The effect of surgery or medication on pain and quality of life in women with endometrioma. A systematic review and meta-analysis.

For patients with endometrioma it is unclear what treatment: surgery and/or medication, is more effective in reducing pain and improving quality of life (QoL). This systematic review and meta- analysis aimed to provide an overview of the existing evidence on the effects of surgery and/or medication (i.e. analgesics and/or hormonal medication) on pain and QoL. A search through CENTRAL, MEDLINE and Embase was conducted. The study population had to be women treated for endometrioma. Retrospective or prospective studies reporting about QoL and/or the following types of pain were reviewed: dysmenorrhea, dyspareunia, chronic pelvic pain, and pain that was not well defined in the included article (referred to as pain). We performed a meta-analysis on mean visual analogue scale (VAS) scores and proportions of patients experiencing different types of pain over time. QoL was described narratively. Out of 11.515 articles, 76 studies including 7148 patients were included for the systematic review. The meta-analysis consisted of 52 studies including 4556 patients. No studies compared medication with surgery. And there were no studies on analgesics. Meta-analysis showed that surgery and/or medication often reduced VAS scores and proportions of all types of pain over time. Surgery and medication combined seems more effective in reducing VAS scores of pain compared to surgery alone, but not to medication alone (estimated mean difference = 0.17, p < 0.0001 and -0.98, p = 0.0339). QoL improved after medication (follow up ≤ 12 months) and QoL was unchanged or worsened after surgery and medication combined (follow up ≤ 24 months). However, these were results from a total of 5 studies. Both surgery and medication reduce endometriosis-related pain in patients with endometrioma. However, there is lack of uniform, good quality data comparing surgery with medication to draw firm conclusions. For better-informed treatment decisions, further studies including a standardized core-outcome set at fixed follow-up times, are necessary.

Efficiency based updating of evidence based surgical guidelines - Experiences from a multidisciplinary guideline upon Minimally Invasive Surgery.

Background: Updating evidence-based clinical practice guidelines is an onerous process and there is a call for more efficient determination of key questions that need updating. Especially for surgical techniques it is unclear if new evidence will result in substantial changes after wide implementation and if continuous updating is always necessary. Objectives: This study analyses the impact of updating a surgical guideline and proposes suggestions for optimising this process. Materials and methods: The Dutch Minimally Invasive Surgery guideline was developed in 2011 and updated in 2021. For both versions a multidisciplinary guideline working group (GDG) was created, that determined key questions. Changes in conclusions and recommendations were analysed by the GDG and statements for expected change of recommendations in the future were made. Results: 15 key questions were formed, of which 12 were updates of the previous guideline. For only 27% of the updated key questions, the conclusions changed. In ten years, the body grew only marginally for most key questions and quality of the evidence did not improve substantially for almost all key questions. However, in this first update of the MIC guideline, many recommendations did change due to a more robust interpretation of the conclusions by the GDG. Based on analysis of this updating process, the GDG expects that only four out of 15 recommendations may change in the future. Conclusion: We propose an additional step at the end of guideline development and updating, where the necessity for updating in the future is determined for each key question by the GDG, using their valuable knowledge gained from developing or updating the guideline. For surgical guidelines, the authors suggest updating key issues if it includes a relatively newly introduced surgical- or adapted technique or a new patient group. Low quality or small body of evidence should not be a reason in itself for updating, as this mostly does not lead to new evidence-based conclusions. This new step is expected to result in a more efficient prioritising of key questions that need updating. What's new?: By adding one additional step at the end of the updating process, the future updating process could become more efficient.

Psychological impact over time of women with pregnancy loss due to gestational trophoblastic disease compared with miscarriage.

