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乳牛の黄体血流量に基づく新規受胚牛選定法と超早期妊娠診断法に関する研究

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Title

乳牛の黄体血流量に基づく新規受胚牛選定法と超早期妊娠

診断法に関する研究( 本文(Fulltext) )

Author(s)

金澤, 朋美

Report No.(Doctoral

Degree)

博士(獣医学) 甲第485号

Issue Date

2017-03-13

Type

博士論文

Version

ETD

URL

http://hdl.handle.net/20.500.12099/56199

※この資料の著作権は、各資料の著者・学協会・出版社等に帰属します。

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ங∵ࡢ㯤య⾑ὶ㔞࡟ᇶ࡙ࡃ

᪂つཷ⬇∵㑅ᐃἲ࡜㉸᪩ᮇዷፎデ᩿ἲ࡟㛵ࡍࡿ◊✲

2016 ᖺ

ᒱ㜧኱Ꮫ኱Ꮫ㝔㐃ྜ⋇་Ꮫ◊✲⛉

㸦ᒾᡭ኱Ꮫ㸧

㔠⃝ ᭸⨾

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┠ḟ ⥴ゝ 1 ➨1❶ ࣍ࣝࢫࢱ࢖ࣥ✀ཷ⬇∵࡟࠾ࡅࡿ⬇⛣᳜㸦ET㸧᫬ࡢ㯤య⾑ὶ㔞ࢆ⏝࠸ࡓཷ⬇∵ 㑅ᐃ 1-1. ᗎㄽ 6 1-2. ヨ㦂 1㸸ET ᫬ࡢ㯤య⾑ὶ㠃✚㸦BFA㸧ࢆ⏝࠸ࡓཷ⬇∵㑅ᐃ᪉ἲࡢ᳨ウ 7 1) ᮦᩱཬࡧ᪉ἲ 7 2) ⤖ᯝ 13 1-3. ヨ㦂 2㸸ET ᫬ࡢ BFA ࢆ⏝࠸ࡓཷ⬇∵㑅ᐃ᪉ἲࡢ෌⌧ᛶࡢ᳨ド 15 1) ᮦᩱཬࡧ᪉ἲ 15 2) ⤖ᯝ 17 1-4. ⪃ᐹ 18 1-5. ᑠᣓ 21 ᅗ⾲ 22 ➨2 ❶ ࣍ࣝࢫࢱ࢖ࣥ✀ཷ⬇∵࡟࠾ࡅࡿ ET ᚋࡢ㯤య⾑ὶ㔞ࢆ⏝࠸ࡓ㉸᪩ᮇዷፎデ᩿ 2-1. ᗎㄽ 39

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2-4. ⪃ᐹ 43 2-5. ᑠᣓ 46 ᅗ⾲ 47 ➨3 ❶ ᛶ⭢่⃭࣍ࣝࣔࣥᨺฟ࣍ࣝࣔࣥ㸦GnRH㸧〇๣ᢞ୚࡟ࡼࡿ㯤య⾑ὶ㔞࡜㉸᪩ ᮇዷፎデ᩿⢭ᗘ࡬ࡢᙳ㡪 3-1. ᗎㄽ 54 3-2. ᮦᩱཬࡧ᪉ἲ 55 3-3. ⤖ᯝ 58 3-4. ⪃ᐹ 60 3-5. ᑠᣓ 64 ᅗ⾲ 65 ➨4 ❶ ⥲ᣓ 81 ㅰ㎡ 88 ཧ⪃ᩥ⊩ 89

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␎ㄒ⾲ P4 㸸 Progesterone 㸦ࣉࣟࢪ࢙ࢫࢸࣟࣥ㸧 E2 㸸 Estradiol-17ș 㸦࢚ࢫࢺࣛࢪ࣮࢜ࣝ㸧 CL 㸸 Corpus luteum 㸦㯤య㸧 DF 㸸 Dominant follicle 㸦୺ᖍ༸⬊㸧 GnRH 㸸 Gonadotropin-releasing hormone㸦ᛶ⭢่⃭࣍ࣝࣔࣥᨺฟ࣍ࣝࣔࣥ㸧 hCG   㸸 Human chorionic gonadotropin㸦ࣄࢺ⤧ẟᛶᛶ⭢่⃭࣍ࣝࣔࣥ㸧 FSH 㸸 Follicle stimulating hormone㸦༸⬊่⃭࣍ࣝࣔࣥ㸧

LH 㸸 Luteinizing hormone㸦㯤యᙧᡂ࣍ࣝࣔࣥ㸧 BFA 㸸 Blood flow area㸦⾑ὶ㠃✚㸧

TAMV 㸸 Time-averaged maximum velocity㸦᫬㛫ᖹᆒ᭱኱⾑ὶ㏿ᗘ㸧 VEGF  㸸 Vascular endothelial growth factor㸦⾑⟶ෆ⓶⣽⬊ቑṪᅉᏊ㸧

FGF 㸸 Basic fibroblast growth factor㸦⥺⥔ⱆ⣽⬊ቑṪᅉᏊ㸧

BCS 㸸 Body condition scores㸦࣎ࢹ࢕࣮ࢥࣥࢹ࢕ࢩࣙࣥࢫࢥ࢔㸧 ET   㸸 Embryo transfer㸦⬇⛣᳜㸧

AI 㸸 Artificial insemination㸦ேᕤᤵ⢭㸧

EIA 㸸 Enzyme immune assay㸦㓝⣲ච␿ ᐃἲ㸧

HRP 㸸 ࣌ࣝ࢜࢟ࢩࢲ࣮ࢮ

OPD 㸸 ࢜ࣝࢯࣇ࢙ࢽࣞࣥࢪ࢔࣑ࣥ

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⥴ゝ ࢘ࢩࡣྂࡃ࠿ࡽୡ⏺୰࡛㣗⏝ࡸ㎰⪔࡟⏝࠸ࡽࢀ㸪2013 ᖺࡢᅜ㝿㐃ྜ㣗⣊㎰ᴗᶵ 㛵㸦FAO㸧ࡢ⤫ィ࡛ࡣ㸪ୡ⏺࡛ 14 ൨ 6800 ୓㢌ࡀ㣫㣴ࡉࢀ࡚࠸ࡿࠋ᪥ᮏ࡛ࡣ㸪ᘺ⏕ ᫬௦࠿ࡽ✄సࡀᗈࡲࡾ㸪ࡑࢀ࡜࡜ࡶ࡟⏣⏿ࢆ⪔ࡍ㝿ࡢ㈗㔜࡞ປാຊ࡜ࡋ࡚࢘ࢩࡀ㔜 ⏝ࡉࢀࡓࠋ᫂἞᫬௦௨㝆㸪㣗⫗ᩥ໬ࡢᬑཬ㸪ᐃ╔࡟క࠸㸪㣫㣴㢌ᩘࡀቑຍࡋ㸪2015 ᖺࡢ㎰ᯘỈ⏘┬ࡢ⤫ィ࡟ࡼࢀࡤ㸪ங⏝∵137 ୓㢌㸪⫗⏝∵ 249 ୓㢌ࡀ᪥ᮏ࡛㣫㣴ࡉ ࢀ࡚࠸ࡿࠋ୺࡟㸪ங⏝∵࡜ࡋ࡚࣍ࣝࢫࢱ࢖ࣥ✀∵㸪⫗⏝∵࡜ࡋ࡚㯮ẟ࿴✀∵ࡀ㣫㣴 ࡉࢀ㸪⏕ங㸪ங〇ရ࡜⫗ࡀ⏕⏘ࡉࢀ࡚࠸ࡿࠋ⌧௦࡛ࡣ㸪㣗⣊࡟ຍ࠼㸪∵⓶ࡀ⾰ᩱ࡜ ࡋ࡚㸪⣅ᒀࡀሁ⫧⫧ᩱࡢཎᩱ࡜ࡋ࡚฼⏝ࡉࢀ㸪࢘ࢩࡣࣄࢺࡢ⏕ά࡟ࡣḞࡃࡇ࡜ࡢ࡛ ࡁ࡞࠸㔜せ࡞ᐙ␆࡛࠶ࡿࠋ ⫗⏝∵⦾Ṫ㎰ᐙ࡛ࡣ㸪㞤∵ࢆዷፎ㸪ศፔࡉࡏ㸪ࡑࡢᏊ∵ࢆᏊ∵ᕷሙ࡛㈍኎ࡍࡿࠋ ⫗⏝∵⫧⫱㎰ᐙ࡛ࡣ㉎ධࡋࡓ⫧⫱⣲∵ࢆ2 ᖺ㛫㣫⫱ᚋฟⲴࡋ㸪⫗ࢆ㈍኎ࡍࡿࡇ࡜࡛ ཰┈ࢆᚓ࡚࠸ࡿࠋࡲࡓ㸪㓗㎰ᐙ࡟࠾࠸࡚ࡶ㸪ங⏝∵ࡀศፔࡍࡿࡇ࡜࡛ึࡵ࡚⏕ஙࢆ ᦢࡿࡇ࡜ࡀ࡛ࡁ㸪⏕ங࡜⏕ࡲࢀࡓᏊ∵ࢆ㈍኎ࡍࡿࡇ࡜࡛཰┈ࢆᚓ࡚࠸ࡿࠋࡘࡲࡾ㸪 ⫗ࡸ⏕ஙࡢ⏕⏘ࡢࡓࡵ࡟ࡣ㸪㞤∵ࡀዷፎ㸪ศፔࡍࡿࡇ࡜ࡀᚲせ࡛࠶ࡾ㸪㞤∵ࡀຠ⋡ Ⰻࡃዷፎ㸪ศፔࢆ⧞ࡾ㏉ࡋ㸪1 ᖺ 1 ⏘ࢆᐇ⌧ࡍࡿࡇ࡜ࡀ⤒Ⴀୖ㔜せ࡜࡞ࡿࠋ᪥ᮏ࡟ ࠾࠸࡚ࡣ㸪1950 ᖺ࡟ᐙ␆ᨵⰋቑṪἲࡀไᐃࡉࢀ㸪ேᕤᤵ⢭㸦AI㸧ᬑཬࡢᇶ♏ࡀ☜❧ ࡋ㸪⌧ᅾ࡛ࡣ࡯࡜ࢇ࡝ࡢங⏝∵࠾ࡼࡧ⫗⏝∵ࡀ AI ࡟ࡼࡗ࡚⏕⏘ࡉࢀ࡚࠸ࡿ㸦34㸧ࠋ ࡋ࠿ࡋ࡞ࡀࡽ㸪㏆ᖺ㸪᪥ᮏࡢࡳ࡞ࡽࡎୡ⏺ྛᆅ࡛ AI ࡢཷ⫾⋡ࡀᖺࠎపୗࡋ㸦42㸪 44㸧㸪⫗⏝∵㎰ᐙ࡜㓗㎰ᐙࡢ⤒῭ⓗ࡞ᦆኻ࡟⧅ࡀࡗ࡚࠸ࡿ㸦32㸧ࠋཷ⫾⋡ࡢపୗࡢཎ

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ࡀஹ㐍ࡋ㸦92㸪98㸧㸪Ⓨ᝟඙ೃࡀᚤᙅ໬㸪⾑୰ࣉࣟࢪ࢙ࢫࢸࣟࣥ㸦P4㸧⃰ᗘࡀῶᑡࡋ ࡚ཷ⫾⋡ࡢపୗࡀᘬࡁ㉳ࡇࡉࢀ࡚࠸ࡿ࡜⪃࠼ࡽࢀ࡚࠸ࡿ㸦42, 44㸧ࠋ ዷፎࡢᡂ❧࡜⥔ᣢ࡟㔜せ࡞ᙺ๭ࢆᯝࡓࡋ࡚࠸ࡿ P4 ࡣ㸪ࣄࢺࢆࡣࡌࡵ࡜ࡋࡓከࡃ ࡢ့ங㢮࡟ᗈࡃᏑᅾࡋ㸪୺࡟༸ᕢࡢ㯤య࠿ࡽศἪࡉࢀࡿࠋ࢘ࢩ࡟࠾࠸࡚㸪ዷፎࡢᡂ ❧࡜⥅⥆࡟ࡣ㸪ᶵ⬟ⓗ࡞㯤యࡀᏑᅾࡋP4ࡀ⥔ᣢࡉࢀࡿࡇ࡜ࡀᚲせ࡛࠶ࡿ㸦45㸪57㸪 60㸧ࠋᐇ㝿㸪࢘ࢩ࡛ࡣ P4ࡢ⏕⏘ẕᆅ࡛࠶ࡿ㯤యࢆྵࡴ༸ᕢࢆዷፎ᪩ᮇ࡟㝖ཤࡍࡿ࡜ ዷፎࡀ⥅⥆࡛ࡁ࡞࠸㸦88㸧ࠋࡑࡢࡓࡵ㸪㯤యᶵ⬟ࡢ㞀ᐖ࡜ࡑࢀ࡟క࠺Ꮚᐑෆ P4 ⃰ᗘ ࡢపୗࡶཷ⫾⋡ࡢపୗࡢཎᅉࡢ1 ࡘ࡜ࡋ࡚⪃࠼ࡽࢀ࡚࠸ࡿ㸦46㸧ࠋP4ࢆ⏘⏕ࡍࡿ㯤 యࡣ㸪⏕యෆ࡟࠾࠸࡚᭱ࡶ⾑⟶࡟ᐩࢇࡔ⤌⧊ࡢ 1 ࡘ࡛࠶ࡾ㸦97㸧㸪༸ᕢື⬦࠿ࡽศ ᒱࡍࡿࡽࡏࢇື⬦ࡀ㯤యࢆྲྀࡾᅖࡴࡼ࠺࡟⾑⟶⥙ࢆⓎ㐩ࡉ࡚࠸ࡿ㸦40㸪100㸧ࠋ᤼༸ ᚋෆ༸⬊⭷࠿ࡽⓎ㐩ࡋࡓ⾑⟶ࡀ᤼༸❐࡬࡜౵ධࡋ࡚⾑⟶⥙ࢆᵓ⠏ࡋ㸪㯤య⣽⬊࡬⾑ ᾮࢆ౪⤥ࡍࡿࠋࡇࡢ⾑⟶᪂⏕ࡣ㸪㯤య⣽⬊࡛P4ࢆ⏕ྜᡂࡍࡿࡓࡵ࡟ᚲせ࡞ᇶ㉁ࡢ㍺ ㏦࡜P4ࢆ඲㌟ᚠ⎔࡬㐠ᦙࡍࡿࡓࡵ࡟ᚲせ࡛࠶ࡿ㸦11㸧ࠋᚑࡗ࡚㸪㯤యࡢ⾑⟶ᙧᡂࡣ ࢘ࢩࡢዷፎᡂ❧࡜⥔ᣢ࡟ᚲせ୙ྍḞ࡛࠶ࡾ㸪⾑⟶ᙧᡂࡢከᐻࡀ㯤యᶵ⬟ࡢ⥔ᣢ㸪ዷ ፎࡢᡂྰ࡟㛵୚ࡋ࡚࠸ࡿ࡜⪃࠼ࡽࢀࡿࠋ ࢘ࢩࡢ⏕⏘ᛶࢆࡼࡾྥୖࡉࡏࡿ┠ⓗ࡛㸪1970 ᖺ௦ᚋ༙࠿ࡽ⬇⛣᳜㸦ET㸧ᢏ⾡ࡀ ᛴ㏿࡟ᐇ⏝໬ࡉࢀࡓ㸦85㸧ࠋ㏆ᖺ࡛ࡣ㸪㑇ఏⓗᨵⰋࡸᕼᑡ⢭ᾮࡢ᭷ຠ฼⏝㸪ᛶุู⬇ ࡢຠ⋡ⓗ࡞⏕⏘➼ࢆ┠ⓗ࡜ࡋ࡚ᗈࡃᬑཬࡋ㸦8㸪86㸧㸪ET ࡣ AI ࡜ྠᵝ࡟Ꮚ∵ࡢ⏕⏘ ᪉ἲ࡜ࡋ୍࡚⯡ⓗ࡟⾜ࢃࢀ࡚࠸ࡿࠋලయⓗ࡟ࡣ㸪⫗㉁ࡸ⏘ஙᛶࡀඃࢀࡓ㞤∵࡟ᛶ⭢ ่⃭࣍ࣝࣔࣥ๣ࡢᢞ୚࡟ࡼࡿ㐣๫᤼༸ㄏ㉳ฎ⨨ࢆ⾜࠸㸪ඃⰋ࡞✀㞝∵ࢆ஺㓄ࡍࡿࡇ ࡜࡛⬇ࢆ⏕⏘ࡍࡿࠋᅇ཰ࡉࢀࡓ⬇ࢆ௚ࡢ࢘ࢩ࡟⛣᳜ࡍࡿࡇ࡜࡛㸪ຠ⋡ⓗ࡟ඃⰋ࡞㑇 ఏᙧ㉁ࢆᣢࡘᚋ⥅∵ࢆ⏕⏘ࡍࡿࡇ࡜ࡀ࡛ࡁࡿࠋࡑࡢࡓࡵ㸪᥇⬇㢌ᩘ㸪ET 㢌ᩘ࡜ࡶ࡟

