Dilatation and curettage increases the risk of subsequent preterm birth: a systematic review and meta-analysis.

STUDY QUESTION: Could dilatation and curettage (D&C), used in the treatment of miscarriage and termination of pregnancy, increase the risk of subsequent preterm birth? SUMMARY ANSWER: A history of curettage in women is associated with an increased risk of preterm birth in a subsequent pregnancy compared with women without such history. WHAT IS KNOWN ALREADY: D&C is one of the most frequently performed procedures in obstetrics and gynaecology. Apart from the acknowledged but relatively rare adverse effects, such as cervical tears, bleeding, infection, perforation of the uterus, bowel or bladder, or Asherman syndrome, D&C has been suggested to also lead to an increased risk of preterm birth in the subsequent pregnancy. STUDY DESIGN, SIZE, DURATION: In the absence of randomized data, we conducted a systematic review and meta-analysis of cohort and case-control studies. PARTICIPANTS/MATERIALS, SETTING, METHODS: We searched OVID MEDLINE and OVID EMBASE form inception until 21 May 2014. We selected cohort and case-control studies comparing subsequent preterm birth in women who had a D&C for first trimester miscarriage or termination of pregnancy and a control group of women without a history of D&C. MAIN RESULTS AND THE ROLE OF CHANCE: We included 21 studies reporting on 1 853 017 women. In women with a history of D&C compared with those with no such history, the odds ratio (OR) for preterm birth <37 weeks was 1.29 (95% CI 1.17; 1.42), while for very preterm birth the ORs were 1.69 (95% CI 1.20; 2.38) for <32 weeks and 1.68 (95% CI 1.47; 1.92) for <28 weeks. The risk remained increased when the control group was limited to women with a medically managed miscarriage or induced abortion (OR 1.19, 95% CI 1.10; 1.28). For women with a history of multiple D&Cs compared with those with no D&C, the OR for preterm birth (<37 weeks) was 1.74 (95% CI 1.10; 2.76). For spontaneous preterm birth, the OR was 1.44 (95% CI 1.22; 1.69) for a history of D&C compared with no such history. LIMITATIONS, REASONS FOR CAUTION: There were no randomized controlled trials comparing women with and without a history of D&C and subsequent preterm birth. As a consequence, confounding may be present since the included studies were either cohort or case-control studies, not all of which corrected the results for possible confounding factors. WIDER IMPLICATIONS OF THE FINDINGS: This meta-analysis shows that D&C is associated with an increased risk of subsequent preterm birth. The increased risk in association with multiple D&Cs indicates a causal relationship. Despite the fact that confounding cannot be excluded, these data warrant caution in the use of D&C for miscarriage and termination of pregnancy, the more so since less invasive options are available. STUDY FUNDING/COMPETING INTERESTS: This study was funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-82310-97-12066.

MisoREST: surgical versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage: a randomized controlled trial.

STUDY QUESTION: Is curettage more effective than expectant management in case of an incomplete evacuation after misoprostol treatment for first trimester miscarriage? SUMMARY ANSWER: Curettage leads to a higher chance of complete evacuation but expectant management is successful in at least 76% of women with an incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. WHAT IS KNOWN ALREADY: In 5-50% of the women treated with misoprostol, there is a suspicion of incomplete evacuation of the uterus on sonography. Although these women generally have minor symptoms, such a finding often leads to additional curettage. STUDY DESIGN, SIZE, DURATION: From June 2012 until July 2014, we conducted a nationwide multicenter randomized controlled trial (RCT). Women who had had primary misoprostol treatment for miscarriage with sonographic evidence of incomplete evacuation of the uterus were randomly allocated to either curettage or expectant management (1:1), using a web-based application. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 59 women in 27 hospitals; 30 were allocated to curettage and 29 were allocated to expectant management. A successful outcome was defined as sonographic finding of an empty uterus 6 weeks after randomization. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics of both groups were comparable. Empty uterus on sonography or uneventful clinical follow-up was seen in 29/30 women (97%) allocated to curettage compared with 22/29 women (76%) allocated to expectant management (RR 1.3, 95% CI 1.03-1.6) with complication rates of 10% versus 10%, respectively (RR 0.97, 95% CI 0.21-4.4). In the group allocated to curettage, no woman required re-curettage, while two women (6.7%) underwent hysteroscopy (for other or unknown reasons). In the women allocated to expectant management, curettage was performed in four women (13.8%) and three women (10.3%) underwent hysteroscopy. LIMITATIONS, REASONS FOR CAUTION: Due to a strong patient preference, mainly for expectant management, the targeted sample size could not be included and the trial was stopped prematurely. WIDER IMPLICATIONS OF THE FINDINGS: In women suspected of incomplete evacuation of the uterus after misoprostol, curettage is more effective than expectant management. However, expectant management is equally safe and prevents curettage for most of the women. This finding could further restrain the use of curettage in the treatment of first trimester miscarriage. STUDY FUNDING/COMPETING INTERESTS: This study was funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-82310-97-12066. There were no conflicts of interests. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR3310, http://www.trialregister.nl TRIAL REGISTRATION DATE: 27 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 12 June 2012.

