Obstetrician & Gynecologist Physician at the “American Hospital” of Tirana, Albania.
Spitali Amerikan, prane Spitalit Ushtarak Qendror Universitar,(Laprakë) Tirana, Albania.
Heterotopic pregnancy was reported for the first time in 1708 by Duverney during an autopsy. (1) Heterotopic pregnancy has traditionally been regarded as an extremely rare event. In a spontaneous conception cycle, its incidence is rare (1.25:10 000 – 1:30 000).(2, 3) Recently, the incidence has been rising in step with increasing risk factors for ectopic pregnancy and the increasing use of ovulation induction and new assisted reproductive techniques in infertile couples. The presented case is a spontaneous heterotopic pregnancy in a woman without risk factors for ectopic pregnancy and not undergoing ovulation induction or assisted reproductive techniques.
A 28 year old G3P2 Caucasian female was referred to our hospital at the 8th week of amenorrhea with intermittent increasing pelvic pain and vaginal bleeding during the last 48h. The pregnancy test was positive.
Clinical Examination: During the examination, she was found to be pale, restless with tenderness over the suprapubic region. The abdomen was soft. Blood pressure was 110/70 mm Hg and the heart rate was 90 /min. There was also suprapubic tenderness, mostly at the right side.
On physical examination the uterus was increased in size (equivalent to a 8-9 weeks), painless and with a normal consistence. At ill defined right annexal mass was noted. The cul de sac Douglas was also painful. The left annex was normal.
An ultrasound and serial serum samples of β-hCG was indicated to rule out an ectopic pregnancy (EP). The symptoms and the bimanual examination were more likely in favor of an ectopic pregnancy rather than of a threatening abortion. The probability of ectopic pregnancy in a female without risk factors presented with abdominal pain, positive urine pregnancy test and vaginal hemorrhage is 39 %.(4) This probability increase at 54% in the presence of risks factors for ectopic pregnancy. (5)
The transvaginal ultrasound revealed a normal single live intrauterine gestation and a coexisting right tubal heterotopic pregnancy. The left annex was unremarkable and no free fluid was seen. Both pregnancies have their own gestational sacs and their own live embryos (heart beats in real time) with a CRL = 1,7 cm and 1.85 cm consistent with 8 weeks and a few days of menstrual age. (Image 1) (Video clip)
The diagnosis of a heterotopic pregnancy in our case was not difficult. Though, the ultrasound finding of an intrauterine normal pregnancy in the same time with a tubal ectopic pregnancy is very rare.
Intraoperatory findings showed a non-ruptured right tubal ectopic pregnancy situated on the ampularis side of the right tube, and a pregnant uterus at the 8-9 weeks of amenorrhea. A right total salpingectomy was performed. (Figure 3, 4, 5) Pathologic examination of the surgical specimen revealed the presence of chorionic villi and confirmed the diagnosis of a right tubal ectopic pregnancy.
The post-operatory evolution was satisfactory; the patient was discharged home 48h after the surgery. Another TV ultrasound was performed 48 h after the surgery, just before the patient was discharged home. The ultrasound did not discover any abnormal finding on the remaining intrauterine pregnancy, which proceeded uneventfully to 39 weeks. She gives birth by C-Section to a healthy infant of 3500 grams.
Heterotopic pregnancy is simultaneous development of a gestation within the uterine cavity and a gestation outside the uterine cavity (usually tubal pregnancy).
In the general population, the risk factors are the same for ectopic pregnancy and for heterotopic pregnancies:
- Pelvic surgery
- Intrauterine device
- Pelvic inflammatory disease
- Ovulation induction and assisted reproductive techniques (ART).
The additional risk factors in the population of females undergoing ovulation induction or ART are: (6, 7) Increased incidence of super ovulation, increased incidence of tubal defects and Technical factors during embryo transfer that may increase the risk for ectopic pregnancy (embryos retrograde passage).
The incidence of heterotopic pregnancy is rising because of the rising of these risk factors due to the assisted reproductive techniques. In the general population the incidence is 1.25:10 000 – 1:30 000 and in the population of females undergoing ART the incidence is 1:100. (8, 9)
Abdominal pain, annex mass, peritoneal irritation and enlarged uterus are common signs. Unlike the classic forms of ectopic pregnancy, the serial serum samples of β-hCG can be mislead in the diagnosis of heterotopic pregnancy. The serial serum samples of β-hCG are useful in diagnosis only if it is negative, to rule out an ectopic pregnancy. The positive results are not useful because a heterotopic pregnancy demonstrates normal β-hCG values due to the presence of the normal intrauterine gestation.
Transvaginal ultrasound, however, has increased the correct diagnosis likelihood up to 91%. During the ultrasound examination, the suspicion of an ectopic pregnancy raised by the no visualization of an intrauterine pregnancy when the b-hCG exceeds a threshold level. For the transvaginal ultrasound this discriminatory value of b-hCG is 1500 mIU/mL. (10, 11) The identification of an intrauterine gestational sac mostly reduces the possibility of an ectopic pregnancy, but reduces the vigilance during the annex scanning as well. This may delay the diagnosis of a concomitant ectopic pregnancy (heterotopic).
In some cases, a ruptured ectopic pregnancy make it impossible for the ultrasound examination and in this case the diagnosis of an intrauterine pregnancy may be delayed. (12) Moreover, the emergency presented by an incomplete abortion may delay the diagnosis of an ectopic concomitant pregnancy (heterotopic pregnancy), even if an ultrasound examination is performed before the D & C. Once again, this is due to the reduced vigilance during the ultrasound examination of the annexes after the diagnosis of incomplete abortion was made.
