View source for Ectopic pregnancy

{{Short description|Female reproductive system health issue}}
{{Infobox medical condition (new)
| name            = Ectopic pregnancy
| synonyms        = EP, eccyesis, extrauterine pregnancy, EUP, tubal pregnancy ''(when in fallopian tube)''
| image           = Ectopic pregnancy on laparoscopy.png
| caption         = [[Laparoscopic]] view, looking down at the [[uterus]] (marked by <span style="color:blue;">blue arrows</span>). In the left [[fallopian tube]], there is an ectopic pregnancy and [[hematosalpinx|bleeding]] (marked by <span style="color:red;">red arrows</span>). The right tube is normal.
| field           = [[Obstetrics and Gynaecology]]
| symptoms        = [[Abdominal pain]], [[vaginal bleeding]]<ref name=Crochet2013/>
| complications   =
| onset           =
| duration        =
| types           =
| causes          =
| risks           = [[Pelvic inflammatory disease]], [[tobacco smoking]], prior tubal surgery, history of [[infertility]], use of [[assisted reproductive technology]]<ref name=Cec2014/>
| diagnosis       = Blood tests for [[human chorionic gonadotropin]] (hCG), [[ultrasound]]<ref name=Crochet2013/>
| differential    = [[Miscarriage]], [[ovarian torsion]], [[acute appendicitis]],<ref name=Crochet2013/> [[corpus luteum cyst]] rupture<ref>{{Cite journal |last=Bauman |first=Renato |last2=Horvat |first2=Gordana |date=December 2018 |title=MANAGEMENT OF RUPTURED CORPUS LUTEUM WITH HEMOPERITONEUM IN EARLY PREGNANCY – A CASE REPORT |journal=Acta Clinica Croatica |volume=57 |issue=4 |pages=785–788 |doi=10.20471/acc.2018.57.04.24 |pmc=6544092 |pmid=31168219}}</ref>

| prevention      =
| treatment       = [[methotrexate]], surgery<ref name=Cec2014/>
| medication      =
| prognosis       = Mortality 0.2% (developed world), 2% (developing world)<ref name=WHO2015Mort/>
| frequency       = ~1.5% of pregnancies (developed world)<ref name=kirk2013/>
| deaths          =
}}
<!-- Definition and symptoms -->
'''Ectopic pregnancy''' is a [[Complications of pregnancy|complication of pregnancy]] in which the embryo attaches outside the [[uterus]].<ref name=kirk2013/> Signs and symptoms classically include [[abdominal pain]] and [[vaginal bleeding]], but fewer than 50 percent of affected women have both of these symptoms.<ref name=Crochet2013/> The pain may be described as sharp, dull, or crampy.<ref name=Crochet2013/> Pain may also spread to the shoulder if bleeding into the abdomen has occurred.<ref name=Crochet2013/> Severe bleeding may result in a [[tachycardia|fast heart rate]], [[Syncope (medicine)|fainting]], or [[Shock (circulatory)|shock]].<ref name=kirk2013/><ref name=Crochet2013/> With very rare exceptions, the [[fetus]] is unable to survive.<ref>{{Cite journal |vauthors=Zhang J, Li F, Sheng Q |date=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>

<!-- Cause and diagnosis -->
Overall, ectopic pregnancies annually affect less than 2% of pregnancies worldwide.<ref name=kirk2013/>
Risk factors for ectopic pregnancy include [[pelvic inflammatory disease]], often due to [[chlamydia infection]]; [[tobacco smoking]]; [[endometriosis]]; prior tubal surgery; a history of [[infertility]]; and the use of [[assisted reproductive technology]].<ref name="Cec2014" /> Those who have previously had an ectopic pregnancy are at much higher risk of having another one.<ref name="Cec2014" /> Most ectopic pregnancies (90%) occur in the [[fallopian tube]], which are known as tubal pregnancies,<ref name="Cec2014" /> but [[Implantation (embryology)|implantation]] can also occur on the [[cervix]], [[ovary|ovaries]], caesarean scar, or within the [[abdomen]].<ref name="Crochet2013">{{Cite journal |vauthors=Crochet JR, Bastian LA, Chireau MV |date=April 2013 |title=Does this woman have an ectopic pregnancy?: the rational clinical examination systematic review |journal=JAMA |volume=309 |issue=16 |pages=1722–9 |doi=10.1001/jama.2013.3914 |pmid=23613077 |s2cid=205049738}}</ref> Detection of ectopic pregnancy is typically by blood tests for [[human chorionic gonadotropin]] (hCG) and [[ultrasound]].<ref name=Crochet2013/> This may require testing on more than one occasion.<ref name=Crochet2013/> Other causes of similar symptoms include: [[miscarriage]], [[ovarian torsion]], and [[acute appendicitis]].<ref name=Crochet2013/>

<!-- Treatment -->
Prevention is by decreasing risk factors such as chlamydia infections through screening and treatment.<ref name=Nama2009/> While some ectopic pregnancies will miscarry without treatment,<ref name=Cec2014/> the standard treatment for ectopic pregnancy is a procedure to either remove the embryo from the fallopian tube or to remove the fallopian tube altogether. The use of the medication [[methotrexate]] works as well as surgery in some cases.<ref name=Cec2014/> Specifically it works well when the [[beta-HCG]] is low and the size of the ectopic is small.<ref name=Cec2014/> Surgery such as a [[salpingectomy]] is still typically recommended if the tube has ruptured, there is a fetal heartbeat, or the woman's [[vital sign]]s are unstable.<ref name=Cec2014/> The surgery may be [[laparoscopic]] or through a larger incision, known as a [[laparotomy]].<ref name=kirk2013/> Maternal morbidity and mortality are reduced with treatment.<ref name="Cec2014">{{Cite journal |vauthors=Cecchino GN, Araujo Júnior E, Elito Júnior J |date=September 2014 |title=Methotrexate for ectopic pregnancy: when and how |journal=Archives of Gynecology and Obstetrics |volume=290 |issue=3 |pages=417–23 |doi=10.1007/s00404-014-3266-9 |pmid=24791968 |s2cid=26727563}}</ref>

