In order to estimate the salt and potassium intake in a population and to compare their annual trends, we developed a simple method to estimate population mean levels of 24-h urinary sodium (24HUNaV) and potassium (24HUKV) excretion from spot urine specimens collected at any time. Using 591 Japanese data items from the INTERSALT study as a gold standard, we developed formulas to estimate 24-h urinary creatinine (24HUCrV), 24HUNaV and 24HUKV using both spot and 24-h urine collection samples. To examine the accuracy of the formulas, we applied these equations to 513 external manual workers. The obtained formulas were as follows: (1) PRCr (mg/day) = −2.04 × age + 14.89 × weight (kg) + 16.14 × height (cm) − 2244.45; (2) estimated 24HUNaV (mEq/day) = 21.98 × XNa 0.392 ; (3) estimated 24HUKV (mEq/day) = 7.59 × XK 0.431 ; where PRCr = predicted value of 24HUCr, SUNa = Na concentration in the

PurposeThe present study aimed to analyze the endometrial and vaginal microbiome among a Japanese infertile population by sequencing and the impact of the endometrial and vaginal environment on implantation.MethodsIn total, 102 infertile (79 in vitro fertilization [IVF] and 23 non‐IVF) patients and seven healthy volunteers were recruited from August to December, 2017. Endometrial fluid and vaginal discharge samples for sequencing were collected by using an intrauterine insemination catheter. The bacterial status of the endometrium and vagina were analyzed.ResultsThe Lactobacillus‐dominated microbiota (>90% Lactobacillus spp.) in the endometrium vs vagina was 38% (30/79) vs 44.3% (44/79) in the IVF patients, 73.9% (17/23) vs 73.9% (17/23) in the non‐IVF patients, and 85.7% (6/7) vs 85.7% (6/7) in the healthy volunteers. The percentage of endometrial Lactobacillus in the healthy volunteers was highly stable within the same menstrual cycle and even in the following cycle. The major taxonomies were Gardnerella, Streptococcus, Atopobium, Bifidobacterium, Sneathia, Prevotella, and Staphylococcus. Fifteen patients achieved pregnancy by a single vitrified‐warmed blastocyst transfer during this study; the median percentage of Lactobacillus in the pregnant women was 96.45 ± 33.61%.ConclusionA considerable percentage of non‐Lactobacillus‐dominated (NLD) microbiota was found in the endometrium of Japanese infertile women. Increasing the endometrial level of the Lactobacilli to >90% might favor the implantation outcome of NLD infertile patients.

PurposeThe present study aimed to analyze the pregnancy outcomes of IVF patients presenting Lactobacillus‐dominated microbiota (LDM) or non‐Lactobacillus‐dominated microbiota (NLDM) of their endometrium and to report cases who were treated for NLDM concurrently with antibiotics and prebiotic/probiotic supplements in a Japanese infertile population.MethodsNinety‐two IVF patients were recruited from August 2017 to March 2018. Endometrial fluid samples for sequencing were collected using an IUI catheter. The bacterial status of the endometrium and the pregnancy outcomes were analyzed. For cases with NLDM, antibiotics and prebiotics/probiotics were administered according to their individual microbial conditions.ResultsForty‐seven cases (51.1%) presented LDM and 45 cases (48.9%) presented NLDM at initial analysis. Nine Patients with NLDM were treated by antibiotics and prebiotics/probiotics, and successfully became Lactobacillus‐dominant. Pregnancy rates by single vitrified‐warmed blastocyst transfers were higher in the LDM group (58.9% per patient and 36.3% per FBT) than in the NLDM group (47.2% per patient and 34.7% per FBT) but not significantly different.ConclusionThe results of this study could not necessarily prove the clear benefit of establishing Lactobacillus‐dominated endometrium in terms of pregnancy outcome, but there is significance in searching for endometrial microbial status of infertile patients and recovering Lactobacillus‐dominated endometrium might benefit implantation.

