GIFT (Gamete Intrafallopian Transfer)

Definition

GIFT stands for Gamete Intrafallopian Transfer, a procedure to help couples with infertility problems to conceive. It was developed as a variation of the In Vitro Fertilisation (IVF) procedure, in which fertilisation is achieved externally in a glass dish (“vitrum” = Latin for “glass”) in the laboratory.

The main difference between IVF and GIFT is that in the latter procedure, the gametes (eggs and sperms) are transferred directly to the fallopian tubes. Thus, fertilisation occurs internally, in the natural environment of the woman's body. (The fallopian tubes are the part of the female reproductive system that convey the eggs from the ovaries to the uterus.)

Zygote Intrafallopian Transfer (ZIFT)

Zygote Intrafallopian Transfer (ZIFT) is a similar procedure to GIFT except that, instead of a mixture of eggs and sperms, a newly fertilised egg (zygote) is transferred to the fallopian tubes. While GIFT is done as a single procedure, which means that the eggs are aspirated, mixed with the sperms and the mixture than transferred into one of the tubes, ZIFT is done in two steps, whereby transfer of the fertilised egg is done 18-52 hours after egg retrieval, to allow time for fertilisation to first take place in the laboratory.

Stages in the GIFT procedure

Preparation for a GIFT treatment cycle

At the initial consultation, your doctor will consider whether you are suitable for GIFT treatment, and, if so, will discuss all the aspects of a treatment cycle with you. It may be necessary to first undergo an assessment laparoscopy. Laparoscopy is a surgical procedure that makes use of a laparoscope, a device consisting of a tube and optical system for viewing inside the abdomen. During this investigation, a chromopertubation (injecting a dye into the fallopian tubes) can be performed to ensure that the tubes are open. Laparoscopy also allows the doctor to assess the abdominal and pelvic cavity to make sure that there are no other previously undiagnosed pelvic abnormalities.

In some cases, a hysterosalpingogram (an X-ray of the uterus and tubes) may be performed to ascertain that the tubes are open.

Once the preliminary investigations have been completed, you will be ready to proceed with a treatment cycle. A GIFT treatment cycle involves three stages:

1. Ovarian stimulation and monitoring

To maximise the chances of successful fertilisation, your doctor will prescribe fertility drugs, for example a combination of gonadotropins and Clomifene or a GnRH agonist and gonadotropins, to induce the ovaries to produce several mature eggs. (A woman normally releases only one egg per month.)

Your response to the fertility drugs will be monitored with ultrasound scans and blood tests for hormone levels to assess the development of the eggs and the endometrium (uterine lining).

When the eggs are mature enough and the endometrium sufficiently developed, it is likely that you will receive an injection of human chorionic gonadotropin (hCG), such as Pergonal®, to stimulate the final maturation process for the release of the eggs from the ovaries and to time the egg retrieval step. The retrieval of the eggs is performed about 36 hours after the hCG injection.

2. Egg retrieval and sperm processing

When the eggs are mature, they are removed ("retrieved") using laparoscopy. This involves passing a fine, hollow needle through a small incision in the abdominal wall to retrieve the eggs from their follicles within the ovaries, while observing the process through the laparoscope. For the laparoscopy general anaesthesia is required. Alternatively, for example with ZIFT, egg collection may be carried out transvaginally under ultrasound scan guidance, whereby a needle is passed through the vaginal wall into the follicles of the ovaries. The retrieved eggs are kept in a culture medium.

About an hour prior to egg retrieval, a semen sample is collected by masturbation. The sperms are placed in a test tube, washed by spinning the test tube in a centrifuge, and then evaluated. The most active sperms swim to the top of the test tube where they are selected.

The eggs are examined microscopically to determine their maturity. Minutes after retrieval, at least two eggs are drawn up and mixed with 500 000 sperms. Usually, three eggs are mixed with a million sperms and this mixture is placed inside a special catheter.

3. Gamete transfer

While the patient is still under anaesthesia, the next step is the transfer of the gametes (eggs mixed with sperms) into the outer end of one of the fallopian tubes. Under laparoscopic view, the doctor inserts the special catheter containing the gametes and injects them directly into the fallopian tube.

The transfer can also be done transcervically by passing a catheter through the cervix into the uterus and then into one of the fallopian tubes, where the gametes are discharged. This latter approach, however, is not as successful and is less often used.

Hopefully, the transferred gametes will unite in the fallopian tube, as they would normally in a fertile female. If fertilisation occurs, the developing embryos will move to the uterus for the natural implantation process, as in a normal pregnancy.

After the procedure

From the start until a successful positive pregnancy test, one cycle of GIFT (or ZIFT) takes 28 to 30 days. The GIFT procedure itself takes about 40 to 60 minutes. With GIFT, egg retrieval and gamete transfer are performed during the same operation. Even though this involves minor surgery, you will be able to go home the same day. (With ZIFT, you need to return the following day for gamete transfer.)

After the procedure, you may be given pessaries of progesterone to support the lining of the uterus. You will need to rest and report for a pregnancy test about two weeks later. If pregnancy has not occurred, the treatment cycle will be repeated. Usually, four to six GIFT cycles are recommended.

Any eggs left over after the procedure will be mixed with sperms in the laboratory. If considered suitable, any resultant embryos may be frozen to be used for a transfer at a later stage.

