Details of a Researcher - BABA Tsuyoshi

Papers - BABA Tsuyoshi

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Japan Society of Obstetrics and Gynecology revised diagnostic criteria for polycystic ovary syndrome: JSOG2024 criteria.

Hiroki Noguchi, Akira Iwase, Takeshi Iwasa, Haruhiko Kanasaki, Fuminori Kimura, Koji Kugu, Kazuki Saito, Tsuyoshi Baba, Tetsuaki Hara, Saki Minato, Rie Yanagihara, Toshiya Matsuzaki

The journal of obstetrics and gynaecology research 51 ( 1 ) e16152 2025.01 [International journal]

Japanese patients with polycystic ovary syndrome (PCOS) exhibit distinct body type characteristics, such that the rate of overweight/obese women is remarkably low. In addition, hyperandrogenism is relatively rare among Japanese PCOS patients. Therefore, these factors are considered in PCOS diagnostic criteria used in Japan. Diagnostic criteria for PCOS were recently revised by the Japan Society of Obstetrics and Gynecology based on a nationwide survey of PCOS and released on December 5, 2023 (JSOG2024). JSOG2024 criteria diagnosed PCOS according to the following three items: (1) irregular menstrual cycle/chronic anovulation, (2) polycystic ovarian morphology or elevated serum anti-Müllerian hormone (AMH) level, and (3) hyperandrogenism or high luteinizing hormone. The presence of all three items is required to diagnose PCOS, after excluding other diseases with symptoms similar to PCOS. We also established AMH cut-off values by age and a system for evaluating ovarian findings useful for both the JSOG2024 and Rotterdam criteria. We anticipate that the JSOG2024 criteria with cut-off values will enhance the treatment of Japanese patients with PCOS and those of other ethnicities with low obesity and hirsutism.

Phenotypes and clinical laboratory data for polycystic ovary syndrome cases: A nationwide survey in Japan.

Hiroki Noguchi, Takeshi Iwasa, Akira Iwase, Haruhiko Kanasaki, Fuminori Kimura, Koji Kugu, Kazuki Saito, Tsuyoshi Baba, Tetsuaki Hara, Toshiya Matsuzaki

The journal of obstetrics and gynaecology research 50 ( 12 ) 2346 - 2356 2024.12 [International journal]

AIM: Describe the current phenotypes and clinical laboratory data regarding polycystic ovary syndrome (PCOS) in Japan, taking into account ethnic differences and obesity status. METHODS: Data for 986 PCOS cases and 965 control cases were collected using a nationwide survey in Japan. Obese/overweight (body mass index [BMI] ≥25 kg/m2) and non-obese/overweight (BMI <25 kg/m2) cases were compared. RESULTS: Japanese PCOS cases predominantly involved non-obese/overweight patients, accounting for 75% of all cases. Among non-obese/overweight PCOS cases, the incidence of both amenorrhea and clinical/biochemical hyperandrogenism was significantly lower than in obese/overweight PCOS cases, whereas the rate of elevated serum luteinizing hormone (LH) level was significantly higher. Even though the incidence of hirsutism in Japan is only 13.5%, the detection rate for hyperandrogenism increased by as much as 30.4% when hirsutism was added to the Japan Society of Obstetrics and Gynecology (JSOG) criteria for the diagnosis of hyperandrogenism in addition to elevated serum total testosterone level. When evaluated based on timing of blood sampling, the LH level and LH/follicle-stimulating hormone ratio determined at the initial consultation involving a chief complaint of irregular menstrual cycle (after confirming the absence of follicles measuring ≥1 cm in diameter) were significantly higher than on days 2-3 or 4-6 of the menstrual cycle. CONCLUSIONS: Ethnic differences, including obesity status, affected the phenotype and clinical laboratory data of Japanese PCOS patients, such as the incidence rates of clinical/biochemical hyperandrogenism and the rate of elevated basal LH level. Adding hirsutism to the JSOG 2024 criteria would enhance the accuracy of PCOS diagnosis and enhance consistency with the Rotterdam 2003 criteria. Measuring basal LH level is useful for assessing the endocrinologic characteristics of Japanese PCOS cases, as well as lean Asian PCOS cases, but the timing of blood sampling can affect the result.

Microbiological investigation of pregnancies following vaginal radical trachelectomy using 16S rRNA sequencing of FFPE placental specimens.

Risa Tsunematsu, Tasuku Mariya, Mina Umemoto, Shiori Ogawa, Wataru Arai, Suguru E Tanaka, Kyota Ashikawa, Terufumi Kubo, Yoshiyuki Sakuraba, Tsuyoshi Baba, Shinichi Ishioka, Toshiaki Endo, Tsuyoshi Saito

FEBS open bio 2024.09 [International journal]

This study examined the risk of intrauterine infection associated with radical trachelectomy (RT) in early-stage cervical cancer patients. This procedure preserves fertility but is linked to increased risk of intrauterine infection due to cervical defects during pregnancy. DNA was extracted from the formalin-fixed paraffin-embedded (FFPE) placental specimens of 23 pregnant post-RT patients and 16S rRNA gene sequencing was used for bacterial identification. The prevalence of Lactobacillus crispatus and Burkholderia stabilis was significantly higher in the non-chorioamnionitis group. In contrast, alpha diversity analysis using the PD index showed significantly higher diversity in the chorioamnionitis group (P = 0.04). The demonstrated relationship between chorioamnionitis and microbial diversity affirms the importance of controlling the genital bacterial flora in pregnancies following RT.

IB3期の子宮頸癌に対して術前化学療法後に広汎子宮頸部摘出術を施行し分娩となった1例

佐藤冴子, 染谷真行, 玉手雅人, 松浦基樹, 森下美幸, 馬場剛, 石岡伸一, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 71回 48 - 48 2024.09

Cut-off value for anti-Müllerian hormone in the diagnostic criteria for polycystic ovary syndrome in the Japanese population.

Hiroki Noguchi, Takeshi Iwasa, Akira Iwase, Haruhiko Kanasaki, Fuminori Kimura, Koji Kugu, Kazuki Saito, Tsuyoshi Baba, Tetsuaki Hara, Toshiya Matsuzaki

The journal of obstetrics and gynaecology research 2024.06 [International journal]

AIM: To establish cut-off values for anti-Müllerian hormone (AMH) and antral follicle count (AFC) in the diagnostic criteria for polycystic ovary syndrome (PCOS) applicable to the Japan Society of Obstetrics and Gynecology (JSOG) 2024 criteria and the Rotterdam/International Evidence-Based Guideline for the assessment and management of PCOS (IEBG) 2023 criteria based on a nationwide survey, respectively, taking into account age, assays, and structure of the diagnostic criteria. METHODS: Data were collected for 986 PCOS cases and 965 control cases using a national survey in Japan and used to establish cut-off values for AMH and AFC. RESULTS: Serum AMH levels were significantly higher in the PCOS group compared to the control group. Serum AMH showed a significant negative correlation with age and significant positive correlation with AFC in both groups. In multiple regression analysis, serum AMH level was independently affected by AFC and total testosterone. AMH cut-off values suitable for the JSOG 2024 criteria and the Rotterdam/IEBG 2023 criteria were separately established for the 20-29 and 30-39 years of age groups, respectively, and for Access, Lumipulse and Elecsys/ECLusys, respectively. AFC cut-off values suitable for the JSOG 2024 criteria and Rotterdam/IEBG 2023 criteria were also established separately. AFC exhibited statistically greater variability than AMH. CONCLUSION: The serum AMH level is the biochemical representation of ovarian findings in PCOS and considered objective and highly reliable. Therefore, it could serve as a surrogate for AFC as a marker of polycystic ovarian morphology in diagnostic criteria.

低置胎盤の分娩管理の変化と,それに伴う周産期転帰の変化について

染谷真行, 古来愛香, 真里谷奨, 馬場剛, 石岡伸一, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 60 ( Suppl.1 ) P382 - P382 2024.06

妊娠中期に多量出血を伴わずに原因不明の産科DICを発症した2例

齋藤晋平, 染谷真行, 真里谷奨, 馬場剛, 石岡伸一, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 60 ( Suppl.1 ) P336 - P336 2024.06

妊娠後期に急性腹症と肝酵素上昇を認め,総胆管結石として待機的管理を行った1例

宮下夕稀子, 染谷真行, 真里谷奨, 馬場剛, 石岡伸一, 岡村直樹, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 60 ( Suppl.1 ) P395 - P395 2024.06

子宮移植までのマイルストーン

玉手雅人, 馬場剛, 和田渚, 古来愛香, 幅田周太朗, 小川万梨絵, 松浦基樹, 齋藤豪

日本生殖医学会雑誌 ( (一社)日本生殖医学会 ) 69 ( 1-2 ) 122 - 122 2024.04

がん患者の妊孕性温存に関する情報提供の現状と課題

古来愛香, 玉手雅人, 馬場剛, 長尾沙智子, 小川万梨絵, 森下美幸, 久野芳佳, 齋藤豪

日本生殖医学会雑誌 ( (一社)日本生殖医学会 ) 69 ( 1-2 ) 121 - 121 2024.04

経過観察中に自然軽快した広汎性卵巣浮腫の2症例

馬場剛, 遠藤俊明, 新開翔太, 真里谷奨, 染谷真行, 森下美幸, 岩崎雅宏, 石岡伸一, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 76 ( 臨増 ) S - 383 2024.02

当科における最近10年間のCesarean hysterectomy症例の検討

齋藤晋平, 石岡伸一, 新開翔太, 真里谷奨, 染谷真行, 小川万梨絵, 森下美幸, 馬場剛, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 76 ( 臨増 ) S - 592 2024.02

妊孕性温存療法後、胚移植に至った症例に関する検討

久野芳佳, 馬場剛, 齋藤晋平, 古来愛香, 長尾沙智子, 玉手雅人, 小川万梨絵, 森下美幸, 遠藤俊明, 齋藤豪

日本がん・生殖医療学会誌 ( (一社)日本がん・生殖医療学会 ) 7 ( 1 ) 112 - 112 2024.01

当科における卵巣組織凍結の報告と北海道内の同技術の認識について

古来愛香, 玉手雅人, 春日芙貴子, 長尾沙智子, 小川万梨絵, 池田桂子, 久野芳佳, 森下美幸, 馬場剛, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 67 ( 1 ) 85 - 85 2023.12

Pregnancy-specific beta-1-glycoprotein 6 is a potential novel diagnostic biomarker of placenta accreta spectrum.

Hazuki Kashiwagi, Tasuku Mariya, Mina Umemoto, Shiori Ogawa, Yoshihiko Hirohashi, Yuya Fujibe, Terufumi Kubo, Masayuki Someya, Tsuyoshi Baba, Shinichi Ishioka, Toshihiko Torigoe, Tsuyoshi Saito

Medical molecular morphology 2023.10 [Domestic journal]

Early diagnosis is essential for the safer perinatal management of placenta accreta spectrum (PAS). We used transcriptome analysis to investigate diagnostic maternal serum biomarkers and the mechanisms of PAS development. We analyzed eight formalin-fixed paraffin-embedded placental specimens from two placenta increta and three placenta percreta cases who underwent cesarean hysterectomy at Sapporo Medical University Hospital between 2013 and 2019. Invaded placental regions were isolated from the uterine myometrium and RNA was extracted. The transcriptome difference between normal placenta and PAS was analyzed by microarray analysis. The PAS group showed markedly decreased expression of placenta-specific genes such as LGALS13 and the pregnancy-specific beta-1-glycoprotein (PSG) family. Term enrichment analysis revealed changes in genes related to cellular protein catabolic process, female pregnancy, autophagy, and metabolism of lipids. From the highly dysregulated genes in the PAS group, we investigated the expression of PSG family members, which are secreted into the intervillous space and can be detected in maternal serum from the early stage of pregnancy. The gene expression level of PSG6 in particular was progressively decreased from placenta increta to percreta. The PSG family, especially PSG6, is a potential biomarker for PAS diagnosis.

子宮移植実現に向けた献体トレーニング

玉手雅人, 松浦基樹, 長尾沙智子, 黒川晶子, 秋元太志, 馬場剛, 齋藤豪

Organ Biology ( (一社)日本臓器保存生物医学会 ) 30 ( 3 ) 111 - 111 2023.10

Endocrinological and Metabolic Heterogeneity is low in Japanese Women with Polycystic Ovary Syndrome.

Tsuyoshi Baba, Toshiaki Endo, Tasuku Mariya, Yoshika Kuno, Hiroyuki Honnma, Mika Kanaya, Tsuyoshi Saito

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC 102217 - 102217 2023.09 [International journal]

OBJECTIVE: This study aims to evaluate the endocrine differences among polycystic ovary syndrome (PCOS) phenotypes in Japanese women. METHODS: 118 Japanese women that we diagnosed with PCOS agreed to be included in the study. The study group was classified into the following four phenotypes: A) hyperandrogenism (HA); ovulatory disorder (OvD) and polycystic ovary morphology (PCOM); B) HA and OvD; C) HA and PCOM; and D) OvD and PCOM. We also recruited 66 healthy Japanese women to the study as control participants. Age, body mass index, androgens, luteinizing hormone, follicle-stimulating hormone, and insulin resistance index were evaluated and compared. RESULTS: The proportions of phenotypes A, B, C, and D were 57/120 (47.5%), 4/120 (3.3%), 13/120 (10.8%), and 46/120 (38.3%), respectively. The proportion of phenotype B was too small; therefore, phenotypes A and B were grouped as classical PCOS for intergroup comparisons. The luteinizing hormone/follicle-stimulating hormone ratio in the classical PCOS group was higher than that in the phenotype D group (P < 0.001). Androgen concentrations in the phenotype D group were significantly lower than those in the other groups (P < 0.01). Phenotype D was more common in lean women with PCOS. The surrogate marker of insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) was not different irrespective of PCOS and its phenotypes. CONCLUSION: Except for androgens, endocrine differences by PCOS phenotype are not evident, suggesting that diversity among patients with PCOS is relatively low in Japanese women.

