A L J O A T U N R I N R A E L P Case Report

P L E R A Perinatal Journal 2012;20(2):63-67 I N N R A U T A L J O

A case of heterotopic in a spontaneous cycle

Cihangir Mutlu Ercan, Mehmet Sak›nc›, U¤ur Keskin, Hakan Çoksüer, Ercan Bal›kç›, Ali Ergün Department of and Gynecology, Gülhane Military Medical Faculty, Ankara, Turkey

Abstract Spontan siklusta heterotopik gebelik olgusu Objective: Heterotopic pregnancy is a condition in which Amaç: Heterotopik gebelik; intrauterin ve ekstrauterin gebeli¤in extrauterine and intrauterine pregnancy coincides. It is encoun- birlikte bulundu¤u, özellikle risk faktörleri bulunmad›¤›nda olduk- tered very rarely especially in the absence of risk factors. The inci- ça nadir rastlan›lan bir durumdur. Son y›llarda yard›mc› üreme dence of heterotopic pregnancy has increased in recent years due tekniklerindeki geliflmeler sonucunda heterotopik gebelik insidan- to the developments in assisted reproductive technologies (ART). s›nda art›fl meydana gelmifltir. Bu olgu sunumunda heterotopik ge- In this case report, we aimed to emphasize the early diagnosis and beliklerin erken tan› ve uygun yaklafl›mla tedavileri sonucu morta- proper management of heterotopic with its mortality lite, morbidite oranlar›n› ve gelecekteki fertilite aç›s›ndan önemi- and morbidity rates and importance for future fertility. ni vurgulamay› hedefledik. Case: Seven-weeks pregnant women by the date of her last men- Olgu: Son adet tarihine göre 7 haftal›k gebe olan hastan›n antena- strual period had undergone dilatation and curettage (D&C) in tal takiplerinde, missed abortus saptanmas› üzerine bir baflka sa¤- another medical center upon the diagnosis of a missed abortus. l›k merkezinde dilatasyon küretaj ifllemi uygulanm›flt›r. ‹fllem son- She applied to the same center after the procedure with the com- ras› kas›k a¤r›s› flikayetiyle yine ayn› merkeze baflvuran hastan›n plaint of groin pain and was referred to our tertiary center because yap›lan β-hCG takiplerinin plato yapmas› üzerine klini¤imize sevk of the plateaud β-hCG levels during her follow-up. Her gyneco- edilmifltir. Klini¤imizde olgunun jinekolojik ve ultrasonografik logic and ultrasonographic examination in our clinic suggested an muayenesinde sa¤ tubal ektopik gebelik saptanm›fl olup laparosko- extrauterine pregnancy and the patient underwent a laparoscopy. pik sa¤ lineer salpingotomi operasyonu uygulanm›flt›r. Heteroto- A tubal was detected at the right tube and a lin- pik gebelik tan›s› küretaj ve laparoskopi de al›nan materyallerin ear salpingotomy was performed. Heterotopic pregnancy diagno- patolojik incelemeleri sonuçlar› ile do¤rulanm›flt›r. sis was confirmed with the pathological examination reports of the Sonuç: Özellikle üremeye yard›mc› tedavi teknikleri sonucu olu- samples obtained in D&C and laparoscopy. flan gebelikler olmak üzere, tüm gebeliklerin ilk trimesterinde, ka- Conclusion: The heterotopic pregnancy diagnosis should be kept r›n a¤r›s› flikayeti ile baflvuran olgular›n ay›r›c› tan›s›nda heteroto- in mind in the differential diagnosis of women who applied with pik gebelik ak›lda tutulmal› ve zaman›nda uygun flekilde tedavi the complaint of abdominal pain in the first trimester of pregnan- edilmelidir. cy especially in pregnancies occurring after ART and should be managed appropriately on time. Key words: Heterotopic pregnancy, ART pregnancies, linear Anahtar sözcükler: Heterotopik gebelik, üremeye yard›mc› teda- salpingotomy. vi teknikleri gebelikleri, lineer salpingotomi.

Introduction scar or abdominal located.[1] It was first defined by Presence of intrauterine and extrauterine pregnancies Duverney in 1708 as the autopsy finding in a patient at the same time is called as heterotopic pregnancy. who died due to ruptured ectopic pregnancy and also [2] Although extrauterine pregnancy is usually on tubes, it had intrauterine pregnancy. Its reported prevalence is may be rarely ovarian, cervical, cornual, old cesarean 0.08% in normal conception.[3] However, this rate

Correspondence: Hakan Çoksüer, MD. GATA Gülhane Askeri T›p Akademisi Available online at: www.perinataljournal.com/20120202007 Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, Etlik, Ankara, Turkey. doi:10.2399/prn.12.0201007 e-mail: [email protected] QR (Quick Response) Code: Received: April 4, 2012; Accepted: July 24, 2012

