What is the difference between hcg and beta hcg

Amniotic fluid and fetal circulation in late pregnancy. J Reprod Med. Schneider DT, Calaminus G, Gobel U: Diagnostic value of alpha 1-fetoprotein and beta-human chorionic gonadotropin in infancy and childhood.

Pediatr Hematol Oncol. After delivery, miscarriage, or pregnancy termination, human chorionic gonadotropin hCG falls with a half-life of 24 to 36 hours, until prepregnancy levels are reached. An absent or significantly slower decline is seen in patients with retained products of conception.

Gestational trophoblastic disease GTD is associated with very considerable elevations of hCG, usually above 2 multiples of the medians for gestational age persisting or even rising beyond the first trimester. Teratomas in children may overproduce hCG, even when benign, resulting in precocious pseudopuberty. Levels may be elevated to similar levels as seen in testicular cancer. Among nonreproductive tumors, hepatobiliary tumors hepatoblastomas, hepatocellular carcinomas, and cholangiocarcinomas and neuroendocrine tumors eg, islet cell tumors and carcinoids are those most commonly associated with hCG production.

Many hCG-producing tumors also produce other embryonic proteins or antigens, in particular alpha fetoprotein AFP. AFP should, therefore, also be measured in the diagnostic workup of such neoplasms. Complete therapeutic response in hCG-secreting tumors is characterized by a decline in hCG levels with an apparent half-life of 24 to 36 hours and eventual return to concentrations within the reference range.

GTD and some tumors may produce hyperglycoslated hCG with a longer half-life, but an apparent half-life of more than 3 days suggests the presence of residual hCG-producing tumor tissue. A rise in hCG levels above the reference range in patients with hCG-producing tumors that had previously been treated successfully, suggests possible local or distant metastatic recurrence.

Despite strenuous efforts at standardization, different human chorionic gonadotropin hCG assays show only modest agreements with each other. Therefore, whenever serial monitoring of hCG concentration is required, the same assay should be used for all measurements.

Transient elevations of serum hCG can occur following chemotherapy in patients with susceptible tumors, due to massive tumor cell lysis; these transient elevations should not be confused with tumor progression.

Normal serum levels of hCG do not always exclude tumor persistence since tumors may undergo transition to differentiated teratomas, which may not produce hCG. In postmenopausal women, hCG levels ranging from 3. HCGn, are valuable for the characterization of antibody specificity. Antibodies that do not recognize HCGn will miss this variant, which occurs especially in urine but also in the serum of some cancer patients Cole et al.

When the reference reagents were prepared, the potential utility of HCGh was not recognized and a standard for this variant was not prepared. If HCGh assays become clinically accepted, a standard will be desirable. However, identification of a suitable source is problematic; although HCGh occurs in urine during early pregnancy Kovalevskaya et al.

It is well known that the carbohydrate composition of HCG produced by tumours may vary considerably, and HCGh is therefore not a well-defined entity Birken, This does not justify the introduction of a new name in the scientific literature. Part of the variation between different immunoassays is caused by the use of impure calibrators, and improved agreement may be obtained by replacing the calibrators in commercial assays by pure HCG preparations Cole et al.

However, this is only one cause of between-method discrepancies, careful selection of antibodies and assay design being equally important Stenman et al. The midcycle LH surge is essential for normal oocyte maturation and ovulation.

In ART, administration of partially purified urinary HCG preparations has been used for decades as a surrogate for LH to achieve final oocyte maturation and ovulation in controlled ovarian hyperstimulation COH protocols.

Urinary HCG has been the drug of choice, but there are now other options, i. A single dose of 15 —30 IU of rLH gives the highest efficacy to safety ratio. Moreover, it has recently been suggested that replacement of urinary HCG by rLH in agonist cycles results in a significantly lower pregnancy rate Aboulghar and Al-Inany, This form of treatment has been suggested to prevent the ovarian hyperstimulation syndrome OHSS Orvieto, In clinical studies, ovulation induction with the GnRH agonist buserelin resulted in significantly more mature oocytes, but significantly lower implantation and clinical pregnancy rates were obtained than those by conventional ovulation induction with urinary HCG Humaidan et al.

