Abnormal Development - Ectopic Implantation

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Tubal pregnancy historic.jpg

International Classification of Diseases (iCD-10) Chapter XV Pregnancy Childbirth - O00 Ectopic pregnancy
ICD-11 (beta) - JA01 Ectopic pregnancy - Any condition characterized by implantation of the embryo outside the endometrium and endometrial cavity during pregnancy.

Introduction

Tubal Pregnancy

Ectopic implantation or ectopic pregnancy (Greek, ektopos = "out of place") refers to the abnormal implantation of the blastocyst. Implantation of the blastocyst normally occurs within the body of the uterus, also called eutopic implantation. Ectopic implantation can occur at number of sites outside the uterine body. The most common form of human ectopic pregnancy is when implantation occurs within the uterine tube, described as a tubal pregnancy. Note that the endocrine signals blocking the menstrual cycle and indicating a pregnancy will still be released following this ectopic implantation. Ectopic pregnancies are therefore often identified by early ultrasound scans.


Ectopic pregnancy is also a high-risk maternal medical condition with an approximate incidence of 1.5 to 2 % in reported pregnancies. There is some indication that the incidence may be increasing (United States has increased from 4.5 per 1,000 pregnancies in 1970 to an estimated 19.7 per 1,000 pregnancies in 1992[1])


The risk factors for tubal ectopic pregnancy include: tubal damage by infection (particularly Chlamydia trachomatis) or surgery, smoking and in vitro fertilization therapy. Prolonged tubal damage is often described as pelvic inflammatory disease and "scarring" can affect the cilia-mediated transport of the blastocyst during the first week of development.


This is also the most common cause of pregnancy-related deaths in the first trimester. A recent United Kingdom enquiry into maternal deaths[2], identified ectopic pregnancy as the fourth most common cause of maternal death (73% of early pregnancy deaths).


Ectopic sites are named according to the anatomical location: Tubal (Ampullary, Isthmic, Cornual), Cervical and Ovarian. A study of 1800 surgically treated ectopics between 1992 and 2001 identified implantation sites by frequency: interstitial (2.4%), isthmic (12.0%), ampullary (70.0%), fimbrial (11.1%), ovarian (3.2%) or abdominal (1.3%).[3]


International Classification of Diseases: Chapter XV Pregnancy Childbirth - O00 Ectopic pregnancy | O01 Hydatidiform mole


Ectopic Links: ectopic pregnancy | implantation | Week 2 | placenta abnormalities | trophoblast | uterus | Chlamydia | Ultrasound - Ectopic Pregnancy | ultrasound | Ectopic Implantation Research
Historic Embryology  
1895 Ectopic pregnancy | 1914 Infundibulum implantation | 1915 Tubal gestation | Historic 1920 Paper | 1921 Extra-uterine pregnancy | 1922 Tubal pregnancy1934 Early ectopic
Carnegie Tubal Embryos: 109 | 1390 | 1544 | 175 | 256 | 389 | 390 | 3956 | 4160 | 422 | 431 | 4476 | 5048 | 5206 | 576 | 6097 | 6150 | 6551 | 657 | 6631 | 6686 | 670 | 6750 | 6909 | 6950 | 7433 | 7897 | 7900 | 8005 | 8098 | 8147 | 8179 | 8235 | 8355 | 899 | 966

