Ectopic pregnancy and miscarriage

What is the effectiveness of compared with salpingotomy in improving outcomes in women with tubal ?

Study details Participants Interventions Methods Outcomes and Results Comments

Full citation Sample size Interventions Details Results Limitations

Tahseen,S., Wyldes,M., A N=150 Salpingectomy This is a retrospective study Spontaneous intrauterine Retrospective comparative case- (n=97) carried out in the East pregnancy rate (number/total controlled study of Characteristics Birmingham Hospitals (%)) Not reported whether women laparoscopic vs Salpingotomy (Teaching) NHS Trust, UK. were trying to conceive laparotomy management (n=25) All patients operated on Salpingectomy: 38/97 (39.2) of ectopic pregnancy: an Not reported separately for laparoscopically for EP Salpingotomy: 12/25 (48) Outcome of intrauterine evaluation of reproductive salpingectomy and during the study period were pregnancy is not reported performance after radical salpingotomy groups identified. A control group vs conservative treatment was selected randomly from Unclear how fertility data was of tubal ectopic pregnancy, Inclusion criteria those operated on by obtained Journal of Obstetrics and laparotomy. Hospital case Gynaecology, 23, 189-190, Ectopic pregnancy notes were reviewed for Generally poor methodological 2003 details. An attempt was reporting made to contact all patients

Ref Id Exclusion criteria regarding contraceptive use. No baseline characteristics Only one spontaneous IUP reported for salpingectomy vs. 69637 Not reported or EP was included per salpingotomy groups patient in the analysis. Country/ies where the Subsequent fertility was Unexplained missing data from study was carried out analysed in relation to initial 28/150 women treatment method and the UK state of the contralateral Blinding of participants and/or tube. those assessing outcomes is not Study type reported.

Retrospective comparative observational study Other information

Both laparotomies and Aim of the study laparoscopies were done.

Not reported Follow-up was 32.7 months (SD 8.4) in the arm and

556 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Study dates 34.6 months (SD 9.7) in the laparotomy arm. Averages are 1996 to 2000 not reported for salpingectomy/salpingotomy groups. Source of funding

Not reported Full citation Sample size Interventions Details Results Limitations

Giambelli,E., Candiani,M., N=114 Salpingectomy During the study period, Need for further intervention Retrospective Natale,A., Gruft,L., (n=59) data was gathered from 114 (number/total (%)) De,MarinisS, Sambruni,I., Characteristics consecutive patients Unclear how fertility data was Colombo,P., Busacca,M., Salpingotomy undergoing laparoscopic Salpingectomy: 0/59 (0) obtained Laparoscopic treatment of (n=55) surgery for ectopic Salpingostomy: 4/55 (7.3) ectopic pregnancy: Age/years (average (range)): pregnancy. (Note: 3 received a single 45% loss to follow-up for fertility Analysis of 114 32.3 (21 - 41) (Note: these dose of methotrexate on days outcomes (63/114 were followed consecutive cases, Italian Conservative treatment 7-10; 1 received a laparotomy up) Journal of Gynaecology Gestational procedures are referred to as consisted of a simple, linear, on day 15. One further patient and Obstetrics, 8, 5-9, age/weeks (mean (range)) : longitudinal salpingotomy on showed a very long period of The number of women receiving 1996 7.4 (6 - 13) ablative surgery and conservative the antimesenteric tubal slow decline of hCG but was each type of surgery that desired margin by a thin diathermal monitored to resolution future pregnancy is not reported, Ref Id surgery in some Site of ectopic pregnancy parts of the paper) tip. Enucleation of the without need for a further therefore denominators for future (number/total (%)) trophoblastic tissue was intervention and therefore has pregnancy rates cannot be 77300 performed by a suction- not been included here). calculated. Ampullar: 100/114 (87.7) irrigation instrument. In Country/ies where the Isthmic: 10/114 (8.8) some cases oxitocine had Outcome of intrauterine study was carried out Subsequent intrauterine Cornual: 2/114 (1.8) been previously injected into pregnancy (%) pregnancies is not reported. the tubal wall to help Italy Ovarian: 1/114 (0.9) Peritoneal: 1/114 (0.9) haemostasis and tissue Salpingectomy: 62.5 Baseline characteristics not asportation. No tubal suture reported separately for Study type Salpingostomy: 53.8 Condition of tube, split by was performed after ectopic salpingectomy/salpingostomy treatment type (number/total pregnancy removal. Tissue groups. Retrospective comparative was extracted from the Ectopic pregnancy (%) observational study (%)) abdominal cavity by an Blinding of participants and/or endoscopic bag. Salpingectomy: 5.1 those assessing outcomes is not Unruptured: 103/114 (90.4) Salpingostomy: 7.8 Aim of the study - Conservative: 55/103 (53.3) reported. - Ablative: 48/103 (46.6) Laparoscopic salpingectomy was performed with bipolar It is unclear what the All ruptured ectopics received

557 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

To analyse the efficacy of Ruptured: 11/114 (9.6) forceps and scissors denominators are for future radical surgery. laparoscopy in the - Conservative: 0/11 (0) according to the standard pregnancies. However, a total treatment of ectopic - Ablative: 11/11 (100) technique, and the tube was of 22 women had an Other information pregnancy. extracted from the abdomen intrauterine pregnancy and 2 Contralateral tube condition, with an endoscopic bag. women had another ectopic pregnancy, out of a total of 37 All patients received laparoscopy. Study dates split by treatment type (number/total (%)) Both types of intervention women who were followed up were followed by accurate and desired a further January 1993 to October Normal: 84/114 washing of the peritoneal pregnancy. 1995 - Conservative: 44/84 (52.4) cavity and asportation of - Ablative: 40/84 (47.6) blood clots to prevent trophoblastic persistence Source of funding Pathologic: 30/114 (26.3) due to surgical - Conservative: 11/30 (36.7) dissemination. The patients Not reported - Ablative: 19/30 (63.3) were discharged 24-36 hours after laparoscopy.

Inclusion criteria Serum hCG was measured before treatment, and it was Treatment for ectopic used as one of the criteria pregnancy by laparoscopy for judging which mode of management to perform and Exclusion criteria its efficacy. Post-treatment blood samples were taken on dats 3, 7 and 14 to Not reported diagnose persistence of trophoblastic tissue. The criteria used to evaluate the treatment were clinical conditions, hCG absolute and serial values, ultrasound, the possible monitoring period, desire for future pregnancy and patient consensus. Acute abdominal pain required urgent surgical treatment using laparoscopy or laparotomy. hCG>3000 also indicated surgery. Values

558 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

<1500 led to request for further samples and ultrasound after 24-48 hours to exclude the possibility of intrauterine pregnancy. For other values, expectant, medical or surgical treatment was indicated based on the pattern of change. A counselling session was given to the patient to evaluate her openness to a period of serum hCG monitoring and expectant or medical management acceptability.

The choice of salpingectomy or salpingostomy was decided based on tubal conditions, contralateral tubal conditions, patient's age, desire for future pregnancy and other obstetric and gynaecological history (sterility, previous ectopic, PID). All the patients were informed that both kinds of procedures were possible.

Persistent ectopic pregnancy was defined as the growth or plateau value of serum hCG after treatment that requires further intervention.

63 patients were followed up for 6 months after surgery,

559 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

of which 37 desired pregnancy. Full citation Sample size Interventions Details Results Limitations

Parker,J., Permezel,M., N=203 Salpingectomy This study was a Need for further intervention Retrospective Thompson,D., Review of (n=103) retrospective analysis of 203 (number/total (%)) the management of ectopic (This is the total number of consecutive cases of Characteristics of women at pregnancy in a major cases of ectopic pregnancy Salpingostomy ectopic pregnancy treated at Salpingectomy: 1/103 (1.0) baseline are not reported - there teaching hospital: treated during the study (n=50) the Royal Women's Hospital (Note: treated with could have been unreported Laparoscopic surgical period; however 153 were during the study period. 114 methotrexate IMI) differences between the arms. treatment and persistent treated by salpingectomy or of these women had a ectopic pregnancy, salpingostomy, and therefore laparoscopic surgical Salpingostomy: 6/50 (12) Unclear what drove the choice of Australian and New constitute the main procedure. In a further 10 (Note: treated with procedure. Zealand Journal of population of interest for this patients an initial methotrexate IMI (n=2), Obstetrics and review) laparoscopic treatment was laparoscopic salpingectomy Blinding of participants and/or Gynaecology, 34, 575-579, abandoned and a (n=2), laparoscopic those assessing outcomes is not 1994 Characteristics laparotomy was performed fimbriectomy (n=1), and reported. due to inadequate access laparoscopic resection (n=1).

Ref Id (adhesions, obesity), A further 2 women received Details of surgical procedures not Type of treatment given technical problems, or expectant management, reported. 77505 (number/total) uncontrolled haemorrhage. however they have not been The remainder of the included here) Country/ies where the Other information Laparoscopy surgically treated patients study was carried out - Salpingectomy: 52/203 had a laparotomy, and a Note: all cases of persistent - Salpingostomy: 47/203 further 30 women received Australia - Fimbrial expression: 4/203 ectopic pregnancy occurred methotrexate (n=6) or following laparoscopic - Fimbriectomy: 1/203 expectant management Study type treatment. - Removal of tubal abortion: (n=24). 4/203 Retrospective comparative - Excision peritoneal ectopic: Serum beta-hCG was observational study 1/203 determined by 2 assays - Ectopic pregnancy not during the study period. An seen: 3/203 Aim of the study immunoradiometrc system - Injection with methotrexate: was used from June to 2/203 November 1992, and after To determine the number that, a 2-site of patients managed by Laparotomy chemiluminometric different treatment - Salpingectomy: 51/203 immunoassay was used. methods and to determine - Salpingostomy: 3/203 the incidence of persistent

560 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments ectopic pregnancy (PEP) - Fimbrial expression: 2/203 following laparoscopic - Removal of tubal abortion: surgical treatment. 1/203 - Resection of ovary: 2/203 Study dates Medical treatment - Methotrexate orally: 3/203 June 1st 1992 to August - Methotrexate intramuscular 31st 1993 injection (IMI): 3/203

Source of funding Expectant management: 24/203 Not reported Inclusion criteria

Treated for ectopic pregnancy

Exclusion criteria

Not reported Full citation Sample size Interventions Details Results Limitations

Silva,P.D., Schaper,A.M., N=143 Salpingectomy A prospective database Subsequent intrauterine Lack of intention-to-treat: patients Rooney,B., Reproductive (n=26) containing demographic pregnancy (number/total (%)) who underwent laparoscopic outcome after 143 (However, the true population data, clinical variables, and salpingectomy for persistent laparoscopic procedures of interest for this review Salpingostomy reproductive outcome was a. Any intrauterine pregnancy ectopic were followed in the for ectopic pregnancy, question is N=86, which is (n=60) maintained on 143 women salpingectomy category. Obstetrics and the number of women who had laparoscopic Salpingectomy: 14/26 (53.8) Gynecology, 81, 710-715, attempting to conceive treatment for ectopic Salpingostomy: 36/60 (60) Blinding of participants and/or 1993 following a salpingectomy or pregnancy during the study those assessing outcomes is not salpingostomy) period. The setting for the b. Live birth reported.