<!-- Epidemiology and history -->
The rate of ectopic [[pregnancy]] is about 11 to 20 per 1,000 live births in developed countries, though it may be as high as 4% among those using [[assisted reproductive technology]].<ref name="kirk2013">{{Cite journal |vauthors=Kirk E, Bottomley C, Bourne T |year=2014 |title=Diagnosing ectopic pregnancy and current concepts in the management of pregnancy of unknown location |journal=Human Reproduction Update |volume=20 |issue=2 |pages=250–61 |doi=10.1093/humupd/dmt047 |pmid=24101604 |doi-access=free}}</ref> It is the most common cause of death among women during the first trimester at approximately 6-13% of the total.<ref name=Cec2014/> In the [[Developed country|developed world]] outcomes have improved while in the developing world they often remain poor.<ref name="Nama2009">{{Cite journal |vauthors=Nama V, Manyonda I |date=April 2009 |title=Tubal ectopic pregnancy: diagnosis and management |journal=Archives of Gynecology and Obstetrics |volume=279 |issue=4 |pages=443–53 |doi=10.1007/s00404-008-0731-3 |pmid=18665380 |s2cid=22538462}}</ref> The risk of death among those in the developed world is between 0.1 and 0.3 percent while in the developing world it is between one and three percent.<ref name="WHO2015Mort">{{Cite web |last=Mignini L |date=26 September 2007 |title=Interventions for tubal ectopic pregnancy |url=http://apps.who.int/rhl/gynaecology/lmcom2/en/ |url-status=dead |archive-url=https://web.archive.org/web/20150402121902/http://apps.who.int/rhl/gynaecology/lmcom2/en/ |archive-date=2 April 2015 |access-date=12 March 2015 |website=who.int |publisher=The WHO Reproductive Health Library}}</ref> The first known description of an ectopic pregnancy is by [[Al-Zahrawi]] in the 11th century.<ref name=Nama2009/> The word "ectopic" means "out of place".<ref>{{Cite book |last=Cornog |first=Mary Wood |url=https://books.google.com/books?id=cyD059eY2RYC&pg=PA313 |title=Merriam-Webster's vocabulary uilder |date=1998 |publisher=Merriam-Webster |isbn=9780877799108 |location=Springfield, Mass. |page=313 |archive-url=https://web.archive.org/web/20170910181336/https://books.google.com/books?id=cyD059eY2RYC&pg=PA313 |archive-date=2017-09-10 |url-status=live |name-list-style=vanc}}</ref>
{{TOC limit|3}}

== Signs and symptoms ==
[[File:Ectopic Pregnancy.png|thumb|upright=2|Ectopic pregnancy]]
Up to 10% of those with ectopic pregnancy have no symptoms, and one-third have no [[medical sign]]s.<ref name=kirk2013/> In many cases the symptoms have low [[sensitivity and specificity|specificity]], and can be similar to those of other [[Genitourinary disorders|genitourinary]] and [[gastrointestinal disorder]]s, such as [[appendicitis]], [[salpingitis]], rupture of a [[corpus luteum cyst]], miscarriage, ovarian torsion or [[urinary tract infection]].<ref name=kirk2013/> Clinical presentation of ectopic pregnancy occurs at a mean of 7.2 weeks after the last normal menstrual period, with a range of four to eight weeks. Later presentations are more common in communities deprived of modern diagnostic ability.{{cn|date=September 2024}}

Signs and symptoms of ectopic pregnancy include increased hCG, vaginal bleeding (in varying amounts), sudden lower abdominal pain,<ref name=kirk2013/> pelvic pain, a tender cervix, an adnexal mass, or adnexal tenderness.<ref name=Crochet2013/> In the absence of ultrasound or [[human chorionic gonadotrophin|hCG]] assessment, heavy vaginal bleeding may lead to a misdiagnosis of miscarriage.<ref name=kirk2013/> [[Nausea]], [[vomiting]] and [[diarrhea]] are more rare symptoms of ectopic pregnancy.<ref name=kirk2013/>

Rupture of an ectopic pregnancy can lead to symptoms such as [[abdominal distension]], [[Tenderness (medicine)|tenderness]], [[peritonism]] and [[hypovolemic shock]].<ref name=kirk2013/> Someone with a ruptured ectopic pregnancy may experience pain when lying flat and may prefer to maintain upright posture as intrapelvic blood flow can lead to swelling of the abdominal cavity and cause additional pain.<ref>{{Cite journal |vauthors=Skipworth RJ |date=December 2011 |title=A new clinical sign in ruptured ectopic pregnancy |journal=Lancet |volume=378 |issue=9809 |pages=e27 |doi=10.1016/s0140-6736(11)61901-6 |pmid=22177516 |s2cid=333306 |doi-access=free}}</ref>

=== Complications ===

[[File:FluidMorisonsPouchEctop.PNG|thumb|Blood in [[Morrison's pouch]] between the liver and kidney due to a ruptured ectopic pregnancy]]

The most common complication is rupture with internal bleeding which may lead to hypovolemic shock. Damage to the fallopian tubes can lead to difficulty becoming pregnant in the future. The woman's other fallopian tube may function sufficiently for pregnancy. After the removal of one damaged fallopian tube, pregnancy remains possible in the future. If both are removed, in-vitro fertilization remains an option for women hoping to become pregnant.<ref>{{Cite web |title=Ectopic pregnancy |url=http://nhp.gov.in/disease/gynaecology-and-obstetrics/ectopic-pregnancy |url-status=dead |archive-url=https://web.archive.org/web/20210828072425/https://www.nhp.gov.in/disease/gynaecology-and-obstetrics/ectopic-pregnancy |archive-date=28 August 2021 |access-date=4 December 2018}}</ref><ref>{{Cite book |title=Pediatric clinical advisor : instant diagnosis and treatment |date=2007 |publisher=Mosby Elsevier |isbn=978-0-323-03506-4 |edition=2 |pages=180–181}}</ref><ref>{{Cite journal |vauthors=Tenore JL |date=February 2000 |title=Ectopic pregnancy |journal=American Family Physician |volume=61 |issue=4 |pages=1080–8 |pmid=10706160}}</ref>