©2012 Perinatal Medicine Foundation Ercan CM et al.

increases up to 1 in 100 pregnancies in infertile women curettage material was reported as “chorial villi sur- treated by assisted reproductive technologies (ART).[4] rounded by syncytial cells, and endometrium including Heterotopic pregnancy which may cause inferior desidual cells”; and the case was taken into follow-up β pelvic and groin pains or acute abdominal indications when -hCG values of the case was found as 3,200 especially in first trimester also may cause severe IU/L before curettage and as 3,900 IU/L after curet- β maternal morbidity and even mortality if it is diag- tage. When -hCG values of the case was found as nosed lately.[5] Therefore, although it is not a common 4,900 IU/L four days later, the patient was referred to pathology, heterotopic pregnancy possibility should our clinic with the diagnosis of “gestational tro- not be ignored in the differential diagnosis of patients phoblastic disease”. who applied with the complaint of acute abdominal In the pelvic examination of the patient performed pain in the first trimester. By reviewing the literature, in our clinic, right lower quadrant sensitivity was β we aimed in our study to present a heterotopic preg- detected and -hCG value was reported as 4,500 IU/L. nancy case which developed after natural conception Gestational trophoblastic disease was considered as and that we established its early diagnosis and treated pre-diagnosis and then remaining placenta pieces and accordingly. heterotopic pregnancy were considered. In the trans- vaginal ultrasonographic (TV USG) examination, it was observed that was in normal sizes, endome- Case Report trial echo was thin and regular, left adnexa was natural Thirty-two-year-old (gravida 2, parity 0) patient who and there was mass lesion measuring 15x20 mm on applied to a secondary healthcare organization upon right adnexal canal (Figure 1a) which was consistent the complaint of menstrual delay after natural cycle with ectopic gestational focus; so the diagnosis was was diagnosed as pregnant for 7 weeks and missed interpreted as heterotopic pregnancy. . Dilatation and curettage (D&C) was applied Treatment alternatives were suggested to the to the patient upon her request in the same center. The patient and surgery was decided since she did not accept patient applied to the same health center 4 days later methotrexate treatment. Right tubal ampullary ectopic with the complaint of groin pain and minimal right pregnancy focus was focused in the laparoscopy (Figure adnexal sensitivity was found on gynecologic examina- 1b), right linear salpingotomy was applied to the case tion, the uterine cavity was found normal, endometrial and she was discharged with full recovery on first post- echo was found thin and both adnexal regions were operative day. Our diagnosis was confirmed when the found natural. The pathology result of dilatation and material taken by laparoscopy was reported as “tubal

ab

Figure 1. (a) Ultrasonography and (b) surgery images of the case.