Ref Id study was a rural tertiary centre staffed by a 260- Salpingectomy: 10/26 (38.5) Length of follow-up not reported. 77584 Characteristics physician multispeciality Salpingostomy: 19/60 (31.7) group, and the tendency to Apart from one, every case of Country/ies where the Type of operation sub-specialisation led to the Repeat ectopic pregnancy ruptured ectopic was managed (number/total (%)) treatment of about 90% of with a salpingectomy (not

561 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments study was carried out the ectopic pregnancies on (number/total (%)) reported what % of the ectopics a. All ectopic pregnancies one authors service. were ruptured). Ectopics treated USA (N=143) Salpingectomy: 2/26 (7.7) by salpingectomy were also Reproductive outcome for Salpingostomy: 11/60 (18.3) significantly larger than those Study type Salpingostomy: 80/143 (55.9) those patients attempting treated with salpingostomy. Salpingectomy: 52/143 (36.4) pregnancy was reviewed Prospective comparative Partial salpingectomy: 3/143 periodically by telephone Other information observational study (2.1) interview, letter or chart Need for further intervention Removal of fimbrial abortion: review. 5/143 (3.5) It is reported that 8 women 2 women were lost to follow-up Aim of the study Removal of abdominal Laparoscopy salpingostomy that were "conservatively from the women attempting implantation: 2/143 (1.4) used fine unipolar treated" needed further conception who received a To analyse reproductive Salpingo-oophorectomy: electrocoagulation and intervention (5 surgeries and salpingostomy or salpingectomy outcome after laparoscopic 1/143 (0.7) vasopressin. Salpingectomy 3 MTX). However, (1 from each arm). procedures for ectopic used bipolar conservative surgery is not pregnancy, with particular b. Women who had or were electrocoagulation and defined in the paper There were significantly higher attention to laparoscopic trying to conceive (n=95) scissors. During the study (therefore unclear which rates of any tubal damage, and salpingectomy period, the appearance of women would constitute the damage due to adhesive disease, Salpingostomy: 60/95 (63.2) the opposite tube did not population), and no in the women who did not become pregnant when Study dates Salpingectomy: 26/95 (27.4) influence the choice of denominator is given. This Partial salpingectomy: 2/95 surgery type. Contralateral outcome also has not been compared to those who did (2.1) adhesions were lysed, but reported for the other become pregnant (intrauterine August 1987 to August Removal of fimbrial abortion: contralateral cuff "radical" arm, who were not pregnancies only) 1991 4/95 (4.2) salpingostomy was not followed up in the same way. Removal of abdominal performed for tubal Due to lack of information, All women for whom reproductive Source of funding implantation: 2/95 (2.1) occlusion. Patients treated this outcome will not be outcome was assessed received Salpingo-oophorectomy:1/95 with conservative reported in the GRADE table. a laparoscopy. Gundersen Medical (1.1) procedures were followed Foundation up with weekly Characteristics of those who postoperative hCG titres to had a baby or were trying to screen for persistent viable conceive trophoblastic tissue. Salpingectomy or partial a. Age/years (mean (SD) salpingectomy was performed in all cases of Salpingectomy: 29.3 (5.3) ruptured ectopic pregnancy, Salpingostomy: 28.6 (4.6) except for one patient with a (p=0.552) small rupture site.

b. Parity (mean (SD)) The reproductive outcomes

562 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

of women treated by Salpingectomy: 1.04 (1.04) laparoscopic salpingostomy Salpingostomy: 0.63 (0.78) and laparoscopic (p=0.049) salpingectomy were analysed for rates of c. Diameter of swelling/cm intrauterine pregnancies, (mean (SD)) live births, miscarriages, elective abortions, and Salpingectomy: 4.0 (1.6) repeat ectopic pregnancies. Salpingostomy: 2.9 (1.1) Life table analysis was (p=0.001) performed for intrauterine pregnancy rates. Patients d. Tubal damage (n (%) who underwent laparoscopic salpingectomy for persistent - Any ectopic were followed in the Salpingectomy: 15 (57.7) salpingectomy category. Salpingostomy: 33 (55.0) Reproductive outcome was (p=0.817) analysed using the variables of age, parity, diameter of - Adhesive disease gestation site, evidence of Salpingectomy: 15 (57.7) prior tubal damage (i.e. Salpingostomy: 29 (48.3) contralateral adhesive (p=0.425) disease, history of tuboplasty, or previous - Previous ectopic pregnancy ectopic pregnancy), and Salpingectomy: 1 (3.9) length of follow-up. Three Salpingostomy: 5 (8.3) women treated by (p=0.453) laparotomy were not included in the analysis of - Tuboplasty reproductive outcome (one Salpingectomy: 3 (11.5) had a ruptured intersitial Salpingostomy: 14 (23.3) pregnancy, one presented (p=0.207) with hypovolemic shock, and one had a concomitant pelvic neoplasm). One patient with concomitant hyperstimulation was Inclusion criteria treated with methotrexate and not included, and neither were patients treated

563 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Receiving laparoscopic with removal of abdominal treatment for pregnancies, irrigation of ectopic pregnancy from one fimbrial abortion, and partial of the authors salpingectomy.

Analysis Exclusion criteria Univariate analyses of Not directly reported, pregnancy rates by type of however in the analysis of procedure, age, parity, size reproductive outcomes, any of EP, and evidence of prior women receiving tubal damage was done. management other than Multivariate analysis was salpingectomy or done using a backwards salpingostomy were not stepped regression. included. Full citation Sample size Interventions Details Results Limitations

Tulandi,T., Guralnick,M., N=58 Salpingectomy 34 women found to have an Cumulative probability of Retrospective Treatment of tubal ectopic (n=24) unruptured ampullary intrauterine pregnancy (%) pregnancy by Characteristics ectopic at laparotomy were Method of selection of controls salpingotomy with or Salpingotomy (with randomly assigned to a. At 12 months not reported without tubal suturing and or without tubal undergo salpingotomy salpingectomy.[Erratum Age/years (mean (SD)) suturing) without tubal suturing (n=15) Salpingectomy: 21 Unclear whether participants appears in Fertil Steril (n=34) or with tubal suturing (n=19). Salpingotomy: 32* were attempting to get pregnant 1991 Jun;55(6):1213-4], Salpingotomy without Fertility and Sterility, 55, suturing: 30.3 (0.9) All operations were b. At 24 months Method of follow-up not reported. 53-55, 1991 Salpingotomy with suturing: performed by the first 31.5 (0.8) author. The procedure was Salpingectomy: 26 Their cumulative probabilities do

Ref Id Salpingectomy: 30.5 (0.9) done by first injecting a Salpingotomy: 47* not completely match the solution of diluted denominator, therefore it is likely 77644 Gestational age/weeks vasopressin into the * calculated by the technical that women have been lost to (mean (SD)) adjacent mesosalpinx and team by combining the data follow-up and not reported. Country/ies where the into the wall of the tube on for participants who received study was carried out Salpingotomy without the antemesosalpinx side of salpingotomy with and No raw values reported. suturing: 6.3 (0.3) the dilated tube. A 10 - 15 without suturing. Canada Salpingotomy with suturing: mm longitudinal incision Blinding of participants and/or 6.4 (0.2) along the area of maximal those assessing outcomes is not Study type Salpingectomy: 6.8 (0.2) Cumulative probability of distension of the tube was ectopic pregnancy (%) reported.

564 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Randomised controlled then made with the use of trial comparing Size of pregnancy/cm an insulated microdiathermy a. At 12 months Study dates not reported salpingotomy with and (range): 2 - 3 needle, and the product of without suturing, conception was gently Salpingectomy: 0 Other information comparing them with Inclusion criteria removed. Haemostasis was Salpingotomy: 24* historical controls achieved by light application of microdiathermy needle b. At 24 months All participants received undergoing salpingectomy. Unruptured ampullary ectopic laparotomy Therefore, for the and by ligating the vessels pregnancy diagnosed at in the misosalpinx with 6-0 Salpingectomy: 13 purposes of this review laparotomy question, it is a Vicryl. The tubal incision Salpingotomy: 31* retrospective comparative was either left open to heal observational study Exclusion criteria by secondary intention, or * calculated by the technical approximated with 2 to 3 team by combining the data interrupted sutures of 6-0 for participants who received Aim of the study Recurrent tubal pregnancy Vicryl. During the procedure, salpingotomy with and Ruptured tube peritoneal surfaces were without suturing. All data for To compare reproductive continuously irrigated with EP was calculated from a performance of women Solitary tube Ringer's lactate solution. No graph after conservative patients received antibiotics, treatment of ectopic corticosteroids, pregnancy by antihistamines, or dextran. salpingotomy with or without tubal suturing, and The reproductive outcome then to compare results of these patients was then with those after compared with 24 patients salpingectomy. who underwent salpingectomy for their unruptured ampullary Study dates ectopic pregnancy. The data were analysed by the Not reported Student's t-test, ANOVA and life-table analysis. Source of funding

Not reported

565 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Full citation Sample size Interventions Details Results Limitations

Mol,B.W.J., Hajenius,P.J., N=255 Radical surgery All patients who underwent Need for further intervention Part of the study data was Engelsbel,S., (n=157) primary surgical treatment (number of women/total (%)) collected retrospectively. Ankum,W.M., Characteristics for tubal pregnancy in the Van,derVeenF, Conservative Academic Medical Center a. Overall Tubal rupture was significantly Hemrika,D.J., surgery (January 1992 to December more common in those Bossuyt,P.M.M., An Type of surgery performed (n=98) 1995) and the Onze Lieve Radical: 1/157 (0.6) undergoing radical surgery, when economic evaluation of (number/total (%)) Vrouwe Gasthuis Conservative: 18/98 (18.4) compared to those undergoing laparoscopy and open (September 1993 to conservative surgery. surgery in the treatment of Radical open surgery: December 1995) in b. In those undergoing open tubal pregnancy, Acta 118/255 (46.3) Amsterdam were included. surgery Radical and conservative surgery Obstetricia et Radical laparoscopy: 39/255 Data on patients operated are not defined. Gynecologica (15.3) on prior to September 1993 Radical: 0/118 (0) Scandinavica, 76, 596- Conservative open surgery: was collected Conservative: 1/22 (4.5) Other information 600, 1997 22/255 (8.6) retrospectively; the Conservative laparoscopy: remainder was collected c. In those undergoing

Ref Id 76/255 (29.8) prospectively. 287 patients laparoscopy were initially included, but 77878 Gestational age/days (mean 16 were excluded due to Radical: 1/39 (2.6) (SD)) shock, 3 due to heterotopic Conservative: 17/76 (22.4) Country/ies where the pregnancy, and 13 due to study was carried out Radical open surgery: 51.8 insufficient data. Therefore, (Note: 17 women received (14.3) the study population was systemic MTX on an The Netherlands Radical laparoscopy: 51.1 255 patients. outpatient basis, 1 patient (11.2) had a salpingectomy and 1 Study type Conservative open surgery: The diagnosis of tubal was managed expectantly. 1 48 (9.8) pregnancy resulted from woman required a second Prospective observational Conservative laparoscopy: transvaginal ultrasounds reintervention, in the form of study 48.7 (10.2) and serum hCG monitoring, radical open surgery, after (p=0.89) with confirmation at either MTX treatment failure) (Note: some data was laparoscopy or open collected retrospectively) Presence of peritubal surgery. Four groups of Need for a blood transfusion adhesions (number/total (%)) patients could be (number of women/total (%)) Aim of the study distinguished: radical Radical open surgery: 39/118 surgery performed by open a. Overall (33.1) surgery, radical surgery To assess the impact of Radical laparoscopy: 19/39 performed by laparoscopy, the introduction of Radical: 10/157 (6.4) (48.7) conservative surgery laparoscopy in the Conservative: 1/98 (1.0) Conservative open surgery: performed by open surgery,

566 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments treatment of ectopic 4/22 (18.2) and conservative surgery pregnancy on medical Conservative laparoscopy: performed by laparoscopy. b. In those undergoing open costs 2/76 (2.6) The choice of treatment surgery (p=0.17) depended on the clinical Study dates situation and the skills of the Radical: 9/118 (7.6) Tubal rupture (number/total operating gynaecologist. Conservative: 1/22 (4.5) (%)) January 1992 to December Persistent trophoblast was c. In those undergoing 1995 Radical open surgery: 40/118 defined as rising or laparoscopy (33.9) plateauing postoperative Source of funding Radical laparoscopy: 6/39 serum hCG concentrations. Radical: 1/39 (2.6) (15.4) This complication was Conservative: 0/76 (0) Dutch Health Insurance Conservative open surgery: treated by systemic Council, Amstelveen 2/22 (9.1) administration of Conservative laparoscopy: methotrexate (MTX) or by Complication rate (number of 2/76 (2.6) surgery, depending on the women/total (%)) (p<0.01) clinical situation of the (Note: these were all in patient. patients treated with open Inclusion criteria surgery) Costs for each procedure were calculated from the Radical: 2/157 (1.3) Undergoing primary surgical resource use recorded, and (1 case of pneumonia, 1 treatment for tubal pregnancy an economic analysis was urinary tract infection) performed. (Note: only Conservative: 3/98 (3.1) Exclusion criteria outcomes relevant to this (1 case of pneumonia, 1 review will be recorded urinary tract infection, 1 Shock here). thrombo-embolism)

Heterotopic pregnancy Outcomes will be reported for the overall comparison Insufficient data between conservative and radical surgery, and then stratified by whether the surgery was laparoscopic or open.

