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Both In Vitro Fertilisation (IVF) and Intra-Cytoplasmic Sperm Injection (ICSI) fall under the umbrella term of ‘assisted conception’. IVF is a much better-known and more established procedure. The first IVF baby, Louise Brown was born in Oldham, UK on July 25, 1978. On the other hand, ICSI is a newer technique, with the first child was born in Singapore in April 1989.
The main difference between the two methods is that in IVF nature is mimicked by adding a large number of sperm to a dish with a number of eggs, with the hope of fertilisation by the strongest sperm. In ICSI, a single sperm is injected directly into the egg to fertilise.
What is IVF?
Here, the eggs are fertilised outside of the body and the resulting embryo is transferred into the womb. Following the pioneering work of Gynaecologist Patrick Steptoe and Scientist Robert Edwards in the 1970s, the technique has been refined over the years. Over sixty thousand babies have been born in the UK from IVF and currently about 2% of babies born every year in the UK are ‘IVF babies’.
Who is it for?
IVF was originally introduced to help women with blocked or damaged fallopian tubes achieve live births, but it now represents the ultimate treatment for any form of infertility that fails to respond to other conventional treatment. UK law currently allows any woman below the age of 55 years to have this treatment. We are comfortable treating women using their own eggs below the age of 45 and 51 years of age using donated eggs.
How is it regulated?
The Human Fertilisation and Embryology Authority (HFEA) was established in 1991 to license clinics that offer IVF, monitor the treatment, and regulate research that involves human eggs, sperm and embryos. It publishes an annual guide of clinics.
How is the procedure performed?
It is important to understand that IVF is a complex process of up to 7 weeks from start to finish. It may take longer to know whether it is successful. The more prepared you are going in, the better you can cope with the demands of the treatment.
IVF Treatment Steps:
An initial assessment includes a full interview and examination of the female and/or male partner. Blood tests like Follicle Stimulating Hormone (FSH), Luteinising Hormone (LH), Oestradiol, Anti-Mullerian Hormone and blood count are performed to establish the woman's hormone profile. Couples undergo a virology screen for HIV, hepatitis B, hepatitis C and syphilis. The male partner's sperm sample is assessed for count, movement, proportion of normal forms of sperm and presence of antibodies. Urine is obtained from both partners to exclude genital tract infections.
Counselling is not mandatory, but can be of immense help in preparing yourself with some of the difficulties you may encounter. We would encourage you to take advantage of our on-site counselling services.
The mainstay of IVF is controlled stimulation of the ovaries to generate growth of many eggs. Two different types of injections are used, which are typically started at the early and late stages in the menstrual cycle. Pelvic ultrasound scans and blood tests are used to monitor the response to stimulation. This continues until the eggs are mature enough to be collected.
Mature eggs are collected from the ovaries in theatre usually under sedation but sometimes under full general anaesthesia. Usually, this is done by gently guiding a needle into the ovaries through the vagina under ultrasound control. On occasion, the eggs are collected by laparoscopy (keyhole surgery). Women typically spend half the day in hospital and are able to return home about lunchtime that day. We usually commence a five-day course of antibiotics from the egg collection.
Mixing eggs with sperm
The male partner produces a semen sample on the day of egg collection after two to four day abstinence from ejaculation, to ensure good-quality sperm. Tests determine the highest quality semen, which is inseminated into the eggs, which is left overnight in an incubator. The inseminated eggs are checked the next morning to see how many have been fertilised.
The embryos are cultured in a special lab incubator and one or two of the best quality embryos are transferred into the womb two to five days later. The procedure does not usually require any anaesthetic or sedation. We discuss and agree the number of embryos to be transferred beforehand but generally encourage most women to have single embryo transfer. Any good quality embryos that have not been utilised can be frozen for the couple's future use.
We advise women to continue with their normal schedule following embryo transfer. Hormone pessaries are given afterwards to help the developing embryos. If treatment is unsuccessful, a period will begin one to two weeks after the transfer. Women who have not had a period by this time are offered a pregnancy test and if positive, a pelvic examination follows.
What can go wrong?
Three out of four women will complete the treatment without any difficulties or problems. Common problems encountered include:
- Poor response to stimulation – although the ovarian reserve test gives us an indication of how you will likely react to treatment, we sometimes encounter poor stimulation response. There is the option to use a higher dose of stimulation drugs in a subsequent cycle.
- Excessive response to stimulation – this can result in a condition called 'ovarian hyperstimulation syndrome' that affects one in ten women. It can cause abdominal pain and bloating, vomiting, shortness of breath and fatigue. Severe cases may require hospitalisation or even become life-threatening, but this is fortunately very rare.
