Search

BACKGROUND Several GnRH antagonist protocols are currently used during COS in the context of ART treatments; however, questions remain regarding whether these protocols are comparable in terms of efficacy and safety. OBJECTIVE AND RATIONALE A systematic review followed by a pairwise and network meta-analyses were performed. The systematic review and pairwise meta-analysis of direct comparative data according to the PRISMA guidelines evaluated the effectiveness of different GnRH antagonist protocols (fixed Day 5/6 versus flexible, ganirelix versus cetrorelix, with or without hormonal pretreatment) on the probability of live birth and ongoing pregnancy after COS during ART treatment. A frequentist network meta-analysis combining direct and indirect comparisons (using the long GnRH agonist protocol as the comparator) was also performed to enhance the precision of the estimates. SEARCH METHODS The systematic literature search was performed using Embase (Ovid), MEDLINE (Ovid), Cochrane Central Register of Trials (CENTRAL), SCOPUS and Web of Science (WOS), from inception until 23 November 2021. The search terms comprised three different MeSH terms that should be present in the identified studies: GnRH antagonist; assisted reproduction treatment; randomized controlled trial (RCT). Only studies published in English were included. OUTCOMES The search strategy resulted in 6738 individual publications, of which 102 were included in the systematic review (corresponding to 75 unique studies) and 73 were included in the meta-analysis. Most studies were of low quality. One study compared a flexible protocol with a fixed Day 5 protocol and the remaining RCTs with a fixed Day 6 protocol. There was a lack of data regarding live birth when comparing the flexible and fixed GnRH antagonist protocols or cetrorelix and ganirelix. No significant difference in live birth rate was observed between the different pretreatment regimens versus no pretreatment or between the different pretreatment protocols. A flexible GnRH antagonist protocol resulted in a significantly lower OPR compared with a fixed Day 5/6 protocol (relative risk (RR) 0.76, 95% CI 0.62 to 0.94, I2 = 0%; 6 RCTs; n = 907 participants; low certainty evidence). There were insufficient data for a comparison of cetrorelix and ganirelix for OPR. OCP pretreatment was associated with a lower OPR compared with no pretreatment intervention (RR 0.79, 95% CI 0.69 to 0.92; I2 = 0%; 5 RCTs, n = 1318 participants; low certainty evidence). Furthermore, in the network meta-analysis, a fixed protocol with OCP resulted in a significantly lower OPR than a fixed protocol with no pretreatment (RR 0.84, 95% CI 0.71 to 0.99; moderate quality evidence). The surface under the cumulative ranking (SUCRA) scores suggested that the fixed protocol with no pretreatment is the antagonist protocol most likely (84%) to result in the highest OPR. There was insufficient evidence of a difference between fixed/flexible or OCP pretreatment/no pretreatment interventions regarding other outcomes, such as ovarian hyperstimulation syndrome and miscarriage rates. WIDER IMPLICATIONS Available evidence, mostly of low quality and certainty, suggests that different antagonist protocols should not be considered as equivalent for clinical decision-making. More trials are required to assess the comparative effectiveness of ganirelix versus cetrorelix, the effect of different pretreatment interventions (e.g. progestins or oestradiol) or the effect of different criteria for initiation of the antagonist in the flexible protocol. Furthermore, more studies are required examining the optimal GnRH antagonist protocol in women with high or low response to ovarian stimulation.

ObjectivesAnetumab ravtansine is an antibody-drug conjugate consisting of a fully human anti-mesothelin monoclonal antibody conjugated to cytotoxic maytansinoid tubulin inhibitor DM4. Mesothelin is highly expressed in ovarian cancer. This phase Ib study determines the safety, pharmacokinetics, and anti-tumor activity of anetumab ravtansine and pegylated liposomal doxorubicin in mesothelin-expressing platinum-resistant ovarian cancer.MethodsAnetumab ravtansine (5.5 or 6.5 mg/kg) and pegylated liposomal doxorubicin (30 mg/m2) were administered intravenously every 3 weeks to 65 patients with platinum-resistant epithelial ovarian cancer. Mesothelin expression was assessed by central immunohistochemistry. Adverse events, tumor response (RECIST 1.1), and progression-free survival were determined. Biomarker samples were assessed by ELISA and next-generation sequencing.ResultsIn dose escalation, nine patients received anetumab ravtansine across two doses (5.5 or 6.5 mg/kg). The maximum tolerated dose of anetumab ravtansine was 6.5 mg/kg every 3 weeks and no dose-limiting toxicities were observed. In dose expansion, 56 patients were treated at the maximum tolerated dose. The most common treatment-emergent adverse events of any grade were nausea (47.7%), decreased appetite (43.1%), fatigue (38.5%), diarrhea (32.3%), and corneal disorder (29.2%). In all treated patients the objective response rate was 27.7% (95% CI 17.3% to 40.2%), including one complete (1.5%) and 17 partial responses (26.2%), with median duration of response of 7.6 (95% CI 3.3 to 10.2) months and median progression-free survival of 5.0 (95% CI 3.2 to 6.0) months. In an exploratory analysis of a sub-set of patients (n=19) with high mesothelin expression who received ≤3 prior lines of systemic therapy, the objective response rate was 42.1% (95% CI 20.3% to 66.5%) with a median duration of response of 8.3 (95% CI 4.1 to 12.0) months and median progression-free survival of 8.5 (95% CI 4.0 to 11.4) months.ConclusionsAnetumab ravtansine and pegylated liposomal doxorubicin showed tolerability and promising clinical activity. These results established the dose schedule and the mesothelin-positive target population of this combination for a phase III study in platinum-resistant ovarian cancer.Trial registration numberNCT02751918.

Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.

OBJECTIVE: Progression-free survival (PFS) is an important early efficacy endpoint in ovarian cancer (OC) and its relevance to patients should be assessed. PRIMA, a phase III trial, assessed niraparib in patients with OC; this post hoc analysis examined the relationship between disease progression in OC and health-related quality of life (HRQoL). METHODS: The PRIMA trial randomized patients with advanced OC responsive to first-line platinum-based chemotherapy to once daily maintenance oral niraparib or placebo. This post hoc analysis evaluated the impact of disease progression on HRQoL by comparing HRQoL at the last visit pre-progression to end of treatment (EoT), and after 4, 8, 12, and 24 weeks. Assessments included the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), the European Quality of Life Five Dimension Five Level questionnaire (EQ-5D-5L) and EQ Visual Analogue Scale (EQ-VAS), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC-QLQ-C30), and the EORTC Quality of Life Questionnaire Ovarian Cancer module (EORTC-QLQ-OV28). RESULTS: This post hoc analysis included 733 patients. Mean FOSI, EQ-5D-5L, and EQ-VAS scores deteriorated from last visit pre-progression to EoT and remained low up to 24-week follow-up. Least squares mean changes from last visit pre-progression to EoT were -2.1 (95% confidence interval -2.4, -1.7) for FOSI, -4.6 (-5.6, -3.5) for the EQ-5D-5L index, and -7.9 (-9.6, -6.3) for EQ-VAS. CONCLUSIONS: Disease progression negatively impacted HRQoL in patients with OC. PFS is clinically relevant, and prolonging PFS may preserve HRQoL. ispartof: GYNECOLOGIC ONCOLOGY vol:166 issue:3 pages:494-502 ispartof: location:United States status: published

INTRODUCTION: Older patients are at higher risk of chemotherapy-induced toxicity, raising interest in less toxic anti-HER2 regimens for older persons with HER2-positive (HER2+) metastatic breast cancer (MBC). PATIENTS AND METHODS: This phase II study randomized (1:1) patients with HER2+ MBC, aged 70+ or frail 60+, to first line chemotherapy with metronomic oral cyclophosphamide (M) + Trastuzumab (T) and Pertuzumab (P) or TP alone. T-DM1 was offered in case of progression. RESULTS: In total, 39 and 41 patients were randomized to TP and TPM arm respectively. Median follow-up is 54.0 months. 24-month PFS was 18.7% (95% CI 8.2-32.4) and 28.7% (95% CI 15.8-43.0), respectively. A total of 49 (61.3%) patients died of whom 37 (75.5%) from disease progression; number of deaths per arm was 27 (69.2%) for TP and 22 (53.7%) for TPM. There was no significant difference in OS between the two arms (median OS TP vs TPM: 32.1 vs 37.5 months, p 0.25). Among the 40 patients who have started T-DM1 after disease progression on TP/TPM, PFS rate at 6 months after start of T-DM1 was 43.6% (95% CI: 27.7-58.5) and grade 3 or higher AE occurred in 18 pts (45%). CONCLUSIONS: Metronomic chemotherapy-based dual blockade (TPM), followed by T-DM1 after progression, provides an active and relatively well tolerated treatment option in an older/frail HER2+ MBC population, with a median survival of over 3 years. Nevertheless, the majority of this older/frail population died from breast cancer, highlighting the need for well tolerated and efficacious treatments in these patients. ispartof: BREAST vol:64 pages:100-111 ispartof: location:Netherlands status: published

BACKGROUND The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40–60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates. OBJECTIVE AND RATIONALE The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men. SEARCH METHODS A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated. OUTCOMES A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08–3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03–3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10–4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44–6.77, P = 0.43). The literature was at moderate or severe risk of bias. WIDER IMPLICATIONS This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings.