64 Perinatal Journal A case of heterotopic pregnancy in a spontaneous cycle

ectopic” and “chorionic villus and desidual cells” were terone levels are significant in diagnosis and follow-up confirmed in the pathological examination of paraffin as well as determination of pregnancy ultrasonograph- block preparations asked from external centers. ically. Serial progesterone measurements may deter- mine bad prognosis of pregnancy. Howevery, serial β- Discussion hCG follow-ups do not help due to accompanying intrauterine pregnancy. The most significant method Heterotopic pregnancy incidence was reported as for the diagnosis of heterotopic pregnancy is high-res- 1/30,000 in 1948 by the study of Devoe and Pratt. olution TV USG. In high risk patients and especially However, the classical incidence which is known as ART practices, both for intrauterine pregnancy diag- 1/30,000 in the literature has been revised as 1/3889 in nosis and differential diagnosis of ectopic and hetero- recent analyses and it is anticipated that this rate may topic pregnancies after 4-6 weeks increase up to 1/100 in the cycles of assisted reproduc- [5,6] later, it is recommended to perform routine ultrasono- tive technologies. graphic evaluation.[12] The risk factors increasing ectopic pregnancy inci- Although it is reported that only 10% of previous dence, which are previous pelvic inflammatory disease series of heterotopic pregnancy cases which are hardly (PID), intrauterine device (IUD), assisted reproductive diagnosed can be diagnosed during preoperative peri- technology, endometriosis, previous abdominal sur- od, ultrasonography sensitivity is 56% and final diag- gery, tubal surgery and sexually transmittable diseases, nosis can be established only by surgery,[13] it is report- [7] are also valid for heterotopic pregnancies. These risk ed that 66% of cases in new series can be diagnosed by factors can be categorized within two groups for het- ultrasonography.[14] Today, such increase in preopera- erotopic pregnancies: (1) while assisted reproductive tive diagnosis rates depends on basically two reasons: technologies increases the risk associated with the Firstly, developments on the quality of sonographic number of transferred embryo (if more than one), and imaging have helped to detected abnormal indications (2) other risk factors are associated with tubal dam- at earlier periods, and secondly, ART practices have [1] age. not only increased heterotopic pregnancy prevalence Although extrauterine gestational focus is generally but also have contributed to remind the possibility of one in heterotopic pregnancy, there are also hetero- heterotopic pregnancy during ultrasonographic exami- topic triplet pregnancies in the literature defined as nation.[1] two gestational sacs in one tube and one gestational sac If there is no risk factor in spontaneous heterotopic in each tube, and reported after natural conception or pregnancies such as infertility, pelvic inflammatory dis- [8,9] assisted reproductive technology (ART) practices. ease, ectopic pregnancy history, the possibility of het- First symptoms of the heterotopic pregnancy are erotopic pregnancy is not reminded since early period abdominal pain and vaginal bleeding as in ectopic of ectopic pregnancy is asymptomatic and normal pregnancy. However, when a patient with such symp- intrauterine pregnancy is observed in these pregnan- toms also has intrauterine pregnancy, it is usually cies, and thus the diagnosis is delayed. In the first ignored that there may be an accompanying ectopic examination of our case performed at an external cen- pregnancy and symptoms are most likely associated ter, final diagnosis was not reached for such reasons with normal or pathological intrauterine pregnancy.[1] and the patient was referred to our clinic with the pre- Early diagnoses of these pregnancies are of vital impor- diagnosis of . tance in terms of mortality, morbidity and future fertil- Treatment method is determined by the hemody- ity of patient. However, in case of a normal intrauter- namic condition of the patient, localization of ectopic ine pregnancy, a suspicious lesion ultrasonographically pregnancy, expectation of the family about intrauterine seen on adnexal region can be interpreted as hemor- pregnancy and the experience of surgeon. In patients rhagic corpus luteum and this may delay the diagno- with disordered hemodynamia, emergency laparotomy [10] sis. . In these cases, maternal mortality is reported as may be suggested or laparoscopic surgery may be sug- 1% and mortality rate of intrauterine is reported gested in the presence of or experienced anesthesia and [11] as 45-65%. surgery team.[15] If the hemodynamia of patient is sta- Management of heterotopic pregnancy should be ble, conservative methods can be used on appropriate customized according to case. β-hCG and proges- indications as well as preferring laparoscopy. In cases

