CDC's Guiding Principles to Promote an Equity-Centered Approach to Public Health Communication.

A public health practitioner's mission is to protect and promote the health of all people in all communities. Components of being successful in that mission include understanding who is at risk of negative outcomes, identifying effective actions to promote and protect health, and communicating information accordingly. Information must be scientifically rigorous, provide appropriate contextualizing information, and refer to and visually represent people through words and images in respectful ways. Public health communication objectives include that the audience accepts, understands, and acts on the information to protect and promote health. This article describes the impetus for, development of, and public health applications and implications of principles to guide communication efforts. CDC's Health Equity Guiding Principles for Inclusive Communication is a web-based resource published in August 2021 that offers - but does not mandate - guidance and recommendations for public health practice. The resource can help public health practitioners and their partners consider social inequities and diversity, think more inclusively about the people they serve, and adapt to the cultural, linguistic, environmental, and historical situation of each population or audience of focus. Users are encouraged to have conversations about the Guiding Principles as they plan and develop communication products and strategies in collaboration with communities and partners and build a shared vocabulary consistent with how communities and groups of focus see and understand themselves, because words matter. As the public health field renews its focus on shifting the paradigm toward equity, a language and narrative shift is a vital intervention.

Uterine CD56+ cell density and euploid miscarriage in women with a history of recurrent miscarriage: A clinical descriptive study.

In women with a history of recurrent miscarriage, the uterine CD56+ cell density in subjects with subsequent euploid miscarriage was significantly higher than those with subsequent aneuploid miscarriage. Both endometrial and embryonic factors should be investigated when interpreting uterine CD56+ cell density results relating to recurrent miscarriage.

A randomised controlled trial to assess the clinical effectiveness and safety of the endometrial scratch procedure prior to first-time IVF, with or without ICSI.

STUDY QUESTION: What is the clinical-effectiveness and safety of the endometrial scratch (ES) procedure compared to no ES, prior to usual first time in vitro fertilisation (IVF) treatment? SUMMARY ANSWER: ES was safe but did not improve pregnancy outcomes when performed in the mid-luteal phase prior to the first IVF cycle, with or without intracytoplasmic sperm injection (ICSI). WHAT IS KNOWN ALREADY: ES is an 'add-on' treatment that is available to women undergoing a first cycle of IVF, with or without ICSI, despite a lack of evidence to support its use. STUDY DESIGN, SIZE, DURATION: This pragmatic, superiority, open-label, multi-centre, parallel-group randomised controlled trial involving 1048 women assessed the clinical effectiveness and safety of the ES procedure prior to first time IVF, with or without ICSI, between July 2016 and October 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants aged 18-37 years undergoing their first cycle of IVF, with or without ICSI, were recruited from 16 UK fertility clinics and randomised (1:1) by a web-based system with restricted access rights that concealed allocation. Stratified block randomisation was used to allocate participants to TAU or ES in the mid-luteal phase followed by usual IVF with or without ICSI treatment. The primary outcome was live birth after completing 24 weeks gestation within 10.5 months of egg collection. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 1048 women randomised to TAU (n = 525) and ES (n = 523) were available for intention to treat analysis. In the ES group, 453 (86.6%) received the ES procedure. IVF, with or without ICSI, was received in 494 (94.1%) and 497 (95.0%) of ES and TAU participants respectively. Live birth rate was 37.1% (195/525) in the TAU and 38.6% (202/523) in the ES: an unadjusted absolute difference of 1.5% (95% CI -4.4% to 7.4%, P = 0.621). There were no statistical differences in secondary outcomes. Adverse events were comparable across groups. LIMITATIONS, REASONS FOR CAUTION: A sham ES procedure was not undertaken in the control group, however, we do not believe this would have influenced the results as objective fertility outcomes were used. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest trial that is adequately powered to assess the impact of ES on women undergoing their first cycle of IVF. ES was safe, but did not significantly improve pregnancy outcomes when performed in the mid-luteal phase prior to the first IVF or ICSI cycle. We recommend that ES is not undertaken in this population. STUDY FUNDING/COMPETING INTEREST(S): Funded by the National Institute of Health Research. Stephen Walters is an National Institute for Health Research (NIHR) Senior Investigator (2018 to present) and was a member of the following during the project: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Clinical Trials and Evaluation Committee (2011-2017), NIHR HTA Commissioning Strategy Group (2012 to 2017); NIHR Programme Grants for Applied Research Committee (2020 to present); NIHR Pre doctoral Fellowship Committee (2019 to present). Dr. Martins da Silva reports grants from AstraZeneca, during the conduct of the study; and is Associate editor of Human Reproduction and Editorial Board member of Reproduction and Fertility. Dr. Bhide reports grants from Bart's Charity and grants and non-financial support from Pharmasure Pharmaceuticals outside the submitted work. TRIAL REGISTRATION NUMBER: ISRCTN number: ISRCTN23800982. TRIAL REGISTRATION DATE: 31 May 2016. DATE OF FIRST PATIENT'S ENROLMENT: 04 July 2016.

