Research Question: What are the effects of using a fertility education chatbot (i.e., automatic conversation program) on knowledge, intentions to improve preconception behaviour, and anxiety?Design: A three-armed, randomized, controlled trial was conducted using an online social research panel. Participants included 927 women aged 20-34 years who were randomly allocated to one of three groups: a fertility education chatbot (intervention group, IG), a document about fertility and preconception health (control group 1, CG1), or a document about an irrelevant topic (control group 2, CG2). Participants' scores on the Cardiff Fertility Knowledge Scale and the State-Trait Anxiety Inventory, their intentions to optimise preconception behaviours (e.g., taking folic acid), and the free-text feedback provided by chatbot users were assessed.Results: A repeated-measures analysis of variance showed significant fertility knowledge gains after the intervention in the IG (+9.1 points) and CG1 (+14.9 points) but no significant change in CG2 (+1.1 points). Post-test increases in the intentions to optimise behaviours were significantly higher in the IG than in CG2 and were similar to those in CG1. Post-test state anxiety scores were significantly lower in the IG than in CG1 and CG2. User feedbacks about the chatbot suggested technical limitations (e.g., low comprehension of users' words) and pros and cons of using the chatbot (e.g., convenient versus coldness).Conclusions: Providing fertility education using a chatbot improved fertility knowledge and intentions to optimise preconception behaviour without increasing anxiety, but the improvement in knowledge was small. Further technical development and exploration of personal affinity for technology is required.

Lynch syndrome (LS) is an autosomal-dominant inherited disorder mainly caused by a germline mutation in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and is associated with increased risk for various cancers, particularly colorectal cancer and endometrial cancer (EC). Women with LS account for 2% to 6% of EC patients; it is clinically important to identify LS in such individuals for predicting and/or preventing additional LS-associated cancers. PMS2 germline mutation (PMS2-LS) is the rarest contribution to LS etiology among the 4 LS-associated MMR germline mutations, and its detection is complicated. Therefore, prudent screening for PMS2-LS is important as it leads to an efficient LS identification strategy. Immunohistochemistry is recommended as a screening method for LS in EC. Isolated loss of PMS2 (IL-PMS2) expression is caused not only by PMS2-LS but also by MLH1 germline mutation or MLH1 promoter hypermethylation (MLH-PHM). This study aimed to determine the association between MLH1-PHM and IL-PMS2 to avoid inappropriate genetic analysis. We performed MLH1 methylation analysis and MLH1/PMS2 germline mutation testing on the IL-PMS2 cases. By performing MMR-immunohistochemistry on 360 unselected ECs, we could select 8 (2.2%) cases as IL-PMS2. Heterogenous MLH1 staining and MLH1-PHM were detected in 4 of 8 (50%) IL-PMS2 tumors. Of the 5 IL-PMS2 patients who underwent genetic analysis, 1 had PMS2 germline mutation with normal MLH1 expression (without MLH1-PHM), and no MLH1 germline mutation was detected. We suggest that MLH1 promoter methylation analysis for IL-PMS2 EC should be performed to exclude sporadic cases before further PMS2 genetic testing.

Recently, a new technique was developed for non-catalytically mixing microdroplets. In this method, an alternating-current (AC) electric field is used to promote the antigen–antibody reaction within the microdroplet. Previously, this technique has only been applied to histological examinations of flat structures, such as surgical specimens. In this study, we applied this technique for the first time to immunofluorescence staining of three-dimensional structures, specifically, mammalian eggs. We diluted an antibody against microtubules from 1:1,000 to 1:16,000, and compared the chromatic degree and extent of fading across dilutions. In addition, we varied the frequency of AC electric-field mixing from 5 Hz to 46 Hz and evaluated the effect on microtubule staining. Microtubules were more strongly stained after AC electric-field mixing for only 5 minutes, even when the concentration of primary antibody was 10 times lower than in conventional methods. AC electric-field mixing also alleviated microtubule fading. At all frequencies tested, AC electric-field mixing resulted in stronger microtubule staining than in controls. There was no clear difference in a microtubule staining between frequencies. These results suggest that the novel method could reduce antibody consumption and shorten immunofluorescence staining time.

Although medical treatment of unruptured ectopic pregnancy using methotrexate has been established, development of more potent and safer medical treatment is needed due to limited indications and side effects of methotrexate. Brain-derived neurotrophic factor (BDNF) signals through its receptor tyrosine kinase B (TrkB) to regulate the growth of malignant trophoblastic, choriocarcinoma cell. We investigated possible involvement of this signaling system in nonmalignant human trophoblast growth in both ectopic and intrauterine pregnancy. Here, we demonstrated the expression of BDNF in syncytiotrophoblasts and extravillous trophoblasts (EVTs) together with TrkB in cytotrophoblasts and EVTs in human placental villi during both normal and ectopic pregnancies. Treatment of cultured villous explants with soluble TrkB ectodomain or a Trk receptor inhibitor K252a suppressed cytotrophoblast differentiation by inhibiting EVT outgrowth reflected by decreased levels of an EVT marker, human leukocyte antigen-G. These inhibitors also decreased cytotrophoblast proliferation and cellular viability based on histopathological analyses and monitoring glucose metabolism, together with increased apoptosis in cytotrophoblasts based on in situ terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end-labeling and caspase-3/7 assays. After xenotransplantation of human placental villi into SCID mice as an in vivo model of ectopic pregnancy, treatment with K252a suppressed transplanted villi growth as reflected by decreased cytotrophoblast differentiation and proliferation, reduced tissue levels of chorionic gonadotropin-β, and increased apoptosis and caspase-3/7 activities. Thus, paracrine signaling by the BDNF/TrkB system is important for human cytotrophoblast differentiation, proliferation, and survival, and inhibition of BDNF/TrkB signaling in cytotrophoblasts could provide a novel medical treatment for ectopic pregnancy.

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