IVF treatment is a multi-step process involving ovarian stimulation, egg retrieval and fertilization and embryo transfer. There are two main methods of ovulation stimulation used in IVF. These two methods are commonly referred to as the Long Protocol and the Short Protocol. For the Long Protocol, the IVF cycle begins with the administration of an injectable medication known as a GnRH agonist.

This medication is given (self-administered on a daily basis) beginning on day 21 of the prior cycle to when the IVF will occur, to suppress gonadotropin secretion by the pituitary gland. The function of the GnRH agonist is to allow synchronous development of the eggs once the ovulation stimulation medication (FSH) begins and to prevent spontaneous ovulation of mature eggs later in the cycle. Once sufficient suppression of the ovaries have been achieved, the patient will begin to take FSH which acts to stimulate the development of mature eggs. The goal is to get several eggs to mature together, not just a few. With the Short Protocol, the use of a GnRH agonist is not used. The ovulation induction begins with the use of injectable FSH on the third day of the cycle. When the first follicle reaches a diameter of 13-14 mm, a second medication is added. This medication is a GnRH antagonist which acts to restrict spontaneous ovulation until the maximum number of follicles reach mature size together.

Since maturing ovarian follicles (which contain the eggs) increase in size and secrete estrogen into the circulation, follicular growth and maturation are assessed by measuring the size of individual follicles with vaginal ultrasound and by measuring blood levels of estrogen. When monitoring indicates that follicles have developed sufficiently, final maturation is initiated by injection of human chorionic gonadotropin HCG) and the retrieval of the eggs is scheduled approximately 36 hours later.

The egg retrieval procedure is performed under conscious sedation with anaesthesia and, although the patient is conscious, a combination of medications is used to facilitate patient comfort and relaxation. A vaginal probe is placed in the vagina and mature follicles are identified. A needle that is mounted on the side of the vaginal probe is guided through the wall of the vagina and into each of the follicles that are viewed with the ultrasound probe. The follicular fluid containing the eggs is then aspirated into culture tubes for subsequent in vitro fertilization. This fluid is then viewed by the laboratory staff for the egg.

A semen sample is provided either shortly before or after the egg retrieval. The sample is assessed, appropriately processed and placed into the culture dish containing defined media and the eggs. Approximately 20 hours later, fertilization is assessed by identifying the appearance of male and female pronuclei in the newly formed embryo. The fertilized eggs (now called embryos) are cultured under strict conditions and examined carefully on a daily basis to assess their progress. On the third day of culture, the embryos are assessed and 2-3 are selected for placement into the uterus. The decision as to how many are transferred depends largely on the age of the woman and how many times she has undergone IVF in the past unsuccessfully. The best quality embryos are chosen for placement and remaining embryos are either frozen as day 3 embryos or cultured to the blastocyst stage (day 5) and then frozen.

On the day of embryo transfer continuing embryo development is assessed. The embryo transfer procedure is a simple and painless procedure. No anesthesia is required. The woman is asked to drink 2 or more glasses of water an hour before the procedure. This ensures the bladder is full. This is necessary to improve adequate visualization of the uterus at the time of embryo transfer. A speculum is placed into the vagina and the cervix brought into view by the physician. An abdominal ultrasound is used to help guide the placement of the embryos in the uterus. The embryos are loaded into a catheter in the laboratory and the catheter is passed through the cervix into the uterus and the embryos are deposited inside the uterus. Though it is not necessary to remain lying down after the embryos are replaced in the uterus, many women will choose to have a relaxing day.

There is a 12-day wait between the embryo transfer and the expected date of the next period. During this time, it is important to continue taking progesterone supplementation and prenatal vitamins. After 12 days, a pregnancy test is done. During this time, the patient is encouraged to abstain from intercourse, restrict exercise to everyday activity only, and remain relaxed.

Risks
There are a number of risks associated with IVF.

Ovarian Hyperstimulation Syndrome (OHSS)
OHSS is a condition that can arise with the use of the medications used to stimulate the ovaries (FSH). The exact cause of OHSS is not known but it is thought to arise from the stimulate of a hormone called VEGF that then leads to leaky vessels in the body. This can lead to accumulation of fluid around the ovaries and other organs in the abdomen, even fluid in the lungs. This can happen in up to 10% of IVF cases but is only severe leading to hospitalization in less than 1%. Hospitalization can be recommended because of severe abdominal discomfort, decreased urine output and excessive thickening of the blood that may lead to blood clots. OHSS is characterized by enlargement of the ovaries, fluid retention and weight gain. Symptoms of OHSS include feeling bloated, abdominal discomfort, nausea, vomiting, and in extreme cases – difficulty breathing.

If the risk of OHSS is high, some of the following may be recommended

• Record weight daily
• Measure abdominal girth at the umbilicus (i.e. belly button level)
• Encourage fluid intake. Fluids should include water and electrolyte-containing fluids (Gatorade).
• Monitor your urine output.

In some cases, it might be necessary to drain some fluid from the abdomen. This can be done by passing a fine needle through the vagina or through the abdominal wall to drain the fluid.

Although extremely severe cases are uncommon, OHSS can be life threatening. However, the condition is self limiting. It usually resolves on its own, or by doing what is prescribed above. However, it can persist longer (up to 3 weeks) in women who are pregnant.

Multiples
As the success of IVF has increased over the years, the risk of multiples has increased also. Because of this most physicians will limit the number of embryos being replaced to no more than 3 in women over the age of 35 and 1-2 in women less than this age. Obviously, by limiting the number of embryos replaced, it is possible to limit the risk of triplets and beyond. Even twins can carry significant risks. These include premature delivery, developmental abnormalities and underweight babies. Maternal risks of twins and triplet pregnancies include hypertension of pregnancy and gestational diabetes. So, although in most cases the outcome with twins is good, there are significantly increased risks over singleton pregnancies. Triplets and quadruplets can have even greater risks of pregnancy. If a pregnancy with triplets or more does occur, some couples may consider selective reduction to avoid these high risks.

Other Risks
As with other surgical procedures, bleeding, infection and allergic reactions to medications are occasionally encountered. Though the egg retrieval is considered a minor surgical procedure and complications are very rare, they can still occur.

Pregnancy Outcome
Pregnancies conceived by couples with a history of infertility are considered higher risk than pregnancies conceived by couples that do not have a history of infertility. These pregnancies are at increased risk of delivering prematurely and with babies of low birth weight. This is even with singleton pregnancies. The risk is higher when it is with twins or triplets. Some studies suggest that pregnancies conceived through IVF and ICSI may be at increased risk of some physical abnormalities of the babies though this is not for certain.