IVF

IVF literally means fertilisation outside the body. This treatment is now used to effectively treat a range of infertility conditions.

IVF was originally used in cases where the Fallopian tubes were blocked, absent or damaged, but it may also be used to treat infertility due to a number of other causes such as endometriosis, unexplained infertility, male factor infertility, ovulation problems that are difficult to treat by simpler means, or a combination of infertility factors.

There are certain circumstances where IVF is not possible or recommended. These include cases where the woman does not have a womb, where there are reasons which would make it hazardous to carry out IVF e.g. previous pelvic abscess or inaccessible ovaries, or where it would be dangerous to embark upon a pregnancy because of some serious underlying medical condition.

Upper age limits are used as a guide for IVF treatment on the basis of success rates. At the Centre for Reproductive Medicine we treat women up to the age of 45 with their own eggs, or 49 with donor eggs. It should be born in mind, however, that success rates with IVF treatment reduce dramatically after the female reaches 40.

The success of IVF treatment is influenced by various factors, including the woman's age, the cause and duration of infertility and whether the woman has been pregnant before. A good general rule is that a couple embarking upon IVF/ICSI has a 1 in 5 chance of having a live birth with each attempt. The particular circumstances that affect your individual chance will be discussed with you, and our most up to date results will be provided to you - patient information booklet.

Multiple pregnancy and the number of embryos replaced

Successful IVF treatment carries a higher chance of multiple pregnancy than spontaneous conception. Multiple pregnancy carries specific risks and whilst it may seem initially an attractive option (complete family in one go!), patients are often not aware of the risks both to themselves and the baby of multiple pregnancy. Because of this our treatment aims to reduce the chance of a multiple pregnancy whilst maximising the chance of you getting pregnant. To achieve this we will replace no more than 1 or 2 embryos depending on some of the factors mentioned above but particularly on the woman's age. The current UK guidelines (about to be revised) allow the replacement of 2 embryos in women under 40 and no more than 3 in older women. Currently in this unit, the incidence of triplets as a result of IVF/ICSI, is less than 1% and the twin rate between 25-35%.

Please also see our patient information booklet for further information

A summary of IVF treatment

The woman is given fertility drugs to stimulate her ovaries to produce the development of more eggs than would occur naturally. The egg develops in a a follicle which is a small fluid filled cyst within the ovary which grows from 2 to 20 mm in the space of 2 weeks. Normally there is one egg in each fully grown follicle and we often talk about follicles synonymously with eggs. The chances of pregnancy are increased if more than one egg can be obtained and fertilised. The number and size of the developing follicles in the ovaries is measured by ultrasound scans.

The final preparation for egg collection involves a hormonal injection called HCG given to the woman 36 hours prior to removal of eggs. This injection causes final maturing of the egg, mimics the natural process which normally triggers ovulation and is essential if the egg is to be removed.

The eggs are collected vaginally using an ultrasound probe to guide a fine needle into the ovary. This is normally carried out under a heavy sedation anaesthetic (this means you will be asleep and not know anything about the procedure). The ultrasound probe is introduced into the vagina, the ovaries are visualised and then an aspiration needle (attached to the probe) is passed through the top of the vagina into the follicles. The fluid within the follicles is sucked out and then examined in our IVF laboratory for the eggs to be identified. In rare situations, the eggs may be collected laparoscopically if the ovaries prove to be inaccessible using the ultrasound scan.

After egg collection, the eggs are incubated for a short time and the sperm is then added to the eggs. The mixture is incubated in the laboratory for a further 24-48 hours. If the semen is normal, fertilisation usually takes place. The first signs of fertilisation are shown by the presence of the pronuclei within the egg. If this has occurred, the zygote should then divide into two, and subsequently three, four or more cell embryos. The fertilised eggs (now called embryos) are returned to the womb 48-72 hours after egg collection. We refer to this as an embryo transfer.

No more than two embryos are transferred into the womb through the cervix. The transfer procedure is one of the most important events in IVF. It is generally a painless procedure, similar to a cervical smear and on average takes up to 15 minutes. On rare occasions this procedure may take longer.