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⏝✀ࡢᚋ⥅㞤∵ࡀᏳᐃⓗ࡟⏕⏘࡛ࡁࡿࡼ࠺࡞ࡗࡓࠋࡉࡽ࡟㸪㯮ẟ࿴✀Ꮚ∵ࡣ㸪ங⏝ ✀Ꮚ∵ࡸ஺㞧✀Ꮚ∵࡟ẚ㍑ࡋ࡚ 2㹼5 ಸ㧗್࡛㈍኎ࡉࢀ࡚࠸ࡿࠋࡑࡢࡓࡵ㸪᪥ᮏ࡛ ࡣ㓗㎰ᐙ࡟࠾࠸࡚㯮ẟ࿴✀∵࠿ࡽ⏕⏘ࡉࢀࡓ⬇ࡢ⛣᳜ࡀቑຍࡋ࡚࠸ࡿࠋࡲࡓ㸪ᬬ⇕ ᮇ࡟࠾࠸࡚ࡣ㸪༸Ꮚࡢ㉁ࡢపୗ㸦3㸧㸪ཷ⢭⋡ࡢపୗ㸦70㸧㸪ཷ⢭┤ᚋࡢ⬇ࡢṚ⁛㸦17㸪 70㸧࡟ࡼࡾ AI ࡢཷ⫾⋡ࡀపୗࡍࡿࠋࡇࢀ࡟ᑐࡋ࡚㸪ET ࡣᬬ⇕ᮇ࡟࠾ࡅࡿཷ⫾⋡ࡀ AI ࡟ẚ㍑ࡋ࡚㧗࠸ࡇ࡜࠿ࡽ㸪ᬬ⇕ᮇ࡛ࡢ฼⏝ࡶ㐍ࡵࡽࢀ࡚࠸ࡿ㸦7㸧ࠋࡋ࠿ࡋ࡞ࡀࡽ㸪 ET ࡢཷ⫾⋡ࡣ 1980 ᖺ௦࠿ࡽᨵၿࡋ࡚࠾ࡽࡎ㸪෾⤖⬇࡟ẚ㍑ࡋ࡚ཷ⫾⋡ࡢ㧗࠸᪂㩭 ⬇࡟࠾࠸࡚ࡶ⣙ 50%࡛࠶ࡿ㸦27㸪57㸧ࠋ≉࡟㸪ᮍ⤒⏘∵࡟ẚ㍑ࡋ࡚⤒⏘∵ࡢཷ⫾⋡ ࡀప࠸㸦79㸪82㸧ࠋ ௨๓ࡼࡾ㸪ET ࡢཷ⫾࡟ᙳ㡪ࡍࡿせᅉࡢゎᯒࡀ㐍ࡵࡽࢀ㸦12㸪28㸪57㸪64㸧㸪P4ࡣ ࢘ࢩࡢET ࡟࠾࠸࡚ࡶཷ⫾࡟ᙳ㡪ࢆཬࡰࡍ୺せ࡞せᅉ࡛࠶ࡿ࡜ࡉࢀ࡚࠸ࡿ㸦57㸪64㸧ࠋ ࡋ࠿ࡋ࡞ࡀࡽ㸪P4ࡢ ᐃ࡟ࡣ᫬㛫࡜⤒㈝ࡀ᥃࠿ࡿࡓࡵ㸪⮫ᗋ⌧ሙ࡟࠾࠸࡚⾑୰ P4⃰ ᗘࢆᇶ‽࡜ࡋࡓཷ⬇∵ࡢ㑅ᐃࢆ⾜࠺ࡇ࡜ࡣᅔ㞴࡛࠶ࡿࠋ㯤య㠃✚㸦᭱኱┤ᚄ࡛ ᐃ ࡋࡓ㯤య᩿㠃✚㸧ࡣ⾑୰P4⃰ᗘ࡜┦㛵ࡋ࡚࠸ࡿࡓࡵ㸪㉸㡢Ἴデ᩿⿦⨨ࢆ⏝࠸࡚㯤య 㠃✚ࢆィ ࡍࡿࡇ࡜࡛ P4ࡢ ᐃࡢ௦⏝࡟࡞ࡿ࡜ゝࢃࢀ࡚࠸ࡿ㸦4㸪36㸪65㸧ࠋࡑࡢ ࡓࡵ㸪⌧ᅾ㸪ET ๓࡟┤⭠᳨ᰝࡸ㉸㡢Ἴデ᩿⿦⨨࡟ࡼࡗ࡚ィ ࡉࢀࡓ㯤య㠃✚ࡣ㸪ཷ ⬇∵ࡢ㑅ᐃᇶ‽࡜࡞ࡗ࡚࠸ࡿࠋࡋ࠿ࡋ࡞ࡀࡽ㸪㯤య㠃✚ࢆᣦᶆ࡜ࡋࡓཷ⬇∵ࡢ㑅ᐃ ࡛ࡣཷ⫾⋡ࡢྥୖ࡟⧅ࡀࡗ࡚࠾ࡽࡎ㸪ࡑࡢ฼⏝࡟ࡣ㝈⏺ࡀ࠶ࡿ࡜⪃࠼ࡽࢀࡿࠋᏊ∵ ࢆຠ⋡ⓗ࡟⏕⏘ࡍࡿࡓࡵ㸪᪂ࡓ࡞㯤యᶵ⬟ホ౯᪉ἲࡢ☜❧࡜ET ࡢཷ⫾⋡ࡢྥୖࡀ ồࡵࡽࢀ࡚࠸ࡿࠋ ㏆ᖺ㸪᪂ࡋ࠸㯤యᶵ⬟ࡢホ౯᪉ἲ࡜ࡋ࡚㸪㯤యࡢ⾑ὶ㔞ࡀ╔┠ࡉࢀ࡚࠸ࡿ㸦30㸪

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㸦49㸪76㸧ࠋࡇࡢࡇ࡜࠿ࡽ㸪1990 ᖺ௦࠿ࡽ࢘ࢩࡸ࣐࡛࢘ࡢ⮫ᗋデ᩿ᢏ⾡࡬ࡢᛂ⏝ࡀ ヨࡳࡽࢀ࡚ࡁࡓ㸦10㸪49㸧ࠋࡲࡓ㸪༸ᕢࡢ⾑ὶࢆᥥฟࡍࡿࡇ࡜ࡀ࡛ࡁࡿࡓࡵ㸪᤼༸๓ ࡢ༸⬊ࡸᙧᡂᮇࡲࡓࡣ㏥⾜ᮇࡢ㯤యࡢ⾑ὶືែࡀ◊✲ࡉࢀ࡚ࡁࡓ㸦1㸪2㸪30㸧ࠋ㯤య ᙧᡂᮇ࡟ࡣ㯤యࡢᡂ㛗࡜࡜ࡶ࡟⾑ὶ㔞ࡀቑຍࡋ㸦1㸪30㸧㸪㯤య㏥⾜ᮇ࡟ࡣ୍㐣ᛶࡢ ⃭ቑ࡜ࡑࡢᚋ࡟㏿ࡸ࠿࡞ῶᑡࡀ㉳ࡇࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗ࡚࠸ࡿ㸦2㸧ࠋࡲࡓ㸪㯤య ㏥⾜ᮇ࡟࠾࠸࡚⾑୰P4⃰ᗘࡢపୗࡣ㯤య㠃✚ࡢῶᑡ࡟ඛ⾜ࡍࡿ㸦30㸧ࠋࡇࢀ࡟ᑐࡋ ࡚㸪㯤య⾑ὶ㔞࡜⾑୰P4⃰ᗘࡢᾘ㛗ࡣྠㄪࡋ࡚࠸ࡿࡇ࡜࠿ࡽ㸪㯤యᶵ⬟ࡢホ౯᪉ἲ ࡜ࡋ࡚ࡢ᭷⏝ᛶࡀ♧၀ࡉࢀ࡚࠸ࡿ㸦30㸪52㸧ࠋࡋ࠿ࡋ࡞ࡀࡽ㸪⌧ᅾࡲ࡛ཷ⬇∵࡟࠾ࡅ ࡿ ET ๓ᚋࡢ㯤య⾑ὶ㔞ࡢኚ໬ࡸཷ⫾࡜ࡢ㛵㐃ᛶࡣ᫂ࡽ࠿࡟࡞ࡗ࡚࠾ࡽࡎ㸪㯤య⾑ ὶ㔞ࡣཷ⬇∵㑅ᐃࡢᣦᶆ࡜ࡋ࡚౑⏝ࡉࢀ࡚࠸࡞࠸ࠋ ࡜ࡇࢁ࡛㸪࢘ࢩ࡟࠾ࡅࡿዷፎデ᩿ࡣ㸪AI ᚋ 40 ᪥௨㝆࡟┤⭠᳨ᰝ࡟ࡼࡾ⫾⭷ࢫࣜ ࢵࣉࢆ☜ㄆࡍࡿࡇ࡜࡛⾜ࢃࢀ࡚ࡁࡓ㸦90㸧ࠋ2000 ᖺ௦࡟ධࡾᦠᖏᆺ㉸㡢Ἴデ᩿⿦⨨ ࡀᬑཬࡋ㸪AI ᚋ 25㸫29 ᪥௨㝆࡟㯤యࡢᏑᅾࡸ⫾Ꮚ࠾ࡼࡧ⫾Ꮚᚰᢿࡢ☜ㄆ࡟ᇶ࡙࠸ ࡚᪩ᮇዷፎデ᩿ࡀ⾜ࢃࢀࡿࡼ࠺࡟࡞ࡗ࡚࠸ࡿ㸦26㸪87㸧ࠋࡋ࠿ࡋ㸪࢘ࢩࡢⓎ᝟࿘ᮇࡣ ᖹᆒ 21 ᪥࡛࠶ࡿࡓࡵ㸪⌧ᅾࡢ᪩ᮇዷፎデ᩿࡛ࡣ୙ዷ࡛࠶ࡗࡓሙྜࡣḟᅇࡢⓎ᝟ࢆ ぢⴠ࡜ࡍྍ⬟ᛶࡀ࠶ࡾ㸪⦾Ṫຠ⋡ࡢపୗࡢཎᅉ࡜࡞ࡗ࡚࠸ࡿࠋᚑࡗ࡚㸪Ⓨ᝟࿘ᮇࡢ 21 ᪥ࡼࡾ๓ࡢዷፎデ᩿㸦㉸᪩ᮇዷፎデ᩿㸧᪉ἲࢆ☜❧ࡍࡿࡇ࡜ࡀ࡛ࡁࢀࡤⓎ᝟Ⓨぢ ⋡㸪ᤵ⢭⋡࠾ࡼࡧཷ⫾⋡ࡢྥୖ࡟⧅ࡀࡿࡶࡢ࡜⪃࠼ࡽࢀࡿࠋ ୍᪉㸪 ௨๓ࡼࡾ AI ᚋࡲࡓࡣ ET ๓ᚋ࡟ᛶ⭢่⃭࣍ࣝࣔࣥᨺฟ࣍ࣝࣔࣥ㸦GnRH㸧 〇๣ࢆᢞ୚ࡋ㸪ཷ⫾⋡ࢆྥୖࡉࡏࡿヨࡳࡀ⾜ࢃࢀ࡚ࡁࡓࠋGnRH ࡣ㸪⏕యෆ࡟࠾࠸ ࡚どᗋୗ㒊࡛⏘⏕㸪ศἪࡉࢀ㸪࢘ࢩࡢ⦾Ṫᶵ⬟ࢆไᚚࡍࡿどᗋୗ㒊-⬻ୗᆶయ-༸ᕢ ㍈࡟࠾࠸࡚㔜せ࡞ᙺ๭ࢆᯝࡓࡋ࡚࠸ࡿ㸦16㸧ࠋGnRH ࡣ⬻ୗᆶయ࡟స⏝ࡋ㯤యᙧᡂ

