Nonsurgical treatment of heterotopic pregnancy: a report of six cases

Vol. 60, No.3, September 1993

FERTILITY AND STERILITY Copyright

©

Printed on acid-free paper in U. S. A.

1993 The American Fertility Society

Nonsurgical treatment of heterotopic pregnancy: a report of six cases

Herve Fernandez, M.D.* Christophe Lelaidier, M.D. Severin Doumerc, M.D.

Patrick Fournet, M.D. Franc;ois Olivennes, M.D. Rene Frydman, M.D.

Department of Obstetrics and Gynecology, Antoine BecIRre Hospital, Clamart, France

Objective: To evaluate nonsurgical management of heterotopic pregnancy. Design: Retrospective case series. Setting: Department of Obstetrics and Gynecology (Antoine Beciere Hospital, Clamart, France, Paris-Sud University). Patients: Six women with heterotopic pregnancy who conceived in four cases after ovulation induction. Intervention: Transvaginal ultrasound (US)-guided aspiration/injection of potassium chloride (KCl) was performed in three cornual pregnancies with alive embryo. Expectant management was realized in three other cases. The regression was followed by serial US examination. Main Outcome Measures: Early and late complications related to the procedure, outcome of intrauterine pregnancy (IUP). Results: Five of six patients were treated successfully (3 with KCl and 2 after expectant management). Three of these five patients had a spontaneous vaginal delivery, and two abortions occurred in the remaining two patients. Salpingectomy had to be performed in one case 10 days after medical treatment. This twin pregnancy ended with an abortion at 23 weeks of amenorrhea. Four cornual heterotopic pregnancies were treated successfully. No complication occurred after the initial management. Conclusion: Ultrasound permits a reliable and early diagnosis of heterotopic pregnancy. In such cases nonsurgical management is an efficient alternative with a good IUP prognosis. Fertil Steril 1993;60:428-32 Key Words: Ectopic pregnancy, expectant management, heterotopic pregnancy, selective reduction

The coexistence of intrauterine pregnancy (IUP) and ectopic pregnancy (EP) is usually called heterotopic pregnancy. Bilateral EPs are not included in this definition. As reported by Novak (1), the first case was reported by Duverney in 1708 as an autopsy finding. The estimated rate of occurrence was between 1 to 30,000 and 1 to 2,600 (2, 3). In 1983, Reece et al. (4) found from literature data 589

Received January 22, 1993; revised and accepted May 13, 1993. * Reprint requests: Herve Fernandez, M.D., Department of Obstetrics and Gynecology, Antoine Beciere Hospital, 157, rue de la porte de trivaux, 92141 Clamart, France.

428

Fernandez et al.

Heterotopic pregnancy without surgery

well-documented heterotopic pregnancies. Subsequently, many cases have been reported, showing an increasing incidence related to the transfer of multiple embryos or oocytes in assisted reproductive technology (ART) (5-7). Laparotomy remains the main treatment procedure because of the high incidence of acute ruptured EP. The availability of high resolution sonography using vaginal probes has improved the diagnosis performance, and the EP is now often confirmed before the rupture of the tube. Therefore, a therapeutic dilemna occurs when the EP lies within the uterine cornual because surgical excision jeopardizes the IUP prognosis. During the past 10 Fertility and Sterility

years, series have reported the results of nonsurgical management of EP either by expectant management or by medical treatment such as methotrexate (MTX), prostaglandin (PG), hyperosmolar glucose, potassium chloride (KC1). The treatment by KCl previously has been used by Robertson et al. (8) in heterotopic pregnancy, including interstitial pregnancy. Potassium chloride was selected as a minimally invasive treatment of heterotopic pregnancy avoiding the exposure of IUP to MTX or PGs. In the present study, we report six cases of heterotopic pregnancy managed by nonsurgical treatment .. MATERIALS AND METHODS

