In Vitro Fertilization (IVF)
In vitro fertilisation (IVF) was introduced about 30 years ago and since then millions of children have been born thanks to this unique use of science.
Originally developed to assist conception in women who have blocked or damaged fallopian tubes, IVF was so successful it is now being used to treat other causes of infertility, such as sperm disorders, unexplained infertility and endometriosis.
IVF involves adding prepared sperm to a dish containing eggs or injecting a single sperm inside the egg (ICSI). The sperm swim to the eggs and attempt to fertilise them. Once fertilised, the embryos are monitored and transferred back into the uterus at the correct time.
Intra Cytoplasm Sperm Injection (ICSI)
ICSI is an assisted reproductive procedure used as part of a wider IVF program. This fertility treatment is used mainly in cases of male infertility when the quality of the sperm is causing infertility. ICSI involves selecting a single sperm which is injected into an egg. The eggs can be sourced either from the intended mother or a donor egg (frozen or fresh).
Who is ICSI for?
ICSI is often recommended if other problems with the sperm have been identified that:
- Prevent sperm binding to the egg
- Cause failure to fertilise or an unexpectedly low fertilisation rate (below 20%)
- Have been collected from the testicles or epididymis (TESA/PESA)
IVF & ICSI Treatment Steps
1. Ovarian Simulation
After preparation, a scan confirms the ovaries are quiet (2-3 weeks in a down regulated cycle or during a period on the short cycle) and the lining of the womb is thin.
Women on the down regulation regime will continue their nasal sniff or down-regulation injection along with the stimulation injections until further instructions.
Injections are self-administered via dose adjustable pen, ampoules or vials which are mixed with water for injection. We show you the technique and will provide a DVD or written instructions. You will be given a detailed timetable with the days of injections and the dates for scans for you to take home.
Usual duration of treatment is 10-12 days. Regular interval scans and blood tests, if required, will be organised to monitor the response of ovaries to the injections. On a scan we see follicles which may contain eggs. We advise that you take these injections around the same time every day.
Common side effects of the stimulation injections include abdominal bloating, nausea, diarrhoea, weight gain, fatigue, and occasionally a localised reaction at the injection site. Most women feel fine on the injections and those who have had the down regulation phase usually feel much better once they start.
2. Egg Collection
The egg collection is the next step of the treatment cycle and it is performed in an operating theatre, under strong sedation and painkillers or occasionally a general anaesthetic.
When the follicles have reached the right stage of maturity and size on the scan, a trigger injection (Gonasi , Ovitrelle or Suprecur ) is administered exactly 35 to 36 hours before your scheduled egg collection. The timing of this injection is extremely important and should be adhered to very strictly. This injection is always administered in the evening. The day after the injection there are no medications, but you will be asked to fast that night.
On the morning of the egg collection, you will attend the centre at 08:30. You will have been advised to refrain from sex for 3-5 days beforehand to ensure that the sperm quality on the day is optimal.
Your partner will have to produce a semen sample around the time of your egg collection which must occur at the treatment centre and not at home as per the HFEA recommendations.
Identities are checked and once once under sedation or anaesthetic, our specialist(s), will spend 20-30 minutes retrieving the eggs from your ovaries. Each egg sac (follicle) in the ovary is located and punctured under ultrasound scan guidance using a fine needle and the fluid in each sac is drawn into a sterile warm tube that is examined under the microscope. A mature egg may not be retrieved from every follicle. Some ‘empty’ follicles contain eggs that stopped growing and disappear. Others contain eggs that are too young to fertilise.
You may feel slightly bloated and uncomfortable for up to 48 hours following the procedure. Painkillers such as paracetamol or ibuprofen can help and are safe to use.
Some light vaginal staining on the day of the procedure is normal and comes from the needle site.
You will be started on progesterone support (Cyclogest suppositories and/or Lubion injection) once or twice a day, as per your agreed protocol. Progesterone is a hormone that encourages good development of the womb lining in preparation for the embryos.
The suppositories continue to the day of the pregnancy test, and beyond if the test is positive. In some cases we may add oestrogen tablets, blood thinning injections (Clexane) and steroids to improve the chances of pregnancy if we feel you may benefit from it.
