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Meta-Analysis
. 2007 Jan 24;2007(1):CD000324.
doi: 10.1002/14651858.CD000324.pub2.

Interventions for tubal ectopic pregnancy

P J Hajenius  1 , F Mol, B W J Mol, P M M Bossuyt, W M Ankum, F van der Veen
Affiliations
Meta-Analysis

Interventions for tubal ectopic pregnancy

P J Hajenius et al. Cochrane Database Syst Rev. .

Abstract

Background: Treatment options for tubal ectopic pregnancy are; (1) surgery, e.g. salpingectomy or salpingo(s)tomy, either performed laparoscopically or by open surgery; (2) medical treatment, with a variety of drugs, that can be administered systemically and/or locally by various routes and (3) expectant management.

Objectives: To evaluate the effectiveness and safety of surgery, medical treatment and expectant management of tubal ectopic pregnancy in view of primary treatment success, tubal preservation and future fertility.

Search strategy: The Cochrane Menstrual Disorders and Subfertility Group's Specialised Register, Cochrane Controlled Trials Register (up to February 2006), Current Controlled Trials Register (up to October 2006), and MEDLINE (up to October 2006) were searched.

Selection criteria: Randomised controlled trials (RCTs) comparing treatments in women with tubal ectopic pregnancy.

Data collection and analysis: Data extraction and quality assessment was done independently by two reviewers. Differences were resolved by discussion with all reviewers.

Main results: Thirty five studies have been analysed on the treatment of tubal ectopic pregnancy, describing 25 different comparisons.

Surgery: Laparoscopic salpingostomy is significantly less successful than the open surgical approach in the elimination of tubal ectopic pregnancy (2 RCTs, n=165, OR 0.28, 95% CI 0.09, 0.86) due to a significant higher persistent trophoblast rate in laparoscopic surgery (OR 3.5, 95% CI 1.1, 11). However, the laparoscopic approach is significantly less costly than open surgery (p=0.03). Long term follow-up (n=127) shows no evidence of a difference in intra uterine pregnancy rate (OR 1.2, 95% CI 0.59, 2.5) but there is a non significant tendency to a lower repeat ectopic pregnancy rate (OR 0.47, 95% 0.15, 1.5). Salpingostomy alone is significantly less successful than when combined with a prophylactic single shot methotrexate (2 RCTs, n=163, OR 0.25, 95% CI 0.08-0.76) to prevent persistent trophoblast.

Medical treatment: Systemic methotrexate in a fixed multiple dose intramuscular regimen has a non significant tendency to a higher treatment success than laparoscopic salpingostomy (1 RCT, n=100, OR 1.8, 95% CI 0.73, 4.6). No significant differences are found in long term follow-up (n=74): intra uterine pregnancy (OR 0.82, 95% CI 0.32, 2.1) and repeat ectopic pregnancy (OR 0.87, 95% CI 0.19, 4.1). One single dose intramuscular methotrexate is significantly less successful than laparoscopic salpingostomy (4 RCTs, n=265, OR 0.38, 95% CI 0.20, 0.71). With a variable dose regimen treatment success rises, but shows no evidence of a difference compared to laparoscopic salpingostomy (OR 1.1, 95% CI 0.52, 2.3). Long term follow-up (n=98) do not differ significantly (intra uterine pregnancy OR 1.0, 95% CI 0.43, 2.4, ectopic pregnancy OR 0.54, 95% CI 0.12, 2.4). The efficacy of systemic single dose methotrexate alone is significantly less successful than when combined with mifepristone (2 RCTs, n=262, OR 0.59, 95% CI 0.35, 1.0). The same goes for the addition of traditional Chinese medicine (1 RCT, n=78, OR 0.08, 95% CI 0.02, 0.39). Local medical treatment administered transvaginally under ultrasound guidance is significantly better than a 'blind' intra-tubal injection under laparoscopic guidance in the elimination of tubal ectopic pregnancy (1 RCT, n=36, methotrexate OR 5.8, 95% CI 1.3, 26; 1 RCT, n=80, hyperosmolar glucose OR 0.38, 95% CI 0.15, 0.93). However, compared to laparoscopic salpingostomy, local injection of methotrexate administered transvaginally under ultrasound guidance is significantly less successful (1 RCT, n=78, OR 0.17, 95% CI 0.04, 0.76) but with positive long term follow up (n=51): a significantly higher intra uterine pregnancy rate (OR 4.1, 95% CI 1.3, 14) and a non significant tendency to a lower repeat ectopic pregnancy rate (OR 0.30, 95% CI 0.05, 1.7). EXPECTANT MANAGEMENT: Expectant management is significantly less successful than prostaglandin therapy (1 RCT, n=23, OR 0.08, 95% CI 0.02-0.39).

