In Vitro Fertilisation

Transcription

1 This booklet is designed as a general guide to your forthcoming IVF treatment cycle. It will help you to understand what will happen during your treatment. There will be detailed discussions at your consultations and staff are available at any time to answer questions. IVF can be combined with other techniques such as ICSI (Intracytoplasmic Sperm Injection). This leaflet deals with IVF and ICSI in general terms, including the implications and risks of treatment, the freezing of embryos and the use of embryos for research. The different drug stimulation regimes are briefly covered in this guide, but more detailed information that applies to your treatment will be given to you in an additional leaflet. Index IVF (In Vitro Fertilisation)... 1 What is In Vitro Fertilisation?... 2 Why has IVF been suggested to us?... 2 Why might IVF help?... 2 Is treatment available on the NHS?... 3 What is the cost of treatment?... 3 Is there a counselling service?... 3 What happens before we start treatment?... 3 How many treatment cycles will I have?... 6 What types of treatment are there?... 6 What happens in a treatment cycle?... 7 What happens if I have a positive result? What happens if I have a negative result? Can I try again if the treatment did not work? Issues to Consider with IVF Ovarian Hyperstimulation Syndrome (OHSS) for Patients requiring ICSI (Intracytoplasmic Sperm Injection) Embryo Freezing and Storage Using Human Embryos for Training and Research IVF Treatment Cycle - Summary Where can we get further information? Ref No 23 Page 1/28

2 What is In Vitro Fertilisation? In vitro fertilisation means fertilisation outside the body. It is a method that has helped many couples to have babies since 1978 when it was first used successfully. All centres providing treatment are licensed and monitored by the Human Fertilisation and Embryology Authority (HFEA). In a treatment cycle the woman undergoes stimulation of the ovaries with fertility hormones so that several eggs can be obtained. IVF involves the culture of eggs with sperm in a laboratory to create fertilised eggs, which develop into embryos. The embryos are allowed to grow for up to five days and then one embryo is transferred into the woman's uterus. In some cases two are transferred. The embryologists select the best quality embryo(s) to be replaced to give you the best chance of achieving a pregnancy. For one out of three couples there may be sufficient embryos to freeze. However, this very much depends of the quality of the embryos.. Why has IVF been suggested to us? Infertility is a significant problem affecting about one in six of all couples wanting a baby. IVF treatment is just one of the treatments available for fertility problems. It may be appropriate if: The woman has blocked fallopian tubes or endometriosis The male has a reduced sperm quality The infertility is unexplained Many couples have multiple infertility problems. Each problem may only be mild and not warrant IVF on its own. However, when combined with other problems, IVF becomes the most appropriate treatment. Why might IVF help? IVF was first developed to treat couples whose principal cause of infertility was tubal damage since IVF simply bypasses the tubes. However, the technique is now also used for a range of other conditions. Male factor problems can be treated with IVF since a high number of motile (swimming) sperm can be placed around each egg, thus helping fertilisation to occur. Very severe sperm problems can be overcome through the injection of a single sperm into the egg. This process is called ICSI (Intracytoplasmic Sperm Injection). Unexplained infertility can be treated by IVF, and may work by increasing the numbers of eggs and embryos. This enables selection of the best embryo(s) for replacement therefore increasing the chances that an embryo will implant. Ref No 23 Page 2/28

3 In some cases the IVF procedure may actually uncover the cause of a couple s infertility by identifying a problem with the eggs, sperm (or both) or embryos. Is treatment available on the NHS? NHS funded treatment is available for some couples, but the amount of funding and the criteria for treatment varies between different regions. These issues will be discussed with you at the time of referral. If your circumstances change, you may not remain eligible for NHS treatment. One of the requirements for eligibility of NHS funding is for the female partner having treatment to have a body mass index (BMI) between Therefore, during your consultation your BMI will be checked and recorded. Maintaining a healthy body weight can improve your chances of achieving a pregnancy and is safer for you during pregnancy. A pre-conception advice leaflet can be collected from our reception. The nurses and counsellors are also available for advice and support. What is the cost of treatment? If you are not eligible for NHS funded treatment, you may self-fund treatment. Our cost per standard treatment cycle includes HFEA fees (where appropriate), consultations relating to treatment, drugs, monitoring, HIV tests, counselling and early pregnancy monitoring. The package excludes non-routine investigations, costs associated with embryo freezing and anaesthetic costs for patients who are advised for medical reasons to have an egg collection under general anaesthesia. A consultation fee will be charged if patients have attended for a medical consultation and decide not to continue with a treatment. You will be given a costed treatment plan to outline all costs which may be incurred. Is there a counselling service? A counselling service is available before, during and after treatment. What happens before we start treatment? 1) Investigations: Fertility investigations will have been carried out in the infertility clinic prior to referral. These investigations may involve hormone tests during your menstrual cycle to ensure that you are able to produce eggs and tests to check that your fallopian tubes and uterus are normal. A semen analysis will also be done to help us to decide which treatment is most appropriate for you (IVF or ICSI). Ref No 23 Page 3/28

