Periodicity in the Levels of Serum Plasminogen Activator Inhibitor-1 is a Robust Prognostic Factor for Embryo Implantation and Clinical Pregnancy in Ongoing IVF Cycles

Overview

Journal J Hum Reprod Sci

Date 2014 Nov 15

PMID 25395746

Citations 1

Authors

Bindu N Mehta

Nirmalendu Nath

Natachandra Chimote

Affiliations

Soon will be listed here.

Abstract

Context: Plasminogen activator inhibitor-1 (PAI-1) has been inversely correlated to proteolytic extracellular-matrix degradation exerted by urokinase-type (u-PA) and tissue-type plasminogen activators (t-PA). Any pathological disturbance in PAI-1 levels may lead to several pregnancy complications.

Aims: To assess the influence of periodicity in serum PAI-1 levels on embryo implantation and clinical pregnancy outcome in IVF cycles.

Settings And Design: Prospective study of 120 IVF cycles at private infertility centre.

Material And Methods: Endometrial response (ER) assessment by measuring Endometrial thickness (cm) and echopattern (grade). Serum PAI-1(ng/ml) measurement by ELISA method on day of hCG, day of ET and days 7 and 14 of ET. Main outcome measure was clinical pregnancy.

Statistical Analysis: Student "t" test, ANOVA, Post-test for linear trend, Pearson Correlation.

Results: PAI-1 levels declined from dhCG to dET (318.8 ± 36.1 to 176.1 ± 28.4) whereas they increased steadily from dET to d7 to d14ET (176.1 ± 28.4 to 285.2 ± 30.4 to 353.5 ± 150.4; P = 0.0004) in pregnant group (n = 31). Conversely, dhCG to dET levels increased in both nonpregnant (n = 75; 173.8 ± 18.3 to 280.8 ± 26.1) and biochemical pregnancy BCP (n = 14; 172.7 ± 31.1 to 216 ± 30.1) groups. The rising pattern from dET to d7 to d14ET was not observed in non-pregnant and BCP groups. ER thickness and grade shared significant correlation with serum PAI-1 on dET (Pearson r: ER = 0.28, Grade = 0.29) and d7ET (Pearson r: ER = 0.40, Grade = 0.23).

Conclusions: Periodicity in serum PAI-1 levels offers a robust prognostic factor for predicting clinical pregnancy outcome. The dhCG to dET PAI-1 transition is a decisive factor for either transferring embryos in same/ongoing cycle or cryopreserving them and postponing ET to subsequent natural cycle.

Citing Articles

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Deryabin P, Griukova A, Shatrova A, Petukhov A, Nikolsky N, Borodkina A Cell Cycle. 2019; 18(6-7):742-758.

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References

Paulson R, Sauer M, Lobo R . Embryo implantation after human in vitro fertilization: importance of endometrial receptivity. Fertil Steril. 1990; 53(5):870-4. DOI: 10.1016/s0015-0282(16)53524-9. View

Casslen B, Ohlsson K . Cyclic variation of plasminogen activation in human uterine fluid and the influence of an intrauterine device. Acta Obstet Gynecol Scand. 1981; 60(2):97-101. View

Staun-Ram E, Shalev E . Human trophoblast function during the implantation process. Reprod Biol Endocrinol. 2005; 3:56. PMC: 1289292. DOI: 10.1186/1477-7827-3-56. View

Bausero P, Cavaille F, Meduri G, Freitas S, Perrot-Applanat M . Paracrine action of vascular endothelial growth factor in the human endometrium: production and target sites, and hormonal regulation. Angiogenesis. 2003; 2(2):167-82. DOI: 10.1023/a:1009292506879. View

Bischof P, Campana A . A model for implantation of the human blastocyst and early placentation. Hum Reprod Update. 1996; 2(3):262-70. DOI: 10.1093/humupd/2.3.262. View

van Hinsbergh V . Impact of endothelial activation on fibrinolysis and local proteolysis in tissue repair. Ann N Y Acad Sci. 1992; 667:151-62. DOI: 10.1111/j.1749-6632.1992.tb51607.x. View