A comparison of transcriptomic profiles in endometrium during window of implantation between women with unexplained recurrent implantation failure and recurrent miscarriage.

The endometrium becomes receptive to the embryo only in the mid-luteal phase, but not in the other stages of the menstrual cycle. Endometrial factors play an important role in implantation. Women with recurrent miscarriage and recurrent implantation failure have both been reported to have altered expression of receptivity markers during the window of implantation. We aimed to compare the gene expression profiles of the endometrium in the window of implantation among women with unexplained recurrent implantation failures (RIF) and unexplained recurrent miscarriages (RM) by RNA sequencing (RNA-Seq). In total 20 patients (9 RIF and 11 RM) were recruited. In addition 4 fertile subjects were included as reference. Endometrium samples were precisely timed on the 7th day after luteal hormone surge (LH + 7). All the 24 endometrium samples were extracted for total RNA. The transcriptome was determined by RNA-Seq in the first 14 RNA samples (5 RIF, 6 RM and 3 fertile). Differentially expressed genes between RM and RIF were validated by quantitative real-time PCR (qPCR) in all 24 RNA samples (9 RIF, 11 RM and 4 fertile). Transcriptomic profiles of RM and RIF, but not control samples, were separated from each other by principle component analysis (PCA) and support vector machine (SVM). Complementary and coagulation cascades pathway was significantly up-regulated in RIF while down-regulated in RM. Differentially expressed genes C3, C4, C4BP, DAF, DF and SERPING1 in complement and coagulation cascade pathway between RM and RIF were further validated by qPCR. This study compared endometrial transcriptome among patients with RIF and RM in the window of implantation; it identified differential molecular pathways in endometrium between RIF and RM, which potentially affect the implantation process.

Measurement of uterine natural killer cell percentage in the periimplantation endometrium from fertile women and women with recurrent reproductive failure: establishment of a reference range.

BACKGROUND: Uterine natural killer cells are the major leukocytes present in the periimplantation endometrium. Previous studies have found controversial differences in uterine natural killer cell percentage in women with recurrent reproductive failure compared with fertile controls. OBJECTIVE: We sought to compare the uterine natural killer cell percentage in women with recurrent reproductive failure and fertile controls. STUDY DESIGN: This was a retrospective study carried out in university hospitals. A total of 215 women from 3 university centers participated in the study, including 97 women with recurrent miscarriage, 34 women with recurrent implantation failure, and 84 fertile controls. Endometrial biopsy samples were obtained precisely 7 days after luteinization hormone surge in a natural cycle. Endometrial sections were immunostained for CD56 and cell counting was performed by a standardized protocol. Results were expressed as percentage of positive uterine natural killer cell/total stromal cells. RESULTS: The median uterine natural killer cell percentage in Chinese ovulatory fertile controls in natural cycles was 2.5% (range 0.9-5.3%). Using 5th and 95th percentile to define the lower and upper limits of uterine natural killer cell percentage, the reference range was 1.2-4.5%. Overall, the groups with recurrent reproductive failure had significantly higher uterine natural killer cell percentage than the controls (recurrent miscarriage: median 3.2%, range 0.6-8.8%; recurrent implantation failure: median 3.1%, range 0.8-8.3%). However, there was a subset of both groups (recurrent miscarriage: 16/97; recurrent implantation failure: 6/34) that had lower uterine natural killer cell percentage compared to fertile controls. CONCLUSION: A reference range for uterine natural killer cell percentage in fertile women was established. Women with recurrent reproductive failure had uterine natural killer cell percentages both above and below the reference range.

