Prophylactic methotrexate after linear salpingostomy: a decision analysis

Objective: To compare two strategies for managing women after linear salpingostomy for treatment of tubal pregnancy: observation and prophylactic methotrexate.

Design: Decision analysis.

Setting: Outpatient tertiary-care center.

Patient(s): One thousand hypothetical women treated with a linear salpingostomy for ectopic pregnancy.

Intervention(s): Observation after salpingostomy and treatment of persistent ectopic pregnancy with a single dose of methotrexate (current standard of care) versus treatment with prophylactic methotrexate at the time of salpingostomy.

Main Outcome Measure(s): Number of ruptured ectopic pregnancies, surgical procedures, complications, and cost for each group (observation vs. prophylaxis).

Result(s): Prophylactic methotrexate results in fewer cases of tubal rupture (0.4% vs. 3.7%) and fewer procedures (1.9% vs. 4.7%) at a lower cost ($67.55 less/patient) compared with observation alone. Methotrexate-associated complications occur more frequently with prophylaxis (5.5% vs. 0.8%). Certain conditions change which strategy is preferable. Observation is the best strategy when the persistent ectopic pregnancy rate is <9%, the success of prophylaxis is <95%, the complication rate associated with methotrexate is >18%, or the rupture rate of persistent ectopic pregnancies is <7.3%.

Conclusion(s): Prophylactic methotrexate at the time of linear salpingostomy for the treatment of ectopic pregnancy is preferable to observation as long as certain conditions exist.     

Three Recurrent Ectopic Pregnancies Case Report and Review of the Literature

EDITORIAL COMMENT: We accepted this case report for publication not solely because of its unusual anecdotal interest, or for its glimpse into reproductive requirements and wishes of women in Saudi Arabia, but for its summary of the literature on repeat ectopic pregnancy which should interest readers. Although preservation of the Fallopian tube by laparascopic salpingostomy is becoming the established treatment of unruptured ectopic pregnancy, we are unaware of a prospective trial comparing subsequent fertility in women with salpingostomy versus partial salpingectomy for unruptured ectopic pregnancy when the opposite Fallopian tube appears normal. In the present case there is no evidence that the preserved tube was useful from the reproductive point of view, although it remained patent. One reviewer of this paper performed a medline search and found that 'there are no prospective studies and only a few retrospective reports comparing fertility rates after salpingostomy and salpingectomy. Three major retrospective studies found no significant difference infertility or incidence of repeat ectopic pregnancy between the 2 procedures, but salpingostomy carries a 5–8% risk of persistent ectopic pregnancy, contributing to increased morbidity and cost. Fertility after ectopic pregnancy is affected much more by the status of the contralateral tube than by the procedure performed, with fertility rates exceeding 80% after salpingectomy when the opposite tube is normal'(A).
A. Rulin MC. Is salpingostomy the surgical treatment of choice for unruptured tubal pregnancy? Obstet Gynecoi 1995; 86: 1010–1013.
Summary: Further studies on the obstetric performance of women after recurrent ectopic pregnancies are needed to adequately counsel women who are still interested in future fertility, even after their third ectopic pregnancy.     

A Pragmatic and Evidence-Based Management of Ectopic Pregnancy

The incidence of ectopic pregnancy is approximately 2% of all pregnancies, and it remains the leading cause of death in early pregnancy. Over 95% of ectopic pregnancies are tubal pregnancies, and the remainders are nontubal pregnancies. The highest risk factor for ectopic pregnancy is a previous tubal pregnancy followed by previous tubal surgery, tubal sterilization, tubal pathology, and current intrauterine device use. The apparent increase in the incidence of nontubal ectopic pregnancy including heterotopic pregnancy may be attributed to the increasing number of pregnancies because of in vitro fertilization treatment. In most cases, an ectopic pregnancy can be treated medically with a single dose of methotrexate. Surgical treatment is still needed in women who are hemodynamically unstable and in those who do not fulfill the criteria for methotrexate treatment. Usually surgical treatment can be performed by laparoscopy and in some cases by hysteroscopy. Laparotomy is rarely needed even in women with intraperitoneal bleeding.     

