Fertility Treatment Options
Advances in fertility therapies allow patients having difficulty starting their families to become parents, more than ever before. At first glance, the different fertility treatment options seem confusing. However, the different levels of fertility therapy can be simplified into three categories: fertility pills, such as Clomiphene Citrate; fertility injections, a process known as Controlled Ovarian Hyperstimulation; and, In Vitro Fertilization, often called test tube babies.
Clomiphene Citrate (Clomid™)
Clomiphene citrate, or clomiphene for short, is better known as Clomid™ and has been used to help women become pregnant for more than 50 years. Clomiphene is the fertility drug that most patients try first because it is easy, inexpensive and significant side effects are rare.
Clomiphene is a pill that you take for about five days each month, typically starting on the third or fifth day after your period begins. If you do not have regular periods each month, you probably do not ovulate on a predictable basis and clomiphene will help regulate your time of ovulation. If you already have regular periods, clomiphene tends to lengthen the number of days from when your period starts to when you ovulate and extend your overall cycle length.
How it Works
Clomiphene works by making part of your brain (the hypothalamus and pituitary) believe that your ovaries are not producing enough estrogen. As a result, this part of the brain sends a stronger signal to your ovaries to make more estrogen. The signal from your brain is called follicle stimulating hormone (FSH). Each follicle in the ovary contains fluid, hormone producing cells and an egg preparing for ovulation. FSH can be thought of as egg stimulating hormone. Therefore, when you take clomiphene, your brain makes more FSH than normal.
FSH increases your chance of pregnancy by stimulating the ovaries to release more estrogen, more progesterone and often more than one egg. The hormones, estrogen and progesterone (short for pro-gestation hormone) are critical to prepare your uterus for pregnancy. Even if your ovaries are already making these hormones, they may not make enough on a consistent basis.
Without fertility drugs, women typically release only one egg per month. With clomiphene, you may release two or more eggs providing sperm with more targets. Whereas more eggs increase your chance of pregnancy, more eggs also increases your chance of twins, or more babies. The goal of all fertility specialists is one healthy baby at a time. Any number of babies more than one is a high-risk pregnancy. After all of the time you spent trying to conceive, you want to minimize the risks you take during pregnancy.
Potential Side Effects
Fortunately, the risk of twins with clomiphene is small relative to other fertility therapies, about 7%, and the risk of triplets or more is very small, less than 1%. However, with clomiphene your risk of twins is significantly higher than the general population, which is slightly above 1%. Other side effects with clomiphene are temporary, such as irritability or mood swings. Since your brain does not register any estrogen in your body, you may experience hot flashes, similar to menopausal women, but your hot flashes will stop shortly after you finish taking the clomiphene. Uncommonly, the extra stimulation of your ovaries will result in a cyst, which can be uncomfortable. If a cyst on the ovary occurs, your doctor will simply withhold the clomiphene for the next month and the cyst usually goes away on its own. Other infrequent and temporary side effects with clomiphene include trouble sleeping (likely related to nighttime hot flashes), headaches, nausea, or visual disturbances.
In order to optimize your chances of pregnancy during the month that you are taking clomiphene your doctor may recommend using an ovulation predictor kit (OPK). In general, sperm lives longer than eggs and if an egg is not fertilized shortly after ovulation, then the egg degenerates. Since the OPK predicts ovulation approximately twenty-four hours in advance, the chances of becoming pregnant are best when sperm are waiting in the Fallopian tubes prior to, or at the time of, ovulation. This means timing intercourse or intrauterine insemination the day of and the day after the OPK turns positive.
Clomiphene with intercourse is a common starting point for most couples. If pregnancy does not occur in a few months, or if sperm counts are low, your doctor may add intrauterine insemination (IUI) to the clomiphene therapy. IUI is a simple procedure where washed and concentrated sperm are placed with a small catheter (plastic straw) through the cervix to the top of the uterus. The IUI procedure is very similar to a Pap smear and takes about the same amount of time. Fresh sperm from the male partner is collected and processed on the day that the IUI will occur. Alternatively, frozen sperm from a donor can be thawed and used for IUI.
Compared with intercourse, IUI places more sperm at the right place at the right time. IUI is used when sperm counts are mildly to moderately low, when there is a problem with sperm passing through the cervix or when clomiphene with intercourse have been unsuccessful. Some studies suggest that the combination of fertility drugs and IUI is twice as successful in achieving pregnancy compared to fertility drugs and intercourse. Although less convenient than intercourse, IUI is essentially risk free, with very rare reports of infection.
Controlled Ovarian Hyperstimulation (COH)
COH is a stronger form of therapy than clomiphene involving the use of injectable FSH or a combination of FSH with another ovary-stimulating hormone, called luteinizing hormone (LH). Whereas clomiphene makes your brain secrete more FSH, injecting FSH in the lower abdomen bypasses the brain and directly exposes your ovaries to more FSH than your brain could possibly make in one month, with or without clomiphene. Pregnancy rates are higher with COH/IUI compared to clomiphene therapy, but so are the risks of multiple pregnancies and other side effects.
If you have very infrequent periods and clomiphene did not regulate your menstrual cycles by inducing ovulation, then COH is the next step. Similarly, COH may be an option if you did not become pregnant after three to six ovulatory cycles with clomiphene. There are some specific conditions where COH may be the initial form of treatment. Some brand names of FSH are Bravelleô, FollistimÆ and Gonal-fô, and one form of FSH/LH is MenopurÆ.
