The history of in vitro fertilization

The sperm had already been discovered in 1677. 150 years later, in 1827, ova were found in female bodies for the first time. But it was not until the middle of the 19th century that it was recognized that pregnancies result from the meeting of sperm and ova. Until then, pregnancies were considered a great biological mystery. Since then, doctors have been trying to help childless couples achieve family happiness. For couples who were unable to have children naturally, the only option until the end of the 1970s was adoption. In the meantime, the desire to have children no longer has to remain unfulfilled. Medicine has developed a method of treating infertility: artificial insemination or in vitro fertilization (IVF), in which female eggs are fertilized with sperm in the laboratory.

How it all began

In the late 1950s, the British physiologist Robert Edwards (1925-2013) experimented with egg and sperm cells from animals and humans and studied the processes of reproduction. Gynecologist Patrick Steptoe (1913-1988) was also interested in artificial insemination. In the early 1960s, he treated many patients who were infertile due to blocked fallopian tubes. He learned early on the then-modern method of laparoscopy, which allowed him to puncture ovarian follicles under visual control using a camera, and thus to retrieve eggs, fertilize them outside the body with a sperm cell, keep them alive for several days, and transfer the embryo transvaginally back into the uterus.

Edwards contacted Steptoe. The two scientists were now able to determine the optimal time to retrieve an egg, and along the way, both were able to refine the procedure more and more. With the birth of Louise Brown, now 42, born on July 25, 1978, the scientists Steptoe and Edwards had made IVF a success for the first time. Both are thus considered the founders of modern reproductive medicine. Robert Edwards received the Nobel Prize in Medicine in 2010.

In 1982, the first German baby conceived in vitro was born in Erlangen. In 1990, the German Bundestag passed the first Embryo Protection Act. This created a legal framework for in vitro fertilization in this country as well.

The further development of IVF

The first live birth after in vitro fertilization was achieved in a natural, unstimulated cycle. In order to achieve an increased success rate, reproductive physicians replaced IVF in the natural cycle with IVF in the FSH stimulated cycle – this stimulated treatment became the standard treatment for IVF. Advancements in IVF have continued steadily over the past three decades. Oocytes can now be retrieved by vaginal ultrasound through the vagina rather than laboriously through laparoscopy. Intracytroplasmic sperm injection (ICSI) has made it possible since 1991 for men with reduced sperm quality, such as low sperm count or reduced sperm motility, to become fathers. Oocytes and embryos can now be stored for longer periods. Other new developments included cryopreservation of fertilized eggs, polar body and preimplantation genetic diagnosis. The last two innovations are concerned with the genetic health of embryos.

There are now about 130 specialized practices or “fertility centers” in Germany, which perform about 90,000 treatments annually. The German IVF Registry has been collecting, documenting and evaluating data from the field of human reproductive medicine in Germany since 1982.

IVF procedure

IVF was developed for women in whom the fallopian tubes have been blocked or removed. Nowadays, so-called unexplained infertility is also considered an indication for IVF treatment. The indications for IVF are becoming broader and broader. There is also talk of a commercialization of reproductive medicine. These developments are criticized in a publication by Prof. Edwards from 2007. In it, he describes modern methods of follicle stimulation and ovulation induction as too extreme and too costly (Edwards 2007).

In IVF, fertilization of the egg takes place outside the body in a glass dish. At the beginning of in vitro fertilization, the woman’s ovaries are stimulated to mature the egg with the help of hormones (gonadotropin). The doctor checks the progress by means of ultrasound. Once the eggs have matured, ovulation can be artificially induced.

Then the mature follicles are punctured (transvaginal follicle puncture), the oocytes are examined under the microscope and transferred to a nutrient medium. Then the eggs are fertilized with the partner’s prepared sperm. After one day in the incubator, it is possible to check under the microscope whether the in vitro fertilization was successful. If this is the case, the reproductive physician can transfer a maximum of three embryos to the woman’s uterus after one to two days (embryo transfer). In this case, the success rates for live births are 20-30%.

The use of reproductive technology and the handling of embryos are regulated in Germany by the Embryo Protection Act. According to the law, the fertilized egg cell capable of development is considered an embryo from the moment of nuclear fusion. In Germany, a maximum of three eggs fertilized in the laboratory may mature into embryos. Parents decide beforehand whether to have one, two or three embryos – the more, the higher the success rate, but also the likelihood of having twins or even triplets.

Outlook

Another innovation is an individual stimulation treatment in the context of IVF developed by the Leipzig research group led by Prof. Alexander. Here, both the pre-cycles and the cycle biology (pre-cycles) of the woman are taken into account and used for a personalized therapy. For this purpose the continuous body core temperature with OvulaRing is used.

References

German IVF Register. https://www.deutsches-ivf-register.de/

Edwards RG.2007. IVF, IVM, natural cycle IVF, minimal stimulation IVF – time for a rethink. Reproductive BioMedicine Online Vol 15. No 1. 106-119; www.rbmonline.com/Article/2789 on web 18 May 2007.

Embryo Protection Act: https://www.gesetze-im-internet.de/eschg/BJNR027460990.html