4 Further investigations may be required and these will be fully discussed with you. 2) First appointment: At this visit the doctor will review your medical history and investigations to ensure that IVF is appropriate. The doctor will also explain what is involved in the treatment, pregnancy rates and the risks of treatment. If you require further investigations, these will be arranged before treatment commences. On arrival for this appointment photographic evidence is required for you and your partner to confirm your identity. This can be in the form of a passport or photographic driving license. Treatment cannot commence without this evidence as it is a requirement of the HFEA. The main issues that will be discussed are: a) Confidentiality: Under the terms of the Human Fertilisation and Embryology Act we cannot pass on details of your treatment to anyone not covered by a treatment licence. This means that we cannot tell your GP or referring doctor about your treatment. However, we can pass on details if you provide us with written consent to disclosure. We will discuss this further with you and ask you to sign a form specifying what information may be passed on and to whom. Usually, this will be your GP, referring doctor and other people directly connected to your treatment or ongoing medical care. We will also ask you to allow information to be passed to people in administration services (for example to process NHS funding or self funding payments for your treatment), and to people auditing the department, and to researchers. During the course of treatment we have a legal obligation to collect information. This information is passed to the HFEA, where it is held securely on a computer register. we have to collect includes personal details, such as your name(s), date(s) of birth and some medical details such as the cause of your fertility problems. Additionally, we have to collect and pass to the HFEA details of treatments undertaken and the outcomes for example pregnancies and babies born. The HFEA keeps a register because it has a legal obligation to tell adults, who may ask in the future, whether they were born as a result of a licensed treatment (IVF or treatment with donor sperm, eggs or embryos). With your consent this data might also be used to provide both medical and non-medical researchers with unique and vital information. This will, for instance, allow them to study the health and wellbeing of mothers and children born after treatment. However, all research would need to be approved by the HFEA before the data can be used. Ref No 23 Page 4/28

5 By completing the disclosure of identifying information form you will be allowing identifying information about your treatment to be shared with researchers. You can change or withdraw your consent at anytime by asking us for new forms. Identifying information about your treatment or any children born as a result of treatment could be released to researchers. Whilst your identity is needed to retrieve the information, the researchers will then anonymise your data. The law does not allow for identifying donor information held on the HFEA register to be disclosed for research purposes. Therefore, donors and those receiving treatment using donor gametes or embryos should not complete this part of the new consent form. Clinics hold more detailed information about patients which the HFEA do not have access to and, therefore, cannot be shared or placed on the HFEA register. b) Consent: Before beginning treatment we must obtain your written informed consent. This means that you have been given information about the procedures, had the opportunity to receive counselling and had time to think about your decision. You may choose to change or withdraw your consent at any time before sperm, eggs or embryos are used in treatment. If you are unable to sign the consent due to injury, physical illness or physical disability someone can to sign for you, providing that it is witnessed and under your instruction. c) Welfare or the Child We are required by law to consider the Welfare of the Child before offering treatment. Further information about this can be found in our leaflet titled Welfare of the Child for Patients. d) Screening for HIV and Hepatitis B and C You and your partner will undergo blood tests to screen for HIV (Human Immunodeficiency Virus), Hepatitis B and C and HTLV I and II. The HFEA ruled in 2001 that all individuals freezing sperm or embryos must have a blood test to screen for HIV and Hepatitis B and C. This is to rule out the very small chance of any cross contamination of the viruses in the storage vessels. Both partners must be tested. Our clinic screens all patients for these infections before treatment so that the results are available before embryos, sperm or eggs are frozen. If you apply for life insurance you will be asked if you are HIV positive. You should not be asked if you have ever had an HIV test or if you have ever tested negative. Therefore, you will not be discriminated against for having a test in the course of fertility treatment. Ref No 23 Page 5/28

6 If you have a positive test, we will provide counselling, and referral to a specialist for advice about your future health. e) Booking treatment If you wish to proceed with IVF, we will agree a month that you will be able to start your treatment. We will predict the week that your period is due, and the start of your treatment is the day your period begins, If you wish to change your treatment booking date it is very important to inform the unit, (please ring reception), as whilst we consider every booking to be important we do often have a waiting list for IVF and someone else could use your booking slot if you are changing to a later month... NHS Patients may have to go back to their GP for re-referral if the booking is changed without a medical reason. 3) Nurse consultation: An appointment will be arranged with a member of our nursing team. The purpose of this appointment is to ensure that you have all the resources to manage your IVF treatment safely and confidently. There will be written information and also web sites / DVDs to ensure that you are fully informed. The nurse will assist you to complete all the necessary consent forms. The injections that are needed will be demonstrated and you will have a chance to practice. You will also be provided with a self-injection kit to take home. At this appointment your booking date will be reviewed and your name listed in the week you expect your period. How many treatment cycles will I have? There is no recommended set number of treatments. We will offer you a follow-up appointment after each cycle to review how the treatment progressed and to offer recommendations for future treatment. What types of treatment are there? There are a number of different drug regimes for ovarian stimulation. We will ensure that you receive the most appropriate regime for your circumstances. This will depend on a number of factors such as your age, cycle length and baseline hormone levels. Each of the different treatment regimes is fully described in separate treatment guides. You will be given the appropriate guide for your treatment. Ref No 23 Page 6/28

