Preparation for IVF
It is essential that you be fully informed prior to the commencement of IVF. This involves several consultations both with Dr McIlveen or Dr Woolcott and the staff of Genea's Newcastle clinic at Lingard Hospital. This information plus an additional booklet supplied by Genea form the basis of your preparation. Interviews with the counselling, nursing and on occasions, scientific staff, complete this preparation.
The counselling session concentrates mainly on the potential moral and ethical issues that surround the use of IVF, although comprehensive emotional supportive counselling is available on request. The interview with the IVF nurse coordinator deals with the day to day practicalities of using the treatment such as instruction on the use of medications and your treatment timetable and plan.
Before treatment is undertaken it is necessary to have a number of pre-treatment tests. These are dominantly for potential infectious diseases (AIDS, Hepatitis B, Hepatitis C, Syphilis & Chlamydia) but also include some tests usually carried out during early pregnancy (Rubella immunity, blood group, blood antibodies, blood count & iron levels) and on occasions genetic tests for Cystic Fibrosis, Thalassaemia and Haemochromatosis.
Commencing an IVF Cycle
To commence a treatment of IVF you should contact Genea's Newcastle clinic (02 4902 7000) at Lingard Hospital on the first day of your period in the month before your intended treatment (that is one month in advance). Inform the nurse coordinator that you wish to start an IVF cycle and they will make all the necessary arrangements to ensure you have the correct medications and instructions.
It is important to also contact the centre to ensure that your referral from your local doctor is up to date before commencing any treatment cycle of IVF. Major problems have been caused by not checking the validity of referrals. The Health Insurance Commission shows no leniency in this situation and they will not pay any Medicare rebate. This could lead to you being an extra two thousand dollars or more out of pocket following treatment.
Hormone treatment
When ovulation normally occurs, one egg is released from the ovary. The aim of the hormone treatment for IVF is to make the ovary produce multiple eggs. On every day of the reproductive life (from birth to approximately 50 years) of a woman, many eggs are available for ovulation. If the right set of hormone signals are present, some of these eggs start to develop towards ovulation. The best, most advanced egg becomes dominant and releases hormones into the surrounding ovary which suppresses the remaining susceptible eggs. The hormone treatment used in IVF recruits more of the eggs that usually would have been suppressed and wasted to ovulate. Put another way, the IVF hormone treatment allows more eggs to get to the point of ovulation.
What happens to you - The procedure & methods
There are four types of hormone / drugs used in the first half of an IVF treatment cycle.
- Oral Contraceptive Pill or related hormones are used to provide a reliably constant hormone environment prior to the use of the actual treatment for IVF. This is a highly successful method of ensuring the maximum proportion of patients can commence treatment
- Gonadotrophin Releasing Hormone Agonist (GnRH agonist). Synarel (Nafarelin) and Lucrin (Luprelide) are the brand names (and chemical names) of these drugs. They are almost identical to hormones produced by an area of the brain called the Hypothalamus. These drugs initially stimulate a gland at the base of the brain, called the Pituitary Gland, to release the ovulation hormone, called Follicle Stimulating Hormone (FSH). After a brief period of release the Pituitary gland then stops producing FSH so there is no further attempt to ovulate. The drug is used up until the time of egg collection. Suppression of the body’s natural urge to ovulate is necessary to prevent selection of just one egg and to maximize pregnancy rates from IVF.
- Follicle Stimulating Hormone (FSH). This hormone is given daily by injection, which is different to its natural pattern of release. Given in this fashion the FSH forces the ovary to make available more eggs than would normally be the case.
- Human Chorionic Gonadotrophin (HCG). Normally a hormone known as luteinising hormone (LH) is released from the pituitary gland to finally make the ovary release an egg. HCG is very similar in chemical structure to LH and is used to mimic this message. It promotes final maturation of the eggs, which have developed as a result of FSH treatment. Ovulation does not occur as the eggs are collected 2 to 4 hours before this would naturally happen.
What you have to do
Synarel is given by nasal spray, twice daily
Lucrin is given as an injection, once a day
FSH requires daily injection.
These injections are subcutaneous, that is just underneath the skin, and can be administered by yourself or your partner. If preferred you may attend the Genea's Newcastle clinic for these injections.
HCG requires an intra-muscular injection, that is deeper into the arm, buttock or thigh.
Benefits & Advantages
As mentioned above, the aim of IVF hormone stimulation is to obtain more eggs than would normally be the case. The main advantage is that this gives the scientist a greater chance of producing at least one top quality embryo. The main benefit is that this maximizes pregnancy rates. In fact when ovarian hormone stimulation is not used pregnancy rates are less than 5%.