OBJECTIVES: To calculate 3D-segmented total lung volume (TLV) in fetuses with thoracic anomalies using deformable slice-to-volume registration (DSVR) with comparison to 2D-manual segmentation. To establish a normogram of TLV calculated by DSVR in healthy control fetuses. METHODS: A pilot study at a single regional fetal medicine referral centre included 16 magnetic resonance imaging (MRI) datasets of fetuses (22-32 weeks gestational age). Diagnosis was CDH (n = 6), CPAM (n = 2), and healthy controls (n = 8). Deformable slice-to-volume registration was used for reconstruction of 3D isotropic (0.85 mm) volumes of the fetal body followed by semi-automated lung segmentation. 3D TLV were compared to traditional 2D-based volumetry. Abnormal cases referenced to a normogram produced from 100 normal fetuses whose TLV was calculated by DSVR only. RESULTS: Deformable slice-to-volume registration-derived TLV values have high correlation with the 2D-based measurements but with a consistently lower volume; bias -1.44 cm3 [95% limits: -2.6 to -0.3] with improved resolution to exclude hilar structures even in cases of motion corruption or very low lung volumes. CONCLUSIONS: Deformable slice-to-volume registration for fetal lung MRI aids analysis of motion corrupted scans and does not suffer from the interpolation error inherent to 2D-segmentation. It increases information content of acquired data in terms of visualising organs in 3D space and quantification of volumes, which may improve counselling and surgical planning. ispartof: PRENATAL DIAGNOSIS vol:42 issue:5 pages:628-635 ispartof: location:England status: published

ispartof: EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY vol:44 issue:2 pages:1-13 status: published

Background Perinatal mental health is a major public health concern. In Turkey, public hospitals operate pregnancy schools which provides an opportunity to integrate an evidence-based Thinking Healthy Programme (THP) for perinatal depression. The aim of this study is to adapt the THP for universal use in the group setting and to understand its acceptability and feasibility for integration into the existing antenatal care programme for both face-to-face and online delivery. Methods Following an expert-led adaptation process using the Bernal Framework, field testing was conducted on a group of women and facilitators followed by in-depth interviews (n:8) and group discussions (n = 13). Data were analysed using Thematic Framework Analysis. Results Minor but significant adaptations were made to the individually delivered THP for use in the universal group pregnancy schools. Initial findings indicate that the THP-group version was acceptable to its target population and could be integrated into the antenatal care plan for delivery during face-to-face and online group classes. Conclusion THP is transferable to the Turkish cultural and healthcare context. The THP–group version has the potential to add value to Turkey’s existing perinatal healthcare programme.

OBJECTIVES: To evaluate the concordance of conventional autopsy (CA) and postmortem magnetic resonance (MR) after termination of pregnancy (TOP) in fetuses with prenatally detected central nervous system (CNS) anomalies. Second, to determine the most informative postmortem investigation in parental counseling. METHODS: All TOPs between 2006 and 2016 with prenatally detected CNS involvement and having a postmortem MR and CA as postmortem examinations were retrospectively analyzed and concordance levels were established. RESULTS: Of 764 TOPs, 255 cases had a CNS anomaly detected prenatally (33.4%). Fetal genetic anomalies (n = 40) and cases without both postmortem MR and CA were excluded, leaving 68 cases for analysis.Disagreement between postmortem MR and CA was observed in 22 cases (32.4%). In eight cases (11.8%), more information was obtained by CA compared with MR. However, only two cases with major additional findings were found when compared with prenatal diagnosis. In 14 cases (20.6%), MR was superior to CA either because of additional cerebral anomalies undetected by CA (n = 5) and/or because of severe autolysis hindering pathology of the CNS (n = 9). CONCLUSIONS: Our data point out that an adequate postmortem evaluation, valuable in parental counseling, can be provided by a postmortem MR in 97% of the cases.Key PointsAn adequate postmortem evaluation, valuable in parental counseling, can be provided by a postmortem (PM) magnetic resonance (MR) in the majority of cases.PM MR is an excellent postmortem imaging tool for the brain.In cases with brain autolysis, PM MR is often the only informative PM investigation tool.PM MR is an essential adjunct to CA in the PM evaluation of pregnancies terminated for a central nervous system (CNS) anomaly. ispartof: JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE vol:36 issue:1 ispartof: location:England status: accepted

The opinion on the mechanisms underlying the pathogenesis of preeclampsia still divides scientists and clinicians. This common complication of pregnancy has long been viewed as a disorder linked primarily to placental dysfunction, which is caused by abnormal trophoblast invasion, however, evidence from the previous two decades has triggered and supported a major shift in viewing preeclampsia as a condition that is caused by inherent maternal cardiovascular dysfunction, perhaps entirely independent of the placenta. In fact, abnormalities in the arterial and cardiac functions are evident from the early subclinical stages of preeclampsia and even before conception. Moving away from simply observing the peripheral blood pressure changes, studies on the central hemodynamics reveal two different mechanisms of cardiovascular dysfunction thought to be reflective of the early-onset and late-onset phenotypes of preeclampsia. More recent evidence identified that the underlying cardiovascular dysfunction in these phenotypes can be categorized according to the presence of coexisting fetal growth restriction instead of according to the gestational period at onset, the former being far more common at early gestational ages. The purpose of this review is to summarize the hemodynamic research observations for the two phenotypes of preeclampsia. We delineate the physiological hemodynamic changes that occur in normal pregnancy and those that are observed with the pathologic processes associated with preeclampsia. From this, we propose how the two phenotypes of preeclampsia could be managed to mitigate or redress the hemodynamic dysfunction, and we consider the implications for future research based on the current evidence. Maternal hemodynamic modifications throughout pregnancy can be recorded with simple-to-use, noninvasive devices in obstetrical settings, which require only basic training. This review includes a brief overview of the methodologies and techniques used to study hemodynamics and arterial function, specifically the noninvasive techniques that have been utilized in preeclampsia research.

