The Past and Future of In Vitro Fertilization

Meanings, Beginnings, History, and Future of the "Test Tube Baby"

A petri dish with eggs and sperm for in vitro fertilization
Thanks to the bravery and persistence of early researchers and doctors, in vitro fertilization offers hope to millions of infertile couples.. Science Photo Library / Science Photo Library / Getty Images

The literal meaning of the phrase in vitro is "within the glass.” It is a Latin term, which more generally refers to anything occurring in a laboratory setting. This is the opposite of in vivo, which means within the body (or literally, "within the living").

In vitro fertilization, better known as IVF, is an assisted reproductive technology in which fertilization takes place in the lab instead of inside the body.

Ever since the world’s first IVF baby was born in 1978, in vitro fertilization has given hope to millions of couples who could not conceive a child in any other way.

Today, IVF is a mainstream – albeit expensive – fertility treatment.

An estimated 6.5 million IVF-conceived babies have been born around the world. Less than 5% of fertility patients require IVF. These so-called “test tube babies” are as healthy and normal as typically conceived children.

But it wasn’t that long ago that IVF was a brand new technology, highly controversial, and even illegal.

How Does In Vitro Fertilization Work?

Here's a very short explanation of what happens during IVF:

The woman takes fertility drugs, which stimulates the development of extra oocytes (or eggs) in the ovaries. This takes place over a number of days.

Then, the mature eggs are removed from the ovary (either from the intended mother or from an egg donor.

) This is done with an ultrasound-guided needle.

In the lab, the retrieved eggs are combined with sperm (from either the intended father or from a sperm donor.)

The egg and sperm are put together in a petri dish, where hopefully a sperm cell will fertilize an egg cell. A fertilized human egg cell is called an embryo.

The resulting embryo then develops for a few more days in the lab. This is done under very carefully controlled conditions.

Next, one or two of the healthiest embryos are transferred to the intended mother’s (or a surrogate’s) uterus. Any extra embryos are frozen for future cycles.

Hopefully, a pregnancy will result. IVF success rates are good, but pregnancy is never a guarantee.

You can get a detailed explanation of the modern IVF process here:

What Is a “Test Tube Baby?”

"Test tube baby" is a term sometimes used by the media to refer to children conceived with in vitro fertilization (IVF).

Despite the name, "test tube babies" are not developed in a test tube. Test tubes are not part of the modern IVF process at all.

With IVF, the egg is fertilized in a petri dish. (Not a test tube.) When the embryo is between three and five days old, it is transferred to the uterus.

To be clear, the embryo does not develop into a fetus in the lab. That idea belongs to the realms of science fiction.

The embryo transferred is a collection of living and developing cells – not what anyone would think of as a “fetus.”

The term test tube baby was first used in the 1930s. Then, it was used to refer to artificial insemination -- not IVF.

Artificial insemination is when specially washed semen is directly transferred into a woman’s uterus via the cervix. It is an in vivo fertilization – in the body – and not in vitro, in the lab, like IVF.

An early reference to the phrase “test tube baby” is found in a book published in 1934 by Panurge Press, written by Dr. Hermann Rohleder.

The book, entitled Test Tube Babies: A History of the Artificial Impregnation of Human Beings, is described as, "including a detailed account of its technique, together with personal experiences clinical cases, a review of the literature, and medical and legal aspects involved."

This book is about artificial insemination, not IVF. IVF had not yet been invented.

When the first human egg was fertilized outside of the body in 1944, the term test tube baby began to refer to IVF babies.

Louise Joy Brown, the world’s first IVF baby, is still frequently referred to as the world’s “first test tube” baby. (More on her below.)

Most in the fertility world consider the term offensive and inappropriate because of the negative, sci-fi imagery it conjures up.

The History and Controversy of In Vitro Fertilization

The road to successful IVF treatment was long and trying.

Thanks to the bravery and persistence of the early scientists and doctors, the technology of in vitro fertilization is available today.

First In Vitro Fertilization Takes Places in Rabbits

In 1934, Dr. Gregory Pincus successfully fertilized rabbit eggs in the lab. He did not use male rabbits in the process.

Through a process known as parthenogenesis, he was able to take eggs from female rabbits, force fertilization of the eggs through chemical means, and then transfer the fertilized eggs back into the female reproductive tract of a rabbit.

His work caused great controversy and concern. The experiments and negative publicity led him to lose his tenure at Harvard University.

But not everyone saw Dr. Pincus’ work as unethical. Some saw hope and promise.

