Intracytoplasmic Sperm Injection (ICSI)
IntroductionIntracytoplasmic sperm injection (ICSI) is a technique for achieving fertilisation in the laboratory in situations where the semen quality is poor and sperm cannot penetrate the egg on its own. In the ICSI procedure a single sperm is injected directly into the egg, using a fine pipette. The introduction and successful application of ICSI was led by Professor Van Steirteghem at the Free University in Brussels, Belgium. The first ICSI baby was born in 1992 (the first IVF baby was born in 1978).
The stages of ICSI treatment cycle is very similar to that of standard IVF. The main difference is in the laboratory procedure, with ICSI being more labour intensive. As n IVF, ICSI treatment cycle involves ovarian stimulation with injections, ultrasound scanning (through the vagina) to monitor development of follicles (eggs), collection of eggs under intravenous sedation, injection of a sperm into each egg, and finally transfer of embryos into the womb.
When is ICSI used?ICSI is used in the following situations:
- Couples who have undergone IVF and had total failure of fertilisation or recurrent low fertilisation rate (25% or less)
- Where sperm has to be surgically extracted from the testes
- Poor sperm quality with one or more of the following abnormalities - low sperm count, poor motility, high number of abnormal sperm, and high level of sperm-surface antibodies
- With ejaculatory dysfunction , such as retrograde ejaculation - a sufficient number of sperm cells can be recovered from urine and used for ICSI
- Paraplegic males - using Testicular/Epididymal sperm extraction and ICSI (Electroejaculation and IVF is also an option)
- Oncology - male patients starting chemotherapy or radiotherapy should have semen samples frozen for use in the future. Sperm quality of the frozen-thawed sperm may be grossly impaired in which case ICSI offers an excellent chance of achieving fertilisation.
- High Antisperm antibodies in semen (75% or more sperm in the ejaculate coated with antisperm antibodies)
Possible risks associated with ICSISome of the eggs collected may not be of suitable quality for sperm injection. If a very low number of eggs are collected none of them may be suitable for the ICSI procedure.
ICSI is a very delicate procedure. Around 10% of eggs collected may be damaged during the sperm injection process. Such damaged eggs cannot be used for treatment.
Babies born following ICSI treatment may have a slightly higher risk of congenital abnormalities than babies born after conventional IVF. In one study, there has been a slightly increased number of chromosomal abnormalities found (1.5%, against the background risk of 0.4%). It is also possible that some cases of severe male infertility may be a result of a genetic abnormality that may be passed on to any male offspring born as a result of ICSI.
Tests prior to ICSI treatmentIn addition to a detailed history and examination, some tests will be carried out on both partners. Tests on the male partner will include Semen analysis and in some cases, blood test to check FSH level, Karyotype(Chromosomes) and Cystic fibrosis carrier status.
The female partner requires blood tests to check AMH level and Rubella immunity.
Drugs used in ICSI treatment
- A nasal spray (e.g. Nafarelin or Buserelin spray or injection) which suppresses the hormones produced by a woman in a normal menstrual cycle and enable greater control over when the eggs are produced. The spray needs to be taken 3 times per day. Each dose consists of one sniff only. This treatment starts on day 21 of your cycle, i.e. on day 21 after the start of your period.
- Follicular Stimulating Hormone (FSH) Injection (e.g. Menopur, Gonal-F) These injections are administered daily and it stimulates the development of multiple ovarian follicles. There is a wide variation amongst women in the number of follicles (eggs) developed in response to the same dose of the hormone. This response is also dependent of the cause of your subfertility and your age. The growth of the ovarian follicles and the development of the endometrium are monitored by serial ultrasound scanning.
- Human Chorionic Gonadotrophin (HCG) (e.g. Pregnyl or Ovitrelle) When the follicles are considered to be mature enough and the endometrium appropriately developed you will be told when to have the HCG injection, to cause further maturation of the eggs. It is essential that this injection is given at precisely the prescribed time. This is usually given at night between 7.00pm and 12.00 midnight. The egg recovery will be planned about 36-38 hours after the HCG injection. Progesterone Pessaries are used to support the endometrium and encourage implantation.
Possible side effects of the drugsThe nasal spray may cause symptoms such as hot flushes, feeling or depression and irritability, headaches and restlessness at night. These are often mild and short lived and are no cause for concern.
