In vitro fertilization
In vitro fertilization (IVF) is a treatment for infertility in which a woman’s eggs (oocytes) are fertilized by sperm in a laboratory dish. One or more of the fertilized eggs (embryos) are then transferred into the woman’s uterus, where it is hoped they will implant and produce a pregnancy.
Who should consider IVF?
IVF is usually considered by couples who have:
- Absent or blocked fallopian tubes
- Severe male factor infertility (sperm ounts or sperm motility is low)
- Endometriosis, after failing treatment with other therapies
- Infrequent ovulation, after failing treatment with other therapis
- Unexplained infertility, after failing treatment with other therapies
- Ovarian failure, although donor eggs would be required in this case
Although IVF has a high rate of success in helping couples to become pregnant, it has some disadvantages as well, including high costs, potential risks from fertility medications and invasive procedures used, as well as an increased rate of multiple gestation (ie, twins or triplets). There may also be an increased risk of some pregnancy complications, such as preterm birth, and ectopic pregnancies can occur.
The IVF procedure consists of several steps that take place over a period of weeks:
- Education of the couple about the complex steps involved in IVF, its risks and benefits, and techniques for giving injections at home.
- Stimulation of the ovaries to produce several eggs
- Retrieval of the eggs from the ovaries and obtaining a semen sample
- Fertilization of the eggs with sperm and growth of the embryos in the laboratory
- Transfer of one or more embryos into the uterus
More than one cycle of IVF treatment is often necessary before pregnancy occurs. Unfortunately, some women will not become pregnant despite multiple IVF attempts. Ovarian stimulation — The first step of the IVF procedure involves the use of fertility medications to increase the number of eggs (follicles) that develop in the ovaries and control the time of ovulation . The stimulation regimen is selected based upon the woman’s diagnosis and the physician’s preferences. Many clinicians will prescribe a birth control pill for the woman to take for one or more weeks before beginning IVF. The pill helps to prevent the woman’s body from releasing hormones that could stimulate natural ovulation.
- The woman is given injections of a medication (a GnRH agonist) that helps to prevent the body from releasing hormones that could stimulate ovulation or allow premature ovulation. This medication is started approximately one week after starting the birth control pill , or on the second day of the cycle.The injection can be given under the skin in most cases and is not painful.
- The woman is asked to report on the first or second day of menstrual bleeding to schedule an appointment for blood tests and an ultrasound. The first day of menstrual bleeding is considered day one of the cycle.
- On day 1 or 2, a pelvic ultrasound to evaluate ovaries, and blood testing to measure hormone levels is done. If these tests are OK, injections with FSH to stimulate the growth of egg follicles is started.
- After a few days of injections, a pelvic ultrasound to measure follicle growth, and a blood test to measure hormone levels are done. Depending upon the results of these tests, the dose of FSH may be increased or decreased. Blood testing and pelvic ultrasound may be repeated several times during a cycle.
- In some cases, a class of medication called a GnRH antagonist will be recommended instead of the GnRH agonist. In this case, stimulation with FSH is started immediately after stopping the birth control pill and the antagonist is added once the follicles have reached a certain size (often around 14 mm). This medication helps to prevent premature ovulation.
The goal of stimulation is to have at least two follicles that are approximately 15 to 18 mm in size. When blood testing and ultrasound measurements show that the follicles are “ready”, an injection of hCG to trigger ovulation is given. hCG stands for human chorionic gonadotropin. hCG is usually injected under the skin at a particular time in the evening. This allows the follicles to be ready for egg retrieval during a window of time, approximately 36 hours later. Side effects of treatment — FSH injections do not cause side effects directly. However, the ovaries become enlarged during treatment, which can cause abdominal swelling and discomfort, and in more severe cases, nausea or even vomiting. Ovarian hyperstimulation syndrome (OHSS) is a condition in which the side effects of ovarian enlargement and abdominal swelling become extreme. The woman may develop severe abdominal pain, vomiting, and if untreated, blood clots in the legs or lungs and fluid imbalances in the blood. Mild forms of OHSS occur in 2 to 6 percent of women undergoing ovulation induction for IVF. Severe cases of OHSS occur in approximately 1 percent of cases. The risk of OHSS can be reduced by canceling the IVF cycle when blood estrogen levels become too high or there are too many follicles seen on ultrasound.
The IVF cycle may be cancelled before hCG is given or after the oocyte retrieval. If the cycle is cancelled after oocytes are retrieved, they are often fertilized and cryopreserved for use in a subsequent cycle. Because symptoms of OHSS peak approximately three to five days after egg retrieval, the decision to freeze all embryos may be delayed until this time. Egg retrieval — Approximately 32 to 36 hours after injecting hCG, a procedure is performed to retrieve the eggs. The physician inserts an ultrasound probe into the vagina and then uses a needle to withdraw the egg from each follicle. The procedure takes approximately 15 to 30 minutes, depending upon how many follicles are present. This is generally done while the woman is sedated. Serious complications of oocyte retrieval are uncommon, but side effects such as pelvic cramping, light bleeding, and vaginal discharge often occur. If these problems are persistent or become severe, it is important to call a healthcare provider as soon as possible. Abdominal swelling and discomfort may also be signs of early ovarian hyperstimulation syndrome (OHSS)
After the retrieval, the woman will be monitored in a recovery area for a few hours and then allowed to go home.