In Vitro Fertilization Attempted With Human Eggs

In 1937, Dr. John Rock sent an unsigned editorial to the New England Journal of Medicine entitled “What a boon for the barren women with closed tubes,” praising the potential of in vitro fertilization in humans.

In 1938, Dr. Rock hired Dr. Pincus’ former technician – Miriam Menkin.

Miriam Menkin and Dr. Pincus then spent the next six years attempting in vitro fertilization of human ova.

During their research, they collected 800 human ova and tried to fertilize 138.

Finally, in the spring of 1944, Pincus and Menkin decided to lengthen the amount of time the egg and sperm were together in the petri dish.

They were finally able to successfully fertilize four eggs. They did not attempt to transfer those fertilized eggs into a woman’s uterus.

Controversy and Further Research on Human Egg Development

In 1949, Pope Dius XII condemned fertilization outside of the body.

But this did not stop progress.

In 1951, Dr. Landrum Shettles attempted to replicate Dr. Pincus’ fertilization of human eggs in the lab. He was successful.

Dr. Shettles was also able to keep the fertilized egg alive and developing until day six. (Day six is when an embryo would typically implant itself into the uterine lining.)

He went to publish Ovum Humanum, a book containing over 1,000 pictures of the human egg at various stages of development.

Dr. Robert Edwards’ Begins IVF Research

In the meantime, in England, Dr. Robert Edwards was attempting in vitro fertilization with mice eggs. He was successful and wanted to do the same with human eggs. He tried for years but had no luck.

In 1965, Dr. Edwards traveled to America, where he met with Doctors Howard and Georgeanna Jones at John Hopkins University.

Dr. Howard Jones was a reproductive surgeon, treating infertility surgically. His wife, Dr. Georgeanna Jones, was a reproductive endocrinologist. She treated infertility with non-surgical methods.

Dr. Edwards told the Jones’ about his hope of discovering a method of in vitro fertilization for couples who couldn’t conceive otherwise.

The Jones’ agreed to help him, and together, they successfully fertilized a human ovum.

More Controversy, Followed by More Progress

After returning to England, Dr. Edwards wanted to try transferring a fertilized egg back into a woman’s uterus.

That’s when Dr. Edward met Dr. Patrick Steptoe.

Dr. Steptoe had invented a then-new surgical procedure known as laparoscopy. This is a surgical technique where a small incision is made in the abdomen, and a camera and tools are put through that incision.

Through laparoscopy, a mature human egg could be retrieved from a woman’s ovaries. This would be far less invasive than the other surgical options at the time.

Dr. Jones told Dr. Steptoe of his dream of IVF treatment. They decided to work together.

Back across the ocean, in America, the American Medical Association was speaking out against IVF. They insisted that research involving "human fetal tissue" must stop.  

The American Fertility Society thought differently.

Then headed by Dr. Georgeanna Jones, the AFS stated that research on in vitro fertilization must continue.

And it did. But with continued controversy and risk to the doctors involved.

The First Attempt at IVF Treatment Is Thwarted

Dr. Shettles remained determined to bring into the world the first in vitro fertilized baby. Doris and Dr. John Del-zio volunteered to be the first IVF parents with the help of Dr. Shettles.

Doris and Dr. John Del-zio suffered from infertility for five years. A ruptured ovarian cyst had led to blocked fallopian tubes in Doris. She had had three attempted surgical repairs of her tubes and three attempts at artificial insemination. None of the treatments were successful.

Dr. Shettles said IVF could be a possible answer and offered to help.

However, Dr. Shettles’ university was not privy to his plans. In fact, he was going against the direct instruction of his superiors. He also chose to ignore ethical guidelines on research in humans.

On September 12th, 1973, Dr. Shettles retrieved eggs from Doris, sperm from John, and put them together in a glass vial.

Then, he placed the vial in an incubator, where he planned to keep it for a few days to allow fertilization and embryo development.

But before fertilization and embryo transfer could occur, one of Dr. Shettles’ colleagues reported his unapproved experiment.

The vial was taken out of the incubator prematurely, and Dr. Shettles was confronted on his attempted IVF experiment. The possibility of a first IVF baby was lost.

In the aftermath, Dr. Shettles was forced to resign from his position at Columbia-Presbyterian.

The First IVF Pregnancy Occurs in England

Back in England, in 1975, Dr. Edwards and Dr. Steptoe finally achieved the first successful IVF pregnancy.

But the pregnancy was ectopic – the embryo implanted into the fallopian tube – and the pregnancy ended in miscarriage.

In the meantime, in America, more obstacles to IVF research were put into place.

Federal grants were no longer allowed to be used for the purposes of “fetal research” (which would include IVF research) unless the study was first approved by the National Ethics Board.

