Infertility is typically diagnosed as an inability of a couple of reproductive age to achieve conception after one year of sexual intercoursewithout contraception. These categories are often further subdivided into primary infertility, patients without any prior pregnancies, and secondary infertility, referred to as couples who are experiencing infertility after having had previous conceptions.

There are multiple causes of infertility and in many patients more than one cause for infertility maybe present. Accordingly, a thorough evaluation is required. Common causes of infertility can include abnormal sperm parameters in 35% of cases, ovulation and egg quality disorders in 25% of cases, pelvic adhesions, endometriosis, fallopian tube disorders, uterine disorders and in 5%-10% of all infertile couples specific factors are not identified as a cause of their infertility.

Most of the tests required for the evaluation of infertility must be done at particular times in the menstrual cycle. Treatment is seldom helpful until the investigation is completed. Above all, success in establishing pregnancy requires a period of close cooperation between the couple and the medical team. Our specially trained physicians, nurses, technicians, and secretarial staff at our centers work hard to make your visit as positive and productive as possible.

What are the requirements for normal fertility?
>> The male must produce a sufficient number of normal, motile sperm, which travel through unobstructed pathways, and are released from the penis as an ejaculate.

>> The sperm must be deposited in the female vagina at the appropriate time during the menstrual cycle when they can penetrate the cervical mucus, ascend through the uterus and fallopian tubes, and fertilize the egg.

>> The woman must produce a healthy and mature egg which is released from the ovary. After the ovary releases the egg, the egg must move down the fallopian tube so that it may encounter sperm and be fertilized.

>> The fertilized egg must move into the uterus and implant in a matured endometrium (the uterine lining) which will nourish its further development.

Semen analysis
One of the first steps in the evaluation of infertile couples typically includes a semen analysis. A semen sample is typically collected 2-4 days after the last sexual encounter. After the semen is collected through masturbation, it is analyzed for volume, the number of sperm present, the number of sperm which are motile, and an overall assessment of the percent that appear normal under a microscope. Normal values for a semen analysis include a volume of 3-5 mL, a count of >20 million per mL, motility of >50%, and morphology with >6% being normal based upon strict morphology.

Assessment of Eggs and Ovulation
There are several methods that can be utilized to assess ovulation. In addition to assessing ovulation, we are also interested in the "quality" of the eggs themselves (which is often referred to as 'ovarian reserve'). It has been clearly demonstrated that as each woman ages, both the number and quality of eggs available to achieve pregnancy continues to decline. This decrease is termed 'reduced ovarian reserve.

Measurement of urinary LH:
Another method for measuring ovulation is through an ovulation predictor kit, which assesses the urine for the presence of a hormone (luteinizing hormone) which is present in high concentrations before ovulation. Urinary ovulation predictor kits are generally performed for 4 or 5 days during the mid cycle beginning around cycle day 11. There is a change in the color of the test when the concentration of luteinizing hormone increases in the urine. This predicts in advance when ovulation is occurring and is often helpful in timing inseminations and intercourse for the most fertile time of the woman's cycle.

Evaluation of cervical mucus:
Cervical mucus is secreted from the cervix around the time of ovulation. This cervical mucus is crucial as it provides a method for the sperm to travel from the vagina into the uterus. The cervical mucus evaluation is typically performed through a regular speculum examination and assessment of the quality and quantity of cervical mucus present around the time of ovulation.

Post coital tests:
Post coital test is very similar to a cervical mucus evaluation, however, it is conducted 4-12 hours after sexual intercourse around the expected time of ovulation. This evaluation can provide insights into not only the quantity and quality of mucus present, but also an estimate into the concentration of sperm available and an assessment of the sperm and mucus interactions.

Hysterosalpingogram:
A hysterosalpingogram is often referred to as an HSG and is a method to evaluate the shape of the inside of the cervix, uterine cavity, and fallopian tubes. This is a very important test to evaluate if the uterus has a normal configuration and if fallopian tubes are open and normal in appearance.

The test is performed by injecting a small amount of fluid into the uterus, which blocks all x-ray beams. While this fluid is being injected into your uterus, x-ray beams are used to visualize the flow of the fluid and the configuration of your uterus and fallopian tubes. This entire tests takes approximately 3-5 minutes and preliminary results are available immediately.

This test is typically performed early in the menstrual cycle after the cessation of menstrual flow and prior to ovulation. It is very important for our office to set up this appointment within a day or so after your period ends.

Laparoscopy:
The infertility evaluation often also requires an assessment of the condition of the outside of your uterus, fallopian tubes, and ovaries. This evaluation checks for the presence or absence of adhesions, endometriosis and other disorders that can result in infertility.

The doctor can then view the reproductive organs during this procedure. If adhesions or endometriosis are present they can be treated during the same procedure. The entire surgery typically takes less than an hour and the vast majority of patients are released from the hospital within 3-4 hours after surgery.

Clomiphene citrate (marketed as Clomid and Serophene) was first synthesized in 1956 and introduced for clinical trials in 1960. Since then it has been widely used as a 'first line' approach to increase the growth and maturation of ovarian follicles (the small 'cysts' in the ovary where the egg develops). Clomiphene citrate is typically administered on either days 3-7 or days 5-9 of the menstrual cycle with day #1 defined as the first day of normal menstrual flow.

Clomiphene tablets are taken orally and it is best to take them at the same time each day. The "fertile time" or the time of ovulation usually occurs 5-8 days after the last clomiphene tablet is taken.

It is up to the physician to determine how clomiphene cycles should be monitored. Early in treatment, it is common for patients to take clomiphene citrate for 5 days each month and return for a follow-up examination in 3 months if they do not become pregnant. For various reasons, the physician may wish to monitor the cycles more closely. He or she may use a combination of ovulation predictor kits and/or ultrasounds to determine the number of follicles present, the rate of growth and to help pinpoint the time of ovulation.

