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2006-03-28-16 Ectopic pregnancy with negative serum hCG level © Manson

Ectopic pregnancy with negative serum HCG level 

Francois Manson, MD


Case report: This is a 31-year-old woman with no significant medical history except for 2 normal previous pregnancies. This patient, using and IUD for contraception, was referred to our service because a mild pelvic pain and mild vaginal bleeding. The symptoms started three months ago and seemed to be accentuated in the last 15 days with recent deep dyspareunia and anal pain during defecation. Clinically, the low abdomen was sensitive. There was a small amount of vaginal bleeding. The uterus was in a normal size. There was a painful little mass in the cul-de-sac.

The serum HCG level was negative (< 4 UI/l), white blood cells were at 8.700 with 6.699 neutrophils, the C reactive protein was 13 (normal < 6) and sedimentation speed was 14/37. The following images were obtained. Due to the moderate pelvic pain, a laparoscopy had been performed, showing a hemoperitoneum with a rupture of the left tube. After salpingectomy, the histology revealed the presence of an ectopic pregnancy, associated with clots. The final diagnosis was left ectopic tubal pregnancy rupture with negative serum HCG level.

Note the non specific ultrasound aspect of the mass and the poor vascularization with energy Doppler

Note the fresh blood during the surgery confirming the acute rupture


Ectopic pregnancy is a common gynecology disease with an increased frequency during the last 20 years (4). Chronic ectopic pregnancy can be differentiate from an ectopic pregnancy accordingly to the clinical presentation (6). The clinical symptoms of a chronic ectopic pregnancy include a mild pelvic pain and irregular vaginal bleeding during several weeks (1).

This minor symptomatology is secondary to repeated episodes of small bleeding from the pregnancy in the tube (in contrast with acute ectopic pregnancy which results of one single major bleeding). Those minor repeated bleeding lead to a formation of a hematocele which contains clots and active or inactive trophoblastic tissue. Secondarily, the persistence of the hematocele induce an inflammatory response (6,11), that could explain the inflammatory syndrome as in our case.

For Ugur (6), the majority of the cases (91%) of chronic ectopic pregnancy have a positive HCG level due to the presence of active trophoblastic tissue. This finding is a very important tool for the correct and early diagnosis. For Bedi, the positive bHCG can be present in only 50% of the cases (1).This difference could be explained by the improvement of the sensivity of the serum HCG tests during the 2 or 3 past decades. In fact, it is posssible to think that, at least a part of chronic ectopic pregnancy with negative serum HCG level described in the eightees, will be positive for HCG nowadays.

So, ectopic pregnancy with negative serum HCG level is a rare particular form of chronic ectopic pregnancy. In consequence, acute rupture of ectopic pregnancy with negative serum HCG level is a very uncommon event. Only a few cases are reported on Medline.

In the majority of the cases, chronic ectopic pregnancy with negative hCG result of the involution of active trophoblastic ectopic tissue leading to a negative HCG level as demonstrated by Hochner-Celnikier ( 8 ).

But Taylor (3), described a rupture of chronic ectopic pregnancy with persistent active ectopic trophoblastic tissue. In this case, the negativity of the HCG level was due to a deficient production of this hormone by a viable and active trophoblastic tissue. Two others theorical mechanisms have been described by Taylor (3) to explain serum negative HCG levels :

  • persistant of a very small mass of active trophoblastic tissue producing little HCG responsible of a non detectable serum level (even with the modern tests)
  • enhanced clearance from serum of nascent hormone (unkown process)

Among those patients with chronic ectopic pregnancy with negative HCG, three outcomes are possible:

  • spontaneous recovery with progressive disappearance of the symptoms 
  • persistent minor signs with echographic pelvic abnormal findings justifying surgical exploration
  • and in a few cases, occurrence of an acute rupture and a surgical treatment is required immediately (

For Ugur et Nishijima, acute tubal rupture may be due to inflammatory changes of the hematocele. (6,11) This rupture could be responsible for a massive intra-abdominal bleeding with hemorrhagic shock. (2.4)

The surgical treatment (salpingectomy) of chronic ectopic pregnancy with negative HCG should be indicate in all cases to exclude the possibility of a tubal tumor. The conservative treatment is not an option for these cases because a cancer must be excluded.

At last, if tube is the most habitual localization for ectopic pregnancy, a rupture of a ovarian pregnancy with negative HCG has been reported in the literature by Fejgin.


  1. Bedi DG, Moeller D, Fagan CJ, Winsett MZ. Chronic ectopic pregnancy. A comparison with acute ectopic pregnancy. Eur J Radiol. 1987 Feb;7(1):46-8.
  2. Lonky NM, Sauer MV. Ectopic pregnancy with shock and undetectable beta-human chorionic gonadotropin. A case report. J Reprod Med. 1987 Jul;32(7):559-60.
  3. Taylor RN, Padula C, Goldsmith PC. Pitfall in the diagnosis of ectopic pregnancy: immunocytochemical evaluation in a patient with false-negative serum beta-hCG levels. Obstet Gynecol. 1988 Jun;71(6 Pt 2):1035-8.
  4. Kalinski MA, Guss DA.Hemorrhagic shock from ruptured ectopic pregnancy in a patient with a negative urine pregnancy test result.  Ann Emerg Med. 2002 Jul;40(1):102-5.
  5. Brennan DF, Kwatra S, Kelly M, Dunn M. Chronic ectopic pregnancy--two cases of acute rupture despite negative beta hCG. J Emerg Med. 2000 Oct;19(3):249-54.
  6. Ugur M, Turan C, Vicdan K, Ekici E, Oguz O, Gokmen O. Chronic ectopic pregnancy: a clinical analysis of 62 cases. Aust N Z J Obstet Gynaecol. 1996 May;36(2):186-9.
  7. Maccato ML, Estrada R, Faro S. Ectopic pregnancy with undetectable serum and urine beta-hCG levels and detection of beta-hCG in the ectopic trophoblast by immunocytochemical evaluation. Obstet Gynecol. 1993 May;81(5 ( Pt 2 )):878-80.
  8. Hochner-Celnikier D, Ron M, Goshen R, Zacut D, Amir G, Yagel S. Rupture of ectopic pregnancy following disappearance of serum beta subunit of hCG. Obstet Gynecol. 1992 May;79(5 ( Pt 2 )):826-7.
  9. Fejgin M, Cohen I, Ben-Nun I, Siegal A, Ben-Adaret N.
    Acute rupture of an ovarian pregnancy associated with a negative serum B-HCG.
    Int J Gynaecol Obstet. 1986 Oct;24(5):369-71.
  10. Kim SW, Ha YR, Chung SP. Ruptured intersticial pregnancy presenting with negative beta-hCG and hypovolémic shock. Am J Emerg Med. 2005 Jan;23(1):89.
  11. Nishijima K, Shukumani K, Tsuyoshi H, Hattori Y, Yoshida Y. Ruptured interstitial pregnancy caused by inactive chorionic villi presenting with negative serum beta-hCG. Am J Emerg Med. 2005 Jan;23(1):89.


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