Ec topic pregnancy: Current clinical trends JAMES

D.

ROBERT

KITCHIN M.

WALLACE SIVA W.

WEIN. C.

III, M.D.

NUNLEY,

THIAGARAJAH, NORMAN

Charlotfes~~ille,

M.D.

THORNTON,

JR.,

M.D.

M.B.B.S.(SRI JR..

LANKA) M.D.

Virginia

During the 16 year period ending in November, 1976, 191 cases of ectopic pregnancy were managed at the University of Virginia Hospital. The overall incidence was l/126 deliveries but during the last 3 years of the study the incidence was l/60 deliveries. Only 56 patients have had a subsequent conception. Thirteen have had a recurrent ectopic implantation. Only 36 women (23.7% of those available for follow-up) have had subsequent term pregnancies. &topic pregnancy continues to be a major gynecologic problem and the potential for subsequent fertility is poor. (AM.J. OBSTET.GYNECOL.~~~:~~O,~~~~.)

rrH~ DIAGNOSIS and managment of ectopic pregnancy continues to be a major problem in gynecology. The Committee on Maternal Health of the Medical Society of Virginia has determined that during the 8 year period from 1970 through 1977, 14 of the 91 maternal deaths ( 15.4%) attributable to maternal causes were related to complications of ectopic pregnancy. In addition, considerable evidence indicates that the incidence of this disorder may be increasing.‘-6 There is remarkable uniformity in the reported potential for successful subsequent pregnancy in these patients. The outlook is generally bleak in that less than half are likely to conceive again and only about one third can expect to produce a living child.‘. ‘, 7-‘x In 1961, Thornton and associatesI reviewed 189 cases of ectopic pregnancy managed at the University of Virginia Hospital. The purpose of this report is to present an additional 16 years’ experience with this problem at the same institution and to review some of the current clinical trends with particular emphasis on available evidence regarding subsequent fertility.

Metedal and methods Between July 1, 1962, and November 1, 1978, there were 23,987 deliveries at the University of Virginia From the Department University

of Virginia

of Obstetrics and Gynecology, School of Medicine.

Presented at the Forty-first Annual Meeting of the South Atlantic Association of Obstetricians and Gynecologists, Hot Springs, Virginia, January 28-T I, 1979. Reprint requests: Dr. James D. Kitchin III, Department of Obstetrics and Gynecology, lJniver@y of Virginia School of Medicine, Charlottesville, Virginia 22908.

870

Hospital. During this period, 191 ectopic pregnancies were treated in 178 women, an incidence of 0.80% or l/126 deliveries. However, during the most recent 10 years of this study, the incidence has increased to 1.12% or 1 per 90 deliveries, and since 1975 there has been one ectopic pregnancy for every 60 deliveries (1.69%). An intrauterine contraceptive device (IUD) was in place at the time of ectopic implantation in 20 cases (10.5%). In 36 cases there had been no previous pregnancies and in 48 there had been only one prior pregnancy. However, in 107 (56%) pregnancy had occurred two or more times before (Table I). Among the IUD wearers, 75% had more than 1 prior pregnancy. The majority of information included in this report was obtained from retrospective analysis of hospital records, operating room records, and pathology files. Of the 178 patients under consideration recent documentation of their subsequent medical history was available in 123. In an effort to extend the follow-up in the others, a questionnaire primarily directed toward establishing subsequent fertility was sent to 5.5 women. Twenty-six of these were not returned. Thus, adequate follow-up is limited to 152 patients. ResMlte Menstrual history (Table IF). In most cases (53.4%) patients described a normal menstrual period 4 to 8 weeks prior to admission. However, in 20.4% (including 30% of those wearing an IUD) there was no history of a missed period. In 60 (3 1.4%) cases there was no vaginal bleeding or “spotting” since the most recent OOOZ-9378/79/160670+07$00.70/0~

1979'Thr C. V. Mosb\ Cu.

