Fetal Sac Research Articles

O-088 Performance of a commercial artificial intelligence software for embryo selection (Embryoscope/KIDScore™) on predicting biopsied and non-biopsied blastocyst clinical pregnancy according to score subgroups

Abstract Study question How informative is the score grade of KIDScore version 3 for day 5 blastocyst for clinical pregnancy in biopsied and non-biopsied embryos? Summary answer Potential clinical pregnancy is predicable according to score grades (above 7.0), regardless the use of PGT-A, in blastocysts on day 5. What is known already Time-lapse technology has promoted, along with the use of artificial intelligence (A.I.), a new spectrum of tools to improve embryo selection. Several software and algorithms have been launched in ART field in the last years, with the perspective of providing a substantial boost in IVF outcomes. KIDScore is one of these new tools, developed based on morphology and morphokinetics of embryo development with known clinical outcome and validated with transfer of blastocyst on day 3 or 5. Yet, it is highly recommended an in-house validation of any A.I. tool before it started to be apply in clinical decisions. Study design, size, duration Retrospective cohort study in a single private IVF center. Positive or negative clinical pregnancy (fetal heartbeat and gestational sac presence/absence) record of patient’s autologous and donated cycles using fresh and frozen oocytes, with or without PGT-A embryos transfers using the Embryocope® Plus incubator, that underwent single embryo transfers (total sET, n = 415; euploid = 228, non-biopsied = 187) of blastocysts developed on day 5 were included. Biochemical pregnancy and miscarriage were excluded of this analysis. Participants/materials, setting, methods Negative and positive clinical pregnancy KIDScoreTMDay 5’s were stratified in three subgroups, according to V3 score intervals: subgroup 1: range between 1.0-3.9 (n = 29), subgroup 2: 4.0-6.9 (n = 154) and subgroup 3: 7.0-9.9 (n = 232). sET of euploid embryos (n = 228) were also analyzed in the described subgroups (subgroup 1: n = 17; subgroup 2: n = 93 and subgroup 3: n = 118, respectively). For the analysis, Mann-Whitney, Chi-square and Fisher tests were used for statistical analysis, values of p < 0.05 were considered significant. Main results and the role of chance Maternal age between overall positive and negative pregnancies were similar (38,48±3,86 versus 38,75±3,83,p = 0,3573). When comparing score subgroups, overall positive clinical pregnancy rates were significant different [subgroup 1: 20.7% (6/29); subgroup 2: 43.5% (67/154); subgroup 3: 63.8% (148/232),p < 0.0001]. When analyzing subgroup 1 versus subgroup 2 there was also a difference in positive clinical pregnancy (p = 0.023) and subgroup 3 also showed a higher rate in clinical pregnancy when compared to subgroup 1 and 2 together (scores from 1.0 to 6.9,p < 0.0001). Analyzing only euploid embryos, the results on positive clinical pregnancy were also significant different between subgroups [subgroup 1: 35.3% (6/17); subgroup 2: 45.2% (42/93); subgroup 3: 61.0% (72/118),p = 0,024, and subgroup 1 + 2 versus subgroup 3,p = 0,0115]. Maternal age between positive and negative clinical pregnancies in PGT-A cycles were similar (37,81±1,61 versus 38,38±3,25,p = 0,069). Analyzing only non-biopsied embryos, the results on positive clinical pregnancy were also significant different between subgroups [subgroup 1: 0.0% (0/12); subgroup 2: 41.0% (25/61); subgroup 3: 66.7% (76/114),p = 0,0343, and subgroup 1 + 2 versus subgroup 3,p < 0.0001]. Maternal age between positive and negative clinical pregnancies in non-biopsied cycles were also similar (39,40±4,75 versus 39,22±4,43,p = 0,7816). Positive clinical pregnancy in subgroup 3 were similar in biopsied and non-biopsied subgroups (61% versus 66.7%,p = 0.4133). Limitations, reasons for caution The retrospective nature and low data of subgroup 1 (1.0-3.9 score), since they naturally are the last option to be chosen for transfer. Wider implications of the findings Differences on positive clinical pregnancy between subgroups (mainly scores greater than 7.0) reinforce the use of A.I. as a complementary tool for embryo selection. Interestingly, positive clinical pregnancy in 7.0-9.9 subgroup were similar in euploid and non-biopsied embryos, strengthening another potential application of A.I. in transposing embryo aneuploidy barrier. Trial registration number Not Applicable

P–656 Examination of the clinical significance of the two-step ovulation induction method (DuoStim)