CDC Grand Rounds: National Amyotrophic Lateral Sclerosis (ALS) Registry Impact, Challenges, and Future Directions.

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a rapidly progressive fatal neurologic disease. Currently, there is no cure for ALS and the available treatments only extend life by an average of a few months. The majority of ALS patients die within 2-5 years of diagnosis, though survival time varies depending on disease progression (1,2). For approximately 10% of patients, ALS is familial, meaning it and has a genetic component; the remaining 90% have sporadic ALS, where etiology is unknown, but might be linked to environmental factors such as chemical exposures (e.g., heavy metals, pesticides) and occupational history (3).

Dietary treatment of Crohn's disease: perceptions of families with children treated by exclusive enteral nutrition, a questionnaire survey.

BACKGROUND: Diet is strongly associated with the aetiology of Crohn's Disease (CD) and exclusive enteral nutrition (EEN) is the primary induction treatment in paediatric CD. This study explored opinions around the use of EEN and alternative novel, solid food-based diets (SFDs) expressed by paediatric patients with CD, previously treated with EEN and their parents. METHODS: This anonymous questionnaire surveyed families of CD patients treated with EEN over 1 year. Two questionnaire forms were completed; one asking the patients' opinions and another referring to their main carer. This questionnaire explored participants' demographic characteristics; acceptability of a repeat EEN course to treat a future flare (EEN repeat); their opinion on how difficult EEN would be compared to an example SFD; and their intention to participate in a future clinical trial assessing the therapeutic efficacy of an SFD in CD. RESULTS: Forty-one families of CD patients were approached with 29 sending replies (71%). Most of our participants were positive on completing another EEN course, however the majority would choose an SFD alternative (Patients:66, Parents:72%). Both patients and their parents rated EEN to be more difficult to adhere to compared to an example SFD (p < 0.05), and their ratings were strongly correlated (EEN:r = 0.83, SFD:r = 0.75, p < 0.001). The majority of our respondents would agree to participate in a clinical trial assessing an SFD's effectiveness (Patients:79, Parents:72%) for the management of active CD. CONCLUSIONS: While patients with CD and their families would accept an EEN repeat, the majority would prefer an SFD alternative. CD families surveyed are supportive of the development of solid food-based dietary treatments.

Structured Mentoring for Workforce Engagement and Professional Development in Public Health Settings.

Mentoring is commonly used to facilitate professional growth and workforce development in a variety of settings. Organizations can use mentoring to help achieve broader personnel goals including leadership development and succession planning. While mentorship can be incorporated into training programs in public health, there are other examples of structured mentoring, with time commitments ranging from minutes to months or longer. Based on a review of the literature in public health and aggregated personal subject matter expertise of existing programs at the Centers for Disease Control and Prevention, we summarize selected mentoring models that vary primarily by time commitments and meeting frequency and identify specific work situations to which they may be applicable, primarily from the federal job experience point of view. We also suggest specific tasks that mentor-mentee pairs can undertake, including review of writing samples, practice interviews, and development of the mentee's social media presence. The mentor-mentee relationship should be viewed as a reciprocally beneficial one that can be a source of learning and personal growth for individuals at all levels of professional achievement and across the span of their careers.

CDC Grand Rounds: Chronic Fatigue Syndrome - Advancing Research and Clinical Education.