OBJECTIVES: Pregnancy loss, occurring after miscarriage or after gestational trophoblastic disease, has a psychological impact. Besides pregnancy loss, women diagnosed with gestational trophoblastic disease have to deal with a prolonged period of follow-up and potential advice to postpone a future pregnancy. We studied the severity and course of the psychological impact after gestational trophoblastic disease and miscarriage, to identify whether women with gestational trophoblastic disease need different psychological care. METHODS: A prospective multicenter study using online questionnaires was performed. Women diagnosed with gestational trophoblastic disease or miscarriage received the following questionnaires directly after diagnosis, and after 6, 6, and 12 months: a self-report questionnaire, the Hospital Anxiety and Depression Scale (HADS), the Impact of Event Scale, and the Reproductive Concerns Scale. RESULTS: 74 women with gestational trophoblastic disease and 76 women with miscarriage were included. At baseline, the proportion of women scoring above the cut-off level for the anxiety subscale of the HADS and for the Impact of Event Scale was significantly higher for women with gestational trophoblastic disease than for women after miscarriage (43.2% vs 28.9%, p=0.02 and 87.8% vs 78.9%, p=0.03, respectively). During follow-up, the differences between both groups vanished and only the Impact of Event Scale after 12 months remained significantly different between women with gestational trophoblastic disease and women after miscarriage (62.7% vs 37.3%, p=0.005). All outcomes, except the Reproductive Concerns Scale, showed a significant decline. However, in women who scored above the cut-off level on the HADS-total or Impact of Event Scale at baseline, and women with psychological or psychiatric history, significant higher scores persisted. CONCLUSION: Although women with gestational trophoblastic disease at baseline had more anxiety and distress than women after miscarriage, no significant differences were seen using the HADS-total after 12 months. Using the HADS or Impact of Event Scale directly after pregnancy loss is helpful to identify women at risk of remaining psychological symptoms to provide them with extra psychological support.

Primary ovarian cancer after colorectal cancer: a Dutch nationwide population-based study.

BACKGROUND AND PURPOSE: Women with colorectal cancer (CRC) are at risk not only of developing ovarian metastases, but also of developing a primary ovarian malignancy. Several earlier studies have in fact shown a link between the development of primary ovarian cancer and CRC. The purpose of this study was therefore to determine the risk of developing a primary ovarian cancer in women with prior CRC compared to the general population. METHODS: Data from the Netherlands Cancer Registry were used. All women diagnosed with invasive CRC between 1989 and 2017 were included. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) per 10,000 person-years were calculated. RESULTS: During the study period, 410 (0.3%) CRC patients were diagnosed with primary ovarian cancer. Women with CRC had a 20% increased risk of developing ovarian cancer compared to the general population (SIR = 1.2, 95% CI: 1.1-1.3). The AER of ovarian cancer was 0.9 per 10,000 person-years. The risk was especially increased within the first year of a CRC diagnosis (SIR = 3.3, 95% CI: 2.8-3.8) and in women aged ≤ 55 years (SIR = 2.0, 95% CI: 1.6-2.6). CONCLUSION: This study found a slightly increased risk of primary ovarian cancer in women diagnosed with CRC compared to the general population. However, this may be partly attributable to surveillance or detection bias. Nevertheless, our findings could be helpful for patient counseling, as CRC patients do not currently receive information concerning the increased risk of ovarian cancer.

Predicting the likelihood of successful medical treatment of early pregnancy loss: development and internal validation of a clinical prediction model.

STUDY QUESTION: What are clinical predictors for successful medical treatment in case of early pregnancy loss (EPL)? SUMMARY ANSWER: Use of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start are predictors for successful medical treatment in case of EPL. WHAT IS KNOWN ALREADY: Success rates of medical treatment for EPL vary strongly, between but also within different treatment regimens. Up until now, although some predictors have been identified, no clinical prediction model has been developed yet. STUDY DESIGN, SIZE, DURATION: Secondary analysis of a multicentre randomized controlled trial in 17 Dutch hospitals, executed between 28 June 2018 and 8 January 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with a non-viable pregnancy between 6 and 14 weeks of gestational age, who opted for medical treatment after a minimum of 1 week of unsuccessful expectant management. Potential predictors for successful medical treatment of EPL were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques. MAIN RESULTS AND THE ROLE OF CHANCE: 237 out of 344 women had a successful medical EPL treatment (68.9%). The model includes the following variables: use of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start. The model shows a moderate capacity to discriminate between success and failure of treatment, with an AUC of 67.6% (95% CI = 64.9-70.3%). The model had a good fit comparing predicted to observed probabilities of success but might underestimate treatment success in women with a predicted probability of success of ∼70%. LIMITATIONS, REASONS FOR CAUTION: The vast majority (90.4%) of women were Caucasian, potentially leading to less optimal model performance in a non-Caucasian population. Limitations of our model are that we have not yet been able to externally validate its performance and clinical impact, and the moderate accuracy of the prediction model of 0.67. WIDER IMPLICATIONS OF THE FINDINGS: We developed a prediction model, aimed to improve and personalize counselling for medical treatment of EPL by providing a woman with her individual chance of complete evacuation. STUDY FUNDING/COMPETING INTEREST(S): The Triple M Trial, upon which this secondary analysis was performed, was funded by the Healthcare Insurers Innovation Foundation (project number 3080 B15-191). TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT03212352.

Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development - the 2Close study: a multicentre randomised controlled trial.

BACKGROUND: Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility. METHODS: Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective. DISCUSSION: This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound. TRIAL REGISTRATION: Dutch Trial Register ( NTR5480 ). Registered 29 October 2015.

Opportunistic salpingectomy in women undergoing hysterectomy: Results from the HYSTUB randomised controlled trial.

OBJECTIVE: To evaluate whether opportunistic salpingectomy in premenopausal women undergoing hysterectomy for benign indications is both hormonally and surgically safe, compared with hysterectomy without salpingectomy. STUDY DESIGN: In this multicentre randomised controlled trial, women were randomised to undergo either hysterectomy with opportunistic bilateral salpingectomy (intervention group) or standard hysterectomy with preservation of the Fallopian tubes (control group). MAIN OUTCOME MEASURES: The primary outcome was the difference in serum anti-Müllerian hormone concentration (ΔAMH), measured pre-surgery and 6 months post-surgery. Secondary outcomes were surgical outcomes and duration of hospital stay. The sample size was powered at 50 participants per group (n=100) to compare ΔAMH after hysterectomy with salpingectomy to ΔAMH after standard hysterectomy. RESULTS: Between March 2013 and December 2016, 104 women, aged 30-55 years, were randomly allocated to hysterectomy with opportunistic bilateral salpingectomy (n=52) or standard hysterectomy (n=52). The baseline characteristics did not differ between the two groups. The median ΔAMH was -0.14pmol/L (IQR -1.47-0.95) in the intervention group and 0.00pmol/L (IQR -1.05-0.80) in the control group (p=0.49). The addition of salpingectomy did not impair surgical results and it did not affect duration of hospital stay. CONCLUSION: Addition of opportunistic bilateral salpingectomy during hysterectomy did not result in a larger effect on ovarian reserve when compared with hysterectomy alone, neither did it affect surgical outcomes. Therefore, opportunistic salpingectomy seems to be a safe procedure in premenopausal women undergoing hysterectomy for benign gynaecological conditions.

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.

Spontaneous haemoperitoneum in pregnancy and endometriosis: a case series.

OBJECTIVE: To report pregnancy outcomes of SHiP (spontaneous haemoperitoneum in pregnancy) and the association with endometriosis. DESIGN: Retrospective case note review. SETTING: Dutch referral hospitals for endometriosis. SAMPLE: Eleven women presenting with 15 events of SHiP. METHODS: In collaboration with the Dutch Working Group on Endometriosis, unpublished cases of SHiP that occurred in the Netherlands between 2010 and 2015 were retrieved. MAIN OUTCOME MEASURES: Maternal and perinatal mortality and morbidity. RESULTS: SHiP occurred predominantly in the second and third trimester of pregnancy. The earliest and major presenting symptom was an acute onset of abdominal pain, often combined with low haemoglobin levels or signs of fetal distress. Imaging was a diagnostic tool when free peritoneal fluid could be observed. For surgical treatment of the bleeding site, a midline laparotomy was mostly needed, the median estimated amount of blood loss was 2000 mL. No fetomaternal or perinatal mortality was reported, despite a high rate of preterm births (54.5%). In all women, endometriosis was diagnosed at a certain moment in time and therefore was probably involved in the pathogenesis of SHiP. Four women showed recurrence of SHiP. In one of these cases the second event of SHiP occurred in a subsequent pregnancy. CONCLUSION: Pregnancy outcomes of SHiP are improving when compared with previous reports, with absent fetomaternal and perinatal mortality in this recent series. Growing knowledge and adequate multidisciplinary intervention may have contributed to these favourable results. Increasing awareness of this serious complication of pregnancy is advocated, especially in women diagnosed with endometriosis. TWEETABLE ABSTRACT: Growing awareness of SHiP is advocated, especially in women diagnosed with endometriosis.

