Understanding Infertility
Assisted Reproductive Technology (ART) is a science still in its infancy – the first in vitro fertilization (IVF) baby, Louise Brown, was born only 40 years ago in 1978.[1] However, the ART process dates back even further.
In 1878, embryologist Samuel Schenk attempted IVF on mammalian eggs. In 1934, scientists Gregory Pincus and Ernst Enzmann combined rabbit egg and sperm in the glass of a watch and placed the embryo into another rabbit (where a pregnancy occurred within the body, or “in vivo”.)[2] Scientists Miriam Menken and John Rock retrieved more than 800 eggs (oocytes) from women in 1948. However, the first live birth of rabbits thanks to IVF was achieved in 1959 by Min Chueh Chang, who used eggs from white rabbits and sperm from black rabbits to create a living offspring.[3]
In terms of humans, the first IVF pregnancy was reported in 1973 by Australian professors Carl Woods and John Leeton; this trial resulted in what we now call a chemical pregnancy. It wasn’t until scientist Robert Edwards and gynecologist Patrick Steptoe succeeded in 1978 that the world’s first “test tube baby” was born.
Although ART and IVF have helped millions of couples since, the concept of IVF was at first understandably controversial. Other scientists viewed Edwards and Steptoe’s research as “unethical and immoral.”[4] After being denied funding, the two men used volunteers to continue their research in secret at a base in Oldham, England.
The first IVF treatments weren’t as sophisticated as in current times. The first IVF women were required to stay for weeks in inpatient treatment and had to give urine samples every three hours for hormone level checks. If hormones indicated ovulation, eggs “had to be collected exactly 26 hours later.”[5] Currently, harvesting is done at 12 hours before ovulation. Additionally, egg collection was done via laparoscopy – in which a tube was placed through the belly button in order to extract the eggs.[6]
Since that time, different aspects of the current ART protocols were discovered and added to the process. Human menopausal gonadotropin (hMG), a stimulant to create more eggs, was studied and added during the early 80s. However, its introduction led to a new problem – “premature ovulation due to multi-follicular development.” To combat this, gonadotropin releasing hormone agonist (GnRHa) became included starting in 1984 to combat the early surge of luteinizing hormone (or the ovulation hormone.)
The first reported successful case of donor eggs occurred in 1984. This new breakthrough allowed women with premature ovarian failure (POF) a chance of conception. In current years, the donor egg demographic has shifted from women with POF to those who are “of advanced reproductive age.”
After this increase of egg production and retrieval during IVF cycles, the problem of preservation quickly arose. In early cases of IVF, remaining eggs or embryos were either discarded or donated. Cryopreservation techniques continued to improved throughout the 1980s and today, frozen embryo transfers (FETs) are a possibility.
While laparoscopy was first used as an egg retrieval method, improvements in ultrasound technology led to changes. Reported for the first time in 1987, the method of choice soon became transvaginal follicle aspiration guided by transvaginal ultrasounds. This is still the currently used method today.
Male factor infertility (MFI) also became a point of contention during the early years. The first method of fertilization developed was called partial zona dissection (PZD). This process made a small opening in the zona pellucida (the layer surrounding the plasma membrane of the eggs) in hopes of helping sperm enter the eggs.
After lackluster results, a process called subzonal insemination (SUZI) was introduced. This process placed a few mobile sperm through the perivitelline space – or the space between the zona pellucida and cell membrane of the eggs. Although achieving 20% fertilization using this way, the SUZI method’s results were too low for clinical use.[9]
Then, in the early 1990s, a breakthrough occurred. Intracytoplasmic sperm injection (ICSI) – a procedure in which a single sperm is injected directly into the cytoplasm of the egg – was created. This new technique “demonstrated the fertilization was significantly better” compared to PZD or SUZI methods. Due to this, ICSI is the technique of choice for clinics today.[10]
Another breakthrough came in the early 1990s: the introduction and implementation of pre-implantation genetic diagnosis (PGD). PGD is a technique that tests and identifies genetically normal and abnormal embryos in order to transfer the best quality embryos and lower the risk of transmitting chromosomal abnormalities.[11] The first clinical use of PGD was in 1990 and resulted in two sets of healthy twins. PGD is a technique still use today for infertile couples with recurrent pregnancy loss (RPL) or genetic conditions; this will be explored further in the “Future of Assisted Reproductive Technology” section.
While the IVF process is not even 50 years old, the techniques and developments made during those years is almost unbelievable. In 2010, Robert Edwards won the Nobel Prize in physiology or medicine for his creation of IVF. His hard work represents “a milestone in the development of modern medicine.”[12] We can only imagine where the ART processes will end up in the future, but thanks to the contributions of hundreds of scientists of the past, a child-filled future for infertile couples is a possibility.
[1] Kamel, Remah M. "Assisted Reproductive Technology after the Birth of Louise Brown." Journal of Reproduction & Infertility 14, no. 3 (July/August 2013): 96-109. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799275/.
[2] Zhu, Tian. "The Embryo Project Encyclopedia." In Vitro Fertilization | The Embryo Project Encyclopedia. July 22, 2009. Accessed April 10, 2018. https://embryo.asu.edu/pages/vitro-fertilization.
[3] Kamel.
[4] Brian, Kate. "The Amazing Story of IVF: 35 Years and Five Million Babies Later." The Guardian. July 12, 2013. Accessed April 10, 2018. https://www.theguardian.com/society/2013/jul/12/story-ivf-five-million-babies.
[5] Ibid.
[6] Zhu.
[9] Ibid.
[10] Devroey, P., and A. Van Steirteghem. "A Review of Ten Years Experience of ICSI." Human Reproduction Update 10, no. 1 (2004): 19-28. doi:10.1093/humupd/dmh004.
[11] Harper, Joyce. "Introduction." Preimplantation Genetic Diagnosis, February 27, 2002, 3-12. doi:10.1002/0470846615.ch1.
[12] "The 2010 Nobel Prize in Physiology or Medicine - Press Release." Nobelprize.org. October 04, 2010. Accessed April 10, 2018. https://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html.