STUDY QUESTION: For couples with unexplained subfertility and a poor prognosis for natural conception, is 6 months expectant management (EM) inferior to IUI with ovarian stimulation (IUI-OS), in... Show moreSTUDY QUESTION: For couples with unexplained subfertility and a poor prognosis for natural conception, is 6 months expectant management (EM) inferior to IUI with ovarian stimulation (IUI-OS), in terms of live births? SUMMARY ANSWER: In couples with unexplained subfertility and a poor prognosis for natural conception, 6 months of EM is inferior compared to IUI-OS in terms of live births. WHAT IS KNOWN ALREADY: Couples with unexplained subfertility and a poor prognosis are often treated with IUI-OS. In couples with unexplained subfertility and a relatively good prognosis for natural conception (>30% in 12 months), IUI-OS does not increase the live birth rate as compared to 6 months of EM. However, in couples with a poor prognosis for natural conception (<30% in 12 months), the effectiveness of IUI-OS is uncertain. STUDY DESIGN, SIZE, DURATION: We performed a non-inferiority multicentre randomized controlled trial within the infrastructure of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology. We intended to include 1091 couples within 3 years. The couples were allocated in a 1:1 ratio to 6 months EM or 6 months IUI-OS with either clomiphene citrate or gonadotrophins. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied heterosexual couples with unexplained subfertility and a poor prognosis for natural conception (<30% in 12 months). The primary outcome was ongoing pregnancy leading to a live birth. Non-inferiority would be shown if the lower limit of the one-sided 90% risk difference (RD) CI was less than minus 7% compared to an expected live birth rate of 30% following IUI-OS. We calculated RD, relative risks (RRs) with 90% CI and a corresponding hazard rate for live birth over time based on intention-to-treat and per-protocol (PP) analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Between October 2016 and September 2020, we allocated 92 couples to EM and 86 to IUI-OS. The trial was halted pre-maturely owing to slow inclusion. Mean female age was 34 years, median duration of subfertility was 21 months. Couples allocated to EM had a lower live birth rate than couples allocated to IUI-OS (12/92 (13%) in the EM group versus 28/86 (33%) in the IUI-OS group; RR 0.40 90% CI 0.24 to 0.67). This corresponds to an absolute RD of minus 20%; 90% CI: -30% to -9%. The hazard ratio for live birth over time was 0.36 (95% CI 0.18 to 0.70). In the PP analysis, live births rates were 8 of 70 women (11%) in the EM group versus 26 of 73 women (36%) in the IUI-OS group (RR 0.32, 90% CI 0.18 to 0.59; RD -24%, 90% CI -36% to -13%) in line with inferiority of EM. LIMITATIONS, REASONS FOR CAUTION: Our trial did not reach the planned sample size, therefore the results are limited by the number of participants. WIDER IMPLICATIONS OF THE FINDINGS: This study confirms the results of a previous trial that in couples with unexplained subfertility and a poor prognosis for natural conception, EM is inferior to IUI-OS. Show less
Rennert, K.N.; Breuking, S.H.; Schuit, E.; Bekker, M.N.; Woiski, M.; Boer, M.A. de; ... ; Hermans, F.J.R. 2021
Objective To assess the association between preterm birth and cervical length after arrested preterm labor in high-risk pregnant women.Methods In this post-hoc analysis of a randomized clinical... Show moreObjective To assess the association between preterm birth and cervical length after arrested preterm labor in high-risk pregnant women.Methods In this post-hoc analysis of a randomized clinical trial, transvaginal cervical length was measured in women whose contractions had ceased 48 h after admission for threatened preterm labor. At admission, women were defined as having a high risk of preterm birth based on a cervical length of < 15 mm or a cervical length of 15-30 mm with a positive fetal fibronectin test. Logistic regression analysis was used to investigate the association of cervical length measured at least 48 h after admission and of the change in cervical length between admission and at least 48 h later, with preterm birth before 34 weeks' gestation and delivery within 7 days after admission.Results A total of 164 women were included in the analysis. Women whose cervical length increased between admission for threatened preterm labor and 48 h later (32%; n=53) were found to have a lower risk of preterm birth before 34weeks compared with women whose cervical length did not change (adjusted odds ratio (aOR), 0.24 (95% CI, 0.09-0.69)). The risk in women with a decrease in cervical length between the two time points was not different from that in women with no change in cervical length (aOR, 1.45 (95% CI, 0.62-3.41)). Moreover, greater absolute cervical length after 48 h was associated with a lower risk of preterm birth before 34 weeks (aOR, 0.90 (95% CI, 0.84-0.96)) and delivery within 7 days after admission (aOR, 0.91 (95% CI, 0.82-1.02)). Sensitivity analysis in women randomized to receive no intervention showed comparable results.Conclusion Our study suggests that the risk of preterm birth before 34weeks is lower in women whose cervical length increases between admission for threatened preterm labor and at least 48 h later when contractions had ceased compared with women in whom cervical length does not change or decreases. (C) 2021 The Authors. Show less
Noorduyn, J.C.A.; Teuwen, M.M.H.; Graaf, V.A. van de; Willigenburg, N.W.; Schavemaker, M.; Dijk, R. van; ... ; Escape Res Grp 2021
Purpose Although physical therapy is the recommended treatment in patients over 45 years old with a degenerative meniscal tear, 24% still opt for meniscal surgery. The aim was to identify those... Show morePurpose Although physical therapy is the recommended treatment in patients over 45 years old with a degenerative meniscal tear, 24% still opt for meniscal surgery. The aim was to identify those patients with a degenerative meniscal tear who will undergo surgery following physical therapy. Methods The data for this study were generated in the physical therapy arm of the ESCAPE trial, a randomized clinical trial investigating the effectiveness of surgery versus physical therapy in patients of 45-70 years old, with a degenerative meniscal tear. At 6 and 24 months patients were divided into two groups: those who did not undergo surgery, and those who did undergo surgery. Two multivariable prognostic models were developed using candidate predictors that were selected from the list of the patients' baseline variables. A multivariable logistic regression analysis was performed with backward Wald selection and a cut-off of p < 0.157. For both models the performance was assessed and corrected for the models' optimism through an internal validation using bootstrapping technique with 500 repetitions. Results At 6 months, 32/153 patients (20.9%) underwent meniscal surgery following physical therapy. Based on the multivariable regression analysis, patients were more likely to opt for meniscal surgery within 6 months when they had worse knee function, lower education level and a better general physical health status at baseline. At 24 months, 43/153 patients (28.1%) underwent meniscal surgery following physical therapy. Patients were more likely to opt for meniscal surgery within 24 months when they had worse knee function and a lower level of education at baseline at baseline. Both models had a low explained variance (16 and 11%, respectively) and an insufficient predictive accuracy. Conclusion Not all patients with degenerative meniscal tears experience beneficial results following physical therapy. The non-responders to physical therapy could not accurately be predicted by our prognostic models. Show less
The septate uterus has an estimated prevalence of 0.2% to 2.3% in women of reproductive age and is associated with impaired reproductive outcomes, the biologic basis of which is unclear. The... Show moreThe septate uterus has an estimated prevalence of 0.2% to 2.3% in women of reproductive age and is associated with impaired reproductive outcomes, the biologic basis of which is unclear. The standard-of-care treatment for septate uterus is hysteroscopic septum resection. The evidence base for this procedure entails observational studies and nonrandomized comparative studies, resulting in relatively low-quality evidence and conflicting professional society guidelines.This large, multicenter cohort study aimed to determine whether hysteroscopic septum resection improves reproductive outcomes compared with expectant management in women with a septate uterus who wish to conceive. Data on women with septate uterus between January 2000 and August 2018 were obtained from 18 centers in the Netherlands, 2 centers in the United States, and 1 center in the United Kingdom. Additionally, women declining participation in a separate 2015 randomized controlled trial examining differences between septum resection and expectant management were invited for participation prospectively. Data involving baseline characteristics, treatment, and pregnancies that occurred prior to