Interventions for tubal ectopic pregnancy.

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.

[1]  D. Jurkovic,et al.  The ESEP study: Salpingostomy versus salpingectomy for tubal ectopic pregnancy; The impact on future fertility: A randomised controlled trial , 2008, BMC women's health.

[2]  A. Khademi,et al.  Comparison of success rates in the medical management of ectopic pregnancy with single-dose and multiple-dose administration of methotrexate: a prospective, randomized clinical trial. , 2006, Fertility and sterility.

[3]  T. Bourne,et al.  The non‐surgical management of ectopic pregnancy , 2005, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[4]  T. Bourne,et al.  Diagnostic accuracy of varying discriminatory zones for the prediction of ectopic pregnancy in women with a pregnancy of unknown location , 2005, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[5]  M. Candiani,et al.  Pre- and post-treatment patterns of human chorionic gonadotropin for early detection of persistence after a single dose of methotrexate for ectopic pregnancy. , 2004, European journal of obstetrics, gynecology, and reproductive biology.

[6]  J. Coiffic,et al.  Traitement médical des grossesses extra-utérines : un essai clinique randomisé comparant méthotrexate-mifépristone et placebo-méthotrexate , 2004 .

[7]  S. Van Huffel,et al.  The use of a new logistic regression model for predicting the outcome of pregnancies of unknown location , 2004 .

[8]  D. Jurkovic,et al.  Expectant management of tubal ectopic pregnancy: prediction of successful outcome using decision tree analysis , 2004, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[9]  H. Masuzaki,et al.  Laparoscopic salpingotomy for tubal pregnancy: comparison of linear salpingotomy with and without suturing. , 2004, Human reproduction.

[10]  R. Arora,et al.  A randomized controlled comparison of minialpartomy and lapartomy in ectopic pregnancy cases. , 2003, Indian journal of medical sciences.

[11]  S. Chevret,et al.  Medical treatment of ectopic pregnancies: a randomized clinical trial comparing methotrexate-mifepristone and methotrexate-placebo. , 2003, Human reproduction.

[12]  P. Thonneau,et al.  Ectopic pregnancy in African developing countries , 2003, Acta obstetricia et gynecologica Scandinavica.

[13]  H. Kaya,et al.  Intratubal methotrexate for prevention of persistent ectopic pregnancy after salpingotomy. , 2002, The Journal of the American Association of Gynecologic Laparoscopists.

[14]  A. Golan,et al.  Methotrexate versus hyperosomolar glucose in the treatment of extrauterine pregnancy , 2001, Archives of Gynecology and Obstetrics.

[15]  B. Woelfer,et al.  Expectant management of early pregnancies of unknown location: a prospective evaluation of methods to predict spontaneous resolution of pregnancy , 2001, BJOG : an international journal of obstetrics and gynaecology.

[16]  C. Farquhar,et al.  A randomised trial comparing single dose systemic methotrexate and laparoscopic surgery for the treatment of unruptured tubal pregnancy , 2001, BJOG : an international journal of obstetrics and gynaecology.

[17]  C. Farquhar,et al.  An economic evaluation of single dose systemic methotrexate and laparoscopic surgery for the treatment of unruptured ectopic pregnancy , 2001, BJOG : an international journal of obstetrics and gynaecology.

[18]  D. Elmoghazy,et al.  Prevention of persistent ecpopic pregnancy with single dose methotrexate after surgical conservation of the tube , 2000 .

[19]  P. Bossuyt,et al.  Interventions for tubal ectopic pregnancy. , 2000, The Cochrane database of systematic reviews.

[20]  P. Bossuyt,et al.  Implementation of probabilistic decision rules improves the predictive values of algorithms in the diagnostic management of ectopic pregnancy. , 1999, Human reproduction.

[21]  P. Bossuyt,et al.  Treatment of tubal pregnancy in the netherlands: an economic comparison of systemic methotrexate administration and laparoscopic salpingostomy. , 1999, American journal of obstetrics and gynecology.

[22]  F. Veen,et al.  Fertility outcome after systemic methotrexate and laparoscopic salpingostomy for tubal pregnancy , 1999, The Lancet.

[23]  R. Paulson,et al.  Resolution of Hormonal Markers of Ectopic Gestation: A Randomized Trial Comparing Single‐Dose Intramuscular Methotrexate With Salpingostomy , 1998, Obstetrics and gynecology.

[24]  P. Bossuyt,et al.  Serum human chorionic gonadotropin measurement in the diagnosis of ectopic pregnancy when transvaginal sonography is inconclusive. , 1998, Fertility and sterility.

[25]  R. Frydman,et al.  Randomized trial of conservative laparoscopic treatment and methotrexate administration in ectopic pregnancy and subsequent fertility. , 1998, Human reproduction.

