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In recent years assisted reproductive technologies, including methods that use donor sperm and eggs, have been developed that help many people who in the past would not have been able to have a child. Unfortunately, infertility workups can be intrusive, costly, and emotionally exhausting. Many doctors (including myself) begin with the easiest, least expensive, least invasive tests, especially those that yield meaningful information. If these do not get at the cause, we can move to more difficult, invasive tests.

Most infertility tests can be done by an ordinary gynecologist. But if testing reveals a significant problem with ovulation or blockage of the fallopian tubes, your gynecologist may refer you to a reproductive endocrinologist. A specialist of this sort has had two or three years of training beyond regular gynecology training and can do complex surgery and manage the procedures of assisted reproductive technology.

What does a basic infertility workup include?

An ordinary infertility workup, the kind your gynecologist can do (with the help of a laboratory), may include tests that will determine whether your partner’s sperm are vigorous and capable of fertilizing an egg, whether your reproductive anatomy is generally healthy and normal, and whether your female hormones are doing their job adequately.

History And Pelvic Exam

The first step is a history and a pelvic examination. Your doctor will be interested in your general medical history and your menstrual history. Do you have regular periods? How heavy are they? How long is your cycle? Do you have cramps? Have you ever had pelvic inflammatory disease or another sexually transmitted disease? Your sexual history is also important. Are you currently monogamous? How many sexual partners have you had in the past? How many has your husband (or current partner) had?

The pelvic exam for an infertility workup is similar to the usual gynecological exam. Your caregiver will check to see if your uterus and ovaries are normal in size and “move well.” Endometriosis and pelvic inflammatory disease can cause scarring that “glues” down your reproductive organs, hindering their freedom to move slightly within your pelvis.

The Infertility Workup: Noninvasive Laboratory Tests

Other Diagnostic Tests

Endometrial Biopsy

An endometrial biopsy, a small sample of the lining of the uterus taken for diagnostic purposes, is the gold standard of fertility investigation. The procedure can show whether the uterine lining is thickening and maturing as menstruation approaches, a sure sign that ovulation has occurred and a necessity for supporting a fertilized egg. Because the biopsy shows the effect of progesterone on the lining of the uterus, it should be done toward the end of the menstrual cycle, when progesterone has had a week or so to work. Usually it is performed around days 23-25.

How is an endometrial biopsy done?

The procedure can be done in about two minutes in an office setting without anesthesia. A sharp tool (a curette) or a suction device is slipped through the cervix into the uterus and used to scrape away or suck out little samples of the lining.

Over the years the tools have gotten more sophisticated. The pipelle, a relatively new gadget from France, is narrower than earlier tools and easier to insert through the cervix; it samples tissue by suction rather than by scraping. My patients tell me it is a real improvement over the older technology.

Does an endometrial biopsy hurt?

While it is not painless, most women say it is manageable. Try taking an over-the-counter painkiller like Motrin or Aleve ahead of time to make the procedure less uncomfortable.

Can you have an endometrial biopsy during a cycle when you are attempting to getpregnant?

Doctors have different policies on this issue. Some women are concerned that if they are pregnant, the physician might remove the fertilized egg along with the biopsy sample. There is no danger that the procedure will damage the fetus; either it will remove the whole fertilized egg or it will leave the pregnancy undisturbed. However, some women prefer not to conceive during the cycle when they are to have an endometrial biopsy.

What can an endometrial biopsy show?

Your physician is hoping to see signs that the endometrium is preparing to receive the fertilized egg. If that is indeed the case, the microscope will show that the endometrial tissue is thicker and has more blood vessels, giving the tissue sample the classic appearance for the day of the cycle on which the test was done. If your cycle is normal, a pathologist (a doctor trained to look at tissue samples for diagnostic purposes) can look at a sample of the endometrium, even a small piece, and tell the day of the cycle — day 18, day 27, or whatever.

An endometrial biopsy is especially valuable for diagnosing inadequate luteal phase, a condition in which the egg gets fertilized and continues on its path to the uterus, but does not implant properly because the uterine lining does not thicken in time to accept and support it. (The luteal phase is the second half of the menstrual cycle, after ovulation.)

How does an endometrial biopsy help diagnose inadequate luteal phase?

The procedure is a little complicated and involves counting backward from the day the woman gets her period.

Sasha decides to go ahead with an endometrial biopsy after earlier testing shows that she is probably ovulating and that her husband has plenty of viable sperm.