Some Recent Findings

Abnormal implantation sites
  • Rates of pelvic inflammatory disease and ectopic pregnancy in Australia, 2009-2014[4] "To analyse yearly rates of pelvic inflammatory disease (PID) and ectopic pregnancy (EP) diagnosed in hospital settings in Australia from 2009 to 2014. METHODS: We calculated yearly PID and EP diagnosis rates in three states (Victoria, New South Wales, Queensland) for women aged 15-44 years using hospital admissions and emergency department (ED) attendance data, with population and live birth denominators. ...For EP, in 2014 the rate of all admissions was 17.4 (95% CI 16.9 to 17.9) per 1000 live births and of all ED presentations was 15.6 (95% CI 15.1 to 16.1). Comparing 2014 with 2009, the rates of all EP admissions (aIRR 1.06, 95% CI 1.04 to 1.08) and rates in EDs (aIRR 1.24, 95% CI 1.18 to 1.31) were higher. PID and EP remain important causes of hospital admissions for female STI-associated complications. Hospital EDs care for more PID cases than inpatient departments, particularly for young women." Australian statistics | bacterial infection
  • Comparison of double- and single-dose methotrexate protocols for treatment of ectopic pregnancy (EP)[5] "For treatment of EP, double-dose methotrexate had efficacy and safety comparable to that of single-dose methotrexate; it had better success among patients with moderately high β-hCG and led to a shorter follow up."
  • Misdiagnosis of cervical ectopic pregnancy (CEP)[6] "Misdiagnosis of CEP upon initial presentation is a common occurrence. Transvaginal ultrasound performed by a qualified practitioner may increase detection and prevent treatment delay."
  • Human tubal ectopic pregnancy and knockout mouse models.[7] "Tubal abnormalities and dysfunction, such as altered contractility or abnormal ciliary activity, have been speculated to lead to tubal ectopic pregnancy. To elucidate the cellular and molecular mechanisms of the tubal transport process, several knockout (KO) mouse models have been developed. This review summarizes what has been learned from studies of the Fallopian tube in caspase-1, cannabinoid receptor and Dicer1 KO mice."
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Ectopic Pregnancy

Katharina Laus, Pooja Louis, Laura Douglass A Novel Approach to Management of Angular Pregnancies: A Case Series. J Minim Invasive Gynecol: 2018; PubMed 30107240

Lakmini Pinnaduwage, Joanne Honeyford, Elyse Lackie, Modupe Tunde-Byass The Sustained Value of an Early Pregnancy Assessment Clinic in the Management of Early Pregnancy Complications: A 10-Year Retrospective Study. J Obstet Gynaecol Can: 2018, 40(8);1017-1023 PubMed 30103874

Niyazi Tug, Mehmet Akif Sargin, Murat Yassa Multidose Methotrexate Treatment of Ectopic Pregnancies with High initial β-Human Chorionic Gonadotropin: Can Success Be Predicted? Gynecol. Obstet. Invest.: 2018;1-8 PubMed 30099453

Melissa J Chen, Helen Pymar, Mitchell D Creinin Controversies in family planning: persistently elevated serum human chorionic gonadotropin levels after aspiration abortion. Contraception: 2018; PubMed 30096290

Cherie Q Marfori, Mollie Kotzen Angular vs. interstitial pregnancy: A case report highlighting diagnostic nuances with stark management differences. Case Rep Womens Health: 2018, 19;e00068 PubMed 30094196


Search term: Tubal Pregnancy

Mark A Barone, Zuhura Mbuguni, Japhet Ominde Achola, Annette Almeida, Carmela Cordero, Joseph Kanama, Adriana Marquina, Projestine Muganyizi, Jamilla Mwanga, Daniel Ouma, Caitlin Shannon, Leopold Tibyehabwa Safety of Tubal Occlusion by Minilaparotomy Provided by Trained Clinical Officers Versus Assistant Medical Officers in Tanzania: A Randomized, Controlled, Noninferiority Trial. Glob Health Sci Pract: 2018; PubMed 30120168

Niyazi Tug, Mehmet Akif Sargin, Murat Yassa Multidose Methotrexate Treatment of Ectopic Pregnancies with High initial β-Human Chorionic Gonadotropin: Can Success Be Predicted? Gynecol. Obstet. Invest.: 2018;1-8 PubMed 30099453

Samuel J Kroon, Jacques Ravel, Wilhelmina M Huston Cervicovaginal microbiota, women's health, and reproductive outcomes. Fertil. Steril.: 2018, 110(3);327-336 PubMed 30098679

