Publications by authors named "Yukiko Katagiri"

32 Publications

Optimal individualization of patient-oriented ovarian stimulation in Japanese assisted reproductive technology clinics, a review for unique setting with advanced-age patients.

J Obstet Gynaecol Res 2022 Jan 13. Epub 2022 Jan 13.

Department of Obstetrics and Gynecology, Saitama Medical University, Saitama, Japan.

Ovarian stimulation is a key issue in assisted reproductive technology (ART) treatment. ART practice in Japan is unique with various types of ovarian stimulation protocols, which may contribute to lower pregnancy rates compared to other countries. This review aims to clarify optimal individualized ovarian stimulation for improving the pregnancy rate per one oocyte retrieval cycle in Japan. We performed a literature review to describe ovarian stimulation, classification of infertile women depending on ovarian reserve and response, and Japanese ART data and discussed optimal conventional and mild ovarian stimulation protocols in Japan. According to Japanese ART registry data, the live birth rate of 30-35-year-old women was 32%-37% per ET cycle; therefore, four to five embryos are calculatedly needed when aiming a cumulative live birth rate of ≥80%. Mild stimulation aimed at collecting 5-10 oocytes can be alternative choice as an optimal ovarian stimulation protocol in young women. In 40-year-old women, the live birth rate is 18.8%, resulting in eight or more embryos as necessary. Conventional stimulation must be required in women with advanced age. In poor responders, however, mild stimulation may be sufficient for maximumly extracting their ovarian function. In Japan, mild ovarian stimulation can be selected in patients with a good prognosis and poor responders; however, conventional ovarian stimulation is necessary for women in advanced age.
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http://dx.doi.org/10.1111/jog.15150DOI Listing
January 2022

Trocar-site hernia following laparoscopic salpingo-oophorectomy in a middle-aged Japanese woman: an initial case report after 40 years of experience at a single center and a brief literature review.

BMC Womens Health 2022 Jan 8;22(1). Epub 2022 Jan 8.

Department of Obstetrics and Gynecology, Toho University, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8751, Japan.

Background: In gynecology, the number of laparoscopic surgeries performed has increased annually because laparoscopic surgery presents a greater number of advantages from a cosmetic perspective and allows for a less invasive approach than laparotomy. Trocar site hernia (TSH) is a unique complication that causes severe small bowel obstruction and requires emergency surgery. Its use has mainly been reported with respect to gastrointestinal laparoscopy, such as for cholecystectomy. Contrastingly, there have been few reports on gynecologic laparoscopy because common laparoscopic surgeries, such as laparoscopic salpingo-oophorectomy, are considered low risk due to shorter operative times. In this study, we report on a case of a woman who developed a TSH 5 days postoperatively following a minimally invasive laparoscopic surgery that was completed in 34 min.

Case Presentation: A 41-year-old woman who had undergone laparoscopic salpingo-oophorectomy 5 days previously presented with the following features of intestinal obstruction: persistent abdominal pain, vomiting, and inability to pass stool or flatus. A computed tomography scan of her abdomen demonstrated a collapsed small bowel loop that was protruding through the lateral 12-mm port. Emergency surgery confirmed the diagnosis of TSH. The herniated bowel loop was gently replaced onto the pelvic floor and the patient did not require bowel resection. After the surgical procedure, the fascial defect at the lateral port site was closed using 2-0 Vicryl sutures. On the tenth postoperative day, the patient was discharged with no symptom recurrence.

Conclusions: The TSH initially presented following laparoscopic salpingo-oophorectomy; however, the patient did not have common risk factors such as obesity, older age, wound infection, diabetes, and prolonged operative time. There was a possibility that the TSH was caused by excessive manipulation during the tissue removal through the lateral 12-mm port. Thereafter, the peritoneum around the lateral 12-mm port was closed to prevent the hernia, although a consensus around the approach to closure of the port site fascia had not yet been reached. This case demonstrated that significant attention should be paid to the possibility of patients developing TSH. This will ensure the prevention of severe problems through early detection and treatment.
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http://dx.doi.org/10.1186/s12905-021-01528-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742918PMC
January 2022

Dynamic changes in serum steroid hormone during the first trimester of pregnancy between infertile women conceiving with and without hormone replacement therapy.

Heliyon 2021 Oct 29;7(10):e08100. Epub 2021 Sep 29.

Department of Obstetrics and Gynecology, Toho University Graduate School of Medicine, 5-21-16 Omorinishi Ota-ku, Tokyo, Japan.

Objective: Recent advances in cancer treatment and reproductive medicine have made the post-treatment quality of life an important concern for cancer survivors. We aimed to evaluate the safety of sex hormone (estradiol and progesterone) replacement therapy (HRT) in women who conceived by assisted reproductive technology (ART) with hormone receptor-positive breast cancer.

