LAUSR

I read with interest the article by Bar et al. [1], which indicates that endometrial scratching should be considered as an additional tool for patients with recurrent implantation failure (RIF). It appears especially effective in a particular subgroup of patients with adequate uterine cavities, normal ovarian reserves, optimal ovarian responses to gonadotropin treatment, and high-quality embryos. The authors highlighted the increase rates of clinical pregnancy, implantation, and live birth in patients who had undergone endometrial scratching. The implantation rate in RIF patients rose by between 6% and 44%. Though endometrial scratching may be a useful tool for RIF patients, in the study of Bar et al., the women who underwent to endometrial scratching had a higher percentage of top embryo quality than those who did not receive endometrial scratching (34.8% vs. 19.6%, respectively, p = 0.01). The multivariate analysis showed a link between high-quality embryos and conception [1]. Highquality embryos are central to the definition of RIF. With this in mind, only blastocysts, as opposed to embryos transferred on day 3, should be considered as such. Although, RIF is one of the most common conditions affecting IVF outcomes. There is not universally accepted definition. Concerning the effect of embryo quality on RIF, various techniques have been proposed for selecting the best embryos for transfer. Nowadays, pre-implantation genetic screening (PGT-A) is the only technique capable of defining a normal embryo based on chromosomal status [2]. The major cause of pregnancy loss and implantation failure is based on chromosomal aneuploidies. Although PGT-A could not improve the live birth rate per patient, it reduced the overall incidence of pregnancy loss in patients with RIF [3]. Furthermore, Busnelli et al. established that the estimated prevalence of RIF is 15% [3]. The study included a relatively young age group, women between 18 and 39 years old. Although this population has a good prognosis considering the risk of chromosomal abnormalities increases in women over 35. Similarly, during the 2019 ASRM Congress, a study analyzing 4515 patients was presented. In this study, 94.9% of the patients who had up to three consecutive single embryo transfers (SET) of euploid embryos achieved a pregnancy. Implantation or pregnancy rates were highest for the first euploid transfer (69.4%). Implantation rates for the second euploid embryo transfer stood at 59.3%, at 59.2% for the third [5]. This study suggested that true RIF is rare. Given that the implantation rate is high in all transfers, the 5% of embryos that fail to implant after three embryo transfers is likely due in part to statistical probability. In addition, this study demonstrated that subsequent embryo transfers increase the likelihood of a successful outcome. According to Bar et al. [1], endometrial scratching may be useful for a subgroup of patients. However, without the use of PGT-A, the usefulness the endometrial scratching may be overestimated in women with a high risk of aneuploidy. In such cases, endometrial scratching might be useful for RIF. However, we should consider euploid embryos in the analysis of future studies. In other words, both blastocyst stage and genetically normal embryos must be considered. RIF refers to a medical diagnosis that is amenable to several treatment strategies. The term is given to a clinical presentation that has a range of possible causes. Nevertheless, in RIF patients, embryo and endometrial assessment are crucial to increasing success rates. Furthermore, clinical studies concerning RIF should be specific about patient inclusion and exclusion criteria to avoid possible bias in the selection of patients. Perhaps, it is time for a new definition of RIF, taking into account new IVF techniques and laboratory improvements. Nowadays, we cannot discuss RIF without considering both euploid embryos status and the blastocyst stage for transfer. * Mauro Cozzolino [email protected]