Over five million children have been conceived by assisted reproductive technology (ART) since the first live birth from in vitro fertilization in 1978. ART babies represent >1% of babies in the USA, >2% in Japan and >3% in Australia. New insights into mammalian reproduction contributed to this achievement, including the appreciation for intricate processes taking place along the female reproductive tract prior to fertilization. There is mounting evidence for “cryptic female choice” (sperm selection after insemination). The female reproductive tract uses a molecular dialogue to weed out all but a tiny fraction of inseminated sperm. Criteria for selection include species identity, maturation state, functional competence, and sperm cell surface, mostly defined by the composition of the sperm glycocalyx (“sugar coat”). Further molecular dialogues between the endometrium and the embryo determine successful implantation, establishment of placentation and its maintenance. Modern ART most commonly uses intra-cytoplasmic sperm injection (ICSI) to achieve fertilization whereby a single sperm is injected into an ovum in vitro. The resulting embryos are monitored for quality before being frozen or transferred into the womb. What are the risks associated with by-passing the evolutionary norm of cryptic female choice and exposing human gametes and embryos to in vitro conditions?