Methods: We measured serum E2 and P4 levels at 4-10 weeks of gestation in women who conceived naturally or after timed intercourse or intrauterine insemination for infertility without HRT for luteal support (non-HR group; n = 135). We conducted a retrospective comparison of the values from the non-HR group with those of women who conceived by ART with HRT for infertility (HR group; n = 75).

Results: Serum E2 levels were significantly higher in the non-HR group than in the HR group at 5, 6, and 8 weeks of gestation. Similarly, serum P4 levels were significantly higher in the non-HR group than in the HR group at 4, 5, and 6 weeks of gestation.

Conclusions: This study suggests that in cancer reproductive medicine for hormone-dependent breast cancer survivors, HRT administered during the first trimester of a pregnancy after primary disease treatment may not increase the sex hormone levels to levels above those seen in spontaneous pregnancy.
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http://dx.doi.org/10.1016/j.heliyon.2021.e08100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502902PMC
October 2021

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

J Obstet Gynaecol Res 2021 Oct 5;47(10):3437-3446. Epub 2021 Aug 5.

Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan.

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.
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http://dx.doi.org/10.1111/jog.14954DOI Listing
October 2021

Genetic counseling prior to assisted reproductive technology.

Reprod Med Biol 2021 Apr 31;20(2):133-143. Epub 2020 Dec 31.

Department of Obstetrics and Gynecology Faculty of Medicine Toho University Tokyo Japan.

Background: Reproductive medicine deals with fertility and is closely related to heredity. In reproductive medicine, it is necessary to provide genetic information for the patients prior to assisted reproductive technology (ART). Japan Society for Reproductive Medicine (JSRM) requires doctors involved in reproductive medicine to have standard knowledge of reproductive genetics and knowledge of reproductive medicine, which is covered in their publication, "required knowledge of reproductive medicine."

Methods: With the aim of providing straightforward explanations to patients in the clinical situation at pre-ART counseling, we provide the following five topics, such as (a) risk of birth defects in children born with ART, (b) chromosomal abnormalities, (c) Y chromosome microdeletions (YCMs), (d) possible chromosomal abnormal pregnancy in oligospermatozoa requiring ICSI (intracytoplasmic sperm injection), and (e) epigenetic alterations.

Main Findings: The frequency of chromosome abnormalities in infertile patients is 0.595%-0.64%. YCMs are observed in 2%-10% of severe oligospermic men. High incidence of spermatozoa with chromosomal abnormalities has been reported in advanced oligospermia and asthenozoospermia that require ICSI. Some epigenetic alterations were reported in the children born with ART.

Conclusion: Certain genetic knowledge is important for professionals involved in reproductive medicine, even if they are not genetic experts.
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http://dx.doi.org/10.1002/rmb2.12361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022097PMC
April 2021

Assisted reproductive technology in Japan: A summary report for 2018 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology.

Reprod Med Biol 2021 Jan 20;20(1):3-12. Epub 2020 Nov 20.

Department of Obstetrics and Gynecology Faculty of Medicine The University of Tokyo Tokyo Japan.

Purpose: Since 2007, the Japan Society of Obstetrics and Gynecology (JSOG) has collected cycle-based data for assisted reproductive technology (ART) in an online registry. Here, we present the characteristics and treatment outcomes of ART cycles registered during 2018.

Methods: The Japanese ART registry consists of cycle-specific information for all ART treatment cycles implemented at 621 participating facilities. We conducted descriptive analyses for such cycles registered for 2018.

Results: In total, 454 893 treatment cycles and 56 979 neonates were reported in 2018: both increased from 2017. The mean maternal age was 38.0 years (standard deviation ± 4.7). Of 247 402 oocyte retrievals, 118 378 (47.8%) involved freeze-all-embryos cycles; fresh embryo transfer (ET) was performed in 50 463 cycles: a decreasing trend since 2015. A total of 199 914 frozen-thawed ET cycles were reported, resulting in 69 357 pregnancies and 49 360 neonates born. Single ET (SET) was performed in 82.2% of fresh transfers and 83.4% of frozen-thawed cycles, with singleton pregnancy/live birth rates of 97.2%/97.2% and 97.0%/97.2%, respectively.

Conclusions: Total ART cycles and subsequent live births increased in 2018. SET was performed in over 80% of cases, and the mode of ET has shifted continuously from using fresh embryos to frozen-thawed ones compared with previous years.
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http://dx.doi.org/10.1002/rmb2.12358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812461PMC
January 2021

DuoStim: a new option for fertility preservation for a woman with Turner syndrome.

Gynecol Endocrinol 2020 Dec 18;36(12):1144-1148. Epub 2020 Sep 18.

Department of Obstetrics and Gynecology, Faculty of Medicine, Toho University, Ota-ku, Japan.

