8Management of ectopic pregnancy

8.1. Introduction

The early diagnosis of ectopic pregnancy has increased with the advent of ultrasound and serum β-human chorionic gonadotrophin (hCG) level assessment. Treatment options include surgical, medical and, rarely, expectant management. Surgery, by means of salpingectomy or salpingotomy, is performed laparoscopically or by open surgery. The most commonly used drug for the medical treatment of ectopic pregnancies is methotrexate. This can be administered either systemically or locally, or both, by various routes and requires constant vigilance of effect and evaluation by serial follow-up.

The broader range of treatments for ectopic pregnancy has allowed women's choice to be an integral part of the decision-making process. This chapter examines the evidence for the effectiveness and safety of surgical and medical treatment of tubal ectopic pregnancy in view of primary treatment success, tubal preservation and future fertility.

8.2. Surgical compared with medical management of ectopic pregnancy

Review question

How effective is surgical management of tubal ectopic pregnancy compared with medical management for improving women's clinical and psychological outcomes?

Description of included studies

Ten studies were included in this review (Colacurci et al., 1998; Dias Pereira et al., 1998; Fernandez et al., 1995; Fernandez et al., 1998; Hajenius et al., 1997; Moeller et al., 2009; Nieuwkerk et al., 1998; Saraj et al., 1998; Sowter et al., 2001b; Zilber et al., 1996).

All the included studies are randomised trials: three were conducted in the Netherlands (Hajenius et al., 1997; Dias Pereira et al., 1998; Nieuwkerk et al., 1998), two in France (Fernandez et al., 1995; Fernandez et al., 1998), one in Denmark (Moeller et al., 2009), one in the USA (Saraj et al., 1998;), one in Israel (Zilber et al., 1996), one in New Zealand (Sowter et al., 2001b) and one in Italy (Colacurci et al., 1998).

All included studies compared medical and surgical management of ectopic pregnancy and reported at least one priority outcome. Surgical management consisted of salpingotomy/salpingostomy in all of the included trials except for one (Sowter et al., 2001b) where some women (n = 7/28) were treated with salpingectomy for various reasons. Medical management in all included trials consisted of systemic or local injection of methotrexate. Eight trials (Colacurci et al., 1998; Dias Pereira et al., 1998; Fernandez et al., 1998; Hajenius et al., 1997; Moeller et al., 2009; Nieuwkerk et al., 1998; Saraj et al., 1998; Sowter et al., 2001b) compared systemic methotrexate with surgery. In three of these trials (Nieuwkerk et al., 1998; Dias Pereira et al., 1998; Hajenius et al., 1997) women were treated with multiple doses of methotrexate and in the remaining five trials they were treated with a single dose of intramuscular methotrexate injection. Three trials (Fernandez et al., 1995; Fernandez et al., 1998; Zilber et al., 1996) compared local injection of methotrexate to surgery for management of ectopic pregnancy. Local injection in the three trials consisted of direct injection of methotrexate into the pregnancy site under laparoscopic guidance. One trial (Fernandez et al., 1998) compared local or systemic injection of methotrexate to surgery for management of ectopic pregnancy.

The trials were conducted in economically developed countries and their populations include women with confirmed ectopic pregnancy. Further details, including the duration of follow-up, can be found in the evidence tables in Appendix H.

Evidence profile

Outcomes are reported in three evidence profiles:

Table 8.1. GRADE summary of findings for comparison of surgery with systemic methotrexate.

Table 8.1

GRADE summary of findings for comparison of surgery with systemic methotrexate.

Table 8.2. GRADE summary of findings for comparison of surgery with local methotrexate.

Table 8.2

GRADE summary of findings for comparison of surgery with local methotrexate.

Table 8.3. GRADE summary of findings for comparison of surgery with systemic and local methotrexate.

Table 8.3

GRADE summary of findings for comparison of surgery with systemic and local methotrexate.

In the outcomes with high heterogeneity (I2 greater than 60%), the technical team used a random effects model (the remaining outcomes used fixed effects models) and explored the heterogeneity with sensitivity analyses.

Success rate (surgery compared with systemic methotrexate)

Overall heterogeneity (69%) was not reduced by excluding the trial with multi-dose methotrexate; however, the heterogeneity was reduced to some extent (56%) by excluding the trial that treated some women (n = 6/28) with salpingectomy.

Hospital stay (surgery compared with local methotrexate)

Excluding the study with small sample size (less than 50) reduced the heterogeneity from 100% to 0%. The change could be a result of different hospitals' policies regarding the hospital stay following the treatment.