== Causes ==

There are a number of risk factors for ectopic pregnancies. However, in as many as one-third<ref name="pmid16099295">{{Cite journal |vauthors=Farquhar CM |year=2005 |title=Ectopic pregnancy |journal=Lancet |volume=366 |issue=9485 |pages=583–91 |doi=10.1016/S0140-6736(05)67103-6 |pmid=16099295 |s2cid=26445888}}</ref> to one-half<ref name="pmid18232175">{{Cite journal |vauthors=Majhi AK, Roy N, Karmakar KS, Banerjee PK |date=June 2007 |title=Ectopic pregnancy--an analysis of 180 cases |journal=Journal of the Indian Medical Association |volume=105 |issue=6 |pages=308, 310, 312 passim |pmid=18232175}}</ref> no risk factors can be identified. Risk factors include: [[pelvic inflammatory disease]], infertility, use of an [[intrauterine device]] (IUD), previous exposure to [[diethylstilbestrol]] (DES), tubal surgery, intrauterine surgery (e.g. [[Dilation and curettage|D&C]]), [[smoking]], previous ectopic pregnancy, [[endometriosis]], and [[tubal ligation]].<ref>{{Cite web |title=BestBets: Risk Factors for Ectopic Pregnancy |url=http://www.bestbets.org/bets/bet.php?id=921 |url-status=live |archive-url=https://web.archive.org/web/20081219012137/http://www.bestbets.org/bets/bet.php?id=921 |archive-date=2008-12-19}}</ref><ref>{{Cite journal |display-authors=6 |vauthors=Rana P, Kazmi I, Singh R, Afzal M, Al-Abbasi FA, Aseeri A, Singh R, Khan R, Anwar F |date=October 2013 |title=Ectopic pregnancy: a review |journal=Archives of Gynecology and Obstetrics |volume=288 |issue=4 |pages=747–57 |doi=10.1007/s00404-013-2929-2 |pmid=23793551 |s2cid=42807796}}</ref> A previous induced [[abortion]] does not appear to increase the risk.<ref>{{Cite book |title=Management of Unintended and Abnormal Pregnancy: Comprehensive Abortion Care |date=2011 |publisher=John Wiley & Sons |isbn=9781444358476 |chapter=16 Answering questions about long term outcomes |chapter-url=https://books.google.com/books?id=iK7xrRr2p9sC&pg=RA1-PT376 |archive-url=https://web.archive.org/web/20170910181336/https://books.google.com/books?id=iK7xrRr2p9sC&pg=RA1-PT376 |archive-date=2017-09-10 |url-status=live}}</ref> The IUD does not increase the risk of ectopic pregnancy, but with an IUD if pregnancy occurs it is more likely to be ectopic than intrauterine.<ref name="Tubal ectopic pregnancy">{{Cite journal |vauthors=Kumar V, Gupta J |date=November 2015 |title=Tubal ectopic pregnancy |journal=BMJ Clinical Evidence |volume=2015 |pmc=4646159 |pmid=26571203}}</ref> The risk of ectopic pregnancy after chlamydia infection is low.<ref>{{Cite journal |vauthors=Bakken IJ |date=February 2008 |title=Chlamydia trachomatis and ectopic pregnancy: recent epidemiological findings |journal=Current Opinion in Infectious Diseases |volume=21 |issue=1 |pages=77–82 |doi=10.1097/QCO.0b013e3282f3d972 |pmid=18192790 |s2cid=30584041}}</ref> The exact mechanism through which chlamydia increases the risk of ectopic pregnancy is uncertain, though some research suggests that the infection can affect the structure of fallopian tubes.<ref>{{Cite journal |vauthors=Sivalingam VN, Duncan WC, Kirk E, Shephard LA, Horne AW |date=October 2011 |title=Diagnosis and management of ectopic pregnancy |journal=The Journal of Family Planning and Reproductive Health Care |volume=37 |issue=4 |pages=231–40 |doi=10.1136/jfprhc-2011-0073 |pmc=3213855 |pmid=21727242}}</ref>

{| class="wikitable"
|+Risk factors <ref>{{Cite journal |vauthors=Marion LL, Meeks GR |date=June 2012 |title=Ectopic pregnancy: History, incidence, epidemiology, and risk factors |journal=Clinical Obstetrics and Gynecology |volume=55 |issue=2 |pages=376–86 |doi=10.1097/GRF.0b013e3182516d7b |pmid=22510618}}</ref><ref name="ESHRE2015" />
! colspan="2" |Relative risk factors
|-
|High
|Tubal sterilization, IUD, prior ectopic, PID (pelvic inflammatory disease), endometriosis, SIN (salpingitis isthmica nodosa)
|-
|Moderate
|Smoking, having more than 1 partner, infertility, chlamydia
|-
|Low
|Douching, age greater than 35, age less than 18, GIFT (gamete intrafallopian transfer)
|}

=== Tube damage ===
[[File:EUG 2.png|thumb|Left fallopian tube with an ectopic pregnancy in a 25-year-old woman after a [[salpingectomy]]]]
Tubal pregnancy is when the egg is [[Implantation (embryology)|implanted]] in the fallopian tubes. Hair-like [[Cilium|cilia]] located on the internal surface of the fallopian tubes carry the fertilized egg to the uterus. Fallopian cilia are sometimes seen in reduced numbers subsequent to an ectopic pregnancy, leading to a hypothesis that cilia damage in the fallopian tubes is likely to lead to an ectopic pregnancy.<ref name="Lyons">{{Cite journal |vauthors=Lyons RA, Saridogan E, Djahanbakhch O |year=2006 |title=The reproductive significance of human Fallopian tube cilia |journal=Human Reproduction Update |volume=12 |issue=4 |pages=363–72 |doi=10.1093/humupd/dml012 |pmid=16565155 |doi-access=free}}</ref> Women who smoke have a higher chance of an ectopic pregnancy in the fallopian tubes. Smoking leads to risk factors of damaging and destroying cilia.<ref name="Lyons" /> As cilia degenerate, the amount of time it takes for the fertilized egg to reach the uterus will increase. The fertilized egg, if it does not reach the uterus in time, will hatch from the non-adhesive [[zona pellucida]] and implant itself inside the fallopian tube, thus causing the ectopic pregnancy.{{cn|date=September 2024}}