Introduction: Turner syndrome (TS) is associated with hypergonadotropic hypogonadism due to gonadal dysgenesis, which results in premature ovarian failure and subsequent infertility. Therefore, counseling and evaluation for fertility preservation are required as early as possible for women with TS.

Case Presentation: A 23-year-old unmarried woman with mosaic TS (45, X [4/30] 46, XX [26/30]) presented to the pediatric department of our hospital for fertility counseling; she was accompanied by her mother. She was referred to the reproduction center of our hospital for ovarian reserve assessment and counseling regarding fertility preservation. We decided to retrieve oocytes using DuoStim as the controlled ovarian stimulation protocol. During the first and second oocyte retrievals, a total of 17 (9 and 8, respectively) mature metaphase II oocytes were cryopreserved.

Conclusion: DuoStim may be a useful option for fertility preservation for women with TS and reduced ovarian reserve. This new strategy may obtain the required number of oocytes in the shortest time and preserve the future fertility of women with TS.
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http://dx.doi.org/10.1080/09513590.2020.1822805DOI Listing
December 2020

Differences in the effects of organisational climate on burnout according to nurses' level of experience.

J Nurs Manag 2021 Mar 23;29(2):194-205. Epub 2020 Sep 23.

Department of Nursing, College of Nursing, Kanto Gakuin University, Yokohama, Japan.

Aim: To elucidate the orientation of burnout prevention in line with the experience level of nurses by examining the impact of organisational climate on burnout by nursing experience level.

Background: While the relationship between a nurse and the organisation where they work changes depending on the nurse's experience level, there is a dearth of research that takes into account the nursing experience level in exploring the relationship between organisational climate and burnout.

Method: A cross-sectional questionnaire survey was conducted with 1,102 nurses. Nursing experience was divided into six levels. Two scales for organisational climate and the Maslach burnout inventory were used.

Results: There were effects between the organisational climate and exhaustion/depersonalization, depending on the experience level. Novices with low scores for head nurses' considerations towards staff felt the highest level of emotional exhaustion. For advanced beginners, a sense of control significantly determined emotional exhaustion.

Conclusions: There was a difference in the relationship between organisational climate and burnout in experience level, suggesting different intervention directions.

Implications For Nursing Management: There is a direction of intervention suitable for each experience level, suggesting the need to respond to each accordingly.
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http://dx.doi.org/10.1111/jonm.13137DOI Listing
March 2021

Noninvasive prenatal testing aids identification of tetrasomy 18p: A case report.

Case Rep Womens Health 2020 Jul 25;27:e00236. Epub 2020 Jun 25.

Department of Obstetrics and Gynecology, Toho University Omori Medical Center, Japan.

Tetrasomy 18p syndrome (Online Mendelian Inheritance in Man 614290) is a rare chromosomal disorder that is seen in approximately 1 in every 180,000 live births. It is caused by the presence of isochromosome 18p, which is a supernumerary marker composed of two copies of the short arms of chromosome 18. Isochromosome 18p is one of the most commonly observed isochromosomes. We report tetrasomy 18p syndrome diagnosed prenatally after noninvasive prenatal testing (NIPT) was positive for trisomy 18. Tetrasomy 18p was finally diagnosed by G-banding and fluorescence hybridization of chromosome 18p, before invasive confirmatory testing the karyotype findings by NIPT showed an increase in the DNA fragments from chromosome 18p, indicating duplication of chromosome 18p. NIPT can detect not only trisomy 13, 18, and 21, but also structural chromosomal anomalies, such as deletions and duplications. An NIPT report "positive for trisomy 18" indicates the possibility of tetrasomy 18p, and detailed analysis of NIPT data can reveal subchromosomal copy number variations, to a certain extent, before definitive diagnostic testing.
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http://dx.doi.org/10.1016/j.crwh.2020.e00236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334301PMC
July 2020

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

BMC Pregnancy Childbirth 2020 Feb 17;20(1):112. Epub 2020 Feb 17.

Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan.

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.
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http://dx.doi.org/10.1186/s12884-020-2763-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027219PMC
February 2020

Assisted reproductive technology in Japan: A summary report for 2017 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology.

Reprod Med Biol 2020 Jan 21;19(1):3-12. Epub 2019 Nov 21.

Department of Urology Graduate School of Medicine Chiba University Chiba Japan.

Purpose: The Japan Society of Obstetrics and Gynecology (JSOG) has collected cycle-based assisted reproductive technology (ART) data in an online registry since 2007. Herein, we present the characteristics and treatment outcomes of ART cycles registered during 2017.

Methods: We collected cycle-specific information for all ART cycles implemented at participating facilities and performed descriptive analysis.