Key content Continuing financial constraints on the UK’s National Health Service means the need for clinicians to provide high-quality care in a cost-effective way has never been greater. While the medical education system equips doctors with skills to provide safe clinical care, it should also provide an understanding of healthcare costs and cost-effectiveness analysis. Value-based care is becoming a key paradigm in women’s health services, where clinicians must employ strategies for delivering value, rationalising costs and capitalising on the use of emerging technologies. The calculation of value of an intervention for providers and service users may differ; care must be taken to ensure this concept is adapted for, and not imposed on healthcare systems. Engaging trainees in systems transformation and embedding the concepts of ‘do no financial harm’ are essential to ensure sustainable healthcare services. Learning Objectives To understand the principles of value-based health care. To highlight the importance of adopting ‘cost-conscious’ care within daily clinical practice. To learn the differences between ‘cost’, ‘charge’, ‘price’ and ‘reimbursement. To encourage developing value-based competencies for future medical workforce through utilising out of programme placements and digital resources. Ethical Issues The ethical obligation of clinicians to consider cost may encompass justice and equity. However, the impact of practicing value-based health care is yet to be evaluated.

Objective. To describe molecular and clinical characteristics of patients with high-grade recurrent ovarian carcinoma (HGOC) who had long-term responses to the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib. Methods. This post hoc analysis pooled patients from Study 10 (NCT01482715; Parts 2A and 2B; n = 54) and ARIEL2 (NCT01891344; Parts 1 and 2; n = 491). Patients with investigator-assessed complete or partial response per RECIST were classified based on duration of response (DOR): long (≥1 year), intermediate (6 months to

The aim of this study was to assess the effect of continued smoking before and during pregnancy on mid-trimester fetal head development. A total of 250 pregnant women enrolled in the study. All participants were confirmed to be smokers or non-smokers by verifying breath carbon monoxide readings. Biparietal diameter (BPD), head circumference (HC), lateral ventricle (LV), and cisterna magna (CM) were evaluated by ultrasound between 20-22 weeks of pregnancy. Gender and gestational age-adjusted BPD z- scores were not statistically different between smokers and non-smokers (-0.75 ± 1.6 vs -0.51 ± 1, p = .3). HC measurements and z- scores were significantly lower in the smoking group than in the non-smoking groups (183.38 ± 14.56 vs. 189.28 ± 12.53, p = .003, 0.18 ± 1.39 multiple of median (MoM) vs. 0.56 ± 0.92, respectively, p = .023). At linear regression analysis, maternal smoking was the only independent factor associated with fetal HC z score (p = .041). In conclusion, continued smoking during pregnancy reduces fetal HC and has no effect on BPD, LV, or CM measurements at mid-gestation.IMPACT STATEMENTWhat is already known on this subject? Smoking during pregnancy is one of the most common environmental factors affecting fetal and neonatal growth and well-being. Despite the well-known effects of smoking on somatic growth, current studies have shown that it selectively affects some parts of the fetal brain, even in appropriately growing fetuses.What do the results of this study add? Continued smoking during pregnancy reduces fetal HC and has no effect on BPD, LV or CM measurements at mid-gestation. Since smoking is well known for its early and late childhood behavioral and neurological consequences, smaller mid-trimester fetal HC measurements should bring maternal smoking to mind as one of the potentially reversible causes.What are the implications of these findings for clinical practice and/or further research? The harmful effects of smoking start before the third trimester and antenatal counseling should be started early in the gestation. Every effort should be made to quit smoking before or early in pregnancy.

