The acronym hCG or Beta hCG refers to human chorionic gonadotrophin hormone. Its blood concentration is widely used as a pregnancy test since it is a method with high accuracy.
When taken at the right time and interpreted correctly, it has a very high success rate. BhCG can be obtained through blood or urine tests.
In this article, we address the following points about human chorionic gonadotrophin:
- How it is produced.
- How the test is done.
- How to interpret its values.
- Differences between hCG and Beta hCG
- Cases of false negative hCG.
- Cases of false positive hCG.
HOW HCG IS PRODUCED
Human chorionic gonadotropin is an important hormone necessary for the maintenance and development of gestation. It is produced by the trophoblast, the embryo’s cell group that gives origin to the placenta.
About six days after fertilization of the ovum by the sperm, the forming embryo reaches the wall of the uterus and lodges in it. From that moment on, the hCG hormone produced by the trophoblast can reach the mother’s bloodstream, which makes it possible to detect it by ultra-sensitive laboratory tests.
As the embryo and placenta develop, more hCG is produced and released into the mother’s circulatory system. In the first weeks of gestation, hCG levels double every 2 or 3 days. If the rate of increase of human chorionic gonadotrophin in the first 30 days of pregnancy is markedly low, there may be something wrong with pregnancy, such as non-viable fetus or ectopic pregnancy.
WHEN DOES HCG BECOME DETECTABLE?
Current techniques can only detect hCG from the 3rd or 4th weeks of pregnancy counted from the date of the last menstrual period.
Since the 4th week of pregnancy is usually the time at which the next menstruation should come, we always suggest that the patient wait for the menstruation not to show up for the test. In this way, we minimize the risk of false negative results.
BETA HCG VALUES THROUGHOUT PREGNANCY
In general, hCG values are as follows over the weeks of pregnancy:
- Women who are not pregnant, or less than 3 weeks pregnant:: less than 5 mIU/mL.
- 3 weeks of pregnancy: between 5 and 50 mIU/mL.
- 4 weeks of pregnancy: between 5 and 426 mIU/mL.
- 5 weeks of pregnancy: between 18 and 7,340 mIU/mL.
- 6 weeks of pregnancy: between 1,080 and 56,500 mIU/mL.
- 7 to 8 weeks of pregnancy: between 7,650 and 229,000 mIU/mL.
- 9 to 12 weeks of pregnancy: between 25,700 and 288,000 mIU/mL.
- 13 to 16 weeks of pregnancy: between 13,300 and 254,000 mIU/mL.
- 17 to 24 weeks of pregnancy: between 4,060 and 165,400 mIU/mL.
- 25 to 40 weeks of pregnancy: between 3,640 and 117,000 mIU/mL.
Warning: the above values are for guidance only. They are not a rule and other references may have different values. If your hCG is different, do not panic, as this does not necessarily mean that there is something wrong with your pregnancy. The most important thing is the growth rate of the hormone in the first few weeks.
The hCG values for multiple-fetus pregnancies, whether twins or triplets, are usually higher because there are more sources of chorionic gonadotropin production.
Usually, the hCG peak occurs around the 10th week of pregnancy. The levels then begin to fall until the 20th week, when they stabilize, remaining more or less constant up to the day of delivery.
If you look at the values given above, you will notice that there may be a huge variation between human chorionic gonadotrophin values throughout the weeks of pregnancy. A pregnant woman in the 8th week may have hCG of 9,000, while another with the same gestational age, a hCG of 150,000. Therefore, hCG values are not useful for determining gestation time.
HOW THE BETA HCG EXAM IS DONE
If you are an attentive reader, by now you may be wondering why I sometimes write hCG, while at others, beta hCG (BhCG). After all, what is the difference between hCG and beta hCG?
HCG is a hormone composed of two large molecules, called the alpha subunit (or alpha fraction) and beta subunit (or beta fraction). The first is structurally similar to several other hormones, such as follicle-stimulating hormone (FSH) or luteinizing hormone (LH). The second one is unique and is found in no other hormone. Therefore, to reduce the risk of cross-reaction with other hormones and hence the occurrence of false positives, laboratories only search for the beta fraction.
The hCG produced by the fetus passes into the mother’s bloodstream and is filtered by the kidneys, being part of it then eliminated by the urine. As such, beta hCG can be dosed in both the blood and urine of the woman. Except for in rare cases, which will be explained later, if BhCG is detected in the woman’s blood or urine, she is pregnant.
There are basically two ways to evaluate the presence of BhCG: qualitative BhCG and quantitative BhCG.
