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In Vitro Fertilization (IVF)

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Definition:
In vitro fertilization (IVF) is a process by which egg cells are fertilized by sperm outside the womb, in vitro. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed. The process involves hormonally controlling the ovulatory process, removing ova (eggs) from the woman’s ovaries and letting sperm fertilise them in a fluid medium. The fertilised egg (zygote) is then transferred to the patient’s uterus with the intent to establish a successful pregnancy. The first “test tube baby”, Louise Brown, was born in 1978.

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In vitro fertilization (IVF) is a procedure in which eggs (ova) from a woman’s ovary are removed. They are fertilized with sperm in a laboratory procedure, and then the fertilized egg (embryo) is returned to the woman’s uterus.

The term in vitro, from the [Latin] root meaning within the glass, is used, because early biological experiments involving cultivation of tissues outside the living organism from which they came, were carried out in glass containers such as beakers, test tubes, or petri dishes. Today, the term in vitro is used to refer to any biological procedure that is performed outside the organism it would normally be occurring in, to distinguish it from an in vivo procedure, where the tissue remains inside the living organism within 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 labs and biology labs. However, in vitro fertilisation is usually performed in the shallower containers called Petri dishes. (Petri-dishes may also be made of plastic resins.) However, the IVF method of Autologous Endometrial Coculture is actually performed on organic material, but is yet called in vitro. This is used when parents are having infertility problems or they want to have multiple births.

IVF has been used successfully since 1978, when the first child to be conceived by this method was born in England. Over the past 20 years, thousands of couples have used this method of ART or similar procedures to conceive.

Other types of assisted reproductive technologies might be used to achieve pregnancy. A procedure called intracytoplasmic sperm injection (ICSI) uses a manipulation technique that must be performed using a microscope to inject a single sperm into each egg. The fertilized eggs can then be returned to the uterus as in IVF. In gamete intrafallopian tube transfer (GIFT) the eggs and sperm are mixed in a narrow tube and then deposited in the fallopian tube, where fertilization normally takes place. Another variation on IVF is zygote intrafallopian tube transfer (ZIFT). As in IVF, the fertilization of the eggs occurs in a laboratory dish. And, similar to GIFT, the embryos are placed in the fallopian tube (rather than the uterus as with IVF).

Purpose
IVF is one of several assisted reproductive techniques (ART) used to help infertile couples to conceive a child. If after one year of having sexual intercourse without the use of birth control a woman is unable to get pregnant, infertility is suspected. Some of the reasons for infertility are damaged or blocked fallopian tubes, hormonal imbalance, or endometriosis in the woman. In the man, low sperm count or poor quality sperm can cause infertility.

IVF is one of several possible methods to increase the chances for an infertile couple to become pregnant. Its use depends on the reason for infertility. IVF may be an option if there is a blockage in the fallopian tube or endometriosis in the woman, or low sperm count or poor quality sperm in the man. There are other possible treatments for these conditions, such as surgery for blocked tubes or endometriosis, which may be attempted before IVF.

IVF will not work for a woman who is incapable of ovulating or with a man who is not able to produce at least a few healthy sperm.

Diagnosis/Preparation

Once a woman is determined to be a good candidate for in vitro fertilization, she will generally be given fertility drugs to stimulate ovulation and the development of multiple eggs. These drugs may include gonadotropin-releasing hormone agonists (GnRHa), Pergonal, Clomid, or human chorionic gonadotropin (hcg). The maturation of the eggs is then monitored with ultrasound tests and frequent blood tests. If enough eggs mature, a physician will perform the procedure to remove them. The woman may be given a sedative prior to the procedure. A local anesthetic agent may also be used to reduce discomfort during the procedure.

The screening procedures and treatments for infertility can become a long, expensive, and, sometimes, disappointing process. Each IVF attempt takes at least an entire menstrual cycle and can cost $5,000–10,000, which may or may not be covered by health insurance. The anxiety of dealing with infertility can challenge both individuals and their relationship. The added stress and expense of multiple clinic visits, testing, treatments, and surgical procedures can become overwhelming. Couples may want to receive counseling and support through the process.

