Good practice recommendations on add-ons in reproductive medicine

STUDY QUESTION: Which add-ons are safe and effective to be used in ART treatment? SUMMARY ANSWER: Forty-two recommendations were formulated on the use of add-ons in the diagnosis of fertility problems, the IVF laboratory and clinical management of IVF treatment. WHAT IS KNOWN ALREADY: The innovative nature of ART combined with the extremely high motivation of the patients has opened the door to the wide application of what has become known as 'add-ons' in reproductive medicine. These supplementary options are available to patients in addition to standard fertility procedures, typically incurring an additional cost. A diverse array of supplementary options is made available, encompassing tests, drugs, equipment, complementary or alternative therapies, laboratory procedures, and surgical interventions. These options share the common aim of stating to enhance pregnancy or live birth rates, mitigate the risk of miscarriage, or expedite the time to achieving pregnancy. STUDY DESIGN, SIZE, DURATION: ESHRE aimed to develop clinically relevant and evidence-based recommendations focusing on the safety and efficacy of add-ons currently used in fertility procedures in order to improve the quality of care for patients with infertility. PARTICIPANTS/MATERIALS, SETTING, METHODS: ESHRE appointed a European multidisciplinary working group consisting of practising clinicians, embryologists, and researchers who have demonstrated leadership and expertise in the care and research of infertility. Patient representatives were included in the working group. To ensure that the guidelines are evidence-based, the literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, recommendations were based on the professional experience and consensus of the working group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 46 independent international reviewers. A total of 272 comments were received and incorporated where relevant. MAIN RESULTS AND THE ROLE OF CHANCE: The multidisciplinary working group formulated 42 recommendations in three sections; diagnosis and diagnostic tests, laboratory tests and interventions, and clinical management. LIMITATIONS, REASONS FOR CAUTION: Of the 42 recommendations, none could be based on high-quality evidence and only four could be based on moderate-quality evidence, implicating that 95% of the recommendations are supported only by low-quality randomized controlled trials, observational data, professional experience, or consensus of the development group. WIDER IMPLICATIONS OF THE FINDINGS: These guidelines offer valuable direction for healthcare professionals who are responsible for the care of patients undergoing ART treatment for infertility. Their purpose is to promote safe and effective ART treatment, enabling patients to make informed decisions based on realistic expectations. The guidelines aim to ensure that patients are fully informed about the various treatment options available to them and the likelihood of any additional treatment or test to improve the chance of achieving a live birth. STUDY FUNDING/COMPETING INTEREST(S): All costs relating to the development process were covered from ESHRE funds. There was no external funding of the development process or manuscript production. K.L. reports speakers fees from Merck and was part of a research study by Vitrolife (unpaid). T.E. reports consulting fees from Gynemed, speakers fees from Gynemed and is part of the scientific advisory board of Hamilton Thorne. N.P.P. reports grants from Merck Serono, Ferring Pharmaceutical, Theramex, Gedeon Richter, Organon, Roche, IBSA and Besins Healthcare, speakers fees from Merck Serono, Ferring Pharmaceutical, Theramex, Gedeon Richter, Organon, Roche, IBSA and Besins Healthcare. S.R.H. declares being managing director of Fertility Europe, a not-for-profit organization receiving financial support from ESHRE. I.S. is a scientific advisor for and has stock options from Alife Health, is co-founder of IVFvision LTD (unpaid) and received speakers' fee from the 2023 ART Young Leader Prestige workshop in China. A.P. reports grants from Gedeon Richter, Ferring Pharmaceuticals and Merck A/S, consulting fees from Preglem, Novo Nordisk, Ferring Pharmaceuticals, Gedeon Richter, Cryos and Merck A/S, speakers fees from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S, Theramex and Organon, travel fees from Gedeon Richter. The other authors disclosed no conflicts of interest. DISCLAIMER: This Good Practice Recommendations (GPRs) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and are based on the scientific evidence available at the time of preparation.ESHRE GPRs should be used for information and educational purposes. They should not be interpreted as setting a standard of care or bedeemedinclusive of all proper methods of care, or be exclusive of other methods of care reasonably directed to obtaining the same results.Theydo not replace the need for application of clinical judgement to each individual presentation, or variations based on locality and facility type.Furthermore, ESHRE GPRs do not constitute or imply the endorsement, or favouring, of any of the included technologies by ESHRE

