The diagnostic “magic bullet” in early pregnancy is still the HCG assay, a specific pregnancy marker that has been given more diagnostic significance due to advances in testing technology. The expert consensus recommends the measurement of HCG in early pregnancy for diagnosis and monitoring, but there are still some misconceptions about its clinical application that need to be further identified. How to monitor serum HCG during early pregnancy How to know if you are pregnant? The easiest way is to buy a test stick and test your urine, the early pregnancy test stick is to measure the presence of HCG in urine, if you want to test more accurately, you can go to the hospital to measure the HCG value in blood. The most specific diagnostic marker for early pregnancy is the HCG level measurement. HCG was discovered early and used as a diagnostic indicator for early pregnancy. With the advancement of testing technology, the accuracy of the test is getting higher and higher, and it is only gradually given more diagnostic significance. However, in the clinical application, we still have some misconceptions that need further understanding. HCG is a glycoprotein secreted by embryonic trophoblast cells and consists of two subunits, α-chain and β-chain. β-chain is specific and has a stable proportional relationship with total HCG, so the value of βHCG in serum is often measured. HCG is secreted at the embryonic 8-cell stage, i.e. on the 3rd day of egg fertilization, but it has to reach a certain amount in the blood circulation before it can be detected. The difference between serum and urine concentrations is not significant, but blood tests are more accurate and stable and can be quantified. Theoretically, the blood concentration of HCG should be higher than 5-10 IU/L, and a very sensitive urine test can detect weak and positive results, which is also called “early pregnancy” diagnosis. The normal range of serum HCG measurement is very wide. We usually calculate the time of pregnancy according to the first day of the last menstrual period, which is medically called the “time of menopause”, and everyday we call it the pregnancy period or pregnancy week. ① 2 weeks after ovulation, that is, when menstruation should come, i.e. 28 days of pregnancy or 4 weeks of pregnancy, the blood HCG level is about 100 IU/L; ② until more than 40 days of pregnancy or 6-7 weeks of pregnancy, the HCG level increases rapidly, 1.6-2 times every 48 hours; ③ at 56-70 days of pregnancy or 8-10 weeks of pregnancy, the peak value is about 100,000 IU/L; ④ by 18-20 weeks of pregnancy, the serum HCG level is about 100,000 IU/L; ④ at 18-20 weeks of pregnancy, the serum HCG level is about 100,000 IU/L. At 18-20 weeks of gestation, serum HCG level decreases to 10,000-20,000 IU/L, and then this level is maintained until full-term delivery; ⑤ 3 weeks after delivery, it returns to normal. So our ideal time to monitor HCG should be before 6-8 weeks of pregnancy. When the menstrual cycle is irregular, we may not be able to measure the pregnancy period, which may hinder the judgment of the HCG value. We can estimate the time of pregnancy and refer to the HCG test value through the comprehensive evaluation of the past menstrual pattern, basal body temperature measurement, ovulation test paper, time of intercourse, vaginal ultrasound examination, time of early pregnancy reaction, and double examination of the uterus. Since the rapid increase of serum HCG in early pregnancy has a certain pattern, the “doubling test” is commonly used to monitor the pregnancy status in clinical practice. If the serum HCG increases 1.6-2 times in the same laboratory at 48-hour intervals before the 6th to 7th week of pregnancy, the pregnancy status is normal. If the rate of increase is lower than this, it indicates the possibility of embryonic dysplasia or ectopic pregnancy. However, it should be noted that the doubling test is not an absolute predictor, it only reflects the state of embryonic trophoblast development at that particular time period, indirectly reflecting the embryonic development, the accuracy rate is about 75%, about 17% of ectopic pregnancy early stage can also show normal doubling of HCG. At the same time, we should pay attention to the time period of monitoring, some pregnant women are already more than 2 months pregnant and still doing the HCG “doubling test”, which is not reasonable, at this time the vaginal ultrasound examination has more diagnostic significance. HCG diagnosis in ectopic pregnancy Theoretically, the blood HCG level in ectopic pregnancy does not correspond to the gestational period, is below the average level, or the doubling test is not normal. This is very difficult to determine before the 45th day of pregnancy. Usually