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๣ࡣ㸪⮫ᗋ⌧ሙ࡟࠾࠸࡚༸ᕢ㟼Ṇ㸪᤼༸㞀ᐖ࠾ࡼࡧ༸⬊ᄞ⭘ࡢ἞⒪࡟୍⯡ⓗ࡟⏝࠸ ࡽࢀ࡚࠸ࡿࠋAI ᚋࡲࡓࡣ ET ๓ᚋࡢ GnRH 〇๣ࡢᢞ୚࡟ࡼࡿ㸪ཷ⫾ᛶࡸ⾑୰ P4⃰ ᗘ࡟ᑐࡍࡿຠᯝ࡟㛵ࡋ࡚ᩘከࡃࡢ◊✲ࡀ࡞ࡉࢀ࡚࠸ࡿࡀ㸪ࡑࡢ⤖ᯝࡣ୍ᵝ࡛ࡣ࡞࠸ 㸦31㸪54㸪62㸪72㸪73㸪91㸧ࠋGnRH 〇๣ࡢᢞ୚࡟ࡼࡾ LH ࡀᛴቑࡋ㸪ඹᏑࡍࡿ┤ ᚄ10 mm ௨ୖࡢ୺ᖍ༸⬊ࡀ᤼༸ࡋ㸪๪㯤యࡀᙧᡂࡉࢀࡿ㸦69㸪72㸪73㸪94㸧ࠋࡑࢀ ࡟ࡼࡾ㸪⾑୰P4⃰ᗘࡀቑຍࡍࡿ࡜࠸࠺ሗ࿌㸦72㸪73㸧ࡶ࠶ࡿࡀ㸪ቑຍࡋ࡞࠸࡜࠸࠺ ሗ࿌㸦83㸧ࡶ࠶ࡿࠋࡲࡓ㸪ཷ⫾⋡ࡀྥୖࡍࡿ࡜࠸࠺ሗ࿌㸦73㸪83㸪91㸧ࡶ࠶ࡿࡀ㸪 ཷ⫾⋡ࡢྥୖࡀㄆࡵࡽࢀ࡞࠸࡜ࡍࡿሗ࿌㸦21㸧ࡶ࠶ࡿࠋࡲࡓ㸪LH ࡢศἪࡀ่⃭ࡉ ࢀࡿࡇ࡜࠿ࡽ㸪᪤Ꮡࡢ㯤యᶵ⬟ࢆ㈿άࡍࡿ࡜⪃࠼ࡽࢀࡿࡀ㸪㯤యᶵ⬟ࡢ⥔ᣢ࡟㔜せ ࡛࠶ࡿ㯤య⾑ὶ㔞࡟ᑐࡍࡿຠᯝࡣ඲ࡃ᫂ࡽ࠿࡟࡞ࡗ࡚࠸࡞࠸ࠋ ᮏ◊✲࡛ࡣ㸪ዷፎࡢᡂ❧࡟ᚲ㡲࡛࠶ࡿ P4 ࡢ⏘⏕࡟ࡣ㯤యࡢ⾑⟶ᙧᡂࡀ㔜せ࡛࠶ ࡿࡇ࡜࠿ࡽ㸪㯤య⾑ὶ㔞ࡢホ౯ࡀཷ⬇∵ࡢዷፎண ࡘࡲࡾ ET ๓ࡢཷ⫾ᛶࡢホ౯ࡸ ET ᚋࡢ㉸᪩ᮇዷፎデ᩿࡟᭷⏝࡛ࡣ࡞࠸࠿࡜⪃࠼ࡓࠋࡑࡇ࡛➨ 1 ❶࡛ࡣ㸪ཷ⫾∵࡜ ୙ཷ⫾∵࡟࠾ࡅࡿ ET ๓࠿ࡽ ET ᫬ࡢ㯤య⾑ὶ㔞ࢆẚ㍑ࡋ㸪㯤య⾑ὶ㔞ࡀ᪂ࡓ࡞ཷ ⬇∵㑅ᐃ᪉ἲ࡜ࡋ࡚᭷⏝࡛࠶ࡿ࠿ࢆ᳨ウࡋ㸪ᚑ᮶࠿ࡽ⏝࠸ࡽࢀ࡚࠸ࡿ㯤య㠃✚ࡸ⾑ ₢P4⃰ᗘ࡜ࡢ⢭ᗘࡢẚ㍑ࢆ⾜ࡗࡓࠋࡑࡢ⤖ᯝ㸪ET ᫬ࡢ㯤య⾑ὶ㠃✚ࡀཷ⬇∵㑅ᐃ ࡟᭷⏝࡛࠶ࡿࡇ࡜ࡀぢ࠸ฟࡉࢀࡓࠋ➨2 ❶࡛ࡣ㸪ཷ⫾∵࡜୙ཷ⫾∵࡟࠾࠸࡚ ET ࠿ ࡽ7 ᪥ᚋࡢ㯤య⾑ὶ㔞ࢆẚ㍑ࡋ㸪㉸᪩ᮇዷፎデ᩿᪉ἲ࡜ࡋ࡚᭷⏝࡛࠶ࡿ࠿ࢆ᳨ウࡋ ࡓࠋࡑࡢ⤖ᯝ㸪ET7 ᪥ᚋࡢ㯤య⾑ὶ㠃✚࡜⾑ὶ㏿ᗘࡀ㉸᪩ᮇዷፎデ᩿࡟᭷⏝࡛࠶ࡿ ࡇ࡜ࡀศ࠿ࡗࡓࠋࡉࡽ࡟➨3 ❶࡛ࡣ㸪㯤యᶵ⬟ࢆቑᙉࡉࡏࡿ᪉ἲ࡜ࡋ࡚௨๓ࡼࡾ⏝ ࠸ࡽࢀ࡚࠸ࡿ㸪ET ๓ࡢ GnRH 〇๣ᢞ୚ࡀ㯤య⾑ὶ㔞࠾ࡼࡧ㯤య⾑ὶ㔞࡟ᇶ࡙ࡃཷ

(11)

➨1❶ ࣍ࣝࢫࢱ࢖ࣥ✀ཷ⬇∵࡟࠾ࡅࡿ⬇⛣᳜㸦ET㸧᫬ࡢ㯤య⾑ὶ㔞ࢆ⏝࠸ࡓཷ⬇ ∵㑅ᐃ 1-1. ᗎㄽ ࢘ࢩࡢዷፎࡢᡂ❧࡜⥔ᣢ࡟ࡣ㯤య࠿ࡽ⏘⏕ࡉࢀࡿP4ࡀᚲせ୙ྍḞ࡛࠶ࡾ㸦45㸪 57㸪60㸧㸪ET ࡟࠾࠸࡚⾑୰ P4⃰ᗘࡀཷ⫾࡟ᙳ㡪ࢆཬࡰࡍ୺せ࡞せᅉ࡛࠶ࡿ࡜ࡉ ࢀ࡚࠸ࡿ㸦57㸪64㸧ࠋࡋ࠿ࡋ㸪⾑୰ P4⃰ᗘࡢ ᐃ࡟ࡣ᫬㛫࡜⤒㈝ࡀ࠿࠿ࡿࡓࡵ㸪 ཷ⬇∵㑅ᐃᇶ‽࡜ࡋ࡚⏝࠸ࡿࡇ࡜ࡣᅔ㞴࡛࠶ࡿࠋ⾑୰P4⃰ᗘ࡜㯤య㠃✚࡟ࡣṇ ࡢ┦㛵ࡀぢࡽࢀࡿࡇ࡜ࡀศ࠿ࡗ࡚࠸ࡿ㸦4㸪36㸪65㸧ࠋࡇࡢࡇ࡜࠿ࡽ㸪ཷ⬇∵ࡢ 㑅ᐃ᫬࡟┤⭠᳨ᰝࡸ㉸㡢Ἴデ᩿⿦⨨ࢆ⏝࠸࡚㯤య┤ᚄࡸ㯤య㠃✚ࢆィ ࡍࡿࡇ ࡜࡛㯤యᶵ⬟ࡢホ౯ࢆ⾜࠸㸪ཷ⬇∵ࡢ㑅ᐃࢆ⾜ࡗ࡚࠸ࡿࠋࡲࡓ㸪ET ࡢཷ⫾⋡ࢆ ྥୖࡉࡏࡿࡓࡵ࡟㸪ཷ⬇∵ࡢ㯤య㠃✚ࡸ⾑୰P4⃰ᗘࡔࡅ࡛ࡣ࡞ࡃ㸪ඹᏑࡍࡿ༸ ⬊㠃✚㸦᭱኱┤ᚄ࡛ィ ࡋࡓ᩿㠃✚㸧࠾ࡼࡧ⾑୰࢚ࢫࢺࣛࢪ࣮࢜ࣝ㸦E2㸧⃰ᗘ࡟ ᇶ࡙ࡁཷ⬇∵ࢆ㑅ᐃࡍࡿ᪉ἲࡀ◊✲ࡉࢀ࡚ࡁࡓ㸦12㸪28㸪56㸪64㸪84㸧ࠋࡋ࠿ࡋ㸪 ཷ⫾⋡ࡢྥୖ࡟ࡣ⧅ࡀࡗ࡚࠾ࡽࡎ㸪㯤య㠃✚ࡸ༸⬊㠃✚ࢆᇶ‽࡜ࡋࡓཷ⬇∵ࡢ 㑅ᐃ࡟ࡣ㝈⏺ࡀ࠶ࡿ࡜⪃࠼ࡽࢀࡿࠋࡲࡓ㸪㏆ᖺ㸪㉸㡢Ἴࢻࣉࣛἲࢆ⏝࠸࡚᤼༸๓ ࡢ༸⬊ࡸ㯤యᙧᡂᮇࡲࡓࡣ㏥⾜ᮇࡢ㯤యࡢ⾑ὶືែࡢゎᯒࡀ⾜ࢃࢀ࡚࠸ࡿ㸦1㸪 2㸪30㸧ࠋ㯤య⾑ὶ㔞ࡣ⾑୰ P4⃰ᗘ࡜┦㛵ࡋ࡚࠾ࡾ㸪㯤యᶵ⬟ࡢホ౯᪉ἲ࡜ࡋ࡚ ࡢ᭷⏝ᛶࡀ♧၀ࡉࢀ࡚࠸ࡿ㸦30㸪52㸧ࡋ࠿ࡋ㸪ཷ⬇∵ࡢ ET ๓࠿ࡽ ET ᫬ࡢ㯤య ⾑ὶ㔞࡜ཷ⫾ᛶ࡜ࡢ㛵㐃ᛶࡣ඲ࡃ᫂ࡽ࠿࡜࡞ࡗ࡚࠾ࡽࡎ㸪㯤య⾑ὶ㔞ࡣཷ⬇∵ 㑅ᐃࡢᇶ‽࡜ࡋ࡚౑⏝ࡉࢀ࡚࠸࡞࠸ࠋ ࡑࡇ࡛㸪ᮏ❶࡛ࡣ㉸㡢Ἴࢻࣉࣛἲࢆ⏝࠸࡚ཷ⬇∵ࡢET ๓࠿ࡽ ET ᫬ࡢ㯤య⾑

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ࡋ࡚᭷⏝࡛࠶ࡿ࠿ࢆ᳨ウࡋ㸪ᚑ᮶࠿ࡽ⏝࠸ࡽࢀ࡚࠸ࡿ㯤య㠃✚ࡸ⾑₢P4⃰ᗘ࡜ ዷፎண ࡢ⢭ᗘࡢẚ㍑ࢆ⾜ࡗࡓࠋ 1-2. ヨ㦂1㸸ET ᫬ࡢ㯤య⾑ὶ㠃✚㸦BFA㸧ࢆ⏝࠸ࡓཷ⬇∵㑅ᐃ᪉ἲࡢ᳨ウ 1) ᮦᩱཬࡧ᪉ἲ ౪ヨື≀ ⮫ᗋⓗ࡟೺ᗣ࡛㸪ศፔᚋ50 ᪥௨ୖ⤒㐣ࡋṇᖖ࡞Ⓨ᝟࿘ᮇࢆ᭷ࡍࡿ࣍ࣝࢫࢱ࢖ ࣥ✀⤒⏘∵65 㢌㸦4.21 ± 0.27 ṓ㸪2.50 ± 0.23 ⏘㸪ᖹᆒsᶆ‽ㄗᕪ㸧ࢆ౪ヨࡋ ࡓࠋ౪ヨ∵ࡣᐑᇛ┴ෆ 1 㓗㎰ᐙࡢࣇ࣮ࣜࢫࢺ࣮ࣝ∵⯋࡟࡚஝ⲡ࠾ࡼࡧ⃰ཌ㣫ᩱ ࡀΰྜࡉࢀࡓTMR ࡀ⤥୚ࡉࢀ㸪⮬⏤㣧Ỉ࡛ࡁࡿ≧ἣ࡛㣫㣴ࡉࢀ࡚࠸ࡓࠋ඲㢌ࡀ 1 ᪥ 2 ᅇᦢஙࡉࢀ㸪ᖹᆒங㔞ࡣ 28.29 ± 2.42kg/᪥㸦ᖹᆒ s ᶆ‽ㄗᕪ㸧࡛࠶ࡗ ࡓࠋ࣎ࢹ࢕࣮ࢥࣥࢹ࢕ࢩࣙࣥࢫࢥ࢔㸦BCS㸧ࡣ Edomonson ࡽ㸦20㸧ࡢ᪉ἲ࡟ ᇶ࡙ࡁⓎ᝟᪥࡟ ᐃࡋ㸪3.50 ± 0.08 㸦ᖹᆒ s ᶆ‽ㄗᕪ㸧࡛࠶ࡗࡓࠋ ᐇ㦂᪉ἲ  ౪ヨ∵࡟ࡣ⮬↛࡟Ⓨ᝟ࡀⓎ⌧ࡋࡓ࢘ࢩ㸦n = 34㸧࡜Ⓨ᝟ྠᮇ໬ฎ⨨ࢆ⾜ࡗࡓ࢘ ࢩ (n = 31) ࢆ౑⏝ࡋࡓࠋⓎ᝟Ⓨ⌧᪥ࢆ Day 0 ࡜ࡋ㸪Day 3, 5 ࠾ࡼࡧ 7 ࡟㉸㡢 Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚㯤య㠃✚㸦᭱኱┤ᚄ࡛ࡢ᩿㠃✚㸧㸪㯤యෆ⭍㠃✚㸦᭱኱ ┤ᚄ࡛ࡢ㯤యෆ⭍ࡢ᩿㠃✚㸧㸪㯤య⤌⧊㠃✚㸦㯤య㠃✚࡜㯤యෆ⭍㠃✚ࡢᕪ㸧㸪୺

