Frozen Embryo Transfer (FET) was initially developed to overcome the problem of supernumerary embryos obtained after in vitro fertilization (IVF) ± intra-cytoplasmic sperm injection (ICSI). The relatively recent improvement of embryo survival with vitrification throughout the last 15 years led to significantly better clinical outcome in FET cycles, and subsequently supported the implementation of single embryo transfer, maintaining comparable cumulative pregnancy rate, while decreasing the prevalence of multiple pregnancies and their complications [1]. Altogether, this resulted in a worldwide trend towards increasing use of FET cycles. According to the European Society of Human Reproduction and Embryology (ESHRE), in Europe in 2016, FET cycles indeed represented 35.5% of all ART cycles in 2018 in Europe, as compared to only 15% in 2008 [2].

Despite decades of active tobacco control policies and restrictive laws, smoking still remains a global public health issue, being one of the major causes of premature mortality in both men and women, either by cancer or stroke. In the field of reproduction, the harmful effects of active (or second-hand) smoking on pregnancy outcome have been well established for decades, particularly via an increased risk of ectopic pregnancy (15-fold increase), miscarriage (2-fold increase), placenta previa, in utero growth retardation, and prematurity as compared to non-smokers [[3], [4], [5]]. Its adverse effects on female fertility have also been extensively documented, both for natural pregnancies and after assisted reproductive technology (ART) cycles. For instance, deleterious effects on steroidogenesis [6], folliculogenesis [7], ovarian reserve [8], endometrial receptiveness and implantation [8,9] have been reported. Although most probably reversible after smoking cessation, the overall risk of infertility has been shown to be 2 times higher in smoking than in non-smoking women [10]. However, the impact of female smoking on ART outcomes remains somewhat controversial in the literature, even if most studies reported poorer clinical outcome in smoking women undergoing IVF than in non-smoking ones [[11], [12], [13]].

Interestingly and quite surprisingly, no study (to our knowledge) has specifically focused on the potential harmful effects of female smoking on Live Birth Rate (LBR) after FET cycles. Actually, whether smoking affects equivalently endometrial receptiveness after controlled ovarian stimulation (COS) followed by fresh embryo transfer or after hormonal replacement therapy (HRT) cycle remains to be explored. As the use of FET is rapidly growing worldwide, especially at the blastocyst stage (frozen blastocyst transfer - FBT), it seems therefore relevant to specifically evaluate whether female smoking status is significantly associated with clinical outcome after FBT cycle.

The aim of this study was to determine the effect of female smoking status on live birth rate (LBR) after frozen blastocyst transfer (FBT) cycle with Hormonal Replacement Treatment.