IVF Step 1: Prevention of Ovulation
("Switching off" your own reproductive hormone production.)
A women's reproductive cycle is controlled by the pituitary gland. This tiny gland releases hormones (chemical messages) that tell the eggs when to grow and when to be released. Hormones released from the pituitary gland stimulate the growth of follicles. A follicle is an immature egg that is surrounded by a sac of fluid that needs to grow and develop before the egg can be collected. Once the pituitary senses that the follicle is mature enough, it will release a surge of hormone to burst the follicle and release the egg (ovulation).
Turning off the reproductive cycle in this way allows the doctors more control over the cycle. If the pituitary gland is not "switched off" it may release hormones that will cause the follicles to burst (ovulate). If we were able to produce a good group of follicles, it would be disastrous if a hormone was released to stimulate ovulation. Ovulation would mean that all the follicles would be spontaneously ruptured and no eggs would be collected for IVF treatment. Better IVF pregnancy results are acheived by temporarily suppressing the release of reproductive hormones from the pituitary gland.
This can be acheived in two ways either by switching off the pituitary gland for the whole cycle as in the long protocol ("down regulation") or switching off the pituitary gland just for a few days when ovulation is more at risk, as in the short protocol. The type of protocol used for your treatment will be discussed with you fully prior to your treatment cycle commencing.
The short protocol allows your own naturally occuring hormones to help with the stimulation in the first five days of the cycle. An injection of a drug called Cetrotide is then given from the sixth day of stimulation and will prevent the pituitary from releasing a surge of a hormone to burst the follicles and release the eggs prematurely. Cetrotide is a gonadatrophin-releasing hormone (GnRH) antagonist and will be taken daily until egg collection.
The drugs used to switch off your whole reproductive cycle are called gonadatrophin-releasing hormone agonists, or GnRH agonists for short. They may include Buserlin (also called Suprecur) and Goserelin, a one-off injection, (also called Zoladex). You will need to take the Buserelin every day and these are given by injection. The staff at the Unit will teach you how to administer these yourself.
Having your reproductive cycle turned off, tricks your body into thinking it is going through the menopause. Because of this, you may experience symptoms similar to those of the menopause such as hot flushes, headaches, mood swings, dizziness, lack of concentration, dry mouth and vaginal soreness. Don't worry - this artificial menopause is only temporary and these symptoms will stop once you stop taking the drugs.
Why is a mock embryo transfer carried out?
The private treatment room in which your mock embryo transfer will take place
A mock embryo transfer will be carried out before your treatment begins. It is normally carried out when you come for your initial appointment (see step 1 - Prevention of Ovulation) or when you come for your first monitoring scan.
The mock embryo transfer is a practice for when you have your embryos put into your womb (see step 6). It allows the nurse to take measurements of your womb and to spot any potential problems early, so that we can be prepared when you have your embryos put back for real.
The mock embryo transfer will be carried out in a private treatment room. A small plastic tube will be inserted into your womb via the natural opening in your cervix. It is normally painless and takes only a few minutes.
IVF Step 2: Stimulation of Follicle Production
You will be given drugs to encourage the formation of follicles in the ovaries. These are given by injection and the nurses will discuss how these drugs are given. If you are taking down regulation drugs, you will need to carry on taking these throughout the stimulation process.
A follicle is simply an immature egg, surrounded by a sac of fluid, which develops wihtin the ovary. As the follicle develops it grows until it is 18 to 20 mm when the egg is mature. It is at this size that the follicle will be triggered by hormones from the pituitary gland to ovulate.
During the IVF cycle, drugs are given to encourage the development of follicles in the ovary. The drugs do however stimulate the ovaries to produce more follicles than would normally grow in a menstrual cycle. The number of follicles that develop depends on many factors, including your age and the hormone test results. An average patient will hopefully get 8 to 10 follicles. The drugs that stimulate follicle production are called Merional, Menopur, Gonal F and Fostimon. They are administered by daily subcutaneous injections. The nurses will give you all the information that you need to perform the injections and a DVD to watch to help you.
Your drug regime will be personal to you, taking into account the results of your blood tests. It is vital that you ask the nurses if you are not sure about the dose or the injections, as if you make a mistake it can be difficult to rectify.
How will I be monitored?
All parts of your cycle will be closely monitored using vaginal ultrasound scanning techniques. A probe, called a transducer is placed into the vagina. The probe is covered with a condom to reduce infection and a gel for lubrication. The probe sends out sound-waves which reflect off the body structures. A computer receives these waves and uses them to create a picture of the uterus and ovaries. The scan is painless and safe.
