- Methods of Evaluating Infertility
Infertility can be caused by the dysfunction of one or more reproductive organs of either the male or female. Endometriosis, amenorrhea, ovarian dysfunction, and uterine disorders are just a few conditions that can cause female infertility. More than one cause of infertility can be present at a time. A woman who suspects she is infertile should seek a thorough medical examination by an infertility specialist. It is very important that the male partner be evaluated as well since 40% of the time there is a male factor. Treatment options are dependent upon the cause, yet most causes of infertility are amenable to some form of intervention.
Methods of evaluating infertility include the following:
- Ovulation Prediction – Luteinizing hormone (LH) is the hormone that triggers the release of the egg from the follicle. Ovulation prediction kits can be used to time intercourse. It has largely replaced BBT monitoring.
- Estradiol – Estradiol is released by the developing follicle. As more follicles develop, estradiol levels increase. Low levels of estradiol may indicate that the follicle does not contain a healthy egg.
- Follicle Stimulating Hormone (FSH) Assay – FSH is a hormone responsible for the development of the egg. FSH is measured on day 3 of the menstrual cycle. An elevated FSH is associated with a low chance of pregnancy.
- Progesterone – Progesterone is a female hormone produced after ovulation. Blood is drawn 4-9 days after predicted ovulation to determine if ovulation has occurred.
- Laparoscopy – Laparoscopy is a surgical outpatient procedure that allows the physician to diagnose and treat pelvic disorders, such as endometriosis. The physician can determine if tubes are open, scarring is present, or if there are uterine abnormalities.
- Semen Analysis – The semen analysis is one of the first tests ordered in the infertility evaluation. A sperm sample is obtained to determine the concentration, the shape and the ability of the sperm to swim in straight lines.
- Sperm Antibodies – These antibodies incapacitate the sperm before it can pass through the cervix and reach the egg, or they may impair fertilization of the egg.
- Evaluating the Uterus
Uterine disorders are just one of a few conditions that can cause female infertility. Methods of evaluating the uterus include the following:
- Sonohysterography is a valuable, safe, easy and cost-effective new technique for examining the inside lining of the uterus. Sonohysterography can be used to evaluate abnormal bleeding, infertility and recurrent pregnancy loss. It also can define abnormalities such as possible polyps and fibroids that are detected on X-ray hysterosalpingography and pelvic ultrasound. Sonohysterography involves instilling a small amount of electrolyte fluid into the uterus using a thin catheter that is placed through the vagina into the uterus. There may be some cramping associated with the procedure and a small risk of infection. Sonohysterography can distinguish between polyps and fibroids and clearly identifies their location and size. In the case of a normal sonohysterogram one might avoid unnecessary surgery. When an abnormality is found, it allows for proper surgical planning and perhaps avoidance of a purely diagnostic surgical procedure.
- Ultrasound is performed using a probe that is applied to the lower abdomen, or inserted into the vagina, while sound waves are passed through the surrounding organ systems. These sound waves penetrate tissues of different density to different degrees, thus creating an impression similar to an X-ray. Unlike X-ray studies, ultrasound has no known negative side effects. Vaginal probe ultrasonography is commonly used to monitor follicular development and visually confirm that the egg has been released from the follicle. Ultrasonography is also used to monitor the developing fetus and diagnose many other conditions.
- Hysterosalpingogram (HSG) is an X-ray examination used to outline the inside of the uterus and the Fallopian tubes. The HSG is recommended for various reasons, but is usually done to verify that the Fallopian tubes are open. The HSG is performed on day five to 12 of the menstrual cycle. A radiologist will take X-ray pictures of the abdomen as dye is slowly injected through a catheter that has been inserted into the uterus. You may watch on a television monitor as dye fills the uterus and Fallopian tubes. Several X-rays are taken during the procedure, but radiation exposure is minimal. Cramping may be felt as the catheter is introduced and as the dye is injected. Allergic reaction to the dye, which contains iodine, may occur. There is also a small risk of infection associated with the procedure; this is increased if you have a history of pelvic inflammatory disease (PID). After the procedure, you may wish to have someone drive you home due to cramping. If you are scheduled for the HSG, you will receive complete instructions.