Chronic fatigue syndrome (CFS) is a complex and serious illness that is often misunderstood. Experts have noted that the terminology "chronic fatigue syndrome" can trivialize this illness and stigmatize persons who experience its symptoms (1). The name was coined by a group of clinicians convened by CDC in the late 1980s to develop a research case definition for the illness, which, at the time, was called chronic Epstein-Barr virus syndrome. The name CFS was suggested because of the characteristic persistent fatigue experienced by all those affected and the evidence that acute or reactivated Epstein-Barr virus infection was not associated with many cases (2). However, the fatigue in this illness is striking and quite distinct from the common fatigue everyone experiences. A variety of other names have been used, including myalgic encephalomyelitis (ME), ME/CFS, chronic fatigue immune dysfunction, and most recently, systemic exertion intolerance disease (3). The lack of agreement about nomenclature need not be an impediment for advancing critically needed research and education. The term ME/CFS will be used in this article.

The effect of a high progesterone concentration before oocyte retrieval on the peri-implantation endometrium.

In this single-centre, prospective cohort study, the effect of high progesterone level before oocyte retrieval on endometrial morphology and uterine natural killer cell (uKN) count in the peri-implantation period was investigated. A total of 106 women undergoing IVF treatment who did not proceed to fresh embryo transfer were included. Endometrial samples were obtained 7 days after HCG administration. Multiple regression analysis was used to identify factors affecting the results of histological staging and uNK cell count. Progesterone level on the day after HCG administration was the only significant variable associated with the results of histological staging (P = 0.004). Endometrial development in women with high progesterone level was significantly (P < 0.001) more advanced than that of women with normal progesterone; progesterone level on the day of HCG administration was the only significant variable associated with uNK cell count. The median (range) of uNK cell count of 9.6% (2.3-21.6%) in women with high progesterone was significantly (P < 0.001) higher than the median (range) of uNK cell count of 5.7% (1.4-18.7%) in women with normal progesterone. High progesterone level before oocyte retrieval was correlated with advancement in endometrial development as well as increased uNK cell count.

CDC Grand Rounds: Prevention and Control of Skin Cancer.

Skin cancer is the most common cancer in the United States, and most cases are preventable. Persons with certain genetic risk factors, including having a lighter natural skin color; blue or green eyes; red or blonde hair; dysplastic nevi or a large number of common moles; and skin that burns, freckles, or reddens easily or becomes painful after time in the sun, have increased risk for skin cancer. Persons with a family or personal history of skin cancer, especially melanoma, are also at increased risk. Although these genetic factors contribute to individual risk, most skin cancers are also strongly associated with ultraviolet (UV) radiation exposure. Most UV exposure comes from the sun, although some persons use UV-emitting indoor tanning devices (e.g., beds, booths, and lamps).

Serial changes in two immune checkpoint receptors and ligands, Tim-3/Gal-9 and PD-1/PD-L1 in peripheral blood prior to miscarriage: Comparison with pregnancies resulting in a live birth.

PROBLEM: Immune checkpoints Tim-3/Gal-9 and PD-1/PL-1 are involved in the maintenance of maternal-fetal immune tolerance systematically and locally. This study aimed to compare the serial changes of Tim-3/Gal-9, and PD-1/PL-1 in peripheral blood over a 4-week period after blastocyst transfer, between women who had a live birth and those who miscarried. METHODS OF STUDY: Serial blood samples were obtained on the day of ET, and 9, 16, 23, and 30 days after ET for the measurement of Tim-3 and PD-1 expressions on various lymphocytes by flow cytometry. Concentrations of serum Gal-9 and PD-L1 were measured by ELISA. RESULTS: In pregnancies that resulted in a live birth, a significant and sustained increase in the proportion of Tim-3+ pNK cells was observed from the 9th to 30th days after ET, whilst the concentration of serum PD-L1 was significantly increased on the 23rd and 30th days after ET when compared to the day of ET. In pregnancies that later miscarried, none of the parameters were significantly changed across all the time points examined. When comparing the results between the two groups, the proportion of Tim-3+ CD56dim NK cells in the women who had a live birth was significantly higher than that in women who miscarried from the 9th to 30th day after ET. CONCLUSION: A significant and sustained increase in the proportion of Tim-3+ pNK cells was observed in pregnancies resulting in a live birth but not in pregnancies resulting in a miscarriage, suggesting the changes may be associated with successful pregnancy outcomes.

