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.

Operative laparoscopy in The Netherlands: Diffusion and acceptance.

OBJECTIVE: To evaluate and update the current status of the implementation of operative laparoscopy in gynaecology in The Netherlands by assessing diffusion and acceptance of each specific procedure per hospital. STUDY DESIGN: In 2003 a questionnaire was sent to all hospitals (n = 102), which addressed the total number and type of laparoscopic procedures performed in 2002 stratified by level of difficulty (level 1: diagnostic laparoscopy, sterilization, tubal patency tests; level 2: adhesiolysis, ectopic pregnancy (EP), laparoscopic treatment of endometriosis, cystectomy, oophorectomy, LAVH, tubal surgery for infertility; level 3: myomectomy, total laparoscopic hysterectomy (TLH) and sacropexy). Data were compared to previously published data of 1994. RESULTS: Response rate was 79% (81/102). Diffusion and acceptance of level 2 procedures increased significantly, except endometriosis and tubal surgery for infertility. Diffusion of LAVH was only 58%. Four percent of hysterectomies were LAVH. TLH and sacropexy were not performed. The diffusion of myomectomy increased significantly (p = 0.01), whereas its acceptance remained low. CONCLUSIONS: Although the diffusion of operative procedures has increased over the last decade, acceptance is still limited, especially for laparoscopic hysterectomy. The implementation of operative gynaecological laparoscopy in The Netherlands seems to develop at a slow pace.

A role for the fibrinolytic system in postsurgical adhesion formation.

OBJECTIVE: To look for evidence of a fibrinolytic insufficiency as a cause of adhesion formation. DESIGN: Retrospective and prospective study. SETTING: University medical center. PATIENT(S): Retrospective study: 50 patients undergoing laparoscopy, divided into patients with and without endometriosis. Prospective study: 18 patients undergoing infertility surgery involving a second-look laparoscopy. INTERVENTION(S): During all surgical procedures, adhesions were scored, and peritoneal fluid and plasma were collected. MAIN OUTCOME MEASURE(S): Parameters of the fibrinolytic system were measured to establish a possible relation with the presence and formation of adhesions. RESULT(S): In patients with endometriosis and adhesions, significantly higher peritoneal fluid concentrations were found for plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), and plasminogen, compared with patients with endometriosis but without adhesions. In the prospective study, initial peritoneal PAI-1 concentrations correlated significantly with the extent of adhesion formation (r(s) = 0.49) and adhesion-improvement scores (r(s) = -0.52). Also, the change in concentration of tPA and fibrinogen from the initial surgical procedure to the second-look laparoscopy correlated significantly with adhesion-improvement scores (DeltatPA: r(s)= 0.50; Deltafibrinogen: r(s) = -0.64). CONCLUSION(S): This first prospective study in humans adds further weight to the hypothesis that adhesions are caused by an insufficiency in peritoneal fibrinolytic activity. Plasminogen activator inhibitor-1 is a potential marker for the identification of patients at risk for developing adhesions.

Ectopic pregnancy: when is expectant management safe?

This study was conducted to evaluate expectant management in asymptomatic patients with an initial serum beta-hCG titer of <2,500 IU/l and to determine the independent ability of initial serum beta-hCG titers and trend of serum beta-hCG to predict successful expectant management. A cohort of patients (N = 418) with suspected ectopic pregnancy (EP) between January 1991 and July 2008 is described. Three groups were defined: group I (n = 182), immediate surgical intervention (<24 h); group IIa (n = 130), unsuccessful expectant management (surgical intervention during follow-up), and group IIb (n = 99), successful expectant management (spontaneous regression of trophoblast). Hospital protocol was not complied in 35 cases (Table 1). Beta-hCG levels >3,000 IU/l occur in our expectant management group; however, none of these cases were successful. Unnecessary surgery was prevented in 14% (n = 7) of asymptomatic patients with initial beta-hCG of >2,000 IU/l. The success rate of expectant management was 49%, without a rise in complication rate or number of acute cases. In conclusion, the initial serum beta-hCG cutoff level of 2,000 IU/l is not a rigid upper limit for accepting expectant management in suspected EP and best practice is case specific. In asymptomatic patients, the serum beta-hCG cutoff level of at least 2,500 IU/l can be used for expectant management. This cutoff could be higher, but interpretation is limited due to censure in follow-up inherent to the predefined clinical protocol. There is no gain in including patients for expectant management with initial serum beta-hCG level >3,000 IU/l.

