In Vitro Fertilisation (IVF) and Intracytoplasmic sperm injection (ICSI)

Egg collection

Approximately 35-38 hours after the time of your hCG injection the egg recovery will be performed. This is performed in the Procedure rooms with the help of an Ultrasound machine. It is very similar to vaginal scanning except that we take sterile precautions to protect you and the eggs.

Preparation

It is important to be as relaxed as possible for the egg recovery. Familiarity with your team will allow you to dispel some of the anxiety and fear. Your ovaries are considerably larger than their normal size which can lead to a dull ache and tenderness in the lower part of your abdomen before, during and after the egg collection. You will be advised to take an analgesic suppository on arrival and a further intravenous sedation and analgesia just before the procedure. We intend to relieve your discomfort as far as is possible. This is a short procedure and you should still be prepared for some discomfort as the needle enters the ovary. This procedure is outpatient based, you should be able to return home a few hours after the procedure.

It is necessary for your husband/partner/or a relative to drive you home and stay with you for the remaining part of the day. As you have received sedatives you should refrain from operating machinery, driving and should retire to bed after your return home.
 
We will tell you the number of eggs collected during and at the end of the egg collection. Very occasionally the eggs can be difficult to identify and we will need to have another look in the laboratory. So your final egg number may be slightly less

The Natural versus The IVF cycle

Naturally the ovary continuously recruits and develops the eggs. The egg develops over 60-90 days but only the last 14 days are in the menstrual cycle and when we can make changes. Normally the ovary recruits a group of eggs and the number allocated each month vary with the ovarian reserve of eggs and certain conditions such as polycystic ovaries. In older women or when ovaries have been affected by a past illness/treatment, the total number of eggs in the ovary goes down and hence the number it can allocate per month also reduces.

From the number allocated normally one follicle is visibly larger by the 4th-5th day of the menstrual cycle and has started to grow ahead of others. This dominant follicle prevents other follicles from growing that month. By giving you stimulating drugs however we can allow more than one egg to develop. Naturally the glands interact and prepare for ovulation as the hormone levels rise. Normally this would only happen when the single follicle reaches a mature stage. However when more than one follicle is growing, the hormone levels go up faster and to higher levels which can confuse the Interacting glands to send messages related to ovulation prematurely. This will affect the quality of egg development. Hence we give medication to inactivate these glands. Often this will start before the stimulating hormones as in the long protocol' but we can also use other hormones with similar effects but during the stimulation phase as in the 'short protocol'.

Fertilisation represents a complex series of changes and interaction between the sperm and the egg. Normally the egg matures within the growing 'follicle', which is a small fluid filled sac like structure with in the ovary. The follicle stimulating hormone (FSH) allows development and maturation of the follicle and its egg. The luteinising hormone (LH/hCG) allows the mature follicle to prepare the egg for fertilisation. In natural cycles, only one follicle and egg develops fully. By contrast in an IVF cycle, the ovary is stimulated with hormones to allow multiple eggs to develop simultaneously. At the appropriate time these eggs are removed after they have completed their maturation in the ovary. The egg is surrounded by a shell called the `zona pellucida' and a group of cells called the `cumulus oophorus'.

Naturally after the sperm are ejaculated in the vagina, they swim upwards, through the womb and into the fallopian tubes where they expect to meet the egg. On the other hand in an IVF cycle, the sperm meets the egg within the laboratory dish approximately 3 to 7 hours after the egg collection. The sperm then has to dissolve the cumulus cells to reach and fertilise the egg. Once the sperm reach the zona pellucida, it undergoes a series of changes before entering and fertilising the egg. Immediately after this the egg undergoes a complex reaction that will stop any more sperm from entering except when it is not of a good quality when this may happen. In couples with very low sperm counts or other defects of sperm function, a single sperm is injected into the egg to assist fertilisation. This procedure is called ICSI (Intracytoplasmic Sperm Injection). This is described in detail elsewhere in this booklet.

After fertilisation, the egg forms a single-cell embryo which will then undergo a series of divisions. On the second day the embryo would have reached the 2 to 4-cell stage. By day 3 the embryos have 5-8 cells within. This is when the embryos are usually transferred. After culture to day 3-5 and with continued development, the embryo will become a tight ball of cells, `the morula' by day 4 and a `blastocyst' by day 5 or 6. At this stage, the embryo is ready to implant. If further development continues within the body after implantation, the embryo will release the hCG that can be detected with a pregnancy test.

In nature only 1 in 4 embryos implant and carry on development to be recognised as a pregnancy. Nearly 40-50% embryos are genetically abnormal both in nature and also when formed in the laboratory. The risk of abnormal embryos increases progressively with the age of both the female and the male partner.

When more than one embryo is transferred, your chance of becoming pregnant is increased but your chance of multiple pregnancy is also higher. The law permits a transfer of a maximum of 3 embryos in women >40 years in age because the risk of multiple pregnancy is very low in this group. In suitable patients, prolonged culture to day 3 or day 5 improves the selection of embryos for transfer when a single embryo may achieve the same success rate as two but without a high risk of a twin or a triplet pregnancy.

Consents

You will be asked to sign appropriate consent forms after you have read the information booklets, attended the new patient seminar, your concerns and questions have been answered and you have discussed the medical and ethical issues.

Both partners are required to sign all of the consent forms before we can proceed with your treatment.

The consents cover the following subjects that are discussed in detail below:

  1. Right of Confidentiality
  2. Your wishes regarding:
  • freezing of eggs / sperm / embryos
  • research on eggs / sperm / embryos
  • long -term storage of eggs / sperm / embryos
  • posthumous use of eggs / sperm / embryos

Your consent advises us of your informed choice but does not commit you to undergo any form of treatment. You always have the right to change your mind until, but not after the event. It is therefore very important that all issues are thoroughly considered beforehand and that sudden and unexpected changes that you may regret later do not happen.

You have the following relevant issues to consider:

Confidentiality

All information regarding your treatment is strictly confidential and subject to both the HFEAct and the Data Protection Act. We may communicate with your general practitioner, referring consultant and other carers only with your written consent. However you should be aware that medical practitioners by virtue of their knowledge and experience may already know or understand the nature of treatment that might be undertaken in your specific circumstance.

