Adherence to guideline-based quality indicators in early pregnancy care in hospitals with and without an early pregnancy assessment unit.

RESEARCH QUESTION: How do hospitals with and without an early pregnancy assessment unit (EPAU) adhere to guideline-based quality indicators for an EPAU relating to logistics, access to services and quality of early pregnancy care? DESIGN: A qualitative interview study assessing the adherence to 19 quality indicators in four hospitals with an EPAU and four hospitals without an EPAU in the Netherlands. For each quality indicator, a ratio for guideline adherence was calculated. Overall non-adherence per hospital was defined as less than 100% adherence to the 19 quality indicators. RESULTS: Non-adherence was seen in three indicators (3/19 [16%]) for hospitals with an EPAU and in five indicators (5/19 [26%]) for hospitals without an EPAU. A standard digital system for the registration of ultrasound findings and clear explanation of all treatment options was present in all hospitals with an EPAU and in three hospitals without an EPAU. Certified ultrasound training for working staff members was absent in all hospitals. A discrete waiting area was present in one hospital with an EPAU compared with none of the hospitals without an EPAU. Self-referrals from women with a previous ectopic pregnancy was accepted in one hospital with and in one hospital without an EPAU. CONCLUSIONS: Non-adherence to guideline-based quality indicators for an EPAU was about the same for hospitals with and without an EPAU in the Netherlands.

Cost-effectiveness of salpingotomy and salpingectomy in women with tubal pregnancy (a randomized controlled trial).

STUDY QUESTION: Is salpingotomy cost effective compared with salpingectomy in women with tubal pregnancy and a healthy contralateral tube? SUMMARY ANSWER: Salpingotomy is not cost effective over salpingectomy as a surgical procedure for tubal pregnancy, as its costs are higher without a better ongoing pregnancy rate while risks of persistent trophoblast are higher. WHAT IS KNOWN ALREADY: Women with a tubal pregnancy treated by salpingotomy or salpingectomy in the presence of a healthy contralateral tube have comparable ongoing pregnancy rates by natural conception. Salpingotomy bears the risk of persistent trophoblast necessitating additional medical or surgical treatment. Repeat ectopic pregnancy occurs slightly more often after salpingotomy compared with salpingectomy. Both consequences imply potentially higher costs after salpingotomy. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation of salpingotomy compared with salpingectomy in an international multicentre randomized controlled trial in women with a tubal pregnancy and a healthy contralateral tube. Between 24 September 2004 and 29 November 2011, women were allocated to salpingotomy (n = 215) or salpingectomy (n = 231). Fertility follow-up was done up to 36 months post-operatively. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: We performed a cost-effectiveness analysis from a hospital perspective. We compared the direct medical costs of salpingotomy and salpingectomy until an ongoing pregnancy occurred by natural conception within a time horizon of 36 months. Direct medical costs included the surgical treatment of the initial tubal pregnancy, readmissions including reinterventions, treatment for persistent trophoblast and interventions for repeat ectopic pregnancy. The analysis was performed according to the intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Mean direct medical costs per woman in the salpingotomy group and in the salpingectomy group were €3319 versus €2958, respectively, with a mean difference of €361 (95% confidence interval €217 to €515). Salpingotomy resulted in a marginally higher ongoing pregnancy rate by natural conception compared with salpingectomy leading to an incremental cost-effectiveness ratio €40 982 (95% confidence interval -€130 319 to €145 491) per ongoing pregnancy. Since salpingotomy resulted in more additional treatments for persistent trophoblast and interventions for repeat ectopic pregnancy, the incremental cost-effectiveness ratio was not informative. LIMITATIONS, REASONS FOR CAUTION: Costs of any subsequent IVF cycles were not included in this analysis. The analysis was limited to the perspective of the hospital. WIDER IMPLICATIONS OF THE FINDINGS: However, a small treatment benefit of salpingotomy might be enough to cover the costs of subsequent IVF. This uncertainty should be incorporated in shared decision-making. Whether salpingotomy should be offered depends on society's willingness to pay for an additional child. STUDY FUNDING/COMPETING INTERESTS: Netherlands Organisation for Health Research and Development, Region Västra Götaland Health & Medical Care Committee. TRIAL REGISTRATION NUMBER: ISRCTN37002267.