A prospective study comparing the inflammation-related cytokine and chemokine profile from the day of blastocyst transfer to 7 weeks of gestation between pregnancies that did or did not result in a miscarriage.

The dynamics of maternal immunomodulation is essential in early pregnancy. In our previous study, successful implantation is characterized by a transient increase of pro-inflammatory cytokines followed by a switch to an anti-inflammatory state in peripheral blood around 3-6 days after embryo transfer (ET). In this study, we aimed to extend the time points to compare the cytokine and chemokine profiles between women who did or did not subsequently miscarry. We utilized precisely timed serum samples on the day of ET and 3, 6, 9, 16, 23 and 30 days after ET in women undergoing single blastocyst transfer. Our analysis revealed a significant alteration in cytokine profile after day ET+ 9 between the two groups. Regarding pro-inflammatory cytokine profile, there was a significant increase in IL-17 on days ET+ 16, + 23, and + 30 (50.60 ± 9.97 vs 37.09 ± 3.25, 53.20 ± 8.13 vs 36.51 ± 3.34, 57.06 ± 8.83 vs 33.04 ± 3.11 pg/mL), TNF-α on days ET+ 23 and + 30 (73.90 ± 12.42 vs 50.73 ± 3.55, 74.16 ± 12.46 vs 46.59 ± 3.21 pg/mL), IFN-γ on day ET+ 30 (69.52 ± 13.19 vs 42.28 ± 7.76 pg/mL) in women who miscarried compared to women who had a live birth. In contrast, the concentrations of anti-inflammatory cytokines IL-10 on days ET+ 23 and + 30 (26.23 ± 2.11 vs 38.30 ± 4.64, 23.77 ± 2.06 vs 39.16 ± 4.99 pg/mL) and TGF-ß1 on day ET+ 30 (20.30 ± 1.25 vs 23.81 ± 0.88 ng/mL) were significantly decreased in women who miscarried compared to women who had a live birth. While for the chemokine profile, there was no significant alteration observed between the two groups across all the time points. These findings suggest that a sustained anti-inflammatory milieu is concomitant with the maintenance of early pregnancy, while the remarkable pro-inflammatory shift as early as day ET+ 16 in women who subsequently miscarried was observed before the diagnosis of miscarriage.

Endometrial scratch to increase live birth rates in women undergoing first-time in vitro fertilisation: RCT and systematic review.