567 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Full citation Sample size Interventions Details Results Limitations

Colacurci,N., Zarcone,R., N=45 Salpingectomy The authors retrospectively Need for a blood transfusion Retrospective De,Franciscis P., Mele,D., (n=13) analysed the operative (number/total (%)) Mollo,A., de,Placido G., Characteristics course, clinical outcome and Small sample size (N<50) Tubal patency after reproductive performance of Salpingectomy: 0/13 (0) laparoscopic treatment of Salpingotomy (n=32) 45 women with ectopic Salpingotomy: 1/32 (3.1) Unclear how these patients were ectopic pregnancy, Age/years (mean) pregnancy. identified and selected Panminerva Medica, 40, 45-47, 1998 Salpingectomy: 24.5 Subsequent intrauterine 32 were managed by linear pregnancy (number of Not reported whether patients Salpingotomy: 29.2 salpingotomy performed on were trying to conceive Ref Id women/total (%)) the anti-mesenteric border Gestational age/weeks of the tube in the point of Length and method of follow-up 91107 Salpingectomy: 2/11 (18.2) (mean) maximum bulge. The Salpingotomy: 10/26 (38.5) is not reported product of conception was Country/ies where the Salpingectomy: 8.5 flushed out of the incision Outcome of intrauterine study was carried out Salpingotomy: 8.0 using a pressurised flow Repeat ectopic pregnancy pregnancies is not reported from the aquadissector. (number of women/total (%)) Italy Gestation sac diameter/cm Blinding of those assessing The remaining 13 women Salpingectomy: 1/11 (9.1) outcomes is not reported Study type (mean) Salpingotomy: 1/26 (3.8) underwent laparoscopic salpingectomy. No details of the salpingectomy Retrospective comparative Salpingectomy: 2.93 Salpingotomy: 3.3 surgical technique are given (and observational study The authors only analysed very little about the salpingotomy) the patients who showed a Aim of the study (Note: the study was divided normal pelvis and normal Analysis of reproductive outcome into three treatment groups, contralateral tube at the time only includes women with with the salpingotomy group of intraoperative bilateral patent tubes from the To evaluate the operative split in to 2 by hCG > or < examination. The operative salpingotomy arm. course, tubal patency, and 10,000. These have been time and the major reproductive performance combined for the purposes of complications were after laparoscopic Other information this review) recorded. treatment of ectopic Hysterosalpingographic pregnancy in relation to examination was performed initial human chorionic 2-3 months after the gonadotrophin values and operation, and the analysis to the kind of operation. of reproductive outcome only includes the patients

Study dates with bilateral patent tubes (from the salpingotomy

568 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Not reported Inclusion criteria arm).

Source of funding Ectopic pregnancy Statistical analysis was performed using the Exclusion criteria student's t-test, Fisher's Not reported exact test, or chi-squared as appropriate. Not reported Full citation Sample size Interventions Details Results Limitations

Bouyer,J., Job-Spira,N., N=476 Radical This study is based on the Need for further intervention Significant differences between Pouly,J.L., Coste,J., (salpingectomy) Auvergne Ectopic (number/total (%)) tubal rupture, previous ectopic Germain,E., Fernandez,H., (Note: 36 women received (n=178, of which Pregnancy Register. All pregnancy and history of Fertility following radical, medical treatment and their 100 sought to women meeting the Radical: 1/178 (0.6) between the groups at baseline conservative-surgical or outcomes will not be reported become pregnant inclusion criteria were (Note: repeat radical surgery) medical treatment for tubal here, therefore the study again) registered and prospectively Conservative: 14/262 (5.3) Women underwent both pregnancy: A population- population of interest for this followed until the age of 45 (Note: 2 radical, 12 repeat laparotomy and laparoscopy, and based study, British review question is N=440) Conservative years old, to study their conservative surgery) outcomes are not reported Journal of Obstetrics and (salpingotomy) reproductive outcome. The separately Gynaecology, 107, 714- (n=262, of which completeness of the register 721, 2000 Characteristics Repeat ectopic pregnancy 166 sought to is estimated to be 90%. rate (number/total (%)) Outcome of intrauterine become pregnant pregnancies is not reported. Ref Id Age/years (%) again) In each centre, a trained Radical: 10/100 (10) investigator was in charge of Blinding of participants and/or 118736 Conservative: 17/166 (10.2) Radical: case identification, follow up those assessing outcomes is not < 25: 12 and data collection. The reported. Country/ies where the 25 - 29: 24 basic information collected 18-month cumulative rate of study was carried out 30 - 34: 31 for each woman included: spontaneous intrauterine 9.7% of women were lost to ≥ 35: 32 sociodemographic pregnancy (% (95% CI)) follow-up for the fertility France Conservative: characteristics, sexual, outcomes. < 25: 20 gynaecological, reproductive Radical: 57 (44 to 70) Study type 25 - 29: 35 Conservative: 73 (65 to 80) and surgical histories, Other information 30 - 34: 27 conditions of conception, Population based study ≥ 35: 18 smoking habits, results of Hazard ratio (95% CI) 0.56 Chlamydia tests, (0.39 to 0.81) History of infertility (%) Aim of the study characteristics of the ectopic pregnancy, and treatment Radical: 38 procedures used. To investigate the factors Conservative: 23 Adjusted hazard ratios for

569 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments influencing the choice of (p=0.004) For every case, the women intrauterine pregnancies treatment for ectopic were interviewed by (95% CI) pregnancy and to compare Previous miscarriage (%) telephone every six months the subsequent fertility about whether they were a. All women rates of radical, Radical: 30 trying to conceive again, conservative-surgical, or Conservative: 27 whether they had become Radical: 0.72 (0.45 to 1.1) medical treatments. (p=0.57) pregnant again, how long it Conservative: 1 took to become pregnant, (NS) Study dates Previous induced abortion obstetric outcome, time at (%) risk of becoming pregnant, b. Women with infertility use of contraception, and factors, previous EP, 1992 to 1996 Radical: 17 medical measures related to infertility/tubal surgery history, Conservative: 18 infertility. induced pregnancy, or age ≥ Source of funding (p=0.97) 35 (n=173) During the study period, 835 Not reported Previous ectopic pregnancy women were registered, of Radical: 0.60 (0.36 to 1.0) (%) which 476 women met the Conservative: 1 criteria for (NS) Radical: 16 inclusion/exclusion. Of Conservative: 6 these, 46 (9.7%) were lost c. Women with no infertility (p=0.001) to follow-up. Subsequent factors and aged < 35 fertility was therefore (n=118) Induced pregnancy (%) studied for the 291 women who attempted to conceive Radical: 0.85 (0.45 to 1.6) Radical: 9 again at least once during Conservative: 1 Conservative: 6 the study period. (NS) (p=0.32) Treatments were designated Note: adjustments have been Abundant haemoperitoneum as 'radical' (salpingectomy), made for age, university (%) 'conservative surgical' educated, history of infertility, (salpingotomy), and induced pregnancy, tubal Radical: 47 'medical' (methotrexate rupture, normal contralateral Conservative: 18 injection) (details of women tube, nationality (French or (p=0.001) receiving medical not) and size/type of centre. management will not be Tubal rupture (%) reported here, as they are not relevant to this review Radical: 37 question). The surgeries Conservative: 6 were performed by (p=0.001) laparotomy or laparoscopy.

570 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

In some women, the initial Normal contralateral tube (%) treatment was unsuccessful, and they received another Radical: 19 treatment. However, all Conservative: 26 analyses are performed (p=0.16) considering only the initial treatment. Conservative Inclusion criteria surgical treatment was taken as the reference, as it is used most frequently, and Women aged 15 to 44 considered to be the standard treatment for EP. Reside permanently in Auvergne Region, France Analysis

Treated either medically or Two reproductive outcomes surgically for ectopic were evaluated: recurrence pregnancy in one of the of EP, and occurrence of area's health centres spontaneous intrauterine pregnancy. Survival analysis Tubal ectopic pregnancy methods were used, considering the time to Exclusion criteria pregnancy as the cumulative period during Use of contraception at the which the woman was trying time of index ectopic to conceive until she pregnancy became pregnant or was censored. Follow-up was Previously undergone censored if a woman began sterilisation or therapeutic IVF. Cumulative pregnancy bilateral salpingectomy (with rates were calculated using no desire for IVF) Kaplan-Meier estimates. The curves obtained were analysed using both univariate and Cox regression analyses (to take into account confounding variables). The confounders considered were: age, educational level, nationality

571 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

(French origin or not), prior tubal damage, state of contralateral tube, history of infertility,and tubal rupture. The authors also evaluated the size of the treatment centre and whether it was private, public, maternity or surgical. Whether the surgery was laparotomy or laparoscopy was not taken into account, as this is not associated with future fertility.

For the outcome of spontaneous intrauterine pregnancy, the whole sample was analysed. In addition, a subgroup without infertility factors, with no infertility, no history of tubal surgery, and aged younger than 35 were analysed. The authors report that this was done because this group of women would be the main target if a randomised controlled trial was designed. Full citation Sample size Interventions Details Results Limitations

Bangsgaard,N., Lund,C.O., N=276 Salpingectomy Data collection Need for further Retrospective study Ottesen,B., Nilas,L., (n=68) intervention (n) Improved fertility following Characteristics Between January 1992 and Variable length of follow-up, conservative surgical Tubotomy January 1999, 806 surgical Salpingectomy: NR because the questionnaires were treatment of ectopic (n=208) interventions for ectopic Tubotomy: 17 all mailed at one time. pregnancy, BJOG: An Age/years (mean (SD)) pregnancy (EP) were (Note: it is unclear whether International Journal of (Note: these performed at the the denominator is the 208 25% of women were lost to

