When the average person hears a woman is using "fertility drugs," the first thing that often comes to mind is multiple pregnancies like the McCaugheys of Iowa or the Chukwus of Texas. But if managed carefully, the risks of higher order multiples (more than three fetuses) while using fertility drugs are relatively low. Somewhere between 5 to 20 percent of the women who become pregnant while using fertility drugs carry more than one baby.

What Are Fertility Drugs?
Women in treatment for infertility, such as undergoing advanced reproductive technologies (ART) such as intrauterine insemination (IUI) and in vitro fertilization (IVF), use drugs to stimulate their ovaries to produce eggs. These drugs fall into two categories: clomiphene citrate (commonly called Clomid or Serophene), given in pill form; and the injectible medications that are injected either intramuscularly or subcutaneously, depending on the drug and the patient. These include Humegon, Pergonal, Repronex, Fertinex, Follistim and Gonal-F.

While Clomid works by "tricking" the brain into thinking there is insufficient estrogen and indirectly stimulating the ovaries, injectibles, which contain FSH (follicle stimulating hormone), directly stimulate the ovaries. Injectibles are much more expensive than Clomid; they are also much more powerful, but if used correctly, produce far fewer side effects.

In the Beginning, There Was Clomid
Often a woman in the early stages of infertility treatment starts with Clomid. For some women who don't ovulate at all, or who have a weak ovulation, Clomid may be enough. While some doctors give women Clomid (generally with timed intercourse or insemination) without monitoring its effects through ultrasound viewing and blood tests, this is generally not recommended as it is difficult to assess the drug's effects without monitoring the body's reaction.

Dr. Lisa Erickson, a reproductive endocrinologist (RE) in practice at the Center for Reproductive Medicine in Minneapolis, says she recommends no more than three Clomid cycles before moving on to the stronger injectible fertility drugs.

Although Clomid is generally the first fertility drug a woman takes, its side effects can be powerful. Gail Simons, of East Hampton, New York, took Clomid for two cycles and had side effects. "I had severe hot flashes and extreme depression," she says. "I refused to take the Clomid for a third cycle, because it made me feel so awful I was literally crying all the time. I have never felt that depressed and pessimistic in my whole life." Gail moved on to an injectible drug and had no side effects.

Like Gail Simons, Katie Mosher had severe side effects with Clomid, which she took for seven cycles. In addition to hot flashes, Katie suffered from "very bad mood swings and insomnia," she says. "I cried over French fries and never knew why. My husband was great, though, he just smiled and said it was OK because he understood. I, on the other hand, swear never to take Clomid again!"

A recent study suggests that up to 25 percent of the women who use Clomid may find their cervical mucus affected. It is recommended that part of the monitoring process with Clomid include a post-coital test to determine if Clomid is interfering with the production of fertile mucus.

But for every woman like Gail and Katie, there seems to be one like Brenda Price of Ontario, Canada, who describes her side effects on Clomid as "minor," or Kelli Chesterton* of Cupertino, Calif., who did six cycles of Clomid with "little or no side effects. I did ovulate on Clomid." Kelli did have some side effects with her seventh and last Clomid cycle.

Clomid is generally taken in dosages from 50 to 300 milligrams for five days per month, generally beginning on day 3 to 5 of your menstrual cycle. The cost ranges from $30 to $75 per month. Clomid is used in cycles with timed intercourse, sometimes in concert with IUI, seldom with IVF. About 35 to 45 percent of women will become pregnant while using Clomid. About 5 percent of these pregnancies will be twins, with triplet pregnancies being rare.

Next Came the Injectible Drugs
While most women in fertility treatment begin with Clomid, those who move quickly to ART procedures may never take Clomid, but instead move start with injectible medications. Since the introduction of the first injectible fertility drug, Pergonal, these drugs have gained popularity. While some women take injectibles in concert with timed intercourse, their usage is generally limited to IUI and IVF cycles.

The most serious potential side effect of injectible medications is ovarian hyperstimulation syndrome (OHSS), which occurs when a woman's estrogen level skyrockets and she produces many eggs. Though OHSS occurs in less than 5 percent of women who use injectibles, it is a serious and potentially fatal condition that causes the ovaries to swell to several times their normal size. Symptoms of OHSS include sudden pelvic pain, weight gain, nausea, vomiting and dizziness. The doctors of women who have developed or are in danger of developing OHSS generally cancel their ART cycles to avoid it.

Not all women who develop OHSS are in grave danger. It is normal for stimulated ovaries to be slightly swollen and a little painful -- they don't call it superovulation for nothing!

Kelli Chesterton has been through two injectible cycles as part of the protocol for two IVFs. She has used three different injectibles. "I experienced no bad side effects from the drugs. There is a certain full feeling involved when your ovaries begin to swell. It's certainly bearable."

Although one of the medications Kelli used, Follistim, is commonly given subcutaneously (with a needle just below the skin), because Kelli is overweight, she and her doctor decided that the drug would be absorbed better into her system if Kelli took the shots intramuscularly. "I remember the shock after a few days of injections, as my stomach looked like a battle zone. It was purple and black and green from the needles. It hurt to the touch."

Somewhere between 20 and 60 percent of the women who use injectible medications will become pregnant while using them. Variables are many, including the type of ART and infertility factors.

Treatment starts within the first few days of a woman's menstrual cycle and continues anywhere from five to 12 days, depending on how long it takes a woman's egg follicles to mature. A woman using these drugs is monitored by her doctor through vaginal ultrasounds and blood tests to check estrogen levels at least every two to three days.

The dosage prescribed depends on a variety of factors, including the woman's age, body size, and, if she has taken fertility medications previously, her response to them. The medications come in small glass vials called ampules (amps). The medication is powdered, and is mixed with a sterile diluent (liquid) and then injected into the woman. A woman can give herself subcutaneous injections (generally in the stomach, arms or hips), but a woman's husband or partner usually learns to give her intramuscular injections (often given in the buttocks or upper thighs).

A doctor generally prescribes 1 to 8 amps, although the amount used may be increased or decreased during the cycle, depending on follicle development. The cost for the injectible drugs is high -- for one cycle, depending on the drug used, retail pricing and amount prescribed, an injectible cycle can cost between $2,000 and $5,000. That's just for the medication -- monitoring, associated medications and cost of ART procedures are not included in this figure.

Some women and their families worry about a link between fertility medications and cancer. There have been several studies exploring whether or not women using fertility medications may have a higher incidence of ovarian cancer. No study has ever proven that this is the case.

About 20 percent of the women using injectible medications will become pregnant with twins, 3 to 4 percent with triplets and 1 to 2 percent with higher order multiples. In IUI cycles, many doctors will cancel a cycle if the woman produces a large number of follicles (thus increasing her chances of a higher-order multiple pregnancy). And for IVF, many reproductive endocrinologists follow the guidelines established by the Society of Advanced Reproductive Technology (SART), transferring only two embryos to a woman who is younger than 35 and three to a woman older than 35.

Following guidelines like these along with careful physician monitoring of infertility patients helps ensure that women who take fertility drugs do so as safely as possible. Infertility treatment is a hard enough experience without worrying that taking a high-tech path to parenthood is hazardous to your health.

* Name changed to protect the individual's privacy.