If you have a down regulated cycle, a scan will be arranged approximately two weeks after the down regulation appointment to determine if the down regulation drugs are effective. If the ultrasound scan shows down regulation, then you will be given a date to commence the stimulation injections.
Approximately, five to seven days after commencing the stimulation injections we will perform another ultrasound scan. We will count and measure all the follicles seen and measure the endometrium, the lining of the womb. The dose of stimulation drug may be changed depending upon the response by the ovaries. A nurse will discuss your progress with you after the scan and answer any queries you may have.
IVF Step 3: Egg Maturation
Normally after ten to fourteen days of stimulation injections, the follicles should be large enough for ovum retrieval. We normally give two to three days notice for the procedure. The ovum retrieval (OR) procedures are normally performed on Monday, Wednesday and Friday mornings.
A trigger injection of Pregnyl, Ovitrelle, Buserelin or Gonasi will be given to mature the eggs within the follicles ready for retrieval. The trigger injection works in the same way as the natural hormone released from the pituitary to trigger ovulation. However, the eggs will be collected before ovulation occurs.
The trigger injection is given approximately 36 hours before the planned procedure subcutaneously.
IVF Step 4: Preparing your womb to receive the embryos
The lining of your womb (endometrium) will have been well developed during the stimulation part of the cycle by oestrogen produced by the ovary. Once the eggs are removed, a hormone called Progesterone prepares the endometrium ready for implantation of the embryo. Progesterone supplements are usually given until the pregnancy test is taken. This will ensure that the endometrium stays thick and offers the best environment for the developing embryo, giving the embryo the best start.
The supplements that may be prescribed for you depend on your personal circumstances. Utrogestan pessaries or Crinone cream are the most common form of progesterone supplements used in the IVF Unit.
Utrogestan is in a tablet form and is given vaginally. It is started on the same evening as the trigger injection at a dose of 600 mg per night. This is done at bedtime, as drowsiness is a common side effect when Utrogestan is taken. Side effects are rare but local inflammation may cause vaginal discomfort.
Crinone is a cream supplied in a pre-filled vaginal applicator. After embryo transfer Crinone can be commenced daily, inserted vaginally. It is best to insert it before going to bed as the cream may make a little mess. Side effects are rare but local inflammation may cause vaginal discomfort.
IVF Step 5: Ovum Retrieval
This procedure is also called “oocyte capture” and “egg collection.”
Normally after ten to fourteen days of stimulation the follicles should be large enough and mature enough for ovum retrieval. We normally give two to three days notice for the procedure. The Ovum Retrieval (OR) procedures are normally performed by either a nurse trained to perform the procedure, or a consultant.
You will be given instructions by one of the nurses when you attend for the last ultrasound scan to perform you of the course of events. We will also given you details in writing so you can be sure of everything you have to do.
- Abstaining from intercourse 3-6 days before ovum retrieval
- Last dose of stimulation drug normally 2 days before ovum retrieval
- Last dose of down regulation drug or Cetrotide 2 days before ovum retrieval
- Trigger injection, to mature the follicles, 36 hours before ovum retrieval
- Commence Utrogestan tablets, to prepare the endometrium, 2 days before ovum retrieval
- Ibuprofen tablet, for pain relief, 1 hour before ovum retrieval
- Nil by mouth, after a drink at 7 am on the day of ovum retrieval
- Bring slippers and a dressing gown if you have them
- Bring a snack to eat after the procedure
The ovum retrieval is normally carried out in the treatment room at the Hull IVF Unit under ultrasound guidance. Your a partner, relative or a friend can stay with you throughout the procedure if you wish. The team will check your identification details and confirm any allergies before starting the procedure.
The ovum retrieval is usually carried out in the IVF Unit, while you are awake by a nurse or doctor. A nurse will sit with you to administer a sedative and painkilling drugs, directly into the blood steam through a cannula. It takes about one minute for the drugs to take effect and they can be topped up by the nurse if needed. Oxygen will be administered continuously through nasal catheters throughout the procedure. A blood pressure machine will continuously monitor your oxygen levels, blood pressure and pulse. The procedure will not start until you are ready and feeling very relaxed.
A needle is attached alongside the vaginal ultrasound probe and the vaginal skin at the top of the vagina is punctured. The tip of the needle can be clearly seen on the ultrasound monitor screen at all times. You can see this on the screen if you wish. The tip of the needle is carefully guided into each follicle in turn. The fluid is then aspirated and handed over to the laboratory staff. They will examine it for the presence of an egg. Frequently the egg is not seen in the aspirate from the follicle, in which case the follicle is flushed with fluid. Although every effort will be made to find an egg in each follicle, this will not always be possible. The procedure will be repeated on the other side for the other ovary. The time taken to carry out the ovum retrieval will vary from approximately 20 minutes to over an hour and mainly depends upon the number of large follicles present.