Alyssa Hamlin, Jessica L Bauer, Alex J Polotsky, Shona C Murray Ruptured ectopic pregnancy following a cycle of freeze-all in vitro fertilization: A case report. Case Rep Womens Health: 2018, 19;e00067 PubMed 30094195

Quinton Katler, Lindsey Pflugner, Anjali Martinez Management of Bilateral Ectopic Pregnancies after Ovulation Induction Using Unilateral Salpingectomy and Methotrexate for the Remaining Ectopic with Subsequent Intrauterine Pregnancy. Case Rep Obstet Gynecol: 2018, 2018;7539713 PubMed 30069421

About Uterine Tube Anatomy

Female Genital Arteries

Anatomy - there are 3 main parts (regions) to the uterine tube:

  1. isthmus - closest to the uterus (body)
  2. ampulla - middle region, more dilated in diameter and most common site for fertilization.
  3. infundibulum - furthest from the uterus ending in the fimbriae and open to the peritoneum

Blood Supply - arterial supply is from branches of the uterine and ovarian arteries, these small vessels are located within the mesosalpinx (part of the lining of the abdominal cavity).

Lymphatic drainage - through the iliac and lateral aortic nodes.

Innervation - has both sympathetic and parasympathetic fibers. Sensory fibres from thoracic segments (T11-T12) and the first lumbar segment (L1).

Ultrasound Ectopic Implantation

Tubal Ectopic Bicornuate Uterus Ectopic
Ectopic 01.jpg
 ‎‎Ectopic Pregnancy
Page | Play
Bicornuate uterus ectopic movie icon.jpg
 ‎‎Bicornuate Ectopic
Page | Play
Ectopic 01.jpg Ectopic 01 zoom.jpg
Ectopic 01 limbs.jpg Ectopic 01 heart.jpg


Links: Ectopic Implantation | Ultrasound

Computed Tomography Ectopic Implantation

Computed Tomography imaging findings of a 37-year-old woman with interstitial pregnancy.[8] Showing initial CT detection and a subsequent scan following rupture causing a hematoma around uterus and a massive hemoperitoneum.

Ectopic pregnancy CT 01.jpg

Initial CT - gestational sac

Ectopic pregnancy CT 02.jpg

Follow-up CT - massive hemoperitoneum

Ectopic pregnancy CT 03.jpg

CT - hematoma around uterus

Links: Computed Tomography

Magnetic Resonance Imaging Abdominal Ectopic Implantation

2W SPAIR sagittal MRI of lower abdomen demonstrating the placental invasion.[9]
  • Placenta was attached tightly to the mesentery of sigmoid colon and was loosely adhered to the left abdominal sidewall.
  • The fetus was localized at the right of the abdomen and was related to the placenta by a cord.


See also Heterotopic Pregnancy

Abdominal ectopic pregnancy MRI.jpg


Links: Magnetic Resonance Imaging

Statistics

Australia

Rates of pelvic inflammatory disease and ectopic pregnancy in Australia, 2009-2014[4]

"To analyse yearly rates of pelvic inflammatory disease (PID) and ectopic pregnancy (EP) diagnosed in hospital settings in Australia from 2009 to 2014. METHODS: We calculated yearly PID and EP diagnosis rates in three states (Victoria, New South Wales, Queensland) for women aged 15-44 years using hospital admissions and emergency department (ED) attendance data, with population and live birth denominators. ...For EP, in 2014 the rate of all admissions was 17.4 (95% CI 16.9 to 17.9) per 1000 live births and of all ED presentations was 15.6 (95% CI 15.1 to 16.1). Comparing 2014 with 2009, the rates of all EP admissions (aIRR 1.06, 95% CI 1.04 to 1.08) and rates in EDs (aIRR 1.24, 95% CI 1.18 to 1.31) were higher. PID and EP remain important causes of hospital admissions for female STI-associated complications. Hospital EDs care for more PID cases than inpatient departments, particularly for young women."
Links: Australian statistics | bacterial infection