Women with pelvic inflammatory disease (PID) have a high occurrence of ectopic pregnancy.<ref name="Tay">{{Cite journal |vauthors=Tay JI, Moore J, Walker JJ |date=August 2000 |title=Ectopic pregnancy |journal=The Western Journal of Medicine |volume=173 |issue=2 |pages=131–4 |doi=10.1136/ewjm.173.2.131 |pmc=1071024 |pmid=10924442}}</ref> This results from the build-up of [[scar|scar tissue]] in the fallopian tubes, causing damage to cilia.<ref name=speroff/> However, if both tubes were completely blocked, so that sperm and egg were physically unable to meet, then fertilization of the egg would naturally be impossible, and neither normal pregnancy nor ectopic pregnancy could occur. Intrauterine adhesions (IUA) present in [[Asherman's syndrome]] can cause ectopic cervical pregnancy or, if adhesions partially block access to the tubes via the [[Ostium of Fallopian tube|ostia]], ectopic tubal pregnancy.<ref name="Schenker">{{Cite journal |vauthors=Schenker JG, Margalioth EJ |date=May 1982 |title=Intrauterine adhesions: an updated appraisal |journal=Fertility and Sterility |volume=37 |issue=5 |pages=593–610 |doi=10.1016/S0015-0282(16)46268-0 |pmid=6281085 |doi-access=free}}</ref><ref name="Klyszejko">{{Cite journal |vauthors=Kłyszejko C, Bogucki J, Kłyszejko D, Ilnicki W, Donotek S, Koźma J |date=January 1987 |title=[Cervical pregnancy in Asherman's syndrome] |journal=Ginekologia Polska |volume=58 |issue=1 |pages=46–8 |pmid=3583040}}</ref><ref name="Dicker:">{{Cite journal |vauthors=Dicker D, Feldberg D, Samuel N, Goldman JA |date=January 1985 |title=Etiology of cervical pregnancy. Association with abortion, pelvic pathology, IUDs and Asherman's syndrome |journal=The Journal of Reproductive Medicine |volume=30 |issue=1 |pages=25–7 |pmid=4038744}}</ref> Asherman's syndrome usually occurs from intrauterine surgery, most commonly after [[Dilation and curettage|D&C]].<ref name="Schenker" />  Endometrial/pelvic/genital [[tuberculosis]], another cause of Asherman's syndrome, can also lead to ectopic pregnancy as infection may lead to tubal adhesions in addition to intrauterine adhesions.<ref name="Bukulmez">{{Cite journal |vauthors=Bukulmez O, Yarali H, Gurgan T |date=August 1999 |title=Total corporal synechiae due to tuberculosis carry a very poor prognosis following hysteroscopic synechialysis |journal=Human Reproduction |volume=14 |issue=8 |pages=1960–1 |doi=10.1093/humrep/14.8.1960 |pmid=10438408 |doi-access=free}}</ref>

Tubal ligation can predispose to ectopic pregnancy. Reversal of tubal sterilization ([[tubal reversal]]) carries a risk for ectopic pregnancy. This is higher if more destructive methods of tubal ligation (tubal cautery, partial removal of the tubes) have been used than less destructive methods (tubal clipping). A history of a tubal pregnancy increases the risk of future occurrences to about 10%.<ref name=speroff/> This risk is not reduced by removing the affected tube, even if the other tube appears normal. The best method for diagnosing this is to do an early ultrasound.{{cn|date=September 2024}}

=== Endometriosis ===
{{Main|Endometriosis}}

Endometriosis is a disease in which cells similar to those of the [[endometrium]], the tissue covering the inside of the uterus, grow outside the uterus.  An embryo attaching to such lesions leads to an ectopic pregnancy.  Results of a 30 year study of reproductive and pregnancy outcomes, involving 14,000+ women of child-bearing age, were presented at the 2015 [[European Society of Human Reproduction and Embryology]] (ESHRE) annual congress.<ref name="ESHRE2015">{{Cite web |last=Saraswat |first=Lucky |date=2015 |title=ESHRE2015: Endometriosis associated with a greater risk of complications in pregnancy |url=https://endometriosis.org/news/congress-highlights/eshre2015-endometriosis-associated-with-a-greater-risk-of-complications-in-pregnancy/#:~:text=After%20adjustments%20for%20age%20and%20previous%20pregnancy%2C%20results,three%20times%20higher%20for%20ectopic%20pregnancy%20%28OR%202.7%29 |access-date=14 February 2024 |website=endometriosis.org |publisher=European Society of Human Reproduction and Embryology}}</ref> 39% of the study group had surgically confirmed endometriosis. Compared to their peers, the endometriosis subgroup had a 76% higher risk for miscarriage and a 270% higher risk for ectopic pregnancy. The higher endometriosis risks were attributed to increased pelvic inflammation and structural and functional changes in the uterus' lining.{{cn|date=September 2024}}