7 What happens in a treatment cycle? The following section describes the stages in an IVF treatment cycle. 1) Stimulation of the ovaries The first step in IVF involves hormone stimulation of the ovaries in order to produce several eggs. The hormone used is the same as that produced naturally by the body and is called Follicle Stimulating Hormone (FSH). The eggs are formed in small fluidfilled sacs within the ovary called follicles. These follicles reach about 16 to 20mm in size before the egg becomes mature and they are easily visible on ultrasound scan. The growth of the follicles is monitored with regular ultrasound scans and blood tests to measure the levels of hormone (oestrogen) produced by the follicles. 2) There are several fertility drugs that stimulate the development of follicles in the ovaries. Your doctor will advise you on the most appropriate drug for your treatment. All injections are given by very small needles into the abdomen in the fatty tissue just under the skin (sub cutaneous). Different treatment regimes There are three main methods of stimulation. In our clinic the majority of women have an antagonist treatment regime. We will explain which regime is most suitable for you, or, if you are to have a different drug regime, we will discuss this with you. a) Antagonist Day 1: (first day of bleeding), please ring to notify ACU of the start of your cycle Day 2: attend ACU for blood test and ultrasound scan Day 3: start injections of FSH to stimulate the ovaries to develop eggs Day 7: start injections to prevent early ovulation Day 9 or 10: return to ACU for assessment Day 12 to 16: have late night hcg injection, then return to ACU for egg collection 2 days later 2 to 5 days after egg collection: return to ACU for embryo transfer 2 weeks after egg collection: return to ACU for pregnancy test b) Long Protocol Day 1: (first day of bleeding), please ring to notify ACU of the start of your cycle Day 2 (or Day 21): start injections to suppress the hormones of your natural cycle 2 weeks after suppression return to ACU for assessment When suppressed start FSH stimulation Plan is then similar to Antagonist (above), starting FSH stimulation after suppression instead of on Day 3 of cycle Ref No 23 Page 7/28

8 c) Short Protocol Day 1: (first day of bleeding), please ring to notify ACU of the start of your cycle Day 2: attend ACU for blood test, ultrasound scan and first injection The first injection in the Short Protocol is a stimulant which causes a release of hormones to provide a stronger overall stimulation. This protocol is used if the woman is older or when the ovaries do not respond well to standard doses of FSH. Plan is then similar to Antagonist (above), starting FSH stimulation from day 3 3) Monitoring the cycle Your response is monitored carefully with regular vaginal ultrasound scans and blood tests. The first scan and blood tests are scheduled for Day 2 of your cycle to provide a baseline measurement. (If you are on a long protocol you will also have a scan after the first two weeks to ensure that you are suppressed ) With all regimes, once you start stimulation with FSH injections you will have a scan approximately one week later. Scans then continue every 1 to 3 days, depending on follicle sizes and hormone levels. We will monitor your treatment cycle closely to track your follicle development and your response to the FSH injections. If your response is not optimal it may be necessary to stop and review, hopefully to start again perhaps with a modified plan For example: If too few follicles are developing, or the blood oestrogen levels are low, it may be necessary to cancel the cycle. If too many follicles are developing or the blood oestrogen levels are too high, it may be necessary to cancel the cycle. If the ovaries become over stimulated the risk of Ovarian Hyper-stimulation Syndrome (OHSS) is increased. Please see the section at the end of this leaflet for further information about this condition. Triggering ovulation When the ultrasound scan and/or hormone measurements show that an adequate number of follicles are at the correct size (usually after 9 to 12 days), a final hormone injection is given which completes the egg maturing process. This injection causes the follicles to release the eggs; and is timed 36 hours before egg collection, so that the eggs will be mature, but will not have left the ovary. 4) Sperm collection On the same day as the egg collection the male partner will be asked to produce a semen sample. He will be shown to a private room where he will be asked to produce a sample by masturbation. This room is located in a quiet part of the department and Ref No 23 Page 8/28