Background Despite efforts to make maternal health care services available in rural Ethiopia, utilisation status remains low. Therefore, this study aimed to assess maternal health care services’ status and determinants in rural Ethiopia. Methods The study used quasi-experimental pre- and post-comparison baseline data. A pretested, semi-structured, interviewer-administered questionnaire was used to collect data. A multilevel, mixed-effects logistic regression was used to identify individual and communal level factors associated with utilisation of antenatal care (ANC), skilled birth attendance (SBA), and postnatal care (PNC). The adjusted odds ratio (AOR) and corresponding 95% confidence intervals (CI) were estimated with a p-value of less than 0.05, indicating statistical significance. Results Seven hundred and twenty-seven pregnant women participated, with a response rate of 99.3%. Four hundred and sixty-one (63.4%) of the women visited ANC services, while 46.5% (CI: 42–50%) of births were attended by SBA, and 33.4% (CI: 30–36%) had received PNC. Women who reported that their pregnancy was planned (aOR = 3.9; 95% CI: 1.8–8.3) and were aware of pregnancy danger signs (aOR = 6.8; 95% CI: 3.8–12) had a higher likelihood of attending ANC services. Among the cluster-level factors, women who lived in lowlands (aOR = 4.1; 95% CI: 1.1–14) and had easy access to transportation (aOR = 1.9; 95% CI: 1.1–3.7) had higher odds of visiting ANC services. Moreover, women who were employed (aOR = 3.1; 95% CI: 1.3–7.3) and attended ANC (aOR = 3.3; 95% CI: 1.8–5.9) were more likely to have SBA at delivery. The likelihood of being attended by SBA during delivery was positively correlated with shorter travel distances (aOR = 2.9; 95% CI: 1.4–5.8) and ease of access to transportation (aOR = 10; 95% CI: 3.6–29) to the closest healthcare facilities. Being a midland resident (aOR = 4.7; 95% CI: 1.7–13) and having SBA during delivery (aOR = 2.1; 95% CI: 1.2–3.50) increased the likelihood of attending PNC service. Conclusions Overall, maternal health service utilisation is low in the study area compared with the recommended standards. Women’s educational status, awareness of danger signs, and pregnancy planning from individual-level factors and being a lowland resident, short travel distance to health facilities from the cluster-level factors play a crucial role in utilising maternal health care services. Working on women’s empowerment, promotion of contraceptive methods to avoid unintended pregnancy, and improving access to health care services, particularly in highland areas, are recommended to improve maternal health service utilisation.

PURPOSE: To investigate bleeding profile satisfaction and pain and ease of placement with levonorgestrel 19.5 mg IUD in routine clinical practice. METHODS: Women who independently chose levonorgestrel 19.5 mg IUD during routine counselling were invited to participate in this prospective, multinational, observational study. Patient-reported pain and clinician-reported ease of placement were assessed. Bleeding profile satisfaction was evaluated at 12 months/premature end of observation. RESULTS: Most participants (77.8%, n = 878/1129) rated levonorgestrel 19.5 mg IUD placement pain as 'none' or 'mild' and most clinicians (91.1%, n = 1029/1129) rated placement as 'easy'. Pain was more often rated higher in nulliparous compared with parous (p 35 years. CONCLUSION: We observed high bleeding profile satisfaction regardless of age or parity with levonorgestrel 19.5 mg IUD and confirmed that device placement is easy and associated with no more than mild pain in most cases in routine clinical practice. Real-world evidence from the Kyleena® Satisfaction Study in routine clinical practice shows high bleeding profile satisfaction with levonorgestrel 19.5 mg IUD regardless of age or parity. IUD placement was easy and associated with little to no pain for most women. ispartof: EUROPEAN JOURNAL OF CONTRACEPTION AND REPRODUCTIVE HEALTH CARE vol:28 issue:1 pages:1-9 ispartof: location:England status: published

Research question: Can cannabidiol (CBD) be used in the treatment of endometriosis for its anti-inflammatory, antioxidative and antiangiogenic effects? Design: Endometrial implants were surgically induced in 36 female Wistar albino rats. After confirmation of endometriotic foci, the rats were randomized into four groups. In the leuprolide acetate group, rats were given a single 1 mg/kg s.c. leuprolide acetate injection. The other groups were 5 mg/kg CBD (CBD5), saline solution and 20 mg/kg CBD (CBD20); daily i.p. injections were administered for 7 days. After 21 days, the rats were euthanised, and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-a) measurements in blood and peritoneal fluid samples, and immunohistochemical staining for TNF-a, IL-6 and vascular endothelial growth factor (VEGF) of endometriotic tissues were evaluated. Results: Significant reductions in the endometriotic implant surface area (P = 0.0213), serum TOS (P = 0.0491), OSI (P = 0.0056), IL-6 (P = 0.0236), TNF-a (P = 0.0083) and peritoneal fluid OSI (P = 0.0401), IL-6 (P = 0.0205) and TNF-a (P = 0.0045) concentrations were observed in the CBD5 group when compared with the saline solution group. Compared with the saline solution group, increased TAS concentrations in serum (P = 0.0012) and peritoneal fluid (P = 0.0145) were found in the CBD5 group. The CBD5 and leuprolide acetate groups were similar regarding inflammatory and oxidative stress parameters of serum and peritoneal fluid samples. The CBD5 group showed significantly lower mean intensity in both surface epithelium and stromal cells for VEGF (both P = 0.002) and only in surface epithelium cells for IL-6 (P = 0.0108), when compared with the leuprolide acetate group. Conclusion: Due to its anti-inflammatory, antioxidative and antiangiogenic effects, CBD might be a therapeutic agent candidate for endometriosis. Department of Biostatistics ; Reakiro Company ; Bezmialem Vakif University

