Editing Ectopic pregnancy (section)

== Diagnosis ==

An ectopic pregnancy should be considered as the cause of abdominal pain or vaginal bleeding in everyone who has a positive [[pregnancy test]].<ref name=Crochet2013/> The primary goal of diagnostic procedures in possible ectopic pregnancy is to [[triage]] according to risk rather than establishing pregnancy location.<ref name=kirk2013/>

=== Transvaginal ultrasonography ===

An [[ultrasound]] showing a [[gestational sac]] with the fetal heart in the fallopian tube has a very high specificity of ectopic pregnancy. It involves a long, thin transducer, covered with the conducting gel and a plastic/latex sheath and inserted into the vagina.<ref>{{Cite web |date=8 August 2021 |title=Pelvic Ultrasound |url=https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/pelvic-ultrasound |access-date=2022-04-26 |website=www.hopkinsmedicine.org |language=en}}</ref> [[Vaginal ultrasonography|Transvaginal ultrasonography]] has a sensitivity of at least 90% for ectopic pregnancy.<ref name=kirk2013/> The diagnostic ultrasonographic finding in ectopic pregnancy is an adnexal mass that moves separately from the ovary. In around 60% of cases, it is an inhomogeneous or a noncystic adnexal mass sometimes known as the "blob sign". It is generally spherical, but a more tubular appearance may be seen in the case of [[hematosalpinx]]. This sign has been estimated to have a sensitivity of 84% and specificity of 99% in diagnosing ectopic pregnancy.<ref name=kirk2013/> In the study estimating these values, the blob sign had a [[Positive and negative predictive values|positive predictive value]] of 96% and a [[Positive and negative predictive values|negative predictive value]] of 95%.<ref name=kirk2013/> The visualization of an empty extrauterine gestational sac is sometimes known as the "bagel sign", and is present in around 20% of cases.<ref name=kirk2013/> In another 20% of cases, there is visualization of a gestational sac containing a yolk sac or an embryo.<ref name=kirk2013/> Ectopic pregnancies where there is visualization of cardiac activity are sometimes termed "viable ectopic".<ref name=kirk2013/>
<gallery mode="packed">
File:Schematic figure of vaginal ultrasonography in ectopic pregnancy.svg|[[Transvaginal ultrasonography]] of an ectopic pregnancy, showing the field of view in the following image
File:Blob sign of ectopic pregnancy.png|A "blob sign", which consists of the ectopic pregnancy. The ovary is distinguished from it by having follicles, whereof one is visible in the field. This patient had an [[intrauterine device with progestogen|intrauterine device (IUD) with progestogen]], whose cross-section is visible in the field, leaving an ultrasound shadow distally to it.
File:Ectopicleftmass.PNG|Ultrasound image showing an ectopic pregnancy where a [[gestational sac]] and fetus have been formed
</gallery>
[[File:UOTW 61 - Ultrasound of the Week 1.jpg|thumb|A pregnancy not in the uterus<ref>{{Cite web |date=14 October 2015 |title=UOTW#61 - Ultrasound of the Week |url=https://www.ultrasoundoftheweek.com/uotw-61/ |url-status=live |archive-url=https://web.archive.org/web/20170509152013/https://www.ultrasoundoftheweek.com/uotw-61/ |archive-date=9 May 2017 |website=Ultrasound of the Week}}</ref>]]
The combination of a positive pregnancy test and the presence of what appears to be a normal intrauterine pregnancy does not exclude ectopic pregnancy, since there may be either a [[heterotopic pregnancy]] or a "{{visible anchor|pseudosac}}", which is a collection of within the endometrial cavity that may be seen in up to 20% of women.<ref name=kirk2013/>

