Conservative management of ectopic gestation

FERTILITY AND STERILITY

Vol. 51, No.4, April1989

Printed in U.S.A.

Copyright" 1989 The American Fertility Society

Conservative management of ectopic gestation

Michael Vermesh, M.D. Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California

Ectopic gestation affects a large segment of the fertile population in the United States, and its incidence has been steadily increasing in recent years. 1 In 1980 there were 52,200 cases of ectopic gestation in the United States, and in 1983 the Centers for Disease Control reported 69,600 cases, 2 accounting for more than 1% of all reported pregnancies.3 Although maternal mortality from ectopic gestation has declined dramatically in the last 2 decades, the prognosis for subsequent fertility has not improved. Salpingectomy, the traditional treatment for tubal gestation, has resulted in a significant reduction in fertility, without a parallel decrease in the rate of recurrent ectopic pregnancy. The intrauterine pregnancy rate after unilateral salpingectomy is about 40%, 4 •5 and the rate of recurrent ectopic pregnancy in the contralateral tube is about 10% to 15%.5 •6 Over the years, improvements in the treatment of ectopic gestation have been sought that would reduce postoperative morbidity and preserve the childbearing ability of those women who desire it. In 1953 Stromme7 described for the first time a conservative surgical approach to the treatment of tubal gestation. It was not until recently, however, that improvement of diagnostic modalities and microsurgical instrumentation has enabled a widespread use of conservative techniques. The rationale for conservative management is the preservation of reproductive potential. While the repeat ectopic rates after radical and conservative management are similar, the intrauterine pregnancy rate seems to be higher (about 60%) after conservative tubal surgery. 8 •9 Therefore, a conservative therapeutic approach should be attempted in every woman with an isthmic or ampullary tubal gestation who desires future fertility and is hemodynamically stable. The objective of conservative treatment of ectopic gestation is removal of the products of conVol. 51, No.4, April1989

ception while inflicting as little damage to the involved tube as possible. This can be attempted either surgically or nonsurgically. CONSERVATIVE SURGICAL TECHNIQUES

Diagnostic laparoscopy should always be considered when the diagnosis of ectopic gestation is contemplated, except when the patient is hemodynamically unstable. At the time oflaparoscopy, a defin· itive diagnosis of tubal gestation is usually possible. In a patient who desires future fertility, the most conservative procedure should be attempted whenever possible. The choice of surgical technique will be determined by various considerations (Fig. 1): (1) condition of the tube (ruptured, unruptured); (2) location of the gestation within the tube (interstitium, isthmus, ampulla); (3) size of the gestation (~5 em, >5 em); (4) accessibility (presence of adhesions); and (5) complications (uncontrollable bleeding). Based on these considerations the surgeon can choose to perform one of the following procedures by laparoscopy or laparotomy: linear salpingostomy; segmental resection; salpingectomy. The laparoscope normally provides adequate magnification. If further magnification is deemed necessary, a special magnifying glass, which fits over the eyepiece of the laparoscope, can be used. 10 When laparotomy is performed, magnification is not essential, although loupes may be useful. It is imperative, however, that microsurgical techniques be used, and the amount of tissue trauma be minimized, since the basic principle of conservative surgery is the preservation of as much functional tubal tissue as possible. A laparoscopic approach is desirable for removal of a small, unruptured, isthmic or ampullary gestation. The diameter of the ectopic gestation is of importance because a large bulk of tissue may be Vermesh

Conservative management of ectopic gestation

559

(0!18EAVATION, METHOTAEli.ATEl

Figure 1

Conservative management of ectopic gestation.

difficult to remove through a laparoscopic incision. DeCherney et al. 11 considered a diameter of 3 em a reasonable upper limit. Pouly et aLB set the absolute limit at 6 em, and regarded a diameter >4 em as a relative contraindication. Cartwright et alP performed laparoscopic linear salpingostomy on 20 patients. One patient, who had an ectopic gestation measuring 6 em in diameter, hemorrhaged from the ectopic site postoperatively and required an exploratory laparotomy later the same day. In the remainingpatients, with ectopic gestations of 4 em or less in diameter, the procedure was uncomplicated. The author has successfully treated tubal gestations of up to 5 em in diameter by a laparoscopic procedure. 13 Based on these reports and our experience, it can be surmised that the laparoscopic approach probably should not be attempted when the maximum diameter of the gestation is >5 em. The removal of a large bulk of tissue through a small trocar sleeve may be a frustrating experience. Various techniques have been used to facilitate this annoying process: retrieval of the tissue with grasping forceps introduced through the operating channel of the laparoscope, and removal of the grasping forceps and laparoscope as one unit 14 ; insertion of long Palmer polyp forceps instead of a trocar through the supra pubic incision 15 ; or dividing the tissue intra -abdominally and removing it in pieces. We have recently used the 10 mm Semm spoon forceps (Karl Storz, Endoscopy-America, Inc., Culver City, CA), and found this instrument extremely useful for evacuation of tissue from the pelvic cavity. Rupture of an ectopic gestation generally has been considered a contraindication to the laparoscopic approach, 11 •16 although laparoscopic salpingectomy has been accomplished successfully in selected cases. 15•17 It should be emphasized, however, that this procedure requires that the surgeon be familiar with the technique of operative laparoscopy. 560

