In Vitro Fertilisation (IVF)

“I always tell patients not to have an IVF treatment cycle when work is busy, when you are about to move house, have major building work done, or when your mother in law has planned an extended visit! The rule of thumb is to try and clear a bit of space in your diary. The whole experience is stressful enough without other things going on!”

It is beneficial to be in tip top health, or at least to make a few adjustments to improve general health that Miss Matthews will advise on, such as losing or gaining weight, decreasing alcohol consumption, stopping smoking, concentrating on eating healthily, and starting some specific vitamin supplements.

All patients and partners will require blood testing for HIV, Hepatitis and syphilis. A positive test does not necessarily mean that you cannot have treatment, it just means that treatment needs to be adjusted, and that your health, or your partners must be considered first.

Miss Matthews will provide a written treatment schedule with the likely dates of all appointments, procedures and when medications will commence and finish. This may change depending on your response to treatment. Appointments for scans are flexible and may be arranged before or after work and at weekends, depending on Miss Matthews’ schedule and your response to treatment.

All the medication required for treatment will be delivered to your home (or an alternative address at your request) a week or so before treatment commences.

Various consent forms that are required by CRM London will be provided as a pack with your prescription for you to read at leisure at home. Miss Matthews will go through each in detail with yourself and your partner, and explain some of the more technical and legal aspects to ensure that you are confident about signing each one.

You will be asked to arrange an appointment to see the nurses at CRM to which you should bring the completed consents and either your passports, or national identity cards.

The first medication usually starts on the 21st day of the period cycle (the first day of bleeding is day 1).

This medicine stops the ovaries working temporarily to ensure that your own hormones do not disrupt the action of the subsequent hormone injections designed to stimulate egg growth.

The medicine can be given as a single injection, daily injections, or most commonly a daily nasal inhaler (similar to some hay-fever treatments).

This medication commonly causes side effects that vary between individuals but may include: hot flushes, sweats at night time, tearfulness, irritability, headaches, and a delayed, heavier or longer period bleed during treatment.

Although this phase can be uncomfortable, it is short-lived over a 2-3 week period, and with this in mind, the majority of patients cope admirably, knowing that it is merely a prelude to getting on with the treatment proper.

This medication is not contraceptive, but trying to conceive the month that it starts is inadvisable, as it should not ideally be used at all if there is any possibility of pregnancy.

A scan is arranged before ovarian stimulation starts to ensure that the womb lining is thin, and the ovaries inactive.

This scan is performed either during a period (antagonist or flare cycle), or more often after a 2-3 week phase of down-regulation (day 21 regime).

The injections to stimulate egg growth will have been delivered to your home. They should be kept in the fridge and brought to this first scan appointment.

Women on the routine day 21 down-regulation regime will decrease the dose of their nasal sniff or down-regulation injection the day that the stimulation injections are commenced, and will continue both medications until instructed.

The injections are usually self-administered. Miss Matthews will do the first one with you, and teach the correct technique. Written information to remind you, and in some cases a DVD explaining all the steps for correct administration, are provided for you to take home.

The injections usually come in the form of an easy to use dose adjustable pen. A new sterile needle approximately 1cm long is used for each injection. The needle is usually injected into the tummy skin, but can be given into the thigh, upper arm or bottom.

Some women will be prescribed medication that comes in glass vials and requires a more traditional preparation and administration technique. Miss Matthews will guide you through this and ensure that you are completely comfortable with the procedure before you commence home daily injections.

The stimulation injections continue for 10-16 days, but the usual duration of treatment is 12 days. An ultrasound scan will be arranged on day 7-8 and then on alternate days to monitor egg growth. The injection dose may be increased or decreased depending on the response of the ovaries as treatment progresses.

Common side effects of the stimulation injections include abdominal bloating, nausea, diarrhoea, weight gain and fatigue, and rarely a localised reaction at the injection site. Most women feel fine on the injections, and those who have had a pre-treatment down regulation phase usually feel much better once they start.