USA

Ectopic Pregnancies- United-States 1970-1992.jpg

Ectopic Pregnancies- United-States 1970-1992[1]

Ectopic Pregnancies- United-States 1997-2006.jpg


Links: USA

Ectopic Pregnancy Histology

Tubal pregnancy 01.jpg

CDC Image by Dr. Edwin P. Ewing, Jr., 1972

Stage7 bf5b.jpg

Ed Uthman Image (pathologist in Houston, Texas) section of ectopic (tubal) pregnancy about Carnegie stage 7 in Week 3.

Image version links: ExtraLarge 1712x1206px | Large 1024x721px | Medium 500x352px


Stage15 bf2b.jpg

Ed Uthman Image (pathologist in Houston, Texas) image of of ectopic (tubal) pregnancy about Carnegie stage 15 in Week 5.

Image version links: ExtraLarge 1874 x 2000px | Large 959 x 1024px | Medium 468 x 500px

Tubal Ectopic Pregnancy

Chlamydia infections (Chlamydia trachomatis) are the most common bacterial sexually transmitted infection, often undiagnosed and asymptomatic. The infections can ascend the female genital tract, colonizing the endometrial mucosa, then the uterine tubes. This type of infection is described as pelvic inflammatory disease (PID).
Tubal pregnancy shown after hysterectomy

Interstitial Pregnancy

(cornual pregnancy) A less common type 2 to 4% of ectopic pregnancies. The gestation develops in the uterine portion of the fallopian tube lateral to the round ligament.
Interstitial ectopic pregnancy[10]

Ovarian Ectopic Pregnancy

Clinical operative photograph at the beginning of the procedure of the laparoscopic treatment of the ovarian pregnancy.


Legend

  • u - normal aspect of the uterus.
  • t - left fallopian tube.
  • e - ruptured ectopic pregnancy in the left ovary.
Ovarian ectopic pregnancy 01.jpg

Ovarian Ectopic Pregnancy[11]

Cervical Ectopic Pregnancy

Cervical Ectopic Pregnancy Ultrasound[12]

This form of ectopic pregnancy is a rare high-risk condition and represents less than 1% of all ectopic pregnancies. The reported incidence varies between 1:1,000 to 1:18,000.

Rudimentary Horn Pregnancy

A rare types of ectopic pregnancy (about 1 in 76,000 pregnancies) in most cases the horn is non-communicating. Therefore fertilisation probably occurs by transperitoneal migration. This form untreated can also lead to uterine rupture.

Caesarean Scar Pregnancy

Caesarean scar pregnancy (CSP) is a rare types of ectopic pregnancy (about 1 in 2000 pregnancies), but probably increasing as caesarean rates rise. The gestation is completely surrounded by both myometrium and fibrous tissue of the caesarean section scar and separated from the endometrial cavity and endocervical canal.

A recent review of 17 studies (69 cases of CSP managed expectantly, 52 with and 17 without embryonic/fetal heart beat)[13]

Caesarean scar pregnancy (CSP)
with embryonic/fetal heart activity without embryonic/fetal cardiac activity
  • 13.0% experienced an uncomplicated miscarriage
  • 20.0% required medical intervention
  • 9.9% uterine rupture during the first or second trimester
  • 15.2% required hysterectomy
  • 76.9% women progressed to third trimester
    • 39.2% experienced severe bleeding
  • 74.8% had abnormally invasive placenta at delivery
    • 69.7% had placenta percreta
  • 69.1% experienced an uncomplicated miscarriage
  • 30.9% required medical intervention
  • 13.4% uterine rupture during the first trimester
  • hysterectomy was not required in any case

Heterotopic Pregnancy

Heterotopic pregnancy MRI[14]