- Ovulation Induction
Ovulation is the release of a mature egg from the ovary. Normally this occurs approximately every 28 days. The time from the start of the period to ovulation is variable; however it is usually 14 days from ovulation to the next period. Anovulation is the absence of ovulation. Anovulation is frequently corrected with fertility drugs and called ovulation induction. Ovulation induction is also performed in patients who are ovulatory to increase the chance of pregnancy. Most pregnancies occur in three cycles of a particular therapy.
Commonly prescribed drugs include: clomiphene citrate, human chorionic gonadotropin, follicle stimulating hormone and human menopausal gonadotropin.
Clomiphene citrate (CC) is often used to correct ovulatory disturbances. Approximately 80% of individuals will ovulate and approximately 40% will achieve a pregnancy using CC. CC is usually started at a dose of 50 - 100 mg daily by mouth on days 3 to 5 of the cycle and continued for 5 days. Ovulation usually occurs a week after the last dose of CC, from days 12 through 21 of the cycle. The total cycle may be as long as 35 days. Documentation of ovulation may be confirmed with a day 21 progesterone blood test, basal body temperature chart or a urine ovulation predictor kit. If ovulation is not achieved, the dose is increased by 50 mg increments usually to a maximum dose of 150 mg daily.
The side effects of CC include:
- Hot flashes (10%),
- Abdominal discomfort (5%),
- Nausea and vomiting (2.2%),
- Headache ( 1.3% ),
- Visual symptoms (1.5%),
- Mood swings
The risks of CC include multiple pregnancy, ovarian cysts, torsion (twisting of the ovary), and ovarian hyperstimulation syndrome. An increased risk of ovarian cancer has been debated and the data are conflicting, however it is recommended to minimize the number of cycles to those necessary.
Baseline ultrasound or pelvic exam should be performed in consecutive cycles to avoid large cyst formation. Visual symptoms usually resolve within two weeks. CC should be discontinued if visual symptoms occur and an alternative therapy utilized. The multiple pregnancy rate is approximately 5%, almost entirely twins; however, rare cases of higher order multiples have been reported. Once ovulation has been achieved, higher doses of CC do not appear to have any beneficial effects. One should reassess therapy after 3 ovulatory cycles if no conception occurs. The pregnancy rate with additional cycles is low, although the ovulatory rate remains high.
CC may alter the quality of the lining of the uterus and the cervical mucous. CC may make the lining of the uterus thin. If this occurs the chance of pregnancy is low. This may be corrected by adjusting the dosage of CC or using FSH is subsequent cycles. CC may make cervical mucous thick and impermeable to sperm. Intrauterine insemination of sperm bypasses the cervical mucous and may increase the chance of pregnancy.
Human chorionic gonadotropin (hCG) is often added to CC or FSH cycles. HCG causes the ovary to release an egg and help time inseminations. Ovulation usually occurs 36-72 hours after hCG is given. HCG will cause pregnancy tests to be falsely positive.
Follicle stimulating hormone (FSH) is the hormone that stimulates eggs to mature in the ovary. Recombinant FSH is manufactured in the laboratory. These products do not contain Luteinizing hormone (LH), a hormone that helps regulate the menstrual cycle and egg production (ovulation). Human menopausal gonadotropin (hMG) contains equal parts of FSH and LH that are derived from the urine of menopausal women. FSH may be used in women who cannot make their own FSH, who failed CC or to increase the chance of pregnancy in ovulatory women. FSH treatment requires careful monitoring. Risks include a multiple pregnancy rate of 20-30% and ovarian hyperstimulation syndrome rate of 1%. An increased risk of ovarian cancer has been debated and the data are conflicting; however, it is recommended to minimize the number of cycles to those necessary.
FSH is usually begun on the third day of the cycle by either subcutaneous or intramuscular injection. The daily dose is adjusted after monitoring with ultrasound and estradiol blood tests. The injections usually last 7-12 days, but may take longer if the ovaries are slow to respond. Once a mature egg is identified on ultrasound ovulation is triggered with hCG or LH. The cycle may be cancelled if too few or too many eggs develop.