Moreover, the rate of early pregnancy loss was higher, probably due to luteal phase deficiency. This has been confirmed in other studies, and a lower probability of ongoing pregnancy was achieved with the GnRH agonist triptorelin than with urinary HCG Kolibianakis et al.

At present, HCG appears to be the most reliable way to trigger final oocyte maturation both in antagonist and in agonist cycles Griesinger et al. It seems that similar characteristics and dynamics of luteal phase estradiol E 2 and progesterone are obtained after ovarian stimulation for IVF using GnRH agonists or antagonists Friedler et al.

Luteal phase support after ART results in an increased pregnancy rate compared with placebo or no treatment. Urinary HCG can also be used for other clinical applications.

Thus low-dose HCG has been used alone to complete controlled ovarian stimulation Filicori et al. Even more interesting is the effect of HCG on uterine receptivity. In a recent study, administration of HCG to oocyte recipients was shown to increase endometrial thickness on the day of embryo transfer and to improve the implantation rates Tesarik et al. This suggests that HCG might affect endometrial function independently of ovarian function by stimulating endometrial growth and maturation and by enhancing endometrial angiogenesis, thereby extending the implantation window Filicori et al.

Recently, HCG produced by recombinant techniques in Chinese hamster ovary cells has become commercially available. Furthermore, the use of rHCG was associated with significantly better patient tolerance Abdelmassih et al. However, the content of rHCG is based on the mass of the peptide moiety only Gervais et al.

This is comparable with that of highly purified urinary HCG but, according to the earlier mentioned studies, the activity may be even higher.

These calculations are based on the typical carbohydrate structure of urinary HCG, and the carbohydrates of rHCG are only slightly different; the N-linked carbohydrates are of the same type as those in urinary HCG, but part of the O-linked carbohydrate chains on the CTP is different Gervais et al.

So far, this has not been reported to cause any adverse effects indicating that the carbohydrate moieties are not immunogenic. Vaitukaitis et al. IFCC recommends that assays should be exactly defined according to what they measure, e. Although specific assays for HCG and its various forms can be established with polyclonal antisera, virtually all presently used assays utilize monoclonal antibodies or a combination of a monoclonal antibody and a polyclonal antiserum.

Monoclonal antibodies with known epitope specificity facilitate design of assays specific for each form of HCG Bidart et al. The epitopes of 28 antibodies from various manufacturers and research groups have been determined in a collaborative study. On the basis of this information, the specificity of an assay in which these antibodies are used can be deduced Berger et al.

Exact information on assay specificity is obtained by analysing the reference reagents with the final assay Birken et al. Most epitopes are not dependent on variation in carbohydrate composition Schwartz et al. Antibodies B and CTP , which were prepared against aberrantly glycosylated HCG isolated from the urine of a choriocarcinoma patient, recognize carbohydrate epitopes Kovalevskaya et al.

That of B comprises the biantennary core 2 o -glycan on Ser and adjacent peptide structures whereas CTP reacts with a sialylated glycan on Ser Birken, This nomenclature is an oversimplification of the actual complexity of the carbohydrate heterogeneity of HCG Birken, Serum samples are preferred for quantitative HCG determinations whereas urine samples are mainly used for pregnancy tests. Presently, virtually all commercial assays are based on the sandwich principle Cole et al.

Such assays show no cross-reactivity with LH, but because CTP antibodies tend to have only moderate affinity Berger et al. Some of the most sensitive assays for HCG are based on this principle Pettersson et al. Immunoassays based on the binding inhibition principle, i. Urine samples are mainly useful for the identification of false-positive results in serum samples Stenman et al.

Some assays measure several degraded forms of HCG de Medeiros et al. The most common use of HCG determinations is the detection of pregnancy with a semi-quantitative pregnancy test, which mostly is performed on a urine sample, but serum, plasma or whole blood can also be used with some tests. The pregnancy test is considered one of the most useful and reliable laboratory tests available Chard, Determination of the sensitivity of a pregnancy test depends on the standards used. HCGn, is a potential problem Butler et al.