PURPOSE: Infertility is a stressful condition for couples and can affect patients\" circadian rhythm and sleep quality. The goal of this study is to assess differences in chronotype and sleep quality between infertile and fertile people. METHODS: A cross-sectional study was conducted. The infertile patient population consisted study group. Primiparous patients without any known gynecological disease who presented for routine cervical cancer screening follow-up were included in the control group. The Turkish version of the Morningness-Eveningness Questionnaire (MEQ) and Pittsburg Sleep Quality Index (PSQI) scores were evaluated between groups. RESULTS: A total of 227 patients were assessed. There were 110 patients in the study (infertile) group and 117 patients in the control (fertile) group. The evening chronotype proportion (23.6 vs. 0.9%, p < 0.001) was higher in the infertile group. The median of MEQ score was significantly higher in the fertile patients (50, IQR = 43 - 55 vs. 56, IQR = 51 - 59; p < 0.001), and the median of PSQI score was significantly higher in the infertile patients (5, IQR = 4 - 6, vs. 4, IQR = 3 - 5; p < 0.001). CONCLUSIONS: In this study, we found significantly worse sleep quality, and more evening chronotype in the patients with infertility.

This study compared the cost per live birth and cost-effectiveness of the originator recombinant human follicle-stimulating hormone follitropin alfa (r-hFSH-alfa) and r-hFSH-alfa biosimilars for ovarian stimulation prior to assisted reproductive technology treatment in Spain. A decision tree model was developed, comprising pregnancy and live birth for one treatment cycle with fresh embryo transfer. Clinical inputs were based on a recent meta-analysis by Chua et al. [4]. Cost inputs were extracted from publicly available Spanish sources. The costs per live birth were lower with originator r-hFSH-alfa (€18,138) versus r-hFSH-alfa biosimilars (€20,377). The incremental cost-effectiveness ratio was €7208 for originator r-hFSH-alfa versus biosimilars. Drug acquisition costs for originator r-hFSH-alfa represented 10.5% of total costs in the base case analysis, and 6.2% in a treatment cycle resulting in live birth with one fresh embryo transfer. Results from the sensitivity analyses confirmed the robustness of the findings. ispartof: BEST PRACTICE & RESEARCH CLINICAL OBSTETRICS & GYNAECOLOGY vol:85 issue:Pt B pages:203-216 ispartof: location:Netherlands status: published

Objective In the PALOMA-2 trial, palbociclib in combination with letrozole prolonged progression-free survival (PFS) and exhibited an acceptable safety profile in patients with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ABC). This post hoc analysis of PALOMA-2 evaluated the efficacy and safety of palbociclib plus letrozole in patients with preexisting conditions grouped by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC). Methods Postmenopausal patients without prior treatment for ABC were randomized 2:1 to receive palbociclib (125 mg/d on a 3 weeks on/1 week off schedule) plus letrozole (2.5 mg/d, continuous) or placebo plus letrozole. Patients were grouped by the following MedDRA SOC preexisting conditions: gastrointestinal, musculoskeletal, metabolic, and vascular/cardiac. Median PFS was estimated by the Kaplan-Meier method, and treatment emergent adverse events (AEs) were compared between treatment arms within each preexisting condition subgroup. Results At baseline, 276 (41.4 %) patients had preexisting gastrointestinal disorders, 390 (58.6 %) had musculoskeletal disorders, 259 (38.9 %) had metabolic disorders, and 382 (57.4 %) had vascular/cardiac disorders. Baseline characteristics were similar between subgroups and between each arm within subgroups. Regardless of baseline preexisting condition, palbociclib plus letrozole prolonged PFS compared with placebo plus letrozole. Treatment-emergent AEs associated with palbociclib plus letrozole and dose modifications due to AEs were similar across preexisting condition subgroups. Conclusion This post hoc analysis of PALOMA-2 demonstrated a favorable effect of palbociclib on PFS and a safety profile consistent with previous observations, regardless of underlying preexisting condition. Pfizer Inc (NCT01740427)., Highlights • Preexisting conditions can affect the safety and efficacy of breast cancer therapies. • This is a post hoc analysis of patients with preexisting conditions from PALOMA-2. • Palbociclib prolonged median PFS, regardless of preexisting condition. • Within each treatment arm, AEs were similar regardless of preexisting condition.

