Anticentromere antibodies are the most potent antinuclear antibodies in reducing live birth outcomes after ICSI.

RESEARCH QUESTION: How, and to what extent, do anticentromere antibodies (ACA) reduce live birth outcomes after ICSI? STUDY DESIGN: Retrospective cohort study of infertile women aged 30-43 years who underwent ICSI between September 2016 and March 2021. Women with a history or current diagnosis of symptomatic connective tissue disease were excluded. Immunofluorescence staining detected antinuclear antibodies (ANA). Staining pattern and titre (cut-off, 1:160) were used to divide infertile women into three groups: positive for ACA (ACA+) (n = 28); positive for ANA other than ACA (ANA+) (n = 77); and negative for both ACA and ANA (control) (n = 3723). RESULTS: Cumulative live birth rate (CLB) was lowest in ACA+ (7%, 31% and 46% in ACA+, ANA+ and control, respectively) (ACA+ versus control, P < 0.0001; ACA+ versus ANA+, P = 0.011; ANA+ versus control, P = 0.012). A small impairment in meiosis I and a larger impairment in meiosis II, fertilization and embryo cleavage caused the decrease. Multiple pronuclei formation increased (RR versus control, 5.33; 95% CI 4.26 to 6.65) and good-quality blastocyst development decreased (RR 0.34; 95% CI 0.22 to 0.53). Multiple logistic regression analysis showed that ACA was associated with CLB outcome (OR 0.08, 95% CI 0.02 to 0.36); the other four ANA staining patterns were not. CONCLUSIONS: The effect of ACA on live birth outcomes is strongest after ICSI among ANA, primarily through the impairment of meiosis II and subsequent stages. Repeated ICSI failure and eggs with multiple pronuclei may warrant specific testing for ACA.

Validation of the Japanese version of the quality of life-Alzheimer's disease for nursing homes.

OBJECTIVES: This study aims to validate the Japanese version of Quality of Life-Alzheimer's Disease for Nursing Homes (QOL-AD NH). This is the modified version of QOL-AD, initially developed for residents living with dementia in long-term care settings. METHODS: Psychometric assessment was conducted in a sample of 101 residents and their professional care staff to obtain self-ratings and proxy-ratings of QOL, respectively. Residents' behavior was observed using Dementia Care Mapping (DCM) method, and their mood/engagement (ME) value was evaluated as a proxy measure of QOL. RESULTS: Self-ratings were higher than proxy-ratings (t = 10.22, p<.001), with moderate correlation (r=.51, p<.001) and strong internal consistency (α=.87 for both). The exact agreement between the two groups was 38.23%. Convergent validity was confirmed with ME value and positive engagements of DCM. Exploratory factor analysis was performed for further validity testing. Three factors - self and life overall, social environment, and physical and psychological health, accounted for 85.9% of the total variance with Cronbach's α of .87, .73, .90, respectively. CONCLUSION: Using a validated Japanese version of the QOL-AD NH may help assess the QOL of older residents living in long-term care settings to improve the continuum of care for dementia.

Evaluation of the clinical performance of noninvasive prenatal testing at a Japanese laboratory.

AIM: We aimed to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of noninvasive prenatal testing (NIPT) in high-risk pregnant women. METHODS: Pregnant women who underwent GeneTech NIPT, the most commonly used NIPT in Japan, between January 2015 and March 2019, at Japan NIPT Consortium medical sites were recruited for this study. The exclusion criteria were as follows: pregnant women with missing survey items, multiple pregnancy/vanishing twins, chromosomal abnormalities in the fetus other than the NIPT target disease, and nonreportable NIPT results. Sensitivity and specificity were calculated from the obtained data, and maternal age-specific PPV and NPV were estimated. RESULTS: Of the 45 504 cases, 44 263 cases fulfilling the study criteria were included. The mean maternal age and gestational weeks at the time of procedure were 38.5 years and 13.1 weeks, respectively. Sensitivities were 99.78% (95% confidence interval [95% CI]: 98.78-99.96), 99.12% (95% CI: 96.83-99.76), and 100% (95% CI: 88.30-100) for trisomies 21, 18, and 13, respectively. Specificities were more than 99.9% for trisomies 21, 18, and 13, respectively. Maternal age-specific PPVs were more than 93%, 77%, and 43% at the age of 35 years for trisomies 21, 18, and 13, respectively. CONCLUSION: The GeneTech NIPT data showed high sensitivity and specificity in the detection of fetal trisomies 21, 18, and 13 in high-risk pregnant women, and maternal age-specific PPVs were obtained. These results could provide more accurate and improved information regarding NIPT for genetic counseling in Japan.

