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​Cihat Şen, ​Nicola Volpe

Cecilia Villalain, Daniel Rolnik, M. Mar Gil

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Murat Yayla

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Resul Arısoy

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A case of heterotopic pregnancy in a spontaneous cycle. Perinatal Journal 2012;20(2):63-67 DOI: 10.2399/prn.12.0202007

Author(s) Information

Cihangir Mutlu Ercan,
Mehmet Sakıncı,
Uğur Keskin,
Hakan Çoksüer,
Ercan Balıkçı,
Ali Ergün

  1. Gülhane Askeri Tıp Akademisi Kadın Hastalıkları ve Doğum Anabilim Dalı- Ankara TR
Publication History

Manuscript Received: April 04, 2012

Conflicts of Interest

No conflicts declared.

Heterotopic pregnancy is a condition in which extrauterine and intrauterine pregnancy coincides. It is encountered very rarely especially in the absence of risk factors. The incidence of heterotopic pregnancy has increased in recent years due to the developments in assisted reproductive technologies (ART). In this case report, we aimed to emphasize the early diagnosis and proper management of heterotopic pregnancies with its mortality and morbidity rates and importance for future fertility.
  Seven-weeks pregnant women by the date of her last menstrual period had undergone dilatation and curettage (D&C) in another medical center upon the diagnosis of a missed abortus. She applied to the same center after the procedure with the complaint of groin pain and was referred to our tertiary center because of the plateaud b-hCG levels during her follow-up. Her gynecologic and ultrasonographic examination in our clinic suggested an extrauterine pregnancy and the patient underwent a laparoscopy. A tubal ectopic pregnancy was detected at the right tube and a linear salpingotomy was performed. Heterotopic pregnancy diagnosis was confirmed with the pathological examination reports of the samples obtained in D&C and laparoscopy. 
 The heterotopic pregnancy diagnosis should be kept in mind in the differential diagnosis of women who applied with the complaint of abdominal pain in the first trimester of pregnancy especially in pregnancies occurring after ART and should be managed appropriately on time.

