History of in vitro fertilisation

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The history of in vitro fertilisation (IVF) goes back more than half a century. In 1959 the first birth in a nonhuman mammal resulting from IVF occurred, and in 1978 the world's first baby conceived by IVF was born. As medicine advanced, IVF was transformed from natural research to a stimulated clinical treatment. There have been many refinements in the IVF process, and today millions of births have occurred with the help of IVF all over the world.

Contents

Steps prior to human IVF

Prior to the development of IVF in humans, Walter Heape, a physician and professor at the University of Cambridge, was doing research on reproduction in animals. In 1891, Heape reported the first successful embryo transfer in a mammal. [1] [ better source needed ] [2]

As early as 1934, Gregory Goodwin Pincus and Ernst Vincenz Enzmann tried to perform IVF in rabbits. Although the pregnancy was successful, it was later determined that the fertilisation occurred in vivo (in the body). [3]

Miriam Menkin was the first to extract an intact fertilised egg. [4] In 1948, John Rock and Miriam Menkin retrieved over 800 oocytes, of which 138 were exposed to spermatozoa in vitro. They published their findings in the American Journal of Obstetrics and Gynecology. [1] [5] There was a transient biochemical pregnancy reported by Australian Foxton School researchers in 1953. [6] [ failed verification ]

In 1958, Anne McLaren and John Biggers published a landmark paper in the journal Nature, outlining how they had successfully grown mouse embryos in vitro and transferred them into female mice. This showed it was possible to mix a sperm and an egg outside a women's reproductive system and create a healthy embryo.

In 1959, Min Chueh Chang at the Worcester Foundation, proved fertilisation in vitro was capable of proceeding to a birth of a live rabbit. Chang's discovery was seminal, as it clearly demonstrated that oocytes fertilised in vitro were capable of developing if transferred into the uterus. [7]

Early, non-viable pregnancies

The first pregnancy achieved through in vitro human fertilisation of a human oocyte was reported in The Lancet from the Monash University team of Carl Wood, John Leeton and Alan Trounson [8] in 1973, although it lasted only a few days and would today be called a biochemical pregnancy. Landrum Shettles attempted to perform IVF in 1973, but his departmental chairman interdicted the procedure at the last moment. [9] [10] There was also an ectopic pregnancy reported by Patrick Steptoe and Robert Edwards in 1976.[ citation needed ]

Early babies

Steptoe and Robert Edwards started collaborating in human IVF research in 1968. [3] In 1977, Steptoe and Edwards successfully carried out a pioneering conception which resulted in the birth of the world's first baby to be conceived by IVF, Louise Brown, on 25 July 1978 in Oldham General Hospital, Greater Manchester, UK. [11] [12] [13] Her younger sister, Natalie Brown, was the first person conceived with IVF to have children of her own, in 1999. [14] [15] [16]

In October 1978, it was reported that Subash Mukhopadhyay, a physician from Hazaribagh, India was performing experiments on his own with primitive instruments and a household refrigerator and this resulted in a test tube baby, later named as "Durga" (alias Kanupriya Agarwal) who was born on 3 October 1978. [17] However, state authorities prevented him from presenting his work at scientific conferences [18] and, in the absence of scientific evidence, his work is not recognised by the international scientific community. These days, however, Mukhopadhyay's contribution is acknowledged in works dealing with the subject. [19] [ better source needed ]

Steptoe and Edwards were responsible for the world's first confirmed boy conceived by IVF, Alastair Montgomery, born on 14 January 1979 in Glasgow. [20] A team led by Ian Johnston and Alex Lopata were responsible for Australia's first baby conceived by IVF, Candice Reed, born on 23 June 1980 in Melbourne. [21] [ verification needed ]

Development of stimulated IVF treatments

It was the subsequent use of stimulated cycles with clomiphene citrate and the use of human chorionic gonadotrophin (hCG) to control and time oocyte maturation, thus controlling the time of collection, that converted IVF from a research tool to a clinical treatment.