Since January 1, 1985,525 EPs have been treated in our department. Twenty-five of the 525 (4.8%) EPs were heterotopic. During the same period, 19,155 patients delivered infants at term. Thus, the heterotopic pregnancy rate (PR) was 1 of 1,300 deliveries. Six of 25 heterotopic pregnancies justified either expectant management (n = 3) or selective embryo reduction (n = 3). Expectant management was indicated in case of absence of clinical signs. Minimally invasive treatment was indicated in case of cornual pregnancy with embryo heart activity. Other heterotopic pregnancies were treated by laparoscopy as usually indicated in tubal pregnancy associated with evolutive IUP. Standard data collection forms were used to record the details of patient history (risk factor of ectopic gestation, previous surgery), the occurrence of pregnancy (spontaneous, controlled ovarian hyperstimulation [COR], IVF), diagnosis of heterotopic pregnancy (abdominal pain, vaginal bleeding, hCG level, diameter of hematosalpinx, volume of hemoperitoneum), indication of nonsurgical procedure, and outcome of the EP and intrauterine pregnancy (IUP). The selective embryo reduction for cornuallocation was offered to the patient as an alternative to laparotomy. In three cases, (nos. 2, 3, and 6), the patient elected this procedure. Patients were treated with a single dose ofKCl (2 milliequivalents of KCl in 2-mL volume). Under sonographic control (Toshiba SCL 7713, 5-MRz transvaginal probe; Toshiba, Paris, France), an 18-gauge needle was inserted into a needle introducer and was used to penetrate the ectopic sac. The procedure was realized without anesthesia. The ectopic sac was aspirated, followed by an injection into the sac, and asystole was noted on ultrasound (US). The aspiration was performed to minimize the risk of cornual Vol. 60, No.3, September 1993

rupture. In one case (no. 4) of cornual gestation, expectant management was chosen because of the absence of clinical signs, and of a small ectopic gestationnal sac with embryo without heart activity. In two cases (nos. 1 and 5), the expectant management procedure was elected. In case 1, the IUP was unknown at time of laparoscopy, and the patient was included in a trial of expectant management as previously described (9). The IUP was diagnosed 4 days later by ultrasonography indicated for an increasing hCG level. Case 5 was diagnosed after selective embryo reduction in multiple pregnancies. The initial number of embryos (n = 4) was reduced to two, and EP was diagnosed a few hours later during the control of effectiveness of reduction procedure. Because the location of that ectopic sac made it relatively difficult to reach when there is an ascitis due to ovarian hyperstimulation, we refrained from additional manipulation at the time, assuming, with the agreement of the patient, that the ectopic sac without embryo would undergo natural evolution. After nonsurgical management of the ectopic gestation, the ongoing IUP precluded following hCG levels for resolution of trophoblastic proliferation. Therefore, USs were performed initially on days 2, 5, 10, and then weekly until the risk of rupture from persistent trophoblastic proliferation was presumed to disappear, i.e., approximately 8 weeks. RESULTS

Five of six heterotopic pregnancies were treated successfully. Tables 1 and 2 present the characteristics of patients with the management and outcome of the six heterotopic pregnancies. The mean age of the six patients was 27.7 years (range, 25 to 32 years). Three of them had a past history of surgery and risk factors of EP. Four of them had a COR hyperstimulation for IVF (3 cases) or lUI (1 case). In four cases, the ectopic gestation was located in the cornua, which is the main indication of the nonsurgical management. Treatment was performed at 51.3 ± 8.6 days of amenorrhea (mean ± SD), and the initial hCG level was 32,200 mIUI mL (range, 8,000 to 95,000 mIU/mL). The size of the hematosalpinx was <3 cm in all cases, despite the evidence of embryo heart activity in three patients. We observed one expectant management failure. The patient presented with hypogastric pain 10 days later, and despite the absence of hemoperitoneum a laparoscopic salpingectomy was performed. Although no postoperative complication was Fernandez et al.

Heterotopic pregnancy without surgery

429

Table 1

Characteristics of Patients Patient 1

Age (y) Parity Risk factor of EP

2

25 0

32 0 Tubal factor

4

5

6

25 0

26

30

Yes

No

Yes

28 0 Tubal factor previous EP Salpingotomy forEP No

No No Protocolt (IUP unknown) at time of treatment

No Yes Cornual

No No Cornual

No Yes Cornual

Prior surgery Spontaneous pregnancy COH IVF Indication of nonsurgical treatment

3

Salpingoplasty

* Pelvic inflammatory disease.

o

PID* Salpingoplasty No Yes No Uncontrolled ovarian hyperstimulation with ascitis

No Yes Cornual

t Protocol of expectant management of EP (9).