The egg collection is the most daunting step of an IVF cycle for most people, as it is performed in an operating theatre, and requires strong sedation and painkillers, or occasionally a general anaesthetic.

When the egg development on scan is satisfactory, the stimulation injections, and the down-regulation treatment finishes, and a single injection of a different hormone (called Pregnyl or Ovitrelle) is given exactly 36 hours before your scheduled time for egg collection. This injection is always administered in the evening. The day after the injection there are no medications to take, but, depending on the time of your egg collection, you will be asked to fast from bedtime that night.

On the morning of the egg collection, you will be asked to attend CRM London 30 minutes before the operation. You will have been advised to refrain from sex for 3-5 days beforehand, to ensure that the sperm quality on the day is optimal. A semen sample is produced whilst the egg collection is being performed. Once the nurse has checked you in, you will change into an operating gown and be escorted through into the operating room. The embryologist and anaesthetist will introduce themselves and confirm your identity, and of course Miss Matthews will also be there.

An anaesthetist will insert a drip into your arm to administer intravenous drugs that send you off to sleep throughout the procedure.

Miss Matthews, or if previously arranged, one of the CRM doctors, will spend 20-30 minutes retrieving the eggs from your ovaries. Each egg sac (follicle) in the ovary is located and punctured under ultrasound scan guidance using a fine needle that passes easily through the vaginal skin. The fluid in each sac is drawn into a sterile warm tube that is passed to the embryologist to examine under the microscope. Eggs can be easily seen floating in the fluid, and each is carefully placed in a warm labelled dish with some nutrient fluid in the laboratory. A mature egg is not retrieved from every follicle. Some ‘empty’ follicles contain eggs that stopped growing and disappear. Others contain eggs that are too young to fertilise.

At the end of the procedure, Miss Matthews will insert both a painkilling and an antibiotic suppository, and you will wake up just as you are returned to the recovery room. Miss Matthews will tell you how many eggs were collected, and a drink and light snack will be provided.

The embryologist will speak to you about the eggs and sperm before you leave about 2 hours later, and make arrangements to contact you at home the following day. You will commence twice daily suppositories (called Cyclogest or Uterogestan) the evening of your egg collection. These contain progesterone, a hormone that encourages good development of the womb lining in preparation for the embryos. The suppositories continue to the day of the pregnancy test, and beyond if the test is positive.

In the Laboratory:
The sperm sample is prepared to select out the best sperm to use.

Couples having IVF will have approximately 200,000 good quality sperm added to each egg in a small dish that is then carefully placed in an incubator to keep the eggs and sperm at body temperature.

Couples having ICSI will have a single selected sperm injected into each egg, and these are then placed in the incubator as above.

Very strict guidelines in the laboratory ensure that the identity of each egg and sperm is checked at each step, and all these checks are witnessed by two people. This is to ensure that mix-ups do not occur. Sterile conditions are maintained in the laboratory at all times.

The dishes are removed from the incubator on the morning after the egg collection and examined under the microscope for signs of fertilisation. On average, 70% of eggs injected (ICSI) or inseminated (IVF) will fertilise normally. The remainder either show no signs of fertilisation, or may have fertilised abnormally (eg. sometimes two sperm penetrate the egg. These embryos can never develop normally).

The fertilised eggs are called embryos. All the normal embryos are carefully replaced into the incubator for another 1-4 days, and are checked daily during this time to monitor development.

The embryologist will call to let you know how many embryos you have, and to plan when the embryo transfer is likely to take place. Miss Matthews will also call you to discuss the results.

Side effects of the egg collection:
You will feel bloated and uncomfortable following the procedure. The use of proprietary painkillers at home such as Paracetamol or Nurofen is fine, but any pains normally settle within 48 hours. The bloating will continue for a week or so during which time vigorous exercise is not advised, but you will be able to return to work.