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.

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.

Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus.

BACKGROUND: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from decreased mast cell activation and impaired intestinal inflammation. OBJECTIVE: To quantify mast cell activation and inflammation in patients undergoing conventional and minimal invasive surgery. METHODS: (1) Mast cell activation (ie, tryptase release) and pro-inflammatory mediator release were determined in peritoneal lavage fluid obtained at consecutive time points during open, laparoscopic and transvaginal gynaecological surgery. (2) Lymphocyte function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) mRNA as well as leucocyte influx were quantified in non-handled and handled jejunal muscle specimens collected during biliary reconstructive surgery. (3) Intestinal leucocyte influx was assessed by 99mTc-labelled leucocyte single photon emission computed tomography (SPECT) - computed tomography (CT) scanning before and after abdominal or vaginal hysterectomy. RESULTS: (1) Intestinal handling during abdominal hysterectomy resulted in an immediate release of tryptase followed by enhanced interleukin 6 (IL6) and IL8 levels. None of the mediators increased during minimal invasive surgery except for a slight increase in IL8 during laparoscopic surgery. (2) Jejunal ICAM-1 and iNOS mRNA transcription as well as leucocyte recruitment were increased after intestinal handling. (3) Leucocyte scanning 24 h after surgery revealed increased intestinal activity after abdominal but not after vaginal hysterectomy. CONCLUSIONS: This study demonstrates that intestinal handling triggers mast cell activation and inflammation associated with prolonged postoperative ileus. These results may partly explain the faster recovery after minimal invasive surgery and encourage future clinical trials targeting mast cells to shorten postoperative ileus.

[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.

[Uterine artery embolisation in the treatment of uterine fibroids: outcomes of randomised trials]. / Embolisatie als behandeling van uterus myomatosus: resultaten uit gerandomiseerd onderzoek.

In the past so years, uterine artery embolisation has gained popularity in the treatment of uterine fibroids compared with traditional surgical interventions. This was based on promising results from a few non-randomised studies, which reported success rates of 95 to 98%. Were these rates accurate? Two recent randomised studies (the Dutch EMMY trial and the Scottish REST trial) showed that, in patients with symptomatic uterine fibroids, the time to recovery and return to work was significantly shorter after embolisation than after surgery (hysterectomy or myomectomy). However, embolisation was insufficiently effective in approximately 20% of patients, who required further treatment. Despite this, quality of life after one and two years in both treatment arms were identical. Embolisation, therefore, may be a valid treatment alternative in patients with symptomatic fibroids who are candidates for hysterectomy.

[The guideline 'Recurrent miscarriage' (first revision) of the Dutch Society for Obstetrics and Gynaecology]. / Richtlijn 'Herhaalde miskraam' (eerste herziening) van de Nederlandse Vereniging voor Obstetrie en Gynaecologie.

