What "infertility treatments" are we talking about?
Normally, women release one egg during their fertile "window"; have intercourse during that time and pregnancy occurs. About 40% of the time, couples who are having trouble conceiving, an egg is not being released (i.e anovulation or no ovulation). Many medications are used to overcome this and clomiphene citrate (Clomid) is the grandfather of infertility medications in the modern era. The drug is designed to trick a woman's brain into releasing a little extra of her own FSH (the hormone responsible for egg growth) and ultimately get women who don't ovulate - TO OVULATE.
HOWEVER, for women who have unexplained infertility (no obvious etiology of the infertility exists which affects 10% of couples), clomiphene citrate can be used to increase the number of eggs that a woman releases during her fertile window from 1 -> to 2 and sometimes 3. Now, the reason the natural multiple rate is low (about 3-4%), is because women only release one egg; creating a state in which you increase that yield only increases the chance of twins or more!
With clomiphene citrate the likelihood of twins is 8%; triplets is 1%
Not everyone responds to clomiphene citrate, though and stronger medications are required. These are injectable medications and they are purified extracts of the hormones responsible for egg growth (FSH for example). Giving these medications increases the number of eggs that grow in the ovary dramatically! There are two scenarios in which patients get injectable medications: 1) controlled ovarian hyperstimulation with intrauterine insemination aka COH-IUI or 2) in vitro fertilization (IVF)
Let's talk about these treatments separately.
1. In COH-IUI, fertilization occurs in the woman's body. Patients are given injectable medications and monitored closely with frequent vaginal ultrasound and blood work (3-4x/week) for usually a 10-14 day period. When the time is right, a different hormone (HCG) is given to cause final maturation and release of the eggs that have grown up to that point and then an IUI (i.e artificial insemination) is performed. Often times there are more than 2 eggs released in order to maximize the likelihood that sperm will fertilize an egg.
With COH-IUI the likelihood of twins can be as high as 20%; triplets and higher 5%
2. In IVF, controlled ovarian hyperstimulation is performed with certain tweaks that allow the physician to completely "control" the communication between the woman's brain and ovaries. The goal is the same: make as many eggs as possible. HOWEVER the difference in IVF vs COH-IUI is that the eggs are retrieved via a minor surgical procedure and are then fertilized in a dish in the lab. The resulting embryos are grown for 3-5 days in the lab after which time an embryo transfer is performed whereby the embryos are then placed back into the uterus. In IVF, the decision on how many embryos to place back into the uterus is controlled unlike in COH-IUI where the number of fertilization events are out of the hands of the physician/patient.
With IVF, the likelihood of twins can vary by clinic and patient age but can be as high as 25-30%, triplets and higher are <2%
Normally, women release one egg during their fertile "window"; have intercourse during that time and pregnancy occurs. About 40% of the time, couples who are having trouble conceiving, an egg is not being released (i.e anovulation or no ovulation). Many medications are used to overcome this and clomiphene citrate (Clomid) is the grandfather of infertility medications in the modern era. The drug is designed to trick a woman's brain into releasing a little extra of her own FSH (the hormone responsible for egg growth) and ultimately get women who don't ovulate - TO OVULATE.
HOWEVER, for women who have unexplained infertility (no obvious etiology of the infertility exists which affects 10% of couples), clomiphene citrate can be used to increase the number of eggs that a woman releases during her fertile window from 1 -> to 2 and sometimes 3. Now, the reason the natural multiple rate is low (about 3-4%), is because women only release one egg; creating a state in which you increase that yield only increases the chance of twins or more!
With clomiphene citrate the likelihood of twins is 8%; triplets is 1%
Not everyone responds to clomiphene citrate, though and stronger medications are required. These are injectable medications and they are purified extracts of the hormones responsible for egg growth (FSH for example). Giving these medications increases the number of eggs that grow in the ovary dramatically! There are two scenarios in which patients get injectable medications: 1) controlled ovarian hyperstimulation with intrauterine insemination aka COH-IUI or 2) in vitro fertilization (IVF)
Let's talk about these treatments separately.