observed, a late spontaneous abortion of the twin pregnancy occurred at 23 weeks of amenorrhea. In three of five other successfully treated heterotopic pregnancies, IUPs progressed uneventfully to term with three singleton spontaneous vaginal deliveries and three healthy infants. In the two other cases treated by KCI, spontaneous abortion occurred, respectively, at 8 and 10 weeks gestation, i.e., 3 weeks and 6 weeks after the medical treatment. The regression of the ectopic gestation followed with serial US examination demonstrated progressive hematosalpinx degeneration in an average of 6 Table 2

o

weeks (range, 4 to 7). This time period does not seem to depend on the evolution of IUP. We have not observed a transient drop in hCG levels in successfully treated patients. DISCUSSION

Heterotopic gestation is a dizigotic gestation in which both oocytes come from the same or separate follicles, presumably fertilized at the same coitus. Although various reports of superfetation have appeared in literature, its existence in humans remains unconfirmed. In 1948, Devoe and Pratt (2)

Presentation, Management, and Outcome of the Heterotopic Pregnancy Patient 1

Day of amenorrhea Abdominal pain Vaginal bleeding HCG (mlU ImL) Hematosalpinx (mm) Hemoperitoneum (mL) Expectant management Medical treatment Outcome of EP

Outcome of pregancy

2

4

3

6

5

49

50

56

44

66

43

Yes 8,000 20

Yes 25,205 20

No 25,000 20

No 25,000 10

No 95,000 25

No 15,000 20 50

Yes

Yes

Kcl Success

Kcl Success

Success

Spontaneous abortion (8 weeks)

Spontaneous abortion (10 weeks)

Failure (salpingectomy 10 days later for pain) Abortion of twin pregnancy at 23 weeks' gestation

Yes Success

Term (NSD)*

Term NSD

Kcl Success

Term NSD

* Normal spontaneous vaginal delivery.

430

Fernandez et al.

Heterotopic pregnancy without surgery

Fertility and Sterility

reported an incidence of 1 of 30,000 deliveries. Since this period, many factors influenced this rate. First, sexually transmitted diseases (STD) increased the EP rate in developed countries with a threefold rate (10). Similar risk factors between EPs and heterotopic pregnancies explained their increasing rate. Second, incidences of EP and twin pregnancies have increased since the use of ovulation induction. Therefore, the heterotopic PR is estimated between 1:2,600 and 1:7,000 delivered infants. The specificity of our department in assisted reproductive technology (ART) explains a high incidence of combined gestations, i.e., 1:1,300. Conversely, in 1970 Rahman et al. (11) found a similar incidence to that observed in 1940 in Europe and the United States. We explain these results because of a low rate of STD and the rare use of ovulation induction in Saoudia. Data became available for pregnancies resulting from ART. This specific population presents two major risk factors of ectopic gestation: ovulation induction and tubal disease which indicates IVF (12, 13). The high incidence of heterotopic PR observed after IVF is the result of an intensive screening of EP, even if, there is evidence of IUP. A preoperative diagnosis appears very rarely in literature data. Only 10% of heterotopic pregnancies were diagnosed in the old series (14). However, with technical US progress and vaginal US development (15-17), precise diagnosis becomes possible earlier. Conversely, hCG is useless for heterotopic pregnancy diagnosis because hCG rates are normal. In literature data, laparotomy remains the main treatment procedure of heterotopic pregnancy. However, laparoscopy recently has been reported as an effective treatment (6, 7, 15) without endangering the IUP. The choice of surgical procedure should be based on the condition of the tube (ruptured or unruptured), the implantation location, size, and surgical experience. Avoidance of intrauterine or intraperitoneal hemorrhage is crucial if the tube is preserved. In these cases of conservative treatment, the decreasing hCG level after operative performance can be misleading because hCG concentration testifies only of the intrauterine gestation. In our series, four cornual pregnancies were managed by a successfull nonsurgical approach. The high-resolution US with color-flow Doppler equipment (1) can contribute to a clear diagnosis, effective management, and follow-up of selected cases of heteropic pregnancies with ectopic cornual pregnancy. Therefore, it seemed important to offer a Vol. 60, No.3, September 1993