The interrelation between microbial immunoglobulin coating, vaginal microbiota, ethnicity, and preterm birth.

BACKGROUND: Vaginal microbiota composition is associated with spontaneous preterm birth (sPTB), depending on ethnicity. Host-microbiota interactions are thought to play an important underlying role in this association between ethnicity, vaginal microbiota and sPTB. METHODS: In a prospective cohort of nulliparous pregnant women, we assessed vaginal microbiota composition, vaginal immunoglobulins (Igs), and local inflammatory markers. We performed a nested case-control study with 19 sPTB cases, matched based on ethnicity and midwifery practice to 19 term controls. RESULTS: Of the 294 included participants, 23 pregnancies ended in sPTB. We demonstrated that Lactobacillus iners-dominated microbiota, diverse microbiota, and ethnicity were all independently associated with sPTB. Microbial Ig coating was associated with both microbiota composition and ethnicity, but a direct association with sPTB was lacking. Microbial IgA and IgG coating were lowest in diverse microbiota, especially in women of any ethnic minority. When correcting for microbiota composition, increased microbial Ig coating correlated with increased inflammation. CONCLUSION: In these nulliparous pregnant women, vaginal microbiota composition is strongly associated with sPTB. Our results support that vaginal mucosal Igs might play a pivotal role in microbiota composition, microbiota-related inflammation, and vaginal community disparity within and between ethnicities. This study provides insight in host-microbe interaction, suggesting that vaginal mucosal Igs play an immunomodulatory role similar to that in the intestinal tract. Video Abstract.

Methotrexate or expectant management in women with an ectopic pregnancy or pregnancy of unknown location and low serum hCG concentrations? A randomized comparison.

STUDY QUESTION: What is the treatment success rate of systemic methotrexate (MTX) compared with expectant management in women with an ectopic pregnancy or a pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations? SUMMARY ANSWER: In women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations, expectant management is an alternative to medical treatment with single-dose systemic MTX. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: MTX is often used in asymptomatic women with an ectopic pregnancy or a PUL with low and plateauing serum hCG concentrations. These pregnancies may be self-limiting and watchful waiting is suggested as an alternative, but evidence from RCTs is lacking. The results of this RCT show that expectant management is an alternative to treatment with systemic MTX in a single-dose regimen in these women. STUDY DESIGN, SIZE, DURATION: A multicentre RCT women were assigned to systemic MTX (single dose) treatment or expectant management, using a web-based randomization program, block randomization with stratification for hospital and serum hCG concentration (<1000 versus 1000-2000 IU/l). The primary outcome measure was an uneventful decline of serum hCG to an undetectable level (<2 IU/l) by the initial intervention strategy. Secondary outcome measures included additional treatment, side effects and serum hCG clearance time. PARTICIPANTS, SETTING, METHODS: From April 2007 to January 2012, we performed a multicentre study in The Netherlands. All haemodynamically stable women >18 years old with both an ectopic pregnancy visible on transvaginal sonography and a plateauing serum hCG concentration <1500 IU/l or with a PUL and a plateauing serum hCG concentration <2000 IU/l were eligible for the trial. MAIN RESULTS: We included 73 women of whom 41 were allocated to single-dose MTX and 32 to expectant management. There was no difference in primary treatment success rate of single-dose MTX versus expectant management, 31/41 (76%) and 19/32 (59%), respectively [relative risk (RR) 1.3 95% confidence interval (CI) 0.9-1.8]. In nine women (22%), additional MTX injections were needed, compared with nine women (28%) in whom systemic MTX was administered after initial expectant management (RR 0.8; 95% CI 0.4-1.7). One woman (2%) from the MTX group underwent surgery compared with four women (13%) in the expectant management group (RR 0.2; 95% CI 0.02-1.7), all after experiencing abdominal pain within the first week of follow-up. In the MTX group, nine women reported side effects versus none in the expectant management group. No serious adverse events were reported. Single-dose systemic MTX does not have a larger treatment effect compared with expectant management in women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations. WIDER IMPLICATIONS OF THE FINDINGS: Sixty percent of women after expectant management had an uneventful clinical course with steadily declining serum hCG levels without any intervention, which means that MTX, a potentially harmful drug, can be withheld in these women. BIAS, LIMITATION AND GENERALISABILITY: A limitation of this RCT is that it was an open (not placebo controlled) trial. Nevertheless, introduction of bias was probably limited by the strict criteria to be fulfilled for treatment with MTX. STUDY FUNDING: This trial is supported by a grant of the Netherlands Organization for Health Research and Development (ZonMw Clinical fellow grant 90700154). TRIAL REGISTRATION: ISRCTN 48210491.

