In Vitro Fertilization (IVF): The Procedure

]]> Ovulation Induction

In a normal menstrual cycle, the ovaries produce one mature egg per month. In the ovulation induction stage of an IVF cycle, ovarian stimulation medications are used to induce the ovaries to produce multiple mature eggs. Multiple eggs are needed to increase the chances of fertilization and normal embryo development. In addition, more than one embryo is often transferred into the uterus to increase the chances of pregnancy.

Medications used for ovarian stimulation include:

• Human menopausal gonadotropins, or hMG (Pergonal, Humegone, Repronex)
• Follicle stimulating hormone, or FSH (Follistim, Gonal-F, Bravelle)
• Human chorionic gonadotropin, or hCG (Profasi, APL, Pregnyl, Novarel, Ovidrel)
• Clomiphene citrate (Clomid, Serophene)

Clomiphene citrate is administered orally, while the others are given by injection. Since clomiphene citrate is less potent than the other medications, it is not often used in IVF cycles.

Ovarian stimulation medications are generally given for 8-14 days. These medications are most often used in conjunction with one of the following medications to prevent premature ovulation:

• Gonadotropic releasing hormone (GnRH) agonists (Lupron and Synarel)
• GnRH antagonists (Antagon and Cetrotide)

During ovulation induction, the ovaries are monitored using vaginal ultrasound. Using the ultrasound, your physician can track the development of ovarian follicles. In addition, blood samples can be used to monitor your hormonal response to the ovulation drugs. The hormone estrogen tends to increase as follicles develop, and progesterone levels increase after ovulation.

When an appropriate number of follicles have developed, your will take an hCG injection or other medication to “trigger” maturation of the eggs. About 34-36 hours after the hCG injection, your eggs will be retrieved.

It is important to note that 10% to 20% of IVF cycles are cancelled prior to the hCG injection. This may occur for a number of reasons, but is usually due to an inadequate number of follicles developing.

Risks associated with ovulation induction include ovarian hyperstimulation syndrome (OHSS), which occurs when the ovaries are overstimulated. OHSS may require additional treatments and/or a hospital stay. In addition, there is a risk of short- and long-term adverse events associated with fertility medications.

Egg Retrieval and Fertilization

Egg retrieval is a minor surgical procedure that can be performed in a physician’s office or in an outpatient clinic. Before the procedure, intravenous pain medications are generally administered.

Vaginal ultrasound-guided aspiration is used to retrieve the eggs. To begin, your physician will insert an ultrasound into your vagina to locate the mature follicles. Then, he or she will guide a needle through your vagina and into the follicles, where the eggs are aspirated, or removed. Unfortunately, it is possible that no eggs will be retrieved.

This procedure usually takes less than 30 minutes and may be accompanied by some cramping, which usually resolves within a day. Because the ovaries are enlarged, a feeling of fullness and/or abdominal pressure that lasts several weeks is not unusual.

The retrieved eggs are examined in the laboratory, and those that are mature and of good quality will be placed in to a dish that will await fertilization by sperm in an incubator.

Your partner will be asked to provide a fresh semen specimen after 2-3 days of refraining from ejaculation, which is placed in the dish with the eggs. The sperm cells usually penetrate the egg within hours, and approximately 40% to 70% of the mature eggs will fertilize. One to six days after fertilization, one or more embryos is transferred into your uterus, a process called embryo transfer.

In some instances, the sperm and eggs are not left to fertilize on their own. Instead, a technique called intracytoplasmic sperm injection (ICSI) is used. In ICSI, a single sperm is injected directly into the egg in an attempt to achieve fertilization. ICSI is used in approximately 40% of all IVF cycles in the US and can be beneficial when the sperm and eggs are less likely to fertilize on their own.

Another technique, called assisted hatching (AH), is sometimes used. AH involves making a hole in the embryo’s zona pellucida, or “shell,” just before transfer to facilitate the hatching of the embryo. In older women or couples who have previous failed IVF attempts, AH may increase pregnancy rates.

Egg retrieval is generally a safe procedure, but it is possible that anesthesia-related problems may occur. In addition, it is possible that excessive bleeding, infection, or, rarely, rupture of an ovary may occur.

Embryo Transfer

After the embryos have developed normally, usually for 3-5 days, you will return to the clinic for embryo transfer, in which the embryos are inserted into your uterus. It is important to note that not all IVF cycles result in viable embryos, and some cycles will be cancelled before transfer. No anesthesia is necessary during embryo transfer, although some women take a mild sedative to help them relax.

Depending on a number of factors, including age, results of previous IVF attempts, embryo quality, and personal preference, you and your physician will decide how many embryos to transfer. On the day of the transfer, an embryologist (scientist that specializes in embryo development) will determine the highest quality embryos, which will be used for transfer.

To begin the procedure, an embryologist will draw one or more embryos and a small amount of the liquid into a catheter, which is a long, thin tube with a syringe on one end. Your physician will guide the catheter through your vagina and cervix, into your uterus. In an ultrasound-guided transfer, an abdominal ultrasound is used to help your physician place the embryos in your uterus.

Embryo transfer is generally painless, but may result in some mild cramping. There are no major health risks associated with embryo transfer, but the following are possible complications associated with IVF:

• Multiple pregnancy
• Ectopic pregnancy]]> (embryo develops outside the uterus)

After the procedure, you may be instructed to stay in bed for 15 minutes to six hours; then you will be allowed to go home. After embryo transfer, women are generally advised to stay on bed rest or limit activities for 1-2 days. In the days leading up to and following embryo transfer, you will most likely take progesterone supplementation by injection or suppository to maximize you chances of pregnancy.

If any embryos remain after the transfer, they may be frozen—a process called embryo cryopreservation. Frozen embryos may be stored for several years and thawed for use in future transfers. Not all embryos will survive the freezing process, and the live birth late is lower in frozen embryo transfers than in fresh ones.

You will take a blood pregnancy test about two weeks after the transfer to determine if a pregnancy has occurred.

Variations of IVF

There are several variations of IVF, including:

• Gamete Intrafallopian Transfer (GIFT) —During egg retrieval, which is performed under general anesthesia, the eggs and sperm are immediately transferred into a catheter and transferred into a fallopian tube. Since fertilization cannot be confirmed and embryo quality cannot be documented, this procedure is best when at least one fallopian tube is open and functional and sperm count is adequate.
• Zygote Intrafallopian Transfer (ZIFT) —A combination of traditional IVF and GIFT, this procedure involves fertilization in a laboratory followed by transfer into the fallopian tubes. In ZIFT, fertilization can be confirmed, but the growth of the embryos cannot be documented.

GIFT and ZIFT procedures are performed to more closely mimic the events that take place in unassisted reproduction, in which the embryo is fertilized in the fallopian tube before it moves to the uterus to implant.