Preoperative predictors of postsurgical adhesion formation and the Prevention of Adhesions with Plasminogen Activator (PAPA-study): results of a clinical pilot study.

OBJECTIVE: To identify predictors of postsurgical adhesion formation in peritoneal fluid and plasma, and assess efficacy and safety of reteplase (recombinant plasminogen activator [r-PA]). DESIGN: Prospective randomized study. SETTING: University Medical Center. PATIENT(S): Twenty-six abdominal myomectomy patients with early second-look laparoscopy (ESL). INTERVENTION(S): Randomization to IP treatment with 1 mg reteplase in 300 mL Ringer's lactate or 300 mL Ringer's lactate only. Scoring of adhesions and collecting peritoneal fluid during both surgical procedures and collecting plasma samples at ten time points. MAIN OUTCOME MEASURE(S): Incidence, severity, and extent of adhesions at ESL. Concentrations of C-reactive protein (CRP), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), and fibrin degradation products (FbDPs). RESULT(S): Significant correlation between the extent of uterine adhesion formation and preoperative plasma levels of CRP (r(s) = 0.558), PAI-1 (r(s) = 0.413), and the change in tPA concentration in peritoneal fluid from initial surgery to ESL (Delta+PA: r(s) = -0.636). No significant differences in adhesion scores between treatment and control groups. CONCLUSION(S): Our finding that preoperative plasma CRP and PAI-1-levels are significantly correlated with extent of adhesion formation points to a role of chronic inflammation in the disease process. Results are highly indicative for the paradigm that adhesions are caused by an insufficiency in peritoneal fibrinolytic capacity. For successful adhesion prevention therapy relatively high amounts of r-PA are required.

Complications of laparoscopy: an inquiry about closed- versus open-entry technique.

OBJECTIVE: The purpose of this study was to determine the amount of complications and the incidence of open- versus closed-entry (either by Veress needle or first trocar) technique in gynecologic laparoscopy in The Netherlands. STUDY DESIGN: Questionnaire analysis of members of the Dutch Society for Gynaecological Endoscopy and Minimal Invasive Surgery was combined with a Medline literature search. Data related to complications on entry from January 1,1997, through December 31, 2001, were collected by questionnaire and were separated into group I (Veress needle or first trocar) and group II (open-entry technique). The number of laparoscopy procedures, years of experience, and indications to perform the chosen entry technique were collected. RESULTS: Response rate was 98%. The procedures were performed by 187 gynecologists in 74 hospitals (72%) in The Netherlands. Groups I and II were comparable to each other, with respect to type of clinic (teaching vs nonteaching hospital), the number of procedures, and the experience of gynecologists. One hundred six gynecologists (57%) used only the closed-entry technique. This group reported 31 complications (0.1%) in 31,532 procedures. Even in the case of patients who were at risk for entry-related complications (previous laparotomy, obesity), pneumoperitoneum was established by the closed-entry technique. However, most gynecologists used an alternative insufflation point (eg, Palmer's point). The remaining 81 gynecologists used both entry techniques. However, the open-entry technique was used on special indications and in only 2.0% of cases (range: 1-20%). These special indications were suspected adhesions or previous laparotomy (90%) and obese (7%) or very thin patients (3%). These 81 gynecologists reported 20,027 closed-entry procedures and 579 open-entry procedures and complication rates of 0.12% and 1.38%, respectively (P<.001). Significantly more visceral lesions were found (P<.001) at open-entry technique in group II. Our literature search showed a calculated average entry complication rate for the closed-entry technique for visceral and vascular lesions of 0.44 of 1000 procedures and 0.31 of 1000 procedures, respectively. CONCLUSION: Although 43% of the gynecologists in this study performed the open-entry technique in laparoscopy, Dutch gynecologists seldom use this technique. When it is performed in selected patients, the number of complications is not reduced necessarily. In contrast to published data of general surgeons' findings, the number of entry-related complications in the open technique was significantly higher than the closed-entry technique. There is no evidence to abandon the closed-entry technique in laparoscopy. However, the selection of patients for an open- or alternative-entry procedure is still recommended.