=== Other ===

Although some investigations have shown that patients may be at higher risk for ectopic pregnancy with advancing age, it is believed that age is a variable which could act as a surrogate for other risk factors. Vaginal douching is thought by some to increase ectopic pregnancies.<ref name=speroff/> Women exposed to [[diethylstilbestrol|DES]] in utero (also known as "DES daughters") also have an elevated risk of ectopic pregnancy.<ref name="Schrager2004">{{Cite journal |vauthors=Schrager S, Potter BE |date=May 2004 |title=Diethylstilbestrol exposure |url=http://www.aafp.org/afp/2004/0515/p2395.html |url-status=live |journal=American Family Physician |volume=69 |issue=10 |pages=2395–400 |pmid=15168959 |archive-url=https://web.archive.org/web/20150402101957/http://www.aafp.org/afp/2004/0515/p2395.html |archive-date=2015-04-02}}</ref> However, DES has not been used since 1971 in the United States.<ref name=Schrager2004/> It has also been suggested that pathologic generation of [[nitric oxide]] through increased [[iNOS]] production may decrease [[Fallopian tube|tubal ciliary]] beats and smooth muscle contractions and thus affect embryo transport, which may consequently result in ectopic pregnancy.<ref>{{Cite journal |vauthors=Al-Azemi M, Refaat B, Amer S, Ola B, Chapman N, Ledger W |date=August 2010 |title=The expression of inducible nitric oxide synthase in the human fallopian tube during the menstrual cycle and in ectopic pregnancy |journal=Fertility and Sterility |volume=94 |issue=3 |pages=833–40 |doi=10.1016/j.fertnstert.2009.04.020 |pmid=19482272}}</ref> Low socioeconomic status may also be a risk factor for ectopic pregnancy.<ref name="pmid23726169">{{Cite journal |vauthors=Yuk JS, Kim YJ, Hur JY, Shin JH |date=August 2013 |title=Association between socioeconomic status and ectopic pregnancy rate in the Republic of Korea |journal=International Journal of Gynaecology and Obstetrics |volume=122 |issue=2 |pages=104–7 |doi=10.1016/j.ijgo.2013.03.015 |pmid=23726169 |s2cid=25547683}}</ref>

== 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 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 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 has 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 an 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 outcome 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 with the aim of differentiating 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 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 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 |last=Luis Izquierdo |first=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. 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 the 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 |last=Chopra |first=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 removal of an ectopic pregnancy to assure 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 tumour.<ref name=kirk2013/>

=== Differential diagnosis ===

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

== Treatment ==

=== Expectant management ===

Most women with a [[#Pregnancy of unknown location|PUL]] are followed up with serum hCG measurements and repeat [[Vaginal ultrasonography|TVS]] examinations until a final diagnosis is confirmed.<ref name=kirk2013/> Low-risk cases of PUL that appear to be failing pregnancies may be followed up with a urinary pregnancy test after two weeks and get subsequent telephone advice.<ref name=kirk2013/> Low-risk cases of PUL that are likely intrauterine pregnancies may have another TVS in two weeks to access viability.<ref name=kirk2013/> High-risk cases of PUL require further assessment, either with a TVS within 48 h or additional hCG measurement.<ref name=kirk2013/>

=== Medical ===

Early treatment of an ectopic pregnancy with methotrexate is a viable alternative to surgical treatment<ref name="pmid17591007">{{Cite journal |vauthors=Mahboob U, Mazhar SB |year=2006 |title=Management of ectopic pregnancy: a two-year study |journal=Journal of Ayub Medical College, Abbottabad |volume=18 |issue=4 |pages=34–7 |pmid=17591007}}</ref> which was developed in the 1980s.<ref>[http://www.ectopicpregnancy.co.uk/for-professionals/perspectives/history-and-diagnosis/ "History, Diagnosis and Management of Ectopic Pregnancy"] {{webarchive|url=https://web.archive.org/web/20151005225652/http://www.ectopicpregnancy.co.uk/for-professionals/perspectives/history-and-diagnosis/ |date=2015-10-05 }}</ref> If administered early in the pregnancy, methotrexate terminates the growth of the developing embryo; the developing embryo may then be either resorbed by the woman's body or pass with a [[Menstrual cycle|menstrual period]]. Contraindications include ectopic embryonic mass >&nbsp;3.5&nbsp;cm and evidence of ruptured fallopian tube, as well as renal or hepatic dysfunction.<ref>{{Cite journal |last=Kim |first=Peter Y. |last2=Vallee |first2=Cecelia de La |date=1997-03-01 |title=Isthmic ectopic gestation: A contraindication to methotrexate therapy? |url=https://linkinghub.elsevier.com/retrieve/pii/S0002937897705763 |journal=American Journal of Obstetrics & Gynecology |language=English |volume=176 |issue=3 |pages=711–712 |doi=10.1016/S0002-9378(97)70576-3 |issn=0002-9378}}</ref>

Also, it may lead to the inadvertent termination of an undetected intrauterine pregnancy, or severe abnormality in any surviving pregnancy.<ref name=kirk2013/> Therefore, it is recommended that methotrexate should only be administered when hCG has been serially monitored with a rise less than 35% over 48 hours, which practically excludes a viable intrauterine pregnancy.<ref name=kirk2013/>

For nontubal ectopic pregnancy, evidence from randomised clinical trials in women with CSP is uncertain regarding treatment success, complications and side effects of methotrexate compared with surgery ([[Uterine artery embolization|uterine arterial embolization]] or uterine arterial chemoembolization).<ref>{{Cite journal |last=Long |first=Y |last2=Zhu |first2=H |last3=Hu |first3=Y |last4=Shen |first4=L |last5=Fu |first5=J |last6=Huang |first6=W |date=1 July 2020 |title=Interventions for non-tubal ectopic pregnancy. |journal=The Cochrane Database of Systematic Reviews |volume=2020 |issue=7 |pages=CD011174 |doi=10.1002/14651858.CD011174.pub2 |pmc=7389314 |pmid=32609376}}</ref>

The United States uses a multi dose protocol of methotrexate (MTX) which involves four doses of intramuscular along with an intramuscular injection of folinic acid to protect cells from the effects of the drugs and to reduce side effects. In France, the single dose protocol is followed, but a single dose has a greater chance of failure.<ref>{{Cite journal |display-authors=6 |vauthors=Marret H, Fauconnier A, Dubernard G, Misme H, Lagarce L, Lesavre M, Fernandez H, Mimoun C, Tourette C, Curinier S, Rabishong B, Agostini A |date=October 2016 |title=Overview and guidelines of off-label use of methotrexate in ectopic pregnancy: report by CNGOF |journal=European Journal of Obstetrics, Gynecology, and Reproductive Biology |volume=205 |pages=105–9 |doi=10.1016/j.ejogrb.2016.07.489 |pmid=27572300}}</ref>

===Surgery===
[[File:Ectopic pregnancy1981.jpg|thumb|Surgical treatment: Laparoscopic view of an ectopic pregnancy located in the left fallopian tube, hematosalpinx is present on the left, the right tube is of normal appearance]]

[[File:salpingectomy1981.jpg|thumb|The left fallopian tube containing the ectopic pregnancy has been removed (salpingectomy).]]