(Greek, heteros = other) Clinical term for a very rare pregnancy of two or more embryos, consisting of both a uterine cavity embryo implantation and an ectopic implantation. The ectopic implantation usually identified by prenatal scanning as occurring within the uterine tube (tubal pregnancy) though has also been identified as abdominal pregnancies.[14][15]

Ectopic Molar Pregnancy

Ectopic molar pregnancy 01.jpg

Left-sided unruptured ampullary ectopic pregnancy at laparoscopy.[16]


Links: Hydatidiform Mole

Ruptured Ectopic

Ruptured ectopic pregnancy 01.jpg

Ruptured ectopic pregnancy[17]

Methotrexate

(MTX, amethopterin) Drug with several different uses including the treatment of ectopic pregnancy[18] and for the induction of medical abortions. Acts as a antimetabolite and antifolate (folic acid antagonist) drug that inhibits DNA synthesis in actively dividing cells, including trophoblasts, and therefore has other medical uses include cancer and autoimmune disease treatment. Treatment success in ectopic pregnancy relates to serum β human chorionic gonadotropin (β-hCG) concentration.


Links: Medline Plus

International Classification of Diseases

The International Classification of Diseases (ICD) World Health Organization's classification used worldwide as the standard diagnostic tool for epidemiology, health management and clinical purposes.

The two main codes cover O00 Ectopic pregnancy and O01 Hydatidiform mole.

Note that there is an additional code covering complications of the clinical treatment O08 Complications following abortion and ectopic and molar pregnancy This code is provided primarily for morbidity coding. For use of this category reference should be made to the morbidity coding rules and guidelines in Volume 2.


Links: O00 Ectopic pregnancy | O01 Hydatidiform mole | Chapter XV Pregnancy Childbirth | International Classification of Diseases