Fertility after ectopic pregnancy

In the period July 1983 to March 1985, 264 women had surgery for ectopic pregnancy at Grady Memorial Hospital; 76 had postoperative hysterosalpingograms. Of these, 55 (76.4%) women were followed up for 3 to 41 months (mean, 23.8) to determine subsequent fertility. During the follow-up period, 30 pregnancies occurred among the 55 patients; 24 were intrauterine and 6 were repeat ectopic pregnancies. In the surgical group of 39 patients with salpingectomy, 60.8% of those desiring pregnancy achieved an intrauterine pregnancy. Of the 12 patients with salpingostomy, the three who desired pregnancy achieved it (100%). In the tubal abortion group, the two women desiring pregnancy conceived (100%). There were six repeat ectopic pregnancies (10.9%). Of the ectopic pregnancies, one occurred in the salpingectomy group (2.6%), four in the salpingostomy group (33.3%), and one in the tubal abortion group (25%). Five of the six ectopic gestations were found in the contralateral fallopian tube. Hysterosalpingographic evidence of contralateral tubal patency was a good prognostic indicator for subsequent intrauterine pregnancy. By contrast, one half of study patients with findings suggesting tubal occlusion still achieved an intrauterine pregnancy.     

Reproductive performance of women after two tubal ectopic pregnancies

Twenty-four women who had undergone total salpingectomy due to ectopic pregnancy and who subsequently underwent a laparotomy for a second ectopic pregnancy in their opposite tube were treated by the author. Treatment consisted of linear salpingostomy (n = 20) and partial salpingectomy (n = 4). The intrauterine pregnancy rate after linear salpingostomy in women who attempted to conceive was 50%, and the incidence of a third ectopic pregnancy was 27.8%. These findings suggest that linear salpingostomy should be considered in the management of a second tubal pregnancy in women with a single tube. The high incidence of a third ectopic pregnancy, however, is concerning.     

Reproductive performance after methotrexate treatment of ectopic pregnancy

The purpose of this study was to examine return of reproductive potential, hysterosalpingographic findings, and time to conception in patients treated with methotrexate and citrovorum factor for unruptured ectopic pregnancy. Fifty-seven patients with unruptured ectopic pregnancies less than 3.0 cm in greatest dimension were treated with methotrexate and citrovorum factor. The mean time from resolution of the ectopic pregnancy to return of menses was 26.0 (0 to 157) days. Forty-four patients were available for follow-up (2 to 15 months). Nineteen of 23 patients who had hysterosalpingograms demonstrated patency in the ipsilateral tube. Fourteen patients desired pregnancy; 11 of 14 (78.6%) were successful, with 10 of 11 (90.9%) having an intrauterine pregnancy, whereas one of 14 (9.1%) were extrauterine gestations. The mean time from first attempt to achieving pregnancy was 2.3 (1 to 4) months. We conclude that methotrexate and citrovorum factor treatment of unruptured ectopic pregnancy is associated with subsequent tubal patency and does not impair return of menses. Most importantly, the pregnancy rates after this form of therapy appear to be better than those achieved by traditional surgical methods, and are comparable to results after laparoscopic salpingostomy.     

Treatment of ectopic pregnancy by transvaginal intratubal methotrexate administration

Twelve women with tubal pregnancies were treated with intratubal transvaginal methotrexate injection (1 mg/kg body weight). Serum beta-hCG levels decreased in all patients, and the resolution time from injection to undetectable beta-hCG levels was 14-120 days. In spite of declining serum beta-hCG and unruptured tubal pregnancy, two patients subsequently requested definitive treatment for their ectopic pregnancies and underwent surgery. Four of six women found to have a living embryo in their gestational sacs required a repeat methotrexate injection; one of these also required a local potassium chloride injection. The tubal pregnancies resolved in nine patients treated with methotrexate alone. During resolution, we noted a gradually increasing resistance index of the blood flow in the region of the gestation, but the tube became distended to 4.4 +/- 0.4 cm before gradually decreasing in size. No complications or side effects were encountered. These findings suggest that intratubal transvaginal methotrexate administration can provide a safe alternative to surgical treatment for patients with early unruptured tubal ectopic pregnancy. However, the presence of a living embryo makes the ectopic pregnancy more resistant to methotrexate treatment.     