Abstract Study question Do culture results of eggs obtained by double stimulation (DuoStim), where eggs are collected twice in one cycle, differ from a conventional fertility drug method? Summary answer The culture results of eggs acquired via the DuoStim cycle versus those acquired via a widely used conventional fertility drug method did not differ significantly. What is known already For patients with reduced ovarian reserve, the random start method, in which ovarian stimulation can start at any time during the menstrual cycle, is being used. As the pituitary gland is suppressed by progesterone during the luteal phase, endogenous luteinizing hormone surges are less likely to occur and ovulation is more easily avoidable. Previous reports showed that ovarian stimulation during the follicular and luteal phases of the same menstrual cycle resulted in similar blastocyst formation rates with normal chromosome numbers, which seems to be time-consuming. The DuoStim method is considered useful in cases in which time is at a premium. Study design, size, duration Between June 2019–December 2020, 562 egg collection cycles were performed in women ≥36 years. Ovulation cycles were evaluated in the conventional ovulation induction cycle (Co) group and DuoStim cycle (DS) group (subclassified into D1 group [first egg collection in cycle] and D2 group [second egg collection]. Post-insemination culture results were evaluated. Participants/materials, setting, methods Participants were women ≥36 years. Infusion method was IVF, and blastocysts of Gardner classification 3BB or higher were designated as good blastocysts, and blastocysts of 3AA or higher were designated as the best blastocysts. Confirmation of the fetal sac was defined as clinical pregnancy for the single freeze-thaw blastocyst transplant cycle. Chi-square and t-tests were used for statistical analysis. P ≤ 0.05 indicated statistical significance. Main results and the role of chance The average number of eggs acquired per cycle was 6.9 in the Co group and 3.5 in the DS group, and the egg maturation rate was 88.0% in the Co group and 95.7% in the DS group, which showed significant differences. The 2PN rate, blastocyst arrival rate, and Day 5 good blastocyst arrival rate in the obtained mature eggs were 66.5%, 66.5%, and 38.3% in the Co group and 70.9%, 70.5%, and 34.4% in the DS group and were not significantly different. Similarly, when a comparative study was conducted between the D1 group and D2 group, rates were 67.5%, 69.0%, and 31.0% in the D1 group and 74.4%, 71.9%, and 37.5% in the D2 group, with no significant difference noted. Rates of clinical pregnancy and post-transplantation miscarriage were 41.1% and 17.8% in the Co group and 16.6% and 0% in the DS group, respectively, with no significant difference, although rates in the Co group tended to be better. Limitations, reasons for caution The fertilization method was evaluated only by IVF. The transplantation method was freeze-thaw embryo transfer by hormone replacement cycle, and the target age was 36 years or older. Wider implications of the findings: DuoStim, which increases the number of acquired eggs, is useful when eggs must be collected as soon as possible. Regarding the clinical pregnancy rate after transplantation, better results were obtained for eggs acquired by the conventional fertility method, but it was necessary to repeat the number of attempts. Trial registration number Not applicable

P–695 Establishing predictors of the mode of conception in fertility patients presenting with a clinical pregnancy

