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Chorionic gonadotropin

Human chorionic gonadotropin (hCG) is a peptide hormone produced in pregnancy, that is made by the embryo soon after conception and later by the trophoblast (part of the placenta). Its role is to prevent the disintegration of the corpus luteum of the ovary and thereby maintain progesterone production that is critical for a pregnancy in humans. hCG may have additional functions, for instance it is thought that it affects the immune tolerance of the pregnancy. Early pregnancy testing generally is based on the detection or measurement of hCG. more...

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The drugs Pregnyl®, Follutein®, and Ovidrel® use chorionic gonadoptropin as the active ingredient in their product. These preparations are used in assisted conception in lieu of luteinizing hormone to trigger ovulation.

Structure

hCG is a glycoprotein composed of 237 amino acids with a molecular mass of 36.7 kDa. It is heterodimeric, with an α (alpha) subunit identical to that of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). Its β (beta) subunit is unique to hCG.

Function

hCG promotes the maintenance of the corpus luteum and causes it to secrete the hormone progesterone. Progesterone enriches the uterus with a thick lining of blood vessels and capillaries so that it can sustain the growing fetus.

Because of its similarity to LH and FSH, hCG can also be used clinically to induce ovulation in the ovaries as well as testosterone production in the testes. As the most abundant biological source is women who are presently pregnant, some organizations collect urine from gravidae to extract hCG for use in fertility treatment.

Pregnancy testing

Pregnancy tests measure the levels of hCG in the blood or urine to indicate the presence or absence of a fertilized egg. In particular, most pregnancy tests employ an antibody that is specific to the β-subunit of hCG (βhCG). This is important so that tests do not make false positives by confusing hCG with LH and FSH. (The latter two are always present at varying levels in the body, while hCG levels are negligible except during pregnancy.) The urine test is a chromatographic immunoassay that can detect levels of βhCG as low as 25-100 mIU/ml. The urine should be the first urine of the morning when hCG levels are highest. If the specific gravity of the urine is above 1.015, the urine should be diluted. The serum test, using 2-4 mL of venous blood, is a radioimmunoassay (RIA) that can detect βhCG levels as low as 5 mIU/ml and allows quantitation of the βhCG concentration. The ability to quantitate the βhCG level is useful in the evaluation of ectopic pregnancy and in monitoring germ cell and trophoblastic tumors.

Hydatiform moles ("molar pregnancy") may produce high levels of βhCG, despite the absence of an embryo. This can lead to false positive readings of pregnancy tests.

Tumor marker

βhCG is also secreted by some cancers including teratomas, choriocarcinomas and islet cell tumors. When a patient is suspected of harboring a teratoma (often found in the testes and ovaries but also in the brain as a dysgerminoma), a physician may consider measuring βhCG. Elevated levels cannot prove the presence of a tumor, and low levels do not rule it out (an exception is in males who do not naturally produce βhCG). Nevertheless, elevated βhCG levels fall after successful treatment (e.g. surgical intervention or chemotherapy), and a recurrence can often be detected by the finding of rising levels.

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Hydatidiform mole
From Gale Encyclopedia of Medicine, 4/6/01 by Carol A. Turkington

Definition

A hydatidiform mole is a relatively rare condition in which tissue around a fertilized egg that normally would have developed into the placenta instead develops as an abnormal cluster of cells. (This is also called a molar pregnancy.) This grapelike mass forms inside of the uterus after fertilization instead of a normal embryo. A hydatidiform mole triggers a positive pregnancy test and in some cases can become cancerous.

Description

A hydatidiform mole ("hydatid" means "drop of water" and "mole" means "spot") occurs in about 1 out of every 1,500 (1/1,500) pregnancies in the United States. In some parts of Asia, however, the incidence may be as high as 1 in 200 (1/200). Molar pregnancies are most likely to occur in younger and older women (especially over age 45) than in those between ages 20-40. About 1-2% of the time a woman who has had a molar pregnancy will have a second one.

A molar pregnancy occurs when cells of the chorionic villi (tiny projections that attach the placenta to the lining of the uterus) don't develop correctly. Instead, they turn into watery clusters that can't support a growing baby. A partial molar pregnancy includes an abnormal embryo (a fertilized egg that has begun to grow) that does not survive. In a compete molar pregnancy there is a small cluster of clear blisters or pouches that don't contain an embryo.

If not removed, about 15% of moles can become cancerous. They burrow into the wall of the uterus and cause serious bleeding. Another 5% will develop into fast-growing cancers called choriocarcinomas. Some of these tumors spread very quickly outside the uterus in other parts of the body. Fortunately, cancer developing from these moles is rare and highly curable.

