In vitro fertilisation: Difference between revisions

|Speciality=Reproductive Endocrinologyendocrinology &and Infertilityinfertility

IVF is a type of [[assisted reproductive technology]] used for [[infertility]] treatment, [[gestational surrogacy]], and, in combination with [[pre-implantation genetic testing]], avoiding transmission of genetic conditions. A fertilised egg from a donor may [[Implantation (embryology)|implant]] into a surrogate's uterus, and the resulting child is genetically unrelated to the surrogate. Some countries have banned or otherwise regulate the availability of IVF treatment, giving rise to [[fertility tourism]]. Restrictions on the availability of IVF include costs and age, in order for a person to carry a healthy pregnancy to term. Children born through IVF are colloquially called '''test tube babies'''.

In July 1978, [[Louise Brown]] was the first child successfully born after her mother received IVF treatment.<ref>{{Cite news|date=24 July 2018|title=Louise Brown: World's first IVF baby's family archive unveiled|language=en-GB|work=BBC News|url=https://www.bbc.com/news/uk-england-bristol-44940929|access-date=29 July 2021}}</ref> Brown was born as a result of natural-cycle IVF, where no stimulation was made. The procedure took place at Dr Kershaw's Cottage Hospital (nowlater Dr Kershaw's Hospice) in [[Royton]], Oldham, England. [[Robert Edwards (physiologist)|Robert Edwards]] was awarded the [[Nobel Prize in Physiology or Medicine]] in 2010. The physiologist co-developed the treatment together with [[Patrick Steptoe]] and embryologist [[Jean Purdy]] but the latter two were not eligible for consideration as they had died and the Nobel Prize is not awarded posthumously.<ref name="Moreton">{{cite news | title = World's first test-tube baby Louise Brown has a child of her own | url = https://www.independent.co.uk/life-style/health-and-families/health-news/worlds-first-testtube-baby-louise-brown-has-a-child-of-her-own-432080.html | newspaper = Independent | access-date = 21 May 2010 | quote = The 28-year-old, whose pioneering conception by in-vitro fertilisation made her famous around the world. The fertility specialists Patrick Steptoe and [[Robert Geoffrey Edwards|Bob Edwards]] became the first to successfully carry out IVF by extracting an egg, impregnating it with sperm and planting the resulting embryo back into the mother | location=London | vauthors = Moreton C | date=14 January 2007}}</ref><ref name="ReferenceA">{{cite journal | vauthors = Gosden R | title = Jean Marian Purdy remembered – the hidden life of an IVF pioneer | journal = Human Fertility | volume = 21 | issue = 2 | pages = 86–89 | date = June 2018 | pmid = 28881151 | doi = 10.1080/14647273.2017.1351042 | s2cid = 5045457 }}</ref>

The Latin term [[in vitro]], meaning "in glass", is used because early biological experiments involving cultivation of tissues outside the living organism were carried out in glass containers, such as beakers, test tubes, or Petri dishes. Today,The themodern scientific term "in vitro" is used to referrefers to any biological procedure that is performed outside the organism in which it would normally have occurred, to distinguish it from an [[in vivo]] procedure (such as [[insemination|in vivo fertilisation]]), where the tissue remains inside the living organism in which it is normally found.

The second successful birth of a 'test tube baby' occurred in India on October 3, 1978, just 67 days after Louise Brown was born. The girl, named Durga, was conceived in vitro using a method developed independently by [[Subhash Mukhopadhyay (physician)|Subhash Mukhopadhyay]], a physician and researcher from [[Hazaribag]]. Mukhopadhyay had been performing experiments on his own with primitive instruments and a household refrigerator.<ref>{{cite magazine |date=19 October 1978 |title=India reveals deep-frozen test-tube baby |url=https://books.google.com/books?id=Bik2nThZSYoC&pg=PA159 |magazine=[[New Scientist]] |page=159 |access-date=4 September 2021 |vauthors=Jayaraman KS }}{{Dead link|date=December 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> However, state authorities prevented him from presenting his work at scientific conferences,<ref>{{cite web |date=5 October 2010 |title=Test tube triumph & tragedy – Nobel for UK scientist stirs memory of a Bengal doctor |url=https://www.telegraphindia.com/india/test-tube-triumph-tragedy-nobel-for-uk-scientist-stirs-memory-of-a-bengal-doctor/cid/472542 |access-date=22 May 2012 |work=[[The Telegraph (India)|The Telegraph]]}}</ref> and it was many years before Mukhopadhyay's contribution was acknowledged in works dealing with the subject.<ref>{{cite AV media |url=https://www.youtube.com/watch?v=nkEko0DybuQ |title=Test Tube Baby |date=23 August 2013 |publisher=Educational Multimedia Research Centre, Kolkata |access-date=4 September 2021 |website=[[YouTube]]}}</ref>{{better source needed|date=September 2021}}

