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.


Tubal Pregnancy

Human development during week 2 is about implantation and the endocrine signaling to block the normal menstrual cycle. The blastocyst implantation process should normally and does occur within the body of the uterus. There are a number of additional abnormal sites of implantation that are outside the uterine body, these are described as ectopic implantation or ectopic pregnancy (Greek, ektopos = "out of place").

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

Links: Implantation | Week 2 | Placenta - Abnormalities | Chlamydia | Ultrasound - Ectopic Pregnancy | Ultrasound | Ectopic Implantation Research | Historic 1920 Paper

Some Recent Findings

Abnormal implantation sites
  • Comparison of double- and single-dose methotrexate protocols for treatment of ectopic pregnancy (EP)[4] "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)[5] "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.[6] "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.
  • References appear in this list based upon the date of the actual page viewing.

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

ACOG Practice Bulletin No. 193: Tubal Ectopic Pregnancy. Obstet Gynecol: 2018, 131(3);e91-e103 PubMed 29470343
ACOG Practice Bulletin No. 193 Summary: Tubal Ectopic Pregnancy. Obstet Gynecol: 2018, 131(3);613-615 PubMed 29470339

Miguel H Bronchud, Francesc Tresserra, Bernat Serra Zantop Epigenetic changes found in uterine decidual and placental tissues can also be found in the breast cancer microenvironment of the same unique patient: description and potential interpretations. Oncotarget: 2018, 9(5);6028-6041 PubMed 29464052

Locke Uppendahl, Caitlin Chiles, Stephanie Shields, Fanglong Dong, Elizabeth Kraft, Jennifer Duong, James Delmore Appropriate Use of Prophylactic Antibiotic Agents in Gynecologic Surgeries at a Midwestern Teaching Hospital. Surg Infect (Larchmt): 2018; PubMed 29451847

Michael S Hester, Natalia Tulina, Amy Brown, Guillermo Barila, Michal A Elovitz Intrauterine Inflammation Reduces Postnatal Neurogenesis in the Hippocampal Subgranular Zone and Leads to Accumulation of Hilar Ectopic Granule Cells. Brain Res.: 2018; PubMed 29448014

Search term: Tubal Pregnancy

ACOG Practice Bulletin No. 193: Tubal Ectopic Pregnancy. Obstet Gynecol: 2018, 131(3);e91-e103 PubMed 29470343
ACOG Practice Bulletin No. 193 Summary: Tubal Ectopic Pregnancy. Obstet Gynecol: 2018, 131(3);613-615 PubMed 29470339

Thor Haahr, Jane Zacho, Merethe Bräuner, K Shathmigha, Jørgen Skov Jensen, Peter Humaidan Reproductive outcome of patients undergoing in vitro fertilization treatment and diagnosed with bacterial vaginosis or abnormal vaginal microbiota: a systematic PRISMA review and meta-analysis. BJOG: 2018; PubMed 29469992

Mianne van Kessel, Rachel Tros, Jur Oosterhuis, Walter H Kuchenbecker, Elly M Vernooij, Marlies Y Bongers, Ben Willem J Mol, Carolien A Koks The prognostic capacity of transvaginal hydrolaparoscopy to predict non-IVF conception. Reprod. Biomed. Online: 2018; PubMed 29456102

Xiaoming Yu, He Cai, Xingbang Zheng, Junyan Feng, Jing Guan Tubal restorative surgery for hydrosalpinges in women due to in vitro fertilization. Arch. Gynecol. Obstet.: 2018; PubMed 29445925

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.[7] 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.[8]
  • 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


Ectopic Pregnancies- United-States 1970-1992.jpg

Ectopic Pregnancies- United-States 1970-1992[9]

Ectopic Pregnancies- United-States 1997-2006.jpg

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.


  • 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

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.

Heterotopic Pregnancy

Heterotopic pregnancy MRI[13]

(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.[13][14]

Ectopic Molar Pregnancy

Ectopic molar pregnancy 01.jpg

Left-sided unruptured ampullary ectopic pregnancy at laparoscopy.[15]

Links: Hydatidiform Mole

Ruptured Ectopic

Ruptured ectopic pregnancy 01.jpg

Ruptured ectopic pregnancy[16]


(MTX, amethopterin) Drug with several different uses including the treatment of ectopic pregnancy[17] 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