572 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Obstetrics and Salpingectomy: 30.1 (4.45) procedures are Department of Obstetrics women followed up who were follow-up for fertility outcomes, Gynaecology, 110, 765- Tubotomy: 29.0 (3.97) also referred to as and Gynaecology, Hvidovre attempting to conceive, or the because they did not return their 770, 2003 (p = 0.06) "radical" and University Hospital, whole study population. 9 questionnaires. A further 31 "conservative" Denmark. The following were initially treated with women had emigrated or died Ref Id Nulliparity (number/total surgery at some data was obtained MTX, of which 7 were and were therefore (%)) points in the paper) retrospectively from medical successful and 2 had a uncontactable. If they are 121838 files: baseline demographic salpingectomy, 7 initially had included in the loss to follow-up Salpingectomy: 33/68 (49) data, location of EP, a salpingectomy, and 1 had a calculation, the loss to follow-up Country/ies where the Tubotomy: 131/208 (63) ruptured tube, operation repeat salpingotomy) is 30%. study was carried out (p < 0.05) method, presence of adhesions, condition of Spontaneous intrauterine There were some significant Denmark History of induced abortion contralateral salpinx, pregnancy rate differences between the two (number/total (%)) and surgical history. (number/total (%)) groups at baseline (although Study type some of these were adjusted for Salpingectomy: 21/61 (38) Subsequent fertility was a. Full-term birth in the multivariate analysis). Retrospective cohort study Tubotomy: 58/208 (28) elucidated using a mailed questionnaire. Questions Salpingectomy: 21/68 (30.9) Both laparotomies and History of miscarriage included: desire for laparoscopies were performed. Aim of the study Tubotomy: 88/208 (42.3) (number/total (%)) pregnancy, treatment for infertility, and pregnancy b. Any spontaneous Other information To evaluate fertility after Salpingectomy: 13/68 (19) achieved after operation. intrauterine pregnancy salpingectomy or tubotomy Tubotomy: 58/208 (28) The outcome of the for ectopic pregnancy pregnancy was reported as Salpingectomy: 39/68 (57.4) History of abdominopelvic live birth, miscarriage, Tubotomy: 161/208 (77.4) Study dates surgery (number/total (%)) induced abortion or ectopic pregnancy. For those giving (Note: The outcomes were as Salpingectomy: 9/68 (13) birth, the last menstrual date follows: Surgeries conducted Tubotomy: 23/208 (11) was calculated assuming between January 1992 and Salpingectomy: 21 full-term delivery at 40 weeks births, 9 miscarriages, and 1 January 1999 History of fertility surgery gestation. For miscarriage induced abortion (number/total (%)) or elective abortion, an Tubotomy: 88 full-term birth, Follow-up was in June average gestational age of 8 2000 36 miscarriages, 5 induced Salpingectomy: 7/68 (10) weeks was used for abortions, and 4 continuing Tubotomy: 16/208 (8) calculation of last menstrual pregnancies) Source of funding date. The questionnaire was Peri-operative adhesion mailed in June 2000, which Repeat ectopic pregnancy Not reported (number/total (%)) resulted in at least 18 months follow-up for all rate (number/total (%)) Salpingectomy: 30/68 (44) women. Tubotomy: 64/208 (31) Salpingectomy: 8/68 (11.8)

573 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

(p < 0.05) Study population Tubotomy: 28/208 (13.5)

Peri-operative contralateral Of the 651 women who pathology (number/total underwent surgery for their Hazard ratio for the (%)) first EP during that time, 46 occurrence of spontaneous did not meet the age criteria, intrauterine Salpingectomy: 17/68 (25) 11 had previously been pregnancy (95% CI) Tubotomy: 30/208 (14) sterilised, 28 had other (p < 0.05) types of surgery, and 48 - Univariate analysis: were not histologically Salpingectomy: 0.582 Rupture (number/total (%)) verified. In 39 cases, the EP (0.393 to 0.861) was as a result of fertility Tubotomy: 1 Salpingectomy: 19/68 (28) treatment, and 31 women Tubotomy: 7/208 (3) were not available for follow- - Multivariate analysis: (p < 0.001) up (death/emigration). Salpingectomy: 0.630 Therefore, 473 women (0.421 to 0.940) IUCD in situ (number/total satisfied selection criteria Tubotomy: 1 (%)) and were sent a questionnaire. 355 (75%) Salpingectomy: 4/68 (6) women returned the Tubotomy: 10/208 (5) questionnaire, and of these, Hazard ratio for the 79 had not attempted occurrence of repeat Type of surgery conception. Therefore, 276 ectopic pregnancy (95% CI) women were included in the - Laparoscopy analysis. The characteristics - Univariate analysis: Salpingectomy: 52/68 (76) of the 118 women lost to Salpingectomy: 0.785 Tubotomy: 193/208 (93) follow-up did not differ (0.358 to 1.724) significantly from those Tubotomy: 1 - Laparotomy available for analysis with Salpingectomy: 16/68 (23) respect to surgical - Multivariate analysis: Tubotomy: 15/208 (7) intervention. Salpingectomy: 0.782 (0.348 to 1.755) Tubotomy: 1 Inclusion criteria Analysis

The women were divided (Note: the multivariate First, spontaneous, into two groups based on analysis is adjusted for age, histologically verified tubal whether they had received contralateral tube pathology ectopic pregnancy radical surgery and previous fertility (salpingectomy) or operation) Treated with salpingectomy conservative surgery

574 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

or linear tubotomy (tubotomy). Cumulative probabilities of spontaneous Aged 17 to 38 years old intrauterine pregnancy over time were calculated using Actively attempting to the Kaplan-Meier estimator. conceive post-operatively The starting point for the calculations was the date of Exclusion criteria the operation. The endpoint was the date of accomplished spontaneous Previously sterilised intrauterine pregnancy. If pregnancy was obtained Bilateral salpingectomy through infertility treatment (28 in conservative group, 12 in radical group), the woman was censored from the analysis on the date the treatment began. The endpoint for women who did not become pregnancy was the last date of contact. Cumulative probabilities of repeated ectopic pregnancy were calculated in the same way.

Cox proportional hazard regression analysis was used to compare the effect of conservative surgery with radical surgery, and to take into account potential confounding factors through multivariate analysis. The covariate factors were tested for time consistency, log linearity, and additivity before the analysis was performed. Potential confounders adjusted for in

575 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

the multivariate analysis were: age, contralateral tube pathology and previous fertility surgery. Full citation Sample size Interventions Details Results Limitations

Becker,S., Solomayer,E., N=261 Salpingectomy 261 patients presenting with Need for further Intention-to-treat analysis was not Hornung,R., Kurek,R., (n=51) a subsequently confirmed intervention (number/total done. The 4 patients who Banys,M., Aydeniz,B., (However, only 196 patients ectopic pregnancy (%)) underwent a subsequent Franz,H., Wallwiener,D., Salpingotomy underwent routine surgical salpingectomy for persistent Fehm,T., Optimal desired a new pregnancy and therefore constitute the main (n=145) treatment. Treatment Salpingectomy: NR ectopic pregnancy were included treatment for patients with included a diagnostic Salpingotomy: 9/183 (4.9) in the salpingectomy ectopic pregnancies and a population of interest for this review question) laparoscopy, followed by (Note: 4 salpingectomy, 4 group. Those who underwent history of fertility-reducing either a laparoscopic treatment with MTX, 1 repeat methotrexate treatment (n=4) or factors, Archives of salpingectomy, or a salpingotomy) repeat salpingotomy (n=1) were Gynecology and Characteristics laparoscopic linear included in the salpingotomy Obstetrics, 283, 41-45, salpingotomy with tubal group. 2011 Subsequent intrauterine The following data is reported conserving removal of the pregnancy (number/total for the total population who EP. Baseline characteristic data is not Ref Id (%)) were available for follow-up reported separately for those (N=261), and for those with a The decision of which undergoing salpingectomy and 121843 Salpingectomy: 25/51 (49.0) desire for pregnancy (n=196). surgical approach to take Salpingotomy: 122/145 salpingotomy, therefore there was left to the surgeon may be unreported differences Country/ies where the (84.1) (done intraoperatively), and between the two populations. study was carried out Age/years (median (range)) (p<0.01) was based on the individual (Note: there is some situation. The authors report Median duration of follow-up is Germany Total: 31 (19 - 43) inconsistency in reporting, but Desiring pregnancy: 30 (19 - that a large EP or ruptured this appears to be any IUP reported for whole study EP made a salpingectomy population, but no further details Study type 42) because the paper states that more likely; however the 129 women reported at least are reported (e.g. any split by decision was also based on type of surgery). Nulliparity (number/total one successful delivery) Prospective follow-up consideration of the factors study (%)) such as peritubal adhesions. Blinding of participants and/or Repeat ectopic pregnancy those assessing outcomes is not Total: 126/261 (48) (number/total (%)) Aim of the study Patients were recruited for reported. Desiring pregnancy: 109/196 (56) prospective follow-up, following informed consent Salpingectomy: 7/51 (13.7) There is a discrepancy in the To evaluate the about the nature of the Salpingotomy: 11/145 (7.6) reporting of how many reproductive outcome after Presence of fertility- study. Basic information (p=0.2) pregnancies ended in delivery, salpingotomy when reducing risk factors about each patient was therefore only overall intrauterine compared with (number/total (%))

576 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments salpingectomy, particularly obtained (see Reproductive outcome, pregnancy rates have been with regards to the pre- - Previous abdominal characteristics), and stratified by presence or reported here. existing presence of surgery: patients were then absence of fertility- fertility-reducing factors. Total: 113/261 (43) contacted over a 5-year reducing factors Other information Desiring pregnancy: 81/196 period and interviewed (number/total (%)) Study dates (41) about subsequent reproductive events. a. Patients with fertility- Time to conception - Previous induced Information regarding desire reducing factors (n=111) Not reported abortion: for future pregnancy and 85% of all reproductive events Total: 16/261 (6) history of subsequent - Intrauterine pregnancy took place within the first 2 years Source of funding Desiring pregnancy: 8/196 (4) pregnancies was recorded. Salpingectomy: 17/43 (39.5) after the initial EP. 10% occurred 196 women (75%) reported Salpingotomy: 51/68 (75) in the third year, 5% in the fourth year and 0% in the fifth year. Not reported - Previous miscarriage: an active desire for a new (p<0.01) Total: 71/261 (27) pregnancy following Desiring pregnancy: 47/196 completion of treatment, and - Ectopic pregnancy (24) were followed up for a Salpingectomy: 7/43 (16.3) median of 5 years. The Salpingotomy: 9/68 (13.2) - Previous ectopic effect of fertility reducing (NS) pregnancy: factors on outcomes was Total: 49/261 (19) also examined. b. Patients without fertility- Desiring pregnancy: 40/196 reducing factors (n=85) (20) Chi-squared test was used to examine the relationship - Intrauterine pregnancy - Previous pelvic between categorical factors. Salpingectomy: 8/8 (100) inflammatory disease: p<0.05 was considered Salpingotomy: 71/77 (92.2) Total: 39/261 (15) statistically significant. (NS) Desiring pregnancy: 30/196 (15) - Ectopic pregnancy Salpingectomy: 0/8 (0) - Peritubal adhesions: Salpingotomy: 2/77 (2.6) Total: 78/261 (30) (NS) Desiring pregnancy: 59/196 (30) (Note: fertility reducing factors are listed as contralateral Type of surgery tube damage, history of PID, (number/total (%)) history of abdominal surgery, previous ectopic pregnancy, - Salpingectomy: previous miscarriage, Total: 78/261 (30) previous induced abortion) Desiring pregnancy: 51/196

577 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

(26)

- Salpingotomy: Total: 183/261 (70) Desiring pregnancy: 145/196 (74)

Note: - 111 women had at least one fertility-reducing factor, of which 43 had a salpingectomy and 68 had a salpingotomy. - 85 women had no fertility- reducing factors, of which 8 had a salpingectomy and 77 had a salpingotomy.