However, nicking of HCG occurs mainly during storage of urine Birken et al. Some pregnancy tests have been shown to underestimate HCGh Butler et al. There is considerable variation in the performance of pregnancy tests sold to the general public Cole et al. The secretion of pituitary HCG is regulated by GnRH, and elevated levels in post-menopausal women are suppressed by estrogen treatment Stenman et al. The serum concentrations fluctuate in a pattern similar to that of LH Odell and Griffin, Taken together, these results indicate that most HCG in normal serum is derived from the pituitary Stenman et al.

Low-level expression of the genes for both HCG subunits occurs in the testis, breast, prostate and skeletal muscle Bellet et al. The concentrations do not increase with age Alfthan et al. One IU corresponds to 0. The upper reference limits for HCG based on the These values have been determined by highly sensitive immunofluorometric assays Alfthan et al.

Most commercially available assays are less sensitive and because of this and variation in assay calibration, higher upper reference limits need to be used for many assays.

Because of differences in calibration and specificity between various methods, it is desirable that reference values are determined separately for each assay.

However, reference values for such methods have not been established. The values in Table III have been determined by specific methods and are strictly valid only for these Alfthan et al. Other than the pregnancy test itself, urine measurements are seldom used for monitoring of pregnancy or cancer, but the reference limits are of value when urine samples are used to confirm false-positive results with serum assays.

The serum concentrations of HCG start increasing 7—10 days after the LH peak or 4—7 days after implantation Lenton et al. During early pregnancy, the HCG concentrations increase exponentially doubling on average every 1. After this, the levels decrease levelling out at 13—15 weeks and increase moderately again until weeks 30—33, after which there is a moderate decrease towards term Alfthan et al.

Serum concentrations of HCG during normal pregnancy. Reference values for serum HCG during the first 40 days after embryo transfer based on serial samples from 20 women. The lines denote the upper and lower reference limits and the median, respectively. The values were determined by a time-resolved immunofluorometric method Pettersson et al. Because of between-method differences in calibration, it is essential that the reference values be established separately for each assay.

The results are based on samples from 97 women. The HCG immunoreactivity in pregnancy urine is more heterogeneous than that in serum, and therefore the results are strongly dependent on the specificity of the assay used. When measured by specific assays, the HCG concentrations in urine correlate strongly with those in serum. The large day-to-day and within-day variation limits the clinical utility of quantitative urine assays. The variation in urinary HCG concentration can be reduced by normalizing against urine density or urine creatinine concentration.

However, this eliminates only part of the variation and serum assays are therefore better suited for quantitation. Because quantitative urine assays are not used for monitoring of pregnancy, appropriate reference values have not been established. Quantitative determinations of HCG are used to predict complications especially in early pregnancy, e. The various lines represent women with a normal pregnancy thin line , ectopic pregnancy thick line and early pregnancy loss or biochemical pregnancy broken line.

Rapid identification of early pregnancy loss is of value in ART. A failing pregnancy is usually associated with a slower than normal increase in serum HCG, which gradually turns into a decrease Korhonen et al. Pregnancy outcome can be predicted with fairly high accuracy using a single HCG determination in serum 12—16 days after embryo transfer Schmidt et al.

A threatening abortion can be identified more accurately by serial determinations of serum HCG, and the patients are usually highly motivated to participate in intense monitoring. The increase in serum HCG level is exponential, i. However, the rate of increase varies considerably between individuals. On the basis of the range of increase rates observed, various formulas and algorithms for identification of early pregnancy loss have been developed. For the identification of a threatening abortion, the slowest increase in a successful pregnancy is important.

A slower increase is thus a strong indication for an imminent abortion Barnhart et al. This indicates that implantation is delayed Korhonen et al. Determination of HCG in combination with sonography is used to detect complications later in pregnancy.