Vermesb

Conservative management of ectopic gestation

Cornual (interstitial) gestation, whether ruptured or unruptured, should never be treated laparoscopically because of the high risk of uncontrollable hemorrhage. The use of prophylactic injection of vasopressin (Pitressin, Parke-Davis, Morris Plains, NJ) for hemostasis is controversial. Pouly et aLB recommended injection of 5 IU of vasopressin diluted in 20 ml of saline into the mesosalpinx. StangePB advocated the injection of 4 IU in 20 ml directly into the tubal wall only after other techniques for hemostasis have failed. It is noteworthy to remember that vasopressin only stops bleeding from very small vessels, and that its use is not free of complications. The intravascular injection of vasopressin may induce a pronounced increase in blood pressure, and at least one case of postoperative pulmonary edema has been attributed to its use.B Another important issue involves closure of the tubal incision after linear salpingostomy. The edges of the incision can be either closed at the time of surgery (salpingotomy) or allowed to heal by secondary intention (salpingostomy). DeCherney and Kase 5 either closed the incision in two layers or left the incision open and employed a running locked suture for hemostasis. DeCherney et al. 11 left the operative site open after laparoscopic salpingostomy. Semm10 described a laparoscopic method of reapproximation with the Ethi-endosuture using the extracorporeal knot. Bruhat et al. 16 preferred to leave the tubal incision open. Reich et aU 7 initially used Klepinger bipolar forceps to pinch the cut ends together; however, they later abandoned this technique in favor of Bruhat's method. Nelson et al. 19 compared primary and secondary closure of ampullary salpingotomy in the rabbit and found no statistically significant difference in subsequent pregnancy rates, nidation indices, or percentages of adhesions. Based on these data, it seems reasonable to conclude that primary closure of the tubal wall is unnecessary. While linear salpingostomy and segmental resection have become standard procedures and will be described in detail, another conservative surgical method remains controversial. This procedure, termed "milking," consists of evacuation of a distal ampullary or fimbrial gestation by either digital expression or suction through the infundibular end of the tube. Unfortunately, this technique has been associated with continued bleeding from the implantation site, unacceptably high rates (33.3%) of recurrent ectopic gestation, 20 and persistence of trophoblastic tissue requiring a second operative procedure. 16 These complications have been attribFertility and Sterility

uted to incomplete removal of the gestational products and trauma to the endosalpinx. 21 Budowick et al. 22 observed that the developing trophoblast infiltrated through the tubal wall into an extraluminallocation. Thus, attempts at forcible expression will result in tubal damage and incomplete removal. In contrast, Pauerstein et al. 23 demonstrated that the majority of unruptured tubal gestations were intraluminal, implying that digital expression may be justified. Indeed, Sherman et al. 24 recently reported excellent results with this procedure. In their series of 31 patients, there were no postoperative complications, 92% of patients conceived, and there were no repeat ectopic gestations. These authors attributed their success to proper selection of patients and to improvements in diagnosis and operative management.

to 2 em over the gestation, using hook scissors. Since the products of conception are under pressure, they usually will extrude spontaneously, or will be easily removed with fine forceps. The ectopic site should be irrigated carefully with Ringer's lactate, and any remaining tissue should be removed gently from the ectopic bed. Hemostasis can be accomplished with careful coagulation by electrocautery or laser. If bleeding persists, vasopressin 5 IU in 20 ml of saline can be injected into the mesosalpinx or the tubal wall. If these measures fail to provide hemostasis, laparotomy should be strongly considered. Removal of trophoblastic tissue through the laparoscope, and the choice of primary versus secondary closure of the tubal incision, was discussed previously. Segmental Resection (Partial Salpingectomy)

LAPAROSCOPIC TECHNIQUES

For laparoscopic treatment of ectopic gestation, either a double- or triple-puncture technique can be used. When a double-puncture technique is chosen, a 10 or 11 mm operative laparoscope is introduced through the primary incision just inferior to the umbilicus. A 5 mm accessory trocar is introduced through a suprapubic puncture site. The advantage of using only two punctures is offset by the smaller field of vision provided by the operative laparoscope, and the proximity of the instrument handles to the operator's head. The latter drawback can be overcome by the use of a laparoscopic video camera. A triple-puncture technique allows more flexibility. A smaller (5 or 7 mm) primary puncture is used for introduction of a nonoperative, panoramic laparoscope. A 5 mm trocar is inserted on the side contralateral to the operative site. The suprapubic site is used for introduction of atraumatic grasping forceps for stabilization of the tube. The operative instruments are inserted through the lateral puncture site. The lateral trocar then can be replaced with a 10 mm sleeve for evacuation of tissue. Linear Salpingostomy (Salpingotomy)

Linear salpingostomy is most suitable for unruptured isthmic or ampullary gestations not larger than 5 em in diameter. The first stage is aspiration of the hemoperitoneum. Next, atraumatic forceps are introduced through the suprapubic site and used to stabilize the tube, close to the ectopic site. The antimesenteric border of the tubal gestation is incised with either a fine needle electrode or an operative laser. The incision then is extended to 1 Vol. 51, No.4, April1989

Laparoscopic segmental resection is the procedure of choice for a ruptured isthmic or ampullary gestation, especially when the contralateral tube is irreversibly damaged or absent. Shapiro and Adler25 reported the first successful procedure of this type. The procedure has since been widely per~ formed, using several techniques. 14·26•27 After aspiration of the hemoperitoneum, the segment of tube containing the gestation is grasped and elevated. The tube proximal and distal to the ectopic is coagulated with bipolar forceps and then divided with hook scissors or laser. The mesosalpinx then is coagulated and cut in a similar fashion. The segment is removed entirely or in pieces through a 10 mm sleeve, as previously described. LAPAROTOMY