9 is specially designed for this purpose. In the room there is a TV/DVD and a selection of DVDs. However, you may like to consider bringing some magazines of your own if you think it necessary. In exceptional circumstances you may be able to produce your sample at home, but this must be discussed with a member of the embryology staff Normal intercourse throughout your cycle will not interfere with your treatment. However, a period of sexual abstinence (including masturbation) of 2 to 5 days is recommended before producing the sample to ensure the best possible sperm quality. It you have no sperm in your ejaculate then it may be necessary to retrieve sperm by a surgical procedure (PESA / TESA). This can be carried out prior to treatment or on the day of egg collection and will be discussed in full with the doctor in advance. If you have sperm in storage that has previously been frozen then this can also be used. The sample will be thawed on the day of egg collections. Sometimes the sperm quality may be poorer on the treatment day than previous samples and it may be necessary to change your treatment plan. This can be for example from IVF to ICSI. An embryologist would explain this to you and you would both need to complete a consent form. In the very rare occasions no suitable sperm are found in your sample we may have to either freeze the eggs or attempt to retrieve sperm surgically (PESA/TESA). 5) Egg collection On the morning of egg collection you should not have anything to eat or drink (you can have some water), unless the nurse tells you otherwise. The procedure is carried out under ultrasound guidance, using the same kind of scan machine that you have become used to during your routine monitoring scans. Egg collection is performed under mild sedation of intra venous Paracetamol and Fentanyl, not general anaesthetic. You can both come into our theatre, and you can bring in a CD of music to help you relax. The procedure usually takes between minutes. If you feel sick during or after your egg collection a nurse can give you anti sickness medicine or insert an acupuncture pin which can help with nausea / vomiting. Alternatively we can insert the pin prior to egg collection if you have had previous problems. Please ask the nursing team if you would like to consider this. A needle attached to the vaginal scan probe is passed into the ovary, and each egg is removed in turn. You will hear a call by the embryologist each time an egg is found so that you will know how many eggs are collected. After the egg collection you will rest in the unit for a short while, and then you can go home. You will be a little drowsy from the sedative drugs. Although the actual procedure is very short your total stay in the unit 3-4 hours. Ref No 23 Page 9/28

10 You must be escorted home and must not drive or operate machinery for 24 hours. 6) Fertilisation and embryo culture The eggs are placed in a labelled dish in specialised culture medium and incubated. After 3-6 hours, sperm will be added. This process is called insemination. If ICSI is required it will be performed instead of insemination. Please see the further information at the end of this leaflet if ICSI is required for your treatment. The following day, the eggs are inspected under a microscope to see whether the eggs have fertilised. The fertilised eggs will develop into embryos and will be cultured in the laboratory to enable the embryologists to select the best quality embryo(s) for transfer. The embryologist will contact you on usually on days 1, 3 and 5 to update you on fertilisation and how your embryos are developing. All procedures in the laboratory are witnessed and strict protocols are followed to meet HFEA requirements. The dishes and tubes in which we place your eggs, sperm and embryos are electronically tagged. Such tagging systems are endorsed by HFEA as the best way to avoid any chance of mixing the wrong eggs, sperm or embryos. 7) Blastocyst culture: The fertilised egg has to go through various developmental stages before it can implant into the lining of the uterus and develop into a viable pregnancy. The first stage of development occurs during the two days following egg collection after which the embryo divides into two cells. Recent scientific advances now enable us to keep the embryos in culture for a further few days so that they can continue growing and dividing until they reach the next stage of development (day five or day six). This stage is called the blastocyst stage To culture the embryos to this stage requires a special fluid which protects and nourishes them allowing them to grow and develop. This fluid is called culture medium and is similar to the fluids secreted naturally by the fallopian tubes and the uterus which co-ordinates the development of the embryo. Normally embryos stay in the fallopian tubes for a few days after fertilisation, only passing in to the uterus when they get to the blastocyst stage. Keeping the embryos in the laboratory until they reach the blastocyst stage is therefore much closer to what happens naturally. What are the advantages of growing embryos to the blastocyst stage? Whether created naturally or in the laboratory, only about half of all embryos are capable of reaching the blastocyst stage. This is due to natural selection, a process that only allows the best embryos to implant and progress to a normal pregnancy. The poor embryos gradually slow down and stop developing at some point during those Ref No 23 Page 10/28

11 first few days. With blastocyst transfer we can avoid raising your hopes by not replacing embryos that have no potential to continue to develop. At the early stages of development it is difficult to tell which embryos have the potential to continue growing and therefore we normally replace more than one embryo. By observing embryo development for longer and culturing the embryos to the blastocyst stage we believe that the chance of pregnancy might be improved. This process of embryo selection we believe will maximise your chance of a pregnancy when having just one embryo replaced. What are the disadvantages of blastocyst transfer? There is a very small risk that none of your embryos will reach the blastocyst stage. This means you may have no embryos for transfer and no chance of pregnancy. If this happens we are fairly confident that your embryos would have failed to continue developing even if we had replaced them earlier. We will only usually give you the option of blastocyst transfer if you have at least 3-4 excellent quality embryos on day 3 of their development (3 days after egg collection). Although this would be very disappointing, we will have gathered more information about your embryos and may be able to use such information to guide you towards future treatment options. Blastocyst transfer will not be suitable for everyone. The embryologists will telephone you on a daily basis after your egg collection and will advise the best plan for you individually. 8) Embryo transfer a) The technique Embryo transfers can take place two, three or five days after egg collection. Whether created naturally, or in the laboratory, all embryos are different in quality, and only a select few will have the ability to develop into a pregnancy. Poor quality embryos gradually slow down and stop developing. Allowing embryos to remain in the laboratory for up to 5 days allows for embryo selection will improve your chance of a pregnancy occurring. At 5 days old the best quality embryos will have reached the blastocyst stage. However, if we know on day 2 or 3 which is the best embryo then we will talk to you about going ahead with the embryo transfer sooner than day 5. Embryo transfer is quick and simple and usually completely painless. The embryo(s) is/are gently transferred into the uterus by using a soft catheter (specialised fine tube). In most circumstances ultrasound guidance is used, and you will need a full bladder for this procedure. Ref No 23 Page 11/28