Results: In total, 448,210 treatment cycles and 56,617 neonates (1 in 16.7 neonates born in Japan) were reported in 2017, increased from 2016; the number of initiated fresh cycles decreased for the first time ever. The mean patient age was 38.0 years (standard deviation 4.6). A total 110,641 of 245,205 egg retrieval cycles (45.1%) were freeze-all cycles; fresh embryo transfer (ET) was performed in 55,720 cycles. A total 194,415 frozen-thawed ET cycles were reported, resulting in 66,881 pregnancies and 47,807 neonates born. Single ET (SET) was performed in 81.8% of fresh transfers and 83.4% of frozen cycles, with singleton pregnancy/live birth rates of 97.5%/97.3% and 96.7%/96.6%, respectively.

Conclusions: Total ART cycles and subsequent live births increased continuously in 2017, whereas the number of initiated fresh cycles decreased. SET was performed in over 80% of cases, and ET shifted from using fresh embryos to frozen ones.
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http://dx.doi.org/10.1002/rmb2.12307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955594PMC
January 2020

Annual report of Reproductive Endocrinology Committee, Japan Society of Obstetrics and Gynecology, 2019.

J Obstet Gynaecol Res 2019 Oct 9;45(10):1975-1979. Epub 2019 Aug 9.

Department of Obstetrics and Gynecology, Graduate School of Medicine Science, Kanazawa University, Kanazawa, Ishikawa, Japan.

The Japan Society of Obstetrics and Gynecology Reproductive Endocrinology Committee summarizes the activities of each subcommittee below from April 2017 to March 2019. Current important issues regarding reproductive medicine were examined and discussed from social, political, ethical and scientific viewpoints. A nation-wide survey targeted at OB/GYN facilities revealed the usual procedure in diagnosis and management of fertility-desiring POI patients and fertility outcomes of the patients. How to introduce and adapt FIGO AUB systems to obstetric and gynecologic practices in Japan was examined and discussed.
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http://dx.doi.org/10.1111/jog.14074DOI Listing
October 2019

Safety of uterine fundal pressure maneuver during second stage of labor in a tertiary perinatal medical center: A retrospective observational study.

Taiwan J Obstet Gynecol 2019 May;58(3):375-379

Department of Obstetrics and Gynecology, Toho University Omori Medical Center, Japan.

Objective: This study aimed to evaluate the conformity of the indications and implementation status of uterine fundal pressure maneuver (UPFM) and to examine its safety according to the Japan Society of Obstetrics and Gynecology (JSOG) guidelines.

Materials And Methods: We selected all the patients (n = 265) who were treated with UFPM between January 2015 and March 2017. We first evaluated the conformity of the indications and implementation status of UFPM concerning the guidelines for obstetrical practice in Japan, 2017. Second, we retrospectively examined maternal and fetal adverse events (AEs) to determine the safety of UFPM.

Results: In total, 265 patients underwent UFPM; of all the UFPM-assisted deliveries, 189 patients (72%) were evaluated for conformity. Of these 189 patients, 181 (95.7%) were confirmed to be compliant. Laceration of the birth canal was the most frequently occurring maternal AE, followed by cervical laceration. No cases of uterine rupture, severe AEs leading to an extended hospital stay, and maternal deaths were observed. Although fetal AEs requiring admission to neonatal intensive care unit (NICU) were recorded for 33 patients (12.5%), all newborns developed normally without sequela.

Conclusion: The findings of this study may support the validity of the 2017 guidelines. Because it is difficult to find evidence of the safety of use of UFPM, it is essential to accumulate experiences and results learned in clinical practice to build a consensus in the future using the current 2017 guidelines as a standard as done in the current study.
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http://dx.doi.org/10.1016/j.tjog.2018.10.033DOI Listing
May 2019

Genome-wide DNA methylation analysis in obese women predicts an epigenetic signature for future endometrial cancer.

Sci Rep 2019 04 23;9(1):6469. Epub 2019 Apr 23.

Department of Obstetrics and Gynecology, Graduate School of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan.

Aberrant DNA methylation is associated with the oncogenesis of a variety of human cancers, including endometrial cancer (EC), the seventh most common cancer among women. Obesity is known to be a high-risk factor for EC; however, whether obesity influences DNA methylation in the presymptomatic uterus and if this influences EC development remain unclear. Here, we performed genome-wide DNA methylation analysis of isolated endometrial epithelial cells obtained from obese presymptomatic participants. Using the Illumina MethylationEPIC array (850 K), we identified 592 differentially methylated regions (DMRs), most of which undergo hypomethylated changes. These DMRs were enriched for pyrimidine metabolism, Epstein-Barr virus infection, and B cell signaling pathways, indicating obesity-related dysregulation of certain metabolic processes in the presymptomatic uterus. Comparison of the DMRs with those in stage I EC revealed that 54 DMRs overlapped; additionally, B cell signaling and Epstein-Barr virus infection pathways were shared between the presymptomatic uterus of obese women and stage I EC with greater hypomethylation in women with EC than in presymptomatic obese women. These findings indicated that obesity influences DNA methylation in presymptomatic endometrial epithelial cells, and persistent dysregulation of DNA methylation in obese women may result in EC development.
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http://dx.doi.org/10.1038/s41598-019-42840-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478742PMC
April 2019

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

Prenat Diagn 2019 01 10;39(2):100-106. Epub 2019 Jan 10.