A small amount of [[Echogenicity|anechogenic]]-free fluid in the [[recto-uterine pouch]] is commonly found in both intrauterine and ectopic pregnancies.<ref name=kirk2013/> The presence of [[echogenic]] fluid is estimated at between 28 and 56% of women with an ectopic pregnancy, and strongly indicates the presence of [[hemoperitoneum]].<ref name=kirk2013/> However, it does not necessarily result from tubal rupture but is commonly a result from leakage from the [[distal tubal opening]].<ref name=kirk2013/> As a rule of thumb, the finding of free fluid is significant if it reaches the [[Fundus (uterus)|fundus]] or is present in the [[vesico-uterine pouch]].<ref name=kirk2013/> A further marker of serious intra-abdominal bleeding is the presence of fluid in the [[Hepatorenal recess of subhepatic space|hepatorenal recess of the subhepatic space]].<ref name=kirk2013/>

Currently, [[Doppler ultrasonography]] is not considered to significantly contribute to the diagnosis of ectopic pregnancy.<ref name=kirk2013/>

A common misdiagnosis is of a normal intrauterine pregnancy is where the pregnancy is implanted laterally in an [[arcuate uterus]], potentially being misdiagnosed as an [[interstitial pregnancy]].<ref name=kirk2013/>

=== Ultrasonography and β-hCG ===
[[File:Algorithm in pregnancy of unknown location.svg|thumb|upright=1.55|[[Medical algorithm|Algorithm]] of the management of a pregnancy of unknown location, that is, a positive pregnancy test but no pregnancy is found on [[transvaginal ultrasonography]].<ref name=kirk2013/> If serum hCG at 0&nbsp;hours is more than 1000 IU/L and there is no history suggestive of complete miscarriage, the ultrasonography should be repeated as soon as possible.<ref name=kirk2013/>]]

Where no intrauterine pregnancy (IUP) is seen on ultrasound, measuring [[Human chorionic gonadotropin|β-human chorionic gonadotropin]] (β-hCG) levels may aid in the diagnosis. The rationale is that a low β-hCG level may indicate that the pregnancy is intrauterine but yet too small to be visible on ultrasonography. While some physicians consider that the threshold where an intrauterine pregnancy should be visible on transvaginal ultrasound is around 1500&nbsp;mIU/mL of β-hCG, a review in the JAMA Rational Clinical Examination Series showed that there is no single threshold for the β-human chorionic gonadotropin that confirms an ectopic pregnancy.  Instead, the best test in a pregnant woman is a high-resolution transvaginal ultrasound.<ref name=Crochet2013/> The presence of an adnexal mass in the absence of an intrauterine pregnancy on transvaginal sonography increases the likelihood of an ectopic pregnancy 100-fold (LR+ 111).  When there are no adnexal abnormalities on transvaginal sonography, the likelihood of an ectopic pregnancy decreases (LR- 0.12). An empty uterus with levels higher than 1500 mIU/mL may be evidence of an ectopic pregnancy, but may also be consistent with an intrauterine pregnancy which is simply too small to be seen on ultrasound. If the diagnosis is uncertain, it may be necessary to wait a few days and repeat the blood work. This can be done by measuring the β-hCG level approximately 48 hours later and repeating the ultrasound. The serum hCG ratios and [[logistic regression]] models appear to be better than absolute single serum hCG level.<ref>{{Cite journal |display-authors=6 |vauthors=van Mello NM, Mol F, Opmeer BC, Ankum WM, Barnhart K, Coomarasamy A, Mol BW, van der Veen F, Hajenius PJ |year=2012 |title=Diagnostic value of serum hCG on the outcome of pregnancy of unknown location: a systematic review and meta-analysis |journal=Human Reproduction Update |volume=18 |issue=6 |pages=603–17 |doi=10.1093/humupd/dms035 |pmid=22956411 |doi-access=free}}</ref> If the β-hCG falls on repeat examination, this strongly suggests a spontaneous abortion or rupture. The fall in serum hCG over 48 hours may be measured as the hCG ratio, which is calculated as:<ref name=kirk2013/>
<math>hCG~ratio = \frac{hCG~at~48h}{hCG~at~0h}</math>

An hCG ratio of 0.87, that is, a decrease in hCG of 13% over 48 hours, has a sensitivity of 93% and specificity of 97% for predicting a failing [[#Pregnancy of unknown location|pregnancy of unknown location]] (PUL).<ref name=kirk2013/> The majority of cases of ectopic pregnancy will have serial serum hCG levels that increase more slowly than would be expected with an IUP (that is, a ''suboptimal rise''), or decrease more slowly than would be expected with a failing PUL. However, up to 20% of cases of ectopic pregnancy have serum hCG doubling times similar to that of an IUP, and around 10% of EP cases have hCG patterns similar to a failing PUL.<ref name=kirk2013/>