Alcohol drinking at high doses is a risk factor for head and neck cancer, and exposure to acetaldehyde, the principle metabolite of alcohol, is supposed to account for the increased risk. Individuals homozygous for the *2 variant allele of aldehyde dehydrogenase 2 (ALDH2) are unable to metabolize acetaldehyde, which prevents them from alcohol drinking, whereas *1*2 have 6-fold higher blood acetaldehyde concentration postalcohol consumption with respect to *1*1. According to the concept of Mendelian randomization, because this polymorphism is distributed randomly during gamete formation, its association with head and neck cancer should be not confounded by smoking. We carried out a meta-analysis of ALDH2 and head and neck cancer searching for relevant studies on Medline and Embase up to January 31, 2008, and investigated the consistency between the expected odds ratio (OR) among drinkers from the largest pooled analysis among never smokers and the observed OR from this meta-analysis by an interaction test. Six studies were selected (945 cases, 2,917 controls). The OR of head and neck cancer among *2*2 was 0.53 [95% confidence interval (95% CI), 0.28-1.00] relative to *1*1 and 1.83 (95% CI, 1.21-2.77) among *1*2. The expected OR for head and neck cancer due to alcohol intake among *1*1 was 1.38 (95% CI, 0.88-2.17) and the observed OR among *1*1 compared with 2*2 from this meta-analysis was 1.88 (95% CI, 1.00-3.57; P for interaction = 0.43). Besides showing the effectiveness of the Mendelian randomization approach, these findings support the theory that alcohol increases head and neck cancer risk through the carcinogenic action of acetaldehyde. (Cancer Epidemiol Biomarkers Prev 2009;18(1):248-54)

AimThis study aimed to assess the efficacy of the endometrial receptivity array (ERA) as a diagnostic tool and the impact of personalized embryo transfer (pET) for the treatment of patients with recurrent implantation failure (RIF) in Japan.MethodsFifty patients with a history of RIF with frozen‐thawed blastocyst transfers were recruited from July, 2015 to April, 2016. Endometrial sampling for the ERA and histological dating and a pET according to the ERA were performed. The receptive (R) or non‐receptive (NR) status of the endometrium as a result of the first ERA, endometrial dating, and pregnancy rates after the pET were analyzed.ResultsOf the patients with RIF, 12 (24%) were NR. Among them, eight (66.7%) were prereceptive. A clinical follow‐up was possible in 44 patients who underwent the pET. The pregnancy rates were 58.8% per patient and 35.3% per first pET in the R patients and 50.0% per patient and 50.0% per first pET in the NR patients. Discrepancies between the ERA results and histological dating were seen more in the NR patients than in the R patients.ConclusionsFor patients with unexplained RIF, there is a significance in searching for their personal window of implantation (WOI) using the ERA, considering the percentage of those who were NR and the pregnancy rates that resulted from the pET. By transferring euploid embryos in a personal WOI, much better pregnancy rates are expected.

To investigate in vivo interactions between antioxidant vitamins C and E, sparing effects of vitamin C on vitamin E as well as those of vitamin E on vitamin C were evaluated using inherently scorbutic [Osteogenic Disorder Shionogi (ODS)] rats. Rats were divided into four groups (control, vitamin E-deficient, vitamin C-deficient and simultaneously vitamins C and E-deficient). The levels of vitamins C and E in tissues were determined at 0, 14 and 21 d of deficiency. On d 14, the vitamin E concentration in plasma, liver, brain and lung of the vitamin C-deficient group was significantly lower than that of the control, in agreement with the literature concerning the sparing of vitamin E by ascorbate. The vitamin E concentration of the vitamin C-deficient group also was significantly lower in plasma, heart, liver, lung and kidney than that of the control group on d 21. On the basis of two-way ANOVA, significant interactions between vitamins C and E were observed on d 21 for vitamin E concentration in these tissues. The ascorbate level in plasma, heart, liver, muscle and kidney of the vitamin E-deficient group was significantly lower than that of the corresponding control group on d 21. Significant interactions between vitamins C and E were observed on d 21 for vitamin C concentration in these tissues. These results suggest a sparing effect of vitamin E on vitamin C, an effect that was observed for the first time in this study. These results suggest that the interaction between vitamins C and E exists in vivo and that the extent of the interaction depends on the tissue. Thiobarbituric acid reactive substances (TBARS) in plasma and liver of the vitamin C-deficient rats were significantly higher than those of the control and the vitamin E-deficient groups on d 21, suggesting that the deficiency of vitamin C caused a larger increase in oxidative stress than the deficiency of vitamin E. TBARS of the liver in rats deficient in both vitamins C and E were significantly higher than those in all other groups, suggesting an additive effect of the deficiencies of vitamins C and E on hepatic TBARS. These data suggest that in vivo, vitamins E and C interact, and each can exert sparing effects in the absence of the other.

