Norah M. van Mello

Pregnancy of unknown location: a consensus statement of nomenclature, definitions, and outcome

OBJECTIVE To improve the interpretation of future studies in women who are initially diagnosed with a pregnancy of unknown location (PUL), we propose a consensus statement with definitions of population, target disease, and final outcome. DESIGN A review of literature and a series of collaborative international meetings were used to develop a consensus for definitions and final outcomes of women initially diagnosed with a PUL. RESULT(S) Global differences were noted in populations studied and in the definitions of outcomes. We propose to define initial ultrasound classification of findings into five categories: definite ectopic pregnancy (EP), probable EP, PUL, probable intrauterine pregnancy (IUP), and definite IUP. Patients with a PUL should be followed and final outcomes should be categorized as visualized EP, visualized IUP, spontaneously resolved PUL, and persisting PUL. Those with the transient condition of a persisting PUL should ultimately be classified as nonvisualized EP, treated persistent PUL, resolved persistent PUL, or histologic IUP. These specific categories can be used to characterize the natural history or location (intrauterine vs. extrauterine) of any early gestation where the initial location is unknown. CONCLUSION(S) Careful definition of populations and classification of outcomes should optimize objective interpretation of research, allow objective assessment of future reproductive prognosis, and hopefully lead to improved clinical care of women initially identified to have a PUL.

Salpingotomy versus salpingectomy in women with tubal pregnancy (ESEP study): an open-label, multicentre, randomised controlled trial.

BACKGROUND Tubal ectopic pregnancy can be surgically treated by salpingectomy, in which the affected Fallopian tube is removed, or salpingotomy, in which the tube is preserved. Despite potentially increased risks of persistent trophoblast and repeat ectopic pregnancy, salpingotomy is often preferred over salpingectomy because the preservation of both tubes is assumed to offer favourable fertility prospects, although little evidence exists to support this assumption. We aimed to assess whether salpingotomy would improve rates of ongoing pregnancy by natural conception compared with salpingectomy. METHODS In this open-label, multicentre, international, randomised controlled trial, women aged 18 years and older with a laparoscopically confirmed tubal pregnancy and a healthy contralateral tube were randomly assigned via a central internet-based randomisation program to receive salpingotomy or salpingectomy. The primary outcome was ongoing pregnancy by natural conception. Differences in cumulative ongoing pregnancy rates were expressed as a fecundity rate ratio with 95% CI, calculated by Cox proportional-hazards analysis with a time horizon of 36 months. Secondary outcomes were persistent trophoblast and repeat ectopic pregnancy (expressed as relative risks [RRs] with 95% CIs) and ongoing pregnancy after ovulation induction, intrauterine insemination, or IVF. The researchers who collected data for fertility outcomes were masked to the assigned intervention, but patients and the investigators who analysed the data were not. All endpoints were analysed by intention to treat. We also did a (non-prespecified) meta-analysis that included the findings from the present trial. This trial is registered, number ISRCTN37002267. FINDINGS 446 women were randomly assigned between Sept 24, 2004, and Nov 29, 2011, with 215 allocated to salpingotomy and 231 to salpingectomy. Follow-up was discontinued on Feb 1, 2013. The cumulative ongoing pregnancy rate was 60·7% after salpingotomy and 56·2% after salpingectomy (fecundity rate ratio 1·06, 95% CI 0·81-1·38; log-rank p=0·678). Persistent trophoblast occurred more frequently in the salpingotomy group than in the salpingectomy group (14 [7%] vs 1 [<1%]; RR 15·0, 2·0-113·4). Repeat ectopic pregnancy occurred in 18 women (8%) in the salpingotomy group and 12 (5%) women in the salpingectomy group (RR 1·6, 0·8-3·3). The number of ongoing pregnancies after ovulation induction, intrauterine insemination, or IVF did not differ significantly between the groups. 43 (20%) women in the salpingotomy group were converted to salpingectomy during the initial surgery because of persistent tubal bleeding. Our meta-analysis, which included our own results and those of one other study, substantiated the results of the trial. INTERPRETATION In women with a tubal pregnancy and a healthy contralateral tube, salpingotomy does not significantly improve fertility prospects compared with salpingectomy. FUNDING Netherlands Organisation for Health Research and Development (ZonMW), Region Västra Götaland Health & Medical Care Committee.

Ectopic pregnancy: how the diagnostic and therapeutic management has changed

Nowadays ectopic pregnancy often can be diagnosed before the womans condition has deteriorated, which has altered the former clinical picture of a life-threatening disease into a more benign condition. This review describes the historical developments in the diagnostic and therapeutic management of ectopic pregnancy leading up to current clinical practice. The first attempts to diagnose ectopic pregnancy originate from the beginning of the 20th century.

Ectopic pregnancy and pelvic inflammatory disease: a renewed epidemic?

