The increasing success of in vitro fertilization (IVF) has come mainly from advances in the way doctors grow and select embryos. When transferred into a woman's womb, however, only a minority of these embryos implant in the lining of the uterus, also known as the endometrium. “The reason,” says Steven L. Young, professor of obstetrics and gynecology at the University of North Carolina at Chapel Hill, “lies primarily with an inability to evaluate if the endometrium is ready for the embryo.” If it is not, embryos will not implant, much like good seed will not grow in bad soil.

Scientists know that the endometrium undergoes dramatic changes during the menstrual cycle and becomes receptive to embryo implantation during only a short period a few days after ovulation. They have yet to find a reliable way to figure out when and if a patient's uterus is ready to accept a hard-won embryo.

Ongoing studies are just starting to provide some answers. Linda Giudice and her colleagues at the University of California, San Francisco, have used genomic analysis to identify a group of genes that turn on and off at different phases of the menstrual cycle. Nicholas S. Macklon, professor of obstetrics and gynecology at the University of Southampton in England, has found that the protein content of endometrial fluid changes depending on whether it is in a receptive or nonreceptive stage. If validated in clinical trials, the finding might lead to the development of a laboratory test that could determine on the spot if a patient is ready for embryo transfer.

Such tests and treatments are still several years away. But just as the challenges ahead are great, so are the potential rewards. If researchers can determine the molecular processes that predict when an embryo can implant, Macklon notes, they may transform the diagnosis and treatment of infertility.