This was followed by a total of 14 pregnancies resulting in nine births in 1981 with the Monash University team. Howard W. Jones and Georgeanna Seegar Jones [22] at the Eastern Virginia Medical School in Norfolk, Virginia, further improved stimulated cycles by incorporating the use of a follicle-stimulating hormone (uHMG). This then became known as controlled ovarian hyperstimulation (COH). Another step forward was the use of gonadotrophin-releasing hormone agonists (GnRHA), thus decreasing the need for monitoring by preventing premature ovulation, and more recently gonadotrophin-releasing hormone antagonists (GnRH Ant), which have a similar function. The additional use of the oral contraceptive pill has allowed the scheduling of IVF cycles, which has made the treatment far more convenient for both staff and patients.

Subsequent refinements

The ability to freeze and subsequently thaw and transfer embryos has significantly improved the feasibility of IVF use. [23] In 1983, Alan Trounson and Linda Mohr reported the first pregnancy which used embryo cryopreservation (frozen human embryos). However, this embryo was not carried to term. In December 1983, the first baby was born using this method which happened to be twins. [24]

The ability to freeze and preserve a woman's eggs to be used at a later date has also had impacts on IVF use. In 1986, Dr. Christopher Chen reported the first pregnancy which used oocyte cryopreservation (frozen eggs). The ability to freeze sperm has also been possible for generations. Both of these options have been beneficial in IVF use to allow people who must undergo radiation or menopause to still have children. [25]

Another important development in IVF was when egg donation became publicly available. The pregnancy from egg donation occurred in 1983. In the United States, the first child born from egg donation occurred on February 3, 1984. This has allowed for those who are unable to conceive a child due infertility, or lack of eggs to become parents. [26]

The other very significant milestone in IVF was the development of the intracytoplasmic sperm injection (ICSI) of single sperms by Gianpiero D. Palermo et al.in Brussels (UZ Brussel), 1992.

[27]

This has enabled men with minimal sperm production to achieve pregnancies. ICSI is sometimes used in conjunction with sperm recovery, using a testicular fine needle or open testicular biopsy. Using this method, some men with Klinefelter's syndrome, and so would be otherwise infertile, have occasionally been able to achieve pregnancy. [23] [28] Thus, IVF has become the ultimate solution for most fertility problems, moving from tubal disease to male factor, idiopathic subfertility, endometriosis, advanced maternal age, and anovulation not responding to ovulation induction.

Recognition

Robert Edwards was awarded the 2010 Nobel Prize in Physiology or Medicine "for the development of in vitro fertilization". [29] Steptoe and Jean Purdy were not eligible for consideration as the Nobel Prize is not awarded posthumously. [30] Carl Wood was dubbed "the father of IVF (in vitro fertilisation)" for having pioneered the use of frozen embryos. [31]

Statistics of successful IVF treatments

In the US, ART cycles started in 2006 resulted in 41,343 births (54,656 infants), which is slightly more than 1% of total US births. [32] In 2012 it was estimated that five million children had been born worldwide using IVF and other assisted reproduction techniques. [33]

The Society for Assisted Reproductive Technology (SART) reported that in 2012 alone IVF resulted in about 61,740 babies born in the United States. The CDC estimates that IVF results in about 1 to 2 percent of births in the United States every year. [34]

It is estimated that in 2016 IVF resulted in about 76,930 live-born infants in a single year in the United States. As of 2015 over one million babies have been born as a result of IVF in the U.S. and over 8 million world wide. [35]

Related Research Articles

<span class="mw-page-title-main">In vitro fertilisation</span> Assisted reproductive technology procedure

In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro. The process involves monitoring and stimulating a woman's ovulatory process, removing an ovum or ova from their ovaries and letting a man's sperm fertilise them in a culture medium in a laboratory. After the fertilised egg (zygote) undergoes embryo culture for 2–6 days, it is transferred by catheter into the uterus, with the intention of establishing a successful pregnancy.

