الفهرس 
IVF, AN OVERVIEWOnly 14 pages are availabe for public view
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Abstract
R
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.
This randomized controlled clinical trial was conducted at Ain Shams University Maternity Hospital (IVF unit) to compare the pregnancy rate between two groups of women with repeated unexplained implantation failure, one group (n=40) underwent sequential embryo transfer (ET) on day 3 (D3) and day 5 (D5), the other one (n=40) underwent embryo transfer on day 3.
Regarding basal descriptive data; there was no significant difference between sequential ET and D3 ET group regarding age, BMI, infertility duration, number of failed ICSI trials, number of oocytes, number of fertilized oocytes, number of embryos, FSH, LH, TSH, serum prolactin, AMH and progesterone with p= 0.135, 0.076, 0.113, 0.108, 0.103, 0.149, 0.736, 0.817, 0.806, 0.888, 0.976, 0.587 and 0.703.
Regarding IVF-ET outcomes; statistical analysis of current results showed that number of chemical pregnancy, clinical pregnancy and ongoing pregnancy were significantly higher in sequential ET group than D3 ET group with p= 0.045, 0.039, and 0.032.
It is important to note that this technique is suitable for patients having an adequate number of good quality embryos to be replaced on both days of transfer and thus not suitable for poor responders.
The strengths of current study were due to it was randomized controlled trial with minimal percent of bias, every effort was made to ascertain that all follow-up data were correct, and only complete information was included in data analysis and all clinical assessment, IVF-ET, and assessment of study outcomes were done by the same team.
The limitations of current study were due to COVID 19 pandemic, inclusion of women with good ovarian response precluded studying the role of sequential transfer in poor ovarian responders, using HMG precluded the studying the effect of other types of gonadotropins, relatively small sample size and side effects of study medications.
According to our study, we recommend that if there are no contraindications, sequential IVF ET on day 3 and day 5 could be a hopeful option in patients with repeated IVF–embryo transfer failures. Further studies with larger sample size and using different modalities of ovarian stimulation and different categories of infertile patients, are warranted. Additionally, Long term follow up of neonatal outcome will be necessary in further study.