Laparotomy should be performed when the laparoscopic approach is difficult or when the patient is hemodynamically unstable. Both linear salpingostomy and segmental resection are performed in a manner very similar to that described for laparoscopy. Through an abdominal incision, the hemoperitoneum is aspirated and the other pelvic organs are packed away. The affected tube then is elevated and either a linear salpingostomy or a segmental resection is performed. It is important to use microsurgical techniques to reduce tissue damage. Linear Salpingostomy

A linear incision 1 to 2 em long is made on the antimesenteric border of the tube, over the ectopic gestation. The products of conception easily can be removed with a scalpel handle, fine forceps, or suction. The tube then is thoroughly irrigated with Vermesh Conservative management of ectopic gestation

561

Ringer's lactate, and bleeding points are identified and coagulated. To reduce bleeding further, vasopressin can be injected into the mesosalpinx or the tubal wall, as described for laparoscopy. If bleeding from the implantation site persists, it usually can be controlled by ligating the mesenteric vessels underneath with 4-0 or 5-0 polyglactin sutures. Alternatively, the surgeon may compress the mesosalpinx just below the operative site between the index and middle fingers for 5 minutes. 18 If bleeding persists despite these measures, a segmental resection of the tube should be performed. Segmental Resection

This is most appropriate for a ruptured isthmic or ampullary gestation, but also has been recommended for unruptured isthmic gestation. 14·28 U nder these conditions, a segmental resection may be preferable to linear salpingostomy, since the site of ectopic gestation represents an area of preexisting tubal pathology. 29 Furthermore, it has been shown that the developing trophoblast infiltrates into the tubal wall, between the muscularis and serosa, and therefore is not confined solely within the luminal aspect of the tube. 22 Isthmic implantations tend to have more intramural trophoblast, while those in the distal ampulla are located more intraluminally.30 Segmental resection is performed by elevating the involved segment of tube, dividing its proximal and distal portions, and incising the mesosalpinx adjacent to the tube. Anastomosis of the proximal and distal segments can be delayed, or performed immediately, after patency of both portions of the tube is verified. Stangel and Gomel14 described a technique of immediate anastomosis, which differs from that performed in the nonpregnant state. Only three sutures were placed, and reapproximation was accomplished in one layer, including both the muscular and serosal layers. This procedure proved effective only in isthmic gestations, however. Advantages of delaying anastomosis include operating on less edematous tissues and the opportunity to verify more accurately patency of the proximal segment. Furthermore, anastomosis may not be necessary at all, since there is about a 50% chance of conception through the contralateral tube. The disadvantages of delaying anastomosis include the potential need for a second major operation, and the risk of ectopic pregnancy in the ipsilateral distal stump. 31 ·32 Because of the latter concern, it has been recommended to place these patients on oral contraceptives until the time of anastomosis. 21 562

Vermesh Conservative management of ectopic gestation

NONSURGICAL TREATMENT

Despite the recent improvement in pregnancy rates, and a decrease in morbidity after conservative surgery for ectopic pregnancy, the outcome is still far from ideal. Recently, several nonsurgical methods have been employed, with varying degrees of success, in the treatment of small unruptured tubal gestations. The emergence of these methods has been boosted by the development of sensitive and rapid assays for human chorionic gonadotropin (hCG), and improved ultrasound technology, that facilitate early diagnosis and accurate monitoring of ectopic gestations. These modalities include: (1) expectant management; (2) methotrexate; (3) RU 486; and (4) prostaglandins. Expectant Management

Expectant management was practiced as early as 1955 by Lund. 33 However, of 119 patients so treated, 51 subsequently required surgical intervention. In 1979, Wone 34 treated 90% of 800 cases of possible ectopic gestation expectantly along with various Chinese medicinal plants. Two patients died during treatment. More recent reports35·36·36A of spontaneous resolution of ectopic gestation suggest that surgery may not be necessary in selected cases. In one study,36 10 patients had hysterosalpingography (HSG) 3 months after laparoscopy. The tubes were patent in 7 and obstructed in 3. In 7 patients, a second-look laparoscopy showed normal-appearing tubes. Fernandez et al. 36A treated expectantly 14 women with a laparoscopically confirmed diagnosis of ectopic gestation. The inclusion criteria included a hematosalpinx < 2 em in diameter in the ampulla, and a hemoperitoneum < 50 ml. In 10 patients the tubal gestation spontaneously resolved, whereas 4 women required reoperation. The authors concluded that the probability of a spontaneous resolution was high when the serum hCG level at diagnosis was< 1000 miU/ml. In contradistinction, Cole and Corlett37 found dense adhesions in 72% of patients with chronic ectopic gestations, and Gomel and Filmar38 demonstrated that chorionic villi are capable of surviving and causing tubal destruction for at least 15 months after the demise of a pregnancy. Expectant management may be associated with an inflammatory reaction at the site of the ectopic gestation, and may not be the method of choice for patients who desire future fertility. It may, however, have merit in the management of persistent ectopic gestation, following conservative tubal surgery (see below). Fertility and Sterility

