Changes in hCG in ectopic pregnancy and their diagnostic value

During pregnancy, multiple changes occur in a woman's body. Some of them are visible to the naked eye, while others are so hidden that they can only be detected by ultrasound or laboratory diagnostics. For example, changes in hormonal levels, which are especially noticeable before external symptoms indicating disturbances appear, can only be determined in a laboratory. Thus, the level of hCG in an ectopic pregnancy will be significantly lower than normal, and the causes of elevated levels of this hormone can be gestational diabetes or chromosomal pathologies of the fetus.

It is precisely by laboratory means that doctors sometimes accidentally detect serious pregnancy pathologies already at an early stage. And although it is difficult to judge specific diseases based on a single analysis of hCG or AFP, a change in hormone levels allows one to suspect the disease in time and take the necessary steps to treat it, and, if necessary, terminate the pathological pregnancy.

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Who is prescribed the hCG test and when?

A general blood test and urine test, which are mandatory for women when diagnosing pregnancy, including ectopic pregnancy, and registering, can tell a lot about the health of the expectant mother. But they do not provide sufficient information about the development of the fetus at different stages of pregnancy and its localization. But bearing a child is a rather complex and lengthy process, each stage of which is accompanied by certain changes in laboratory indicators, which can only be tracked by conducting special tests and analyses.

One of such special tests during pregnancy is the study of the level of human chorionic gonadotropin (hCG). What is hCG? It is a specific hormone that is practically absent in a healthy person outside of pregnancy. In men, detection of chorionic gonadotropin in the blood is possible only in the development of oncological diseases of the reproductive system (teratoma/seminoma of the testicle). Such neoplasms are most often detected in boys and young men. In this case, the hCG test helps to clarify the diagnosis.

An increase in the level of human chorionic gonadotropin in a woman most likely indicates the onset of pregnancy. The fact is that the embryo is responsible for the production of this unusual hormone, or rather its membrane, which provides nutrition to the fetus and is called the chorion. That is why the hormone is called chorionic. Later, when the placenta is formed (approximately in the 3rd-4th month of pregnancy), it also begins to produce hCG, but in smaller quantities.

The chorion is the outer shell of the fetus, which supports the function of the temporary endocrine gland (corpus luteum) from the moment of conception until the formation of the placenta. The vital activity of the corpus luteum, which produces estrogens and progesterone, necessary for maintaining pregnancy, is maintained precisely due to the production of chorionic gonadotropin. That is, these processes are interconnected and aimed at preparing the woman's body for bearing a child. It is not surprising that gonadotropin begins to be produced by the chorion almost from the moment of conception, as soon as the father's sperm merges with the mother's egg.

The level of pregnancy hormone increases noticeably day by day until the 8-12th week of pregnancy, after which it gradually declines, which is due to the body's preparation for childbirth. After all, when the formation of the placenta ends in the second trimester of pregnancy, all the main organs and systems of the child are already formed and begin to function. This is already a full-fledged little person who is gradually preparing for independent existence outside the mother's womb.

Why is hCG so important during pregnancy? Because it is precisely thanks to it that the necessary level of all other hormones in the female body is maintained, including estrogens and progesterone, which is very important for the normal course of pregnancy. It is clear that a deviation of the hCG level from normal values will indicate certain disorders.

What are the indications for conducting an hCG test:

• It is prescribed to women who have a delay or absence of menstruation without any other symptoms of pregnancy. An increase in the level of chorionic gonadotropin will be evidence of conception, otherwise we are talking about some disorders in the reproductive system.
• Using the analysis, pregnancy can be determined at a very early stage, since an increase in the level of hCG in urine is noted already on the 6-8th day after conception (this is one of the fastest methods for determining pregnancy), and in venous blood even on the 2-3rd day.
• The study is prescribed if there is a suspicion of multiple pregnancy, when two or more embryos are growing and maturing in a woman’s womb at the same time.
• The analysis is especially relevant if the doctor has reason to suspect an ectopic or frozen pregnancy, which require immediate surgical intervention and termination of pregnancy (hCG in case of an ectopic pregnancy or cessation of fetal development in the womb will deviate from the norm).
• after a spontaneous miscarriage or unprofessional abortion, there are situations when embryonic and placental tissues are not completely removed from the body, which poses a danger to the woman's health. The presence of chorion and placenta remnants will be indicated by a high level of hCG, which they produce; normally, in the absence of pregnancy, hCG should not exceed 5 IU per ml of blood.

It should be said that this analysis is currently prescribed to pregnant women without any indications. This delicate period in a woman's life has several critical phases: 8, 12-14, 16-18 weeks of pregnancy. It is at this time that a frozen pregnancy or other pathologies are most likely to occur. In this regard, screening studies are carried out, prescribed specifically for these critical phases, which makes it possible to timely diagnose pregnancy complications.

An increase in hCG values indicates how the fetus is growing and developing. Therefore, an hCG test, along with a blood test for alpha-fetoprotein and estriol, is part of a complex of prenatal diagnostics of fetal development pathologies.