Qualitative investigation of the factors that generate ambivalent feelings in women who give birth after receiving negative results from non-invasive prenatal testing.

BACKGROUND: Women who receive negative results from non-invasive prenatal genetic testing (NIPT) may find that they later have mixed or ambivalent feelings, for example, feelings of accepting NIPT and regretting undergoing the test. This study aimed to investigate the factors generating ambivalent feelings among women who gave birth after having received negative results from NIPT. METHODS: A questionnaire was sent to women who received a negative NIPT result, and a contents analysis was conducted focusing on ambivalent expressions for those 1562 women who responded the questionnaire. The qualitative data gathered from the questionnaire were analyzed using the N-Vivo software package. RESULTS: Environmental factors, genetic counseling-related factors, and increased anticipatory anxiety, affected the feeling of ambivalence among pregnant women. Furthermore, pregnant women desired more information regarding the detailed prognosis for individuals with Down syndrome and living with them and/or termination, assuming the possibility that they were positive. CONCLUSIONS: Three major interrelated factors affected the feeling of ambivalence in women. Highlighting and discussing such factors during genetic counseling may resolve some of these ambivalences, thereby enhancing the quality of decisions made by pregnant women.

Classification of factors involved in nonreportable results of noninvasive prenatal testing (NIPT) and prediction of success rate of second NIPT.

OBJECTIVE: To evaluate the reasons for nonreportable cell-free DNA (cfDNA) results in noninvasive prenatal testing (NIPT), we retrospectively studied maternal characteristics and other details associated with the results. METHODS: A multicenter retrospective cohort study in pregnant women undergoing NIPT by massively parallel sequencing (MPS) with failed cfDNA tests was performed between April 2013 and March 2017. The women's data and MPS results were analyzed in terms of maternal characteristics, test performance, fetal fraction (FF), z scores, anticoagulation therapy, and other details of the nonreportable cases. RESULTS: Overall, 110 (0.32%) of 34 626 pregnant women had nonreportable cfDNA test results after an initial blood sampling; 22 (20.0%) cases had a low FF (<4%), and 18 (16.4%) cases including those with a maternal malignancy, were found to have altered genomic profile. Approximately half of the cases with nonreportable results had borderline z score. Among the women with nonreportable results because of altered genomic profile, the success rate of retesting using a second blood sampling was relatively low (25.0%-33.3%). Thirteen (11.8%) of the women with nonreportable results had required hypodermic heparin injection. CONCLUSIONS: The classification of nonreportable results using cfDNA analysis is important to provide women with precise information and to reduce anxiety during pregnancy.

Age-specific values of Access anti-Müllerian hormone immunoassay carried out on Japanese patients with infertility: a retrospective large-scale study.