Authors' conclusions: In the surgical treatment of tubal ectopic pregnancy laparoscopic surgery is a cost effective treatment. An alternative nonsurgical treatment option in selected patients is medical treatment with systemic methotrexate. Expectant management can not be adequately evaluated yet.

PubMed Disclaimer

Conflict of interest statement

The reviewers were investigators on the randomised controlled trial comparing systemic methotrexate in a multiple dose regimen versus laparoscopic salpingostomy (Hajenius 1997), which was funded by a grant from the Health Insurance Funds Council, Amstelveen, The Netherlands (OG 93/007) from 1993 to 1996.

Prof F van der Veen is a member of the Dutch Society against Quackery. He regrets to include studies with complementary alternative medicines.

Figures

1.1
1.1. Analysis
Comparison 1 laparoscopic salpingostomy versus salpingostomy by open surgery, Outcome 1 primary treatment success.
1.2
1.2. Analysis
Comparison 1 laparoscopic salpingostomy versus salpingostomy by open surgery, Outcome 2 persistent trophoblast.
1.3
1.3. Analysis
Comparison 1 laparoscopic salpingostomy versus salpingostomy by open surgery, Outcome 3 tubal patency.
1.4
1.4. Analysis
Comparison 1 laparoscopic salpingostomy versus salpingostomy by open surgery, Outcome 4 subsequent intrauterine pregnancy.
1.5
1.5. Analysis
Comparison 1 laparoscopic salpingostomy versus salpingostomy by open surgery, Outcome 5 repeat ectopic pregnancy.
2.1
2.1. Analysis
Comparison 2 minilaparotomy versus laparotomy, Outcome 1 primary treatment success.
3.1
3.1. Analysis
Comparison 3 salpingostomy without tubal suturing versus salpingostomy with tubal suturing, Outcome 1 primary treatment success.
3.2
3.2. Analysis
Comparison 3 salpingostomy without tubal suturing versus salpingostomy with tubal suturing, Outcome 2 persistent trophoblast.
3.3
3.3. Analysis
Comparison 3 salpingostomy without tubal suturing versus salpingostomy with tubal suturing, Outcome 3 tubal patency rate.
3.4
3.4. Analysis
Comparison 3 salpingostomy without tubal suturing versus salpingostomy with tubal suturing, Outcome 4 subsequent intrauterine pregnancy.
3.5
3.5. Analysis
Comparison 3 salpingostomy without tubal suturing versus salpingostomy with tubal suturing, Outcome 5 repeat ectopic pregnancy.
4.1
4.1. Analysis
Comparison 4 salpingostomy alone versus combined with medical treatment, Outcome 1 primary treatment success.
4.2
4.2. Analysis
Comparison 4 salpingostomy alone versus combined with medical treatment, Outcome 2 persistent trophoblast.
4.3
4.3. Analysis
Comparison 4 salpingostomy alone versus combined with medical treatment, Outcome 3 tubal preservation.
4.4
4.4. Analysis
Comparison 4 salpingostomy alone versus combined with medical treatment, Outcome 4 tubal patency.
5.1
5.1. Analysis
Comparison 5 Systemic MTX versus laparoscopic salpingostomy, Outcome 1 primary treatment success.
5.2
5.2. Analysis
Comparison 5 Systemic MTX versus laparoscopic salpingostomy, Outcome 2 persistent trophoblast.
5.3
5.3. Analysis
Comparison 5 Systemic MTX versus laparoscopic salpingostomy, Outcome 3 tubal preservation.
5.4
5.4. Analysis
Comparison 5 Systemic MTX versus laparoscopic salpingostomy, Outcome 4 tubal patency.
5.5
5.5. Analysis
Comparison 5 Systemic MTX versus laparoscopic salpingostomy, Outcome 5 subsequent intra uterine pregnancy.
5.6
5.6. Analysis
Comparison 5 Systemic MTX versus laparoscopic salpingostomy, Outcome 6 repeat ectopic pregnancy.
6.1
6.1. Analysis
Comparison 6 local MTX versus laparoscopic salpingostomy, Outcome 1 primary treatment success.
6.2
6.2. Analysis
Comparison 6 local MTX versus laparoscopic salpingostomy, Outcome 2 persistent trophoblast.
6.3
6.3. Analysis
Comparison 6 local MTX versus laparoscopic salpingostomy, Outcome 3 tubal preservation.
6.4
6.4. Analysis
Comparison 6 local MTX versus laparoscopic salpingostomy, Outcome 4 tubal patency.
6.5
6.5. Analysis
Comparison 6 local MTX versus laparoscopic salpingostomy, Outcome 5 subsequent intra uterine pregnancy.
6.6
6.6. Analysis
Comparison 6 local MTX versus laparoscopic salpingostomy, Outcome 6 repeat ectopic pregnancy.
7.1
7.1. Analysis
Comparison 7 MTX transvaginally under sonographic guidance versus MTX under laparoscopic guidance, Outcome 1 primary treatment success.
7.2
7.2. Analysis
Comparison 7 MTX transvaginally under sonographic guidance versus MTX under laparoscopic guidance, Outcome 2 persistent trophoblast.
8.1
8.1. Analysis
Comparison 8 MTX transvaginally under sonographic guidance versus systemic single dose MTX im, Outcome 1 primary treatment success.
8.2
8.2. Analysis
Comparison 8 MTX transvaginally under sonographic guidance versus systemic single dose MTX im, Outcome 2 persistent trophoblast.
8.3
8.3. Analysis
Comparison 8 MTX transvaginally under sonographic guidance versus systemic single dose MTX im, Outcome 3 tubal preservation.