If you are providing a fresh semen sample, the male partner will be taken to a private room to produce the semen sample for the IVF/ICSI treatment. A sample pot will be provided and labelled. No other pot will be accepted. Your partner will be taken to the dedicated room in the Unit for the production of semen and left in privacy. Our advice is, in order to produce the best quality sperm, that the male partner should abstain from intercourse or masturbation for 3-6 days before the ovum retrieval procedure, thus maximising the number of healthy, active sperm in the sample.
After the procedure, you can rest in the recovery room until you feel well enough to go home. This can be any time from half an hour to an hour. Tea/coffee and biscuits are provided for you. If required, the main hospital cafe available to purchase food/beverages from.
Do not return to work after the procedure. Rest for the remainder of the day.
Do not drive, as the medication you have taken can make you very drowsy.
Avoid cooking until the morning after the procedure to help avoid accidents.
In very few cases, ovum retrieval will be carried out vaginally or by laparoscopy in the operating theatre and with the help of a general anaesthetic.
What happens to the eggs and sperm in the laboratory?
Your eggs will be taken to the laboratory as they are collected. Your partner’s sperm will also be processed in the laboratory. They will be looked after by our dedicated team of embryologists. The eggs and sperm will be kept separately in an incubator. This is a special cupboard that keeps the temperature and chemical conditions around the eggs and sperm similar to conditions found naturally in the body.
A few hours after your egg collection procedure has taken place, the embryologist will mix your eggs with your partner’s sperm. The dish containing the eggs and sperm will then be returned to the incubator to allow fertilisation to take place.
The egg is said to be “fertilised” when a single sperm has burrowed its way through the tough outer coating of the egg. When the sperm reaches the core of the egg, it tells the egg to divide into two cells. These cells then divide again and keep dividing each day until a tiny ball of cells is formed. This ball of cells is the earliest stage in the growth of a baby. It is called an “embryo.”
The embryologist will check on the dish approximately 18 hours later, to see if the sperm and eggs have become embryos.
We will telephone you to let you know if your eggs have fertilised or not. You can expect this call 2-3 days after your egg collection procedure has taken place.
IVF Step 6: Replacing the fertilised eggs
This procedure is called an “embryo transfer” or a “blastocyst transfer.”
We will telephone you to let you know when your eggs have fertilised. We will then keep you updated on your embryos’ progress until you come in to have them transferred to your womb.
Embryos are usually transferred to your womb approximately 2-5 days after your egg collection procedure has taken place.
The team will advise you on the best day/stage for your embryo transfer to be carried out, based on how your embryos are developing and information from previous treatment cycles. Blastocysts are simply embryos that have been allowed a little more time to mature in the laboratory. They are the next stage in the growth of the embryo. Blastocysts are usually transferred to your womb approximately five days after your egg collection procedure has taken place.
You will need to keep days 2-5 days after your egg collection procedure free, as we may telephone you on any one of these days to tell you that your embryos are ready to be transferred to your womb. You will need to be prepared to come to the Unit immediately, in case we need to see you very soon. Your partner will need to come with you to the Unit for the embryo transfer. This is because both partners will need to sign the consent form, should you wish to have any spare embryos frozen and stored.
The embryo / blastocyst transfer will be carried out in the same way as the mock embryo transfer that you had before your treatment started. It will be carried out in the treatment room at the IVF Unit. A small plastic tube will be threaded into your womb via the natural opening in your cervix. This tube will be used to gently place the embryos/blastocysts in your womb. The embryo/blastocyst transfer is usually quick and painless.
By law, there is a limit to the number of embryos/blastocysts that can be transferred to your womb at any one time. This is because there is a risk of multiple pregnancy (twins, triplets, etc.) if more than one embryo/blastocyst is transferred. Although the idea of having twins or triplets may sound good to you, it has to be remembered that multiple pregnancy carries many serious health risks to both the mother and the babies, including an increased risk of losing the pregnancy (miscarriage).
The Hull IVF Unit has a single embryo transfer policy and will only replace a single embryo in women whose chances of successful treatment are good, thus reducing the risk of multiple pregnancy. Each case is decided on an individual basis. We are permitted to transfer a maximum of three embryos in women over 40, but only in exceptional circumstances.
After your embryo/blastocyst transfer has taken place you will walk back to the recovery room to get ready for home. You will be given clear, written information on what you should do next. This information will include:
- How long you should continue to use the progesterone cream/pessaries for (see step 4).
