In vitro fertilization (IVF) is a process by which an egg is fertilised by sperm outside the body: in vitro . The process involves monitoring and stimulating a woman's ovulatory process, removing an ovum or ova (egg or eggs) from the woman's ovaries and letting sperm fertilise them in a liquid in a laboratory. The fertilised egg (zygote) is cultured for 2–6 days in a growth medium and is then implanted in the same or another woman's uterus, with the intention of establishing a successful pregnancy.

IVF techniques can be used in different types of situations. It is a technique of assisted reproductive technology for treatment of infertility. IVF techniques are also employed in gestational surrogacy, in which case the fertilised egg is implanted into a surrogate's uterus, and the resulting child is genetically unrelated to the surrogate. In some situations, donated eggs or sperms may be used. Some countries ban or otherwise regulate the availability of IVF treatment, giving raise to fertility tourism. Restrictions on availability of IVF include to single females, to lesbians and to surrogacy arrangements. Due to the costs of the procedure, IVF is mostly attempted only after less expensive options have failed.

The first successful birth of a "test tube baby", Louise Brown, occurred in 1978. Louise Brown was born as a result of natural cycle IVF where no stimulation was made. Robert G. Edwards, the physiologist who developed the treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. With egg donation and IVF, women who are past their reproductive years or menopause can still become pregnant. Adriana Iliescu held the record as the oldest woman to give birth using IVF and donated egg, when she gave birth in 2004 at the age of 66, a record passed in 2006.

IVF may be used to overcome female infertility where it is due to problems with the fallopian tubes, making fertilisation in vivo difficult. It can also assist in male infertility, in those cases where there is a defect in sperm quality; in such situations intracytoplasmic sperm injection (ICSI) may be used, where a sperm cell is injected directly into the egg cell. This is used when sperm has difficulty penetrating the egg, and in these cases the partner's or a donor's sperm may be used. ICSI is also used when sperm numbers are very low. When indicated, the use of ICSI has been found to increase the success rates of IVF.

According to the British NICE guidelines, IVF treatment is appropriate in cases of unexplained infertility for women that have not conceived after 2 years of regular unprotected sexual intercourse.[1] This rule does not apply to all countries. (See infertility.)

IVF is also considered suitable in cases where any of its expansions is of interest, that is, a procedure that is usually not necessary for the IVF procedure itself, but would be virtually impossible or technically difficult to perform without concomitantly performing methods of IVF. Such expansions include preimplantation genetic diagnosis (PGD) to rule out presence ofgenetic disorders, as well as egg donation or surrogacy where the woman providing the egg isn't the same who will carry the pregnancy to term.

The major complication of IVF is the risk of multiple births. This is directly related to the practice of transferring multiple embryos at embryo transfer. Multiple births are related to increased risk of pregnancy loss, obstetrical complications, prematurity, and neonatal morbidity with the potential for long term damage. Strict limits on the number of embryos that may be transferred have been enacted in some countries (e.g. Britain, Belgium) to reduce the risk of high-order multiples (triplets or more), but are not universally followed or accepted. Spontaneous splitting of embryos in the womb after transfer can occur, but this is rare and would lead to identical twins. A double blind, randomised study followed IVF pregnancies that resulted in 73 infants (33 boys and 40 girls) and reported that 8.7% of singleton infants and 54.2% of twins had a birth weight of < 2,500 grams (5.5 lb).

Recent evidence also suggest that singleton offspring after IVF is at higher risk for lower birth weight for unknown reasons.

Spread of infectious disease By sperm washing, the risk that a chronic disease in the male providing the sperm would infect the female or offspring can be brought to negligible levels. In males with hepatitis B, The Practice Committee of the American Society for Reproductive Medicine advises that sperm washing is not necessary in IVF to prevent transmission, unless the female partner has not been effectively vaccinated. In females with hepatitis B, the risk of vertical transmission during IVF is no different from the risk in spontaneous conception. However, there is not enough evidence to say that ICSI procedures are safe in females with hepatitis B in regard to vertical transmission to the offspring. Regarding potential spread of HIV/AIDS, Japan's government prohibited the use of in vitro fertilisation procedures for couples 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 in vitro fertilisation for couples with HIV, the 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.