But because the board wouldn't officially be created until June of 1978, progress came to a brief pause.

The First IVF Baby Is Conceived and Born

Back in England, Dr. Edwards and Dr. Steptoe continued their attempts at IVF treatment.

On November of 1976, Lesley and John Brown met Dr. Steptoe.

Lesley’s fallopian tubes were blocked. Dr. Steptoe told the Browns that in vitro fertilization may be able to help them. They agreed to the treatment.

On November 10th, 1977, Dr. Steptoe retrieved eggs from Lesley Brown’s ovaries via laparoscopic surgery. Using John Brown’s sperm, Dr. Edwards put the eggs and sperm together in a petri dish, and fertilization successfully took place.

After two days, the resulting embryo was transferred back into Lesley’s uterus.

Pregnancy occurred and was a success!

On July 25th, 1978, Louise Joy Brown – the world’s very first IVF baby – was born via cesarean section. She was 5 pounds, 12 ounces.

Healthy, happy, and normal.

Hope of an IVF Baby in American Returns

That same year, in America, Dr. Georgeanna and Howard Jones retired from John-Hopkins University. They decided to move to Norfolk, Virginia to open a fertility clinic.

On the day of Louise Joy Brown’s birth, a reporter interviewed Dr. Howard Jones in Norfolk. The reporter asked if an IVF baby were possible in America.

Dr. Jones replied that it was completely possible, all they needed was money to make it happen.

Dr. Jones later received a phone call from a former fertility patient offering funds to open the first IVF clinic in America.

But more time would pass before an IVF baby would be born in the USA.

More IVF Babies Conceived and Born Around the World

Controversy continued to arise and get in the way of in vitro fertilization research and progress in America.

While this was happening, around the world, more IVF babies were arriving.

On January 4th, 1978, Alastair MacDonald was born -- the second IVF baby and first IVF boy.

On June 23rd, 1980, the first Australian IVF baby was born – Candice Elizabeth Reed.

On October 2nd, 1981, the first IVF baby born to American parents arrived – but the treatment and birth occurred in England. Her name is Samantha Steel.

In America, the Jones’ continued to fight for the ability to open and run their IVF clinic.

First American In Vitro Baby Arrives!

Finally, after clearing several political hurdles, the first American IVF clinic opened on March 1st, 1980.

In the first year after opening, the Jones’ attempted 23 IVF embryo transfers in Norfolk, VA. They were unsuccessful.

In the meantime, in Massachusetts, Judy and Roger Carr were struggling to conceive.

The Carr’s infertility story started with a pregnancy that came quickly but ended quickly as well. Their first pregnancy was ectopic, and Judy lost one of her fallopian tubes. They tried to get pregnant again, conceived quickly again, but had another ectopic pregnancy. Judy lost her second fallopian tube.

Natural conception was now completely impossible.

While Judy was recovering from surgery, she received a pamphlet about the IVF clinic in Norfolk, VA. IVF was not only unavailable in Massachusetts at that time, it was also illegal.

The Carrs contacted the Jones and were invited to come to their IVF clinic. They proceeded with IVF treatment.

On April 17th, 1981, Judy’s fertilized egg was transferred into her uterus. It was a success.

Finally, on December 28th, 1981, at 7:46 am, Elizabeth Jordan Carr was born via cesarean section. America’s first IVF baby.

Healthy, happy, and normal.

In Vitro Fertilization Then Vs. Now

The procedure for IVF looks very different today than it did when it was first invented.

The first IVF patients were required to remain hospitalized during most of their treatment cycle. In order to measure hormone levels, they had to collect all of their urine.

Now, IVF patients are able to be at home and work. They no longer need to collect all their urine. Blood work is used to evaluate hormone levels. IVF patients do need to come into the fertility clinic frequently for blood work and ultrasounds. But the treatment is no longer a round-the-clock endeavor.

During the early days of IVF, when their hormone levels indicated ovulation, the egg retrievals had to be scheduled exactly 26 hours later. This sometimes meant doing the procedure in the middle of the night.

Today, injectable fertility drugs are used to control when ovulation occurs. This allows scheduling the egg retrievals at more normal hours of the day. It also allows doctors to have more control of the entire ovulation process, increasing the odds for success.

In the beginning, egg retrieval required invasive surgery. Laparoscopy was required. This is a surgical technique where a small incision is made in the abdomen, and a camera and tools are put through that incision.

Today, an ultrasound-guided needle is used to retrieve the eggs. This is significantly less invasive, less risky, and involves a shorter recovery time.

Possible Future of IVF: In Vitro Fertilization Now In Vivo?

