Does tubal ectopic pregnancy with hemoperitoneum always require surgery?
Article first published online: 14 MAY 2009
DOI: 10.1002/uog.6384
Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.
Issue
Ultrasound in Obstetrics & Gynecology
Volume 33, Issue 6, pages 711–715, June 2009
Abstract
Objective
Hemoperitoneum is accepted as an indication for surgery in women with tubal ectopic pregnancy. The aim of this pilot study was to evaluate the feasibility of managing such women non-surgically.
Methods
This was a prospective observational study. Women with tubal ectopic pregnancy and hemoperitoneum detected on transvaginal sonography (TVS) were managed as inpatients either expectantly or with methotrexate (MTX). Inclusion criteria for conservative management were: compliance, clinical stability, absence of acute abdomen, stable hemoglobin level on two measurements (0 and 12–24 h apart), serum human chorionic gonadotropin (hCG) < 5000 IU/L, absence of fetal cardiac activity on TVS and absence of significant hemoperitoneum, defined as blood above the level of the uterine fundus and/or in Morison's pouch (hepatorenal space). Subsequent management was based upon the hCG ratio at 48 h. All the women were managed as inpatients until the abdominal pain settled and the serum hCG levels were falling.
Results
Forty-one women with tubal ectopic pregnancy presented between November 2006 and March 2008. Eight women (20%) fulfilled the entry criteria. The median gestational age at diagnosis was 49 (interquartile range, 38–52.5) days. All women presented with lower abdominal pain/right iliac fossa or left iliac fossa pain. Hemoglobin levels ranged from 11.2 to 14.2 g/dL at presentation and from 12.0 to 14.8 g/dL after 12–24 h. 6/8 (75%) women were managed expectantly and 2/8 (25%) received MTX. All women had resolution of their ectopic pregnancy within 3 weeks with no complications.
Conclusions
This pilot study suggests that the finding of hemoperitoneum on ultrasound examination may not be an absolute contraindication to conservative management of tubal ectopic pregnancy. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.
Introduction
An ectopic pregnancy in the Fallopian tube, if not treated, can cause tubal rupture, hemoperitoneum and even death1. The combination of transvaginal sonography (TVS) and serum human chorionic gonadotropin (hCG) levels has proven to be reliable for the early diagnosis of ectopic pregnancy. Probabilistic models including physical, ultrasound and laboratory findings (serum hCG and progesterone levels) have improved the management of ectopic pregnancy, especially in women who have a pregnancy of unknown location2–5. As a consequence, the clinical presentation of ectopic pregnancy has changed from a life-threatening disease necessitating emergency surgery to a more benign condition. This in turn has resulted in major changes in the options available for therapeutic management, favoring more conservative approaches such as medical or even expectant ‘watch and see’ management6–14.
The presence of hemoperitoneum on ultrasound examination in women with a tubal ectopic pregnancy is an established absolute contraindication for methotrexate (MTX) or expectant management. Based on published data, these women are managed surgically6–9. This ultrasound-based diagnosis of hemoperitoneum of any degree, however, does not necessarily indicate the presence of tubal rupture or hemodynamic instability. Fluid in the pouch of Douglas may be present in up to 80% of cases of ectopic pregnancy, whether ruptured or not15, 16, and the proportion of ruptured Fallopian tubes is markedly higher among patients with a hemoperitoneum of ≥ 300 mL17. Compared with stable women, hemodynamically unstable women have significantly more free blood in the abdomen and significantly lower hemoglobin levels18–20.
In this pilot study, we aimed to investigate whether women with the diagnosis of tubal ectopic pregnancy with hemoperitoneum on ultrasound scan could be managed non-surgically.
Patients and Methods
This was a prospective observational pilot study. All women reviewed in the Acute Gynaecology Unit (AGU) at Nepean Hospital between November 2006 and February 2008 with the sonographic diagnosis of a tubal ectopic pregnancy were evaluated for their eligibility. The AGU is an ultrasound-based clinic open five mornings a week 0900–1300. It evaluates pregnant and non-pregnant women with acute gynecological complaints, utilizing ultrasound at the initial clinical interface.
All women with a tubal ectopic pregnancy and hemoperitoneum detected on ultrasound examination underwent a complete clinical assessment that included assessment of vital signs (pulse and blood pressure) to determine clinical stability and abdominal palpation to assess for the presence or absence of an acute abdomen. Transvaginal and transabdominal ultrasound scans were performed, as well as serum hCG measurements at 0 and 48 h. Those women who fulfilled the following inclusion criteria were included in the final study: compliance, ultrasound diagnosis of a tubal ectopic pregnancy, clinical stability, absence of an acute abdomen, stable hemoglobin level on two separate measurements (0 and 12–24 h later), serum hCG < 5000 IU/L at presentation, absence of fetal cardiac activity on TVS and absence of significant hemoperitoneum on TVS.
