Treatment of Infertility

When specific causes of infertility are identified, the obvious first line of treatment is to restore the reproductive system to normal. For instance, when a fibroid or septum is found within the uterine cavity, surgical removal is the treatment of choice. In the case of ovulation problems, ovulation induction will often result in pregnancy. In cases of unexplained infertility, nonspecific treatment is used, since the subtle causes of infertility can often be overcome with this approach.

In cases where the cause of fertility is known but cannot be resolved, the goal of treatment is to circumvent the problem. This approach is often required in the presence of severely abnormal semen analyses. Traditionally, this problem is treated with donor sperm. More recently, severely abnormal semen analyses can often be successfully treated by injecting sperm into each egg during IVF. Another of these situations is tubes blocked by scar tissue, for which the most common treatment is IVF.

In general, the least expensive, simplest and lowest risk treatment options are employed first. If these are not successful, more invasive options can be used. Fertility treatments are covered by insurance to a variable degree, if at all, in most areas of the country. For this reason, financial considerations should be taken into account when making treatment decisions.

Surgical Treatment

Operative Laparoscopy

Gynecologic problems discovered at the time of laparoscopy can often be effectively treated. Endometriosis can be removed or destroyed. Tubal adhesions can be removed, and the fallopian tubes can be re-opened. However, in either case, the reproductive tissues cannot be returned to their pre-disease state, and a large percentage of adhesions recur. These patients continue to be at increased risk of having a tubal pregnancy even after treatment. Although surgical treatment improves fertility rates, many patients will require assisted reproductive techniques, such as IVF, to achieve pregnancy.

Operative Hysteroscopy

Operative hysteroscopy is similar to diagnostic hysteroscopy. However, because a larger scope is required to perform intrauterine surgery, operative hysteroscopy is routinely performed in the operating room under general anesthesia as an outpatient procedure. This technique is an effective method for removing fibroids, a uterine septum or endometrial polyps.

Ovulation Induction

Ovulation induction refers to the use of medications to induce or stimulate ovulation. Some medications are taken orally (for example, clomiphene citrate) and others are given by injection (for example, FSH). These medications indirectly or directly stimulate the ovaries so that ovulation is more likely to occur.

Clomiphene Citrate

Clomiphene citrate is the most common medication used for ovulation induction. This oral medication acts as an anti-estrogen. When taken for 5 days early in the menstrual cycle, it increases the hormones that stimulate the ovaries: LH and FSH, as mentioned above. This increases the chance of ovulation and often results in the release of more than one egg. For this reason, the primary risk of clomiphene citrate is twins, which occur in up to 7-10% of patients who become pregnant, and the rate of triplets is 1%.

Clomiphene citrate is most often initiated without ultrasound monitoring with good results. If pregnancy has not occurred during unmonitored cycles, cycles are often monitored with transvaginal ultrasound. In patients with PCOS, metformin (an oral diabetes medicine) is sometimes added to clomiphene citrate for ovulation induction.

Follicle Stimulating Hormone

Follicle Stimulating Hormone (FSH) is an injectable medication used to stimulate ovulation. This medication is much more expensive than clomiphene citrate, and the response of an individual woman is somewhat variable. For this reason, it is important to monitor cycles carefully with ultrasound and serum estradiol levels to minimize the risk of multiple pregnancies and ovarian hyperstimulation. Even with careful monitoring, the rate of twins is more than 30% and the risk of triplets or more is at least 5%.

Intrauterine Insemination

Intrauterine insemination (IUI), the most common form of artificial insemination, is a fertility treatment commonly used to increase the number of sperm that reach the egg. The doctor or nurse injects a washed sperm sample through the cervix and into the uterus. The sperm sample can be from either the patient’s partner or a donor. IUI is performed as close as possible to the time ovulation occurs.

IUI appears to improve pregnancy rates in infertile patients regardless of cause, presumably by dramatically increasing the number of motile sperm that reach the egg. IUI is commonly used as a specific treatment for men with abnormal semen analyses. Although several tests have been developed to try to determine fertilization ability of sperm, none has been shown to be highly accurate in predicting pregnancy after IUI.

In Vitro Fertilization

In vitro fertilization (IVF) is another treatment for infertility, regardless of cause. It is the treatment of choice for women with blocked tubes, men with severely abnormally semen analyses and women who require donor eggs, or a gestational carrier. The essence of IVF is to stimulate the ovaries to make a number of mature eggs, remove these eggs from the ovaries, fertilize them with sperm in the laboratory and place resulting embryos into the uterus.

The first step for IVF is to give the woman a medication to prevent release of the eggs prior to the planned removal. This is most commonly done with injections of a drug called leuprolide acetate, which prevents ovulation.