A yolk sac is visible by day 38 and fetal heart motion by day 43 Cacciatore et al. Ectopic pregnancy is mostly treated surgically or with methotrexate, but some patients recover spontaneously and can be treated conservatively. These patients are monitored by assay of serum HCG, and sinking levels indicate spontaneous resolution. Women with known risk factors of ectopic pregnancy can be screened by sonography and assay of serum HCG.

By this approach, an ectopic pregnancy can be detected on average at a gestational age of 37 days, which in most cases is before development of clinical symptoms Cacciatore et al. This facilitates early tube-sparing therapy. Even higher detection rates were obtained with a combination of first and second trimester screening Malone et al. HCG is an extremely sensitive and specific marker for gestational trophoblastic disease GTD and for some germ cell tumours of the testis. GTD comprises a spectrum of tumours ranging from hydatidiform mole to choriocarcinoma.

Choriocarcinoma often develops after a molar disease, and the risk associated with a complete mole is higher than after an incomplete mole. GTD may also develop after an ectopic pregnancy and occasionally in women without evidence of clinical pregnancy Seckl et al. Placental site trophoblastic tumour is a rare and therapy-resistant type of choriocarcinoma that develops after a pregnancy Baergen et al. A relapse of GTD is usually detected on the basis of an increasing serum HCG before the tumour is large enough to be detected by any other method.

Therefore, therapy of a relapse is directed on the basis of the HCG value Bagshawe, Carcinoma was diagnosed about days after application of a Levonova contraceptive device.

Testicular germ cell tumours are of two main types, seminomas and non-seminomatous germ cell tumours NSGCTs. Ovarian germ cell tumours are rare, but those containing trophoblastic components usually produce HCG Stenman et al.

With the first specific RIAs for HCG, elevated immunoreactivity was observed in serum from a large proportion of patients with non-trophoblastic tumours Braunstein et al. However, changes in the levels did not reliably reflect the course of the disease Rutanen and Seppala, This was probably explained by the increased level of serum HCG derived from the pituitary caused by ovariectomy Stenman et al.

This topic has recently been reviewed Stenman et al. Many of the first studies on ectopic expression of HCG-like immunoreactivity in cancer were performed on cervical and ovarian cancer cell lines Braunstein et al. Because HCG is a very sensitive tumour marker when pregnancy has been excluded, an elevated HCG level in serum is a strong indication for a trophoblastic or a germ cell tumour.

Therefore, patients without any other evidence of cancer but with a falsely elevated HCG value have been inappropriately treated with chemotherapy, which occasionally has caused severe complications Rotmensch and Cole, It is therefore important to be aware of this possibility and to know how to identify such results.

The causes of false and apparently false-positive results are listed in Table IV. This topic has recently been reviewed Braunstein, Most false-positive results are caused by antibodies to animal immunoglobulins Igs in the serum of the patients.

So-called heterophilic antibodies to animal Igs occur in the blood of everyone. Rheumatoid factors are anti-Ig antbodies that also may react with animal antibodies. Virtually, all HCG assays are presently sandwich assays using a capture antibody bound to a solid phase and a detector antibody that is labelled, usually with a fluorophore, an enzyme or a chemoluminescent substance.

Most assays use mouse monoclonal antibodies both as capture and as detector antibodies. The capture antibody catches HCG from the sample, and the detector antibody binds to another epitope on HCG, forming a sandwich.

The concentration of HCG is directly proportional to the amount of bound detector antibody. An anti-animal Ig in the sample will give rise to a sandwich by bridging capture and detector antibodies causing a false-positive result. Because Igs from various species are highly homologous, the same antibody can react with Igs from different animals.

Thus, the use of catcher and detector antibodies from different species, e. Assay manufacturers are aware of this problem and add Igs that block the interferences. However, some patient sera contain such high concentrations of heterophilic antibodies that the blocking is insufficient and a false-positive result is obtained.