Sasha has had thirty-two-day cycles since she was 15 years old, so we plan the test on day 28, four days before her period is due. By the criteria that pathologists use, that day is called day 24. Though Sasha thinks of herself as having thirty-two-day cycles, the pathologist evaluates her biopsy as if she (and every other woman who menstruates) has twenty-eight-day cycles. There are always fourteen days between ovulation and menstruation, though there may eighteen or twelve or some other number of days between menstruation and ovulation. Pathologists are only interested in the second half of the cycle.

So Sasha has a biopsy on day 24. The pathologist looks at the sample and decides that what he sees looks like a typical endometrial lining for day 24, or maybe day 23 or day 25. This is good news (pathologists are allowed to be wrong by a day or two): the assessment means that Sasha is ovulating well enough to produce the hormones that will cause her endometrium to build up and support a fertilized egg.

If Sasha’s tissue sample looks as if it were taken on day 16 or day 17 (and her period arrives three days later), then something is wrong. Her endometrium will not be ready to accept a fertilized egg. We call this time a lag phase or delay, a time when her uterine lining should be building up but is not.

Are there other symptoms for inadequate luteal phase?

Women with inadequate luteal phase are often in their mid-30s and beyond, when they probably are producing less progesterone than in younger days. Symptoms may include spotting or staining just before the menstrual period.

Can inadequate luteal phase be treated?

If your endometrial biopsy suggests inadequate luteal phase, your physician may suggest a repeat biopsy a couple of months later, to determine whether the results of the first test were a fluke or whether this problem happens with some regularity. Some doctors do not ask for a second test, deciding that if you have the problem once you probably will have it again.

The two therapies for inadequate luteal phase are hormones to bring about ovulation and progesterone to support the endometrium in the second half of the cycle.

Usually Clomid is used to stimulate ovluation. The progesterone must be natural progesterone (not any of the synthetic kinds used in birth control pills or for other kinds of therapy). Natural progesterone is available in oral and vaginal forms.

The first person to describe inadequate luteal phase was Georgeanna Seegar Jones, a gynecologist trained at the Johns Hopkins University School of Medicine. She and her husband, Dr. Howard Jones, are perhaps better known for being the first in the United States to do in vitro fertilization, in 1981 creating “test tube babies.” Together the couple founded the Jones Institute for Reproductive Medicine in Norfolk, Virginia.

(As an aside, I diagnosed myself with inadequate luteal phase when I was trying to get pregnant for the second time. I took Clomid, which worked on the second cycle and gave my husband and me our son. When I had the honor of meeting Dr. Jones, I thanked her for our darling Max.)

Hysterosalpingogram

Also called an HSG or hysterogram, this long name describes an imaging procedure for viewing the uterus (Greek, hystero) and the fallopian tubes (Greek, salpingo). The purpose of the test is to find out whether the fallopian tubes are open to the passage of egg and sperm, so that fertilization, which usually takes place in one of the tubes, can occur.

How is a hysterogram done?

Usually the test is performed in a radiology department. You lie in the dorsal lithotomy position, on your back with your feet up in stirrups; the radiologist holds the cervix with a special instrument and injects radio-opaque dye into your uterus through a thin tube, using a fluoroscope to watch the results on a screen so that she can tell right away if something is wrong. The radiologist will also take an x-ray picture to document the procedure. If the tubes are open, your doctor can see the dye squirt out through the fallopian tubes; if not, the x-ray will show where the blockage is.

What is the best time of the month to do a hysterogram?

With infertility testing, timing is important. The ideal time for a hysterogram is after the menstrual period and before ovulation, so that during the procedure none of the menstrual flow or a fertilized egg can be swept backward toward the open end of the tubes by the dye which is pushed into the tubes. The ideal time is around day 8,9, or 10 of the cycle.

Is a hysterogram painful?

The procedure sounds painful, and it can be uncomfortable. According to most of my patients it is not as distressing as an endometrial biopsy (though one patient told me it was the worst thing she ever endured). The entire test takes between two and five minutes. Most women get up and go home or back to work immediately afterward. You can certainly take Motrin or Advil or some other nonsteroidal anti-inflammatory painkiller before the procedure, just as you might for an endometrial biopsy.

What are the advantages of a hysterogram?

The hysterogram is an important test because about 25 percent of female infertility involves a tubal problem. It gives instantaneous results, as opposed to an endometrial biopsy, where you wait several days while the pathologist looks at the tissue samples. Another benefit is that many women do get pregnant within two or three months after the procedure, perhaps because pushing the dye through the tubes clears them out, even though they are not blocked by tubal disease. Since this test seems to have therapeutic benefits as well as diagnostic ones, we do it fairly early in the infertility workup.

Can a hysterogram give false results?

Yes, hysterograms can have false positive and false negative results. False positives come about because some women have a tubal spasm while the test is going on. There is no mechanical obstruction, but the tubes tighten up so that the dye will not pass through. Thus the test falsely suggests that the tubes are blocked when they are only in spasm.