Guideline adherence in ectopic pregnancy management.

BACKGROUND: Evidence-based guidelines have been issued for ectopic pregnancy (EP), covering both diagnostic and therapeutic management. In general, guidelines aim to reduce practice variation and to improve quality of care. To assess the guideline adherence in the management of EP, we developed guideline-based quality indicators and measured patient care in various hospitals. METHODS: A panel of experts and clinicians developed quality indicators based on recommendations from the Dutch guideline on EP management, using the systematic RAND-modified Delphi method. With these indicators, patient care was assessed in six Dutch hospitals between January 2003 and December 2005. For each quality indicator, a ratio for guideline adherence was calculated. Overall adherence was reported, as well as adherence per hospital type, i.e. academic, teaching and non-teaching hospitals. RESULTS: Out of 30 guideline-based recommendations, 12 quality indicators were selected covering procedural, structural and outcome aspects of care. For 317 women surgically treated for EP, these aspects were assessed. Overall adherence to the guideline was 75%. The highest adherence (98%) was observed for performing transvaginal sonography during the diagnostic workup. The lowest adherence (21%) was observed for performing salpingotomy in case of contra-lateral tubal pathology. Wide variance in adherence (0-100%) existed between academic, teaching and non-teaching hospitals. CONCLUSIONS: The overall guideline adherence was reasonable, with ample room for improvement in various aspects of care. Further research should focus on the barriers for guideline dissemination and adherence, to further improve the management of EP.

Salpingotomy or salpingectomy in tubal ectopic pregnancy: what do women prefer?

There is an ongoing debate whether tubal ectopic pregnancy should be treated by salpingotomy or salpingectomy. It is unknown which treatment women prefer in view of the potentially better fertility outcome but disadvantages of salpingotomy. This study investigated women surgically treated for tubal ectopic pregnancy and subfertile women desiring pregnancy and their preferences for salpingotomy relative to salpingectomy by means of a web-based discrete choice experiment consisting of 16 choice sets. Scenarios representing salpingotomy differed in three attributes: intrauterine pregnancy (IUP) chance, risk of persistent trophoblast and risk of repeat ectopic pregnancy. An 'opt out' alternative, representing salpingectomy, was similar for every choice set. A multinomial logistic regression model was used to analyse relative importance of the attributes. This study showed that the negative effect of repeat ectopic pregnancy was 1.6 times stronger on the preference of women compared with the positive effect of the spontaneous IUP rate. For all women, the risk of persistent trophoblast was acceptable if compensated by a small rise in the spontaneous IUP rate. The conclusion was that women preferred avoiding a repeat ectopic pregnancy to a higher probability of a spontaneous IUP in the surgical treatment of tubal ectopic pregnancy. An ectopic pregnancy occurs when a fertilized egg gets stuck inside the Fallopian tube where it starts growing instead of passing on to the uterus. This may lead to serious problems, such as internal bleeding and pain. Therefore, in the majority of women, it is necessary to remove the ectopic pregnancy by means of an operation. Two types of surgery are being used in removing the ectopic pregnancy. A conservative approach, salpingotomy, preserves the tube but bears the risk of incomplete removal of the pregnancy tissue (persistent trophoblast), which then needs additional treatment, and of a repeat ectopic pregnancy in the same tube in the future. A radical approach, salpingectomy, bears no risk of persistent trophoblast and limits the risk of repeat tubal pregnancy, but leaves only one tube for reproductive capacity. It is unknown which type of operation is better, especially for future fertility. We investigated women's preferences between these two treatments for ectopic pregnancy, i.e. does a better fertility prognosis outweigh the potential disadvantages of persistent trophoblast and an increased risk for ectopic pregnancy in the future? The study results show in the surgical treatment of tubal ectopic pregnancy that women preferred avoiding a repeat ectopic pregnancy to gaining a higher chance of a spontaneous intrauterine pregnancy. The risk of additional treatment in the case of persistent trophoblast after salpingotomy was acceptable if compensated by a small rise in intrauterine pregnancy rate.