Pain or bloating that worsens should be reported to Miss Matthews.

Some light vaginal staining on the day of the procedure is normal. This blood comes from the two tiny needle puncture sites at the top of the vagina, and not from the womb itself. Staining that continues, or becomes a proper bleed should be reported to Miss Matthews.

The embryo transfer is arranged 2-5 days after the egg collection. The two best embryos are routinely chosen for transfer, but sometimes it is more appropriate to replace one or three embryos (3 embryos may only be considered if you are over 40 years old and have had previous failed treatments). Miss Matthews will discuss this with you both beforehand, as will the embryologist on the day of the transfer.

Your partner may accompany you into the procedure room for the embryo transfer. Your legs will be placed in stirrups and sterile drapes used to protect your modesty. Your identity will be double checked by the embryologist and a nurse. Miss Matthews will also verify your identity. The magnified embryos can be seen on the mounted TV screen in the procedure room. Your name will be etched on the base of the dish.

Miss Matthews will insert a speculum into the vagina to visualise the cervix (neck of the womb). It feels the same as having a smear test done.

The embryos that have been chosen for transfer are then drawn into a very fine catheter tube, which is given to Miss Matthews who passes the catheter through the entrance to the cervix and onwards, very gently, into the womb cavity where the embryos are expelled. The catheter is then very slowly and carefully withdrawn, and checked by the embryologist.

The whole procedure takes about 10 minutes. There is no need to rest afterwards.

You will be advised to continue the suppository treatment (cyclogest or uterogestan). A urine pregnancy test should be performed 12-14 days later. Miss Matthews can do the test with you at the office if you prefer.

Treatment protocols
The routine protocol for IVF/ICSI treatment involves a 2-3 week phase of ‘down-regulation’ drugs, followed by 12-14 days of stimulation injections. This is called the luteal phase long down-regulation protocol.

Other treatment protocols that may be suggested include:
• The follicular phase long down-regulation protocol
• The short antagonist protocol (uses different drugs over 2 weeks only)
• The flare protocol
• The step down protocol

Miss Matthews will discuss which treatment protocol suits your needs best.

Other adjuvant drugs are sometimes used during the course of a treatment cycle. These may include: heparin injections, steroids, oestrogen, aspirin and the contraceptive pill.

Ovarian hyperstimulation is a potentially life threatening but rare complication of IVF treatment. It complicates 3-5% of treatment cycles, and is mild in most, resolving by itself with time with no need for medical intervention.

Occasional severe cases require hospital admission, and rarely admission to an intensive care unit for specialist management. The condition occurs after egg collection, and tends to be more severe if embryos are replaced and if pregnancy occurs. OHSS is more likely if more than 20 eggs are collected.

Symptoms include: increasing abdominal bloating and pain following egg collection, shortness of breath, a reduction in urine output, and palpitations. An ultrasound scan will reliably diagnose the problem. The ovaries will be grossly enlarged and clear protein rich fluid called ascites collects in the tummy cavity. Severe OHSS is also associated with a fluid collection around the lungs and heart. Blood tests demonstrate lowered protein levels in the blood, altered liver function, and in severe cases, a thickening of the blood that can be associated with an increased tendency to develop a clot in the legs (DVT) or lungs (Pulmonary embolus).
Treatment of mild OHSS can be at home, and involves drinking plenty of protein rich fluid (like milk), rest, painkillers, and of course regular medical reviews.

Women who have moderate or severe OHSS will require hospital admission. OHSS can be avoided in most cases by tailoring the dose of stimulation injections to you; depending on your age, cause of infertility, weight, previous response to stimulation injections, and scan findings.

Women whose ovaries are obviously over-stimulated during the course of treatment, and are therefore at high risk, have the cycle stopped before egg collection. The injections can be restarted at a lower dose once the ovaries have settled down in a few weeks.
Other women who have the egg collection, but in the days following that start to develop symptoms, will have all embryos frozen and are given medicine to help settle the condition more quickly. A frozen embryo transfer cycle can then be arranged. Some cases of OHSS cannot be predicted. All women are advised to look out for symptoms following egg collection and embryo transfer.