PURPOSE: The Kyleena® Satisfaction Study (KYSS) aimed to assess satisfaction and continuation with levonorgestrel-releasing intrauterine system (LNG-IUS) 12 (Kyleena®) in routine clinical practice and to evaluate factors that influence satisfaction. MATERIALS AND METHODS: This prospective, observational, multicentre, single-arm cohort study, with 1-year follow-up, was conducted in Belgium, Canada, Germany, Mexico, Norway, Sweden, Spain and the United States from 2017 to 2018. During routine counselling, women who independently selected to use LNG-IUS 12 were invited to participate in the study. KYSS assessed LNG-IUS 12 satisfaction, continuation and safety. RESULTS: Overall, there were 1126 successful LNG-IUS 12 placements, with insertion attempted in 1129 women. Most participants (833/968, 86.1%, 95% CI 83.7-88.2%, with satisfaction outcome data available) reported satisfaction with LNG-IUS 12 at 12 months (or at the final visit if the device was discontinued prematurely). Satisfaction was not associated with age, parity or motivation for choosing LNG-IUS 12. The majority of women (919/1129, 81.4%) chose to continue after 12 months. Discontinuation was not correlated with age or parity. Overall, 191 women (16.9%) reported a treatment-emergent adverse event. CONCLUSIONS: Results from KYSS provide the first real-world evidence assessing LNG-IUS 12, and demonstrate high satisfaction and continuation rates irrespective of age or parity. Clinical trial registration: NCT03182140. ispartof: EUROPEAN JOURNAL OF CONTRACEPTION AND REPRODUCTIVE HEALTH CARE vol:26 issue:6 pages:462-472 ispartof: location:England status: published

BACKGROUND: Population-based administrative data have rarely been used to compare the birth prevalence, risk factors for occurrence, and mortality of congenital diaphragmatic hernia (CDH) subtypes. OBJECTIVES: We used a national birth cohort to identify CDH subtypes and compared their birth prevalence, relationship with maternal age after accounting for sociodemographic factors, and 1-year mortality rates. METHODS: Linked hospital admission and death records were used to identify isolated and complex CDH cases (involving additional anomalies) among singleton livebirths in England between 2002 and 2018. The prevalence of each CDH subtype per 10,000 livebirths was estimated overall and by infant, birth and maternal characteristics. The relationship between maternal age and each subtype relative to no CDH was examined using multivariable log-binomial regression to estimate risk ratios (RRs). One-year mortality rates were examined using Kaplan-Meier curves and the hazard ratio (HR) of complex versus isolated CDH was calculated using Cox regression. RESULTS: Among 9.5 million livebirths, we identified 1285 with isolated CDH and 1150 with complex CDH. The overall prevalence of isolated and complex CDH was 1.4 (95% confidence interval [CI] 1.3, 1.4) and 1.2 (95% CI 1.1, 1.3) per 10,000 livebirths, respectively. Only complex CDH was associated with maternal age. Compared with maternal age 25-34 years, complex CDH risk was elevated for maternal age

ispartof: EARLY HUMAN DEVELOPMENT vol:174 ispartof: location:Ireland status: published

© 2022 John Wiley & Sons Ltd.Objectives: Cell-free DNA has been found in all body fluids, but DNAs emerging from locations that are not in direct contact with breath in exhaled breath condensate (EBC) are yet to be found. The potential of EBC for prenatal and cancer screening prompted us to investigate whether fetal DNA is present in maternal EBC. Method: A total of 20 pregnant women\"s EBC and blood samples were collected. Four Y chromosome-specific assays were tested on all EBC and plasma samples by quantitative PCR (qPCR). The best-performing assay was used for digital droplet PCR (ddPCR) on all EBC and the six plasma samples. Results: The sex of the fetuses was accurately determined from plasma samples. DNA sequences could not be properly amplified in EBC samples by the qPCR. By ddPCR, the Y chromosome sequence was amplified in two of the 11 EBC samples, from women carrying male fetuses (2/11), and the Y chromosome sequence was not amplified in the EBC of women carrying female fetuses (9/9). Exhaled breath condensate ddPCR result\"s specificity was 100%, the detection rate of Y chromosome was 18.18% (2/11), and the corrected accuracy was 59.09%. Conclusion: Our finding of \"the presence of fetal DNA in maternal EBC\", despite the low detection rate, might have a major impact on prenatal diagnosis and cancer screening.

