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History Based on the findings of Min Chueh Chang's application of in vitro fertilisation on animals, the technique was specifically developed for humans in the United Kingdom by Doctors Patrick Steptoe and Robert Edwards. The first so-called "test-tube baby", Louise Brown, was born in Oldham, England, as a result on July 25, 1978 amid intense controversy over the safety and morality of the procedure.• Major pioneering developments in IVF also occurred in Australia under the leadership of Carl Wood, Alan Trounson and Ian Johnston.•• The world's third IVF baby, Candice Reed was born on June 23, 1980 in Melbourne, Australia. Subhash Mukhopadhyay became the fourth physician in India, and the second in the world after Steptoe and Edwards, to perform the first in vitro fertilisation resulting in a test tube baby "Durga" (alias Kanupriya Agarwal) on October 3 1978. Facing social ostracism, bureaucratic negligence, reprimand and insult instead of recognition from the Marxist West Bengal government and refusal of the Government of India to allow him to attend international conferences, he committed suicide in his Calcutta residence in 1981. The first successful IVF treatment in the USA (producing Elizabeth Jordan Carr) took place in 1981 under the direction of Doctors Howard Jones and Georgeanna Seegar-Jones in Norfolk, Virginia. Since then IVF has exploded in popularity, with as many as 1% of all births now being conceived in-vitro, with over 115,000 born in the USA to date. At present, the percentage of children born after IVF or intracytoplasmic sperm injection (ICSI) has been up to 4% of all babies born in Denmark. Indications Initially IVF was developed to overcome infertility due to problems of the fallopian tube, but it turned out that it was successful in most other infertility situations as well. The introduction of intracytoplasmic sperm injection (ICSI) addresses the problem of male infertility to a large extent. Thus, for IVF to be successful it may be easier to say that it requires healthy ova, sperm that can fertilise, and a uterus that can maintain a pregnancy. Cost considerations generally place IVF as a treatment when other less expensive options have failed. This means that IVF can be used for females already gone through pregnancy. The donated oocyte can be fertilised in a crucible. If the fertilisation is successful, the fertilised egg will be transferred into the uterus, within which it will develop into an embryo. Ovarian stimulation Treatment cycles are typically started on the third day of menstruation and consist of a regimen of fertility medications to stimulate the development of multiple follicles of the ovaries. In most patients injectable gonadotropins (usually FSH analogues) are used under close monitoring. Such monitoring frequently checks the oestradiol level and, by means of gynaecologic ultrasonography, follicular growth. Typically approximately 10 days of injections will be necessary. Endogenous ovulation is blocked by the use of GnRH agonists or GnRH antagonists. Oocyte retrieval
IVF laboratory In the laboratory, the identified eggs are stripped of surrounding cells and prepared for fertilisation. In the meantime, semen provided by the male partner is prepared for fertilisation by removing inactive cells and seminal fluid. The sperm and the egg are incubated together (at a ratio of about 75,000:1) in the culture media for about 18 hours. By that time fertilisation should have taken place and the fertilised egg would show two pronuclei. In situations where the sperm count is low a single sperm is injected directly into the egg using intracytoplasmic sperm injection (ICSI). The fertilised egg is passed to a special growth medium and left for about 48 hours until the egg has reached the 6-8 cell stage. Laboratories have developed grading methods to judge oocyte and embryo quality. Typically, embryos that have reached the 6-8 cell stage are transferred three days after retrieval. In many American programmes, however, embryos are placed into an extended culture system with a transfer done at the blastocyst stage, especially if many good-quality day-3 embryos are available. Blastocysts may give higher pregnancy rates if embryo quality is in doubt. However, many studies have shown no difference in pregnancy rates between day-3 and day-5 transfers. In Europe, day-2 transfers are common. Embryo transfer Embryos are graded by the embryologist based on the number of cells, evenness of growth and degree of fragmentation. The number to be transferred depends on the number available, the age of the woman and other health and diagnostic factors. In countries such as the UK and New Zealand, a maximum of two embryos are transferred except in unusual circumstances. This is to limit the number of multiple pregnancies. The embryos judged to be the "best" are transferred to the patient's uterus through a thin, plastic catheter, which goes through her vagina and cervix. Often, several embryos are passed into the uterus to improve chances of implantation and pregnancy. Post-transfer The patient has to wait two weeks before she returns to the clinic for the pregnancy test. During this time she may receive progesterone—a hormone that keeps the uterus lining thickened and suitable for implantation. Many IVF programmes provide additional medications as part of their protocol. Acupuncture According to the latest reports published in Fertility and Sterility, if done correctly, Acupuncture significantly improves IVF success rate. Acupuncture is integrated into the treatment protocols by many progressive fertility clinics in the United States. A study of hypnotherapy also suggests a higher success rate when integrated with treatment *. Chance of a successful pregnancy is approximately 20-30% for each IVF cycle, although selected clinics are now able to quote rates up to 50% per cycle. * There are many factors that determine success rates including the age of the patient, the quality of the eggs and sperm, the duration of the infertility, the health of the uterus, and the medical expertise. It is a common practice for IVF programmes to boost the pregnancy rate by placing