Culture time to optimize embryo cell-free DNA analysis for frozen-thawed blastocysts undergoing noninvasive preimplantation genetic testing for aneuploidy.

OBJECTIVE: To investigate the ideal time in culture to optimize embryo cell-free deoxyribonucleic acid (cfDNA) analysis in frozen-thawed blastocysts undergoing noninvasive preimplantation genetic testing for aneuploidy (PGT-A). Cell-free DNA is released into the spent blastocyst media (spent media) by the embryo. However, the optimal timing to determine maximal cfDNA in the case of frozen-thawed blastocysts undergoing noninvasive PGT-A remains to be elucidated. DESIGN: In this prospective observational study, 135 spent media and corresponding whole blastocysts were collected from January 2021 through March 2022. SETTING: Private fertility clinics. PATIENTS: Day-5 frozen-thawed blastocysts were cultured for 8 hours (Day-5 Short) or 24 hours (Day-5 Long), whereas day-6 frozen-thawed blastocysts were cultured for 8 hours (Day-6 Short). The spent media and whole blastocysts were then collected for further analysis. Spent media and whole blastocysts were amplified using whole genome amplification and sequenced using next-generation sequencing. MAIN OUTCOME MEASURES: Informativity and concordance rates between cfDNA in spent media and whole blastocyst DNA were compared according to the different times in culture. RESULTS: When comparing time in culture, informativity rates for spent media were significantly higher for Day-5 Long and Day-6 Short (>91%) compared with the Day-5 Short group (<60%). A similar trend was observed for cases with and without a previous PGT-A. Regarding blastocyst expansion grade, informativity rates were lower on Day-5 Short compared with Day-5 Long and Day-6 Short, regardless of expansion degree. This decrease was significant for Gardner-grade expansion grades 3, 4, and 5-6. In addition, for a similar time in culture, the grade of expansion did not have an impact on the informativity rates. For concordance rates, no significant differences were observed among the 3 groups. In all cases, concordance rates were 90.5% for Day-5 Short, 93.6% for Day-5 Long, and 92.3% for Day-6 Short. No impact of the expansion grade was observed on concordance rates. CONCLUSION: Noninvasive PGT-A in frozen-thawed blastocysts yields very high concordance rates with whole blastocysts, possibly limiting the need for invasive PGT-A and making it available for a wider range of patients.

Ansiedad y depresión en el embarazo. Variables asociadas durante el periodo de pandemia COVID-19 / Anxiety and depression in pregnancy. Associated variables during the covid-19 pandemic period

Objetivo: Evaluar la asociación entre edad, paridad, nacionalidad, estudios, empleo y apoyo de la pareja con la depresión y ansiedad durante el embarazo. Determinar el impacto de la evolución de la pandemia COVID-19 en los niveles de ansiedad y depresión de las participantes. Método: Estudio descriptivo correlacional transversal realizado en el Osakidetza/Servicio Vasco de Salud, Atención primaria, Bizkaia (España). Participaron 295 gestantes entre ocho y 41 semanas. Se midió la asociación entre edad, paridad, nacionalidad, nivel de estudios, empleo, apoyo de la pareja y tasas de incidencia de COVID-19 durante el periodo del estudio y las puntuaciones de depresión (medido con la Escala de Depresión Posnatal de Edimburgo) y de ansiedad (medido con la subescala de ansiedad estado-rasgo del State-Anxiety Inventory [STAI-S]) durante el embarazo. Se construyó un modelo de regresión logística y se estimaron las odds ratios (OR) y sus intervalos de confianza de 95% (IC 95%). Resultados: La puntuación media en ansiedad fue de 18,75 puntos (DE = 8,69) y en depresión 6,45 puntos (DE = 4,32). Las mujeres que esperaban su segundo hijo o más obtuvieron puntuaciones más altas en depresión (OR 2,51 [IC 95%: 1,26-5,01]) y ansiedad (OR 1,98 [IC 95%: 1,01-3,89]). Haber cursado estudios universitarios se asocia con puntuaciones más bajas en depresión (OR 0,28 [IC 95%: 0,11-0,77]) y ansiedad (OR 0,2 [IC 95%:0,08-0,54]). Una buena calidad en la relación de pareja se asocia con menores niveles de ansiedad (OR 0,45 [IC 95%: 0,24-0,81). La puntuación media en ansiedad y depresión se relacionan con la incidencia de casos COVID-19; la puntuación en ansiedad fue significativamente más alta en los periodos de mayor incidencia. Conclusiones: Mayor atención emocional a las gestantes con bajo nivel de estudios, multíparas y con un débil apoyo de su pareja, permitiría reducir la ansiedad y depresión en el embarazo. Situaciones de emergencia sanitaria afectan a la salud mental durante la ges...(AU)