In both cases, the complete ultrasound examination of the entire pelvis can make accurate diagnosis. The ultrasound examination of an incipient pregnancy does not terminate with the identification of the intrauterine gestational sac, especially in those patients presented with risk factors for ectopic pregnancy. The ultrasound image of two gestational sacs, with their embryos presenting heart beats, one intrauterine and the other ectopic, is a rare finding. The presence of an annex mass is a much more frequent finding in an ectopic pregnancy (65-85% of cases). (13, 14, 15) This is the same for the heterotopic pregnancy. In the remaining 20% of cases, no annex mass can be detected.
The Doppler examination gives additional information to a suspicious annex mass. (16) During the transabdominal ultrasound, the finding of an increased velocimetry and a low RI (characteristics for the trophoblastic development) has a sensitivity of 53-73% in the diagnosis of a ectopic pregnancy. On the transvaginal examination, the sensitivity arises up to 96%.
Differential diagnosis of a heterotopic pregnancy is made with the following conditions:
* Normal intrauterine pregnancy with ruptured (or not) ovarian cyst
* Normal intrauterine pregnancy with acute appendicitis.
* First trimester pathology of an intrauterine pregnancy (abortion)
* Other tubal pathologies
The treatment of choice is surgery: salpingectomy or by either laparotomy or laparoscopy. An alternative option is salpingocentesis with Methotrexate or KCL inside the ectopic gestational sac. (17, 18)
After the surgical resection of the ectopic pregnancy, 65-70% of the intrauterine fetuses enters the third trimester and is born alive. Maternal prognosis is very good, especially when the diagnosis is made earlier.
1. Duverney JG, in Jombert CA (ed): Oeuvres Anatomiques. Paris, 1708, p 355
2. DeVoe RW, Pratt JH. Simultaneous intrauterine and extrauterine pregnancy. Am J Obst Gynecol 56: 1119, 1948.
3. Bello GV, Schonolz D, Moshirpur J, Jeng DY, Berkowitz RL: Combined pregnancy: the Mount Sinai experience. Obstet Gynecol Surv 1986 Oct;41(10):603-13.
4. Mol BW, Van der Veen F, Bossuyt PM. Implementation of probabilistic decision rules improves the predictive values of algorithms in the diagnostic management of ectopic pregnancy. Hum Reprod 1999; 14:285562.
5. Mol BW, Van der Veen F, Bossuyt PM. Implementation of probabilistic decision rules improves the predictive values of algorithms in the diagnostic management of ectopic pregnancy. Hum Reprod 1999;14:285562.
6. Goldman GA, Fisch B, Ovadia J, et al.: Heterotopic pregnancy after assisted reproductive technologies. Obstet Gynecol Surv 47: 217, 1992
7. Yovich JL, McColm SC, Turner SR, et al: Heterotopic pregnancy from in vitro fertilization. J in Vitro Fert Embryo Transf. 2:146, 1985
8. Tal J, Haddad S, Gordon N, et al: Heterotopic pregnancy after ovulation induction and assisted reproductive technologies: a literature review from 1971 to 1993. Fertil Steril 66:1, 1996
9. Habana A, Dokras A, Giraldo JL, et al: Cornual heterotopic pregnancy: contemporary management options. Am J Obstet Gynecol 182:1264, 2000
10. Barnhart K, Mennuti MT, Benjamin I, et al: Prompt diagnosis of ectopic pregnancy in an emergency department setting. Obstet Gynecol 84:1010, 1994
11. Barnhart KT, Simhan H, Kamelle SA: Diagnostic accuracy of ultrasound, above and below the beta-hCG discriminatory zone. Obstet Gynecol 94:583, 1999
12. D.A. Adekanle, H. Ekomaye, P. B. Olaitan: Heterotopic Pregnancy With A Live Female Infant: A Case Report . The Internet Journal of Gynecology and Obstetrics. 2007. Volume 7 Number 1.
13. Nyberg DA, Mack LA, Jeffrey RB, Laing FC. EndovaginaL sonographic evaluation of ectopic pregnancy: a prospective study. AJR Am J Roentgenol 1987;149: 1181– 6.
14. Fleisher AC, Pennell RG, McKee MS, et al. Ectopic pregnancy: features at transvaginal sonography. Radiology 1990;174:375– 8.
15. Cacciatore B. Can the status of tubal pregnancy be predicted with transvaginal sonography? A prospective comparison of sonographic, surgical, and serum Hcg findings. Radiology 1990;177:481– 4.
16. Taylor KJ, Ramos IM, Feyock AL, et al: Ectopic pregnancy: Duplex Doppler evaluation. Radiology 173:93, 1989
17. Robertson EE, Moye MA, Hanse JN, et al: Reduction of ectopic pregnancy by injection under ultrasound control. Lancet 1:974, 1987
18. Michael D.Scheiber1 and Marcelle I.Cedars2, Successful non-surgical management of a heterotopic abdominal pregnancy following embryo transfer with cryopreserved–thawed embryos- Human Reproduction vol.14 no.5 pp.1375–1377, 1999
19. Stabile Isabel – Ectopic Pregnancy. Diagnostic si management. Cambridge university Press. 1966, 10-11, 124-125