The history of in vitro fertilization

Researchers discovered sperm as early as 1677. But it wasn’t until 150 years later, in 1827, that they found egg cells in female bodies for the first time. However, it wasn’t until the mid-19th century that it was recognized that Pregnancies are the result of the union of sperm and egg cells. Until then, pregnancy had been considered a great biological mystery. Since then, medical professionals have been working to help childless couples achieve the joy of family life. For couples who were unable to conceive naturally, adoption was the only option until the late 1970s. Nowadays, the Desire to have children will no longer go unfulfilled. Researchers developed artificial insemination, also known as in vitro fertilization (IVF), to treat infertility. In this process, they fertilize female eggs with sperm in the laboratory.

How it all began

In the late 1950s, British physiologist Robert Edwards (1925–2013) experimented with animal and human eggs and sperm and studied the processes of reproduction. The 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 mastered the then-modern method of laparoscopy early on, which enabled him to puncture ovarian follicles under visual guidance using a camera, thereby retrieving eggs, fertilizing them with a sperm cell outside the body, keeping them alive for several days, and transferring the embryo back into the uterus transvaginally.

Edwards contacted Steptoe. The two scientists were then able to determine the optimal time for retrieving an egg, and in this way, they were able to continually refine the procedure. With the birth of Louise Brown on July 25, 1978, scientists Steptoe and Edwards had successfully performed IVF for the first time. Both are thus considered the founders of modern reproductive medicine. Robert Edwards received the Nobel Prize in Medicine in 2010.

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

Advances in IVF

The first live birth following in vitro fertilization was achieved during a natural, unstimulated cycle. To increase the success rate, reproductive medicine specialists replaced IVF in a natural cycle with IVF in an FSH-stimulated cycle—this stimulated treatment became the standard approach in IVF. The development of IVF has progressed steadily over the past three decades. Today, reproductive medicine specialists retrieve eggs through the vagina using vaginal ultrasound, rather than performing a laborious laparoscopy. Since 1991, intracytoplasmic sperm injection (ICSI) has also made it possible for men with reduced sperm quality—such as low sperm count or reduced sperm motility—to become fathers. Eggs and embryos can now be stored for longer periods. Other recent developments include the cryopreservation of fertilized eggs, as well as polar body and preimplantation genetic testing. The latter two innovations focus on the genetic health of the embryos.

There are now approximately 130 specialized clinics, or “fertility centers,” in Germany, which perform about 90,000 treatments annually. Since 1982, the German IVF Registry has been collecting, documenting, and analyzing data on human reproductive medicine in Germany.

The IVF Process

IVF was developed for women whose fallopian tubes are blocked or have been removed. Today, so-called unexplained infertility is also considered an indication for IVF treatment. Doctors are increasingly expanding the indications for IVF. Critics also speak of a commercialization of reproductive medicine. Prof. Edwards criticized these developments as early as 2007 in a publication. 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 small glass dish.  At the start of in vitro fertilization, the woman’s ovaries are stimulated with hormones (gonadotropin) to promote egg maturation. The doctor monitors the process using ultrasound. Once the eggs have matured, ovulation can be artificially induced.

The mature follicles are then aspirated (transvaginal follicular aspiration), the eggs are retrieved under a microscope, and transferred to a culture medium. The eggs are then fertilized with the partner’s processed sperm. After one day in the incubator, a microscope can be used to determine whether the in vitro fertilization was successful. If so, the reproductive specialist can transfer a maximum of three embryos into the woman’s uterus after one to two days (embryo transfer). The success rates for live births range from 20% to 30%.

The use of assisted reproductive technology and the handling of embryos are regulated in Germany by the Embryo Protection Act. Under this law, a fertilized, viable egg is considered an embryo from the moment of nuclear fusion. In Germany, no more than three eggs fertilized in a laboratory may be allowed to develop into embryos. The parents decide in advance on one, two, or three embryos—the more embryos, the higher the success rate, but also the greater the likelihood of having twins or even triplets.

Outlook

Another innovation is a personalized stimulation treatment developed by Prof. Alexander’s research group in Leipzig as part of IVF. This approach takes into account both the woman’s previous cycles and her cycle biology (previous cycles) and uses this information to tailor the treatment. To this end, continuous Core Body Temperature with OvulaRing used.

References

German IVF Registry. 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