IVF

In vitro fertilisation (IVF) literally means fertilisation outside the human body. This treatment is now used to effectively to treat a range of medical conditions leading to subfertility.

IVF was originally used in women where the Fallopian tubes were blocked, absent or damaged, but it is now routinely used to treat subfertility 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 subfertility factors.

There are certain circumstances where IVF treatment 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 for the woman to have IVF treatment e.g. previous pelvic abscess or inaccessible ovaries, or where it would be dangerous to embark upon a pregnancy because of a 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 50 with donor eggs. It should be born in mind, however, that success rates with IVF treatment reduce dramatically after the woman reaches 40 years of age.

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. The results section of our website contains an overview of our current success rates. 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 during your consultation at the CRM.

 

Multiple pregnancy and the number of embryos replaced

Having a multiple birth is the single greatest health risk associated with fertility treatment. Multiple births carry risks to both the health of the mother and to the health of the unborn babies. Twins or triplets are more likely to be premature and to have below-normal birth weight.

Our treatment aims to reduce the chance of a multiple pregnancy whilst maximising the chance of you getting pregnant.

If you are a suitable patient, the risk of having twins is greatly reduced by having single embryo transfer (SET) without significantly affecting your chance of becoming pregnant.

Depending on your age, the number of previous unsuccessful IVF / ICSI cycles you have had (where embryo transfer has taken place) and the quality of your embryos, you will have either one or two embryos transferred. We will not know for sure until the day of the embryo transfer as we do not know the quality of the embryos before then.

Our current policy is:

For women aged under 37 years:

  • In the first full IVF / ICSI cycle use single embryo transfer
  • In the second full IVF / ICSI cycle use single embryo transfer if 1 or more top-quality embryos are available. Consider using 2 embryos if no top-quality embryos are available
  • In the third full IVF / ICSI cycle transfer no more than 2 embryos
  • For women aged 37–39 years:
  • In the first and second full IVF / ICSI cycles use single embryo transfer if there are 1 or more top-quality embryos. Consider double embryo transfer if there are no top-quality embryos.
  • In the third full IVF / ICSI cycle transfer no more than 2 embryos.
  • When considering the number of fresh or frozen embryos to transfer in IVF / ICSI treatment for women aged 40–42 years, consider double embryo transfer.

If you are an egg recipient then it is the age of the egg donor rather than your age that will be taken into account.

Please note that this policy applies to both fresh and frozen embryo transfers

An embryologist will talk to you before your embryo transfer and let you know how many embryos will be transferred. Embryos which have reached the blastocyst stage but have not been transferred may be suitable for freezing; we will discuss this with you at the time. You will be able to ask the embryologist any questions you may have before we go ahead with the transfer.

Currently in this unit, the incidence of triplets as a result of IVF/ICSI is less than 1% and the twin rate approximately 6%.

 

A summary of IVF treatment

The woman is given fertility medications to stimulate her ovaries to produce many more eggs than she would in a normal menstrual cycle. The egg develops in a follicle which is a small fluid filled cyst within the ovary which grows from 2 to 20 mm in an average of two weeks. Normally there is one egg in each fully grown follicle and often the term "follicles" may be used synonymously with eggs. The chances of pregnancy are increased if more than one egg can be retrieved and fertilised. The number and size of the developing follicles in the ovaries is measured by pelvic ultrasound examination.

The final preparation for egg collection involves administering a hormonal injection called HCG which is given to the woman 36 hours prior to removal of eggs. This injection causes final maturation of the egg, and mimics the natural process which normally triggers ovulation. This step is essential for egg retrieval from the ovary.

The eggs are collected transvaginally using an ultrasound probe to guide a fine needle into the ovary. This procedure is carried out under a heavy sedation anaesthetic (this means you will be asleep and will have no recollection of the procedure when you wake up). 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 aspirated which is then examined in our IVF laboratory by an embryologist who identifies eggs in the follicular fluid.

The male partner produces a semen sample the same day when the woman has her egg collection. 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 hours. If the semen is normal, we expect an average of 70% of the eggs to fertilise. The first signs of fertilisation are demonstrated microscopically by the presence of pronuclei within the egg. If this has occurred, the embryo should then divide into two, and subsequently three, four or more cells. The embryos are returned to the womb either 2, 3 or 5 days after egg collection. We refer to this as an embryo transfer.