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.

The value of fine needle aspiration cytology diagnosis in ovarian masses in children and adolescents.

STUDY QUESTION: Is ovarian cytology a reliable predictor for a malignant ovarian mass? SUMMARY ANSWER: Cytology of an ovarian mass in children and adolescents cannot be used to exclude malignancy. WHAT IS KNOWN ALREADY: It is hard to predict malignancy in case of an ovarian mass in a child or adolescent. The most common reason to perform fine needle aspiration cytology (FNAC) is to exclude malignancy. Ovarian cytology has shown varying results in adults, but test performance in a younger population is unknown. STUDY DESIGN, SIZE, DURATION: This was a retrospective diagnostic test accuracy study. We used a nationwide registry, the PALGA database, to select girls aged 18 or younger with matching ovarian cytology and histology reports available between 1990 and 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Histology diagnoses were classified according to the WHO classification of ovarian pathology. Cytology diagnoses were classified as benign, borderline malignant or malignant. Cases with inconclusive cytology diagnoses were excluded from the analysis of diagnostic accuracy. Diagnostic accuracy was calculated using a 2 × 2 table. MAIN RESULTS AND THE ROLE OF CHANCE: Included were 552 girls under the age of 18 who had a cytology and a histology report of the same ovary available in the PALGA database. In 523 (94.7%) patients the mass was benign; 19 (3.4%) patients had a borderline malignancy and 9 (1.7%) patients had a malignant tumour. The histology diagnosis was unknown in one patient due to torsion of the ovary. Cytological diagnosis was inconclusive in 96 patients (17.4%). Cytology had a sensitivity of 32.0% and a specificity of 99.8%. Post-test probability of malignancy with positive cytology was 88.9%; the post-test probability of a malignancy with negative cytology was 3.8%, compared with a pre-test probability of 5.5%. LIMITATIONS, REASONS FOR CAUTION: This study was retrospective, using data gathered over 24 years. Cytology was retrieved during surgery or at the pathology department in 86.6% of the cases and pathologists were not blinded, which can be a cause for bias. WIDER IMPLICATIONS OF THE FINDINGS: Since the sensitivity is low, FNAC is not a recommended diagnostic tool in children. The post-test probability of a negative test compared with the incidence in our population resulted in a minimal difference not worth an invasive procedure. STUDY FUNDING/COMPETING INTERESTS: No study funding was received and no competing interests are present. TRIAL REGISTRATION NUMBER: NA.

External validation of the paediatric risk of malignancy index.

OBJECTIVE: This study aimed to validate the paediatric risk of malignancy index (PRMI), as previously published. DESIGN: External validation study. SETTING: Academic hospital: Radboud University Medical Center. POPULATION: Female paediatric patients under the age of 18 years diagnosed with, or treated for, an adnexal mass between January 1999 and October 2013. METHODS: Information was collected on diagnosis, presenting symptoms, and signs and imaging characteristics. The PRMI was calculated for each patient. Sensitivity, specificity, and positive and negative predictive values were calculated, and the results were visualised using a receiver operating characteristic curve (ROC curve). MAIN OUTCOME MEASURES: Histological diagnosis, discriminative performance using the area under the curve (AUC) of the ROC curve and sensitivity and specificity. RESULTS: Seventy-eight patients were included, with a median age of 12 years. A malignant mass was found in 17 patients (21.8%). The PRMI with a cut-off value of 7 resulted in a sensitivity of 70.1% (95% CI 44.1-89.6%) and a specificity of 85.3% (95% CI 73.8-93.0%). The area under the ROC curve was 0.868 (95% CI 0.756-0.980). CONCLUSIONS: The PRMI showed less discriminative capacity than originally published, but its performance was still good; however, further prospective validation studies are needed to define whether the model is useful in daily clinical practice.

Integration of patient characteristics and the results of Chlamydia antibody testing and hysterosalpingography in the diagnosis of tubal pathology: an individual patient data meta-analysis.