Reproductive potential after methotrexate treatment of ectopic gestation in a community hospital.

OBJECTIVE: To compare the rates of ipsilateral tubal patency after methotrexate treatment versus conservative surgical treatment in a small community hospital lacking personnel dedicated to methotrexate management. STUDY DESIGN: From hospital and clinic records, cases of ectopic gestation within a six-year interval were identified. Method of treatment and location of the ectopic gestation were documented by review of records and confirmed by patient interviews. Women desiring fertility were offered hysterosalpingography (HSG) to evaluate tubal patency. HSG was performed under fluoroscopy with water-soluble contrast medium. RESULTS: HSG was completed in 11 cases of linear salpingostomy and 11 cases of ectopic gestations treated by methotrexate. Ipsilateral patency was documented in 8 of 11 (72%) tubes treated by linear salpingostomy and 9 of 11 (81%) methotrexate-treated tubes. One methotrexate case had a prior ipsilateral ectopic treated by salpingostomy, and two additional cases had a prior contralateral ectopic removed by salpingectomy. Each of these three cases had ipsilateral tubal patency after methotrexate for the most recent ectopic gestation. CONCLUSION: Data from this study suggest comparable tubal patency rates after methotrexate and conservative surgery. Comparable tubal patency outcomes were obtained in our community hospital despite a less-rigorous-than normal follow-up protocol.     

输卵管妊娠后再次妊娠的探讨

对输卵管妊娠后有生育要求的５８例行输卵管切除术，１５例行输卵管开窗术，３０例应用药物保守治疗。结果：１０３例治疗后６７例宫内妊娠，９例再次异位妊娠。     

Hydrosalpinx – Salpingostomy,salpingectomy or tubal occlusion

Tubal factors account for approximately 25% of cases of infertility, and the most severe manifestation of tubal disease is hydrosalpinx, accounting for 10–30% of tubal diseases. Hydrosalpinx is a distension or dilatation of the fallopian tube in the presence of a distal tubal occlusion, and the most common cause is pelvic inflammatory disease. Women with hydrosalpinges have lower implantation and pregnancy rates in assisted reproductive technology (ART), due to a combination of mechanical and chemical factors thought to disrupt the endometrial environment. Current guidance is removal of the tube by salpingectomy (preferably laparoscopically) before IVF treatment. Salpingostomy, or distal tubal plastic surgery in the management of hydrosalpinx, is an alternative for women desiring natural conception, although ectopic pregnancy rates as high as 10% have been reported. Proximal tubal occlusion with Essure^® devices placed hysteroscopically can be considered particularly in cases of distorted pelvic anatomy or pelvic adhesions making abdominal surgery complex. However, low clinical pregnancy and live birth rates have been reported with the use of these devices before IVF. In this review, we discuss salpingostomy, salpingectomy and tubal occlusion as possible management options for the reproductive women with hydrosalpinx.     

A Systematic Review and Meta-analysis of Surgical Treatment of Ectopic Pregnancy with Salpingectomy versus Salpingostomy