If bleeding has already occurred, surgical intervention may be necessary. However, whether to pursue surgical intervention is an often difficult decision in a stable patient with minimal evidence of blood clot on ultrasound.{{Citation needed|date=December 2009}}

Surgeons use laparoscopy or laparotomy to gain access to the pelvis and can either incise the affected fallopian tube and remove only the pregnancy ([[Salpingectomy|salpingostomy]]) or remove the affected tube with the pregnancy ([[salpingectomy]]). The first successful surgery for an ectopic pregnancy was performed by [[Lawson Tait|Robert Lawson Tait]] in 1883.<ref>{{Cite web |title=eMedicine - Surgical Management of Ectopic Pregnancy: Article Excerpt by R Daniel Braun |url=http://www.emedicine.com/med/byname/Surgical-Management-of-Ectopic-Pregnancy.htm |url-status=live |archive-url=https://web.archive.org/web/20071013220421/http://emedicine.com/med/byname/Surgical-Management-of-Ectopic-Pregnancy.htm |archive-date=2007-10-13 |access-date=2007-09-17}}</ref> It is estimated that an acceptable rate of PULs that eventually undergo surgery is between 0.5 and 11%.<ref name=kirk2013/> People that undergo salpingectomy and salpingostomy have a similar recurrent ectopic pregnancy rate of 5% and 8% respectively. Additionally, their intrauterine pregnancy rates are also similar, 56% and 61%.<ref>{{Cite journal |vauthors=Brady PC |date=October 2017 |title=New Evidence to Guide Ectopic Pregnancy Diagnosis and Management |journal=Obstetrical & Gynecological Survey |volume=72 |issue=10 |pages=618–625 |doi=10.1097/OGX.0000000000000492 |pmid=29059454}}</ref>

[[Autotransfusion]] of a woman's own blood as drained during surgery may be useful in those who have a lot of bleeding into their abdomen.<ref>{{Cite journal |vauthors=Selo-Ojeme DO, Onwude JL, Onwudiegwu U |date=February 2003 |title=Autotransfusion for ruptured ectopic pregnancy |journal=International Journal of Gynaecology and Obstetrics |volume=80 |issue=2 |pages=103–10 |doi=10.1016/s0020-7292(02)00379-x |pmid=12566181 |s2cid=24721754 |doi-access=free}}</ref>

Published reports that a re-implanted embryo survived to birth were debunked as false.<ref>{{Cite journal |vauthors=Smith R |date=May 2006 |title=Research misconduct: the poisoning of the well |journal=Journal of the Royal Society of Medicine |volume=99 |issue=5 |pages=232–7 |doi=10.1177/014107680609900514 |pmc=1457763 |pmid=16672756}}</ref>

== Prognosis ==

When ectopic pregnancies are treated, the prognosis for the mother is very good in Western countries; maternal death is rare, although treatment nearly always requires removal of the nonviable fetus. For instance, in the UK, between 2003 and 2005 there were 32,100 ectopic pregnancies resulting in 10 maternal deaths (meaning that 1 in 3,210 women with an ectopic pregnancy died).<ref>{{Cite web |title=Ectopic Pregnancy |url=http://patient.info/doctor/ectopic-pregnancy-pro |url-status=live |archive-url=https://web.archive.org/web/20151014214331/http://patient.info/doctor/ectopic-pregnancy-pro |archive-date=2015-10-14 |access-date=2015-10-22}}</ref> In 2006–2008 the UK Confidential Enquiry into Maternal Deaths found that ectopic pregnancy is the cause of 6 maternal deaths (0.26/100,000 pregnancies).<ref name="Tubal ectopic pregnancy" />

In the developing world, however, especially in Africa, the death rate is very high, and ectopic pregnancies are a major cause of death among women of childbearing age.{{cn|date=September 2024}}

In women having had an ectopic pregnancy, the risk of another one in the next pregnancy is around 10%.<ref>{{Cite book |last=Bayer |first=Steven R. |url=https://books.google.com/books?id=sqPSBQAAQBAJ&pg=PA143 |title=The Boston IVF Handbook of Infertility: A Practical Guide for Practitioners Who Care for Infertile Couples, Third Edition |last2=Alper |first2=Michael M. |last3=Penzias |first3=Alan S. |date=2011 |publisher=CRC Press |isbn=9781841848181 |name-list-style=vanc}}</ref>

=== Future fertility ===

Fertility following ectopic pregnancy depends upon several factors, the most important of which is a prior history of infertility.<ref name="isbn0-8247-0844-X">{{Cite book |title=Advances in Reproductive Endocrinology and Infertility: Current Trends and Developments |vauthors=Tulandi T, Tan SL, Tan SL, Tulandi T |publisher=Informa Healthcare |year=2002 |isbn=978-0-8247-0844-3 |pages=240}}<!--|access-date=2009-12-21--></ref> The treatment choice does not play a major role; a randomized study in 2013 concluded that the rates of intrauterine pregnancy two years after treatment of ectopic pregnancy are approximately 64% with radical surgery, 67% with medication, and 70% with conservative surgery.<ref>{{Cite journal |vauthors=Fernandez H, Capmas P, Lucot JP, Resch B, Panel P, Bouyer J |date=May 2013 |title=Fertility after ectopic pregnancy: the DEMETER randomized trial |journal=Human Reproduction |volume=28 |issue=5 |pages=1247–53 |doi=10.1093/humrep/det037 |pmid=23482340 |doi-access=free}}</ref> In comparison, the cumulative pregnancy rate of women under 40 years of age in the general population over two years is over 90%.<ref name="nice2013">[http://guidance.nice.org.uk/CG156 Fertility: assessment and treatment for people with fertility problems] {{webarchive|url=https://web.archive.org/web/20130223023043/http://guidance.nice.org.uk/CG156 |date=2013-02-23}}. [[NICE guidelines|NICE clinical guideline]] CG156 – Issued: February 2013</ref>