Department of Obstetrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.

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.
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http://dx.doi.org/10.1002/pd.5408DOI Listing
January 2019

Fetal cell-free DNA fraction in maternal plasma for the prediction of hypertensive disorders of pregnancy.

Eur J Obstet Gynecol Reprod Biol 2018 May 26;224:165-169. Epub 2018 Mar 26.

Department of Obstetrics and Gynecology, Fujita Health University, Aichi, Japan.

Objective: The purpose of this study is to compare the fetal fractions during non-invasive prenatal testing (NIPT) in singleton pregnancies according to gestational age and maternal characteristics to evaluate the utility of this parameter for the prediction of pregnancy complications including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP).

Study Design: This study was a multicenter prospective cohort study. The present data were collected from women whose NIPT results were negative. The relationships between the fetal fractions and the gestational age, maternal weight and height, and incidences of miscarriage, preterm delivery, and pregnancy complications including GDM, HDP and placental abruption were assessed.

Results: A total of 5582 pregnant women with verified NIPT negative results were registered in the study. The demographic characteristics of the study populations were statistically analyzed, and the women with HDP tended to have a low fetal fraction in samples taken during early gestation. The area under the curve (AUC) in a receiver operating characteristic curve (ROC) analysis was 0.608 for women with HDP.

Conclusion: A low fetal fraction on NIPT might be correlated with future HDP. However, predicting HDP during early pregnancy in women with a low fetal fraction might be difficult.
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http://dx.doi.org/10.1016/j.ejogrb.2018.03.048DOI Listing
May 2018

Ultrasound-guided laparotomic oocyte retrieval during surgery for fertility preservation in a case of tumor recurrence after a unilateral salpingo-oophorectomy.

Reprod Med Biol 2018 01 16;17(1):98-102. Epub 2018 Jan 16.

Graduate School of Medicine Faculty of Medicine Department of Obstetrics and Gynecology Toho University Tokyo Japan.

Case: A 28 year old unmarried woman underwent a unilateral salpingo-oophorectomy and was suspected of having a malignant tumor in the remaining ovary. After consultation with the patient and her family, it was decided to cryopreserve the unfertilized oocytes. In order to reduce the risk of puncturing or rupturing the tumor when performing the oocyte retrieval from the ovary that was affected by the malignant tumor, it was chosen to use direct laparotomic oocyte retrieval during surgery, instead of conventional transvaginal retrieval. In order to further reduce the risk of tumor rupture, an ultrasound was used in the laparotomy field to precisely puncture only the follicle and thus avoid the tumor. A total of 11 oocytes was retrieved and 10 of them were cryopreserved in the MII phase.

Outcome: By using an ultrasound at the same time as the oocyte retrieval, it was possible to avoid the ovarian tumor site. Furthermore, by checking and puncturing the follicles, it became possible to retrieve oocytes from the healthy parts of the ovary with greater precision. The combined use of an ultrasound with oocyte retrieval can be considered to be an effective method because it can be performed relatively easily.

Conclusion: The authors believe that not only macroscopic, but also ultrasonic, methods are useful to reduce the risk of tumor rupture.
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http://dx.doi.org/10.1002/rmb2.12076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768966PMC
January 2018

Current status of non-invasive prenatal testing in Japan.

J Obstet Gynaecol Res 2017 Aug 6;43(8):1245-1255. Epub 2017 Jun 6.

Department of Obstetrics and Gynecology, Osaka University Faculty of Medicine, Suita, Osaka, 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.
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http://dx.doi.org/10.1111/jog.13373DOI Listing
August 2017

Factors affecting parental decisions to terminate pregnancy in the presence of chromosome abnormalities: a Japanese multicenter study.

Prenat Diagn 2016 Dec 21;36(12):1121-1126. Epub 2016 Nov 21.

Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan.

Objective: To investigate the rates of termination of pregnancy (TOP) for fetal chromosomal abnormalities and factors related to such parental decision in Japan.

Methods: A multicenter retrospective cohort study of chromosomal abnormalities diagnosed before 22 weeks of gestation between April 2008 and March 2015. The pregnancy outcomes and parental decisions were investigated.

