Purpose: To describe refractory infertility cases that preserved many failed in vitro fertilization (IVF) cycles to achieve the goal of delivering a baby. Methods: Case reports with a description of the various approaches and change in strategy that finally led to success. Results: Factors causing repeated failures in these cases included adverse effects of the controlled ovarian hyperstimulation regimen on the uterine environment, failure to realize that the sperm from a male with a low hypo-osmotic swelling test can cause embryo implantation failure unless intracytoplasmic sperm injection is performed, and the discovery that sperm abnormalities rather than exclusively oocyte problems can lead to embryo fragmentation. Conclusions: It is imperative that infertility specialists individualize cases – especially ones that have failed several cycles – and stop using the same process that has repeatedly failed. They should stop and think if there are some less common but important factors they may have overlooked. Merely recommending donor oocytes without exploring other options is inappropriate.