BACKGROUND: The ovarian reserve in women is known to correlate with anti-Müllerian hormone (AMH) levels, and currently the latest, third-generation, fully-automated AMH immunoassays, such as Access and Cobas, are beginning to be used for measuring AMH levels. However, the age-specific reference values obtained for AMH levels have been based on samples from an American population, measured using first-generation immunoassays. In this study, we attempted to determine the age-specific AMH reference values based on a large set of samples taken from Japanese infertile women measured by Access so that they could be used by infertility centers treating Japanese and those with similar racial and life-style characteristics. METHODS: The study included 5483 Japanese patients who enrolled in infertility treatment programs at two in-vitro fertilization centers, Shimbashi YUME Clinic and Natural ART Clinic Nihombashi in Tokyo, and who had their serum AMH levels measured between December 2015 and November 2017 by Access. Each patient was represented only once in the study. The mean, median, and standard deviation values were obtained from the measured values for single-year intervals from 28 through 48 years of age (21 age groups in total). The 3D-fitted curve of age-specific mean and median values measured by Access was obtained by regression analysis. RESULTS: The mean and median values decreased with advancing age (mean: R2 = 0.9864; median: R2 = 0.9926). In all age groups, the mean values were higher than the median values; however, the differences between these values decreased with increasing age. CONCLUSIONS: The age-specific AMH reference values measured by Access in this study may serve as a useful diagnostic marker in infertility centers, especially those treating Japanese patients or patients with similar characteristics.

A Novel Treatment for Cervical and Cesarean Section Scar Pregnancies by Transvaginal Injection of Absolute Ethanol to Trophoblasts: Efficacy in 19 Cases.

STUDY OBJECTIVE: To evaluate the efficacy of a nonsurgical treatment for cervical pregnancy (CP) and cesarean section scar pregnancy (CSP). DESIGN: Retrospective clinical study (Canadian Task Force classification III). SETTING: Private assisted reproductive technology practice. PATIENTS: Nineteen women with CP (n = 16) or CSP (n = 3), including 6 patients with positive fetal heartbeat. INTERVENTION: Transvaginal local injection of absolute ethanol (AE) into the hyperechoic ring (lacunar space) around the gestational sac under ultrasound guidance. MEASUREMENTS AND MAIN RESULTS: Serum beta-human chorionic gonadotropin (ß-hCG) was measured at frequent intervals, and ultrasound and/or magnetic resonance imaging was used to observe the gestational sac. In 9 patients, the serum ß-hCG level was effectively reduced with a single AE injection at 2 hours. In the remaining 10 patients, the level decreased but then increased in 4 and slowly decreased in the other 6; all of these 10 patients required 2 to 5 repeat AE injections. In all patients, serum ß-hCG level was reduced by 50% within 3 days and decreased to <10% of the initial level within 14 days. In 18 patients (95%), the level was decreased to 1.0 mIU/mL within 40 days. Seven patients were treated on an outpatient basis. Twelve patients received no anesthesia. Five patients subsequently became pregnant, and each had a live birth. There was no recurrent CP or CSP. The procedure was successful in all 19 patients. CONCLUSION: This procedure is an effective treatment for CP or CSP that could be used in place of conventional surgical interventions and medical treatment using MTX.

Levothyroxine supplementation improves serum anti-Müllerian hormone levels in infertile patients with Hashimoto's thyroiditis.

AIM: Thyroid dysfunction and autoimmunity are associated with an adverse effect on fertility. An aberrant high thyroid stimulating hormone level is associated with diminished ovarian reserve in women of reproductive age; however, the utility of levothyroxine (LT4) replacement for infertile patients with subclinical hypothyroidism is still under discussion. The aim of this study was to investigate whether LT4 supplementation for infertile patients with subclinical hypothyroidism improves impaired ovarian function. METHODS: We measured levels of serum thyroid-related hormones and a biomarker of ovarian function, anti-Müllerian hormone (AMH) in infertile women from 2014 to 2015. Out of a consecutive 1431 infertile patients, 311 patients with an elevated thyroid stimulating hormone level (≥ 2.5 µIU/mL) underwent detailed thyroid examinations, including blood tests of thyroid antibodies. We recruited 174 infertile patients, excluding patients with factors impacting ovarian and thyroid function. We evaluated alterations in AMH and thyroid related hormone levels during LT4 supplementation and infertility treatment with assisted reproductive technology. RESULTS: After LT4 supplementation, no significant change in the average AMH level was detected overall. However, the AMH level in 35 patients with Hashimoto's disease increased significantly after treatment (1 month 1.3 ± 0.5 fold, P = 0.007; 3 months 1.3 ± 0.4 fold, P = 0.040). The AMH level in patients with thyroglobulin antibody-positive and thyroid peroxidase antibody-negative also significantly increased after LT4 treatment (1 and 3 months 1.5 fold; P = 0.023). CONCLUSION: In the patients with Hashimoto's disease, preconception LT4 treatment may relieve adverse effects, including autoimmune antibodies, and support follicular development.

