Correlationship of plasminogen activator inhibitor-1 (PAI-1) and mullerian inhibiting substance (MIS) in follicular fluid with endometrial receptivity and pregnancy outcome in ART cycles

Abstract

OBJECTIVE: Plasminogen activator inhibitor -1 (PAI-1)and Mullerian inhibiting substance (MIS) also known as antimullerian hormone (AMH) in follicular fluid were estimated to evaluate their relationships with endometrial receptivity and pregnancy outcome in ART cycles. DESIGN: Prospective study of 124 IVF cycles. MATERIALS AND METHODS: Controlled ovarian hyperstimulation in all women (Mean age: 30.8 ± 0.4 yrs, BMI: 24.66 ± 0.4) was done with gonadotropin (225 IU / day). Oocyte retrieval was done 34 hours after hCG administration. PAI-1 and MIS concentrations per mg of protein by ELISA and serum E2 and P by RIA method in FF were estimated. Conventional luteal phase support was given in all cycles. Seven days after embryo transfer (ET), serum P, 17OHP and E2 along with transvaginal sonography for endometrial response were measured. Measurement of β hCG on day 14 of ET indicated pregnancy outcome. By the end of sixth week, presence of gestational sac with cardiac activity confirmed clinical pregnancy. Statistical analysis, viz.t test, correlation coefficient and receiver operator characteristics ROC AUC of PAI-1 to determine the cutoff value for achieving pregnancy, was done using Graph pad Prism version 5.0. RESULTS: Out of 124 IVF cycles, six cycles were abandoned due to no response and in eight cycles no ETs were done. A mean of 2.5 ± 0.1 embryos was transferred in 110 IVF cycles. Out of 46 pregnancies (PR: 41.8 %) that resulted, 6 turned out as biochemical pregnancies. The cycles were divided into pregnant and non-pregnant groups. Both FF PAI-1 and FF MIS levels in pregnant group were significantly low (P value: <0.0001) as compared to non-pregnant group. FF MIS strongly correlated with FF PAI-1 and D7 OHP in pregnant group (Pearson r: 0.4515 and 0.3321 respectively). Serum17- OHP levels and endometrial thickness on D7 in non-pregnant group showed inverse correlation with FF PAI-1 (Pearson r = - o.3324). Though sr. P in both groups remained almost unchanged, 17- OHP and E2 levels were found to be significantly high (0.05 and 0.005 respectively) in pregnant group as compared to non-pregnant group on D7 of ET. CONCLUSIONS: MIS seemed to regulate the activity of PAI-1 in ART cycles. Lower PAI-1 activity in follicular fluid seemed to denote the promotion or triggering factor for increased proteolytic activity at the endometrial level to prepare a favorable bed for invasion of trophoblasts of the embryo, which facilitated its implantation.