Table 1

Methotrexate Therapy of Ectopic Pregnancy

Author

Year

No. cases

Location of pregnancy

Tanaka et al. 42 Chotiner43 Brandes et al. 44 Oryetal.'5

1982 1985 1986 1986

1 1 1 6

Interstitial Tubal Cornual Ampullary

Cowan et al. 46

1986

1

Higgins and Schwartz47

1986

1

Ichinoe et al. 48

1987

23

Persistent Ampullary Persistent Ampullary Tubal

Sauer et al. 49

1987

21

Tubal

Methotrexate

Methotrexate has been known for years to be effective in the treatment of trophoblastic disease. The first reports of methotrexate therapy for extrauterine gestations were in cases of abdominal pregnancies.39-41 Recently, interest has been rekindled by reports of the treatment of unruptured tubal gestations with this folinic acid antagonist (Table 1).42-49 In 1982, Tanaka et al. 42 treated an unruptured interstitial gestation with a 15-day course of intramuscular methotrexate, with subsequent preservation of tubal patency. Ory et al. 45 treated 6 subjects, with unruptured ampullary gestations, with 4 intravenous injections of methotrexate (1.0 mg/kg) and 4 intramuscular (IM) injections of citrovorum factor (0.1 mg/kg). One patient developed an acute abdomen and required salpingectomy. Two patients received blood transfusions, and 3 patients experienced stomatitis or gastritis. Rodi et al. 50 reported complete resolution of seven unruptured ectopic gestations within 5 to 50 days of a single course of methotrexate (1.0 mg/kg IM X 4 doses) and citrovorum factor (0.1 mg/kg). The same group of investigators49 recently reported the results of 21 patients treated by the same protocol. All, except one with intra-abdominal bleeding, resolved without surgery. They concluded that methotrexate may be used safely to treat selected (s;3 em) unruptured ectopic gestations. Ichinoe et al. 48 treated 23 patients with IM injections of methotrexate (0.4 mg/kg/day for 5 days) every other week. Resolution of ectopic gestation was obtained in 22 patients (95.7%) within 6 to 47 days (mean, 29.7 days). Patency of the oviducts was established by HSG or laparoscopy in 10 of 19 patients (52.6%). Severe side effects were not observed; however, changes in liver function tests and slight Vol. 51, No.4, April1989

Complications (No. cases) None Leukopenia None Hemoperitoneum (1) Blood transfusion (2) Stomatitis, gastritis (3) Stomatitis Abdominal pain Impaired liver function (4) Bone marrow suppression (1) Hemoperitoneum (2) Impaired liver function Stomatitis, dermatitis (5)

bone marrow suppression were noted in 5 cases. Further studies are needed to determine whether or not methotrexate is safer than laparoscopic surgery, and to compare the subsequent intrauterine and recurrent ectopic pregnancy rates. RU486

This antiprogesterone recently has been shown to be an effective abortifacient agent.51 In the process of demonstrating the effectiveness of this agent as an abortifacient, however, there have been failed attempts in which a tubal gestation was discovered later. 52 In addition, a single attempt at treating a patient with residual ectopic pregnancy has met with failure. 53 This patient subsequently was treated successfully with methotrexate. Prostaglandins

There are no clinical studies of the treatment of ectopic pregnancies with prostaglandins. However, in vitro administration of prostaglandin F 2,. (PGF 2,.) has been shown to induce a marked increase in the activity of tubal musculature, and reduction of the hCG-induced increase in progesterone production by the corpus luteum.54 It also is of interest that 15(s)-15-methyl PGF2,. has been shown to induce tubal contractions in vivo.55 These results suggest that PGF2,. may be useful in the medical treatment of ectopic pregnancy. Postoperative Management

It is not always possible to guarantee complete removal of all trophoblastic tissue, and functional residual trophoblast may remain in the affected tube and result in growth and delayed hemorrhage.5s-5s Vermesh

Conservative management of ectopic gestation

563

Table2

Management of Persistent Ectopic Pregnancy

Author

Year

Patients

Primary procedure

Management

Kelly et al. 62 Johnson et al. 57 Kamrava et al. 60 Richards58 Rivlin et al. 56 Cowan et al. 46 Higgins and Schwartz47 Cartwright et al. 12 Poulyetal.8

1979 1980 1983 1984 1985 1986 1986 1986 1986

Kenigsberg et al. 53 DiMarchi et al. 61

1987 1987

Bell et al. 63

1987

1 1 1 1 1 1 1 2 11 4 1 3 1 1

Salpingostomy (L)" Fimbrial expression (L) Fimbrial expression (L) Salpingostomy (L) Salpingotomy (L) Fimbrial expression (L) Salpingotomy (L) Salpingostomy (S)b Salpingostomy (S) Fimbrial expression (S) Salpingostomy (L) Salpingostomy (L) Fimbrial expression (L) Salpingostomy (L)

Salpingectomy Salpingectomy Expectant Salpingectomy Salpingectomy Methotrexate Methotrexate Expectant Salpingostomy (9) Salpingectomy (6) RU 486 and methotrexate Salpingectomy (3) Expectant (1) Partial salpingectomy

• L, laparotomy.