当科における卵巣組織凍結の現状報告と北海道における小児科医の卵巣組織凍結に対する意識調査

長尾沙智子, 玉手雅人, 春日芙貴子, 西村庸子, 松浦基樹, 久野芳佳, 馬場剛, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 65回 387 - 387 2023.07

均衡型染色体転座に対するPGT-SRを実施した当院症例の解析結果から考察する遺伝カウンセリング時の適正な情報提供について

葛西彩乃, 真里谷奨, 石川亜貴, 馬場剛, 遠藤俊明, 尾崎守, 櫻井晃洋

日本遺伝カウンセリング学会誌 ( (一社)日本遺伝カウンセリング学会 ) 44 ( 2 ) 133 - 133 2023.06

不育症カップルがPGT-SR受検を決定する因子と意思決定支援に求められる遺伝カウンセリングのあり方についての検討

久々宇千恵, 石川亜貴, 真里谷奨, 馬場剛, 遠藤俊明, 櫻井晃洋

日本遺伝カウンセリング学会誌 ( (一社)日本遺伝カウンセリング学会 ) 44 ( 2 ) 155 - 155 2023.06

巨大腺筋症に対する開腹子宮頸管縫縮術を施行し,救命可能週数まで妊娠継続できた一絨毛膜二羊膜双胎の1例

常松梨紗, 石岡伸一, 馬場剛, 真里谷奨, 染谷真行, 新開翔太, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 59 ( Suppl.1 ) P322 - P322 2023.06

Aggressive angiomyxoma(AAM)合併妊娠の一例

古来愛香, 石岡伸一, 新開翔太, 常松梨紗, 真里谷奨, 染谷真行, 松浦基樹, 馬場剛, 齋藤剛

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 59 ( Suppl.1 ) P438 - P438 2023.06

Clinical application of long-read nanopore sequencing in a preimplantation genetic testing pre-clinical workup to identify the junction for complex Xq chromosome rearrangement-related disease.

Tasuku Mariya, Yui Shichiri, Takeshi Sugimoto, Rie Kawamura, Syunsuke Miyai, Hidehito Inagaki, Eiji Sugihara, Keiko Ikeda, Tsuyoshi Baba, Aki Ishikawa, Michiko Ammae, Yoshiharu Nakaoka, Tsuyoshi Saito, Akihiro Sakurai, Hiroki Kurahashi

Prenatal diagnosis 43 ( 3 ) 304 - 313 2023.02 [International journal]

OBJECTIVE: Xq chromosome duplication with complex rearrangements is generally acknowledged to be associated with neurodevelopmental disorders such as Pelizaeus-Merzbacher disease (PMD) and MECP2 duplication syndrome. For couples who required a PGT-M (pre-implantation genetic testing for monogenic disease) for these disorders, junction-specific PCR is useful to directly detect pathogenic variants. Therefore, pre-clinical workup for PGT-M requires the identification of the junction of duplicated segments in PMD and MECP2 duplication syndrome, which is generally difficult. METHODS: In this report, we used nanopore long-read sequencing targeting the X chromosome using an adaptive sampling method to identify breakpoint junctions in disease-causing triplications. RESULTS: By long-read sequencing, we successfully identified breakpoint junctions in one PMD case with PLP1 triplication and in another MECP2 triplication case in a single sequencing run. Surprisingly, the duplicated region involving MECP2 was inserted 45 Mb proximal to the original position. This inserted region was confirmed by FISH analysis. With the help of precise mapping of the pathogenic variant, we successfully re-established STR haplotyping for PGT-M and avoided any potential misinterpretation of the pathogenic allele due to recombination. CONCLUSION: Long-read sequencing with adaptive sampling in a PGT-M pre-clinical workup is a beneficial method for identifying junctions of chromosomal complex structural rearrangements. This article is protected by copyright. All rights reserved.

当科における卵巣組織凍結の現状報告と北海道における小児科医の卵巣組織凍結に対する意識調査

古来愛香, 玉手雅人, 春日芙貴子, 長尾沙智子, 西村庸子, 松浦基樹, 久野芳佳, 馬場剛, 齋藤豪

日本がん・生殖医療学会誌 ( (一社)日本がん・生殖医療学会 ) 6 ( 1 ) 49 - 53 2023.02

【緒言】小児・思春期・若年成人(children,adolescents and young adults:C-AYA)世代のがんサバイバーが増加することにともない、QOL向上の意識が高まり妊孕性温存法も発展しつつある。当科では、小児がん患者の卵巣組織凍結保存を実施してきた。今回、当院での卵巣組織凍結保存の現状報告(研究1)、および北海道内の小児科医における卵巣組織凍結に対する意識調査(研究2)について報告する。【対象と方法】研究1:2012年12月～2021年6月までに当科で卵巣組織凍結保存を目的とした卵巣摘出術手術20例を対象に、年齢、原疾患、コンサルトから手術までの期間、周術期経過、合併症などの背景を集積した。研究2:北海道内の悪性疾患を診療する小児科医に卵巣組織凍結の認識を匿名でアンケート調査した。【結果】研究1:初診時平均年齢は18.8±8.49歳。原疾患は、血液腫瘍13例、脳腫瘍3例、乳癌2例、軟部腫瘍2例であった。手術までの期間は3-99日(平均31.5±21.5日)、全例腹腔鏡手術であった。研究2:アンケートは5施設18名から回収した。卵巣組織凍結について認識している人が18名(100%)、情報提供をしたことがある人が13名(72.2%)であった。卵巣組織凍結の情報提供をしたが治療の同意が得られない理由としては、経済的理由(保険適応外)、手術のリスク、原疾患治療の遅れ、エビデンスが乏しい、などがあげられた。【結語】卵巣組織凍結保存は微小残存がん病巣(MRD:minimal residual disease)のリスクがあるが、月経発来前の女児に対して唯一の妊孕性温存療法である。しかし、社会的要因によって普及には至っていない。今後、凍結卵巣融解移植成績の発信や卵巣組織凍結の説明方法の均てん化などにより一層卵巣組織凍結という選択肢を提示していきたい。症例治療が滞りなく円滑に進むよう、主治医、生殖医、婦人科腫瘍医の連携が重要であり、今後尽力したい。(著者抄録)

中心核ミオパチーの児出産を契機に発見された1型リアノジン受容体(RYR1)遺伝子のバリアントを有する妊婦の一例

古来愛香, 石岡伸一, 新開翔太, 真里谷奨, 常松梨紗, 染谷真行, 小川万梨絵, 森下美幸, 馬場剛, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 75 ( 臨増 ) S - 459 2023.02

中心核ミオパチーの児出産を契機に発見された1型リアノジン受容体(RYR1)遺伝子のバリアントを有する妊婦の一例

古来愛香, 石岡伸一, 新開翔太, 真里谷奨, 常松梨紗, 染谷真行, 小川万梨絵, 森下美幸, 馬場剛, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 75 ( 臨増 ) S - 459 2023.02

Letrozole increases preantral follicle growth and decreases estradiol production without impairing follicle survival.

Fukiko Kasuga-Yamashita, Tsuyoshi Baba, Sachiko Nagao, Yuya Fujibe, Miyuki Morishita, Yoshika Kuno, Tasuku Mariya, Hiroyuki Honnma, Toshiaki Endo, Tamotsu Kiya, Tsuyoshi Saito

Journal of ovarian research 15 ( 1 ) 136 - 136 2022.12 [International journal]

BACKGROUND: Letrozole has been reported to be effective in treating anovulation, preventing ovarian hyperstimulation syndrome (OHSS), and retrieving oocytes in breast cancer patients. However, the role and mechanism of letrozole in follicular development remain unclear. RESULTS: We treated mouse preantral follicles with various treatments; we found no significant difference in follicle survival rates in the letrozole (LET) group compared with the control group, but the average diameter of follicles in the LET group tended to be larger (CTRL vs. LET 30, p = 0.064; CTRL vs. LET 100, p = 0.025). The estradiol concentrations in culture media of the LET group were significantly lower than those observed in the control group (CTRL vs. LET 30, p = 0.038; CTRL vs. LET 100, p = 0.025). We further found a marked increase in follicle-stimulating hormone receptor (FSHR) gene expression in response to letrozole treatment (CTRL vs. LET 30, p = 0.075; CTRL vs. LET 100, p = 0.034). This result suggested that increased FSHR expression promotes follicle development. Letrozole inhibited aromatase activity, but the effect was limited. Letrozole did not significantly reduce vascular endothelial growth factor (VEGF) gene expression. CONCLUSIONS: Letrozole may promote follicle development by increasing the expression of FSHR. Letrozole may be useful for fertility preservation of patients with estrogen-dependent cancers such as breast cancer and various other cancers. Whether letrozole has a direct effect in reducing OHSS requires further investigation.

Self-administration of gender-affirming hormones and supratherapeutic dosing are relatively common in Japanese transgender women.

Tsuyoshi Baba, Toshiaki Endo, Utako Ikeda, Hiroshi Ikeda, Koji Ichihara, Naoya Masumori, Tsuyoshi Saito

The journal of obstetrics and gynaecology research 48 ( 8 ) 2208 - 2213 2022.08 [International journal]

AIM: This study was performed to determine the proportion of transgender women with self-adjusted hormone administration and excess dosing. METHODS: The medical records of 87 transgender women who visited our gender clinic from 2010 through 2019 were reviewed. The complete blood count and serum concentrations of D-dimer, gonadotropins, and sex steroids were compared between transgender women who were self-administering gender-affirming hormones and women not using such hormones. RESULTS: Fifty-eight of 87 (66.7%) transgender women had contravened the guideline and self-adjusted their hormone administration. The hormonal data of one woman with hypopituitarism were eliminated from the analyses. The serum gonadotropin and testosterone levels were significantly lower in the self-administration group than in the hormone-naïve group. Gonadotropin levels below the lower limit of normal were found in 32/86 (37.2%) transgender women. The testosterone levels in six transgender women were not analyzed because these women had undergone sex reassignment surgery before visiting our hospital. Testosterone levels below the lower limit of normal men were found in 36/80 (45.0%) transgender women. Unexpectedly, 29/36 (80.6%) transgender women who were classified as having suppressed serum testosterone levels had testosterone levels of <0.6 ng/mL, which corresponds to the levels in cisgender women. The white blood cell count and hemoglobin concentration were significantly different between the groups. CONCLUSION: Self-initiated hormonal treatments seem to affect the serum concentrations of gonadotropin and sex steroids and the complete blood count. The prevalence of transgender women with self-adjusted use of gender-affirming hormones is high, and an excess dose of hormones occasionally occurs.

当科における分娩時hysterectomy症例の検討

石岡伸一, 染谷真行, 柏木葉月, 藤部佑哉, 真里谷奨, 馬場剛, 斎藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 58 ( Suppl.1 ) 297 - 297 2022.06

児の緩和的対応を前提とした新生児予後不良な妊娠における,適切な医療体制について

染谷真行, 古来愛香, 真里谷奨, 馬場剛, 石岡伸一, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 58 ( Suppl.1 ) 310 - 310 2022.06

妊娠中の脳腫瘍に対し,周期的なテモゾロミド投与を行った一例

齋藤晋平, 古来愛香, 真里谷奨, 馬場剛, 石岡伸一, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 58 ( Suppl.1 ) 323 - 323 2022.06

液体クロマトグラフィー・タンデム質量分析(LC-MS/MS)法にて診断した偽性高テストステロン血症の一例

小川万梨絵, 馬場剛, 春日芙貴子, 玉手雅人, 池田桂子, 森下美幸, 久野芳佳, 遠藤俊明, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 66 ( 1 ) 55 - 58 2022.03

日常診療におけるホルモン検査は,主に免疫学的測定法を用いて行われるが,時に臨床所見と検査所見の乖離をみることがある。今回,無月経を主訴に来院された女性で,男性化徴候がないにもかかわらず高テストステロン血症を呈した偽性高テストステロン血症の症例を経験したので報告する。症例は17歳女性,続発性無月経のため前医を受診したところ,高テストステロン血症を認めた。経腹超音波検査で明らかな卵巣腫瘍もなく,また単純MRIでも明らかな副腎腫瘍もないため,精査加療目的に当科に紹介受診となった。当科初診時の免疫学的測定法で遊離テストステロンは基準値内であったが,総テストステロンは前医同様に高値であった。男性化徴候がないことと,総テストステロン値と遊離テストステロン値とに大きな乖離を認めたため,異好抗体による偽性高値を疑い液体クロマトグラフィー-タンデム質量分析(liquid chromatography-tandem mass spectrometry:LC-MS/MS)法にてテストステロン測定を行った。結果は総テストステロンも遊離テストステロンも基準値内であった。今回使用した免疫学的測定法において,総テストステロン検査にはヒツジ由来の抗体が,遊離テストステロン検査にはウサギ由来の抗体が用いられていたため,当患者の血漿中にヒツジの抗体に非特異的に反応する異好抗体の存在が疑われた。無月経の原因として,2年前に減量を行い,BMI:22から16に低下して以来無月経となった経緯があり,体重減少性無月経が第一に考えられた。今回LC-MS/MSにて測定を行うことで,侵襲の高い選択的副腎・卵巣静脈血サンプリングを回避し診断することができた。臨床所見と検査所見に乖離がある場合には,異好抗体の存在を念頭に検査法を検討する必要がある。(著者抄録)

胎児超音波にて屈曲肢骨異形成症を疑い,胎盤絨毛の遺伝子検査で診断確定した一例

小川万梨絵, 寺本瑞絵, 染谷真行, 石堂茉泉, 新開翔太, 真里谷奨, 池田桂子, 森下美幸, 久野芳佳, 馬場剛, 石岡伸一, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 74 ( 臨増 ) S - 374 2022.02

CD138免疫染色と子宮内microbiotaのcombined testに子宮内pH測定を加えた慢性子宮内膜炎の病態整理

遠藤俊明, 池田詩子, 逸見博文, 本間寛之, 木谷保, 真里谷奨, 久野芳佳, 馬場剛, 山田秀人, 東口篤司, 藤井美穂, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 74 ( 臨増 ) S - 359 2022.02

Guidelines for Reproductive Medicine in Japan.

Mitsutoshi Yamada, Tomonori Ishikawa, Takeshi Iwasa, Hajime Oishi, Satoko Osuka, Kenji Oka, Shuichi Ono, Masanori Ono, Makoto Orisaka, Haruhiko Kanasaki, Yasushi Kawano, Kazuhiro Kawamura, Hiroshi Kishi, Fuminori Kimura, Shinnosuke Kuroda, Akira Kuwahara, Hideyuki Kobayashi, Akira Komiya, Hidekazu Saito, Kenji Sato, Suguru Sato, Koji Shiraishi, Hiromitsu Shirasawa, Tatsuya Suzuki, Yasushi Takai, Seido Takae, Toshifumi Takahashi, Tsuyoshi Takiuchi, Masahito Tachibana, Isao Tamura, Hiroshi Tamura, Seung Chik Jwa, Tsuyoshi Baba, Miyuki Harada, Tetsuya Hirata, Atsushi Fukui, Yusuke Fukuda, Shinichiro Fukuhara, Tetsuo Maruyama, Yasushi Yumura, Osamu Yoshino, Yasushi Hirota, Akira Tsujimura, Naoaki Kuji, Yutaka Osuga

Reproductive medicine and biology 21 ( 1 ) e12483 2022 [Domestic journal]

PGT-SRの結果とStengel-R法による主たる不均衡型転座の予測との一致率

遠藤俊明, 馬場剛, 久野芳佳, 池田詩子, 本間寛之, 逸見博文, 稲木誠, 原鐵晃, 尾崎守, 倉橋浩樹, 斎藤豪

日本IVF学会誌 ( (一社)日本IVF学会 ) 24 ( 2 ) 60 - 60 2021.09

Prenatal alcohol exposure and adverse fetal growth restriction: findings from the Japan Environment and Children's Study.