Some physicians use a drug called Glucogon to relax the tubes. If the hysterogram shows obstruction, the tubes can be viewed directly with a laparoscope. But the procedure requires anesthesia and is more invasive. Laparoscopy will show whether the tubes are blocked or simply in spasm.

A second problem is that the dye can spill out the ends of the tubes, even if they are not functioning properly. Infection may have damaged the hair-like projections inside the tube that help move the egg along, but tube still looks open even though it does not function correctly. Nor can a hysterogram rule out endometriosis if the disease is not actually blocking the tube.

Can hysterograms have complications?

There is about a l-percent chance of infection. If you have had pelvic inflammatory disease, a hysterogram can make the old infection flare up again and your risk rises to about 3.5 percent. If you do have a history of pelvic inflammatory disease and your doctor recommends a hysterogram, remind her before you go for the test. She may advise preventive antibiotics. Women who have previously had an ectopic pregnancy, tubal surgery, or a ruptured appendix may also be at increased risk for infection and may benefit from preventive antibiotic therapy.

What happens if the hysterogram shows blocked fallopian tubes?

If the test suggests that your tubes are blocked, your doctor may wish to have those results verified by a laparoscopy. If the laparoscopy confirms tubal blockage, you are a candidate for in vitro fertilization or tubal surgery.

Can the x-rays and dye used during a hysterogram damage a fetus?

No, neither the minimal x-ray exposure nor the dye has been shown to cause any problems later. Because the hysterogram should be done before ovulation, women are unlikely to be pregnant during the procedure.

Can blocked fallopian tubes be treated?

There is a surgical procedure called a tuboplasty, during which a surgeon cuts out the blocked portion of the tubes and then reattaches the ends. It has only about a 30-percent chance of success, so infertility specialists often prefer in vitro fertilization if they discover tubal blockage. The decision depends on the condition of the fallopian tubes, the location and extent of the blockage, and so on.

If the blockage is near the ovary, at the end of the tube where the fimbriae reach out and sweep the egg into the tube, unblocking the tube has a reasonable chance of success. This operation is called a fimbrioplasty But if the blockage is near the uterus, tubal surgery is much more difficult. The surgeon can cut out the obstruction and then attempt to re-implant the narrow end of the tube into the main body of the uterus. This kind of very delicate surgery should only be undertaken by someone who has performed it many times.

Insurance companies will sometimes pay for tubal surgery but not for in vitro fertilization. In an ideal world, cost would not be a major consideration in such an important decision; in the real world, it is often a factor.

Postcoital Test

The next test I usually prescribe is a postcoital test, which checks the woman’s cervical mucus and looks for incompatibilities between it and her partner’s sperm. Although there is no magic order in which to do fertility tests, I tend to hold off on this one because it does not have a very high yield (only about 5 percent of couples have incompatibility problems). The test is not painful but it does put a direct demand on the couple and may be psychologically difficult.

Problems with cervical mucus can be physical: the mucus can be too thick for the sperm to swim upstream or there can be too little of it. Or there can be problems of incompatibility between this man’s sperm and this woman’s immune system, which may produce antibodies that kill the sperm.

How is a postcoital test done?

The couple has intercourse two to twelve hours before the examination. The time depends on the physician’s individual style of investigation: some doctors prefer to do the test only an hour after intercourse, others wait eight hours.

You go to your gynecologist’s office and have a pelvic exam. The doctor takes a sample of your cervical mucus, puts it on a slide, and looks at it under the microscope. The sample will show immediately whether the mucus has the right consistency — thin, clear, and stretchy like egg white. It will also reveal how the sperm are progressing. Ideally, the test should show lots of active, forward-moving sperm. Sometimes it shows only a few sperm, suggesting a low sperm count. Sometimes it shows a great many dead sperm, killed by antibodies in the cervical mucus or possibly dead before they entered the vagina.

Can a postcoital test substitute for a semen analysis?

If the man absolutely refuses to have a semen analysis (and I find that difficult to accept), a postcoital test will give some of the relevant information. If the postcoital test shows plenty of active, forward-moving sperm, then we know that sperm production is not a problem. However, if the postcoital test shows many sperm, but most or all are dead, then there is no way to tell whether the sperm was not viable to begin with or the cervical mucus has killed it. A semen analysis is necessary to get the vital information.

When during the cycle is a postcoital test done?

