Objective. The COVID-19-pandemic caused drastic healthcare changes worldwide. To date, the impact of these changes on gynecological cancer healthcare is relatively unknown. This study aimed to... Show moreObjective. The COVID-19-pandemic caused drastic healthcare changes worldwide. To date, the impact of these changes on gynecological cancer healthcare is relatively unknown. This study aimed to assess the impact of the COVID-19-pandemic on surgical gynecological-oncology healthcare. Methods. This population-based cohort study included all surgical procedures with curative intent for gynecological malignancies, registered in the Dutch Gynecological Oncology Audit, in 2018-2020. Four periods were identified based on COVID-19 hospital admission rates: 'Pre-COVID-19', 'Firstwave', 'Interimperiod', and'Second wave'. Surgical volume, perioperative care processes, and postoperative outcomes from 2020 were compared with 2018-2019. Results. A total of 11,488 surgical procedureswere analyzed. For cervical cancer, surgical volume decreased by 17.2% in 2020 compared to 2018-2019 (mean 2018-2019: n= 542.5, 2020: n= 449). At nadir (interimperiod), only 51% of the expected cervical cancer procedures were performed. For ovarian, vulvar, and endometrial cancer, volumes remained stable. Patients with advanced-stage ovarian cancer more frequently received neoadjuvant chemotherapy in 2020 compared to 2018-2019 (67.7% (n = 432) vs. 61.8% (n = 783), p = 0.011). Median time to first treatmentwas significantly shorter in all four malignancies in 2020. For vulvar and endometrial cancer, the length of hospital staywas significantly shorter in 2020. No significant differences in complicated course and 30-day-mortality were observed. Conclusions. The COVID-19-pandemic impacted surgical gynecological-oncology healthcare: in 2020, surgical volume for cervical cancer dropped considerably, waiting time was significantly shorter for all malignancies, while neoadjuvant chemotherapy administration for advanced-stage ovarian cancer increased. The safety of perioperative healthcare was not negatively impacted by the pandemic, as complications and 30-day-mortality remained stable. (C) 2022 The Authors. Published by Elsevier Inc. Show less
Dijk, M.M. van; Vissenberg, R.; Fliers, E.; Post, J.A.M. van der; Hoorn, M.L.P. van der; Weerd, S. de; ... ; Goddijn, M. 2022
Background: Women positive for thyroid peroxidase antibodies (TPO-Ab) have a higher risk of recurrent pregnancy loss. Evidence on whether levothyroxine treatment improves pregnancy outcomes in... Show moreBackground: Women positive for thyroid peroxidase antibodies (TPO-Ab) have a higher risk of recurrent pregnancy loss. Evidence on whether levothyroxine treatment improves pregnancy outcomes in women who are TPO-Ab positive women with recurrent pregnancy loss is scarce. The aim of this study was to determine if levothyroxine increases live birth rates in women who were TPO-Ab positive with recurrent pregnancy loss and normal thyroid function. Methods: The T4LIFE trial was an international, double-blind, placebo-controlled, phase 3 study done in 13 secondary and tertiary hospitals in the Netherlands, one tertiary hospital in Belgium, and one tertiary hospital in Denmark. Women (18-42 years) who were TPO-Ab positive, had two or more pregnancy losses, and had a thyroid stimulating hormone (TSH) concentration within the institutional reference range were eligible for inclusion. Women were excluded if they had antiphospholipid syndrome (lupus anticoagulant, anticardiolipin IgG or IgM antibodies, or beta 2-glycoprotein-I IgG or IgM antibodies), other autoimmune diseases, thyroid disease, previous enrolment in this trial, or contraindications for levothyroxine use. Before conception, women were randomly assigned (1:1) to receive either levothyroxine or placebo orally once daily. The daily dose of levothyroxine was based on preconception TSH concentration and ranged from 0.5-1.0 mu g/kg bodyweight. Levothyroxine or placebo was continued until the end of pregnancy. The primary outcome was live birth, defined as the birth of a living child beyond 24 weeks of gestation measured in the intention-to-treat population. The trial was registered within the Netherlands Trial Register, NTR3364 and with EudraCT, 2011-001820-39. Results: Between Jan 1, 2013, and Sept 19, 2019, 187 women were included in the study: 94 (50%) were assigned to the levothyroxine group and 93 (50%) were assigned to the placebo group. The trial was prematurely stopped when 187 (78%) of the 240 predefined patients had been included because of slow recruitment. 47 (50%) women in the levothyroxine group and 45 (48%) women in the placebo group had live births (risk ratio 1.03 [95% CI 0.77 to 1.38]; absolute risk difference 1.6% [95% CI -12.7 to 15.9]). Seven (7%) women in the levothyroxine group and seven (8%) in the placebo group reported adverse events, none of them were directly related to the study procedure. Interpretation: Compared with placebo, levothyroxine treatment did not result in higher live birth rates in euthyroid women with recurrent pregnancy loss who were positive for TPO-Ab. On the basis of our findings, we do not advise routine use of levothyroxine in women who are TPO-Ab positive with recurrent pregnancy loss and normal thyroid function. Copyright (C) 2022 Elsevier Ltd. All rights reserved. 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
BACKGROUND Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from... Show moreBACKGROUND Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. METHODS In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcutaneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events. RESULTS Live-birth rates did not differ significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5% in the group receiving aspirin plus nadroparin (combination-therapy group), 50.8% in the aspirin-only group, and 57.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, -2.6 percentage points; 95% confidence interval [CI], -15.0 to 9.9; aspirin only vs. placebo, -6.2 percentage points; 95% CI, -18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1% in the combination-therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95% CI, -10.8 to 15.0; aspirin alone vs. placebo -5.4 percentage points; 95% CI, -18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups. CONCLUSIONS Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage. (Current Controlled Trials number, ISRCTN58496168.) Show less