Inclusion criteria

Clinically proven tubal ectopic pregnancy (EP)

At least 18 years old

Exclusion criteria

History of previous ectopic pregnancies

Pre-operative decision to remove the tube, regardless of the intraoperative situation

578 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Full citation Sample size Interventions Details Results Limitations

DeCherney,A., Kase,N., N=98 Radical surgery The hospital charts of 98 Delivery of a viable Retrospective The conservative surgical (salpingectomy or women with a tubal ectopic intrauterine pregnancy management of unruptured Characteristics salpingo- pregnancy (EP) during the (number/total (%)) Unclear how they followed up ectopic pregnancy, oophorectomy) study period were reviewed. women to elucidate subsequent Obstetrics and (n=50) 50 had radical surgery for Radical: 21/50 (42) fertility Gynecology, 54, 451-455, Age/years (mean) both ruptured and Conservative: 19/48 (39.6) 1979 Conservative unruptured EP. Radical Length of follow-up varied, and Radical: 29.3 surgery (linear surgery is defined as the was not reported separately for Ref Id Conservative: 28.3 Repeat ectopic pregnancy salpingostomy) removal of a tube, or tube (number/total (%)) the conservative and radical (n=48) and ovary at the time of groups. 121877 surgery. In this study, Radical: 6/50 (12) conservative treatment Inconsistency of reporting for Country/ies where the Conservative: 9/48 (18.8)* Inclusion criteria consisted of a linear repeat EP rate in conservatively study was carried out salpingostomy. The * This value is reported on managed group operation was not chosen USA Ampullary ectopic pregnancy two separate occasions in the based on the severity of the study, however a rate of Unclear whether laparotomy or condition, but was the laparoscopy was performed; not Study type 11.6% is reported in the table Exclusion criteria choice of the operating reported how many women had physician. Radical treatment oophorectomy in addition to Retrospective comparative Tubal abortion was used primarily in salpingectomy. observational study ruptured EP, whereas all of Isthmic ectopic pregnancy those treated conservatively Those with ruptured EP all had Aim of the study had unruptured EP. Patients radical treatment (% rupture is Ectopic not in in both groups were not reported) matched for age and parity. To evaluate conservative This was achieved by Blinding of participants and/or management of ectopic selecting 48 salpingotomy those assessing outcomes is not pregnancy patients and then finding reported. suitable radical cases. Study dates Pairing was based on age Unclear how cases were selected and parity from the same for inclusion 1973 to 1977 year. Other information Conservative surgical

Source of funding technique All patients were trying to Not reported The tube was grasped in the conceive area over the EP, and the

579 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

antimesenteric wall was incision. The products of conception were evacuated by blunt and sharp dissection. Cautery was used to control bleeding along the edges of the tube and at the base of the site of implantation. Continuous, vigorous saline lavage was used throughout. Neither operating microscope or loupes were used, although principles of good microsurgery were followed. Closure by primary or secondary intention was accomplished with a 5-0 vicryl suture. No attempt was made at surgery to determine the patency of the contralateral tube.

80% of the cases in the conservative arm received prophylactic antibiotics, and 45% received dexamethasone and promethazine intra- abdominally every 4 hours after surgery for 12 doses. 5% of conservatively managed cases received intra-abdominal low molecular weight dextran. 15% of the radically treated group received antibiotics at some point during their course of treatment. None received dexamethasone,

580 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

promethazine, or low molecular weight dextran.

Outcomes evaluated

The groups were compared for their outcomes. Viable pregnancies and repeat EP were reported. Miscarriages were not included in the statistics. The average duration of follow-up was 2.4 years, but varied from 1 to 4 depending on when the surgery was done. Full citation Sample size Interventions Details Results Limitations dela,Cruz A., N=90 Radical surgery A retrospective chart review Intrauterine pregnancy within Retrospective study Cumming,D.C., Factors (salpingectomy) was performed to identify 3 years (number of determining fertility after Characteristics (n=56) women who had undergone women/total (%)) Details of surgical methods are conservative or radical surgery for ectopic not reported. Not reported surgical treatment for Conservative pregnancy at the University a. Term pregnancy whether participants had a ectopic pregnancy, Fertility Age/years (mean (SEM)) surgery (linear of Alberta Hospital during laparoscopy or laparotomy and Sterility, 68, 871-874, salpingostomy) the study period. 193 Radical: 21/56 (37.5) 1997 Radical: 28.0 (0.6) (n=34) women were identified, Conservative: 16/34 (47.1) When comparing overall data, Conservative: 27.7 (0.9) however 103 were excluded and the data stratified by history

Ref Id (NS) because they did not *RR (95% CI) 0.8 (0.49 of infertility, the number of term attempt conception (n=36), to 1.3) pregnancies reported in each 121881 Gravidity (mean (SEM)) had a history of previous EP group do not match - 1 term (n=46), had an absent b. Miscarriage pregnancy is misclassified in one Country/ies where the Radical: 2.1 (0.2) contralateral tube (n=5), of the analyses. study was carried out Conservative: 2.7 (0.3) were lost to follow-up (n=9), Radical: 6/56 (10.7) (NS) or refused to participate Conservative: 7/34 (20.6) 9/193 (4.7%) of the original Canada (n=7). A subset of 90 ectopic pregnancy patients were Previous infertility (n (%)) women who fit the inclusion c. Any intrauterine lost to follow-up. Study type criteria was then identified. pregnancy (term + Radical: 30 (54) miscarriage) Other information Retrospective comparative Conservative: 13 (38) Conservative surgery (NS) consisted of a linear Radical: 27/56 (48.2)

581 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments study salpingostomy. Radical Conservative: 23/34 (67.6) The % reported in the Previous PID (n (%)) surgery was defined as stratification above do not match Aim of the study salpingectomy. *RR (95% CI) 0.71 (0.5 those reported in the paper, Radical: 26 (46) to 1.02) because the authors used the Conservative: 14 (41) Data obtained from the chart To examine factors total with/without infertility as their review included age, denominator and did not split it by determining choice of Past IUD use (n (%)) obstetric history, menstrual radical or conservative Repeat ectopic pregnancy type of surgery. history, past infertility, within 3 years (number of surgical procedure for Radical: 15 (27) history of pelvic infections, tubal ectopic pregnancy, women/total (%)) Conservative: 4 (12) and use of IUCD. A copy of and evaluate subsequent (p=0.09) the surgical report was pregnancy rates. Radical: 10/56 (17.9) obtained, and when Conservative: 4/34 (11.8) Tubal adhesions (n (%)) available from the chart, Study dates information about *RR (95% CI) 1.52 (0.52 to Radical: 30 (54) subsequent fertility was 4.46) 1987 to 1991 Conservative: 14 (41) noted. The chart data, and (NS) any further information concerning subsequent STRATIFIED ANALYSES Source of funding Abnormal contralateral tube reproductive history, was (n (%)) verified by direct contact Intrauterine pregnancy rate Not reported with all patients. (term + miscarriage), stratified Radical: 24 (43) by past infertility (number of Conservative: 12 (35) The main outcome measure women/total (%)) (NS) was the occurrence of a live birth or ectopic pregnancy at a. Past infertility (n=43) No risk factor (n (%)) 3 years of follow-up after the index ectopic pregnancy. Radical: 10/30 (33.3) Radical: 12 (21) Conservative: 7/13 (53.8) Conservative: 11 (31) (NS) * RR (95% CI) 0.62 (0.30 to 1.26)

Inclusion criteria b. No past infertility (n=47)

Undergoing surgery for a first Radical: 16/26 (61.5) ectopic pregnancy during the Conservative: 17/21 (81.0) study period *RR (95% CI) 0.76 (0.53 Subsequently attempting to 1.10) conception

582 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Traceable for follow-up Term pregnancy rate, stratified by past infertility Exclusion criteria (number of women/total (%))

a. Past infertility Absent contralateral tube Radical: 8/30 (26.7) No attempt to conceive Conservative: 3/13 (23.1)

Lost to follow-up *RR (95% CI) 1.16 (0.36 to 3.67)

b. No past infertility

Radical: 12/26 (46.2) Conservative: 14/21 (66.7)

*RR (95% CI) 0.69 (0.41 to 1.16)

Ectopic pregnancy rate, stratified by past infertility (number of women/total (%))

a. Past infertility

Radical: 10/30 (33.3) Conservative: 3/13 (23.1)

*RR (95% CI) 1.44 (0.47 to 4.40)

b. No past infertility

Radical: 0/26 (0) Conservative: 1/21 (4.8)

*RR (95% CI) 0.27 (0.01

583 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

to 6.34)

* calculated by the NCC technical team Full citation Sample size Interventions Details Results Limitations

Gruft,L., Bertola,E., N=115 Salpingectomy The medical records of 265 Live births (number/total (%)) Retrospective comparative Luchini,L., Azzilonna,C., (n=71) women who consecutively observational study Bigatti,G., Parazzini,F., underwent surgery for Salpingectomy: 23/71 (32.4) Determinants of Characteristics Salpingotomy ectopic pregnancy at the Salpingotomy: 12/44 (27.3) 33% of the original patients who reproductive prognosis Obstetric and Gynaecology underwent surgery for ectopic after ectopic pregnancy, Age at surgery/years (n (%)) (n=44) Clinic, Milan, between 1985 pregnancy could not be Human Reproduction, 9, and 1990 were reviewed. contacted 1333-1336, 1994 ≤29: 54 (47) 3-year cumulative live birth Information regarding rate (%) 30-34: 41 (36) operative findings, condition Blinding not reported Ref Id ≥35: 20 (17) of the contralateral tube, Salpingectomy: 38 and surgical procedures Variable length of follow-up. 121913 Salpingotomy: 37 Contralateral tube status (n were collected. Length of follow-up is not (%)) reported separately for the Country/ies where the Note: it is reported that out of salpingectomy and salpingotomy study was carried out All subjects who could be 70 pregnancies, 13 were Intact: 49 (43) located were interviewed by arms Non-intact: 19 (17) ectopic, but does not report Italy telephone in order to obtain how many women this was information on their general Baseline characteristics are not and what type of surgery they reported separately for those Study type (note: missing data from 42 characteristics, reproductive women, and in 5 there was had. However, they do report undergoing different types of outcomes, contraceptive that there was no significant an absent tube) habits, active attempts at surgery, therefore there could Retrospective relationship between type of pregnancy, and subsequent have been significant differences observational study surgery and the risk of at baseline (i.e. status of other pregnancies. Information recurrent ectopic pregnancy. was obtained for 177 tube) Aim of the study Women analysed did not women (67%), and of these differ from those lost to 62 reported that they had Other information To analyse the follow-up for the outcomes of: not attempted another determinants of age, type of surgery, and pregnancy. Therefore, the All laparotomy reproductive prognosis and contralateral tube status. analysis included 115 ectopic pregnancy women who reported active recurrence rate in a series attempts at pregnancy. Data of women who underwent Inclusion criteria was obtained up to October conservative or radical 1992. The median length of

584 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments surgery for ectopic Undergoing laparotomic follow-up was 26 months pregnancy surgery for ectopic pregnancy (range 2 - 83).

Study dates Attempting another Analysis pregnancy 1985 to 1990 (interval The length of follow-up was when the surgeries were Exclusion criteria the time of surgery to the conducted) time of the interview. The Not reported cumulative proportion of Follow-up data was women who became obtained up to October pregnant or gave birth was 1992 calculated by the product- limit method, and the curves obtained were compared Source of funding using the log-rank test. The odds ratios and Not reported corresponding 95% confidence intervals of a further ectopic pregnancy were calculated. Full citation Sample size Interventions Details Results Limitations

Kuroda,K., Takeuchi,H., N=83 Salpingectomy During the study period, 180 Subsequent intrauterine Retrospective Kitade,M., Kikuchi,I., (n=40) laparoscopic surgeries were pregnancy (number/total (%)) Shimanuki,H., Kumakiri,J., Characteristics performed for tubal Not reported whether the Kobayashi,Y., Kuroda,M., Linear pregnancies, of which 163 Salpingectomy: 17/40 (42.5) participants in each arm were Takeda,S., Assessment of salpingo(s)tomy were treated with Salpingo(s)tomy: 24/43 (55.8) attempting to conceive or not. tubal disorder as a risk Age/years (mean (SD)) (n=43) laparoscopic linear factor for repeat ectopic salpingo(s)tomy or Unclear why only 83/163 women pregnancy after Salpingectomy: 30.3 (5.2) salpingectomy. The focus of Repeat ectopic pregnancy were followed up for at least 6 laparoscopic surgery for Salpingo(s)tomy: 30.2 (4.4) this study was the post- (number/total (%)) months. Length of follow-up in tubal pregnancy, Journal of (p=0.930) operative pregnancy in 83 each arm is not reported. Obstetrics and women who were monitored Salpingectomy: 7/40 (17.5) Gynaecology Research, Gestational age/weeks for at least 6 months. Salpingo(s)tomy: 4/43 (9.3) Outcome of intrauterine 35, 520-524, 2009 (mean (SD)) pregnancy is not reported. Tubal pregnancy

Ref Id Salpingectomy: 7.1 (1.2) management protocol Choice of surgical procedure was Salpingo(s)tomy: 6.9 (1.2) affected by future fertility desires. (p=0.585)