Abstract Study question What are the predictors for pregnancies conceived spontaneously (SC), by ovulation induction+/-insemination (OI±IUI) or via In-Vitro Fertilization(IVF), and what proportion of pregnancies were conceived with each method? Summary answer Pregnancies were conceived by SC(27.7%), OI±IUI(33%) or IVF(39.2%).Unexplained infertility positively-predicted SC and OI±IUI-conceptions. Male factor-infertility demonstrated the opposite trend, positively predicting IVF. Endometriosis negatively-predicted SC. What is known already Spontaneous conception (SC) occurs regularly among infertility patients. Most studies have evaluated predictors of pregnancy among women with infertility who were trying to conceive. Few studies have addressed the role of different factors on the mode of conception in infertility patients who were pregnant. Factors found in some studies to be related with a SC were younger female age, shorter duration of infertility, fewer failed IVF cycles, and diagnosis of unexplained-infertility. Study design, size, duration We conducted a retrospective cohort study at a University fertility-center over a six-month period in 2019 and 2020. We reviewed viability scans of 285-patients. Mode of conception was recorded as Spontaneous, OI±IUI, or IVF. Patients’ demographics, obstetric and fertility diagnosis as well as base-line hormones and ovarian reserve testing were extracted to calculate predictors for the mode of conception. Pregnancy was defined as an intra-uterine fetal sac on a transvaginal ultrasound in the 1st-trimester. Participants/materials, setting, methods Parametric analysis was done using ANOVA and Tukey’s post-hoc test. Nonparametric analysis was performed using the chi-square test. Predictors of the mode of conception were calculated by multivariate regression analysis using the variables not in the equation model including the following parameters: male and female age, gravidity, parity, ectopic-pregnancies, infertility diagnosis, baseline serum: FSH, estradiol, TSH, AMH, and AFC. Data is presented as mean ±SD or percentage. P < 0.05 was significant. IRB approval was obtained. Main results and the role of chance 79 (27.7%) of pregnancies were SC, 94 (33%) resulted from OI±IUI, and 112 (39.2%) from IVF. Demographics didn’t differ between the groups including: female age(p = 0.06), male age(p = 0.79), gravidity (p = 0.47), parity(p = 0.7), ectopic-pregnancies(p = 0.07), baseline serum FSH(p = 0.29), estradiol(p = 0.65), TSH(p = 0.56), AMH(p = 0.42), and AFC(p = 0.06). Infertility diagnoses differed when comparing SC, OI±IUI and IVF conceptions respectively: Unexplained (22.7%, 22.3%, 15.1%, p = 0.03), Male-Factor(MF) (25%, 27.6%, 42.8%, p = 0.042), Tubal-factor (2.5%, 2.1%, 13.4, p = 0.002) and Ovulation-disorders/PCOS (24%, 32%, 12.5% p = 0.002). Endometriosis trended higher in women with IVF (p = 0.09). A positive predictor for SC was unexplained infertility(p = 0.0001). A negative predictor was endometriosis(p = 0.005). SC was sub-significantly less likely in the presence of MF (p = 0.057). Unexplained-infertility was a positive predictor for OI±IUI pregnancies(p = 0.047), whereas MF was a negative predictor(p = 0.0001). As for IVF-conceptions, MF was a positive predictor(p = 0.008), while unexplained-infertility negatively predicted conception by IVF(p = 0.018). Ovulation-disorders/PCOS trended lower in women with IVF (p = 0.052). While baseline serum estradiol levels were similar between groups (means 194–218pmol/L), multivariate regression showed it to be a predictor for OI±IUI and IVF conceptions. The clinical significance of this finding is not clear. Interestingly, female age and ovarian reserve were not found to predict one type of conception over another. Other possible predictors in the model were not significant. Limitations, reasons for caution This retrospective cohort may hide underlying bias. Clinical pregnancies were evaluated and not live birth. Our cohort represents patients that conceived and do not offer information about the entire sub-fertile population that is treated in our center, which is also a strength as it’s a novel way of evaluating predictors. Wider implications of the findings: Among patients that conceived spontaneously, advanced age and ovarian reserve did not play a negative role. Predictors of pregnancy were confirmed as expected with the majority of unexplained infertility conceptions occurring spontaneously or with OI+/-IUI, patients with Male factor infertility often conceived by IVF, and ovulation disorders by OI+/-IUI. Trial registration number NA

Kupffer cell restoration after partial hepatectomy is mainly driven by local cell proliferation in IL-6-dependent autocrine and paracrine manners.

Kupffer cells (KCs), which are liver-resident macrophages, originate from the fetal yolk sac and represent one of the largest macrophage populations in the body. However, the current data on the origin of the cells that restore macrophages during liver injury and regeneration remain controversial. Here, we address the question of whether liver macrophage restoration results from circulating monocyte infiltration or local KC proliferation in regenerating livers after partial hepatectomy (PHx) and uncover the underlying mechanisms. By using several strains of genetically modified mice and performing immunohistochemical analyses, we demonstrated that local KC proliferation mainly contributed to the restoration of liver macrophages after PHx. Peak KC proliferation was impaired in Il6-knockout (KO) mice and restored after the administration of IL-6 protein, whereas KC proliferation was not affected in Il4-KO or Csf2-KO mice. The source of IL-6 was identified using hepatocyte- and myeloid-specific Il6-KO mice and the results revealed that both hepatocytes and myeloid cells contribute to IL-6 production after PHx. Moreover, peak KC proliferation was also impaired in myeloid-specific Il6 receptor-KO mice after PHx, suggesting that IL-6 signaling directly promotes KC proliferation. Studies using several inhibitors to block the IL-6 signaling pathway revealed that sirtuin 1 (SIRT1) contributed to IL-6-mediated KC proliferation in vitro. Genetic deletion of the Sirt1 gene in myeloid cells, including KCs, impaired KC proliferation after PHx. In conclusion, our data suggest that KC repopulation after PHx is mainly driven by local KC proliferation, which is dependent on IL-6 and SIRT1 activation in KCs.