  1. Centers for Disease Control and Prevention (CDC) Ectopic pregnancy--United States, 1990-1992. MMWR Morb. Mortal. Wkly. Rep.: 1995, 44(3);46-8 PubMed 7823895
  2. Confidential Enquiry into Maternal Deaths (CEMD) Why Mothers Die 2000–2002 PDFPDF2
  3. J Bouyer, J Coste, H Fernandez, J L Pouly, N Job-Spira Sites of ectopic pregnancy: a 10 year population-based study of 1800 cases. Hum. Reprod.: 2002, 17(12);3224-30 PubMed 12456628
  4. Hossam O Hamed, Salah R Ahmed, Abdullah A Alghasham Comparison of double- and single-dose methotrexate protocols for treatment of ectopic pregnancy. Int J Gynaecol Obstet: 2012, 116(1);67-71 PubMed 22035883
  5. Valerie I Shavell, Mazen E Abdallah, Mark A Zakaria, Jay M Berman, Michael P Diamond, Elizabeth E Puscheck Misdiagnosis of cervical ectopic pregnancy. Arch. Gynecol. Obstet.: 2012, 285(2);423-6 PubMed 21748311
  6. Ruijin Shao Understanding the mechanisms of human tubal ectopic pregnancies: new evidence from knockout mouse models. Hum. Reprod.: 2010, 25(3);584-7 PubMed 20023297
  7. Byung Seok Shin, Mi-Hyun Park Incidental detection of interstitial pregnancy on CT imaging. Korean J Radiol: 2009, 11(1);123-5 PubMed 20046504 | PMC2799642 | Korean J Radiol.
  8. Recep Yildizhan, Ali Kolusari, Fulya Adali, Ertan Adali, Mertihan Kurdoglu, Cagdas Ozgokce, Numan Cim Primary abdominal ectopic pregnancy: a case report. Cases J: 2009, 2;8485 PubMed 19918376 | Cases J.
  9. Centers for Disease Control and Prevention (CDC) Ectopic pregnancy--United States, 1990-1992. MMWR Morb. Mortal. Wkly. Rep.: 1995, 44(3);46-8 PubMed 7823895
  10. M Sami Walid, Richard L Heaton Diagnosis and laparoscopic treatment of cornual ectopic pregnancy. Ger Med Sci: 2010, 8; PubMed 20725587 | German Medical Science
  11. Serena Resta, Eliana Fuggetta, Federica D'Itri, Simona Evangelista, Adele Ticino, Maria Grazia Porpora Rupture of Ovarian Pregnancy in a Woman with Low Beta-hCG Levels. Case Rep Obstet Gynecol: 2012, 2012;213169 PubMed 23198195 | Case Rep Obstet Gynecol.
  12. Mohammad R Mohebbi, Kurt A Rosenkrans, Eric E Luebbert, Tauhni T Hunt, Michael J Jung Ectopic pregnancy in the cervix: a case report. Case Rep Med: 2011, 2011;858241 PubMed 22110520 | PMC3205779
  13. 13.0 13.1 Sue Yazaki Sun, Edward Araujo Júnior, Julio Elito Júnior, Liliam Cristine Rolo, Felipe Favorette Campanharo, Stéphanno Gomes Pereira Sarmento, Luciano Marcondes Machado Nardozza, Antonio Fernandes Moron Diagnosis of heterotopic pregnancy using ultrasound and magnetic resonance imaging in the first trimester of pregnancy: a case report. Case Rep Radiol: 2012, 2012;317592 PubMed 23259128 | Case Rep Radiol.
  14. Gabriela Gayer Images in clinical medicine. Abdominal ectopic pregnancy. N. Engl. J. Med.: 2012, 367(24);2334 PubMed 23234516 | N Engl J Med.
  15. Najoua Bousfiha, Sanaa Erarhay, Adnane Louba, Hanan Saadi, Chahrazad Bouchikhi, Abdelaziz Banani, Hind El Fatemi, Med Sekkal, Afaf Laamarti Ectopic molar pregnancy: a case report. Pan Afr Med J: 2012, 11;63 PubMed 22655097
  16. Bahareh Samiei-Sarir, Christopher Diehm Recurrent ectopic pregnancy in the tubal remnant after salpingectomy. Case Rep Obstet Gynecol: 2013, 2013;753269 PubMed 24151570 | PMC3789312 | Case Rep Obstet Gynecol.
  17. T G Stovall, F W Ling Single-dose methotrexate: an expanded clinical trial. Am. J. Obstet. Gynecol.: 1993, 168(6 Pt 1);1759-62; discussion 1762-5 PubMed 8317518


J L V Shaw, S K Dey, H O D Critchley, A W Horne Current knowledge of the aetiology of human tubal ectopic pregnancy. Hum. Reprod. Update: 2010, 16(4);432-44 PubMed 20071358

Ruijin Shao Understanding the mechanisms of human tubal ectopic pregnancies: new evidence from knockout mouse models. Hum. Reprod.: 2010, 25(3);584-7 PubMed 20023297

Juan Manuel Corpa Ectopic pregnancy in animals and humans. Reproduction: 2006, 131(4);631-40 PubMed 16595714


N Exalto, G P Vooys, J W Meyer, W P Lange Ovarian pregnancy: a morphologic description. Eur. J. Obstet. Gynecol. Reprod. Biol.: 1980, 11(3);179-87 PubMed 7194809

C E Purslow Tubal Pregnancy showing Foetus undergoing Dissolution. Proc. R. Soc. Med.: 1915, 8(Obstet Gynaecol Sect);68 PubMed 19978839

E Matsunaga, K Shiota Ectopic pregnancy and myoma uteri: teratogenic effects and maternal characteristics. Teratology: 1980, 21(1);61-9 PubMed 7385056

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Cite this page: Hill, M.A. (2018, February 23) Embryology Abnormal Development - Ectopic Implantation. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Ectopic_Implantation

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