Guidelines on Chemotherapy in Advanced Stage Gynecological Malignancies: An Evaluation of 224 Professional Societies and Organizations

BACKGROUND: Clinical practice guidelines are important for guiding practice, but it is unclear if they are commensurate with the available evidence. METHODS: We examined guidelines produced by cancer and gynecological societies and organizations and evaluated their coverage of and stance towards chemotherapy for advanced stage disease among 4 gynecological malignancies (breast, ovarian, cervical, endometrial cancer) where the evidence for the use of chemotherapy is very different (substantial and conclusive for breast and ovarian cancer, limited and suggesting no major benefit for cervical and endometrial cancer). Eligible societies and organizations were identified through systematic internet searches (last update June 2009). Pertinent websites were scrutinized for presence of clinical practice guidelines, and relative guidelines were analyzed. RESULTS: Among 224 identified eligible societies and organizations, 69 (31%) provided any sort of guidelines, while recommendations for chemotherapy on advanced stage gynecological malignancies were available in 20 of them. Only 14 had developed their own guideline, and only 5 had developed guidelines for all 4 malignancies. Use of levels of evidence and grades of recommendations, and aspects of the production, implementation, and timeliness of the guidelines did not differ significantly across malignancies. Guidelines on breast and ovarian cancer utilized significantly more randomized trials and meta-analyses. Guidelines differed across malignancies on their coverage of disease-free survival (p = 0.033), response rates (p = 0.024), symptoms relief (p = 0.005), quality of life (p = 0.001) and toxicity (p = 0.039), with breast and ovarian cancer guidelines typically covering more frequently these outcomes. All guidelines explicitly or implicitly endorsed the use of chemotherapy. CONCLUSIONS: Clinical practice guidelines are provided by the minority of professional societies and organizations. Available guidelines tend to recommend chemotherapy even for diseases where the effect of chemotherapy is controversial and recommendations are based on scant evidence

Brazilian multicenter study on prevalence of preterm birth and associated factors

<p>Abstract</p> <p>Background</p> <p>The occurrence of preterm birth remains a complex public health condition. It is considered the main cause of neonatal morbidity and mortality, resulting in a high likelihood of sequelae in surviving children. With variable incidence in several countries, it has grown markedly in the last decades. In Brazil, however, there are still difficulties to estimate its real occurrence. Therefore, it is essential to establish the prevalence and causes of this condition in order to propose prevention actions. This study intend to collect information from hospitals nationwide on the prevalence of preterm births, their associated socioeconomic and environmental factors, diagnostic and treatment methods resulting from causes such as spontaneous preterm labor, prelabor rupture of membranes, and therapeutic preterm birth, as well as neonatal results.</p> <p>Methods/Design</p> <p>This proposal is a multicenter cross-sectional study plus a nested case-control study, to be implemented in 27 reference obstetric centers in several regions of Brazil (North: 1; Northeast: 10; Central-west: 1; Southeast: 13; South: 2). For the cross sectional component, the participating centers should perform, during a period of six months, a prospective surveillance of all patients hospitalized to give birth, in order to identify preterm birth cases and their main causes. In the first three months of the study, an analysis of the factors associated with preterm birth will also be carried out, comparing women who have preterm birth with those who deliver at term. For the prevalence study, 37,000 births will be evaluated (at term and preterm), corresponding to approximately half the deliveries of all participating centers in 12 months. For the case-control study component, the estimated sample size is 1,055 women in each group (cases and controls). The total number of preterm births estimated to be followed in both components of the study is around 3,600. Data will be collected through a questionnaire all patients will answer after delivery. The data will then be encoded in an electronic form and sent online by internet to a central database. The data analysis will be carried out by subgroups according to gestational age at preterm birth, its probable causes, therapeutic management, and neonatal outcomes. Then, the respective rates, ratios and relative risks will be estimated for the possible predictors.</p> <p>Discussion</p> <p>These findings will provide information on preterm births in Brazil and their main social and biological risk factors, supporting health policies and the implementation of clinical trials on preterm birth prevention and treatment strategies, a condition with many physical and emotional consequences to children and their families.</p

The Raine study had no evidence of significant perinatal selection bias after two decades of follow up: A longitudinal pregnancy cohort study