In case of various pregnancy pathologies, the hCG test can be performed dynamically, i.e. with an interval of 2 days. The fact is that during the normal course of pregnancy, the levels of human chorionic gonadotropin in the blood double during this period. In case of an ectopic pregnancy and especially in case of a frozen pregnancy, the growth of hCG levels is much less intense.

Preparation and technique of analysis

To determine the level of human chorionic gonadotropin during pregnancy, various laboratory diagnostic methods are used. The simplest analysis option is considered to be test strips, the mechanism of action of which is based on an increase in the level of hCG after conception.

A pregnancy test can be purchased at any drugstore or even in grocery supermarkets. It is a light strip with a reagent applied to it, which changes color when in contact with urine, resulting in a second strip appearing, indicating pregnancy.

The fact is that 6-8 days after conception, the urine already contains a sufficient level of gonadotropin to diagnose pregnancy. Another thing is that the sensitivity of most tests allows detecting pregnancy only after 2 or more weeks. The most accurate are considered to be jet and digital tests, which do not need to be dipped into a container with urine or dripped onto them, but placed under a fresh stream.

10 seconds of contact of the test strip with urine is enough for the reaction to begin, and its result can be seen after 1-10 minutes depending on the hCG level. But if in conventional tests the concentration of the hormone and the period of pregnancy can be judged mainly by the intensity of the color of the strip that appears, then the electronic version of the test will provide information in digital form.

This hCG test is quite suitable for determining pregnancy, but it can say little about its duration and the nature of its course. That is, conventional hCG tests for ectopic pregnancy will be uninformative. They will show the presence of pregnancy in any case, but one can only guess about the level of gonadotropin and the dynamics of its growth. An insufficiently intense color of the second strip or its absence during repeated tests may seem suspicious.

The digital test is more interesting in this regard, because it allows you to evaluate the concentration of the hormone, and with repeated analysis, even evaluate how much the hCG level has increased over a certain period of time. Such changes give a higher percentage of true results in the first 2 months of pregnancy, after which such incidents as a negative pregnancy test result are possible.

A urine test for human chorionic gonadotropin is performed in a laboratory in a similar way. In this case, a pregnant woman will need to submit fresh morning urine for analysis. Why morning urine? Because the concentration of gonadotropin is affected by the amount of liquid consumed. The more water a woman drinks, the lower the concentration of the pregnancy hormone will be, which will distort the true results. It is also not recommended to drink a lot of liquid the day before the test, especially before going to bed.

In case of ectopic pregnancy and other complications, it is considered most appropriate to conduct a blood test for hCG. Gonadotropin is detected in the blood faster than in urine, and the results of the blood test are considered the most accurate. Blood is taken from a vein, after which the liquid part is separated using a centrifuge and reagents are added. The device for conducting the analysis converts quantitative results into digital ones, which are used to diagnose the course of pregnancy.

Any test has diagnostic value if its results are reliable, so before conducting the test, certain preparation is often required. Ideally, blood, like urine, should be donated in the morning before breakfast, some time after waking up. But even if blood has to be donated at another time, to increase the accuracy of the tests, it is recommended to refrain from eating and limit water intake for 5-7 hours before taking blood for analysis.

Ectopic pregnancy

Almost every woman dreams of one day becoming a happy mother of her own baby. But to do this, she has to conceive and bear the child. Fertilization of the egg occurs after it enters the fallopian tube, but this is not enough for the normal development of pregnancy. Subsequently, the duo, from which the human embryo is formed, must travel through the fallopian tube directly to the uterus, where it is fixed for permanent residence 2-3 weeks after conception.

But sometimes it happens that the egg does not have time to implant in the uterus in the allotted time and it has to "settle" in another place. Most often, the place of its localization is the fallopian tube itself, less often the fertilized egg is fixed near the ovary, in the abdominal cavity or cervix. In any case, if the embryo develops outside the uterus, they talk about a pathology called "ectopic pregnancy".

This situation is considered unsuitable for the normal development of the child, especially if the fetus has attached itself inside the fallopian tube. The size of the lumen of the fallopian tube is not designed for the increase of the fertilized egg, which occurs as the fetus grows and develops, so the fetus will lag behind in development and soon die. There is simply no point in maintaining such a pregnancy.

Moreover, an ectopic pregnancy poses a threat to the life of a pregnant woman. The small lumen of the fallopian tube and the insufficient elasticity of its walls are a risk factor for rupture of the organ as the fetus grows in size. This is an extremely dangerous situation, which causes severe pain and profuse internal bleeding. If the patient does not receive timely assistance, the woman is at risk of death. And even if doctors manage to save her life, it will no longer be possible to restore the damaged fallopian tube, which means the chance of getting pregnant will be extremely low. After all, even after timely intervention, the chances of pregnancy are halved.

In the first months after conception, it is almost impossible to distinguish an ectopic pregnancy from a normal one without special examinations. A woman may even develop toxicosis in the early stages, the mammary glands swell, menstruation stops or turns into a monthly scanty spotting.