BACKGROUND: Tubal patency tests are routinely performed in the diagnostic work-up of subfertile patients, but it is unknown whether these diagnostic tests add value beyond the information obtained by medical history taking and findings at physical examination. We used individual patient data meta-analysis to assess this question. METHODS: We approached authors of primary studies for data sets containing information on patient characteristics and results from tubal patency tests, such as Chlamydia antibody test (CAT), hysterosalpingography (HSG) and laparoscopy. We used logistic regression to create models that predict tubal pathology from medical history and physical examination alone, as well as models in which the results of tubal patency tests are integrated in the patient characteristics model. Laparoscopy was considered to be the reference test. RESULTS: We obtained data from four studies reporting on 4883 women. The duration of subfertility, number of previous pregnancies and a history of previous pelvic inflammatory disease (PID), pelvic surgery or Chlamydia infection qualified for the patient characteristics model. This model showed an area under the receiver operating characteristic curve (AUC) of 0.63 [95% confidence interval (CI) 0.61-0.65]. For any tubal pathology, the addition of HSG significantly improved the predictive performance to an AUC of 0.74 (95% CI 0.73-0.76) (P < 0.001). For bilateral tubal pathology, the addition of both CAT and HSG increased the predictive performance to an AUC of 0.76 (95% CI 0.74-0.79). CONCLUSIONS: In the work-up for subfertile couples, the combination of patient characteristics with CAT and HSG results gives the best diagnostic performance for the diagnosis of bilateral tubal pathology.

Chlamydia trachomatis IgG seropositivity is associated with lower natural conception rates in ovulatory subfertile women without visible tubal pathology.

BACKGROUND: The relation between Chlamydia trachomatis infection and subsequent tubal damage is widely recognized. As such, C. trachomatis antibody (CAT) testing can be used to triage women for immediate tubal testing with hysterosalpingography (HSG) or laparoscopy. However, once invasive tubal testing has ruled out tubal pathology, CAT serology status is ignored, as its clinical significance is currently unknown. This study aimed to determine whether positive CAT serology is associated with lower spontaneous pregnancy rates in women in whom HSG and/or diagnostic laparoscopy showed no visible tubal pathology. METHODS: We studied ovulatory women in whom HSG or laparoscopy showed patent tubes. Women were tested for C. trachomatis immunoglobulin G (IgG) antibodies with either micro-immunofluorescence (MIF) or an ELISA. CAT serology was positive if the MIF titre was ≥ 1:32 or if the ELISA index was >1.1. The proportion of couples pregnant without treatment was estimated at 12 months of follow-up. Time to pregnancy was considered censored at the date of the last contact when the woman was not pregnant or at the start of treatment. The association between CAT positivity and an ongoing pregnancy was evaluated with Cox regression analyses. RESULTS: Of the 1882 included women without visible tubal pathology, 338 (18%) had a treatment-independent pregnancy within 1 year [estimated cumulative pregnancy rate 31%; 95% confidence interval (CI): 27-35%]. Because of differential censoring after 9 months of follow-up, regression analyses were limited to the first 9 months after tubal testing. Positive C. trachomatis IgG serology was associated with a statistically significant 33% lower probability of an ongoing pregnancy [adjusted fecundity rate ratio 0.66 (95% CI 0.49-0.89)]. CONCLUSIONS: Even after HSG or laparoscopy has shown no visible tubal pathology, subfertile women with a positive CAT have lower pregnancy chances than CAT negative women. After external validation, this finding could be incorporated into existing prognostic models.

Chlamydia antibody testing and diagnosing tubal pathology in subfertile women: an individual patient data meta-analysis.

