A Beginner’s Guide To Fertility Treatments

Fertility treatments can involve medication, surgery or both to increase the chances of an egg fertilizing (when sperm cells penetrate the egg) and implanting in the uterus. Scientists began studying fertility in the 1600s, but it took hundreds of years to develop treatments like synthetic hormones, which were first used in the 1940s, and in vitro fertilization, which was popularized in the 1980s after the birth of the first IVF baby in 1978.

Fertility remains an exciting field with constant advancements. Today, the most commonly used fertility treatments are:

• Oral medications
• Intrauterine insemination (IUI)
• In vitro fertilization (IVF)
• Laparoscopic surgery
• Injectable medications (gonadotropins), which are most often used alongside IVF

There are also lesser-used fertility treatments, such as GIFT, ZIFT and assisted hatching.

The right treatment for you depends on your age, your goals and underlying conditions you or your sperm-providing partner might have.

Other options include using donated eggs, donated sperm and/or donated embryos, as well as using a gestational carrier or surrogate to carry a baby.

Who Might Need a Fertility Treatment?

If you’re younger than 35 years old and have been trying to get pregnant for a year, you are likely a good candidate for fertility treatments. If you’re 35 or older, many clinics advise making an appointment after six months of trying, as fertility decreases with age. Fertility treatments may also help if you’ve been able to get pregnant, but have suffered recurrent pregnancy loss.

If you’re having trouble getting pregnant, your doctor typically starts with a fertility evaluation to help pinpoint which treatments may be the most successful for you. This evaluation typically involves:

• A review of your medical history
• A physical exam
• A pelvic exam
• Bloodwork analyzing for health or hormonal abnormalities
• An x-ray of the uterus and fallopian tubes (called an HSG)
• A sonogram looking at the uterus and ovaries

Patients who are candidates for fertility treatments may have:

• Polycystic ovary syndrome
• Endometriosis
• Blocked fallopian tubes
• Low egg count
• Unexplained infertility

Your sperm-providing partner will also undergo a fertility evaluation to assess the health and motility of their sperm. Depending on the results, your doctor may suggest your partner receive treatment before you move forward with any of the fertility treatments described in this article. Or, with some sperm-related issues, the recommendation may be to skip straight to IUI or IVF.

If you’re 45 or older, most clinics limit treatment to IVF performed with donated eggs or embryos, and will likely decline treatment after age 55, per American Society for Reproductive Medicine recommendations.

Oral Medications

If your fallopian tubes are not blocked and your partner’s sperm tests come back normal, you may be a candidate for an oral fertility medication. These medications are typically small, inexpensive pills taken once a day for about five days during your menstrual cycle. The most common oral medications are clomiphene citrate, sold under the brand name Clomid, and letrozole, sold under the brand name Femara. Metformin is also used, although less commonly.

These drugs each work a little differently, but ultimately, they “send feedback to the brain to release more hormones which stimulate the ovary,” says Dr. Marsh. Perhaps counterintuitively, the science hinges on lowering your estrogen levels (or at least making your brain think that’s what’s happening). Why? The hormone that helps your eggs mature—called follicle-stimulating hormone, or FSH—can also increase your estrogen levels. When your estrogen dips, your pituitary gland compensates by pumping out more FSH to right the ship, so to speak.

If you don’t ovulate regularly, this surge of FSH may help you release an egg. If you do ovulate regularly, an oral fertility medication may lead to superovulation—a menstrual cycle in which you release more than one egg.

The idea is to “try to increase the odds of sperm and egg meeting in a given cycle,” says Kenan Omurtag, M.D., division director of the department of reproductive endocrinology and infertility at the Washington University School of Medicine in St. Louis.

Here are some basics on how these medications differ. Your doctor will advise on which, if any, oral fertility medication is right for you.

Clomiphene Citrate (Clomid)

Clomid is often the starting point in cases of unexplained fertility, which is when “the patient has regular cycles, the patient’s tubes are open and the partner’s sperm is normal,” says Dr. Omurtag.

The medication binds to a group of receptors in your brain that would typically bind with estrogen—almost like taking estrogen’s regular parking spot. This “tricks your brain into thinking your estrogen levels are low,” says Abigail Mancuso, M.D., a reproductive endocrinologist with University of Iowa Health Care in Des Moines, Iowa. In response, your brain releases more FSH, or follicle-stimulating hormone, a hormone that helps eggs mature in your ovaries, encouraging ovulation, she says.

Typically you take a tablet a day for five days, beginning around the third day of your menstrual cycle, and have sex timed to your fertile window (typically the six days of your menstrual cycle that you’re able to get pregnant). If unsuccessful, your doctor may increase dosage to two or three tablets a day during your next menstrual cycle.