Aftercare
After the IVF procedure is performed, the woman can resume normal activities. A pregnancy test can be done approximately 12–14 days after the procedure to determine if it was successful.

Risks Factors and Complications
The risks associated with in vitro fertilization include the possibility of multiple pregnancy (since several embryos may be implanted) and ectopic pregnancy (an embryo that implants in the fallopian tube or in the abdominal cavity outside the uterus). There is a slight risk of ovarian rupture, bleeding, infections, and complications of anesthesia. If the procedure is successful and pregnancy.

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Forin vitrofertilization, hormones are administered to the patient, and then eggs are harvested from her ovaries (A). The eggs are fertilized by sperm donated by the father (B). Once the cells begin to divide, one or more embryos are placed into the woman’s uterus to develop (C). (Illustration by GGS Inc.)

is achieved, the pregnancy carries the same risks as any pregnancy achieved without assisted technology.

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 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 < 2500 g.[6] However 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 has been a controversial topic in IVF. Many studies do not show a significant increase after use of IVF, and some studies suggest higher rates for ICSI, whereas others do not support this finding. In 2008, an analysis of the data of the National Birth Defects Study in the US found that certain birth defects were significantly more common in infants conceived with IVF, notably septal heart defects, cleft lip with or without cleft palate, esophageal atresia, and anorectal atresia; the mechanism of causality is unclear.[8]

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 Hospital, located in Tokyo, to use in vitro fertilisation for couples with HIV, the Health, Labour and Welfare Ministry 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 the AIDS virus from sperm.

Normal Results:
Success rates vary widely among clinics and among physicians performing the procedure. A couple has about a 10% chance of becoming pregnant each time the procedure is performed. Therefore, the procedure may have to be repeated more than once to achieve pregnancy.

Abnormal results include ectopic or multiple pregnancy that may abort spontaneously or that may require termination if the health of the mother is at risk.

Morbidity and Mortality Rates:
The most common cause of morbidity is ecotopic pregnancy. Pain is associated with most components of the procedure. Mortality as a result of IVF is extremely rare.

Alternatives
Other types of assisted reproductive technologies might be used to achieve pregnancy. A procedure called intracytoplasmic sperm injection (ICSI) utilizes a manipulation technique that must be performed using a microscope to inject a single sperm into each egg. The fertilized eggs can then be returned to the uterus, as in IVF. In gamete intrafallopian tube transfer (GIFT), the eggs and sperm are mixed in a narrow tube, and then deposited in the fallopian tube, where fertilization normally takes place. Another variation on IVF is zygote intrafallopian tube transfer (ZIFT). As in IVF, the fertilization of the eggs occurs in a laboratory dish. And, similar to GIFT, the embryos are placed in the fallopian tube, rather than in the uterus as with IVF

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Resources:
http://en.wikipedia.org/wiki/In_vitro_fertilisation
http://www.answers.com/topic/in-vitro-fertilisation

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IVF

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Introduction:
IVF or in vitro fertilization (IVF) is a process by which egg cells are fertilized by sperm outside the woman’s womb, in vitro. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed. The process involves hormonally controlling the ovulatory process, removing ova (eggs) from the woman’s ovaries and letting sperm fertilize them in a fluid medium. The fertilized egg (zygote) is then transferred to the patient’s uterus with the intent to establish a successful pregnancy.

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IVF was developed in the 1970s. The first British test tube baby was Louise Brown, who was born in 1978.Some 30,000 test tube babies have been born in the UK since then.
There are several different techniques, but the main process involves the women taking fertility drugs to help her produce more eggs.The eggs are then harvested and fertilised in the laboratory.
The woman is given hormone drugs to prepare her womb to receive the fertilised eggs. The fertilised eggs are placed inside the womb and a normal pregnancy follows.