Some religions are ethically against the idea of fertilization outside the body.

The GIFT procedure, invented by Dr. Shettles in 1979, allows for fertilization to occur inside the body. But the technique is invasive and doesn’t have great success rates.

The gamete intrafallopian transfer (GIFT) procedure is a fertility treatment somewhat similar to IVF. In it, the woman usually takes fertility drugs to stimulate her ovaries. Her eggs are then retrieved from the ovaries via an ultrasound-guided needle.

But unlike IVF, fertilization of the egg does not take place in the lab. Instead, the egg and sperm are transferred to the fallopian tubes, where fertilization would normally take place.

Because of the low success rates and invasiveness of the procedure, GIFT is rarely done today.

A brand new technology may make fertilization inside the body available to all IVF couples.

A device called AneVivo is currently being developed in the United Kingdom. It received approval from the Human Fertilization and Embryology Authority (HFEA) in September of 2015.

Researchers involved in the development of the new device believe embryo health can be further improved if the embryos spend less time in the lab and more time in the natural environment of the uterus.

The new technique involves putting egg and sperm cells inside the very small capsule. (The capsule is just one centimeter long and one millimeter wide.)

This capsule is then transferred into the uterus for 24 hours. During this time, hopefully, conception will take place.

After the prescribed time, the capsule is removed. Doctors then open the capsule and select healthy embryos to transfer back to the uterus.

Not only would this new technology possibly solve religious concerns (for some), it may also provide a more natural environment for conception.

It will also allow women the experience of conception occurring inside their own body.

More on IVF treatment today:

Sources:

Bavister BD1. “Early history of in vitro fertilization.” Reproduction. 2002 Aug;124(2):181-96. http://www.reproduction-online.org/content/124/2/181.long

Bednar, Chuck. “New IVF technique may spell the end of ‘test tube babies.’” ReOrbit.com. Published January 20, 2016. http://www.redorbit.com/news/health/1113412113/new-ivf-technique-may-spell-the-end-of-test-tube-babies-012016/

Brian, Kate. “The amazing story of IVF: 35 years and five million babies later.” The Guardian. Published Friday 12 July 2013 12.34 EDT.  http://www.theguardian.com/society/2013/jul/12/story-ivf-five-million-babies

Cohen, Paula. “Dr. Howard Jones, pioneer behind first U.S. IVF baby, dies at 104.” CBS News. Published July 31, 2015. http://www.cbsnews.com/news/doctor-behind-first-u-s-ivf-baby-dr-howard-jones-dies-at-104/

Cohen J1, Trounson A, Dawson K, Jones H, Hazekamp J, Nygren KG, Hamberger L. “The early days of IVF outside the UK.” Hum Reprod Update. 2005 Sep-Oct;11(5):439-59. Epub 2005 May 27. http://humupd.oxfordjournals.org/content/11/5/439.long

Howard Jones Jr., MD. Eastern Virginia Medical School. https://www.evms.edu/evms_news/howard_jones/

Kamel, Remah MA. “Assisted Reproductive Technology after the birth of Louise Brown.” Gynecology & Obstetrics.  http://www.omicsonline.org/assisted-reproductive-technology-after-the-birth-of-louise-brown-2161-0932.1000156.pdf

LaVietes, Stuart. “Dr. L. B. Shettles, 93, Pioneer in Human Fertility.” The New York Times. Published on February 16, 2003. http://www.nytimes.com/2003/02/16/nyregion/dr-l-b-shettles-93-pioneer-in-human-fertility.html

On This Day: Obituary. “Dr. Pincus, Developer of Birth-Control Pill, Dies.” The New York Times. August 23, 1967.  http://www.nytimes.com/learning/general/onthisday/bday/0409.html

Test Tube Babies: American Experience. “The Del-Zio's Lawsuit.” http://www.pbs.org/wgbh/americanexperience/features/general-article/babies-del-zios-lawsuit-1978/

Test Tube Babies: American Experience. “Biography: Howard and Georgeanna Jones.” http://www.pbs.org/wgbh/americanexperience/features/biography/babies-bio-joness/

Test Tube Babies: American Experience. “Biography: Doris and John Del-Zio.” http://www.pbs.org/wgbh/americanexperience/features/general-article/babies-biography-del-zios/

Test Tube Babies: American Experience. “Biography: Judy and Roger Carr.” http://www.pbs.org/wgbh/americanexperience/features/biography/babies-bio-carrs/

Test Tube Babies: American Experience. “Timeline: The History of In Vitro Fertilization.” http://www.pbs.org/wgbh/americanexperience/features/timeline/babies/

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