Once we have disclosed the information to the unlicensed individuals it can no longer be controlled by the HFEAct but it will still be regulated by the Data Protection Act and General Law of Confidentiality. In general practice, information will be accessible to other GPs and staff working within the practice even if your consent specifically named only one of the several GPs in your practice. When changing GPs, your medical records will be transferred to your new GP practice without our involvement or written named consent from you.

From time to time your notes may be inspected for audit by HFEA members, Health Care Commission, Patient Safety Agency (PSA) and National Care Standards Commission.

You have a right to decline consent for communication but we need to consider your reasons for declining consent in our assessments.

We generally advise to keep your G.P. informed as they are your primary carers, will also be committed to confidentiality and can help you in an emergency but only if they are fully informed.

Sometimes patients request their GP to keep written information regarding assisted conception separate from the practice notes so that this information is not freely available to all the staff in their surgery. You may discuss this option when required with your GP.
 
Freezing of Eggs, Sperm and Embryos

Please note that you have to decide the fate of your spare gametes and /or embryos and that we act as per your written consents.

Regarding Surplus Sperm:
This issue becomes relevant where patients cannot give gametes when required e.g. in case of men requiring electro-ejaculation or surgical sperm retrieval. You may choose to freeze the spare sperm for your future use or discard them.

Embryo freezing: At the time of embryo transfer, we will discuss the fertilisation, growth rate and grade of embryos which is based on the embryo’s appearance. We will offer embryo freezing when deemed appropriate. Approximately 60% of embryos judged suitable for freezing survive and embryos with lower grades would have an even lower chance of survival. Before undertaking a frozen embryo transfer cycle, we try to ensure (as much as is possible) that upon thaw you would have at least some embryos suitable for transfer.

Embryo freezing can only be performed with your prior written consent. The legal storage limit for embryos is a maximum of 5 years from the date of freezing and this can be extended to 10 years if in the interim the female partner has reached the peri-menopausal years. 

The embryos are your property and responsibility. You also have to decide the fate of the embryos in the event of death or mental incapacitation. They deserve similar considerations as those for your unborn future child. Therefore we strongly advise you to always remain in touch with us, to advise us of your change in address, intentions and suggest that you consider replacement of your frozen embryos at the earliest possible opportunity.

Prolonged culture: With your written consent, embryos can be maintained in culture until they stop growing or develop into the blastocyst (usually on day 5 or 6 after egg collection). Embryos generally will stop growth within this stage. The day 3, 4 or 5 embryos generally have a higher developmental potential. We cannot keep embryos in culture for observation alone unless there is a clear instruction from you to preserve them when appropriate.

Embryo donation: You can consider donating your embryos to help another couple. This is very similar to egg and sperm donation, you would be required to have implication counselling and the necessary screening tests. We will advise you to consider this option for your frozen embryos after you have completed your family or decided to discontinue all future treatment for yourself.

Embryo research:  Please see the relevant section below for details.

Humanely discard the spare embryos: Only good quality embryos can be successfully frozen, donated to another couple or used for research. If you do not wish prolonged culture with a view to freezing then you must instruct us to humanely discard your spare embryos.

Please see IVF consent forms for further details. We emphasise that these choices are entirely personal.

Long term storage

Long tern storage is primarily for the storage of gametes and/or embryos prior to chemo or radiotherapy for cancer. We will be pleased to provide specific information on the length of storage permitted legally in your case. This can be quite a long storage period and up to your 55th birthday or for a total of 55 years. However this does not mean that the trust will be able to keep the sperm for this length of time. The duration of storage is agreed with yourself after discussion with your specialist, bearing in minds your reproductive intentions, how your fertility will be affected by chemo or radio therapy and your prognosis.

Posthumous use of gametes and embryos

Men can opt to permit their female partner to use their sperm or embryos created with them posthumously. There are ethical and legal concerns that you must consider very carefully before making a choice. We like you to have a discussion with the counsellor when considering implications of posthumous use of gametes to your future child.

Ethical issues: In your considerations the 'Rights and Welfare of your Future Child/Children' must be paramount. These considerations must also precede and exceed your own wishes. The law clearly states that the child has a 'right to have a father or a father figure for paternal nurturing'. It is our statutory obligation to ensure that this right is upheld. For instance, the law asks us to identify and counsel individuals who will have 'parental responsibility' and who will be 'responsible for the paternal nurturing of your child'.

Legal issues: The HFEAct provides that where a man's sperm or embryos created with his sperm  are used after his death, that he is not to be treated as the father of the child, except for the purpose of recording on the Register of Births as the Deceased father subject to the Human Fertilisation (Deceased Fathers) Act 2003 being fulfilled and for no other purpose. For instance, the child will have no entitlements to the man's estate and if desired separate provisions will have to be made by the individuals concerned. The posthumous use of gametes or embryos is only possible if the sperm / embryos have been stored in the man's lifetime and with his written consent. The unit has a statutory duty to consider the Welfare of Future Children born posthumously and to assess what arrangements have been put in place to meet the future child's needs when treatment is requested.

Embryo Research

This is a HFEA licensed and very carefully regulated activity. All centres have to obtain specific research licenses for the projects that they may conduct or be a participant. This section intends to make you broadly aware of the issues that surround egg / sperm / embryo research and does not in any way constitute a request from us for you to participate.

In suitable circumstances (usually when considering the future of the frozen tissues / eggs / sperm / embryos in our centre) you may be asked, among others, an option to consider donation to research. We will be pleased to provide the necessary detail regarding the ethically approved project if we can accept your donation. If there are no active research projects, we may be unable to accept the donation when the stored eggs/ sperm / embryos may have to be allowed to perish when the storage period expires. 

All research is experimental and gametes or embryos used or created during the project cannot be transferred for treatment and after completion of the research they must be allowed to perish.

You are not obliged to take any decision and your decision to participate or not in any research project will not affect your treatment. If you intend to withdraw for any reason during a research trial, you are free to do so at any time as long as the project has not already been conducted.