Objective: To assess the association between age, parity, nationality, educational level, employment and partner support with depression and anxiety during pregnancy. To determine the impact of the evolution of the COVID-19 pandemic on the anxiety and depression levels of the participants. Method: Cross-sectional descriptive correlational study carried out in the Osakidetza/Basque Health Service, Primary Care, Bizkaia (Spain). A total of 295 pregnant women between 8 and 41 weeks participated. The association between age, parity, nationality, educational level, employment, partner support and COVID-19 incidence rates during the study period and depression (measured with the Edinburgh Postnatal Depression Scale) and anxiety (measured with the State-Anxiety Inventory/STAI-S subscale) scores during pregnancy was measured. A logistic regression model was constructed and odds ratios and their 95% confidence intervals were estimated. Results: The mean score was 18.75 points for anxiety (SD 8.69) and 6.45 points for depression (SD 4.32). Women expecting their second or later child had higher scores for depression (OR 2.51 [95%IC: 1.26-5.01]) and anxiety (OR 1.98 [95%IC: 1.01-3.89]). Having completed university studies was associated with lower scores in depression (OR 0.28 [95%IC: 0.11-0.77]) and in anxiety (OR 0,2 [95%IC: 0.08-0.54]). A good relationship with the partner was associated with lower levels of anxiety (OR 0.45 [95%IC: 0.24-0.81]). The mean anxiety and depression scores are related to the incidence of COVID-19 cases; the anxiety score was significantly higher in periods of higher incidence. Conclusions: Greater emotional care for pregnant women with low educational level, multiparous and with weak support from their partner, would reduce anxiety and depression in pregnancy. Health emergency situations affect mental health during gestation.(AU)

Anxiety and depression in pregnancy: associated variables during the COVID-19 pandemic period.

OBJECTIVE: To assess the association between age, parity, nationality, educational level, employment and partner support with depression and anxiety during pregnancy. To determine the impact of the evolution of the COVID-19 pandemic on the anxiety and depression levels of the participants. METHOD: Cross-sectional descriptive correlational study carried out in the Osakidetza/Basque Health Service, Primary Care, Bizkaia (Spain). A total of 295 pregnant women between 8 and 41 weeks participated. The association between age, parity, nationality, educational level, employment, partner support and COVID-19 incidence rates during the study period and depression (measured with the Edinburgh Postnatal Depression Scale) and anxiety (measured with the State-Anxiety Inventory/STAI-S subscale) scores during pregnancy was measured. A logistic regression model was constructed and odds ratios and their 95% confidence intervals were estimated. RESULTS: The mean score was 18.75 points for anxiety (SD=8.69) and 6.45 points for depression (SD=4.32). Women expecting their second or later child had higher scores for depression (OR 2.51[95%IC: 1.26-5.01)) and anxiety (OR 1.98 [95%IC: 1.01-3.89]). Having completed university studies was associated with lower scores in depression (OR 0.28 [95%IC: 0.11-0.77]) and in anxiety (OR 0,2 [95%IC: 0.08-0.54]). A good relationship with the partner was associated with lower levels of anxiety (OR 0.45 [95%IC: 0.24-0.81]). The mean anxiety and depression scores are related to the incidence of COVID-19 cases; the anxiety score was significantly higher in periods of higher incidence. CONCLUSIONS: Greater emotional care for pregnant women with low educational level, multiparous and with weak support from their partner, would reduce anxiety and depression in pregnancy. Health emergency situations affect mental health during gestation.

Does the birth plan match what is relevant to women? Preferences of Spanish women when giving birth.

BACKGROUND: To support women in making shared decisions, it is important to know what is relevant to them. The aim is to explore which of the options included in birth plans (BP) are of most interest to women, and which are more controversial. In addition, the possible association of this variability with personal characteristics. METHODS: The data are part of a cross-sectional descriptive study, carried out in xxx, on the clinimetric characteristics of two instruments to measure women's needs in labour and postpartum. Women were recruited consecutively by their midwives during pregnancy check-ups, receive a link to a digital questionnaire and were allowed to provide links to the questionnaires to other pregnant women. Women were asked to determine their level of agreement with statements about the birth environment, accompaniment, pain relief, medical intervention and neonatal care. The relationship between agreement with each statement, socio-demographic variables and fear of childbirth (W-DEQ-A) was analysed using a combination of descriptive statistics to analyse frequencies, and regression models to test the effect of socio-demographic variables and fear of childbirth on those items with the greatest variability. RESULTS: Two hundred forty-seven women responded. More than 90% preferred a hospital delivery, with information about and control over medical intervention, accompanied by their partner and continuous skin-to-skin contact with the newborn. There are other questions to which women attach less importance or which show greater variability, related to more clinical aspects, like foetal monitoring, placenta delivery, or cord clamping… Various factors are related to this variability; parity, nationality, educational level, risk factor or fear of childbirth are the most important. CONCLUSIONS: Some items referring to the need for information and participation are practically unanimous among women, while other items on technical interventions generate greater variability. That should make us think about which ones require a decision after information and which ones should be included directly. The choice of more interventional deliveries is strongly associated with fear of childbirth.