(13)

7 ࡟㯤య┤ᚄࡀ 20mm ௨ୖ࡛࠶ࡿࡇ࡜ࢆ☜ㄆࡋ㸪58 㢌ࡢ࢘ࢩ࡟㯮ẟ࿴✀∵ࡢ⬇ ࢆ1 ࡘ⛣᳜ࡋࡓࠋᑦ㸪Day 7 ࡢ㉸㡢Ἴ᳨ᰝ࠾ࡼࡧ᥇⾑ࡣ ET ๓࡟⾜ࡗࡓࠋDay 30 ࡟㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚ዷፎデ᩿ࢆ⾜ࡗࡓࠋヨ㦂 1 ࡢࣉࣟࢺࢥ࣮ࣝࡢᶍ ᘧᅗࢆFig. 1-1.࡟♧ࡋࡓࠋ Ⓨ᝟ྠᮇ໬᪉ἲ ౪ヨ∵ࡢ࠺ࡕ34 㢌ࡣⓎ᝟ྠᮇ໬ฎ⨨ࢆ⾜ࢃࡎ㸪⮬↛࡟Ⓨ᝟ࡀⓎ⌧ࡋࡓ࢘ࢩࢆ ౑⏝ࡋࡓ㸦⮬↛Ⓨ᝟⩌㸧ࠋⓎ᝟Ⓨ⌧᪥ࢆDay 0 ࡜ࡋࡓࠋྠᮇ໬Ⓨ᝟⩌㸦n = 31㸧 ࡣSiqueira ࡽ㸦77㸧ࡢ᪉ἲ࡟ᇶ࡙ࡁ㸪௨ୗࡢ᪉ἲ࡛Ⓨ᝟ྠᮇ໬ฎ⨨ࢆ⾜ࡗࡓ㸹 Day 㸫12 ࡟ 2mg ࢚ࢫࢺࣛࢪ࣮࢜ࣝᏳᜥ㤶㓟࢚ࢫࢸࣝ〇๣㸦EB㸹࢚ࢫࢺࣛࢪ࢜ ࣮ࣝὀࠕKSࠖ㸹ඹ❧〇⸆ᰴᘧ఍♫㸪ᮾி㸪᪥ᮏ㸧ࡢ➽⫗ෆᢞ୚࡜⭐ෆ࡟ 1.9 g ࣉ ࣟࢪ࢙ࢫࢸࣟࣥ⭐ෆ␃⨨ᆺᚎᨺ๣ 㸦CIDR 1900㸹ࢰ࢚ࢸ࢕ࢫ࣭ࢪࣕࣃࣥᰴᘧ఍ ♫㸪ᮾி㸪᪥ᮏ㸧ࡢᤄධ㸪Day 㸫2 ࡟ CIDR1900 ࡢᢤཤ࠾ࡼࡧ 500 μg ࡢࣉࣟ ࢫࢱࢢࣛࣥࢪࣥ㸦PG㸧F2α 㢮⦕య〇๣㸦ࢡࣟࣉࣟࢫࢸࣀ࣮ࣝ㸹࢚ࢫࢺ࣓ࣛ࢖ࢺ㸹 ࢼ࢞ࢭ་⸆ရᰴᘧ఍♫㸪රᗜ㸪᪥ᮏ㸧ࡢ➽⫗ෆᢞ୚㸪ࡑࡢ24 ᫬㛫ᚋ㸦Day 㸫1㸧 ࡟ 1mgEB ࡢ➽⫗ෆᢞ୚ࢆ⾜ࡗࡓࠋⓎ᝟ྠᮇ໬᪉ἲࡢࣉࣟࢺࢥ࣮ࣝࡢᶍᘧᅗࢆ Fig. 1-2.࡟♧ࡋࡓࠋ ET  ࣍ࣝࢫࢱ࢖ࣥ✀⤒⏘∵ࡢ Day 7 ࡟࠾ࡅࡿᶵ⬟ⓗ㯤యࡢࢧ࢖ࢬࡣ┤ᚄ 19 ࠿ࡽ 28mm ࡜ሗ࿌ࡉࢀ࡚࠾ࡾ㸦50㸪93㸧㸪┤ᚄ 20mm ௨ୖࡢ㯤యࢆᣢࡘ∵࡛ࡣ 20mm ᮍ‶ࡢ∵࡟ẚ㍑ࡋ࡚ET ࡢཷ⫾⋡ࡀ㧗࠸࡜ࡉࢀ࡚࠸ࡿ㸦56㸧ࠋᚑࡗ࡚㸪Day 7 ࡟

(14)

Embryo Transfer Society㸦http://www.iets.org/㸧ࡢศ㢮࡟ᇶ࡙ࡁ㸪quality grade 1 ࠾ࡼࡧ developmental stage 4 ࡢ⬇㸦᪂㩭⬇㸹n = 22㸪෾⤖⼥ゎ⬇㸹n = 36㸧 ࢆ౑⏝ࡋࡓࠋ⛣᳜ჾࡣື≀⏝ཷ⢭༸ὀධ࢝ࢸ࣮ࢸࣝ㸦ࣔ 4 ྕ㸹࣑ࢧ࣡་⛉ᕤᴗ ᰴᘧ఍♫㸪Ⲉᇛ㸪᪥ᮏ㸧ࢆ౑⏝ࡋ㸪㯤యഃࡢᏊᐑゅ῝㒊࡟1 ࡘࡢ⬇ࢆ⛣᳜ࡋࡓࠋ ዷፎデ᩿  ET ᚋ 23 ᪥ࡘࡲࡾ Day 30 ࡟㸪7.5MHz ࣜࢽ࢔ࣉ࣮ࣟࣈࡀ௜ᒓࡋࡓ⤒┤⭠㉸

㡢Ἴ⏬ീデ᩿⿦⨨ 㸦Tringa V linear㸹Esaote SpA㸪Genoa㸪Italy㸧ࢆ⏝࠸࡚⫾

ᏊࡢᏑᅾ࠾ࡼࡧᚰᢿࢆᣦᶆ࡜ࡋ࡚⾜ࡗࡓࠋ ༸ᕢࡢ㉸㡢Ἴ᳨ᰝ  ㉸㡢Ἴ᳨ᰝࡣDay 3㸪5 ࠾ࡼࡧ 7 ࡟⾜ࡗࡓࠋ㯤య࡜୺ᖍ༸⬊ࡢᙧែࡣ㸪7.5MHz ࡢࣜࢽ࢔ࣉ࣮ࣟࣈࡀ௜ᒓࡋࡓ⤒┤⭠㉸㡢Ἴ⏬ീデ᩿⿦⨨㸦MyLab five㸹Esaote SpA㸪Genoa㸪Italy㸧ࢆ⏝࠸࡚ B-࣮ࣔࢻ࡟ࡼࡾほᐹࡋࡓࠋࣉ࣮ࣟࣈࢆᡭᣦ࡜ࡶ ࡟┤⭠ෆ࡟ᤄධࡋ㸪ᕥྑ୧ഃ༸ᕢࡢ᩿ᒙീࢆほᐹࡋ㸪୺ᖍ༸⬊ࡲࡓࡣ㯤యࡢ┤ᚄ ࡀ᭱኱࡟࡞ࡿࡼ࠺࡟㟼Ṇ⏬ࢆグ㘓ࡋ㸪ࣃࢯࢥࣥୖ࡟㟼Ṇ⏬ࢆ⛣ືࡉࡏ㸪 㯤య㠃 ✚ࠊ㯤యෆ⭍㠃✚࠾ࡼࡧ୺ᖍ༸⬊㠃✚ࢆ ᐃࡋࡓࠋࡲࡓ㸪Day 7 ࡟࠾࠸࡚୺ᖍ༸ ⬊ࡢ఩⨨ࢆ☜ㄆࡋ㸪ྠ୍༸ᕢෆ࡟㯤య࡜ඹᏑࡍࡿሙྜࢆྠഃ⩌㸪㯤యࡀᏑᅾࡍࡿ ༸ᕢ࡜ࡣ཯ᑐഃࡢ༸ᕢ࡟Ꮡᅾࡍࡿሙྜࢆᑐഃ⩌࡜ࡋࡓࠋ  㯤య⾑ὶࡣ㸪7.5MHz ࡢࣜࢽ࢔ࣉ࣮ࣟࣈࡀ௜ᒓࡋࡓ⤒┤⭠㉸㡢Ἴ⏬ീデ᩿⿦

(15)

ฟࡋࡓ (Fig. 1-3.)ࠋ

 㯤య㠃✚㸪㯤యෆ⭍㠃✚㸪୺ᖍ༸⬊㠃✚࠾ࡼࡧBFA ࡣ㸪グ㘓ࡋࡓ⏬ീࢆࣃࢯ

ࢥࣥෆ࡟ྲྀࡾ㎸ࡳ㸪Image J㸦version 1.49㸹the U.S. National Institutes of

Health㸦http://imagej.nih.gov/ij/㸧㸪USA㸧ࢆ⏝࠸࡚⟬ฟࡋࡓࠋ㯤య⤌⧊㠃✚ࡣ㸪 㯤య㠃✚࠿ࡽ㯤యෆ⭍㠃✚ࢆᕪࡋᘬ࠸࡚⟬ฟࡋࡓࠋ  ༸ᕢື⬦࠿ࡽศᒱࡋ༸ᕢᐇ㉁ෆࢆ㉮⾜ࡍࡿࡽࡏࢇື⬦ࡢ㯤యഃᇶ㒊࡟ࣉ࣮ࣟ ࣈࢆྜࢃࡏ㸪⾑ὶ㏿ᗘࢆ ᐃࡋTAMV ࢆ⟬ฟࡋࡓࠋ⾑ὶ㏿ᗘ ᐃ㒊఩ࢆ Fig. 1-4.࡟♧ࡋࡓࠋ ⾑₢P4⃰ᗘࡢ ᐃ  ㉸㡢Ἴ᳨ᰝ᫬㸦Day 3㸪5 ࠾ࡼࡧ 7㸧࡟ 21G ᥇⾑㔪࡜࣊ࣃࣜࣥຍ┿✵᥇⾑⟶ 㸦࣋ࣀࢪ࢙ࢡࢺϩ┿✵᥇⾑⟶㸪TERUMO㸪ᮾி㸪᪥ᮏ㸧ࢆ⏝࠸㸪ᑿ㟼⬦ࡼࡾ 10ml ࡢ᥇⾑ࢆ⾜ࡗࡓࠋ᥇⾑ᚋ┤ࡕ࡟ị෭ࡋ㸪30 ศ௨ෆ࡟⾑₢ࢆ 3,000g㸪15 ศ㛫㐲ᚰ ศ㞳ᚋ㸪P4 ᐃࡲ࡛㸫30Υ࡛෾⤖ಖᏑࡋࡓࠋ  ෾⤖ಖᏑࡉࢀࡓ⾑₢ࢆ ᐃ┤๓࡟ᐊ ࡟࡚⼥ゎࡋ㸪㓝⣲ච␿ ᐃἲ㸦EIA㸧࡟ ࡼࡾ⾑₢୰P4⃰ᗘࢆ ᐃࡋࡓࠋணࡵ㸪96 ✰ࣉ࣮ࣞࢺ࡟ᢠ࢘ࢧࢠ IgG ᢠయ㸦Cappel㸪 Cochranville㸪PA㸪USA㸧ࢆ྾╔ࡉࡏࡿࡇ࡜࡛㸪➨஧ᢠయᅛ┦໬ࣉ࣮ࣞࢺࢆస 〇ࡋࡓࠋලయⓗ࡟ࡣ㸪➨஧ᢠయ࡜ࡋࡓᢠ࢘ࢧࢠ IgG ᢠయࢆ➨஧ᢠయᕼ㔘ᾮ㸦50 mM NaCO3-NaHCO3(pH9.6)㸧࡛㸪15 μg/mL ࡟ᕼ㔘ࡋ㸪ᕼ㔘ࡋࡓ➨஧ᢠయᾮࢆ ࣉ࣮ࣞࢺࡢྛ࢙࢘ࣝ࡟100 μL ࡎࡘศὀࡋࡓࠋ➨஧ᢠయࢆࣉ࣮ࣞࢺ࡟྾╔ࡉࡏᅛ ┦໬ࡉࡏࡿࡓࡵ㸪ࣉ࣮ࣞࢺࢆࢩ࣮ࣝࡋ࡚㸪4Υ࡛ 2 ᪥㛫㟼⨨ࡋࡓࠋࡑࡢᚋ㸪ྛ࢘ ࢙ࣝࢆ200 μL ࡢࣈࣟࢵ࢟ࣥࢢᾮ㸦20 mM Tris-HCl (pH7.2), 0.5% (w/v) ∵⾑Ύ

(16)