=== Other methods ===

==== Direct examination ====
A [[laparoscopy]] or laparotomy can also be performed to visually confirm an ectopic pregnancy. This is generally reserved for women presenting with signs of an [[acute abdomen]] and [[hypovolemic shock]].<ref name="kirk2013" /> Often, if a tubal abortion or tubal rupture has occurred, it is difficult to find the pregnancy tissue. A laparoscopy in very early ectopic pregnancy rarely shows a normal-looking fallopian tube.{{cn|date=September 2024}}

==== Culdocentesis ====
[[Culdocentesis]], in which fluid is retrieved from the space separating the vagina and rectum, is a less commonly performed test that may be used to look for internal bleeding. In this test, a needle is inserted into the space at the very top of the vagina, behind the uterus, and in front of the rectum. Any blood or fluid found may have been derived from a ruptured ectopic pregnancy.{{cn|date=June 2022}}

==== Progesterone levels ====
[[Progesterone]] levels of less than 20&nbsp;nmol/L have a high [[predictive value]] for failing pregnancies, whilst levels over 25 nmol/L are likely to predict viable pregnancies, and levels over 60&nbsp;nmol/L are strongly so. This may help in identifying failing PUL that are at low risk and thereby needing less follow-up.<ref name=kirk2013/> [[Inhibin A]] may also be useful for predicting spontaneous resolution of PUL, but is not as good as progesterone for this purpose.<ref name=kirk2013/>

==== Mathematical models ====
There are various mathematical models, such as logistic regression models and Bayesian networks, for the prediction of PUL outcomes based on multiple parameters.<ref name=kirk2013/> Mathematical models also aim to identify PULs that are ''low risk'', that is, failing PULs and IUPs.<ref name=kirk2013/>

==== Dilation and curettage ====
[[Dilation and curettage]] (D&C) is sometimes used to diagnose pregnancy location to differentiate between an EP and a non-viable IUP in situations where a viable IUP can be ruled out. Specific indications for this procedure include either of the following:<ref name=kirk2013/>
* No visible IUP on transvaginal ultrasonography with a serum hCG of more than 2000&nbsp;mIU/mL.
* An abnormal rise in hCG level.  A rise of 35% over 48 hours is proposed as the minimal rise consistent with a viable intrauterine pregnancy.
* An abnormal fall in hCG level, such as defined as one of less than 20% in two days.

=== Classification ===

==== Tubal pregnancy ====

The vast majority of ectopic pregnancies implant in the fallopian tube. Pregnancies can grow in the fimbrial end (5% of all ectopic pregnancies), the ampullary section (80%), the isthmus (12%), and the cornual and interstitial part of the tube (2%).<ref name="speroff">{{Cite book |title=Clinical Gynecological Endocrinology and Infertility, 6th Ed. |vauthors=Speroff L, Glass RH, Kase NG |publisher=Lippincott Williams & Wilkins (1999) |year=1999 |isbn=978-0-683-30379-7 |page=1149ff}}</ref> Mortality of a tubal pregnancy at the isthmus or within the uterus (interstitial pregnancy) is higher as there is increased vascularity that may result more likely in sudden major internal bleeding. A review published in 2010 supports the hypothesis that tubal ectopic pregnancy is caused by a combination of retention of the embryo within the fallopian tube due to impaired embryo-tubal transport and alterations in the tubal environment allowing early implantation to occur.<ref>{{Cite journal |vauthors=Shaw JL, Dey SK, Critchley HO, Horne AW |date=January 2010 |title=Current knowledge of the aetiology of human tubal ectopic pregnancy |journal=Human Reproduction Update |volume=16 |issue=4 |pages=432–44 |doi=10.1093/humupd/dmp057 |pmc=2880914 |pmid=20071358}}</ref>