Development and evaluation of the psychometric properties of a digital questionnaire for the evaluation of perinatal psychosocial needs.

BACKGROUND: If the purpose of maternal education is for women to take control of their own health and that of their family in the process, it is essential to have a simple instrument that allows them to self-assess, globally, how prepared they are to face future childbirth and maternity. As there is nothing similar in our area, the objective of this study was to design a complete, specific measurement questionnaire, with good metric quality and in digital format, for the assessment of perinatal psychosocial needs. METHODS: A cross-sectional study was carried out, to evaluate the psychometric properties of a digital measurement questionnaire. The questionnaire was developed in 4 steps following the recommendations of the International Test Commission. The participants were 263 pregnant women who were recruited in primary health care appointments in the Basque Healthcare Service (Osakidetza); they completed the newly created questionnaire and all the test selected as gold standard. Their mean age was 33.55 (SD = 4.73). The analysis of the psychometric characteristics was based on mixed expert judgment procedures (focus group of healthcare professionals, item assessment questionnaire and interviews with users) and quantitative procedures (EFA, CFA, association with the gold standard and classification agreement index, ordinal alpha and McDonald's omega). RESULTS: The final version of the questionnaire was made up of 55 items that evaluate 8 aspects related to perinatal psychosocial well-being (anxious-depressive symptoms, pregnancy acceptance, partner support, coping, internal locus of control, childbirth self-efficacy, perception of childbirth as a medicalized event, and fear of childbirth). Various tests were made of the validity and reliability of the scores, providing metric guarantees for their use in our context. CONCLUSIONS: The use of this complete, quick-to-use tool with good psychometric properties will allow pregnant women to take stock of their situation, assess whether they have the necessary resources in the psychological and social sphere, and work together with midwives and other health professionals in the areas that are lacking.

Development and evaluation of the psychometric properties of a digital questionnaire for the self-management of health and well-being in the postpartum period.

BACKGROUND: Despite the fact that the Global Strategy for Women's, Children's and Adolescents' Health (2016-2030) recognises the special importance of care for women during the postpartum period, thus highlighting the need to identify and measure any condition that may affect the welfare of pregnant women in any way, this is one of the most neglected stages in the health system. Given the absence in our area of global, efficient instruments, the objective of this study was to design a complete, specific measurement tool with good metric qualities in digital format for the evaluation of self-reported health and well-being during the puerperium, to conform to what was proposed by the ICHOM. METHODS: A cross-sectional study was carried out to evaluate the psychometric characteristics of a digital measurement tool. The development of the tool was carried out in 4 steps, following the recommendations of the International Test Commission. It was tested on 280 puerperas attending primary healthcare appointments in the Basque Healthcare System (Osakidetza), and they did the newly created survey, answering all the questions that had been selected as the gold standard. The average age of the women was 34.93 (SD = 4.80). The analysis of the psychometric characteristics was based on mixed procedures of expert judgment (a focus group of healthcare professionals, an item evaluation questionnaire and interviews with users) and quantitative evaluations (EFA, CFA, and correlation with gold standard, ordinal alpha and McDonald's omega). RESULTS: The final version of the tool comprised 99 items that evaluate functional state, incontinence, sexuality, breastfeeding, adaptation to the role of mother and mental health, and all of these questions can be used globally or partially. It was found that the scores were valid and reliable, which gives metric guarantees for using the tool in our area. CONCLUSIONS: The use of this comprehensive concise tool with good psychometric properties will allow women to take stock of their situation, assess if they have the necessary resources, in psychological and social terms, and work together with midwives and other healthcare professionals on the most deficient areas.

Human embryo live imaging reveals nuclear DNA shedding during blastocyst expansion and biopsy.