The success rate depends on variable factors such as age of the birthing personwoman, cause of infertility, embryo status, reproductive history, and lifestyle factors. Younger candidates of IVF are more likely to get pregnant. People older than 41 are more likely to get pregnant with a donor egg.<ref name="mayoclinic.org">{{Cite web|title = In vitro fertilization (IVF) Results – Mayo Clinic|url = http://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/basics/results/prc-20018905|website = www.mayoclinic.org|access-date = 5 November 2015}}</ref> People who have been previously pregnant are in many cases more successful with IVF treatments than those who have never been pregnant.<ref name="mayoclinic.org" />

The live birth rate is the percentage of all IVF cycles that lead to a live birth. This rate does not include [[miscarriage]] or [[stillbirth]]; multiple-order births, such as twins and triplets, are counted as one pregnancy.

A 20192021 summary compiled by the Society for Assisted Reproductive Technology (SART) which reports the average IVF success rates in the United States per age group using non-donor eggs compiled the following data:<ref name="2019 Clinic Summary Report">{{cite web|url=https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0 |title=2019Final ClinicNational Summary Report|work=Society for Assisted2021 Reproductive Technology|url-status=dead|archive-url=https://web.archive.org/web/20200204120048/https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0|archive#donor-datefresh-egg |website=4National FebruarySummary Report 2020|access-date=2128 April 20222024}}</ref>

| Live birth rate (%) || 5554 || 4140.5 || 26.8 || 13.43 || 4.3

The 2019 summary compiled by the SART the following data for non-donor eggs (first embryo transfer) in the United States:<ref name="2019 Clinic Summary Report">{{cite web|url=https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0|title=2019 Clinic Summary Report|work=Society for Assisted Reproductive Technology|url-status=dead|archive-url=https://web.archive.org/web/20200204120048/https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0|archive-date=4 February 2020|access-date=21 April 2022}}</ref>

Other [[Risk factor (epidemiology)|determinants]] of outcome of IVF include:

* A [[body mass index]] (BMI) over 27 causes a 33% decrease in likelihood to have a live birth after the first cycle of IVF, compared to those with a BMI between 20 and 27.<ref name=dh2009/> Also, pregnant people who are obese have higher rates of [[miscarriage]], [[gestational diabetes]], [[hypertension]], [[thromboembolism]] and problems during [[childbirth|delivery]], as well as leading to an increased risk of fetal [[congenital abnormality]].<ref name=dh2009/> Ideal body mass index is 19–30.,<ref name=nice/> and many clinics restrict this BMI range as a criterion for initiation of the IVF process.<ref name="pmid30963351">{{cite journal | vauthors = Kelley AS, Badon SE, Lanham MS, Fisseha S, Moravek MB | title = Body mass index restrictions in fertility treatment: a national survey of OB/GYN subspecialists | journal = J Assist Reprod Genet | volume = 36 | issue = 6 | pages = 1117–1125 | date = June 2019 | pmid = 30963351 | pmc = 6603101 | doi = 10.1007/s10815-019-01448-3 }}</ref>

The eggs are retrieved from the patient using a transvaginal technique called [[transvaginal oocyte retrieval|transvaginal]], ultrasound aspiration involving an ultrasound-guided needle piercingbeing theinjected vaginalthrough wallfollicles toupon reach the ovariescollection. Through this needle, folliclesthe canoocyte beand follicular fluid are aspirated, and the follicular fluid is then passed to an embryologist to identify ova. It is common to remove between ten and thirty eggs. The retrieval process, which lasts approximately 20 to 40 minutes, is performed under [[conscious sedation]] or [[general anesthesia]] to ensure patient comfort. Following optimal follicular development, the eggs are meticulously retrieved using transvaginal ultrasound guidance with the aid of a specialised ultrasound probe and a fine needle aspiration technique. The follicular fluid, containing the retrieved eggs, is expeditiously transferred to the embryology laboratory for subsequent processing.<ref>IVF Process, Methods and Solutions https://techxplore.online/ivf-process-methods-and-solutions/ {{Webarchive|url=https://web.archive.org/web/20230609095407/https://techxplore.online/ivf-process-methods-and-solutions/ |date=9 June 2023 }}</ref>