Cytogenetic analysis of the retained products of conception after missed abortion following blastocyst transfer: a retrospective, large-scale, single-centre study.

Cytogenetic analysis of the retained products of conception (POC) is the most effective test for identifying miscarriage causes. However, there has been no large-scale study limited to blastocyst transfer. This study retrospectively reports the findings of 1030 cases in which POC analysis was performed after missed abortion following single blastocyst transfer performed at the Shinbashi Yume Clinic. We identified 19.4% as normal karyotypes and 80.6% as aneuploid. These cases broke down into: 62.3% trisomy; 7.8% double trisomy; 0.5% triple or quadruple trisomy; 1.3% monosomy 21; 3.2% monosomy X; 0.1% 47,XXY; 1.0% polyploidy; 1.0% mixed; 1.1% embryonic mosaicism; and 2.4% structural anomalies. In samples with normal karyotypes, 49.5% were female while 50.5% were male. The occurrence of trisomy and double trisomy were both significantly more frequent in the ≥38 years group than in the ≤37 years group (P < 0.01). Trisomy was significantly more frequently associated with fetal heartbeat (P < 0.01); double trisomy, polyploidy and normal karyotype were significantly more frequent with no fetal heartbeat (P < 0.01). There was no significant difference in the frequency of chromosomal abnormalities between the number of miscarriages or blastocyst quality. Thus, POC cytogenetic testing is highly valuable for ascertaining the cause of miscarriage.

Current status of non-invasive prenatal testing in Japan.

AIM: The purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan. METHODS: Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. RESULTS: From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. CONCLUSION: Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.

Quality of Life of SGA Children with Short Stature Receiving GH Treatment in Japan.

The objective of this study was to compare the quality of life (QOL) of small for gestational age (SGA) children with short stature with that of children with normal height, and examine the effects of growth hormone (GH) treatment on the QOL of the SGA children using questionnaires administered to their parents or guardians. The results showed that QOL in daily living of SGA children with short stature was lower than that of normal children based on the perceptions of their parents or guardians. In addition, GH treatment improved the physical domain of QOL of SGA children with short stature. This study suggests that GH treatment can improve QOL and reduce psychosocial problems related to short stature.

Higher education in gerontology: A comparison of master's programs in Japan, Taiwan, and Turkey.

As of 2015, there is only one master's program of gerontology acknowledged by each of the following countries: Japan, Taiwan, and Turkey. All three programs have fewer than 15 years of history. These three countries differ in society types based on the proportion of older adults, rate of population aging, and population size. However, in terms of gerontological education, they seem to share great commonalities. Common challenges are a lack of awareness of the field of gerontology, insufficient numbers of gerontology programs and faculty members to produce trained gerontologists within society, and the inadequacy of opportunities for trained gerontologists to play an active role in various fields. This study intends not only to compare the differences and similarities among three countries and programs, but also to elucidate characteristics of a unique gerontology program in each country and identify challenges and possibilities from the perspective of gerontological educators.

Posttraumatic Growth Following the Loss of a Pet.

The current study examined Posttraumatic Growth (PTG) experienced by bereaved pet owners in the United States, French-Canada, Japan, and Hong Kong following the death of their pet. Using qualitative methodology, we analyzed responses of participants who answered "yes" to a question about experiencing PTG and explored to what extent the cross-cultural responses mapped onto the five factors of the Posttraumatic Growth Inventory (PTGI). For the U.S. sample, 58% of responses mapped onto the PTGI. For French-Canada, 72% of responses mapped onto the PTGI. For Japan, 50% of responses mapped onto the PTGI and for Hong Kong, 39% of responses mapped onto the PTGI. We also explored emergent categories related to PTG for individuals who have lost a pet and discerned the unique aspects for PTG across cultures.