Kazutoshi Cho, Sumitaka Kobayashi, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Yasuaki Saijo, Yoshiya Ito, Kazuo Sengoku, Tsuyoshi Baba, Hisanori Minakami, Yuichi Nakamura, Reiko Kishi

Pediatric research 92 ( 1 ) 291 - 298 2021.06 [International journal]

BACKGROUNDS: Japanese studies on the association between maternal alcohol consumption and fetal growth are few. This study assessed the effect of maternal alcohol consumption on fetal growth. METHODS: This prospective birth cohort included 95,761 participants enrolled between January 2011 and March 2014 in the Japan Environment and Children's Study. Adjusted multiple linear and logistic regression models were used to assess the association between prenatal alcohol consumption and infant birth size. RESULTS: Consumption of a weekly dose of alcohol in the second/third trimester showed a significant negative correlation with standard deviation (SD; Z) scores for body weight, body length, and head circumference at birth, respectively. Consumption of a weekly dose of alcohol during the second/third trimester had a significant positive correlation with incidences of Z-score ≤ -1.5 for birth head circumference. Associations between alcohol consumption in the second/third trimester and Z-score ≤ -1.5 for birth weight or birth length were not significant. Maternal alcohol consumption in the second/third trimester above 5, 20, and 100 g/week affected body weight, body length, and head circumference at birth, respectively. CONCLUSION: Low-to-moderate alcohol consumption during pregnancy might affect fetal growth. Public health policies for pregnant women are needed to stop alcohol consumption during pregnancy. IMPACT: This study examined the association between maternal alcohol consumption and fetal growth restriction in 95,761 pregnant Japanese women using the prospective birth cohort. Maternal alcohol consumption in the second/third trimester more than 5, 20, and 100 g/week might affect fetal growth in body weight, body length, and head circumference, respectively. The findings are relevant and important for educating pregnant women on the adverse health effects that prenatal alcohol consumptions have on infants.

What is the most anticipated change induced by treatment using gender-affirming hormones in individuals with gender incongruence?

Naoya Masumori, Tsuyoshi Baba, Teruo Abe, Koji Niwa

International journal of urology : official journal of the Japanese Urological Association 28 ( 5 ) 526 - 529 2021.05 [International journal]

OBJECTIVES: To identify the most eagerly anticipated change resulting from hormone therapy using gender-affirming hormones for patients with gender incongruence undergoing a clinical trial. METHODS: Patients diagnosed with gender identity disorders based on the International Classification of Diseases 10th revision classification at three institutions in Japan for whom hormone therapy using gender-affirming hormones was initiated were analyzed. They were asked what the most anticipated change was due to gender-affirming hormone that they had thought of between giving informed consent and the first administration of the drug. RESULTS: The responders were 336 transgender men who were administered androgens and 48 transgender women who received estrogens. The median age at commencement of hormone therapy was 24 years for transgender men and 28 years for transgender women. For transgender men, the most frequent answer was cessation of menses (52.7%) followed by a deepened voice (32.4%). For transgender women, breast development (35.4%) was the most anticipated change, followed by gynoid fat deposition (29.2%). CONCLUSIONS: Cessation of menses in transgender men and breast development/gynoid fat deposition in transgender women might represent primary end-points in clinical trials evaluating the efficacy of hormonal treatment in these patients.

Mediating Factors Between Parental Socioeconomic Status and Small for Gestational Age in Infants: Results from the Hokkaido Study on Environment and Children's Health.

Naomi Tamura, Tomoyuki Hanaoka, Kumiko Ito, Atsuko Araki, Chihiro Miyashita, Sachiko Ito, Sumitaka Kobayashi, Yoichi Ito, Hisanori Minakami, Kazutoshi Cho, Toshiaki Endo, Tsuyoshi Baba, Kazuo Sengoku, Toshinobu Miyamoto, Katsuhiko Ogasawara, Reiko Kishi

Maternal and child health journal ( SPRINGER/PLENUM PUBLISHERS ) 25 ( 4 ) 645 - 655 2021.04 [International journal]

OBJECTIVES: Previous studies indicated a significant association between small for gestational age (SGA) in infants and their parents' socioeconomic status (SES). Thus, this study aimed to examine if parental factors, such as maternal smoking, and the pre-pregnancy body mass index (BMI) could mediate the associations between parental SES and SGA. METHODS: The participants of this study were pregnant women who enrolled in an ongoing birth cohort study, the Hokkaido study, during the first trimester of their pregnancies. A total of 14,593 live singleton births were included in the statistical analysis, of which 1011 (6.9%) were SGA. Two structural equation models were employed to evaluate the associations between parental SES, parental characteristics, and SGA. RESULTS: The effect of low SES on SGA was directly mediated by maternal pre-pregnancy BMI, smoking during the third trimester, and alcohol consumption during the first trimester in the first model, which was based the assumption of independent associations between mediating factors. In the second model, which additionally considered the mediating factors from the first model, smoking during pregnancy mediated decline in parental SES, consequently increased SGA. Moreover, an increase in pregnancy smoking status increased the prevalence of lower maternal pre-pregnancy BMI and its effect on SGA. CONCLUSIONS FOR PRACTICE: In this study, we observed the independent mediating effect of maternal pre-pregnancy BMI, smoking, and alcohol consumption during pregnancy on low SES and, consequently, SGA, with the additional mediating pathway of SES to smoking to low BMI on SGA.

PSGファミリーの異常浸潤性胎盤診断バイオマーカーとしての可能性

柏木葉月, 真里谷奨, 新開翔太, 染谷真行, 小川万梨絵, 森下美幸, 馬場剛, 石岡伸一, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 73 ( 臨増 ) S - 611 2021.03

高次施設における帝王切開率抑制の試み

染谷真行, 新開翔太, 真里谷奨, 小川万梨絵, 森下美幸, 馬場剛, 石岡伸一, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 73 ( 臨増 ) S - 367 2021.03

早産期の誘発分娩により帝王切開を回避し得たタナトフォリック骨異形成症の1例

佐藤由梨, 染谷真行, 長尾沙智子, 新開翔太, 真里谷奨, 森下美幸, 馬場剛, 石岡伸一, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 65 ( 1 ) 85 - 85 2021.03

開腹子宮頸部縫縮術(TAC)後妊娠初期流産症例に対するmethotrexate(MTX)療法の一例

石堂茉泉, 石岡伸一, 藤部佑哉, 鈴木美紀, 嶋田浩志, 真里谷奨, 馬場剛, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 56 ( 1 ) 198 - 202 2020.05

34歳。子宮頸癌のため腟式広汎子宮頸部摘出術+骨盤リンパ節郭清術の既往で有った。その2年後に体外受精により妊娠し、妊娠19週で帝王切開による分娩となった。この分娩から3年後にテフロンテープを用いた開腹子宮頸部縫縮術(TAC)を施行し、TAC後6ヵ月で体外受精にて妊娠したが、妊娠8週で稽留流産となった。流産後3ヵ月経過しても子宮内容物が排出されず絨毛組織の筋層内浸潤が疑われ、流産後12週よりMTX投与1日20mg・5日間を2週間毎に開始し、3コース終了後に血清ヒト絨毛性ゴナドトロピン値がほぼ正常化した。治療終了後3ヵ月で月経が再開し、その後に再度妊娠8週相当で流産となったが、子宮内容物は流産判明から1ヵ月以内に自然排出された。さらに6ヵ月後に体外受精で妊娠し、妊娠33週6日に帝王切開にて男児1912g、アプガースコア8/9点を出産し、術後経過順調で8日目に退院した。

Prune Belly Syndromeの女児が出生後に総排泄腔遺残も疑われた1例

藤部佑哉, 真里谷奨, 蛯谷由真, 水柿祐子, 川俣あかり, 水内将人, 森下美幸, 馬場剛, 石岡伸一, 長岡由修, 石郷岡哲郎, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 64 ( 1 ) 108 - 109 2020.03

当院で出生した先天性疾患児の出生前診断状況および遺伝学的対応に関する検討

真里谷奨, 斉藤公仁, 水柿祐子, 藤部佑哉, 川俣あかり, 水内将人, 森下美幸, 馬場剛, 水上都, 石川亜貴, 石岡伸一, 櫻井晃洋, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 64 ( 1 ) 108 - 108 2020.03

子宮内膜症及び腺筋症の合併が癒着胎盤を呈した妊娠の1例

蛯谷由真, 藤部佑哉, 真里谷奨, 水柿祐子, 川俣あかり, 水内将人, 森下美幸, 馬場剛, 石岡伸一, 菅原太郎, 杉田真太郎, 長谷川匡, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 64 ( 1 ) 114 - 114 2020.03

若手産婦人科医の腹腔鏡手技トレーニングにおけるタイムトライアルの有用性の検討

長尾沙智子, 玉手雅人, 藤部佑哉, 西村庸子, 松浦基樹, 寺本瑞絵, 馬場剛, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 64 ( 1 ) 102 - 102 2020.03

Pioglitazone suppresses excessive follicular development in murine preantral follicles.

Sachiko Nagao, Tsuyoshi Baba, Yuya Fujibe, Sayaka Adachi, Keiko Ikeda, Miyuki Morishita, Yoshika Kuno, Hiroyuki Honnma, Toshiaki Endo, Tamotsu Kiya, Tsuyoshi Saito

Journal of ovarian research 12 ( 1 ) 82 - 82 2019.08 [International journal]

Polycystic ovary syndrome (PCOS) is an endocrine disease that is common in women in their reproductive period. Patients with this disease suffer from anovulation and hyperandrogenism. Ovulation induction with exogenous gonadotropin often causes ovarian hyperstimulation syndrome because many small antral follicles pause in their growth. Treatment with insulin sensitizers is reportedly effective for both anovulation associated with PCOS, and suppression of excessive follicular growth; however, the underlying mechanism of action remains unknown. Although pioglitazone is known as an insulin sensitizer, it also has a potent modulator of cell growth and apoptosis irrespective of insulin resistance. To clarify the effect of pioglitazone on follicular growth, we performed in vitro culture of murine preantral follicles. Secondary follicles (100-160 μm in diameter) isolated from 6-week-old ICR mice were individually cultured for 13 days. Culture conditions were as follows: 1) follicle-stimulating hormone (FSH; 33 mIU/mL; control), 2) FSH plus dihydrotestosterone (DHT; 500 ng/mL), 3) FSH plus pioglitazone (5 ng/mL), and 4) FSH plus DHT/pioglitazone. Survival rate and follicle diameter were evaluated, and concentrations of estradiol (E2) and vascular endothelial growth factor (VEGF) in culture media were measured. mRNA expression of various growth-promoting factors and Vegf within follicles were also assessed. Although no significant differences were observed with regard to survival rate, follicle diameters on day 13 were significantly different.Compared with the control group, the DHT group showed enhanced growth, while groups administered pioglitazone showed stagnation of the accelerated growth induced by DHT. Although DHT treatment enhanced the expression of bone morphogenetic protein 2 (Bmp2) mRNA, pioglitazone exposure suppressed induction of Bmp2 mRNA by DHT. Vegf mRNA and protein expression were also significantly reduced when pioglitazone was added to culture media containing DHT.Administration of pioglitazone negatively affected follicular growth and VEGF levels, which may suppress excessive follicular growth and prevent ovarian hyperstimulation syndrome.

重症子宮内膜症を有する不妊治療における手術とART介入のタイミング

森下美幸, 長尾沙智子, 新開翔太, 久野芳佳, 真里谷奨, 馬場剛, 遠藤俊明, 齋藤豪

日本産科婦人科内視鏡学会雑誌 ( (一社)日本産科婦人科内視鏡学会 ) 35 ( Suppl.I ) 252 - 252 2019.08

Obstetrical prognosis of patients who underwent vaginal radical trachelectomy during pregnancy.

Mina Umemoto, Shinichi Ishioka, Yuko Mizugaki, Yuya Fujibe, Tasuku Mariya, Akari Kawamata, Masahito Mizuuchi, Miyuki Morishita, Tsuyoshi Baba, Tsuyoshi Saito

The journal of obstetrics and gynaecology research 45 ( 6 ) 1167 - 1172 2019.06 [International journal]

AIM: Radical trachelectomy (RT) with pelvic lymphadenectomy has become an option for young patients with early invasive uterine cervical cancer who decide to maintain their fertility. However, this operative method entails a high risk for the following pregnancy due to its radicality. Therefore, RT for pregnant patients can be a challenge both for gynecologic oncologists and obstetricians. METHODS: We have performed vaginal RT for five pregnant patients with uterine cervical cancer stage 1B1 according to the method of Dargent et al. The operations were performed between 16 and 26 weeks of pregnancy, and the patients were followed up carefully according to the follow-up methods we reported previously. RESULTS: Vaginal RT was performed for five patients without any troubles. Four of the patients continued their pregnancies until almost 34 weeks or longer under our previously published follow-up schedule. The pregnancy of one patient was terminated at 26 weeks due to recurrence of the cancer. CONCLUSION: Expansion of vaginal RT for pregnant patients with uterine cervical cancer could be a practical option for pregnant patients with early invasive uterine cervical cancer.

Androgen potentiates the expression of FSH receptor and supports preantral follicle development in mice.

Yuya Fujibe, Tsuyoshi Baba, Sachiko Nagao, Sayaka Adachi, Keiko Ikeda, Miyuki Morishita, Yoshika Kuno, Masahiro Suzuki, Masahito Mizuuchi, Hiroyuki Honnma, Toshiaki Endo, Tsuyoshi Saito

Journal of ovarian research 12 ( 1 ) 31 - 31 2019.04 [International journal]

Hyperandrogenism is one of the cardinal symptoms in polycystic ovary syndrome and plays a key role in the pathogenesis of polycystic ovary syndrome. However, the precise effects and mechanisms of excess androgen during follicular development are still unclear. Here we investigated the effects of androgen on mouse follicle development in vitro. Androgen did not affect the growth of follicles smaller than 160-180 μm in the presence of follicle-stimulating hormone (FSH). However, in the presence of low FSH, androgen supported the growth of follicles larger than 160-180 μm, a size at which growing follicles acquire FSH-dependency. Androgen did not change the mRNA expression of various growth-promoting factors but did increase mRNA expression of the FSH receptor. We suggest that androgen has a positive impact on follicle development by augmentation of the actions of FSH. Therefore, FSH-responsive but FSH-independent follicles grow in the presence of a certain level of FSH or androgen, and androgen compensates for FSH deficiency in FSH-dependent follicles.