b

Pouly et al. 8 reported 15 (4.8%) such cases out of 321 patients who had undergone conservative laparoscopic surgery. Of those patients, 7 underwent a second laparoscopic procedure, 6 required a salpingectomy via laparotomy, and 2 had a conservative operation via laparotomy. Rivlin 59 reviewed 5 case reports of persistent ectopic gestation, and recommended that salpingectomy be the standard of care. Higgins and Schwartz47 and Kenigsberg et al. 53 each reported one case of persistent ectopic pregnancy successfully treated with methotrexate. Kamrava et al. 60 reported one case of persistent low levels of ~-hCG following fimbria! expression. The patient was managed successfully by observation and close monitoring. Cartwright et al. 12 performed laparoscopic linear salpingostomy on 20 patients. Of those, 2 patients (10%) demonstrated an initial rise of serum~- hCG level, suggesting persistence of trophoblastic tissue. Both were asymptomatic and were managed expectantly. Recently, DiMarchi et al. 61 reported 4 cases (4.8%) of persistent ectopic pregnancy out of 84 patients who had a conservative operation (salpingotomy or fimbria! expression). Three patients required repeat laparotomy and salpingectomy, and one was managed expectantly. From these reports and those of others (Table 2), it is difficult to draw conclusions concerning the incidence and optimal management of persistent ectopic gestation following conservative surgery. It is clear, however, that serum ~-hCG should be measured at frequent intervals (every 3 to 6 days) after conservative surgery, until its disappearance. In an asymptomatic patient, expectant management may be sufficient if serum ~-hCG titers decline slowly or persist at a low level (100 to 200 miU/ml). A symptomatic patient or one in whom ~-hCG titers increase or persist at high lev564

Vermesh

Conservative management of ectopic gestation

S, laparoscopy.

els, should have a second-look laparoscopy. If the location of the trophoblastic tissue can be determined, a conservative surgical approach (linear salpingostomy, segmental resection) may be adequate. In other instances, a salpingectomy may be necessary. Reproductive Outcome

Most patients undergoing conservative tubal surgery for an ectopic gestation will attempt to conceive soon thereafter. It is advisable to place these patients on oral contraceptives or a barrier method of contraception for 1 month following a linear salpingostomy to allow any edema or inflammation to subside. Those patients who are scheduled for a secondary closure procedure following segmental resection should be given contraception until the time of the second operation. 21 An HSG and/or a second-look laparoscopy may be Table 3 Factors Significantly Associated with Postoperative Fertility of 151 Patients with Primary Ectopic Pregnancy•

Factor Mean age (years ±SD) History of sterility Adhesions or t1,1bal disease or both Unruptured ectopic pregnancy

Fertile patientsb (n = 114)

Infertile patients< (n = 37)

Significant difference

26.2 ± 4.7 17 (15%)

28.0 ± 4.4 15(41%)

<0.05 <0.003

20 (18%)

19 (51%)

<0.001

77 (68%)

17 (46%)

<0.03

(P)

• From Sherman D, Langer R, Sadovsky G, Bukovsky I, Caspi E: Improved Fertility Following Ectopic Pregnancy. Fertil Steril37:497, 1982. Reproduced with permission of the publisher, The American Fertility Society. b Subsequent intrauterine pregnancies. c Subsequent sterility or repeat ectopic pregnancy only.

Fertility and Sterility

Table 4

Pregnancy Rates Following Segmental Resection for Ectopic Gestation Author

Swolin and Fall66 Janecek and DeGrandi 67 Stangel and Gomel' 4 Gomel68 Siegler et al. 69 DeCherney ad Boyers 30 Patton70

Year

Patients

Time of anastomosis

1972

42

Intraoperative

1978 1980 1980 1981 1985 1986

6 7 6 8 6 1

Intraoperative Intraoperative Elective Intraoperative Elective Intraoperative

Ectopic pregnancies

10

6

3 2" 4" 6

0 0 0 0 0 0

4

1 30 (39.5%)

76

Total a

Intrauterine pregnancies

7 (9.2%)

A single remaining tube.

considered if conception has not occurred 6 months after the procedure. The subsequent conception rate in women with an ectopic pregnancy is about 60%, with only about one half of these resulting in live birth. 64 The reproductive outcome largely is dependent on the type of procedure, but is also influenced by other factors, including age, parity, tubal disease, and whether or not the ectopic gestation has ruptured65 (Table 3). The rates of intrauterine (39.5%) and recurrent ectopic pregnancies (9.2%) after segmental resection are shown in Table 4. These rates are not different from those following a total salpingectomy. The more conservative procedure, however, offers the distinct advantage of preserving the affected tube. As shown in Table 4, six intrauterine pregnancies occurred after segmental resection and anastomosis of single remaining tubes. 14•68 These patients would not have conceived had a total salpingectomy been performed. Linear salpingostomy (or salpingotomy) seems to result in a higher rate of subsequent intrauterine pregnancy than either total or partial salpingectomy (Table 5). 71 - 74 However, the more favorable Table 5 Pregnancy Rates Following Linear Salpingostomy (or Salpingotomy) for Ectopic Gestation

Author

Year

Patients

Percent intrauterine pregnancies

Vehaskari 71 Timonenand Nieminen 20 Jarvin en et al. 72 Bukovsky et al. 73 DeCherney and Kase 5 DeCherney et a1. 74 DeCherney et al. 11 Pouly et al. 8

1960

88

49

16

1967 1972 1979

185 43 20

49 60 70

12 9 5

1979

48

39

8

1980

9

55

0

1981 1986

16 118

50 64

527

54%

Total

Vol. 51, No.4, April1989

Percent ectopics

reproductive outcome may in part reflect a selection bias, since linear salpingostomies were performed in cases of small unruptured gestations, whereas salpingectomies were usually performed in cases of ruptured ectopic gestations. The advantage of conservative over radical surgery becomes more evident when treating ectopic gestations in solitary tubes (Table 6) 75 - 78 In these cases, a conservative approach is the only one that preserves reproductive potential. SUMMARY