[26]  L. Fedele,et al.  Intramesosalpingeal injection of oxytocin in conservative laparoscopic treatment for tubal pregnancy: preliminary results. , 1998, Human reproduction.

[27]  P. Bossuyt,et al.  Systemic methotrexate therapy versus laparoscopic salpingostomy in patients with tubal pregnancy. Part I. Impact on patients' health-related quality of life. , 1998, Fertility and sterility.

[28]  P. Bossuyt,et al.  Systemic methotrexate therapy versus laparoscopic salpingostomy in tubal pregnancy. Part II. Patient preferences for systemic methotrexate. , 1998, Fertility and sterility.

[29]  N. Colacurci,et al.  Time length of negativization of hCG serum values after either surgical or medical treatment of ectopic pregnancy. , 1998, Panminerva medica.

[30]  Z. Alfirevic,et al.  Mifepristone in combination with methotrexate for the medical treatment of tubal pregnancy: a randomized, controlled trial. , 1998, Human reproduction.

[31]  P. Bossuyt,et al.  Fertility after conservative and radical surgery for tubal pregnancy. , 1998, Human reproduction.

[32]  D. Cumming,et al.  Factors determining fertility after conservative or radical surgical treatment for ectopic pregnancy. , 1997, Fertility and sterility.

[33]  F. Veen,et al.  Randomised trial of systemic methotrexate versus laparoscopic salpingostomy in tubal pregnancy , 1997, The Lancet.

[34]  K. Barnhart,et al.  Postoperative day 1 serum human chorionic gonadotropin level as a predictor of persistent ectopic pregnancy after conservative surgical management. , 1997, Fertility and sterility.

[35]  H. Hepp,et al.  Fertility after organ-preserving surgery of ectopic pregnancy: results of a multicenter study. , 1997, Fertility and sterility.

[36]  K. Hordnes,et al.  Reproductive outcome after treatment of ectopic pregnancy with local injection of hypertonic glucose , 1997, Acta obstetricia et gynecologica Scandinavica.

[37]  T. Tulandi,et al.  Current status of surgical and nonsurgical management of ectopic pregnancy. , 1997, Fertility and sterility.

[38]  D. Mishell,et al.  Methotrexate Prophylaxis for Persistent Ectopic Pregnancy After Conservative Treatment by Salpingostomy , 1997, Obstetrics and gynecology.

[39]  B. Mol,et al.  Serum human chorionic gonadotropin clearance curves in patients with interstitial pregnancy treated with systemic methotrexate. , 1996, Fertility and sterility.

[40]  P. Ylöstalo,et al.  Low‐Dose Oral Methotrexate With Expectant Management of Ectopic Pregnancy , 1996, Obstetrics and gynecology.

[41]  A. Shulman,et al.  Controversies and problems in the current management of tubal pregnancy. , 1996, Human reproduction update.

[42]  I. Bukovsky,et al.  Laparoscopic salpingostomy versus laparoscopic local methotrexate injection in the management of unruptured ectopic gestation. , 1996, American journal of obstetrics and gynecology.

[43]  P. Bossuyt,et al.  Conservative versus radical surgery for tubal pregnancy , 1996, Acta obstetricia et gynecologica Scandinavica.

[44]  C. Chapron,et al.  Salpingectomy - the laparoscopic surgical choice for ectopic pregnancy. , 1996, Human reproduction.

[45]  M. Uğur,et al.  Prophylactic vasopressin during laparoscopic salpingotomy for ectopic pregnancy. , 1996, The Journal of the American Association of Gynecologic Laparoscopists.

[46]  H. Fernandez,et al.  [Role of conservative therapy and medical treatment in ectopic pregnancy: literature review and clinical trial comparing medical treatment and conservative laparoscopic treatment]. , 1996, Contraception, fertilite, sexualite.

[47]  E. Cosmi,et al.  Comparison of local injection of methotrexate and linear salpingostomy in the conservative laparoscopic treatment of ectopic pregnancy. , 1996, The Journal of the American Association of Gynecologic Laparoscopists.

[48]  M. Ryynänen,et al.  Severe intraperitoneal hemorrhage in ectopic pregnancy , 1996, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[49]  I. Clausen.  Conservative versus radical surgery for tubal pregnancy , 1996, Acta obstetricia et gynecologica Scandinavica.

[50]  T. Falcone,et al.  Methotrexate: local versus intramuscular. , 1996, Fertility and sterility.

[51]  T. Matsuwaki,et al.  Local injection of methotrexate dissolved in saline versus methotrexate suspensions for the conservative treatment of ectopic pregnancy. , 1995, Human reproduction.

[52]  T. Matsuwaki,et al.  A new approach to methotrexate and lipiodol suspensions for ectopic pregnancy: preliminary in vitro and animal experiments. , 1995, Journal of obstetrics and gynaecology.