ObjectiveTo evaluate the fertility outcomes of salpingectomy compared with those of salpingostomy among patients treated for tubal ectopic pregnancies, including a separate analysis of women with risk factors along with a review of the surgical technique.Data SourcesSystematic review and meta-analysis from 1990 to the present through PubMed, Embase, CINAHL, and Ovid MEDLINE. The search string included “tubal pregnancy” or “ectopic” as well as “salpingectomy” and various terms describing salpingotomy.Methods of Study SelectionArticles studying women who underwent surgical management of an ectopic pregnancy and the contrasted outcomes of salpingectomy vs salpingostomy were reviewed. The primary outcomes included subsequent intrauterine pregnancy (IUP) and repeat ectopic pregnancy (REP).Tabulation, Integration, and ResultsTwo randomized controlled trials (RCTs), which consisted mostly of patients classified as low risk, and patients from 16 cohort studies were included. In the RCTs, there was no significant difference in the odds of subsequent IUP in patients who underwent a salpingectomy compared with those who were treated with salpingotomy (odds ratio [OR] 0.97; 95% confidence interval [CI], 0.71–1.33). However, a significant and clinically meaningful difference was noted in the cohort studies, with the patients having a lower chance of IUP after salpingectomy (OR 0.45; 95% CI, 0.39–0.52). No significant difference was noted in the OR for a REP in the randomized trials (OR 0.77; 95% CI, 0.41–1.47), but the patients followed in the cohort studies had a cumulatively higher risk of REP after a salpingostomy (OR 0.73; 95% CI, 0.60–0.90).The subgroup analysis examining women within the studies with risk factors for tubal pathology found an even more impressive lowering in the odds of a subsequent IUP in patients classified as at-risk who were treated with salpingectomy (OR 0.30; 95% CI, 0.17–0.54), with a change in the direction of the odds for an REP rate favoring those who were treated with salpingostomy (OR 1.96; 95% CI, 0.88–4.35).ConclusionSalpingectomy has clear advantages over salpingostomy, and RCTs consisting mainly of patients classified as low risk show no difference in outcomes between salpingectomy and salpingostomy. However, in cohort studies inclusive of all patients, the likelihood of a subsequent spontaneous IUP is decreased in patients treated with salpingectomy, and salpingostomies may be especially underused in women with risk factors for tubal disease.     

Conservative surgical management of isthmic ectopic pregnancies

During the 12-month study interval ending March 30, 1986, there were 203 ectopic pregnancies at Grady Memorial Hospital, a ratio of one ectopic gestation per 34 deliveries. Twenty patients with isthmic ectopic pregnancies were selected for treatment by one of three operative modalities. Seven patients with ruptured isthmic ectopic pregnancies underwent segmental tubal resection without reanastomosis. All four patients who underwent segmental tubal resection with primary microsurgical reanastomosis had postoperative hysterosalpingograms demonstrating bilateral tubal patency. One pregnancy has occurred in this group. Nine patients underwent linear salpingostomy. In five of the six patients who had postoperative hysterosalpingography, patency of the involved fallopian tube was demonstrated. Four of these nine patients, including one patient with contralateral tubal occlusion, have conceived. We conclude that linear salpingostomy for isthmic ectopic pregnancies is as effective as segmental tubal resection with primary microsurgical reanastomosis in achieving tubal patency.     

Persistent ectopic pregnancy following laparoscopic linear salpingostomy.

As the surgical approach for ectopic pregnancies evolves from radical to conservative procedures, the potential hazard of persistent ectopic pregnancy has become increasingly pertinent. From September 1, 1986 to August 31, 1989, 11 women with persistent ectopic pregnancy after laparoscopic salpingostomy were diagnosed and treated at Yale-New Haven Hospital. Persistent ectopic pregnancy was suspected in nine cases because of symptoms and in two because of plateauing beta-hCG titers. Ten of 11 patients underwent repeat surgery. Eight had partial or complete salpingectomy of the involved ipsilateral tube, two had repeat salpingostomies, and one was treated with methotrexate. When the 11 women with persistent ectopic pregnancies were compared with 70 patients treated successfully by laparoscopic salpingostomy using multivariate stepwise logistic regression, smaller size of the ectopic (P less than .01) and fewer days of amenorrhea (P less than .05) predicted persistent ectopic pregnancy after laparoscopic salpingostomy. Based upon our experience, we believe that earlier-treated ectopic pregnancies (ie, fewer than 42 days of amenorrhea) and/or smaller ectopics (ie, 2.0 cm or less in diameter) require treatment with particular caution and close postoperative surveillance.     