GnRH agonists and antagonists are synthetic hormones that are administered by injection to control the release of LH. GnRH analogues are used to prevent the spontaneous release of an egg.
Side Effects of Medications - there are many types of gonadotropins used alone or in combination for ovulation induction. During the use of these drugs careful monitoring is required to minimize the risk of side effects, discussed below.
Ovarian Hyperstimulation (OHSS) - occurring in 1 to 5 percent of cycles, the chance of OHSS is increased in women with polycystic ovarian syndrome and in conception cycles. When severe, it can result in blood clots, kidney damage, ovarian twisting (torsion), and chest and abdominal fluid collections. In severe cases, hospitalization is required for monitoring, but the condition is transient, lasting only a week or so. Occasionally, drawing fluid out of the chest or abdominal cavity helps. The best prevention is to not give hCG to induce ovulation at the end of an overly vigorous stimulation cycle.
Multiple Gestation - up to 20 percent of pregnancies resulting from gonadotropins are multiple, in contrast to a rate of 1 to 2 percent in the general population. While most of these pregnancies are twins, a significant percentage are triplets or higher. High order multiple gestation pregnancy is associated with increased risk of pregnancy loss, premature delivery, infant abnormalities, handicap due to the consequences of very premature delivery, pregnancy induced hypertension, gestational diabetes, hemorrhage, and other significant maternal complications.
Ectopic (Tubal) Pregnancies - while ectopic pregnancies occur 1 to 2 percent of the time, in gonadotropin cycles the rate is slightly increased at 1 to 3 percent. These can be treated with medicine or surgery. Combined tubal and intrauterine pregnancies (heterotopic pregnancies) occasionally occur with hMG and need to be treated with surgery.
Birth Defects - the rate of birth defects after gonadotropin cycles is no higher than in the general population, at 2 to 3 percent. Furthermore, these children are developmentally no different than their peers.Adnexal Torsion (Ovarian Twisting) - less than 1 percent of the time, the stimulated ovary can twist on itself, cutting off its own blood supply. Surgery is required to untwist or even remove it.
Gonadotropins and Ovarian Cancer - the risk of ovarian cancer seems, in part, to be related to the number of times a woman ovulates. Infertility increases this risk; birth control pill use decreases it. Controversial data exists that associate ovulation stimulation drugs, like gonadotropins, with the risk of future ovarian cancer. While research is underway to help clarify this issue, the careful use of gonadotropins is still RSS021 reasonable, especially considering that pregnancy and breast feeding reduce cancer risk.
- Minimally Invasive Surgery
Evaluation and correction of many reproductive organ abnormalities is frequently feasible through minimally invasive surgery (MIS). Thanks to technological advances, what used to be major gynecologic surgery can now be done on an outpatient basis. This means minimal incisions and significantly shorter recovery time for the patient.
- Laparoscopy can lead to the diagnosis of many gynecological problems including endometriosis, fibroid tumors, ovarian cysts, ectopic pregnancies, and adhesions: Most infertile patients require laparoscopy for a complete evaluation. It involves placement of carbon dioxide gas into the abdominal cavity, creating a space that allows placement of a telescope-type device (laparoscope), approximately 0.5 inches in diameter, into the abdomen. While looking through the laparoscope, the surgeon can see the reproductive organs including the uterus, fallopian tubes, and ovaries. If problems are identified, they often can be surgically corrected using instruments guided through the laparoscope. The risks of laparoscopy are minimal, but includes anesthesia related complications, bleeding, infection and injury to abdominal organs. Certain conditions increase the possibility of complications. Individuals who have had a previous operation in the abdomen, especially involving the bowel, or history of bowel or pelvic adhesions are at an increased risk. Other conditions that lead to a higher risk of complications are evidence of infection in the abdomen, a large growth or tumor within the abdomen, and obesity. After a laparoscopy, the naval area is usually tender and your abdomen may be bruised. Your shoulders may hurt from the gas placed in the abdomen, and because of the effects of the anesthesia, you may feel nauseated and weak. You will be able to resume normal activities after a few days.