After the retrieval procedure, the eggs are combined with sperm in a laboratory dish so they will fertilize. In general, approximately 50 percent of oocytes become fertilized. In cases of severe male factor infertility, fertilization is achieved by intracytoplasmic sperm injection (ICSI). ICSI is an option for all men with severe male factor infertility, regardless of their sperm count. Only mature oocytes can be injected. Fertilization rates with ICSI range from 50 to 70 percent.
Approximately two to five days after the retrieval, one or more eggs that have been fertilized (embryos) are placed in the woman’s uterus using a thin, flexible catheter inserted through the cervix. Some women have mild cramping during the procedure. Anesthesia is not usually needed for this procedure. Following the transfer procedure, the woman is generally encouraged to rest at home for several hours. Although studies do not show that rest increases the chance of pregnancy, many women prefer not to resume their normal activities immediately. Most clinicians will prescribe a progesterone medication to improve the chances that the embryo will implant inside the uterus. This medication is started either on the day of retrieval or the day of transfer. There are several ways to administer progesterone, with the most common being a vaginal gel or suppository, or an injection given into a muscle.
How many embryos to transfer?
The number of embryos transferred depends upon the woman’s or couple’s preferences, the previous history of pregnancy and miscarriage, the woman’s age, and the quality of the embryos. Younger women (under age 35) in their first cycle of IVF are often encouraged to have only one or two embryos transferred. If multiple attempts of IVF are not successful in achieving pregnancy, a physician may recommend transferring more than one or two embryos to increase the chances of pregnancy. However, this may also increase the risk of multiple gestation (twins, triplets). The rate of implantation is lower among women over age 40 years. As a result, more embryos are often transferred in these women. However, older women who are receiving eggs from younger donors (eg, donor eggs) have a rate of implantation similar to that of younger women, and are generally advised to transfer no more than one or two embryos.
Storing Unused Embryos
Embryos that are not transferred may be stored by freezing them (called cryopreservation). Because some embryos do not survive the thawing process, the chances of a successful pregnancy using frozen embryos is usually lower than that when using fresh embryos.
The embryos may be cryopreserved for an unlimited period of time. However, most couples are encouraged to choose one of the following options:
- Transfer the embryos at a later date
- Donate them for research or for use by another couple (“embryo adoption”)
- Dispose of the embryos
Testing for pregnancy after IVF
Blood testing — Approximately two weeks after the embryo transfer, a blood or urine test for hCG, the hormone that signifies pregnancy, can be done. Home urine pregnancy testing is not as sensitive for detecting an early pregnancy as blood testing.
- If the first blood hCG level is < 5 IU/L, the woman is not pregnant.
- If the first hCG level is >10 IU/L, the test is usually repeated 48 hours later to confirm that the levels are increasing. The hCG level should approximately double every 48 hours during the first 21 days after embryo transfer.
- If the second hCG level does not double or decreases, the blood test may be repeated again 48 hours later. Depending upon the situation, there is a possibility that the pregnancy is not viable. hCG levels do not increase or begin to decline when the pregnancy is not progressing normally.
If the hCG levels increase as expected, a pelvic ultrasound may be done three to four weeks after the transfer. At this time, it is usually possible to see a gestational sac inside the uterus. The gestational sac is a fluid-filled sac containing the embryo. At five to six weeks of pregnancy (four to five weeks after the transfer), the yolk sac is usually visible. The yolk sac provides nourishment to the embryo early in development. A heart beat is usually visible by 6 to 6.5 weeks of pregnancy (4 to 4.5 weeks after the transfer).
When IVF is not successful
In vitro fertilization has a reasonable rate of success in most cases. Overall, approximately 27 percent of IVF cycles will end in a live birth, and the cumulative chances of success are higher when more than one cycle of IVF is done However, an individual’s chance of success depends on several factors, including the woman’s age, cause of infertility, and treatment approach. For example, the live birth rate for each IVF cycle started is approximately 30 to 35 percent for women under age 35; 25 percent for women ages 35 to 37; 15 to 20 percent for women ages 38 to 40; and 6 to 10 percent for women over 40. It can be difficult to deal with the emotional highs and lows of infertility treatment. This is especially true if the woman (and her partner) have been trying to conceive for a long time, if treatment is not covered by insurance, or if there are any underlying problems in the couple’s life (eg, medical, family or partner, job, financial).