Laboratories have developed grading methods to judge ovocyte and [[embryo]] quality. In order to optimise [[pregnancy rate]]s, there is significant evidence that a morphological scoring system is the best strategy for the selection of embryos.<ref name=Rebmann>{{cite journal | vauthors = Rebmann V, Switala M, Eue I, Grosse-Wilde H | title = Soluble HLA-G is an independent factor for the prediction of pregnancy outcome after ART: a German multi-centre study | journal = Human Reproduction | volume = 25|issue = 7 | pages = 1691–1698 | date = July 2010 | pmid = 20488801 | doi = 10.1093/humrep/deq120 | doi-access = free }}</ref> Since 2009 where the first [[time-lapse microscopy]] system for IVF was approved for clinical use, morphokinetic scoring systems has shown to improve to [[pregnancy rate]]s further.<ref name="Meseguer">{{cite journal | vauthors = Meseguer M, Rubio I, Cruz M, Basile N, Marcos J, Requena A | title = Embryo incubation and selection in a time-lapse monitoring system improves pregnancy outcome compared with a standard incubator: a retrospective cohort study | journal = Fertility and Sterility|volume=98|issue=6|pages=1481–9.e10|date=December 2012 | pmid = 22975113 | doi = 10.1016/j.fertnstert.2012.08.016 | doi-access = free }}</ref> However, when all different types of [[time-lapse embryo imaging]] devices, with or without morphokinetic scoring systems, are compared against conventional embryo assessment for IVF, there is insufficient evidence of a difference in live-birth, pregnancy, stillbirth or miscarriage to choose between them.<ref>{{cite journal|vauthors=Armstrong S, Bhide P, Jordan V, Pacey A, Marjoribanks J, Farquhar C|title=Time-lapse systems for embryo incubation and assessment in assisted reproduction | journal = The Cochrane Database of Systematic Reviews|volume=5|issue=5|pages=CD011320|date=May 2019|pmid=31140578|pmc=6539473|doi = 10.1002/14651858.CD011320.pub4 }}</ref> Active efforts to develop a more accurate embryo selection analysis based on Artificial Intelligence and Deep Learning are underway. Embryo Ranking Intelligent Classification Assistant ([[Embryo Ranking Intelligent Classification Algorithm|ERICA]]),<ref>{{Cite web|url=https://embryoranking.com/ |title = ERICA Embryo Ranking &#124; Artificial Intelligence for Assisted Reproduction}}</ref> is a clear example. This Deep Learning software substitutes manual classifications with a ranking system based on an individual embryo's predicted genetic status in a non-invasive fashion.<ref>{{Cite journal | doi=10.1016/j.fertnstert.2019.07.715| title=Artificial vision and machine learning designed to predict PGT-A results|journal=Fertility and Sterility| volume=112| issue=3| pages=e231| year=2019| vauthors = Chavez-Badiola A, Farias AF, Mendizabal-Ruiz G, Drakeley AJ, Garcia-Sánchez R, Zhang JJ | doi-access=free}}</ref> Studies on this area are still pending and current feasibility studies support its potential.<ref>{{cite journal|vauthors = Chavez-Badiola A, Flores-Saiffe Farias A, Mendizabal-Ruiz G, Garcia-Sanchez R, Drakeley AJ, Garcia-Sandoval JP|title=Predicting pregnancy test results after embryo transfer by image feature extraction and analysis using machine learning|journal = Scientific Reports|volume = 10|issue=1|pages=4394|date=March 2020|pmid=32157183|pmc=7064494|doi = 10.1038/s41598-020-61357-9|bibcode = 2020NatSR..10.4394C}}</ref>

Regarding potential spread of [[HIV/AIDS]], Japan's government prohibited the use of IVF procedures in which both partners are infected with HIV. Despite the fact that the ethics committees previously allowed the [[Ogikubo, Tokyo]] Hospital, located in Tokyo, to use IVF for couples with HIV, the [[Ministry of Health, Labour and Welfare (Japan)|Ministry of Health, Labour and Welfare]] of Japan decided to block the practice. Hideji Hanabusa, the vice president of the Ogikubo Hospital, states that together with his colleagues, he managed to develop a method through which scientists are able to remove HIV from sperm.<ref>{{cite web |date=21 July 2008 |title=Japan Bans in Vitro Fertilisation for HIV Couples |url=http://www.infoniac.com/health-fitness/japan-bans-in-vitro-fertilization-for-hiv-couples.html |publisher=Infoniac.com |access-date=3 August 2013 |archive-date=19 September 2013 |archive-url=https://web.archive.org/web/20130919204101/http://www.infoniac.com/health-fitness/japan-bans-in-vitro-fertilization-for-hiv-couples.html |url-status=dead }}</ref>