自然消失した子宮動脈仮性動脈瘤の超音波パワードップラー法所見の変化

嶋田浩志, 野藤五沙, 鈴木美紀, 幅田周太朗, 藤部佑哉, 水内将人, 馬場剛, 石岡伸一, 齋藤豪

超音波医学 ( (公社)日本超音波医学会 ) 46 ( Suppl. ) S719 - S719 2019.04

Association Between Maternal Serum Folate Concentrations in the First Trimester and the Risk of Birth Defects: The Hokkaido Study of Environment and Children's Health

Kumiko Ito, Tomoyuki Hanaoka, Naomi Tamura, Seiko Sasaki, Chihiro Miyashita, Atsuko Araki, Sachiko Ito, Hisanori Minakami, Kazutoshi Cho, Toshiaki Endo, Tsuyoshi Baba, Toshinobu Miyamoto, Kazuo Sengoku, Akiko Tamakoshi, Reiko Kishi

JOURNAL OF EPIDEMIOLOGY ( JAPAN EPIDEMIOLOGICAL ASSOC ) 29 ( 4 ) 164 - 171 2019.04 [Refereed] [International journal]

Background: Low red blood cell folate concentrations during early pregnancy might cause neural tube defects. However, the association between folate concentrations and birth defects of other neural crest cell-derived organs remains unknown. We investigated the associations between birth defects and first-trimester serum folate concentrations in a birth-cohort study in Japan.Methods: In total, 14,896 women who were prior to 13 weeks of gestation were enrolled from 2003 through 2012. Birth defect information was obtained from medical records and questionnaires. The association between folate levels in the first trimester and birth defects categorized as ICD-10 cord defects and neural crest cell-derived organ defects was examined. The crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per log-transformed folate concentration were calculated using logistic regression.Results: Blood samples were obtained at a mean of 10.8 weeks of gestation. Median serum folate level was 16.5 (interquartile range, 13.4-21.5) nmol/L, and the deficiency level (less than 6.8 nmol/L) was 0.7%. There were 358 infants with birth defects. The adjusted odds ratio for any birth defect, ventricular septal defects, and cleft lip was 0.99 (95% CI, 0.74-1.32), 0.63 (95% CI, 0.30-1.33), and 4.10 (95% CI, 0.96-17.58), respectively. There were no significant associations between first-trimester maternal serum folate and the risk of birth defects.Conclusions: We were unable to demonstrate a relationship between maternal serum folate in the first trimester and birth defects. Potential confounding factors may have influenced our results.

The roles of metformin and pravastatin on Placental endoplasmic reticulum stress and Placental growth factor in human villous-like trophoblastic BeWo cells

Masahiro Suzuki, Masahito Mizuuchi, Tsuyoshi Baba, Yuya Fujibe, Yoshihiko Ino, Shinichi Ishioka, Tsuyoshi Saito

Sapporo Medical journal ( Sapporo Medical University ) 87 ( 1-6 ) 75 - 84 2018.12

Preeclampsia (PE) is related to an imbalance of angiogenic factors. Placental growth factor (P1GF) is reduced in early onset PE. Recent evidence indicates that metformin and statins may suppress endoplasmic reticulum (ER) stress. We previously reported that the unfolded protein response activated by ER stress down-regulated P1GF protein expression and predicted these drugs could prevent placental ER stress and up-regulate P1GF protein expression in trophoblast-like cells. In this study, we aimed to establish the effects of these drugs on P1GF and activating transcription factor 4 (ATF4) protein expression. We confirmed that P1GF messenger RNA (mRNA) levels were decreased under ER stress induced by thapsigargin and that ATF4 mRNA was increased under the same conditions and then administered metformin to it. Transcript analysis showed increased P1GF mRNA compared with thapsigargin only treatment and that this was dependent on metformin levels. Under ER stress, western blot showed high levels of ATF4 and phosphorylated-eukaryotic initiation factor 2 subunit a (p-eIF2a) but low levels of P1GF protein. By contrast, compared with thapsigargin alone, ATF4 and p-eIF2a levels were low and P1GF levels were high when metformin and thapsigargin were given, but these were again dependent on metformin concentrations. Western blot also confirmed that pravastatin attenuated ER stress and increased P1GF protein expression. In conclusion, metformin and pravastatin suppressed ER stress and restored P1GF levels in trophoblastlike cells. However, although these results indicate that these drugs have a potential for preventing or treating PE, the lack of clarity on the mechanism requires further study.

Rare case of occult testosterone-producing ovarian tumor that was diagnosed by selective venous hormone sampling.

Yoshika Kuno, Tsuyoshi Baba, Takafumi Kuroda, Mizue Teramoto, Naoki Hirokawa, Toshiaki Endo, Tsuyoshi Saito

Reproductive medicine and biology 17 ( 4 ) 504 - 508 2018.10 [Domestic journal]

CASE: A 32 year old woman was referred because of secondary amenorrhea, hirsutism, and voice deepening. OUTCOME: The blood testosterone level was markedly high. A transvaginal ultrasound revealed a small region in the left ovary, but whether or not it was a tumor was unclear. Therefore, selective ovarian venous sampling was performed. Consequently, the testosterone level was selectively increased in a blood sample that was taken from the left ovarian vein, the tumor was successfully localized, and a laparoscopic left oophorectomy was performed. Although the left ovary appeared to be normal at laparoscopy, the androgen-secreting tumor was located within it. The tumor was diagnosed as a Leydig cell tumor by histopathological analyses. CONCLUSION: This report demonstrates that selective blood sampling from ovarian veins before an operation is effective in localizing an androgen-producing ovarian tumor that is difficult to diagnose by imaging studies.

2009年IOM指針に基づいた推奨妊娠中体重増加における出生児体重の検討

嶋田浩志, 高田さくら, 恐神博行, 水内将人, 馬場剛, 石岡伸一, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 54 ( 2 ) 717 - 717 2018.06

Bakriバルーンの前置胎盤・低置胎盤帝王切開症例における予防的止血効果の検討

梅本美菜, 黒田敬史, 水内将人, 野呂薫, 柏木葉月, 伊野善彦, 杉田菜穂子, 鈴木将裕, 森下美幸, 馬場剛, 石岡伸一, 齋藤豪

日本産婦人科・新生児血液学会誌 ( 日本産婦人科・新生児血液学会 ) 28 ( 1 ) 30 - 31 2018.05

当院前置胎盤・低置胎盤の帝王切開時にBakriバルーンを使用した14例を対象に、予防的止血効果に関する検討を行った。その結果、全例がBakriによる止血奏効例で、Bakri予防使用群は6例、非予防使用群は8例であった。分娩第3期の出血量は2群間で有意差を認めなかったが、分娩第4期の出血量はBakri予防使用群で有意に少なかった。今回の検討から、帝王切開時におけるBakriの予防的使用は、前置・低置胎盤に対する術中および分娩第4期の止血法として有効であることが示唆された。

Pioglitazone is effective for multiple phenotyepes of the Zucker fa/fa rat with polycystc ovary morphology and insulin resistance.

Miyuki Morishita, Toshiaki Endo, Tsuyoshi Baba, Yoshika Kuno, Keiko Ikeda, Tamotsu Kiya, Hiroyuki Honnma, Tsuyoshi Saito

Journal of ovarian research 11 ( 1 ) 24 - 24 2018.03 [International journal]

BACKGROUND: Hyperandrogenism and insulin resistance may be related to the etiology of PCOS. Zucker fa/fa rats with polycystic ovary are obese, have insulin resistance without diabetes mellitus or hyperandrogenism and can be utilized as PCOS model rats without effects of hyperandrogenemia. PCOS patients are reported to have elevated levels of serum anti-Mullerian hormone (AMH), which has an inhibitory action on folliculogenesis, and low levels of serum adiponectin, which blocks apoptosis and induces biological effects in some tissues. Pioglitazone, an insulin sensitizer, is administered to PCOS patients with insulin resistance to induce ovulation but the mechanisms by which this occurs have not been elucidated. METHODS: We purchased 4-week-old female fatty Zucker fa/fa rats as well as lean Zucker +/+ rats for use as control rats with normal insulin sensitivity. The Zucker fa/fa rats were administered pioglitazone (2.5 mg/kg body weight/day) or a vehicle every day for 14 days in separate groups. The Zucker +/+ rats were also administered the vehicle. After 2 weeks of treatment, they were euthanized and we obtained serum samples and both ovaries and determined the body weight, ovarian weight, and serum AMH, adiponectin, testosterone, and androstenedione levels. We also examined ovarian histology to check follicle numbers by using hematoxylin-eosin staining, and the number of atretic follicles using Tdt-mediated dUTP nick end labeling (TUNEL) methods. RESULTS: The Zucker fa/fa rats used as PCO model rats and Pioglitazone treated PCO model rats were significantly heavier than the Zucker +/+ control rats (p < 0.05) at 15 day old. Pioglitazone treatment did not influence body weight or ovarian weight in either group. However, the total number of follicles was significantly larger in the PCO model rats than in the control rats (P < 0.05). Although pioglitazone treatment appeared to decrease the total number of follicles in the PCO model rats, the decrease was not statistically significant. However, pioglitazone treatment significantly decreased the total number of atretic follicles and the rate of atreteic follicles in the PCO model rats (P < 0.05). The serum AMH level was significantly higher in the PCO model rats than in the control rats. Pioglitazone treatment significantly decreased the serum AMH level and significantly increased the serum adiponectin level in the PCO model rats (P < 0.05). Serum testosterone and androstenedione levels were quite low or undetectable in the 3 groups of rats, and were not influenced by pioglitazone treatment. CONCLUSION: In this study, pioglitazone treatment reduced the serum AMH level and increased the serum adiponectin level in PCO model rats. These effects are related to reduction of the total number of atretic follicles and rate of atretic follicles. This proves that pioglitazone treatment improves healthy follicle growth in these PCO model rats with insulin resistance.

Transabdominal cerclage (TAC) for patients with ultra-short uterine cervix after uterine cervix surgery and its impact on pregnancy

Shinichi Ishioka, Miseon Kim, Yuko Mizugaki, Saori Kon, Kyoko Isoyama, Masahito Mizuuchi, Miyuki Morishita, Tsuyoshi Baba, Takao Sekiya, Tsuyoshi Saito

Journal of Obstetrics and Gynaecology Research ( Blackwell Publishing ) 44 ( 1 ) 61 - 66 2018.01 [Refereed] [International journal]

Aim: Patients with an ultra-short uterine cervix as a result of large conization, repeated conization or radical trachelectomy (RT), are at high risk of preterm premature rupture of the membrane, which leads to preterm birth. We have commenced performing transabdominal cerclage (TAC) of the uterine cervix for these patients. In this study, we examined the safety of TAC and its impact on pregnancy. Methods: We have performed TAC in 11 patients before pregnancy: in six after large cervical operations, such as repeated conization and in five for difficulties with cervical cerclage after RT. After laparotomy, a Teflon thread was placed in the avascular space between the uterine vessels and the uterine muscle, and tied. The clinical course of the patients after TAC and their pregnancy course were retrospectively reviewed. Results: TAC was performed safely without any complications. The mean operative duration was 53 ± 10 min, and the mean blood loss during the operation was 49 ± 64 mL. Seven women conceived within 2 years after TAC. Their pregnancy courses were favorable. Five of the women underwent scheduled cesarean sections, while two pregnancies are ongoing. Conclusions: Although there are risks of various complications as a result of the use of non-absorbable thread and the need for two extra laparotomies, TAC can be a safe and useful option for patients who show cervical incompetence after large uterine cervical operations, such as RT or large conization.

Prevalence and risk of birth defects observed in a prospective cohort study: The Hokkaido study on environment and children’s health

Tomoyuki Hanaoka, Naomi Tamura, Kumiko Ito, Seiko Sasaki, Atsuko Araki, Tamiko Ikeno, Chihiro Miyashita, Sachiko Ito, Hisanori Minakami, Kazutoshi Cho, Toshiaki Endo, Tsuyoshi Baba, Toshinobu Miyamoto, Kazuo Sengoku, Reiko Kishi, H. Goudarzi, M. Minatoya, S. Kobayashi, K. Yamazaki, S. Nishihara, Y. Ait Bamai, R. Miura, S. Kobayashi, A. Uno, S. Katoh, T. Baba, T. Yila, T. Braimoh, I. Kashino, S. Nakajima, T. Baba, Y. Saijyo, E. Yoshioka, T. Miyamoto, K. Okuyama, F. Sata, T. Kita

Journal of Epidemiology 28 ( 3 ) 125 - 132 2018 [Domestic journal]

© 2017 Tomoyuki Hanaoka et al. Background: Prevalence rates of all anomalies classified as birth defects, including those identified before the 22nd gestational week, are limited in published reports, including those from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). In our birth cohort study, we collected the data for all birth defects after 12 weeks of gestation. Methods: Subjects in this study comprised 19,244 pregnant women who visited one of 37 associated hospitals in the Hokkaido Prefecture from 2003 through 2012, and completed follow-up. All birth defects after 12 weeks of gestation, including 55 marker anomalies associated with environmental chemical exposures, were recorded. We examined parental risk factors for birth defects and the association between birth defects and risk of growth retardation. Results: Prevalence of all birth defects was 18.9=1,000 births. The proportion of patients with birth defects delivered between 12 and 21 weeks of gestation was approximately one-tenth of all patients with birth defects. Among those with congenital malformation of the nerve system, 39% were delivered before 22 weeks of gestation. All patients with anencephaly and encephalocele were delivered before 22 weeks of gestation. We observed different patterns of parental risk factors between birth defect cases included in ISBDSR and cases not included. Cases included in ISBDSR were associated with an increased risk of preterm birth. Cases not included in ISBDSR were associated with an increased risk of being small for gestational age at term. Conclusions: Data from our study complemented the data from ICBDSR. We recommend that birth defects not included in ICBDSR also be analyzed to elucidate the etiology of birth defects.