multiple embryos during embryo transfer. A flip side of this practice is a higher risk of multiple pregnancy, itself associated with obstetric complications. IVF programmes generally publish their pregnancy rates, however comparisons between clinics are difficult as many variables determine outcome. Furthermore, these statistics depend strongly on the type of patients selected. There are many reasons why pregnancy may not occur following IVF and embryo transfer, including Complications 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., England) 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 does occur, but is rare (<1%) and would lead to identical twins. Recent evidence suggest that singleton offspring after IVF is at higher risk for lower birth weight for unknown reasons. Another risk of ovarian stimulation is the development of ovarian hyperstimulation syndrome. If the underlying infertility is related to abnormalities in spermatogenesis, it is plausible, but too early to examine that male offspring is at higher risk for sperm abnormalities. Birth defects The issue of birth defects remains a controversial topic in IVF. A majority of studies do not show a significant increase after use of IVF. Some studies suggest higher rates for ICSI , while others do not support this finding.• Major birth defect include chromosomal abnormalities, genetic imprinting defects, and multiple organ abnormalities. Hansen et al conducted a systematic review of published studies (including ICSI) and found a 30-40% increase risk of birth defects associated with assisted reproductive technology when compared to children born after spontaneous conception.• Possible explanations offered were the underlying cause of the infertility, factors associated with IVF/ICSI, culture conditions, and medications, however, the actual cause is not known. Embryo cryopreservation If multiple embryos are generated, patients may choose to freeze embryos that are not transferred. Those embryos are placed in liquid nitrogen and can be preserved for a long time. There are currently 500,000 frozen embryos in the United States (See http://www.motherjones.com/news/feature/2006/07/souls_on_ice.html) The advantage is that patients who fail to conceive may become pregnant using such embryos without having to go through a full IVF cycle. Or, if pregnancy occurred, they could return later for another pregnancy. Oocyte cryopreservation Cryopreservation of unfertilised mature oocytes has been successfully accomplished, e.g. in women who are likely to lose their ovarian reserve due to undergoing chemotherapy.• Ovarian tissue cryopreservation Cryopreservation of ovarian tissue is of interest to women who want to preserve their reproductive function beyond the natural limit, or whose reproductive potential is threatened by cancer therapy. Research on this issue is promising. Developments Intracytoplasmic sperm injection (ICSI) is a more recent development associated with IVF which allows the sperm to be directly injected in to the egg using micromanipulation. This is used for sperm that have difficulty penetrating the egg and when sperm numbers are very low. ICSI results in success rates equal to IVF fertilisation. Preimplantation genetic diagnosis (PGD) can be performed on embryos prior to the embryo transfer. A similar, but more general test has been developed called Preimplantation genetic haplotyping (PGH). Jane Mohr, 38, of Manhattan Beach Calif., gave birth to the nation's first set of triplets born 21 months apart due to in vitro fertilisation (IVF) and long-term embryo storage. Jane gave birth November 29, 1988 to two daughters, Mollie McKenna and Hannah Christina Mohr, nearly two years after the birth of her son, Cooper Patrick Mohr. Issues Certain ethical issues have been raised from the beginning when IVF was introduced. These concerns include: Separating the traditional mother-father model The IVF process requires sperm, eggs, and a uterus, of course. To achieve a pregnancy any of these requirements can be provided by a third party (or more parties): third party reproduction. This has created additional ethical and legal concerns. The use of IVF provides also greater range of options for single people and same-sex couples wishing to have children. Although both groups already raise children, IVF facilitates this process. Some people object that this could give psychological problems to the child if they grow up without a mother/father role-model. A number of cases have achieved notoriety: Pregnancy past menopause While menopause has set a natural barrier to further conception, IVF has allowed women to be pregnant in their fifties and sixties. Women whose uteruses has been appropriately prepared receive embryos that originated from an egg of an egg donor. Therefore, their children are not genetically linked to them. Even after menopause the uterus is fully capable to carry out its function. Currently, the oldest woman to give birth is Adriana Iliescu, age 66, from Romania. Religious objections The Roman Catholic Church is opposed to in vitro fertilisation in all instances and advocates that infertility is a call from God to adopt children. It "infringes the child's right to be born of a father and mother known to him and bound to each other by marriage." Also, embryos are discarded in the process causing them, according to the Church, to die. Some estimates of the numbers of embryos involved reach 6 million. Catholics and those of other faiths see embryos as human lives with the same rights as all others and, therefore, view this procedure as always unacceptable. However, the Church allows the use of more natural techniques which seek to treat the underlying causes of infertility. Regulatory events While in the United States IVF programmes operate under voluntary guidelines, programmes in many other countries are subject to regulations that regulate many aspects of IVF practice. In such settings regulations may dictate: Notes The spelling fertilisation is a British variant of fertilization. The spelling fertilization is used in American and Canadian English, and often in academic British English. | |||||||||||
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