In vitro fertilisation (IVF) is a process of fertilisation in which an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating the ovulatory process, then removing an ovum or ova (egg or eggs) from the ovaries and enabling sperm to fertilise them in a culture medium in a laboratory. After a 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.
IVF is a type of assisted reproductive technology (ART) used to treat infertility, enable gestational surrogacy, and, in combination with pre-implantation genetic testing, avoid the transmission of abnormal genetic conditions. When a fertilised egg from egg and sperm donors implants in the uterus of a genetically unrelated surrogate, the resulting child is also genetically unrelated to the surrogate. Some countries have banned or otherwise regulated the availability of IVF treatment, giving rise to fertility tourism. Financial cost and age may also restrict the availability of IVF as a means of carrying a healthy pregnancy to term.
In July 1978, Louise Brown was the first child successfully born after her mother received IVF treatment. 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 in Royton, Oldham, England. Robert Edwards, surviving member of the development team, was awarded the Nobel Prize in Physiology or Medicine in 2010.
When assisted by egg donation and IVF, many women who have reached menopause, have infertile partners, or have idiopathic female-fertility issues, can still become pregnant. After the IVF treatment, some couples get pregnant without any fertility treatments. In 2023, it was estimated that twelve million children had been born worldwide using IVF and other assisted reproduction techniques. A 2019 study that evaluated the use of 10 adjuncts with IVF (screening hysteroscopy, DHEA, testosterone, GH, aspirin, heparin, antioxidants, seminal plasma, and PRP) suggested that (except for hysteroscopy) these adjuncts should be avoided until there is more evidence to show that they are safe and effective.
Terminology 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. The modern scientific term "in vitro" refers 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 in vivo fertilisation), where the tissue remains inside the living organism in which it is normally found.
A colloquial term for babies conceived as the result of IVF, "test tube babies", refers to the tube-shaped containers of glass or plastic resin, called test tubes, that are commonly used in chemistry and biology labs. However, IVF is usually performed in Petri dishes, which are both wider and shallower and often used to cultivate cultures.
IVF is a form of assisted reproductive technology.
History
The first successful birth of a child after IVF treatment, Louise Brown, occurred in 1978. Louise 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 (now Dr Kershaw's Hospice) in Royton, Oldham, England. Robert G. Edwards, the physiologist who co-developed the treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. His co-workers, Patrick Steptoe and Jean Purdy, were not eligible for consideration as the Nobel Prize is not awarded posthumously.
The second successful birth of a 'test tube baby' occurred in India on 3 October 1978, just 70 days after Louise Brown was born. The girl, named Durga, was conceived in vitro using a method developed independently by Subhash Mukhopadhyay, a physician and researcher from Hazaribag. Mukhopadhyay had been performing experiments on his own with primitive instruments and a household refrigerator. However, state authorities prevented him from presenting his work at scientific conferences, and it was many years before Mukhopadhyay's contribution was acknowledged in works dealing with the subject.
Adriana Iliescu held the record as the oldest woman to give birth using IVF and a donor egg, when she gave birth in 2004 at the age of 66, a record passed in 2006. After the IVF treatment, some couples can get pregnant without any fertility treatments. In 2018, it was estimated that eight million children had been born worldwide using IVF and other assisted reproduction techniques.
Medical uses
Indications
IVF may be used to overcome female infertility when it is due to problems with the fallopian tubes, making in vivo fertilisation 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 have difficulty penetrating the egg. ICSI is also used when sperm numbers are very low. When indicated, ICSI has been found to increase the success rates of IVF.
According to the UK's National Institute for Health and Care Excellence (NICE) guidelines, IVF treatment is appropriate in cases of unexplained infertility for people who have not conceived after 2 years of regular unprotected sexual intercourse.
In people with anovulation, it may be an alternative after 7–12 attempted cycles of ovulation induction, since the latter is expensive and easier to control.
Success rates IVF success rates are the percentage of all IVF procedures that result in favourable outcomes. Depending on the type of calculation used, this outcome may represent the number of confirmed pregnancies, called the pregnancy rate, or the number of live births, called the live birth rate. Due to advances in reproductive technology, live birth rates by cycle five of IVF have increased from 76% in 2005 to 80% in 2010, despite a reduction in the number of embryos being transferred (which decreased the multiple birth rate from 25% to 8%).