- How long you should wait before you do a pregnancy test.
It is important that you follow these instructions carefully. If you carry out the pregnancy test too early, it may give a false positive result. This is where the test says that you are pregnant, when you actually are not. This happens because the drugs used during the treatment cycle will still be in your body. These drugs are detected by the pregnancy test as a false “pregnancy.” A false positive result would be extremely distressing, which is why we ask patients to wait.
You will need to take it easy after your embryo/blastocyst transfer. We advise patients to rest completely for the rest of the day and avoid stressful situations for the next two weeks. This may mean that you have to take time off work, if you find your job particularly stressful.
It will not be necessary for you to remain lying down after the procedure. Lying down for a long period of time will not increase the chance of the embryo/blastocyst implanting in your womb. You can also use the toilet as normal, as the embryos will not be affected.
Storing spare embryos/blastocysts
Spare embryos and blastocysts can be frozen and stored for use in future treatment cycles.
This will make future treatment cycles easier and cheaper, as it will mean fewer injections and no egg collection procedure.
However, freezing spare embryos or blastocysts for storage is not a suitable option for everyone. The freezing and thawing out process is very tough on embryos and blastocysts and many do not survive. The embryos and blastocysts have to be of the very best quality if they are to have any chance of surviving freezing and thawing.
Your best embryo or blastocyst will be the one selected to be transferred to your womb, so it is likely that any spares will be of a poorer quality. It is for this reason that we do not recommend storage to all our patients.
An embryologist will talk to you before you have your embryo/blastocyst transferred, to discuss whether or not your embryos/blastocysts would be suitable for freezing. Both partners will need to come to the embryo/blastocyst transfer, as you will both be required to sign the consent form before storage can take place.
The consent form will cover issues such as what the Unit should do with the embryos in the unfortunate event of one partner dying or becoming incapacitated. Either partner can change their mind and withdraw their consent at any time.
The Unit will only be allowed to store your embryos for the period of time agreed on the consent form. We will contact you annual and again when you are nearing the end of your agreed storage period to ask you what you would like us to do next. If we cannot contact you, we will be forced to take your embryos out of storage and allow them to degenerate (break down). It is for this reason that you must keep us up to date if you change your contact details.
If you choose to have another cycle of treatment with your stored embryos, this will be known as a “frozen embryo transfer,” or FET for short. For more information about frozen embryo transfers, please refer to our patient information booklet.
IVF Step 7: Pregnancy testing
You will be given a pregnancy test after your embryo/blastocyst transfer. The nurse will give you a date on which you should do the test. You must wait until this date to do the test, as doing the test earlier may give a false positive result. (A false positive is when the test says that you are pregnant when you actually are not.) False positive pregnancy tests are very distressing, which is why we ask patients to wait.
However, we understand that waiting to do the test can be very stressful. Please do not forget, our dedicated team of specialist counsellors are available if you feel you need someone to talk things over with. Counselling is available free of charge before, during and after your treatment.
If you experience a period after the treatment you should still do the pregnancy test. This is because we have known patients in the past who have had bleeding, despite being pregnant.
However, a period usually means that you are not pregnant. You can expect to have a period 12-16 days after your embryo/blastocyst transfer if this is the case.
Vaginal bleeding can also occur as the embryos/blastocysts try to implant in your womb. If you experience any bleeding you should contact us. Continue with your progesterone cream or pessaries.
You should call us after you have done the pregnancy test to let us know what the result is. If the result is negative, you may not feel ready to speak to us in person. If this is the case, you may want to call out of hours and leave an answerphone message.
If your pregnancy test is negative we will provide you with support to help you through this difficult time. We hold weekly meetings in the Unit where we look carefully at treatment cycles that have not been successful or that had to be stopped mid-cycle. We do this to see if there is anything that could have been done differently. The weekly meetings also enable us to make recommendations to improve the chances of future cycles being successful.
We will send you a letter to let you know when this meeting has taken place. You are welcome to hear the findings of this meeting, if you wish. You may choose to have this over the phone or face-to-face at a follow-up appointment.
If your pregnancy test is positive, you should let us know straight away. We will arrange an ultrasound scan to confirm that you are pregnant. This scan will be carried out in about 3 weeks time. This is because we need to wait for the baby to grow to a certain size before the heartbeat can be seen on the scan. You will also need to come to the Unit to collect a supply of pessaries, which you will need to carry on taking until the ultrasound scan confirms that the pregnancy is viable.
You antenatal care (the care that you receive during pregnancy) will not be carried out at the Unit. You will need to get in contact with your GP and let him know that you are pregnant, so that he can arrange appropriate care for you.