Other risks to the egg provider/retriever A risk of ovarian stimulation is the development of ovarian hyperstimulation syndrome, particularly if hCG is used for inducing final oocyte maturation. This results in swollen, painful ovaries. It occurs in 30% of patients. Mild cases can be treated with over the counter medications and cases can be resolved in the absence of pregnancy. In moderate cases, ovaries swell and fluid accumulated in the abdominal cavities and may have symptoms of heartburn, gas, nausea or loss of appetite. In severe cases patients have sudden excess abdominal pain, nausea, vomiting and will result in hospitalisation.

During egg retrieval, there’s a small chance of bleeding, infection, and damage to surrounding structures like bowel and bladder (transvaginal ultrasound aspiration) as well as difficulty in breathing, chest infection, allergic reactions to medication, or nerve damage (laproscopy). Ectopic pregnancy may also occur if a fertilised egg develops outside the uterus, usually in the fallopian tubes and requires immediate destruction of the foetus. IVF does not seem to be associated with an elevated risk of cervical cancer, nor with ovarian cancer or endometrial cancer when neutralising the confounder of infertility itself. Nor does it seem to impart any increased risk for breast cancer. Regardless of pregnancy result, IVF treatment is usually stressful for patients. Neuroticism and the use of escapist coping strategies are associated with a higher degree of distress, while the presence social support has a relieving effect. A negative pregnancy test after IVF is associated with an increased risk for depression in women, but not with any increased risk of developing anxiety disorders.Pregnancy test results do not seem to be a risk factor for depression or anxiety among men.

Predictors of success
The main potential factors that influence pregnancy (and live birth) rates in IVF have been suggested to be maternal age, sperm quality, duration of infertility or subfertility, bFSH and number of oocytes, all reflecting ovarian function.Optimal woman’s age is 23–39 years at time of treatment.
Antral follicle count, with higher count giving higher success rates.Biomarkers that affect the pregnancy chances of IVF include:

  • Anti-Müllerian hormone levels, with higher levels indicating higher chances of pregnancy, as well as of live birth after IVF, even after adjusting for age.
    Factors of semen quality for the sperm provider.
  • Level of DNA fragmentation[ as measured e.g. by Comet assay, advanced maternal age and semen quality.
  • Women with ovary-specific FMR1 genotypes including het-norm/low have significantly decreased pregnancy chances in IVF.
  • Progesterone elevation (PE) on the day of induction of final maturation is associated with lower pregnancy rates in IVF cycles in women undergoing ovarian stimulation using GnRH analogues and gonadotrophins. At this time, compared to a progesterone level below 0.8 ng/ml, a level between 0.8 and 1.1 ng/ml confers an odds ratio of pregnancy of approximately 0.8, and a level between 1.2 and 3.0 ng/ml confers an odds ratio of pregnancy of between 0.6 and 0.7. On the other hand, progesterone elevation does not seem to confer a decreased chance of pregnancy in frozen–thawed cycles and cycles with egg donation.
  • Characteristics of cells from the cumulus oophorus and the membrana granulosa, which are easily aspirated during oocyte retrieval. These cells are closely associated with the oocyte and share the same microenvironment, and the rate of expression of certain genes in such cells are associated with higher or lower pregnancy rate.
  • An endometrial thickness (EMT) of less than 7 mm decreases the pregnancy rate by an odds ratio of approximately 0.4 compared to an EMT of over 7 mm. However, such low thickness rarely occurs, and any routine use of this parameter is regarded as not justified.

Other determinants of outcome of IVF include:

  • Tobacco smoking reduces the chances of IVF producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%.
  • 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. Also, pregnant women who are obese have higher rates of miscarriage, gestational diabetes, hypertension, thromboembolism and problems during delivery, as well as leading to an increased risk of fetal congenital abnormality. Ideal body mass index is 19–30.
  • Salpingectomy or laparoscopic tubal occlusion before IVF treatment increases chances for women with hydrosalpinges
  • Success with previous pregnancy and/or live birth increases chances
  • Low alcohol/caffeine intake increases success rate
  • The number of embryos transferred in the treatment cycle
  • Embryo quality
  • Some studies also suggest the autoimmune disease may also play a role in decreasing IVF success rates by interfering with proper implantation of the embryo after transfer.