Background: Cohort studies may increase or decrease their selection bias as they progress through time. The Western Australian Pregnancy Cohort (Raine) Study has followed 2868 children for over two decades; from fetal into adult life. This paper analyses the cohort over time, assessing potential bias that may come and go with recruitment, retention and loss of participants. Methods: Linked data from all births in Western Australian over the 3 years the Raine Cohort was recruited were obtained to compare perinatal characteristics and subsequent health outcomes between the Western Australian (WA) contemporaneous birth population and the Raine Cohort at five time points. Perinatal exposure-outcome comparisons were employed to assess bias due to non-participation in Raine Study subsets. Results: There were demographic differences between the Raine Study cohort and its source population at recruitment with further changes across the period of follow up. Despite these differences, the pregnancy and infant data of those with continuing participation were not significantly different to the WA contemporaneous birth population. None of the exposure-outcome associations were significantly different to those in the WA general population at recruitment or at any cohort reviews suggesting no substantial recruitment or attrition bias. Conclusions: The Raine Study is valuable for association studies, even after 20 years of cohort reviews with increasing non-participation of cohort members. Non-participation has resulted in greater attrition of socially disadvantaged participants, however, exposure-outcome association analyses suggest that there is no apparent resulting selection bias

Periodontal disease and some adverse perinatal outcomes in a cohort of low risk pregnant women

Objective: To evaluate the association of periodontal disease (PD) in pregnancy with some adverse perinatal outcomes. Method: This cohort study included 327 pregnant women divided in groups with or without PD. Indexes of plaque and gingival bleeding on probing, probing pocket depth, clinical attachment level and gingival recession were evaluated at one periodontal examination below 32 weeks of gestation. The rates of preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA) neonates and prelabor rupture of membranes (PROM) were evaluated using Risk Ratios (95%CI) and Population Attributable Risk Fractions. Results: PD was associated with a higher risk of PTB (RRadj. 3.47 95% CI 1.62-7.43), LBW (RRadj. 2.93 95% CI 1.36-6.34) and PROM (RRadj. 2.48 95% CI 1.35-4.56), but not with SGA neonates (RR 2.38 95% CI 0.93 - 6.10). Conclusions: PD was a risk factor for PT, LBW and PROM among Brazilian low risk pregnant women

Individualized Cost-Effectiveness Analysis

John Ioannidis and Alan Garber discuss how to use incremental cost-effectiveness ratios (ICER) and related metrics so they can be useful for decision-making at the individual level, whether used by clinicians or individual patients

Live birth rates and perinatal outcomes when all embryos are frozen compared with conventional fresh and frozen embryo transfer: a cohort study of 337,148 in vitro fertilisation cycles

BACKGROUND: It is not known whether segmentation of an in vitro fertilisation (IVF) cycle, with freezing of all embryos prior to transfer, increases the chance of a live birth after all embryos are transferred. METHODS: In a prospective study of UK Human Fertilisation and Embryology Authority data, we investigated the impact of segmentation, compared with initial fresh embryo followed by frozen embryo transfers, on live birth rate and perinatal outcomes. We used generalised linear models to assess the effect of segmentation in the whole cohort, with additional analyses within women who had experienced both segmentation and non-segmentation. We compared rates of live birth, low birthweight (LB

Cell–cell and cell–matrix dynamics in intraperitoneal cancer metastasis

The peritoneal metastatic route of cancer dissemination is shared by cancers of the ovary and gastrointestinal tract. Once initiated, peritoneal metastasis typically proceeds rapidly in a feed-forward manner. Several factors contribute to this efficient progression. In peritoneal metastasis, cancer cells exfoliate into the peritoneal fluid and spread locally, transported by peritoneal fluid. Inflammatory cytokines released by tumor and immune cells compromise the protective, anti-adhesive mesothelial cell layer that lines the peritoneal cavity, exposing the underlying extracellular matrix to which cancer cells readily attach. The peritoneum is further rendered receptive to metastatic implantation and growth by myofibroblastic cell behaviors also stimulated by inflammatory cytokines. Individual cancer cells suspended in peritoneal fluid can aggregate to form multicellular spheroids. This cellular arrangement imparts resistance to anoikis, apoptosis, and chemotherapeutics. Emerging evidence indicates that compact spheroid formation is preferentially accomplished by cancer cells with high invasive capacity and contractile behaviors. This review focuses on the pathological alterations to the peritoneum and the properties of cancer cells that in combination drive peritoneal metastasis