puncture procedure that did not involve both general anesthesia and surgical removal of a significant portion of the uterine cornua which may endanger the IUP and lead to cesarean delivery if the pregnancy is achieved. In spite of the failure of our expectant management, nonsurgical treatment with KCI puncture could appear safe in cases of uncontrolled ovarian hyperstimulation because laparoscopy could be dangerous' difficult, and could threaten the evolution of intrauterine multiple pregnancy. However, these preliminary successful results cannot contribute to define predictive criteria for treatment failure. For example, the determinate of hCG levels, usually helpful in EP, cannot be used in such circumstances because of the hCG secretion from the intrauterine embryo alive. Since the reports of Robertson et al. (8) and Leach et al. (18) who successfully managed an heterotopic pregnancy with an injection of KCI under vaginal sonography, this agent has been selected to avoid IUP exposure to MTX or prostaglandins. Although, we report two successful expectant management, we believe the puncture is efficient because the likelihood of success in these cases, i.e., small hCG secretion by EP, is difficult to define. However, the accuracy of the puncture could be primordial. The prognosis of the intrauterine gestation is usually good because of the early US diagnosis before surgical or nonsurgical intervention and the avoidance of potential detrimental effects of hem orrhagic shock on the intrauterine gestation. However, in the reports of in vitro heterotopic pregnancies, none of the cornual heterotopic pregnancies have been reported with IUP survival. In our series, the four concomitant IUPs survived. These observations open up new perspectives for management of heterotopic pregnancy especially in the case of cornual pregnancy.

REFERENCES 1. Novak E. Combined intrauterine and extrauterine pregnancy. Surg Gynecol Obstet 1926;43:26-37. 2. DeVoe RW, Pratt JH. Simultaneous intrauterine and extrauterine pregnancy. Am J Obstet Gynecol 1948;56:111926. 3. Richards SR, Stempel LE, Carlton BD. Heterotopic pregnancy: reappraisal of incidence. Am J Obstet Gynecol 1982;142:928-30. 4. 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. 5. Dimitry ES, Subak-Sharpe R, Mills M, Margara R, Win-

Fernandez et al.

Heterotopic pregnancy without surgery

431

6.

7.

8.

9.

10.

11.

ston R. Nine cases of heterotopic pregnancies in 4 years of in vitro fertilization. Fertil Steril1990;53:107-10. Li HP, Balmaceda JP, Zouves C, Cittadini E, Figuerosa Casas P, Johnston 1. Heterotopic pregnancy associated with gamete intra-fallopian transfer. Hum Reprod 1992;7:131-5. Goldman GA, Fisch B, OvadiaJ, Tadir Y. Heterotopicpregnancy after assisted reproductive technologies. Obstet Gynecol Surv 1992;47:217-21. Robertson DE, Moye MA, Hansen IN. Reduction of ectopic pregnancy by injection under ultrasound control. Lancet 1987;1:974-6. Fernandez H, Rainhorn JD, Papiernik E, Bellet D, Frydman R. Spontaneous resolution of ectopic pregnancy. Obstet GynecoI1988;71:171-4. Coste J, Job-Spira N, Fernandez H, Papiernik E, Spira A. Risk factors for ectopic pregnancy: a case-control study in France, with special focus on infectious factors. Am J of Epidemiol 1991;133:839-49. Rahman J, Rahman MS, Al-Suleiman SA. Combined abdominal and intrauterine pregnancy. J R Soc Med 1982;75:41-2.

432

Fernandez et al.

Heterotopic pregnancy without surgery

12. Simpson EL, Coleman BG, Sondheimer SJ, Arger PH, Mintz MC. In vitro fertilization and embryo transfer complicated by simultaneous ectopic and intrauterine twin gestation. J Ultrasound Med 1986;5:49-51. 13. Y ovich JL, Stanger JD, Tuvic FA, Hahnel R. Combined pregnancy after gonadotrophine therapy. Obstet Gynecol 1984;63:855-8. 14. Winer AE, Bergman WD, Fields C. Combined intra and extra-uterine pregnancy. Am J Obstet Gynecol 1957; 74:170-4. 15. Bello GV, Schonholz D, Morhipu J, Jeng DY, Berkowitz RL. Combined pregnancy: the Mont Sinal experience. Obstet Gynecol Surv 1986;41:603-13. 16. Yagel S, Hurtwitz A, Ron M, Palti Z. Ultrasonic detection of heterotopic pregnancy: a case report. J Clin Ultrasound 1983;11:502-7. 17. Timor-Tritsch IE, Monteagudo A, Matera C, Veit C. Sonographic evolution of cornual pregnancies treated without surgery. Obstet Gynecol 1992;79:1044-9. 18. Leach RE, Ney JA, Ory SJ. Selective embryo reduction of an interstitial heterotopic gestation. Fetal Diagn Ther 1992;7:41-5.

Fertility and Sterility