<span class="mw-page-title-main">Intracytoplasmic sperm injection</span> In vitro fertilization procedure

Intracytoplasmic sperm injection is an in vitro fertilization (IVF) procedure in which a single sperm cell is injected directly into the cytoplasm of an egg. This technique is used in order to prepare the gametes for the obtention of embryos that may be transferred to a maternal uterus. With this method, the acrosome reaction is skipped.

Gamete intrafallopian transfer (GIFT) is a tool of assisted reproductive technology against infertility. Eggs are removed from a woman's ovaries, and placed in one of the fallopian tubes, along with the man's sperm. The technique, first attempted by Steptoe and Edwards and later pioneered by endocrinologist Ricardo Asch, allows fertilization to take place inside the woman's uterus.

<span class="mw-page-title-main">Human Fertilisation and Embryology Authority</span>

The Human Fertilisation and Embryology Authority (HFEA) is an executive non-departmental public body of the Department of Health and Social Care in the United Kingdom. It is a statutory body that regulates and inspects all clinics in the United Kingdom providing in vitro fertilisation (IVF), artificial insemination and the storage of human eggs, sperm or embryos. It also regulates human embryo research.

<span class="mw-page-title-main">Patrick Steptoe</span> English gynaecologist (1913–1988)

Patrick Christopher Steptoe CBE FRS was an English obstetrician and gynaecologist and a pioneer of fertility treatment. Steptoe was responsible with biologist and physiologist Robert Edwards and the nurse and embryologist Jean Purdy for developing in vitro fertilisation. Louise Joy Brown, the first test-tube baby, was born on 25 July 1978. Edwards was awarded the 2010 Nobel Prize in Physiology or Medicine for his work on the development of in vitro fertilisation; Steptoe and Purdy were not eligible for consideration because the Nobel Prize is not awarded posthumously.

<span class="mw-page-title-main">Assisted reproductive technology</span> Methods to achieve pregnancy by artificial or partially artificial means

Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes or embryos, and/or the use of fertility medication. When used to address infertility, ART may also be referred to as fertility treatment. ART mainly belongs to the field of reproductive endocrinology and infertility. Some forms of ART may be used with regard to fertile couples for genetic purpose. ART may also be used in surrogacy arrangements, although not all surrogacy arrangements involve ART. The existence of sterility will not always require ART to be the first option to consider, as there are occasions when its cause is a mild disorder that can be solved with more conventional treatments or with behaviors based on promoting health and reproductive habits.

<span class="mw-page-title-main">Embryo transfer</span> Method of assisted reproduction

Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy. This technique - which is often used in connection with in vitro fertilization (IVF) - may be used in humans or in other animals, in which situations and goals may vary.

<span class="mw-page-title-main">Robert Edwards (physiologist)</span> English physiologist and pioneer in reproductive medicine (1925–2013)

Sir Robert Geoffrey Edwards was a British physiologist and pioneer in reproductive medicine, and in-vitro fertilisation (IVF) in particular. Along with obstetrician and gynaecologist Patrick Steptoe and nurse and embryologist Jean Purdy, Edwards successfully pioneered conception through IVF, which led to the birth of Louise Brown on 25 July 1978. They founded the first IVF programme for infertile patients and trained other scientists in their techniques. Edwards was the founding editor-in-chief of Human Reproduction in 1986. In 2010, he was awarded the Nobel Prize in Physiology or Medicine "for the development of in vitro fertilization".

Egg donation is the process by which a woman donates eggs to enable another woman to conceive as part of an assisted reproduction treatment or for biomedical research. For assisted reproduction purposes, egg donation typically involves in vitro fertilization technology, with the eggs being fertilized in the laboratory; more rarely, unfertilized eggs may be frozen and stored for later use. Egg donation is a third-party reproduction as part of assisted reproductive technology.

<span class="mw-page-title-main">Bourn Hall Clinic</span> Hospital in Cambridgeshire, England

Bourn Hall Clinic in Bourn, Cambridgeshire, England, is a centre for the treatment of infertility. The original building, Bourn Hall, is about 400 years old. Since becoming a medical centre, it has been greatly extended.