Occasionally, the woman will experience period-like pain during the procedure, but this is generally short-lived. We encourage the male partners to be present during this special time, if they wish to do so. After the procedure, women are encouraged to carry on with their normal routine as there is no evidence to suggest that bed rest has a positive effect.

What steps are involved in IVF?

1. Preliminary tests: including a detailed semen analysis, blood tests for hormone levels such as FSH and LH, screening for viruses such as HIV, Hepatitis B and C, as well as Rubella and swabs from the cervix and vagina for bacteria and chlamydia.
2. Pre-treatment information and implication session.
3. Down regulation (or switching off) of the pituitary gland with a nasal spray or daily injection to stop the ovaries working temporarily; this phase usually takes 2-3 weeks.
4. Stimulation of the ovaries with gonadotrophins, drugs given by daily injection to cause the production of several eggs at the same time; this phase usually lasts 10-15 days.
5. Monitoring the development of the "egg sacs" (follicles) with ultrasound and occasional blood tests (for oestrogen levels).
6. Egg removal from the ovaries by a small surgical procedure, performed as a day case under sedation or light anaesthetic.
7. Insemination of the eggs in the laboratory by the sperm (this is where additional ICSI may be performed).
8. Replacement of fertilised eggs (embryos) inside the womb 2-5 days after egg retrieval.

Follow-up to confirm pregnancy or discuss the reasons for a negative result.

Natural cycle IVF/ICSI

Consists of IVF (or ICSI) carried out as a part of a natural cycle. No drugs are used to stimulate the ovary to produce multiple eggs and the treatment relies on the spontaneous growth of one follicle. Hence, the drawbacks are the possibility of spontaneous ovulation occurring prior to egg retrieval, that the single egg cannot be retrieved, that the egg is not of sufficient quality to be used, or that the egg fails to fertilise in the laboratory (and that therefore no embryo transfer takes place). For these reasons the success rate of natural cycle IVF/ICSI (about 7% per cycle, according to published data) is significantly lower than for stimulated cycles, which are rarely carried out.

Natural cycle IVF/ICSI is sometimes used in circumstances where the use of drugs for ovarian stimulation is not appropriate, where ovarian stimulation confers no benefit, or where the patient chooses not to have stimulation.

Ovarian stimulation

In a natural cycle just a single egg is usually produced, but IVF is more successful if two embryos are transferred. To achieve this drugs are given by injection to stimulate more follicles (fluid filled spaces in the ovary which contain an egg) to produce eggs. The drugs are tailored to each patients needs. Before ovarian stimulation can start, down-regulation is carried out to prevent premature ovulation and to aid cycle management. This requires either injections or nasal spray.

Consents

Informed consent from both partners is required before stimulation. The consent forms, which are a legal requirement, will be discussed in full with a consultant or nurse during the monitoring period. There are several consents which are required:

• Human Fertilisation and Embryology Authority (HFEA) Consent for both man and women. This requires you to specify the immediate use of sperm or egg and provide consent to storage of the embryo and its use in the event of your personal circumstances changing in the future.
• Hospital consent (both sign this).
• Consent to disclose information - this is another HFEA consent which enables us to contact your GP and, if necessary during the course of your treatment, other health care professionals about your treatment.

Monitoring

Cycle/follicle tracking involves a series of internal ultrasound scans and blood tests during your menstrual cycle to determine if and when you ovulate.

How?

• Transvaginal ultrasound scans
• Blood tests - There are a number of blood tests that are important for us take, to enable us to assess if there is a problem with your hormones. These need to be taken at certain times within your menstrual cycle and you will be told exactly when they need to be taken. We will also check if you are immune to rubella (German Measles). If you are not immune you will need to have the rubella vaccination and wait a month before you try and get pregnant.

These are carried out from 8.00am.

Why?

• To check follicular growth
• To allow action if growth is not satisfactory
• To monitor the risk of ovarian hyperstimulation (OHSS)
• To decide the optimum time for egg recovery

Response and decision-making

A meeting is held to discuss individual patient's results and the next appropriate action. When the scan and blood results indicate sufficient follicle number and size a late evening injection of HCG is given to complete maturation of the eggs. Egg collection is performed 36 hours after the injection is given.