Proper preimplantation development is essential to assemble a blastocyst capable of implantation. Live imaging has uncovered major events driving early development in mouse embryos; yet, studies in humans have been limited by restrictions on genetic manipulation and lack of imaging approaches. We have overcome this barrier by combining fluorescent dyes with live imaging to reveal the dynamics of chromosome segregation, compaction, polarization, blastocyst formation, and hatching in the human embryo. We also show that blastocyst expansion mechanically constrains trophectoderm cells, causing nuclear budding and DNA shedding into the cytoplasm. Furthermore, cells with lower perinuclear keratin levels are more prone to undergo DNA loss. Moreover, applying trophectoderm biopsy, a mechanical procedure performed clinically for genetic testing, increases DNA shedding. Thus, our work reveals distinct processes underlying human development compared with mouse and suggests that aneuploidies in human embryos may not only originate from chromosome segregation errors during mitosis but also from nuclear DNA shedding.

Coping strategies during pregnancy and their relationship with anxiety and depression.

How individuals perceive and cope with stressful situations may determine their level of anxiety or depression. The identification of coping strategies (CS) in pregnancy could help prevent depression and anxiety (D&A), and their consequent effects on the health of the mother and the baby. A cross-sectional descriptive correlational study was conducted to identify the CS most commonly used by pregnant women in a Spanish population and to evaluate the association of these CS with D&A. A consecutive sample of 282 pregnant women over 18 years of age were recruited when attended midwife consultations and through snowball sampling between December 2019 and January 2021 in the Basque public health system. CS were measured using the RevisedPrenatal Coping Inventory (NuPCI) questionnaire, assigning the score to an avoidant, preparatory or spiritual scale. Cutoff points were established to categorize anxiety and depressive symptomatology, using the STAI-S and EPDS scales. Multivariate logistic regression models were constructed to analyze the association between CS and D&A. The results show that the higher the score on the avoidance subscale, the higher the likelihood of having an anxiety disorder (OR: 8.88  (95 percent Confidence Interval [CI] 4.26-20.1), and depressive symptoms (OR: 8.29 (95 percent CI 4.24-17.4). Multiparous women are more likely to have anxiety (OR: 3.41  (95 percent CI 1.58-7.5) or depressive symptomatology (OR: 4.1 (95 percent CI 2.04-8.53) during pregnancy. These results highlight the need to consider the evaluation of CS used during pregnancy to tailor the care provided, but further studies on the implementation and effectiveness of interventions are needed.

Cell-free deoxyribonucleic acid analysis in preimplantation genetic testing.

Detection of chromosomal aneuploidies and monogenic disorders in preimplantation embryos is essential for selecting the best embryo for transfer during in vitro fertilization to achieve a healthy pregnancy. Preimplantation genetic testing (PGT) is typically performed on preimplantation embryos to select a genetically normal embryo for transfer. A trophectoderm biopsy is necessary for PGT; this is an invasive procedure to the embryo that requires specialized equipment and highly trained embryologists, resulting in high costs associated with in vitro fertilization treatment. Moreover, the biopsy procedure may increase the likelihood of developing pregnancy complications, such as preeclampsia and hypertensive disorders. Therefore, there is a need for noninvasive embryo screening strategies. The presence of cell-free deoxyribonucleic acid in the embryo culture medium presents an opportunity to screen for genetic abnormalities. Cell-free deoxyribonucleic acid is released by embryos in the latter stages of preimplantation development, and its analysis has been proposed as a noninvasive approach for PGT. Here, we review studies reporting the concordance rates between cell-free deoxyribonucleic acid and trophectoderm biopsies, or whole blastocysts, in couples undergoing PGT. Noninvasive PGT results are promising for aneuploidy detection, with some early evidence of successful clinical application. Further research is required to explore its application for the detection of structural rearrangements and monogenic disorders.

EMAeHealth, a digital tool for the self-management of women's health needs during pregnancy, childbirth and the puerperium: protocol for a hybrid effectiveness-implementation study.

INTRODUCTION: EHealth can help health service users take a more active role in decision-making and help health professionals guide the patient in this process. A digital tool has been designed to support maternal education (ME), and it is organised into four areas: (1) information, (2) communication, (3) health self-management and (4) clinical data. The main objective of the study is to evaluate the effectiveness of the EMAeHealth digital tool, and assess its usability and acceptability under routine conditions. METHODS AND ANALYSIS: Hybrid implementation-effectiveness design: (1) A cluster randomised, prospective, longitudinal, multicentre clinical trial to evaluate the effectiveness of EMAeHealth in (A) improving health-related quality of life (primary outcome), (B) improving self-efficacy for labour and childbirth and self-efficacy in breast feeding and (C) reducing the number of visits to the obstetric emergency services and health centre in situations of 'non-pathological pregnancy', 'false labour pains' and 'non-pathological puerperium'. The EMAeHealth intervention plus usual care will be compared with receiving only usual care, which includes traditional ME. N=1080 participants, 540 for each study arm. Two measurements will be made throughout the pregnancy and three in the first 16 weeks post partum. (2) A mixed-method study to evaluate the usability and acceptability of the tool, barriers and facilitators for its use, and implementation in our health system: focus groups (women, professionals and agents involved) and a quantitative analysis of implementation indicators. ANALYSIS: It will be carried out by intention to treat, using mixed models taking into account the hierarchical structure of the data and per protocol to evaluate the effectiveness of the express use of the digital tool. ETHICS AND DISSEMINATION: Clinical Research Ethics Committee of Euskadi, Spain, (Ref: PI2020044) approved this study. The results will be actively disseminated through manuscript publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04937049.