Qualitative BhCG does not provide values, it only reveals whether there is human chorionic gonadotrophin at relevant values circulating in the mother’s blood. This form is widely used in pharmacy pregnancy tests that use urine as a research source. These tests only say whether the test is positive or negative.
Quantitative BhCG is the form used in most blood tests. As such, the result is given in values, usually in milli-international units per milliliter (mIU/mL). Most laboratories consider pregnancy values above 25 mIU/mL.
HOW TO INTERPRET THE HCG VALUES
It is important to note that urine pregnancy tests do not serve to establish the definitive pregnancy diagnosis. Even when they are positive, you need to confirm the result through the blood test, which is the most reliable pregnancy test.
Most blood tests can detect minimal levels of hCG of 5 mIU/ml, but there are already super-sensitive tests that detect the presence of even 1 mIU/ml.
Most laboratories use the following reference values:
- hCG below 5 mIU/mL = negative result, no ongoing pregnancy.
- hCG between 5 and 25 mIU/mL = undefined result: usually indicates no ongoing pregnancy, but may be the case of a very recent pregnancy, when there has not yet been time for enough hCG produced to be detected in the blood. In these cases, the test should be repeated after three days.
- hCG above 25 mIU/mL = positive result: indicates ongoing pregnancy.
It is always important to pay attention to the laboratory reference values. In most cases, laboratories use the value of 25 mIU/mL as a threshold. However, depending on the chemical method used, the value considered positive may be lower or higher.
Normally, for the embryo to implant in the uterus and its hCG to reach relevant levels in the pregnant woman’s bloodstream, 7 to 14 days after sexual intercourse are necessary. In general, we only indicate that the test is performed after the delayed menses because, before that, it is unlikely that there has been enough time for the BhCG values to be high enough to be detected in the exams.
CASES OF FALSE NEGATIVE BETA HCG
The main cause of a false negative BhCG is that the examination is done very early. Some women are nervous about having had unprotected sex and end up taking the pregnancy test a few days later, even before any menstrual delay. It’s no use taking the test so soon because if you are pregnant, it is possible that the embryo has not yet reached the uterus. If the embryo has not yet implanted in the uterus, there is no way to have hCG in the mother’s blood.
State-of-the-art tests can detect increases of BhCG with only 1 day of menstrual delay. However, to reduce the risk of a false negative, we suggest that the test is performed only after a week of menstrual delay. Keep in mind that you cannot totally exclude a pregnancy if the negative result has been obtained with less than 1 week of menstrual delay. However, a negative result with more than 2 weeks of menstrual delay makes the hypothesis of a pregnancy very unlikely.
In women with a very irregular menstrual cycle, whether or not menstruation is delayed may not be so simple. In these cases, we suggest performing the test only 14 days after unprotected intercourse.
The amount of hCG in urine is lower than in blood, so the risk of a false negative is greater in this method.
Lastly, the use of medications does not cause false negatives, including contraceptives, the morning-after pill, antidepressants, antibiotics, etc. Infections also do not change the outcome.
CASES OF FALSE POSITIVE BETA HCG
With the current BhCG detection techniques, false positive cases are rare. I will cite some situations in which a false positive result is possible.
Among these cases is that of fetal death occuring soon after implantation of the embryo in the uterus. In this situation, BhCG may be positive, but, as there has been a miscarriage, there will be no development of pregnancy. Miscarriages that occur so early may go unnoticed, as the embryo is still microscopic.
Some women who are undergoing treatment to become pregnant may use hCG drugs. In these cases, the BhCG detected in the tests may be only a remnant of the medicine administered days before. In general, after 2 weeks of discontinuation, this BhCG has already been eliminated, no longer interfering with pregnancy tests.
Other medications do not cause false positive beta hCG, including contraceptives, morning-after pills, antidepressants, antibiotics, clomiphene or any other hormone.
Very rarely, patients who have recently had mononucleosis may have false positive BhCG (with low values).
In older women, near menopause, the pituitary, a gland in the brain, may begin to secrete small amounts of hCG, enough to maintain values just above 25 mIU/mL.
Some tumors are producers of human chorionic gonadotrophin, as in gestational trophoblastic disease, which encompasses the following pathologies:
- Hydatidiform mole (partial or complete).
- Invasive mole.
- Placental trophoblastic tumor.
These diseases produce tumors from abnormal proliferation of trophoblast cells. The hCG production of these trophoblastic tumors may be very large, often above 100,000, and in some cases, in excess of 500,000 mIU/mL.
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- Pregnancy Diagnosis – Medscape.
- Human Chorionic Gonadotropin: Testing in pregnancy and gestational trophoblastic disease and causes of low persistent levels – UpToDate.
- Clinical Gynecologic Endocrinology and Infertility. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.