Volume Number

134 8

period and there was no difference in the incidence of this symptom among the IUD users. Pain. Lower abdominal or pelvic pain was present in 189 cases and in 84 (44%) was less than 24 hours in duration. In 55 cases (28.8%) pain had been present for 1 to 7 days, and in 50 (26.2%) pain had existed for more than 1 week. The IUD group did not diff-er from the other patients with regard to either the incidence of pain or its duration. Physical findings (Table III). Adnexal tenderness was present in 180 cases (94.2%), and in 71 cases it was bilateral. A palpable adnexal mass was present in less than half of cases (43%) and in 16 of 82 (19.5%) was noted on the side opposite to that of the gestation. A palpable mass was slightly more common in the IUD group. An enlarged uterus was infrequent in both groups. Clinical shock, present in 33 cases (17.3%) overall, was twice as common in the IUD group (30%). None of the IUD patients presented with fever. Culdocentesis was performed in 42 cases and yielded nonclotting blood in all but three. Laboratory tests. Preoperative hematocrits ranged from 15% to greater than 40% and correlated poorly with clinical shock. Of those patients with initial hematocrits less than 26%, 10 of 26 (38.5%) were in shock, but seven of 75 women (9.3%) with hematocrits greater than 35% were in clinical shock as well. Erythrocyte sedimentation rate and leukocyte cqunts were variable and of no diagnostic value. Pregnancy tests were performed in 70 cases and were positive in 50. Cervical mucus was examined in relatively few patients but showed ferning in 80%. Operative findings. The anatomic distribution of the ectopic implantations is detailed in Table IV. There were three ovarian pregnancies in this series (all in IUD users) for an incidence of 1 in 63.7 ectopic pregnancies, or 1 in 6.7 ectopic pregnancies in women with an IUD. The location of the corpus luteum was recorded in 84 of the 191 cases and was noted to be on the same side as the ectopic implantation in 57 and on the opposite side in 27. The corpus luteum was ipsilateral to the pregnancy in all nine cases in IUD users in whom this observation was made. Twenty-eight patients had anatomic changes consistent with prior inflammatory disease in both the affected and contralateral fallopian tube. Operative procedure. Immediate celiotomy was performed in 153 cases. Diagnostic laparoscopy preceded celiotomy in 27 cases and in another 11 cases diagnostic posterior colpotomy preceded celiotomy. Salpingectomy was performed in all cases of tubal implantation except one in which the products of conception were “stripped out.” (This patient had a subsequent ectopic pregnancy in the same tube 3 months later.) Two of the

Ectopic

Table

pregnancy:

Current

clinical

I. Parity in 191 cases of ectopic

trends

871

pregnancy

Cases Previous pregnancies (No.) 0 1 2 3 r4

without IUDs (171)

Cares with IUDs (20,

No.

%

No.

7%

No.

%

34 45 32 23 37

20.5 26.3 18.7 13.4 21.6

2 3 7

10 15 35 5 35

36 48 39 24 44

19.4 25.1 20.4 12.6 23.0

Table II. Menstrual pregnancy

~4 wk. 4-8 wk. 8-12 wk. > 12 wk.

33 91 29 18

history

19.3 53.2 17.0 10.5

Table III. Physical findings of ectopic pregnancy

:

Total cases (191)

in 191 cases of ectopic

6 11 3 -

30 55 15

39 102 32 18

20.4 53.4 16.8 9.4

in 191 cases Cares (I 91)

Findings Adnexal

tenderness:

Unilateral Bilateral Bilateral (with

No.

%

180

94.2

109 unilat-

60 11

era1 predominance)

Peritoneal signs Adnexal mass Adnexal “fullness” Clinical shock Enlarged uterus Fever (r37.8)

146 82 34 33 27 13

76.4 43.0 17.8 17.3 14.1 6.8

ovarian pregnancies were managed by oophorectomy and one by partial oophorectomy. Course in hospital. One patient had a wound dehiscence, and two had febrile complications associated with coexistent pelvic inflammatory disease. The latter were the only two patients in this series with significant postoperative febrile morbidity. There was one postoperative death. A 35-year-old multiparous woman was admitted with a mistaken diagnosis of incomplete abortion. Curettage was performed and she was discharged the next day. Four days later she returned with a ruptured ampullary ectopic pregnancy. Postoperatively, she developed pulmonary edema, congestive heart failure, and arrhythmia and died a few hours later. The cause of death was thought

872

Kitchin

et al.

Table IV. Operative of ectopic pregnancy

findings

in 19 1 cases

Of Right fallopian

tube:

89

Ampulla Isthmus Interstitial L!ftfallopian tube: Ampulla Isthmus Interstitial

75 13 1

51.6 43.4 7.6

8 7 0

40 35 0

97 82 13

1 9 7 i 1 3 2

5 45 35 5 5 15

2 89 75 12 2 3

Ovaly: Right

0 0

0.6 46.8 39.8 6.4 0.6 0 0

Left

0

0

I

10 .i

2 1

2

1.2

0

0

2

80 68

11 1

Other”

*One in a noncommunicating one bilateral:

left atipulla

(acute)

Table V. Subsequent fertility with ectopic pregnancy

rudimentary and right

status *

1.0 0.6 1.0 horn;

(chronic).

in 178 patients

I

preeancy: Contraception Surgical sterilization Unknown cause

No.*

100

No subsequent

Died Su4~quent

46.6 39.3 6.3 1 .O 1.6

uterine

isthmus

Patients Fertility

50.8 42.9 6.8 1.1

20 37 41 2 56 36f: 13 7 26

pregnancy.