[53]  P. Bergsjø,et al.  Treatment of ectopic pregnancy by local injection of hypertonic glucose: A randomized trial comparing administration guided by transvaginal ultrasound or laparoscopy , 1995, Acta obstetricia et gynecologica Scandinavica.

[54]  Suspected ectopic pregnancy. What to do when human chorionic gonadotropin levels are below the discriminatory zone. , 1995, The Journal of reproductive medicine.

[55]  A. Strandell,et al.  A cost-effectiveness study of a randomised trial of laparoscopy versus laparotomy for ectopic pregnancy , 1995, The Lancet.

[56]  P. Bossuyt,et al.  Pregnancy: Clearance curves of serum human chorionic gonadotrophin for the diagnosis of persistent trophoblast , 1995 .

[57]  R. Frydman,et al.  Ultrasound-guided injection of methotrexate versus laparoscopic salpingotomy in ectopic pregnancy. , 1995, Fertility and sterility.

[58]  R. Frydman,et al.  Treatment of unruptured tubal pregnancy with methotrexate: pharmacokinetic analysis of local versus intramuscular administration. , 1994, Fertility and sterility.

[59]  J. Bondis,et al.  Transvaginal intra-amniotic injection of methotrexate in early ectopic pregnancy. Advantages over the laparoscopic approach. , 1994, Early human development.

[60]  G. Thompson,et al.  Intra-amniotic methotrexate versus CO2 laser laparoscopic salpingotomy in the management of tubal ectopic pregnancy--a prospective randomized trial. , 1994, Fertility and sterility.

[61]  J. Brumsted,et al.  Efficacy and safety of single-dose systemic methotrexate in the treatment of ectopic pregnancy. , 1994, Fertility and sterility.

[62]  P. Ylöstalo,et al.  Serum human chorionic gonadotropin dynamics during spontaneous resolution of ectopic pregnancy. , 1994, Fertility and sterility.

[63]  Z. Katz,et al.  Declining beta-human chorionic gonadotropin level may provide false security that tubal pregnancy will not rupture. , 1994, European journal of obstetrics, gynecology, and reproductive biology.

[64]  B. Lindblom,et al.  [Fertility after conservative surgical treatment of ectopic pregnancy, evaluated by a randomized trial]. , 1993, Ugeskrift for laeger.

[65]  J. Abbott,et al.  Ruptured ectopic pregnancy after medical management: current conservative management strategies. , 1993, The American journal of emergency medicine.

[66]  W. Ankum,et al.  Transvaginal sonography and human chorionic gonadotrophin measurements in suspected ectopic pregnancy: a detailed analysis of a diagnostic approach. , 1993, Human reproduction.

[67]  W. Ankum,et al.  Laparoscopy: a dispensable tool in the diagnosis of ectopic pregnancy? , 1993, Human reproduction.

[68]  K. Käär,et al.  Comparison of a local injection of hyperosmolar glucose solution with salpingostomy for the conservative treatment of tubal pregnancy. , 1993, Fertility and sterility.

[69]  F. Ling,et al.  Single-dose methotrexate: an expanded clinical trial. , 1993, American journal of obstetrics and gynecology.

[70]  R. Frydman,et al.  Methotrexate treatment of ectopic pregnancy: 100 cases treated by primary transvaginal injection under sonographic control , 1993 .

[71]  P. Ylöstalo,et al.  Expectant management of ectopic pregnancy. , 1992, European journal of obstetrics, gynecology, and reproductive biology.

[72]  P. Lundorff.  Treatment of ectopics and subsequent adhesion formation. , 1993, Progress in clinical and biological research.

[73]  C. Nager,et al.  Operative laparoscopy versus laparotomy for the management of ectopic pregnancy: a prospective trial. , 1992, Fertility and sterility.

[74]  S. Yagel,et al.  Rupture of ectopic pregnancy following disappearance of serum beta subunit of hcg , 1992, Obstetrics and gynecology.

[75]  B. Lindblom,et al.  Fertility outcome after conservative surgical treatment of ectopic pregnancy evaluated in a randomized trial. , 1992, Fertility and sterility.

[76]  D. Guzick,et al.  Lack of resolution of ectopic pregnancy by intratubal injection of methotrexate. , 1992, Fertility and sterility.

[77]  M. Vermesh,et al.  Reproductive outcome after linear salpingostomy for ectopic gestation: a prospective 3-year follow-up. , 1992, Fertility and sterility.

[78]  R. Collins,et al.  Outcome of laparoscopic versus traditional surgery for ectopic pregnancies. , 1992, Fertility and sterility.

[79]  A. Shulman,et al.  Conservative treatment of ectopic pregnancy and its effect on corpus luteum activity. , 1992, Gynecologic and obstetric investigation.

[80]  J. Brosens,et al.  Conservative laparoscopic treatment of ectopic pregnancies using the CO2‐laser , 1991, British journal of obstetrics and gynaecology.

