In this procedure fertilisation of the eggs and the first few days of embryo development occur outside the body. Hormonal drugs are administered to increase the number of eggs growing within the ovaries and their development is monitored by blood tests and ultrasound scans. At the appropriate time maturation of the eggs is triggered by another drug and the eggs are aspirated from the ovary using a needle guided by ultrasound. The eggs are then placed with sperm and both are cultured together overnight in carefully controlled conditions. Eggs that have fertilised are then cultured for a further 1-4 days. During this time a series of checks helps identify the embryo(s) with the greatest developmental potential and one or two embryos are selected for transfer into the uterus.
For a detailed, step-by-step guide to IVF, visit our website www.ivf-lings.co.nz here.
ICSI is a variation of IVF. Instead of the sperm and eggs being mixed in a test tube, a single sperm is injected into each mature egg. ICSI is used when sperm quality is too poor for conventional IVF to work. ICSI allows almost any man with sperm, either in his semen or in his testis, to try IVF.
IMSI is a process that uses advanced new technology incorporating 6000x magnification to detect abnormalities in sperm so only the best are selected and individually injected into the eggs. IMSI is indicated for couples where the male partner has significant known sperm problems, and also for those couples who have experienced recurrent unexplained implantation failure during IVF or miscarriage which could be due to sperm problems.
From the early days of IVF people have tried to increase the chance of pregnancy in IVF by transferring more than one embryo. But transferring more than one embryo also raises the possibility of multiple pregnancies. As IVF methods improved, clinics stopped transferring three embryos in younger women to limit the chance of triplets. Now that the chance of each embryo implanting in the uterus has improved even further (see the diagram), Fertility Associates is encouraging Single Embryo Transfer (SET) in younger women. SET is also a trend in Australia and northern Europe.
The implantation rate (chance of implanting in the uterus per embryo transferred) for women up to the age of 37 having IVF at Fertility Associates’ clinics
What is so bad about twins? Having a twin pregnancy triples most risks associated with pregnancy – such as stillbirth, a serious brain haemorrhage, serious infection, respiratory distress and cerebral palsy. Overall about 20% of twin pregnancies have some problem compared to 6% of singleton pregnancies. Until recently, the problems associated with twins were considered a reasonable compromise for the increased chance becoming pregnant when two embryos were transferred.
The following table summarises a vast amount of information from medical and scientific studies about twins. The actual numbers can vary somewhat from study to study, but the table gives an average picture.
In the table, the figures for stillbirth and death soon after birth come from the register of Australian-New Zealand IVF pregnancies, but most of the other information is about twins in general.
||Risk for Twins
|To the mother
| Hospitalisation for ovarian hyper-stimulation syndrome (OHSS) in an IVF pregnancy
|| 4.6% of pregnancies
|| 9% of pregnancies
|| 2 times higher
| Mother dying in childbirth
|| 5 per 100,000 births
|| 15 per 100,000 births
|| 3 times higher
| To the children
| Stillbirth or death soon after birth (neonatal and perinatal death)
|| 2.8% of children
|| 6.3% of children
|| 2.5 times higher
| Baby admitted to neonatal intensive care unit (NICU) after birth
|| 15% of children
|| 48% of children
|| 3 times higher
| A serious brain haemorrhage around birth
|| 5 times higher
| Serious infection
|| 3 times higher
| Respiratory distress
|| 6 times higher
| Cerebral palsy
|| 0.23% of children
|| 1.3% of children
|| 5 times higher
| Some handicap
|| 2.5% of deliveries
|| 7.4% of deliveries
|| 3 times higher
| Estimate of any problem (death, abnormality, or some handicap)
|| 6% of deliveries
|| 20% of deliveries
|| 3 times higher
Having twins also carries considerable costs for public hospital care, with the average hospital cost of birth and neonatal care in New Zealand being approximately six times higher for twins than a singleton birth.
Of course the large majority of twins are fine and many of the problems around birth are temporary or, if ongoing, not too severe. Nevertheless, a twin pregnancy carries significant extra risks that can be eliminated by SET.
When we reviewed Fertility Associates’ results for the years 2000-2002, we found that 47% of women aged 25 to 35 had a delivery after the transfer of two good quality embryos, with over a third of the deliveries being twins. An alternative would be to transfer only one embryo (SET) and to freeze the ‘second’ good quality embryo, instead of transferring it fresh. If this was done, we calculated that the overall chance of delivery in this group of patients from the same two embryos would have been a very respectable 40%, but only 2% of deliveries would have been twins (due to identical twins).
Fertility Associates now very strongly recommends SET for women 35 and younger having their first or second IVF cycle, who have at least one good quality embryo on the third day after egg collection and this is a requirement for publicly funded treatment. We are pleased to report that the preliminary pregnancy rates from people choosing SET in 2004 is as high as we expected.
This is an option in IVF or ICSI. A small hole is made in the soft shell of the embryo before it is replaced in the uterus. There is some evidence that assisted hatching can improve pregnancy rates in some groups of IVF patients, mainly those who are older or who have had several IVF cycles without success, or those replacing frozen thawed embryos.
Most embryos are transferred into the uterus on the third day after fertilisation when they are at the six to eight cell stage before they become blastocysts. The blastocyst is the final stage of embryo development before the embryo hatches and implants into the uterus to give rise to pregnancy. This occurs on about day 5-6 after fertilisation. In the late 1990s scientists discovered how to grow human embryos well to the blastocyst stage and get good pregnancy rates. Therefore there is now a trend to replacing embryos at this stage.
In theory, blastocyst culture offers the possibility of a higher pregnancy rate mainly due to better embryo selection. Many embryos, whether they arise naturally or after IVF, have chromosome abnormalities, which we cannot yet easily detect. These abnormalities stop the embryo developing much beyond the 8-cell stage, or day 3 of development after egg collection. With blastocyst culture the embryologists can choose embryos on the basis of their ability to develop, rather than on their physical appearance at an earlier stage.
In practice, even with the new culture medium, it is likely that embryo culture in the laboratory will not be as good as in the body. Blastocyst culture for routine use is still in development.
When there have been embryos frozen following in vitro fertilisation, they can be thawed and transferred into the uterus at a later stage. This usually entails several bloods tests to time ovulation during a natural cycle. In some cases it is necessary to control a cycle using drugs to prepare the uterus for implantation. Embryos are transferred into the uterus at the appropriate time, as they are in an IVF cycle.
These are jargon for various techniques to obtain sperm from the epididymis or testis from men who have no sperm in their ejaculate (azoospermia). If the cause of the azoospermia is an obstruction then the sperm retrieval procedure is usually simple and can be done under local anaesthetic with sperm being frozen for future use. If the cause is “non-obstructive” then the procedure will be more complex and best results are achieved with microsurgical techniques.
The testis and epididymis, and ways of retrieving sperm
Often more than two or three embryos are produced in an IVF cycle. Good quality 'spare' embryos can be frozen, and later thawed to give another chance of pregnancy. Freezing and thawing have to be done under special conditions; about 60-70% of embryos can survive the procedure. When embryos are to be thawed the woman's menstrual cycle is monitored with blood tests to make sure the embryos are replaced at the right time of the menstrual cycle.