Ovarian Hyperstimulation Syndrome (OHSS)This complication arises if your ovaries respond excessively to stimulation. Young women with polycystic ovary syndrome are particularly at risk of OHSS. It is much less common in women aged over 35 years. Clinically the condition is characterised by grossly enlarged ovaries, varying degree of fluid collection in the abdomen, abdominal swelling and pain. If there is significant risk of OHSS the cycle may be abandoned. If there have been any embryos created from the cycle then they may be frozen and used in a later treatment cycle.
In mild cases, the woman has a feeling of abdominal heaviness, swelling and pain. There is very little or no fluid collection in the abdomen. In general this does not require hospital admission and will settle with rest and simple pain killers at home.
In moderate cases, abdominal discomfort is pronounced and nausea, vomiting and occasional diarrhoea occurs. Hospital admission for observation is often necessary.
In severe cases, fluid may collect in the abdominal and chest cavities and there may be difficulty in breathing. There may also be problems with blood clotting and the kidneys failing to produce urine. Hospital admission is essential. Fortunately, however, such cases are rare.
Mild and moderate hyperstimulation do not require any active therapy other than observation and symptomatic treatment (re: painkillers, increase oral fluid intake). Severe hyperstimulation can occur in up to 2% of cases and needs hospitalisation and prompt treatment.
Egg CollectionAbout 36-38 hours after your HCG injection the egg recovery will be performed. This procedure is carried out under intravenous sedation. Using an ultrasound vaginal probe a needle is used to aspirate follicles through the vagina and the eggs are kept in culture medium. The whole procedure takes about 30-40 minutes and you should be fit enough to go home 2 to 3 hours later.
We will tell you how many eggs have been collected. The risk of complications from the egg collection procedure is minimal, there is less than a 1% risk of pelvic infection and heavy bleeding is uncommon. About 4-5 hours after egg collection the eggs will be mixed with your partner/husband’s sperm.
The following morning the eggs are examined for signs of fertilisation. We will telephone you at an agreed time to tell you if fertilisation has occurred and if so, how many eggs have fertilised. Usually the fertilised eggs will then undergo the process of cell division to become embryos - which will be put back into your womb on the second day after egg recovery.
Embryo TransferThis is normally carried out 2-3 days after the egg collection and only if embryos are formed. You are able to see the embryos prior to transfer on a TV monitor in the embryo transfer room. You can also take a photo of the embryos using your mobile phone camera (or any camera). Embryo transfer is carried out using a fine catheter passed through the cervix and injecting the embryos into the uterus in a very small volume of culture medium. This technique does not normally require sedation. You will need to rest in the hospital for some time following embryo replacement. Many women prefer to go home and rest after this procedure. You should take things easy for the rest of the day and can resume your normal activities the following day. You will be given a list of do’s and don’ts following the procedure.
How Many Embryos are Transferred?The recommendation by the HFEA and the Royal College of Gynaecologists is that one or two embryos should be replaced in women under 40 years of age. This is to reduce the chance of multiple pregnancies. Multiple pregnancies carry a high risk of miscarriage, premature birth and other obstetric complications and are associated with a higher than normal risk of long term neurological problems in the baby.
In women who are 40 years or more, replacement of three embryos may be considered.
What happens to surplus embryos?If you have surplus embryos and provided they of suitable quality for freezing, they can be frozen and kept in storage for you if you so wish. If the embryos are not of suitable quality for freezing or if you do not wish to store them, they will be allowed to perish.
What is involved when you have your embryos frozen?When you have embryos frozen you undertake an agreement with the hospital to store the embryos for up to 10years. The cost of embryo freezing is £440 (includes storage for 12 months). You will be sent a letter asking you whether you want to continue with storage each year. You must inform the hospital if there is a change in your circumstances e.g. change of partner, name or address.
Chances of successThis depends on your individual circumstances, e.g. your age, the cause of your subfertility and the sperm quality will influence the likelihood of success.
Pregnancy testYou will be asked to come to the hospital for a pregnancy test fourteen days after the embryo replacement. If the test is positive we will ask you to return two weeks later for an ultrasound scan.
If you fail to conceive it is necessary to have a review consultation. At this time we will have an opportunity to discuss those factors that may have become apparent during your treatment and consequently may require modification in further attempts.