Master Class

The Art of Controlling Multiples


The most common complication of assisted reproductive technologies is multiple gestation, particularly triplet and higher-order pregnancy. As we all know, multiple gestation leads to an increased risk of complications in both the fetuses and the mother.

Ovulation induction results in a 20% increase in multiples, the majority of which are twins. In vitro fertilization (IVF) results in a 40% increase in multiples; 32% of these are twins. Unfortunately, we're not making progress in decreasing these rates. Knowing that most patients look at two things—pregnancy rates and cost—when they choose an infertility clinic, many competitive clinics are implanting more than the recommended number of embryos in order to achieve the highest pregnancy rates.

At any opportunity along the spectrum of general to specialized ob.gyn. care, we need to educate and encourage patients to look beyond the pregnancy rates and instead focus on the numbers of embryos transferred and the implantation rates. If we are successful, we could probably make some progress in decreasing the multiple pregnancies associated with assisted reproductive technology (ART). At a basic level, we can ensure that infertility evaluations and treatments are timely, thorough, individualized, and well explained to our patients. In doing so, we will provide good care, and perhaps we can keep the patients' feelings of desperation, which are valid and understandable, somewhat in check.

Infertility Diagnosis, Work-Up

A diagnosis of infertility is usually made when couples have been trying for more than 1 year to become pregnant. Fecundity drops after the age of 27 years, more significantly after the age of 35 years, and dramatically after 40 years. I recommend that, for women older than age 35, we not wait until a year is up, but rather begin a basic infertility work-up after 6 months. These women deserve a more aggressive approach.

After 6 months in a patient who is older than 35, or after 1 year in younger patients, we should provide the basics: blood testing to check ovarian reserve, a hysterosalpingogram to ensure that the uterus is normal and that tubes are patent, and a semen analysis. It is important to use an infertility laboratory for the semen analysis. Regular laboratories usually do not check for Kruger morphology, which is critical.

Examinations should include a check on thyroid function. Approximately 2% of women in the reproductive age group have hypothyroidism or subclinical hypothyroidism, which can affect fertility but is treatable. It's also important to know if a woman has had endometriosis or previous pelvic surgeries. Diagnostic operative laparoscopies can be performed by general ob.gyns. to rule out or treat endometriosis if they feel comfortable doing the procedure.

When you take the patient's history, certain questions—such as “When did your mother enter menopause?”—are critical because they may lead to an early diagnosis and, appropriately, to a more aggressive treatment approach. Perimenopause—during which time ovarian reserve is compromised—usually begins 5-10 years earlier than menopause. If I know that a patient's mother went into menopause at age 40, I will work through infertility treatment more quickly, as I would with older patients. Testing for ovarian reserve in women younger than 35 is too often dismissed. It shouldn't be.

It's well known that smoking and exposure to secondhand smoke decrease fecundity. They increase rates of abnormal ovarian reserve, oocyte atresia, and miscarriage. In IVF patients, they increase IVF failure and the number of IVF cycles needed to conceive. One prospective study showed that for each year of active smoking, there is a 9% decrease in the success of ART. Smoking also affects the sperm cell. Even if sperm look normal, smoking has been shown to lead to damage of the genetic material, causing abnormalities in sperm count, motility, morphology, and function.

The good news is that many of the effects of smoking are reversible. The duration of smoking may affect the degree of reversibility, but certainly we have the opportunity to improve fecundity and the success of fertility treatment if we identify smokers and work hard to help them with cessation.

Starting Treatment

If all of these basic work-ups are normal and the patient is younger than 32 years of age we can proceed with a trial of Clomid (clomiphene citrate). I recommend treatment with Clomid for 3-4 months, because most patients who will achieve pregnancy will do so within the first three to four cycles. After several months, the chances of a pregnancy are significantly decreased, and other treatment options need to be considered. Treatment with Clomid alone for longer than 6 months really isn't fair to the patient, and neither is the use of Clomid in patients older than age 37.


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