Aspirin is sometimes prescribed to women for the purpose of increasing the chances of conception by IVF, but there is insufficient evidence to show that it actually works.A 2013 review and metaanalysis of randomised controlled trials of acupuncture as an adjuvant therapy in IVF found no overall benefit, and concluded that an apparent benefit detected in a subset of published trials where the control group (those not using acupuncture) experienced a lower than average rate of pregnancy requires further study, due to the possibility ofpublication bias and other factors.
A Cochrane review came to the result that endometrial injury performed in the month prior to ovarian hyperstimulation appeared to increase both the live birth rate and clinical pregnancy rate in IVF compared with no endometrial injury. However, there was a lack of data reported on the rates of adverse outcomes such as miscarriage, multiple pregnancy, pain and/or bleeding.
For females, intake of antioxidants (such as N-acetyl-cysteine, melatonin, vitamin A, vitamin C, vitamin E, folic acid, myo-inositol, zinc or selenium have not been associated with a significantly increased live birth rate or clinical pregnancy rate in IVF according to Cochrane reviews.On the other hand, oral antioxidants given to the men in couples with male factor or unexplained subfertility resulted in significantly higher live birth rate in IVF.
A Cochrane review in 2013 came to the result that there is no evidence identified regarding the effect of pre-conception lifestyle advice on the chance of a live birth outcome.

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birth outcome.\n\nFind more about related issues\n\nSources\n\nIn vitro fertilisation \u2015sourced from Wikipedia licensed under CC BY-SA 3.0\nFertilization \u2015sourced from Wikipedia licensed under CC0 1.0\nExcept where otherwise noted, content on this site is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License, involving multiple copyrights under different terms listed in the Sources section.", "tified regarding the effect of pre-conception lifestyle advice on the chance of a live birth outcome.\n\nFind more about related issues\n\nSources\n\nIn vitro fertilisation \u2015sourced from Wikipedia licensed under CC BY-SA 3.0\nFertilization \u2015sourced from Wikipedia licensed under CC0 1.0\nExcept where otherwise noted, content on this site is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License, involving multiple copyrights under different terms listed in the Sources section.", "tified regarding the effect of pre-conception lifestyle advice on the chance of a live birth outcome.\n\nFind more about related issues\n\nSources\n\nIn vitro fertilisation \u2015sourced from Wikipedia licensed under CC BY-SA 3.0\nFertilization \u2015sourced from Wikipedia licensed under CC0 1.0\nExcept where otherwise noted, content on this site is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License, involving multiple copyrights under different terms listed in the Sources section.", "tified regarding the effect of pre-conception lifestyle advice on the chance of a live birth outcome.\n\nFind more about related issues\n\nSources\n\nIn vitro fertilisation \u2015sourced from Wikipedia licensed under CC BY-SA 3.0\nFertilization \u2015sourced from Wikipedia licensed under CC0 1.0\nExcept where otherwise noted, content on this site is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License, involving multiple copyrights under different terms listed in the Sources section.", "tified regarding the effect of pre-conception lifestyle advice on the chance of a live birth outcome.\n\nFind more about related issues\n\nSources\n\nIn vitro fertilisation \u2015sourced from Wikipedia licensed under CC BY-SA 3.0\nFertilization \u2015sourced from Wikipedia licensed under CC0 1.0\nExcept where otherwise noted, content on this site is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License, involving multiple copyrights under different terms listed in the Sources section.", "tified regarding the effect of pre-conception lifestyle advice on the chance of a live birth outcome.\n\nFind more about related issues\n\nSources\n\nIn vitro fertilisation \u2015sourced from Wikipedia licensed under CC BY-SA 3.0\nFertilization \u2015sourced from Wikipedia licensed under CC0 1.0\nExcept where otherwise noted, content on this site is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License, involving multiple copyrights under different terms listed in the Sources section.", "tified regarding the effect of pre-conception lifestyle advice on the chance of a live birth outcome.\n\nFind more about related issues\n\nSources\n\nIn vitro fertilisation \u2015sourced from Wikipedia licensed under CC BY-SA 3.0\nFertilization \u2015sourced from Wikipedia licensed under CC0 1.0\nExcept where otherwise noted, content on this site is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License, involving multiple copyrights under different terms listed in the Sources section."]}