The management of ectopic gestation has become more challenging than ever before. The recent progress in diagnostic modalities, i.e., ultrasound and sensitive ~-hCG assays, has enabled early detection of ectopic gestation and a change in treatment goals. The traditional catastrophic presentation of a ruptured ectopic gestation and hemoperitoneum no longer is common. Today this condition is typically diagnosed before a rupture occurs, while the patient is only minimally symptomatic. Accordingly, treatment has shifted from an immediate life-saving intervention, into conservative methods of management, directed at preserving fertility and reducing morbidity. As experience is being gained rapidly in the various conservative treatment methods, their respective merits Table 6 Results of Conservative Surgery for Tubal Pregnancy in Women with a Solitary Tube

Author

Year

No. of patients desiring pregnancy

0 22

Henri-Suchet et al. 75 DeCherney et al. 9 Langer et aV6 Valle and Lifchez 77 Oelsner et al. 78 Pouly et al. 8

1979 1982 1982 1983 1986 1986

14 12 8 11 21 24

8 6 5 11 10 11

13%

Total

90

51 (57%)

Vermesh

IUP

Conservative management of ectopic gestation

EUP 2 2 2 0 9 7 22 (24%)

565

can be evaluated. Laparoscopic linear salpingostomy is the treatment of choice for small, unruptured, isthmic or ampullary gestations. Laparoscopic segmental resection is most suitable for ruptured tubal gestations. These procedures should be performed via laparotomy only if the patient is hemodynamically unstable. In selected cases, nonsurgical treatment methods, i.e., expectant management or methotrexate, may be considered. Serial serum ,8-hCG measurements following a conservative treatment is mandatory to rule out persistence of trophoblastic tissue. 79 Further prospective randomized studies are needed, to compare different conservative treatment methods in regard to their respective safety, reproductive outcome, and economic feasibility. REFERENCES 1. Westrom L, Bengtsson LPH, Mardh P A: Incidence, trends and risks of ectopic pregnancy in a population of women. Br Med J 282:15, 1981 2. Centers for Disease Control: Ectopic pregnancy-United States, 1981-1983. MMWR 35:289, 1986 3. Centers for Disease Control: Ectopic pregnancies-United States, 1979-1980. MMWR 33:201, 1984 4. Ploman L, Wicksell F: Fertility after conservative surgery in tubal pregnancy. Acta Obstet Gynecol Scand 39:143, 1960 5. DeCherney AH, Kase N: The conservative surgical management of unruptured ectopic pregnancy. Obstet Gynecol 54:451, 1979 6. Schenker JG, Eyal Z, Polishuk WZ: Fertility after tubal surgery. Surg Gynecol Obstet 135:74, 1972 7. Stromme WB: Salpingostomy for tubal pregnancy: report of a successful case. Obstet Gynecol87:757, 1953 8. Pouly JL, Mahnes H, Mage G, Canis M, Bruhat MA: Conservative laparoscopic treatment of 321 ectopic pregnancies. Fertil Steril46:1093, 1986 9. DeCherney AH, Maheaux R, Naftolin F: Salpingostomy for ectopic pregnancy in the sole patent oviduct: reproductive outcome. Fertil Steril37:619, 1982 10. Semm K: Advances in pelviscopic surgery. Curr Probl Obstet Gynecol 5:20, 1982 11. DeCherney AH, Romero R, Naftolin F: Surgical management ofunruptured ectopic pregnancy. Fertil Steril35:21, 1981 12. Cartwright PS, Herbert CM III, Maxson WS: Operative laparoscopy for the management of tubal pregnancy. J Reprod Med 31:589, 1986 13. Vermesh M, Silva PD, Rosen GF, Stein AL, Fossum GT, Sauer MV: Management of unruptured ectopic gestation by linear salpingostomy: a prospective, randomized clinical trial of laparoscopy versus laparotomy. Obstet Gynecol 73: 400,1989 14. Stangel JJ, Gomel V: Techniques in conservative surgery for tubal gestation. Clin Obstet Gynecol 23:1221, 1980 15. Dubuisson JB, Aubriot FX, Cardone V: Laparoscopic salpingectomy for tubal pregnancy. Fertil Steril47:225, 1987 16. Bruhat MA, Mahnes H, Mage G, Pouly JL: Treatment of ectopic pregnancy by means oflaparoscopy. Fertil Steril33: 411,1980 17. Reich H, Freifeld ML, McGlynn F, ReichE: Laparoscopic treatment of tubal pregnancy. Obstet Gynecol69:275, 1987 566