Causes & symptoms

The cause of hydatidiform mole is unclear; some experts believe it is caused by problems with the chromosomes (the structures inside cells that contain genetic information) in either the egg or sperm, or both. It may be associated with poor nutrition, or a problem with the ovaries or the uterus. A mole sometimes can develop from placental tissue that is left behind in the uterus after a miscarriage or childbirth.

Women with a hydatidiform mole will have a positive pregnancy test and often believe they have a normal pregnancy for the first three or four months. However, in these cases the uterus will grow abnormally fast. By the end of the third month, if not earlier, the woman will experience vaginal bleeding ranging from scant spotting to excessive bleeding. She may have hyperthyroidism (overproduction of thyroid hormones causing symptoms such as weight loss, increased appetite, and intolerance to heat). Sometimes, the grapelike cluster of cells itself will be shed with the blood during this time. Other symptoms may include severe nausea and vomiting and high blood pressure. As the pregnancy progresses, the fetus will not move and there will be no fetal heartbeat.

Diagnosis

The physician may not suspect a molar pregnancy until after the third month or later, when the absence of a fetal heartbeat together with bleeding and severe nausea and vomiting indicates something is amiss.

First, the physician will examine the woman's abdomen, feeling for any strange lumps or abnormalities in the uterus. A tubal pregnancy, which can be life threatening if not treated, will be ruled out. Then the physician will check the levels of human chorionic gonadotropin (hCG), a hormone that is normally produced by a placenta or a mole. Abnormally high levels of hCG together with the symptoms of vaginal bleeding, lack of fetal heartbeat, and an unusually large uterus all indicate a molar pregnancy. An ultrasound of the uterus to make sure there is no living fetus will confirm the diagnosis.

Treatment

It is extremely important to make sure that all of the mole is removed from the uterus, since it is possible that the tissue is potentially cancerous. Often, the tissue is naturally expelled by the fourth month of pregnancy. In some instances, the physician will give the woman a drug called oxytocin to trigger the release of the mole that is not spontaneously aborted.

If this does not happen, however, a vacuum aspiration can be performed to remove the mole. In a procedure similar to a dilatation and curettage (D & C), a woman is given an anesthetic (to deaden feeling during the procedure), her cervix (the structure at the bottom of the uterus) is dilated and the contents of the uterus is gently suctioned out. After the mole has been mostly removed, gentle scraping of the uterus lining is usually performed.

If the woman is older and does not want any more children, the uterus can be surgically removed (hysterectomy) instead of a vacuum aspiration because of the higher risk of cancerous moles in this age group.

Because of the cancer risk, the physician will continue to monitor the patient for at least two months after the end of a molar pregnancy. Since invasive disease is usually signaled by high levels of hCG that don't go down after the pregnancy has ended, the woman's hCG levels will be checked every two weeks. If the levels don't return to normal by that time, the mole may have become cancerous.

If the hCG level is normal, the woman's hCG will be tested each month for six months, and then every two months for a year.

If the mole has become cancerous, treatment includes removal of the cancerous issue and chemotherapy. If the cancer has spread to other parts of the body, radiation will be added. Specific treatment depends on how advanced the cancer is.

Women should make sure not to become pregnant within a year after hCG levels have returned to normal. If a woman were to become pregnant sooner than that, it would be difficult to tell whether the resulting high levels of hCG were caused by the pregnancy or a cancer from the mole.

Prognosis

A woman with a molar pregnancy often goes through the same emotions and sense of loss as does a woman who has a miscarriage. Most of the time, she truly believed she was pregnant and now has suffered a loss of the baby she thought she was carrying. In addition, there is the added worry that the tissue left behind could become cancerous.

In the unlikely case that the mole is cancerous the cure rate is almost 100%. As long as the uterus was not removed, it would still be possible to have a child at a later time.

Key Terms

Dilatation and curettage (D & C)
Dilating the cervix and scraping the lining of the uterus with an instrument called a curette.
Placenta
The circular, flat organ that connects the fetus via the umbilical cord to the uterus for oxygen, food, and elimination of wastes.

Further Reading

For Your Information

    Books

  • Carlson, Karen J., Stephanie A. Eisenstat, and Terra Ziporyn. The Harvard Guide to Women's Health. Cambridge, MA: Harvard University Press, 1996.
  • Ryan, Kenneth J., Ross S. Berkowitz, and Robert L. Barbieri. Kistner's Gynecology, 6th ed. St. Louis: Mosby, 1995.

Gale Encyclopedia of Medicine. Gale Research, 1999.

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