==== Nontubal ectopic pregnancy ====

Two percent of ectopic pregnancies occur in the ovary, cervix, or are intra-abdominal. Transvaginal ultrasound examination is usually able to detect a [[cervical pregnancy]]. An [[ovarian pregnancy]] is differentiated from a tubal pregnancy by the [[Spiegelberg criteria]].<ref>{{WhoNamedIt|synd|2274|Spiegelberg's criteria}}</ref>

While a fetus of ectopic pregnancy is typically not viable, very rarely, live babies have been delivered from [[abdominal pregnancy]] or C-section scar ectopic pregnancy. In the former situation, the [[placenta]] sits on the intra-abdominal organs or the [[peritoneum]] and has found sufficient blood supply. This is generally bowel or mesentery, but other sites, such as the renal (kidney), liver or hepatic (liver) artery, or even the aorta, have been described. Support to near viability has occasionally been described, but even in [[Third World]] countries, the diagnosis is most commonly made at 16 to 20 weeks' gestation. Such a fetus would have to be delivered by laparotomy. Maternal morbidity and mortality from extrauterine pregnancy are high, as attempts to remove the placenta from the organs to which it is attached usually lead to uncontrollable bleeding from the attachment site. If the organ to which the placenta is attached is removable, such as a section of the bowel, then the placenta should be removed together with that organ. This is such a rare occurrence that true data is unavailable and reliance must be made on anecdotal reports.<ref>{{Cite news |date=2005-08-30 |title='Special' baby grew outside womb |url=http://news.bbc.co.uk/1/hi/england/beds/bucks/herts/4197194.stm |url-status=live |archive-url=https://web.archive.org/web/20070212010650/http://news.bbc.co.uk/1/hi/england/beds/bucks/herts/4197194.stm |archive-date=2007-02-12 |access-date=2006-07-14 |work=BBC News}}</ref><ref>{{Cite news |date=2005-03-09 |title=Bowel baby born safely |url=http://news.bbc.co.uk/2/hi/health/671390.stm |url-status=live |archive-url=https://web.archive.org/web/20070211233539/http://news.bbc.co.uk/2/hi/health/671390.stm |archive-date=2007-02-11 |access-date=2006-11-10 |work=BBC News}}</ref><ref name="pmid17957101">{{Cite journal |vauthors=Zhang J, Li F, Sheng Q |year=2008 |title=Full-term abdominal pregnancy: a case report and review of the literature |journal=Gynecologic and Obstetric Investigation |volume=65 |issue=2 |pages=139–41 |doi=10.1159/000110015 |pmid=17957101 |s2cid=35923100}}</ref> However, the vast majority of abdominal pregnancies require intervention well before [[fetal viability]] because of the risk of bleeding.