- Injuries during egg recovery – the needle used for the egg recovery may cause injury to the organs in the pelvis (such as the bladder, intestines, and blood vessels) but this is rare.
- Pelvic infections – there is a small risk of infection following the egg collection and severe cases may result in pelvic pus collection. We prescribe antibiotics after egg collection as a preventative measure.
- Multiple pregnancies – there is a risk of multiple pregnancies, particularly with replacement of more than one embryo, which is why we encourage women to have single embryo replacement.
- Abnormalities in babies – babies born following IVF treatment have slightly greater risks of structural and genetic/chromosomal abnormalities.
Donated Sperm, Eggs and Embryos
IVF can be undertaken with donated sperm and eggs, also called gametes. The HFEA has strict regulations governing treatment with donated gametes and these will be discussed with any couple to whom they apply. Some women cannot produce their own eggs due to premature menopause, so need donated eggs or embryos. Women with abnormal eggs and those with a genetic abnormality can also use donated eggs or embryos. Men who cannot produce their own sperm can utilise donated sperm.
Any healthy man, woman or couple that is free of genetic or transmittable diseases can potentially donate their gametes after undergoing a screening process. Factors considered include detailed examination, blood tests for chromosomes and infections like HIV, hepatitis B, hepatitis C, syphilis and cytomegalovirus, and cervical swabs.
Egg sharing is a special form of egg donation, whereby two women undergo IVF treatment simultaneously. The recipient effectively pays for the treatment, and eggs are retrieved from another donor which have a better chance of becoming embryos. All previously described processes remain the same.
Ethical Issues with Gamete Donation
There are implications of using donated gametes that all involved parties need to be aware of:
- Payment of donors – this is a contentious issue and the legislation concerning it varies from country to country. The current UK legislation holds that sperm, egg and embryo donation should be performed altruistically and not attract any form of payment, except where this is to cover loss of income or reasonable expenses incurred by the donor in the process of the donation.
- Egg sharing – couples contemplating egg sharing should agree on all aspects of the treatment thoroughly beforehand and agree a plan of how the eggs are shared and how any future problems are dealt with. These include success in one but not the other couple.
- Anonymity – legislation in the UK has recently changed to give offspring of sperm, egg and embryo donation cycles the right to find out the identity of their genetic parents once they reach their eighteenth birthday.
- Legal parents – current legislation in the UK holds that a married man and woman receiving treatment are the legal parents of any child that results. For unmarried couples, both partners are not automatically awarded legal parent status and have to apply for this at the time of consenting to treatment or through the courts.
- Informing the child – most clinics recognise that children have the right to know about their conception and some arrange a yearly reunion for children born from this and other forms of assisted conception methods to reinforce the normality of such children. Counselling is available at all licensed clinics to discuss the implications of using donated gametes.
FROZEN EMBRYO REPLACEMENT
Couples with frozen embryos can have these transferred without the need to undergo another stimulation cycle. Frozen embryos have a 60-90% chance of surviving freezing. The embryos can be transferred in natural or hormone-prepared cycles. Natural cycles are suitable for women with regular ovulation while those with irregular periods need preparation of the womb using hormone tablets, pessaries (vaginal tablets) and injections. The artificial hormones used to prepare the womb will need to be continued for some time after the transfer; generally up to 12 weeks if pregnancy ensues. Details of transfer procedures, number of embryos transferred and what happens afterwards will be discussed fully with couples.
IVF TREATMENT SUCCESS RATES:
In vitro fertilisation has made it possible for many couples to fulfil their dreams of having children, although treatment is not always successful. Factors that improve the chances of success include: young female age (particularly under thirty), previous pregnancies, and short duration of infertility. Success is measured professionally by pregnancy and life-birth rates and current average rates in the UK are detailed in the table below.
|Age Groups||Fresh IVF/ICSI cycles||Frozen embryo cycles||IVF with Donated Eggs||IVF with Donated Sperm||DI cycles without drugs||DI cycles with drugs|
|< 35 years||32.8%||28.3%||30.7%||31.2%||21.6%||13.4%|
|> 44 years||2.0%||-||29.3%||-||-||-|
Table 1. Live birth rates for assisted conception cycles in the UK; HFEA published results 2014.
What is ICSI?
Intra-Cytoplasmic Sperm Injection (ICSI) refers to the technique of injecting a single sperm into the centre (cytoplasm) of the egg.
Why is it necessary?