--In 2007, the Dutch Society for Obstetrics and Gynaecology issued a revised version of the 1999 guideline on recurrent miscarriage. --The new guideline was developed according to the principles of evidence-based guideline development and includes levels of evidence. --The guideline contains recommendations for effective diagnosis and treatment and explicitly mentions certain diagnostic tests and treatments that should be avoided. --After a thorough investigation of a couples'-history, the type of diagnostic tests that should be offered to the couple can be determined. Patients with a low risk of having cytogenetic abnormalities or thrombophilia may be excluded from parental karyotyping and thrombophilia screening, respectively. --Women with confirmed antiphospholipid antibody syndrome should be offered anticoagulation treatment before and during subsequent pregnancies. --Effective therapy for unexplained recurrent miscarriage is lacking. However, the probability of a successful future pregnancy is high. This probability can be estimated based on the number of previous miscarriages and maternal age.

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.

Fertility and obstetric outcomes after curettage versus expectant management in randomised and non-randomised women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage.

OBJECTIVE: To assess fertility and obstetric outcomes in women treated with curettage or undergoing expectant management for an incomplete miscarriage after misoprostol treatment. STUDY DESIGN: Between June 2012 and July 2014, we conducted a multicentre randomised clinical trial (RCT) with a parallel cohort study for non-randomised women, treated according to their preference. In the RCT 30 women were allocated curettage and 29 expectant management. In the cohort 197 women participated; 65 underwent curettage and 132 women underwent expectant management. Primary outcome was curation, defined as either an empty uterus on sonography at six weeks or an uneventful clinical follow-up. We used questionnaires to assess fertility and obstetric outcome of the first new pregnancy subsequent to study enrolment. RESULTS: Curation was seen in 91/95 women treated with curettage (95.8%) versus 134/161 women managed expectantly (83.2%) (p=0.003). The response rate was 211/255 (82%). In 198 women pursuing a new pregnancy, conception rates were 92% (67/73) in the curettage group versus 96% (120/125) in the expectant management group (OR 0.96, 95% CI 0.89;1.03, p=0.34), with ongoing pregnancy rates of 87% (58/67) versus 78% (94/120), respectively (OR 1.12, 95% CI 0.99;1.28, p=0.226). Preterm birth rates were 1/46 in the curettage group versus 8/81 in the expectant management group (OR 0.22, 95% CI 0.03;1.71 P=0.15). Caesarean section rates were 23% and 24% for women in the curettage group and expectant management group respectively. CONCLUSION: In women with an incomplete evacuation of the uterus after misoprostol treatment, curettage and expectant management does not lead to different fertility and pregnancy outcomes, as compared to expectant management.

MisoREST: Surgical versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage: A cohort study.

OBJECTIVE: To assess the effectiveness of curettage versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. STUDY DESIGN: We conducted a multicenter cohort study alongside a randomized clinical trial (RCT) between June 2012 until July 2014. 27 Dutch hospitals participated. Women with an incomplete evacuation after misoprostol treatment for first trimester miscarriage who declined to participate in the RCT, received treatment of their preference; curettage (n=65) or expectant management (n=132). A successful outcome was defined as an empty uterus on sonography at six weeks or uneventful clinical follow-up. We furthermore assessed complication rate and (re)intervention rate RESULTS: Of the 197 women who declined to participate in the RCT, 65 preferred curettage and 132 expectant management. A successful outcome was observed in 62/65 women (95%) in the surgical group versus 112/132 women (85%) in the expectant group (RR 1.1, 95% CI 1.03-1.2), with complication rates of 6.2% versus 2.3%, respectively (RR 2.7, 95% CI 0.6-12). CONCLUSION: In women with an incomplete evacuation of the uterus after misoprostol treatment, expectant management is an effective and safe option. This finding could restrain the use of curettage in women that have used misoprostol in the treatment of first trimester miscarriage.

[The practice guideline 'Miscarriage' (second revision) from the Dutch College of General Practitioners; a response from the perspective of gynaecology]. / De standaard 'miskraam' (tweede herziening) van het nederlands huisartsen genootschap; reactie vanuit de gynaecologie.