[81]  R. Hemmings,et al.  Rupture of ectopic pregnancy in women with low and declining serum beta-human chorionic gonadotropin concentrations. , 1991, Fertility and sterility.

[82]  M. Hahlin,et al.  Adhesion formation after laparoscopic surgery in tubal pregnancy: a randomized trial versus laparotomy. , 1991, Fertility and sterility.

[83]  F. Ling,et al.  Single-Dose Methotrexate for Treatment of Ectopic Pregnancy , 1991, Obstetrics and gynecology.

[84]  R. Frydman,et al.  Conservative management of ectopic pregnancy: prospective randomized clinical trial of methotrexate versus prostaglandin sulprostone by combined transvaginal and systemic administration. , 1991, Fertility and sterility.

[85]  H. Kiss,et al.  Prostaglandin versus expectant management in early tubal pregnancy. , 1991, Prostaglandins, leukotrienes, and essential fatty acids.

[86]  M. Hahlin,et al.  Laparoscopic surgery in ectopic pregnancy: A randomized trial versus laparotomy , 1991, Acta obstetricia et gynecologica Scandinavica.

[87]  M. Canis,et al.  The Drop in the Level of hCG After Conservative Laparoscopic Treatment of Ectopic Pregnancy , 1991 .

[88]  T. Tulandi,et al.  Treatment of tubal ectopic pregnancy by salpingotomy with or without tubal suturing and salpingectomy. , 1991, Fertility and sterility.

[89]  M. Diamond,et al.  Persistent Ectopic Pregnancy Following Laparoscopic Linear Salpingostomy , 1990, Obstetrics and gynecology.

[90]  P. Ylöstalo,et al.  Diagnosis of ectopic pregnancy by vaginal ultrasonography in combination with a discriminatory serum hCG level of 1000 IU/1 (IRP) , 1990, British journal of obstetrics and gynaecology.

[91]  P. Lang,et al.  Conservative treatment of ectopic pregnancy with local injection of hyperosmolar glucose solution or prostaglandin-F2α: a prospective randomised study , 1990, The Lancet.

[92]  B. Lindblom,et al.  Second-look laparoscopy after ectopic pregnancy. , 1990, Fertility and sterility.

[93]  P. Lang,et al.  LOCAL APPLICATION OF HYPEROSMOLAR GLUCOSE SOLUTION IN TUBAL PREGNANCY , 1989, The Lancet.

[94]  E. Newlands,et al.  The role of low‐dose methotrexate and folinic acid in gestational trophoblastic tumours (GTT) , 1989, British journal of obstetrics and gynaecology.

[95]  M. Sauer,et al.  Management of Unruptured Ectopic Gestation by Linear Salpingostomy: A Prospective, Randomized Clinical Trial of Laparoscopy Versus Laparotomy , 1989, Obstetrics and gynecology.

[96]  P. D. Silva.  A laparoscopic approach can be applied to most cases of ectopic pregnancy. , 1988, Obstetrics and gynecology.

[97]  P. Husslein,et al.  TREATMENT OF TUBAL PREGNANCY BY PROSTAGLANDINS , 1988, The Lancet.

[98]  M. Sauer,et al.  Nonsurgical management of unruptured ectopic pregnancy: an extended clinical trial. , 1987, Fertility and sterility.

[99]  J. Sama,et al.  Expectant management of presumed ectopic pregnancies. , 1987, Fertility and sterility.

[100]  H. Taubert,et al.  Spontaneous recovery of ectopic pregnancy: a preliminary report. , 1987, European journal of obstetrics, gynecology, and reproductive biology.

[101]  L. Hamberger,et al.  LOCAL PROSTAGLANDIN F2α INJECTION FOR TERMINATION OF ECTOPIC PREGNANCY , 1987, The Lancet.

[102]  R. Tamura,et al.  Conservative treatment of ectopic pregnancy with methotrexate. , 1986, American journal of obstetrics and gynecology.

[103]  Cho Hc.  Nonsurgical management of ectopic pregnancy associated with severe hyperstimulation syndrome. , 1985, Obstetrics and gynecology.

[104]  Burke Rk,et al.  The effect of in vitro sperm capacitation on sperm velocity and motility as measured by an in-office, integrated, microcomputerized system for semen analysis. , 1985 .

[105]  S. Fujimoto,et al.  Treatment of interstitial ectopic pregnancy with methotrexate: report of a successful case. , 1982, Fertility and sterility.

[106]  D. Serr,et al.  Nonoperative management of ectopic pregnancy. A preliminary report. , 1982, The Journal of reproductive medicine.

[107]  L. Cala.  Cerebral absorption of metrizamide. , 1981, Lancet.

[108]  A. Purdie.  Ectopic pregnancy. , 1963, The Practitioner.