1. In COH-IUI, fertilization occurs in the woman's body. Patients are given injectable medications and monitored closely with frequent vaginal ultrasound and blood work (3-4x/week) for usually a 10-14 day period. When the time is right, a different hormone (HCG) is given to cause final maturation and release of the eggs that have grown up to that point and then an IUI (i.e artificial insemination) is performed. Often times there are more than 2 eggs released in order to maximize the likelihood that sperm will fertilize an egg.
With COH-IUI the likelihood of twins can be as high as 20%; triplets and higher 5%
2. In IVF, controlled ovarian hyperstimulation is performed with certain tweaks that allow the physician to completely "control" the communication between the woman's brain and ovaries. The goal is the same: make as many eggs as possible. HOWEVER the difference in IVF vs COH-IUI is that the eggs are retrieved via a minor surgical procedure and are then fertilized in a dish in the lab. The resulting embryos are grown for 3-5 days in the lab after which time an embryo transfer is performed whereby the embryos are then placed back into the uterus. In IVF, the decision on how many embryos to place back into the uterus is controlled unlike in COH-IUI where the number of fertilization events are out of the hands of the physician/patient.
With IVF, the likelihood of twins can vary by clinic and patient age but can be as high as 25-30%, triplets and higher are <2%
Both COH-IUI and IVF put a patient at risk for something called ovarian hyperstimulation syndrome (OHSS). The injectable medications radically stimulate the ovaries, and the ovaries naturally grow in size; however the response can be so dramatic that the ovaries become large enough to cause severe discomfort, difficulty breathing, and leakage of fluid into the abdominal cavity. Additionally, an increase viscosity of the blood can occur placing the patient at risk for blood clots. Needless to say, severe OHSS is fortunately a rare event but milder forms of OHSS are common. See this document for a good overview.
COH-IUI has historically been the culprit behind the rise in higher order multiples over the last 20 years, and recent evidence combined with the increased improvements IVF may be rendering COH-IUI obsolete. Furthermore, the ability to limit the number of embryos transferred in IVF has helped reduce the higher order multiple rate over the last 10 years.
For patients without insurance coverage for infertility treatments often times cost plays a role in the management process. While treatment with clomiphene citrate (+/- IUI) can be approximately $400/cycle ($50 for the medication and $350 for the IUI). Treatment with COH-IUI can be as much as $3000/cycle because the injectable medications are expensive and the duration and intensity of treatment can vary widely based on the reason for the couple's infertility.
Three to four cycles of each infertility treatment are typically performed to maximize the chance of pregnancy after which time if pregnancy is not achieved the treatment is deemed a "failure" and more aggressive options are considered. IVF can cost upwards of $9000 plus approximately $3000-5000 for the cost of the medications, however there is a better chance of pregnancy (upwards of 60% in women <35 years of age) with a lower chance of higher order multiples.
The table below summarizes the approximate pregnancy, twin/high order multiple rates, and costs of common infertility treatments*
| Treatment | Pregnancy Rate | Twin Rate | Triplet or higher | Cost/cycle ($) |
| Clomiphene citrate (CC) | 4-5% | 8% | 1% | 50 |
| CC + IUI | 5-10% | 5-10% | 1% | 400 |
| COH-IUI | 15-20% | 20% | 5% | 3000 |
| IVF | 50-60% | 25-30% | <2% | 9000-15000 |
* actual costs vary widely based on clinic, reason for infertility, and insurance coverage; pregnancy rates are based on age <35 and assume that baseline fecundability of infertile couple is <1%.
The risk of twins remains real and the risk of triplets or higher has to be in the back of both patient and physician's mind when discussing common treatments for infertility. In the next part of these three part series we will discuss the risks associated with carrying a twin or triplet pregnancy. Stay Tuned!
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