The term in vitro, from the Latin root meaning in glass, is used, because early biological experiments involving cultivation of tissues outside the living organism from which they came, were carried out in glass containers such as beakers, test tubes, or petri dishes. Today, the term in vitro is used to refer to any biological procedure that is performed outside the organism it would normally be occurring in, to distinguish it from an in vivo procedure, where the tissue remains insided the living organism within 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 labs and biology labs. However in vitro fertilization is usually performed in the shallower containers called petri dishes. (Petri-dishes may also be made of plastic resins.) However, the IVF method of Autologous Endometrial Coculture is actually performed on organic material, but is yet called in vitro.

Around 6,000 babies a year are born in the UK to otherwise infertile couples as a result of in vitro fertilisation.

But the techniques used often arouse huge controversy and some say the process can falsely raise would-be parents’ hopes since it only has a success rate of around 15%.

There have also been cases of fertilised eggs being mixed up in the laboratory and the wrong embryo being transferred to the woman, leading to fears about how the process is carried out.

New techniques coming on stream:

One of the biggest and most controversial advances in IVF in recent years has been the introduction of a technique called ICSI – intra-cytoplasmic sperm injection.

This works by injecting a single sperm directly into an egg.

Some people fear the technique could increase the risk of genetic defects that make the donor infertile being passed on to babies.

ICSI was introduced during the 1990s, but new advances are helping men with a very low sperm count to benefit from it.

These include operations to search for sperm which can be retrieved and injected into an egg.

Another advance being developed at St George’s Hospital in London involves a 3D ultrasound device which helps to spot fertility problems before IVF begins.

For example, it can test whether there are any blockages in a woman’s fallopian tubes that could harm her chances of having a healthy pregnancy.

Other doctors at the hospital are pioneering a technique that could mean an end to hormone treatments and the painful retrieval of eggs from infertile women.

The technique involves collecting thousands of immature eggs from the ovary and developing them in the laboratory.

It works by removing a bit of the skin of the ovary which masks the place where immature eggs develop.

It takes five months to grow there properly and lots of nourishment.

The eggs can be frozen so that they can be used whenever the woman wants.

Again, the technique is controversial because it means a woman could store the eggs and use them at any age.

It is likely to be available in the next 10 years, say doctors at the hospital.

Dr Ian Findlay is also developing a test that can check for 10 genetic abnormalities in one go before a fertilised egg is placed in the womb. He said: “This could lead to a dramatic reduction in miscarriages as the vast majority of miscarriages are due to abnormalities.”

The politics of IVF

IVF is only successful in 15% of cases and a recent report from the College of Health shows that success rates vary widely across the country.

Only 18% of IVF treatment is funded by the NHS and waiting times can differ greatly.

It can cost up to £2,000 per cycle for a couple to go private.

Most couples have three cycles at an average cost of £3,420.

One way of getting free treatment is for women to donate their eggs to other infertile couples.

Opponents of IVF argue that it falsely raises would-be parents’ hopes that they will be able to have a baby when the chances are not that high.

They also argue that it can be a traumatic experience to go through repeated IVF attempts, only to find that the woman does not get pregnant.

Another possible drawback is the fact that IVF treatment increases the chance of having multiple births which the couple may not have planned for.

One to two per cent of pregnant women give birth to more than one child, but with fertility treatment the odds are raised to 25%.

Most of the babies born are twins, but bigger births are on the rise.

Many doctors are worried that they are being put under increasing pressure to use more of the fertility drugs to produce more eggs and so increase the chance of the woman getting pregnant.

Some believe fertility drugs could cause ovarian cancer.

Liz Tiberis, author of ‘No Time to Die’, believes her ovarian cancer was the result of nine attempts at IVF.

But fertility doctors say the link has not been proven.

The Cancer Research Campaign is investigating.

Who regulates the IVF process?

In the UK, the Human Fertilisation and Embryology Authority regulates and licenses fertility clinics under the 1990 Human Fertilisation and Embryology Act.

One area of controversy involves the processes clinics have for ensuring mix-ups do not occur over embryos.

This follows a US case where one woman wrongly received the fertilised egg of another.

Fertility experts say procedures in the UK are very tight and there is unlikely to be the same mix-up here.