8.4
8.4. Analysis
Comparison 8 MTX transvaginally under sonographic guidance versus systemic single dose MTX im, Outcome 4 subsequent intrauterine pregnancy.
8.5
8.5. Analysis
Comparison 8 MTX transvaginally under sonographic guidance versus systemic single dose MTX im, Outcome 5 repeat ectopic pregnancy.
9.1
9.1. Analysis
Comparison 9 MTX under laparoscopic guidance versus the same regimen in combination with systemic MTX im, Outcome 1 primary treatment success.
10.1
10.1. Analysis
Comparison 10 single dose MTX versus fixed multiple dose MTX both im, Outcome 1 primary treatment success.
10.2
10.2. Analysis
Comparison 10 single dose MTX versus fixed multiple dose MTX both im, Outcome 2 persistent trophoblast.
11.1
11.1. Analysis
Comparison 11 25 mg/m2 versus the standard 50 mg/m2 MTX both single dose im, Outcome 1 primary treatment success.
11.2
11.2. Analysis
Comparison 11 25 mg/m2 versus the standard 50 mg/m2 MTX both single dose im, Outcome 2 persistent trophoblast.
11.3
11.3. Analysis
Comparison 11 25 mg/m2 versus the standard 50 mg/m2 MTX both single dose im, Outcome 3 treatment success with variable MTX dose.
11.4
11.4. Analysis
Comparison 11 25 mg/m2 versus the standard 50 mg/m2 MTX both single dose im, Outcome 4 tubal preservation.
11.5
11.5. Analysis
Comparison 11 25 mg/m2 versus the standard 50 mg/m2 MTX both single dose im, Outcome 5 tubal patency.
11.6
11.6. Analysis
Comparison 11 25 mg/m2 versus the standard 50 mg/m2 MTX both single dose im, Outcome 6 subsequent intra uterine pregnancy.
11.7
11.7. Analysis
Comparison 11 25 mg/m2 versus the standard 50 mg/m2 MTX both single dose im, Outcome 7 repeat ectopic pregnancy.
12.1
12.1. Analysis
Comparison 12 MTX in lipiodol suspensions versus MTX in saline both under laparoscopic guidance, Outcome 1 primary treatment success.
12.2
12.2. Analysis
Comparison 12 MTX in lipiodol suspensions versus MTX in saline both under laparoscopic guidance, Outcome 2 persistent trophoblast.
12.3
12.3. Analysis
Comparison 12 MTX in lipiodol suspensions versus MTX in saline both under laparoscopic guidance, Outcome 3 tubal preservation.
12.4
12.4. Analysis
Comparison 12 MTX in lipiodol suspensions versus MTX in saline both under laparoscopic guidance, Outcome 4 tubal patency.
12.5
12.5. Analysis
Comparison 12 MTX in lipiodol suspensions versus MTX in saline both under laparoscopic guidance, Outcome 5 subsequent intrauterine pregnancy.
13.1
13.1. Analysis
Comparison 13 MTX versus prostaglandins both under sonographic guidance combined with systemic administration of the drug, Outcome 1 primary treatment success.
13.2
13.2. Analysis
Comparison 13 MTX versus prostaglandins both under sonographic guidance combined with systemic administration of the drug, Outcome 2 tubal patency.
14.1
14.1. Analysis
Comparison 14 single dose systemic MTX im alone versus in combination with oral mifepristone, Outcome 1 primary treament success.
14.2
14.2. Analysis
Comparison 14 single dose systemic MTX im alone versus in combination with oral mifepristone, Outcome 2 persistent trophoblast.
14.3
14.3. Analysis
Comparison 14 single dose systemic MTX im alone versus in combination with oral mifepristone, Outcome 3 tubal preservation.
14.4
14.4. Analysis
Comparison 14 single dose systemic MTX im alone versus in combination with oral mifepristone, Outcome 4 tubal patency.
15.1
15.1. Analysis
Comparison 15 single dose systemic MTX im alone versus in combination with EP2, Outcome 1 primary treatment success.
15.2
15.2. Analysis
Comparison 15 single dose systemic MTX im alone versus in combination with EP2, Outcome 2 subsequent intra uterine pregnancy.
15.3
15.3. Analysis
Comparison 15 single dose systemic MTX im alone versus in combination with EP2, Outcome 3 repeat ectopic pregnancy.
16.1
16.1. Analysis
Comparison 16 hyperosmolar glucose under laparoscopic guidance versus other treatments, Outcome 1 primary treatment success.
16.2
16.2. Analysis
Comparison 16 hyperosmolar glucose under laparoscopic guidance versus other treatments, Outcome 2 persistent trofoblast.
16.3
16.3. Analysis
Comparison 16 hyperosmolar glucose under laparoscopic guidance versus other treatments, Outcome 3 tubal patency.
16.4
16.4. Analysis
Comparison 16 hyperosmolar glucose under laparoscopic guidance versus other treatments, Outcome 4 subsequent intra uterine pregnancy.
16.5
16.5. Analysis
Comparison 16 hyperosmolar glucose under laparoscopic guidance versus other treatments, Outcome 5 repeat ectopic pregnancy.
17.1
17.1. Analysis
Comparison 17 expectant management versus medical treatment, Outcome 1 primary treatment success.
17.2
17.2. Analysis
Comparison 17 expectant management versus medical treatment, Outcome 2 tubal preservation.
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References