Monitoring treatment response
There are two types of monitoring used to see how the ovary is responding to FSH treatment. These are blood tests for hormone levels, which assess how well the ovary is functioning, and ultrasound to see how the follicles are developing.
- Hormone blood testing is usually performed on several occasions throughout your treatment. A test is carried out the day prior to the commencement of treatment with Gonadotrophin Releasing Hormone Agonist (Synarel), then again on the first day of FSH therapy, followed by a thired test on the 8th day of FSH therapy. The final test is performed two or three days prior to the egg collection procedure. These tests measure the levels of the hormones Oestradiol, Progesterone and Luteinising Hormone (LH) in your blood. Essentially the higher the Oestradiol level the greater your response to treatment. As a rough guide one egg is collected for every 1000 units of Oestradiol measured in the blood.
- Ultrasound monitoring is performed on the 8th day of FSH therapy and then on one or two more occasions prior to the egg collection procedure. The ultrasound is performed using the trans-vaginal approach. An instrument is placed in the vagina which will produce a picture on the ultrasound screen. The number of follicles being produced by the FSH therapy can be visualized. The higher the number of follicles the greater the number of eggs that might be retrieved. Not all follicles contain eggs however. Generally we expect to retrieve eggs from 60% of follicles. This number is highly variable.
Egg collection
What happens to you - The procedure & methods
Egg collection involves a trans-vaginal ultrasound guided needle aspiration of the ovaries. Put simply, a needle is passed through the top wall of the vagina directly into the ovary.The fluid in the cystic structures which contain the eggs (called follicles) is aspirated (sucked out). The fluid that is collected is then given to a scientist who examines it to see if there are any eggs using a microscope. Not every follicle contains an egg, so the number of eggs that are retrieved is always less than the number of follicles visible.
The procedure is usually performed using local anaesthesia with the aid of intravenous sedatives and pain relief. Most people tolerate the egg collection very well and do not need a general anaesthesia. If you wish, you can ask in advance to have a general anaesthetic, especially if you have a low pain threshold. A general anaesthetic may be suggested for you by one of the staff under certain circumstances.
What you have to do
It is best not to eat or drink on the morning of your egg collection. Arrive atGenea's Newcastle clinic one hour before the allocated time. The nursing or administrative staff of the hospital will complete the necessary details and give you instructions. Wear loose fitting clothes. Although they will be supplied by the hospital, you should bring along some additional sanitary pads.
Benefits & Advantages
Egg collection is a necessary part of IVF.
No eggs - no pregnancy!
Side effects & Complications
The risks of egg collection procedures are very low. Significant complication rates are less than 1%. Complications that do occur tend to be short lived and not cause long term harm. Bleeding and pelvic infection can occur after any surgical procedure. As egg collection procedures are carried out under ultrasound guidance, sometimes it is difficult to see the ovaries especially if you are overweight. It is possible for the needle to pass out of the ovary into the bowel.
Fertilization
Patient egg, sperm and embryo identification
Genea is accredited by the National Association of Testing Authorities (NATA) the Reproductive Technology Accreditation Committee of the Fertility Society of Australia (RTAC) and has obtained ISO 9001-2000 accreditation for quality management. As part of this accreditation the laboratory is required to have to independent pieces of identifying information on all biological specimens which includes all containers for eggs, sperm and embryos. This methodology is strictly followed to avoid any potential confusion.
Sperm Supply
Sperm are a essential part of IVF. A semen sample needs to be provided on the day of egg collection. The scientist at Sydney IVF Newcastle will inform you of the best time for the sample to be available. It is common for men to feel some anxiety about producing a semen sample on demand. If you think this will be difficult for you please notify the clinic in advance. Occasionally, there are no sperm in the semen and they need to be extracted directly from the testis or epididymis (tubules just next to the testis). This is generally performed in advance of the egg collection procedure and the sperm are frozen. It might be necessary to repeat this on the day of egg collection if the sperm do not survive freezing.
Fertilization Methods
The most common method of fertilization is to place concentrated sperm with the eggs in a small amount of culture fluid. This generally results in about 50% to 75% of eggs fertilizing and becoming embryos. The alternative is intracytoplsmic sperm injection (ICSI).