Hemoperitoneum was defined as the presence of free fluid with fine, diffuse echoes21, 22, and the presence of clots was noted if there were heterogeneous areas within the fluid23. A detailed evaluation of the hemoperitoneum with TVS and transabdominal sonography (TAS) was performed in order to exclude bleeding beyond the pelvis. Significant hemoperitoneum was defined qualitatively on TVS as the presence of blood above the level of the uterine fundus (Figure 1) or around the ovary17, 24 and/or blood in Morison's pouch (the space between Gerota's fascia of the right kidney and Glisson's capsule of the liver) on TAS (Figure 2)25, 26.
Figure 1. Transvaginal ultrasound image (mid-sagittal section) showing significant hemoperitoneum i.e. blood above the uterine fundus (dashed line).
Figure 2. Transabdominal ultrasound image showing absence of fluid in Morison's pouch (hepatorenal space, arrows), which can exclude the presence of significant hemoperitoneum.
The diagnosis of an ectopic pregnancy was made if an adnexal mass was visualized on TVS with one of the following features in the absence of an intrauterine pregnancy: (1) an inhomogeneous adnexal mass or ‘blob sign’ that moved separately from the ovary; (2) an empty gestational sac with a hyperechoic ring or ‘bagel sign’; or (3) a gestational sac containing a yolk sac or fetal pole with or without cardiac activity27.
Subsequent management was based upon the hCG ratio (ratio of serum hCG at 48 h : hCG at 0 h)28, 29. If the hCG ratio was < 1, i.e. hCG levels were falling, they were managed expectantly; if the hCG ratio was > 1, i.e. hCG levels were increasing, women received MTX. All the women were managed as inpatients until the abdominal pain settled and the serum hCG levels were falling. Resolution of ectopic pregnancy was defined as hCG < 5 IU/L at follow-up.
Women were admitted as inpatients and monitoring of vital signs was carried out hourly for the first 12 h, then every 2 h for the next 12 h, then every 6 h. Hemoglobin was checked twice a day for the first 24 h then daily or every 48–72 h. The women were instructed to report any increase in lower abdominal pain. Ultrasound scanning was repeated only in those women with increasing lower abdominal pain. Serum hCG levels were checked at 48 h and if falling, i.e. hCG ratio < 1, then weekly until negative. If serum hCG levels were increasing at 48 h, i.e. hCG ratio > 1, then MTX was given as a single dose protocol at a dose of 50 mg/sq m6. These women were followed up with monitoring of serum hCG levels at days 1, 4 and 7. If the serum hCG level fell by > 15% between days 4 and 7, then weekly blood tests were arranged thereafter. If the serum hCG level fell by < 15% between days 4 and 7, then a second dose of MTX was given on day 7. Women were followed up as inpatients until complete resolution of symptoms and/or the serum hCG levels were falling in accordance with the protocol.
We ensured that the decision could be reconsidered and conservative management terminated if the patient deteriorated at any time during the course of observation (deteriorating vital signs or hemoglobin decrease to < 10 g/dL, increasing abdominal tenderness or signs of peritoneal irritation, progressive marked increase in hemoperitoneum on serial ultrasound scans, increasing hCG).
Results
Forty-one women were managed for a tubal ectopic pregnancy in the AGU of the Nepean Hospital in the study period. Eight (20%) women fulfilled the inclusion criteria for this study and were offered conservative management as inpatients. Demographic and clinical characteristics of the eight women who were managed conservatively are presented in Table 1. Six women were eligible for expectant management and two for MTX administration. The median age was 24.5 (interquartile range (IQR), 23–27) years and median gestational age at diagnosis on the basis of the last menstrual period was 49 (IQR, 38–52.5) days. Two women were unsure of their dates. All the women complained of vaginal bleeding, one with clots. Six women had mild to moderate abdominal pain (visual analog scale (VAS) score < 5). Ultrasound diagnosis of ectopic pregnancy was made by visualization of a ‘blob sign’27 in six women and of a ‘bagel sign’27 in two women.
| Characteristic | Value |
|---|---|
| |
| Age (years) | 24.5 (23–27) |
| Gravidity | 1 (0–2.25) |
| Parity | 0.5 (0–1.25) |
| Gestational age (days) | 49 (38–52.5) |
| Serum hCG level at 0 h (IU/L) | 881 (695–1224) |
| Size of ectopic mass at TVS (mm) | 18 (15–20) |
| Endometrial thickness (mm) | 6.6 (4.9–9.6) |
| Maximum diameter of hemoperitoneum (mm) | 30 (22–32) |
| Hemoglobin at 0 h (g/dL) | 11.2–14.2 |
| Hemoglobin at 12–24 h (g/dL) | 12.0–14.8 |
Median endometrial thickness was 6.6 (IQR, 4.9–9.6) mm. Median maximum diameter of the hemoperitoneum in a mid-sagittal section including the uterus and the pouch of Douglas was 30 (IQR, 22–32) mm. Serum hCG at 0 h ranged from 411 to 2829 IU/L, with a median value of 881 (IQR, 695–1224) IU/L. Two women had hCG ratios of 1.35 and 1.15, respectively, and therefore they were given MTX. Both women required only one dose of MTX. The median hCG ratio for those who were managed expectantly was 0.53 (IQR, 0.36–0.59). Hemoglobin level ranged from 11.2 to 14.2 g/dL at presentation and from 12.0 to 14.8 g/dL after 12–24 h.