During research projects, cells of the embryo or the gametes may be fixed in what is called 'secondary research' that may have genetic applications.

For confidentiality, the gametes and embryos are anonymised. Currently all anonymisation is irreversible i.e. no specific feedback regarding your eggs / sperm / embryos is possible.

You will be offered implication counselling if, in a genetic research proposal, the anonymisation was reversible. In this case you may be able to get feedback after the research in case we have findings that may be relevant to you.

If the unit took part in Stem Cell research, you will receive more specific information about that project. In that case you will need to be aware that any stem cell lines created may continue indefinitely and that these lines may be later used in other relevant research projects.

A Typical IVF or ICSI Cycle

This section has been written in the expected order of various steps in treatment. You may find helpful to refer to this section  regularly during treatment.

a. First clinic appointment where diagnosis is known. A full discussion of the relevant aspects of your treatment takes place in the clinic. We aim to minimise your visits and do not repeat investigations unless deemed essential for the conduct of your treatment.

b. Screening tests. These tests are arranged as explained above at your first appointment in the clinic.
 
c. New Patient's Seminar. We very strongly recommend that you attend this open seminar by the team. Dates are available on request from the unit.

d. Follow up clinic visit. You will attend the clinic for discussion of screening tests and you have this opportunity to clarify any outstanding issues that have arisen in your mind with respect to your treatment. At this visit, you will receive a prescription and also be advised to see the nurse co-ordinator on your way out so that the NHS funded patients can be given a start date for your treatment within the government target of 18 weeks. The NHS self funded patients will be added to the waiting list and the nurse co-ordinator will provide an estimate of the month in which you may receive treatment.

e. Appointment with the Finance officer. The Unit's finance officer will provide the invoice for the NHS fee paying patients, receipt payment and book a nurse consultation appointment in the weeks prior to your treatment start date.

f. Consultation with the Nurse Specialist. Both Partners must attend this appointment (see details) because you both will be required to sign consents, receive instruction for self administration of injections and a cycle plan.

g. Suppression of your natural hormones. When the 'long protocol' is used, your naturally produced hormones are suppressed from the 1st or the 21st day of the menstrual cycle using a nasal spray, a daily injection or a single depot preparation. This is maintained until you are ready to receive hCG and can in total last for approximately 5 to 7 weeks.  When the 'short protocol' is used, we prescribe a second injection in parallel with the stimulation drugs from an appropriate stage. A baseline scan is performed, usually prior to starting this phase, unless you have had another recent scan within the preceding 3 months.

h. Ovarian Stimulation. Hormones are administered in this period to help your ovaries produce multiple eggs. This treatment can lasts for approximately 9-14 days. In women receiving the 'long protocol' a pre-stimulation / down regulation scan will be performed before to confirm that natural hormones have been suppressed. You will receive further scans to monitor growth of the follicles.

i. HCG injection. This injection prepares the eggs for ovulation and is given late in the night (usually between 10 p.m. and 2.00 a.m.).

j. Egg Collection. The eggs are collected approximately 35 to 38 hours after the hCG injection.

k. Insemination or ICSI. Male partner gives a sperm sample for preparation and insemination of the eggs by the direct method or by the ICSI procedure.

l. Checking Fertilisation. You will receive a telephone call with necessary information on the day after egg collection.

m. Embryo Transfer and Hormonal Support.  The embryos are replaced in the womb and you will receive further medication afterwards to provide hormonal support in this phase of the cycle.

n. Luteal phase monitoring. This is provided to all those women who we feel could be at risk of developing ovarian hyperstimulation syndrome.

o. Pregnancy test. You are given a date for the pregnancy test at the time of embryo transfer.

p. Pregnancy scan or Follow-up consultation. This is arranged after the pregnancy test and the outcome of treatment is known.

Treatment Protocols

As explained in the section above, we need to stimulate the ovary with hormones so that all eggs available for development in that cycle do not see ovulatory changes prematurely. This interacting gland is called 'the pituitary'  and is located behind the eyes in front of the brain. We have several commonly used protocols.

Long protocol

In this protocol we inactivate the pituitary before we start stimulating the ovary. This period of inactivation is termed as 'downregulation' or 'suppression'. We can use a number of ways to achieve this effect. As it takes longer to complete this cycle (5-7 weeks) it is called the 'Long Protocol'. This protocol is more suited to women with satisfactory ovarian reserve. It is also popular as it allows us to start stimulation on any day of the week that suits you and the unit. Please see below the relevant detail.

Short protocol

Using this protocol we try to achieve the inactivation of the pituitary gland by using a different preparation. This medication is given as a single daily injection whilst the follicles are developing starting before the hormone levels have reached a critical stage. This effect can be assessed indirectly by measuring the size of the follicles and generally happens on day 6 of stimulation. Thus you may require an additional early scan to decide when to start this medication. As periods can arrive at any time of the week, we sometimes use the oral contraceptive pill for a few days so that we can still start stimulation on right day for you and the unit.  This protocol can be used for all women, with good and also the reduced ovarian reserve. Using this protocol the cycle is shorter (4 weeks) and the treatment outcome is known early, hence the name 'short protocol'.

Flare protocol

Unlike the long protocol, ovarian suppression is not performed in advance. Both hormones for suppression of the pituitary and for stimulation of the ovary are started together on the first day of the menstrual cycle. This allows us to use the initial stimulation that occurs with these hormones to recruit more follicles. This protocol is reserved for women with much reduced ovarian reserve.

Downregulation or the Suppression phase

As explained above, during your IVF cycle the response from other glands (the pituitary) may interfere and affect the maturation of eggs. As this can lead to a lessening of your success rate, when using the Long Protocol we choose to inactivate this gland before stimulating your ovaries.

Baseline scan

A vaginal scan is performed before starting any medication unless the scan performed as part of Pre-assessments was done within the last 3 months. This is to ensure that there are no new developments that we should be aware of before starting the drugs.

Pre-stimulation or Down regulation scan

The scan is repeated at the appropriate time after starting the suppression phase. This should show inactive ovaries and a thin lining of the womb. The usual time taken for this phase is 10 days to 2 weeks.