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. Rarely this procedure may take longer. Occasionally, the woman may experience a 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 ( with some exceptions) 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 concentrations 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 or a single depot injection to stop the ovaries working temporarily; this phase usually takes 2-3 weeks.
  4. Stimulation of the ovaries with gonadotrophins, medications given by daily injection to help the production of several eggs simultaneously 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 concentrations).
  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.
  9. 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 menstrual cycle. No medications are used to stimulate the ovary to produce multiple eggs and the treatment relies on the spontaneous growth of one follicle. Hence, the possibilities are that spontaneous ovulation may occur prior to egg retrieval, that the single egg may not be retrieved, that the egg is not of optimum quality to be used, or that the egg fails to fertilise in the laboratory (and that therefore embryo transfer does not take place). The success rate of natural cycle IVF/ICSI (about 7% to 20% per treatment cycle, according to published data) is significantly lower than that of stimulated cycles, and is therefore are rarely performed.
Natural cycle IVF/ICSI is used in circumstances where the use of medications for ovarian stimulation is not appropriate, or where ovarian stimulation confers no benefit, or where the patient chooses not to have stimulation.

 

Ovarian stimulation

In a natural menstrual cycle, only a single egg is generally produced, but IVF treatment is more successful if we have a selection of embryos to select the best one for embryo transfer. In order to achieve this medications are given by injection to stimulate productions of more follicles (fluid filled spaces in the ovary which contain an egg) and therefore several eggs. The dosage of medications 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 treatment. 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.
  • Child welfare form of the HFEA which takes into account the welfare of the resulting child and children in the family.
  • Monitoring

Cycle/follicle tracking involves a series of internal ultrasound scan examinations and blood tests during your menstrual cycle to monitor the growth of your follicles and time of ovulation.

How?

  • Transvaginal ultrasound scans
  • Blood investigations- 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 are taken at specific times within your menstrual cycle and you will be advised 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.

Why?

  • To check follicular growth
  • To enable modification of medications if follicular 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 pelvic scan and blood results indicate sufficient follicle numbers 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

A sedation or general anaesthetic is recommended as the procedure may be painful. Pelvic ultrasound examination is used to guide the needle through 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 (please note these figures are averages across all patients):

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

 

Sperm collection

A semen sample is produced by the male partner on the morning of egg collection. This requires the male partner to attend the CRM with his female partner and to produce a semen specimen in the department. There are facilities available for this. The best quality semen sample is obtained after 2-3 days of abstinence from ejaculation. Shorter or longer abstinence times are not recommended.

 

Insemination of the eggs


IVF - In-Vitro Fertilisation

If the sperm sample is suitable for IVF, a fixed number and concentration of the sperm is mixed with the eggs and left to fertilise overnight in an incubator within controlled culture conditions. The concentration of semen 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 such as the egg shell (zona). 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 abnormal 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. Two days after your egg collection, the embryos should have divided to contain 2-4 cells. By Day 3 after egg collection the embryo should have 6-8 cells. On Day 5 a blastocyst (an advanced embryo) should be formed.


Embryo transfer

This is normally carried out without an anaesthetic. The procedure similar to having a cervical smear test and is carried out in the operation theatre and takes approximately 15 - 20 minutes. Your partner or someone else if you wish 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 embryo(s) is replaced is known as the "Luteal Phase." Since medications are used to suppress hormones prior to the IVF cycle beginning the amount of progesterone in the blood after embryo replacement may be reduced. Therefore, it is advised that progesterone is administered 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) or Injection Gestone 100mg everyday or alternate days intramuscularly.


Frozen Embryos

Embryos freezing is performed at the blastocyst stage, but only good quality embryos are suitable for freezing. The embryologist will discuss with you about the quality of the embryos and whether any of the spare embryos are suitable for freezing. 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 11-14 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 a few weeks later. This will provide visual confirmation of whether pregnancy is progressing. At this stage the CRM will discharge a patient back to their GP following their first scan. If sadly the scan does not show a clinical pregnancy, patients 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 was 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 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 having a refresher information session with the nurses.