Methotrexate does not affect future fertility treatments. The number of oocytes that were retrieved before and after treatment with methotrexate does not change.<ref>{{Cite journal |vauthors=Ohannessian A, Loundou A, Courbière B, Cravello L, Agostini A |date=September 2014 |title=Ovarian responsiveness in women receiving fertility treatment after methotrexate for ectopic pregnancy: a systematic review and meta-analysis |journal=Human Reproduction |volume=29 |issue=9 |pages=1949–56 |doi=10.1093/humrep/deu174 |pmid=25056087 |doi-access=free}}</ref>

In case of ovarian ectopic pregnancy, the risk of subsequent ectopic pregnancy or infertility is low.<ref name="pmid25709640">{{Cite journal |vauthors=Goyal LD, Tondon R, Goel P, Sehgal A |date=December 2014 |title=Ovarian ectopic pregnancy: A 10 years' experience and review of literature |journal=Iranian Journal of Reproductive Medicine |volume=12 |issue=12 |pages=825–30 |pmc=4330663 |pmid=25709640}}</ref>

There is no evidence that massage improves fertility after ectopic pregnancy.<ref name="pmid29593844">{{Cite journal |vauthors=Fogarty S |date=March 2018 |title=Fertility Massage: an Unethical Practice? |journal=International Journal of Therapeutic Massage & Bodywork |volume=11 |issue=1 |pages=17–20 |pmc=5868897 |pmid=29593844}}</ref>

== Epidemiology ==

[[File:Tubal Pregnancy with embryo.jpg|thumb|An opened oviduct with an ectopic pregnancy at about seven weeks' gestational age<ref>{{Cite journal |last=Uthman |first=Ed |name-list-style=vanc |date=2014 |title=Tubal pregnancy with embryo |journal=WikiJournal of Medicine |volume=1 |issue=2 |doi=10.15347/wjm/2014.007 |doi-access=free}}</ref>]]

The rate of ectopic pregnancy is about 1% and 2% of that of live births in developed countries, though it is as high as 4% in pregnancies involving assisted reproductive technology.<ref name=kirk2013/> Between 93% and 97% of ectopic pregnancies are located in a fallopian tube.<ref name=Crochet2013/> Of these, in turn, 13% are located in the [[isthmus of uterine tube|isthmus]], 75% are located in the [[Ampulla of uterine tube|ampulla]], and 12% in the [[Fimbriae of uterine tube|fimbriae]].<ref name=kirk2013/> Ectopic pregnancy is responsible for 6% of maternal deaths during the first trimester of pregnancy making it the leading cause of maternal death during this stage of pregnancy.<ref name=Crochet2013/>

Between 5% and 42% of women seen for ultrasound assessment with a positive pregnancy test have a pregnancy of unknown location, that is a positive pregnancy test but no pregnancy visualized at transvaginal ultrasonography.<ref name=kirk2013/> Between 6% and 20% of pregnancy of unknown location are subsequently diagnosed with actual ectopic pregnancy.<ref name=kirk2013/>

== Society and culture ==

[[Salpingectomy]] as a treatment for ectopic pregnancy is one of the common cases when the [[Principle of double effect#Medicine|principle of double effect can be used]] to justify accelerating the death of the embryo by doctors and patients opposed to outright abortions.<ref name="How does the principle of double-effect relate to ectopic pregnancies?">{{Cite web |last=Delgado |first=George |name-list-style=vanc |title=Pro-Life Open Forum, Apr 10, 2013 (49min40s) |url=http://www.catholic.com/audio-player/8236 |url-status=dead |archive-url=https://web.archive.org/web/20150402110050/http://www.catholic.com/audio-player/8236 |archive-date=2 April 2015 |access-date=2 September 2014 |website=Catholic answers}}</ref>

In the [[Catholic Church]], there are moral debates on certain treatments.  A significant number of Catholic moralists consider use of methotrexate and the salpingostomy procedure to be not "morally permissible" because they destroy the embryo; however, situations are considered differently in which the mother's health is endangered, and the whole fallopian tube with the developing embryo inside is removed.<ref>{{Cite web |last=Pacholczyk |first=Tad |author-link=Tadeusz Pacholczyk |name-list-style=vanc |title=When Pregnancy Goes Awry |url=http://www.ncbcenter.org/Page.aspx?pid=940 |archive-url=https://web.archive.org/web/20111123115757/http://www.ncbcenter.org/Page.aspx?pid=940 |archive-date=2011-11-23 |website=Making Sense Out of Bioethics (blog) |publisher=[[National Catholic Bioethics Center]]}}</ref><ref>Anderson, MA et al. [http://johnpaulbioethics.org/finalproofs.pdf Ectopic Pregnancy and Catholic Morality] {{webarchive|url=https://web.archive.org/web/20160418071158/http://johnpaulbioethics.org/FinalProofs.pdf |date=2016-04-18 }}. National Catholic Bioethics Quarterly, Spring 2011</ref>

Organizations exist that provide information and support to help those who experience ectopic pregnancy. Studies show that people can experience post-traumatic stress, depression, and anxiety for which they would need specialist therapies.<ref>{{Cite journal |title=Post-traumatic stress, anxiety and depression following miscarriage and ectopic pregnancy: a multicenter, prospective, cohort study. |journal=Farren J, Jalmbrant M, Falconieri N, et al. Am J Obstet Gynecol 2020;222:367.e1-22}}</ref> Partners can also experience post-traumatic stress.<ref>{{Cite web |date=9 October 2020 |title=Post-traumatic stress experienced by partners following miscarriage |url=https://www.imperial.ac.uk/news/206373/post-traumatic-stress-experienced-partners-following-miscarriage/#:~:text=One%20in%2012%20partners%20experience,ectopic%20pregnancy%20before%2012%20weeks}}</ref>

== Live birth ==

There have been cases where ectopic pregnancy lasted many months and ended in a live baby delivered by laparotomy.

