Efficacy of Sequential Embryo Transfer in Improving Pregnancy Rate in Women with Repeated Unexplained Implantation Failure

Abstract

epeated implantation failure (RIF) is determined when transferred embryos fail to implant following several in vitro fertilization (IVF) treatment cycles. Considering the current success rate of IVF treatments and the mean number of embryos transferred in each cycle, it is recommended to define RIF as failure of implantation in at least three consecutive IVF attempts, in which 1–2 embryos of high grade quality are transferred in each cycle. Repeated IVF–embryo transfer failures may occur for a variety of reasons typically include reduced endometrial receptivity secondary to uterine cavity anomalies, thin endometrium, abnormal changes in adhesion molecules expression and embryonic developmental abnormalities, such as low embryo quality due to a poor culture environment and genetic factors. Improving the clinical pregnancy rate in these patients is a challenge faced by clinicians and improving endometrial receptivity is essential to increase the success rate. Successful embryo implantation could be considered as a result of the intimate communication between the embryo and maternal endometrium. These two worlds need to be in full synchronization in a specific time-frame, called “Window of implantation” (WOI). In this period, lasting approximately two days, a 6–8 day human embryo has a chance to be attached into the surface endometrial layer, composed of epithelial cells and to be implanted into the stromal cell layer. Finding the best moment in the menstrual cycle for embryo transfer is a crucial step in overcoming the infertility problems in patients with repeated implantation failures (RIF). Displacement of the WOI during the midluteal phase occurs in at least 25% of RIF patients. Some authors report even higher incidence of more than 30% out-of-phase endometrium in patients with implantation failures. Most of them were found to have their WOI shifted later in the cycle and the endometrium of these women was characterized as preceptive. Changing the time of embryo transfer is a reasonable solution in these cases. Blastocyst transfer is an approach aiming to improve the IVF/ET in repeated IVF/ET failures. However, the results of this approach depend on the number of fertilized oocytes and the quality of the fertilized embryos. Ledee-Bataille et al. reported similar implantation rate of day 3 embryos vs day 5 embryos in prospective randomized study. Moreover, cancelation of the entire treatment cycle can happen due to failure of the embryos to develop to blastocyst stage with unfavorable emotional and economic consequences. Thus, sequential transfer approach has the advantage of blastocyst transfer without exposing the whole cycle to the risk of cancelation.