IN VITRO FERTILISATION (IVF)
What is IVF?
IVF is short for in vitro fertilisation and is typically referred to as ‘assisted conception’. It involves the fertilisation of eggs by sperm outside the body and transfer of the resulting embryo into the womb. The first IVF baby (Louise Brown) was born in Oldham (England) on 25 July 1978 following the pioneering work of a Gynaecologist (Patrick Steptoe) and Scientist (Robert Edwards). The technique of IVF has been refined over the years making it possible for many couples to now achieve their dream of having children. Over sixty thousand babies have been born in the UK from IVF and currently about 2% of babies born every year in the UK result from IVF treatment.
Who is IVF 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. The law as it currently stands in the UK allows any woman below the age of 55 years to have IVF treatment. We are comfortable treating women using their own eggs below the age of 45 years and up to the age of natural menopause (about 51 years) using donated eggs.
How is IVF performed?
IVF involves a long and complex process that may take up to 7 weeks from start to finish and even longer to know whether it is successful. Appreciation of and adequate preparation for this will help couples cope with the often rigorous demands of the treatment.
Initial assessment
There needs to be an initial assessment for IVF that includes a full interview of both partners and sometimes examinations of the female and/or male partner. Blood tests are performed to establish the woman’s hormone profile (FSH, LH, Oestradiol and Anti-Mullerian Hormone), rubella status, blood count and blood group. The couple undergo 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
Counselling is available but not mandatory for couples undergoing IVF and can be of immense help in coming to terms with some of the difficulties they may encounter. Although not a compulsory requirement, couples are encouraged to utilise the opportunity for counselling.
Ovarian stimulation
The mainstay of IVF is controlled stimulation of the ovaries to generate growth of many eggs. This is achieved using two different types of injections, one to suppress the ovaries so that the woman does not ovulate before this is desirable and the other to stimulate growth of eggs. These are typically started at two specific points in the menstrual cycle; on day 2/3 in short cycles and around day 21 in long cycles. 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.
Egg collection
Mature eggs are collected from the ovaries in theatre usually under sedation but sometimes under full general anaesthesia. The eggs are gently sucked out through a long needle that is guided into the ovaries through the vagina under ultrasound control. Rarely, 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.
Mixing eggs with sperm
The male partner is required to produce a semen sample by masturbation on the day of egg collection after 2-4 day abstinence from ejaculation to ensure good quality sperm. The sperm is specially prepared to select the best quality ones for use. For IVF, the sperm is mixed with eggs (inseminated) and the mixture is left overnight in an incubator. The inseminated eggs are checked the next morning to see how many have fertilised (become embryos). We usually commence a five-day course of antibiotics from the egg collection.
Embryo transfer
The embryos are grown (cultured) in a special incubator in the lab and the best quality 1-2 embryos are transferred into the womb on days 2, 3 or 5 after egg collection. We never transfer more than two embryos. Embryo transfer is performed in theatre under ultrasound guidance. The embryos are gently sucked into a soft tube that is passed through the neck of the womb under ultrasound guidance into the top half of the womb where they are released. 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 for treatment can be frozen for the couple’s use in future.
Afterwards
We advise women to continue with their normal schedule following embryo transfer as evidence suggests doing otherwise is not helpful; there is no advantage taking time off work. Hormone pessaries (vaginal tablets) or occasionally injections are given afterwards to help the developing embryos. If treatment is unsuccessful a period will begin usually between 7 and 14 days after the transfer. Women who have not had a period by this time are offered a pregnancy test about two weeks after transfer and if positive, pelvic ultrasound scans three weeks later.
What can go wrong?