BACKGROUND: In vitro fertilisation is a widely used reproductive technique that can be undertaken with or without intracytoplasmic sperm injection. The endometrial scratch procedure is an in vitro fertilisation 'add-on' that is sometimes provided prior to the first in vitro fertilisation cycle, but there is a lack of evidence to support its use. OBJECTIVES: (1) To assess the clinical effectiveness, safety and cost-effectiveness of endometrial scratch compared with treatment as usual in women undergoing their first in vitro fertilisation cycle (the 'Endometrial Scratch Trial') and (2) to undertake a systematic review to combine the results of the Endometrial Scratch Trial with those of previous trials in which endometrial scratch was provided prior to the first in vitro fertilisation cycle. DESIGN: A pragmatic, multicentre, superiority, open-label, parallel-group, individually randomised controlled trial. Participants were randomised (1 : 1) via a web-based system to receive endometrial scratch or treatment as usual using stratified block randomisation. The systematic review involved searching electronic databases (undertaken in January 2020) and clinicaltrials.gov (undertaken in September 2020) for relevant trials. SETTING: Sixteen UK fertility units. PARTICIPANTS: Women aged 18-37 years, inclusive, undergoing their first in vitro fertilisation cycle. The exclusion criteria included severe endometriosis, body mass index ≥ 35 kg/m2 and previous trauma to the endometrium. INTERVENTIONS: Endometrial scratch was undertaken in the mid-luteal phase of the menstrual cycle prior to in vitro fertilisation, and involved inserting a pipelle into the cavity of the uterus and rotating and withdrawing it three or four times. The endometrial scratch group then received usual in vitro fertilisation treatment. The treatment-as-usual group received usual in vitro fertilisation only. MAIN OUTCOME MEASURES: The primary outcome was live birth after completion of 24 weeks' gestation within 10.5 months of egg collection. Secondary outcomes included implantation, pregnancy, ectopic pregnancy, miscarriage, pain and tolerability of the procedure, adverse events and treatment costs. RESULTS: One thousand and forty-eight (30.3%) women were randomised to treatment as usual (n = 525) or endometrial scratch (n = 523) and were followed up between July 2016 and October 2019 and included in the intention-to-treat analysis. In the endometrial scratch group, 453 (86.6%) women received the endometrial scratch procedure. A total of 494 (94.1%) women in the treatment-as-usual group and 497 (95.0%) women in the endometrial scratch group underwent in vitro fertilisation. The live birth rate was 37.1% (195/525) in the treatment-as-usual group and 38.6% (202/523) in the endometrial scratch group: an unadjusted absolute difference of 1.5% (95% confidence interval -4.4% to 7.4%; p = 0.621). There were no statistically significant differences in secondary outcomes. Safety events were comparable across groups. No neonatal deaths were recorded. The cost per successful live birth was £11.90 per woman (95% confidence interval -£134 to £127). The pooled results of this trial and of eight similar trials found no evidence of a significant effect of endometrial scratch in increasing live birth rate (odds ratio 1.03, 95% confidence interval 0.87 to 1.22). LIMITATIONS: A sham endometrial scratch procedure was not undertaken, but it is unlikely that doing so would have influenced the results, as objective fertility outcomes were used. A total of 9.2% of women randomised to receive endometrial scratch did not undergo the procedure, which may have slightly diluted the treatment effect. CONCLUSIONS: We found no evidence to support the theory that performing endometrial scratch in the mid-luteal phase in women undergoing their first in vitro fertilisation cycle significantly improves live birth rate, although the procedure was well tolerated and safe. We recommend that endometrial scratch is not undertaken in this population. TRIAL REGISTRATION: This trial is registered as ISRCTN23800982. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 10. See the NIHR Journals Library website for further project information.

The endometrial scratch is a simple procedure that involves 'scratching' the lining of the womb (the endometrium). Several small studies have shown that undertaking this before the first in vitro fertilisation cycle may improve live birth rates; however, other studies have contradicted this. This large study was carried out to confirm whether or not having an endometrial scratch before the first in vitro fertilisation cycle would increase the number of women having a live birth compared with those having 'usual' in vitro fertilisation treatment (known as the 'control' group). We collected information about pregnancy, miscarriage, stillbirth, pain during the procedure and costs of treatment to find out if there were any meaningful differences. A total of 1048 women aged between 18 and 37 years were randomly allocated to the two groups, so participants had a 50% chance of having the endometrial scratch. Women were followed up throughout their pregnancy to ascertain the outcome of their in vitro fertilisation cycle. Although the live birth rate was 1.5% higher in the endometrial scratch group (38.6%) than in the control group (37.1%), the difference was not large enough to show any benefit of having the procedure. Other outcomes did not differ significantly between the two groups. However, the procedure was safe and tolerable. We found that the cost of treatment was, on average, £316 per participant higher in the group that received endometrial scratch than in the control group; the difference was not large enough to show that receiving endometrial scratch was more cost-effective. We combined the results of this trial with those of previous trials that looked to answer a similar question, and found that, overall, the endometrial scratch procedure does not enhance the chances of achieving a live birth. We conclude that endometrial scratch before first-time in vitro fertilisation does not improve the outcome of treatment, and we recommend that this procedure is not undertaken prior to a first cycle of in vitro fertilisation.