The clinical value of serum alpha-fetoprotein

Alpha fetoprotein (AFP) is a major fetal serum globulin structurally and functionally related to albumin. During fetal development, AFP is produced sequentially by the fetal yolk sac, gastrointestinal tract, and liver. Thus normal production of AFP is unique to fetal development, making it an ideal marker for early fetal evaluation. Since its introduction into obstetric practice, maternal serum alpha-fetoprotein (MSAFP) screening has become the earliest non-invasive biochemical test to provide information regarding the fetus, thereby promoting access to earlier diagnosis, enabling families to make informed reproductive choices, and designing appropriate strategies for prenatal care and delivery. Normally, fetal AFP concentration levels continue to decrease through infantile stage (0 to 2 years), down to adult levels (0 – 8ng/ml). However, AFP is frequently re-expressed in patients affected by hepatocellular carcinoma (HCC) and yolk-sac tumors (YST) therefore used in clinical practice as a tumor marker. To improve the specificity of AFP, glycoforms of AFP are determined and used in the differential/early diagnosis, follow up of treatment and prognostication of patients with AFP secreting tumors. Alpha-fetoprotein is also used as a biochemical diagnostic and prognostic marker for prolonged jaundice in newborns.

Icaritin promotes apoptosis and inhibits proliferation by down-regulating AFP gene expression in hepatocellular carcinoma

BackgroundIcaritin, an active ingredient of the Chinese herb Epimedium, plays an anti-tumor role in liver cancer by inhibiting the proliferation of hepatocellular cells and promoting their apoptosis. In China, phase II and a large phase III clinical trial of icaritin reagent for the treatment of hepatocellular cancer is under-going, but the specific mechanism of icaritin action was unclear. Alpha-fetoprotein (AFP), an oncofetal protein, produced in the healthy fetal liver and yolk sac. Intracellular AFP promoted cellular proliferation and inhibited cellular apoptosis in hepatocellular carcinoma (HCC). The study was aimed to investigate the effect of icaritin on HCC through p53/AFP pathway.MethodsReal-time RT PCR and western blot were used to detect p53 and AFP expression levels in HCC cells treated with icaritin. The mechanism of icaritin affecting p53 expression was verified by ubiquitination experiment, and the binding activity of icaritin on p53 in AFP promoter region was verified by luciferase experiment. EdU, MTT and flow cytometry were used to determine whether icaritin affected HCC cellular proliferation and apoptosis through p53/ AFP pathway. Expression levels of p53 and AFP in xenograft mouse model were determined by western blotting.ResultsOur results showed icaritin inhibited AFP expression at mRNA and protein level. AFP was also identified as the target gene of the p53 transcription factor. Icaritin abrogated murine double minute (Mdm) 2-mediated p53 ubiquitination degradation to improve the stability of p53. Up-regulated p53 protein levels then transcriptionally inhibited the AFP promoter. Icaritin-mediated decrease of AFP through Mdm2/p53 pathways inhibited HCC cellular proliferation and promoted HCC cellular apoptosis.ConclusionOur findings revealed the mechanism of icaritin in promoting apoptosis and inhibiting proliferation in liver cancer cells. The regulatory mechanism of icaritin in AFP protein down-regulation provides a theoretical and experimental basis for further research into new drugs for the treatment of liver cancer.

4 Placental Hofbauer Cells As a Proxy Cell Type for Fetal Brain Microglia

Both placental and brain immune activation have been reported in maternal obesity-exposed (MATOB) offspring, and MATOB offspring have an increased risk for autism spectrum disorder, ADHD, and cognitive deficits. Microglia, the resident brain immune cells, have been implicated in these morbidities. Hofbauer cells (HBCs), resident fetal placental macrophages, and microglia, resident brain macrophages, share a common embryonic origin in the fetal yolk sac in mice and humans. Because direct evaluation of microglial function in a living human fetus or neonate is impossible, we sought to determine whether HBCs could serve as a more accessible biologic surrogate for fetal brain microglia in MATOB and control murine pregnancy. C57BL6/J dams were fed either a 60% high-fat diet or 10% fat control diet for 14 weeks pre-breeding and during pregnancy. At e17.5, fetal brain microglia and corresponding placental macrophages were isolated from fresh tissue. We performed single-cell RNA-sequencing on microglia and matched placental macrophages (10x Genomics, N=16, 4 replicates/group). 77,999 cells were sequenced. Canonical microglial and HBC markers were expressed in both cell types. Unsupervised analyses identified clusters within and across samples that share a significant fraction of “marker genes” (expressed more highly in cells from that cluster than in all other cells). Subsets of HBCs closely resembled subsets of microglia, with overlap analysis of marker genes demonstrating numerous clusters with 80-100% overlap between microglia and HBCs. This was true for both MATOB and CD. ScRNA-Seq elucidated novel shared gene programs and cell states that define HBCs and microglia. Shared gene programs in HBCs and microglia suggest that HBCs may be used as a proxy cell type to assay fetal brain microglial programming, in both MATOB and control mouse pregnancy. This finding may have broader implications for assaying the impact of maternal exposures beyond obesity on fetal brain development.