Egg collection

General anaesthetic is recommended. Ultrasound views are used to guide the needle through the side of the vaginal wall into the ovarian follicles. This is a day-case procedure, which takes approximately 30 minutes. You should be well enough to go home approximately 2-4 hours after egg collection.

How many eggs are needed? To optimise the success of each cycle, the following figures need to be considered:

• 80% of follicles will contain an egg
• 80% of eggs collected will be mature
• 60-70% of the mature eggs will fertilise
• 90-95% of the fertilised eggs will cleave and form embryos

Sperm collection

Samples are produced on the morning of egg collection. This requires the male partner to attend the CRM with his partner and to produce a semen specimen in the department. There are facilities available for this. It is best if the couple abstain from intercourse for a couple of days prior to this to optimise the quality of the specimen.

Insemination of the eggs

IVF - In-Vitro Fertilisation

If the sperm sample is suitable for IVF, a concentration of the sperm will be mixed with the eggs and left to fertilise overnight in culture conditions. The concentration used depends on sperm count, motility, morphology and other relevant factors.

ICSI - Intracytoplasmic Sperm Injection

Sperm samples not suitable for IVF may require ICSI. This method involves injecting a single sperm directly into the egg, bypassing many of the egg's natural barriers. ICSI is always used for surgically retrieved sperm.

Fertilisation, division & cleavage

The morning after insemination, eggs are checked for signs of fertilisation. Normally fertilised eggs have two "pronuclei". Some eggs may fertilise abnormally, showing more or less pronuclei. These eggs and resulting embryos are not suitable for use. This also happens in natural conception but is rarely detected as the embryo will not form a viable pregnancy. Approximately 24 hours after checking for signs of fertilisation, the eggs are checked again for signs of cleavage. At this stage the embryos should contain 2-4 cells. This is known as Day 2. By Day 3 the embryo should contain 6-8 cells. On Day 5 a blastocyst (a more advanced embryo) should be formed

Embryo transfer and how many embryos to replace

This is normally carried out without an anaesthetic. The procedure similar to having a smear test taken is carried out in theatre and takes approximately 15 - 20 minutes. Your partner or alternative support partner is welcome to accompany you during this procedure. After a short rest period you are free to go home.

Hormonal Support after the replacement of the embryo(s)

The time after the embryos are replaced is known technically as the Luteal Phase. Becasue of the use of the drugs to suppress hormones prior to the IVF cycle beginning. The level of progesterone after emrbyo replacement may be reduced. For this reason it is advised that progesterone is given to help support the implantation of the embryos. Luteal Phase hormonal Support is started on the evening of the egg collection regardless of day of embryo transfer. This is given in the form of a natural progesterone called Cyclogest administered as pessaries placed rectally or vaginally (400 mg daily).

Frozen Embryos

Embryos may be frozen at any stage but only good quality embryos are classed as suitable for freezing. The embryologist will discuss with you the quality of the embryos and whether the spare embryos are of good enough quality to freeze. Around two thirds of embryos survive the freeze/thaw process. Frozen embryo replacement can be carried out in a cycle supported by HRT or in a "natural" cycle.

Pregnancy

A urine test to check for a pregnancy is carried out 14 days after embryo transfer. Couples are normally asked to attend the CRM for this test. If there is any doubt about the result of the urine test we will carry out a blood test to check the pregnancy hormone level. If the pregnancy test is positive luteal phase support is continued and an ultrasound scan will be arranged for two weeks later. This will hopefully give visual confirmation of how the pregnancy is progressing. The Centre will discharge a paerson back to their GP following their first scan, three weeks after a positive test. If sadly the scan does not show a clinical pregnancy couples have the opportunity to see one of the consultants to discuss their management. Our Counsellor is also available to help at this difficult time.

If the pregnancy test is negative, our infertility nurse practitioner will discuss the circumstances of the treatment and why it may have been unsuccessful. The consultant will write to you detailing the treatment and your future options or you can make a review appointment to attend the clinic. If this has been your first treatment and spare embryos have been placed in storage, the nurse will be able to plan with you the replacement of the frozen embryos after 2-3 months gap. If there are no spare embryos the nurse can also plan a further attempt at full treatment again after a gap of 2-3 months, which will involve a refresher information session.