What Are Gonadotropins?
Gonadotropins are fertility drugs that contain follicle stimulation hormone (FSH), luteinizing hormone (LH) or a combination of the two, used to stimulate ovulation. They are known informally as injectables, as they are administered by injection only. Gonadotropins also exist naturally in the body, playing a pivotal role in ovulation.
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.
There are two basic types of gonadotropins: recombinant gonadotropins and urinary-extracted gonadotropins (which include human menopausal gonadotropins (hMG), purified FSH and highly purified FSH.) Recombinant gonadotropins are created in a laboratory using recombinant DNA technology, while urinary-extracted gonadotropins are extracted and purified from the urine of postmenopausal women. (Their urine is naturally high in FSH.)
Recombinant FSH gonadotropins on the market include Gonal-F and Follistim.
Currently, Luveris is the only recombinant LH gonadotropin available.
Purified urine-extracted FSH gonadotropins include Bravelle and Fertinex.
Human menopausal gonadotropins (hMG), which contain FSH and LH, include Humegon, Menogon, Pergonal and Repronex.
Menopur is a highly purified hMG.
How Do Gonadotropins Work?
To better understand how gonadotropins work, you should first understand how the female reproductive system works. You can get a step-by-step explanation of the female reproductive cycle here.
Normally, your pituitary gland should produce FSH and LH at the beginning of your menstrual cycle. The FSH is sent out, while LH is stored until just before ovulation.
FSH tells the follicles in your ovaries to wake-up and start growing. FSH stands for "follicle stimulating hormone," which makes perfect sense given what it does.
Gonadotropins 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, or ovulate. During treatment with gonadotropins, you may be given either an injection of rLH or, more commonly, hCG, which acts like LH and will trigger ovulation.
What Can You Expect During Treatment with Gonadotropins?
Your doctor will probably tell you to let him or her know when you get your period. 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 (like pregnancy or 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). You should ask your doctor or nurse to demonstrate how to safely perform the injections.
Then, your hormone levels, specifically estradiol, and the follicles on your ovaries will be closely monitored with blood work and ultrasound every few days. How often 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, which could result in a multiple pregnancy or a potentially dangerous side effect of fertility drugs, ovarian hyperstimulation syndrome (OHSS).
Based on hormone levels and the size of your largest follicle(s), your doctor may then order an injection of hCG. This is also known as the "trigger shot" because it triggers ovulation to occur approximately 36 hours later. He or she should also tell you which days you should have intercourse to "catch" the egg.
Once ovulation occurs, depending on your treatment protocol, 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.
The treatment may be canceled in the middle, before the trigger shot, if your doctor suspects the ovaries have been hyperstimulated. This is to avoid a serious case of OHSS and high-order multiples. Your doctor may also, in this situation, tell you to refrain from intercourse. Pregnancy can increase the chances of a high-order pregnancy and, if you develop OHSS, complicate your recovery.
What Are the Risks Associated with Gonadotropins?
Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of gonadotropin therapy. Mild OHSS occurs in 10% to 20% of women taking gonadotropins, while serious OHSS occurs 1% of the time. Serious OHSS can be deadly if ignored or not treated properly, and so it's important you are familiar with the symptoms.
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, compared with just 1% to 2% of naturally conceived pregnancies. Most multiple pregnancies with gonadotropins are twins, but up to 5% are triplets or more.
Multiple pregnancies, including twin pregnancies, are risky for the mother and the babies. Close monitoring and canceling a treatment cycle if more than three follicles develop or estradiol levels are very high can help prevent a multiple pregnancy. Some studies have been able to get the rate of multiples pregnancies as low as 5% by starting at a low dose, using slow increases only when necessary and close monitoring.
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The risk of ectopic pregnancy and miscarriage is 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, specifically pregnancy-induced high blood pressure and placental abruption, may be slightly increased as compared to a naturally conceived pregnancy. Whether this 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 for Gonadotropins?
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 about 7.7%; with younger patients having higher live birth rates. 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%.
While older studies may have found higher pregnancy rates with gonadotropins than this recent large study, it's possible the higher success rate came at the expense of higher risk for OHSS and multiple pregnancy.
What Is the Cost of Gonadotropin Treatment?
Gonadotropin treatment that is not an IUI or IVF cycle can cost anywhere between $500 to $5,000, especially when you take into account blood work and ultrasound monitoring. The price varies because different women will need different amounts of the drug.
Your insurance company may pay for part of treatment, all of the treatment or none of the treatment. You may need to pay your fertility clinic in full and then ask for a refund from your insurance, or the clinic may handle the insurance claims for you.
Speak to your doctor before your treatment cycle and make sure you understand the potential costs of treatment, as well as your insurance benefits and whether the clinic expects you to process claims. You don't want to be surprised by a high bill at the end.
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Greene, Robert A. and Tarken, Laurie. (2008). Perfect Hormone Balance For Fertility. United States of America: Three Rivers Press.
R Homburg, CM Howles. "Low-dose FSH therapy for anovulatory infertility associated with polycystic ovary syndrome: rational, results, reflections refinements." Human Reproduction Update. Update (1999) 5 (5): 493-499. doi: 10.1093/humupd/5.5.493.
Sarhan A, Beydoun H, Jones HW Jr, Bocca S, Oehninger S, Stadtmauer L. "Gonadotrophin ovulation induction and enhancement outcomes: analysis of more than 1400 cycles." Reproductive biomedicine online. 2011 Aug;23(2):220-6. Epub 2011 May 15.
Side Effects of Gonadotropins: Patient Fact Sheet. American Society for Reproductive Medicine. Accessed online August 14, 2011.
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