BACKGROUND: The Chlamydia IgG antibody test (CAT) shows considerable variations in reported estimates of test accuracy, partly because of the use of different assays and cut-off values. The aim of this study was to reassess the accuracy of CAT in diagnosing tubal pathology by individual patient data (IPD) meta-analysis for three different CAT assays. METHODS: We approached authors of primary studies that used micro-immunofluorescence tests (MIF), immunofluorescence tests (IF) or enzyme-linked immunosorbent assay tests (ELISA). Using the obtained IPD, we performed pooled receiver operator characteristics analysis and logistic regression analysis with a random effects model to compare the three assays. Tubal pathology was defined as either any tubal obstruction or bilateral tubal obstruction. RESULTS: We acquired data of 14 primary studies containing data of 6191 women, of which data of 3453 women were available for analysis. The areas under the curve for ELISA, IF and MIF were 0.64, 0.65 and 0.75, respectively (P-value < 0.001) for any tubal pathology and 0.66, 0.66 and 0.77, respectively (P-value = 0.01) for bilateral tubal pathology. CONCLUSIONS: In Chlamydia antibody testing, MIF is superior in the assessment of tubal pathology. In the initial screen for tubal pathology MIF should therefore be the test of first choice.

The capacity of hysterosalpingography and laparoscopy to predict natural conception.

BACKGROUND: Laparoscopy has been claimed to be superior to hysterosalpingography (HSG) in predicting fertility. Whether this conclusion is applicable to a general subfertile population can be questioned as data in support of this claim were collected in third line centres. The aim of this study was to assess the prognostic capacity of HSG and laparoscopy in a general subfertile population. METHODS: In 38 centres, we prospectively studied a cohort of patients referred for subfertility between 2002 and 2004, who underwent HSG and/or laparoscopy as part of their subfertility work-up. Follow-up started immediately after tubal testing and ended 12 months thereafter. Time to pregnancy was censored at the of date last contact, when the woman was not pregnant or at the start of treatment. Kaplan-Meier curves for the occurrence of spontaneous intrauterine pregnancy were constructed for patients without tubal pathology, for those with unilateral tubal pathology and for patients with bilateral tubal pathology at HSG or laparoscopy. Multivariable Cox regression analysis was used to calculate fecundity rate ratios (FRRs) to express associations between tubal pathology and the occurrence of an intrauterine pregnancy. RESULTS: Of the 3301 included patients, 2043 underwent HSG only, 747 underwent diagnostic laparoscopy only and 511 underwent both. At HSG, 322 (13%) patients showed unilateral tubal pathology and 135 (5%) showed bilateral tubal pathology. At laparoscopy, 167 (13%) showed unilateral tubal pathology and 215 (17%) showed bilateral tubal pathology. Multivariable analysis resulted in FRRs of 0.81 [95% confidence interval (CI): 0.59-1.1] for unilateral, and 0.28 (95% CI: 0.13-0.59) for bilateral, tubal pathology at HSG. The FRRs at laparoscopy were 0.85 (95% CI: 0.47-1.52) for unilateral, and 0.24 (95% CI: 0.11-0.54) for bilateral, tubal pathology. CONCLUSIONS: Patients with unilateral tubal pathology at HSG and laparoscopy had a moderate reduction in pregnancy chances, whereas those with bilateral tubal pathology at HSG and laparoscopy had a severe reduction in pregnancy chances. This reduction was similar for HSG and laparoscopy, suggesting that HSG and laparoscopy have a comparable predictive capacity for natural conception.

Are patient characteristics associated with the accuracy of hysterosalpingography in diagnosing tubal pathology? An individual patient data meta-analysis.

BACKGROUND: Conventional meta-analysis has estimated the sensitivity and specificity of hysterosalpingography (HSG) to be 65% and 83%. The impact of patient characteristics on the accuracy of HSG is unknown. The aim of this study was to assess by individual patient data meta-analysis whether the accuracy of HSG is associated with different patient characteristics. METHODS: We approached authors of primary studies reporting on the accuracy of HSG using findings at laparoscopy as the reference. We assessed whether patient characteristics such as female age, duration of subfertility and a clinical history without risk factors for tubal pathology were associated with the accuracy of HSG, using a random intercept logistic regression model. RESULTS: We acquired data of seven primary studies containing data of 4521 women. Pooled sensitivity and specificity of HSG were 53% and 87% for any tubal pathology and 46% and 95% for bilateral tubal pathology. In women without risk factors, the sensitivity of HSG was 38% for any tubal pathology, compared with 61% in women with risk factors (P = 0.005). For bilateral tubal pathology, these rates were 13% versus 47% (P = 0.01). For bilateral tubal pathology, the sensitivity of HSG decreased with age [factor 0.93 per year (P = 0.05)]. The specificity of HSG was very stable across all subgroups. CONCLUSIONS: The accuracy of HSG in detecting tubal pathology was similar in all subgroups, except for women without risk factors in whom sensitivity was lower, possibly due to false-positive results at laparoscopy. HSG is a useful tubal patency screening test for all infertile couples.