In IVF approximately 100,000 good quality sperm are added to each egg in a small dish and then placed in a specialised incubator to keep the eggs and sperm at body temperature.
ICSI treatment is different and involves a single selected sperm being injected into each egg. These are then placed in the incubator as above.
Laboratories are very strict at performing identity checks and at every stage double witnessing is carried out by 2 qualified individuals to avoid any errors.
The morning after the egg collection, the dish is examined under the microscope and fertilisation is studied. On an average, 70% of eggs injected (ICSI) or 60% inseminated (IVF) will fertilise normally.
The embryos which cleave are carefully replaced into the incubator for another 1-4 days. These are checked daily and the embryologist confirms the embryo quantity, quality and the likely time of transfer, which is dependent on embryo development.
5. Embryo Transfer
Embryos can be transferred on day 2, 3 or 5 or in rare instances on day 6 after egg collection. Embryos on day 5 are called blastocyst and if embryos reach the blastocyst stage in the laboratory, the chances of achieving a pregnancy increase substantially. Neither of the centres have any additional charges for day 5 or day 6 transfers.
Therefore embryo culture is assessed and embryos can be transferred on day 3 (When they become 6 to 8 cells) or if they are of good quality and can be cultured to day 5 embryos (Blastocysts) Dr. Mark, Dr. Tiri or Dr. Davis will discuss this in detail with you at the appropriate stage of your treatment after discussing it with the embryologists.
Usual practice is to choose the two strongest embryos for replacement but it may be more appropriate to transfer one or three embryos. Partners may be present for the embryo transfer.
A speculum into the vagina to view the cervix. The embryos that have been chosen for transfer are then drawn into a very fine catheter tube which is passed through the entrance to the cervix and onwards, into the womb cavity where they are expelled. The catheter is then slowly and carefully withdrawn and checked by the embryologist.
The procedure feels no different to having a smear test, takes about 10 minutes and there is no need to rest afterwards.
Additional IVF/ICSI Procedures
Surplus embryos may be frozen after IVF treatment for use at a later date to create more siblings, or if the treatment cycle was unsuccessful.
Frozen embryos have a similar or better success rate than fresh embryos in our care for younger patients.
- Frozen embryo replacement cycles show less asynchrony of the endometrium (lining of the womb).
- Success rates increase from 10 to 15% or more compared to aggressive stimulation.
- Ovarian hyper stimulation syndrome (with life threatening risks) is almost completely prevented.
- IVF cycles have a much higher success rates.
A blastocyst is the term given to an embryo that has been growing for 4-6 days. In nature, embryos implant at the blastocyst stage and thus the transfer of blastocyst embryos has an increased chance of implantation.
We aim to perform a blastocysts culture for all patient , though sometimes we may need to transfer or freeze embryos earlier if there are fewer embryos of embryos of less good quality
We feel that every effort should be made to improve the chances of a pregnancy therefore there is no additional charge for blastocyst culture.
Assisted hatching is believed to be associated with an increased pregnancy rate in selected patients. This technique involves the creation of a small hole in the embryo shell (zona) with a laser, or the use of a chemical process which thins and weakens the zona, just before the embryo is transferred into the womb.
It is useful for women whose embryos have been identified as having a zona that appears particularly thick, or is suspected of being harder than normal. This enables the embryo to hatch out and may help implantation. There is very little evidence that assisted hatching will improve pregnancy rates.
VF/ICSI Treatment Protocol
Treatment protocols are the method of which the fertility specialists take control of the hormones to ensure the best outcome. These protocols vary depending on circumstances.
Down Regulation Protocol
This is also known as the “Long Protocol” and is the commonest one used for IVF treatment. It ensures that your own hormones do not interfere with the action of the subsequent hormone injections which are designed to stimulate egg growth. It is given as daily injections and usually starts on day 21 of your cycle.
The medicine stops the ovaries working temporarily. This phase can be mildly uncomfortable, but lasts for just a 2-3 week period and the majority of patients cope well. A scan after 2-3 weeks confirms that the signal switch-off has happened, though in a few cases it may take longer.