CoMix Europe Working Group: Daniela Paolotti, André Karch, Veronika Jäger, Joaquin Baruch, Tanya Melillo, Henrieta Hudeckova, Magdalena Rosinska, Marta Niedzwiedzka-Stadnik, Krista Fischer, Sigrid Vorobjov, Hanna Sõnajalg, Christian Althaus, Nicola Low, Martina Reichmuth, Kari Auranen, Markku Nurhonen, Goranka Petrović, Zvjezdana Lovric Makaric, Sónia Namorado, Constantino Caetano, Ana João Santos, Gergely Röst, Beatrix Oroszi, Márton Karsai, Mario Fafangel, Petra Klepac, Natalija Kranjec, Cristina Vilaplana, Jordi Casabona. CoMix Europe Working Group: Sónia Namorado, Constantino Caetano, and Ana João Santos (Department of Epidemiology, National Institute of Health Dr Ricardo Jorge, Portugal) Background: Evidence and advice for pregnant women evolved during the COVID-19 pandemic. We studied social contact behaviour and vaccine uptake in pregnant women between March 2020 and September 2021 in 19 European countries. Methods: In each country, repeated online survey data were collected from a panel of nationally-representative participants. We calculated the adjusted mean number of contacts reported with an individual-level generalized additive mixed model, modelled using the negative binomial distribution and a log link function. Mean proportion of people in isolation or quarantine, and vaccination coverage by pregnancy status and gender were calculated using a clustered bootstrap. Findings: We recorded 4,129 observations from 1,041 pregnant women, and 115,359 observations from 29,860 non-pregnant individuals aged 18-49. Pregnant women made slightly fewer contacts (3.6, 95%CI = 3.5-3.7) than non-pregnant women (4.0, 95%CI = 3.9-4.0), driven by fewer work contacts but marginally more contacts in non-essential social settings. Approximately 15-20% pregnant and 5% of non-pregnant individuals reported to be in isolation and quarantine for large parts of the study period. COVID-19 vaccine coverage was higher in pregnant women than in non-pregnant women between January and April 2021. Since May 2021, vaccination in non-pregnant women began to increase and surpassed that in pregnant women. Interpretation: Limited social contact to avoid pathogen exposure during the COVID-19 pandemic has been a challenge to many, especially women going through pregnancy. More recognition of maternal social support desire is needed in the ongoing pandemic. As COVID-19 vaccination continues to remain an important pillar of outbreak response, strategies to promote correct information can provide reassurance and facilitate informed pregnancy vaccine decisions in this vulnerable group. HPRU in Modelling & Health Economics,NIHR200908,European Union’s Horizon 2020 research and innovation programme,EpiPose 101003688,TransMID 682540,TransMID 682540,TransMID 682540,EpiPose 101003688,Wellcome Trust,213589/Z/18/Z,National Institute for Health Research,CV220-088—COMIX,CV220-088—COMIX,CV220-088— COMIX,Global Challenges Research Fund,ES/P010873/1,Medical Research Council,MC_PC_19065,NIHR,PR-OD-1017-20002 HPRU in Modelling & Health Economics (NIHR200908: KLMW); European Union Horizon 2020 research and innovation programme – (EpiPose 101,003,688: AG, WJE). Wellcome Trust (213,589/Z/18/Z: ESP). European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (TransMID 682,540: CF, PN, NH). This research was partly funded by the Global Challenges Research Fund (GCRF) project RECAP managed through RCUK and ESRC (ES/P010873/1: CIJ). NIHR (PR-OD-1017–20,002: WJE) UK MRC (MC_PC_19065—Covid 19: Understanding the dynamics and drivers of the COVID-19 epidemic using real-time outbreak analytics: WJE). info:eu-repo/semantics/publishedVersion

Objective. Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN.Methods. We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up.Results. Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was di-agnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor >= 30 mm. Bilateral ra-diotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence.Conclusion. The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). On behalf of all GROINSS-V I and II participants: C.F. Levenback, R.H. Hermans, J. Bouda, A. Sharma, D. Luesley, P. Ellis, D.J. Cruickshank, T.J. Duncan, K. Kieser,C. Palle, N.M. Spirtos, D.M. O'Malley, M.M. Leitao, M. Geller, K. Dhar, V. Asher, D.H. Tobias, C. Borgfeldt, J.S. Lea,M. Lood, J. Bailey, B. Eyjolfsdottir, S. Attard-Montalto, K.S. Tewari, P. Persson, R. Manchanda, P. Jensen, L. Van Le

Objective: Recently, some pregnant women in Türkiye are hesitant to undergo gestational diabetes mellitus (GDM) screening tests and this trend is more common. The objective of the study is to assess the pregnant women’s knowledges, decisions, reasons for hesitations about having the GDM screening tests and test rejection rates. Material and Methods: This cross-sectional study included 647 pregnant women who applied for an antenatal outpatient clinic and who had not yet been diagnosed with GDM and a survey was conducted using questionnaire designed by the authors. Results: At the beginning, 287 (44.4%) of the participants declared that they would have glucose challenge test, 169 (26.1%) would not and 191 (29.5%) were undecided. The rejection rate was lower in those who had knowledge about the screening tests. After a short information about the content of tests, 30% of the women who decided not to have the test and 78.3% of those who were undecided at the beginning, decided to have the test (p=0.001). Conclusion: The knowledge level of pregnant women about diabetes screening and diagnosis influences their decision-making. Organizing well-planned trainings for patients and healthcare professionals using public institutions and media may be effective in reducing the burden of diabetes on social health and the economic indicators.