Editing Human chorionic gonadotropin (section)

==Testing==
[[File:Pregnancy test series starting to show positive.jpg|thumb|A series of hCG tests taken at one-day intervals, gradually showing positive at the beginning of a pregnancy.]]
[[Blood]] or [[urine]] tests measure hCG. These can be [[pregnancy test]]s. hCG-positive can indicate an implanted [[blastocyst]] and [[mammalian embryogenesis]] or can be detected for a short time following  childbirth or pregnancy loss. Tests can be done to diagnose and monitor [[germ cell tumor]]s and [[gestational trophoblastic disease]]s.

Concentrations are commonly reported in thousandth international units per milliliter (mIU/mL). The international unit of hCG was originally established in 1938 and has been redefined in 1964 and in 1980.<ref>{{cite journal | vauthors = Peters AJ | title = The Diagnosis of Pregnancy | veditors = von Dadelszen P | journal = Global Library of Women's Medicine | date = May 2008 | doi = 10.3843/GLOWM.10093 |url=http://www.glowm.com/index.html?p=glowm.cml/section_view&articleid=93}}</ref> At the present time, 1 international unit is equal to approximately 2.35×10<sup>−12</sup> moles,<ref>{{cite web|url=http://www.nibsc.ac.uk/documents/ifu/99-688.pdf|title=WHO Reference Reagent Human Chorionic Gonadotrophin (Purified) NIBSC code: 99/688 Instructions for use (Version 3.0, Dated 05/11/2007)|url-status=dead|archive-url=https://web.archive.org/web/20121203215926/http://www.nibsc.ac.uk/documents/ifu/99-688.pdf|archive-date=2012-12-03}}</ref> or about 6×10<sup>−8</sup> grams.<ref>{{cite journal | vauthors = Canfield RE, Ross GT | title = A new reference preparation of human chorionic gonadotrophin and its subunits | journal = Bulletin of the World Health Organization | volume = 54 | issue = 4 | pages = 463–472 | year = 1976 | pmid = 1088359 | pmc = 2366462 }}</ref>

It is also possible to test for hCG to have an approximation of the gestational age.<ref>{{cite book| vauthors = Wallach J |title=Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|year=2014|isbn=978-1-4511-9176-9|edition=10th|location=Philadelphia}}</ref>

===Methodology===

Most tests employ a monoclonal antibody, which is specific to the ''β-subunit'' of hCG (β-hCG). This procedure is employed to ensure that tests do not make [[Type I and type II errors|false positives]] by confusing hCG with LH and FSH. (The latter two are always present at varying levels in the body, whereas the presence of hCG almost always indicates pregnancy.){{cn|date=September 2023}}

Many hCG immunoassays are based on the [[Immunoassay#Two-site, noncompetitive immunoassays|sandwich principle]], which uses antibodies to hCG labeled with an enzyme or a conventional or luminescent dye.
Pregnancy urine dipstick tests are based on the [[lateral flow test|lateral flow]] technique.
* The [[urine test]] may be a ''chromatographic [[immunoassay]]'' or any of several other test formats, home-, physician's office-, or laboratory-based.<ref name="henry">{{cite book | vauthors = McPherson RA, Pincus MR |title=Henry's Clinical Diagnosis and Management by Laboratory Methods |publisher=Saunders |location=Philadelphia |year=2006 |isbn=978-1-4160-0287-1 |edition=21st}}{{Page needed|date=December 2011}}</ref>  Published detection thresholds range from 20 to 100 mIU/mL, depending on the brand of test.<ref>{{cite web| vauthors = Waddell RS | year=2006| title=FertilityPlus.org| work=Home Pregnancy Test hCG Levels and FAQ| url=http://www.fertilityplus.org/faq/hpt.html| access-date=2006-06-17| url-status=dead| archive-url=https://web.archive.org/web/20060615212054/http://www.fertilityplus.org/faq/hpt.html| archive-date=2006-06-15}}</ref> Early in pregnancy, more accurate results may be obtained by using the first urine of the morning (when urine is most concentrated). When the urine is dilute ([[specific gravity]] less than 1.015), the hCG concentration may not be representative of the blood concentration, and the test may be falsely negative.
* The [[blood plasma|serum]] test, using 2-4 mL of venous blood, is typically a chemiluminescent or fluorimetric immunoassay<ref name="henry" /> that can detect βhCG levels as low as 5 mIU/mL and allows quantification of the βhCG concentration.

===Reference levels in normal pregnancy===
The hCG levels grow exponentially after conception and implantation.<ref>{{cite web |date=22 August 2017 |title=Guideline To HCG Levels During Pregnancy |url=http://americanpregnancy.org/while-pregnant/hcg-levels/ |publisher=American Pregnancy Association}}</ref> hCG levels typically peak around weeks 8-11 of pregnancy and are generally higher in the first trimester compared to the second trimester.