identification of septate uterus (OB history) and following septate uterus diagnosis (follow-up) were obtained via medical record. Septate uterus was defined by the treating physician and ascertained with hysterosalpinography, 3D ultrasound, MRI, saline or gel infusion sonohysterography, or hysteroscopy combined with laparoscopy. The primary outcome measurement was live birth, and secondary outcomes included ongoing pregnancy, early pregnancy loss, preterm birth, and fetal malpresentation. Comparative analysis between septum resection and expectant management arms involved only the first live birth or ongoing pregnancy in follow-up. Cox proportional regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for differences in live birth and ongoing pregnancy rate between women in the 2 arms while accounting for follow-up time.A total of 257 women were confirmed eligible and included in the study for analysis, of which 151 underwent septum resection, and 106 underwent expectant management. In women who underwent resection compared with expectant management, a lower proportion was of White origin, more women had a history of subfertility, a lesser percentage had previous live birth (16.6% vs 36.8%, P < 0.001), and ascertainment of the septate uterus was significantly different (P < 0.001). Themedian duration of follow-up was 46 months, and 53% of women who had septum resection had at least 1 live birth compared with 71.7% who had expectant management (HR, 0.71; 95% CI, 0.49-1.02). There was no significant difference in cumulative live birth between the groups. When restricting analysis to 1 year following septate uterus diagnosis, 32 women who underwent resection had a live birth (21.2%) compared with 36 women who underwent expectant management (37.1%) (HR, 0.45; 95% CI, 0.27-0.75). Womenwith 1 or more previous pregnancy losses undergoing septumresection were found to have an increased risk of pregnancy loss compared with women who had expectant management (OR, 2.65; 95% CI, 1.05-6.67).This multicenter cohort study demonstrates that more than 50% of women with a septate uterus who wish to conceive had a live birth. The results show that septum resection does not lead to improved birth outcomes or a decrease in risk of pregnancy loss or preterm birth compared with expectant management in these women. Show less
STUDY QUESTION: Does septum resection improve reproductive outcomes in women with a septate uterus?SUMMARY ANSWER: In women with a septate uterus, septum resection does not increase live birth rate... Show moreSTUDY QUESTION: Does septum resection improve reproductive outcomes in women with a septate uterus?SUMMARY ANSWER: In women with a septate uterus, septum resection does not increase live birth rate nor does it decrease the rates of pregnancy loss or preterm birth, compared with expectant management.WHAT IS KNOWN ALREADY: The septate uterus is the most common uterine anomaly with an estimated prevalence of 0.2-2.3% in women of reproductive age, depending on the classification system. The definition of the septate uterus has been a long-lasting and ongoing subject of debate, and currently two classification systems are used worldwide. Women with a septate uterus may be at increased risk of subfertility, pregnancy loss, preterm birth and foetal malpresentation. Based on low quality evidence, current guidelines recommend removal of the intrauterine septum or, more cautiously, state that the procedure should be evaluated in future studies.STUDY DESIGN, SIZE, DURATION: We performed an international multicentre cohort study in which we identified women mainly retrospectively by searching in electronic patient files, medical records and databases within the time frame of January 2000 until August 2018. Searching of the databases, files and records took place between January 2016 and July 2018. By doing so, we collected data on 257 women with a septate uterus in 21 centres in the Netherlands, USA and UK.PARTICIPANTS/MATERIALS, SETTING, METHODS: We included women with a septate uterus, defined by the treating physician, according to the classification system at that time. The women were ascertained among those with a history of subfertility, pregnancy loss, preterm birth or foetal malpresentation or during a routine diagnostic procedure. Allocation to septum resection or expectant management was dependent on the reproductive history and severity of the disease. We excluded women who did not have a wish to conceive at time of diagnosis. The primary outcome was live birth. Secondary outcomes included pregnancy loss, preterm birth and