Evidence statements

Surgery compared with systemic methotrexate

Success rate

One meta-analysis of five studies did not find a statistically significant difference in the success rate in women who received surgical management compared with women who received medical management. The evidence for this finding was of moderate quality.

Future pregnancy rate

One meta-analysis of two studies did not find a statistically significant difference in future pregnancy rate in women who received surgical management compared with women who received medical management with systemic methotrexate. The evidence for this finding was of low quality.

Recurrent ectopic pregnancy

One meta-analysis of two studies did not find a statistically significant difference in recurrent ectopic pregnancy rate in women who received surgical management compared with women who received medical management with systemic methotrexate. The evidence for this finding was of moderate quality.

Resolution time

One meta-analysis of three studies found that resolution time was shorter in women who received surgical management compared with women who received medical management with systemic methotrexate. This finding was statistically significant. The evidence for this finding was of moderate quality.

Hospital stay

One study found that hospital stay was longer in women who received surgical management compared with women who received medical management with systemic methotrexate. This finding was statistically significant. The evidence for this finding was of moderate quality.

Need for further intervention

One meta-analysis of three studies found that the need for further intervention was lower in women who received surgical management compared with women who received medical management with systemic methotrexate. This finding was statistically significant. The evidence for this finding was of high quality.

Tubal preservation

One study did not find a statistically significant difference in tubal preservation in women who received salpingotomy compared with women who received medical management with systemic methotrexate. The evidence for this finding was of high quality.

Homolateral tubal patency

One study did not find a statistically significant difference in homolateral tubal patency in women who received surgical management compared with women who received medical management with systemic methotrexate. The evidence for this finding was of moderate quality.

Pain score 2 days after confirmative laparoscopy

One study did not find a statistically significant difference in pain scores 2 days after confirmative laparoscopy in women who received surgical management compared with women who received medical management with systemic methotrexate. The evidence for this finding was of moderate quality.

Pain score 2 weeks after confirmative laparoscopy

One study did not find a statistically significant difference in pain scores 2 weeks after confirmative laparoscopy in women who received surgical management compared with women who received medical management with systemic methotrexate. The evidence for this finding was of moderate quality.

Pain score 16 weeks after confirmative laparoscopy

One study did not find a statistically significant difference in pain scores 16 weeks after confirmative laparoscopy in women who received surgical management compared with women who received medical management with systemic methotrexate. The evidence for this finding was of moderate quality.

Depression score 2 weeks after confirmative laparoscopy

One study did not find a statistically significant difference in depression scores 2 weeks after confirmative laparoscopy in women who received surgical management compared with women who received medical management with systemic methotrexate. The evidence for this finding was of moderate quality.

Depression score 16 weeks after confirmative laparoscopy

One study did not find a statistically significant difference in depression scores 16 weeks after confirmative laparoscopy in women who received surgical management compared with women who received medical management with systemic methotrexate. The evidence for this finding was of moderate quality.

Overall quality of life score 2 days after confirmative laparoscopy

One study found that overall quality of life scores 2 days after confirmative laparoscopy were lower in women who received surgical management compared with women who received medical management with systemic methotrexate. This finding was statistically significant and the evidence for this finding was of moderate quality.

Overall quality of life score 2 weeks after confirmative laparoscopy

One study found that overall quality of life scores 2 weeks after confirmative laparoscopy was lower in women who received surgical management compared with women who received medical management with systemic methotrexate. This finding was statistically significant and the evidence for this finding was of moderate quality.

Overall quality of life score 16 weeks after confirmative laparoscopy

One study did not find a statistically significant difference in overall quality of life scores 16 weeks after confirmative laparoscopy in women who received surgical management compared with women who received medical management with systemic methotrexate. The evidence for this finding was of moderate quality.

Surgery compared with local methotrexate

Success rate

One meta-analysis of two studies did not find a statistically significant difference in the success rate in women who received surgical management compared with women who received medical management with local methotrexate. The evidence for this finding was of moderate quality.

Future pregnancy rate

One meta-analysis of two studies did not find a statistically significant difference in future pregnancy rate in women who received surgical management compared with women who received medical management with local methotrexate. The evidence for this finding was of low quality.

Recurrent ectopic pregnancy

One meta-analysis of two studies did not find a statistically significant difference in pregnancy rate in women who received surgical management compared with women who received medical management with local methotrexate. The evidence for this finding was of moderate quality.

Resolution time

One study found that resolution time was shorter in women who received surgical management compared with women who received medical management with local methotrexate. This finding was statistically significant. The evidence for this finding was of moderate quality.

