IVF (IN VITRO FERTILISATION) AND GIFT (GAMETE INTRA FALLOPIAN TRANSFER)

What is IVF?

In vitro fertilisation (IVF) is a technique in which egg cells are fertilised by sperm outside the woman's womb. IVF is a major treatment in infertility when other methods of achieving conception have failed.

The process involves hormonally controlling the ovulatory process, removing ova (eggs) from the woman's ovaries and letting sperm fertilise them in a fluid medium. The fertilised egg (zygote) is then transferred to the patient's uterus with the intent to establish a successful pregnancy.

What is GIFT?

Gamete intrafallopian transfer (GIFT) is an infertility treatment in which eggs are removed from a woman's ovaries, and placed in one of the fallopian tubes, along with the man's sperm. This allows fertilization to take place inside the woman's body.

It takes, on average, four to six weeks to complete a cycle of GIFT. First, the woman must take a fertility drug to stimulate egg production in the ovaries. The doctor will monitor the growth of the ovarian follicles, and once they are mature, the woman will be injected with Human chorionic gonadotropin (hCG). The eggs will be harvested approximately 36 hours later, mixed with the man's sperm, and placed back into the woman's Fallopian tubes using a laparoscope.

A woman must have at least one normal fallopian tube in order for GIFT to be suitable. It is used in instances where the fertility problem relates to sperm dysfunction, and where the couple has idiopathic (unknown cause) infertility. Some patients may prefer the procedure to IVF for ethical reasons, since the fertilization takes place inside the body.

As with most fertility procedures, success depends on the couple's age and the woman's egg quality. It is estimated that approximately 25-30% of GIFT cycles result in pregnancy, with a third of those being multiple pregnancies.

Many specialists in infertility would look at GIFT as a procedure that is outdated (2004) as pregnancy rates in IVF tend to be equal or better and do not require laparoscopy.

IVF Method

Ovarian stimulation

Treatment cycles are typically started on the third day of menstruation and consist of a regimen of fertility medications to stimulate the development of multiple follicles of the ovaries. In most patients injectable gonadotropins (usually FSH analogues) are used under close monitoring. Such monitoring frequently checks the oestradiol level and, by means of gynaecologic ultrasonography, follicular growth. Typically approximately 10 days of injections will be necessary. Endogenous ovulation is blocked by the use of GnRH agonists or GnRH antagonists.

Oocyte retrieval

When follicular maturation is judged to be adequate, human chorionic gonadotropin (β-hCG) is given. This agent, which acts as an analogue of luteinising hormone, would cause ovulation about 36 hours after injection, but a retrieval procedure takes place just prior to that, in order to recover the egg cells from the ovary. The eggs are retrieved from the patient using a transvaginal technique involving an ultrasound-guided needle piercing the vaginal wall to reach the ovaries. Through this needle follicles can be aspirated, and the follicular fluid is handed to the IVF laboratory to identify ova. The retrieval procedure takes about 20 minutes and is usually done under conscious sedation or general anaesthesia.

IVF laboratory

In the laboratory, the identified eggs are stripped of surrounding cells and prepared for fertilisation. In the meantime, semen is prepared for fertilisation by removing inactive cells and seminal fluid. The sperm and the egg are incubated together (at a ratio of about 75,000:1) in the culture media for about 18 hours. By that time fertilisation should have taken place and the fertilised egg would show two pronuclei. In situations where the sperm count is low a single sperm is injected directly into the egg using intracytoplasmic sperm injection (ICSI). The fertilised egg is passed to a special growth medium and left for about 48 hours until the egg has reached the 6-8 cell stage.

Laboratories have developed grading methods to judge oocyte and embryo quality. Typically, embryos that have reached the 6-8 cell stage are transferred three days after retrieval.

Embryo transfer

Embryos are graded by the embryologist based on the number of cells, evenness of growth and degree of fragmentation. The number to be transferred depends on the number available, the age of the woman and other health and diagnostic factors. In countries such as the UK, Australia and New Zealand, a maximum of two embryos are transferred except in unusual circumstances. This is to limit the number of multiple pregnancies. The embryos judged to be the "best" are transferred to the patient's uterus through a thin, plastic catheter, which goes through her vagina and cervix. Several embryos may be passed into the uterus to improve chances of implantation and pregnancy.

Post-transfer

The patient has to wait two weeks before she returns to the clinic for the pregnancy test. During this time she may receive progesterone—a hormone that keeps the uterus lining thickened and suitable for implantation. Many IVF programmes provide additional medications as part of their protocol.

Success rates

Chance of a successful pregnancy is approximately 15% for each IVF cycle, although selected clinics are now able to claim rates up to 50% per cycle. There are many factors that determine success rates including the age of the patient, the quality of the eggs and sperm, the duration of the infertility, the health of the uterus, and the medical expertise. It is a common practice for IVF programmes to boost the pregnancy rate by placing multiple embryos during embryo transfer. A flip side of this practice is a higher risk of multiple pregnancy, itself associated with obstetric complications.

IVF programmes generally publish their pregnancy rates. However, comparisons between clinics are difficult as many variables determine outcome. Furthermore, these statistics depend strongly on the type of patients selected.

There are many reasons why pregnancy may not occur following IVF and embryo transfer, including

• The timing of ovulation may be misjudged, or ovulation may not be able to be predicted or may not occur
• Attempts to obtain eggs that develop during the monitored cycle may be unsuccessful
• The eggs obtained may be abnormal or may have been damaged during the retrieval process
• A semen specimen may not be able to be provided
• Fertilization of eggs to form embryos may not occur
• Cleavage or cell division of the fertilised eggs may not take place
• The embryo may not develop normally
• Implantation may not occur
• Equipment failure, infection and/or human error or other unforeseen and uncontrollable factors, which may result in the loss of or damage to the eggs, the semen sample and/or the embryos.

Potential Complications

The major complication of IVF is the risk of multiple births. This is directly related to the practice of transferring multiple embryos at embryo transfer. Multiple births are related to increased risk of pregnancy loss, obstetrical complications, prematurity, and neonatal morbidity with the potential for long term damage. Strict limits on the number of embryos that may be transferred have been enacted in some countries (e.g., England) to reduce the risk of high-order multiples (triplets or more), but are not universally followed or accepted. Spontaneous splitting of embryos in the womb after transfer does occur, but is rare (<1%)>

Another risk of ovarian stimulation is the development of ovarian hyperstimulation syndrome.