A case of indomitable vomiting in an ectopic pregnancy. Injection of morphine into the fetal sac. Recovery

A patient, tall and strong, about 30 years old, a woman was always healthy and only a month before that she began to feel sometimes cramp-like pains in the lower abdomen and notice leucorrhoea, which either intensified or weakened. Menstruation is correct from the age of 13, but the last meager regulations on April 30 were caused artificially, and on the third day there were pains with contractions, bringing the patient to fainting.

A case of tubal pregnancy with rupture of the fetal sac; gluttony; recovery

A woman of 25 years old, gave birth 4 times completely safely. In the middle of the 3rd month of the 5th pregnancy, there were severe pains in the right side of the abdomen, loss of strength, severe anemia, pulse almost imperceptible. Ice pack; suppositories from opia. The next morning, the pulse improved.

A case of lateral extrauterine pregnancy. Operation 14 days after the death of the fetus. Extirpation (as much as possible) of a fertile beetle. Convalescence

The author describes a very interesting and rare case of extrauterine pregnancy, where an operation was performed with the subsequent removal of the fetal sac.

Epigenetic and transcriptional regulation of osteoclast differentiation.

Osteoclasts are derived from mononuclear phagocyte lineage cells and are indispensable for bone resorption. Recent findings suggest that fetal yolk sac macrophage progenitors give rise to neonatal osteoclasts, while hematopoietic stem cell-derived cells, such as monocytes, contribute to maintaining osteoclast syncytia in vivo. Osteoclast differentiation is dependent on macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) signaling that mediates global epigenetic and transcriptional changes. PU.1 is a transcription factor that establishes cell type-specific enhancer landscapes in osteoclast precursors and mature osteoclasts by collaborating with interferon regulatory factor-8 (IRF8) and nuclear factor of activated T-cells (NFATc1), respectively. Irf8 and Nfatc1 genes are tightly controlled by epigenetic mechanisms such as DNA methylation and histone modifications during osteoclastogenesis. Thus, key transcription factors orchestrate osteoclast-specific transcription regulatory networks through epigenetic modifications. In this review, we discuss recent advances in our understanding of the molecular mechanisms involved in osteoclast development.

The Canadian Assisted Reproductive Technologies Register (CARTR) Plus database: a validation study.