For patients with unexplained infertility, Dr. Mancuso quotes a 10% to 15% chance of a successful pregnancy and live birth, based on current medical literature, though success rates are hard to predict. In one study in the New England Journal of Medicine, which looked at 750 women ages 18 to 40 assigned to take either clomiphene citrate or letrozole, 19.1% of patients who took clomiphene citrate achieved a successful pregnancy resulting in a live birth^[1]Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371(2):119-129. . Success rates often vary with age. On average, a 33-year-old who is a good candidate for Clomid will have slightly more success than a 34-year-old, who will have slightly more success than a 35-year-old, and so on.

Letrozole (Femara)

If your fallopian tubes are open and sperm is normal but you’re not having regular periods, your doctor may try letrozole, which is often sold under the brand name Femara.

Letrozole is a common first-line fertility treatment in patients with polycystic ovarian syndrome (PCOS), a condition that can lead to irregular periods. Unlike Clomid, which only tricks the brain into thinking estrogen levels are low, letrozole actually does affect estrogen production. The drug is an aromatase inhibitor, meaning it blocks aromatase, an enzyme in your fat tissue, from producing estrogen. Letrozole is marketed as a drug for breast cancer patients, but it’s extremely common for fertility providers to use since reduced estrogen levels can boost production of FSH, one of the hormones important in inducing ovulation.

Typically, you take one to three 2.5-milligram tablets daily for five days during your menstrual cycle and have sex timed to your ovulation window. Research suggests a higher dosage may be beneficial in patients who don’t have success with standard dosage^[2]Pritts EA, Yuen AK, Sharma S, Genisot R, Olive DL. The use of high dose letrozole in ovulation induction and controlled ovarian hyperstimulation. ISRN Obstet Gynecol. 2011;2011:242864. .

In the New England Journal of Medicine study, 27.5% of patients ages 18 to 40 who took letrozole achieved a successful pregnancy resulting in a live birth^[1]Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371(2):119-129. . As with Clomid, success rates are hard to predict and often decrease slightly with age.

Price of Oral Medications

One cycle of any of these medications will likely cost less than $10 if covered by insurance and about $20 to $50 a cycle if not covered, depending on where you live. It’s common for oral fertility medication to be covered, though it depends on your insurance.

Side Effects of Oral Medications

The most common side effects of Clomid include hot flashes, mood swings and pelvic pain.

Meanwhile, the most common side effects of letrozole include fatigue and dizziness. Talk to your doctor for a full list of potential side effects, including rare complications.

Because of the chance of superovulation, taking Clomid or letrozole may lead to multiple births (such as twins or triplets). “We usually quote about an 8% to 10% risk of twins, and a less than 1% risk of triplets or higher order multiples,” says Dr. Mancuso.

Most providers will stop and reevaluate after three to six months of treatment with oral fertility medication.

Injectable Medications (Gonadotropins)

You can also stimulate your ovaries by injecting medication into the fatty tissue around your abdomen or thighs. Menopur, Follistim, Ovidrel, Gonal-F and Luveris are among the brand names you may encounter when discussing injectable fertility medications with your doctor.

Doctors refer to these medications as gonadotropins. In your body, gonadotropins are naturally occurring hormones that regulate ovarian function. The medications are man-made versions of these same hormones, namely follicle stimulating hormone (FSH) and luteinizing hormone (LH)—”powerful hormones that can release multiple eggs at once from the ovary,” says Dr. Marsh.

These days, it’s rare to use injectable medication alone. Rather, gonadotropins are primarily used in tandem with IVF, a process that allows the patient and doctor to choose how many embryos to implant in the uterus. Without that control, the use of gonadotropins often leads to twins, triplets or higher multiples because they are so powerful.

“[The TLC show] Jon and Kate Plus Eight, the sextuplets, that’s from injectable medication,” says Dr. Omurtag. “In the late 1990s [and] in the 2000s, a lot of those stories [of multiple births] were related to the use of gonadotropins. Then, over the first 10 years of the millennium, IVF success rates improved to the point where it didn’t really make sense to do those injectable treatments. It made sense to move straight to IVF.”

Using Injectable Medications Outside of IVF

For the last decade, the use of gonadotropins outside of an IVF cycle has largely been limited to the 5% to 10% of patients who don’t ovulate and thus won’t respond to oral medication, says Dr. Omurtag.

Recently, “you’re starting to see more niche use of gonadotropins outside of IVF,” he adds. For example, a doctor may suggest gonadotropins alone if you are in your late 30s and have a low egg count. Gonadotropins might also be paired with IUI in cases where the risk of multiple births is deemed low.