Surgical management of ectopic pregnancy

Laparoscopic salpingostomy remains the definitive and universal treatment of ectopic pregnancy in patients who are hemodynamically stable and who wish to preserve their fertility. The reproductive performance after salpingostomy appears to be equivalent or better than salpingectomy, but the recurrent ectopic pregnancy rate may be slightly greater. Expectant management has a poor efficacy and unproven benefit in subsequent reproductive outcome. Its use should be limited to situations in which the ectopic pregnancy is suspected but cannot be detected by transvaginal ultrasound. Methotrexate is an alternative to surgical treatment in selected patients who fulfill strict inclusion criteria, including compliance with follow-up evaluation. A large, prospective, randomized trial with significant power is needed, however, to study the prognostic factors for methotrexate success. The most practical and efficient method of methotrexate administration is a single intramuscular injection. Those who do not meet the criteria for methotrexate therapy should be treated surgically, which can be done by laparoscopy. Interstitial pregnancy also can be treated with methotrexate. Otherwise, a cornual resection or salpingotomy can be done. Although, it is feasible by laparoscopy, the laparoscopic approach should be done only by those who have an expertise in laparoscopic suturing. Abdominal and ovarian pregnancies are best treated surgically. Further, the diagnosis usually is established by laparoscopy, and an appropriate surgical treatment can be conducted at the same time.     

Laparoscopic treatment of extensive pelvic adhesions, including hydrosalpinx

Sixty-seven women with extensive pelvic adhesions, including hydrosalpinx, underwent a laparoscopic surgical procedure over the past eight years. Only cases in which ovum pickup was greatly impaired by adhesions were included. Cases of extensive endometriosis or acute adhesions were excluded. Recent innovations in technique were used, including aquadissection, electrodissection, scissors dissection and laparoscopic suturing. Two women suffered transient unilateral brachial plexus injury; there were no other complications. No laparotomies were required. The viable pregnancy rate was 78% (21 of 27) for women who underwent salpingoovariolysis on the most favorable adnexa and 28.5% (2 of 7) for those with salpingostomy for hydrosalpinx. There was one ectopic pregnancy (3%). The outcome for 34 laparoscopically treated women compared favorably with that for 30 women with similar tubal factor infertility who were treated with laparotomy microsurgery; the viable pregnancy rate was 75% (9 of 12) for laparotomy salpingoovariolysis and 53% (8 of 15) for laparotomy salpingostomy, with an ectopic rate of 13% (4 of 30).     

Reproductive outcome in patients treated by oral methotrexate or laparoscopic salpingotomy for the management of tubal ectopic pregnancy

OBJECTIVE: To determine the reproductive outcome of women who have received methotrexate or been treated by laparoscopic salpingotomy (LS) for ectopic tubal pregnancy. STUDY DESIGN: The study consisted of 123 participants, all women with tubal pregnancies, who had been treated either by methotrexate per os or by laparoscopic salpingotomy. The reproductive outcome of these women was estimated after a follow-up time-period of ten years. RESULTS: In the methotrexate group, consisting of 34 women, the fertility rate was 82% with a mean interval time to conceive of 9.4 months after the treatment. In the group treated by LS, consisting of 89 women, the fertility rate was 82.6% and the mean interval time to conceive was 11.7 months. CONCLUSION: The reproductive outcome of the women who received either per os treatment of methotrexate or LS for tubal pregnancy, remains high. Both therapeutic methods constitute reliable solutions for managing ectopic pregnancy.     

Heterotopic Pregnancy Complicating In Vitro Fertilization

Summary: A review was undertaken of the cases of heterotopic pregnancy resulting from in vitro fertilization/embryo transfer (IVF/ET) and frozen embryo replacement (FER) in a 6-year cohort of women at National Women's Hospital in Auckland. The incidence of heterotopic pregnancy was 2.9% (5 cases) in 173 clinical pregnancies resulting from 901 embryo replacements. Of the 5 women with heterotopic pregnancy, 1 had unilateral tubal patency and 4 had bilateral tubal blockage; 3 had 'high responder' peak serum oestradiol levels (greater than 9,000 pmol/L) prior to oocyte pick-up (OPU); 3 had a serum human chorionic gonadotrophin beta subunit (beta-HCG) level greater than 600 IU/L on Day 14 following embryo transfer (ET) in the absence of a multiple intrauterine gestation on subsequent ultrasound scan. In the 4 women in whom unequivocal diagnosis of heterotopic pregnancy was not made on the initial ultrasound scan, there was delay in appropriate management, in 1 for more than 5 months. In conclusion, early IVF pregnancies require a transvaginal ultrasound scan performed by a sonographer experienced in the diagnosis of ectopic pregnancy and management of early pregnancy complications by clinicians in close consultation with the IVF centre itself. No single risk factor, laboratory test or combination of these is sensitive or specific enough to predict the occurrence of heterotopic pregnancy. The first-line surgical treatment of heterotopic pregnancy should be laparoscopic salpingectomy with excision of all except the intramural portion of the affected Fallopian tube.     

