How animal embryo research led to the first documented human IVF

Research studies using animal gametes led to the first documented human IVF in 1969. A key contribution was the development of a reliable culture medium for IVF of hamster oocytes, which was then used successfully with human gametes in the laboratory. This article describes how this was accomplished. Hamster IVF was obtained using a bicarbonate-buffered culture medium based on Tyrode's solution. A dose-response experiment showed that IVF in this species was highly dependent on the pH of the culture medium. At pH 7.2 or less, very few oocytes were penetrated and spermatozoa did not undergo acrosome reactions. Over the pH range 7.3-7.5, 40% of oocytes were fertilized in vitro, while at pH 7.6 or higher, more than 75% of oocytes were fertilized and most spermatozoa exhibited acrosome reactions. There was no apparent effect of pH on sperm motility. These experiments showed that in the hamster, fertilization in vitro is highly pH dependent, most likely through pH effects on the sperm acrosome reaction and sperm:zona binding. The data led to formulation of a culture medium, Tyrode-B, that consistently supported high levels of IVF of hamster oocytes. When this medium was used for human gametes, IVF was observed and documented for the first time. Spermatozoa penetrating through the zona pellucida and sperm components within the ooplasm were detected, and some oocytes exhibited two pronuclei. These observations suggested that human IVF might be useful for alleviation of infertility.