Regardless of the location of the embryo, it is surrounded by a protective membrane (chorion), which produces human chorionic gonadotropin, which means that the level of hCG in an ectopic pregnancy will increase. How can the analysis help in such a situation? Because hCG in uterine and ectopic pregnancy differ significantly.

HCG levels in ectopic pregnancy

An ectopic pregnancy is a situation in which the fetus cannot develop normally. While it is small and can easily fit into the lumen of the fallopian tube, development can proceed normally, as evidenced by a regularly increasing level of human chorionic gonadotropin. But gradually the dynamics of hCG growth in ectopic pregnancy changes.

To better understand the difference between the growth of hCG levels in uterine and ectopic pregnancies, you need to know the level of human chorionic gonadotropin in the absence of pregnancy. It is believed that the concentration of this specific hormone changes every 1.5-2 days, during which the levels almost double. That is, by measuring hCG at intervals of even a couple of days, you can already draw certain conclusions about how the pregnancy is progressing.

There is no point in describing the daily changes in hCG during pregnancy; it is enough to consider its norm by week during normal fetal development, and then compare the hCG norms with the indicators observed during an ectopic pregnancy.

If a woman is not pregnant, gonadotropin may not be detected in her blood or may be present in quantities not exceeding 5 IU/ml. This is the so-called reference point. A further increase in hCG will indicate pregnancy in women or oncology in men. But since chorionic gonadotropin begins to be secreted from the moment of conception, its levels may rise to 20-35 IU/ml in the first week of pregnancy.

During the first to second week of pregnancy, when the fetus is still on its way to the uterus, the hCG content in a woman's blood fluctuates between approximately 20 and 350 IU/ml. We emphasize the word "approximately" because different laboratories determine the concentration of gonadotropin during pregnancy using different methods, which can give different results. Therefore, each institution of this nature has developed its own tables that determine the hCG norms for normal and pathological pregnancy.

Let us give an example of one of these tables, where the first column will reflect the gestational age in weeks, and the second will reflect the upper and lower limits of the hCG norm in IU per ml of blood.

1-2	25-156
2-3	101-4870
3-4	1110-31500
4-5	2560-82300
5-6	23100-151000
6-7	27300-233000
7-11	20900-291000
11-16	6140-103000
16-21	4720-80100
21-39	2700-78100

If the results of the tests you receive fit within the framework of the table above, this should not be considered a reason to panic. The table is provided strictly for informational purposes and based on it we can see how hCG levels rapidly increase until the 7th to 11th week of pregnancy and then gradually begin to decrease.

We have considered the dynamics of human chorionic gonadotropin during normal pregnancy and correct fetal positioning, but what is hCG during ectopic pregnancy? In general, the picture is identical: first, there is an increase in hCG levels, and then a drop. But the increase in hCG levels in this case is noticeably lower than during a normally developing pregnancy.

Thus, during the first two weeks of pregnancy, there may not be any difference in the increase in chorionic gonadotropin. But already in the 3rd-4th week, the indicators may be 2 or more times less than expected for this period. The maximum level of hCG in an ectopic pregnancy usually does not exceed 75,000 IU/ml, while in a normal pregnancy during the same period, the indicators will reach 291,000 IU/ml.

As we can see, the difference is noticeable. A low level of human chorionic gonadotropin is an indicator that the fetus is lagging behind in development, and if it is localized in the fallopian tube, this is inevitable. And it does not matter how the fetus was conceived. In vitro fertilization, when the fertilized egg is implanted directly into the woman's uterus, there are also situations when the embryo changes its location, slipping into the fallopian tube or abdominal cavity, where it subsequently attaches and grows. HCG in ectopic pregnancy after IVF has the same dynamics as in natural conception, which did not end with the movement of the egg into the uterus.

If an ectopic pregnancy is not detected in the first weeks after conception, a slow increase in hCG levels is observed until approximately 7-8 weeks, and then falls. At this stage, the fetus most often freezes, when it stops developing and dies, which is most likely if it is in the wrong position. But such a break can happen earlier.

The hCG level in a frozen pregnancy never reaches high values and after the death of the embryo begins to rapidly decrease. But it can approach the normal level for non-pregnant women only after a spontaneous miscarriage or abortion, and then only if there are no particles of embryonic tissue or placenta left in the mother's body.

In case of ectopic pregnancy and embryo retention in the fallopian tube, spontaneous embryo rejection does not occur, even if the fetus has frozen. In this case, with a continuing pathological pregnancy, the hCG level will be extremely low and surgical intervention is unavoidable.

Changes in hCG during ectopic pregnancy that differ from the norm allow us to suspect a pathology, but this is not enough to make an accurate diagnosis. A decrease in the levels of this hormone is also observed with a threat of miscarriage caused by a delay in the development of the embryo or placental insufficiency. Even symptoms such as pain in the lower abdomen and spotting brown or red discharge are not specific, and it is impossible to make a diagnosis based on them. Therefore, to confirm an ectopic pregnancy, ultrasound results are also important, which will show the absence of a fetus in the uterus in the presence of other symptoms of pregnancy.