The potential of preoperative beta-hCG and progesterone levels to predict failure of laparoscopic linear salpingostomy in ectopic pregnancies

STUDY OBJECTIVE: To estimate the association between preoperative beta-human chorionic gonadotropin (hCG) and progesterone levels, and success of linear salpingostomy in treatment of tubal pregnancy. DESIGN: Retrospective case control study (Canadian Task Force classification II-1). SETTING: Women's general hospital. PATIENTS: Three hundred five women undergoing laparoscopic linear salpingostomy for ectopic pregnancy. INTERVENTION: Examination of risk factors for surgical failure of salpingostomy by analyzing corresponding receiver operating curves. MEASUREMENTS AND MAIN RESULTS: In 305 women, intervention was successful in 272 and failed in 33, as assessed by either postoperative hemorrhage (16) or rising beta-hCG values (14); 3 women had both. Of 295 patients in whom beta-hCG was evaluated preoperatively, 149 (50.5%) had values of 1000 mU/ml. or less; 75% had progesterone levels of 10 ng/ml or below. No association was found between preoperative beta-hCG and progesterone levels and the success of linear salpingostomy. CONCLUSION: Preoperative beta-hCG and progesterone levels are of no significance with regard to success of linear salpingostomy for treatment of tubal pregnancy.     

Retrospective analysis of laparoscopic salpingostomy and conservative expectant management of tubal ectopic pregnancy

Purpose  To identify predictive factors for successful expectant management of ectopic pregnancy and to evaluate the prognosis for fertility after expectant management and laparoscopic salpingostomy. Methods  Forty-six cases of expectant management and eighty cases of laparoscopic salpingostomy for tubal ectopic pregnancy were retrospectively analyzed. Subjects were classified in three groups: those who underwent laparoscopic salpingostomy, those treated by expectant management only, and those treated by expectant management but requiring additional treatment. Results  The rates of tubal patency, intrauterine pregnancy and repeated ectopic pregnancy in the laparoscopic salpingostomy group were 75, 40, and 16%. The rates in the expectant management group were not significantly different: 72, 42 and 15%. Finally, the rates in the extra treatment group were 75, 39 and 15%. Success rate of expectant management was 54%. In 93% of cases expectant management was successfully completed when the initial levels of urinal hCG were less than 3000 mIU/ml and the levels of hCG 48 h later were less than 80% of the initial levels. However, expectant management alone was insufficient and required extra treatment in 90% of cases when the initial levels of hCG were 3000 mIU/ml and above or when the levels of hCG level 48 h later was 80% of initial levels and above. Conclusions  Expectant management in combination with salpingostomy is not only minimally invasive but also a useful way to preserve fertility. Initial urine hCG levels and their variation over time can help predict whether expectant management will succeed.     

Fertility outcome following combined methotrexate treatment of unruptured extrauterine pregnancy

Objective To assess the effectiveness of systemic treatment with methotrexate in combination with local injection for unruptured tubal pregnancy, and to evaluate reproductive function following treatment.
Design Prospective, open clinical study.
Setting University clinic.
Population Sixty-seven women with unruptured tubal pregnancy.
Methods Systemic methotrexate (intramuscular methotrexate 0.5 mg/kg for up to five days) in combination with local application of 12.5 mg methotrexate via laparoscopy.
Main outcome measures The subsequent surgical intervention required and future fertility.
Results In 89.6% of women no further surgical intervention was required and 47 women (81%) experienced subsequently an intrauterine pregnancy. In 39 of 40 women who underwent hysterosalpingo-graphy following treatment, patency of the affected tube was observed.
Conclusions Combined local and systemic methotrexate treatment for unruptured tubal pregnancy seems to be more effective than each therapeutic modality alone.