STUDY QUESTIONAre data accurately documented in the Canadian Assisted Reproductive Technologies Register (CARTR) Plus database?SUMMARY ANSWERMeasures of validity were strong for the majority of variables evaluated while those with moderate agreement were FSH levels, oocyte origin and elective single embryo transfer.WHAT IS KNOWN ALREADYHealth databases and registries are excellent sources of data. However, as these databases are typically not established for the primary purpose of performing research, they should be evaluated prior to utilization for research both to inform the study design and to determine the extent to which key study variables, such as patient characteristics or therapies provided, are accurately documented in the database. CARTR Plus is Canada’s national register for collecting extensive information on IVF and corresponding pregnancy outcomes, and it has yet to be validated.STUDY DESIGN, SIZE, DURATIONThis study evaluating the data translation CARTR Plus database examined IVF cycles performed in 2015 using data directly from patient charts. Six clinics across Canada were recruited to participate, using a purposive sampling strategy. Fixed random sampling was employed to select 146 patient cycles at each clinic, representing unique patients. Only a single treatment cycle record from a unique patient at each clinic was considered during chart selection.PARTICIPANTS/MATERIALS, SETTING, METHODSTwenty-five data elements (patient characteristics, treatments and outcomes) were reabstracted from patient charts, which were declared the reference standard. Data were reabstracted by two independent auditors with relevant clinical knowledge after confirming inter-rater reliability. These data elements from the chart were then compared to those in CARTR Plus. To determine the validity of these variables, we calculated kappa coefficients, sensitivity, specificity, positive predictive value and negative predictive value with 95% CI for categorical variables and calculated median differences and intraclass correlation coefficients (ICC) for continuous variables.MAIN RESULTS AND THE ROLE OF CHANCESix clinics agreed to participate in this study representing five Canadian provinces. The mean age of patients was 35.5 years, which was similar between the two data sources, resulting in a near perfect level of agreement (ICC = 0.99; 95% CI: 0.99, 0.99). The agreement for FSH was moderate, ICC = 0.68 (95% CI: 0.64, 0.72). There was nearly perfect agreement for cycle type, kappa = 0.99 (95% CI: 0.98, 1.00). Over 90% of the cycles in the reabstracted charts used autologous oocytes; however, data on oocyte source were missing for 13% of cycles in CARTR Plus, resulting in a moderate degree of agreement, kappa = 0.45 (95% CI, 0.37, 0.52). Embryo transfer and number of embryos transferred had nearly perfect agreement, with kappa coefficients greater than 0.90, whereas that for elective single or double embryo transfer was much lower (kappa = 0.55; 95% CI: 0.49, 0.61). Agreement was nearly perfect for pregnancy type, and number of fetal sacs and fetal hearts on ultrasound, all with kappa coefficients greater than 0.90.LARGE-SCALE DATAN/ALIMITATIONS, REASONS FOR CAUTIONCARTR Plus contains over 200 variables, of which only 25 were assessed in this study. This foundational validation work should be extended to other CARTR Plus database variables in future studies.WIDER IMPLICATIONS OF THE FINDINGSThis study provides the first assessment of the quality of the data translation process of the CARTR Plus database, and we found very high quality for the majority of the variables that were analyzed. We identified key data points that are either too often lacking or inconsistent with chart data, indicating that changes in the data entry process may be required.STUDY FUNDING/COMPETING INTEREST(S)This study was funded by Canadian Institutes of Health Research (CIHR) (Grant Number FDN-148438) and by the Canadian Fertility and Andrology Society Research Seed Grant (Grant Number: N/A). The authors report no conflict of interest.TRIAL REGISTRATION NUMBERNot applicable.

M2-like cells from the macrophage lineage might play a central role in closure of the embryonic neural tube

Herein it is hypothesized that M2-like macrophages or pre-macrophages of fetal origin might play a central role in development and closure of the neural tube. Early in embryonic development, pre-macrophages arise from the fetal yolk sac and track through the bloodstream to reach diverse embryonic tissues, where they mature. Most of these macrophages exhibit an M2-like phenotype. The critical period for neural tube closure is contained within the period of yolk sac-derived pre-macrophage tracking and distribution, which poses a question: might these pre-macrophages or macrophages exert an influence on the closing neural tube? Evidence suggests that perturbations in macrophage polarization or M2 macrophage function might contribute to the failure of neural tube closure associated with diabetes mellitus, one carbon metabolism (including folic acid deficit), inositol, arachidonic acid, and sphingosine-1-phosphate, as well as in the teratogenicity of nitric acid, valproic acid, and fumonisin. The influence of each of these factors is interpreted in light of potential interactions with M2-like macrophages or macrophage progenitors on the developing neural tube. By placing these anti inflammatory macrophages at the center of various epigenetic, neurochemical, and signaling processes suspected to be involved in neural tube closure, potential associations are revealed between macrophages and embryonic structural developmental processes such as collagen and actin dynamics. The choice of this model is also an attempt to explain why some etiologies for failure of neural tube closure are rescued by folic acid, whereas other etiologies are rescued only by formate, inositol, or not at all.

Do Women over 35 Years Old Who Have Undergone a Myomectomy Require More Acupuncture Sessions to Become Pregnant?

Background: To evaluate whether ≥ 3 adjunct acupuncture sessions accompanying embryo transfer, increases the chance of pregnancy amongst post-myomectomy women aged ≥ 35 years. Methods: This was a prospective study carried out at Nordica Fertility Center. Following written informed consent, 75 patients undergoing assisted reproduction therapy and who had good quality embryos, were age-matched and grouped into post-myomectomy (n = 24) and normal women who had no evidence of fibroids or previous myomectomy (n = 51). Between 1 and 3 sessions of acupuncture were performed on 6 post-myomectomy and 19 infertile women who had not undergone myomectomy, while > 3 acupuncture sessions were performed on 18 post-myomectomy and on 32 normal patients, approximately 25 minutes before and after embryo transfer. Results: A positive pregnancy test was defined as ultrasonographic evidence indicating presence of a fetal sac 6 weeks after embryo transfer. Of the 5 post-myomectomy women who were pregnant, only 1 (20.0%) received 1-3 adjunct acupuncture sessions whilst the remaining 4 (80.0%) received > 3 acupuncture sessions. Of the 11 normal pregnant women, 5 (45.4%) received 1-3 adjunct acupuncture sessions while 6 (54.5%) received > 3 adjunct acupuncture sessions. Conclusion: Pregnancy rates in infertile post-myomectomy women may be improved by > 3 adjunct acupuncture sessions.