[Interstitial pregnancy: a rare type of ectopic pregnancy]. / De interstitiële graviditeit: niet zomaar een extra-uteriene.

Three women, aged 21, 28 and 37 years, respectively, were diagnosed with interstitial pregnancies. The first patient presented with lateral abdominal pain, the second patient was asymptomatic and consulted the physician for a routine first trimester scan and the third patient had painless vaginal bleeding in the first trimester. Each was treated with systemic methotrexate in a multiple dose regimen, which was successful in the latter two patients. The first patient was discharged in good condition after her last methotrexate injection, but developed severe abdominal pain and collapsed at home after the interstitial pregnancy had ruptured. She underwent surgery and recovered. Today, the incidence of ectopic pregnancy in the Netherlands is around 8 per 1000 live births. Interstitial pregnancies, which nidate in the portion of the fallopian tube embedded in the uterine wall, account for 2-3% of all ectopic pregnancies. A urinary pregnancy test should be performed for any fertile woman with abdominal pain or abnormal vaginal bleeding. If the result is positive, the patient should be referred to a gynaecologist for transvaginal ultrasound to exclude ectopic pregnancy. In case of a pregnancy of unknown location, one should search for specific ultrasound markers of non-tubal ectopic pregnancy and assess serum human chorionic gonadotropin (HCG). Interstitial ectopic pregnancy should be considered if the serum HCG level is above 2000 U/l.

Patient-centered early pregnancy care: a systematic review of quantitative and qualitative studies on the perspectives of women and their partners.

BACKGROUND: Early pregnancy complications, defined as miscarriage, recurrent miscarriage or ectopic pregnancy, affect the physical and psychological well-being of intended parents. Research in this field so far has focused mainly on improving accuracy of diagnostic tests and safety and effectiveness of therapeutic management. An overview of aspects of care valued by women and/or their partners is missing. OBJECTIVE AND RATIONALE: This systematic review aims to provide an overview of aspects of care valued by women and/or their partners faced with early pregnancy complications and to identify potential targets for improvement in early pregnancy healthcare. SEARCH METHODS: We searched five electronic databases for empirical quantitative or qualitative studies on patients' perspectives of early pregnancy care in July 2017. We first identified aspects of early pregnancy care valued by women and/or their partners based on qualitative and quantitative data and organized these aspects of care according to the eight dimensions of patient-centered care. Second, we extracted the assessment of service quality from women and/or their partners on each of these aspects of care based on quantitative data. Third, we combined the findings on patients' values with the findings of service quality assessment to identify potential targets for improvement in five groups according to how likely these targets are to require improvement. OUTCOMES: The search yielded 6240 publications, of which 27 studies were eligible for inclusion in this review. All included studies focused on miscarriage or recurrent miscarriage care. We identified 24 valued aspects of care, which all covered the eight dimensions of patient-centered care. The most frequently reported valued aspect was 'being treated as an individual person experiencing a significant life event rather than a common condition'. Assessment of service quality from women and/or their partners was available for 13 of the 24 identified aspects of care. Quantitative studies all documented service quality as problematic for these 13 aspects of care. We thus identified 13 potential targets for improvement in the patient-centeredness of miscarriage and recurrent miscarriage care of which none were very likely, four were likely, six were unlikely and three were very unlikely, to require improvement. The four likely potential targets for improvement were 'Understandable information provision about the etiology of pregnancy', 'Staff discussing patients' distress', 'Informing patients on pregnancy loss in the presence of a friend or partner' and 'Staff performing follow-up phone calls to support their patients after a miscarriage'. WIDER IMPLICATIONS: It is important for clinicians to realize that women and their partners undergoing a miscarriage experience a significant live event and appreciate an individual approach. Future qualitative studies are needed to explore the identified potential targets for improvement of (recurrent) miscarriage care and to explore patients' perspectives in women suspected and treated for ectopic pregnancy.

