In vitro fertilization (IVF) is a procedure that helps individuals or couples get pregnant. An IVF procedure involves several steps, known as an “IVF cycle.” First, a patient takes fertility drugs to stimulate their ovaries to produce many eggs. The eggs are then retrieved from the ovaries. (In some cases, eggs from a donor may be used, so these first steps may be omitted.)

The eggs are then fertilized with sperm (in a petri dish) in a laboratory. One or more fertilized eggs—or embryos—are then transferred to a patient’s uterus. Pregnancy occurs when the embryo attaches to the lining of the uterus. The embryo develops and grows over the next nine months, until a baby is born.

IVF has been used successfully for over four decades. Over 10 million babies have been born from IVF around the world. Today, there are over 500,000 IVF deliveries every year worldwide. In 2018, IVF accounted for about 2% of all births in the United States.

The likelihood of having a baby with IVF is related to the age of the patient (or donor). The number and quality of eggs tend to be higher in younger patients. Sometimes, patients must undergo more than one cycle to have a baby. In some cases, however, they do not get pregnant, even after several IVF cycles.

“The first baby born through IVF is not even 50 years old,” says Emre Seli, MD, medical director of the Yale Fertility Center and the Yale In Vitro Fertilization (IVF) Program. “Since then, we have learned how to freeze embryos and eggs, and perform diagnostic procedures in the embryo. Every day, a new procedure is being offered to women and men with infertility.”

During natural conception, an egg is fertilized by sperm. Usually, during an individual’s menstrual cycle, a single egg is released from one of the ovaries. The egg then travels to one of the fallopian tubes. Sperm enters the vagina and travels through the cervix and uterus, then to a fallopian tube, where it fertilizes the egg. Over the next three to five days, the fertilized egg moves to the uterus and attaches to the endometrium (the lining of the uterus), where it grows and develops until the birth of a baby.

In IVF, an individual’s eggs are fertilized with sperm “in vitro.” In vitro is a Latin phrase that means “in glass.” In IVF, it means that fertilization occurs outside the body, in a laboratory dish under controlled conditions. IVF is the most common type of assisted reproductive technology (ART).

IVF treatments can be expensive, and may include blood and imaging tests, medications, procedures for removing eggs and implanting embryos, laboratory work involved in fertilizing the eggs, and embryo storage. In the U.S., each IVF cycle costs over $15,000 on average, and some people may need to undergo more than one cycle. Often, insurance plans do not cover fertility treatments, and only some states mandate that insurance companies cover IVF treatments.

The procedure is used to help people with various forms of infertility have children, including:

• Those with blocked or damaged fallopian tubes that prevent sperm from reaching the egg or the fertilized egg from reaching the uterus
• Those with endometriosis, a condition in which endometrium-like tissue is found outside the uterus
• Those with male factor infertility due to decreased sperm count and/or motility, or abnormal sperm shape
• Those with primary ovarian insufficiency (POI), a condition in which an individual’s ovaries stop working before age 40. In POI, the ovaries stop releasing eggs or no longer release them regularly.
• Individuals who have had their ovaries removed
• Those with age-related fertility decline due to a decreased number (also called diminished ovarian reserve or DOR) or quality of eggs
• Those with unexplained infertility

IVF may also be used in other situations when fertility is not an issue, including:

• People who plan to use donor eggs to get pregnant. Candidates for egg donation include patients:
  • Who are born without functioning ovaries or who have had their ovaries surgically removed; patients with POI
  • Who are postmenopausal
  • Who have a history of recurrent pregnancy loss
  • Who have a history of failed IVF cycles and/or are poor responders to ovarian stimulation.
  