࡛ 4Υ࡟ಖᏑࡍࡿࡇ࡜࡟ࡼࡾ㸪➨஧ᢠయᅛ┦໬ࣉ࣮ࣞࢺࡢࣈࣟࢵ࢟ࣥࢢࢆ⾜ࡗ ࡓࠋ EIA ゎᯒࡣ㸪స〇ࡋࡓ➨஧ᢠయᅛ┦໬ࣉ࣮ࣞࢺࢆ౑⏝ࡋ㸪⾑₢୰ P4࡜࣌ࣝ࢜ ࢟ࢩࢲ࣮ࢮ㸦HRP㸧ᶆ㆑ P4 㸦Cosmo Bio㸪FKA-301㸪ᮾி㸪᪥ᮏ㸧ࢆ㸪ᢠ P4 ᢠయ㸦࢘ࢧࢠ⏤᮶㸪Cosmo Bio㸪ᮾி㸪᪥ᮏ㸧࡛ ➇ྜㄆ㆑ࡉࡏ㸪HRP ࡢᇶ㉁࢜ ࣝࢯࣇ࢙ࢽࣞࣥࢪ࢔࣑ࣥ㸦OPD㸪Wako㸪኱㜰㸪᪥ᮏ㸧ࡀ HRP ࡢ཯ᛂ࡟ࡼࡾ 492 nm ࡟྾཰ᴟ኱ࢆᣢࡘᛶ㉁ࢆ฼⏝ࡋ᳨ฟࡋ㸪⾑₢୰ P4ࡢᐃ㔞ࢆ⾜ࡗࡓࠋලయⓗ ࡟ࡣ㸪➨஧ᢠయᅛ┦໬ࣉ࣮ࣞࢺ࠿ࡽࣈࣟࢵ࢟ࣥࢢ⁐ᾮࢆྲྀࡾ㝖࠸ࡓᚋ㸪ྛ࢙࢘ࣝ

ࢆ250 μL ࡢὙίᾮ㸦10 mM Tris-HCl (pH7.5)㸪0.3 M NaCl㸪0.1% (v/v) Tween20㸧

࡛ὙίࡋࡓࠋὙίᚋࡢྛ࢙࢘ࣝ࡟㸪ணࡵ㸪άᛶⅣฎ⌮ࡋࡓ࢘ࢩ⾑Ύ࡛ᕼ㔘ࡋࡓᶆ ‽ᾮ㸦36㸪12㸪4.0㸪1.33㸪0.33 ng/mL㸧ཬࡧ⾑₢ࢆྛ࢙࢘ࣝ࡟ 25 μL ࡎࡘศὀ ࡋࡓࠋᑦ㸪ᶆ‽ᾮࡢస〇࡟ࡣ㸪ࢩࢢ࣐♫࠿ࡽ㉎ධࡋࡓ P4㸦SIGMA-ALDRICH㸪 St. Louis㸪USA㸧ࢆ⏝࠸ࡓࠋᘬࡁ⥆ࡁ㸪100 μL ཯ᛂᾮ㸦50 mM Tris ⦆⾪ᾮ (pH7.5)㸪0.2% (w/v) BSA㸪10% (w/v) ࢳ࣓ࣟࢧ࣮ࣝ㸧ࢆྛ࢙࢘ࣝ࡟ศὀࡋࡓࠋ ࡉࡽ࡟㸪཯ᛂᾮ࡛80 ୓ಸᕼ㔘ࡋࡓᢠ P4ᢠయ㸦࢘ࢧࢠ⏤᮶㸪FKA-302E㸪Cosmo Bio㸪ᮾி㸪᪥ᮏ㸧100 μL ࡜ Tris ⦆⾪ᾮ࡛ 16 ୓ಸᕼ㔘ࡋࡓ HRP ᶆ㆑ P4100 μL ࢆྛ࢙࢘ࣝ࡟ศὀࡋ㸪ࣉ࣮ࣞࢺࢆࢩ࣮ࣝࡋ࡚㸪ᖖ ࡛ 3 ᫬㛫᣺┞࢖࣮ࣥ࢟ࣗ࣋ ࢺࡋࡓࠋ࢖࣮ࣥ࢟ࣗ࣋ࢺᚋ㸪ࣉ࣮ࣞࢺࢆ4 ᅇὙίࡋࡓࠋὙίᚋ㸪100 μL ࡢᇶ㉁ ᾮ㸦0.2 M ࢡ࢚ࣥ㓟⦆⾪ᾮ(pH4.5)㸪0.03% (v/v) H2O2㸪0.05% (w/v) OPD㸧ࢆྛ ࢙࢘ࣝ࡟ศὀࡋ㸪ᬯᡤ࡟࡚30 ศ㛫࢖࣮ࣥ࢟ࣗ࣋ࢺࡋࡓࠋHRP ࡟ࡼࡿ OPD ࡢⓎ Ⰽ཯ᛂࢆ೵Ṇࡉࡏࡿࡓࡵ࡟㸪3M ࡢ◲㓟ࢆ 50μL ࡎࡘྛ࢙࢘ࣝ࡟ຍ࠼ࡓࠋ1 ศ㛫

(17)

⤫ィฎ⌮

 ⤖ᯝࡣࡍ࡭࡚ᖹᆒ್ s ᶆ‽ㄗᕪ࡛♧ࡋࡓࠋ᪂㩭⬇࡜෾⤖⼥ゎ⬇ࡢཷ⫾⋡㸪⮬

↛Ⓨ᝟⩌࡜ྠᮇ໬Ⓨ᝟⩌ࡢ⛣᳜⋡࡜ཷ⫾⋡࠾ࡼࡧ୺ᖍ༸⬊ࡢྠഃ⩌࡜ᑐഃ⩌ࡢ ཷ⫾⋡ࡢẚ㍑ࢆ⾜࠺ࡓࡵ࡟㸪ࣇ࢕ࢵࢩ࣮ࣕࡢ┤᥋☜⋡ィ⟬ἲࢆ⏝࠸ࡓࠋཷ⫾⩌࡜

୙ཷ⫾⩌࡟࠾࠸࡚㸪㯤య㠃✚㸪㯤య⤌⧊㠃✚㸪୺ᖍ༸⬊㠃✚㸪BFA㸪TAMV㸪BFA/

㯤య㠃✚ẚ㸪BFA/㯤య⤌⧊㠃✚ẚ㸪Day 3 ࢆᇶ‽࡜ࡋࡓ BFA ࡜ TAMV ࡢ┦ᑐ

ⓗኚ໬࠾ࡼࡧ⾑₢P4⃰ᗘࡢᖹᆒ್ࡢ 2 ⩌㛫ࡢᕪࡢ᳨ᐃࢆ⾜࠺ࡓࡵ࡟㸪ྛỈ‽ࡢ ⧞ࡾ㏉ࡋᅇᩘࡀ␗࡞ࡿ஧ඖ㓄⨨ศᩓศᯒࢆ⾜࠸඲యࡢኚ໬ࡢ᭷ពᛶࢆㄪ࡭ࡓࠋ ஺஫స⏝ࡀ᭷ព࡛࠶ࡗࡓሙྜ㸪Day ẖ࡟ Bonferroni ࡢከ㔜ẚ㍑᳨ᐃࢆ⾜ࡗࡓࠋ ࡲࡓ㸪୺ᖍ༸⬊ࡢྠഃ⩌࡜ᑐഃ⩌࡟࠾ࡅࡿ㯤య㠃✚㸪㯤య⤌⧊㠃✚㸪୺ᖍ༸⬊㠃 ✚㸪BFA㸪TAMV ࠾ࡼࡧ⾑₢ P4⃰ᗘࡢᖹᆒ್ࡢ 2 ⩌㛫ࡢᕪࡢ᳨ᐃࢆ⾜࠺ࡓࡵ ࡟㸪Student ࡢ t ᳨ᐃࢆ⾜ࡗࡓࠋ⤫ィฎ⌮࡟ࡣ⤫ィฎ⌮ࢯࣇࢺ࢙࢘࢔ SPSS 13 㸦SPSS Japan㸪ᮾி㸪᪥ᮏ㸧ࢆ⏝࠸ࡓࠋ༴㝤⋡ 5%ᮍ‶㸦P < 0.05㸧࡛᭷ពᕪ࠶ ࡾ࡜ࡋࡓࠋDay 7 ࡟࠾ࡅࡿዷፎண ᅉᏊ࡜ࡋ࡚࡝ࡢᅉᏊࡀ᭱ࡶඃࢀ࡚࠸ࡿ࠿ࢆ ㄪ࡭ࡿࡓࡵ࡟㸪ࣟࢪࢫࢸ࢕ࢵࢡᅇᖐศᯒࢆ⾜ࡗࡓࠋᚑᒓኚᩘࡣཷ⫾ࡢᡂྰ㸪⊂❧ ኚᩘ࡟ࡣ 10 ᅉᏊ㸦ᖺ㱋㸪⏘Ṕ㸪ศፔᚋ᪥ᩘ㸪BCS㸪୺ᖍ༸⬊㠃✚㸪㯤య㠃✚㸪 㯤య⤌⧊㠃✚㸪BFA㸪TAMV ࠾ࡼࡧ⾑₢ P4⃰ᗘ㸧ࢆ⏝࠸ࡓࠋ ᚑ᮶࠿ࡽ⏝࠸ࡽࢀ࡚࠸ࡿ 3 ࡘࡢዷፎண ᅉᏊ㸦㯤య㠃✚㸪㯤య⤌⧊㠃✚㸪⾑ ₢P4⃰ᗘ㸧࡜᪂ࡋ࠸ᅉᏊ㸦BFA ࠾ࡼࡧ TAMV㸧ࡢዷፎண ⢭ᗘࡢẚ㍑ࢆ⾜࠺ࡓ

ࡵ࡟㸪receiver operating characteristics㸦ROC㸧ゎᯒࢆ⾜ࡗࡓࠋROC ᭤⥺ࢆ

(18)

2) ⤖ᯝ Ⓨ᝟ྠᮇ໬᪉ἲ㸪⬇ࡢ✀㢮࠾ࡼࡧ⏘Ṕࡢẚ㍑ ⮬↛Ⓨ᝟⩌࠾ࡼࡧྠᮇ໬Ⓨ᝟⩌࡟࠾ࡅࡿ⛣᳜⋡࠾ࡼࡧཷ⫾⋡ࢆTable1-1.࡟♧ ࡋࡓࠋ⛣᳜⋡㸪ཷ⫾⋡࡜ࡶ࡟୧⩌࡟࠾࠸࡚᭷ព࡞ᕪࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋࡲࡓ㸪 ᪂㩭⬇࡜෾⤖⼥ゎ⬇ࡢཷ⫾⋡ࡣྛࠎ63.6%㸦14/22㸧㸪55.6%㸦20/36㸧࡛࠶ࡾ㸪᭷ ព࡞ᕪࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋᚑࡗ࡚㸪Ⓨ᝟ྠᮇ໬᪉ἲ࡜⬇ࡢ✀㢮࡟ࡼࡿᙳ㡪ࡣ⪃ ៖ࡏࡎ㸪඲࡚ࡲ࡜ࡵ࡚ゎᯒࢆ⾜ࡗࡓࠋ Day 30 ࡟࠾ࡅࡿዷፎデ᩿ᚋ㸪౪ヨ∵ࢆཷ⫾⩌㸦n = 34㸧࡜୙ཷ⫾⩌㸦n = 24㸧 ࡟ศ㢮ࡋ㸪ྛ㡯┠ࢆẚ㍑᳨ウࡋࡓࠋ୧⩌࡟࠾ࡅࡿᖺ㱋㸪⏘Ṕ㸪ศፔᚋ᪥ᩘ࠾ࡼࡧ BCS ࢆ Table 1-2.࡟♧ࡋࡓࠋ඲࡚ࡢ㡯┠࡛୧⩌࡟࠾࠸࡚᭷ព࡞ᕪࡣㄆࡵࡽࢀ࡞ ࠿ࡗࡓࠋ 㯤య⾑ὶ㔞ࡢ᥎⛣

BFA ࡢ᥎⛣ࢆ Fig. 1-5. A ࡟♧ࡋࡓࠋヨ㦂ᮇ㛫୰㸪୧⩌࡟࠾࠸࡚ BFA ࡣḟ➨

࡟ቑຍࡋ㸪Day 7 ࡟࠾࠸࡚ཷ⫾⩌ࡀ୙ཷ⫾⩌࡟ẚ㍑ࡋ࡚᭷ព࡟㧗࠸್ࢆ♧ࡋࡓ

㸦P < 0.01㸧ࠋ

TAMV ࡢ᥎⛣ࢆ Fig. 1-5. B ࡟♧ࡋࡓࠋヨ㦂ᮇ㛫୰㸪୧⩌࡟࠾࠸࡚ TAMV ࡣ ḟ➨࡟ቑຍࡋ᭷ព࡞ᕪࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ

(19)

BFA/㯤య㠃✚ẚࡣ Day 7 ࡟࠾࠸࡚ཷ⫾⩌ࡀ୙ཷ⫾⩌࡟ẚ㍑ࡋ࡚᭷ព࡟㧗࠸್ࢆ

♧ࡋࡓ㸦P < 0.01㸧ࠋBFA/㯤య⤌⧊㠃✚ẚࡣヨ㦂ᮇ㛫୰ཷ⫾⩌ࡀ୙ཷ⫾⩌࡟ẚ㍑

ࡋ࡚᭷ព࡟㧗ࡃ᥎⛣ࡋࡓ㸦P < 0.01㸧ࠋ

⮬↛Ⓨ᝟⩌࠾ࡼࡧྠᮇ໬Ⓨ᝟⩌࡟࠾ࡅࡿBFA ࠾ࡼࡧ TAMV ࡢ᥎⛣ࢆ Fig.