Results: Among 931 fetuses with chromosome abnormalities, the total TOP rate was 75.1% (699/931). TOP rates were 89.3% (585/655) in autosomal aneuploidies and 40.8% (51/125) in sex chromosome aneuploidies. Trisomy 21 showed the highest TOP rate (93.8% [390/416]) followed by trisomy 18 (84.5% [163/193]) and trisomy 13 (71.9% [23/32]). Indications for karyotyping were related to a parental decision for TOP (p < 0.01): in cases of autosomal aneuploidy, with fetal abnormal ultrasound findings as the reference value, diagnoses made following positive results at non-invasive prenatal testing (adjusted odds ratio [OR]: 13.7, 95% confidence interval [CI] 4.07-45.9) and those because of advanced maternal age (adj. OR 2.91, 95% CI 1.15-7.35) were significantly more frequent.

Conclusions: In Japan, pregnancies with fetal trisomy 21 are more likely to result in TOP when diagnosed in utero than any other chromosome anomaly. The indications for prenatal karyotyping strongly affect the decision to TOP. © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/pd.4947DOI Listing
December 2016

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

J Hum Genet 2016 Dec 8;61(12):995-1001. Epub 2016 Sep 8.

Department of Obstetrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, 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.
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http://dx.doi.org/10.1038/jhg.2016.96DOI Listing
December 2016

Thyroid Dysfunction in Neonates Born to Mothers Who Have Undergone Hysterosalpingography Involving an Oil-Soluble Iodinated Contrast Medium.

Horm Res Paediatr 2015 25;84(6):370-5. Epub 2015 Sep 25.

Department of Pediatrics, Toho University Omori Medical Center, Tokyo, Japan.

Background/aims: Patients developing neonatal thyroid dysfunction following maternal hysterosalpingography (HSG) involving the use of oil-soluble iodinated contrast medium (ethiodized oil) have been reported. The present study aimed to investigate the frequency and risk factors for neonatal thyroid dysfunction following HSG.

Methods: We studied 212 infants born to mothers who had become pregnant after undergoing HSG involving the use of ethiodized oil.

Results: Five of the 212 infants tested positive during congenital hypothyroidism screening; this frequency (2.4%) was higher than the recall rate among first congenital hypothyroidism screening results (0.7%) in Tokyo, Japan. Two of the 5 screening-positive infants showed hypothyroidism, and 3 showed hyperthyrotropinemia. The urinary iodine concentrations in 4 out of the 5 screening-positive infants were 1,150, 940, 1,570, and 319 μg/l. The subjects were divided into thyroid dysfunction (n = 5) and normal thyroid function (n = 207) groups. The median dosage of ethiodized oil in the thyroid dysfunction group was significantly higher than in the normal thyroid function group (20 vs. 8 ml, p = 0.033).

Conclusion: When infertile women undergo HSG, the dosage of oil-soluble iodinated contrast medium should be as low as possible to minimize the risk of fetal or neonatal thyroid dysfunction.
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http://dx.doi.org/10.1159/000439381DOI Listing
October 2016

Preparation of goreisan suppository and pharmacokinetics of trans-cinnamic acid after administration to rabbits.

Biol Pharm Bull 2014 ;37(11):1736-41

Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka.

Goreisan suppository is prepared as a hospital preparation, and successfully used for the treatment of diarrhea and vomiting in young children with common cold. While clinical efficacy of the suppository has been reported, few studies have been carried out to clarify the preparation procedure and pharmacokinetics of the suppository. In this study, trans-cinnamic acid (CA) was used as a representative substance of goreisan constituents, and assayed by HPLC-UV. We investigated the properties of goreisan suppositories prepared using various sizes of pulverized goreisan extract granules, in vitro dissolution profiles using the reciprocating dialysis tube method, and pharmacokinetics in rabbits compared with those for goreisan enema. Mass and content uniformity tests on the suppositories of three size fractions, 0-75, 75-150, and 150-300 µm, showed good acceptance for all kinds of suppository. Storage stability at 4°C was maintained until 4 months. In vitro dissolution of CA from the suppository was proportional to time until 45 min, and slower than that from the enema. Finally, 80% of CA had dissolved at 60 min. Pharmacokinetic study in rabbits revealed that the area under the plasma concentration-time curve from 0 to 120 min (AUC0-120 min) of the suppository was twice that of the enema. Moreover, from a study in rabbits using CA injection and CA suppository, we revealed that CA was rapidly and well absorbed from the rectum, showing 84% absolute bioavailability. Thus, we illustrated the defined preparation procedure of the suppository and the superiority of the suppository over the enema. This study will support evidence that the suppository is fast-acting and efficacious in clinical use.
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http://dx.doi.org/10.1248/bpb.b14-00317DOI Listing
June 2015

Maturation-associated Dbf4 expression is essential for mouse zygotic DNA replication.

Dev Growth Differ 2014 Dec 27;56(9):625-39. Epub 2014 Oct 27.

Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omorinishi Otaku, 143-8540, Tokyo, Japan.