<span class="mw-page-title-main">Oocyte cryopreservation</span> Procedure to preserve a womans eggs (oocytes)

Oocyte cryopreservation is a procedure to preserve a woman's eggs (oocytes). This technique has been used to postpone pregnancy. When pregnancy is desired, the eggs can be thawed, fertilized, and transferred to the uterus as embryos. Several studies have shown that most infertility problems are due to germ cell deterioration related to aging. The procedure's success rate varies depending on the age of the woman,, as well as depending on health and genetic indicators. In 1986, the first human birth of oocyte oocyte cryopreservation was reported.

<span class="mw-page-title-main">In vitro maturation</span> Artificial maturation of harvested immature egg cells

In vitro maturation (IVM) is the technique of letting the contents of ovarian follicles and the oocytes inside mature in vitro. It can be offered to women with infertility problems, combined with In Vitro Fertilization (IVF), offering women pregnancy without ovarian stimulation.

Fertility preservation is the effort to help cancer patients retain their fertility, or ability to procreate. Research into how cancer, ageing and other health conditions effect reproductive health and preservation options are growing. Specifically sparked in part by the increase in the survival rate of cancer patients.

The Genetics & IVF Institute (GIVF) is an international provider of infertility and genetics services and products, and also engages in biomedical research in these fields. The Institute was founded in 1984 by Dr. Joseph D. Schulman and associates. GIVF headquarters are in Fairfax, VA, US, and its facilities include locations in Pennsylvania, Minnesota, California, and Texas in the United States, as well as in China, Mexico, and several other countries.

Cryopreservation of embryos is the process of preserving an embryo at sub-zero temperatures, generally at an embryogenesis stage corresponding to pre-implantation, that is, from fertilisation to the blastocyst stage.

Partner-assisted reproduction, reception of oocytes from partner (ROPA), reciprocal IVF,shared motherhood, partner IVF or co-IVF is a method of family building that is used by couples who both possess female reproductive organs. The method uses in vitro fertilization (IVF), a method that means eggs are removed from the ovaries, fertilized in a laboratory, and then one or more of the resulting embryos are placed in the uterus to hopefully create a pregnancy. Reciprocal IVF differs from standard IVF in that two partners are involved: the eggs are taken from one partner, and the other partner carries the pregnancy. In this way, the process is mechanically identical to IVF with egg donation. Reciprocal IVF offers the highest chance for pregnancy and a lower chance of a multiple births.

Jacques Cohen is a Dutch embryologist based in New York, U.S. He is currently Director at Reprogenetics LLC, Laboratory Director at ART Institute of Washington at Walter Reed National Military Medical Center, and Scientific Director of R & D at IVF-online.

Simon Fishel is an English physiologist, biochemist and pioneering in vitro fertilisation (IVF) specialist.

<span class="mw-page-title-main">Jean Purdy</span> English embryologist and fertility nurse (1945-1985)

Jean Marian Purdy was a British nurse and embryologist and a pioneer of fertility treatment. Purdy was responsible with Robert Edwards and Patrick Steptoe for developing in vitro fertilisation. Louise Joy Brown, the first test-tube baby, was born on 25 July 1978, and Purdy was the first to see the embryonic cells dividing. Edwards was awarded the 2010 Nobel Prize in Physiology or Medicine for his work on the development of in vitro fertilisation; however, because the Nobel Prize is not awarded posthumously, neither Purdy nor Steptoe were eligible for consideration. Purdy was a co-founder of the Bourn Hall Clinic but her role there and in the development of IVF was ignored for 30 years.

<span class="mw-page-title-main">Use of assisted reproductive technology by LGBT people</span>

Lesbian, gay, bisexual, and transgender people people wishing to have children may use assisted reproductive technology. In recent decades, developmental biologists have been researching and developing techniques to facilitate same-sex reproduction.

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