Intracytoplasmic sperm injection (ICSI)
ICSI is a treatment for severe male factor infertility. ICSI can be used when sperm count and/or the motility (swimming) of the sperm is below normal ranges. The experience of IVF clinics in Australia and overseas indicate that ICSI can be used when there are very few sperm in number, as long as there is evidence that some of the sperm are alive. More recently sperm from the epididymis or the testes have been shown to achieve fertilization and pregnancies.
What happens during ICSI
The ICSI process is an extension of the IVF Programme from the couples' point of view. The woman is required to have the standard regimen of drugs to stimulate her ovaries so that a number of eggs can be recovered. Once the eggs are collected the partner is asked to produce a sperm sample by masturbation (or if no sperm are present, by an operation to collect them from the epididymis or testes). The biologist then selects one sperm from the washed sample and transfers that single sperm to the inside of an egg using a very long thin pipette (needle). One sperm per egg is used. The process is very time consuming and there can be potential damage to the egg(s) due to excessive manipulation. It is thought that up to 20% of eggs may rupture or burst when the sperm is injected, and a number of eggs may not correctly absorb the chromosomes from the sperm. The technique is more complicated than routine IVF and consequently is more susceptible to environmental stress.
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The results from ICSI
The incidence of abnormalities in pregnancies as a result of ICSI is slightly higher than with IVF. This is not believed to be due to the procedure itself but because of underlying genetic abnormalities in the male partner. If you have a low sperm count then this may be due to a genetic abnormality which could then increase the risks for the pregnancy. Your doctor will discuss this with you and may suggest certain genetic tests before proceeding with treatment. Long term follow up studies of ICSI conceived children show they perform just as well at school as their IVF and naturally conceived peers.
Fertilization rates are similar to those obtained using routine IVF with normal sperm parameters. Some couples still fail to achieve fertilization. If you choose to use the process, you should be aware of these risks and appreciate that technical and other problems that can occur throughout the cycle.
Couples considering ICSI should take the opportunity to discuss the technique in greater detail with a biologist. Sometimes you may be asked to produce several sperm samples in order to verify the reproducibility of recovering some motile sperm.
Embryo Culture
This involves growing the embryos in a fluid which is designed to mimic the composition of the fallopian tube. It is a complex salt solution, which also contains amino acids, glucose and other components necessary for very early embryo development. Usually embryos are cultured for 5 days to what is known as Blastocysts. Blastocyst culture has now been proven to be of benefit in selecting the best available embryos and thus maximising the prospects of pregnancy
Blastocyst Culture
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| Development of embryos from day 2 to day 6 of in vitro culture | ||
Since the invention of in-vitro fertilisation, scientists have attempted to fertilize and grow embryos to their optimal state before placing them back into the uterus. Accepted techniques have change over time. Until recently the usual practice was to culture embryos in a complex solution of different chemicals and substances for approximately 48-72 hours before transferring them back to the uterus. From the beginnings of IVF. scientists have attempted to prolong the culture of embryos in the laboratory in an effort to maximize the prospect of pregnancy. Up until recently this has been notoriously unsuccessful. Developments over the last 5 years, however, have led to an improvement in culture media, the addition of certain amino acids, and a reduction in the amount of glucose. This has improved the capability of IVF culture medium to sustain embryos in the laboratory for a longer period of time - for 5-6 days. Embryos at this point are known as blastocysts as they develop a fluid collection surrounded by large numbers of cells.
Sydney IVF has now conclusively demonstrated the superiority of culturing of embryos to the blastocyst stage and producing pregnancy rates through IVF equal to the best in the world.
Benefits & Advantages
The major benefit of blastocyst culture is the ability to reduce the number of embryos available for transfer by excluding the poorer embryos. Some embryos of lesser quality are unable to continue growing beyond for more than 3 to 4 days. We are then left with the ‘best quality’ embryos with the highest probability of pregnancy. However there is no guarantee of pregnacy and the quality of embryos cultured 5 to 6 days can vary widely.
Side Effects & Complications
There are a number of potential disadvantages to blastocyst culture. Some peoples’ embryos may not develop beyond the first few days of life and may not make it to the blastocyst stage. In this situation no embryo transfer takes place, despite having a large number of eggs produced from treatment. However if the embryos had been transferred earlier it is unlikely pregnancy would have occurred as it likely development would also have stalled inside the body. Hence we find out earlier rather than later that the cycle has been unsuccessful. Although this can be very devastating in some ways it can give us more information about what is going on.