All the women had normal vital signs at presentation and all remained hemodynamically stable throughout the duration of follow-up. They all had resolution of their ectopic pregnancy with a serum hCG level < 5 IU/L within 3 weeks from admission with no major complications (i.e. conversion to surgery, need of blood transfusion or any other major morbidity). The maximum time spent in hospital for the group was 4 days.
Discussion
This is the first prospective study to challenge the idea that surgery is mandatory in women with a tubal ectopic pregnancy and hemoperitoneum on ultrasound examination6, 8, 9. Lipscomb et al. retrospectively evaluated the role of fluid in the pelvis in the medical management of ectopic pregnancy and found that it was not a predictor of success7. Hemoperitoneum does not represent an absolute contraindication to the conservative management of ectopic pregnancy. Although this is a small study, the results are potentially encouraging, as, to the best of our knowledge, it is the first study to report a series of women with ectopic pregnancy and hemoperitoneum successfully treated with conservative management.
The presence of blood in the pelvis does not necessarily indicate tubal rupture of the ectopic pregnancy. Even if a tubal rupture has occurred, nearly half of the women affected do not have active bleeding at surgery20. We hypothesize that hemoperitoneum could also represent a spillage from the fimbrial end of an intact hematosalpinx, as in the case of tubal miscarriage. We believe that blood in the pelvis should not be the determining factor for surgical intervention; rather the global clinical state of the woman should be the overriding consideration when making the decision on whether or not to perform surgery. When choosing the best treatment, the clinician's attention should therefore focus on a complete clinical evaluation, taking into account the clinical stability of the woman, the hCG ratio and a qualitative evaluation of the intra-abdominal bleeding on ultrasound examination. Fauconnier et al.17 derived an ultrasound-based prediction model for significant hemoperitoneum in ectopic pregnancy based on the presence of moderate to severe spontaneous pelvic pain, the presence of intraperitoneal fluid above the uterine fundus or around the ovary on TVS, and the presence of a serum hemoglobin concentration of < 10 g/dL. A woman with none of these three criteria would have a probability of 5.3% for hemoperitoneum ≥ 300 mL. When two or more criteria were present, the probability for hemoperitoneum ≥ 300 mL reached 92.6%17.
In our study, we have also considered the absence of fluid in the Morison's pouch (hepatorenal space) as a criterion for the exclusion of significant hemoperitoneum. Free intraperitoneal fluid found in Morison's pouch in patients with suspected ectopic pregnancy may reflect the presence of significant hemoperitoneum and is predictive of the need for operative intervention25, 26. The mean quantity of free fluid for visualization of an anechoic stripe in Morison's pouch has been demonstrated to be 440 mL in the Trendelenburg position at 5 degrees, and 670 mL in the supine position30. Therefore the absence of fluid in the Morison's pouch can potentially exclude the presence of an intra-abdominal hemorrhage of > 440 mL.
The major limitation of this pilot study is indeed represented by the small numbers. Only 20% of the women who presented with a tubal ectopic pregnancy fulfilled the inclusion criteria. We believe, however, that avoiding laparoscopic salpingectomy in 20% of women in our tubal ectopic pregnancy population represents a good result. We acknowledge that our protocol needs to be tested prospectively in other populations in order to validate its general application. A randomized trial comparing surgery and expectant management is not available but following this pilot study, we would highly recommend that such a study be undertaken. Without that evidence, practice can only be based on small observational studies. There is observational evidence to suggest that the avoidance of surgery may be associated with a decreased recurrent ectopic pregnancy rate, and slightly improved future intrauterine pregnancy rates31–36. Needless to say, conservative management is free from operative laparoscopy and anesthetic risks. The downside to such an approach is that the failure rates may be as high as 35% for single-dose MTX9 and 52% for expectant management12 and therefore close follow-up is essential. The maximum duration of admission in our group was 4 days. Economically, many hospitals could not sustain long-term inpatient management, so a comprehensive economic analysis in the context of a prospective randomized controlled trial could clarify the cost-effectiveness of this approach.
It cannot be overemphasized that the key to success in the conservative management of tubal ectopic pregnancy in the presence of blood in the pelvis on ultrasound scan is careful selection of women who fulfill strict inclusion criteria. These women need strict follow-up/monitoring and there needs to be a preparedness on behalf of the gynecological team to undertake surgery when required. We believe that the ultrasound diagnosis of tubal ectopic pregnancy and the presence of hemoperitoneum is not an absolute contraindication to conservative therapies. Instead it is the overall clinical state of the woman combined with a qualitative assessment of blood in both the pelvis and Morison's pouch that is more important. We believe that future studies should focus on the development and prospective testing of models for the prediction of significant hemoperitoneum in women with tubal ectopic pregnancy. This may result in a reappraisal of the current approach to tubal ectopic pregnancy and ultrasound evidence of blood in the pelvis. We believe conservative management might be feasible in patients with a tubal ectopic pregnancy and absence of significant hemoperitoneum. This small pilot study has shown encouraging results, however until there is more evidence to support our management strategy, such an approach should only be considered in the context of a prospective randomized trial.
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