One study did not find a statistically significant difference in resolution time in women who received surgical management compared with women who received medical management with local methotrexate. The evidence for this finding was of moderate quality.

Hospital stay

One meta-analysis of three studies found that hospital stay was longer in women who received surgical management compared with women who received medical management with local methotrexate. This finding was statistically significant and the evidence for this finding was of moderate quality.

Need for further intervention

One meta-analysis of two studies did not find a statistically significant difference in the need for further intervention in women who received surgical management compared with women who received medical management with local methotrexate. The evidence for this finding was of moderate quality.

Surgery compared with methotrexate (systemic and local)

Future spontaneous ongoing or term pregnancy

One study did not find a statistically significant difference in the rate of future spontaneous continuing or term pregnancy in women who received surgical management compared with women who received medical management with methotrexate (systemic or local). The evidence for this finding was of low quality.

Recurrent ectopic pregnancy

One study did not find a statistically significant difference in recurrent ectopic pregnancy in women who received surgical management compared with women who received medical management with methotrexate (systemic or local). The evidence for this finding was of low quality.

Health economics

A new economic model was developed for this guideline to assess the cost effectiveness of different treatment strategies for ectopic pregnancy. The model is described in more detail in Section 10.4.

The model compared the cost effectiveness of three treatment strategies in a population of women diagnosed with an ectopic pregnancy but not requiring urgent surgical intervention:

  • laparoscopic salpingectomy
  • laparoscopic salpingotomy

In the base–case analysis the evaluation took the form of a cost minimisation analysis with the assumption that all women recover and that any differences in morbidity only exist in the very short term. Methotrexate was the cheapest option at £1432 followed by laparoscopic salpingectomy at £1608. Laparoscopic salpingotomy, because of its relatively high re-intervention rate and follow-up costs, was the most expensive strategy at £2205. A probabilistic sensitivity analysis of one million Monte Carlo simulations found that methotrexate was cheapest in 99.65% of the simulations with a 0.35% probability that laparoscopic salpingectomy was cheapest.

A number of one-way sensitivity analyses suggested that the ordinal ranking of strategies in terms of their cost was not affected by large changes in parameter values. A further sensitivity analysis relaxed the assumption about equivalence in treatment outcomes and estimated an incremental gain in quality adjusted life years (QALYs) for the surgical alternatives when compared to methotrexate. This found that laparoscopic salpingotomy was dominated by laparoscopic salpingectomy (a higher cost than laparoscopic salpingectomy with no QALY gain). The incremental cost effectiveness ratio of laparoscopic salpingectomy against methotrexate was calculated to be almost £84,000 per QALY which would not normally be considered cost effective using advisory willingness to pay thresholds suggested by NICE (NICE, 2009).

Evidence to recommendations

Relative value placed on the outcomes considered

The guideline development group (GDG) identified future reproductive outcomes as very important from the woman's perspective.

The group also felt that outcomes such as the chances of treatment success, the likelihood of needing another intervention and the length of time required for follow-up would be important considerations for women, as well as having cost implications.

Women's experiences of care and psychological outcomes were identified as being important. However, evidence was only found for psychological outcomes and was not available for women's experience of care. The effects demonstrated were short term, with no significant differences shown after 2 weeks in most cases and 4 months in the remainder.

Consideration of clinical benefits and harms

The evidence in this review showed that women undergoing medical treatment required a longer period of recovery and follow-up than women who had laparoscopic surgery. In some women, the time to resolution was up to 6–7 weeks. Medical treatment was also associated with a higher need for further intervention, which could include surgery or an additional dose of methotrexate. In addition, the GDG recognised that some women may have contraindications to surgery or have a personal desire to avoid a surgical procedure; therefore medical treatment would be appropriate in such circumstances. For women choosing to have methotrexate treatment, the GDG agreed that systemic administration was preferable, as it is easier to administer, less invasive and in line with current practice.

The GDG noted that the studies considered in this review had specific inclusion criteria for women with an ectopic pregnancy who were felt to be at low risk for tubal rupture. Thus they felt that for women who fell outside of these criteria, methotrexate treatment was not an appropriate choice of treatment. Evidence from Sowter et al. (2001b) showed that the chance of treatment failure was increased in women with higher initial hCG levels. At an initial hCG below 1000 international units per litre (IU/l), women had a 12% chance of requiring further treatment, but at an hCG over 1500 IU/l this rose to 70%. Given this finding, the group recommended that methotrexate only be offered as a first-line treatment for women with an hCG of less than 1500 IU/l (and with an ectopic pregnancy with an adnexal mass smaller than 35 mm).