Heterotopic pregnancy, ART pregnancies, linear salpingotomy

Presence of intrauterine and extrauterine pregnancies at the same time is called as heterotopic pregnancy. Although extrauterine pregnancy is usually on tubes, it may be rarely ovarian, cervical, cornual, old cesarean scar or abdominal located.[1] It was first defined by Duverney in 1708 as the autopsy finding in a patient who died due to ruptured ectopic pregnancy and also had intrauterine pregnancy.[2] Its reported prevalence is 0.08% in normal conception.[3] However, this rate increases up to 1 in 100 pregnancies in infertile women treated by assisted reproductive technologies (ART).[4]
Heterotopic pregnancy which may cause inferior pelvic and groin pains or acute abdominal indications especially in first trimester also may cause severe maternal morbidity and even mortality if it is diagnosed lately.[5] Therefore, although it is not a common pathology, heterotopic pregnancy possibility should not be ignored in the differential diagnosis of patients who applied with the complaint of acute abdominal pain in the first trimester. By reviewing the literature, we aimed in our study to present a heterotopic pregnancy case which developed after natural conception and that we established its early diagnosis and treated accordingly.
Thirty-two-year-old (gravida 2, parity 0) patient who applied to a secondary healthcare organization upon the complaint of menstrual delay after natural cycle was diagnosed as pregnant for 7 weeks and missed abortion. Dilatation and curettage (D&C) was applied to the patient upon her request in the same center. The patient applied to the same health center 4 days later with the complaint of groin pain and minimal right adnexal sensitivity was found on gynecologic examination, the uterine cavity was found normal, endometrial echo was found thin and both adnexal regions were found natural. The pathology result of dilatation and curettage material was reported as “chorial villi surrounded by syncytial cells, and endometrium including desidual cells”; and the case was taken into follow-up when b-hCG values of the case was found as 3,200 IU/L before curettage and as 3,900 IU/L after curettage. When b-hCG values of the case was found as 4,900 IU/L four days later, the patient was referred to our clinic with the diagnosis of “gestational trophoblastic disease”.
In the pelvic examination of the patient performed in our clinic, right lower quadrant sensitivity was detected and b-hCG value was reported as 4,500 IU/L. Gestational trophoblastic disease was considered as pre-diagnosis and then remaining placenta pieces and heterotopic pregnancy were considered. In the transvaginal ultrasonographic (TV USG) examination, it was observed that uterus was in normal sizes, endometrial echo was thin and regular, left adnexa was natural and there was mass lesion measuring 15x20 mm on right adnexal canal (Figure 1a) which was consistent with ectopic gestational focus; so the diagnosis was interpreted as heterotopic pregnancy.
Treatment alternatives were suggested to the patient and surgery was decided since she did not accept methotrexate treatment. Right tubal ampullary ectopic pregnancy focus was focused in the laparoscopy (Figure 1b), right linear salpingotomy was applied to the case and she was discharged with full recovery on first postoperative day. Our diagnosis was confirmed when the material taken by laparoscopy was reported as “tubal ectopic” and “chorionic villus and desidual cells” were confirmed in the pathological examination of paraffin block preparations asked from external centers.
Heterotopic pregnancy incidence was reported as 1/30,000 in 1948 by the study of Devoe and Pratt. However, the classical incidence which is known as 1/30,000 in the literature has been revised as 1/3889 in recent analyses and it is anticipated that this rate may increase up to 1/100 in the cycles of assisted reproductive technologies.[5,6]
The risk factors increasing ectopic pregnancy incidence, which are previous pelvic inflammatory disease (PID), intrauterine device (IUD), assisted reproductive technology, endometriosis, previous abdominal surgery, tubal surgery and sexually transmittable diseases, are also valid for heterotopic pregnancies.[7] These risk factors can be categorized within two groups for heterotopic pregnancies: (1) while assisted reproductive technologies increases the risk associated with the number of transferred embryo (if more than one), and (2) other risk factors are associated with tubal damage.[1]
Although extrauterine gestational focus is generally one in heterotopic pregnancy, there are also heterotopic triplet pregnancies in the literature defined as two gestational sacs in one tube and one gestational sac in each tube, and reported after natural conception or assisted reproductive technology (ART) practices.[8,9]