The Centers for Disease Control and Prevention's maternal health response to 2009 H1N1 influenza.

We describe the efforts of the Maternal Health Team, which was formed to address the needs of pregnant and breastfeeding women during the Centers for Disease Control and Prevention's (CDC's) 2009 pandemic influenza A (2009 H1N1) emergency response. We examined the team's activities, constructed a timeline of key pandemic events, and analyzed the Maternal Health 2009 H1N1 inquiry database. During the pandemic response, 9 guidance documents that addressed the needs of pregnant and breastfeeding women and their providers were developed by the Maternal Health Team. The Team received 4661 maternal health-related inquiries that came primarily from the public (75.5%) and were vaccine related (69.3%). Peak inquiry volume coincided with peak hospitalizations (October-November 2009). The Maternal Health 2009 H1N1 inquiry database proved useful to identify information needs of the public and health care providers during the pandemic.

Successful implantation is associated with a transient increase in serum pro-inflammatory cytokine profile followed by a switch to anti-inflammatory cytokine profile prior to confirmation of pregnancy.

OBJECTIVE: To compare the changing peripheral levels of inflammation-related cytokine profile during a 9-day period after blastocyst transfer between women who did and did not conceive. DESIGN: Prospective, observational, and longitudinal study. SETTING: University-affiliated hospital. PATIENT(S): Forty-seven women with infertility who were undergoing single day-5 blastocyst transfer were recruited. INTERVENTION(S): This prospective observational and longitudinal study on 47 women with infertility was performed in an in vitro fertilization unit from December 2018 to August 2019. The amounts of a range of cytokines was measured on serial blood samples obtained during a 9-day period after blastocyst transfer. MAIN OUTCOME MEASURE(S): Serial blood samples were obtained on the day of embryo transfer, and 3, 6, and 9 days afterward for measurement of serum interferon gamma (IFN-γ), tumor necrosis factor alpha, interleukin (IL)-2, IL-4, IL-10, IL-12, IL-13, IL-17, IL-18, and IL-22 using cytometric bead arrays; transforming growth factor beta 1 (TGF-ß1) was measured using commercial enzyme-linked immunosorbent assay kits. RESULT(S): The cytokine profile was similar between the women who conceived and those who did not on the day of blastocyst transfer. In women who conceived, IFN-γ and IL-17 (pro-inflammatory cytokines) exhibited a transient and significant increase on day 3 after blastocyst transfer, which decreased to the baseline levels by day 6. Meanwhile, IL-10 (anti-inflammatory cytokine) was increased significantly on days 6 and 9, and TGF-ß1 (anti-inflammatory cytokine) was increased significantly on day 9 after blastocyst transfer. In women who did not conceive, there was a more pronounced increase in IFN-γ and IL-17 (pro-inflammatory cytokines) on day 3, which was sustained on days 6 and 9 without a switch to an anti-inflammatory cytokine profile. CONCLUSION(S): Among women who conceived after blastocyst embryo transfer, there was a transient and modest increase in serum pro-inflammatory cytokine profile (IFN-γ and IL-17) 3 days after blastocyst transfer, which was followed by a switch to anti-inflammatory cytokine profile (increase IL-10 and TGF-ß1) by 6 days after blastocyst transfer and the latter increase was sustained 9 days after blastocyst transfer, when pregnancy was confirmed.

Recommendations for the optimal use of mesalazine in the management of patients with mild to moderate ulcerative colitis.