1-8. A ࡜ B ࡟♧ࡋࡓࠋBFA ࠾ࡼࡧ TAMV ࡣྠᵝ࡟᥎⛣ࡋ㸪୧⩌㛫࡛᭷ព࡞ᕪࡣ ㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ 㯤యࠊ୺ᖍ༸⬊࠾ࡼࡧ⾑₢P4⃰ᗘࡢ᥎⛣  ཷ⫾⩌࠾ࡼࡧ୙ཷ⫾⩌࡟࠾ࡅࡿ㸪㯤య㠃✚㸪㯤య⤌⧊㠃✚㸪୺ᖍ༸⬊㠃✚࠾ࡼ ࡧ⾑₢P4⃰ᗘࡢ᥎⛣ࢆFig. 1-9.࡟♧ࡋࡓࠋヨ㦂ᮇ㛫୰ḟ➨࡟ቑຍࡋ㸪ཷ⫾⩌࠾ ࡼࡧ୙ཷ⫾⩌࡛᭷ព࡞ᕪࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ ⮬↛Ⓨ᝟⩌࠾ࡼࡧྠᮇ໬Ⓨ᝟⩌࡟࠾ࡅࡿ㸪㯤య㠃✚㸪㯤య⤌⧊㠃✚㸪୺ᖍ༸⬊ 㠃✚࠾ࡼࡧ⾑₢ P4⃰ᗘࡢ᥎⛣ࢆ Fig. 1-8. C-F ࡟♧ࡋࡓࠋ୧⩌㛫࡛ྠᵝ࡟᥎⛣ ࡋ㸪᭷ព࡞ᕪࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ ୺ᖍ༸⬊ࡢྠഃ⩌࡜ᑐഃ⩌࡟࠾ࡅࡿ୺ᖍ༸⬊㠃✚㸪㯤య㠃✚㸪㯤య⤌⧊㠃✚㸪 BFA㸪TAMV㸪⾑₢ P4⃰ᗘ࠾ࡼࡧཷ⫾⋡ࡢẚ㍑ࢆ Table1-3.࡟♧ࡋࡓࠋ㯤య㠃 ✚㸪㯤య⤌⧊㠃✚㸪BFA㸪TAMV㸪⾑₢ P4⃰ᗘ࠾ࡼࡧཷ⫾⋡࡟ࡣ୧⩌㛫࡛᭷ព ࡞ᕪࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ୺ᖍ༸⬊㠃✚ࡣྠഃ⩌ࡀᑐഃ⩌࡟ẚ㍑ࡋ࡚᭷ព࡟㧗 ࠸್ࢆ♧ࡋࡓ㸦P < 0.05㸧ࠋ 㯤య⾑ὶ㔞࡟ࡼࡿዷፎண   ཷ⫾ࡢᡂྰࢆᚑᒓኚᩘ㸪10 ᅉᏊ㸦ᖺ㱋㸪⏘Ṕ㸪ศፔᚋ᪥ᩘ㸪BCS㸪୺ᖍ༸⬊

(20)

ࡶࡢࢆTable 1-4.࡟♧ࡋࡓࠋDay 7 ࡟࠾࠸࡚㸪BFA ࡢࡳࢆண ᅉᏊ࡜ࡋࡓ༢ᅇ ᖐᘧࡀࡑࡢ௚ࡢ༢ᅇᖐᘧࡸ㔜ᅇᖐᘧ࡜ẚ㍑ࡋ࡚᭱ࡶඃࢀ࡚࠸ࡓࠋᚑ᮶࠿ࡽ⏝࠸

ࡽࢀ࡚ࡁࡓ㯤య㠃✚㸪㯤య⤌⧊㠃✚࠾ࡼࡧ⾑₢ P4⃰ᗘࡣዷፎண ࡟᭷⏝࡛ࡣ࡞

ࡃ㸪Day 7 ࡟࠾ࡅࡿ P್ࡣࡑࢀࡒࢀ0.458㸪0.620 ࠾ࡼࡧ 0.715 ࡛࠶ࡗࡓࠋ

 ROC ゎᯒࡢ⤖ᯝࢆ Fig. 1-10.࡟♧ࡋࡓࠋDay 7 ࡟࠾࠸࡚㸪BFA ࡀዷፎண ࡟

᭱ࡶඃࢀࡓᅉᏊ࡛࠶ࡿࡇ࡜ࡀศ࠿ࡗࡓࠋࡉࡽ࡟㸪Day 7 ࡟࠾ࡅࡿዷፎண ࡢࡓࡵ ࡢ࢝ࢵࢺ࢜ࣇ್ࡢẚ㍑ࢆTable 1-5.࡟♧ࡋࡓࠋBFA ࡢ࢝ࢵࢺ࢜ࣇ್ࢆ 0.43 cm2 ࡟タᐃࡍࡿࡇ࡜࡛㸪㧗࠸ឤᗘ㸦79.4%㸧࡜≉␗ᗘ㸦75.0%㸧ࢆྠ᫬࡟ᚓࡿࡇ࡜ࡀ ࡛ࡁࡓࠋ 1-3. ヨ㦂2㸸ET ᫬ࡢ BFA ࢆ⏝࠸ࡓཷ⬇∵㑅ᐃ᪉ἲࡢ෌⌧ᛶࡢ᳨ド 1) ᮦᩱཬࡧ᪉ἲ ౪ヨື≀ ヨ㦂1 ࡜ྠᵝ࡟㸪⮫ᗋⓗ࡟೺ᗣ࡛㸪ศፔᚋ 50 ᪥௨ୖ⤒㐣ࡋṇᖖ࡞Ⓨ᝟࿘ᮇࢆ ᭷ࡍࡿ࣍ࣝࢫࢱ࢖ࣥ✀⤒⏘∵38 㢌㸦4.02 ± 0.31 ṓ㸪 2.12 ± 0.20 ⏘㸪 ᖹᆒ s ᶆ‽ㄗᕪ㸧ࢆ౪ヨࡋࡓࠋ౪ヨ∵ࡣヨ㦂 1 ࡜ྠ୍㎰ሙ࡟࡚㣫㣴ࡉࢀ㸪㣫㣴ᙧែ࠾ ࡼࡧ⤥㣵≧ἣࡣྠᵝ࡛࠶ࡗࡓࠋBCS ࡣ Edomonson ࡽ㸦20㸧ࡢ᪉ἲ࡟ᇶ࡙ࡁⓎ ᝟᪥࡟ ᐃࡋ㸪3.41 ± 0.06㸦ᖹᆒ s ᶆ‽ㄗᕪ㸧࡛࠶ࡗࡓࠋ

(21)

࠶ࡿࡇ࡜ࢆ☜ㄆࡋET ࢆ⾜࠸㸪Day 30 ࡟⤒┤⭠㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚ዷ

ፎデ᩿ࢆ⾜ࡗࡓࠋヨ㦂2 ࡢࣉࣟࢺࢥ࣮ࣝࡢᶍᘧᅗࢆ Fig. 1-11. ࡟♧ࡋࡓࠋ

༸ᕢࡢ㉸㡢Ἴ᳨ᰝ

 Day 7 ࡟࠾ࡅࡿ㯤య┤ᚄ࠾ࡼࡧ BFA ࡣ㸪7.5MHz ࡢࣜࢽ࢔ࣉ࣮ࣟࣈࡀ௜ᒓࡋ

ࡓ⤒┤⭠㉸㡢Ἴ⏬ീデ᩿⿦⨨㸦MyLab five㸹Esaote SpA㸪Genoa㸪Italy㸧ࢆ⏝

࠸࡚color-flow Doppler mapping mode ࡟ࡼࡾほᐹࢆ⾜ࡗࡓࠋBFA ࡢ᳨ᰝ᪉ἲ

ࡣ㸪ࣉ࣮ࣟࣈࢆᡭᣦ࡜࡜ࡶ࡟┤⭠ෆ࡟ᤄධࡋ㸪㯤యࡢ᩿ᒙീࢆほᐹࡋࡓࠋ㯤య┤ ᚄࡀ᭱኱࡟࡞ࡿࡼ࠺࡞㟼Ṇ⏬ࢆグ㘓ࡋ㸪ヨ㦂 1 ࡜ྠᵝࡢ᪉ἲ࡛ BFA ࢆ⟬ฟࡋ ࡓࠋ ET ヨ㦂1 ࡜ྠᵝ࡟㸪Day 7 ࡟㯤యࢧ࢖ࢬࡀ┤ᚄ 20mm ௨ୖ࡛࠶ࡿࡇ࡜ࢆ☜ㄆࡋ ྠ୍ᢏ⾡⪅ࡀET ࢆ⾜ࡗࡓࠋ㐣๫᤼༸ㄏ㉳ฎ⨨࠾ࡼࡧ AI ࢆ⾜ࡗࡓ㯮ẟ࿴✀∵࠿

ࡽᅇ཰ࡉࢀ㸪quality grade 1 ࠾ࡼࡧ developmental stage 4 ࡢ⬇㸦᪂㩭⬇㸹n

= 18㸪෾⤖⼥ゎ⬇㸹n = 20㸧ࢆ౑⏝ࡋࡓࠋ⛣᳜ჾࡣື≀⏝ཷ⢭༸ὀධ࢝ࢸ࣮ࢸࣝ

㸦ࣔ4 ྕ㸹࣑ࢧ࣡་⛉ᕤᴗᰴᘧ఍♫㸪Ⲉᇛ㸪᪥ᮏ㸧ࢆ౑⏝ࡋ㸪㯤యഃࡢᏊᐑゅ῝

㒊࡟1 ࡘࡢ⬇ࢆ⛣᳜ࡋࡓࠋ

ዷፎデ᩿

ET ᚋ 23 ᪥ࡘࡲࡾ Day 30 ࡟ 7.5MHz ࣜࢽ࢔ࣉ࣮ࣟࣈࡀ௜ᒓࡋࡓ⤒┤⭠㉸㡢

(22)

BFA ࡢ ᐃ

 ヨ㦂 1 ࡜ྠᵝ࡟㸪㯤య⾑ὶࡣ 7.5MHz ࡢࣜࢽ࢔ࣉ࣮ࣟࣈࡀ௜ᒓࡋࡓ⤒┤⭠㉸

㡢Ἴ⏬ീデ᩿⿦⨨㸦MyLab five㸹Esaote SpA㸪Genoa㸪Italy㸧ࢆ⏝࠸࡚

color-flow Doppler mapping mode ࡟ࡼࡾほᐹࢆ⾜ࡗࡓࠋ㯤య⾑ὶࡢ᳨ᰝ᪉ἲࡣࣉࣟ ࣮ࣈࢆᡭᣦ࡜࡜ࡶ࡟┤⭠ෆ࡟ᤄධࡋ㸪㯤య࡟┤⭠ቨࢆ௓ࡋ࡚ࣉ࣮ࣟࣈࢆᐦ╔ࡉ ࡏ࡚᩿ᒙീࢆほᐹࡋࡓࠋ㯤య⾑ὶࡣ㯤య┤ᚄࡀ᭱኱࡟࡞ࡿࡼ࠺࡞㟼Ṇ⏬ࢆグ㘓

ࡋ㸪BFA ࢆ⟬ฟࡋࡓࠋBFA ࡣ㸪グ㘓ࡋࡓ⏬ീࢆࣃࢯࢥࣥෆ࡟ྲྀࡾ㎸ࡳ㸪Image

J 㸦 version 1.49 㸹 the U.S. National Institutes of Health

㸦http://imagej.nih.gov/ij/㸧㸪USA㸧ࢆ⏝࠸࡚⟬ฟࡋࡓࠋ ㄪᰝ㡯┠  ヨ㦂1 ࡛タᐃࡋࡓ BFA ࡢ࢝ࢵࢺ࢜ࣇ್ 0.43 cm2௨ୖࡢ࢘ࢩࢆ᳨ᰝ㝧ᛶ⩌㸦n = 15㸧㸪0.43 cm2ᮍ‶ࡢ࢘ࢩࢆ᳨ᰝ㝜ᛶ⩌㸦n = 23㸧࡜ࡋࡓࠋ㝧ᛶⓗ୰⋡㸦ཷ⫾ ࡍࡿ࡜ุᐃࡋࡓ࢘ࢩࡢ࠺ࡕᐇ㝿࡟ཷ⫾ࡋࡓ࢘ࢩࡢ๭ྜ㸧㸪㝜ᛶⓗ୰⋡㸦ཷ⫾ࡋ࡞ ࠸࡜ุᐃࡋࡓ࢘ࢩࡢ࠺ࡕᐇ㝿࡟ཷ⫾ࡋ࡞࠿ࡗࡓ࢘ࢩࡢ๭ྜ㸧㸪ឤᗘ㸦ཷ⫾ࡍࡿ࢘ ࢩࡢ࠺ࡕཷ⫾ࡍࡿ࡜ุᐃ࡛ࡁࡿ๭ྜ㸧࠾ࡼࡧ≉␗ᗘ㸦ཷ⫾ࡋ࡞࠸࢘ࢩࡢ࠺ࡕཷ⫾ ࡋ࡞࠸࡜ุᐃ࡛ࡁࡿ๭ྜ㸧ࢆ⟬ฟࡋ㸪ヨ㦂1 ࡢ⤖ᯝ࡜ẚ㍑ࡋࡓࠋ 2) ⤖ᯝ  ౪ヨ∵38 㢌୰ 16 㢌ࡀཷ⫾ࡋ㸪ཷ⫾⋡ࡣ 42.1%࡛࠶ࡗࡓࠋヨ㦂 1 ࡛タᐃࡋࡓ