Next, the woman is given injectable FSH, with or without LH, to stimulate her ovaries to develop multiple mature eggs. The cycle is closely monitored by measuring serum estradiol levels and ovarian follicle growth with transvaginal ultrasound. When the follicle size indicates that the eggs are mature, ovulation is triggered with an injection of human chorionic gonadotropin (hCG).

Multiple eggs are removed from the ovaries using an ultrasound-guided transvaginal needle with the patient under anesthesia. The eggs are then fertilized by placing the sperm directly on the egg or by injecting a single sperm into each egg using a technique called intracytoplasmic sperm injection (ICSI). In three to five days, one or more (depending on the age of the woman) of the resulting embryos are transferred through the cervix into the uterus using a catheter and ultrasound guidance. Patients take progesterone to help support the possible pregnancy, and a pregnancy test is performed approximately two weeks after embryo transfer.

Success Rates

Success rates for IVF depend on many factors, including the age of the woman and the cause of infertility. About 35-40% will become pregnant and approximately 80% of those will ultimately deliver a child. Of these women, about 25% will have twins and 1 will have three or more infants.

Complications

Medical complications from IVF are very infrequent. The most common is ovarian hyperstimulation syndrome, which occurs in approximately 5% of patients. This complication is more likely to occur in women with extremely high estradiol levels and is characterized by nausea and vomiting, increased intra-abdominal fluid and, occasionally, shortness of breath. It resolves within weeks with supportive therapy.

3rd Party Reproduction

The use of donor sperm, egges or a gestational carrier has become a common technique to achieve pregnancy for some causes of infertility. Sperm donors are usually anonymous and frozen vials of processed samples are obtained from large donor sperm banks. The donors are tested for multiple genetic and infectious diseases prior to donating. The tests for infectious diseases are repeated six months later, prior to releasing the sample from “quarantine.” These sperm samples are used for IUI or, if required, for IVF. The success rates using donor sperm depends on any other diagnoses the woman might have and on her age.

Egg donors can be either anonymous or known relatives or friends. Eggs must be retrieved transvaginally after ovarian stimulation and are used for IVF. Since the donor must undergo multiple tests and an invasive procedure, use of anonymous donor eggs for IVF more than doubles the cost to the recipient.

A gestational carrier is a women who carries a pregnancy for another woman. The “intended parents” would go through IVF and create embryos, but they would then be put into the uterus of a gestational carrier. This is an option for patients who have medical problems that prohibit pregnancy or if they have significant problems with their uterus or a history of a hysterectomy.

From a medical perspective, the use of donor eggs and sperm is a reasonable option for achieving pregnancy. Psychologically, using donor sperm or eggs is similar to adoption in some ways, since only one member of the couple will be genetically related to the offspring. Although donor sperm is relatively inexpensive, donor eggs are the most expensive infertility treatment option because their use requires IVF. For these reasons, donor sperm or eggs are not acceptable options for all couples.

When Treatment is Not Successful

With modern fertility enhancing techniques, a large percentage of couples will be successful in achieving pregnancy and becoming parents. However, some couples will be unable to achieve pregnancy despite multiple efforts over years. Sometimes, this is because of insurmountable medical problems. These are most often related to an anatomical abnormality of the uterus or an inability to carry a pregnancy for a range of both diagnosable and unknown causes. In many cases, couples exhaust their financial or emotional reserve before achieving success. Couples who undergo fertility treatment should be aware of the options they have if they are unable to achieve their goal of pregnancy.

Adoption is perhaps the most common alternative option chosen by couples who desire to be parents. This long-established alternative can take a number of years and can be as expensive as fertility treatment. Successful adoptive parents have all the joys and rewards of parenthood with the additional responsibilities of adoption. A multitude of adoption aid and support organizations exist to assist those with this interest.

Choosing to Not Have Children – A final option that some couples choose is not to have children. Helping couples come to terms with their loss and determining which alternative plan is most acceptable to both members of the couple often requires the aid of psychological counseling. When couples undergo fertility therapy for a number of years without success, the stress experienced by couples and alternative options to achieving pregnancy should be addressed by their doctor at regular intervals.

Sources:

American Society for Reproductive Medicine. Infertility: an overview, United States. 2003. Birmingham, Ala: American Society for Reproductive Medicine.
Centers for Disease Control and Prevention. 2006 Assisted Reproductive Technology Success Rates, National Summary and Fertility Clinic Report. Atlanta: 2008.
Falcone T, Hurd WW, eds. Clinical Reproductive Medicine and Surgery, New York: Elsevier, 2007.
Van Voorhis BJ. Clinical practice. In vitro fertilization. 2007 N Engl J Med 2007;356:379-86.

Prepared in partnership with Melina Dendrinos, MD, Class of 2008

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