Who is a candidate for in vitro fertilization?

Couples who have been able to conceive naturally may be advised to attempt IVF in order to increase their chances of having a baby. Many of these couples first try other fertility treatments, such as intrauterine insemination (IUI) or timed intercourse with the aid of ovulation predictor kits and/or ovulation medication.  Same-sex couples or single people may also use IVF to have a baby.  

Female-factor infertility is a common reason that people consider IVF.ⁱ Some of these factors include fallopian tube damage, endometriosis, inability to ovulate, advanced age, and/or diminished ovarian reserve. For those with male-factor infertility, IVF, often with the use of intracytoplasmic sperm injection (ICSI), can assist when there is a decreased sperm count, poor motility of sperm, and abnormal shape or size of sperm. It is also a choice of those with unexplained fertility problems, which affects about one-third of women who seek fertility treatments.  

IVF can also be helpful when one or both parents have a genetic disorder or are carriers for the same condition—even if they could conceive without intervention. Preimplantation genetic testing (PGT) can help parents prevent passing on these conditions.  

There are two types of genetic testing for this indication: preimplantation genetic testing for monogenic disorders (PGT-M), which tests for inherited conditions caused by a single gene, and preimplantation genetic testing for structural rearrangements (PGT-SR), which can identify structural chromosomal abnormalities. A third type of PGT called preimplantation genetic testing for aneuploidies (PGT-A) may be used by anyone undergoing IVF to help identify embryos that have a normal number of chromosomes (“euploid”).    

The chances of success with IVF depend on a number of factors, including age, overall health, and the cause and duration of the fertility issues. According to the Centers for Disease Control and Prevention, in 2018 1.9 percent of babies born in the US were conceived using assisted reproductive technologies such as IVF.ⁱⁱ  

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What is the IVF process?

IVF can be a long process involving numerous steps, many of them tied to hormonal cycles.ⁱⁱⁱ  

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Preparation and priming

In preparation for IVF, doctors will order a series of tests and examinations.  

To assess ovarian reserve, which helps estimate the quantity of eggs remaining in the ovaries, doctors will measure the level of anti-müllerian hormone (AMH). AMH plays an important role in regulating the ovarian follicle production process. There is an established relationship between AMH levels and follicle count, pregnancy rate, and live birth rate.^iv  

To further understand a patient’s ovarian reserve, doctors may perform an antral follicle count (AFC); follicles are the fluid-filled sacs within the ovaries that contain eggs. This procedure reveals the number of follicles during a transvaginal ultrasound that images the ovaries. AMH and AFC ovarian reserve testing are often used together to predict ovarian reserve.^v  

Blood tests may be used or required by insurance to assess follicle-stimulating hormone (FSH), which may help in predicting response to ovarian stimulation drugs during IVF.  Doctors may sometimes also test other hormone levels that could impact the IVF process, including luteinizing hormone (LH), thyroid-stimulating hormone, prolactin, and progesterone.  

A complete workup will include an evaluation of the woman's uterus and its endometrial lining. This may involve a saline infusion sonohysterogram (SIS), or a type of ultrasound, and a hysterosalpingogram (HSG), which is an X-ray of the uterus.  

Around this time in the process, a sperm sample is taken from the male partner for testing.  

To prepare for IVF, doctors may prescribe hormones such as birth control pills,^vi growth hormone, estrogen, testosterone (such as AndroGel), or a gonadotropin-releasing hormone (GnRH) agonist (such as Lupron) up to a few menstrual cycles before IVF. Some people may also be told to take natural supplements during the cycles before IVF.  

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Ovarian stimulation ("stimming")  

During a typical menstrual cycle, a woman’s body produces a single egg. However, during the IVF process, multiple eggs are desirable in order to increase the chances of creating a viable embryo. Ovarian stimulation is the process of using fertility drugs to stimulate the ovaries to produce multiple eggs in a single cycle.  

