Reinventing reproduction

In 1959, the first repeatable procedure for fertilizing mammalian ova in vitro was reported in Nature by M. C. Chang. This marked the beginning of assisted reproductive technology and would lead to the development of what are now common practices for helping couples who have difficulties in conceiving naturally.

Chang used capacitated rabbit spermatozoa, collected from the uterus of a mated rabbit in oestrous, and unfertilized ova, collected from rabbits that had been induced to ovulate by the injection of sheep pituitary extract. After culturing ova and spermatozoa together at 38°C for 3–4 hours, ova were transferred to flasks that contained heated (55°C) rabbit serum for ∼18 hours. Fertilized and cleaved ova (36 out of 266) were then transplanted into six rabbits that had been injected with pituitary extract 18 hours previously. Of the 6 recipients, 4 delivered 15 healthy young between them.

Over the next decade, work began on the application of Chang's technique in humans. In 1971, Edwards and colleagues reported the in vitro growth of human oocytes to the blastocyst stage. Previous attempts in mammals had led to embryos that were incapable of sustained growth. The difference in this technique compared with previous attempts was the use of preovulatory oocytes (immature ova) rather than ova collected after ovulation. The method resulted in the birth of the first in vitro fertilized child in 1978 using the natural ovulating cycle (see Steptoe and Edwards, 1978). It also led to the introduction of fertility drugs to boost the collection of oocytes and control the time of ovulation (see Trounson et al., 1981), and to freeze the excess embryos that were created (see Trounson and Mohr, 1983).

In 1987, Laws-King et al. reported a technique that would revolutionize assisted reproductive technology and offer hope to couples where other infertility treatments had failed. The technique — referred to as SUZI (sub-zonal insertion)— involved the microinjection of sperm under the zona pellucida of human oocytes. Using preovulatory oocytes and spermatozoa that had undergone capacitation through chemical exposure, a single spermatozoon was microinjected into the perivitelline space. Five out of seven oocytes fertilized, three went on to cleave and one reached the six-cell stage of cleavage.

The SUZI technique had profound implications for the treatment of severe male infertility, and offered hope to men with completely immotile, immature or abnormal spermatozoa. However, there were drawbacks. When the technique was used for treating infertility, multiple sperm were injected under the zona pellucida to increase the chance of fertilization. This increased the risk of polyspermy, a lethal condition when more than one sperm enters the oocyte.

This problem was overcome in 1992, with the report by Palermo and co-workers of successful human pregnancies in three out of four couples that had previously been unsuccessful with SUZI and other in vitro techniques. Successful fertilization using the ICSI (intracytoplasmic sperm injection) method required the microinjection of just a single spermatozoon into the ooplasm of an oocyte, thereby bypassing spermatozoa binding and penetration into the zona pellucida and the fusion of sperm by the acrosome reaction.

Today, ICSI is commonly used in the treatment of infertility. However, as with most manipulations of nature, there are associated risks; for example, the possibility of inheriting certain genetic conditions might be greater. As technology and medicine evolves, these risks will be measured and hopefully minimized.