  Male same-sex couples and single males may also use donor eggs. Egg donation can be used for any clinical condition in which pregnancy is desired and the patient or their partner(s) cannot provide eggs for fertilization, or when eggs are available but unacceptable for use due to certain chromosomal and genetic conditions.
• People who intend to use a gestational surrogate to carry and deliver their baby. Candidates for using a gestational carrier include patients:
  • Who were born without a functioning uterus or who have had their uterus surgically removed
  • Who have acquired disorders that make their uterus unsuitable for pregnancy, such as extensive fibroids, adenomyosis, or Asherman’s syndrome
  • Who have a medical condition that puts them at significant medical risk if they become pregnant
  • Who have a history of recurrent pregnancy loss
  
  Other candidates for gestational surrogacy and egg donation are males choosing parenthood through assisted reproduction. The use of a gestational carrier is acceptable for any clinical condition in which pregnancy is desired and the patient is unable to carry the pregnancy.
• Preimplantation genetic testing (PGT), which allows embryos produced by IVF to be genetically tested to identify genetic abnormalities before being transferred to an individual. This procedure allows the selection of embryos for transfer that do not have known genetic abnormalities, thereby lowering the risk of passing genetic conditions to a child. PGT can also be used to allow people to have children with specific characteristics, such as sex.

IVF involves several steps that take two or more weeks to complete. Together, these steps are called an IVF cycle. They include:

Step 1. Ovarian stimulation. Normally, a single egg is released from one of the ovaries during a menstrual cycle. In IVF, however, the patient takes fertility drugs that increase the number of eggs their ovaries produce. This allows doctors to collect many eggs from which they can generate embryos and select ones with the best chances of pregnancy, improving the chances of a live birth.

Different fertility drugs are used in a specific order at this step of IVF:

1. Drugs that stimulate the development of multiple follicles in the ovaries. A follicle is a sac that contains an egg. These drugs include follicle-stimulating hormone (FSH), human menopausal gonadotropin (hMG), or both.
2. Drugs that prevent premature ovulation (the release of eggs). Before eggs can be collected and then fertilized in a laboratory, they must first mature in the ovaries. To ensure that the eggs are sufficiently developed and have reached a certain size before they are retrieved, patients take drugs that prevent the early release of eggs, thereby providing them time to mature in the ovaries. Drugs at this step of the procedure may include gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists, and progestins.
3. Drugs that trigger ovulation. When the eggs have sufficiently matured, patients take drugs, such as human chorionic gonadotrophin (hCG) and/or GnRH agonists, that trigger the ovaries to release the eggs.

Some of the medications used as part of ovarian stimulation need to be self-injected over the course of a few days.

During this stage, transvaginal ultrasound and blood tests are used to monitor the growth of eggs and measure hormone levels.

IVF can also be performed without ovarian stimulation. In these cases, typically a single egg is retrieved from an ovary, rather than multiple eggs. This type of IVF is called natural cycle IVF or unstimulated IVF. The pregnancy rate from natural cycle IVF is lower than IVF performed with ovarian stimulation.

Step 2. Egg retrieval. About 36 hours after ovarian stimulation, the eggs are retrieved from the ovaries using a procedure called follicular aspiration. Guided by transvaginal ultrasound, the provider inserts a needle through the vagina and into the ovaries and removes eggs from each follicle. Rarely, the eggs are removed via the abdominal wall. Anesthesia, such as conscious sedation or general anesthesia, is used to manage pain during egg retrieval. Egg retrieval usually takes 15 to 30 minutes.

Step 3. Fertilization. After the eggs are removed from the ovaries, they are mixed with sperm from a partner or donor in a petri dish for fertilization. Fertilization occurs when a sperm penetrates an egg. Typically, around 65% to 80% of the eggs are fertilized in IVF. In some cases, such as male factor infertility, the health care provider may also inject sperm directly into the egg in a procedure called intracytoplasmic sperm injection (ICSI) to improve the chances of fertilization.

Step 4. Embryo culture. After fertilization, the eggs divide and become embryos. The embryos are monitored and grown in a laboratory for around two to five days.

Step 5. Embryo transfer. Embryo transfer may be fresh (in the same cycle as egg retrieval) or frozen (in a subsequent cycle). In contemporary IVF practice, many physicians and patients prefer freezing all embryos and performing frozen embryo transfer (FET) in the cycle that follows (or later). This approach allows the patient to recover from the effects of medications used for egg retrieval and from the physical discomfort of egg retrieval, decreases the risk of ovarian hyperstimulation syndrome (OHSS; more on that below), and allows preimplantation genetic testing.

When fresh transfer is performed, one or more embryos are placed in an individual’s uterus five days after fertilization, with the aim of initiating pregnancy. After embryo transfer, an individual may be prescribed progesterone, a hormone that increases the thickness of the uterine lining, thereby improving the chances that the embryo will attach to it and grow. After fresh embryo transfer, progesterone is usually taken for five to seven weeks.