PurposeTo analyze the pregnancy outcomes of IVF patients presenting eubiotic or dysbiotic endometrium at the time of embryo transfer and to analyze what bacterial profiles are suitable for embryo implantation.MethodsNinety-nine IVF patients under 40 years old undergoing vitrified-warmed blastocyst transfer in HRT cycle had concurrent endometrial microbiome analysis. Samples from the endometrium were taken from the participants at the time of mock transfer; the bacterial profiles at genus level and percentage of lactobacilli in the endometrium of the patients were analyzed.ResultsThirty-one cases (31.3%) had dysbiotic endometrium. The background profiles, pregnancy rates per transfer (52.9% vs 54.8%), and miscarriage rates (11.1% vs 5.9%) were comparable between patients with eubiotic or dysbiotic endometrium. Major bacterial genera other than Lactobacillus detected in the dysbiotic endometrium were Atopobium, Gardnerella, and Streptococcus. Some patients achieved ongoing pregnancies with 0% Lactobacillus in the endometrium. The endometrial bacterial profiles of pregnant cases with dysbiotic endometrium were comparable with those of non-pregnant cases.ConclusionAnalyzing microbiota at the species-level resolution may be necessary for identifying the true pathogenic bacteria of the endometrium and avoiding over-intervention against non-Lactobacillus microbiota. Further studies are necessary for analyzing the mechanism of how the pathogenic bacteria affect embryo implantation.Electronic supplementary materialThe online version of this article (10.1007/s10815-019-01630-7) contains supplementary material, which is available to authorized users.

Problem What are the pregnancy outcomes after the OPtimization of Thyroid function, Immunity, and Uterine Milieu (OPTIMUM) treatment strategy in patients with repeated implantation failure (RIF)? Method of study Infertile women with a history of RIF after more than three embryo transfer (ET) cycles underwent implantation testing, including a hysteroscopy, endometrial biopsy for CD138 immunostaining and bacterial culture, and serum 25‐hydroxyvitamin D3, interferon‐γ‐producing helper T (Th1) cell, IL‐4‐producing helper T (Th2) cell, thyroid‐stimulating hormone, thyroid peroxidase antibody, and thrombophilia screening between April 2017 and August 2018. We treated chronic endometritis with antibiotics, aberrant high Th1/Th2 cell ratios with vitamin D and/or tacrolimus intake, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low‐dose aspirin. Of the 116 RIF women, 88 women with 133 ET cycles were recruited from a questionnaire‐based survey regarding pregnancy outcomes. Fifty‐nine consecutive RIF patients without the OPTIMUM treatment strategy were also recruited as a control. Results The 116 women with RIF after the OPTIMUM treatment strategy were 38.3 ± 3.8 years old and had an implantation failure history over 5 (3‐19) ET cycles. Implantation testing identified impaired intrauterine circumstances in 75 women (64.7%), an aberrant elevated Th1/Th2 cell ratio in 56 women (48.3%), and thyroid abnormalities in 33 women (28.4%). Cumulative ongoing pregnancy rates including spontaneous pregnancy in the patients aged < 40 and ≥ 40 years were 72.7% and 45.5% within two ET cycles, respectively. The pregnancy outcomes in the OPTIMUM group were significantly higher than those in the control. Conclusions The OPTIMUM treatment strategy improved pregnancy outcomes in patients with RIF.