Drugs used

A number of methods can be employed for the same ultimate effect. These, in our programme include the following:

  1. Nafarelin Nasal Spray: This is taken as one sniff in one nostril three times per 24 hours at 8 hourly intervals for first 2 weeks and then twice daily thereafter until the day of HCG. This medication is not suitable for those suffering from hay fever, chronic nasal discharge or who may not remember to use the spray regularly.

  2. The Buserelin Injection: This injection is taken once a day sub-cutaneously with a very fine needle-injection just under the skin. It is given daily at approximately the same time but an absolute and accurate precision is not essential (give or take 30 minutes).

  3. Prostap Depot Injection: This is a once only injection and works for 4-5 weeks in total. This is very convenient for many patients except those with reduced ovarian reserve. If the suppression phase is prolonged because of the agonistic/stimulatory response from the ovary, a 'top-up' with Buserelin/Nafarelin in the later stages of the cycle may be needed.

Side effects

  1. Hot flushes, night sweats, headaches, vaginal bleeding, temperamental behaviour. These are due to a fall in your oestrogen level, usually last for a short time and will disappear once we start stimulating your ovaries.

  2. Agonistic/ stimulatory response: In the initial stages all of the 3 preparations above can stimulate the ovary. This means that a follicle or cyst develops that has to resolve before we can proceed with treatment. It can naturally take up extra 2-3 weeks. If the cyst is aspirated the resolution may be slightly earlier and this requires an extra scan to see it disappear and for the endometrium to become thin. If you are prone to develop agonistic response seen in the form of cysts after starting this medication, we can use the oral contraceptive pill for a few days before starting the downregulation and this usually avoids such problems recurring.

Time to start

This treatment can be started on the first or the second day of your cycle especially when your cycle length is variable. It can also be started on the 21st day of the preceding cycle if your cycle is very regular.

Choices

We can prescribe any one of the above preparations and methods dependent on your preference and knowledge of past response. They are equally effective and are self administered. There is a relatively small difference in their costs with Buserelin being the cheapest.

Important notice:

The Nafarelin nasal spray and/or the Buserelin treatment is continued in the stimulation phase. We will specifically advise in writing when to discontinue which is the day you are advised to take hCG. Those with Prostap normally do not have to take additional medication during the stimulation phase.
the instructions.

Stimulation phase in an IVF/ICSI cycle

There are large variations between patients in the number of eggs recruited and developed in response to the same dose of the stimulating hormones (see below). This response is mainly dependent on the female partner's age, the cause of her sub-fertility, her body weight and past treatments or ovarian surgery. There are other genetic determinants also. Having preformed the pre-treatment assessments, we judge the starting dose bearing in mind your clinical circumstances. When uncertain we may perform additional early scans to use the option of 'stepping-up' or 'stepping down' during the stimulation phase for a better response.

What does it involve?

The hormones (Puregon/ Gonal-F/ Menopur) will be started when your ovaries have been adequately suppressed as judged by your pre-stimulation or the downregulation scan (see previous section).

My choices?

The difference in drugs is mainly in the way they are prepared, their purity, in the way they are administered and their costs. They are equal in terms of their success rate. We often choose them in combination or separately to suit.

How to inject?

Gonal-F, Puregon and Menopur are usually given by a subcutaneous injection (very fine needle-injection in the fat layer under the skin). 

How are they prepared?

Gonal-F and Puregon are synthetic compounds, very pure and with an identical structure to PURE FSH only. Menopur is extracted and purified from menopausal women's urine and is therefore a combination of naturally produced hormones. This can contain protein impurities at a very low level which can rarely give a skin reaction. There are no other reported complications.

Side effects

As stated above, to date the only additional side effect with urinary preparations has been that of an occasional rash on the injection site and rarely a more generalised allergy has been reported. Other risks with protein impurities are purely theoretical and there have been no cases reported to cause concern.

Undesirable effects

This can happen with any of the preparations available. Sometimes the ovaries will recruit a large number of eggs especially in young women and those with Polycystic ovaries. This can put you at risk of developing an illness called The Ovarian Hyper-stimulation Syndrome. (see ‘Risks’ section for further details). We use 'step-up and/or  step-down' method to adjust and protect you from this risk during the stimulation phase.

How effective are they?

We have used the Pure and Urinary preparations quite extensively and are happy with them all.

Who should give the injections?

The injections can be administered yourself or by your partner. We strongly advise you to consider learning self-administration. Independencewill save you time, effort and stress of professionals not being available when needed. However, if you are extremely anxious then you may seek the help of your doctor's nurse.

When to take the injections?

The injection is taken once a day at approximately the same time but an absolute and accurate precision is not essential. We will be able to estimate the day of your egg collection once the growth rate of follicles is established. It will also help in deciding the time of abstinence in preparation for the semen sample to be given on the day of egg collection.

The hCG (Pregnyl) Injection

When your follicles have reached an appropriate size, as assessed by scan, you are ready to be prepared for the egg collection. The hCG injection is essential to bring the eggs to the correct stage of maturation for this stage.

This injection is usually given late in the night normally between 10.00 p.m. and 2.30 a.m. It is specifically timed to be between 35-37 hours before the time of your egg collection.

Important notice: We will give you precise instructions as regards the time and day this injection has to be administered. It is essential that the hCG injection is given as close to the prescribed time as is possible. Please read the instructions before you leave the unit so that you can ask a member of The Centre if you do not understand any of the instructions.

Your Day Off

The day after the hCG injection, you may feel some heaviness or discomfort in the lower part of your abdomen. On this day, do not forget to take your bedtime Lorazepam tablet - this is given to reduce understandable anxiety and so that you can have a good night sleep before you arrive for your egg collection. Please remember that you are advised to refrain from driving or operating any machinery after you have taken the tranquilisers and not doing so could be hazardous for you and others. Please also remember to read the instruction sheet carefully.

Egg collection

Approximately 35-38 hours after the time of your hCG injection the egg recovery will be performed. This is performed in the Procedure rooms with the help of an Ultrasound machine. It is very similar to vaginal scanning except that we take sterile precautions to protect you and the eggs.