585 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

121949 When ectopic pregnancy Past history of ectopic was strongly suspected, and Blinding of participants and/or Country/ies where the pregnancy (n (%)) the patient's pneumocardiac those assessing outcomes is not study was carried out condition was stable, reported. Salpingectomy: 6/40 (15.0) pneumoperitoneal Japan Salpingo(s)tomy: 4/43 (9.30 laparoscopy was performed. The terms "salpingostomy" and (p=0.511) Indications for "salpingotomy" have both been Study type salpingo(s)tomy were a used interchangeably in this Inclusion criteria patient's desire for future study to refer to the same Retrospective comparative conception, and a non- procedure observational study ruptured tubal mass less Tubal pregnancy treated with than 5 cm in greatest Other information laparoscopic linear diameter. Salpingectomy Aim of the study salpingo(s)tomy or was performed if these salpingectomy criteria were not satisfied. To evaluate tubal disorders, including Exclusion criteria Laparoscopy procedure peritubal adhesions, as risk factors for repeat Treated with milking of the Laparoscopy was performed ectopic pregnancy after tube, peritoneal lavage, or using the 4-puncture laparoscopic linear single dose focal method with the patient salpingo(s)tomy or methotrexate (n=17) under general salpingectomy for tubal anaesthesia with pregnancy. Persistent ectopic pregnancy endotracheal intubation, in after linear salpingo(s)tomy the lithotomy position. For Study dates (n=6) linear salpingo(s)tomy, the location of the ectopic Salpingectomy prior to linear pregnancy was confirmed, August 1992 to December and vasopressin was 2005 salpingo(s)tomy (n=4) administered into the No tube remaining after mesosalpinx. The tubal Source of funding salpingectomy (n=5) serosa and muscle layer were incised with scissors Not reported and the ectopic pregnancy removed with grasping forceps. Indigo carmine was infused from the uterine manipulator for the evaluation of tubal muscular damage. The tubal muscle

586 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

layer and serosa were then sutured continuously with Vicryl 3-0.

For salpingectomy, after examining the tubal pregnancy site, we severed the junction of the proximal tube and uterus, cut through the mesosalpinx to the ampulla of the oviduct with bipolar forceps or a LigaSure Atlas sealer, and extirpated the tube. Adhesions to the preserved tube were severed with a monopolar needle. If was present salpingostomy was performed; we identified the thin texture of hydrosalpinx on the distal side of the tube, cut with a monopolar needle, turned over the mucosa and sutured and ligated.

Analysis

Comparisons between the two groups were made using the Student's t-test, the Mann-Whitney test, Fishers exact test or Kruskal Wallis, with p<0.05 as the level of significance.

587 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Full citation Sample size Interventions Details Results Limitations

Langebrekke,A., N=150 Laparoscopic During the study period, 195 Spontaneous intrauterine Retrospective Sornes,T., Urnes,A., salpingectomy women were treated for an pregnancy rate (number/total Fertility outcome after (98 of these women desired a (n=76, of which 40 ectopic pregnancy in the (%)) Varying length of follow-up. The treatment of tubal future pregnancy and hence wanted to Department of Obstetrics average follow-up in each group pregnancy by laparoscopic constitute the conceive) and Gynaecology of the a. Pregnancy at term or > 17 is not reported. laser surgery, Acta main population of interest) Akershus Central Hospital, weeks gestation Obstetricia et Laparoscopic linear Norway. Of these, 150 were Baseline characteristics of the Gynecologica Characteristics salpingotomy treated by operative Salpingectomy: 18/40 (45) study population are not reported. Scandinavica, 72, 547- (n=74, of which 58 laparoscopy and hence Salpingotomy: 38/58 (65.5) 549, 1993 wanted to constitute the population of Details of the surgeries are not Desire for pregnancy conceive) interest. b. Miscarriage given.

Ref Id (number/total) Contraindications to Salpingectomy: 1/40 (2.5) Blinding of participants and/or 121953 Salpingectomy: 40/76 laparoscopy were: Salpingotomy: 2/58 (3.4) those assessing outcomes is not Salpingotomy: 58/74 - haemodynamic instability reported. Country/ies where the - interstitial pregnancy c. Total spontaneous study was carried out Inclusion criteria - unfamiliarity with the intrauterine pregnancies The decision to conserve the endoscopic approach tube was based on factors such Norway Treated for ectopic Salpingectomy: 19/40 (47.5) as desire for pregnancy, past Radical treatment was Salpingotomy: 40/58 (69.0) history, and condition of tubes. Study type pregnancy using laparoscopy chosen for women with no desire for future fertility, and Repeat ectopic pregnancy Other information Retrospective Exclusion criteria cases with a ruptured tubal observational study (number/total (%)) pregnancy or tubal gestation Not reported of more than 5 cm in All laparoscopy Salpingectomy: 4/40 (10) Aim of the study diameter. 76 cases had a Salpingotomy: 4/58 (6.9) laparoscopic salpingectomy. No loss to follow-up In 74 cases, treatment was Not stated conservatively performed by linear salpingotomy with Study dates carbon dioxide laser laparoscopy. December 1988 to October 1990 During January 1992, a questionnaire was sent to all 150 patients. Information

Source of funding was collected on pregnancy desire and outcome, length

588 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Not reported of pregnancy desire, infertility operations, and IVF attempts. In five cases a repeat letter was sent, and five patients were contacted by telephone. The authors obtained a response rate of 100%. The follow-up period ranged from 15 to 37 months. Full citation Sample size Interventions Details Results Limitations

Mecke,H., Semm,K., N=202 Salpingectomy Operative procedure Need for further intervention Retrospective Lehmann-Willenbrock,E., (n=25) (number/total (%)) Results of operative Characteristics A 5-mm optical trocar was Unclear why only 74/153 pelviscopy in 202 cases of Salpingotomy Salpingectomy: 0/25 (0) (48%) women had fertility ectopic pregnancy, introduced into the (n=153) abdominal cavity through an outcomes reported (i.e. were the International Journal of Age/years (mean (range)): 29 Salpingotomy: 14/153 (9.2) rest lost to follow-up or just not Fertility, 34, 93-94, 1997 (19 - 45) umbilical incision. A 5-mm (Note: the study instrument trocar was desiring pregnancy) (Note: re-pelviscopy or Ref Id History of previous tubal population includes introduced through a small a further 24 cases left lateral suprapubic laparotomy for postoperative Unclear how fertility outcomes surgery (number/total (%)) bleeding (n=5), infection were assessed (they were 121982 of tubal abortion in incision. Once the diagnosis whom the tube was was confirmed, a 5-mm (n=1), unexplained pain or followed up for 1-6 years). On contralateral tube: 26/202 positive pregnancy test after Country/ies where the conserved, trocar was introduced on the (13) 10 days (n=5), laparotomy in Baseline characteristics not study was carried out On same tube: 24/202 (12) however they were right side and an 11-mm not part of the trocar in the midline another facility (n=1), reported for haematosalpinx (n=2)) salpingectomy/salpingotomy Germany main comparison of suprapubically. The Future fertility desires interest for this umbilical incision was then groups separately

Study type (number/total (%)) review question) dilated to introduce the 11- Surgical complications mm operation optic. (number/total (%)) Reporting of pain also includes Desire for more children: women with a positive pregnancy Retrospective comparative 166/202 (82.2) a. Infection test 10 days after operation observational study Fresh and coagulated blood No desire for more children: 36/202 (17.8) was removed from the Choice of surgery was partially abdominal by irrigation with Salpingectomy: 0/25 (0) Aim of the study dependent on future fertility saline and suction, and one Salpingotomy: 1/153 (0.7) Inclusion criteria desires. The future fertility of of the following procedures those receiving a salpingectomy Not stated b. Postoperative bleeding was performed: is not reported. Women with a Ectopic pregnancy treated Salpingectomy: 0/25 (0) tubal abortion and those treated

589 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Study dates with pelviscopy during the Salpingectomy: Salpingotomy: 5/153 (3.3) with salpingotomy are lumped study period If the patient had completed together. 1978 to 1987 her family and consented, a Note: the women who Exclusion criteria pelviscopic salpingectomy experienced these Blinding of participants and/or was performed. The tube complications are also those assessing outcomes is not Source of funding was resected with hook included in those requiring reported. Not reported scissors after ligation with further intervention. Not reported three endoloops and then Other information removed through the 11-mm Positive pregnancy test or trocar with the spoon unexplained abdominal forceps. The tubal stump pain 10 days later requiring was then coagulated with diagnostic the point coagulator. pelviscopy (number/total (%))

Tubal abortion: Salpingectomy: 0/25 (0) In the case of tubal abortion, Salpingotomy: 5/153 (3.3) blood and blood clots were removed using an (Note: these are included in aquapurator, and the need for further intervention aspirate was passed above) through a sieve for histological analysis. Materials located between Subsequent intrauterine the fimbria were removed pregnancy (number/total (%)) with biopsy forceps. Salpingotomy was a. Any intrauterine pregnancy performed if there was any doubt concerning the Salpingectomy: NR complete removal of the Conservative treatment: products of conception from 42/74 (56.8) the tube. b. Children born Salpingotomy: In cases of an intact isthmic Salpingectomy: NR or ampullary ectopic Conservative treatment: pregnancy, salpingotomy 34/74 (45.9) was performed. 20-30 ml of POR solution (ornipressin in Repeat ectopic pregnancy saline) was injected into the (number/total (%)) mesosalpinx to achieve

590 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

vasoconstriction. A longitudinal antimesenteric Salpingectomy: NR incision was made in the Conservative treatment: tube with the microscissors 10/74 (13.5) after previous coagulation of the intended incisional site. The products of conception were then removed with 11- mm spoon forceps and biopsy forceps, followed by complete cleaning of the operation site, including irrigation of the tube. Early on, the tube was left open. However, from 1982 to 1985 the wound was closed using catgut endosuture with extracorporal knotting. From 1985 onwards, only 4/0 PDS with intracorporal knotting was used, adapting only the tunica serosa and the most superficial layer of the tunica muscularis when necessary.

In all cases, a full abdominal lavage using saline was done, and a Robinson drain was placed in the cul-de- sac. The total duration of the operation was around 45 minutes and patients were discharged 3-5 days later. Postoperative follow-up with hCG assay was mandatory.