Association of prenatal passive smoking and metabolic gene polymorphisms with child growth from birth to 3 years of age in the Hokkaido Birth Cohort Study on Environment and Children's Health

Titilola Serifat Braimoh, Sumitaka Kobayashi, Fumihiro Sata, Seiko Sasaki, Houman Goudarzi, Thamar Ayo Yila, Atsuko Araki, Chihiro Miyashita, Hisanori Minakami, Tsuyoshi Baba, Kazuo Sengoku, Reiko Kishi

SCIENCE OF THE TOTAL ENVIRONMENT ( ELSEVIER SCIENCE BV ) 605 995 - 1002 2017.12 [Refereed] [International journal]

Although the effects of prenatal passive smoking on birth weight have been reported, the effects of metabolic gene polymorphisms on passive smoking have not been studied. Therefore, we investigated the effects of maternal passive smoking and metabolic gene polymorphisms on child growth up to 3 years of age using cotinine as a biomarker. We included 1356 Japanese participants in a prospective cohort between 2003 and 2007 (cotinine levels at the third trimester <= 0.21 ng/mL and 0.22 to 11.48 ng/mL for non-passive and passive smokers, respectively), and measured child outcomes such as weight, length, head circumference, and Kaup index. Additionally, we analyzed cytochrome P450 1A1 (CYP1A1), epoxide hydrolase 1 (EPHX1), and two N-acetyltransferase 2 (NAT2) genotypes using real-time polymerase chain reaction methods. Associations were investigated using multiple regression models. Kaup index gain from birth up to 3 years of age was significantly smaller in children born to passive smokers than in those born to non-passive smokers (-0.34 kg/m(2); 95% confidence interval: -0.67, -0.01). Maternal CYP1A1 genotype was not associated with prenatal passive smoking and Kaup index gain, but was significantly associated with prenatal passive smoking and head circumference gain from birth up to 3 years of age (-0.75 cm; 95% confidence interval:-1.39, -0.12). Thus, this study suggests that prenatal passive smoking may have potent effects on postnatal growth frombirth up to 3 years of age. Moreover, children with maternal CYP1A1 genotype may be more susceptible to the effects of prenatal passive smoking. (C) 2017 Elsevier B.V. All rights reserved.

当院における死戦期帝王切開を念頭においた産科救急システムの構築

水内将人, 藤部佑哉, 嶋田浩志, 馬場剛, 石岡伸一, 斎藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 53 ( 2 ) 727 - 727 2017.06

Possibility of less radical treatment for patients with early invasive uterine cervical cancer

Miseon Kim, Shinichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Masahito Mizuuchi, Sakura Takada, Tsuyoshi Saito

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH ( WILEY-BLACKWELL ) 42 ( 7 ) 876 - 882 2016.07 [Refereed] [International journal]

AimRadical trachelectomy (RT) with lymphadenectomy has become a standard treatment modality for patients with early invasive uterine cervical cancer who hope to preserve fertility. However, pregnancy after RT has high risks of preterm birth. The possibility of more conservative RT and the application of RT for patients with higher clinical stages were studied. MethodsThe medical charts and specimens of 42 patients who underwent RT and 64 patients who underwent radical hysterectomy were retrospectively studied. Tumor size, distance between the margin of the cancer and the internal orifice of the uterus (os), parametrial invasion, lymph node metastasis and prognoses were investigated. ResultsThe average distances between the inner margin of the cancer and the internal os were 37 mm, 29 mm, 18.7 mm and 14 mm for patients with stage 1 A2, 1B1 ( 2 cm), 1B1 (> 2 cm) and 1B2, respectively. When amputation was performed 10 mm below the internal os, all 10 patients with 1 A2, 57 with 1B1 ( 2 cm), 19 with 1B1 (> 2 cm), and one with 1B2 had a cancer-free margin > 10 mm. Patients with stage 1 A2 had a cancer-free margin > 10 mm even if we amputated the cervix 20 mm below the internal os. Parametrial invasion was detected in two patients with stage 1B1. ConclusionsA simple trachelectomy 20 mm below the internal os with pelvic lymphadenectomy might be possible for stage 1 A2 patients. The present method is best for stage 1B1 patients ( 2 cm). RT for stage 1B1 (>2 cm) or higher stages should be contraindicated.

Obstetrical prognosis of patients with cervical intraepithelial neoplasia (CIN) after "coin-shaped" conization.

Miseon Kim, Shinichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Tsuyoshi Saito

Archives of gynecology and obstetrics 293 ( 3 ) 651 - 7 2016.03 [International journal]

PURPOSE: Uterine cervical conization is related to adverse pregnancy outcomes in subsequent pregnancies. To deal with this problem, we started conservative coin-shaped conization for reproductive-aged patients with cervical intraepithelial neoplasia (CIN). Here we report both the obstetrical and oncological impacts of this operation in comparison with the standard cone-shaped resection. METHODS: A total of 401 women 44 years old or younger were treated in our hospital by CO2 laser conization between 2003 and 2012, and subsequently 50 patients became pregnant. The patients were divided into two groups, a standard cone-shaped conization group (until 2008) and a shallow coin-shaped conization group (beginning in 2008). The pregnancy courses and oncological prognoses of these two groups were studied. RESULTS: Cone height reduction of about 3 mm was done. However, there were no significant differences between the two groups with regard to the occurrence of oncological complications. In the standard conization group, 18 of the 25 patients delivered at term. In the coin-shaped conization group, 20 of the 25 patients delivered at term. There were no significant differences between the two groups with regard to the occurrence of various obstetrical complications. However, the reduction rate of cervical length over the pregnancy was smaller in the coin-shaped group and the number of patients with a short cervix length of 2 cm or less was smaller in the coin-shaped group. CONCLUSIONS: Although conservative coin-shaped conization did not markedly improve the obstetrical prognosis, this operative procedure improved the reduction rate of uterine cervical length over the pregnancy without any increase in oncological complications.

BMI66.5kg/m2の高度肥満妊婦における帝王切開の経験

森下美幸, 嶋田浩志, 馬場剛, 石岡伸一, 遠藤俊明, 齋藤豪

産科と婦人科 ( (株)診断と治療社 ) 83 ( 2 ) 226 - 231 2016.02

Successful delivery after transabdominal cerclage of uterine cervix for cervical incompetence after radical trachelectomy.

Shinichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Yushi Akashi, Miyuki Morishita, Asuka Sugio, Naohiro Kanayama, Tsuyoshi Saito

The journal of obstetrics and gynaecology research 41 ( 8 ) 1295 - 9 2015.08 [International journal]

Pregnancy after radical trachelectomy (RT) has a high risk of prematurity and complications such as preterm premature rupture of the membrane and chorioamnionitis. Placing a cervical cerclage at the time of RT plays an important role in preventing such obstetrical complications. In patients who have trouble with the cervical cerclage, miscarriage during the second trimester seems to be inevitable. We have therefore started preconception transabdominal cerclage (TAC) for these patients. A 36-year-old Japanese woman who had a history of miscarriage due to trouble with the nylon thread used for cerclage, successfully delivered after TAC. TAC is a useful treatment modality to prevent miscarriage for patients who have trouble with cerclage after RT.

治療方針に苦慮した急性Stanford A型大動脈解離合併妊娠

嶋田浩志, 遠藤俊明, 山本雅恵, 杉尾明香, 清水亜由美, 森下美幸, 明石祐史, 馬場剛, 石岡伸一, 齋藤豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 ) 59 ( 1 ) 22 - 26 2015.03

周産期の大動脈解離の発症は非常に稀であるが、40歳未満の大動脈解離の発症の半数は妊娠に合併するといわれている。急性のStanford A型大動脈解離は手術治療が原則であるが、妊娠に合併した場合の治療方針は明確に定まっていない。今回我々は帝王切開術と子宮摘出術の決断に苦慮した急性Stanford A型大動脈解離の一例を経験したので報告する。症例は31歳女性。未経妊未経産。妊娠31週に制御不能な胸痛および背部痛を自覚し、前医を受診した。造影CTで急性Stanford A型大動脈解離と診断され、当院に手術目的に緊急搬送された。治療方針に苦慮したが帝王切開を先行させ、胎児を娩出後に人工血管置換術を一期的に行った。人工血管置換術中の産科的出血を予防するために子宮全摘術を実施した。術後経過は良好で合併症もなく、母子ともに術後24日目に退院した。帝王切開術の施行時期と子宮摘出術の選択に議論の余地はあるが、人工血管置換術時の体外循環による胎児への影響と大動脈解離の死亡率を考慮した場合、妥当な選択だったと考えられる。(著者抄録)

Importance of uterine cervical cerclage to maintain a successful pregnancy for patients who undergo vaginal radical trachelectomy

Miseon Kim, Shin-ichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Yushi Akashi, Miyuki Morishita, Hidefumi Adachi, Tsuyoshi Saito

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY ( SPRINGER JAPAN KK ) 19 ( 5 ) 906 - 911 2014.10 [Refereed] [Domestic journal]

We have performed 36 vaginal radical trachelectomies (RTs) for patients with early invasive uterine cervical cancer and experienced 10 deliveries. Pregnancy after RT has far higher risks of prematurity and complications such as preterm premature rupture of the membrane (pPROM) and chorioamnionitis. We report the significance of transabdominal cerclage in the follow-up of pregnancy after vaginal RT. Our operative procedure is based on that of Dargent et al. We amputated the cervix approximately 10 mm below the isthmus. For the removal of the parametrium, we cut at the level of type II hysterectomy. A nylon suture is also placed around the residual cervix. Pregnancy courses after vaginal RT were studied in 9 patients (10 pregnancies) with respect to cervical length and several infectious signs. Obstetric prognosis after RT was improved with our follow-up modality. Four patients who were followed up with this modality were able to continue their pregnancies until late in the third trimester. However, it was not effective for four patients who showed cervical incompetence due to slack cerclage. They suffered from pPROM without any infectious signs and uterine contraction. Though we performed transabdominal uterine cervical cerclage for one patient in her 19th week of pregnancy, it was unsuccessful. Cervical cerclage placed at the time of RT played an important role in preventing dilatation of the uterine cervix and the subsequent occurrence of pPROM. Transabdominal cervical cerclage should be performed earlier in pregnancy or before pregnancy in patients who have experienced problems with cervical cerclage.

Common hypothetical etiology of excess androgen exposure in female-to-male transsexualism and polycystic ovary syndrome

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Tsuyoshi Saito

Gender Identity: Disorders, Developmental Perspectives and Social Implications ( Nova Science Publishers, Inc. ) 253 - 270 2014.07

Gender identity disorder is recognized as a rare disease. The prevalence of this disorder is different among regions and races. In Japan, the prevalence of female-to-male transsexual (FTM-TS) patients is estimated to be 1 in 12,500 women, which is approximately twice as many as male-to-female transsexual patients. There are two interesting facts in association with FTM-TS: 1) the complication rate of polycystic ovary syndrome (PCOS) is high among FTM-TS patients and 2) natal female patients with congenital adrenal hyperplasia (CAH) tend to have gender identity problems more often than the normal population. PCOS is a common disease and it affects 5-10% of women of reproductive age. PCOS is characterized by ovulation disorder, hyperandrogenism, and polycystic ovarian morphology. Additionally, PCOS is correlated with insulin resistance, and predisposes to type 2 diabetes mellitus, atherosclerosis, and metabolic syndrome. The etiology of PCOS is still obscure, but excess androgen exposure during the fetal period is considered to be a dominant hypothesis. CAH is an autosomal recessive disorder impairing adrenal steroid metabolism, which causes excess androgenemia from the fetal period. A review on 250 natal female cases with CAH showed that 13 (5.2%) of the patients had serious gender identity problems. Surprisingly, the occurrence of FTM-TS in CAH is extremely high. The pathogenesis of FTM-TS is still uncertain. However, excess androgen exposure may be related to FTM-TS according to the above-mentioned findings. In humans, experimental androgen administration to women is impossible. However, cross-sex hormone administration to FTM-TS patients is not associated with any problems because it is a standard tactic for treatment. If excess androgen exposure is a cause of PCOS, androgen-treated FTM-TS patients may be a disease model of PCOS. Assessment of the effects of androgen administration on metabolic parameters is informative because FTM-TS patients with PCOS may have potent insulin resistance. In this chapter, we discuss endocrinological aspects of FTM-TS, the effect of crosssex hormones, and the hypothetical etiology in FTM and PCOS.

Continuous high-dose estrogen controls serum FSH and LH levels: new treatment strategy for extremely low ovarian reserve patients, two case reports.

Hiroyuki Honnma, Yoshimasa Asada, Tsuyoshi Baba, Toshiaki Endo

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 30 ( 5 ) 341 - 4 2014.05 [International journal]

At present, there are no proven therapies to improve ovarian function in women with premature ovarian insufficiency (POI) or in those with extremely low ovarian reserve (LOR). We report successful IVF outcomes achieved with continuous high-dose estrogen supplementation in patients with LOR. Patients were 33- and 42-year-old nulligravidae with high-serum FSH (over 30 IU/L) and undetectable serum AMH (under 0.1 ng/mL) levels; however, neither patient fulfilled the diagnostic criteria for POI. After cycle cancellation and unsuccessful IVF treatment, both patients received conjugated estrogen (CE) supplementation (2.5-3.75 mg/day) from day 2 of their menstrual cycle to the day of HCG administration in their IVF treatment cycles. Following continuous high-dose estrogen supplementation, oocytes were successfully retrieved from both patients and fertilized. Both patients also achieved ongoing pregnancy through frozen-thawed embryo transfer cycles. In conclusion, high-dose estrogen supplementation down-regulated serum FSH and LH within their physiological ranges, which led to functional follicle growth and prevented early luteinization. Further studies will be needed to confirm the effect of this treatment on POI patients and to establish a new and individualized protocol for LOR patients.