The evidence from Sowter et al. (2001b) also showed that at an hCG level below 5000 IU/l, women had an 85% chance of successful treatment with either a first or second dose of methotrexate administration. Given this, they felt that for women with hCG levels between 1500 IU/l and 5000 IU/l, it would still be appropriate to offer medical management, but that surgery should also be offered as a choice, given that women in this group were more likely to require further interventions following medical management.

The GDG members agreed that for women with an hCG level greater than 5000 IU/l, with an adnexal mass greater than 35 mm or with an ectopic pregnancy with a fetal heartbeat visible on ultrasound, surgery should be offered as a first-line treatment, as they were aware of studies that showed an increased risk of rupture for all of these women.

The GDG was aware of cases of women who had experienced a failure of medical treatment and then re-presented later with tubal rupture or other severe symptoms: it was felt, therefore, that follow-up should be mandatory after any medical treatment and that women needed access to 24 hour emergency care. Using their clinical experience, the GDG members agreed that women should have two follow-up appointments in the first week following treatment, and then one appointment per week until a negative pregnancy test is performed. This follow-up protocol would ensure that women in whom medical treatment was not effective would be identified early, before their condition became serious. The GDG agreed that an hCG level which plateaued or rose following medical management should prompt a reassessment of the woman's treatment. Given the potential risks if medical management fails, the group highlighted the importance of this follow-up protocol, and decided that if any difficulties in follow-up were anticipated, women should be advised to have surgery as a first-line treatment.

Consideration of health benefits and resource uses

The GDG noted that, while surgery has the advantage of a shorter resolution time and a reduced need for further intervention, medical management is associated with a shorter stay in hospital. Therefore, the group decided that this area was appropriate for a health economics analysis. Using a cost minimisation approach, the model determined that methotrexate was the preferred treatment approach. Taking this finding into account, but also the potential risks inherent in tubal rupture, the GDG decided to recommend methotrexate as the first-line treatment for women meeting the criteria discussed above; namely those with an unruptured ectopic pregnancy which is smaller than 35 mm with no visible heartbeat and who have an hCG level less than 1500 IU/l.

Quality of evidence

The evidence was derived from randomised controlled trials and ranged in quality from high to low for the outcomes considered. The GDG felt that it was disappointing that studies had not reported more information about outcomes among women with different initial hCG levels and size of ectopic pregnancy. Four studies only included ectopic pregnancies below a certain size (ranging from 35 mm to 40 mm) and only two discussed the effect of hCG values on outcomes.

Information giving and emotional support

The GDG emphasised the importance of providing good quality information to women who are in a clinically stable condition, including accurate information on local management options and appropriate counselling regarding the proposed procedure. The GDG was aware that, for some women, methotrexate might be a clinically appropriate treatment option but would not be acceptable to the woman personally. In these circumstances, the GDG felt that the woman's choice should be supported. For all women with an ectopic pregnancy, the GDG thought that it was important that women were given sufficient information about what to expect during the course of their treatment and recovery. In particular, GDG members felt women should be made aware of the amount of pain and/or bleeding that might be expected, so that women knew that it was a normal part of the treatment process.

It was recognised that ongoing psychological support should be offered from the diagnostic period and during discussions regarding treatment options and the relevant outcomes and into the postoperative period, including information regarding resuming usual activity and details of patient groups to contact for support. The information needs to cover details regarding both physical and emotional recovery.

Other considerations

The GDG noted that these studies looked specifically at women with unruptured ectopic pregnancies and therefore these women were not in extreme pain. The GDG did not feel that women in significant pain were suitable for medical management and therefore they should be offered surgery.

The group also wished to highlight that medical management should only be undertaken once it was confirmed on an ultrasound scan that there was no intrauterine pregnancy.

Recommendations

Image

Table

how they can contact a healthcare professional for post-operative advice if needed, and who this will be and where and when to get help in an emergency.

8.3. Laparotomy compared with laparoscopy for ectopic pregnancy

Review question

What is the effectiveness of laparotomy compared with laparoscopic techniques for managing tubal ectopic pregnancy?

Introduction

Many women with ectopic pregnancies are managed surgically using either laparoscopy and/or laparotomy. There is, however, some variation in practice in the way women with an ectopic pregnancy with similar clinical characteristics are managed. The reasons for this variability are multifactorial, but include differences in surgical training, availability of equipment and surgeon preference. This review aims to consider the evidence comparing laparoscopy and laparotomy to investigate which approach is more effective.