This method overcomes problems of failed or abnormal fertilisation by placing a single sperm directly in the centre of the egg. Problems arise when the sperm may not be the ‘right’ one, or because the injection procedure damages the egg. ICSI is relatively new and as such should still be regarded as experimental.
Who is it for?
We currently use ICSI in couples with reduced semen counts or where there is reduced sperm motility, in which the risk of fertilisation failure is increased, and also those who have previously had very low or no fertilisation in an IVF cycle.
- Sperm concentration less than 15 X 106/ml
- Progressive sperm motility (categories a+b) less than 32%
- Normal sperm morphology less than 2%
- Reduced fertilisation rate after conventional IVF: <40% normal fertilisation with at least 4 mature eggs collected
- Failed fertilisation after conventional IVF
- Use of Epididymal/Testicular sperm
- Use of frozen stored sperm (this is not mandatory but we do recommend it in certain situations)
- Patients who have had ICSI in previous IVF cycles should continue to do so in future cycles
How is it carried out?
On the day of the procedure, the embryologist carefully removes the outer cells from each egg, using an enzyme normally produced by sperm. All eggs can be inseminated by IVF, but only mature eggs can be used in ICSI. The sperm are prepared as normal, the embryologist then picks out individual live sperm, and injects one into each egg, using a special glass needle.
After ICSI the eggs are returned to the incubator overnight and checked for fertilisation the following morning, as for conventional IVF.
ICSI treatment success rates:
Approximately 6 out of every 10 eggs will fertilise successfully with ICSI, similar to IVF. The reasons ICSI fertilisation is not 100% successful are:
- Immature eggs cannot be injected
- Some eggs may be damaged by the injection procedure. This appears to be related to the properties of the inner egg membrane.
- Even when injected directly into the egg, many sperm are not capable of ‘activating’ and fertilising the egg.
After successful fertilisation, embryo development is similar for both methods. Following embryo transfer, pregnancy rates are similar for both procedures. Many clinics report higher success rates for ICSI compared to IVF, but this is only because the women having ICSI are relatively more fertile.
What risks are associated?
ICSI is still a relatively new technique and was not preceded by long-term animal studies, as is usually required for new medical techniques or drugs. It is known that abnormal sperm production (very low sperm count or absent sperm in the ejaculate), can be associated with genetic defects in the male. As ICSI bypasses the normal processes of sperm ‘selection’ and fertilisation, these genetic defects may be transmitted to the children. In rare cases, the egg is damaged by the injection procedure. This can result in damage to the resulting embryo. The full implications of treatment will not be known for many years, and you should be aware of the possible risks of this procedure as detailed below.
Between 3-5% of men with very low sperm counts are more likely to have a rearrangement of their chromosomes responsible for sex determination in babies – known as a balanced translocation. A rearrangement can lead to a chromosome abnormality in any baby conceived. Some men with low sperm counts will have a small deletion of a portion of their Y chromosome i.e. a tiny genetic fragment may be missing. This will not be found in routine chromosome testing. This deletion may be passed on to a baby boy and may cause him to have a lowered sperm count when he grows up.
What happens if your chromosome test shows a rearrangement?
If an abnormality is found, the chance of a pregnancy is less and may increase the chance of miscarriage. The child may be unaffected, but if an abnormality is found in your chromosomes, this your Consultant will discuss everything with you and you would be referred to the Regional Genetics service for further counselling.
The evidence on whether or not babies born after IVF or ICSI treatment have a greater risk of birth defects is not yet completely clear, and more studies are needed in order to gain further insight into these possible effects. In 2005, a major European review of children born after ICSI and IVF (followed up until age 5) found that major birth defects involving the heart, lungs, musculoskeletal or gastrointestinal systems, were present in about 2% of naturally conceived offspring, 4% of children conceived by routine IVF, and in 6% of children conceived after ICSI. A substantial proportion of the abnormalities in the ICSI children were problems in the development of the urinary or genital organs, especially in boys. However, all of them were correctable by surgery and they reflected paternal genetic factors rather than the procedure itself. Minor birth defects were present in about 20% of naturally conceived offspring, 31% of children conceived by routine IVF, and in 29% of children conceived after ICSI. Minor anomalies are those which do not have serious medical, functional or cosmetic consequences for the child. More recent studies reported no difference in the risk for any anomaly or specific anomalies after different types of IVF technologies including ICSI.
Some research papers on follow ups of small numbers of ICSI children suggest possible developmental delay in some children conceived using the ICSI technique. This has not been found in ongoing follow up studies in the UK and Europe.
As with all of our services, if you have any questions or concerns you would like to discuss further, you will have the opportunity to do so at any clinic appointment.