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3 㢌㸪୙ཷ⫾࡛࠶ࡗࡓ࢘ࢩࡣ 20 㢌࡛࠶ࡗࡓࠋ௨ୖࡢࡇ࡜࠿ࡽ㸪㝧ᛶⓗ୰⋡ 86.7 % 㸦13/15㸧㸪㝜ᛶⓗ୰⋡ 87.0 %㸦20/23㸧㸪ឤᗘ 81.3 %㸦13/16㸧࠾ࡼࡧ≉␗ᗘ 90.9 % 㸦20/22㸧࡛࠶ࡗࡓ㸦Table 1-6.㸧ࠋ 1-4. ⪃ᐹ ᮏ❶࡛ࡣ㸪ཷ⫾⩌࡜୙ཷ⫾⩌࡟࠾࠸࡚ ET ๓࠿ࡽ ET ᫬ࡢ㯤య⾑ὶ㔞ࡢ᥎⛣ࢆ ẚ㍑ࡋࡓࠋཷ⫾⩌ࡣ୙ཷ⫾⩌࡟ẚ㍑ࡋ࡚㸪Day 7 ࡟࠾࠸࡚ BFA㸪BFA/㯤య㠃✚ ẚ࠾ࡼࡧBFA/㯤య⤌⧊㠃✚ẚࡀ᭷ព࡟㧗࠸ࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋࡲࡓ㸪Day 7 ࡟࠾࠸࡚ࡣᚑ᮶ࡢ᪉ἲ࡛࠶ࡿ㯤య㠃✚㸪⾑₢ P4⃰ᗘࡸTAMV ࡜ẚ㍑ࡋ࡚ BFA ࡀዷፎண ࡟᭷⏝࡛࠶ࡾ㸪࢝ࢵࢺ࢜ࣇ್ࢆ 0.43cm2࡟タᐃࡍࡿࡇ࡜࡛௚ࡢᅉᏊ ࡟ẚ㍑ࡋ࡚㧗࠸ឤᗘ࡜≉␗ᗘࢆྠ᫬࡟ᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋឤᗘࡣཷ⫾ࡍࡿ࢘ࢩ ࡢ࠺ࡕཷ⫾ࡍࡿ࡜ุᐃ࡛ࡁࡿ๭ྜ㸪≉␗ᗘࡣཷ⫾ࡋ࡞࠸࢘ࢩࡢ࠺ࡕཷ⫾ࡋ࡞࠸ ࡜ุᐃ࡛ࡁࡿ๭ྜ࡛࠶ࡾ㸪ឤᗘ࡜≉␗ᗘࡀ࡜ࡶ࡟㧗࠸࡜⢭ᗘࡀ㧗࠸࡜ゝ࠺ࡇ࡜ ࡀ࡛ࡁࡿࠋᚑࡗ࡚㸪࣮࢝ࣛࢻࣉࣛἲ࡟ࡼࡿBFA ࡢ ᐃࡣཷ⬇∵ࡢཷ⫾ᛶࡢホ౯ ࡸཷ⬇∵ࡢ㑅ᐃ࡟᭷⏝࡛࠶ࡿ࡜⪃࠼ࡽࢀࡓࠋ ヨ㦂 1 ࡼࡾ㸪⮬↛Ⓨ᝟⩌࠾ࡼࡧྠᮇ໬Ⓨ᝟⩌࡟࠾࠸࡚⛣᳜⋡࡜ཷ⫾⋡࡟᭷ព ࡞ᕪࡀㄆࡵࡽࢀ࡞࠿ࡗࡓࠋࡲࡓ㸪୍⯡࡟᪂㩭⬇࡟ẚ㍑ࡋ࡚෾⤖⼥ゎ⬇ࡢཷ⫾⋡ࡣ ప࠸࡜ࡉࢀ࡚࠸ࡿ㸦80㸧ࡀ㸪ᮏ❶࡟࠾࠸࡚᪂㩭⬇࠾ࡼࡧ෾⤖⼥ゎ⬇࡟࠾࠸࡚ཷ⫾ ⋡࡟᭷ព࡞ᕪࡀㄆࡵࡽࢀ࡞࠿ࡗࡓࠋࡇࡢࡇ࡜࠿ࡽ㸪Ⓨ᝟ࡢ✀㢮ࡸ⬇ࡢ✀㢮࡟ࡼࡿ ཷ⫾࡬ࡢᙳ㡪ࡣ࡞࠸࡜⪃࠼ࡽࢀࡓࠋ 㐣ཤࡢ◊✲࠿ࡽ㸪㯤య㠃✚㸪BFA ࠾ࡼࡧ⾑₢ P4⃰ᗘࡣ㯤యࡢⓎ⫱࡟క࠸ቑຍ ࡋ㸪㯤య㏥⾜࡟క࠸ῶᑡࡍࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗ࡚࠸ࡿ㸦30㸪49㸪76㸧ࠋࡲࡓ㸪

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P4⃰ᗘࡘࡲࡾ㯤యᶵ⬟ࡢホ౯࡟᭷⏝࡛࠶ࡿ࡜♧၀ࡉࢀ࡚࠸ࡿ㸦30㸧ࠋᮏ❶࡟࠾࠸ ࡚㸪㯤య㠃✚㸪㯤య⤌⧊㠃✚㸪⾑₢ P4⃰ᗘ㸪BFA ࠾ࡼࡧ TAMV ࡣ㸪Ⓨ᝟ྠᮇ ໬᪉ἲࡸཷ⫾࣭୙ཷ⫾࡟㛵ࢃࡽࡎDay 7 ࡲ࡛ቑຍࡋࡓࠋཷ⫾⩌ࡣ୙ཷ⫾⩌࡟ẚ ㍑ࡋ࡚㸪㯤య㠃✚㸪㯤య⤌⧊㠃✚㸪⾑₢P4⃰ᗘ࠾ࡼࡧTAMV ࡟ᕪࡀㄆࡵࡽࢀ࡞ ࠿ࡗࡓࡀ㸪BFA ࡣ Day 7 ࡟᭷ព࡟㧗࠸್ࢆ♧ࡋࡓࠋࡲࡓ㸪ࣟࢪࢫࢸ࢕ࢵࢡᅇᖐ ศᯒࡢ⤖ᯝ࠿ࡽ㸪ᚑ᮶࠿ࡽཷ⬇∵ࡢ㑅ᐃ࡟⏝࠸ࡽࢀ࡚ࡁࡓ㯤య㠃✚㸪୺ᖍ༸⬊㠃 ✚ࡸ⾑₢P4⃰ᗘ࡛ࡣ࡞ࡃ㸪BFA ࡀཷ⫾࡟ᙳ㡪ࢆཬࡰࡍᅉᏊ࡛࠶ࡿࡇ࡜ࡀ᫂ࡽ࠿ ࡜࡞ࡗࡓࠋP4 ࡣ㯤య⣽⬊ࡼࡾศἪࡉࢀ㸪╔ᗋ࡟ྥࡅࡓᏊᐑ⎔ቃࡢㄪᩚ࡟㔜せ࡞ ᙺ๭ࢆᣢࡕ㸦24㸧㸪⬇ࡢ⏕Ꮡ࡟ᚲせ୙ྍḞ࡛࠶ࡿ㸦15㸪55㸧ࠋP4ࡢ⏕ᡂࡸ඲㌟ᚠ ⎔࡬ࡢᨺฟ࡟ࡣ㯤యࡢ⾑⟶ᙧᡂࡀᚲせ࡛࠶ࡿ㸦11㸪97㸧ࠋࡲࡓ㸪㯤యࡢ࠶ࡿ༸ᕢ ࡜ྠഃࡢ༸⟶ࡸᏊᐑゅࡢP4⃰ᗘࡣᑐഃ࡟ẚ㍑ࡋ࡚㧗࠸ࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ㸦95㸪 96㸧ࠋࡘࡲࡾ㸪⏕యෆ࡛ P4ࡣ୍ᐃࡢ⃰ᗘ࡛ศᕸࡋ࡚࠾ࡽࡎ㸪඲㌟ᚠ⎔࡟஌ࡽࡎ⾑ ⟶ࢆ௓ࡋ࡚༸ᕢ࡜Ꮚᐑ㛫࡛ᒁᡤᚠ⎔ࡍࡿ P4ࡀᏑᅾࡍࡿ࡜⪃࠼ࡽࢀ࡚࠸ࡿ㸦95㸪 96㸧ࠋᮏ❶࡟࠾࠸࡚㸪ཷ⫾⩌࡜୙ཷ⫾⩌࡛⾑₢ P4⃰ᗘ࡟ᕪࡀㄆࡵࡽࢀࡎ㸪Day 7 ࡟࠾࠸࡚ཷ⫾⩌ࡢBFA ࡀ୙ཷ⫾⩌࡟ẚ㍑ࡋ࡚᭷ព࡟㧗࠸ࡇ࡜ࡀࢃ࠿ࡗࡓࠋࡇࡢ ࡇ࡜࠿ࡽ㸪ཷ⫾⩌࡟࠾ࡅࡿ㯤యࡢ㧗࠸⾑⟶ᙧᡂࡘࡲࡾάⓎ࡞⾑ὶࡀ㸪㯤య࡬ࡢᰤ 㣴ࡸ P4ࡢᇶ㉁ࡢ౪⤥㔞ࢆቑຍࡋ㸪ᒁᡤᚠ⎔ࢆ௓ࡋ࡚㯤యഃࡢᏊᐑゅࡢ P4⃰ᗘ ࢆቑຍࡉࡏࡿࡢ࡛ࡣ࡞࠸࠿࡜⪃࠼ࡽࢀࡓࠋᚑࡗ࡚㸪㯤యഃࡘࡲࡾ⬇ࢆ⛣᳜ࡍࡿᏊ ᐑゅࡢP4⃰ᗘࡀቑຍࡍࡿࡇ࡜࡛⬇ࡢ⏕Ꮡࡸ╔ᗋࡀᨵၿࡋࡓ࡜᥎ ࡉࢀࡿࠋ  ヨ㦂1 ࡼࡾ㸪ཷ⫾⩌࡜୙ཷ⫾⩌ࡢ㯤య㠃✚㸪㯤య⤌⧊㠃✚࠾ࡼࡧ⾑₢ P4⃰ᗘ ࡟ᕪࡀㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ㐣ཤࡢሗ࿌࠿ࡽ㸪࣍ࣝࢫࢱ࢖ࣥ✀⤒⏘∵ࡢ Day 7 ࡢ

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P4 ⃰ᗘࡢ᥎⛣࡟ᕪࡀㄆࡵࡽࢀ࡞࠿ࡗࡓ࡜᥎ ࡉࢀࡓࠋࡲࡓ㸪୺ᖍ༸⬊㠃✚࡟ࡘ ࠸࡚ࡶཷ⫾⩌࡜୙ཷ⫾⩌࡛ᕪࡀㄆࡵࡽࢀࡎ㸪ࣟࢪࢫࢸ࢕ࢵࢡᅇᖐศᯒࡢ⤖ᯝ࠿ ࡽࡶ୺ᖍ༸⬊㠃✚ࡣཷ⫾࡟ᙳ㡪ࡋ࡞࠸ࡇ࡜ࡀ♧ࡉࢀࡓࠋET ᫬ࡢ୺ᖍ༸⬊㠃✚࡜ ཷ⫾ᛶ࡟㛵ࡋ࡚ࡣᵝࠎ࡞ሗ࿌ࡀ࡞ࡉࢀ࡚࠸ࡿ㸦47㸪56㸪57㸧ࠋ୺ᖍ༸⬊㠃✚ࡸ⾑ ₢ E2⃰ᗘࡀཷ⫾⋡࡟ᙳ㡪ࢆཬࡰࡋ㸪୺ᖍ༸⬊㠃✚ࡀ኱ࡁࡃ⾑₢ E2⃰ᗘࡀ㧗࠸ ࡜ཷ⫾⋡ࡀపୗࡍࡿ࡜࠸࠺ሗ࿌㸦47㸪57㸧࡜ཷ⫾࡟ᙳ㡪ࢆ୚࠼࡞࠸࡜ࡍࡿሗ࿌ ࡶ࠶ࡿ㸦56㸧ࠋ㏻ᖖ㸪࢘ࢩࡢⓎ᝟࿘ᮇ࡟࠾࠸࡚༸ᕢෆ࡛ࡣ 2㸫3 ᅇࡢ༸⬊⩌ࡢⓎ ⫱ࡀほᐹࡉࢀ㸪ࡑࢀࡒࢀࡢ༸⬊⩌࠿ࡽ᤼༸࡟⮳ࡽ࡞࠸༸⬊ࡀ 1㸫2 ಶⓎ⫱ࡍࡿ 㸦71㸪78㸧ࠋࡘࡲࡾ㸪Ⓨ᝟࿘ᮇࢆ㏻ࡌ࡚㯤య࡟ඹᏑࡍࡿ༸⬊ࡀほᐹࡉࢀࡿ㸦71㸧ࠋ ࡲࡓ㸪Ⓨ᝟࠿ࡽ6㸫7 ᪥ᚋ࡟➨ 1 ༸⬊Ἴ୺ᖍ༸⬊ࡢ┤ᚄࡣ 12.0㸫15.0 mm ࡟㐩 ࡋ㸪ࡑࢀ࡟క࠸⾑୰E2⃰ᗘࡶୖ᪼ࡍࡿ㸦5㸪71㸧ࠋᚑࡗ࡚㸪ET ᫬࡟┤ᚄ 10mm ๓ᚋࡢ୺ᖍ༸⬊ࡀඹᏑࡍࡿࡇ࡜ࡣṇᖖ࡛࠶ࡾ㸪ᮏ❶ࡢ⤖ᯝ࠿ࡽ㸪Day 7 ࡢ㯤య┤ ᚄࡀ20 mm ௨ୖࡢ∵ࢆཷ⬇∵࡜ࡋ࡚㑅ᢥࡋࡓሙྜ㸪୺ᖍ༸⬊㠃✚ࡣཷ⫾࡟ᙳ㡪 ࡏࡎ㸪ཷ⫾ᛶண ࡟ࡣ᭷⏝࡛ࡣ࡞࠸ࡇ࡜ࡀ♧ࡉࢀࡓࠋࡲࡓ㸪Miura ࡽ㸦51㸧ࡣ AI ᚋࡢ➨ 1 ༸⬊Ἴ୺ᖍ༸⬊ࡀ㯤యࡢᏑᅾࡍࡿ༸ᕢ࡜ྠഃ࡟ඹᏑࡋ࡚࠸ࡿ࢘ࢩࡣ㸪 ᑐഃ࡟Ꮡᅾࡋ࡚࠸ࡿ࢘ࢩ࡟ẚ㍑ࡋ࡚㸪༸⬊┤ᚄࡀ኱ࡁࡃཷ⫾⋡ࡀప࠸࡜ሗ࿌ࡋ ࡚࠸ࡿࠋᮏ❶࡛ࡣ㸪ྠഃ⩌ࡣᑐഃ⩌࡟ẚ㍑ࡋ࡚୺ᖍ༸⬊㠃✚ࡣ᭷ព࡟㧗࠸್ࢆ♧ ࡋࡓࡀ㸪ཷ⫾⋡࡟ࡣᕪࡀㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ୺ᖍ༸⬊࠿ࡽ⏘⏕ࡉࢀࡿE2ࡀᒁᡤ ᚠ⎔࡟ࡼࡗ࡚ྠഃࡢᏊᐑࡸ༸⟶࡟ᙳ㡪ࢆ୚࠼ࡿࡇ࡜࡛ AI ࡢཷ⫾⋡ࡀపୗࡍࡿ ࡜⪃࠼ࡽࢀ࡚࠸ࡿ㸦51㸧ࠋᮏ❶࡛ࡣཷ⫾⋡࡟ᕪࡀㄆࡵࡽࢀ࡞࠿ࡗࡓࡇ࡜࠿ࡽ㸪୺ ᖍ༸⬊࠿ࡽ⏘⏕ࡉࢀࡿ E2࡟ࡼࡾᙳ㡪ࢆཷࡅࡿࡢࡣ Day 7 ௨๓ࡢ⬇Ⓨ⏕ึᮇ࡟ 㝈ᐃࡉࢀࡿࡢ࡛ࡣ࡞࠸࠿࡜᥎ ࡋࡓࠋ