Description of included studies

Fourteen studies were included in this review (Baumann et al., 1991; Chatwani et al., 1992; El Tabbakh & El Sayes, 2002; Federici et al., 1994; Lo et al., 1999; Lundorff et al., 1991; Lundorff et al., 1992; Lundorff, 1997; Mehra et al., 1998; Mol et al., 1997; Murphy et al., 1992; Rizzuto et al., 2008; Vermesh et al., 1989; Vermesh & Presser, 1992).

Five of the included studies reported the initial outcomes and follow-up data of two randomised controlled trials conducted in Sweden (Lundorff et al., 1991; Lundorff et al., 1992; Lundorff, 1997) and the USA (Vermesh et al., 1989; Vermesh & Presser, 1992). Nine of the included studies were prospective comparative observational studies conducted in the UK (Baumann et al., 1991; Rizzuto et al., 2008), the USA (Chatwani et al., 1992; Murphy et al., 1992), Italy (Federici et al., 1994), the Netherlands (Mol et al., 1997), Hong Kong (Lo et al., 1999), Kuwait (El Tabbakh & El Sayes, 2002) and India (Mehra et al., 1998).

All studies compared laparotomy with laparoscopy for the management of tubal ectopic pregnancies and reported at least one outcome of interest. However, one observational study also included seven women with non-tubal ectopic pregnancies (Baumann et al., 1991) and another had a specific study population of women with a ruptured ectopic pregnancy and significant haemoperitoneum (Rizzuto et al., 2008) (The findings from this study are reported separately at the end of the evidence profile below).

Evidence profile

Table 8.4. GRADE summary of findings for comparison of laparotomy with laparoscopy for the management of tubal ectopic pregnancy.

Table 8.4

GRADE summary of findings for comparison of laparotomy with laparoscopy for the management of tubal ectopic pregnancy.

Evidence statements

Subsequent viable intrauterine pregnancy

One meta-analysis of two studies did not find a statistically significant difference in the incidence of subsequent viable intrauterine pregnancy for women who received a laparotomy compared with women who received a laparoscopy. The evidence for this outcome was of low quality.

Subsequent intrauterine pregnancy

Three studies and one meta-analysis of two studies did not find a statistically significant difference in the incidence of subsequent intrauterine pregnancy for women who received a laparotomy compared with women who received a laparoscopy. The evidence for this outcome was of very low and quality.

Recurrent ectopic pregnancy

Two studies and one meta-analysis of two studies did not find a statistically significant difference in the incidence of recurrent ectopic pregnancy for women who received a laparotomy compared with women who received a laparoscopy. The evidence for this outcome was of very low and low quality.

Length of hospital stay

Eight studies and one meta-analysis of two studies found that the length of hospital stay was longer in women who received a laparotomy compared with women who received a laparoscopy. This finding was statistically significant. The evidence for this finding was of moderate quality in the meta-analysis of two studies and very low in the other studies.

Need for further surgery

Four studies and one meta-analysis of two studies did not find a statistically significant difference in the need for further surgery for women who received a laparotomy compared with women who received a laparoscopy. The evidence for this outcome was of very low and low quality.

Need for methotrexate

Two studies did not find a statistically significant difference in the need for methotrexate for women who received a laparotomy compared with women who received a laparoscopy. The evidence for this outcome was of low and very low quality.

Need for surgery, methotrexate or expectant management

One study found that the need for surgery, methotrexate or expectant management was lower in women who received a laparotomy compared with women who received a laparoscopy. This finding was statistically significant and the evidence for this finding was of very low quality.

Readmission to hospital

Two studies did not find a statistically significant difference in the need for readmission to hospital for women who received a laparotomy compared with women who received a laparoscopy. The evidence for this outcome was of very low quality.

Abdominal pain

One study did not find a statistically significant difference in the incidence of abdominal pain for women who received a laparotomy compared with women who received a laparoscopy. The evidence for this outcome was of low quality.

Thromboembolic disease

One study did not find a statistically significant difference in the incidence of thromboembolic disease for women who received a laparotomy compared with women who received a laparoscopy. The evidence for this outcome was of very low quality.

Respiratory morbidity

Two studies did not find a statistically significant difference in the incidence of respiratory morbidity for women who received a laparotomy compared with women who received a laparoscopy. The evidence for this outcome was of very low quality.

Need for a blood transfusion

Two studies found that the need for a blood transfusion was higher in women who received a laparotomy compared with women who received a laparoscopy. This finding was statistically significant and the evidence for this finding was of very low quality in both studies. One further study did not find a statistically significant difference in the need for a blood transfusion between the two groups. The evidence for this finding was of very low quality.

