Routine use of cell salvage during cesarean section: A practice evaluation.

INTRODUCTION: Intraoperative cell salvage is a well-documented alternative to donor blood transfusion given the scarcity of donor blood pools and the incumbent risk of allogenic blood transfusion. Its use in obstetrics has been limited by concern over fetal alloimmunization due to the risk of fetomaternal hemorrhage. However, there are a paucity of studies reporting on outcome. The aim of this study was to report on a four-year experience of routine use of intraoperative cell salvage and the impact on subsequent pregnancy outcomes. MATERIAL AND METHODS: This was a tertiary center retrospective service evaluation cohort study and included all women undergoing cesarean section between December 2014 and November 2018 in a tertiary obstetric unit, identifying women who had reinfusion of intraoperative cell salvage. Data regarding index pregnancy as well as subsequent pregnancies at the hospital were extracted from hospital electronic records. Subsequent pregnancy outcome and maternal antibody status in that pregnancy were collected up until November 2022. RESULTS: During the study period, 6656 cesarean sections were performed, with 436 (6.6%) receiving reinfusion of salvaged blood. The mean volume of reinfused blood was 396 mL. A total of 49 (0.7%) women received donor blood transfusion. Of those who received reinfusion of salvaged blood, 79 (18.1%) women had subsequent pregnancies over the eight-year follow-up period. There was one case (0.23%) of fetal cell alloimmunization demonstrated by the presence of anti-D antibodies on the subsequent pregnancy booking bloods. CONCLUSIONS: Routine intraoperative cell salvage may be used to reduce the need for blood transfusion during cesarean section. The risk of fetal cell alloimmunization in a future pregnancy following reinfusion of intraoperative cell salvage is one in 436. Given an apparent small risk of fetal cell alloimmunization, further work is required to establish the safety profile of intraoperative cell salvage in pregnancy.

Quantitative assessment of pregnancy outcome following recurrent miscarriage clinic care: a prospective cohort study.

OBJECTIVES: To measure pregnancy outcome following attendance at a recurrent miscarriage service and identify factors that influence outcome. DESIGN: Prospective, observational electronic cohort study. SETTING: Participants attending a specialist recurrent miscarriage clinic, with a history of two or more pregnancy losses. 857 new patients attended over a 30-month period and were invited to participate. Participant data were recorded on a bespoke study database, 'Tommy's Net'. PARTICIPANTS: 777 women consented to participate (90.7% of new patients). 639 (82%) women continued within the cohort, and 138 were lost to follow-up. Mean age of active participants was 34 years for women and 37 years for partners, with a mean of 3.5 (1-19) previous pregnancy losses. Rates of obesity (maternal: 23.8%, paternal: 22.4%), smoking (maternal:7.4%, paternal: 19.4%) and alcohol consumption (maternal: 50%, paternal: 79.2%) were high and 55% of participants were not taking folic acid. OUTCOME MEASURES: Biannual collection of pregnancy outcomes, either through prompted self-reporting, or existing hospital systems. RESULTS: 639 (82%) women were followed up. 404 (83.4%) reported conception and 106 (16.6%) reported no pregnancy, at least 6 months following registration. Of those that conceived, 72.8% (294/404) had a viable pregnancy. Maternal smoking and body mass index (BMI) over 30 were significantly higher in those who did not conceive (p=0.001) CONCLUSIONS: Tommy's Net provides a secure electronic repository on data for couples with recurrent pregnancy loss and associated outcomes. The study identified that subfertility, as well as repeated miscarriage, maternal BMI and smoking status, contributed to failure to achieve live birth. Study findings may enable comparison of clinic outcomes and inform the development of a personalised holistic care package.

Intralipid infusion at time of embryo transfer in women with history of recurrent implantation failure: A systematic review and meta-analysis.

AIM: Recurrent implantation failure (RIF) affects 10% of couples undergoing assisted conception, often due to poor endometrial receptivity. We conducted a systematic review and meta-analysis to evaluate the effectiveness of Intra-venous intralipid (IVI) in improving pregnancy rates in women with history of RIF using. METHODS: We searched MEDLINE, EMBASE, and CENTRAL for any randomized trials evaluating the use of IVI at the time of embryo transfer in women undergoing assisted conception until September 2020. We extracted data in duplicate and assessed risk of bias using the Cochrane Risk of Bias tools. We meta-analyzed data using a random effect model. RESULTS: We included five randomized trials reporting on 843 women with an overall moderate risk of bias. All trials used 20% IVI solution at the time of embryo transfer compared to normal saline infusion or no intervention (routine care). The IVI group had a higher chance of clinical pregnancy (172 vs 119, risk ratio [RR] 1.55, 95% confidence interval [CI] 1.16-2.07, I2 44.2%) and live birth (132 vs 73, RR 1.83, 95% CI 1.42-2.35, I2 0%) post treatment compared to no intervention. Our findings are limited by the small sample size and the variations in treatment protocols and population characteristics. CONCLUSION: There is limited evidence to support the use of IVI at the time of embryo transfer in women with the history of RIF. More research is needed before adopting it in clinical practice.