Long-term treatment with dehydroepiandrosterone may lead to follicular atresia through interaction with anti-Mullerian hormone

Keiko Ikeda, Tsuyoshi Baba, Miyuki Morishita, Hiroyuki Honnma, Toshiaki Endo, Tamotsu Kiya, Tsuyoshi Saito

JOURNAL OF OVARIAN RESEARCH ( BIOMED CENTRAL LTD ) 7 46 - 46 2014.04 [Refereed] [International journal]

Background: Hyperandrogenism is the primary manifestation of polycystic ovary syndrome (PCOS), which appears to be caused by excess exposure to androgen. As such, androgenized animal models have been developed and investigated to study the etiology of PCOS. Anti-Mullerian hormone (AMH) is known to be associated with follicle growth, and its levels are two to three times higher in women with PCOS than in those with normal ovaries. We studied how duration of androgen administration affects folliculogenesis and AMH expression. Methods: We divided 30 immature (3-week-old) Sprague Dawley rats into six groups. Three groups were injected each evening with dehydroepiandrosterone (DHEA) (6 mg/100 g body weight/0.2 ml sesame oil) for 7, 15 or 30 days, respectively. The three control groups were injected with 0.2 ml of sesame oil for the corresponding lengths of time. Resected ovaries were sectioned and examined to determine follicle numbers at each developmental stage, and immunostained to assess AMH expression. Results: On day 7, follicle numbers and AMH expression levels at each developmental stage of follicle growth were similar in the respective control and DHEA groups. On day 15, the total follicle number (P = 0.041), the percentage of primordial follicles (P = 0.039) and AMH expression were significantly greater in the DHEA than the control group. On day 30, the percentages of primordial (P = 0.005), primary (P = 0.0002) and atretic (P = 0.03) follicles were significantly greater in the DHEA group, whereas the percentage of intermediary follicles (early pre-antral, late preantral, and early antral follicles) was significantly lower in the DHEA group (P = < 0.0001). AMH expression in DHEA-treated rats on day 30 was seen exclusively in the primordial (P = 0.0413) and late antral follicles (p = 0.028). Conclusions: Androgen administration increases AMH production in a process that regulates the growth of primordial follicles. That is, androgen-induced AMH expression provides local negative feedback to folliculogenesis augmented by androgen.

Excessive androgen exposure as an etiological factor of polycystic ovary syndrome

Tsuyoshi Baba, Toshiaki Endo, Sayaka Adachi, Keiko Ikeda, Ayumi Shimizu, Miyuki Morishita, Yoshika Kuno, Hiroyuki Honnma, Tamotsu Kiya, Tsuyoshi Saito

Journal of Mammalian Ova Research ( Japanese Society of Mammalian Ova Research ) 31 ( 1 ) 23 - 30 2014

Polycystic ovary syndrome (PCOS) is a heterogeneous group of disorders characterized by ovulation disorder, hyperandrogenism, and polycystic ovarian morphology (PCOM). Several diagnostic criteria suggest that hyperandrogenism is a core symptom of PCOS. Androgens are believed to cause preantral follicle growth and arrest the growth of antral follicles. This results in accumulation of small antral follicles in the ovaries, thus forming PCOM. Observational studies of patients with female-to-male transsexualism or congenital adrenal hyperplasia indicate that androgen administration to these patients does not produce typical PCOS-like features. However, endogenous androgen exposure in early life may lead to some traits of PCOS in adulthood. To reveal the association between the timing of excess androgen exposure and reproductive function, various animal models have been investigated using androgen administration. Rhesus monkeys exposed to excess androgen during the early fetal period show a PCOS-like phenotype, including metabolic and hypothalamic- pituitary characteristics. This finding implies that exposure to excess androgen during this critical period programs the hypothalamic-pituitary-ovary axis and metabolic organs. Although findings obtained in animal studies will not necessarily be replicated in humans, prenatal androgen excess is the dominant PCOS hypothesis. ©2014 Japan Society for Ova Research.

Difficulty in the management of pregnancy after vaginal radical trachelectomy.

Sakura Takada, Shin-Ichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Miyuki Morishita, Yushi Akashi, Masahito Mizuuchi, Hidefumi Adachi, Miseon Kim, Tsuyoshi Saito

International journal of clinical oncology 18 ( 6 ) 1085 - 90 2013.12 [Domestic journal]

BACKGROUND: We have performed 26 vaginal radical trachelectomies (RTs) for patients with early invasive uterine cervical cancer since 2003 and, to date, have experienced 8 deliveries. The procedure has a high risk for preterm labor and the subsequent occurrence of preterm premature rupture of membranes (pPROM). We report the present situation and the limits of follow-up of pregnancy after vaginal RT. METHODS: Our operative procedure is based on that of Dargent et al. We usually amputate the cervix approximately 10 mm below the isthmus. To remove the parametrium, we cut at the level of type II hysterectomy. Pregnancy courses after vaginal RT were studied in 8 patients with respect to symptoms, cervical length, and several infectious signs. RESULTS: We recommended that patients enter hospital early in their second trimester, and prophylactic daily vaginal disinfection with povidone-iodine and an ulinastatin vaginal suppository were administered. Careful checking for vaginal infectious signs, as well as cervical length and abdominal tension of patients was also performed. Four patients followed up with this modality were able to continue their pregnancies until late in the third trimester. However, this follow-up modality was not effective for patients who showed cervical incompetence due to slack cervical cerclage. They suffered from pPROM at 26 and 19 weeks of gestation. CONCLUSION: We need a new approach for the management of pregnant patients after vaginal RT with cervical incompetence due to slack cervical cerclage to prevent cervical infection.

Assisted reproductive technique increases the risk of placental polyp

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Ayumi Shimizu, Miyuki Morishita, Yoshika Kuno, Hiroyuki Honnma, Tamotsu Kiya, Shin-Ichi Ishioka, Tsuyoshi Saito

Gynecological Endocrinology ( 6 ) 29 ( 6 ) 611 - 614 2013.06 [Refereed] [International journal]

The purpose of this study was to clarify the risk factors and outcomes of placental polyp. This retrospective study was conducted on 1645 patients delivered or aborted in Sapporo Medical University from 2007 through 2011. Transvaginal color Doppler ultrasonography, hysteroscopy, contrast-enhanced MRI or 3D-CT angiography were performed. There were 1532 deliveries and 113 abortions. Seventy-one (4.3%) were ART-conceived and the remaining 1574 (95.7%) were non-ART pregnancies. Fifteen (0.91%) cases were confirmed as having placental polyp. Nine cases of placental polyp were identified among the 1574 (0.57%) as non-ART-related pregnancies, and 6 were identified among the 71 (8.5%) as ART-related pregnancies. Thus, pregnancies achieved through ART showed 20x greater incidence of complicating placental polyp than pregnancies achieved through without ART (p=9.02×10-6 odds ratio, 19.59 95% confidence interval, 5.27-72.84, logistic regression analysis). Evaluation of blood flow within the polyp showed that in five of seven patients with low blood flow, the polyps spontaneously dropped off 79-115 days postpartum. Thus, ART-related pregnancies may be a risk factor of placental polyp, and spontaneous drop-off of the polyp is often observed in cases with low blood flow within the mass. © 2013 Informa UK Ltd.

Failure of GnRH agonist-triggered oocyte maturation: its cause and management.

Yoshimasa Asada, Fumiaki Itoi, Hiroyuki Honnma, Shuji Takiguchi, Noritaka Fukunaga, Yoshiki Hashiba, Tsuyoshi Baba, Toshiaki Endo

Journal of assisted reproduction and genetics 30 ( 4 ) 581 - 5 2013.04 [International journal]

OBJECTIVE: In the present study we investigated the cause of GnRHa's failure to trigger oocyte maturation and present an effective rescue protocol for use when failure occurs. DESIGN: Case reports. SETTING: One in vitro fertilization (IVF) center. PATIENT(S): Eight cases of failure of GnRH agonist (GnRHa)-triggered oocyte maturation and one case of GnRHa successfully triggered oocyte maturation, despite a weak response in the LH-RH test. MAIN OUTCOME MEASURE(S): All cases were successfully rescued by re-triggering maturation using HCG, with seven of the eight patients achieving ongoing pregnancy and successful delivery. RESULT(S): In three patients the cause of the oocyte maturation failure was likely temporal or continuous severe down-regulation of the hypothalamus-pituitary-axis, the cause was unknown in the other five patients. CONCLUSION(S): In cases where GnRHa fails to trigger oocyte maturation, a rescue protocol entailing re-triggering with HCG can produce successful outcomes.

Excessive androgen exposure in female-to-male transsexual persons of reproductive age induces hyperplasia of the ovarian cortex and stroma but not polycystic ovary morphology

Keiko Ikeda, Tsuyoshi Baba, Hiroko Noguchi, Kunihiko Nagasawa, Toshiaki Endo, Tamotsu Kiya, Tsuyoshi Saito

HUMAN REPRODUCTION ( OXFORD UNIV PRESS ) 28 ( 2 ) 453 - 461 2013.02 [Refereed] [International journal]

Does administration of androgen to female-to-male transsexual persons (FTMs) of reproductive age induce polycystic ovary (PCO) morphology? Administration of high-dose androgen to women causes pathognomonic changes to the ovarian cortex and stroma that resemble SteinLeventhal syndrome but it does not induce PCO morphology. Androgen is thought to play a key role in follicular development and to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). In several experimental models, animals given high-dose androgen show ovarian changes similar to those in women with PCOS. In previous human studies, the ovaries of FTMs who received androgen for long periods also exhibited PCO morphology. We conducted a retrospective casecontrol study of women, all without PCOS, undergoing salpingo-oophorectomy. The case group consisted of 11 FTMs taking testosterone (duration range: 17 months to 14 years), while the control group consisted of 10 patients with gynaecologic malignancies who did not receive testosterone. Resected ovaries from both groups were compared histologically with respect to changes in the cortex and stroma, and the number of follicles at each maturation stage. Compared with controls, the FTM group had a thicker ovarian cortex (P 0.0001), and more hyperplastic collagen (P 0.001), ovarian stromal hyperplasia (P 0.003) and stromal luteinization, i.e. luteinized stromal cells with a small dark central nucleus surrounded by clear cytoplasm (P 0.004). Isolated clusters of such stromal luteinized cells were found only in the testosterone-treated ovaries of FTMs. The number of primordial follicles was similar in the two groups (P 0.22). The numbers of early stage (primary, pre-antral and early antral) follicles, which are dependent on androgen, were also similar (P 0.81), as were the numbers of antral follicles (P 0.97). In contrast, significantly greater numbers of atretic follicles were seen in the FTM than that in the control group (P 0.01). In addition to the low numbers in the study groups, the histological changes in FTMs were investigated after testosterone administration, therefore it is possible that some of the observed changes were already present, before androgen administration. Our results are at variance with those of earlier studies and suggest that excessive androgen exposure in women of reproductive age may not be a factor in the pathogenesis of PCOS. None.

Serum anti-Mullerian hormone levels affect the rate of ongoing pregnancy after in vitro fertilization.

Hiroyuki Honnma, Tsuyoshi Baba, Masahiro Sasaki, Yoshiki Hashiba, Hisanori Oguri, Takanori Fukunaga, Toshiaki Endo, Yoshimasa Asada

Reproductive sciences (Thousand Oaks, Calif.) 20 ( 1 ) 51 - 9 2013.01 [International journal]

We used logistic regression analysis to investigate the relationship between serum anti-Mullerian hormone (AMH) levels and the rate of ongoing pregnancy. Retrospective data were collected from 1043 women who had undergone their first cycle of in vitro fertilization (IVF), including 540 cycles of fresh embryo transfer and 503 cycles of frozen-thawed embryo transfer. The patients were divided into 4 groups based on the cutoff values from a receiver-operating characteristic curve: 0.0 to 12.4, 12.5 to 25.5, 25.6 to 44.1, and >44.2 pmol/L. After adjustment for multiple confounders, the serum AMH group was found to be significantly related to the rate of ongoing pregnancy in total cycles (0.0-12.4 vs 12.5-25.5 pmol/L; P = .0088, odds ratio, 1.909: vs 25.6-44.1 pmol/L; P = .0281, odds ratio, 2.109: vs >44.2 pmol/L; P = .0008, odds ratio, 2.840). In conclusion, there appears to be a significant relationship between serum AMH levels and the ongoing pregnancy rate in first IVF treatment cycles after adjustment for multiple confounders.

A myotonic dystrophy 1 patient complicated with placental adherence after miscarriage of one dichorionic diamniotic twin following her tenth in vitro fertilization and embryo transfer

Toshiaki Endo, Tsuyoshi Baba, Asuka Sugio, Miyuki Morishita, Madoka Takahashi, Yushi Akashi, Shinichi Ishioka, Nobutada Tachi, Tomihiro Imai, Mitsuharu Tamakawa, Tsuyoshi Saito

ARCHIVES OF GYNECOLOGY AND OBSTETRICS ( SPRINGER HEIDELBERG ) 286 ( 6 ) 1605 - 1608 2012.12 [Refereed] [International journal]

Weight reduction and pioglitazone ameliorate polycystic ovary syndrome after removal of a Sertoli-stromal cell tumor

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Ayumi Shimizu, Miyuki Morishita, Yoshika Kuno, Hiroyuki Honnma, Tamotsu Kiya, Shin-Ichi Ishioka, Tsuyoshi Saito

International Journal of Women's Health 4 ( 1 ) 607 - 611 2012.11 [Refereed] [International journal]

This report presents an unusual case of Sertoli-stromal cell tumor and polycystic ovary syndrome successfully treated with weight reduction and an insulin-sensitizing agent. A 22-year-old woman, gravida 0, para 0, visited our hospital for the first time with a 12-year history of secondary amenorrhea and hypertrichosis. Transvaginal ultrasonography revealed a solid tumor in the right ovary. Right salpingo-oophorectomy was performed and pathological examination confirmed a Sertoli-stromal cell tumor. The patient's serum androgen levels declined postoperatively, but remained above normal. Pioglitazone treatment for 6 months also significantly reduced serum androgen levels, but they still remained above normal. However, after losing 12 kg of body weight, the patient's serum androgen levels declined to normal, and spontaneous menstruation became regular. Weight reduction with pioglitazone is an effective means of treating hyperandrogenism. © 2012 Baba et al, publisher and licensee Dove Medical Press Ltd.

160kg高度肥満妊婦に対する帝王切開の経験

中嶋千紗, 馬場剛, 森下美幸, 金美善, 足立英文, 明石祐史, 浅野拓也, 嶋田浩志, 杉尾明香, 石岡伸一, 遠藤俊明, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 60回 87 - 87 2012.09

母児ともに救命し得た大動脈解離合併妊娠の3例

嶋田浩志, 岡村直樹, 染谷真行, 齋藤雅恵, 竹田倫子, 浅野拓也, 明石祐史, 馬場剛, 石岡伸一, 遠藤俊明, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 60回 90 - 90 2012.09

Simultaneous presentation of tubal and primary abdominal pregnancies following clomiphene citrate treatment.