With the increase in Cesarean sections performed worldwide,<ref>{{Cite web |title=Rates of Cesarean Delivery -- United States, 1993 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/00036845.htm |access-date=2020-08-11 |website=www.cdc.gov}}</ref><ref>{{Cite journal |vauthors=Betrán AP, Ye J, Moller AB, Zhang J, Gülmezoglu AM, Torloni MR |date=2016-02-05 |title=The Increasing Trend in Caesarean Section Rates: Global, Regional and National Estimates: 1990-2014 |journal=PLOS ONE |volume=11 |issue=2 |pages=e0148343 |bibcode=2016PLoSO..1148343B |doi=10.1371/journal.pone.0148343 |pmc=4743929 |pmid=26849801 |doi-access=free}}</ref> Cesarean section ectopic pregnancies (CSP) are rare, but becoming more common. The incidence of CSP is not well known, however there have been estimates based on different populations of 1:1800–1:2216.<ref>{{Cite journal |vauthors=Jurkovic D, Hillaby K, Woelfer B, Lawrence A, Salim R, Elson CJ |date=March 2003 |title=First-trimester diagnosis and management of pregnancies implanted into the lower uterine segment Cesarean section scar |journal=Ultrasound in Obstetrics & Gynecology |volume=21 |issue=3 |pages=220–7 |doi=10.1002/uog.56 |pmid=12666214 |s2cid=27272542 |doi-access=free}}</ref><ref name="Cesarean scar pregnancy: issues in">{{Cite journal |vauthors=Seow KM, Huang LW, Lin YH, Lin MY, Tsai YL, Hwang JL |date=March 2004 |title=Cesarean scar pregnancy: issues in management |journal=Ultrasound in Obstetrics & Gynecology |volume=23 |issue=3 |pages=247–53 |doi=10.1002/uog.974 |pmid=15027012 |s2cid=36067188 |doi-access=free}}</ref> CSP are characterized by abnormal implantation into the scar from a previous cesarean section,<ref name=":0">{{Cite journal |last1=Luis Izquierdo |first1=M. D. |last2=Mariam Savabi |first2=M. D. |date=16 August 2019 |title=How to diagnose and treat cesarean scar pregnancy |url=https://www.contemporaryobgyn.net/view/how-diagnose-and-treat-cesarean-scar-pregnancy |journal=Contemporary Ob/Gyn Journal |series=Vol 64 No 08 |volume=64 |issue=8 |access-date=2020-08-11}}</ref> and allowed to continue can cause serious complications such as uterine rupture and hemorrhage.<ref name="Cesarean scar pregnancy: issues in" /> Patients with CSP generally present without symptoms, however symptoms can include vaginal bleeding that may or may not be associated with pain.<ref>{{Cite journal |vauthors=Rotas MA, Haberman S, Levgur M |date=June 2006 |title=Cesarean scar ectopic pregnancies: etiology, diagnosis, and management |journal=Obstetrics and Gynecology |volume=107 |issue=6 |pages=1373–81 |doi=10.1097/01.AOG.0000218690.24494.ce |pmid=16738166 |s2cid=39198754}}</ref><ref name=":1">{{Cite journal |vauthors=Ash A, Smith A, Maxwell D |date=March 2007 |title=Caesarean scar pregnancy |journal=BJOG |volume=114 |issue=3 |pages=253–63 |doi=10.1111/j.1471-0528.2006.01237.x |pmid=17313383 |s2cid=34003037 |doi-access=free}}</ref> The diagnosis of CSP is made by ultrasound and four characteristics are noted: (1) Empty uterine cavity with bright hyperechoic endometrial stripe (2) Empty cervical canal (3) Intrauterine mass in the anterior part of the uterine isthmus, and (4) Absence of the anterior uterine muscle layer, and/or absence or thinning between the bladder and gestational sac, measuring less than 5&nbsp;mm.<ref name=":0" /><ref>{{Cite book |title=Williams obstetrics |date=12 April 2018 |isbn=978-1-259-64432-0 |editor-last=F. Gary Cunningham |edition=25th |location=New York |oclc=986236927 |editor-last2=Kenneth J. Leveno |editor-last3=Steven L. Bloom |editor-last4=Jodi S. Dashe |editor-last5=Barbara L. Hoffman |editor-last6=Brian M. Casey |editor-last7=Catherine Y. Spong}}</ref><ref>{{Cite journal |vauthors=Weimin W, Wenqing L |date=June 2002 |title=Effect of early pregnancy on a previous lower segment cesarean section scar |journal=International Journal of Gynaecology and Obstetrics |volume=77 |issue=3 |pages=201–7 |doi=10.1016/S0020-7292(02)00018-8 |pmid=12065130 |s2cid=28083933}}</ref> Given the rarity of the diagnosis, treatment options tend to be described in case reports and series, ranging from medical with methotrexate or KCl<ref>{{Cite journal |vauthors=Godin PA, Bassil S, Donnez J |date=February 1997 |title=An ectopic pregnancy developing in a previous caesarian section scar |journal=Fertility and Sterility |volume=67 |issue=2 |pages=398–400 |doi=10.1016/S0015-0282(97)81930-9 |pmid=9022622 |doi-access=free}}</ref> to surgical with dilation and curettage,<ref>{{Cite journal |vauthors=Shu SR, Luo X, Wang ZX, Yao YH |date=2015-08-01 |title=Cesarean scar pregnancy treated by curettage and aspiration guided by laparoscopy |journal=Therapeutics and Clinical Risk Management |volume=11 |pages=1139–41 |doi=10.2147/TCRM.S86083 |pmc=4529265 |pmid=26345396 |doi-access=free}}</ref> uterine wedge resection,{{citation needed|date=August 2020}} or hysterectomy.<ref name=":1" /> A double-balloon catheter technique has also been described,<ref>{{Cite journal |display-authors=6 |vauthors=Monteagudo A, Calì G, Rebarber A, Cordoba M, Fox NS, Bornstein E, Dar P, Johnson A, Rebolos M, Timor-Tritsch IE |date=March 2019 |title=Minimally Invasive Treatment of Cesarean Scar and Cervical Pregnancies Using a Cervical Ripening Double Balloon Catheter: Expanding the Clinical Series |journal=Journal of Ultrasound in Medicine |volume=38 |issue=3 |pages=785–793 |doi=10.1002/jum.14736 |pmid=30099757 |s2cid=51966025}}</ref> allowing for uterine preservation. The recurrence risk for CSP is unknown, and early ultrasound in the next pregnancy is recommended.<ref name=":0" />