Preparation

It is important to be as relaxed as possible for the egg recovery. Familiarity with your team will allow you to dispel some of the anxiety and fear. Your ovaries are considerably larger than their normal size which can lead to a dull ache and tenderness in the lower part of your abdomen before, during and after the egg collection. You will be advised to take an analgesic suppository on arrival and a further intravenous sedation and analgesia just before the procedure. We intend to relieve your discomfort as far as is possible. This is a short procedure and you should still be prepared for some discomfort as the needle enters the ovary. This procedure is outpatient based, you should be able to return home a few hours after the procedure.

It is necessary for your husband/partner/or a relative to drive you home and stay with you for the remaining part of the day. As you have received sedatives you should refrain from operating machinery, driving and should retire to bed after your return home.
 
We will tell you the number of eggs collected during and at the end of the egg collection. Very occasionally the eggs can be difficult to identify and we will need to have another look in the laboratory. So your final egg number may be slightly less

Giving a Sperm sample

Time

Although the time that the sperm sample is produced is not critical, we would ask that the male partner attends at the specified time in order to avoid an undue delay in treatment. 

Abstinence period

We ask that all men abstain for at least 3 days prior to giving the sample. In men with normal sperm counts this 3 day period is adequate and longer abstinence is neither necessary nor appropriate. However in men with extremely low count (e.g. <1 million per ml) the abstinence period can be longer to ensure that sperm are found on the day of egg collection.

What happens?

Shortly after the sample is given, the sperm are washed and prepared. The live and progressively motile sperm are selected to inseminate the eggs 40-42 hours after your hCG injection i.e. 3-7 hours after the egg collection. Overall 50-70% of the eggs will fertilise but this number is variable in different patients and varies with age (both male and female) and / or the cause of your sub-fertility.

Freeze for Back up

We know that providing sperm sample on demand in an unfamiliar and hospital environment, on a day of the stress of egg collection in your spouse etc can lead to anxiety and difficulties with ejaculation. We ask that you assess this risk carefully for your self and request sperm freezing for a backup if you perceive that you will have a risk. In such scenarios we do have the alternative of providing Viagra like medication for those suitable (it does have risks) or performing an emergency per-cutaneous sperm aspiration from the epididymis under local analgesia. Need less to say that both of these can be very traumatic for you both and there may also be costs incurred. If we are unable to find sperm the treatment may have to be completed at that point and neither freezing of mature eggs nor their survival can be guaranteed. It is therefore better to take precautions than to try and find alternatives in an emergency. *Please do not be embarrassed in discussing this matter with us*.

Fertilisation of the eggs (Insemination or ICSI)

If the sperm count is normal and the sperm preparation is satisfactory we will conclude that the risk of failure of fertilisation is very low (not completely eliminated still) and we will inseminate the eggs with a preparation of the sperm approximately 4 to 5 hours after egg recovery.

If the sperm count or motility is known to be low, there is a substantial increase in the risk of failure of fertilisation. We would have assessed this risk for you as part of our mandatory pre-assessments. In this situation, we would have also advised you of the need of ICSI at your follow-up appointment.

Sometimes the sample given on the day of egg collection is not satisfactory unlike the pre-assessment. In those circumstances we may feel that the risk of sperm not fertilising the eggs is increased. We would discuss this risk with yourself and with your agreement we will proceed with ICSI. Therefore all couples are advised to read through the section of 'risks of ICSI’ very carefully. This is still considered to be an experimental procedure. We therefore ask you to consider this possibility in advance and also consent (if you agree) for this to happen at the time of your nurse consultation. 

Insemination

This simply involves making a preparation of the sperm and transferring a measured number of sperm that are suspended in an appropriate fluid at the correct temperature and ph into the vicinity of the egg. The sperm will then find and fertilise the egg naturally.

Intra-cytoplasmic Sperm Injection

This technique involves injection of one sperm inside the egg under microscopic vision. The egg is very small, smaller than a pin prick and the sperm is smaller still. the procedure is done under 300 times magnification where a sperm is lifted out individually using a micropipette or needle and this then is directed to the shell of the egg penetrating it and the membrane of the egg, the whole sperm left inside the egg. The sperm and the egg have to undergo necessary changes after this for fertilisation to take place.

Checking Fertilisation

This assessment is performed approximately 18-20 hours after insemination or ICSI procedure.

Please ensure that we have your day time contact number. Our embryology team will be pleased to ring you to give you the result of this assessment. If fertilisation has occurred we will also give you a provisional appointment for embryo transfer which could be the following day (day 2 after egg collection), the day after next (day 3) or even on day 5.

Prolonged culture of embryos

Purpose

Prolonged culture of embryos provides us with more time to observe the developmental potential of the embryos and select those suitable for transfer better. It does not make the embryos more or less capable. It also does not help in removing all abnormal embryos from those that are available and your risks will remain as they would be appropriate for male and female partner's age and clinical circumstances. We would have discussed risks in specific circumstances beforehand but you can ask further if you wish when you attend the follow-up appointment before you start your cycle.

Why choose prolonged culture?

This is a clinical decision. We choose to culture the embryos until such time we feel appropriate to select the best for transfer. Hence this is an option for only those couples where a number of equally good embryos are available. Pregnancy rate is higher when appropriately growing day 3 embryos or day 5 blastocysts are transferred than with day 2 embryos or day 6 blastocysts.

When there a lot of embryos with an equivalent appearance and growth, we may put them into prolonged culture in order to differentiate and select those with a better continued growth. It also gives us time to observe when you are at risk of ovarian hyperstimulation so that we can avoid doing a transfer for those who develop problems early but at the same time do not deprive those who remain well from a fresh transfer which has a higher success rate. The developmental potential of fresh embryos tends to be higher than those that are frozen and thawed.

The spare embryos can also be maintained in culture until they are deemed suitable for freezing, stop growing or develop into the blastocysts when they can be frozen also if deemed suitable.

The risk of keeping embryos in culture is that you will find useful information about the embryo's development before your pregnancy test. None may progress sufficiently and despite having a number of embryos, none may be frozen because of suboptimal growth.