During the stimulation phase, doctors will prescribe fertility medications called gonadotropins. These contain hormones such as FSH and LH that are found in the body naturally in order to stimulate follicle growth and ovulation. They are generally taken by self-administered injection.  

There are different protocols used for ovarian stimulation, and doctors select one based on a patient’s individual factors.^vii The two main types of protocols are agonist and antagonist. Typical stimulation drugs include Gonal-F (FSH), Menopur (FSH/LH), Lupron (GnRH agonist) and Cetrotide (GnRH antagonist).  

An agonist protocol uses Lupron to slowly suppress the pituitary, after which ovarian stimulation proceeds. Conversely, an antagonist protocol involves much quicker pituitary suppression, making this a shorter process overall and reducing the chance of ovarian hyperstimulation syndrome (OHSS), a rare but dangerous condition whereby the ovaries swell as an exaggerated response to the fertility medication.^viii While there is no difference in live birth rate between protocols, patients may respond better to one over the other and have fewer side effects based on which regimen they are following.  

In addition to the most frequently-used agonist and antagonist protocols, there are several others that may be indicated depending on a woman’s individual circumstances. The duo stim protocol stimulates egg production twice in a single cycle, during both the follicular and luteal phases. Mini IVF is a protocol involving lower doses of medications, while the flare protocol, which involves taking lower doses of a GnRH agonist, is typically used when a patient does not respond well to other protocols.  

During stims, patients’ cycles are monitored frequently using bloodwork to measure estrogen, LH, and serum progesterone (P4), as well as ultrasounds to monitor follicle count and endometrial lining. Estrogen and follicle counts are monitored to ensure that patients are responding to medications and to determine when to proceed to the next step in the protocol. LH and P4 levels are sometimes tracked to ensure that patients are not ovulating early.  For those planning a fresh embryo transfer, the endometrial lining is measured to ensure adequate thickness and that it has a trilaminar structure, which is ideal for embryo implantation.    

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Triggering  

Triggering is when doctors induce maturation of the oocytes—mature eggs are needed before retrieval, as only mature eggs can be fertilized.  

Once the follicles reach an adequate size, usually 14 to 22 millimeters, patients will inject a trigger medication that will prompt the eggs to undergo maturation, the final step before ovulation. The egg retrieval will be scheduled for about 34 to 36 hours later, to retrieve the eggs prior to actual ovulation.  

The trigger medication is typically a human chorionic gonadotropin (HCG) medication such as Pregnyl or Ovidrel. Alternatively, a GnRH agonist (such as Lupron) may be used to trigger; this is commonly done when there is a high risk of OHSS. Many women take both of these triggers, called dual trigger, to trigger maturation.  

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Egg retrieval

Egg retrieval, also known as follicular aspiration or oocyte pick up, is a surgical procedure whereby a needle is inserted into the ovary (typically through the vagina) in order to suction out eggs for fertilization. This roughly half-hour procedure is performed under general anesthetic, or narcotic conscious sedation, depending on the clinic’s procedures.  

There is some debate about the optimal goal, or a desirable number of eggs to obtain during retrieval. A 2018 study of nearly 14 500 women under 40 published in Fertility and Sterility found that the mean number of eggs retrieved during an IVF cycle was 12.3 for those who eventually gave live birth, and 8.9 for those who did not end up giving birth.^ix  

A study out of Sweden in 2018, meanwhile, looked at 39 387 patients undergoing numerous cycles of IVF and found that retrieving 18 eggs offered the optimal balance between live births and minimal adverse outcomes. The study also reported a 30.3 percent live birth rate for a patient of 34 years old when using 11 eggs or more.^x  

Some patients may freeze their eggs at this point in a process known as egg cryopreservation.  

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Fertilization  

Once the eggs have been retrieved, they are combined with sperm—typically a freshly collected or previously frozen sperm sample from a male partner, or from donor sperm.  