591 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Full citation Sample size Interventions Details Results Limitations

Mol,B.W.J., N=135 Radical surgery All eligible patients who Spontaneous intrauterine Retrospective Matthijsse,H.C., (salpingectomy) underwent primary surgery pregnancy rate (number of Tinga,D.J., Huynh,T., Characteristics (n=79) for tubal pregnancy in the women/total (%)) There were significant differences Hajenius,P.J., Academic Medical Centre, between the two groups at Ankum,W.M., Conservative Amsterdam, and the a. Pregnancy ending in baseline: previous PID, Bossuyt,P.M.M., Age/years (mean (SD)) surgery Academic Hospital, delivery homolateral tubal pathology, van,derVeenF, Fertility (salpingo(s)tomy) Gronigen, during the study contralateral tubal pathology, and after conservative and Radical: 31.4 (4.8) (n=56) period were included. Tubal Radical: 18/79 (22.8) % receiving a laparoscopy. radical surgery for tubal Conservative: 30.1 (5.6) pregnancy was diagnosed Conservative: 22/56 (39.3) pregnancy, Human (P=0.24) by combined transvaginal 14/193 (7%) of women were lost Reproduction, 13, 1804- sonography and serum hCG b. Any intrauterine pregnancy to follow-up. 1809, 1998 Nulliparity (n (%)) measurement. Data on treatment was obtained (Note: this includes delivery, Unclear at what date follow-up

Ref Id Radical: 19 (24) retrospectively from medical miscarriage, elective was done, therefore length of Conservative: 22 (39) files. termination, unknown follow-up may have differed 121992 (p=0.07) outcome) between the groups. During the study period, 237 Country/ies where the Homolateral EP in history (n patients underwent surgery Radical: 24/79 (30.4) Blinding of participants and/or study was carried out (%)) for tubal ectopic pregnancy. (Note: 18 deliveries, 2 those assessing outcomes is not However, 6 were treated by elective termination, 1 reported. The Netherlands Radical: 4 (5) milking or had complete miscarriage, 3 unknown Conservative: 0 (0) expulsions, 24 had only one outcome) Study type Other information (p=0.08) tube, 7 had an EP resulting Conservative: 30/56 (53.6) from IVF, and 7 had both of (Note: 22 deliveries, 2 Retrospective cohort study Contralateral EP in history (n the latter two criteria. Of the elective termination, 6 (%)) remaining 193 patients, 2 miscarriage)

Aim of the study had a heterotopic Radical: 3 (4) pregnancy, 14 were lost to In addition, 18 women had Conservative: 2 (4) follow-up, and 42 patients IUP as a result of IVF (14 To evaluate, by life-table (p=0.91) did not try and conceive from radical, 4 from analysis, the effectiveness again. Therefore, 135 conservative). of conservative and radical Previous tubal surgery (n patients were available for surgery towards fertility (%)) analysis. outcome, and the influence Ectopic pregnancy rate of pre-existing tubal (number of women/total (%)) Radical: 16 (21) Two treatment groups were disease on such Conservative: 5 (9) defined. Radical surgery effectiveness. Radical: 7/79 (8.9) (p=0.07) was defined as salpingectomy, and

592 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Study dates Previous PID (n (%)) conservative as Conservative: 5/56 (8.9) salpingo(s)tomy. Surgery January 1990 to August Radical: 15 (18) was either by laparoscopy 1993 Conservative: 5 (9) or open surgery. (p=0.04) Information on age, parity, 3-year cumulative pregnancy Source of funding Subfertility at time of EP (n previous EP, prior tubal rates (%) (%)) surgery, previous PID, Not reported subfertility, surgical a. Spontaneous IUP Radical: 8 (10) modality, and tubal Conservative: 5 (9) pathology encountered at Radical: 38 (p=0.82) surgery was extracted from Conservative: 62 medical files. Data on (P<0.001) Homolateral tubal pathology subsequent fertility was (n (%)) obtained by reviewing b. Ectopic pregnancy medical files and, when this Radical: 40 (51) information was insufficient, Radical: 23 Conservative: 9 (16) by telephone interviews with Conservative: 28 (p<0.01) patients. In all patients, the (p=0.07) exact time-frame in which Contralateral tubal pathology they were trying to conceive (n (%)) was registered. In the case Fecundity rate ratios for of an IUP, follow-up ended conservative surgery (95% Radical: 38 (48) at the estimated date of CI) Conservative: 15 (27) conception. An IUP was (p=0.01) defined as an ongoing a. Spontaneous IUP pregnancy detected by Laparoscopy (n (%)) ultrasound, or the delivery of Univariate: 2.5 (1.4 to 4.4) a child. The outcome of Multivariate: 1.9 (0.91 to 3.8) Radical: 7 (9) each IUP was registered. If Conservative: 22 (39) an IUP did not occur, follow- b. Repeat EP (p<0.01) up ended on the last day of contact. Repeat EP were Univariate: 1.5 (0.47 to 4.7) Inclusion criteria also registered. Multivariate: 2.4 (0.57 to 11)

Data analysis (Note: they report that the Primary surgery for tubal multivariate analysis adjusted pregnancy during study for other factors prognostic of period Baseline characteristics were compared using fertility but it is unclear exactly Student’s t-test or chi- what these are)

593 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Exclusion criteria squared. Kaplan–Meier curves were constructed, Complete tubal abortion estimating the cumulative Stratified analysis for tubal probability of spontaneous disease and tubal pathology: Treatment by milking or IUP over time, which was 3 year absolute IUP and FRR nettoyage only the primary outcome for conservative vs. radical measure. If an IUP was the surgery in first 18 months Patients with only one tube result of IVF–embryo (95% CI) (radical surgery would transfer, time to pregnancy effectively sterilise these in this patient was - In patients with no history of patients) considered to be censored, tubal disease which meant that the patient Index tubal pregnancy a was included in the analysis Radical: 18/50 (36) result of IVF and embryo until the start of IVF–embryo Conservative: 25/46 (54) transfer transfer only. The Kaplan– FRR (95% CI) 1.4 (0.68 to Meier curves were tested for 2.7) Heterotopic pregnancies statistically significant differences using the log- - In patients with history of Not trying to conceive rank test. The effect of homolateral tubal disease conservative surgery compared with radical Radical: 1/2 (50) surgery was expressed as a Conservative: 0/0 (0) fecundity rate ratio (FRR) FRR (95% CI): NR/NC with a 95% CI, calculated through Cox proportional - In patients with history of hazard regression contralateral tubal disease analysis. Proportionality was tested visually from the Radical: 0/2 (0) Kaplan–Meier curves. To Conservative: 1/2 (50) adjust the FRR of FRR (95% CI): NR/NC conservative surgery for other potential prognostic - In patients with history of factors mentioned above, bilateral tubal disease multivariate analysis was performed. Radical: 5/25 (20) Conservative: 4/8 (50) Analysis was also stratified FRR (95% CI) 3.1 (0.76 to for tubal pathology. Two 12) different definitions of tubal pathology were used: first, a

594 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

medical history of tubal - In patients with no tubal pathology, i.e. previous EP, pathology at surgery previous PID or previous tubal surgery; and second, Radical: 15/31 (48) tubal pathology detected Conservative: 26/41 (63) during surgery of the index FRR (95% CI) 2.0 (0.87 to EP, i.e. presence of 4.8) hydrosalpinx, peritubal adhesions or phimosis. - In patients with homolateral FRRs stratified for both a tubal pathology at surgery history of tubal pathology (absent, homolateral, Radical: 3/15 (20) contralateral or bilateral), Conservative: 1/1 (100) and tubal pathology FRR (95% CI): NR/NC detected at surgery (absent, homolateral, contralateral or - In patients with contralateral bilateral) were calculated. tubal pathology at surgery Interaction between tubal pathology and treatment Radical: 3/8 (37.5) was assessed by Cox Conservative: 2/6 (33.3) regression using the follow- FRR (95% CI) 0.80 (0.13 to up data collected for each 4.9) patient. Three-year cumulative rates were also - In patients with bilateral calculated for repeat EP. tubal pathology at surgery The Kaplan–Meier curves were compared using the Radical: 3/25 (12) log-rank test. In this Conservative: 1/8 (12.5) analysis, time to EP was FRR (95% CI) 1.4 (0.13 to considered to be censored 16) once IUP occurred. Univariate and multivariate Cox regression analysis were used to calculate FRR for repeat EP after conservative surgery compared with radical surgery.

595 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Full citation Sample size Interventions Details Results Limitations

Ory,S.J., Nnadi,E., N=88 Radical surgery In Olmsted County, the Subsequent term pregnancy Retrospective Herrmann,R., O'Brien,P.S., (complete or partial records of 188 women with within 3 years (number/total Melton,L.J.,III, Fertility after (however 5 of these women salpingectomy) a surgically confirmed EP (%)) 53/188 (28.2%) of the original ectopic pregnancy, Fertility did not receive a (n=50) were identified, of which 100 patients with a surgically and Sterility, 60, 231-235, salpingectomy or were eligible for the study Radical: 29/50 (58) confirmed ectopic 1993 salpingo(s)tomy, and Salpingo(s)tomy (see inclusion criteria). The Salpingo(s)tomy: 17/33 (51.5) pregnancy were lost to follow-up therefore the main population (n=33) other 88 were ineligible: 47

Ref Id of interest is N=83) did not attempt conception, * RR (95% CI) 1.13 (0.75 to There was a significant difference and 41 were lost to follow- 1.69) between gravidity, prior infertility, 122007 Characteristics up. and history of prior tubal surgery Repeat ectopic pregnancy between the two groups. Tubal Country/ies where the The fertility histories of the within 3 years (number/total rupture was also more prevalent study was carried out Type of surgery received 100 patients were (%)) in the radical group. (number/total) retrospectively followed from USA 3 to 12.5 years after the Radical: 3/50 (6) 2/50 patients in the radical arm Radical: 50/88 index EP. Pertinent Salpingo(s)tomy: 8/33 (24.2) also had an oophorectomy; their Study type - Partial salpingectomy: 8/50 information regarding age, outcomes are not reported - Complete salpingectomy: gravidity, menstrual pattern, * RR (95% CI) 0.25 (0.07 to separately. Retrospective cohort study 42/50 fertility history, surgical 0.87) history, pelvic infections, Blinding of participants and/or Conservative: 38/88 Aim of the study IUCD use and subsequent those assessing outcomes is not - Salpingo(s)tomy: 33/38 * calculated by NCC technical fertility were obtained from team reported. - Fimbrial expression: 5/38 their complete inpatient and To compare pregnancy outpatient medical records. rates after radical or Other information Two facilities provided conservative surgical Note: the following analyses Age/years (mean (SEM) almost all the care for the treatment for tubal include the women that residents of the county. All laparotomy pregnancy over a 12.5 received fimbrial expression, Radical: 27.7 (0.7) Therefore, the authors year interval (minimum of 3 because outcomes for Conservative: 26.3 (0.7) report that all information Note: When split by specific years), and to assess the salpingo(s)tomy/fimbrial (NS) was consistently available. surgery type: relative contribution of expression are not reported various risk factors to separately. Gravidity (mean (SEM)) A detailed questionnaire future fertility performance. - Partial salpingectomy was sent to the 100 eligible Term delivery: 2/8 (25) Radical: 2.2 (0.3) Term pregnancy rate, subjects, and non- stratified by history of EP: 1/8 (12.5) Study dates Conservative: 1.3 (0.1) respondents were contacted infertility (number/total (%) - Complete salpingectomy (p=0.008) by telephone. Eventually, 88 Term delivery: 27/42 (64.2)

patients responded, and a. With history (n=25) EP: 2/42 (4.8) Prior infertility (%) constitute the study

596 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

1976 to 1985 population. Radical: 18 Radical: 1/9 (11.1) - Salpingo(s)tomy Conservative: 42 50 of the patients had a Conservative: 4/16 (25) Term delivery: 17/33 (51.5) Source of funding (p=0.013) radical procedure, including (p=0.405) EP: 8/33 (24.2) a complete (n=42) or partial - Removal of conceptus through Not reported PID (%) (n=8) salpingectomy, at b. Without history (n=63) ampulla which time the proximal Term delivery: 2/5 (40) Radical: 8 segment was ligated. In Radical: 28/41 (68.3) EP: 0/5 (0) Conservative: 16 addition, 2 patients in this Conservative: 15/22 (68.2) (NS) arm also had an ipsilateral (p=0.993) oophorectomy. 38 patients IUD (%) had a conservative Ectopic pregnancy rate, procedure, of which 33 were stratified by history of Radical: 19 salpingostomies or infertility (number/total (%)) Conservative: 17 salpingotomies and 5 were (NS) fimbrial expressions. 8 a. With history (n=25) patients in the conservative Tubal adhesions (%) group also underwent a Radical: 2/9 (22.2) reparative procedure at Conservative: 5/16 (31.3) Radical: 2 initial laparotomy, (p=0.629) Conservative: 11 comprising salpingolysis or (NS) ovariolysis. All patients in b. Without history (n=63) both groups had a Previous abdominal pelvic remaining contralateral tube. Radical: 2/41 (4.9) surgery (%) The procedures were Conservative: 3/22 (13.6) performed by numerous (p=0.220) Radical: 8 surgeons, including Conservative: 8 residents. (NS) (Note: unclear why a total of 4 EP are reported in the radical Prior tubal surgery (%) arm in the stratified analysis, when only 3 are reported in Radical: 0 the overall analysis) Conservative: 11 (p=0.019)

History of anovulation (%)

Radical: 12 Conservative: 13

597 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

No risk factor identified (%)

Radical: 67 Conservative: 33 (NS)

Inclusion criteria

Surgically confirmed ectopic pregnancy presenting during the study period

First tubal pregnancy

Treated with radical or conservative surgery at laparotomy

Actively attempted conception after surgery

Willing and available to participate in follow-up for at least 3 years

Exclusion criteria

Not reported Full citation Sample size Interventions Details Results Limitations

Sherman,D., Langer,R., N=250 Radical surgery During the study period, 250 Subsequent intrauterine Retrospective Sadovsky,G., Bukovsky,I., (salpingectomy, ectopic pregnancies in 242 pregnancy (number/total (%)) Caspi,E., Improved fertility (However, fertility outcomes salpingo- women were surgically Some patients received other following ectopic are only reported for 151 oophorectomy) treated. Details of age, a. All patients surgical procedures than pregnancy, Fertility and women who had primary EP (n=159) parity, past medical history, a salpingotomy or salpingectomy. Sterility, 37, 497-502, 1982 and conservative/radical IUCD use, diagnostic Radical: 75/104 (72.1) Partial salpingectomy is included surgery, and therefore procedures, operative Conservative: 39/47 (83.0) as a conservative surgery.

