Introducing IVF – In Vitro Fertilisation (USA Fertilization)
IVF literally means fertilisation outside the body.In vitro (Latin: within the glass) refers to the technique of performing a given biological procedure in a controlled environment outside of a living organism; for example in a test tube. IVF means that the eggs are fertilised outside the body. IVF treatment involves removing eggs from the ovary, fertilising them in the laboratory with sperm and replacing them into the woman’s uterus.IVF treatments are highly confidential.
Louise Brown – The first IVF baby – 1979
Louise’s mother had blocked fallopian tubes. Success rates to open blocked fallopian tubes was always low. Some women have had both tubes removed because of ectopic pregnancies. IVF was originally developed to allow women with such problems to achieve pregnancy. IVF has also proven to be effective for other causes of infertility including endometriosis and unexplained infertility or a combination of infertility factors. IVF can be the last hope for the one in seven couples in the UK who have trouble conceiving.Some couples with male factor infertility achieved conception with IVF. A further development of IVF – ICSI (intracytoplasmic sperm injection) involves the usual IVF type protocol but instead of allowing the eggs to fertilise by themselves in a dish of sperm, an embryologist injects a single sperm into each egg. Around 6,000 babies a year are born in the UK to otherwise infertile couples as a result of in vitro fertilisation (IVF). This means that one baby in a hundred is conceived by IVF.
Following Louise Brown, there have been thousands of babies delivered as a result of IVF. The process is stessful and couples undergoing IVF are advised to receive expert local counselling.
What are in vitro fertilisation (IVF) and embryo transfer?
An IVF treatment cycle involves the collection of eggs from the ovaries. Each egg is placed in a special dish together with sperm to facilitate fertilisation and early development of embryos. Eggs, sperm and embryos are very sensitive and they are cared for by embryologists who ensure that they are nurtured in the most perfect environment within special incubators. About two days after egg collection, embryos (Figure 10.2) are transferred into the uterus.
Figure 10.2 – An IVF Embryo – Four cell stage
IVF was initially developed for women who had severe tubal disease or who had their Fallopian tubes removed but this treatment has also proved successful for unexplained infertility and male factor infertility. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed. A typical IVF treatment cycle is outlined in (Figure 10.3). Originally, eggs were collected laparoscopically but we now collect the eggs by ultrasound guidance usually through the vagina.
Figure 10.3 An IVF Treatment Protocol
The IVF pioneers collected just one egg immediately before ovulation but now we use gonadotrophin injections to increase the number of eggs available for collection (superovulation). Natural gonadotrophin release from the pituitary is suppressed (down regulation) by GnRH to prevent ovulation before the eggs are collected. Ultrasound and hormone assays are required to optimise follicular development. In the UK a maximum of three embryos can be transferred into the uterine cavity usually two days after egg collection.
IVF is a complicated treatment requiring dedication from highly trained clinical and embryology staff. In the UK, clinics offering IVF require a licence from a government appointed body ‘The Human Embryology and Fertilisation Authority’ who monitor the work of IVF units. On average, there is a 20% to 30% success rate associated with IVF. This means that there will be an IVF failure for 70 -80 % of treatment cycles. The issue of birth defects remains a controversial topic in IVF. From a theoretical point of view, doctors and scientists are selecting gametes and embryos which is against the biological vogue favouring natural selection. Evidence on IVF thus far has been largely reassuring.
IVF has been a major breakthrough in treating infertility and is responsible for the birth of more than 500,000 healthy children around the world.
An IVF treatment cycle is divided into four main stages: Egg production – Egg recovery – Insemination – Embryo transfer.
Egg Production In IVF
IVF drugs are used to produce several eggs during one cycle.The majority of IVF cycle protocols employ superovulation whereby there is an increased production of a larger-than-normal number of eggs for fertilisation. The drugs used to stimulate the ovaries are called gonadotrophins and include Pergonal, Metrodin, Follistim and Gonal-F. They are injected daily and the response is monitored by ultrasound and oestrogen levels. To prevent spontaneous ovulation (egg release) in an IVF cycle, GnRH analogues are employed.
Egg Recovery In IVF
During an IVF treatment cycle, eggs are removed from the ovary just before ovulation. HCG is injected approximately 36 hours before planned egg collection. The egg collection can be performed either under general anaesthetic or by sedation. You may find the procedure fine and have no discomfort or you may find that you can be uncomfortable afterwards. Paracetomol can be taken to ease any pain. The Egg Collection can take anything from 20 minutes to an hour but you wont know anything about it! When you come round from either the anaesthetic or sedation the hospital will tell you how many eggs they managed to aspirate from the follicles.