This test should be performed right around the time of ovulation. If you have a twenty-eight-day cycle, we do the test around day 13 or 14. If the test is done at the wrong time and misses ovulation by as little as a day or two, it can give misleading results. Suppose you ovulated on day 17 instead of your customary day 14. Your cervical mucus looks as if it is far too thick for sperm to swim through it, but in fact there is no problem at all, just poor timing.

Sometimes I schedule a repeat visit the next month because I think I may have guessed wrong about ovulation, and the couple becomes pregnant in the interim. That is the optimal result of an infertility workup.

How is a sperm antibody problem treated?

Years ago there were various approaches. One was to treat the woman and sometimes the man with anti-inflammatory medications, including steroids, which calm down the immune system’s reactions to antibodies. Another (not very successful) way was to treat the problem as an allergy. The man wore condoms during intercourse for six months, allowing her allergic reaction to subside. Then when the couple tried again for a pregnancy, the allergic response would not kill the sperm. Today a cervical mucus problem is treated with intrauterine insemination.

How does intrauterine insemination work?

Intrauterine insemination is a procedure whereby the sperm are placed up inside the uterus, bypassing the cervical mucus altogether. Although it sounds simple enough, the procedure has one complication. In the normal arrangement of things, semen does not reach the uterus: sperm do, but the seminal fluid does not. Seminal fluid contains prostaglandins, hormone-like substances that make the uterus contract. There fore if ordinary semen is introduced into the uterus, it will cause uterine contractions, which can be very painful and even cause women to go into shock.

For the insemination to succeed, the sperm must be washed free of seminal fluid and then resuspended in a solution similar to salt water. This requires special laboratory equipment, so most physicians cannot do the procedure in an office setting.

Does ordinary artificial insemination work if there is a problem with cervical mucus?

Artificial insemination (called AIH, artificial insemination with husband’s sperm) does not usually succeed with this kind of problem, because the cervical mucus kills the sperm whether they get into the vagina through ordinary intercourse or through artificial means. It is useful occasionally when there is some physical or anatomical problem — for example, an oddly shaped uterus — that might impede the progress of sperm.

Invasive Tests

Laparoscopy

Next on the agenda, and further along in terms of invasiveness, is laparoscopy, an investigative surgical procedure for observing the inside of the pelvis. A laparoscopy can provide information about scarring or adhesions around the fallopian tubes or growths of endometrial tissue outside the uterus, information not revealed by a hysterogram. Often it is the best way to diagnose endometriosis or assess the damage of pelvic inflammatory disease.

A laparoscope is a thin metal tube with light-transmitting fibers that permits your doctor to see inside your pelvis. It can be used in conjunction with small surgical tools to allow the physician to take little samples of the tissue if there is any question about the diagnosis.

Can a laparoscopy be done in an office setting?

In the past, laparoscopy was performed under general anesthesia in a hospital setting with operating room personnel, including an anesthesiologist and a gynecological surgeon. In these present days of cost-conscious medicine, laparoscopies are sometimes performed in surgicenters or offices. Instead of a general anesthetic that puts you to sleep, your doctor will give Novocain to anesthetize your skin, plus some light sedation (perhaps Valium) to make you drowsy. Instead of a regular laparoscope, which is approximately 1 cm in diameter, your doctor may use a smaller instrument, only about 3 mm in diameter. This tiny laparoscope helps to show what is happening in the abdomen, but it is not as useful as the larger version for actually removing endometriosis or doing other procedures.

Laparoscopy generally takes less than an hour. If an operable problem such as scar tissue is discovered, it can be removed through the laparoscope and the procedure may take longer. Laparoscopy should be done by a surgeon trained and experienced in the procedure.

Hysteroscopy

Hysteroscopy is a procedure for looking at the inside of the uterus. A hysteroscope, like a laparoscope, is a long narrow tube with a light at the end; it is inserted through the vagina and cervix into the uterus and does not require an incision. Hysteroscopy is useful in diagnosing fibroids, benign tumors of the uterus, or scarring within the uterus, but is not usually done unless your caregiver has reason to suspect one of these conditions. It can be performed with or without anesthesia. You will be able to do sedentary work the next day and will probably be back to your full schedule a few days later.

Do fibroids interfere with pregnancy?

Most women with fibroids do not have problems with infertility. Only rarely do fibroids prevent conception, for example by blocking the entrance to the fallopian tubes. If they do cause a problem with pregnancy, it is likely to be miscarriage.

What is Ashermans syndrome?

Occasionally hysteroscopy will turn up a condition called Ashermans syndrome, which involves such extensive scarring of uterine lining that menstrual periods cease. It is a complication for women who have had several D&Cs, maybe after miscarriage. If one of my patients stops menstruating after a D&C, I suspect Ashermans syndrome. It can be treated by a combination of surgery and hormonal therapy.

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