References

  1. 1.0 1.1 Centers for Disease Control and Prevention (CDC). (1995). Ectopic pregnancy--United States, 1990-1992. MMWR Morb. Mortal. Wkly. Rep. , 44, 46-8. PMID: 7823895
  2. Confidential Enquiry into Maternal Deaths (CEMD) Why Mothers Die 2000–2002 PDFPDF2
  3. Bouyer J, Coste J, Fernandez H, Pouly JL & Job-Spira N. (2002). Sites of ectopic pregnancy: a 10 year population-based study of 1800 cases. Hum. Reprod. , 17, 3224-30. PMID: 12456628
  4. 4.0 4.1 Goller JL, De Livera AM, Guy RJ, Low N, Donovan B, Law M, Kaldor JM, Fairley CK & Hocking JS. (2018). Rates of pelvic inflammatory disease and ectopic pregnancy in Australia, 2009-2014: ecological analysis of hospital data. Sex Transm Infect , , . PMID: 29720385 DOI.
  5. Hamed HO, Ahmed SR & Alghasham AA. (2012). Comparison of double- and single-dose methotrexate protocols for treatment of ectopic pregnancy. Int J Gynaecol Obstet , 116, 67-71. PMID: 22035883 DOI.
  6. Shavell VI, Abdallah ME, Zakaria MA, Berman JM, Diamond MP & Puscheck EE. (2012). Misdiagnosis of cervical ectopic pregnancy. Arch. Gynecol. Obstet. , 285, 423-6. PMID: 21748311 DOI.
  7. Shao R. (2010). Understanding the mechanisms of human tubal ectopic pregnancies: new evidence from knockout mouse models. Hum. Reprod. , 25, 584-7. PMID: 20023297 DOI.
  8. Shin BS & Park MH. (2010). Incidental detection of interstitial pregnancy on CT imaging. Korean J Radiol , 11, 123-5. PMID: 20046504 DOI.
  9. Yildizhan R, Kolusari A, Adali F, Adali E, Kurdoglu M, Ozgokce C & Cim N. (2009). Primary abdominal ectopic pregnancy: a case report. Cases J , 2, 8485. PMID: 19918376 DOI.
  10. Walid MS & Heaton RL. (2010). Diagnosis and laparoscopic treatment of cornual ectopic pregnancy. Ger Med Sci , 8, . PMID: 20725587 DOI.
  11. Resta S, Fuggetta E, D'Itri F, Evangelista S, Ticino A & Porpora MG. (2012). Rupture of Ovarian Pregnancy in a Woman with Low Beta-hCG Levels. Case Rep Obstet Gynecol , 2012, 213169. PMID: 23198195 DOI.
  12. Mohebbi MR, Rosenkrans KA, Luebbert EE, Hunt TT & Jung MJ. (2011). Ectopic pregnancy in the cervix: a case report. Case Rep Med , 2011, 858241. PMID: 22110520 DOI.
  13. Calì G, Timor-Tritsch IE, Palacios-Jaraquemada J, Monteaugudo A, Buca D, Forlani F, Familiari A, Scambia G, Acharya G & D'Antonio F. (2018). Outcome of Cesarean scar pregnancy managed expectantly: systematic review and meta-analysis. Ultrasound Obstet Gynecol , 51, 169-175. PMID: 28661021 DOI.
  14. 14.0 14.1 Sun SY, Araujo Júnior E, Elito Júnior J, Rolo LC, Campanharo FF, Sarmento SG, Nardozza LM & Moron AF. (2012). Diagnosis of heterotopic pregnancy using ultrasound and magnetic resonance imaging in the first trimester of pregnancy: a case report. Case Rep Radiol , 2012, 317592. PMID: 23259128 DOI.
  15. Gayer G. (2012). Images in clinical medicine. Abdominal ectopic pregnancy. N. Engl. J. Med. , 367, 2334. PMID: 23234516 DOI.
  16. Bousfiha N, Erarhay S, Louba A, Saadi H, Bouchikhi C, Banani A, El Fatemi H, Sekkal M & Laamarti A. (2012). Ectopic molar pregnancy: a case report. Pan Afr Med J , 11, 63. PMID: 22655097
  17. Samiei-Sarir B & Diehm C. (2013). Recurrent ectopic pregnancy in the tubal remnant after salpingectomy. Case Rep Obstet Gynecol , 2013, 753269. PMID: 24151570 DOI.
  18. Stovall TG & Ling FW. (1993). Single-dose methotrexate: an expanded clinical trial. Am. J. Obstet. Gynecol. , 168, 1759-62; discussion 1762-5. PMID: 8317518

Reviews

Shaw JL, Dey SK, Critchley HO & Horne AW. (2010). Current knowledge of the aetiology of human tubal ectopic pregnancy. Hum. Reprod. Update , 16, 432-44. PMID: 20071358 DOI.

Shao R. (2010). Understanding the mechanisms of human tubal ectopic pregnancies: new evidence from knockout mouse models. Hum. Reprod. , 25, 584-7. PMID: 20023297 DOI.

Corpa JM. (2006). Ectopic pregnancy in animals and humans. Reproduction , 131, 631-40. PMID: 16595714 DOI.

Articles

Exalto N, Vooys GP, Meyer JW & Lange WP. (1980). Ovarian pregnancy: a morphologic description. Eur. J. Obstet. Gynecol. Reprod. Biol. , 11, 179-87. PMID: 7194809

Purslow CE. (1915). Tubal Pregnancy showing Foetus undergoing Dissolution. Proc. R. Soc. Med. , 8, 68. PMID: 19978839

Matsunaga E & Shiota K. (1980). Ectopic pregnancy and myoma uteri: teratogenic effects and maternal characteristics. Teratology , 21, 61-9. PMID: 7385056 DOI.

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Cite this page: Hill, M.A. (2018, August 21) Embryology Abnormal Development - Ectopic Implantation. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Ectopic_Implantation

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