In some cases, laboratory mix-ups (misidentified gametes, transfer of wrong embryos) have occurred, leading to legal action against the IVF provider and complex paternity suits. An example is the case of a woman in California who received the embryo of another couple and was notified of this mistake after the birth of her son.<ref>{{Cite journal| vauthors = Ayers C | title=Mother wins $1m for IVF mix-up but may lose son| journal = The Times | year=2004 | url=http://www.timesonline.co.uk/tol/news/world/article465773.ece | archive-url=https://web.archive.org/web/20070208101932/http://www.timesonline.co.uk/tol/news/world/article465773.ece | url-status=dead | archive-date=8 February 2007 }}</ref> This has led to many authorities and individual clinics implementing procedures to minimise the risk of such mix-ups. The [[HFEA]], for example, requires clinics to use a double witnessing system, the identity of specimens is checked by two people at each point at which specimens are transferred. Alternatively, technological solutions are gaining favour, to reduce the manpower cost of manual double witnessing, and to further reduce risks with uniquely numbered [[RFID]] tags which can be identified by readers connected to a computer. The computer tracks specimens throughout the process and alerts the embryologist if non-matching specimens are identified. Although the use of RFID tracking has expanded in the US,<ref>{{cite web|title=Reproductive Clinic Uses RFID to Guarantee Parental Identity|url=http://www.rfidjournal.com/articles/view?3683|archive-url=https://archive.today/20130616002649/http://www.rfidjournal.com/articles/view?3683|url-status=dead|archive-date=16 June 2013| vauthors = Swedberg C |date=15 October 2007|work=RFID Journal}}</ref> it is still not widely adopted.<ref>{{cite book|title=Vertauschte Keimzellen und Embryonen – Analyse reproduktionsmedizinischer Zwischenfälle: Normkontext, Rechtsfolgen, Regelungsbedarf|url=http://www.mohrsiebeck.com/en/book/vertauschte-keimzellen-und-embryonen-9783161591822?no_cache=1| vauthors = Jäschke ML |work=Mohr Siebeck 2020|series = Studien zum Medizin- und Gesundheitsrecht|year = 2020|volume = 2|publisher = Mohr Siebeck|isbn = 9783161591822}}</ref>

In 2008, a California physician transferred 12 embryos to a woman who gave birth to octuplets ([[Suleman octuplets]]). This led to accusations{{by whom|date=January 2024}} that a doctor is willing to endanger the health and even life of people in order to gain money.{{citation needed|date=January 2024}} Robert Winston, professor of fertility studies at Imperial College London, had called the industry "corrupt" and "greedy" stating that "one of the major problems facing us in healthcare is that IVF has become a massive commercial industry," and that "what has happened, of course, is that money is corrupting this whole technology", and accused authorities of failing to protect couples from exploitation: "The regulatory authority has done a consistently bad job. It's not prevented the exploitation of people, it's not put out very good information to couples, it's not limited the number of unscientific treatments people have access to".<ref>{{cite news| url=https://www.theguardian.com/science/2007/may/31/medicineandhealth.health | location= London | work = The Guardian | vauthors = Jha A | title=Winston: IVF clinics corrupt and greedy | date= 31 May 2007}}</ref> The IVF industry has been described as a market-driven construction of health, medicine and the human body.<ref>{{Cite book| vauthors = Dumit J |title=Drugs for life : how pharmaceutical companies define our health|date=2012|publisher=Duke University Press|isbn=978-0-8223-4860-3|location=Durham, NC|oclc=782252371}}</ref>

All pregnancies can be risky, but there are greater risk for birthing parentsmothers who are older and are over the age of 40. As people get older, they are more likely to develop conditions such as gestational diabetes and pre-eclampsia. If the birthing parentmother does conceive over the age of 40, their offspring may be of lower birth weight, and more likely to requires intensive care. Because of this, the increased risk is a sufficient cause for concern. The high incidence of caesarean in older patients is commonly regarded as a risk.<ref>{{CitationCite journal |last1=Šťastná |first1=Anna |last2=Fait |first2=Tomáš |last3=Kocourková |first3=Jiřina |last4=Waldaufová |first4=Eva needed|date=April2022-12-30 2023|title=Does Advanced Maternal Age Comprise an Independent Risk Factor for Caesarean Section? A Population-Wide Study |journal=International Journal of Environmental Research and Public Health |volume=20 |issue=1 |pages=668 |doi=10.3390/ijerph20010668 |doi-access=free |issn=1661-7827 |pmc=9819592 |pmid=36612987}}</ref>