foetal malpresentation. All conceptions during follow-up were registered but for the comparative analyses, only the first live birth or ongoing pregnancy was included. To evaluate differences in live birth and ongoing pregnancy, we used Cox proportional regression to calculate hazard rates (HRs) and 95% CI. To evaluate differences in pregnancy loss, preterm birth and foetal malpresentation, we used logistic regression to calculate odds ratios (OR) with corresponding 95% CI. We adjusted all reproductive outcomes for possible confounders.MAIN RESULTS AND THE ROLE OF CHANCE: In total, 257 women were included in the cohort. Of these, 151 women underwent a septum resection and 106 women had expectant management. The median follow-up time was 46 months. During this time, live birth occurred in 80 women following a septum resection (53.0%) compared to 76 women following expectant management (71.7%) (HR 0.71 95% CI 0.49-1.02) and ongoing pregnancy occurred in 89 women who underwent septum resection (58.9%), compared to 80 women who had expectant management (75.5%) (HR 0.74 (95% CI 0.52-1.06)). Pregnancy loss occurred in 51 women who underwent septum resection (46.8%) versus 31 women who had expectant management (34.4%) (OR 1.58 (0.81-3.09)), while preterm birth occurred in 26 women who underwent septum resection (29.2%) versus 13 women who had expectant management (16.7%) (OR 1.26 (95% CI 0.52-3.04)) and foetal malpresentation occurred in 17 women who underwent septum resection (19.1%) versus 27 women who had expectant management (34.6%) (OR 0.56 (95% CI 0.24-1.33)).LIMITATIONS, REASONS FOR CAUTION: Our retrospective study has a less robust design compared with a randomized controlled trial. Over the years, the ideas about the definition of the septate uterus has changed, but since the 257 women with a septate uterus included in this study had been diagnosed by their treating physician according to the leading classification system at that time, the data of this study reflect the daily practice of recent decades. Despite correcting for the most relevant patient characteristics, our estimates might not be free of residual confounding.WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that septum resection, a procedure that is widely offered and associated with financial costs for society, healthcare systems or individuals, does not lead to improved reproductive outcomes compared to expectant management for women with a septate uterus. The results of this study need to be confirmed in randomized clinical trials. Show less
Objective To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth. Design An economic analysis alongside a randomised clinical... Show moreObjective To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth. Design An economic analysis alongside a randomised clinical trial (the APOSTEL III study). Setting Obstetric departments of 12 tertiary hospitals and seven secondary hospitals in the Netherlands and Belgium. Population Women with threatened preterm birth between 25 and 34 weeks of gestation, randomised for tocolysis with either nifedipine or atosiban. Methods We performed an economic analysis from a societal perspective. We estimated costs from randomisation until discharge. Analyses for singleton and multiple pregnancies were performed separately. The robustness of our findings was evaluated in sensitivity analyses. Main outcome measures Mean costs and differences were calculated per woman treated with nifedipine or atosiban. Health outcomes were expressed as the prevalence of a composite of adverse perinatal outcomes. Results Mean costs per patients were significantly lower in the nifedipine group [singleton pregnancies: euro34,897 versus euro43,376, mean difference (MD) -euro8479 [95% confidence interval (CI) -euro14,327 to -euro2016)]; multiple pregnancies: euro90,248 versus euro102,292, MD -euro12,044 (95% CI -euro21,607 to euro -1671). There was a non-significantly higher death rate in the nifedipine group. The difference in costs was mainly driven by a lower neonatal intensive care unit admission (NICU) rate in the nifedipine group. Conclusion Treatment with nifedipine in women with threatened preterm birth results in lower costs when compared with treatment with atosiban. However, the safety of nifedipine warrants further investigation. Tweetable abstract In women with threatened preterm birth, tocolysis using nifedipine results in lower costs when compared with atosiban. Show less
Dreyer, K.; Eekelen, R. van; Tjon-Kon-Fat, R.I.; Steeg, J.W. van der; Steures, P.; Eijkemans, M.J.C.; ... ; Geloven, N. van 2019