Who can use GIFT?

Your doctor may recommend GIFT as a suitable option if your diagnosis is one of the following:

• Unexplained infertility. GIFT can be a successful option for couples with unexplained infertility, provided the woman has at least one unobstructed fallopian tube.
• Infertility due to immunological factors. Some men produce male antisperm antibodies, which means antibodies which are on the surface of his own sperms. This may cause a large number of the sperms to adhere to one another thereby seriously intervening with their normal forward progression movement. By washing the sperms and allowing them to swim to the top of the test tube, free swimming sperms are selected which improves the chance of fertilisation.
• Infertility caused by cervical factors. A woman may have poor cervical mucus or damage of her cervix due to previous electrocautery, conisation operation or scar formation as a result of birth trauma with the delivery of a previous child. These factors can sometimes be overcome with GIFT if an artificial insemination (injecting sperms through the cervix into the uterus via a catheter) was unsuccessful.
• Mild endometriosis. Endometriosis is a condition in which endometrial tissue builds up outside the uterus in areas called ectopic implants. This can be associated with scar formation and pelvic adhesions then interfering with the normal fallopian tube pick-up mechanism of an egg released during ovulation. In cases with more advanced endometriosis, ectopic tissue accumulation can be so severe, that laparoscopy and GIFT are not possible.
• Selected cases of moderate male infertility.
• Unilateral tubal infertility, given that one fallopian tube is normal. Because ectopic pregnancies occur more often, although an ectopic pregnancy is usually diagnosed early and dealt with appropriately, some medical experts believe that, GIFT should be reserved for cases in which there is no evidence of previous or existing tubal disease. It should not be considered in cases with previous infection or reconstructive tubal surgery, for example for a previous ectopic pregnancy.
• GIFT is sometimes chosen if a couple's religious beliefs prohibit conception outside the body.

Women with blocked fallopian tubes or pelvic adhesions are not suitable for GIFT.

Advantages and disadvantages of GIFT

Advantages

• For selected cases of infertility, GIFT may have a slightly higher success rate than IVF in terms of deliveries per egg retrieval. This may be due to the fact that the GIFT procedure deviates less from the natural conception process. GIFT allows the embryo to arrive and implant in the uterus naturally.
• Although it is said by some clinicians that GIFT is less expensive than IVF (which requires more time because of the incubation period of about 36 hours in the laboratory), the GIFT procedure may be as expensive due to the cost of laparoscopy, general anaesthesia and hospitalisation.
• Because fertilisation takes place within the fallopian tube, GIFT offers an option for people whose religious beliefs prohibit conception outside the body.

Disadvantages and limitations

• You need at least one healthy fallopian tube for GIFT.
• GIFT does not allow for visual confirmation of fertilisation because this occurs inside the body. With IVF, fertilisation can be observed and confirmed in the laboratory. If GIFT is unsuccessful, doctors have no way of knowing the reason for this. It might have failed because the sperms were incapable of fertilising the eggs, because the eggs themselves were not viable, or because other factors were responsible. However, the list of possible factors can be diminished if, for example, excess eggs, harvested during egg retrieval, are fertilised in vitro in the laboratory and lead to embryo development.
• GIFT involves surgery and requires general anaesthesia.
• The chance of a pregnancy with at least one baby is increased by transferring more than one egg to your fallopian tubes during GIFT. However, the chances of conceiving twins or triplets are automatically greater. While you may welcome the possibility of giving birth to more than one baby, a multiple pregnancy increases the risk of complications such as miscarriage.
• The fertility drugs used to stimulate egg production can have side-effects. Recent studies show no increased risk for breast or ovarian cancer among women who have used fertility drugs. One potentially serious side-effect is the ovarian hyperstimulation syndrome. This is characterised by a loss of fluid from the blood circulation and build-up of fluid in the abdominal cavity. As such the blood becomes thicker and is more prone to clot formation. This condition may be accompanied by electrolyte disturbances and may lead to a life threatening situation requiring management in an intensive care unit. Fortunately, this is a rare occurrence, but it emphasises the importance of strict monitoring of all parameters by the doctor after administration of fertility drugs.
• In certain cases, GIFT may increase the risk of ectopic pregnancy, whereby an embryo implants in a fallopian tube or the abdominal cavity instead of in the uterus. The risk does not appear to be significantly higher in cases where the tubes are normal and no other pelvic disease is present. A significant increase in the incidence of ectopic pregnancies has, however, been reported when GIFT is performed in abnormal fallopian tubes. Damage to a fallopian tube might inhibit its normal functioning, with the result that the embryo might not be transported by the tubal cilia (little hair-like structures) toward the uterus in time. The embryo might implant in the wall of the fallopian tube, resulting in an ectopic pregnancy.

Outcome

Outcomes vary depending on your particular fertility problem and age. GIFT has a reasonably high success rate of about 30%.

Factors that may affect GIFT success rates include:

• The age of the woman producing the eggs (younger women usually have healthier eggs and higher success rates)
• The number of eggs produced following ovulation induction by fertility drugs
• The quality of the sperms
• The number of eggs transferred
• The normal health of at least one fallopian tube

Reviewed by Prof B. Schaetzing MD, FCOG(SA), FRCOG, PhD. Part-time Consultant, Dept of Obstetrics & Gynaecology, Faculty of Health Sciences, University of Stellenbosch