It has been argued that developing any approach involving genetic modifications of human embryos is unnecessary because couples at risk of transmitting a serious genetic disease already have a straightforward alternative to prenatal diagnosis and termination of pregnancy with preimplantation genetic diagnosis (PGD)(Cyranoski, 2015). However, this argument does not take into account the burden of PGD, and its low chance of success, as a large number of viable embryos are discarded because they are affected. In weighing the risks and benefits of gene editing technology in the embryo, one needs to consider the potential of genome editing to cure genetic diseases at an early stage of life, and the concept that we have a moral duty to cure affected human embryos instead of discarding them (National Academies of Sciences, Engineering and Medicine, 2017, Hirsch et al., 2017). We elaborate on the results generated in the PGD Centre of Beclere-Necker hospitals (PCBN) in Paris during the last 5 years and consider if there is potential for responsible use of genome editing in the human embryo. In PCBN, PGD has been performed since 2000 and more than 1,000 couples have undergone this procedure (1,939 attempts). PGD is routinely performed on blastomeres, sampled from in-vitro fertilized human embryos, with the aim of only transferring unaffected embryos. Over the last 5 years (2011–2016), 358 couples at risk of transmitting a singlegene disorder have been enrolled, and 78% of initiated ovarian stimulation cycles have yielded oocyte retrievals (ORs)(Figure S1). There were 384 embryo transfers leading to 127 clinical pregnancies (fetal heart beat) and 95 deliveries (18% per OR, similar to the 20% reported by the ESHRE consortium in De Rycke et al., 2015). Due to multiple births common in in-vitro fertilization (IVF), 118 babies were born in total. Of note, the rate of success (18%, measured by the number of deliveries per OR) was lower for PGD couples compared to the rate for couples that underwent IVF for infertility alone during the same period (38% per OR in PCBN). In the PGD cohort, after several attempts, only 95 couples out of the 358 brought home a baby. In other words, PGD, with the goal of having a healthy baby, had a failure rate of 73%. Is it possible to do better?

A significant number of cycles did not result in embryo transfer (n= 141, Table S1). To achieve embryo transfer on day 4 or 5, at least one embryo that is both unaffected and harboring viable hallmarks is needed. Maternal age is known to negatively impact the success of all assisted reproductive technologies but there was no significant difference in maternal age between the couples who achieved embryo transfer (mean age: 32.2 years, range 23–41) versus those who did not (mean age: 31.5 years, range 21–39). The chance of successful transfer correlated with the mean number of good quality embryos available to biopsy, meaning that the embryos harbored viable hallmarks (mean= 5.1 versus 3.2 in transferred and non-transferred patients, respectively). In addition to the presence of viable hallmarks, another factor predictive of achieving embryo transfer was the embryo’s genetic risk, depending on the model of inheritance