The 2021 National report from IBD UK included responses from over 10 000 patients with inflammatory bowel disease, over 70% of whom reported having at least one flare in the last 12 months. As the first-line treatment for patients with mild and moderate ulcerative colitis, the action and delivery mechanisms of mesalazine are crucial for successful management of the disease. The choice of the most appropriate formulation of mesalazine and securing patient concordance and adherence to treatment remains a challenge for healthcare professionals. This article details the outcome of a roundtable discussion involving a group of gastroenterology consultants and specialist nurses which considered the importance of ensuring that patients have individualised mesalazine therapy before escalation to other treatments and gives recommendations for the management of patients with mild or moderate ulcerative colitis.

Early transient suppression of immune checkpoint proteins T-cell immunoglobulin mucin-3 and programmed cell death-1 in peripheral blood lymphocytes after blastocyst transfer is associated with successful implantation.

OBJECTIVE: To compare the changing peripheral levels of immune checkpoint proteins T-cell immunoglobulin mucin-3 (Tim-3)/galectin-9 (Gal-9), and programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) over a 9-day period after blastocyst transfer between women who did and did not conceive. DESIGN: Prospective observational study. SETTING: University teaching hospital. PATIENTS(S): Fifty-one infertile women undergoing day-5 blastocyst transfer. INTERVENTION(S): Serial blood samples obtained on the day of embryo transfer (ET), and 3, 6, and 9 days afterward for measurement of membranous Tim-3 and PD-1 expression on various peripheral lymphocytes by flow cytometry, and serum concentrations of ligands Gal-9 and PD-L1 by ELISA. MAIN OUTCOME MEASURE(S): Membranous Tim-3 and PD-1 expression on lymphocytes and serum Gal-9 and PD-L1 concentrations and comparison of results between pregnant and nonpregnant women. RESULT(S): In women who conceived, the measurements exhibited three different types of response: [1] a transient and statistically significant reduction of Tim-3+NK-like T cells, Tim-3+/PD-1+CD8+ T cells, and Tim-3+/PD-1+CD4+ T cells that returned back to baseline level 9 days after ET; [2] a reduction followed by steady increase to above baseline level on day 9 (Tim-3+CD56dimNK cells); [3] a steady increase in expression after ET to reach a level statistically significantly higher than that of the baseline by day 9 (Tim-3+CD56brightNK cells). Women who did not conceive showed no statistically significant fluctuation in any of the parameters measured across the four time pointswith exception of increased Tim-3 expression on NK cells on day 9. CONCLUSION(S): Successful blastocyst implantation is associated with a reduction of Tim-3 and PD-1 expression in peripheral lymphocytes on days 3 and 6 that is no longer apparent on day 9.

The effect of prednisolone on endometrial uterine NK cell concentrations and pregnancy outcome in women with reproductive failure. A retrospective cohort study.

This retrospective study of prospectively collected data examines the effect of prednisolone therapy on raised uterine Natural Killer cell (uNK) concentrations and pregnancy outcomes in women with recurrent miscarriage (RM) and recurrent implantation failure (RIF) after IVF/ICSI treatment. 136 women diagnosed with RRF who had a timed midluteal endometrial biopsy taken for uNK cell analysis were included. Women with high uNK cell concentrations (n = 45) were treated with prednisolone (10 mg/day) for one month, after which a second biopsy was taken for repeat uNK cell analysis. Women for whom prednisolone caused a decrease in uNK cell concentrations continued on prednisolone until 12 weeks of pregnancy. Pregnancy outcomes (live birth, miscarriage and implantation rates) and pregnancy complications were compared for women who received prednisolone and those who did not. Results showed that the prevalence of high uNK cells was 33.1%. Prednisolone significantly decreased the uNK cell concentration (P < 0.001), however reduction to normal limits was achieved in only 48.3% of patients. There was no difference in any of the pregnancy outcomes or complications between women who had received prednisolone and those who had not. In conclusion, this study showed a relatively high prevalence of raised uNK cells in women with recurrent reproductive failure and confirmed the effect of prednisolone on reducing uNK cell concentrations. We found however no evidence for a significant beneficial effect for prednisolone therapy on pregnancy outcomes. Until the results of an adequately powered RCT become available however, these findings should be considered preliminary.