Attitudes toward medicalization in childbirth and their relationship with locus of control and coping in a Spanish population.

The dominant model of childbirth in most Western countries is medicalized childbirth. Women's beliefs about whether childbirth should be a medicalized process to a greater or lesser degree may be related, in addition to contextual factors, to internal factors. The objective of the study is to find out if women's locus of control (LC) and stress coping strategies (CS) are related to having a more favourable or less favourable attitude towards medicalization (ATMC). A cross-sectional study was carried out with the participation of 248 women recruited in primary care centres by their midwives. All the women filled in answers on a mobile phone app with various different measurement instruments: the questionnaire created by Benyamini to evaluate their ATMC; the Spanish version of the Wallston MLC to evaluate their LC; and the Spanish adaptation of the "Revised Prenatal Coping Inventory (NuPCI)" scale for the assessment of their CS. The women presented a favourable attitude towards medicalization, with a mean ATMC score of 3.42. Both the LC and the CS of women during pregnancy are related to this attitude. Specifically, having an internal LC and using preparative CS both lower the probability of presenting a favourable attitude towards medicalization, while the lack of a paid job raises the probability. For each point in internal locus and preparatory coping, the ATMC score decreased by 0.02 and 0.23 points, respectively, while it increased by 0.18 for not having a paid job. The influence of these psychological factors must be taken into account in the development of content and interventions that promote a more natural birth.

Efectividad de la autotoma del exudado vaginorrectal para el cribado prenatal de la infección por Streptococcus agalactiae. Estudio GALL / Effectiveness of the vagino-rectal exudate self-sampling for prenatal screening of Streptococcus agalactiae infection. GALL study

Objetivo: Evaluar la efectividad de la autotoma del exudado vaginorrectal para el cribado prenatal de la infección por EGB e identificar barreras y facilitadores que encuentra la gestante para esta intervención. Diseño: Estudio transversal de pruebas diagnósticas. Participantes y emplazamiento: Participaron 213 gestantes que acudieron a la consulta de la matrona de atención primaria en 6 centros de salud del Servicio Vasco de Salud/Osakidetza en Bizkaia, que cumplían los criterios de inclusión y aceptaban participar en el estudio. Mediciones principales: Se comparó el resultado del cultivo vaginorrectal obtenido por la gestante con el resultado del cultivo vaginorrectal tomado por la matrona en consulta el mismo día, y se recogieron barreras y facilitadores encontrados por las mujeres en la autotoma. Resultados: Se ha observado que la autotoma como prueba para detectar el EGB tiene una sensibilidad del 93,3% (IC 95%, 78,7-98,2), una especificidad del 99,4% (IC 95%, 96,5-99,9), un valor predictivo positivo del 96% (IC 95% 82,8-99,4) y un valor predictivo negativo del 98,8% (IC 95%, 95,6-99,7). El 27,3% de los encuestadas encontraron alguna dificultad en la recogida, solo el 4,8% no se vieron capacitadas, el 84,2% se sintieron cómodas, el 99,5% consideraron la información proporcionada adecuada y completa, al 94,7% no le resultaron complicados los pasos a seguir, y el 96% están satisfechas con el estudio. Conclusiones: La autotoma del exudado vaginorrectal para la detección del EGB ha resultado ser válida y fiable, lo que permitiría ofrecer esta opción a las gestantes en el cribado sistemático de la infección por EGB.(AU)