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Koninckx 1991 {published data only}
    1. Koninckx PR, Witters K, Brosens J, Stemers N, Oosterlynck D, Meuleman C. Conservative laparoscopic treatment of ectopic pregnancies using the CO2 laser. British Journal of Obstetrics & Gynaecology 1991;98:1254‐9. - PubMed
Laatikainen 1993 {published data only}
    1. Laatikainen T, Tuomivaara L, Kaar K. Comparison of a local injection of hyperosmolar glucose solution with salpingostomy for the conservative treatment of tubal pregnancy. Fertility & Sterility 1993;60:80‐4. - PubMed
Lund 1955 {published data only}
    1. Lund J. Early ectopic pregnancy ‐comments on conservative treatment. Journal of Obstetrics & Gynecology of the British Empire 1955;62:70‐6. - PubMed
Murphy 1992 {published data only}
    1. Murphy AA, Nager CW, Wujek JJ, Kettel LM, Torp VA, Chin HG. Operative laparoscopy versus laparotomy for the management of ectopic pregnancy: a prospective trial. Fertility & Sterility 1992;57:1180‐5. - PubMed
O'Shea 1994 {published data only}
    1. O Shea RT, Thompson GR, Harding A. Intra amniotic methotrexate versus CO2 laser laparoscopic salpingotomy in the management of tubal ectopic pregnancy a prospective randomized trial. Fertility & Sterility 1994;62:876‐8. - PubMed
Porpora 1996 {published data only}
    1. Porpora MG, Oliva MM, Cristofaro A, Montanino G, Cosmi EV. Comparison of local methotrexate and linear salpingostomy in the conservative laparoscopic treatment of ectopic pregnancy. Journal of the American Association of Gynecologic Laparoscopists 1996;3:271‐6. - PubMed

References to studies awaiting assessment

References to ongoing studies

Fernandez 1 {unpublished data only}
    1. Randomized controlled trial between medical treatment by methotrexate versus conservative surgical treatment to evaluate subsequent fertility. Ongoing study 08‐2004.
Fernandez 2 {unpublished data only}
    1. Randomised controlled trial between conservative versus radical surgical treatment to evaluate subsequent fertility. Ongoing study 08‐2004.
Hajenius 1 {unpublished data only}
    1. A randomised controlled trial of salpingostomy versus salpingectomy for tubal pregnancy; impact on future fertility. Ongoing study 01‐09‐2004. - PMC - PubMed
Hajenius 2 {unpublished data only}
    1. Randomised controlled trial of systemic MTX in an intramuscular single shot regimen versus expectant management. Ongoing study 01‐02‐2006.
Jurkovic {unpublished data only}
    1. Randomised double blind placebo controlled trial of single dose methotrexate versus expectant management in women with tubal ectopic pregnancy. Ongoing study 01‐09‐2005.

Additional references

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