we give a little progesterone comfortably orally and instruct the pregnant woman to observe closely the symptoms of vaginal bleeding and abdominal pain and to consult the emergency room whenever there is a situation. In principle, at 40 days of gestation, we can observe the intrauterine gestational sac by vaginal ultrasound, and at 45 days of gestation, we can see the embryonic bud and fetal heartbeat. If at this time the serum HCG >1000 IU ~ 1500 IU and the ultrasound has not yet seen the typical gestational sac in the uterus, the diagnosis of ectopic pregnancy is basically confirmed and it is necessary to stay in the hospital for observation and dynamic ultrasound to see if the gestational sac and fetal heartbeat appear in the fallopian tubes and other areas. Therefore, at this stage of pregnancy, it is important not to refuse the ultrasound, even if the HCG level is only a few hundred units and the ultrasound does not reveal an intrauterine gestational sac, it is important to closely monitor the possibility of ectopic pregnancy. The diagnosis of “embryonic arrest” is much easier than that of ectopic pregnancy. In early pregnancy, the serum HCG level is low, the doubling test is abnormal, the ultrasound observes a gestational sac in the uterus, and in some cases, the germ bud and yolk sac are visible, but no fetal heartbeat is seen on day 45-50 of pregnancy, and after 1 to 2 weeks of extended observation, no fetal heartbeat is seen. In some cases, the fetal heartbeat is not seen at 45-50 days of gestation, and after extended observation for 1-2 weeks, the fetal heartbeat is not seen. This is medically called “inevitable miscarriage” and is also commonly referred to as “embryonic arrest”. At this time, the diagnosis of ultrasound is the most reliable value, other HCG and progesterone levels have no diagnostic significance, it is not recommended to blindly keep the fetus, and there is no need to continue to use progesterone or HCG preparations. It is possible to consult a gynecological clinic for elective clearance and if aneuploidy screening of miscarried chorionic tissue is performed, it is possible to determine the partial cause of this miscarriage. Diagnosis of HCG in biochemical pregnancy A biochemical pregnancy is a very insidious pregnancy state in which the serum HCG level is elevated but significantly lower than the value of a normal pregnancy and quickly falls back to non-pregnant levels, with no evidence of intrauterine gestational sac or extrauterine pregnancy detected by ultrasound. This may be a spontaneous abortion of an early pregnancy or it is also difficult to exclude an ectopic pregnancy of the miscarriage type. There are no uniform boundaries for the diagnostic criteria for blood HCG values in biochemical pregnancies. Some consider a biochemical pregnancy as long as the serum HCG value is greater than the upper limit of normal in this laboratory, total HCG > 10 IU/L, or beta HCG > 3-5 IU/L; some physicians consider a pregnancy loss as long as the serum HCG value is > 25 IU/L. A biochemical pregnancy is not currently considered an “official” spontaneous abortion, and if the HCG value is too low, < 25 IU/L, it may not be counted as a history of abortion for diagnostic purposes. However, a history of repeated biochemical pregnancies needs to be taken into account and relevant tests should be performed according to miscarriage indicators. Key points to remind for blood HCG measurement (1) Blood β-HCG level reaches its peak around 8~10 weeks of pregnancy and then the level starts to decrease, therefore, usually after 6~8 weeks of pregnancy, β-HCG test is no longer recommended for pregnant women to assess pregnancy status, but ultrasound is recommended for diagnosis. Care should be taken to correct the date of menopause in pregnant women with irregular menstruation. (2) If HCG preparations have been injected for fetal preservation in the week before the blood HCG test, the serum HCG level will be disturbed and falsely elevated at this time. (3) Urine HCG is a qualitative or semi-quantitative test that is affected by factors such as the volume of urination, but it can be a very early screen for pregnancy, and if the urine test is negative, the pregnancy status can basically be ruled out. (4) HCG levels in twins are higher than in singletons, but not necessarily doubly elevated, and are not used as a basis for diagnosis of twins. Delicate ultrasound examination can detect it early. (5) Additional differential diagnoses of elevated HCG include trophoblastic disease (chylothorax, etc.), primary ovarian chorionic villous malignancy, and some other malignancies, which, fortunately, are relatively rare and require vigilance and screening if there are abnormal clinical signs.