Clomiphene citrate has been used for many years and is considered a very safe drug. It does, however, have risks and occasionally there may be side-effects. Most patients have no symptoms while taking clomiphene. The side-effects can include abdominal discomfort often described as "fullness and/or soreness," hot flashes, moodiness, or visual disturbances. Acetaminophen (Tylenol®) can help with these symptoms. In a few patients, clomiphene can cause enlargement (a cyst) of the ovary. This will sometimes disappear without treatment, but as a precaution, patients are advised to seek an internal examination as recommended by their physician.

Clomiphene is associated with a 10% incidence of multiple births, but the vast majority of these multiple births are twins. There is no increased risk of birth defects or other complications. Of course, the outcome of a pregnancy cannot be guaranteed.

Ovulation induction is a term that refers to the administration of medication to stimulate ovulation. These medications range from clomiphene to gonadotropins to combinations of the two. Gonadotropins are injectable ovulation stimulating hormones that are identical to the hormones secreted by the body. With the administration of these injectable medications, we are able to increase the circulating levels of these hormones, resulting in the stimulation and growth of multiple eggs. In addition to increasing the number of eggs with the use of gonadotropins, we control timing factors, such as when ovulation occurs, to maximize the chance of becoming pregnant.

A variety of medications are utilized for ovulation induction. Clomiphene citrate is a medication developed in the 1960's which can be used alone or in conjunction with injectable gonadotropins to help stimulate the ovaries.

There are multiple types of gonadotropins available for ovulation induction. The most commonly used gonadotropin at the our centers is a man-made form of follicle stimulating hormone (FSH) which is identical to the hormone secreted from the pituitary gland. Because this formulation is man-made it contains very few impurities and accordingly can be injected directly under the skin with very few local reactions. Other injectable medications include human menopausal gonadotropin (hMG) which contains both FSH and LH. Because of the formulation, the majority of these medications require injections into the muscle.

We closely monitor all cycles involving gonadotropins. We can monitor a patient's response in two ways:

Vaginal ultrasounds - Vaginal ultrasounds can visualize the number of developing eggs and measure their size and growth.

Early in the stimulation cycle we measure estradiol levels and perform vaginal ultrasounds every couple days to assess growth. Towards the end of the cycle we perform these assessments more frequently to control the timing factors that will maximize the chances of becoming pregnant and minimize side effects.

Ovulation induction cycles are usually followed by the administration of human chorionic gonadotropin (hCG), an injection to induce ovulation. Approximately 34 hours after ovulation, intrauterine inseminations are performed. Intrauterine inseminations use specially prepared and concentrated sperm, which helps to maximize the number of sperm available for fertilization.

There are side effects and risks associated with gonadotropin use. The most common side effects of these medications include discomfort or "fullness" in the lower abdomen, bloating, headache or fatigue. Patients can also experience discomfort in the area of injection. Massaging the area or applying heat is often helpful.

Perhaps the most significant risks of using injectable gonadotropins are multiple gestation and ovarian hyperstimulation. Ovulation induction can have up to a 20% incidence of multiple gestation (more than one fetus). The majority of these pregnancies are twins, however, more than two fetuses can sometimes develop. Vaginal ultrasounds help us to determine how many follicles you have developing, but this is only a guide and not a specific count. If you should develop too many follicles, you may be counseled to stop treatment to avoid the risk of multiple pregnancies. Pregnancy with three or more fetuses at a time places both the mother and fetus at high risk for miscarriage, pre-term delivery and bleeding. We at our centers take this risk very seriously and will monitor your progress very closely.

Ovarian hyperstimulation typically occurs 5-7 days after hCG injection. After hCG is given and ovulation occurs, the ovaries will frequently enlarge. If pregnancy results, the ovarian enlargement may persist for up to six weeks. In general, the symptoms associated with ovarian hyperstimulation are mild and may include lower abdominal pain, heaviness and bloating. Sometimes shortness of breath may also develop. It is extremely uncommon for hyperstimulation to result in any severe medical problems or hospitalizations. We will closely follow your progress to avoid problems of ovarian hyperstimulation.

Polycystic ovarian syndrome is a common hormonal disorder that is poorly understood and clinically characterized by irregular menstrual cycles, lack of regular ovulation, abnormal facial hair growth, infertility, obesity and polycystic ovaries (enlarged, cystic ovaries). This disorder affects approximately 6% of all reproductive age women. Recent evidence is overwhelming that polycystic ovarian syndrome is a disorder characterized by insulin resistance and a compensatory elevated insulin levels, which are found in both the overweight and non-overweight women with polycystic ovarian syndrome.

Traditional therapy for women with infertility secondary to polycystic ovarian syndrome has been ovulation induction using clomiphene citrate as a first line agent. Due to the recently recognized elevated insulin levels and insulin resistance, the use of insulin sensitizing agents such as metformin (Glucophage®) for ovulation induction have recently been studied with promising results.

A study recently published in the New England Journal of Medicine, July of 1998 demonstrated that women polycystic ovarian syndrome had increased rates of ovulation when placed on medications that lower insulin levels. Of the women placed on this medication (metformin), 34% achieved spontaneous ovulation without ovulation induction agents, compared to 4% in the placebo control group. Of those women who did not ovulate on metformin, 90% achieved ovulation with 50 mg of clomiphene citrate, compared with 3 of 26 women (8%) in the placebo group.

Insulin lowering agents for ovulation induction in women with Polycystic Ovarian Syndrome are an attractive alternative due to their low cost, minimal side effects and decreased risk for multiple pregnancies compared with other agents.