Objetive: To evaluate the effectiveness of vagino-rectal swab autotomy for prenatal screening for GBS infection and to identify the barriers and facilitators encountered by the pregnant woman for this intervention. Design: Cross-sectional study of diagnostic tests. Participants and site: A total of 213 pregnant women who attended the primary care midwife's office in 6 health centers of the Basque Health Service/Osakidetza in Bizkaia, who met the inclusion criteria and agreed to participate in the study, participated in the study. Main measurements: The result of the vagino-rectal culture obtained by the pregnant woman was compared with the result of the vagino-rectal culture taken by the midwife in consultation on the same day, and the barriers and facilitators encountered by the women in the self-test were collected. Results: Self-testing as a test for GBS was found to have a sensitivity of 93.3% (95% CI 78.7–98.2), a specificity of 99.4% (95% CI 96.5–99.9), a positive predictive value of 96% (95% CI 82.8–99.4) and a negative predictive value of 98.8% (95% CI 95.6–99.7). 27.3% of respondents encountered some difficulty in the collection, only 4.8% did not feel qualified, 84.2% felt comfortable, 99.5% considered the information provided to be adequate and complete, 94.7% did not find the steps to follow complicated, and 96% were satisfied with the study. Conclusions: Self-collection of vagino-rectal exudate for GBS detection has proved to be valid and reliable, which would make it possible to offer this option to pregnant women in the systematic screening for GBS infection.(AU)

[Effectiveness of the vagino-rectal exudate self-sampling for prenatal screening of Streptococcus agalactiae infection. GALL study]. / Efectividad de la autotoma del exudado vaginorrectal para el cribado prenatal de la infección por Streptococcus agalactiae. Estudio GALL.

OBJETIVE: To evaluate the effectiveness of vagino-rectal swab autotomy for prenatal screening for GBS infection and to identify the barriers and facilitators encountered by the pregnant woman for this intervention. DESIGN: Cross-sectional study of diagnostic tests. PARTICIPANTS AND SITE: A total of 213 pregnant women who attended the primary care midwife's office in 6 health centers of the Basque Health Service/Osakidetza in Bizkaia, who met the inclusion criteria and agreed to participate in the study, participated in the study. MAIN MEASUREMENTS: The result of the vagino-rectal culture obtained by the pregnant woman was compared with the result of the vagino-rectal culture taken by the midwife in consultation on the same day, and the barriers and facilitators encountered by the women in the self-test were collected. RESULTS: Self-testing as a test for GBS was found to have a sensitivity of 93.3% (95% CI 78.7-98.2), a specificity of 99.4% (95% CI 96.5-99.9), a positive predictive value of 96% (95% CI 82.8-99.4) and a negative predictive value of 98.8% (95% CI 95.6-99.7). 27.3% of respondents encountered some difficulty in the collection, only 4.8% did not feel qualified, 84.2% felt comfortable, 99.5% considered the information provided to be adequate and complete, 94.7% did not find the steps to follow complicated, and 96% were satisfied with the study. CONCLUSIONS: Self-collection of vagino-rectal exudate for GBS detection has proved to be valid and reliable, which would make it possible to offer this option to pregnant women in the systematic screening for GBS infection.

Non-invasive preimplantation genetic testing for aneuploidies: an update.

Aneuploidy is common among preimplantation human embryos used in assisted reproductive technology. Because abnormal chromosome number can negatively affect reproductive outcome, in-vitro-fertilized embryos routinely undergo aneuploidy testing before transfer into the uterus. This testing typically involves an invasive trophectoderm biopsy of a blastocyst-stage embryo. However, emerging evidence indicates that, during in-vitro development, embryos secrete cell-free DNA into their culture medium; this phenomenon suggests the potential for an alternative, non-invasive assay for aneuploidy. Embryonic cell-free DNA-based assays exhibit high concordance with trophectoderm biopsies, inner cell mass and the whole blastocyst. Yet informativity and concordance rates may be influenced by several factors: the culture day when the medium is collected, contamination with external and/or cumulus cell DNA, and previous manipulation of the embryos. This review discusses non-invasive embryonic cell-free DNA analysis as a biomarker to prioritize blastocysts for transfer to help increase implantation rates and reduce miscarriage rates and time to achieve pregnancy. Ongoing research on the mechanisms underlying embryonic cell-free DNA secretion and how this impacts its role as a biomarker of aneuploidy are also discussed.

Design of the Maternal Website EMAeHealth That Supports Decision-Making During Pregnancy and in the Postpartum Period: Collaborative Action Research Study.

BACKGROUND: Despite the benefit maternal education has for women, it needs new tools to increase its effectiveness and scope, in tune with the needs of current users. OBJECTIVE: We attempted to develop a multifunctional personalized eHealth platform aimed at the self-management of health in relation to maternity, which can be considered a flexible and adaptable maternal education tool. METHODS: The International Patient Decision Aid Standards (IPDAS) were applied. A website prototype was developed for implementation in the public health system using a collaborative action research process, in which experts and patients participate, with qualitative research techniques, as well as focus groups, prioritization, and consensus techniques. RESULTS: We have proposed a website that includes (1) systematically updated information related to clinical practice guidelines, (2) interaction between peers and users/professionals, (3) instruments for self-assessment of health needs as a basis for working on counseling, agreement on actions, help in the search for resources, support in decision-making, and monitoring and evaluation of results, and (4) access for women to their clinical data and the option of sharing the data with other health agents. These components, with different access requirements, would be reviewed through iterative cycles depending on the frequency and effectiveness resulting from their use and would be accessible from any digital device. CONCLUSIONS: A website that supports maternal education should contain not only information, but also resources for individual attention and social support. Its usefulness for the health and satisfaction of women should be evaluated in various different environments.