There appears to be a substantial increase in the risk multiple pregnancy (twins and triplets) when more than one good quality blastocyst is transferred back to the uterus. In some of the initial studies, twin rates of 70% and triplet rates of 40% were produced in selected groups of patients when 3 blastocysts were transferred. The impact on multiple pregnancy rates, however, is much less certain when this type of treatment is applied to everyone undertaking IVF. There is evidence that blastocyst culture increases the risk of identical twin pregnancy (twins from a single embryo). At Genea in Newcastle we recommend that all patients under 40 have only a single embryo transferred back to the uterus.
It would be fair to say that the risks of prolonged culture and blastocyst transfer have not been firmly established. There is no long-term information or studies on the outcome of pregnancies from this method, and there is no knowledge of the potential risk of congenital abnormalities. Based on general principles, however, it is unlikely that there will be an increased abnormality rate for blastocyst culture, given that no known aspect of IVF. treatment to this point has been demonstrated to adversely affect congenital abnormality rates.
Embryo transfer
What happens to you - The procedure & methods
Usually an embryo transfer is a simple procedure. It is similar to having a PAP smear. The procedure involves placing a speculum in the vagina to gain access and a view of the cervix. A fine outer guiding catheter is then placed through the cervix into the uterus and a finer catheter loaded with your embryos is passed through into the uterine cavity. The embryos are then simply injected into the uterine cavity.
What you have to do
Embryo transfers are usually performed at lunch time. You should arrive at the clinic slightly earlier than the allotted time. You will be shown the embryo before its transfer. You will have to simply slip you lower clothes off and hop onto a bed. Generally the whole process takes less than 20 minutes.
Benefits & Advantages
If you don’t have your embryos transferred back to you, you will not get pregnant.
Side effects & Complications
Occasionally embryo transfer can cause cramping as the catheter goes into the cervix. Rarely, it can be quite painful, particularly when there has been a lot of surgery on the cervix in the past. Theoretically infection could be introduced. The procedure is a sterile one and infection is very rare.
Freezing and storage of additional embryos
All undergo rapid freezing (known as vitrifictaion) instead of under going “slow-freeze”. Vitrification involves “snap-freezing” the embryos in a glass like state. It is done fairly quickly and requires a high degree of technical skill. The benefit of vitrification is that embryo survival is improved and therefore the chance of pregnancy is much better. Pregnancy rates per attempt are up to 10% higher with this technique and more embryos survive. Around 90% of embryos survive thawing with this technique.
Please remember that not everyone has extra embryos available for freezing. Frozen embryos are a bonus but not all couples have additional extra blastocysts available.
Luteal phase hormone support
Following embryo transfer it is usual to provide some ongoing hormone treatment to ensure that the lining of the uterus remains as receptive as possible to the developing embryo. This hormone treatment is one of two types: Human Chorionic Gonadotrophin or Progesterone..
- Human Chorionic Gonadotrophin (HCG) is intended to stimulate the ovary to produce Progesterone which in turn tends to keep the uterus receptive to the developing embryo. This treatment is given by injection on days 3 and 5 after egg collection.
- Progesterone is the hormone which is usually produced by the ovary to help maintain the lining of the uterus. It needs to be given by intravaginal pessary usually twice daily from the day of egg collection. It also needs to be continued throughout early pregnancy. As HCG is just as effective in most instances it is usually preferred. However, when a large number of eggs have been collected and there is a higher risk of Hyperstimulation Syndrome, Progesterone is used so that the ovary is not stimulated further.
Waiting for the results of IVF
Waiting the two weeks after embryo transfer, for the result of treatment is said by many couples to be the most difficult part of IVF. Many indicate that this time is harder to deal with than the hormone injections or the egg collection procedure. Try to relax as best you can. Do things you enjoy. There are no restrictions on physical activity. It is not possible to influence the result of treatment at this stage.
Follow up visit or pregnancy ultrasound
Approximately eleven days after embryo transfer the nurses will arrange a pregnancy test (blood test) for you. If you are pregnant they will continue to look after your early pregnancy and organise an ultrasound at around 7-8 weeks. Making an earlier appointment will not help, as a clear view of the pregnancy can not be obtained. At this stage we would also suggest you start to organise antenatal care!
If pregnancy has not occurred we would suggest making an appointment to come back and talk with Dr Woolcott or Dr McIlveen about your cycle. We will use this visit to review treatment and decide if any refinements or improvements might be made for subsequent therapy. It also gives you a chance to discuss how things went and have any questions answered you may have. Should there be additional embryos which have been frozen, a decision on any necessary treatment and the timing of their transfer can be made.