Treatment With Gonadotropins (Gonal-F, Follistim, Ovidrel, and Others)

Gonadotropins are fertility drugs that contain follicle stimulation hormone (FSH), luteinizing hormone (LH), or a combination of the two. These drugs are used to stimulate ovulation. Brand names that may be familiar to you include Gonal-F, Follistim, Ovidrel, Menopur, and Luveris.

Gonadotropins are informally known as injectables because they are only administered by injection. This makes them different from fertility drugs Clomid (clomiphene) and Femara (letrozole), which are pills you take by mouth.

FSH and LH are also known as gonadotropins. The are naturally occurring hormones in the body that play a pivotal role in ovulation.

How Do Gonadotropins Work?

To better understand how gonadotropins work, you must first understand how the female reproductive system works. Read an easy to understand, step-by-step explanation of the female reproductive cycle here.

If you don't have time for that, here's a super quick recap! Normally, your pituitary gland produces FSH and LH at the beginning of your menstrual cycle. The FSH is sent out into the body. LH is stored in the pituitary gland until just before ovulation.

FSH tells the follicles in your ovaries to wake up and grow. FSH stands for "follicle-stimulating hormone." Makes perfect sense, given it stimulates the follicles! Gonadotropin fertility drugs, that are FSH or FSH along with LH, act similarly. They tell the follicles on your ovaries to grow and develop.

LH typically peaks just before ovulation during a natural cycle and helps any mature eggs to go through one last growth spurt and release—in other words, ovulate. During treatment with gonadotropins, you may be given either an injection of rLH or, more commonly, hCG, which acts as a natural LH spike and will trigger ovulation.

What to Expect

Gonadotropins may be used on their own as a fertility aid, or they may also be used as part of an IUI treatment or IVF treatment cycle. Below is an explanation of how they may be used on their own.

When you get your next period, you'll call your doctor. You'll then have some blood work and an ultrasound to make sure there are no complications or reasons you can't be treated in this cycle. (For example, to ensure you aren't pregnant and don't have a benign ovarian cyst.)

Your doctor will likely start you off with 75 to 150 IU of the gonadotropin medication. Depending on which gonadotropin is prescribed, you'll need to give yourself injections just below the skin (subcutaneously) or into the muscle (intramuscularly).

Ask your doctor or nurse to demonstrate how to safely perform the injections. They will likely do this without you asking.

Over the next several days, your hormone levels, specifically estradiol, and the follicles on your ovaries will be closely monitored. This monitoring happens via blood work and ultrasound every few days.

How often? That will depend on your doctor's protocol, how you're responding to the drugs, and how close you are to ovulation. Your medications may be adjusted up or down depending on the ultrasound and hormone results.

The goal is to stimulate the ovaries enough to produce one good egg, but not to overstimulate them. Other stimulation can increase your risks of a multiple pregnancy or ovarian hyperstimulation syndrome (OHSS).

When your hormone levels and follicle size indicate ovulation is close, your doctor may order an injection of hCG. This is also known as the "trigger shot," as it triggers ovulation to occur approximately 36 hours later. Your doctor should also tell you which days to have intercourse, so you can "catch" the egg and get pregnant.

Once ovulation occurs, you may then start taking progesterone. Not everyone will need this, however. Your hormone levels will continue to be monitored, though less frequently. You'll take a pregnancy test at the end of the cycle to determine if treatment was successful.

Sometimes, treatment may be canceled in the middle. This may occur before the trigger shot or even earlier. The most common reason for cycle cancellation is when the doctor suspects the ovaries have been hyperstimulated. Stopping the medications can avoid a serious case of OHSS and high-order multiples (triplets or more).

Your doctor may also tell you to refrain from intercourse. As difficult as it is to hear this, it's very important you follow your doctor's instructions. Pregnancy can increase the chances of a high-order pregnancy, which puts you and your babies at risk. Also, if you develop OHSS, pregnancy can complicate your recovery.

Different Types of Gonadotropins

There are two basic types of gonadotropins: recombinant gonadotropins and urinary-extracted gonadotropins.