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where intrauterine pregnancy is not desired, systemic Conflicts of Interest: No conflicts declared. methotrexate can be used successfully.[16] For cases where intrauterine pregnancy is desired, it is reported References that injecting local potassium chloride, hypertonic solution or low dose of methotrexate into ectopic preg- 1. Talbot K, Simpson R, Price N, Jackson SR. Heterotopic nancy sac terminates ectopic pregnancy without dam- pregnancy. J Obstet Gynaecol 2011;31:7-12. aging intrauterine pregnancy.[17-21] Especially in non- 2. Reece EA, Petrie RH, Sirmans MF, Finster M, Todd WD. tubal heterotopic implantations such as cervical, cor- Combined intrauterine and extrauterine gestations: a review. Am J Obstet Gynecol 1983;146:323-30. nual or cesarean scar, surgical treatment is maternally associated with high bleeding and associated hysterec- 3. Tandon R, Goel P, Saha PK, Devi L. Spontaneous hetero- topic pregnancy with tubal rupture: a case report and review tomy risks. In these cases, any surgical operation of the literature. J Med Case Rep 2009;3:8153. (whether maternal risks are observed or not during sur- 4. Luo X, Lim CE, Huang C, Wu J, Wong WS, Cheng NC. gical operation) on uterus causes intrauterine pregnan- Heterotopic pregnancy following in vitro fertilization and cy to result in at a high possibility. embryo transfer: 12 cases report. Arch Gynecol Obstet Therefore, local treatments mentioned above are the 2009;280:325-9. most suitable approaches in especially non-tubal het- [1,16,19-21] 5. Schroeppel TJ, Kothari SN. Heterotopic pregnancy: a rare erotopic implantations. cause of hemoperitoneum and the acute abdomen. Arch The most basic characteristics distinguishing het- Gynecol Obstet 2006;274:138-40. erotopic pregnancy management from ectopic preg- 6. Hassiakos D, Bakas P, Pistofidis G, Creatsas G. Heterotopic nancy management are the cases where intrauterine pregnancy at 16 weeks of gestation after in-vitro fertilization pregnancy is desired,[1] because the treatment method and embryo transfer. Arch Gynecol Obstet 2002;266:124-5. to be chosen will determine directly the prognosis of 7. Brunham RC, Binns B, McDowell J, Paraskevas M. intrauterine pregnancy in such a case. When intrauter- Chlamydia trachomatis infection in women with ectopic preg- ine component of heterotopic pregnancy is compared nancy. Obstet Gynecol 1986;67:722-6. to normal intrauterine pregnancy, unfortunately 2-3 8. Alsunaidi M.An unexpected spontaneous triplet heterotopic times more miscarriage rate is observed.[22]. On the pregnancy. Saudi Med J 2005;26:136-8. other hand, Survival rates reported as 48-51% report- 9. Jeong H, Park I, Yoon S, Lee N, Kim H, Park S. ed in 1950s associated with prognosis of intrauterine Heterotopic triplet pregnancy with bilateral tubal and pregnancy are reported as 69% nowadays.[14,23] intrauterine pregnancy after spontaneous conception. Eur J Furthermore, in cases where intrauterine pregnancy Obstet Gynecol 2009;142:161-2. continues, it is reported that the risk of observing bad 10. Somers MP, Spears M, Maynard AS, Syverud SA. Ruptured gestational outcomes such as low birth weight and heterotopic pregnancy presenting with relative bradycardia in a woman not receiving reproductive assistance. Ann preterm labor display no significant difference than Emerg Med 2004;43:382-5. normal intrauterine pregnancies.[22] 11. Schenker JG, Ezra Y. Complications of assisted reproductive techniques. Fertil Steril 1994;61:411-22. Conclusion 12. Guirgis RR, Craft IL. Ectopic pregnancy resulting from In all first trimester pregnancies, especially ART preg- gamete intrafallopian transfer and in vitro fertilization. Role nancies, referring with the indications of asymptomatic of ultrasonography in diagnosis and treatment. J Reprod Med 1991;36:793-6. or groin pain and peritoneal irritation symptoms, dif- ferential diagnosis of heterotopic pregnancy should 13. Ankum WM, Van der Veen F, Hamerlynck JV, Lammes FB. Transvaginal sonography and human chorionic certainly be reminded even though normal intrauterine gonadotrophin measurements in suspected ectopic pregnan- pregnancy is followed-up. It should be known that nor- cy: a detailed analysis of a diagnostic approach. Hum Reprod mal TV USG indications will not rule out the diagno- 1993;8:1307-11. sis of heterotopic pregnancy in symptomatic patients 14. Barrenetxea G, Barinaga-Rementeria L, Lopez de Larruzea although TV USG has a significant role in the diagno- A, Agirregoikoa JA, Mandiola M, Carbonero K. Heterotopic sis of such cases. Early diagnosis and proper treatment pregnancy: two cases and a comparative review. Fertil Steril method has an essential significance in terms of main- 2007;87:417.e9-15. taining intrauterine pregnancy healthily and protecting 15. Demirel LC, Bodur H, Selam B, Lembet A, Ergin T. fertility of cases. Laparoscopic management of heterotopic cesarean scar

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pregnancy with preservation of intrauterine gestation and 20. Suzuki M, Itakura A, Fukui R, Kikkawa F. Successful treat- delivery at term: case report. Fertil Steril 2009;91:1293.e5-7. ment of a heterotopic and gestation 16. Nitke S, Horowitz E, Farhi J, Krissi H, Shalev J. Combined by sonographically guided instillation of hyperosmolar glu- intrauterine and twin cervical pregnancy managed by a new cose. Acta Obstet Gynecol Scand 2007;86:381-3. conservative modality. Fertil Steril 2007;88:706.e1-3. 21. Wang C, Chen C, Wang H, Chiueh H, Soong Y. Successful 17. Reece EA, Petrie RH, Sirmans MF, Finster M, Todd WD. management of heterotopic cesarean scar pregnancy com- Combined intrauterine and extrauterine gestations: a review. bined with intrauterine pregnancy after in vitro fertilization- Am J Obstet Gynecol 1983;146:323-30. embryo transfer. Fertil Steril 2007;88:706.e13-6. 18. Oyawoye S, Chander B, Pavlovic B, Hunter J, Gadir AA. 22. Clayton HB, Schieve LA, Peterson HB, Jamieson DJ, Heterotopic pregnancy: successful management with aspira- Reynolds MA, Wright VC. A comparison of heterotopic and tion of cornual/interstitial gestational sac and instillation of intrauterine-only pregnancy outcomes after assisted repro- small dose of methotrexate. Fetal Diagn Ther 2003;18:1-4. ductive technologies in the United States from 1999 to 2002. 19. Taskin S, Taskin EA, Ciftci TT. Heterotopic cesarean scar Fertil Steril 2007;87:303-9. pregnancy: how should it be managed? Obstet Gynecol Surv 23. Winer AE, Bergman WD, Fields C. Combined intra- and 2009;64:690-5. extrauterine pregnancy. Am J Obstet Gynecol 1957;74:170-8.

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