Term pregnancy Recurrent ectopic pregnancy Abortion Lost to follow-up

(178)

I %i 65.8 13.2 24.3 27.0 1.3 36.8 23.7 8.6 4.6 -

*Four patients are included in two categories: One had therapeutic abortion followed by term pregnancy; two had a term pregnancy and a subsequent ectopic pregnancy; one had a spontaneous abortion followed by a term pregnancy with twins. tBased

on

152 patients

available

for

follow-up.

$These 36 women had 45 pregnancies including twins.

one set of

to be related to aspiration. The pathology report from the curettage revealed only decidua. Blood transfusions were not required in 73 cases (38.2%) including 11 of 20 (55%) in IUD wearers. One hundred twelve patients were given 1 to 6 U of blood and six others required more. Subsequent fertility. The duration of follow-up is relatively short in 44 patients (2 years or less). Of 152 women available for review 65.8% have failed to achieve a subsequent pregnancy and in 27% there is no apparent reason. In 56 cases (36.8% of those available to follow-up) there has been a subsequent conception, but only 36

the

J:I

Iyatients

who

hake

root

ac~hit:\ctl

‘t SU~I-

sequent pregnancy (and who have IW hrcn .zterili-/ecl or used conuateption) one is now 1)~)5t11’encrpaus;1I and two have died (one postopet-ati\elv and one of’ an unrclated illness). Forty remain involuntaril!; inter tilt. Only five of the 36 women who were nulliparous at the time of the initial ectopic surgerv have experienced a later term pregnancy ( 13.9%).

Comment Although the overall incidence of ectopic pregnancy in this report ( li 126 deliveries) is comparable to that in the earlier series from this clinic ( 1i 149 deliveries), the trend in the most recent 3 vears is markedly different (l/60 deliveries). It is possible that the increase in incidence may he, in part. apparent rather than real and related to a decrease in the number of normal term deliveries with no concomitant decrease in patients admitted for gynecologic emergencies. It has been suggested by one group that factors which may have been expected to increase the incidence of ectopic pregnancy in recent years include an increased incidence of gonorrhea as well as various family planning methods which reduce intrauterine pregnancy more effectively than ectopic pregnancy (induced abortion, ILJDs, tubal sterilization). However, the same authors” cited a stable incidence of ectopic pregnancy in their chnic since 1950 (1 per 123 deliveries). A detailed epidemiologic study from England and IVales’ indicates an ir~c reasing incidence in the late 1950’s and a sharp increase since 1970. It is obvious that the incidence will vary with the population group under study, hut the weight of the evidence appears to indicate an increase and in no case has any author presented evidence for a decrease. The clinical features of the patients in this report with regard to demographic data, symptoms, and \ physical findings are not notably different from those described earlier bv Thornton and associates and are consistent with generally accepted intormation.” Lower abdominal or pelvic pain is by far the most frequent symptom. Although ahnost half reported acute pain of less than I day’s duration, a significant number (26.2%) had pain for more than a week, an observation which may reflect a persistent low index of’ suspicion for this disorder. Similarly the menstrual pattern was variable, with 20.4% of women reporting no abnormal menstrual history at, all. The more common incidence of “normal” menstrual histories in IUD wearers may be

Volume Number

134 8

attributable in part to the tendency of such patients to consider vaginal bleeding and pelvic pain as “normal” side effects of the IUD arid to the fact that some of these patients sought interruption of pregnancy before symptoms of ectopic gestation developed. Adnexal tenderness and signs of peritoneal irriiation were the most common physical findings. Although an adnexal mass was detected in 43% of cases, it was on the side opposite to that of the gestation in 19.5%, a finding consistent with that in our earlier series. This observation may be ielated to coincident pelvic inflammatory changes, acctimulation of blood and clot in the pelvis, or palpation of a contralateral corpus luteurn. The latter was present in 32% of patients in whom the location of the corpus luteum was noted and has been reported in 15% to 50% of cases in other reports. ‘* Accurate diagnosis and prompt management of ectopic pregnancy depend on clinical suspicion and careful assessment of symptoms and physical findings. Laboratory tests are of negligible value in diagnosis. Information obtained from diagnostic maneuvers such as culdocentesis and diagnostic ultrasound should be interpreted within the context of careful clinical assessment and must not be allowed to delay operative intervention if clinical suspition exists. Diagnostic laparoscopy may be useful but is contraindicated if obvious clinical evidence of an abdominal emergency exists. An association between ectopic pregnancy and the use of IUDs was recognized by Grsfenberg in 1929. A detailed analysis of this correlation by Lehfeldt and associate@ in 1970 suggested that 4.3% of accidental pregnancies occurring in IUD users are likely to be ectopic and that one ectopic pregnancy will occur per 1,000 IUD users per year. It was further concluded that an IUD reduces uterine implantation far more effectively than it reduces either tubal or ovarian implantation. They and others:, I8 point out that the IUD is probably not causal but is simply not protective against ectopic implantation in predisposed patients. Barron and associateszO concluded that ihe overall incidence of ectopic pregnancy may be slightly iower in women using the IUD but that the relative risk in those women who conceive is (using Lehfeldt’s data) increased 2.5fold to ten-fold. Although this association is generally regarded as evidence of a mode of action of the IUD> lx, 21 Weekes and Sutherst** pointed out that the relationship of the IUD and ectopic pregnancy may be indirect, in that IUD users are at increased risk of pelvic inflammatory disease. Soderstrom23 has presented data indicating that 47% of women using the IUD who undergo laparbscopic sterilization have visual