Recombinant gonadotropins are created in a laboratory using recombinant DNA technology. Recombinant FSH gonadotropins on the market include Gonal-F and Follistim. Currently, Luveris is the only recombinant LH gonadotropin available.

Urinary-extracted gonadotropins are extracted and purified from the urine of postmenopausal women. (Their urine is naturally high in FSH.) They include human menopausal gonadotropins (hMG), purified FSH, and highly purified FSH. Purified urine-extracted FSH gonadotropins include Bravelle and Fertinex.

Human menopausal gonadotropins (hMG) contains FSH and LH. This group includes medications like Humegon, Menogon, Pergonal, and Repronex. Menopur is a highly purified hMG. A related drug, human chorionic gonadotropin (hCG), is often part of fertility treatment with gonadotropin injections.

You may know hCG as the pregnancy hormone, but it also happens to be molecularly similar to LH. In a natural cycle, LH triggers ovulation. As part of fertility treatment, an injection of hCG may be used to trigger ovulation. Ovidrel, Novarel, Pregnyl, and Profasi are brand names for hCG injectables.

Associated Risks of Treatment

Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of gonadotropin therapy. Mild OHSS occurs in 10% to 20% of women taking gonadotropins. Serious OHSS occurs 1% of the time and can be deadly if ignored or not treated properly. It's important you are familiar with the symptoms of OHSS.

Another possible risk factor of gonadotropin therapy is a multiple pregnancy. Some studies have found that up to 30% of pregnancies conceived with gonadotropins are twins or more. (This is compared to just 1% to 2% of naturally conceived pregnancies.)

Most multiple pregnancies with gonadotropins are twins. Up to 5% are triplets or more. Multiple pregnancies, including twin pregnancies, have increased risks both for the mother and the babies. Close monitoring of a treatment cycle can help prevent a multiple pregnancy. Many doctors will cancel if more than three follicles develop or if estradiol levels are very high.

Some studies have been able to get the rate of multiples pregnancies as low as 5%, which can be achieved by starting at a low dose, using slow increases only when necessary, and close monitoring.

The risk of ectopic pregnancy and miscarriage is also higher with gonadotropin-conceived pregnancies. Less than 1% of women taking gonadotropins will experience adnexal torsion, or ovarian twisting. This is when the ovary twists on itself and cuts off its own blood supply. Surgery is necessary to untwist or possibly remove the affected ovary.

Your risk of pregnancy complications—like pregnancy-induced high blood pressure and placental abruption—may be also slightly increased compared to a naturally conceived pregnancy. Whether this increased risk is caused by the gonadotropins or the infertility is unclear.

Because gonadotropins are injectable medications, you may also experience soreness near the injection sites. If you suspect an infection, be sure to alert your doctor right away.

What Are the Success Rates?

Your potential for pregnancy success with gonadotropins will depend on a variety of factors, including your age and the cause of infertility.

A 2011 study by The Jones Institute for Reproductive Medicine looked at 1,400 gonadotropin treatment cycles. The overall pregnancy rate was 12%, with the live birth rate of about 7.7%. Younger patients had higher live birth rates.

In this study, by canceling the cycle if three or more dominant follicles developed or estradiol levels were higher than 1500 pg/ml, they were able to keep the multiple pregnancy rate a low 2.6%.

Older studies have found higher pregnancy rates with gonadotropins than this 2011 study. However, it's possible the higher success rate came at the expense of higher risk for OHSS and multiple pregnancy.

Cost of Treatment

Gonadotropin treatment that is not an IUI or IVF cycle can cost anywhere between $500 to $5,000. The higher price takes into account the required blood work and ultrasound monitoring. The also price varies because different women will need different amounts of drugs.

Your insurance company may pay for part of the treatment. Or, they may pay for all of it...or none of it. You may need to pay your fertility clinic in full first. Then, you may need to file for a reimbursement from your insurance yourself, or the clinic may handle the insurance claims for you.

Be sure to clarify all of this with your fertility clinic before you start treatment. You don't want to be surprised by a high bill at the end.