But the Medical Protection Society recently reported the case of an expert who transferred three embryos from one woman into another by mistake.

However, he realised his error in time.

Calls have been made for procedures for matching eggs with mothers to be tightened, for example, by stipulating that doctors have to do a DNA test before implantation goes ahead rather than relying on written records.

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BBC NEWS:31 March , 1999

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Advancing Towards Baby Making

DNA fingerprinting will revolutionise the practice of IVF and eliminate multiple pregnancies.

Given a choice, Gita Kapoor, a 37-year-old banker in Bangalore, would have preferred just one child. She and her software engineer husband knew that with their busy work schedules raising even one child wouldn’t be an easy job. Two years ago, they opted for in vitro fertilisation (IVF) at a fertility clinic in their city. Today the Kapoors are proud parents of a pair of chubby twins — a boy and a girl.

It isn’t that the Kapoors are not happy to have more than one child. But they have two children not by choice but because of an inherent shortcoming in the assisted reproduction technique they opted for.

“So far there is no technique available to choose a single, viable embryo for implantation,” says Dr Trichnopoly Chelvaraj Anand Kumar, a veteran andrologist in Bangalore.

As a result, fertility doctors normally implant more than one embryo to increase the chances of pregnancy. “With a single embryo, the success rate of IVF is about 30 to 35 per cent. It goes up to 45 per cent with two embryos,” says Dr Indira Hinduja, who is the first Indian doctor to have produced a test tube baby in India in the 1980s.

There are a number of problems associated with multiple pregnancies. Often, babies born in a multiple birth are premature, have low birth weight and are prone to infections. Also, their mortality rate is slightly on the higher side, notes Dr Hinduja.

But thanks to a team of medical researchers in Australia and Greece, doctors may soon be able to find a way of successfully employing genetic screening to identify embryos that can lead to healthy babies.

In a paper reported in the latest issue of the journal Human Reproduction, the researchers say that DNA fingerprinting, a technique more commonly used in forensic applications and in resolving parenthood controversies, can be a useful tool in fertility clinics. The technique can help pinpoint a handful of genes that can help spot a better embryo that would lead to a successful pregnancy, says Gayle Jones, a researcher at Monash Immunology and Stem Cell Laboratories, Monash University, Australia.

When a couple attends a fertility clinic for IVF, eggs from the woman are fertilised with sperm from the man and the fertilised eggs are allowed to develop in the laboratory until they reach what doctors call the blastocyst phase, or the early stages of embryo formation. This normally takes about five days.

One of the difficult decisions, even for a better-trained fertility expert, is to decide which fertilised egg is to be chosen. With little help from technology to distinguish a viable blastocyst from a non-viable one, they often resort to implanting more than one to increase the chances. This often leads to multiple pregnancy.

But this need not be the case anymore, say researchers at Monash University and the Centre for Human Reproduction at Genesis Athens Hospital in Greece.

For their study, the scientists removed a few cells each from the outermost layer of the resulting blastocysts of 48 women who attended the clinic for IVF treatment.

Of the 48 women, 25 became pregnant, leading to the delivery of 37 babies. Once the babies were born, blood from the umbilical cords or swabs of cheek cells was collected. Subsequently, the scientists used DNA fingerprinting to see which genes were common to the material collected after delivery as well as the blastocyst biopsy.

“By analysing these genes, we have been able to identify those that are key to the processes involved in embryo implantation,” Jones told KnowHow.

Though it is too early, she thinks that they would be in a position to refine the gene set further to a smaller number of genes that are more highly predictive of a viable blastocyst. “The ability to select a single, most viable embryo from a cohort available for transfer will revolutionise the practice of IVF, not only improving pregnancy rates but also eliminating multiple pregnancies and the attendant complications,” Jones said.

The Monash University researchers hope that the technique would be available for clinical use within a couple of years if they achieve further success.

IVF being the most common and cheapest of all assisted reproductive methods in use, such improvements in its success rate will be a boon to a large number of infertile couples, says Dr Kumar.

Sources:The Telegraph (Kolkata, India)

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