Development of two instruments for assessing maternity health needs: protocol of a clinimetric study.

BACKGROUND: There is an unquestionable need to adapt health care to the needs of each woman, to foster her self-confidence and provide her with the autonomy to manage her own maternity. This involves empowering her to choose and face her model of childbirth and childcare responsibly. The range of self-management health needs tests offered by the scientific community at this stage of life is practically non-existent. In this project, we intend to develop and evaluate the validity, reliability and ease of use of two self-administered analysis instruments for: 1.- Needs of women preparing for childbirth and 2.- Identification of alarm symptoms in the puerperium. METHODS: This is a descriptive study of the clinimetric characteristics and usability of two developed self-applied digital instruments for measuring needs in childbirth and postpartum based on the recommendations made in the consensus-based standards for the selection of health measurement instruments (COSMIN) and by the International Test Commission (ITC). The study consists of two phases: 1 - Evaluation of the clinimetric properties of the two instruments, which were developed and then altered, based on their comprehensibility and global usability estimated from a pilot study and 2 - Pre-implementation study. DISCUSSION: The final product will be two valid, reliable, usable instruments for self-assessment of health needs that are highly acceptable to young couples and the professionals who serve them. They will be a valuable resource for meeting the needs of the population more efficiently and guiding decision-making, and they will contribute to the greater sustainability of the health system.

Optimized NGS Approach for Detection of Aneuploidies and Mosaicism in PGT-A and Imbalances in PGT-SR.

The detection of chromosomal aneuploidies and mosaicism degree in preimplantation embryos may be essential for achieving pregnancy. The aim of this study was to determine the robustness of diagnosing homogenous and mosaic aneuploidies using a validated algorithm and the minimal resolution for de novo and inherited deletions and duplications (Del/Dup). Two workflows were developed and validated: (a,b) preimplantation genetic testing for uniform whole and segmental aneuploidies, plus mixtures of euploid/aneuploid genomic DNA to develop an algorithm for detecting mosaicism; and (c) preimplantation genetic testing for structural rearrangements for detecting Del/Dup ≥ 6 Mb. Next-generation sequencing (NGS) was performed with automatic library preparation and multiplexing up to 24-96 samples. Specificity and sensitivity for PGT-A were both 100% for whole chromosomes and segmentals. The thresholds stablished for mosaicism were: euploid embryos (<30% aneuploidy), low mosaic (from 30% to <50%), high mosaic (50-70%) or aneuploid (>70%). In the PGT-SR protocol, changes were made to increase the detection level to ≥6 Mb. This is the first study reporting an accurate assessment of semiautomated-NGS protocols using Reproseq on pools of cells. Both protocols allow for the analysis of homogeneous and segmental aneuploidies, different degrees of mosaicism, and small Del/Dup with high sensitivity and specificity.

The dawn of the future: 30 years from the first biopsy of a human embryo. The detailed history of an ongoing revolution.

Following early studies showing no adverse effects, cleavage stage biopsy by zona drilling using acid Tyrode's solution, and removal of single blastomeres for preimplantation genetic testing (PGT) and identification of sex in couples at risk of X-linked disease, was performed by Handyside and colleagues in late 1989, and pregnancies reported in 1990. This method was later used for specific diagnosis of monogenic conditions, and a few years later also for chromosomal structural and/or numerical impairments, thereby establishing a valuable alternative option to prenatal diagnosis. This revolutionary approach in clinical embryology spread worldwide, and several other embryo biopsy strategies developed over three decades in a process that is still ongoing. The rationale of this narrative review is to outline the different biopsy approaches implemented across the years in the workflow of the IVF clinics that provided PGT: their establishment, the first clinical experiences, their downsides, evolution, improvement and standardization. The history ends with a glimpse of the future: minimally/non-invasive PGT and experimental embryo micromanipulation protocols. This grand theme review outlines a timeline of the evolution of embryo biopsy protocols, whose implementation is increasing worldwide together with the increasing application of PGT techniques in IVF. It represents a vade mecum especially for the past, present and upcoming operators and experts in this field to (re)live this history from its dawn to its most likely future.

Multicenter prospective study of concordance between embryonic cell-free DNA and trophectoderm biopsies from 1301 human blastocysts.