==== Heterotopic pregnancy ====
{{main|Heterotopic pregnancy}}
In rare cases of ectopic pregnancy, there may be two fertilized eggs, one outside the uterus and the other inside. This is called a [[heterotopic pregnancy]].<ref name=Crochet2013/> Often, the intrauterine pregnancy is discovered later than the ectopic, mainly because of the painful emergency nature of ectopic pregnancies. Since ectopic pregnancies are normally discovered and removed very early in the pregnancy, an ultrasound may not find the additional pregnancy inside the uterus. When hCG levels continue to rise after the removal of the ectopic pregnancy, there is a chance that a pregnancy inside the uterus is still viable. This is normally discovered through an ultrasound.{{cn|date=September 2024}}

Although rare, heterotopic pregnancies are becoming more common, likely due to increased use of IVF. The survival rate of the uterine fetus of a heterotopic pregnancy is around 70%.<ref>{{Cite journal |vauthors=Lau S, Tulandi T |date=August 1999 |title=Conservative medical and surgical management of interstitial ectopic pregnancy |journal=Fertility and Sterility |volume=72 |issue=2 |pages=207–15 |doi=10.1016/s0015-0282(99)00242-3 |pmid=10438980 |doi-access=free}}</ref>

==== Rudimentary horn pregnancy ====
{{main|Rudimentary horn pregnancy}}
A [[pregnancy in a rudimentary horn]] refers to a rare and life-threatening condition that occurs when a fertilized egg implants inside the small rudimentary horn of a [[unicornuate uterus]], which is a type of congenital uterine abnormality caused by the incomplete development of one of the [[Müllerian ducts]]. This type of ectopic pregnancy is often results in rupture of the rudimentary horn between 10 and 15 weeks of gestation, leading to a high risk of morbidity and mortality.<ref>{{Cite journal |last1=Chopra |first1=Seema |last2=Keepanasseril |first2=Anish |last3=Rohilla |first3=Meenakshi |last4=Bagga |first4=Rashmi |last5=Kalra |first5=Jaswinder |last6=Jain |first6=Vanita |date=2009-03-13 |title=Obstetric morbidity and the diagnostic dilemma in pregnancy in rudimentary horn: retrospective analysis |journal=Archives of Gynecology and Obstetrics |publisher=Springer Science and Business Media LLC |volume=280 |issue=6 |pages=907–910 |doi=10.1007/s00404-009-1013-4 |issn=0932-0067 |pmid=19283398 |s2cid=5616550}}</ref>