598 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Ref Id constitute the main Conservative findings, and surgical Although proportions are reported population of interest for this surgery procedures was obtained *RR (95% CI) 0.87 (0.73 for the whole original population, 122046 review) (salpingotomy, from admission records, to 1.04) they are not reported for those milking, resection surgery reports, and included in the analysis of fertility Country/ies where the Characteristics of ovarian pathological files. Data b. In patients with either outcomes. study was carried out pregnancy, partial regarding subsequent history or operative findings salpingectomy) pregnancies, surgical suggestive of coexistent 39/242 (16%) patients were lost Israel Age/years (mean (SD)): 27.8 (n=65) operations, contraceptive sterility factors to follow-up, and only 179 (5.2) measures and death were (77%) had adequate data Study type available via questionnaires Radical: 14/32 (43.8) available. Therefore overall Gestational age/days (mean sent to patients' addresses, Conservative: 16/21 (76.2) missing data/loss to follow-up is (SD)): 52.6 (17.6) Retrospective comparative subsequent medical high. observational study records, and personal *RR (95% CI) 0.57 (0.36 Type of surgery performed interviews. to 0.91) Specific characteristics of those (number/total (%)) receiving conservative and

Aim of the study Laparoscopy was used for c. In patients with otherwise radical surgery are not reported Conservative: 65/250 (26) diagnosis in 69% of cases. normal reproductive history To examine reproductive - Salpingotomy: 43/250 (17) In three cases of very early and organs Includes 4% non-tubal performance subsequent - Milking: 14/250 (6) tubal gestation, it was pregnancies. 42% of cases were to operative removal of - Resection of ovarian initially overlooked but Radical: 61/72 (84.7) ruptured ectopic pregnancy pregnancy: 7/250 (3) discovered during a second Conservative: 23/26 (88.5) - Partial salpingectomy: 1/250 procedure. 88% of cases Outcome of pregnancies is not (0.4) Study dates were operated on during the *RR (95% CI) 0.96 (0.81 reported first 24 hours after to 1.14) Radical: 159/250 (64) admission. Conservative Blinding of participants and/or January 1st 1969 to - Salpingectomy: 136/250 surgical procedures aimed those assessing outcomes is not December 31st 1979 (54) Repeat ectopic pregnancy at preserving the tube were (number/total (%)) reported. - Salpingo-oophorectomy: carried out whenever the 23/250 (9) Source of funding involved tube was not a. All patients Other information severely damaged and Sterilising procedures: Not reported future fertility was desirable. Radical: 6/104 (5.8) 26/250 (10) Salpingotomy was the most Location of ectopic (%) Conservative: 3/47 (6.4) common conservative Adjunctive reconstructive procedure carried out. Tubal: 96 surgery: 45/250 (18) *RR (95% CI) 0.90 (0.24 Ovarian: 4 Among radically treated to 3.46) patients, salpingectomy was Inclusion criteria the treatment. Concomitant b. In patients with either oophorectomy was carried history or operative findings out in the presence of suggestive of coexistent associated ovarian sterility factors

599 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

Ectopic pregnancy pathology. Reconstructive procedures (lysis of Radical: 3/32 (9.4) adhesions and/or Conservative: 1/21 (4.8) Exclusion criteria tuboplasty) were combined with either radical or surgical *RR (95% CI) 1.97 (0.22 Not reported operations in 45 patients to 17.68) who desired future pregnancy. c. In patients with otherwise normal reproductive history Additional measures and organs directed towards the prevention of post-operative Radical: 3/72 (4.2) scar formation included Conservative: 2/26 (7.7) gentle tissue handling, saline irrigations, use of fine *RR (95% CI) 0.54 (0.10 non-absorbable sutures, to 3.06) blood-clot removal, and intra-abdominal instillation of * Calculated by the technical a solution containing team steroids, antibiotics and antihistamines. Post- operative care included chemotherapy with antibiotics, steroids and enzymatic drugs, and hydrotubations. Twenty six sterilising procedures were carried out, seven of which were in repeat ectopic pregnancy cases.

Follow-up

Of the 242 patients under study, 39 (16%) were lost to follow-up. One patient died 2 weeks post-operatively in another hospital of probable massive pulmonary embolism. 23 underwent

600 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

sterilising operations. Adequate data was available for 179 patients, of which 25 used contraception. Therefore, reproductive performance was evaluated in the remaining 154 patients, who were followed for a mean time of 4.18 (SD 2.8) years, with a range of 3 months to 11 years. 70% were followed for more than 2 years. The reproductive outcomes of 151 patients with a primary ectopic pregnancy (3 patients with two previous EP were excluded) are reported below. The authors report that there was no statistically significant difference in length of follow-up between the two arms. Full citation Sample size Interventions Details Results Limitations

Tuomivaara,L., N=323 Salpingectomy During the study period, 523 Subsequent intrauterine Retrospective Kauppila,A., Radical or (n=237) patients underwent surgery pregnancy (number of conservative surgery for for ectopic pregnancy. The women/total (%)) 14% loss to follow-up for fertility ectopic pregnancy? A Characteristics Conservative majority of patients had outcomes. follow-up study of fertility of radical operations, due to a. In all women 323 patients, Fertility and Characteristics are not surgery (n=86) tubal rupture and/or a No characteristics are reported to Sterility, 50, 580-583, 1988 reported separately for grossly normal contralateral Salpingectomy: 170/237 illustrate comparability of salpingectomy and tube. If the patients had (71.7) treatment groups, therefore there

Ref Id conservative surgery arms. suffered from infertility or the Conservative surgery: 59/86 could be unreported differences tube was not ruptured, (68.6) at baseline 122086 Type of surgery received conservative surgery was (number/total (%)) (Note: tubal resection (28), No surgical details are reported - Country/ies where the

601 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments study was carried out chosen. tubal section (14), ovum unclear whether women in the Salpingectomy: 237/323 expression (12), no conservative arm are receiving a Finland (73.4) A questionnaire was sent to manipulation (5)) surgery type relevant to this each patient to analyse review question

Study type Conservative surgery: 86/323 subsequent fertility. The b. Excluding women who had (26.6) questionnaire had questions "no manipulation" Length of follow-up is not Retrospective comparative - Tubal resection: 40/86 on: fertility after operation, reported separately for the two observational study (46.5) time from surgery to first Salpingectomy: 170/237 arms. - Tubal section: 20/86 (23.3) pregnancy, clinical course of (71.7) - Ovum expression: 20/86 Outcome of pregnancy is not Aim of the study pregnancy, infertility, and Tubal resection/section or (23.3) contraception methods. The ovum expression: 54/80 reported in a way that permits - No manipulation: 6/86 (7.0) mean follow-up time was 5.1 (67.5) analysis (very small bar graph) To evaluate the years (range 1 - 11). subsequent fertility of 323 Inclusion criteria 450/523 (86%) of patients Lack of blinding patients who desired Repeat ectopic pregnancy returned the questionnaire, (number of women/total (%)) pregnancy, by paying of which 127 did not wish to Other information special attention to the Desiring pregnancy after an operation for ectopic become pregnant. a. In all women type of surgical Therefore, the outcomes of management, state of the pregnancy 323 women who desired Salpingectomy: 25/237 (10.5) tubes at operation, and pregnancy were analysed parity. Exclusion criteria Conservative surgery: 10/86 using chi-squared test. (11.6)

Study dates Not reported (Note: tubal resection (3), tubal section (2), ovum 1973 to 1982 expression (5), no manipulation (0)) (point at which operations occurred) b. Excluding women who had "no manipulation" Source of funding Salpingectomy: 25/237 (10.5) Tubal resection/section or Not reported ovum expression: 10/80 (12.5)

(Note: % do not exactly match those stated in the paper, because the authors

602 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments

calculate number of ectopics as a proportion of total pregnancies, not women)

Live birth rate (number of women/total (%))

a. In women with an affected contralateral tube

Salpingectomy: 13/30 (43.3) Conservative surgery: 14/19 (73.7)

b. In women with an intact contralateral tube

The authors report that there was no significant difference in fertility with respect to operation method, but raw numbers are not given. Full citation Sample size Interventions Details Results Limitations

Turan,V., Fertility N = 133 Salpingectomy The records of 219 women Subsequent intrauterine Retrospective outcomes subsequent to (n = 62) hospitalised for tubal ectopic pregnancy (n/total (%)) treatment of tubal ectopic (However, 34 patients pregnancy during the study 9/99 (9%) of patients were lost to pregnancy in younger underwent treatment with Salpingostomy period were reviewed. 81 Salpingectomy: 33/55 (60) follow-up Turkish women, Journal of methotrexate and therefore (n = 37) women were excluded as Salpingostomy: 23/35 (65.7) Pediatric and Adolescent the true population of interest per the exclusion criteria. Study population only includes Gynecology, 24, 251-255, for this review is N = 99) (p = 0.942) women 18-28 years old with 2011 Patients were called and concerns about infertility, and asked whether they had an Repeat ectopic pregnancy therefore does not exactly match Characteristics Ref Id intrauterine pregnancy up to (n/total (%)) the population of interest for this 24 months, and for how long review. 155383 Age/years (mean±SD) a period they waited to Salpingectomy: 2/55 (3.6) conceive. 9 patients (7 from Salpingostomy: 6/35 (17.1) There is inconsistency in the Country/ies where the Salpingectomy: 25.3±3.8 the salpingectomy group reported rates within the paper: in Salpingostomy: 25.7±3.6 and 2 from the (p = 0.091) the table it reports that there were

603 Ectopic pregnancy and miscarriage

Study details Participants Interventions Methods Outcomes and Results Comments study was carried out salpingostomy group) could 23 intrauterine pregnancies in the Type of surgery performed not be reached. salpingostomy group and 33 in Turkey (n/total) the salpingectomy group; The Pearson chi-squared however, in the flow chart it Study type Salpingectomy: test was used to compare reports 22 and 34 respectively. - Laparotomy: 23/62 rates of ectopic and The technical team have reported Retrospective comparative - Laparoscopy: 39/62 intrauterine pregnancies the values which most closely observational study Salpingostomy: between the groups. match the % reported in the text - Laparotomy: 15/37 of the results. - Laparoscopy: 22/37 Aim of the study Outcome of the pregnancy is not Inclusion criteria reported To determine intrauterine pregnancy rates and mean Other information time to future pregnancy Tubal ectopic pregnancy that are experienced following tubal ectopic Aged 18-28 pregnancy Concerns about infertility Study dates Exclusion criteria January 1998 to September 2008 Unwillingness for pregnancy and using a contraceptive method Source of funding Previous pelvic or tubal None stated surgery

Pregnancy following IVF

Extratubal ectopic pregnancy

Aged over 28

604