The success rate depends on various factors such as the woman's age, the cause of infertility, embryo status, reproductive history, and lifestyle. Younger candidates of IVF are more likely to get pregnant. People older than 41 are more likely to get pregnant with a donor egg. People who have been previously pregnant are in many cases more successful with IVF treatments than those who have never been pregnant.
Live birth rate 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 2021 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:
< 35 35–37 38–40 41–42 > 42 Live birth rate (%) 54 40.5 26 13.3 4
In 2006, Canadian clinics reported a live birth rate of 27%. Birth rates in younger patients were slightly higher, with a success rate of 35.3% for those 21 and younger, the youngest group evaluated. Success rates for older patients were also lower and decreased with age, with 37-year-olds at 27.4% and no live births for those older than 48, the oldest group evaluated. Some clinics exceeded these rates. It is impossible to determine whether that is due to superior technique or patient selection, since it is possible to artificially increase success rates by refusing to accept the most difficult patients or steering them into oocyte donation cycles (which are compiled separately). Further, pregnancy rates can be increased by the placement of several embryos, at the risk of increasing the chance for multiples.
Because not every IVF cycle that is started will lead to oocyte retrieval or embryo transfer, reports of live birth rates need to specify the denominator, namely, IVF cycles started, IVF retrievals, or embryo transfers. The SART summarised 2008–9 success rates for US clinics for fresh embryo cycles that did not involve donor eggs and gave live birth rates by the age of the prospective mother, with a peak at 41.3% per cycle started and 47.3% per embryo transfer for patients under 35 years of age.
IVF attempts in multiple cycles result in increased cumulative live birth rates. Depending on the demographic group, one study reported 45% to 53% for three attempts, and 51% to 71% to 80% for six attempts.
According to the 2021 National Summary Report compiled by the Society for Assisted Reproductive Technology (SART), the mean number of embryos transferred for patients achieving live birth is as follows:
< 35 35–37 38–40 41–42 > 42 Mean # of transfers 1.33 1.28 1.19 1.11 1.10
Effective from 15 February 2021, the majority of Australian IVF clinics publish their individual success rate online via YourIVFSuccess.com.au. This site also contains a predictor tool.
Pregnancy rate Pregnancy rate may be defined in various ways. In the United States, SART and the Centers for Disease Control (and appearing in the table in the Success Rates section above) include statistics on positive pregnancy test and clinical pregnancy rate.
The 2019 summary compiled by the SART includes the following data for non-donor eggs (first embryo transfer) in the United States:
<35 35-37 38-40 41–42>42 Positive pregnancy test rate (%) 55.1 44.8 32.9 19.18.5 Clinical pregnancy rate (%) 47.5 38.3 27.5 15.56.3
In 2006, Canadian clinics reported an average pregnancy rate of 35%. A French study estimated that 66% of patients starting IVF treatment finally succeed in having a child (40% during the IVF treatment at the centre and 26% after IVF discontinuation). Achievement of having a child after IVF discontinuation was mainly due to adoption (46%) or spontaneous pregnancy (42%).
Miscarriage rate According to a study done by the Mayo Clinic, miscarriage rates for IVF are somewhere between 15 and 25% for those under the age of 35. In naturally conceived pregnancies, the rate of miscarriage is between 10 and 20% for those under the age of 35. Risk of miscarriage, regardless of the method of conception, does increase with age.
Predictors of success The main potential factors that influence pregnancy (and live birth) rates in IVF have been suggested to be maternal age, duration of infertility or subfertility, bFSH and number of oocytes, all reflecting ovarian function. Optimal age is 23–39 years at time of treatment.
Biomarkers that affect the pregnancy chances of IVF include: Antral follicle count, with higher count giving higher success rates. 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. Level of DNA fragmentation as measured, e.g. by Comet assay, advanced maternal age and semen quality. People with ovary-specific FMR1 genotypes including het-norm/low have significantly decreased pregnancy chances in IVF. Progesterone elevation 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.