Price of Injectable Medications

One cycle of gonadotropins likely ranges from $3,000 to $6,000 without insurance coverage, depending on dosage and the market. Insurance coverage is employer-dependent.

Side Effects of Injectable Medications

Side effects of injecting gonadotropins may include:

• Fatigue
• Bloating
• Mood swings
• Nausea
• Bruising at injection site
• Mild pelvic pain or abdominal pain

One potentially serious side effect may be ovarian hyperstimulation syndrome, where the medication sends your follicle growth into overdrive, possibly causing fluid to leak into your abdomen or lungs. This is rare, and most cases are mild and can be easily treated. In extreme cases, ovarian hyperstimulation syndrome is life-threatening and patients need to be hospitalized.

On average, a patient who has gone through three cycles of injectable medications without success should move on to other fertility treatment options.

Intrauterine Insemination (IUI)

If you’re unsuccessful with oral fertility medications, the next step is likely intrauterine insemination, or IUI: injecting sperm directly into the uterus. IUI “puts the sperm closer to the egg so you increase the odds that at least sperm and egg will meet,” says Dr. Omurtag.

Some patients skip trying oral medications alone and immediately turn to IUI, depending on test results and their timeline. If your partner has a low sperm count, or if you’ve been diagnosed with unexplained infertility, you’re an “ideal candidate” for IUI, says Dr. Marsh.

IUI is often paired with oral medication. It can also be done with gonadotropins or with no medication.

What Happens During IUI?

Your doctor washes fresh sperm (collected the same day as the procedure), places it into a catheter and injects it into your uterus. “The wash can take one to two hours, but the procedure takes around five minutes,” says Dr. Marsh. The procedure also involves a speculum exam.

Success Rates of IUI

In cases of unexplained infertility, IUI “probably adds about a 3% to 5% chance of success, being liberal with it,” Dr. Omurtag says. This success rate is why IUI is often used in tandem with medication.

Price of IUI

Expect to pay roughly between $300 and $800 without insurance coverage for the basic procedure. “Some clinics recommend doing mid-cycle ultrasounds to monitor how the patient is responding and then use an injectable medication called a trigger shot to time the IUI, and those things can add to your cost as well,” says Dr. Omurtag. “The trigger shot may be $100, and the ultrasounds can be anywhere from $150 to $400 [as ballpark figures].”

Side Effects of IUI

Side effects may include minimal cramping and spotting. Talk to your doctor for a full list of potential side effects, including rare complications.

If you aren’t successful after three cycles of IUI, your doctor will likely recommend you move on to IVF.

In Vitro Fertilization (IVF)

When it comes to IVF, “it’s taking what you’re doing with the oral medications, with the gonadotropins, and hitting the boost button,” says Dr. Omurtag. “You’re maximizing your ability to get the ovary to make as many eggs as possible.”

During IVF, doctors retrieve your eggs during a short outpatient surgery, inseminate them in a lab and implant the resulting embryos, typically one at a time, in your uterus.

You may skip straight to IVF if your fallopian tubes are blocked, if your partner’s sperm counts are low, if you have severe endometriosis or if you’re freezing eggs or embryos. Or, you may make the decision to try IVF after at least three failed cycles of IUI.

What Happens During IVF?

“There can be many medications that go into an IVF cycle,” says Dr. Marsh. “In my practice, we typically start with oral contraceptive pills to coordinate the start of the cycle and then give gonadotropins to promote growth of multiple eggs simultaneously.”

Most patients inject gonadotropins daily for eight to 14 days. These injections are made with small needles—similar to the needles used for insulin injection—and are typically performed at home. You can self-inject or ask a partner, family member or friend to help. Doctors monitor your progress with blood tests and ultrasounds every few days.

The egg retrieval process is an outpatient surgery that takes anywhere from 10 to 30 minutes and is typically done with anesthesia. Doctors use a needle to suction out the eggs that have matured in your ovaries. From there, an embryologist inseminates the eggs with your partner’s sperm to create embryos, which are left in the lab for three to five days to culture.

Depending on your treatment plan, an embryo may be transferred immediately to your uterus after the culture period, or embryos may be frozen to wait for results of chromosomal and/or genetic testing. “Any excess embryos are frozen to be used later to grow the family, if the first cycle works, or to try again if the first cycle doesn’t work,” says Dr. Omurtag.

The transfer process requires another short, outpatient surgery. It usually doesn’t require anesthesia.

When you’re preparing for an embryo transfer, your doctor may prescribe progesterone shots to help increase the chances of successful implantation.

