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Hardening of the zona pellucida is thought to be influenced by suboptimal culture of embryos in vitro, advancing age in vivo, duration of hormonal stimulation during in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), and smoking. There is some evidence that embryos that have undergone zona manipulation for assisted hatching (AH) tend to implant one day earlier than unhatched embryos. The author's group conducted a Cochrane review in 2003 which was updated in 2007 to determine whether AH of embryos following assisted conception improved live birth and clinical pregnancy rates. The primary outcome measure was live birth rate per woman randomized, as this reflects the take home baby rate that is crucial to any assisted reproduction technology (ART). Significant improvement in clinical pregnancy rate was seen independent of the degree of AH, be it thinning, drilling a small hole in the zona or complete zona removal.
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