Celebrating ICSI's twentieth anniversary and the birth of more than 2.5 million children--the 'how, why, when and where'

The first major breakthrough for the alleviation of tubal infertility occurred in the last quarter of the twentieth century. Louise Brown was born on the 25 July, 1978 inOldham, England as a result of the pioneering work of Bob Edwards and the late Patrick Steptoe with the help of the late Jean Purdy. Bob Edwards received the ‘Nobel Prize for Physiology or Medicine’ for this work in 2010. In the early eighties IVF practice was gradually introduced in many countries and became a successful treatment for the alleviation of longstanding female-factor and idiopathic infertility. However, the hypothesis that bringing the male gametes closer to the oocytes would be an effective treatment in couples with reduced numbers of spermatozoa was not supported. As soon as sperm parameters were below a certain threshold, fertilization of oocytes was much reduced or failed completely. It became obvious that conventional IVF could not solve many cases of male-factor infertility. For couples with a very low sperm count or azoospermia it was necessary to resort to the use of artificial insemination with donor sperm (AID). As a consequence, several groups embarked on research aimed at assisting the fertilization process. Micromanipulation procedures were introduced. The two initial assisted fertilization procedures: zona drilling and partial zona dissectionwere not successful. Zona drilling involvedmaking a hole in the zona pellucida of an oocyte, whichwas then incubated in a sperm suspension. Zona drilling worked well in mice but not in humans. Partial zona dissection was introduced afterwards. A mechanical slit was made in the oocytes, which were then incubated in a sperm suspension. Fertilization was obtained by this method but when it occurred there was a similar percentage of monospermic and polyspermic fertilization. Although some pregnancies and births occurred, inconsistent results meant that partial zona dissection was not widely applied in the clinic. Around the same time a few case reports were published on the next assisted fertilization procedure: subzonal insemination (SUZI), a micromanipulation technique involving the insertion of a few spermatozoa between the zona pellucida and the membrane of the oocyte. We decided to embark on this approach for assisted fertilization. What did we do?