Embryo transfer

As explained above, the fertilised eggs are called `embryos'. These are examined the day following fertilisation and then daily to monitor cell division and growth to determine the day of embryo transfer. If the embryos have not grown after fertilisation, an embryo transfer is not performed.

Risk of a multiple pregnancy

This is a very important clinical matter for both us and you. We know that transfer of multiple embryos increases the likelihood of at least one continuing growth and implanting. However your risk of a multiple pregnancy is also increased with the transfer of multiple embryos. Your chance of conceiving a multiple pregnancy depends most of all upon your own age, cause of sub-fertility and also the programmes overall success rate. Occasionally embryos split to form two identical babies. This risk is also increased with IVF and ICSI.

In the past even though approximately 85-90% of our cycles receive 2 embryos only, 25-30% of all our births were still twins. The risk is greatest in women under 35 years of age and in those who respond well. Legally we are permitted to transfer up to 3 embryos in women above the age of 40 years because of a very much lower multiple pregnancy rate using their own eggs (<1%).

The complications of multiple pregnancies include miscarriage, prematurity, fetal growth retardation, increased risk of pregnancy complications in the mother and the need for delivery by caesarean section. Additional complications of identical twinning include polyhydramnios and twin to twin transfusion syndrome. These complications have high risks for premature delivery. Extremely premature birth has the risk of death in infancy or survival with long-term mental and physical handicap in the children.

Our mission 'One at a time'

Our intention is to give the best chance of a pregnancy but without a high risk of a multiple pregnancy. Whilst trying to come to a decision we balance the probability of a pregnancy against the risks of a multiple pregnancy. We therefore analyse our data extensively and we know of a number of features that will help us identify those couples who are specifically at high risk of a multiple pregnancy. The same couples also have a good chance of getting pregnant even with a single transferred embryo provided we select well. We therefore choose methods of prolonged culture and optimal day of embryo transfer so that we do not compromise your success rate but at the same time we give you a low risk of a multiple pregnancy.

Our embryology team will keep you informed of the embryo's progress and choose the best day for your transfer as per our centre's 'strategy to minimise multiple pregnancies. All couples will have a further discussion on the day of the embryo transfer.

Fetal reduction

The term `fetal reduction' is used for an ultrasound directed procedure that selectively terminates one fetus while permitting the other to continue growth and development as normal. Sometimes this procedure is employed to reduce the number of fetuses that have implanted after infertility treatment e.g. for reducing a triplet pregnancy to twins. Some pregnancies with a triplet implantation will spontaneously reduce to twins or singleton. Details regarding this `natural' risk of 'spontaneous reduction' are available in our annual report and we can discuss this with you. If you have an ongoing triplet pregnancy of non -identical foetuses, then fetal reduction may be considered in line with the requirements of the Abortion Act. Equally you may consider this option if you conceive a set if identical twins with a non-identical triplet at the same time after the transfer of 2 embryos. Further discussion with your obstetrician will be necessary at that time.

This procedure is performed by passing a fine needle into the pregnancy sac and injecting potassium chloride into the fetal heart. The procedure carries a 4-5% risk of miscarriage. The world's combined data suggests that the duration of pregnancy is unlikely to be altered greatly by embryo reduction. Please ask for more up to date information or clarification regarding our own programme

Technique of embryo transfer

Usually at least 80-90% of those eggs that have shown normal fertilisation will grow in culture to day 2. However some of these will slow down or discontinue growth completely between day 3 and day 5. We check the embryos every morning before we call you for an embryo transfer. If there is no growth after fertilisation, we regret that we will need to cancel the transfer and arrange a follow-up. In others, we will discuss the number, growth rate and appearance of the embryos and what we have selected for your transfer when you arrive.

Preparation for embryo transfer

The procedure of embryo transfer itself is quite simple and normally pain free. The embryos are very sensitive to light, temperature and pH changes. Ideally therefore for the embryo survival and growth the transfer procedure should be quick, simple and atraumatic.

We take the following preparation for this to happen.

You are advised to have a full bladder before the transfer because in most circumstances doing so straightens the uterine shape and makes the transfer procedure straightforward.

The outer sheath of the embryo transfer catheter is inserted first to ensure easy insertion of the catheter whilst keeping  the embryos in the correct environment until you are absolutely ready to receive them.

The selected embryos are put into a fine catheter and transferred gently into the uterus in a very small volume of fluid.

Occasionally and especially when the bladder is not full, an instrument to hold and straighten the neck of the womb may become necessary. This can give you temporary discomfort.

The embryos are not visible to the naked eye at this stage but can be seen with the microscope or on the television screen attached via a camera to the microscope. The embryo transfer procedure literally takes under a minute and you do not require pain relief. After the embryo transfer, we will check that the embryos have left the catheter and reached the uterus. Very occasionally, the embryos will not have left the catheter and the transfer procedure has to be repeated. You may rest for a few minutes afterwards before returning home.

After the embryo transfer

You are advised to continue with your daily routine as normal and there is no need to take special rest. However, we would advise you to refrain from strenuous physical exercise, taking of any form of drugs or medicines without checking with us first and avoid contact with contagious illnesses including `flu like illnesses' as much as possible.

You may experience discomfort in the lower part of your abdomen because of enlargement of your ovaries after the egg collection. These once again enlarge to provide hormonal support for the implanting embryos. There are sac-like structures in the ovary called 'corpora lutea' and may be mistakenly called `cysts'. These have an important role and are essential for a pregnancy to take place. This enlargement of the ovary and discomfort after the egg collection is normal and expected. You may take some paracetamol tablets or suppositories safely if needed.

In this cycle your symptoms of premenstrual syndrome are likely to be exaggerated because of high hormone levels. If unluckily you fail to conceive then the pattern of menstruation may also be different.

If you have any worries you can get in touch with us at any time of the day during the week on our direct telephone line and at other times via the hospital switchboard as instructed in the front of this booklet. We would very much advise you to contact us during the working week as far as is possible so that you receive timely advice. We do not mind if you ring us for what you may consider a trivial matter.

