):104–9. doi: 10.1016/s0015-0282(97)81864-x
Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HWG, Behre HM, et al. World Health Organization reference values for human semen characteristics. Human Reproduction Update. 2009; 16(3):231–45. doi: 10.1093/humupd/dmp048
Stenflo J. Structure and Function of Protein C. Seminars in Thrombosis and Hemostasis. 1984; 10(02):109–21. doi: 10.1055/s-2007-1004413
Exner T, Vaasjoki R. Characterisation and some properties of the protein C activator from Agkistrodon Contortrix Contortrix venom. Thrombosis and Haemostasis. 1988; 59:40-44. PMID: 3363532
Behjati R, Modarressi MH, Jeddi-Tehrani M, Dokoohaki P, Ghasemi J, Zarnani AH, et al. Thrombophilic mutations in Iranian patients with infertility and recurrent spontaneous abortion. Annals of Hematology. 2006; 85(4):268–71. doi: 10.1007/s00277-005-0021-0
Younis JS, Ben-Ami M, Izhaki I, Brenner B, Sarig G. Reduced protein C Global assay level in infertile women prior to IVF-ET treatment. Journal of Assisted Reproduction and Genetics. 2013; 31(1):101–7. doi: 10.1007/s10815-013-0131-x
Younis JS, Samueloff A. Gestational vascular complications. Best Practice & Research Clinical Haematology. 2003; 16(2):135–51. doi: 10.1016/s1521-6926(02)00099-3
Fatini C, Conti L, Turillazzi V, Sticchi E, Romagnuolo I, Milanini MN, et al. Unexplained infertility: Association with inherited thrombophilia. Thrombosis Research. 2012; 129(5):e185–e188. doi: 10.1016/j.thromres.2012.02.012
Ferroni P, La Farina F, Palmirotta R, Martini F, Raparelli V, Nigro C, et al. Predictive value of thrombopath determination in women with infertility and pregnancy complications. Clinica Chimica Acta. 2010; 411(1-2):37–42. doi: 10.1016/j.cca.2009.09.035
Azem F. Increased rates of thrombophilia in women with repeated IVF failures. Human Reproduction. 2004; 19(2):368–70. doi: 10.1093/humrep/deh069
Qublan HS, Eid SS, Ababneh HA, Amarin ZO, Smadi AZ, Al-Khafaji FF, et al. Acquired and inherited thrombophilia: implication in recurrent IVF and embryo transfer failure. Human Reproduction. 2006; 21(10):2694–8. doi: 10.1093/humrep/del203
Steinvil A, Raz R, Berliner S, Steinberg DM, Zeltser D, Levran D, et al. Association of common thrombophilias and antiphospholipid antibodies with success rate of in vitro fertilisation. Thrombosis and Haemostasis. 2012; 108(6):1192–7. doi: 10.1160/th12-06-0381
Rudick B, Su HI, Sammel MD, Kovalevsky G, Shaunik A, Barnhart K. Is factor V Leiden mutation a cause of in vitro fertilization failure? Fertility and Sterility. 2009; 92(4):1256–9. doi: 10.1016/j.fertnstert.2009.03.089
Simur A, Ozdemir S, Acar H, Colakoğlu MC, Görkemli H, Balci O, et al. Repeated in vitro fertilization failure and its relation with thrombophilia. Gynecologic and Obstetric Investigation. 2009; 67(2):109–12. doi: 10.1159/000165776
Vaquero E, Lazzarin N, Caserta D, Valensise H, Baldi M, Moscarini M, et al. Diagnostic evaluation of women experiencing repeated in vitro fertilization failure. European Journal of Obstetrics and Gynecology. 2006; 125(1):79-84. doi: 10.1016/j.ejogrb.2005.08.001
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution 3.0 License.