12 b) The number of embryos to transfer and risks of multiple pregnancy The decision as to the number of embryos to be replaced is important and in many cycles we now recommend only one embryo is replaced, especially if embryos are at the blastocyst stage (day 5). HFEA regulations state that in women under the age of 40, a maximum of two embryos can be replaced. In women over the age of 40 three embryos can be replaced in exceptional circumstances with the agreement of a Consultant. The HFEA have also set clinics strict targets to adhere to for the percentage of twin pregnancies a unit can have. The greatest risk to IVF mothers and babies is a multiple birth. Twins have much higher risks of ill health and death compared to singletons. Around half of all twins are born prematurely or with low birth weight (around 90% of triplets) Risk of death in the first week of life is 5 times higher for twins and 9 times higher for triplets Twins have a 4 times higher cerebral palsy risk than singletons (around 8 in 1000 twins will be affected) There are also risks for women carrying twins. Risk of death is small, but doubled for women carrying twins Increased risk of pre-eclampsia and diabetes Increased risk of miscarriage, operative delivery and haemorrhage Historically the high twin birth rate was due to replacing two embryos during IVF treatment. In recent years the HFEA have introduced a strict policy to reduce the multiple birth rate and published results have shown that it is possible to reduce the risk of twins without compromising the chance of achieving a successful pregnancy. This is managed by transferring one embryo to those patients who are most likely to conceive after IVF, and therefore most likely to have twins. Single embryo transfers are carried out in patients under the age of 37, who are having their first cycle of IVF and who have good quality embryos. Transfer of a single blastocyst gives an excellent chance of success. Single embryo transfer may also be recommended for some patients with medical problems when a multiple pregnancy should be avoided. The web site provides excellent information about the issues surrounding the number of embryos to transfer and the risks involved. There may be situations where we recommend two embryos are replaced as there are other factors affect implantation and success rates, e.g. age, embryo quality, endometriosis, tubal disease or whether a woman has been pregnant with IVF before. The number of embryos to be replaced will be discussed with you at medical Ref No 23 Page 12/28

13 consultation. However, the final decision may be influenced by the quality and number of embryos that you have and, therefore, we will discuss this again before your embryo transfer. At this time you will sign a consent form indicating that you agree to the number of embryos to be transferred. The embryologist will speak to you every day throughout your treatment to discuss how your embryos are developing and to discuss your treatment options. 9) Embryos remaining after embryo transfer If there are good quality embryos / blastocysts remaining after embryo transfer they may be cryopreserved (frozen) for future treatment. An embryologist will discuss this with you. They will explain the quality of the embryos and advise whether they are suitable to cryopreserve. Alternatively embryos can be donated for research or allowed to perish. You will find further information about embryo storage at the end of this leaflet. If you are paying for your treatment freezing of embryos will result in an additional charge. In most cases NHS funded treatment will include the cost of freezing. 10) Hormone support In the second half of the cycle the lining of the uterus, the endometrium, has to be supported with progesterone to help the embryo implant. This is called luteal phase support. We will prescribe progesterone to use after the egg collection. Occasionally injections of hcg will be given instead. You will be given full instructions. We will give you advice about lifestyle whilst waiting for your pregnancy test, but usually there is no need for you to change your normal activities during or after treatment, and sexual intercourse can continue as normal. If you are unsure of what you should or should not do, please do not hesitate to ask for advice. 11) Pregnancy test We will make an appointment for you to return to the clinic 14 days after egg collection for a pregnancy test. This test measures a hormone produced by the pregnancy called Human Chorionic Gonadotrophin (hcg) and is very sensitive. We still require a blood sample even if you have started to bleed as it may be possible to have a positive test even though you are bleeding. We will ask you how you would like to be contacted with the result. Usually this will be by telephone later the same day, but you may come into the clinic for the result in person if you wish. Ref No 23 Page 13/28