Placental Macrophages: A Window Into Fetal Microglial Function in Maternal Obesity

Fetal placental macrophages and microglia (resident brain macrophages) have a common origin in the fetal yolk sac. Yolk-sac-derived macrophages comprise the permanent pool of brain microglia throughout an individual’s lifetime. Inappropriate fetal microglial priming may therefore have lifelong neurodevelopmental consequences, but direct evaluation of microglial function in a living fetus or neonate is impossible. We sought to test the hypothesis that maternal obesity would prime both placental macrophages and fetal brain microglia to overrespond to an immune challenge, thus providing a window into microglial function using placental cells.Obesity was induced in C57BL/6 J mice using a 60% high-fat diet. On embryonic day 17.5, fetal brain microglia and corresponding CD11b + placental cells were isolated from fresh tissue. Cells were treated with media or lipopolysaccharide (LPS). Tumor necrosis factor-alpha (TNF-α) production by stimulated and unstimulated cells was quantified via ELISA. We demonstrate for the first time that the proinflammatory cytokine production of CD11b + placental cells is strongly correlated with that of brain microglia (Spearman’s ρ = 0.73, p = 0.002) in the setting of maternal obesity. Maternal obesity-exposed CD11b + cells had an exaggerated response to LPS compared to controls, with a 5.1-fold increase in TNF-α production in placentas (p = 0.003) and 3.8-fold increase in TNF-α production in brains (p = 0.002). In sex-stratified analyses, only male obesity-exposed brains and placentas had significant increase in TNF-α production in response to LPS. Taken together, these data suggest that maternal obesity primes both placental macrophages and fetal brain microglia to overproduce a proinflammatory cytokine in response to immune challenge. Male brain and placental immune response is more marked than female in this setting. Given that fetal microglial priming may impact neuroimmune function throughout the lifespan, these data could provide insight into the male predominance of certain neurodevelopmental morbidities linked to maternal obesity, including cognitive dysfunction, autism spectrum disorder, and ADHD. Placental CD11b+ macrophages may have the potential to serve as an accessible biomarker of aberrant fetal brain immune activation in maternal obesity. This finding may have broader implications for assaying the impact of other maternal exposures on fetal brain development.

LPS-induced maternal inflammation promotes fetal leukocyte recruitment and prenatal organ infiltration in mice.

A pro-inflammatory intrauterine milieu accounts for increased perinatal morbidity and mortality. We asked how maternal inflammation as seen in endotoxemia affects fetal leukocyte recruitment in vivo during late gestation. Inflammation was induced in pregnant LysEGFP-mice by intraperitoneal LPS injection between gestational day 14 and 18 (E14-E18). After 20 h, intravital fluorescence microscopy was performed on fetal yolk sac venules to examine leukocyte rolling (number of rolling cells/min) and adhesion (>30 s). Infiltration of neutrophils into chorion/amnion, lung, and kidney were quantified by immunofluorescence microscopy. At high doses (2 × 1 mg/kg), LPS triggered preterm birth (PTB) and intrauterine fetal death (IUFD), with early gestations at high risk of IUFD and late gestations prone to PTB. Lower LPS dosing (2 × 0.25 mg/kg) did not induce labor, but promoted maternal and fetal cytokine production, as well as neutrophilic infiltration of fetal membranes, as seen in chorioamnionitis (CAM). Baseline fetal leukocyte recruitment increased throughout gestation, and maternal inflammation further augmented adhesion at E16-E18. Enhanced leukocyte recruitment ultimately translated into prominent infiltration of fetal lung and kidney. LPS-induced maternal endotoxemia promotes IUFD, PTB, and fetal leukocyte recruitment depending on gestational age. Our proposed model may serve as a platform to test novel perinatal immune modulators.