First symptoms of the heterotopic pregnancy are abdominal pain and vaginal bleeding as in ectopic pregnancy. However, when a patient with such symptoms also has intrauterine pregnancy, it is usually ignored that there may be an accompanying ectopic pregnancy and symptoms are most likely associated with normal or pathological intrauterine pregnancy.[1] Early diagnoses of these pregnancies are of vital importance in terms of mortality, morbidity and future fertility of patient. However, in case of a normal intrauterine pregnancy, a suspicious lesion ultrasonographically seen on adnexal region can be interpreted as hemorrhagic corpus luteum and this may delay the diagnosis.[10]. In these cases, maternal mortality is reported as 1% and mortality rate of intrauterine fetus is reported as 45-65%.[11]
Management of heterotopic pregnancy should be customized according to case. b-hCG and progesterone levels are significant in diagnosis and follow-up as well as determination of pregnancy ultrasonographically. Serial progesterone measurements may determine bad prognosis of pregnancy. Howevery, serial b-hCG follow-ups do not help due to accompanying intrauterine pregnancy. The most significant method for the diagnosis of heterotopic pregnancy is high-resolution TV USG. In high risk patients and especially ART practices, both for intrauterine pregnancy diagnosis and differential diagnosis of ectopic and heterotopic pregnancies after embryo transfer 4-6 weeks later, it is recommended to perform routine ultrasonographic evaluation.[12]
Although it is reported that only 10% of previous series of heterotopic pregnancy cases which are hardly diagnosed can be diagnosed during preoperative period, ultrasonography sensitivity is 56% and final diagnosis can be established only by surgery,[13] it is reported that 66% of cases in new series can be diagnosed by ultrasonography.[14] Today, such increase in preoperative diagnosis rates depends on basically two reasons: Firstly, developments on the quality of sonographic imaging have helped to detected abnormal indications at earlier periods, and secondly, ART practices have not only increased heterotopic pregnancy prevalence but also have contributed to remind the possibility of heterotopic pregnancy during ultrasonographic examination.[1]
If there is no risk factor in spontaneous heterotopic pregnancies such as infertility, pelvic inflammatory disease, ectopic pregnancy history, the possibility of heterotopic pregnancy is not reminded since early period of ectopic pregnancy is asymptomatic and normal intrauterine pregnancy is observed in these pregnancies, and thus the diagnosis is delayed. In the first examination of our case performed at an external center, final diagnosis was not reached for such reasons and the patient was referred to our clinic with the pre-diagnosis of molar pregnancy.
Treatment method is determined by the hemodynamic condition of the patient, localization of ectopic pregnancy, expectation of the family about intrauterine pregnancy and the experience of surgeon. In patients with disordered hemodynamia, emergency laparotomy may be suggested or laparoscopic surgery may be suggested in the presence of or experienced anesthesia and surgery team.[15] If the hemodynamia of patient is stable, conservative methods can be used on appropriate indications as well as preferring laparoscopy. In cases where intrauterine pregnancy is not desired, systemic methotrexate can be used successfully.[16] For cases where intrauterine pregnancy is desired, it is reported that injecting local potassium chloride, hypertonic solution or low dose of methotrexate into ectopic pregnancy sac terminates ectopic pregnancy without damaging intrauterine pregnancy.[17-21] Especially in non-tubal heterotopic implantations such as cervical, cornual or cesarean scar, surgical treatment is maternally associated with high bleeding and associated hysterectomy risks. In these cases, any surgical operation (whether maternal risks are observed or not during surgical operation) on uterus causes intrauterine pregnancy to result in miscarriage at a high possibility. Therefore, local treatments mentioned above are the most suitable approaches in especially non-tubal heterotopic implantations.[1,16,19-21]
The most basic characteristics distinguishing heterotopic pregnancy management from ectopic pregnancy management are the cases where intrauterine pregnancy is desired,[1] because the treatment method to be chosen will determine directly the prognosis of intrauterine pregnancy in such a case. When intrauterine component of heterotopic pregnancy is compared to normal intrauterine pregnancy, unfortunately 2-3 times more miscarriage rate is observed.[22]. On the other hand, Survival rates reported as 48-51% reported in 1950s associated with prognosis of intrauterine pregnancy are reported as 69% nowadays.[14,23] Furthermore, in cases where intrauterine pregnancy continues, it is reported that the risk of observing bad gestational outcomes such as low birth weight and preterm labor display no significant difference than normal intrauterine pregnancies.[22]