- Hysteroscopy is used to examine the inside of the uterus. This procedure can assist in the diagnosis of abnormal uterine conditions such as internal fibroid tumors, scarring, polyps, and congenital malformations. Therefore, hysteroscopy is an important tool in the study of infertility or abnormal uterine bleeding. Hysteroscopy uses a fluid medium to create a window into the uterine cavity and facilitates removal of polyps or resection of fibroids impinging on the uterine cavity. The hysteroscope is passed through the cervix and into the lower end of the uterus. Complications rarely occur during hysteroscopy. In a few cases, infection of the uterus or fallopian tubes can result. Occasionally, a hole may be made through the back of uterus (perforation). However, this is usually not a serious problem because the perforation spontaneously closes. After a hysteroscopy you can expect cramping similar to that experienced during your menstrual period and to have some vaginal drainage for several days. Most likely, you’ll resume regular activities within one to two days after surgery. You should avoid sexual intercourse for a few days or for as long as bleeding occurs.
- Basal Body Temperature
Knowledge of whether and when ovulation occurs is essential. Identifying the time when ovulation is likely to occur allows for proper planning of intercourse when fertility is optimal. A simple method of estimating the time of ovulation is by charting daily oral temperatures. A woman’s temperature is lower during the first part of the menstrual cycle than it is during the last 2 weeks. The temperature shift occurs near ovulation. Ovulation is assumed to occur when there is a rise of 0.4 to 0.6°F or more between 24-hour readings.
- Use only a special “metabolic” thermometer with a Fahrenheit scale. Learn to read it accurately.
- Shake down the thermometer before you go to bed and place it on your bedside table.
- Take your temperature each morning immediately after waking, before arising, eating, drinking, smoking, or undertaking any type of physical activity. Temperature should be taken for 5 minutes, by the clock. Record your temperature as a solid dot at the intersection of the appropriate temperature and date lines.
- Also indicate, in the appropriate places, when intercourse and menstruation occur. And note, on the chart, any reasons for temperature variation such as illness, infection, insomnia, etc. Be sure to place an “x” on the medication line. Then write in the name of any medication, such as aspirin, acetaminophen, antihistamine, or antibiotic, taken during the month. (See sample chart.)
- Your BBT is an indirect predictor that cannot pinpoint the exact day of ovulation. Therefore, it is important to have sexual relations at the anticipated time of ovulation. Ideally, intercourse should take place at lease every other day beginning 1 to 2 days prior to the anticipated day of ovulation and for a 2-to 3-day period following the upward shift in body temperature. This is your most fertile period.
- Start a new chart when menstrual bleeding begins.
- Urinary LH Testing to Determine Time of Ovulation
During the menstrual cycle, a follicle, which is fluid filled sac containing the egg, develops in the ovary. When the follicle is sufficiently developed, the pituitary gland in the brain releases a surge of luteinizing hormone, or LH. This hormone causes the follicle to rupture, releasing the egg so that it may be captured by the fallopian tube.
By pinpointing the time of ovulation, we can better time procedures such as the post-coital test or intrauterine insemination. Some couples prefer to use the LH kit to time intercourse. If you want to do this, we suggest having intercourse the day or evening of the color change and again on the following day. Sperm live in the reproductive tract for up to seventy-two (72) hours.
We recommend that you obtain either the Clear Plan Easy or First Response test kit at your local pharmacy.
Be sure to do the ovulation predictor test each morning starting 3 days before expected ovulation (cycle day 11 in a 28 day cycle). Empty your bladder at least once after awakening before you collect urine for this test. Follow the directions in the kit, but do test your urine in the morning. If you have any questions, please call our office at (770) 292-2670.
What is Clomiphene?
- Clomiphene stimulates the release of hormones necessary for ovulation to occur.
- Clomiphene is used to stimulate ovulation (the release of an egg) when a woman’s ovaries can produce a follicle but hormonal stimulation is deficient.
- Clomiphene may also be used for purposes other than those listed in this medication guide.
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