A process called intracytoplasmic sperm injection (ICSI) can be used to inject the sperm directly into the egg, and is often used in cases of male factor infertility or when fertilization rates are lower than expected.^xi Some clinics use ICSI for all patients. While the ICSI process may increase fertilization rates, it does not guarantee it.  

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Embryo culture  

Embryo culture is the process of monitoring the inseminated eggs as they develop into embryos. Doctors examine the eggs for evidence of fertilization and evaluate their appearance and growth as they mature.  

During this growth process, once the sperm and the egg have combined into a fertilized egg, the newly formed cell is called a zygote. The zygote then begins to divide, first into two cells, and then four, eight, and so on. A blastocyst is formed five to six days after fertilization; it contains around 100 to 150 cells.^xii The inner cell mass will later become the embryo, and an outer layer of cells —called the trophoblast—later becomes the placenta.  

Embryo transfer  

Embryo transfer involves placing the embryos into the uterus of the parent or gestational carrier.  

The process entails inserting a tube into the woman's uterus through the vagina and passing the embryo or embryos through the tube. A woman becomes pregnant when one or more blastocysts implant into the lining of the uterus. Pregnancy is determined with blood tests (Beta-hCG), typically administered 9-12 days after the procedure.  

The decision of how many embryos to transfer is made by the doctor and patient in advance. If a patient has surplus healthy, potentially viable unused embryos, they can be frozen for future transfers — that patient will not need to undergo the stimming process or retrieval again in order to use these embryos to potentially achieve a pregnancy.  

Some clinics recommend a “freeze-all” strategy, in which all embryos are frozen and transferred after the next menstrual cycle instead of immediately. There are several reasons for this: ovarian stimulation can impact the lining of the uterus and lead to lower pregnancy rates; ovarian simulation may cause the endometrial receptivity to be out of sync with embryo development (in cases of premature luteinization); some patients prefer to have a “break” after going through stimulation and retrieval; the embryos will be undergoing genetic testing.^xiii When frozen embryos are used, this is referred to as a Frozen Embryo Transfer (FET).

A 2020 review found that a freeze-all strategy led to a higher cumulative live birth rate among women who had produced over 10 eggs.^xiv However, for women who do not produce as many eggs, fresh transfers led to a higher live birth rate when compared to those receiving frozen embryos, according to a 2018 report.^xv

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How to choose an IVF clinic?

Those who are considering IVF should spend time researching fertility clinics and physicians. It may be beneficial to schedule consultations with a few different clinics before selecting one.  

The cost of IVF and the availability of publicly-funded care and private insurance coverage vary greatly. The clinic should provide potential clients with a breakdown of all of the different costs for every stage of IVF. Some clinics will offer payment plans.  

Fertility clinic staff should be able to answer important questions such as:  

• Are there particular protocols that the clinic or doctor prefers?  
• Does the clinic provide a one-doctor-per-patient model or a rotational-doctors-per-patient model? Will you see doctors or nurse practitioners for consultations? Who will perform the ultrasound monitoring, retrieval(s), transfer(s)?
• Does the clinic have cut-offs or exclusions regarding age or other factors?  
• Can more than one embryo be transferred (for advanced age or poor prognosis)?  
• Is the doctor for or against PGT? If PGT-A tested, what occurs to the mosaics or abnormal embryos — are doctors willing to transfer them?  
• What are the clinic’s processes for the embryos after treatments cease? Will they destroy or donate to other families (with permission)?  
• Are there certain days of the week where retrievals and transfers are not performed? Does the clinic “batch” patients?
• What is the fertilization rate of the IVF laboratory?
• What is the rate of blastocyst formation for the IVF laboratory?  

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What are the risks of IVF?

IVF is a medical procedure and, as such, there are risks associated with the process.  

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Multiple pregnancy

The risk of multiple pregnancy has traditionally been the biggest health risk of fertility treatments.^xvi It has been estimated that traditionally, roughly 30 percent of IVF pregnancies result in multiple births,^xvii though more recently this figure has been reduced to around 10 percent in some clinics.^xviii This is largely due to single embryo transfer (SET) becoming the preferred practice; selective reduction may also be used to reduce the number of embryos, particularly if there is concern regarding the health of the woman or the developing fetuses.  