A survey on awareness of genetic counseling for non-invasive prenatal testing: the first year experience in Japan.

The purpose of this study is to summarize the results from a survey on awareness of genetic counseling for pregnant women who wish to receive non-invasive prenatal testing (NIPT) in Japan. As a component of a clinical study by the Japan NIPT Consortium, genetic counseling was conducted for women who wished to receive NIPT, and a questionnaire concerning both NIPT and genetic counseling was given twice: once after pre-test counseling and again when test results were reported. The responses of 7292 women were analyzed. They expressed high satisfaction with the genetic counseling system of the NIPT Consortium (94%). The number of respondents who indicated that genetic counseling is necessary for NIPT increased over time. Furthermore, they highly valued genetic counseling provided by skilled clinicians, such as clinical geneticists or genetic counselors. The vast majority (90%) responded that there was sufficient opportunity to consider the test ahead of time. Meanwhile, women who received positive test results had a poor opinion and expressed a low-degree satisfaction. We confirmed that the pre-test genetic counseling that we conducted creates an opportunity for pregnant women to sufficiently consider prenatal testing, promotes its understanding and has possibilities to effectively facilitate informed decision making after adequate consideration. A more careful and thorough approach is considered to be necessary for women who received positive test results.

Changes in estrone and estradiol levels during follicle development: a retrospective large-scale study.

BACKGROUND: The improved reagent for measuring estradiol (E2), the ST AIA-PACK iE2 reagent, has a higher specificity for the measurement of E2 levels than the original ST AIA-PACK E2 reagent, because of its lower cross-reactivity with estrone (E1). As we had E2 data obtained with either of the reagents, we analyzed changes in E1 and E2 levels during follicle development. METHODS: The study included 14371 serum hormone measurements from 4412 patients who underwent oocyte retrieval or frozen/thawed embryo transfer in natural cycle in vitro fertilization in Shinbashi YUME clinic, Tokyo, between June 2011 and May 2014. The age of the patients ranged from 24 to 48 year (mean and standard deviation, 39.8 ± 4.0 year). Patients were categorized into three age groups (<38 year, 38-40 year, and >40 year) and into 10 groups of largest follicle diameter from 11 to 20 mm, with 1-mm intervals. Serum E2 levels were measured in the follicular phase with either the ST AIA-PACK E2 reagent or the ST AIA-PACK iE2 reagent, and the data were compared. Also, for 26 randomly selected samples, E2 was measured using both reagents, together with E1 and E3, and the E1/E2 ratios were compared. RESULTS: E2 concentrations measured with the ST AIA-PACK iE2 reagent were significantly lower than those measured with the ST AIA-PACK E2 reagent in the largest follicle diameter category of 11-17 mm in the <38 year group, in the largest follicle diameter category of 11-18 mm in the 38-40 year group, and in the largest follicle diameter category of 11-15 mm in the >40 year group. The serum E1/E2 ratio in the 26 samples was 3.4 ± 1.1 and 0.7 ± 0.1 in the early follicular phase and in the ovulatory phase, respectively. CONCLUSIONS: The difference between the E2 concentrations measured with the ST AIA-PACK E2 reagent and the ST AIA-PACK iE2 reagent tended to decrease as the follicle diameter increased, particularly in the older patients, which suggests E1 secretion is more abundant in the early follicular phase and in younger patients than in the ovulatory phase and in older patients.

Prevalence of chronic endometritis in patients with infertility due to hydrosalpinx or pelvic peritubal adhesions and effect of laparoscopic surgical correction on pregnancy rates post in vitro fertilization.