14 What happens if I have a positive result? 1) Further pregnancy tests: If the test is positive further pregnancy tests are not usually required. If your result is lower than expected you may need to return for a further blood test to ensure that the hormone level is rising satisfactorily. 2) Pregnancy scan: You will be asked to attend for a scan four to five weeks after your egg collection (this is equivalent to six to seven week s gestation of a naturally conceived pregnancy). This scan is important to ensure that the pregnancy is in the correct place, that it is developing normally and to determine how many pregnancy sacs there are. At this early scan, the pregnancy should be clearly visible inside the uterus as a small fluid filled sac with a tiny fetus within it. It should be possible to identify a heartbeat at this stage. If any problem is found during the scan we will discuss with you and make appropriate plans for further assessment, perhaps in the Early Pregnancy Assessment Unit at the Hallamshire Hospital. We will show you the pregnancy on the monitor and give you a photograph. You will also be given a form summarising your early pregnancy details which you need to take to your GP to book your antenatal care. It is important to register with your GP / midwife by 9 weeks of your pregnancy to allow sufficient time to plan the necessary screening tests which are offered in early pregnancy. You should continue taking folic acid until 12 weeks of pregnancy and Vitamin D throughout your pregnancy 3) Pregnancy outcome: The pregnancy outcome form given after the first pregnancy scan must be returned to inform us of your pregnancy outcome. This is important to enable us to produce accurate statistics and by law we have to report all outcomes to the HFEA. Please complete and return the form no later than four weeks after delivery. Miscarriages please return the outcome form to us even if your pregnancy does not lead to a normal delivery and a healthy baby. We hope that all our pregnancies will lead to happy endings, but we know that occasionally things will not go well for various reasons, and we do need to know all outcomes We are always pleased to receive baby pictures, which we will display anonymously in our photograph albums. Ref No 23 Page 14/28

15 What happens if I have a negative result? A negative result on day 14 means that pregnancy has not occurred. We will discuss your result on the telephone and make plans for a follow up appointment. We realise that you will be very disappointed and ACU staff are always available to offer support and advice. Our counselling service is also available. Can I try again if the treatment did not work? If the treatment has progressed normally it will usually be possible to have further treatment after a follow up appointment with the doctor. If problems have been identified during treatment we will discuss whether it is advisable to try again or if the treatment needs to be modified for your individual circumstances. Issues to Consider with IVF There are a number of issues that you may need to consider before starting treatment. General issues of parental responsibility Any child born as a result of treatment will be legally the child of the husband or male partner and his name should be put on the birth certificate as the legal father. We will obtain written consent from you both acknowledging that you are being treated together. Where a child is born to an unmarried couple, the male partner may not have parental responsibility for that child under the Children Act Unmarried couples are advised to seek their own legal advice about the male partner s rights and responsibilities towards any child who may be born as a result of treatment. In 2003 the law was changed to allow a man to be registered as the father of the child resulting from assisted conception treatment undertaken after a man s death. The law now allows for the deceased man s name, surname, occupation and place of birth to be entered in the birth register, if a consent form is completed. You will therefore be asked to complete the posthumous treatment section on the HFEA consent form to consent to birth registration. However, it is important to understand that this registration does not give the child any legal rights to inheritance or nationality. What is the chance of achieving a pregnancy? Our success rates are available on the HFEA website and on our own website There are many factors that influence a woman s chances of having a live birth. Important factors include the following: Ref No 23 Page 15/28

16 1) The age of the woman The main influence on the chance of pregnancy with treatment is the age of the woman. Successful pregnancy after IVF significantly decreases with age. In addition, the rates of miscarriage and chromosome abnormalities, such as Down s syndrome increase. Other pregnancy complications such as high blood pressure and diabetes also occur more frequently in older mothers. 2) Previous pregnancies Women who have been pregnant before particularly those who have had a previous IVF birth have a higher chance of conceiving with IVF treatment. 3) The duration of infertility The live birth rate is lower the longer a couple has been infertile, whatever the age of the woman. Is there an increased risk of multiple pregnancy? We will try to reduce the risk of having a multiple pregnancy by transferring only one embryo in patients who stand a good chance of success. Rarely an embryo can split after embryo transfer to form identical twins. This means that a single embryo transfer can result in twins and a two embryo transfer could result in triplets. While the prospect of twins may seem attractive, there are many serious risks associated with multiple births as discussed earlier. In some cases the joys of parenthood are greatly reduced by these problems. If a high order pregnancy (triplets or more) occurs as a result of IVF we would discuss the technique of fetal reduction. However, it should be stressed that fetal reduction is not to be regarded as a routine procedure in this event and may have some considerable disadvantages. Are there any other risks of an IVF pregnancy? All pregnancies carry some risk and unfortunately a pregnancy may miscarry or be an ectopic (pregnancy in the Fallopian tube). This is why the early pregnancy scans are important to establish where the pregnancy is and that a heartbeat is present. There is also a very small chance of having a pregnancy correctly placed in the uterus and another in the tube. It is very rare with naturally conceived pregnancies (around 1 in 10,000), but can occur slightly more frequently with IVF. However, it is still very uncommon. Nevertheless, you should always contact your GP or the Early Pregnancy Assessment Unit if you are pregnant and have pain or bleeding in the early stages, even if the scan has shown a pregnancy in the uterus. Ref No 23 Page 16/28