Check J, Choe J, Katsoff D, Summers-Chase D, Wilson C . Controlled ovarian hyperstimulation adversely affects implantation following in vitro fertilization-embryo transfer. J Assist Reprod Genet. 1999; 16(8):416-20. PMC: 3455485. DOI: 10.1023/a:1020565408018. View

Aflalo E, Sod-Moriah U, Potashnik G, Har-Vardi I . Differences in the implantation rates of rat embryos developed in vivo and in vitro: possible role for plasminogen activators. Fertil Steril. 2004; 81 Suppl 1:780-5. DOI: 10.1016/j.fertnstert.2003.10.014. View

Basir G, O W, So W, Ng E, Ho P . Evaluation of cycle-to-cycle variation of endometrial responsiveness using transvaginal sonography in women undergoing assisted reproduction. Ultrasound Obstet Gynecol. 2002; 19(5):484-9. DOI: 10.1046/j.1469-0705.2002.00685.x. View

10.

Hadi F, Chantler E, Anderson E, Nicholson R, McClelland R, Seif M . Ovulation induction and endometrial steroid receptors. Hum Reprod. 1994; 9(12):2405-10. View

11.

Sie P, Caron C, Azam J, Goudemand J, Grandjean H, Boneu B . Reassessment of von Willebrand factor (VWF), VWF propeptide, factor VIII:C and plasminogen activator inhibitors 1 and 2 during normal pregnancy. Br J Haematol. 2003; 121(6):897-903. DOI: 10.1046/j.1365-2141.2003.04371.x. View

12.

Blankenship T, Enders A, King B . Trophoblastic invasion and modification of uterine veins during placental development in macaques. Cell Tissue Res. 1993; 274(1):135-44. DOI: 10.1007/BF00327994. View

13.

Gardner D, Schoolcraft W, Wagley L, Schlenker T, Stevens J, Hesla J . A prospective randomized trial of blastocyst culture and transfer in in-vitro fertilization. Hum Reprod. 1999; 13(12):3434-40. DOI: 10.1093/humrep/13.12.3434. View

14.

ONeill C, Sinosich M, Porter R, Pike I, Saunders D . Failure of implantation in human in vitro fertilization and embryo transfer patients: the effects of altered progesterone/estrogen ratios in humans and mice. Fertil Steril. 1986; 45(1):69-74. DOI: 10.1016/s0015-0282(16)49099-0. View

15.

Schatz F, Aigner S, Papp C, Toth-Pal E, Hausknecht V, Lockwood C . Plasminogen activator activity during decidualization of human endometrial stromal cells is regulated by plasminogen activator inhibitor 1. J Clin Endocrinol Metab. 1995; 80(8):2504-10. DOI: 10.1210/jcem.80.8.7629251. View

16.

Bacharach E, Itin A, Keshet E . In vivo patterns of expression of urokinase and its inhibitor PAI-1 suggest a concerted role in regulating physiological angiogenesis. Proc Natl Acad Sci U S A. 1992; 89(22):10686-90. PMC: 50406. DOI: 10.1073/pnas.89.22.10686. View

17.

OSSOWSKI L . Plasminogen activator dependent pathways in the dissemination of human tumor cells in the chick embryo. Cell. 1988; 52(3):321-8. DOI: 10.1016/s0092-8674(88)80025-4. View

18.

Canipari R, Strickland S . Plasminogen activator in the rat ovary. Production and gonadotropin regulation of the enzyme in granulosa and thecal cells. J Biol Chem. 1985; 260(8):5121-5. View

19.

Schmitt M, Harbeck N, Thomssen C, Wilhelm O, Magdolen V, Reuning U . Clinical impact of the plasminogen activation system in tumor invasion and metastasis: prognostic relevance and target for therapy. Thromb Haemost. 1997; 78(1):285-96. View

20.

Levi A, Drews M, Bergh P, Miller B, Scott Jr R . Controlled ovarian hyperstimulation does not adversely affect endometrial receptivity in in vitro fertilization cycles. Fertil Steril. 2001; 76(4):670-4. DOI: 10.1016/s0015-0282(01)01988-4. View