1.生殖医療 : 過去・現在・未来(特別講演,第63回日本産科婦人科学会・学術講演会)

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In 2010, Dr.R.G. Edwards was awarded the Nobel Prize in Physiology or Medicine for achieving the first successful in-vitro fertilization and embryo transfer (IVF-ET) in the world. His work remains to be one of the greatest accomplishments in the history of reproductive medicine. In 2008, more than 20,000 babies were born by assisted reproductive technology (ART) in Japan. Although there is a wealth of knowledge that forms the basis of ART, the author considers the discovery of acrosome reaction and hyper-activation to be the most important. Since the discovery of these various phenomena that occur to sperm at the time of fertilization, and the realization that capacitation can be generated in vitro, research into IVF began and progressed on many species of mammals. The research outcomes were initially applied in animal husbandry and propagation fields, but before long it led to the clinical application of intractable infertility. While IVF-ET research begun in the 1960's, the first news of success was not announced until 1978. My colleagues and I also started on basic research for establishing human IVF-ET methods in 1979. We discovered that like other mammals, hyper-activation exists in human sperm and their progress into the ovum is propelled by a similar mechanism. However, the substantial difference between humans and other mammals was the wide variation in the time required for capacitation among human individuals. Based on the result of these studies, Tohoku University started the clinical application of IVF-ET. Thirty five trials were needed before the first confirmation of a successful pregnancy (1983). The number of sperm that are required for IVF is extremely small. Therefore, IVF-ET can also be applied to male infertility. However, cases of male infertility, where even a small required number of spermatozoa cannot be collected or the collected sperm is of impaired quality, are observed more often than one might expect. The "new in vitro fertilization method," also known as "micro-insemination" became the focus of examination for such cases. In the beginning, a method called partial zona dissection (PZD) or sub-zonal insemination (SUZI) was introduced, and later, intra-cytoplasmic sperm injection (ICSI), where the sperm is directly injected into the ovum, was attempted. The latter method proved to deliver excellent levels of certainty and safety, and soon the best method of "micro-insemination" came to be known as ICSI. Parermo et al. reported the first success of ICSI in the world in 1992. In Japan, our team at Fukushima Medical University recorded the first success in 1994. The problems related to IVF and ICSI can be organized roughly into 3 categories: (1) side effects of the fertility treatment, (2) possible impact on the next generation, and (3) ethical and social issues. For some time multiple pregnancies had been a major side effect, however, the occurrence decreased rapidly after the Japan Society of Obstetrics and Gynecology issued a notification in 2008 stipulating the principle that "only a single embryo should be transferred." Many researchers admit that miscarriage rates are high with IVF and ICSI, and there is concern regarding an increase in chromosomal abnormalities. The morality of "egg donation" and "surrogate births" is often the focus of debates on the social and ethical issues surrounding ART. The process of a "surrogate birth" is accompanied by many problems such as the risks of the pregnancy and birth itself, the resulting complex family relationships, and the child who may end up in unhappy circumstances, but Japanese laws have not developed appropriately to support them. To this end, the method of forming a gamete with a somatic cell by taking advantage of regenerative medicine techniques is being-developed for sterile married couples in order for them to have their own children without using third party gametes. Gametes can be generated from a somatic cell by the use of a iPS cell or a nuclear transfer-derived embryonic stem cell (ntES cell). We have succeeded in generating ntES cells from mice, and are about to start research into differentiating and inducing these cells to develop into sperm. Many domestic and foreign researchers such as our team are aiming to generate a gamete from a somatic cell. However, the hurdles are many and high, and it will take a considerable amount of time before we may succeed. Fertility treatment which was considered unique 30 years ago is now widely available as a common treatment method. How will ART evolve in next 30 years? As a member of a community dedicated to the discipline of reproductive medicine, I feel a great responsibility to carefully monitor and ensure the development of reproductive medicine for the future.
2011-10-01

1.生殖医療 : 過去・現在・未来(特別講演,第63回日本産科婦人科学会・学術講演会)

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