OBJECTIVE(S): To assess the prevalence of chronic endometritis (CE) in patients with infertility and hydrosalpinx or peritubal adhesions and to examine the effects of laparoscopic surgical correction (LSC) on CE and pregnancy rates post in vitro fertilization and embryo transfer (IVF-ET). STUDY DESIGN: This is a retrospective cohort study at private IVF-ET centers. A total of 438 patients, known to have hydrosalpinx (n = 194) or peritubal adhesions (n = 244), and undergoing IVF treatment between April 1, 2018 and September 30, 2020 were included in the study. Hysterosalpingography, magnetic resonance imaging, and transvaginal ultrasonography were used to diagnose the hydrosalpinx or peritubal adhesions. Laparoscopic examination and surgical correction were performed on patients with CE. IVF-ET was performed after recovery from LSC. RESULTS: CE was present in 45.9% of patients (89/194) with hydrosalpinx and 14.3% with peritubal adhesions (35/244). All the 89 patients with CE and hydrosalpinx underwent laparoscopic salpingostomy and/or fimbrioplasty, and 64 (71.9%) further underwent proximal tubal occlusion. All the 35 patients with CE and peritubal adhesions underwent laparoscopic adhesiolysis and/or fimbrioplasty, and 19 (54.3%) further underwent proximal tubal occlusion. CD138 PC levels after LSC decreased to < 5 in 70 of 124 patients (56.5%) in one menstrual cycle and decreased to < 5 in all cases within 6 months. Of the 66 patients who underwent a single blastocyst transfer, 57 delivered (cumulative live birth rate (LBR): 86.3%). The cumulative LBR of patients treated for CE with LSC (86.3%) was significantly different from those given antibiotic therapy (320 patients; 38.4%; p <.0001) and the CD138-negative groups (811; 31.8%; p <.0001). CONCLUSION: CE is prevalent in patients with hydrosalpinx and/or peritubal adhesions who present with infertility. LSC improved CE without antibiotic therapy, improving the CP and LBR after IVF-ET.

Surgical procedure to conserve the uterus for future pregnancy in patients suffering from massive adenomyosis.

The treatment for severe adenomyosis has usually been hysterectomy, because there is no line of demarcation between diseased and normal tissue. Yet many such women wish to retain their uterus and some even wish to bear children. This report evaluates the efficacy of a new method of adenomyomectomy, where adenomyotic tissues are radically excised and the uterine wall is reconstructed by a triple-flap method, without overlapping suture lines, to prevent uterine rupture in subsequent pregnancies. This is a prospective case series followed for 10 years from June 1998 to August 2008 of 104 women with severe adenomyosis verified histologically and with magnetic resonance imaging. There was a dramatic reduction in both dysmenorrhoea and hypermenorrhoea and all patients returned to having normal menstrual cycles. Of 26 women who wished to conceive, 16 became pregnant, 14 (53.8%)went to term and delivered a healthy baby and there were no cases of uterine rupture. Adenomyosis symptoms recurred in only four out of 104 cases. The procedure thus resulted in a dramatic reduction in symptoms and allowed over half of women who wished to conceive to go to term without uterine rupture.

Influence of fetal stabilization on postnatal status of patients with congenital diaphragmatic hernia.

PURPOSE: Fetal stabilization (FS) is a way to decrease stresses to the fetus during the perinatal period to control persistent pulmonary hypertension in neonates (PPHN). Although FS in congenital diaphragmatic hernia (CDH) patients has been reported, the effect of FS has not been evaluated sufficiently. The present study retrospectively evaluated influences of FS on the postnatal status of CDH patients. METHODS: Twenty-three cases of prenatally diagnosed CDH which were treated after birth in our institution from April 1998 to March 2010 were reviewed. From April 1998 to May 2007, FS was performed by administration of fentanyl and midazolam to the mother before subsequent cesarean section (FS group, n = 10). Beginning from June 2007, FS was discontinued (non-FS, n = 13). RESULTS: At the first postnatal estimation, flow pattern of the ductus arteriosus had no difference between two groups. The oxygenation index of the FS group was significantly higher than that in the non-FS group (p = 0.045). Only the non-FS group had correlations between estimated standardized lung volume (% lung volume) and alveolar-arterial oxygen tension difference (p = 0.022), and between % lung volume and the oxygenation index (p = 0.0037). CONCLUSION: During the period immediately after birth, FS had no obvious therapeutic effect on PPHN, and had a negative impact on respiratory status.