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Naoko Takenami, Ayumi Shimizu, Miyuki Morishita, Hiroyuki Honnma, Hideyuki Ikeda, Tsuyoshi Saito

Archives of gynecology and obstetrics 286 ( 2 ) 395 - 8 2012.08 [International journal]

Abdominal pregnancy is a rare condition that is potentially life-threatening for the mother. We present a case of simultaneous ectopic pregnancies (EPs) in the right fallopian tube and in the vesicouterine pouch. A 26-year-old woman had undergone prior ovulation induction with clomiphene citrate and human chorionic gonadotropin (hCG) at an outside hospital for unexplained infertility. The patient was referred to our hospital for a suspected ectopic pregnancy at 6 weeks gestation. Transvaginal ultrasonography detected a viable fetus at the anterior left side of the uterus; therefore, we suspected a left tubal pregnancy. However, laparoscopic surgery revealed that EPs were located in both the left vesicouterine pouch and in the right fallopian tube. Resection of the right salpinx and abdominal implant were performed. Histopathological examination confirmed the simultaneous presentation of a primary abdominal pregnancy and a right tubal pregnancy. After surgery, the patient's serum hCG level returned to normal. Concurrent EPs and abdominal pregnancy are very rare. However, it should be noted that reproductive technologies sometimes cause unusual clinical situations. A thorough abdominal inspection is needed.

Trophectoderm morphology significantly affects the rates of ongoing pregnancy and miscarriage in frozen-thawed single-blastocyst transfer cycle in vitro fertilization.

Hiroyuki Honnma, Tsuyoshi Baba, Masahiro Sasaki, Yoshiki Hashiba, Hiroshi Ohno, Takanori Fukunaga, Toshiaki Endo, Tsuyoshi Saito, Yoshimasa Asada

Fertility and sterility 98 ( 2 ) 361 - 7 2012.08 [International journal]

OBJECTIVE: To determine which parameter of blastocyst morphology is the most important predictor of ongoing pregnancy or miscarriage. DESIGN: Retrospective analysis. SETTING: One in vitro fertilization (IVF) center. PATIENT(S): Women who underwent a total of 1,087 frozen-thawed single-blastocyst transfer cycles. INTERVENTION(S): First IVF treatment with blastocysts after frozen-thawed cycle. MAIN OUTCOME MEASURE(S): Ongoing pregnancy and miscarriage rates as related to blastocyst morphology (blastocyst expansion, inner cell mass, and trophectoderm), and interaction tests in unadjusted logistic regression models to assess clinical factors affecting outcomes. RESULT(S): After adjustment for trophectoderm, inner cell mass, and age as confounders, trophectoderm was determined to be statistically significantly related to the rate of ongoing pregnancy. Trophectoderm was also statistically significantly related to the miscarriage rate. By contrast, neither inner cell mass nor blastocyst expansion was statistically significantly related. CONCLUSION(S): In frozen-thawed embryo transfer cycles, trophectoderm morphology is statistically significantly related to the rates of ongoing pregnancy and miscarriage after adjusting for confounders. Trophectoderm morphology may be the most important parameter when selecting a single blastocyst for transfer.

Different ovarian response by age in an anti-Müllerian hormone-matched group undergoing in vitro fertilization.

Hiroyuki Honnma, Tsuyoshi Baba, Masahiro Sasaki, Yoshiki Hashiba, Hisanori Oguri, Takanori Fukunaga, Toshiaki Endo, Yoshimasa Asada

Journal of assisted reproduction and genetics 29 ( 2 ) 117 - 25 2012.02 [International journal]

BACKGROUND: Recently, serum anti-Müllerian hormone (AMH) has been used as a good marker of ovarian response during in vitro fertilization (IVF). However, in the clinical setting, we felt that ovarian response was clearly different by age with the same AMH level. Then in this study we evaluated the relationship between serum AMH, age and parameters related to ovarian response and compared these parameters in regard to age within serum AMH-matched group. METHODS AND RESULTS: The relationship of these parameters were evaluated retrospectively in patients undergoing their first IVF cycle under a GnRH agonist flare up protocol (n = 456) between October 2008 and October 2010 in our clinic. To understand the relations between variables described above, principal component analysis (PCA) was performed. PCA revealed patients' age was at the different dimension from serum AMH and other variables. Therefore at first we segregated all patients into Low, Normal and High responder groups by their serum AMH using cut-off value of receiver operator characteristics curve analysis. Secondary, we divided each responder group into four subgroups according to patients' age. The high aged subgroups required a significantly higher dose of gonadotropin and a longer duration of stimulation; however, they had significantly lower peak E2 and a smaller number of total oocytes as well as M2 oocytes compared to the low aged subgroups. CONCLUSIONS: The influence of aging on the ovarian response was clearly seen in all groups; the ovarian response tended to decrease as patients' age increased with the same AMH level. Therefore serum AMH in combination with age is a better indicator than AMH alone.

Continuous follicle-stimulating hormone exposure from pituitary adenoma causes periodic follicle recruitment and atresia, which mimics ovarian hyperstimulation syndrome.

Mika Kanaya, Tsuyoshi Baba, Yoshimitsu Kitajima, Keiko Ikeda, Ayumi Shimizu, Miyuki Morishita, Hiroyuki Honnma, Toshiaki Endo, Tsuyoshi Saito

International journal of women's health 4 427 - 31 2012 [International journal]

CONTEXT: Follicle-stimulating hormone (FSH)-secreting pituitary adenoma is usually a nonfunctioning tumor, but in rare cases it may develop into ovarian hyperstimulation. Several reports have revealed that serum FSH levels are normal to slightly high in patients with combined FSH-secreting pituitary adenoma with ovarian hyperstimulation. This finding is different from iatrogenic ovarian hyperstimulation syndrome (OHSS), which is associated with extremely high levels of FSH. OBJECTIVE: To describe the clinical course of two patients who developed OHSS from FSH-secreting pituitary adenoma. RESULTS: Endocrine studies of the two cases revealed that FSH levels were normal or slightly increased, but luteinizing hormone levels were low to undetectable. Their estradiol (E2) levels were intriguing: levels fluctuated drastically over 6 weeks in Case 1, but stayed flat in Case 2. Ultrasonographic examinations showed bilaterally enlarged multicystic ovaries, and magnetic resonance imaging indicated pituitary tumors. Transsephenoidal resection of the tumors ameliorated the symptoms and pathological diagnosis revealed FSH-secreting pituitary adenomas. CONCLUSION: As is not the case in iatrogenic OHSS, even a small to moderate amount of FSH stimulation, which is continuously secreted by a pituitary adenoma, can cause ovarian hyperstimulation. Although FSH-secreting pituitary adenoma can cause ovarian hyperstimulation, an extremely high amount of E2 biosynthesis from granulosa cells seldom occurs.

A Remarkably Easy Knot-Tying Technique for Single-Incision Laparoscopic Surgery with the SILS Port for Gynecologic Diseases

Toshiaki Endo, Kunihiko Nagasawa, Kota Umemura, Tsuyoshi Baba, Hirofumi Henmi, Tsuyoshi Saito

JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY ( ELSEVIER SCIENCE INC ) 18 ( 4 ) 500 - 502 2011.07 [Refereed] [International journal]

Single-incision laparoscopic surgery (SILS) has been quickly accepted, especially for women, because the cosmetic benefits may be greater than with ordinary laparoscopic surgery. In gynecologic disease, SILS is appropriate for diagnostic laparoscopy, oophorectomy, and salpingectomy, among other conditions. In addition, the knot-tying process for intracorporeal suturing during SILS is a major rate-limiting step and a key determinant of the popularity of SILS. Although a roticulator instrument is useful for creating the needed operative angle, knot tying is still believed to be difficult. We have devised a remarkably simple knot-tying technique that can be applied during SILS with a SILS Port with a Roticulator and a straight-type needle driver. We determined that, after transfixing the needle, the long tail of the thread should be grasped at around 90 degrees relative to the long axis of tip of the Roticulator, which is articulated at 80 degrees. This automatically forms an ideal C-loop because of gravitation. The needle attached to the long tail should face the distal side from the tip of Roticulator (from the surgeon's perspective). The apex of the C-loop is then toward the proximal side from the tip of the Roticulator (from the perspective of the surgeon). This thread position is important during the knot-tying process. The upper arm of the C-loop should then be entwined by applying a series of axial spinning movements to the rod of the needle driver. At this time, the jaws of the needle driver should be kept open so the thread does not slip off of the rod. The benefit of this technique is that it does not require any special skills; any surgeon able to perform intracorporeal suturing should also be able to easily tie knots during SILS. Journal of Minimally Invasive Gynecology (2011) 18, 500-502 (C) 2011 AAGL. All rights reserved.

Distinctive features of female-to-male transsexualism and prevalence of gender identity disorder in Japan.

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Ayumi Shimizu, Hiroyuki Honnma, Hiroshi Ikeda, Naoya Masumori, Tousei Ohmura, Tamotsu Kiya, Takashi Fujimoto, Motoiki Koizumi, Tsuyoshi Saito

The journal of sexual medicine 8 ( 6 ) 1686 - 93 2011.06 [International journal]

INTRODUCTION: The prevalence of transsexualism is thought to differ among socio-geographic backgrounds, and little is known about its prevalence in Japan. Polycystic ovary syndrome (PCOS), which is known to be associated with insulin resistance and metabolic syndrome, is often seen in female-to-male (FTM) transsexual patients. Consequently, detection of PCOS is an important part of health care for these individuals. AIM: The purpose of this study was to assess the prevalence of transsexuality in Japan, as well as the incidences of PCOS and insulin resistance among Japanese FTM transsexual patients. METHODS: One hundred four male-to-female (MTF) and 238 FTM Japanese transsexual patients were studied. Medical histories, including histories of menstrual cycling and hormone treatment, were taken. To exclude other diseases, such as congenital adrenal hyperplasia and hormone-secreting tumors, thorough medical assessments, including transvaginal or transrectal ultrasonography and measurement of serum hormone levels and insulin resistance indexes, were performed. MAIN OUTCOME MEASURES: The diagnosis of PCOS was based on the Rotterdam 2003 criteria. RESULTS: Based on demographic statistics, the prevalences of MTF and FTM transsexuality are about 3.97 and 8.20 per 100,000 people, respectively, making the MTF-to-FTM ratio about 1:2. Of the FTM transsexual patients studied, 128 had not taken hormones before their initial assessment (untreated group); the remaining 50 self-administered androgen. Among the untreated group, 32.0% were diagnosed with PCOS, 30.1% were insulin-resistant, and 31.1% showed hypoadiponectinemia. CONCLUSIONS: The sex ratio among Japanese transsexuals is different than among Caucasians. PCOS and insulin resistance are common findings in FTM transsexual patients at initial presentation.

Changes of uterine blood flow after vaginal radical trachelectomy (VRT) in patients with early-stage uterine invasive cervical cancer.

Kota Umemura, Shin-ichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Yoshiaki Ezaka, Kunihiko Nagasawa, Madoka Takahashi, Masahito Mizuuchi, Nanako Iwami, Hidefumi Adachi, Noriko Takeda, Mitsuharu Tamagawa, Tsuyoshi Saito

International journal of medical sciences 7 ( 5 ) 260 - 6 2010.08 [International journal]

BACKGROUND: Vaginal radical trachectomy (RT) ligates and cuts several arteries supplying the uterus. Changes of blood supply to the uterus in two patients who experienced pregnancy and delivery were studied by using 3-D CT scanning. Effects of changes of blood supply to the uterus on the pregnancy courses were also examined. METHODS: Vascular distribution in the uterus was studied in two patients who received vaginal RT after delivery. Effects of changes of vascular distribution after vaginal RT were studied with respect to pregnancy courses and cervical functions. RESULTS: New arterial vascularization from the ascending branches of uterine arteries or other arteries occurred, and these new vessels seemed to supply blood to the remaining cervix. Differences of fetal growth and histopathological changes in the placenta between the two patients could not be detected. CONCLUSION: Ligation and cutting of several supplying arteries by RT induces new arterial vascularization and it does not seem to affect fetal growth and placental function.

Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats.

Hiroyuki Honnma, Toshiaki Endo, Tamotsu Kiya, Ayumi Shimizu, Kunihiko Nagasawa, Tsuyoshi Baba, Takashi Fujimoto, Hirofumi Henmi, Yoshimitsu Kitajima, Kengo Manase, Shinichi Ishioka, Eiki Ito, Tsuyoshi Saito

Reproductive biology and endocrinology : RB&E 8 73 - 73 2010.06 [International journal]

BACKGROUND: Zucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance. METHODS: In this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7). RESULTS: Ovaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats. CONCLUSIONS: Our findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats.

Spontaneous ovarian hyperstimulation syndrome and pituitary adenoma: incidental pregnancy triggers a catastrophic event.

Tsuyoshi Baba, Toshiaki Endo, Yoshimitsu Kitajima, Hirofumi Kamiya, Osamu Moriwaka, Tsuyoshi Saito

Fertility and sterility 92 ( 1 ) 390.e1-3 2009.07 [International journal]

OBJECTIVE: To report a rare case of spontaneous ovarian hyperstimulation syndrome (OHSS) associated with spontaneous pregnancy and a FSH-secreting pituitary adenoma. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 32-year-old woman with spontaneous OHSS. INTERVENTION(S): Transsphenoidal resection of the tumor. MAIN OUTCOME MEASURE(S): Regression of the symptoms of OHSS and hyperestrogenemia. RESULT(S): At presentation, the patient's ovaries were markedly enlarged and massive ascites was seen. Her serum E(2) level was markedly elevated, but her LH level was low, and FSH was within the normal range. In addition, her TSH level was normal, and hCG was appropriate for the date of pregnancy. Subsequently, the patient developed massive thrombophlebitis in her right internal jugular and subclavian veins. Termination of the pregnancy ameliorated the accumulation of ascites, but ovarian enlargement and hyperestrogenemia persisted. No mutations of the FSH receptor, LH receptor, or aromatase genes were detected, but magnetic resonance imaging (MRI) of the head revealed a pituitary adenoma. After transsphenoidal resection of the tumor, the patient got better. CONCLUSION(S): A gonadotropin-secreting adenoma caused ovarian hyperstimulation (ovarian enlargement and hyperestrogenemia). In addition, spontaneous pregnancy and intrinsic hCG increased vascular permeability, which complicated the patient's disease.