17 We would therefore recommend you do not plan holidays for the first few weeks after your embryo transfer. There is always a small risk (around 2%) that a baby will have some abnormality and IVF does not protect you from this, but the chances are probably no greater than for a natural conception. Does egg collection have any risks? Egg collection is a surgical procedure and, as such, carries risk of complications from sedation (or anaesthesia), bleeding and introduction of infection. However these risks are small and significant problems occur in less than 1:2000 patients. Ovarian Hyper-stimulation Syndrome (OHSS) The drugs used to stimulate the ovaries can occasionally cause the ovaries to over respond and this can lead to a potentially serious condition called Ovarian Hyperstimulation Syndrome (OHSS). How often does OHSS occur? In our clinic significant OHSS affects less than 1% of women undergoing treatment, but it can be serious if appropriate treatment is not given. In its most severe form, or if left untreated, it can be life threatening. Once you start your treatment cycle it is important that you know the symptoms of this condition and how to contact members of the medical team if you need them. What is OHSS? The ovaries become large and leak fluid into the abdomen. This causes swelling and discomfort. The leakage of fluid can cause dehydration and this can make the blood more likely to clot and can affect the way the kidneys and other organs work. Fortunately most cases of OHSS are usually mild to moderate, but in a few cases, if left untreated, it may become severe. If a patient who suffers OHSS becomes pregnant the pregnancy hormones produced by the baby may make the condition temporarily worse. Why does OHSS occur? The condition occurs because the ovaries produce too many follicles and high levels of oestrogen. Therefore, women whose ovaries respond more to the drugs are more likely to get it. Careful monitoring of the treatment cycle can often predict development of OHSS and the treatment cycle is then either cancelled or modified to prevent the condition occurring. However, despite all these precautions, it is not always possible to prevent the condition and it may occur in some women who do not appear to have over responded. Ref No 23 Page 17/28

18 Who is at risk of OHSS? Any woman undergoing stimulation of the ovaries is at risk. Younger women and those with polycystic ovaries are more at risk and we tend to use lower doses of drugs in these women to minimise the risk. When does OHSS occur? The condition only occurs after the injection of hcg (late night injection). If you have symptoms before embryo transfer, the embryos can be frozen and the transfer delayed to allow the condition to subside on its own. What are the symptoms of OHSS? Mild form: Moderate form: Severe form: Abdominal swelling Lower abdominal pain Nausea (feeling sick) As mild plus Diarrhoea Vomiting Dark strong urine You will not necessarily develop all the symptoms at the same time What should I do if I think I have OHSS? As moderate plus Persistent vomiting - unable to tolerate any fluid orally Gross abdominal swelling resulting in shortness of breath You are advised to contact us if you develop any of the above symptoms or feel unwell. If left untreated OHSS can become severe. It is important to drink plenty of fluids to avoid becoming dehydrated. Dark strong urine is an indication of dehydration. You can take Paracetamol or Cocodamol (maximum 8 tablets in 24 hours) for pain relief. Mild OHSS may be relieved by these simple measures, but you should contact us for advice. Sometimes hospital admission is necessary to ensure adequate fluid intake (either orally or through a drip) and adequate pain relief. Who should I contact? Since OHSS is uncommon, your GP or local hospital may not be used to dealing with this condition. Therefore you are advised to contact us directly. Ref No 23 Page 18/28

19 Out-of-hours you can be put through to a nurse from the unit through the main hospital switchboard ( ). If you do need to see another doctor you must mention that you have had treatment and they should liaise with us about you further management. Other risks of treatment The HFEA have advised that patients should be aware of a theoretical risk that the stimulation drugs used in IVF could increase the chance of developing ovarian cancer later in life. However, a number of very large follow up studies have been reassuring and shown no actual increase, but further research is ongoing. for Patients requiring ICSI (Intracytoplasmic Sperm Injection) You may have been advised that your IVF treatment needs to be combined with sperm microinjection. This booklet outlines the principles of ICSI, but if you have any further questions please do not hesitate to contact one of our embryologists. More information about this technique follows. What is ICSI? Intra-Cytoplasmic Sperm Injection (ICSI) was introduced into clinical treatment for certain types of infertility in ICSI involves the injection of a single sperm straight into each egg. ICSI is a routine technique and the results are very similar to conventional IVF. What does ICSI involve? ICSI is similar to conventional IVF in that eggs and sperm are collected from each partner. To achieve fertilisation, a single sperm is taken up in a fine glass needle and injected directly into an egg. The eggs are incubated and examined the following day for fertilisation. Embryos may then be transferred back into the uterus of the woman as in conventional IVF. A small proportion of the eggs collected may either be immature or poor quality and it may not be possible to use these in the ICSI procedure. Also, some eggs may not survive the injection process. In our clinic, this is less than 10% of all eggs injected. When is ICSI used? In conventional IVF the eggs and the sperm are mixed together in a dish and the sperm fertilise the eggs naturally. ICSI bypasses the natural processes involved in a sperm penetrating an egg and so is used when sperm are unable to fertilise the egg naturally. ICSI may be used in the following cases: When the sperm count is very low When the sperm cannot move properly When the sperm have high rates of abnormality Ref No 23 Page 19/28