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18. Stangel J: Newer methods of treatment of ectopic pregnancy. In Ectopic Pregnancy, Edited by AH DeCherney. Rockville, Maryland, Aspen Publishers, 1986, p 89 19. Nelson LM, Margara RA, Winston RML: Primary and secondary closure of ampullary salpingotomy compared in the rabbit. Fertil Steril 45:292, 1986 20. Timonen S, Nieminen U: Tubal pregnancy: choice of operative method of treatment. Acta Obstet Gynecol Scand 46: 327,1967 21. DeCherney AH, Maheux R: Modern management of tubal pregnancy. Curr Probl Obstet Gynecol6:21, 1983 22. Budowick M, Johnson TRB, Genadry R, Parmley TH, Woodruff JD: The histopathology of the developing tubal ectopic pregnancy. Fertil Steril34:169, 1980 23. Pauerstein CJ, Croxatto HB, Eddy CA, Ramzy I, Walters MD: Anatomy and pathology of tubal pregnancy. Obstet Gynecol67:301, 1986 24. Sherman D, Langer R, Herman A, Bukovsky I, Caspi E: Reproductive outcome after fimbrial evacuation of, tubal pregnancy. Fertil Steril47:420, 1987 25. Shapiro HI, Adler DH: Excision of an ectopic pregnancy through the laparoscope. Am J Obstet Gynecol117:290, 1973 26. Soderstrom RM: Unusual uses of laparoscopy. J Reprod Med 15:77, 1975 27. Daniell JF, Pittaway DE: Use of the C0 2 laser in laparoscopic surgery: initial experience with the second puncture technique. Infertility 5:15, 1982 28. Schenker JG, Evron S: New concepts in the surgical management of tubal pregnancy and the consequent postoperative results. Fertil Steril40:709, 1983 29. Stangel JJ, Reyniack V, Stone ML: Conservative surgical management of tubal pregnancy. Obstet Gynecol 48:241, 1976 30. DeCherney AH, Boyers SP: Isthmic ectopic pregnancy: segmental resection as the treatment of choice. Fertil Steril44: 307,1985 31. Silva PD, Paulson RJ, Anderson RE, Lobo RA: Ectopic pregnancy in unrepaired distal tubal remnant after contralateral tubal anastomosis. Fertil Steril47:522, 1987 32. Cartwright PS, Entman SS: Repeat ipsilateral tubal pregnancy following partial salpingectomy: a case report. Fertil Steril 42:64 7, 1984 33. Lund JJ: Early ectopic pregnancy. J Obstet Gynaecol Br Emp 62:70, 1955 34. Wone 1: Traitement de la grossesse extrauterine par la combinasion de la medicine traditionnelle chinoise et de lamedicine moderne. Dakar Med 24:119, 1979 35. Mashiach S, Carp HJA, Serr DM: Nonoperative management of ectopic pregnancy. J Reprod Med 27:127, 1982 36. Garcia AJ, Aubert JM, Sarna J, Josimovich JB: Expectant management of presumed ectopic pregnancies. Fertil Steril 48:395, 1987 36A.Fernandez H, Rainhorn JD, Papiernik E, Bellet D, Frydmim R: Spontaneous resolution of ectopic pregnancy. Obstet Gynecol 71:171, 1988 37. Cole T, Corlett RC: Chronic ectopic pregnancy. Obstet Gynecol59:63, 1982 38. Gomel V, Filmar S: Arrested tubal pregnancy. Fertil Steril 48:1043, 1987 39. Hreshchyshyn MM, Naples JD, Jr, Randall CL: Amethopterin in abdominal pregnancy. Am J Obstet Gynecol93:286, 1965 40. Lathrop JC, Bowles GE: Methotrexate in abdominal pregnancy: report of a case. Obstet Gynecol 32:81, 1968 41. StClair JT, Whealer DA: Methotrexate in abdominal pregnancy. JAMA 21:529, 1969

Fertility and Sterility

42. Tanaka T, Hayashi H, Kutsuzawa T, Fujimoto S, Ichinoe K: Treatment of interstitial ectopic pregnancy with methotrexate: report of a successful case. Fertil Steril37:851, 1982 43. Chotiner HC: Nonsurgical management of ectopic pregnancy associated with severe hyperstimulation syndrome. Obstet Gynecol66:740, 1985 44. Brandes MC, Youngs DD, Goldstein DP, Parmley TH: Treatment of cornual pregnancy with methotrexate: case report. Am J Obstet Gynecol155:655, 1986 45. Ory SJ, Villanueva AL, Sand PK, Tamura RK: Conservative treatment of ectopic pregnancy with methotrexate. Am J Obstet Gynecol154:1299, 1986 46. Cowan BD, McGehee RP, Bates GW: Treatment of persistent ectopic pregnancy with methotrexate and leukovorum rescue: a case report. Obstet Gynecol67:50(s), 1986 47. Higgins KA, Schwartz MB: Treatment of persistent trophoblastic tissue after salpingostomy with methotrexate. Fertil Steril45:427, 1986 48. Ichinoe K, WakeN, Shinkai N, Shiina Y, Miyazaki Y, Tanaka T: Nonsurgical therapy to preserve oviduct function in patients with tubal pregnancies. Am J Obstet Gynecol 156:484, 1987 49. Sauer MV, Gorrill MJ, Rodi IA, Yeko TR, Greenberg LH, Bustillo M, Gunning JE, Buster JE: Nonsurgical management of unruptured ectopic pregnancy: an extended clinical trial. Fertil Steril48:752, 1987 50. Rodi IA, Sauer MV, Gorrill MJ, Bustillo M, Gunning JE, Marshall JR, Buster JE: The medical treatment of unruptured ectopic pregnancy with methotrexate and citrovorum rescue: preliminary experience. Fertil Steril 46:811, 1986 51. Kovacs L, Sas M, Resch BA, Ugocsai G, Swahn ML, Bydeman M, Rowe PJ: Termination of very early pregnancy by RU 486-antiprogestational compound. Contraception 29: 399,1984 52. Paris FX, Henry-Suchet J, Tesquier L, Loysel T, Pez JP, Loffredo V, Roger M, DeBrux J: The value of an antiprogesterone steroid in the treatment of extrauterine pregnancy: preliminary results. Rev Fr Gynecol Obstet 81:33, 1986 53. Kenigsberg D, Porte J, Hull M, Spitz IM: Medical treatment of residual ectopic pregnancy: RU 486 and methotrexate. Fertil Steril4 7:702, 1987 54. Hahlin M, Bokstrom H, Lindblom B: Ectopic pregnancy: in vitro effects of prostaglandins on the oviduct and corpus luteum. Fertil Steril47:935, 1987 55. Croxatto HB, Ortiz M-E, Guiloff E, Ibarra A, Salvatierra AM, Croxatto H-D, Spilman CH: Effect of 15(s)-15-methyl prostaglandin F 2a on human oviductal motility and ovum transport. Fertil Steril 30:408, 1978 56. Rivlin ME, Meeks GR, Cowan BD, Bates GW: Persistent trophoblastic tissue following salpingostomy for unruptured ectopic pregnancy. Fertil Steril43:323, 1985 57. Johnson TRB, Sanborn JR, Wagner KS, Compton AA: Gonadotropin surveillance following conservative surgery for ectopic pregnancy. Fertil Steril 33:207, 1980 58. Richards BC: Persistent trophoblast following conservative operation for ectopic pregnancy. Am J Obstet Gynecol 150:100, 1984 59. Rivlin ME: Persistent ectopic pregnancy: complication of conservative surgery. Int J Fertil30:10, 1985

