EFFECT OF INTRALIPID INFUSION IN PATIENTS WITH RECURRENT IMPLANTATION FALIURE (A RANDOMIZED CONTROLLED TRIAL)

Abstract

Although being an expensive procedure, the success rate of IVF/ICSI procedure is around 30% (Pundir et al, 2014) with the implantation remaining the rate limiting step towards the establishment of pregnancy during IVF treatment (Toukhy et al, 2012). In clinical practice, implantation is often considered to be successful when there is ultrasonographic evidence of an intrauterine gestational sac. Conversely, implantation failure is considered to have occurred if there is a lack of ultrasonographic evidence of an intrauterine gestational sac (Coughlan et al, 2014).

Recurrent implantation failure refers to failure to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles in a woman under the age of 40 years (Coughlan et al, 2014).

The aim of our study was to evaluate the effect of intralipid 20% infusion, once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test on clinical pregnancy rates in women with unexplained recurrent implantation failure and elevated uNK cells in luteal phase endometrial biopsy. 320 women with unexplained recurrent implantation failure undergoing IVF/ICSI cycle were recruited, after fulfilling the inclusion criteria and randomized into two groups: - Study Group: included 160 women with unexplained recurrent implantation failure undergoing a trial of IVF/ICSI. This group received intravenous infusion of intralipid 20%, once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test. - Control Group:included 160 women with unexplained recurrent implantation failure undergoing a trial of IVF/ICSI. This group received intravenous infusion of placebo, once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test.

Our primary outcome was the effect of intralipid 20% infusion on the live birth rate, defined as the number of deliveries (> 28 weeks GA) that resulted in a live born neonate, expressed per 100 embryo transfers Other secondary outcome were taken in consideration and compared among the study and control groups including the effect of intralipid 20% infusion on biochemical pregnancy rate, clinical pregnancy rate, implantation rate, miscarriage rate, incidence of adverse pregnancy outcomes (FGR, preeclampsia, placental abruption and fetal demise) and incidence of adverse drug reactions from intralipid 20% infusion (e.g. thrombophlebitis, nausea and vomiting, headache, allergic reactions, jaundice, transient elevation in liver transaminases, thrombocytopenia or leucopenia). We found that biochemical pregnancy was higher in the study group, with statistical significance when compared with the control group [92 (57.5%) patients in the study group vs 64 (40%) patients in the control group]. Estimated increase was found to be 1.4-fold increase higher than the control group. Also, clinical pregnancy rate in the study group was found to be 2.5-fold higher than the control group (31.8% vs 12.5%) with a proven high statistical significance. Implantation rate was significantly higher in the study group when compared with the control group (17.89% vs 7.33% respectively). In our study, live birth rate in the study group was found to be 3-fold higher than the control group (21.2% vs 6.8%) with a proven high statistical significance. Number needed to treat (NNT) was estimated to be 6.9. Based on our results, we recommend the usage of intralipid 20% intravenous infusion, once between days 4 and 9 of the ovarian stimulation, and again within 7 days of a positive pregnancy test on clinical pregnancy rates in women with unexplained recurrent implantation failure and elevated uNK cells in luteal phase endometrial biopsy.