Success Rates of IVF

About 50% of embryo transfers completed in the U.S. in 2018 resulted in live birth for women younger than 35 years old, according to the most recent CDC data^[3]2018 assisted reproductive technology fertility clinic success rates report. Centers for Disease Control and Prevention. Accessed 07/17/2021. . The number dropped to 44.1% for women ages 35 to 37, 37.6% for women ages 38 to 40 and 26.6% for women ages 41 or 42. For women 43 and older, the rate was 12%. The CDC offers an IVF Success Estimator tool that will calculate your estimated success rate based on your age and other factors. Remember this is an estimate—it’s impossible to predict how the procedure will go for you.

Price of IVF

IVF usually costs somewhere between $15,000 and $20,000. Make sure to ask your clinic if the quoted price includes medication. “For example, in our office, an IVF cycle is about $14,000. But when you add the meds, it can get more expensive,” says Dr. Omurtag.

Medication price depends on many factors, including your age and AMH level (the number that indicates roughly how many eggs are in your ovarian reserve), but may range from $3,000 to $6,000 for the entire treatment. There also may be separate bills for items like anesthesia, which can be a few hundred dollars.

Employers are getting better at including fertility treatments in insurance plans, Dr. Omurtag says, but it’s far from a given.

Side Effects of IVF

Side effects of IVF may include:

• Fatigue
• Bloating
• Mood swings
• Nausea
• Bruising at injection site
• Pelvic pain or abdominal pain
• Vaginal discharge

Like IUI, one potentially serious side effect of IVF may be ovarian hyperstimulation syndrome.

Other Assisted Reproductive Technology (ART)

Less common assisted reproductive technologies include:

• Assisted hatching. With this procedure, doctors use a laser to create a tiny hole in the hard outer layer of an embryo before implantation, typically on the third day of embryo development. This procedure aims to help the embryo break free of the hard outer layer, which is required for it to implant into the uterus. This procedure might be attempted in patients in their late thirties (or older) who have experienced at least one unsuccessful round of IVF. The success of assisted hatching is not well-proven, says Dr. Mancuso.
• Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT). Both of these procedures involve a laparoscopic surgery to inject either gametes (a mixture of egg and sperm) or zygotes (eggs that have been successfully fertilized in a lab) into the fallopian tubes. GIFT and ZIFT are used in less than 1% of fertility treatment cycles in the U.S., according to Dr. Marsh.

Fertility Surgery

Laparoscopic surgery, or simply laparoscopy, is a minimally invasive surgery that can detect and potentially correct issues in your uterus, ovaries and/or fallopian tubes that could be hindering your ability to get pregnant.

Through laparoscopy, a doctor may diagnose and/or treat:

• Blockage of the fallopian tubes, such as fluid from a prior pelvic infection or surgery
• Endometriosis lesions
• Uterine fibroids
• Pelvic adhesions

The procedure typically involves a small incision in the navel—and potentially a few other small incisions nearby—to insert a fiber-optic lens and tiny surgical tools used to cut out or burn off fibroids, lesions or other blockages.

This type of surgery may cost anywhere from $5,000 to $10,000 out of pocket. Depending on your situation, it may help to ask your provider about the possibility of billing the procedure under treatment for endometriosis. “A lot of times, endometriosis surgery will be covered by insurance where fertility isn’t,” says Dr. Mancuso.

Donors, Gestational Carriers and Surrogates

If you aren’t successful with IVF, it may make sense to explore donor eggs, donor sperm or donor embryos. These donations are more common than patients think, says Dr. Omurtag, and they have excellent success rates.

You may learn throughout the fertility treatment process that you’re unable to carry a child or that carrying a child presents a serious health risk. Gestational carriers or surrogates are also options. With a gestational carrier, you provide the embryos to implant. Surrogate is the term for a gestational carrier who also provides eggs.

Considering the fee paid to the donor or gestational carrier, IVF fees, agency fees and legal fees, third-party reproduction often costs into the six figures. There is also what is called a compassionate surrogacy agreement, in which the surrogate, typically a friend or family member, does not take a surrogacy fee. However, with medical and legal fees, the cost will still likely be at least $30,000.

Surrogacy laws vary by state. The National Infertility Association has more information on surrogacy-friendly states.

Insurance coverage for fertility treatments can vary dramatically depending both on your employer and where you live. Nineteen states have passed fertility insurance coverage laws (with 13 of those including IVF coverage), but how this plays out in actually helping you pay for your treatment is complicated. Which treatments must be covered and who must qualify for coverage is different in each state. What’s more, small employers and self-insured employers are often exempt from these laws.

The National Infertility Association, a nonprofit organization that advocates for fertility rights, can help you navigate coverage in your state.

The good news, says Dr. Omurtag, is that more employers are realizing the importance of providing fertility treatment benefits, and more employees have become comfortable asking for them. Employee-led letter-writing campaigns to ask for fertility coverage have been successful at some employers, he adds.

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