*Please note that this is a much specialised form of treatment. Although your G.P. would gladly attempt to help you, he/she will not be fully aware of the details of your treatment or the necessary action. Hence it is in your interest to contact us first and before the problem is too advanced.*

Hormonal Support after the ET

On the day of embryo transfer, you will be given a letter which will explain further essential hormonal support in the second half of your cycle. Firstly this helps your uterus prepare for the embryos better.  Secondly we know that without any support, some women will bleed too early after an embryo transfer and before the embryo implantation has declared itself in the form of hormonal signals. Hence medication is given after the egg collection or embryo transfer to ensure that premature bleeding does not occur and that you have the best chance of maintaining an embryo implantation.

 This support can be given in several ways and clinicians as well as patients can have their preferences:

Progesterone pessaries (Uterogestan or Cyclogest)

These are given in the dose of 200 mgms, 6 hrly or four times every 24 hours. They can also be used rectally as a suppository.

Advantages

Apart from the inconvenience of frequent vaginal and rectal administration, it is painless and easy to administer.

Disadvantages

  1. The medication can flow out of the vagina or the rectum and hence not have the full benefit.

  2. The absorption of the hormone from the vaginal skin into your body can also vary between patients.

  3. Some patients may thus experience premature bleeding despite this support.

  4. Occasionally women can develop an allergic reaction to progesterone in the form of urticaria or skin rashes and sometimes the allergy can be severe.

  5. When you become pregnant, we continue this support in early pregnancy until placenta is well established in the uterus (normally at 9-10 weeks gestation).

Progesterone Injections (Gestone): This is a daily intramuscular injection of progesterone.

Advantages

  1. For some once daily administration is an advantage.

  2. It also ensures that premature bleeding does not occur. In fact most women would not have had bleeding until we do the pregnancy test 14-16 days after the embryo transfer.

  3. There is published scientific evidence for higher success rates with this form of support.

  4. We have an unpublished observation that it provides some protection against the risk of OHSS. This has not been scientifically tested and hence we are conducting a prospective trial.

Disadvantages

  1. This is a painful injection and causes local discomfort. We advise you to rotate sites of injection in order to ensure that no one site becomes excessively inflamed.

  2. Occasionally women can develop an allergic reaction to progesterone in the form of urticaria or skin rashes and sometimes the allergy can be severe.

  3. When you become pregnant, we continue this support in early pregnancy until placenta is well established in the uterus (normally at 9-10 weeks gestation).

Human Chorionic Gonadotrophin

This is a very potent hormone injection. One Injection is given on the day of embryo transfer and another is given three days later.

Advantages

  1. It ensures that premature bleeding does not occur and there is no need for continued support in early pregnancy.

  2. There are only two injections and no other medication is needed during the 2nd half neither of the cycle nor in early pregnancy.

  3. There are no incidences of allergies.

Disadvantages

  1. When given to all patients, this has been associated with an increased risk of ovarian hyperstimulation OHSS). NICE recommends that it should not be used.

Scientific evidence for its sparing and selective use with safety has not been published. We will be conducting a randomised controlled trial for this. In the interim, it is used very sparingly and only when there is minimal or no risk of OHSS.   

The Pregnancy Test

When to come?

You are asked to come to TLCRM, 14 to 16 days after the embryo transfer for a pregnancy test, irrespective of whether you have menstruated or not. This involves you bringing an early morning urine sample. If this test is positive then we will ask you to return to us 2 or 3 weeks later for an ultrasound scan.

We obviously hope that every patient will become pregnant but in reality 55-70% patients depending on your age group do not conceive. You will understandably feel a sense of grief in the event of failure. Please do not hesitate to ask for help in the form of counselling support with our psychologists. We will also arrange a review consultation after the completion of each treatment cycle. At this time we will have an opportunity to discuss those factors that may have become apparent during your treatment and consequently may require modification in further attempts.

Risks

There are no treatments that are completely free of risk. In an IVF cycle there are the following risks:

Ovarian hyperstimulation syndrome

If your ovaries have shown an excessive response then you are at risk of Ovarian Hyperstimulation Syndrome. Everybody receiving drugs for ovarian stimulation in order to produce multiple eggs is at risk. However the risk is not the same in everybody and we have developed clinical tools with which we assess your individual risk. This can vary between mild, moderate, severe and very severe. Young and overweight women with polycystic ovaries are especially 'at risk'.

General advice

You are advised to drink normally and check that you are regularly passing normal amounts of urine. Although mild symptoms are common, severe ovarian hyperstimulation is rare and occurs in only 1-2 % cases. If in doubt, please do not hesitate to contact the IVF team or the on call doctor (as per the instructions in the front) at any time. The switchboard at St James's University hospital will be able to put you in touch with the on call gynaecological registrar at all times.

Management of this risk

We will assess your risk before deciding to give HCG, when we do an egg collection and afterwards until we do an embryo transfer. All women in categories a, b and c below receive monitoring within the unit for early detection of changes and as per our written protocols and those with symptoms will be treated as appropriate. This may include hospitalisation, administration of intravenous fluids and other treatment such as drainage of fluid from body cavities.

  1. When in the category of very severe risk, we would not give HCG, advice abandoning the cycle and starting again with a modified regimen.

  2. When the risk is severe, we may try to curtail the cycle prematurely with medication, will not do an embryo transfer and will freeze all developing embryos.

  3. When the risk is moderately severe we may adopt an expectant individualised approach where we observe your progress carefully whilst we maintain at least some embryos in culture to day 5. If by then you develop signs or symptoms we may freeze all developing embryos still and take other precautions. If you remain well we may perform an elective single embryo transfer.

  4. When in this category, you do not require monitoring or specific treatment but we advise you to contact the unit as and when you have problems and as per the contact address and details on the front of this booklet.

Recognised complications

Fortunately with appropriate risk assessment, prophylactic monitoring, early detection and timely intervention most women will have no problems. Your co-operation is therefore essential in ensuring your safety. It is a self limiting disorder and there are no problems after the cycle is complete. In women who become pregnant the risk period extends into the first trimester of pregnancy & complications up to 12 weeks of gestation have been noted.
 