How it Works
With COH you receive daily injections for about ten days, but this varies for each woman. The COH treatment cycle is monitored closely with frequent ultrasounds of the ovaries and blood draws for estrogen levels in order to make sure that you are receiving enough, but not too much, of the injectable FSH. For example, if the ultrasound of the ovaries shows that too many eggs are beginning to grow, then your FSH dose can be decreased so that only a few eggs actually mature. When the ultrasound and estrogen level show that your eggs are mature, then your doctor will trigger ovulation with a different hormone, called human chorionic gonadotropin (hCG), also known as NovarelÆ and OvidrelÆ. HCG will cause the release of all mature eggs about 36 to 40 hours after the injection. Timing the IUI after hCG is more precise than is possible with an urinary OPK and with COH you no longer have to test your urine.
Frequently, the goal of COH is to stimulate the ovaries to grow and release up to six eggs per month. The more eggs there are, the more likely you are to get pregnant. However, the more eggs there are, the more likely you are to get pregnant with too many babies. The risk of twins, or more, jumps to 20-25% with COH. As with all fertility therapies, the goal is one healthy baby at a time. However, when triplets, or more, are discovered a procedure known as selective reduction is often recommended. At least half of triplet pregnancies are born more than seven weeks before their due date and quadruplets are usually born even earlier. Any baby born prematurely is very fragile and at risk for serious birth-related defects. When selective reduction is performed, usually the number gestations are reduced down to twins.
Another risk of COH is ovarian hyperstimulation syndrome (OHSS). This occurs when you receive too much FSH and/or your ovaries respond too vigorously to the treatment, growing large and painful. OHSS is rarely severe and typically lasts less than one week. Similar to clomiphene, the excess FSH causes the formation of temporary cysts on the ovaries, which requires that you take a month break from fertility treatment. In order to minimize your risk of OHSS and multiple pregnancies with COH, close supervision by an experienced fertility specialist is crucial.
Prior to starting clomiphene or COH, you doctor may recommend laparoscopic surgery to diagnose, and potentially treat, conditions that may be affecting your fertility. Laparoscopy is an outpatient surgery where a camera is inserted through the navel to directly image the ovaries, Fallopian tubes and pelvis. If an abnormality is discovered during laparoscopy, your doctor can surgically correct that problem at the same time in an effort to improve your chances of pregnancy with other fertility therapies.
In Vitro Fertilization (IVF)
IVF is the strongest form of fertility therapy available and was first successful in 1978. The Latin term “in vitro”, translates to “in glass”. Babies born after IVF have been called test tube babies because fertilization with eggs and sperm originally occurred in a glass test tube, instead of a woman’s Fallopian tubes. Some common reasons to pursue IVF are situations where the Fallopian tubes are blocked, sperm counts are low or pregnancy did result with other fertility therapies.
How it Works
IVF starts in a nearly identical fashion to COH, except the dose of the injectable FSH is increased in an attempt to produce a dozen, or more, eggs in one month. As with COH, an hCG injection is given to trigger the eggs to prepare for ovulation. However, an hour or two before the eggs are actually released from the ovaries, an egg retrieval procedure is performed under ultrasound guidance to capture the eggs. The egg retrieval procedure takes about 15 minutes and requires minor sedation.
Fertilization occurs several hours after the egg retrieval, and is confirmed the following morning. In the laboratory, there are two ways to fertilize the eggs with sperm. The first method is conventional fertilization where thousands of sperm are placed next to each egg and nature chooses the best sperm. The second method is known as Intracytoplasmic Sperm Injection (ICSI). ICSI involves taking one sperm and injecting it directly into the egg while using a microscope. ICSI is preferred when there is concern that conventional fertilization may not happen on its own, such as cases of low numbers of moving sperm or abnormally shaped sperm. Even though the fastest, most normal looking sperm are chosen for ICSI, there are theoretical concerns of a slight increase in birth defects with ICSI because nature is not choosing the sperm. As our experience with ICSI continues, more information about the children born from ICSI will be generated.
The fertilized eggs develop into embryos and their progress in the laboratory is observed for several days. Over the years, we realized it is normal that not all eggs fertilize and that not all embryos continue growing, likely due to an underlying problem in the sperm or egg. Fortunately, the process of IVF allows your doctor and the embryology team to choose the best embryos for transfer back into the uterus. Some patients have the luxury of having excess embryos, which can be frozen and transferred years later.
Therefore, the major advantages of IVF over other fertility treatments include, bypassing the Fallopian tubes, overcoming a low sperm count with ICSI, watching fertilization occur, and controlling the quality and number of embryos that reach the uterus. For instance, if two good quality embryos are transferred to the uterus the chances of pregnancy are relatively high, but the chances of triplets, or more, is negligible. Although rare, triplets can occur when only two embryos are transferred if both embryos attach and one splits into identical twins. Anything is possible!
Whereas the risk of twins with IVF, about 30 ñ 40%, is higher than COH, the chances of triplets or more can be much lower when the number of embryos transferred to the uterus is controlled. The risk of OHSS and temporary ovarian cysts are similar with COH and IVF. Complications such as bleeding or infection from the egg retrieval procedure are very, very rare.