In Vitro Fertilization
Basics
In vitro fertilization (IVF), translated literally, means “fertilization in glass.”
An “IVF cycle” is a single attempt of IVF and includes the following steps: pituitary down-regulation, ovarian stimulation, egg harvesting and embryo transfer. Each of these steps is explained later. (See Lupron Down Protocol (pdf), Microdose Agonist Protocol (pdf), and Antagonist Protocol (pdf)).
To date, IVF offers most couples their best chance of conception. IVF has been used to successfully treat a wide array of fertility problems including blocked fallopian tubes, low sperm count, polycystic ovary syndrome, endometriosis and unexplained infertility.
During IVF, the ovaries are stimulated with medication and eggs are harvested from a woman’s ovaries, placed in a laboratory dish, inseminated with sperm, and then observed to see which eggs successfully fertilize and become embryos. Over the next few days, the resulting embryos are observed to see which have the best chance of resulting in pregnancy.
One to five embryos are then placed back into the uterus, depending on the woman’s age, prior IVF cycle outcomes if applicable, and embryo quality (see table of ASRM Embryo Transfer Guidelines). The chance of success depends on many factors including: age of the female partner, prior pregnancy history, cause of infertility and ovarian reserve.
If a woman has excess embryos, these may be frozen for future use.
From the time a woman decides she wants to do IVF, the entire process takes 5-7 weeks until completion.
Why IVF Increases Your Chances of Pregnancy:
IVF maximizes pregnancy rates by using normal human biology to our advantage. In general, women are born with around 2 million eggs. Most of these eggs are in hibernation within the ovary. Every month, a batch of these eggs comes out of hibernation. Typically, one egg from this batch ovulates while others die. Unfortunately, there is no guarantee that the best quality egg is the one that will ovulate.
The reason most of the eggs die is because there is not enough follicle stimulating hormone (FSH) to support the growth of all of the eggs. One egg essentially steals the hormone and the other eggs degenerate.
By stimulating women with injections of FSH, the IVF process saves most of these eggs from being lost. Because multiple eggs are harvested and we get to select the very best embryos to place back in the uterus, the pregnancy rates are generally far higher than what occurs in a normal menstrual cycle.
What are the risks of IVF?
Most couples proceed through IVF and pregnancy without difficulty, but there are some risks associated with IVF. There are risks to the mother and risks to the baby. However, unless you have twins or other underlying conditions, your pregnancy will not be considered “high risk.”
Risks to the mother:
Multiple Gestation
Multiple gestation is the most common of all IVF related risks. Twins occur in 20-30% of successful IVF cycles. Higher numbers of babies can also occur. Multiple gestation places the babies at risk for preterm delivery, and mothers are more likely to have complications of pregnancy including preeclampsia, diabetes, blood clots, preterm labor, cesarian section and postpartum hemorrhage. We adhere closely to the American Society for Reproductive Medicine (ASRM) Guideline on number of embryos to transfer, thus maximizing chances of successful pregnancy while safely limiting the possibilities of twins and higher order gestations (3 or more babies).
Ovarian Hyperstimulation Syndrome (OHSS)
OHSS is a condition in which the ovaries get very large and filled with fluid in response to the gonadotropin medications. Factors are released by the ovaries which cause a woman’s blood vessels to leak fluid into the pelvis. In mild forms of OHSS, a woman may have symptoms of bloating and pelvic discomfort; this occurs in 10-20% of gonadotropin cycles and resolves quickly after treatment ends. In severe cases, a woman may have difficulty urinating, become dehydrated, gain weight rapidly, and have organ complications involving the lungs, kidneys and liver; this is rare, occurring in 1% of cycles. These women may require hospitalization. Women are at increased risk of blood clots when they have OHSS, and any symptoms of leg pain or difficulty breathing should be reported to your physician immediately.
Risk factors for OHSS include:
- Young age
- Low body weight
- Polycystic ovary syndrome (PCOS)
- Higher doses of gonadotropins
- High absolute or rapidly rising estrogen levels
- Previous episodes of OHSS
- High number of developing follicles
There have been cases of death reported as a result of complications from OHSS. Fortunately, severe cases of OHSS are rare. By closely monitoring your response to gonadotropins, your physician can markedly decrease your chances of developing OHSS. However, if you are at risk, your physician may cancel your stimulation for your safety.
Among women who conceive, symptoms of OHSS may worsen at the time pregnancy is detected and may take longer to completely resolve.
Ectopic pregnancy
Ectopic (outside of the uterus) pregnancies usually involve pregnancies that have implanted in the fallopian tubes or less commonly in the cervix, ovary or pelvic cavity. Ectopic pregnancies occur in 1-2% of all pregnancies, but are more common during fertility treatments including IVF due to the fact that we are often transferring more than 1 embryo and the embryos may migrate back into the tubes. Ectopic pregnancy may seriously threaten the health of the mother if undiagnosed or untreated; therefore, severe abdominal pain should be reported to your physician. Treatment involves medical or surgical therapy.