BACKGROUND: The recent identification of embryonic cell-free DNA in spent blastocyst media has opened a new era of possibilities for noninvasive embryo aneuploidy testing in assisted reproductive technologies. Yet, previous studies assessing a limited number of embryos reported variable concordance between embryonic cell-free DNA and trophectoderm biopsies, thus questioning the validity of this approach. OBJECTIVE: This study aimed to evaluate the concordance and reproducibility of testing embryonic cell-free DNA vs trophectoderm DNA obtained from the same embryo in a large sample of human blastocysts and to assess the contribution of the inner cell mass and trophectoderm to embryonic cell-free DNA released to the culture media. STUDY DESIGN: This is an interim analysis of a prospective, observational study among 8 in vitro fertilization centers in 4 continents to assess consistency between noninvasive embryo aneuploidy testing of embryonic cell-free DNA and conventional trophectoderm biopsy. The analysis included 1301 day-6/7 blastocysts obtained in 406 in vitro fertilization cycles from 371 patients aged 20-44 years undergoing preimplantation genetic testing for aneuploidy. Fresh oocytes underwent intracytoplasmic sperm injection or in vitro fertilization. No previous assisted hatching or vitrification was allowed before media collection. Individual spent blastocyst medium was collected from embryos cultured at least 40 hours from day 4. After media collection, conventional preimplantation genetic testing for aneuploidy, comprising trophectoderm biopsy and blastocyst vitrification, was performed. Embryonic cell-free DNA was analyzed blindly after embryo transfer. Inner cell mass and trophectoderm biopsies were also performed in a subset of 81 aneuploid blastocysts donated for research. RESULTS: Embryonic cell-free DNA analyses were 78.2% (866/1108) concordant with the corresponding trophectoderm biopsies. No significant differences were detected among centers ranging from 72.5% to 86.3%. Concordance rates exceeded 86% when all defined steps in the culture laboratory were controlled to minimize the impact of maternal and operator contamination. Sensitivity per center ranged from 76.5% to 91.3% and specificity from 64.7% to 93.3%. The false-negative rate was 8.3% (92/1108), and false-positive rate was 12.4% (137/1108). The 2 fertilization techniques provided similar sensitivity (80.9% vs 87.9%) and specificity (78.6% vs 69.9%). Multivariate analysis did not reveal any bias from patient clinical background, ovarian stimulation protocols, culture conditions, or embryo quality on testing accuracy of concordance. Moreover, concordances of embryonic cell-free DNA with trophectoderm and inner cell mass suggest that the embryonic cell-free DNA originates from both compartments of the human embryo. CONCLUSION: Noninvasive analysis of embryonic cell-free DNA in spent blastocyst culture media demonstrates high concordance with trophectoderm biopsy results in this large multicenter series. A noninvasive approach for prioritizing embryo euploidy offers important advantages such as avoiding invasive embryo biopsy and decreased cost, potentially increasing accessibility for a wider patient population.

Consensus on priorities in maternal education: results of Delphi and nominal group technique approaches.

BACKGROUND: Maternal education is wide-ranging and covers many areas from pregnancy to the immediate postpartum period and childrearing. However, for it to be effective, more resources need to be assigned to key topics. The goal of this study was to identify and prioritize the most important issues in maternal education, so that specific objectives could subsequently be set and learning outcomes evaluated. METHODS: We drew up a comprehensive list of topics addressed in existing maternal education programs, based on a systematic review of information obtained from the Internet and the experience of the research team. The topics were presented to a multidisciplinary panel whose members were asked to rate them from 1 to 9, and consensus of opinion was reached using a two-round Delphi survey, with consensus defined beforehand as 80% agreement among panelists in awarding a score of 7, 8 or 9. The most highly-rated topics were then discussed and again prioritized by a multidisciplinary team of healthcare and non-healthcare experts, using a nominal group technique. RESULTS: Initially, 650 topics were identified and grouped into 80 categories which were then prioritized by 54 healthcare and non-healthcare experts using a Delphi survey with a study participation rate of around 20%. 63 topics were considered very important, so criteria were restricted and only the 24 highest-scoring selected (95% of agreement on scores ≥7 or 80% of agreement on scores ≥8). Using the nominal group technique, a group of 12 experts identified the following priorities: initiation and establishment of breastfeeding, development of a birth plan, identification of problems and self-care postpartum, nutrition and a healthy lifestyle, options for pain management in labor and birth and characteristics of a normal newborn/looking after a newborn baby. CONCLUSION: This study, with a Delphi study and the Consensus among Experts: the nominal group technique, has succeeded in identifying priority topics in maternal education. We need to assess women's needs in relation to these topics, design an intervention to respond to these needs and evaluate its effectiveness.