20 When sperm has been retrieved directly from the epididymis (PESA) or the testicles (TESE), from the urine, or by electro-ejaculation When there are high levels of antibodies in the semen When fertilisation has failed or has been low in previous IVF treatment Are there any risks with ICSI treatment? ICSI may use sperm that would not otherwise be able to fertilise an egg. This has raised concerns about the potential risks to children born as a result of ICSI. Several follow-up studies have now been published, but the first children conceived using ICSI is just reaching adulthood. Consequently, these follow-up studies involve relatively small numbers of children and do not include effects that may only be seen in older children or in the next generation. More studies are needed to confirm the longer term safety of this procedure. The use of ICSI has been potentially linked with certain genetic defects as explained below: 1) Possible inheritance of genetic and chromosomal abnormalities: a) Inheritance of cystic fibrosis gene mutations Some men who have no sperm in their semen are found to have congenital bilateral absence of the vas deferens (CBAVD). In this condition, the tubes that carry sperm from the testes to the penis are missing. Two thirds of men with CBAVD are also carriers of certain cystic fibrosis mutations. If you are a carrier of this condition it will not cause you any other health problems. About 1 in 25 of the wider population may also carry the mutation. This means that if your partner also happens to be a carrier of the mutation, there is a chance that a child born through treatment may have cystic fibrosis. For this reason we offer men with low sperm counts and their partners genetic counselling and testing before proceeding with ICSI. b) Sex chromosome defects and the inheritance of sub-fertility. Chromosomes are the structures in the cell that carry the genetic information. Humans have 46 chromosomes in each cell. Men have one X and one Y chromosome in each cell. Some genes on the Y chromosome are involved in the production of sperm. A small number of sub-fertile men have parts of the Y chromosome missing (deleted) and this may be responsible for their fertility problem. This means that using sperm with such deletions to create an embryo may result in the same type of fertility problem being passed from father to son. Some men with sub fertility have also been shown to have a higher chance of having an abnormal number of chromosomes, in particular the sex chromosomes (X and Y). It is estimated that up to 2.4% of the wider population have a chromosomal abnormality, but up to 3.3% of fathers of ICSI babies have abnormal Ref No 23 Page 20/28

21 chromosomes. Babies born from ICSI treatment may have a slightly increased risk of inheriting these abnormalities. Embryo Freezing and Storage What is embryo storage? It is important to select the best embryo(s) for your transfer, but if good quality embryos remain, these can be frozen for subsequent use. This may avoid the need for repeated drug stimulation, egg retrieval, sperm collection and fertilisation. The embryologist will only recommend that good quality embryos at the correct stage of development be frozen. This is to give you the best chance of success and most patients going through a treatment cycle will not have enough good quality embryos to freeze. In rare circumstances it may be suggested that you freeze all your embryos before transfer if you are at risk of OHSS or if other problems are identified during your treatment. Embryos are frozen at very low temperatures and stored in tanks of liquid nitrogen. The embryos are stored in sealed, double labelled straws in locked and alarmed storage containers. Not all embryos survive the freezing and thawing process. Very occasionally there may be no embryos that survive, although the chance of this happening is reduced by the embryologist only selecting good quality embryos to freeze. Should any remaining embryos not be required for further treatment, they can be donated for the treatment of others, to research or allowed to perish. You and your partner must both provide consent as to the use of these embryos. Your consents must agree before an embryo can be used or donated for treatment or research. How long can embryos be stored? When the updated Human Fertilisation and Embryology Act came in to effect on October 1 st 2009, the initial statutory storage was set at 10 years. In the majority of cases consent will be given for 10 years. After 10 years it may be possible to extend the storage period after discussing this with a doctor and completing a further consent form. It is therefore essential to keep in contact with us and answer the letter we send you annually, because if at the end of your initial 10 years storage we are unable to contact you, we cannot keep your embryos in storage. If you do not answer the initial letter, we will send a further letter by recorded delivery, confirm the address with your GP and try to contact you by phone. If you do not contact us, then by law we have to thaw and allow your embryos to perish on their expiry date. Please do update us if you move house or your circumstances change. In certain circumstances, where either partner is prematurely infertile, or likely to become prematurely infertile, it may be possible to consent to store for longer, up to 55 years. This allows people who have a medical condition (such as early menopause), or who have had treatment that has rendered them completely infertile (such as chemotherapy), to be able to extend their storage. This would need to be discussed with a doctor and a medical statement would be required every 10 years to keep the embryos in storage. If you have Ref No 23 Page 21/28