Evaluating prediction models in reproductive medicine.

Prediction models are used in reproductive medicine to calculate the probability of pregnancy without treatment, as well as the probability of pregnancy after ovulation induction, intrauterine insemination or in vitro fertilization. The performance of such prediction models is often evaluated with a receiver operating characteristic (ROC) curve. The area under the ROC curve, also known as c-statistic, is then used as a measure of model performance. The value of this c-statistic is low for most prediction models in reproductive medicine. Here, we demonstrate that low values of the c-statistic are to be expected in these prediction models, but we also show that this does not imply that these models are of limited use in clinical practice. The calibration of the model (the correspondence between model-based probabilities and observed pregnancy rates) as well as the availability of a clinically useful distribution of probabilities and the ability to correctly identify the appropriate form of management are more meaningful concepts for model evaluation.

The value of medical history taking as risk indicator for tuboperitoneal pathology: a systematic review.

BACKGROUND: Guidelines recommend diagnostic laparoscopy in subfertile women with known co-morbidities in their medical history. Aggregated evidence underpinning these recommendations is, however, currently lacking. OBJECTIVE: The objective of this study was to perform a systematic review and meta-analysis of the available evidence on the association between items reported during medical history taking and tuboperitoneal pathology. SEARCH STRATEGY: MEDLINE (from 1966 to May 2007), EMBASE (from 1960 to January 2007) and bibliographies of retrieved primary articles. SELECTION CRITERIA: All relevant studies that compared medical history with the presence or absence of tubal pathology. DATA COLLECTION AND ANALYSIS: Studies comparing medical history with the presence or absence of tubal pathology were included. A diagnosis of tubal pathology had to be made by hysterosalpingography, laparoscopy or a combination of both. In the absence of invasive tubal testing, tuboperitoneal pathology was considered to be absent in case of intrauterine pregnancy. Homogeneity between studies was assessed, and the association between medical history and tubal pathology was expressed as a common odds ratio with a 95% CI. No language restriction was applied. MAIN RESULTS: We included 32 studies. In cohort studies, strong associations were found for a history of complicated appendicitis (OR 7.2, 95% CI 2.2-22.8), pelvic surgery (OR 3.6, 95% CI 1.4-9.0) and pelvic inflammatory disease (PID) (OR 3.2, 95% CI 1.6-6.6), and in case-control studies, for a history of complicated appendicitis (OR 3.3, 95% CI 1.8-6.3), PID (OR 5.5, 95% CI 2.7-11.0), ectopic pregnancy (OR 16.0, 95% CI 12.5-20.4), endometriosis (OR 5.9, 95% CI 3.2-10.8) and sexually transmitted disease (OR 11.9, 95% CI 4.3-33.3). AUTHOR'S CONCLUSIONS: Subfertile women reporting a history of PID, complicated appendicitis, pelvic surgery, ectopic pregnancy and endometriosis are at increased risk of having tuboperitoneal pathology. In these women, diagnostic laparoscopy should be offered early in the fertility work-up.

[An underestimated technique for the management of shoulder dystocia: the all-fours manoeuvre]. / Een onderschatte techniek voor het opheffen van schouderdystocie: baren op handen en knieën ('all-fours manoeuvre').

In two pregnant women, parturition was complicated by severe shoulder dystocia. Conventional techniques for the management of this complication of labour failed. By means of the all-fours manoeuvre in combination with conventional techniques it was possible to deliver the babies. Both mothers had received epidural anaesthesia, which did not cause any difficulty during the use of the all-fours procedure. Both newborn infants had low 1-minute Apgar scores and suffered from a brachial-plexus injury. No major maternal morbidity was associated with the use of this procedure. These cases emphasize the importance of keeping obstetrical ward personnel well-trained with multidisciplinary simulation sessions, as well as the importance of proper documentation of the management of this complication.