In July 1999, Lori Dalton gave birth by [[caesarean section]] in [[Ogden, Utah]], United States, to a healthy baby girl, Saige, who had developed outside of the uterus. Previous ultrasounds had not discovered the problem. "[Dalton]'s delivery was slated as a routine Caesarean birth at Ogden Regional Medical Center in Utah. When Dr. Naisbitt performed Lori's Caesarean, he was astonished to find Saige within the amniotic membrane outside the womb ... ."<ref>{{Cite news |date=October 1999 |title=Registry Reports |url=http://www.ardms.org/downloads/RegistryReports/Sep99.pdf |url-status=dead |archive-url=https://web.archive.org/web/20101223214452/http://www.ardms.org/downloads/RegistryReports/Sep99.pdf |archive-date=2010-12-23 |access-date=2011-06-22 |work=Volume XVI, Number 5 |publisher=ARDMS The Ultrasound Choice |location=Ogden, Utah}}</ref> "But what makes this case so rare is that not only did mother and baby survive—they're both in perfect health. The father, John Dalton took home video inside the delivery room. Saige came out doing extremely well because even though she had been implanted outside the womb, a rich blood supply from a [[uterine fibroid]] along the outer uterus wall had nourished her with a rich source of blood."<ref>{{Cite news |date=1999-08-05 |title=Miracle baby |url=http://web.ksl.com/dump/news/cc/special/science/ectopic.htm |url-status=dead |archive-url=https://web.archive.org/web/20110930051227/http://web.ksl.com/dump/news/cc/special/science/ectopic.htm |archive-date=2011-09-30 |access-date=2011-06-22 |publisher=Utah News from KSL-TV |location=Ogden, Utah}}</ref>

In September 1999 an English woman, Jane Ingram (age 32) gave birth to triplets: Olivia, Mary and Ronan, with an extrauterine fetus (Ronan) below the womb and [[twins]] in the womb. All three survived. The twins in the womb were taken out first.<ref>{{Cite news |date=2009-09-10 |title=Doctors hail 'miracle' baby |url=http://news.bbc.co.uk/1/hi/health/443373.stm |url-status=live |archive-url=https://web.archive.org/web/20080919160301/http://news.bbc.co.uk/1/hi/health/443373.stm |archive-date=2008-09-19 |work=BBC News}}</ref>

On May 29, 2008, an Australian woman, Meera Thangarajah (age 34), who had an ectopic pregnancy in the [[ovary]], gave birth to a healthy full term 6 pound 3 ounce (2.8&nbsp;kg) baby girl, Durga, via Caesarean section. She had no problems or complications during the 38‑week pregnancy.<ref>{{Cite news |date=2008-05-30 |title=Baby Born After Rare Ovarian Pregnancy |url=http://ap.google.com/article/ALeqM5h7An_4HQLG6rSVO-h1eBIntgYOyAD90VRLKO1 |url-status=dead |archive-url=https://web.archive.org/web/20080603100609/http://ap.google.com/article/ALeqM5h7An_4HQLG6rSVO-h1eBIntgYOyAD90VRLKO1 |archive-date=June 3, 2008 |access-date=2008-05-30 |agency=[[Associated Press]]}}</ref><ref>{{Cite news |last=Cavanagh |first=Rebekah |name-list-style=vanc |date=2008-05-30 |title=Miracle baby may be a world first |url=http://www.news.com.au/story/0,23599,23782145-2,00.html |url-status=dead |archive-url=https://web.archive.org/web/20080530105132/http://www.news.com.au/story/0,23599,23782145-2,00.html |archive-date=2008-05-30 |access-date=2008-05-30}}</ref>

== Animals ==

Ectopic gestation exists in [[mammal]]s other than humans. In [[sheep]], it can go to term, with [[Mammary gland|mammary]] preparation to [[parturition]], and [[childbirth|expulsion efforts]]. The fetus can be removed by caesarean section. Pictures of caesarian section of a euthanized [[domestic sheep|ewe]], five days after parturition signs.
<gallery>
File:Poirtêye foû matrice pate.JPG|Leg of fetal lamb appearing out of the uterus during caesarean section
File:Poirtêye foû matrice saetch1.JPG|External view of fetal sac, necrotic distal part
File:Poirtêye foû matrice saetch2.JPG|Internal view of fetal sac, before resection of distal necrotic part
File:Poirtêye foû matrice saetch3.JPG|Internal view of fetal sac. The necrotic distal part is to the left.
File:Poirtêye foû matrice saetch&coine.JPG|External side of fetal sac, proximal end, with ovary and uterine horn
File:Poirtêye foû matrice saetch ådfoû pwels.JPG|Resected distal part of fetal sac, with attached placenta
</gallery>

== See also ==
* [[Indirect abortion]]
== References ==
{{Reflist}}

== External links ==
{{Medical resources
 | DiseasesDB     = 4089
 | ICD10          = {{ICD10|O|00||o|00}}
 | ICD9           = {{ICD9|633}}
 | ICDO           =
 | OMIM           =
 | MedlinePlus    = 000895
 | eMedicineSubj  = med
 | eMedicineTopic = 3212
 | eMedicine_mult = {{eMedicine2|emerg|478}} {{eMedicine2|radio|231}}
 | MeshID         = D011271
}}
{{commons category|Ectopic pregnancy}}
* [http://www.claripacs.com/case/CL0019 CT of the abdomen showing abdominal ectopic pregnancy]

{{Women's health|state=collapsed}}
{{Pathology of pregnancy, childbirth and the puerperium}}
{{Pregnancy}}
{{Authority control}}

[[Category:Ectopic pregnancy| ]]
[[Category:Wikipedia articles with sections published in WikiJournal of Medicine]]
[[Category:Medical emergencies]]
[[Category:Health issues in pregnancy]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Acute pain]]