In all first trimester pregnancies, especially ART pregnancies, referring with the indications of asymptomatic or groin pain and peritoneal irritation symptoms, differential diagnosis of heterotopic pregnancy should certainly be reminded even though normal intrauterine pregnancy is followed-up. It should be known that normal TV USG indications will not rule out the diagnosis of heterotopic pregnancy in symptomatic patients although TV USG has a significant role in the diagnosis of such cases. Early diagnosis and proper treatment method has an essential significance in terms of maintaining intrauterine pregnancy healthily and protecting fertility of cases.
1. Talbot K, Simpson R, Price N, Jackson SR. Heterotopic pregnancy. J Obstet Gynaecol 2011;31:7-12.
2. Reece EA, Petrie RH, Sirmans MF, Finster M, Todd WD. Combined intrauterine and extrauterine gestations: a review. Am J Obstet Gynecol 1983;146:323-30.
3. Tandon R, Goel P, Saha PK, Devi L. Spontaneous heterotopic pregnancy with tubal rupture: a case report and review of the literature. J Med Case Rep 2009;3:8153.
4. Luo X, Lim CE, Huang C, Wu J, Wong WS, Cheng NC. Heterotopic pregnancy following in vitro fertilization and embryo transfer: 12 cases report. Arch Gynecol Obstet 2009;280:325-9.
5. Schroeppel TJ, Kothari SN. Heterotopic pregnancy: a rare cause of hemoperitoneum and the acute abdomen. Arch Gynecol Obstet 2006;274:138-40.
6. Hassiakos D, Bakas P, Pistofidis G, Creatsas G. Heterotopic pregnancy at 16 weeks of gestation after in-vitro fertilization and embryo transfer. Arch Gynecol Obstet 2002;266:124-5.
7. Brunham RC, Binns B, McDowell J, Paraskevas M. Chlamydia trachomatis infection in women with ectopic pregnancy. Obstet Gynecol 1986;67:722-6.
8. Alsunaidi M.An unexpected spontaneous triplet heterotopic pregnancy. Saudi Med J 2005;26:136-8.
9. Jeong H, Park I, Yoon S, Lee N, Kim H, Park S. Heterotopic triplet pregnancy with bilateral tubal and intrauterine pregnancy after spontaneous conception. Eur J Obstet Gynecol 2009;142:161-2.
10. Somers MP, Spears M, Maynard AS, Syverud SA. Ruptured heterotopic pregnancy presenting with relative bradycardia in a woman not receiving reproductive assistance. Ann Emerg Med 2004;43:382-5.
11. Schenker JG, Ezra Y. Complications of assisted reproductive techniques. Fertil Steril 1994;61:411-22.
12. Guirgis RR, Craft IL. Ectopic pregnancy resulting from gamete intrafallopian transfer and in vitro fertilization. Role of ultrasonography in diagnosis and treatment. J Reprod Med 1991;36:793-6.
13. Ankum WM, Van der Veen F, Hamerlynck JV, Lammes FB. Transvaginal sonography and human chorionic gonadotrophin measurements in suspected ectopic pregnancy: a detailed analysis of a diagnostic approach. Hum Reprod 1993;8:1307-11.
14. Barrenetxea G, Barinaga-Rementeria L, Lopez de Larruzea A, Agirregoikoa JA, Mandiola M, Carbonero K. Heterotopic pregnancy: two cases and a comparative review. Fertil Steril 2007;87:417.e9-15.
15. Demirel LC, Bodur H, Selam B, Lembet A, Ergin T. Laparoscopic management of heterotopic cesarean scar pregnancy with preservation of intrauterine gestation and delivery at term: case report. Fertil Steril 2009;91:1293.e5-7.
16. Nitke S, Horowitz E, Farhi J, Krissi H, Shalev J. Combined intrauterine and twin cervical pregnancy managed by a new conservative modality. Fertil Steril 2007;88:706.e1-3.
17. Reece EA, Petrie RH, Sirmans MF, Finster M, Todd WD. Combined intrauterine and extrauterine gestations: a review. Am J Obstet Gynecol 1983;146:323-30.
18. Oyawoye S, Chander B, Pavlovic B, Hunter J, Gadir AA. Heterotopic pregnancy: successful management with aspiration of cornual/interstitial gestational sac and instillation of small dose of methotrexate. Fetal Diagn Ther 2003;18:1-4.
19. Taskin S, Taskin EA, Ciftci TT. Heterotopic cesarean scar pregnancy: how should it be managed? Obstet Gynecol Surv 2009;64:690-5.
20. Suzuki M, Itakura A, Fukui R, Kikkawa F. Successful treatment of a heterotopic cervical pregnancy and twin gestation by sonographically guided instillation of hyperosmolar glucose. Acta Obstet Gynecol Scand 2007;86:381-3.
21. Wang C, Chen C, Wang H, Chiueh H, Soong Y. Successful management of heterotopic cesarean scar pregnancy combined with intrauterine pregnancy after in vitro fertilization-embryo transfer. Fertil Steril 2007;88:706.e13-6.
22. Clayton HB, Schieve LA, Peterson HB, Jamieson DJ, Reynolds MA, Wright VC. A comparison of heterotopic and intrauterine-only pregnancy outcomes after assisted reproductive technologies in the United States from 1999 to 2002. Fertil Steril 2007;87:303-9.
23. Winer AE, Bergman WD, Fields C. Combined intra- and extrauterine pregnancy. Am J Obstet Gynecol 1957;74:170-8.
Figure 1.
Ultrasound and surgery findings