A controversy in California focused on the question of whether physicians opposed to same-sex relationships should be required to perform IVF for a lesbian couple. Guadalupe T. Benitez, a lesbian medical assistant from San Diego, sued doctors Christine Brody and Douglas Fenton of the North Coast Woman's Care Medical Group after Brody told her that she had "religious-based objections to treating her and homosexuals in general to help them conceive children by artificial insemination," and Fenton refused to authorise a refill of her prescription for the fertility drug Clomid on the same grounds.<ref>{{cite journal | vauthors = Appel JM | title = May doctors refuse infertility treatments to gay patients? | journal = The Hastings Center Report | volume = 36 | issue = 4 | pages = 20–21 | year = 2006 | pmid = 16898357 | doi = 10.1353/hcr.2006.0053 | s2cid = 39694945 }}</ref><ref>{{cite web|date=29 May 2008|title=State high court may give gays another victory|url=https://www.latimes.com/news/local/la-me-doctor29-2008may29,0,592068.story|vauthors=Dolan M|work=Los Angeles Times}}</ref> The California Medical Association had initially sided with Brody and Fenton, but the case, ''[[North Coast Women's Care Medical Group v. Superior Court|]]''North Coast Women's Care Medical Group v. Superior Court'']], was decided unanimously by the California State Supreme Court in favour of Benitez on 19 August 2008.<ref>{{cite web | vauthors = Goldstein J | date = 19 August 2008 | url = https://blogs.wsj.com/health/2008/08/19/california-doctors-cant-refuse-care-to-gays-on-religious-grounds/ | title = California Doctors Can't Refuse Care to Gays on Religious Grounds | work = Wall Street Journal }}</ref><ref name="Bob Egelko 2008">{{cite web | vauthors = Egelko B | date = 19 August 2008 | title = Bob Doctors can't use bias to deny gays treatment | work = San Francisco Chronicle | url = https://www.sfgate.com/health/article/Doctors-can-t-use-bias-to-deny-gays-treatment-3199719.php }}</ref>

In 2000, a website called [[Donor Sibling Registry]] was created to help biological children with a common donor connect with each other.<ref name="IVF donor NPR">{{cite web|title='My Daddy's Name is Donor'|url=https://www.npr.org/templates/story/story.php?storyId=129233185|date=16 August 2010|work=NPR}}</ref><ref name="donor-conceived WP">{{cite news|title=Donor-conceived children use Internet to find relatives and share information|url=https://www.washingtonpost.com/national/health-science/donor-conceived-children-use-internet-to-find-relatives-and-share-information/2011/07/01/gIQA3BiwzK_story.html|newspaper=Washington Post|date=26 September 2011}}</ref>

In February 2024, the [[Alabama Supreme Court]] ruled in ''[[LePage v. Center for Reproductive Medicine]]'' that cryopreserved embryos were "persons" or "extrauterine children". After [[Dobbs v. Jackson Women's Health Organization]] (2022), some antiabortionists had hoped to get a judgement that fetuses and embryos were "person[s]".<ref>{{Cite journal |last1=Feinberg |first1=Rebecca S. |last2=Sinha |first2=Michael S. |last3=Cohen |first3=I. Glenn |date=2024-03-04 |title=The Alabama Embryo Decision—The Politics and Reality of Recognizing "Extrauterine Children" |url=https://doi.org/10.1001/jama.2024.3559 |journal=JAMA |volume=331 |issue=13 |pages=1083–1084 |doi=10.1001/jama.2024.3559 |pmid=38436995 |issn=0098-7484}}</ref>

*[[Surrogacy]], the process in which a surrogate agrees to bear a child for another person or persons, who will become the child's parent(s) after birth. People may seek a surrogacy arrangement when pregnancy is medically impossible, when [[pregnancy risks]] are too dangerous for the intended gestational carrier, or when a single man or a male couple wish to have a child. "[[All in My Family]]" is a documentary about a gay couple pursuing surrogacy as a means to form their own family.