Cdc7 is an S-phase-promoting kinase (SPK) that is required for the activation of replication initiation complex assembly because it phosphorylates the MCM protein complex serving as the replicative helicase in eukaryotic organisms. Cdc7 activity is undetectable in immature mouse GV oocytes, although Cdc7 protein is already expressed at the same level as in mature oocytes or early one-cell embryos at zygotic S-phase, in which Cdc7 kinase activity is clearly detectable. Dbf4 is a regulatory subunit of Cdc7 and is required for Cdc7 kinase activity. Dbf4 is not readily detectable in immature GV oocytes but accumulates to a level similar to that in one-cell embryos during oocyte maturation, suggesting that Cdc7 is already activated in unfertilized eggs (metaphase II). RNAi-mediated knockdown of maternal Dbf4 expression prevents the maturation-associated increase in Dbf4 protein, abolishes the activation of Cdc7, and leads to the failure of DNA replication in one-cell embryos, demonstrating that Dbf4 expression is the key regulator of Cdc7 activity in mouse oocytes. Dormant Dbf4 mRNA in immature GV oocytes is recruited by cytoplasmic polyadenylation during oocyte maturation and is dependent on MPF activity via its cytoplasmic polyadenylation element (CPE) upstream of the hexanucleotide (HEX) in the 3' untranslated region (3'UTR). Our results suggest that Cdc7 is inactivated in immature oocytes, preventing it from the unwanted phosphorylation of MCM proteins, and the oocyte is qualified by proper maturation to proceed following embryogenesis after fertilization through zygotic DNA replication.
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http://dx.doi.org/10.1111/dgd.12180DOI Listing
December 2014

Characterization of S100A11, a suppressive factor of fertilization, in the mouse female reproductive tract.

Mol Reprod Dev 2011 Feb 20;78(2):91-103. Epub 2011 Jan 20.

Department of Physiology, Toho University School of Medicine, Tokyo, Japan.

We recently found that Xenopus dicalcin, present in the extracellular egg-coating envelope, suppresses the efficiency of fertilization in vitro through binding to envelope-constituent glycoproteins. In the present study, we explored the mouse counterpart of Xenopus dicalcin, specifically its localization in the female reproductive tract and its action on mouse fertilization. Our homology and phylogenetic analyses using known S100 proteins showed that S100A11 is most closely related to Xenopus dicalcin. S100A11 was localized in the cytosol of luteal cells, but not in the follicle, in the mouse ovary, and also in the cytosol of the oviductal epithelial cells. In addition, our quantitative analyses revealed preferential expression of S100A11 in the ampullary region of the oviduct and at the estrus stage during the mouse estrous cycle. In the cumulus cell-oocyte complex dissected from the oviduct following ovulation, S100A11 was present in the plasma membrane of cumulus cells, but not in the zona pellucida, which is comparable with Ca(2+) -dependent binding of exogenously applied S100A11 to the plasma membrane of cumulus cells. Pretreatment of the cumulus cell-oocyte complex with recombinant S100A11 substantially reduced the efficiency of in vitro fertilization, but S100A10, the next closest S100 protein to Xenopus dicalcin, had no effect. These results suggested that S100A11 is the mouse counterpart of Xenopus dicalcin, suppresses the fertilization process through its action on cumulus cells, and thereby plays a key role in fertilization success in the mouse.
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http://dx.doi.org/10.1002/mrd.21273DOI Listing
February 2011

[Antimüllerian hormone (AMH)].

Nihon Rinsho 2010 Jul;68 Suppl 7:501-4

Department of Obstetrics and Gynecology, Toho University Omori Medical Center.

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July 2010

Effects of assisted reproduction technology on placental imprinted gene expression.

Obstet Gynecol Int 2010 12;2010. Epub 2010 Jul 12.

Reproduction Center, Department of Obstetrics and Gynecology, Toho University Omori Medical Center, 6-11-1 Omori-Nishi, Ota-ku, Tokyo 143-8541, Japan.

We used placental tissue to compare the imprinted gene expression of IGF2, H19, KCNQ1OT1, and CDKN1C of singletons conceived via assisted reproduction technology (ART) with that of spontaneously conceived (SC) singletons. Of 989 singletons examined (ART n = 65; SC n = 924), neonatal weight was significantly lower (P < .001) in the ART group than in the SC group, but placental weight showed no significant difference. Gene expression analyzed by real-time PCR was similar for both groups with appropriate-for-date (AFD) birth weight. H19 expression was suppressed in fetal growth retardation (FGR) cases in the ART and SC groups compared with AFD cases (P < .02 and P < .05, resp.). In contrast, CDKN1C expression was suppressed in FGR cases in the ART group (P < .01), while KCNQ1OT1 expression was hyperexpressed in FGR cases in the SC group (P < .05). As imprinted gene expression patterns differed between the ART and SC groups, we speculate that ART modifies epigenetic status even though the possibilities always exist.
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http://dx.doi.org/10.1155/2010/437528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913850PMC
July 2011

Serum amyloid A activates nuclear factor-kappaB in rheumatoid synovial fibroblasts through binding to receptor of advanced glycation end-products.