Intraoperative blood loss

Three studies found that intraoperative blood loss was higher in women who received a laparotomy compared with women who received a laparoscopy. This finding was statistically significant. The evidence for this finding was moderate in one study and very low in the others. Three further studies did not find a statistically significant difference in intraoperative blood loss between the two groups. The evidence for this finding was of very low quality.

One study that only included women with tubal rupture and significant haemoperitoneum reported length of hospital stay in a manner that did not allow assessment of statistical significance. In the same study there were no events in either arm for the outcome of need for further surgery. The evidence for these outcomes was of very low quality.

Evidence to recommendations

Relative value placed on the outcomes considered

The GDG identified future reproductive outcomes as the most important outcomes from the woman's perspective.

Length of hospital stay was also considered very important, both from a woman's point of view and in terms of cost to the NHS.

Other outcomes relating to women's experience of care were also seen as important, particularly pain experienced and incidence of complications requiring further care, such as the need for blood transfusion, further surgery and readmission to hospital.

Although reported by many studies, the GDG agreed that intraoperative blood loss is not a useful outcome as it is very difficult to measure/assess accurately. More importantly, even in those studies which reported statistically significant differences in blood loss, the GDG did not consider these differences to be clinically significant.

Consideration of clinical benefits and harms

The evidence suggested there is little difference in clinically significant outcomes between laparotomy and laparoscopy. Laparoscopy is superior in terms of length of hospital stay, with no evidence of any harm compared to laparotomy, including no difference in need for further treatment (either surgical or medical). Two studies showed that fewer women required a blood transfusion following laparoscopy compared with laparotomy (although a third study found no difference between the two treatments) While it was noted that one study (Mol et al., 1997) showed fewer incidences of methotrexate administration, expectant management or further surgery with laparotomy, the GDG believed that this finding was due to the fact that most (84%) of the women in the laparotomy arm received excision surgery to remove the tube and ectopic pregnancy (reported in the paper as ‘radical’ surgery), while the majority (66%) in the laparoscopy arm received conservative surgery.

The group did not feel able to make a strong recommendation due to the poor level of evidence regarding clinical benefits.

Consideration of health benefits and resource uses

The evidence suggested that there is no difference in terms of health benefits between laparoscopy and laparotomy, including the key outcome of subsequent successful pregnancy.

The length of hospital stay is shorter following laparoscopy compared with laparotomy, thus this aspect of care, when combined with the reduced likelihood of a blood transfusion, would use fewer resources. The GDG noted that laparoscopy is associated with the use of expensive equipment which is prone to malfunction if not well maintained and/or renewed regularly. In addition, hospital units that employ disposable equipment will consume limited resources. However, on balance, the group felt that the capital cost of the laparoscopic equipment, when spread across the number of procedures that would be undertaken, would be outweighed by the saving in the number of hospital in-patient bed days. Therefore, the GDG felt it appropriate to recommend laparoscopy as the first-line technique for most surgeries, although it was aware that the availability and presence of competent trained surgical personnel on a 24/7 basis may limit the minimally invasive option of treatment.

Quality of evidence

The quality of the evidence was moderate to very low. Some of the studies included few women so it was difficult to draw any conclusions as the number of adverse events was very low in the study groups. Thus the GDG was unable to draw conclusions about the incidence of thromboembolic complications, need for blood transfusion, abdominal pain or respiratory complications. This was unfortunate, as all of these were considered important outcomes which would impact on women's experience of care as well as resource use.

It is regrettable that there was no evidence about emotional outcomes as these are also considered important.

Information giving and psychological support

While the GDG had prioritised women's experience of care as a key outcome for this review, no data was reported for this. The GDG recognised that the shorter hospital stay associated with laparoscopic surgery was likely to be valued by most women and that being separated from their family and friends for a shorter time was likely to be beneficial in terms of emotional support and reduce the negative psychological impact of surgery.

Other considerations

The GDG was aware that there may be some practitioners who are not competent to perform laparoscopy, particularly in more complex cases. In addition, some surgeons are not comfortable with laparoscopic surgery where the woman is collapsed or haemodynamically unstable.

An additional problem can arise where the laparoscopic equipment is unavailable or not working. The GDG members recognised from their clinical experience that equipment failures may lead to unnecessarily lengthy operations. The decision as to which intervention is most appropriate therefore depends on the relative expertise of the doctor, the equipment available, the complexity of the surgery required and the condition of the woman.

The GDG felt that each unit should have at least some practitioners who are competent to perform laparoscopy. In order to achieve this, further investment in training and equipment may be necessary.