In March 2004, the Dutch College of General Practitioners issued its revised guideline on the management of miscarriage. The older version of the guideline advised expectant management of all patients with first-trimester vaginal bleeding without ultrasonographic evaluation. In contrast, the new version has accepted the importance of ultrasonographic assessment, which offers insight into the patient's prognosis. This enables GPs to discuss the further management options with women in whom a non-vital pregnancy has been diagnosed: expectant management or referral to a unit for removal of the products of conception by means of vacuum curettage. Since the patient's management preferences have now also been acknowledged, the new guideline is better for all parties involved in this common clinical problem.

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.

The prognosis of cervical cancer associated with pregnancy: a matched cohort study.

OBJECTIVE: To assess the effect of pregnancy on the prognosis of cervical cancer and the morbidity of standard treatment. METHODS: We analyzed 44 women with cervical carcinoma associated with pregnancy, who were matched with 44 controls. Matching criteria were age, stage of disease (according to the International Federation of Gynecology and Obstetrics classification), tumor type, treatment modality, and period of treatment. RESULTS: In 23 cases, cervical cancer was diagnosed during pregnancy and in the other 21 cases, within 6 months after delivery. Thirty-nine women had early-stage disease (eight IA, 25 IB, and six IIA), and five had advanced stages (four IIB and one IIIB). The overall 5-year survival rate was 80% among subjects and 82% among controls, whereas the relative risk (RR) of dying within 5 years was 1.12 (95% confidence interval [CI] 0.48-2.65). With regard to the 5-year survival rate (85% for both subjects and controls, the RR of dying was 1.00 [95% CI 0.35-2.83]); no differences were found between subjects and controls for early-stage cervical carcinoma. The size of the group with advanced-stage cervical carcinoma was too small to allow any statistical analysis. No statistically significant differences in survival were observed between cases diagnosed during pregnancy and cases diagnosed after delivery. In addition, the mode of delivery had no effect on survival. Early complications within 6 weeks after treatment were seen 33 times in 25 subjects and 29 times in 23 controls. No differences were observed in the prevalence and type of early complications in subjects versus controls. Late complications after 6 weeks of treatment were seen nine times in nine subjects and 11 times in ten controls. No significant differences were observed in the prevalence and type of late complications in subjects versus controls. CONCLUSION: The prognosis of early-stage cervical cancer is similar in pregnant and nonpregnant patients when standard treatment is given. Because of the limited number of patients, no conclusions can be drawn about advanced-stage cervical cancer. The goal should be standard oncologic treatment, which does not lead to increased morbidity in pregnant patients.

Risk factors for ectopic pregnancy: a meta-analysis.

OBJECTIVE: To review current knowledge on the risk of ectopic pregnancy (EP), with the exception of contraceptive methods. DESIGN: Meta-analysis. SETTING: Case control and cohort studies published between 1978 and 1994 in English, French, German, or Dutch, retrieved by Medline search, crossover search from the papers obtained, and hand-search on recent medical journals. PATIENTS: A total number of 6,718 cases of EP in 27 case control studies and 13,049 exposed women in 9 cohort studies. MAIN OUTCOME MEASURES: Detected studies were tested for homogeneity. If homogeneity was not rejected, Mantel-Haenszel common odds ratios (OR) and 95% confidence intervals were calculated. RESULTS: Previous EP, previous tubal surgery, documented tubal pathology, and in utero diethylstilbestrol (DES) exposure were found to be associated strongly with the occurrence of EP. Previous genital infections (pelvic inflammatory disease [PID], chlamydia, gonorrhoea), infertility, and a lifetime number of sexual partners > 1 were associated with a mildly increased risk. For gonorrhoea, PID, previous EP, previous tubal surgery, and smoking, a higher common OR was calculated when using pregnant controls compared with using nonpregnant controls. CONCLUSIONS: The strong risk in women with a previous EP, previous tubal surgery, documented tubal pathology, or in utero DES exposure justifies the exploration of a screening policy for EP among these women. If a risk factor reduces fertility chances, the OR detected when using pregnant controls is higher than the OR calculated using nonpregnant controls.

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.

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.