Complications occur either as a result of thrombosis in large veins because of thickening of the blood and its sluggish flow or because of collection of fluid in body cavities such as the abdomen or the chest.  Strokes, ascitis, pleural effusions, pericardial effusion, cardiac tamponade and deaths have been reported in the literature. The risk of death is less than 0.01%.

Miscarriage

The risk of miscarriage after a positive pregnancy test alone is approximately 10-20%. This is no different to that after a normal conception. Once the pregnancy sac has been seen and the fetal heart action identified then the risk of miscarriage is substantially less. The risk of a congenital or genetic abnormality in babies born after IVF has not been higher than that in spontaneously conceived pregnancies. Your personal risk is more likely to relate to your age, your family history and whether or not you have a multiple pregnancy. Please see the section on multiple pregnancies for further detail.

Risk of an ectopic pregnancy

The embryos are not ready to implant at the time of their replacement. At that time they are in a very small volume of fluid which we expect to spread like a thin film on the surface of the lining of your womb. The embryo may sit in a fold of the lining of the uterus until it reaches the stage of implantation. The risk of embryo floating away in the direction of the fallopian tube exists in all patients. In normal circumstances we expect that the fine hair in the tube that beat in the direction of the womb will prevent such a migration. However in some cases this may not happen and the embryo enters the tube. Unable to return to implant in the uterus and especially in women with damaged tubes, it may attach itself to the tube and thus a tubal pregnancy occurs. If left undiagnosed, the tube may rupture and internal bleeding may take place. We endeavour to make an early diagnosis by performing an ultrasound scan at 7 weeks of pregnancy (3 weeks after your pregnancy test).

Notes

 

  1. It is therefore important to attend for the pregnancy test even if you have bled and for the scan after a positive test. If a pregnancy sac is not seen on scan, a blood test is taken to measure the pregnancy hormone (hCG) level in your blood. You may be asked to attend for more tests after a few days interval. If this level is rising or static then we may perform a laparoscopy.

  2. If you are unlucky and have a tubal pregnancy then you will require the removal of the tube. We may also counsel you regarding the future of your remaining tube in case it is already known to be irreparably damaged or is found to be such at surgery. We advise you to consider removal of both tubes in those circumstances in order to avoid a recurrence of this complication in future. This is an important decision as it is sterilising and no steps are taken with out your written consent and complete agreement.

  3. For the operation you will be admitted to St James's to prevent an untoward occurrence whilst travelling. The risk of an ectopic pregnancy is approximately 3-4%.

  4. Occasionally you can have a combined intrauterine and an ectopic pregnancy (heterotopic pregnancy). These are more difficult to diagnose. If present, then often but not always, the tubal pregnancy can be removed with out harming the uterine pregnancy.

  5. We perform a risk assessment for this complication too in our pre-assessments. If you are already known to have damaged tubes you may choose to have removal of the tubes (salpingectomy operation) performed before the treatment cycle in order to minimise the risk of this complication. This is a sterilising procedure and future pregnancies will only be possible after IVF. Therefore you have to be completely at terms with your infertility if you undertake this procedure. It is performed in most cases laparoscopically (key hole method) and you do not need prolonged recovery or delay to treatment afterwards.


Risks of the Egg Collection Procedure

At the time of an egg collection a needle is carefully passed through the wall of your vagina into the ovary under ultrasound vision. The risks include those of an infection, bleeding and damage to an internal organ requiring surgery and repair.

Infection

  1. The needle can transfer germs from your vagina into the pelvis and lead to an infection. The risk of this is greater:

    • if you have chronically infected tubes, an active vaginal or pelvic infection, your tubes are swollen or distended with fluid that may still contain bacteria.

    • if you have endometriosis and especially if you have Endometriomas that have to be entered during the egg collection.

    • If you have extensive adhesions incorporating the bowel the risk of bowel injury is increased also.

  2. We advise that both partners undergo screening for genito-urinary infections before they undergo a treatment cycle at least once but it could be prudent that you have screening done before each cycle. It can easily be done via your GP and requires the nurse to take a swab and check your early morning urine samples for NAAT analysis for chlamydia in particular.

  3. We provide vaginal Clindamycin cream during the treatment cycle for you to use from the day of HCG administration (2 nights before egg collection) and maintain this at least until we do your embryo transfer.

  4. We also take further precaution of thoroughly cleaning your vagina before an egg collection and use fluids that contain strong antibiotics. Further we may give additional antibiotics by mouth in special at risk circumstances.

  5. You are advised to let us know if you are suffering from vaginal infections or an offensive discharge.

Bleeding or internal injury

Potentially the needle can also enter a blood vessel leading to internal bleeding or perforate a loop of the small or the large bowel leading to internal infection, need for major surgery and further treatment as appropriate. The risk of this complication is quite remote and less than 0.001%.

Risk of equipment failure

The trust maintains service contracts for all equipment that is regularly serviced. There are also many standard operating procedures in the laboratory that help us have an early warning for problems. Despite all our efforts and very uncommonly equipment failure may sometimes lead to loss of eggs or embryos. This is a 'Category A' incident that will be immediately notified to HFEA, the trust and you. There would usually be a thorough investigation and steps taken to prevent a recurrence of similar problems. The HFEA also operates an Alert system which we use to learn from incidents elsewhere.

Risk of a multiple pregnancy

Most assisted conception procedures carry with them the risk of a multiple pregnancy. Please read the section on the number of embryos to be transferred and multiple pregnancies where this risk has been discussed in greater detail.

Other risks

  1. Although some have raised alarm over the risk of ovarian cancer with the use of hormones, these preparations have been used in treatment since early 1960's without any notified cases that can be directly liked to the use of these hormones. The available evidence suggests that there is no increase in your risk over and above that exists naturally. Infertility per se, delay in first pregnancy, and failure to breast feed, family history, obesity and smoking are known risk factors for the cancer of the ovary and the breast.

  2. There have been no cases of complications with protein impurities in the urinary preparations. Theoretically some have worried that external proteins when injected could transfer viruses or prions that could lead to an illness like CJD at a later date.

This section is there for your information and to reassure you that as far as we know none of the publicised risks have been scientifically confirmed.