Pictures of IVF Egg Recovery. An ultrasound probe is introduced vaginally and a fine needle guided into the follicles to collect the ova. With superovulation several follicles become evident at ultrasound. The collected eggs are transferred to the embryologist, a scientist with special training in nurturing the precious IVF gametes (eggs and sperm)
Generally, on the same day of your egg collection, your partner will be asked to provide a sperm sample, unless one has already been collected and stored.
IVF – Egg Insemmination
The oocytes (eggs) are incubated for 3-6 hours before insemination in Petri dishes. On day 2, approximately 48 hours post egg collection, the embryos are graded from Grade 1 to 5 – Grade 1 embryos are the best.
Embryo Transfer in an IVF cycle
The selected embryos are transferred to a 15% patient’s serum dish and labelled for transfer. The patient is taken into the treatment room adjacent to the embryology laboratory and placed in the lithotomy position. A vaginal speculum is inserted and the cervix wiped with sterile water. A catheter pre-loaded with the embryos is introduced through the cervix into the endometrial cavity. The position of the catheter is checked by abdominal ultrasound. The embryos are slowly discharged from the catheter. The catheter is then carefully removed and checked to see that all the embyos have been released. If there are spare embryos, they can be frozen and kept in reserve for you.
IVF – Single or Double Embryo Transfer?
It has been common practice for IVF programmes to boost the pregnancy rate by placing multiple embryos during embryo transfer. The more embryos replaced during IVF, the greater the chance of pregnancy but there is also an increased chance of multiple pregnancy. In the early days, many embryos were transferred in each IVF cycle and, although this boosted pregnancy rates, triplets, quads and even higher order pregnancies occasionally occurred.
At first it may seem wonderful for a couple with infertility to have a bonus of two babies rather than one, but there is sadly additional costs that may have to be met. All the complications of pregnancy are increased in a twin pregnancy. There are increased risks of miscarriage, premature delivery and operative delivery including caesarean section. Premature delivery is associated with increased chances of morbidity and perinatal mortality (loss of a baby before delivery or in the first week after delivery. Whereas one pregnancy in a hundred will have been conceived by assisted conception in the UK and other developed countries, it has been estimated that 50% of babies requiring care in a special care baby unit are IVF babies. For higher order pregnancy, the risks increase exponentially. To reduce the risks of higher order pregnancies, the option of selective termination of pregnancy was developed.
Successful outcome with IVF has increased as techniques have been refined. At one time, authorities with the power to do so, placed restrictions allowing replacement of just three embryos and then two. For example, in 2001, The Human and Embryology Authority (HFEA), which administers IVF clinics in the UK, decided to reduce the number of embryos that can normally be transferred from three to two. The multiple pregnancy rate for IVF in Europe still approaches one in four. Now, the question is addressed as to whether only one embryo should be transferred.
In women younger than 36 years, single embryo transfer followed by transfer of another single frozen embryo when initial treatment has failed results in similar livebirth rates but with lower incidence of multiple pregnancy.The cost effectiveness of repeated cycles of elective single embryo transfer may be better than double embryo transfer because of the savings from reduced twin pregnancies.
The case for elective single has been contested. It is likely that single embryo transfer will replace double embryo transfer when there would be a high chance of multiple pregnancy although even in those aged 36-39 the elective single embryo transfer policy can still be applied reducing the risk of multiple birth and increasing the safety of assisted reproduction technique (ART) in this age group.
NICE guidelines published in 2004 recommend that suitable couples receive up to three cycles of IVF treatment on the NHS. Only 18% of IVF treatment is funded by the NHS and waiting times can differ greatly. The majority of IVF treatment cycles are undertaken privately and the IVF clinics should provide their patients full details of all likely treatment costs before they start a treatment cycle. The typical cost of one IVF cycle at a private clinic is ?2,500.
IVF is very stressful with highs and lows which means you can become very emotionally drained. There are emotional costs as well as financial cost implications. Most IVF units have counsellors with the experience to assist you to cope with this stress.
An increasing number of fertility specialists and centres offer acupuncture as a part of their IVF protocol, or maintain a list of acupuncturists specialising in infertility. Scientific evidence does not seem to support acupuncture as a means of improving pregnancy rates although it may assist with relaxation.