OBJECTIVE The incidence of ectopic pregnancy (EP) was reported to rise during the 1970s and 1980s; thereafter it remained stable or even declined. We studied whether changes in the incidence of pelvic inflammatory disease (PID) have had an impact on the incidence of EP and we hypothesise about the incidence of EP in the near future. STUDY DESIGN EP and PID hospital admissions from 1980 to 2005 were derived from Dutch Medical Registries and incidence trends were calculated and analysed by joinpoint regression. RESULTS The peak incidence of EP in 1988 (11/1000 live births) was preceded by a peak incidence of admissions for PID in 1983 (0.6/1000 women of all ages). The EP rate declined towards 2005 (7.3/1000 live births) mainly due to a decrease in EP in urban regions and in older aged women (> or =35 years). Presently, women <25 years and born between 1985 and 1990 are again at an increased risk of EP (12/1000 live births) but this rise was not preceded by a peak incidence of admissions for PID. CONCLUSION On a population level, the peak incidence of EP in The Netherlands was preceded by a peak incidence of PID. A renewed rise in the incidence of EP is observed for young women. This may be related to the significant increase in positive tests for genital Chlamydia trachomatis during recent years.

Randomized comparison of health-related quality of life in women with ectopic pregnancy or pregnancy of unknown location treated with systemic methotrexate or expectant management

OBJECTIVE To study the impact on health-related quality of life (HRQoL) of treatment with systemic methotrexate (MTX) or expectant management in women with ectopic pregnancy or pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations. STUDY DESIGN HRQoL was assessed alongside a randomized clinical trial (RCT) with the use of standard self-administered psychometric measure questionnaires. PATIENTS AND SETTING All women who participated in the multicenter RCT comparing treatment with systemic MTX to expectant management in women with ectopic pregnancy or persisting PUL were eligible for the HRQoL measurements. MAIN OUTCOME MEASURE HRQoL measures of three standardized questionnaires (SF-36, RSCL, HADS). RESULTS Data were available for 64 of 73 women (78%) randomized in the RCT. We found no difference in HRQoL between the two treatment groups. The need for additional treatment, i.e. additional MTX injections or surgical intervention, had no impact on HRQoL. CONCLUSION Women treated with MTX or expectant management for an ectopic pregnancy or persisting PUL have comparable quality of life.

Salpingotomy versus salpingectomy in women with tubal pregnancy (European surgery in ectopic pregnancy study): An open-label, multicenter, randomized controlled trial

The standard surgical procedure for treatment of tubal ectopic pregnancy is salpingectomy, in which the affected fallopian tube is removed. A feasible alternative intervention, salpingotomy, has been promoted since 1957. With this procedure, the pregnancy is removed while the affected tube is preserved. There are 2 risks associated with salpingotomy: a repeated ectopic pregnancy in the same tube and a persistent trophoblast requiring additional treatment. Despite these potential drawbacks, salpingotomy has been widely used and often preferred over salpingectomy because it has been assumed that preservation of both tubes increased the prospects for a future pregnancy. However, limited data support this assumption, and it remains unclear whether the potential benefits of salpingotomy outweigh the risks. The aim of this open-label, multicenter, randomized controlled trial was to determine whether salpingotomy improves rates of ongoing pregnancy by natural conception compared with salpingectomy. Participants were 18 years or older with a laparoscopically confirmed tubal pregnancy and a healthy contralateral tube. All had a desire for a future pregnancy. At surgery, they were randomly assigned to receive salpingotomy or salpingectomy. The primary study outcome was ongoing pregnancy by natural conception. Differences between groups in cumulative ongoing pregnancy rates were expressed as a fecundity rate ratio using Cox proportional hazards analysis with a time horizon of 36 months. Secondary study outcomes were persistent trophoblast, repeated ectopic pregnancy, ongoing pregnancy after ovulation induction, intrauterine insemination, and in vitro fertilization. Patients and investigators who analyzed the data were not masked to the assigned intervention, but researchers who collected data for fertility outcomes were unaware of treatment allocation. Data were analyzed according to the intention to treat. The investigators performed a (nonprespecified) meta-analysis that included the data from the present trial. A total of 446 women were randomly assigned to salpingotomy (n = 215) or salpingectomy (n = 231) between 2004 and 2011. The patients were followed until February 1, 2013. There was no significant difference between the groups in the cumulative ongoing pregnancy rate (60.7% after salpingotomy vs 56.2% after salpingectomy; the fecundity rate ratio was 1.06, with a 95% confidence interval [CI] of 0.81–1.38, log-rank P = 0.678.) Persistent trophoblast occurred significantly more frequently in the salpingotomy group (14 [7%] vs 1 [<1%]; relative risk, 15.0; 95% CI, 2.0–113). The risk for repeated ectopic pregnancy was not significantly increased after salpingotomy Copyright