Recommendations

8.4. Salpingectomy compared with salpingotomy for ectopic pregnancy

Review question

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

Introduction

Surgical treatment of ectopic pregnancy can be conservative (preserving the Fallopian tube) or radical (removing the Fallopian tube). Salpingotomy is surgical incision of a Fallopian tube to remove the ectopic pregnancy. Salpingostomy is the surgical formation of an opening in the Fallopian tube where the fimbrial end has been closed by infection or chronic inflammation. In the literature there appears to be a blurring of this definition, with authors apparently using the terms interchangeably and sometimes referring to salpingotomy and salpingostomy within the same paper. The term 'salpingotomy' will be used in this review to cover both salpingotomy and salpingostomy.

Salpingotomy is a conservative approach which preserves the tube but bears the risk of incomplete removal of the pregnancy tissue (persistent trophoblast). Salpingectomy is a radical approach which bears no risk of persistent trophoblast but leaves only one tube for reproductive capacity. It is unknown which type of operation is better, especially for future fertility. The risk of additional treatment in the case of persistent trophoblast after salpingotomy may be acceptable if compensated for by retention of the Fallopian tube and a small rise in intrauterine pregnancy rate.

Description of included studies

Twenty-one studies were included in this review (Bangsgaard et al., 2003; Becker et al., 2011; Bouyer et al., 2000; Colacurci et al., 1998; DeCherney & Kase, 1979; dela Cruz & Cumming, 1997; Giambelli et al., 1996; Gruft et al., 1994; Kuroda et al., 2009; Langebrekke et al., 1993; Mecke et al., 1989; Mol et al., 1997; Mol et al., 1998; Ory et al., 1993; Parker et al., 1994; Sherman et al., 1982; Silva et al., 1993; Tahseen & Wyldes, 2003; Tulandi & Guralnick, 1991; Turan, 2011; Tuomivaara & Kauppila, 1988).

There were no relevant randomised controlled trials identified for this review question. Four of the included studies were prospective observational studies (Becker et al., 2011; Bouyer et al., 2000; Mol et al., 1997; Silva et al., 1993) and the remainder were retrospective observational studies. The studies were conducted in the UK (Tahseen & Wyldes, 2003), Denmark (Bangsgaard et al., 2003), Finland (Tuomivaara & Kauppila, 1988), France (Bouyer et al., 2000), Germany (Becker et al., 2011; Mecke et al., 1989), Italy (Colacurci et al., 1998; Giambelli et al., 1996; Gruft et al., 1994), the Netherlands (Mol et al., 1997; Mol et al., 1998), Norway (Langebrekke et al., 1993), Australia (Parker et al., 1994), the USA (DeCherney & Kase, 1979; Ory et al., 1993; Silva et al., 1993), Canada (dela Cruz & Cumming, 1997; Tulandi & Guralnick, 1991), Turkey (Turan, 2011), Israel (Sherman et al., 1982) and Japan (Kuroda et al., 2009).

The majority of the included studies compared salpingectomy with salpingotomy for the management of tubal ectopic pregnancy: however, in four of the studies some of the participants received a different type of radical or conservative surgery, such as a salpingo-oophorectomy or milking of the tube (DeCherney & Kase, 1979; Mol et al., 1997; Sherman et al., 1982; Tuomivaara & Kauppila, 1988).

Evidence profile

Table 8.5. GRADE summary of findings for comparison of salpingectomy with salpingotomy for the management of tubal ectopic pregnancy.

Table 8.5

GRADE summary of findings for comparison of salpingectomy with salpingotomy for the management of tubal ectopic pregnancy.

Evidence statements

The studies identified for this review question were generally of poor quality. Using GRADE criteria, the evidence was of very low quality for every outcome.

Subsequent live birth or full-term birth

One study found that the proportion of women with a subsequent live birth or full-term birth was lower in women who received a salpingectomy compared with women who received a salpingotomy. This finding was statistically significant. A further seven studies did not find a statistically significant difference in subsequent live birth or full-term birth between the two groups.

Subsequent intrauterine pregnancy

Five studies found that the proportion of women with a subsequent intrauterine pregnancy was lower in women who received a salpingectomy compared with women who received a salpingotomy. This finding was statistically significant. A further ten studies did not find a statistically significant difference in subsequent intrauterine pregnancy between the two groups.

Recurrent ectopic pregnancy

Three studies found that the proportion of women with a recurrent ectopic pregnancy was lower in women who received a salpingectomy compared with women who received a salpingotomy. This finding was statistically significant. A further 12 studies did not find a statistically significant difference in recurrent ectopic pregnancy between the two groups.