When FET is performed, patients receive hormonal supplementation or use their natural cycle to time the transfer to the appropriate stage when their uterus is ready to receive the embryo(s).

To place the embryo(s), a physician inserts a catheter—a thin, flexible tube–that contains the embryos into the vagina, through the cervix, and into the uterus.

In most cases, only one embryo is transferred. Less commonly, two or more are transferred. Transferring two or more embryos may increase the chances of pregnancy, though it also increases the chances of having twins, triplets, or, in some cases, even more children. Multiple pregnancies are associated with a number of complications in the newborns, including preterm birth, and neurologic and respiratory disorders.

Embryos that are not transferred can be frozen and stored indefinitely. This is known as cryopreservation. The frozen embryos can be transferred at a future date or donated to help others get pregnant or for research.

Around eight to 12 days after the embryo transfer, those undergoing IVF treatment should take a blood test to measure the blood level of hCG, a hormone produced during pregnancy—this will confirm pregnancy. If hCG blood testing indicates pregnancy, it will be followed by periodic blood tests to monitor the early pregnancy.

Prenatal care typically begins around six to 10 weeks into a pregnancy. This care usually involves periodic blood and imaging tests, as well as physical exams to detect any complications that may arise.

IVF comes with a risk of certain complications due to ovarian stimulation and retrieval of eggs, including:

• Ovarian hyperstimulation syndrome (OHSS), a condition in which the ovaries become overstimulated due to the use of fertility medications to stimulate the development of eggs. In OHSS, the ovaries swell and leak fluid into the abdominal cavity and chest area. Rarely, OHSS can be life-threatening.
• Blood clots
• Infection
• Abdominal bleeding
• Twisting of the ovary and, in some cases, the fallopian tube, disrupting blood flow
• Allergic reaction to medications used in IVF
• Anesthesia complications

The risk of some pregnancy complications may be increased in patients who conceive with IVF, including:

• Multiple pregnancy risk, most commonly due to the transfer of more than one embryo.
• Disorders of high blood pressure during pregnancy, including eclampsia/preeclampsia and gestational diabetes
• Ectopic pregnancy, when an embryo attaches somewhere other than the lining of the uterus; it affects around 2% of people undergoing IVF.
• Heterotopic pregnancy, when one embryo attaches to the lining of the uterus and another embryo attaches to a site outside the uterus; it occurs in 1 in 100 to 1 in 1,000 pregnancies from IVF.
• Placenta previa, when the placenta entirely or partially covers the opening of the cervix
• Placental abruption, when the placenta detaches prematurely from the wall of the uterus

IVF may also increase the risk for certain complications for the fetus and baby as well, including low birth weight and premature birth.

The outcome for people who undergo IVF may vary based on a number of factors, including the age of the individual whose eggs are used (in the case of donor eggs), previous pregnancy outcomes, and the cause of infertility, among others.

Overall, the chances of a successful outcome are increased further when two or more embryo transfer cycles are completed. In general, younger people have higher success rates than older people.

According to the Society for Assisted Reproductive Technology, in the U.S. in 2021, nearly 45% of embryo transfers in people under 35 years of age resulted in live births for each egg retrieval cycle. Among those aged 35-37, just over 32% led to live births. For people between ages 38 and 40, about 20% resulted in live births, and for those between ages 41 and 42, the rate dropped to just under 10%. For those over age 42, the rate fell to slightly under 3%.

For people planning to undergo IVF, the Centers for Disease Control and Prevention (CDC) provides a free online tool for estimating IVF success.

“The Yale Fertility Center stands as a beacon of expertise in infertility management, led by a faculty that has made profound contributions to advancing the field. From identifying biomarkers of ovarian reserve to pioneering genetic diagnostic tests, our team's research has been instrumental in defining reproductive disorders," says Dr. Seli. "At Yale, we embrace a collaborative, team-based approach, uniting physicians, nurse practitioners, and counselors to deliver personalized, state-of-the-art care. We integrate the latest medical innovations and IVF technology into our practice, tailoring treatments to meet the unique needs of each patient. Furthermore, we're actively engaged in ongoing research endeavors focused on infertility to deepen our understanding of its underlying mechanisms and enhance treatment options."