On July 25, 2018, the world acknowledged the 40th birthday of the world's first "test tube baby," Louise Brown. But the history of IVF dates back much further than 1978. Below is a walk through time that explains how this transformative technology developed, and where it's going next.
Paving the Way for IVF
To fully appreciate the history of IVF, the work of several key figures must first be understood, starting with William Harvey. He wrote a book in 1651 after studying deer fertility, titled "Exercitationes de Generatione Animalium," that contained the phrase "ex ovo omnia," or "from the egg is everything."
Although Aristotle proposed in "On the Generation of Animals" that humans are created by "the mingling of male and female seed" more than 1,000 years earlier, most historians consider Harvey's book to be the true separation between folklore and early reproductive science.
Two decades later, using the newly invented microscope, Anton van Leeuwenhoek conducted the first experiments on human sperm, although they were initially believed to be parasites.
These events eventually led to the first recorded example of IVF. In the 1770s, Lazaro Spallanzani proved that frog oocytes only develop into tadpoles after contact with semen.
Karl Ernst von Baer went on to discover that mammals also had oocytes. He published his 1827 research on dogs and is now often called the "father of modern embryology."
Early Mammalian IVF Experiments
Research by Samuel Leopold Schenk in 1878 was the first experiment in the history of IVF conducted on mammals, using rabbits and guinea pigs. His most important discovery was that cell division could occur outside the body.
In 1934, Gregory Goodwin Pincus and Ernst Enzmann collected and introduced ova and sperm, also from rabbits, outside the body. Although the eggs were transferred back before fertilization occurred, the rabbit did become pregnant. Their work likely inspired the term "test tube baby," referenced in a 1934 book by Hermann Rohleder.
Based on previous mammal experimentation, John Rock and Miriam Friedman Menkin believed human eggs could fertilize outside the body. After six years of research, they succeeded and published their findings in 1944.
1950s-1960s
The modern history of IVF began with research by Min Chueh Chang. He discovered the necessity of sperm capacitation in 1951, as did Colin Austin. This led to the eventual live birth of a rabbit following IVF in 1959.
Robert Edwards also had success with mammalian IVF using mice, but was determined to replicate the process in humans. One major problem he encountered was access to human eggs, which he overcame with the help of Howard and Georgeanna Jones.
Edwards teamed up with Patrick Steptoe and graduate student Barry Bavister in 1968 to retrieve — then performed via laparoscopic surgery — and fertilize human eggs. Even though they did not achieve uterine implantation, they published their findings the following year.
1970s
The first human IVF pregnancy was reported in 1973, courtesy of researchers from Monash University, led by Carl Wood. Unfortunately, it ended in a biochemical pregnancy. Three years later, Steptoe and Edwards reported an ectopic pregnancy as a result of IVF.
In 1976, ultrasound played its first important role in the IVF process. Bernd-Joachim Hackelöer and Manfred Hansmann successfully monitored follicular quantity and size abdominally with a full bladder.
Finally, in 1977, Steptoe and Edwards helped Lesley Brown conceive via IVF, resulting in the Louise Brown's birth.
But the history of IVF doesn't end with Louise.
1980s-1990s
IVF went from experimental research to a clinical treatment in the early 1980s, thanks in large part to the team at Monash University.
They first used follicle-stimulating hormone to induce "controlled ovarian hyperstimulation." They later added gonadotrophin-releasing hormone agonists and gonadotrophin-releasing hormone antagonists to prevent premature ovulation, and oral contraceptives to enable the scheduling of IVF cycles.
In fact, the 1980s marked many firsts, including a frozen embryo baby, a donor egg baby, the introduction of transvaginal egg retrieval under ultrasound guidance, the development of GIFT, the introduction of embryo transfers under abdominal ultrasound guidance, the development of ZIFT, the introduction of ultrasound to evaluate endometrial quality and much more.
The 1990s were also fruitful. Doctors began using vaginal ultrasounds to guide catheters during embryo transfers in 1991. In 1992, Gianpiero D. Palermo invented ICSI to help couples with male factor infertility achieve pregnancy. The same year, the first MIFT baby was born, as was the first baby following preimplantation genetic testing.
At this point, IVF became a path to parenthood for patients with almost any fertility issue. Still, technology continued to improve in the late 1990s, with the introduction of 3D ultrasound to aid egg retrieval in 1998.
2000s-2010s
A baby was born in 2001 following comparative genomic hybridization and cryostorage. The first birth from a frozen donor egg cycle — coordinated by the first commercial donor egg bank — took place in 2005. And in 2015, the Human Fertilization and Embryology Authority in Europe approved a device called AneVivo. The first baby conceived with this technology was born in 2016.
According to an article in Fertility and Sterility, GIFT, ZIFT and MIFT have declined in popularity compared to IVF in recent years, giving rise to variations like natural cycle IVF, mild stimulation IVF, INVOcell, IVM and AUGMENT.
What's Next
Now, the focus is on improving two main areas: preimplantation genetic testing and the cost of treatments. Mosaic embryos are hotly debated; more states have mandated insurance coverage; companies have begun offering employees better fertility benefits; and entrepreneurs and venture capitalists are tackling the cost issue.
The history of IVF is still being written. Only time will tell what the future holds.