Need for further intervention

Three studies found that the need for further intervention was lower in women who received a salpingectomy compared with women who received a salpingotomy. This finding was statistically significant. Two further studies did not find a statistically significant difference in the need for further intervention between the two groups.

Need for a blood transfusion

Two studies did not find a statistically significant difference in the need for a blood transfusion for women who received a salpingectomy compared with women who received a salpingotomy.

Surgical complications

Two studies did not find a statistically significant difference in the incidence of surgical complications for women who received a salpingectomy compared with women who received a salpingotomy.

Health economics

A new economic model was developed for this guideline to assess the cost effectiveness of different treatment strategies for ectopic pregnancy. Please see Section 7.2 for a summary of the model's findings and Section 10.4 for full details of the model.

Evidence to recommendations

Relative value placed on the outcomes considered

The primary outcomes for this question were the reproductive outcomes and the need for further intervention. The likelihood of a future viable intrauterine pregnancy and the possibility of a repeat ectopic pregnancy are thought to be outcomes that are very important to most women. The chance of a further intervention is important for informing women about the likely course of their recovery, as well as having health economic implications. Secondary outcomes for this review included the need for a blood transfusion, incidence of surgical complications and ongoing pain, although evidence was not available for the last of these.

Consideration of clinical benefits and harms

When considering which mode of surgery to recommend, the GDG felt that maintaining the woman's reproductive potential was a priority. Six of the studies showed that the proportion of women with an intrauterine pregnancy or a subsequent live or full-term birth was lower in women who received a salpingectomy, while the remainder showed no significant difference. However, the group noted that the evidence was derived from observational studies, and in many of the papers it was reported that a woman's future reproductive desires and other fertility factors influenced the mode of surgery performed, therefore biasing the results. When multivariate or stratified analysis was performed (adjusting for other factors contributing to fertility, such as tubal pathology and history of infertility), the effect became non-significant in two studies. In two other studies, the difference in the proportion of women with an intrauterine pregnancy or a subsequent live or full-term birth was significant for women with other factors prognostic of infertility, but not for the remainder of the women.

Three out of five studies showed that the need for a further intervention was significantly higher following a salpingotomy. The GDG recognised that this would be an important consideration for women, particularly as the second intervention might include the more radical procedure of salpingectomy.

For the outcome of recurrent ectopic pregnancy, there was a general trend that the incidence was lower among women who received a salpingectomy: however, due to the poor quality of the evidence, the GDG did not feel that the effect was certain enough to base a recommendation on.

Overall, the GDG felt that for women without any coexistent fertility factors, future reproductive potential was unlikely to be strongly affected by which mode of surgery was performed. However, for women with factors prognostic of infertility, the evidence suggested that salpingotomy was associated with a higher chance of a subsequent intrauterine pregnancy (please refer to evidence tables in Appendix H where stratified or adjusted analyses are reported for Becker et al., 2011; Bouyer et al., 2000 and Sherman et al., 1982).

Consideration of health benefits and resource uses

The GDG noted that the evidence showed a higher incidence of further intervention following a salpingotomy, and therefore that the comparison of salpingectomy and salpingotomy should be incorporated in the health economic analysis for management of ectopic pregnancy. The cost minimisation model (see Section 10.4) showed that salpingectomy was preferable to salpingotomy in terms of resource use. Given that the evidence around reproductive outcomes following salpingectomy and salpingotomy was inconclusive, the group felt that for women without any coexistent fertility factors, the recommended surgical treatment should be a salpingectomy.

Quality of evidence

The evidence for this review was of very low quality because it was drawn from observational studies, the majority of which were retrospective. There was a high likelihood of bias in many of the studies, because they had a select population and a woman's future fertility desires and reproductive history contributed to the choice of treatment. However, the GDG felt that the studies which performed stratified or multivariate analyses controlled for some of these factors and therefore presented a more accurate estimate of reproductive outcomes.

Information giving and psychological support

The likelihood of a future viable intrauterine pregnancy and the possibility of a repeat ectopic pregnancy were prioritised as key outcomes as these were felt to be the most important to women. The chance of a further intervention is important for informing women about the likely course of their recovery and a recommendation was made to reflect this.

Other considerations

The GDG also discussed the ongoing European Study in Ectopic Pregnancy (ESEP) study, which is a large multi-centre randomised controlled trial that compares salpingectomy and salpingotomy. Unfortunately, the trial will not be published in time for inclusion in this guideline: however, in light of the fact that this study is being conducted, the GDG did not feel that this area was a priority for a research recommendation.

Recommendations