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.

[Late postpartum eclampsia]. / Late eclampsie post partum.

A 36-year-old woman, who had given birth once before, had an eclamptic epileptic seizure eight days after caesarean delivery of healthy premature twins. Severe headache and loss of vision, leading to blindness, had not been recognised as prodromal signs by the healthcare professionals involved. Thereafter, she suffered a generalised epileptic seizure with tongue bite. She recovered fully after treatment with magnesium sulphate and nifedipine. Eclampsia is a severe condition with high rates of maternal complications, such as abruptio placentae, disseminated intravascular coagulation, neurological problems, pulmonary oedema, acute renal insufficiency and even death. Recognition of prodromal symptoms like headache, visual disturbances and upper abdominal pain is of the utmost importance. Magnesium sulphate intravenously is the treatment of choice. About 25% of the cases of postpartum eclampsia develop 2-28 days after delivery. A history of pre-eclampsia before or during the delivery is often absent. There is a relative increase in the incidence of late postpartum eclampsia, possibly because of misinterpretation ofprodromal symptoms, as illustrated by this case report. Every physician should be able to recognise the symptoms of pre-eclampsia and be aware of the possible consequences.

Screening for ectopic pregnancy in symptom-free women at increased risk.

OBJECTIVE: To determine the ectopic pregnancy rate among symptom-free women at increased risk undergoing a screening program involving transvaginal sonography and serum hCG testing. METHODS: Consecutive symptom-free women at increased risk for ectopic pregnancy were studied prospectively by transvaginal sonography and serum hCG measurement to detect ectopic pregnancy before the onset of symptoms. RESULTS: Between September 1993 and May 1996, 143 symptom-free pregnant women with pregnancies of a gestational age of less than 7 weeks were screened. Eight had ectopic pregnancies, 129 had intrauterine pregnancies, and six had trophoblast in regression. Among the eight women with ectopic pregnancies, one was initially diagnosed as having an intrauterine pregnancy. This women returned 1 week later with abdominal pain, and an ectopic pregnancy with intra-abdominal bleeding was found. Ectopic pregnancies were present in 5.6% (95% confidence interval 2.5%, 10.7%) of the women screened. This was significantly lower than reported in a previous study. CONCLUSION: The ectopic pregnancy rate in the population that was offered screening was low. Thus, it is questionable whether the possible benefits (prevention of complications and reassurance of the woman) outweigh possible detriments (false-positive diagnosis, financial costs, and emotional stress that could be induced by screening.

Are serum human chorionic gonadotropin clearance curves of use in monitoring methotrexate treatment in cervical pregnancy?

OBJECTIVE: To describe the monitoring of an unsuccessful case of methotrexate treatment of cervical pregnancy. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 27-year-old woman, gravida 3, para 1, with a vital cervical pregnancy. INTERVENTION(S): Feticide and methotrexate administered both locally and systemically. MAIN OUTCOME MEASURE(S): Treatment success, defined as elimination of the cervical pregnancy with preservation of the uterus. RESULT(S): Despite reassuringly declining serum hCG concentrations, several episodes of severe vaginal bleeding demanded transfusions of 19 U of packed cells, two angiographic embolizations that were complicated by septicemia, and a balloon catheter tamponade followed by a third angiographic embolization. Ultimately, a hysterectomy was necessary because of uncontrollable vaginal bleeding. CONCLUSION(S): This case report shows that serum hCG monitoring was not helpful in the detection of impending treatment failure. Currently, no guidelines are available to clinicians for predicting treatment failure of methotrexate in patients with cervical pregnancy. Serum hCG clearance curves do enable the timely detection of inadequately declining serum hCG concentrations, for which additional methotrexate can be administered.