About 3 out of 4 women will complete IVF treatment without any difficulties or problems. Common problems encountered include:
- Poor response to stimulation – this affects about 1 in 10 women with development of very few or no eggs at all leading potentially to cancellation of treatment cycles. Although the ovarian reserve test we perform gives us an indication of likely response and allows us to adjust the stimulation drugs accordingly, we often encounter unexpected poor 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 up to 1 in 10 women. It is fortunately mostly mild but can cause abdominal pain and bloating, vomiting, shortness of breath and tiredness. We make every effort to prevent its occurrence by responsible ovarian stimulation but sometimes sadly have to cancel cycles on account of this condition. Hospital admission is necessary for severe cases. Very severe cases may become life threatening, but this is fortunately now 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 give antibiotics after egg collection to help prevent this.
- Multiple pregnancies – there is a risk of multiple pregnancies with IVF/ICSI treatment particularly with replacement of more than one embryo. We make every effort to limit the occurrence of this to fewer than 10% of live births and this effort explains why we encourage women to have single embryo replacement.
- Abnormalities in babies – it is now clear that babies born following IVF treatment have slightly greater risks of structural and genetic/chromosomal abnormalities.
Using donated sperm, eggs and embryos
IVF can be undertaken with donated sperm and/or eggs. Alternatively, already formed embryos can be donated by one couple for use by another. 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 because they have undergone the menopause prematurely and so need donated eggs or embryos. Women with abnormal eggs and those with a genetic abnormality that they do not wish to pass on to their children can also use donated eggs or embryos. Men who cannot produce their own sperm for any reason can utilise donated sperm. Any healthy man, woman or couple that is free of genetic or transmittable diseases can potentially donate their gametes. Potential donors undergo a screening process that includes detailed history and examination, blood tests for chromosomes and infections like HIV, hepatitis B, hepatitis C, syphilis and cytomegalovirus, and cervical swabs. Practical details of how these are undertaken will be discussed with couples for whom they are relevant.
Egg sharing
Egg sharing is a special form of egg donation whereby two women undergo IVF treatment simultaneously that is mostly paid for by one woman (the recipient) and both share the eggs produced by the other woman (the donor). This treatment is beneficial in situations where a female with good ovarian function cannot afford to pay the full cost of IVF treatment but is prepared to be paired up with another female (the recipient) who can afford to pay for treatment but has poor ovarian function. The recipient effectively pays for the treatment and the eggs retrieved from the donor are divided up between donor and recipient using a previously agreed formula. All previously described processes for IVF 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 family doctor, gynaecologist or infertility specialist will usually be able to advise couples of the current legislation governing this form of treatment in their different countries. The current legislation in the UK holds that sperm, egg and embryo (indeed any body tissue) 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 – this practice may make treatment possible for couples that otherwise may not be able to afford it themselves but it has a potential for abuse. Couples contemplating egg sharing should discuss the issues thoroughly beforehand and agree a plan of action especially with regard to how the eggs are shared and how any future problems are dealt with. These include success in one but not the other couple.
- Anonymity – the regulations governing this vary from country to country. 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 – the legislation governing this may vary from country to country and couples need to seek guidance from their healthcare providers about local regulations. 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 – there is currently no legal requirement in the UK for couples that have been successful with donor gamete treatment to inform the children of their origin but this disclosure is strongly encouraged. Most clinics recognize 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 treatment (including DI, IVF and ICSI) 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 IVF stimulation cycle. Frozen embryos have a 60-90% chance of surviving freezing depending on their quality and stage of 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.
How successful is IVF/ICSI?
The technique of IVF has made it possible for many couples to fulfil their dreams of having children but sadly treatment is not always successful. Factors that improve the chance of IVF succeeding include young female age (particularly if less than thirty years old), previous pregnancies, and short duration of infertility. IVF 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% |
35 – 37 years | 29.5% | 24.8% | 34.4% | 30.1% | 12.0% | 12.8% |
38 – 39 years | 21.8% | 23.2% | 32.7% | 19.4% | 8.8% | 8.4% |
40 – 42 years | 13.7% | 16.7% | 32.3% | 13.9% | 4.8% | 3.0% |
43 – 44 years | 4.9% | 10.4% | 34.8% | 4.8% | – | – |
> 44 years | 2.0% | – | 29.3% | – | – | – |