The contributions of resistin and adiponectin gene single nucleotide polymorphisms to the genetic risk for polycystic ovary syndrome in a Japanese population

Tsuyoshi Baba, Toshiaki Endo, Fumihiro Sata, Kunihiko Nagasawa, Hiroyuki Honnma, Yoshimitsu Kitajima, Takuhiro Hayashi, Kengo Manase, Mika Kanaya, Osamu Moriwaka, Hirofumi Kamiya, Hideto Yamada, Hisanori Minakami, Reiko Kishi, Tsuyoshi Saito

GYNECOLOGICAL ENDOCRINOLOGY ( INFORMA HEALTHCARE ) 25 ( 8 ) 498 - 503 2009 [Refereed] [International journal]

Polycystic ovary syndrome (PCOS) is a heterogeneous group of disorders that occur fairly commonly in women of reproductive age and are characterized by a variety of clinical manifestations, including insulin resistance that is independent of obesity. Recent studies suggest that altered adipocytokine gene expression is closely associated with insulin resistance and that single nucleotide polymorphisms (SNPs) modulate the expression and/or function of these genes, thereby affecting insulin sensitivity. With that in mind, we investigated whether SNPs at position 7420 of the resistin gene (RETN) and/or 711377 of the adiponectin gene (ADIPOQ) modulate the susceptibility to PCOS. We evaluated the genotypes of 117 women with PCOS and 380 healthy fertile controls and measured the index of insulin resistance and hormonal profiles in the PCOS women. The RETN 7420G/G homozygous variant genotype occurred significantly more frequently among the PCOS group than among the control group (15.4% vs. 8.4%, p = 0.035). PCOS women with the RETN 7420G/ G genotype also showed significantly higher BMIs and greater insulin resistance than those with RETN 7420 C/C or C/G genotypes. The ADIPOQ SNP at 711377 showed no association with PCOS. We conclude that the RETN G/G at 7420 genotype is associated with PCOS in Japanese women.

Advanced epithelial ovarian carcinoma during pregnancy.

Shin-ichi Ishioka, Takuhiro Hayashi, Toshiaki Endo, Tsuyoshi Baba, Hiroyuki Honma, Tsuyoshi Saito

International journal of clinical oncology 12 ( 5 ) 375 - 8 2007.10 [Domestic journal]

We report a rare case of advanced ovarian mucinous adenocarcinoma in a pregnant woman. A 28-year-old pregnant Japanese woman was diagnosed with an ovarian tumor 8 cm in diameter at a local hospital. She was sent to a private hospital at 25 weeks of gestation because of the growing ovarian tumor. Advanced ovarian carcinoma with widespread intraabdominal dissemination was detected by laparotomy at the hospital and she was referred to our hospital for further management. At 27 weeks of gestation, she underwent cesarean section, followed by abdominal total hysterectomy, and bilateral salpingo-oophorectomy. A girl weighing 879 g was delivered, with Apgar scores of 4 and 6 at 1 and 5 min, respectively. The pathological diagnosis of the tumor was mucinous cystadenocarcinoma grade 2. Although chemotherapy was not effective for her and she died of the disease 4 months after the surgery, her baby grew well and weighed 3750 g 3 months after delivery. For the treatment of such patients, we believe we should choose operative therapy as early as possible after the maturation of the fetus, although there are several reports of successful treatment with the administration of chemotherapy during pregnancy. To determine a better approach for such patients, multidisciplinary staff meetings, including gynecological oncologists, obstetricians, neonatologists, psychologists, and the patient are important.

Polycystic ovary syndrome is associated with genetic polymorphism in the insulin signaling gene IRS-1 but not ENPP1 in a Japanese population.

Tsuyoshi Baba, Toshiaki Endo, Fumihiro Sata, Hiroyuki Honnma, Yoshimitsu Kitajima, Takuhiro Hayashi, Kengo Manase, Mika Kanaya, Hideto Yamada, Hisanori Minakami, Reiko Kishi, Tsuyoshi Saito

Life sciences 81 ( 10 ) 850 - 4 2007.08 [International journal]

Recent studies indicate that insulin resistance resulting from altered post-receptor signaling is associated with polycystic ovary syndrome (PCOS). We hypothesized that insulin receptor substrate-1 (IRS-1) Gly972Arg polymorphism and/or ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Lys121Gln polymorphism predisposes women to PCOS and that these polymorphisms also affect anthropometric variables, glucose metabolism and androgen synthesis. To test those ideas, we studied the genotypes, indexes of insulin resistance, and hormone profiles in 123 Japanese women with PCOS and 380 healthy Japanese controls. We found that there were significantly more IRS-1 972Arg carriers among the PCOS patients than among the healthy controls (10.6% vs. 4.8%, p=0.029), which is consistent with our finding that women carrying the IRS-1 972Arg allele had a significantly increased risk of developing PCOS (odds ratio: 3.31, 95% confidence interval: 1.49-7.35). By contrast, the ENPP1 Lys121Arg polymorphism was distributed equally among PCOS patients and controls. In addition, neither of these polymorphisms studied affected the anthropometric variables, metabolic parameters or androgen levels of women with PCOS. We conclude that the IRS-1 Gly972Arg polymorphism is associated with PCOS in the Japanese population.

Association between polycystic ovary syndrome and female-to-male transsexuality.

Tsuyoshi Baba, Toshiaki Endo, Hiroyuki Honnma, Yoshimitsu Kitajima, Takuhiro Hayashi, Hiroshi Ikeda, Naoya Masumori, Hirofumi Kamiya, Osamu Moriwaka, Tsuyoshi Saito

Human reproduction (Oxford, England) 22 ( 4 ) 1011 - 6 2007.04 [International journal]

BACKGROUND: The aim of this study is to understand the relationship between polycystic ovary syndrome (PCOS), altered hormonal characteristics and insulin resistance in female-to-male (FTM) transsexual patients. METHODS: We studied 69 Japanese FTM cases, aged 17-47 years, who were seen in the Gender Identity Disorder Clinic of Sapporo Medical University Hospital between December 2003 and May 2006. The subjects had never received hormonal treatment or sex re-assignment surgery. Prior to treatment, they received physical examinations entailing measurement of anthropometric, metabolic and endocrine parameters, after which we compared the values obtained according to the presence or absence of PCOS and/or obesity. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Of the 69 participating FTM cases, 40 (58.0%) were found to have PCOS. Of the 49 for whom HOMA-IR was calculated, 15 (30.6%) also showed insulin resistance, whereas of the 59 for whom adiponectin was measured, 18 (30.5%) showed hypoadiponectinaemia. Of 69 for whom androgens were measured, 29 (39.1%) showed hyperandrogenaemia. Insulin resistance was associated with obesity but not with PCOS. In contrast, hyperandrogenaemia was associated with both PCOS and obesity. CONCLUSION: FTM transsexual patients have a high prevalence of PCOS and hyperandrogenaemia.

Significance of matrix metalloproteinases in the pathophysiology of the ovary and uterus.

Toshiaki Endo, Tamotsu Kiya, Taeko Goto, Hirofumi Henmi, Kengo Manase, Hiroyuki Honnma, Tsuyoshi Baba, Shinichi Ishioka, Takuhiro Hayashi, Manabu Chida, Kazuyo Arima, Kiyohiro Yamazaki, Mika Kanaya, Atsushi Azumaguchi, Osamu Moriwaka, Hirofumi Kamiya, Tsuyoshi Saito

Reproductive medicine and biology 5 ( 4 ) 235 - 243 2006.12 [Domestic journal]

Matrix metalloproteinases (MMP) are capable of degrading a variety of extracellular matrix (ECM) proteins and are also involved in the processing of a number of bioactive molecules. Our findings indicate that the functions of MMP in the ovary and uterus are organ-specific and time-dependently vary during the reproductive cycle. Prolactin induces structural luteolysis indicated by loss of luteal weight, protein and DNA within 36 h after pretreatment with ergot alkaloid. MMP activation appears crucial for the selective depletion of protein during luteal involution, which entails loss of ECM accompanied by apoptosis. During GnRHagonist-induced luteolysis, this response was also associated with marked increases in MMP-2, which degraded collagen type IV, and MT1-MMP, which in addition to activating MMP-2 also degrades collagen type I, III and V. We also found that the level of MT1-MMP and MMP-2 expression in the human CL is greater during the late luteal phase than during either the early mid luteal phases or during gestation, respectively. That dehydroepiandrosterone (DHEA) treatment caused the formation of cysts from antral follicles in the ovaries of immature rats while depressing MMP-2 collagenolytic activity and enhancing lysyl oxidase expression highlights the importance of collagen degradation in the process of ovulation and suggests that changes in the activities of these enzymes play a key role in ovarian cystogenesis in polycystic ovary syndrome patients. Furthermore, immunohistochemical analyses showed that MT1-MMP and FasL co-localize with TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive apoptotic granulosa cells in rats treated with DHEA, that the Fas/FasL/Caspase-8 (death receptor-dependent) pathway is pivotal for follicular atresia and that increased levels of MT1-MMP likely play an important role in tissue remodeling during follicular atresia. After parturition, the uterus undergoes involution, a conspicuous feature characterized by a rapid reduction in the collagen content mediated by degradation of extracellular collagen bundles. Our findings strongly suggest that MT1-MMP, MMP-2 and MMP-9 are each time-dependently regulated and play important roles in tissue remodeling during postpartum uterine involution. (Reprod Med Biol 2006; 5: 235-243).

Altered expression of Fas/Fas ligand/caspase 8 and membrane type 1-matrix metalloproteinase in atretic follicles within dehydroepiandrosterone-induced polycystic ovaries in rats.

Hiroyuki Honnma, Toshiaki Endo, Hirofumi Henmi, Kunihiko Nagasawa, Tsuyoshi Baba, Kiyohiro Yamazaki, Yoshimitsu Kitajima, Takuhiro Hayashi, Kengo Manase, Tsuyoshi Saito

Apoptosis : an international journal on programmed cell death 11 ( 9 ) 1525 - 33 2006.09 [International journal]

One of the characteristics of polycystic ovary syndrome (PCOS) is the presence of cystic follicles in various stages of growth and atresia, the latter of which is known to be the result of apoptosis and tissue remodeling. To further investigate the process of follicular atresia, we compared ovarian expression and localization of Fas, Fas ligand (FasL), casapse-8 and membrane-type1 matrix metalloproteinase (MT1-MMP) in rats treated with dehydroepiandrosterone (DHEA) as a model of PCOS, and in control rats. We found that the numbers of TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive follicles were significantly higher in ovaries from PCOS rats than in those from control rats (P < 0.05), as were ovarian levels of FasL mRNA and protein, processed caspase-8 protein and MT1-MMP mRNA. Correspondingly, we also observed an increase in the level of MTI-MMP catalytic activity and a decrease in the level of pro-caspase-8 protein. In addition, immunohistochemical analyses showed that MT1-MMP and FasL co-localize with TUNEL-positive apoptotic granulosa cells within atretic follicles of PCOS ovaries. Our results suggest that under the PCOS-like conditions induced by DHEA, the Fas/FasL/Caspase-8 (death receptor dependent) pathway is pivotal for follicular atresia, and that increased levels of MT1-MMP likely play an important role in tissue remodeling during structural luteolysis.

Hyperstimulation and a gonadotropin-releasing hormone agonist modulate ovarian vascular permeability by altering expression of the tight junction protein claudin-5.

Yoshimitsu Kitajima, Toshiaki Endo, Kunihiko Nagasawa, Kengo Manase, Hiroyuki Honnma, Tsuyoshi Baba, Takuhiro Hayashi, Hideki Chiba, Norimasa Sawada, Tsuyoshi Saito

Endocrinology 147 ( 2 ) 694 - 9 2006.02 [International journal]

We investigated the mechanism by which a GnRH agonist (GnRHa) affects ovarian vascularity, vascular permeability, and expression of the tight junction protein claudin-5 in a rat model of ovarian hyperstimulation syndrome (OHSS). Hyperstimulated rats received excessive doses of pregnant mare serum gonadotropin (PMSG; 50 IU/d) for 4 consecutive days, from d 25 to 28 of life, followed by 25 IU human chorionic gonadotropin (hCG) on d 29. Control rats received 10 IU PMSG on d 27 of life, followed by 10 IU hCG on d 29. GnRHa (leuprolide 100 microg/kg.d) was administered to some hyperstimulated rats either on d 29 and 30 (short-term GnRHa treatment) or from d 25 to 30 (long-term GnRHa treatment). Ovarian vascular density (vessels per 10 mm(2)) and vessel endothelial area (percent) were assessed by immunohistochemical analysis of the distribution of von Willebrand factor, whereas vascular permeability was evaluated based on leakage of Evans blue. High doses of PMSG and hCG significantly increased ovarian weight, vascular permeability, vascular density, and the vessel endothelial area and significantly reduced expression of claudin-5 protein and mRNA. All of these effects were significantly and dose-dependently inhibited by administration of GnRHa. This suggests that reduced expression of claudin-5 plays a crucial role in the increased ovarian vascular permeability seen in OHSS and that its expression can be modulated by GnRHa treatment. Indeed, preventing redistribution of tight junction proteins in endothelial cells and the resultant loss of endothelial barrier architecture might be the key to protecting patients against massive extravascular fluid accumulation in cases of OHSS.

17th Symposium on Gynecology and Colposcopy July 15-16, 1998, Osaka, Japan. Characterization of subclonal cell lines showing high motility derived from an undifferentiated human endometrial cancer cell line

Motoiki Koizumi, Eiki Ito, Satoko Yamashita, Tsuyoshi Baba, Ikuhito Yamanaka, Takahiro Suzuki, Ryuichi Kudo

Gynecologic and Obstetric Investigation 48 ( 3 ) 206 - 210 1999

To examine the relationship between the morphology and the motility of cancer cells, we studied the difference between human endometrial undifferentiated cancer cell lines with different motilities, using light and electron microscopy, immunocytochemistry and RT-PCR. In a transplanted tumor of a cell line with high motility, many connective tissues and microvessels were observed and there were few intercellular spaces, which were ultrastructurally full of extracellular matrix. In the high-motility cell line only cytokeratin 19 was observed, and the level of cytokeratin 19 mRNA was elevated. Thus, motility is suggested to be related to the induction of connective tissues and cytoskeleton.

Cloning and characterization of a cDNA fragment coding β-casein-like protein preferentially expressed in cervical adenocarcinoma cell line CAC-1

Takahiro Suzuki, Motoiki Koizumi, Tsuyoshi Baba, Ryuichi Kudo

Cancer Letters ( Elsevier Ireland Ltd ) 124 ( 2 ) 165 - 171 1998.02

We generated new murine monoclonal antibodies against bovine β-casein. One of eight new monoclonal antibodies generated, 12G2, specifically reacted not only with β-casein, but also with human cervical adenocarcinoma cell line CAC-1. To identify the gene encoding the putative protein (BCLP) defined by monoclonal antibody (mAb) 12G2, a complementary DNA library was constructed. We obtained the inserted cDNA fragment that showed high homology to reported DNA sequences of unknown function in normal human placenta. We think that BCLP was overexpressed or changed its structure by carcinogenesis.

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