Although a womans’ age and the results of hormone tests give an indication of the most appropriate dose of stimulating injection to give to a patient who is commencing their first IVF attempt, everyone responds differently, and in some cases, despite increasing the dose of injections during the course of treatment, few eggs develop. Miss Matthews would not routinely recommend proceeding with an egg collection procedure if fewer than 4 eggs have developed on ultrasound scan after 10-12 days of the stimulating injections. The treatment may be converted into an IUI (intrauterine insemination) cycle, if the fallopian tubes are open and the sperm is normal, but the chance of success with IVF is significantly reduced if 1-3 eggs only are available.

A different stimulation regime, or a higher dose of injections from the start of treatment may be appropriate in the next cycle.

The number of eggs retrieved at egg collection can be predicted by the monitoring ultrasound scans, but very occasionally no eggs are collected from the fluid filled sacs in the ovaries (follicles), despite a satisfactory ultrasound appearance.

Omission, delay or incomplete injection of the Pregnyl or Ovitrelle treatment that should be administered 36 hours before egg collection is sometimes responsible. The nurses will always check to ensure when and how much injection was given before proceeding with the operation.

Rarely, despite the injection, no eggs are collected. This is a poor prognostic sign that indicates a problem with poor egg quality and may prompt a discussion about using a egg donor to achieve pregnancy. 

Approximately 2-4% of couples having an IVF cycle will receive a call from the embryologist on the day after the egg collection to say that none of the eggs collected have fertilised to form embryos. This is more likely of course when only one or two eggs have been collected, but it can happen unexpectedly even when a good number of eggs have been retrieved.

There are two reasons why this might happen; either the quality of the eggs was extremely poor (unhealthy eggs are not capable of fertilisation), or the egg and sperm just didn’t interact well together to allow the sperm to penetrate the egg shell (this applies to IVF treatments only and not ICSI). The latter issue is overcome in a further treatment cycle by performing ICSI, but the former is a poor prognostic factor that probably indicates an irreparable ovarian problem. Further treatment cycles rarely improve the outcome in these cases, and egg donation may be recommended.

Many couples who have been trying for pregnancy for a while, have no objection to the idea of an instant family, but the ideal outcome of a fertility treatment cycle is a healthy pregnancy with the delivery of one healthy baby at a time.

Triplet pregnancies in particular are associated with many more risks, including an increased chance of losing the pregnancy altogether as a miscarriage, higher chances of medical complications for mum in the pregnancy, and a risk of premature delivery, with all the attendant problems. Women who conceive triplets (or more babies) may be advised to consider selective abortion of one or more babies to improve their chances of having at least one healthy child at the end of the pregnancy. This is a scenario that no-one wishes to face, and with this in mind, all fertility specialists in the UK will discuss the risk of multiple pregnancy with you during your treatment cycle.

Women who have specific medical or gynaecological problems (e.g. heart disease, back problems, diabetes) that will make any pregnancy high risk, may be strongly advised to opt for the transfer of a single embryo, as even a twin pregnancy would be associated with an unacceptable risk.

The law in the UK permits the transfer of a maximum of 2 embryos in any one IVF/ICSI treatment, unless the woman is over 40 years, when the transfer of 3 embryos may be considered. This law differs outside the UK, so patients who go abroad for treatment should think very carefully about the benefits and risks of having more embryos transferred, even if the clinic involved side steps the issue in an attempt to bolster their pregnancy rates with no regard for the welfare of the woman or her potential pregnancy.
Whilst most multiple pregnancies that result from fertility treatment involve the development of a baby from different embryos (non-identical twins), it is still possible to have a single embryo split to form identical twins (or rarely triplets). The chance of this happening is higher in older women having treatment.