Ectopic pregnancy: Current clinical trends

873

evidence of “salpingitis” (although cultures may be sterile). Regardless of the exact role of the IUD, it is apparent that patients using the device are at risk and if pregnancy occurs it will be ectopic in 1 of 23 cases6 Thus a high index of suspicion is required especially in view of the frequency of Iower abdominal pain and abnormal bleeding in these women. Seward and associatesz4 have succinctly summarized the appropriate management of IUD wearers when pregnancy is confirmed. If the pregnancy is to be allowed to continue, careful examination and removal of the IUD are done, warning given regarding symptoms of ectopic pregnancy, and close follow-up provided until the pregnancy is established to be intrauterine. If therapeutic abortion is requested (or spontaneous abortion ensues), examination with anesthesia, culdocentesis, and careful examination of the tissue obtained from the uterus are recommended. We believe that frozen-section examination of curettage specimens is advisable in these cases. In the present series five patients (including the one maternal death) were found to have an ectopic pregnancy after an initial diagnosis of either Spontaneous or induced abortion. The occurrence of three ovarian pregnancies among the IUD group in this series (15%) is consistent with that of other reports. *I This is presumably related to the relative ineffectiveness of the device in preventing ovarian implantation as compared with both tubal and intrauterine implantation.6 Coustan and colleaguesz5 suggested that diagnostic laparoscopy may be misleading in cases of suspected ectopic gestation if ovarian pregnancy is not seriously considered, as the superficial appearance may resemble that of an ovarian cyst. Women who have experienced an ectopic pregnancy have a higher subsequent incidence of persistent infertility, recurrent ectopic pregnancy, and pregnancy wastage. Swolin and Fall4 reviewed the literature in 1972 and found that 38% to 70% of patients were infertile after surgery, 25% to 69% had a subsequent normal intrauterine pregnancy, and recurrent ectopic pregnancy occurred in 4% to 25%. These figures will obviously be influenced by differences in the population under study, desire for subsequent pregnancy, coexistent pelvic disease, type of operation performed, other fertility factors, and duration of follow-up. Regardless of such differences the fact remains that no more than half are likely to conceive again, only one third will have a successful term pregnancy, and the risk of another ectopic gestation is increased thirtyfold to fiftyfold.2-4v 7-‘o. l’-13. “-*6, I8 The results of the current study are in accordance with these rather discouraging observations and there is little evidence in

874

Kitchin

et al.

the recent literature to suggest any improvement in the outlook for future fertility. Jeff&ate’s’” proposal in’ 1955 that concomitant ipsilateral oophorectomy he considered in women subjected to salpingectomy in order that the remaining tube be provided with as many ova as possible has been both supported” and refuted.‘. “‘. I6 Available evidence does not clearly establish an advantage in removing a normal ovary and it appears that preservation of’ such ovaries is indicated in these women who already have low fertility potential. The current availability of improved techniques for tubal reconstructive surgery may provide better opportunities for successful subsequent fertility in the future. Timonen and NieminenX found similar rates of successful pregnancy after radical (anything more than tubal reconstruction) and conservative surgery but the recurrence rate of ectopic pregnancy was greater in the conservatively treated group. Others’” have found no difference. Despite the clear risk of’ recurrent ectopic pregnancy it must be re-emphasized that successful pregnancies do occur in about one third of women and that this is a highly significant proportion when it is recognized that many have not had a prior successful gestation. We should be realistic about the prospects for future pregnancy but is is possible that too many salvageable tubes are sacrificed because of defeatism and unwillingness to assume reasonable risks. Bender” suggested that the uninvolved tube should be carefully inspected before the affected tube is excised so that

salpingotomc may be considered 11 the unin\r~l\~ctl tube is rudimentary or hopelessly tlamagrd. tic2 anti others’“. ” stressed the importance of removltrg c.Xot and blood (in an effort to tlecreasc the iucidrnc.c~ of. adhesions and infection) as well as the use of prophylactic antibiotics. M&lin and If‘t’v’ti in a rc