==== Persistent ectopic pregnancy ====

A persistent ectopic pregnancy refers to the continuation of trophoblastic growth after a surgical intervention to remove an ectopic pregnancy. After a conservative procedure that attempts to preserve the affected fallopian tube such as a [[salpingotomy]], in about 15–20%, the major portion of the ectopic growth may have been removed, but some trophoblastic tissue, perhaps deeply embedded, has escaped removal and continues to grow, generating a new rise in hCG levels.<ref>{{Cite journal |vauthors=Kemmann E, Trout S, Garcia A |date=February 1994 |title=Can We predict patients at risk for persistent ectopic pregnancy after laparoscopic salpingotomy? |journal=The Journal of the American Association of Gynecologic Laparoscopists |volume=1 |issue=2 |pages=122–6 |doi=10.1016/S1074-3804(05)80774-1 |pmid=9050473}}</ref> After weeks, this may lead to new clinical symptoms, including bleeding. For this reason, hCG levels may have to be monitored after the removal of an ectopic pregnancy to ensure their decline, also [[methotrexate]] can be given at the time of surgery prophylactically.{{cn|date=June 2022}}

==== Pregnancy of unknown location ====

Pregnancy of unknown location (PUL) is the term used for a pregnancy where there is a positive pregnancy test but no pregnancy has been visualized using transvaginal ultrasonography.<ref name=kirk2013/> Specialized early pregnancy departments have estimated that between 8% and 10% of women attending for an ultrasound assessment in early pregnancy will be classified as having a PUL.<ref name=kirk2013/> The true nature of the pregnancy can be an ongoing viable intrauterine pregnancy, a failed pregnancy, an ectopic pregnancy or rarely a [[#Persisting PUL|persisting PUL]].<ref name=kirk2013/>

Because of frequent ambiguity on ultrasonography examinations, the following classification is proposed:<ref name=kirk2013/>

{| class="wikitable"
! Condition !! Criteria
|-
| Definite ectopic pregnancy || Extrauterine [[gestational sac]] with yolk sac or embryo (with or without cardiac activity).
|-
| Pregnancy of unknown location – probable ectopic pregnancy || Inhomogeneous adnexal mass or extrauterine sac-like structure.
|-
| "True" pregnancy of unknown location || No signs of intrauterine nor extrauterine pregnancy on transvaginal ultrasonography.
|-
| Pregnancy of unknown location – probable intrauterine pregnancy || Intrauterine gestational sac-like structure.
|-
| Definite intrauterine pregnancy || Intrauterine gestational sac with yolk sac or embryo (with or without cardiac activity).
|}

In women with a pregnancy of unknown location, between 6% and 20% have an ectopic pregnancy.<ref name=kirk2013/> In cases of pregnancy of unknown location and a history of heavy bleeding, it has been estimated that approximately 6% have an underlying ectopic pregnancy.<ref name=kirk2013/> Between 30% and 47% of women with pregnancy of unknown location are ultimately diagnosed with an ongoing intrauterine pregnancy, whereof the majority  (50–70%) will be found to have failing pregnancies where the location is never confirmed.<ref name=kirk2013/>

[[File:Histopathology of tubal pregnancy.jpg|thumb|[[Chorionic villus]] on [[histopathological examination]] of a tubal pregnancy]]
{{visible anchor|Persisting PUL}} is where the hCG level does not spontaneously decline and no intrauterine or ectopic pregnancy is identified on follow-up transvaginal ultrasonography.<ref name=kirk2013/> A persisting PUL is likely either a small ectopic pregnancy that has not been visualized, or a retained trophoblast in the endometrial cavity.<ref name=kirk2013/> Treatment should only be considered when a potentially viable intrauterine pregnancy has been definitively excluded.<ref name=kirk2013/> A ''treated persistent PUL'' is defined as one managed medically (generally with methotrexate) without confirmation of the location of the pregnancy, such as by ultrasound, laparoscopy, or uterine evacuation.<ref name=kirk2013/> A ''resolved persistent PUL'' is defined as serum hCG reaching a non-pregnant value (generally less than 5&nbsp;IU/L) after expectant management, or after uterine evacuation without evidence of [[chorionic villi]] on [[histopathological examination]].<ref name=kirk2013/> In contrast, a relatively low and unresolving level of serum hCG indicates the possibility of an hCG-secreting tumor.<ref name=kirk2013/>

=== Differential diagnosis ===

Other conditions that cause similar symptoms include: miscarriage, ovarian torsion, acute appendicitis, ruptured ovarian cyst, [[Kidney stone disease|kidney stone]], and pelvic inflammatory disease, among others.<ref name=Crochet2013/>