Serum human chorionic gonadotropin clearance curves in patients with interstitial pregnancy treated with systemic methotrexate.

OBJECTIVE: To evaluate short-term effectiveness of systemic methotrexate (MTX) in interstitial pregnancy. DESIGN: Case series. SETTING: Two Dutch teaching hospitals. PATIENT(S): Eight consecutive patients with an unruptured interstitial pregnancy. INTERVENTION(S): Four doses of 1.0 mg/kg IM MTX alternated with 0.1 mg/kg oral folinic acid. Serum hCG concentrations were determined before the first MTX injection and followed until levels were undetectable. A second MTX course was started on day 14, if by then serum hCG concentrations were > 40% of the initial value. Serum hCG clearance curves of all patients in the present study were compared with those from our earlier studies, in which a different folinic acid regimen (15 mg orally) was used. MAIN OUTCOME MEASURE(S): Serum hCG clearance curves. RESULT(S): All patients were treated successfully: five with one course and three with two courses. Serum hCG clearance curves of these patients tended to decline more rapidly than those successfully treated with the 15 mg folinic acid regimen. CONCLUSION(S): Systemic MTX is an attractive therapeutic option in the conservative treatment of unruptured interstitial pregnancy. The regimen of four doses of 1.0 mg/kg IM MTX alternated with 0.1 mg/kg folinic acid is effective. Serum hCG clearance curves may serve as a guideline for monitoring MTX treatment, thus enabling a timely detection of impending treatment failure.

Diagnosis of ectopic pregnancy after in vitro fertilization and embryo transfer.

OBJECTIVE: The combination of transvaginal sonography and serum hCG measurement is reliable in the diagnosis of ectopic pregnancy (EP) in spontaneous pregnancies. In patients who became pregnant through IVF-ET, transfer of multiple embryos after IVF could be responsible for the different performance of these tests. We evaluated the discriminative capacity of transvaginal sonography in combination with hCG measurement in the diagnosis of EP after IVF-ET. DESIGN: Prospective cohort study. SETTING AND PATIENT(S): Consecutive patients, pregnant through IVF-ET, who presented with clinically suspected EP. INTERVENTION(S): Transvaginal sonography, serum hCG measurement at 6, 9, and 15 days after ET and after a negative transvaginal sonography. MAIN OUTCOME MEASURE(S): Ectopic pregnancy confirmed at laparoscopy. RESULT(S): Between September 1993 and May 1996, 86 women were included in the study, of whom 24 had an EP. Transvaginal sonography identified 46 intrauterine pregnancies and 5 EPs, but serum hCG could not diagnose EPs in patients in whom transvaginal sonography did not show a gestational sac. Serum hCG measurement 9 days after ET could identify pregnancy failure with 100% specificity at a cut-off value of 18 IU/L, but it could not identify patients with EP with enough certainty to justify immediate treatment. CONCLUSION(S): We recommend single serum hCG measurement 9 days after ET to discriminate between viable and nonviable pregnancies. Transvaginal sonography can be postponed until 5 weeks after ET, except for patients with abdominal pain and/or vaginal bleeding, or patients with a serum hCG level of < 18 IU/L.

Are gestational age and endometrial thickness alternatives for serum human chorionic gonadotropin as criteria for the diagnosis of ectopic pregnancy?