Electroacupuncture of Hegu(LI 4) and Sanyinjiao(SP 6) Assists Medicinal Abortion

To observe the effectiveness of electroacupuncture (EA) therapy in promoting medicinal abortion. Sixty participants with early pregnancy were randomly divided into medication (control) and EA+ medication groups (n=30 in each). Participants in the control group were treated by regular medication (mifepristone and misoprostol tablets), and those of the EA group were treated by EA stimulation (2 Hz/100 Hz, a tolerable strength) of bilateral Hegu(LI 4) and Sanyinjiao(SP 6) for 25 min, and also by the same medication method mentioned in the control group. Participants of both groups were admitted to the hospital for observation on the 3rd day after taking medication. The abdominal pain was assessed by visual analogue scale (VAS) score, and the foetal sac discharge duration and the complete abortion rate were recorded. After the treatment, the VAS scores of both groups were significantly reduced in comparison with their own pre-treatment in each group (P<0.01), and the VAS score of the EA+ medication group was significantly lower than that of the medication group (P<0.01). The foetal sac discharge duration was significantly shorter in the EA+ medication group than in the medication group (P<0.01). The abortion rates showed no significant difference between the two groups (P>0.05). EA stimulation of Hegu(LI 4) and Sanyinjiao(SP 6) has a positive effect in assisting medicinal abortion in reducing abdominal pain and shortening foetal sac discharge duration.

Congenital hepatoblastoma in a neonate

Hepatoblastoma is a rare cause of mass abdomen and distension of abdomen in neonates. In this report, a 1-day-old baby who presented with abdominal distension at birth is being described for its unusual presentation. Diagnosis of hepatoblastoma in the antenatal period is possible with the available imaging modalities such as ultrasound abdomen. Caesarean section is recommended when HBL is antenatally diagnosed as vaginal delivery may cause tumor rupture. Beckwith-Wiedemann syndrome, hemihypertrophy and low birth weight are common associations of HBL. Serum Alpha feto protein (AFP) is the most useful laboratory test for hepatoblastoma and hepatocellular carcinoma. AFP is produced in the fetal liver and yolk sac, and levels decline to adult values during the first 6 months after birth. AFP can be used as a tumour marker for screening and confirmation of diagnosis though it is not a very specific tumour marker. Hepatoblastoma should be considered in the differential diagnosis when a neonate presents with distension of abdomen.

Genetic Rescue Reverses Microglial Activation in Preclinical Models of Retinitis Pigmentosa.

Microglia cells (MGCs) play a key role in scavenging pathogens and phagocytosing cellular debris in the central nervous system and retina. Their activation, however, contributes to the progression of multiple degenerative diseases. Given the potential damage created by MGCs, it is important to better understand their mechanism of activation. Here, we explored the role of MGCs in the context of retinitis pigmentosa (RP) by using four independent preclinical mouse models. For therapeutic modeling, tamoxifen-inducible CreER was introduced to explore changes in MGCs when RP progression halted. The phenotypes of the MGCs were observed using live optical coherence tomography, live autofluorescence, and immunohistochemistry. We found that, regardless of genetic background, MGCs were activated in neurodegenerative conditions and migrated beyond the layers where they are typically found to the inner and outer segments, where degeneration was ongoing. Genetic rescue not only halted degeneration but also deactivated MGCs, regardless of whether the intervention occurred at the early, middle, or late stage of the disease. These findings suggest that halting long-term disease progression may be more successful by downregulating MGC activity while co-administering the therapeutic intervention.

Evaluation of the Relationship between Air Bubbles Depth and Pregnancy Rate in ICSI Cycles

Objective: to determine the relationship between embryo transfer outcome and the distance between fundal endometrial surface and air bubbles assessed by trans-abdominal ultrasound Design: Prospective (cohort) study Setting: This study was conducted in assisted reproductive technology (ART) unit of Ain Shams University Hospital from April 2015 to October 2016. Patient(s): Eighty two women undergoing ICSI were enrolled in and a written informed consent was obtained from each participant. Intervention(s): no patient received any additional procedure or intervention. Outcome measuers: The primary outcome was biochemical pregnancy rate based on serum beta-hCG level at 14 days after ET. Secondary outcome was clinical pregnancy rate using trans-vaginal US examination at 6 – 8 weeks of amenorrhea to detect the presence of fetal sac & pulsation. Results: Implantation, biochemical and clinical pregnancy rates were significantly higher in distance < 10 mm group than ≥ 10 mm group. Conclusion: air bubble used as an identifier of the position of the embryo at ET can be determinative for pregnancy rates. Clinical PRs were higher in cases with air bubbles < 10 mm from fundal endometrial surface.