Adnexal Torsion (Ovarian Twisting)
This is a rare complication (< 1%) of cycles. As the ovaries enlarge, they may twist, cutting off their blood supply and causing engorgement, severe abdominal pain, nausea and vomiting, and sometimes low grade fevers. If untreated, loss of the ovary may occur. Treatment involves surgical untwisting of the ovary.
Egg Retrieval Risks
Internal bleeding is a rare complication. However, any time a needle is placed into the pelvis (such as with an egg retrieval) blood vessels can be lacerated. Usually this bleeding would spontaneously resolve but in extremely rare cases (<1%) surgical therapy may be required to stop internal bleeding.
Damage to other surrounding organs including the bowel and bladder are possible, though very rare. Pelvic infection is also rare, though may occur. It occurs more commonly among women with ovarian endometriomas that are drained at the time of egg retrieval. Finally, pelvic discomfort is common after the procedure.
Ovarian Cancer
Gonadotropins are not thought to increase the risk of ovarian cancer.
Resource Links:
- Use of fertility drugs and risk of ovarian cancer: Danish population based cohort study
(BMJ Medical Journal)
- Fertility Drugs and Ovarian Cancer Not Linked, Study Says
(New York Times)
The exact risks to children conceived after IVF are difficult to study and quantify. While some studies illustrate a higher risk to children born after IVF cycles, it is possible that these risks are due to the underlying state of infertility and not exactly to the IVF treatment itself.
The most common risk to babies born after IVF relates to prematurity if the cycle results in multiple gestation; this is the most common complication of pregnancies derived by IVF. Other complications include a possible small increase in the risk of birth defects and pregnancy complications as described below.
Multiple Gestation Resulting in Preterm Birth
The degree of impairment due to preterm birth is completely related to the timing of the birth; children born more premature have more severe complications and greater risk of long-term impairment. Prematurity may result in complications involving:
- Pulmonary immaturity and difficulty breathing
- Cerebral hemorrhage (bleeding in the brain, possibly causing long term handicaps)
- Intestinal infection and inflammation (necrotizing enterocolitis)
- Visual impairment including blindness
- Poor growth
Birth Defects
The baseline risk of a major birth defect for all children in the United States is 3-5%. IVF pregnancies have an approximate 1-2% higher chance of having a major birth defect (predominately cardiovascular and musculoskeletal abnormalities). The cause for this increase is unknown. Theories include the underlying cause of infertility predisposes to abnormalities, the IVF treatment may pose risk, or perhaps pregnancies derived by IVF are scrutinized more closely and therefore people are more likely to detect abnormalities in this population (ascertainment bias).
Recent attention has focused on the increased incidence of gene imprinting disorders (examples include Angelman syndrome and Beckwith-Wiedemann syndrome) after IVF cycles; however, it is unclear whether these disorders are present in the infertile couple or are induced by the IVF treatment. Abnormal gene imprinting may lead to aberrant gene expression, and subsequent birth defects or cancer later in life. Theories of how IVF may induce such gene changes include changes induced by the extended embryo culture. However, it is important to remember that there is no conclusive evidence that IVF causes these disorders, and overall an exceedingly small number of infants are actually affected with these disorders.
Infants born as the result of ICSI IVF cycles have been shown in some studies to also have an increased risk of birth defects, particularly involving the male genitalia, with a condition known as hypospadias (this involves an abnormal location of the urethra on the penis, and is usually easily corrected in childhood with urologic surgery). Again, this risk is not dramatically higher than the general population and a small number of infants are actually affected with these disorders. Infants born after ICSI cycles also demonstrate a higher incidence of karyotype (number of chromosomes) disorders. However, karyotype abnormalities are more common among men with abnormal semen characteristics that require ICSI for successful fertilization. As most men with such sperm abnormalities are otherwise completely healthy and normal, it is impossible to know if such inherited genetic abnormalities pose any health risks to offspring. Continued research over time may help elucidate this controversy.
Pregnancy Complications to the Baby
Pregnancies derived by IVF more frequently have complications compared to pregnancies conceived spontaneously. Controversy exists regarding the cause of these complications, the underlying cause of infertility itself or the fertility treatment. Complications include slight increases in:
- Perinatal mortality
- Low birth weight (after birth, growth and intelligence are normal)
- Preterm delivery
Other conditions which may occur more commonly after IVF cycles include gestational diabetes, pre-eclampsia, and placenta previa, all of which may pose risks to the fetus. However, current data is unclear as to the cause and prevlanece of these complications among infertile women after IVF.
In summary, research demonstrates a small but real increase in risk of adverse outcomes during pregnancy after IVF. It is important to remember that these risks are small and that the development of IVF and ICSI has allowed countless couples to conceive and deliver healthy children who otherwise would never have been able to have their own children.