OBJECTIVE: To compare gestational age and endometrial stripe thickness measurement with serum hCG measurement as criteria for the diagnosis of ectopic pregnancy (EP). DESIGN: Prospective study. SETTING: Two large teaching hospitals in Amsterdam, The Netherlands. PATIENT(S): Three hundred fifty-four consecutively seen pregnant patients who presented between September 1993 and April 1996 with suspected EP and in whom transvaginal ultrasonogram showed no intrauterine pregnancy or EP. Ultrasonography was performed by one of the study investigators or, during shifts, by the resident on call. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The accuracy of gestational age, endometrial stripe thickness, and serum hCG measurement in the diagnosis of EP was evaluated with receiver operating characteristic curve analysis. RESULT(S): Gestational age and endometrial stripe thickness could not discriminate between patients with EP and patients without EP, whereas serum hCG had an acceptable area under the receiver operating characteristic curve. CONCLUSION(S): Gestational age and endometrial thickness are not useful in the diagnosis of EP. Serum hCG measurement is the diagnostic instrument of choice in patients with suspected EP when transvaginal ultrasonography does not reveal a diagnosis.

Should patients who are suspected of having an ectopic pregnancy undergo physical examination?

OBJECTIVE: To determine whether physical examination is useful for patients with suspected ectopic pregnancy (EP) for whom transvaginal sonography is performed and serum hCG levels are measured. DESIGN: Prospective study. SETTING: Two large teaching hospitals. PATIENT(S): Three hundred eighty-two patients with suspected EP, based on a positive urine pregnancy test and the presence of abdominal pain, vaginal bleeding, or risk indicators. INTERVENTION(S): Abdominal examination, speculum inspection, and digital vaginal examination. MAIN OUTCOME MEASURE: A final diagnosis made by transvaginal sonography, serum hCG measurement, and, if necessary, confirmatory laparoscopy. RESULT(S): One hundred sixteen (30%) of the 382 patients had an EP. At external abdominal examination, rebound tenderness and muscular rigidity had likelihood ratios of 3.7 and 8.0, respectively. Findings at speculum inspection and digital vaginal examination had likelihood ratios between 0.33 and 2.4. Logistic regression analysis showed that the additional information provided by physical examination for the diagnosis of EP is limited compared with the information provided by transvaginal sonography and serum hCG measurement alone. CONCLUSION: On the basis of our results, we believe that vaginal digital examination for patients with suspected EP is unnecessary.

Can noninvasive diagnostic tools predict tubal rupture or active bleeding in patients with tubal pregnancy?

OBJECTIVE: To evaluate the ability of noninvasive diagnostic tools to predict tubal rupture and active bleeding in patients with tubal pregnancy. DESIGN: Prospective cohort study. SETTING: Two large teaching hospitals in Amsterdam, The Netherlands. PATIENT(S): Consecutively seen patients with suspected tubal pregnancy who were scheduled to undergo confirmative laparoscopy. MAIN OUTCOME MEASURE(S): Tubal rupture and/or active bleeding confirmed at laparoscopy. RESULT(S): Sixty-five (23%) of 288 patients had tubal rupture and/or active bleeding at laparoscopy. Abdominal pain, rebound tenderness on abdominal examination, fluid in the pouch of Douglas at transvaginal ultrasound examination, and a low serum hemoglobin level were independent predictors of tubal rupture and/or active bleeding. Pregnancy achieved with the use of IVF-ET and the presence of an ectopic gestational sac or an ectopic mass at ultrasound examination reduced the risk of tubal rupture. Abdominal pain was the most sensitive predictor, with a sensitivity of 95%. CONCLUSION(S): Because the nonsurgical management of tubal pregnancy should be used only when the risk of tubal rupture and/or active bleeding is low, it can be safely applied in only a limited number of patients.

Systemic methotrexate therapy versus laparoscopic salpingostomy in patients with tubal pregnancy. Part I. Impact on patients' health-related quality of life.