The following is a list of serum hCG levels:

''LMP'' is the [[last menstrual period]] dated from the first day of the last menstrual period 

{| class="wikitable"
|-
! weeks since LMP !! mIU/mL
|-
| 3 || 5 – 50
|-
| 4 || 5 – 428
|-
| 5 || 18 – 7,340
|-
| 6 || 1,080 – 56,500
|-
| 7 – 8 || 7,650 – 229,000
|-
| 9 – 12 || 25,700 – 288,000
|-
| 13 – 16 || 13,300 – 254,000
|-
| 17 – 24 || 4,060 – 165,400
|-
| 25 – 40 || 3,640 – 117,000
|-
| Non-pregnant females || <5.0
|-
| Postmenopausal females || <9.5
|}

If a pregnant woman has serum hCG levels that are higher than expected, they may be experiencing a [[multiple pregnancy]] or an abnormal uterine growth. Falling hCG levels may indicate the possibility of a miscarriage. hCG levels which are rising at a slower rate than expected may indicate an [[ectopic pregnancy]].<ref>{{cite web |title=hCG levels |url=https://www.pregnancybirthbaby.org.au/hcg-levels |website=www.pregnancybirthbaby.org.au |access-date=17 January 2023 |language=en-AU |date=21 December 2022}}</ref>

===Interpretation===
The ability to quantitate the βhCG level is useful in monitoring [[germ cell tumor|germ cell]] and [[Gestational trophoblastic disease|trophoblastic tumors]], follow-up care after [[miscarriage]], and diagnosis of and follow-up care after treatment of [[ectopic pregnancy]]. The lack of a visible fetus on vaginal [[ultrasound]] after βhCG levels reach 1500 mIU/mL is strongly indicative of an ectopic pregnancy.<ref>{{cite web | vauthors = Tualndi T | date = February 2022 | veditors = Barbieri RL, Chakrabarti A | title=Ectopic (tubal) pregnancy |url=http://www.uptodate.com/contents/ectopic-tubal-pregnancy-beyond-the-basics|publisher=UpToDate|access-date=1 June 2013}}</ref> Still, even an hCG over 2000 IU/L does not necessarily exclude the presence of a viable intrauterine pregnancy in such cases.<ref name=kirk2013/>

As pregnancy tests, quantitative blood tests and the most sensitive urine tests usually detect hCG between 6 and 12 days after ovulation.<ref name="wilcox">{{cite journal | vauthors = Wilcox AJ, Baird DD, Weinberg CR | title = Time of implantation of the conceptus and loss of pregnancy | journal = The New England Journal of Medicine | volume = 340 | issue = 23 | pages = 1796–1799 | date = June 1999 | pmid = 10362823 | doi = 10.1056/NEJM199906103402304 | doi-access = free }}</ref> It must be taken into account, however, that total hCG levels may vary in a very wide range within the first 4 weeks of gestation, leading to false results during this period.<ref>{{cite journal | vauthors = Butler SA, Khanlian SA, Cole LA | title = Detection of early pregnancy forms of human chorionic gonadotropin by home pregnancy test devices | journal = Clinical Chemistry | volume = 47 | issue = 12 | pages = 2131–2136 | date = December 2001 | pmid = 11719477 | doi = 10.1093/clinchem/47.12.2131 | doi-access = free }}</ref> A rise of 35% over 48 hours is proposed as the minimal rise consistent with a viable intrauterine pregnancy.<ref name=kirk2013>{{cite journal | vauthors = Kirk E, Bottomley C, Bourne T | title = Diagnosing ectopic pregnancy and current concepts in the management of pregnancy of unknown location | journal = Human Reproduction Update | volume = 20 | issue = 2 | pages = 250–261 | year = 2013 | pmid = 24101604 | doi = 10.1093/humupd/dmt047 | doi-access =  }}</ref>

=== Associations with pathologies ===
Gestational trophoblastic disease like [[hydatidiform mole]]s ("molar pregnancy") or choriocarcinoma may produce high levels of βhCG due to the presence of [[syncytiotrophoblasts]], part of the villi that make up the placenta, and despite the absence of an embryo. This, as well as several other conditions, can lead to elevated hCG readings in the absence of pregnancy.{{cn|date=September 2023}}

hCG levels are also a component of the [[triple test]], a screening test for certain fetal chromosomal abnormalities/birth defects. High hCG levels in the maternal serum could suggest [[Down syndrome]], potentially due to continued hCG production by the placenta beyond the first trimester.<ref>{{cite journal | vauthors = Jiang H, Lin Y, He X | title = Association Analysis between Maternal Serum Biomarkers and Fetal Congenital Heart Disease | journal = The Heart Surgery Forum | volume = 26 | issue = 5 | pages = E552–E559 | date = October 2023 | pmid = 37920073 | doi = 10.59958/hsf.6703 | doi-access = free }}</ref>

A study of 32 normal pregnancies came to the result that a [[gestational sac]] of 1–3&nbsp;mm was detected at a mean hCG level of 1150 IU/L (range 800–1500), a [[yolk sac]] was detected at a mean level of 6000 IU/L (range 4500–7500) and [[fetal heartbeat]] was visible at a mean hCG level of 10,000 IU/L (range 8650–12,200).<ref>{{cite journal | vauthors = Giacomello F, Magliocchetti P, Loyola G, Giovarruscio M | title = [Serum beta hCG levels and transvaginal echography in the early phases of pregnancy] | language = it | journal = Minerva Ginecologica | volume = 45 | issue = 7–8 | pages = 333–337 | year = 1993 | pmid = 8414139 }}</ref>