Reproductive outcomes in women and men using complementary and alternative medicine treatment and not receiving artificial reproductive technology: a systematic review.

PURPOSE: Infertility is a global problem, but only a minority of couples access assisted reproductive technologies due to financial and sociocultural barriers. Complementary and alternative medicine are seen as another option. We aimed to determine the impact of complementary and alternative medicine on conception, miscarriage and live birth rates in couples not receiving assisted reproductive technology treatments. METHODS: The electronic databases EMBASE, PubMed, Web of Science and the Allied and Complementary Medicine Database were systematically searched before March 24th 2020. Reference lists of eligible studies were searched for relevant studies. Eligible studies included trials and observational studies that assessed a complementary or alternative medicine and conception, miscarriage or live births in men or women not undergoing fertility treatment. Data were extracted by two independent reviewers using a pre-designed data collection form. The study protocol was published in the PROSPERO database (CRD42018086980). RESULTS: Twenty randomized controlled trials were identified, including 2748 individuals. Most studies did not demonstrate any effect of a complementary or alternative medicine on pregnancy, live birth or miscarriage rates. Limited evidence was found for a positive effect of herbal therapies taken by women on conception rates. There was substantial diversity in quality across the studies. CONCLUSION: There is limited evidence of the effectiveness of complementary and alternative medicine on improving the chances of conception and live births, or increasing miscarriage risk. Owing to the generally sub-optimal quality and heterogeneous nature of the evidence, rigorous studies are needed to determine the impact of complementary and alternative medicine on fertility.

Functionally Selective Inhibition of the Oxytocin Receptor by Retosiban in Human Myometrial Smooth Muscle.

Novel small molecule inhibitors of the oxytocin receptor (OTR) may have distinct pharmacology and mode of action when compared with first-generation oxytocin antagonists when used for the prevention of preterm birth. The aim was to determine the mechanism of action of small molecule OTR antagonists retosiban and epelsiban compared with the currently used peptide-based compound atosiban. Human myometrial samples were obtained at cesarean section and subjected to pharmacological manipulations to establish the effect of antagonist binding to OTR on downstream signaling. Retosiban antagonism of oxytocin action in human myometrium was potent, rapid, and reversible. Inhibition of inositol 1,4,5-trisphosphate (IP3) production followed single-site competitive binding kinetics for epelsiban, retosiban, and atosiban. Retosiban inhibited basal production of IP3 in the absence of oxytocin. Oxytocin and atosiban but not retosiban inhibited forskolin, and calcitonin stimulated 3',5'-cyclic adenosine 5'-mono-phosphate (cAMP) production. Inhibition of cAMP was reversed by pertussis toxin. Oxytocin and atosiban, but not retosiban and epelsiban, stimulated extracellular regulated kinase (ERK)1/2 activity in a time- and concentration-dependent manner. Oxytocin and atosiban stimulated cyclo-oxygenase 2 activity and subsequent production of prostaglandin E2 and F2α. Prostaglandin production was inhibited by rofecoxib, pertussin toxin, and ERK inhibitor U0126. Oxytocin but not retosiban or atosiban stimulated coupling of the OTR to Gα q G-proteins. Oxytocin and atosiban but not retosiban stimulated coupling of the OTR to Gα i G-proteins. Retosiban and epelsiban demonstrate distinct pharmacology when compared with atosiban in human myometrial smooth muscle. Atosiban displays agonist activity at micromolar concentrations leading to stimulation of prostaglandin production.

Maternal obesity-induced decreases in plasma, hepatic and uterine polyunsaturated fatty acids during labour is reversed through improved nutrition at conception.