OBJECTIVE: To compare patients' health-related quality of life after systemic methotrexate therapy versus laparoscopic salpingostomy for tubal pregnancy. DESIGN: Multicenter randomized clinical trial. SETTING: Departments of obstetrics and gynecology of six Dutch hospitals. PATIENT(S): Hemodynamically stable patients with a laparoscopically confirmed unruptured tubal pregnancy without signs of active bleeding, who were randomly assigned to undergo either systemic methotrexate therapy or laparoscopic salpingostomy. INTERVENTION(S): Standard health-related quality of life questionnaires administered before and 2 days, 2 weeks, 4 weeks. and 16 weeks after confirmative laparoscopy. MAIN OUTCOME MEASURE(S): Health-related quality of life. RESULT(S): Health-related quality of life was impaired most severely 2 days after confirmative laparoscopy in both treatment groups and improved during follow-up. Health-related quality of life was impaired more severely after systemic methotrexate therapy than after laparoscopic salpingostomy. Medically treated patients had more limitations in physical functioning, role functioning, and social functioning; had worse health perceptions, less energy, more pain, more physical symptoms, and a worse overall quality of life; and were more depressed than surgically treated patients. CONCLUSION(S): Systemic methotrexate therapy had a more negative impact on patients' health-related quality of life than did laparoscopic salpingostomy. This negative impact on patients' health-related quality of life of systemic methotrexate therapy should be taken into account when deciding on the appropriate therapy for tubal pregnancy.

Systemic methotrexate therapy versus laparoscopic salpingostomy in tubal pregnancy. Part II. Patient preferences for systemic methotrexate.

OBJECTIVE: To investigate patient preferences for systemic methotrexate therapy relative to laparoscopic salpingostomy in the treatment of tubal pregnancy. DESIGN: Preference assessment in controlled clinical study. SETTING: Four hospitals and one infertility clinic. PATIENT(S): Forty patients who had been treated for tubal pregnancy and 40 nonpregnant controls. INTERVENTION(S): Preference for methotrexate therapy relative to salpingostomy was established during an interview. Two scenarios were offered for methotrexate therapy: one with and one without preceding diagnostic laparoscopy. Hypothetical tubal patency rates after methotrexate therapy were varied in both scenarios until patients switched in their initial preference. MAIN OUTCOME MEASURE(S): Preference for systemic methotrexate therapy. RESULT(S): Only a few patients switched in their initial preference when the tubal patency rate after systemic methotrexate therapy was varied. Most preferred methotrexate therapy without an increase in the tubal patency rate in a scenario without preceding diagnostic laparoscopy. A small group never opted for methotrexate therapy even when it would guarantee a 100% tubal patency rate. CONCLUSION(S): Systemic methotrexate therapy would be preferred by most patients as part of a completely nonsurgical management strategy. Tubal patency was a decisive factor for treatment preference in a minority of patients only.

Serum human chorionic gonadotropin measurement in the diagnosis of ectopic pregnancy when transvaginal sonography is inconclusive.

OBJECTIVE: To assess the accuracy of initial and repeated serum hCG measurements in the diagnosis of ectopic pregnancy (EP) in patients in whom transvaginal sonography is inconclusive and to evaluate whether patient characteristics influence the accuracy of serum hCG measurements. DESIGN: Prospective study. SETTING: Two large teaching hospitals in Amsterdam, the Netherlands. PATIENT(S): Three hundred fifty-four consecutively seen pregnant patients with suspected EP and inconclusive transvaginal sonographic findings. INTERVENTION(S): Serum hCG measurements. MAIN OUTCOME MEASURE(S): The performance of repeated serum hCG measurements in the diagnosis of EP was evaluated through the analysis of receiver operating characteristic curves. RESULT(S): Initial serum hCG measurements were more diagnostic in conjunction with sonographic evidence of an ectopic mass or fluid in the pouch of Douglas than in the absence of sonographic abnormalities. On repeated measurement, the course of the serum hCG concentration provided more diagnostic information than did the absolute serum hCG concentration 2 and 4 days after the start of the diagnostic process. CONCLUSION(S): The interpretation of serum hCG measurements should depend on additional findings at transvaginal sonography. A cutoff level of 1,500 IU/L is recommended for patients with an ectopic mass or fluid in the pouch of Douglas; in patients without these findings, the cutoff level should be at least 2,000 IU/L. Four days after the start of the diagnostic process, any rise in the serum hCG concentration makes the diagnosis of EP very likely.