Mouse antibodies are occasionally used for tumour imaging and therapy. This often gives rise to human anti-mouse Ig antibodies HAMA , which cause false-positive results in the same way as heterophilic antibodies, and their effect can also be blocked by the addition of mouse and other animal Igs to the assay buffer. Despite this, a small proportion of the samples will contain more HAMA or heterophilic antibodies than the added Igs are capable of neutralizing. This will lead to a false-positive result, and it is important to keep this possibility in mind and to perform additional studies necessary to identify the condition.

If the sample is available, the effect of heterophilic antibodies can be inhibited or at least reduced by the addition of mouse Ig or mouse serum to the sample Turpeinen et al. Dilution of the sample with buffer or rather the 0-standard usually results in a lower-than-expected result.

Another useful check is to analyse the sample with another method: the degree of interference is virtually always different in different methods Cole et al. It is also advisable to take a new sample. This reveals whether the result is caused by exchange of the sample. A false-positive result is usually similar in a new sample taken within 1—2 weeks, whereas in cancer the concentrations usually increase with time.

At the same time, a urine sample should be obtained. Igs are not excreted into urine, and a negative HCG result in urine is a reliable sign of a false-positive serum result Stenman et al. If the HCG level is only moderately elevated, a negative result in urine may be caused by a very dilute urine, which is recognized by the determination of urine density. In urine with an average density 1. Various complement factors react with antibodies, but the effect is highly dependent on the isotype of the antibody used.

Thus, mouse IgG2 often reacts with complement. In a sandwich assay, the effect is opposite to that of heterophilic antibodies, i. In an inhibition assay, complement will cause a false-positive result. Because of this, most assay manufacturers avoid using IgG2 antibodies. Serum also contains other factors that non-specifically block the antigen—antibody reaction.

This effect can be detected as a higher-than-expected result if the sample is diluted in a buffer devoid of protein. In contrast, the beta hCG is a quantitative test, meaning it reveals not just that the hormone is present in the blood, but in exactly what amounts. The beta-hCG test may be done to confirm pregnancy at an early prenatal doctor's visit as a follow-up to a positive at-home or in-office urine test.

But the beta hCG is not always done or necessary in routine pregnancies. Many practitioners use transvaginal ultrasound at pregnancy confirmation visits to actually see visible evidence of the pregnancy the gestational sac instead. The beta-hCG test is also used when there are concerns about pregnancy complications , including miscarriage. In these situations, repeat tests may be performed every two to three days to evaluate how quickly hCG levels are rising. Early on in pregnancy, the rate of increase is more telling than the actual quantity of the hormone in the blood.

Slow-to-rise hCG levels may indicate a high risk for miscarriage. If you are undergoing fertility treatments , your doctor may order a beta-hCG test just before or when your period is due to see if the efforts were successful. Doctors caring for women taking hCG shots to improve their chances of conception or as part of the intrauterine insemination IUI or in vitro fertilization IVF process need to carefully time a beta-hCG test to ensure that the medication has cleared the body and will not affect test results.

Other uses for the beta-hCG test during pregnancy include:. Unrelated to pregnancy, the beta-hCG test may help diagnose some cancers. The following are the typical ranges of hCG levels during pregnancy. These ranges are just guidelines, as every pregnancy is different.

Remember: Whether you have high or low levels of the hormone is not the key indicator of a healthy pregnancy. This is because many factors can influence total hCG levels, including maternal smoking, body mass index BMI , ethnicity, parity the number of times a woman has given birth , and hyperemesis gravidarum severe morning sickness.

Doctors instead look to see if hCG levels double every 48 to 72 hours from whatever level they started at. They look for this in the initial weeks of pregnancy, as it's normal for hCG levels to peak around 8 to 11 weeks' gestation, then decrease, and level off thereafter. If your hCG levels are low, it is likely that another test will be performed in a few days to confirm if levels are increasing or not.

If your beta-hCG levels are lower than expected and remain low in repeated testing , this may indicate:. If one of these issues is suspected, your practitioner will do other tests, typically a transvaginal ultrasound , to determine the status of your pregnancy. Reasons your beta-hCG levels may be higher than expected include:. If you see your hCG results on a lab report before you have the opportunity to speak about them with your doctor, try not to jump to your own conclusions.