60. Kamrava MM, Taymor ML, Berger MJ, Thompson IE, Seibel MM: Disappearance of human chorionic gonadotropin following removal of ectopic pregnancy. Obstet Gynecol 62:486, 1983 61. DiMarchi JM, Kosasa TS, Kobara TY, Hale RW: Persistent ectopic pregnancy. Obstet Gynecol 70:555, 1987 62. Kelly RW, Martin SA, Strickler RC: Delayed hemorrhage in conservative surgery for ectopic pregnancy. Am J Obstet Gynecol133:225, 1979 63. Bell OR, Awadalla SG, Mattox JH: Persistent ectopic syndrome: a case report and literature review. Obstet Gynecol 69:521, 1987 64. Ectopic pregnancy. In Comprehensive Gynecology, Edited by W Droegemueller, AL Herbst, DR Mishell Jr, MAStenchever. St. Louis, CV Mosby Co., 1987, p 406 65. Sherman D, Langer R, Sadovsky G, Bukovsky I, Caspi E: Improved fertility following ectopic pregnancy. Fertil Steril 37:497, 1982 66. Swolin K, Fall M: Ectopic pregnancy. Acta Eur Fertil3:14 7, 1972 67. Janecek P, DeGrandi P: Chirurgie restauratrice d'emblee dans le traitement des grossesses extrauterines. J Gynecol Obstet Biol Reprod (Paris) 7:261, 1978 68. Gomel V: Clinical results of infertility microsurgery. In Microsurgery in Female Infertility, Edited by PG Crosignani, BL Rubin. London, Academic Press, 1980, p 77 69. Siegler AM, Wang CF, Westoff C: Management ofunruptured tubal pregnancies. Obstet Gynecol Surv 36:599, 1981 70. Patton GW Jr: Conservative surgery for ectopic pregnancy. In Ectopic Pregnancy, Edited by AH DeCherney. Rockville, Maryland, Aspen Publishers, Inc., 1986, p 105 71. Vehaskari A: The operation of choice for ectopic pregnancy with reference to subsequent fertility. Acta Obstet Gynecol Scand 39 (Suppl13):3, 1960 72. Jarvinen PA, Nummi S, Pietila K: Conservative operative treatment of tubal pregnancy with postoperative daily hydrotubations. Acta Obstet Gynecol Scand 51:169, 1972 73. Bukovsky I, Langer R, Herman A, Caspi E: Conservative surgery for tubal pregnancy. Obstet Gynecol53:709, 1979 74. DeCherney AH, Polan ML, KortH, Kase N: Microsurgical technique in the management of tubal ectopic pregnancy. Fertil Steril 34:324, 1980 75. Henry-Suchet J, Tesquier L, Loffredo V, Loron Y, DeBrux J: La chirurgie conservatrice de la grossesse extrauterine. In Oviducte et Fertilite. Edited by I. Brosens et al. Paris, Masson, 1979, p 5 76. Langer R, Bukovsky I, Herman A, Sherman D, Sadovsky G, Caspi E: Conservative surgery for tubal pregnancy. Fertil Steril38:427, 1982 77. Valle JA, Lifchez AS: Reproductive outcome following conservative surgery for tubal pregnancy in women with a single fallopian tube. Fertil Steril39:316, 1983 78. Oelsner G, Rabinovitch 0, Morad J, Mashiach S, Serr DM: Reproductive outcome after microsurgical treatment of tubal pregnancy in women with a single fallopian tube. J Reprod Med 31:483, 1986 79. Vermesh M, Silva PD, Sauer MV, Vargyas JM, Lobo RA: Persistent tubal ectopic gestation: patterns of circulatinghuman chorionic gonadotropin and progesterone, and management options. Fertil Steril50:584, 1988

Received December 22, 1987. Reprint requests: Michael Vermesh, M.D., Women's Hospital Room L-1013, 1240 North Mission Road, Los Angeles, California 90033. Vol. 51, No.4, April1989

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