This medication is not contraceptive and we advise that you use condoms to avoid a pregnancy during this suppressive period.
This is also known as the antagonist protocol and is relatively short in duration. It can be used with the pre-treatment of pill or oestrogen tablets (also known as oestrogen priming) or with the start of the period.
These medications block the ovary from releasing the eggs before they are due for collection. They are administered by an injection around the 5th or 6th day of hormonal stimulation, after a scan and a blood test.
This treatment is usually used in cases of PCO (polycystic ovaries) where it reduces the chances of an over response. It can sometimes be used for your convenience and in the cases of some older women. It is rarely ineffective in blocking natural ovulation from occurring (1-2% when ovulation occurs before egg collection).
As part of the IVF treatment, we may recommend the pill prior to starting the IVF stimulation. Controversial as it may seem, a 3 to 4 week treatment with the pill can sometimes help to prepare the ovaries and improve results.
In some cases, we may give oestrogen tablets to prepare the lining of the womb before the IVF or ICSI treatment commences. This may help women who have had a poor response in a previous treatment cycle or had repeated IVF failures.
In cases where the lining of the womb is thin we may advise 3-4 months of oestrogen priming before IVF.
We may use a small dose of steroid during your IVF treatment cycle, with an agreed protocol, either to improve response or to help lower the natural killer cells (NK) after embryo transfer. We may advise you to have immune blood testing prior to treatment.
The flare protocol combines the injection used for down regulation for a very short period of 3 to 5 days starting day 1-3 of your cycle. This enables a flare of FSH from the pituitary gland and may enhance the action of the stimulating drugs in some women.
1. IVF Risks
Ovarian Hyper Simulation Syndrome (OHSS)
Ovarian hyper stimulation is a rare complication of IVF treatment and occurs when ovaries get over stimulated, It is a serious, but rare, complication of IVF. OHSS is usually mild or moderate and the symptoms are self-limiting but in around 3 to 4% of cases, symptoms may become severe and may require hospitalisation.
To avoid OHSS we may use a trigger injection called Supercur, which significantly reduces the chances of OHSS. This is our preferred option and we use it in our frozen embryos treatment packages.
Some cases of OHSS may not still be predictable. Therefore, all women are advised to look out for symptoms following egg collection and embryo transfer.
Although there are a number of tests to predict the ovarian response, in some cases the ovaries fail to respond adequately to stimulation, resulting in acquiring less than 3 eggs during collection.
An inadequate response indicates a decreased ovarian reserve. Sometimes altering the dosage of FSH does not change the response of the ovaries
The number of eggs retrieved at egg collection can be predicted through monitoring ultrasound scans. Occasionally no eggs are collected despite a satisfactory ultrasound scan. It is possible that the follicle may be empty, resulting in no egg being obtained during the operation.
Though rare, we are often able to warn you before you start the treatment that there is a poor prognostic sign, indicating a problem with poor egg quality. We can then discuss different options, which include an egg donor to achieve pregnancy.
Failure to Fertilise and Cleave
Sometimes eggs may not get fertilised or may stop growing.
Multiple pregnancies, including twins and triplets in particular, are associated risks such as increased chance of miscarriage, premature delivery (and associated infant problems). Some women may be advised to consider selective termination to improve their chances of having at least one healthy child at the end of the pregnancy.
Whilst most multiple pregnancies that result from fertility treatment involve the development of a baby from different embryos (non-identical twins), it is still possible to have a single embryo split to form identical twins (or rarely triplets). The chance of this happening is higher in older women having treatment.
Ectopic Pregnancy & Miscarriage
Up to 5% of IVF/ICSI pregnancies may be ectopic (pregnancy outside the womb) and about 10-12% of pregnancies may result in a miscarriage. Everyone is unique and may have different risks associated with pregnancy depending on their personal medical history.
IVF does not increase the risk of a miscarriage when compared with natural conception.
2. ICSI Risks
ICSI was introduced in 1992 and since then, thousands of healthy children have been born; however it is not known if there are any long-term consequences for children conceived by ICSI.