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Ectopic pregnancy

An ectopic pregnancy occurs when the implanted embryo attaches to somewhere other than the uterine lining, most often in the fallopian tubes. An ectopic pregnancy can cause maternal death if it is not detected and treated and/or removed.  

Previously, IVF was associated with a significantly higher rate of ectopic pregnancy compared to natural conception.^xix But advances in assisted reproductive technology have reduced this rate significantly such that it is now comparable to natural conception, especially when only one embryo is transferred. The risk of ectopic pregnancy increases with each embryo transferred.  

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Ovarian Hyperstimulation Syndrome (OHSS)  

OHSS is a reaction to the ovary-stimulating hormones used during IVF. While most cases of OHSS are mild, the condition can become serious and life-threatening.^xx  

It is estimated that moderate OHSS occurs in three to six percent of ART cycles and severe OHSS in 0.1 to two percent of cycles.^xxi,xxii Overall, the risk of mild OHSS complications in ART cycles may occur in over 20 percent of cycles^xxiii,^xxiv However, it is worth noting that incidence rates for OHSS are variable between studies and populations. In addition, as alternatives to hCG triggers (or lower doses) become more common in at-risk patients, and more freeze-all cycles are conducted, the incidence of OHSS continues to decline.^xxv

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What are the success rates of IVF?

There are numerous factors that impact a woman’s chances of success with IVF. These include the length of time of fertility problems, maternal age, and the presence of reproductive-related health conditions such as endometriosis.^xxvi  

According to the National Health Service in the U.K., the live birth per embryo transfer is 29 percent for those under 35, 23 percent for those between 35 and 37, 15 percent for 38 to 39, nine percent for 40 to 42, three percent for 43 to 44, and two percent for those over 44.^xxvii  

A 2019 retrospective study of 201 couples undergoing IVF with an average age of 34 reported that the pregnancy rate was 21.9 percent and live birth rate was 13.2 percent for the first cycle.^xxviii The study reported that longer duration of fertility problems and more advanced maternal age predicted lower success rates.  

Some statistics are derived from looking at live birth rates after six or more IVF cycles. A study published in 2015 in the Journal of the American Medical Association looked at the cumulative live birth rates of IVF patients after analyzing 257 398 cycles.^xxix This rate continued to increase up to the ninth cycle of IVF, with 65.3 percent of patients achieving a live birth by the sixth cycle. Live birth rates were also stratified by age, with a cumulative live birth rate of 68.4 percent after six cycles for women under 40. For women 40 to 42, the cumulative live birth rate after six cycles was 31.5 percent. For women over 42, all cumulative live birth rates for any number of cycles were less than four percent.  

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Reproductive health and IVF success rates

Certain factors or health conditions may contribute to IVF being less successful.  

In women, this includes severe endometriosis, which was associated with reduced implantation and clinical pregnancy rates in patients undergoing IVF, according to a 2013 meta-analysis.^xxxThe thickness of the endometrial lining can also impact success rates. A 2018 retrospective cohort study found that pregnancy and live birth rates improved with increased endometrial thickness.^xxxi The most significant factor for IVF success rate in females is age. Increasing age is associated with reduced chance of clinical pregnancy and live birth outcomes.^xxxii

In men, many factors contribute to IVF’s possible success. A 2019 study published in Human Reproduction that looked at 2 425 IVF cycles in heterosexual couples with unexplained fertility challenges found that pregnancy and live birth rates worsened with every year of male age, with a significant difference for men over 50 compared to those 40 or younger.^xxxiii  

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Conclusion

IVF is a complex procedure, and one that is not just expensive but emotionally and physically taxing as well. While the outcome is always uncertain, IVF can be a way to achieve a successful pregnancy where other options have failed.

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