J Rheumatol 2008 May 1;35(5):752-6. Epub 2008 Mar 1.

Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.

Objective: Rheumatoid arthritis (RA) is a chronic, symmetric polyarticular joint disease and serum amyloid A (SAA) is an acute-phase protein that is upregulated during the course of RA. We investigated the role of SAA in the pathogenesis of RA.

Methods: Fibroblast-like synovial cells (FLS) were established from RA joints. SAA-stimulated expression of cytokines from FLS was evaluated by ELISA. Nuclear factor-kappaB (NF-kappaB) activation by SAA was evaluated by luciferase assay. NF-kappaB activation and IkappaBalpha degradation were evaluated by Western blotting and nuclear localization of p65 subunit of NF-kappaB in FLS. Expression of receptor for advanced glycation end-products (RAGE) in synovial tissue was evaluated by immunohistochemical study. Effects of preincubation of soluble RAGE on NF-kappaB activation by SAA was evaluated by Western blotting of IkappaBalpha.

Results: SAA stimulated the transcriptional activation by NF-kappaB in a dose-dependent manner and induced expression of the proinflammatory cytokines interleukin 6 (IL-6) and IL-8. Higher expression of RAGE in synovial tissue from patients with RA was noted. SAA induced IkappaBalpha degradation, with the peak effect around 30 minutes. Preincubation of SAA with soluble recombinant RAGE protein prevented SAA-induced IkappaBalpha degradation. SAA stimulation promoted nuclear translocation of NF-kappaB, whereas preincubation of SAA with RAGE inhibited nuclear translocation.

Conclusion: Our data suggested that the SAA-RAGE-stimulated NF-kappaB signaling pathway has an important role in the pathogenesis of RA.
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May 2008

Epigenetics in assisted reproductive technology.

Reprod Med Biol 2007 Jun 14;6(2):69-75. Epub 2007 May 14.

Department of Obstetrics and Gynecology and.

It has been reported that the rates of epigenetic disorders such as Angelman syndrome (AS) and Beckwith-Wiedemann syndrome (BWS) are high in offspring conceived by assisted reproductive technology (ART). Angelman Syndrome is characterized by intellectual disability and BWS is known as large offspring syndrome (LOS). Weight abnormalities have also been reported in cloned animals. Possible factors underlying these findings include inherent gamete characteristics, influence of culture and peculiarity of ART methods. It is important to conclusively determine whether such epigenetic abnormalities are present in children conceived by ART, so as to consider the health of next generations.
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http://dx.doi.org/10.1111/j.1447-0578.2007.00168.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891775PMC
June 2007

Androgen receptor CAG polymorphism (Xq11-12) status and human spermatogenesis: a prospective analysis of infertile males and their offspring conceived by intracytoplasmic sperm injection.

Int J Mol Med 2006 Sep;18(3):405-13

The Center for Reproductive Medicine and Infertility, Weill Medical College of Cornell University, NY 10021, USA.

We determined the association of androgen receptor (AR) (CAG)n lengths among fertile and infertile males and offspring conceived by intracytoplasmic sperm injection (ICSI). Assessment of (CAG)n repeats in the AR was performed in a Caucasian population by gene sequencing in fertile men (n=13), infertile men (n=64), boys conceived after ICSI (n=21), and boys conceived naturally (n=11). In the AZF region of the Y chromosome, a total of 22 STSs were analyzed by multiplex PCR; selected spermatozoa were also analyzed by fluorescent in situ hybridization (FISH) for chromosomes 18, 21, X, and Y. The average age was 43.7+/-7 yr for infertile, 44.8+/-7 yr for fertile men, and 5.0+/-0.5 yr for the children. The mean (CAG)n was 22.2+/-3 for the infertile men and 19.3+/-5 for fertile controls. There was a significant difference in CAG repeat length in the severely oligo-/azoo-spermic men vs. controls (p=0.02). An inverse correlation was evident between CAG length and semen parameters. For ICSI male children, the AR (CAG)n lengths were 21.4+/-3.2 vs. 20.8+/-3.4 for boys conceived naturally. While all peripheral karyotypes of fertile and infertile men were normal, de novo gonosomal abnormalities were observed in the ICSI offspring. The incidence of Y microdeletions was 1.6% in infertile men; all the ICSI sons had an intact Y chromosome. In conclusion, severely oligo- and azoospermic men had longer CAG repeat length than fertile controls, suggesting that certain AR gene mutations may have a negative effect on spermatogenesis. An increased incidence of de novo gonosomal abnormalities was found in the ICSI offspring when compared to children conceived naturally. Our assessment of the polymorphic region of the AR gene, in the absence of other specific genomic abnormalities, suggests that the fertility of children conceived by ICSI may be conserved.
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September 2006
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