Maternal obesity is associated with prolonged and dysfunctional labour, potentially through decreased synthesis of prostaglandins that stimulate myometrial contractions. We assessed the impact of maternal obesity on concentrations of precursor fatty acids (FA) for prostaglandin synthesis and whether any changes could be reversed by improved nutrition post-conception. Wistar rats were fed control (CON) or High-Fat, High-cholesterol (HFHC) diets 6 weeks before mating. At conception half the dams switched diets providing 4 dietary groups: (1) CON, (2) HFHC, (3) CON-HFHC or (4) HFHC-CON. During parturition rats were euthanized and FA composition of plasma, liver and uterus determined. Visceral fat was doubled in rats exposed to the HFHC diet prior to and/or during pregnancy compared to CON. HFHC diet increased MUFAs but decreased omega-3 and omega-6 PUFAs in plasma and liver. Uterine omega-3 FA concentrations were halved in HFHC versus CON rats, but all other FAs were similar. Switching from HFHC to CON diet at conception restored all FA profiles to those seen in CON rats. The increased MUFA and decreased PUFA concentrations in obese HFHC dams may contribute to aberrant prostaglandin synthesis and dysfunctional myometrial activity and it may be possible to reverse these changes, and potentially improve labour outcomes, by improving nutrition at conception.

Can training in advanced clinical skills in obstetrics, neonatal care and leadership, of non-physician clinicians in Malawi impact on clinical services improvements (the ETATMBA project): a process evaluation.

OBJECTIVES: The 'enhancing human resources and the use of appropriate technologies for maternal and perinatal survival in sub-Saharan Africa' (ETATMBA) project is training emergency obstetric and new-born care (EmONC) non-physician clinicians (NPCs) as advanced clinical leaders. Our objectives were to evaluate the implementation and changes to practice. DESIGN: A mixed methods process evaluation with the predominate methodology being qualitative. SETTING: Rural and urban hospitals in 8 of the 14 districts of northern and central Malawi. PARTICIPANTS: 54 EmONC NPCs with 3 years' plus experience. INTERVENTION: Training designed and delivered by clinicians from the UK and Malawi; it is a 2-year plus package of training (classroom, mentorship and assignments). RESULTS: We conducted 79 trainee interviews over three time points during the training, as well as a convenience sample of 10 colleagues, 7 district officers and 2 UK obstetricians. Trainees worked in a context of substantial variation in the rates of maternal and neonatal deaths between districts. Training reached trainees working across the target regions. For 46 trainees (8 dropped out of the course), dose delivered in terms of attendance was high and all 46 spent time working alongside an obstetrician. In early interviews trainees recalled course content unprompted indicating training had been received. Colleagues and district officers reported cascading of knowledge and initial changes in practice indicating early implementation. By asking trainees to describe actual cases we found they had implemented new knowledge and skills. These included life-saving interventions for postpartum haemorrhage and eclampsia. Trainees identified the leadership training as enabling them to confidently change their own practice and initiate change in their health facility. CONCLUSIONS: This process evaluation suggests that trainees have made positive changes in their practice. Clear impacts on maternal and perinatal mortality are yet to be elucidated.

The impact of training non-physician clinicians in Malawi on maternal and perinatal mortality: a cluster randomised controlled evaluation of the enhancing training and appropriate technologies for mothers and babies in Africa (ETATMBA) project.

BACKGROUND: Maternal mortality in much of sub-Saharan Africa is very high whereas there has been a steady decline in over the past 60 years in Europe. Perinatal mortality is 12 times higher than maternal mortality accounting for about 7 million neonatal deaths; many of these in sub-Saharan countries. Many of these deaths are preventable. Countries, like Malawi, do not have the resources nor highly trained medical specialists using complex technologies within their healthcare system. Much of the burden falls on healthcare staff other than doctors including non-physician clinicians (NPCs) such as clinical officers, midwives and community health-workers. The aim of this trial is to evaluate a project which is training NPCs as advanced leaders by providing them with skills and knowledge in advanced neonatal and obstetric care. Training that will hopefully be cascaded to their colleagues (other NPCs, midwives, nurses). METHODS/DESIGN: This is a cluster randomised controlled trial with the unit of randomisation being the 14 districts of central and northern Malawi (one large district was divided into two giving an overall total of 15). Eight districts will be randomly allocated the intervention. Within these eight districts 50 NPCs will be selected and will be enrolled on the training programme (the intervention). Primary outcome will be maternal and perinatal (defined as until discharge from health facility) mortality. Data will be harvested from all facilities in both intervention and control districts for the lifetime of the project (3-4 years) and comparisons made. In addition a process evaluation using both quantitative and qualitative (e.g. interviews) will be undertaken to evaluate the intervention implementation. DISCUSSION: Education and training of NPCs is a key to improving healthcare for mothers and babies in countries like Malawi. Some of the challenges faced are discussed as are the potential limitations. It is hoped that the findings from this trial will lead to a sustainable improvement in healthcare and workforce development and training. TRIAL REGISTRATION: ISRCTN63294155.