(26)

㝧ᛶ⩌ࡣ15 㢌㸪0.43 cm2ᮍ‶ࡢ᳨ᰝ㝜ᛶ⩌ࡣ23 㢌࡛࠶ࡗࡓࠋዷፎデ᩿ࡢ⤖ᯝ㸪 ヨ㦂 1 ࡜ྠᵝ࡟㧗࠸ឤᗘ࡜≉␗ᗘࢆྠ᫬࡟ᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡇࡢࡇ࡜࠿ࡽ㸪 ヨ㦂1 ࡛♧ࡋࡓ BFA ࡢ࢝ࢵࢺ࢜ࣇ್ࡣ㸪ཷ⫾ᛶண ࡟᭷⏝࡛࠶ࡾ෌⌧ᛶࡀ㧗࠸ ࡇ࡜ࡀ♧ࡉࢀࡓࠋ ௨ୖࡢࡇ࡜࠿ࡽ㸪ET ๓ࡢཷ⫾⩌࡜୙ཷ⫾⩌ࡢ㯤య㠃✚㸪㯤య⤌⧊㠃✚㸪୺ᖍ ༸⬊㠃✚㸪BFA㸪TAMV ࠾ࡼࡧ⾑₢ P4⃰ᗘࡢ᥎⛣ࢆẚ㍑ࡋ㸪ዷፎண ࡟᭷⏝࡞ ᅉᏊࢆゎᯒࡋࡓ࡜ࡇࢁ㸪ཷ⫾⩌ࡢDay 7 ࡟࠾ࡅࡿ BFA ࡀ୙ཷ⫾⩌࡟ẚ㍑ࡋ࡚㧗 ࡃ㸪ዷፎண ࡟᭱ࡶ᭷⏝࡛࠶ࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋࡲࡓ㸪BFA ࡢ࢝ࢵࢺ࢜ ࣇ್ࢆ0.43 cm2࡜タᐃࡍࡿࡇ࡜࡛㧗࠸ឤᗘ࡜≉␗ᗘࢆྠ᫬࡟ᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋ 㯤యᶵ⬟ホ౯᪉ἲ࡜ࡋ࡚ᚑ᮶࠿ࡽ⏝࠸ࡽࢀ࡚࠸ࡿ⾑₢P4⃰ᗘࡢ ᐃ࡟ࡣࢥࢫࢺ ࡜᫬㛫ࡀ࠿࠿ࡿࡢ࡟ᑐࡋ㸪BFA ࡢ ᐃࡣ▷᫬㛫࡛⾜࠺ࡇ࡜ࡀྍ⬟࡛࠶ࡿࠋᚑࡗ ࡚㸪≉࡟⮫ᗋ⌧ሙ࡟࠾࠸࡚Day7 ࡢ BFA ࢆ ᐃࡍࡿࡇ࡜ࡀཷ⫾ᛶࡢண ࡘࡲࡾ ཷ⬇∵ࡢ㑅ᐃ࡟᭷⏝࡛࠶ࡿ࡜⪃࠼ࡽࢀࡓࠋ 1-5. ᑠᣓ ET ᫬࡟ཷ⬇∵ࡢ BFA ࢆホ౯ࡍࡿࡇ࡜ࡣཷ⫾ᛶࡢホ౯࡟᭷⏝࡛࠶ࡾ㸪ᚑ᮶࠿ ࡽ⏝࠸ࡽࢀ࡚࠸ࡿ㯤య㠃✚ࡸ⾑₢P4⃰ᗘࡢ ᐃ࡟ẚ㍑ࡋ࡚⢭ᗘࡀ㧗࠸ࡇ࡜ࡀ♧ ࡉࢀࡓࠋࡲࡓ㸪≉࡟⮫ᗋ⌧ሙ࡟࠾࠸࡚ࡣ⾑₢P4⃰ᗘࡢ ᐃࡣᅔ㞴࡛࠶ࡾ㸪᫬㛫 ࡜⤒㈝ࡢ࠿࠿ࡽ࡞࠸BFA ࡢ ᐃࡣཷ⬇∵ࡢ㑅ᐃ࡟᭷⏝࡛࠶ࡿ࡜⪃࠼ࡽࢀࡓࠋ

(27)

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Fig. 1-1. Schematic views of ultrasound examinations and sampling schedules. The day on which the recipient cow had been observed to be in standing estrus was considered to be Day 0. Ultrasound examination of ovaries and blood samplings (Ⴠ) were conducted on Day 3, 5, and 7. Embryo transfer (ET) and pregnancy diagnosis (PD) were conducted on Day 7 and 30, respectively.

(28)

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cows in the spontaneous estrus group (n = 34) was detected without

synchronization. Cows in the synchronized group (n = 31) were treated with the following protocol; estradiol benzoate (EB, 2 mg, i.m.) with a simultaneous

insertion of an intravaginal progesterone (P4)-releasing device containing 1.9 g of

P4(CIDR 1900) on Day –12, prostaglandin-F2α analogue (PGF2α, 500 μg, i.m.) and

CIDR 1900 removal on Day –2, and a second administration of EB (1 mg, i.m.)on Day –1. The day on which the recipient cow had been observed to be in standing estrus was considered to be Day 0.

(29)

Fig. 1-3. Image of the corpus luteum (CL) using color Doppler ultrasonography. The colored area was measured as BFA.

(30)

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Fig. 1-4. Schematic model of the corpus luteum and the spiral artery in cows illustrated by according to Yamada et al. (1995). A: The corpus luteum, B: The spiral artery. The arrow indicates the point where blood flow velocity was measured (the basement of the spiral artery).

(31)

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Fig. 1-5. Changes in the blood flow area (BFA) of the corpus luteum (A) and the time-averaged maximum velocity (TAMV) of the spiral artery (B). Black bars represent the pregnant group (n = 34). White bars show the non-pregnant group (n = 24). Data points show the mean s SEM for each day. The BFA of the pregnant group was significantly higher than those of the non-pregnant group on Day 7. The TAMV did not differ among these groups.

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Fig. 1-8. Changes in the blood flow area (BFA) (A), the time-averaged maximum

velocity (TAMV) (B), plasma P4 concentrations (C), corpus luteum (CL) area (D), CL

tissue area (E), and dominant follicle (DF) area (F). Black bars represent the spontaneous estrus group (n = 34). White bars show the synchronized estrus group (n = 31). Data points show mean s SEM for each day. There were no significant differences between the spontaneous estrus group and the synchronized estrus group.

(37)

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pregnant group (n = 34). White bars show the non-pregnant group (n = 24). Data points show the mean s SEM for each day. In both groups, these trait values gradually increased during the experimental period and did not differ between the groups.

(38)

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Fig. 1-10. Receiver operating characteristic (ROC) curves of the five pregnancy predictors on Day 7. The horizontal and vertical axes are a false positive rate (1 - specificity) and sensitivity, respectively. Thus, the upper left corner is the ideal point of 100% sensitivity and 100% specificity. The BFA provided the most appropriate prediction of pregnancy among the other four single predictors.

Abbreviations: BFA; blood flow area, TAMV; time-averaged maximum velocity, CL; corpus luteum.

(41)

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(43)

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D 3RVLWLYH %)$ t  FP 1HJDWLYH %)$   FP

(44)

➨2❶࣍ࣝࢫࢱ࢖ࣥ✀ཷ⬇∵࡟࠾ࡅࡿ ET ᚋࡢ㯤య⾑ὶ㔞ࢆ⏝࠸ࡓ㉸᪩ᮇዷፎデ᩿ 2-1. ᗎㄽ ࢘ࢩ࡟࠾ࡅࡿዷፎデ᩿ࡣ㸪┤⭠᳨ᰝ࡟ࡼࡗ࡚⾜࠺ሙྜࡣAI ᚋ 40 ᪥௨㝆࡟Ꮚᐑゅ ࡢኴࡉࡸ⫾⭷ࢫࣜࢵࣉࡢ᭷↓࡟ᇶ࡙࠸࡚⾜ࢃࢀ࡚ࡁࡓ㸦90㸧ࠋ㏆ᖺ㸪ᦠᖏᆺ㉸㡢Ἴデ ᩿⿦⨨ࡀ୍⯡ⓗ࡟ᬑཬࡋ࡚ࡁࡓࡇ࡜࠿ࡽ㸪AI ᚋ 25㸫29 ᪥௨㝆࡟㯤యࡢᏑᅾࡸ⫾Ꮚ ࠾ࡼࡧ⫾Ꮚᚰᢿࡢ☜ㄆ࡟ᇶ࡙࠸࡚᪩ᮇዷፎデ᩿ࡀ⾜ࢃࢀࡿࡼ࠺࡟࡞ࡗࡓ㸦26㸪87㸧ࠋ ࡋ࠿ࡋ㸪࢘ࢩࡢⓎ᝟࿘ᮇࡣᖹᆒ 21 ᪥࡛࠶ࡾ㸪⌧ᅾࡢ᪩ᮇዷፎデ᩿࡛ࡣ㸪୙ዷ࡛࠶ ࡗࡓሙྜ࡟ḟᅇࡢⓎ᝟ࢆぢⴠ࡜ࡍ࠿Ⓨぢࡀ㐜ࢀࡿྍ⬟ᛶࡀ࠶ࡿࠋࡇࡢࡇ࡜ࡀ㸪ᤵ⢭ ⋡ࡸཷ⫾⋡ࡢపୗࢆᣍ࠸࡚࠸ࡿࠋᚑࡗ࡚㸪Ⓨ᝟࿘ᮇࡢ 21 ᪥ࡼࡾ๓ࡢዷፎデ᩿㸦㉸ ᪩ᮇዷፎデ᩿㸧᪉ἲࢆ☜❧ࡍࡿࡇ࡜ࡀ࡛ࡁࢀࡤⓎ᝟Ⓨぢ⋡㸪ᤵ⢭⋡࠾ࡼࡧཷ⫾⋡ࡢ ྥୖ࡟⧅ࡀࡿࡶࡢ࡜⪃࠼ࡽࢀࡿࠋ ࡑࡇ࡛㸪ᮏ❶࡛ࡣ㸪ET ࠿ࡽ 7 ᪥ᚋࡘࡲࡾ Day 14 ࡢཷ⬇∵ࡢ㯤య⾑ὶ㔞ࢆゎᯒ ࡋ㸪ཷ⫾∵࡜୙ཷ⫾∵࡟࠾ࡅࡿ㯤యࡢᙧែ࡜⾑ὶ㔞ࡢẚ㍑ࢆ⾜࠸㸪ET ᚋࡢ㯤య⾑ ὶ㔞ࡀ㉸᪩ᮇዷፎデ᩿࡟᭷⏝࡛࠶ࡿ࠿ࢆ᳨ウࡋࡓࠋ 2-2. ᮦᩱཬࡧ᪉ἲ ౪ヨື≀  ➨1-2. ❶࡛ ET ࢆ⾜ࡗࡓ 58 㢌ࢆ౪ヨࡋࡓࠋ

(45)

㯤య⤌⧊㠃✚㸪୺ᖍ༸⬊㠃✚㸪BFA ࠾ࡼࡧࡽࡏࢇື⬦ࡢ㯤యഃᇶ㒊ࡢ TAMV ࢆ  ᐃࡋࡓࠋࡲࡓ㸪㉸㡢Ἴ᳨ᰝ᫬࡟ṇ୰ᑿ㟼⬦ࡼࡾ᥇⾑ࢆ⾜࠸㸪⾑₢P4⃰ᗘࢆ ᐃࡋࡓࠋ Day 30 ࡟㉸㡢Ἴ⏬ീデ᩿⿦⨨ࢆ⏝࠸࡚ዷፎデ᩿ࢆ⾜ࡗࡓࠋࣉࣟࢺࢥ࣮ࣝࡢᶍᘧᅗ ࢆFig. 2-1.࡟♧ࡋࡓࠋ ET  ➨ 1-2. ❶࡜ྠᵝ࡟㸪Day 7 ࡟㯤యࢧ࢖ࢬࡀ┤ᚄ 20mm ௨ୖ࡛࠶ࡿ 58 㢌࡟ྠ୍ ᢏ⾡⪅ࡀ ET ࢆ⾜ࡗࡓࠋ㐣๫᤼༸ㄏ㉳ฎ⨨࠾ࡼࡧ AI ࢆ⾜ࡗࡓ㯮ẟ࿴✀∵࠿ࡽᅇ཰

ࡉࢀ㸪quality grade 1 ࠾ࡼࡧ developmental stage 4 ࡢ⬇㸦᪂㩭⬇㸹n = 22㸪෾⤖

⼥ゎ⬇㸹n = 36㸧ࢆ౑⏝ࡋࡓࠋ⛣᳜ჾࡣື≀⏝ཷ⢭༸ὀධ࢝ࢸ࣮ࢸࣝ㸦ࣔ 4 ྕ㸹࣑

ࢧ࣡་⛉ᕤᴗᰴᘧ఍♫㸪Ⲉᇛ㸪᪥ᮏ㸧ࢆ౑⏝ࡋ㸪㯤యഃࡢᏊᐑゅ῝㒊࡟1 ࡘࡢ⬇ࢆ

⛣᳜ࡋࡓࠋ

ዷፎデ᩿

 ET ᚋ 23 ᪥ࡘࡲࡾ Day 30 ࡟㸪7.5MHz ࣜࢽ࢔ࣉ࣮ࣟࣈࡀ௜ᒓࡋࡓ⤒┤⭠㉸㡢Ἴ

⏬ീデ᩿⿦⨨㸦Tringa V linear㸹Esaote SpA㸪Genoa㸪Italy㸧ࢆ⏝࠸࡚⫾ᏊࡢᏑᅾ

࠾ࡼࡧᚰᢿࢆᇶ‽࡜ࡋ࡚⾜ࡗࡓࠋ

༸ᕢࡢ㉸㡢Ἴ᳨ᰝ

 ㉸㡢Ἴ᳨ᰝࡣ Day 14 ࡟⾜࠸㸪㯤య࡜୺ᖍ༸⬊ࡢᙧែࡣ㸪7.5MHz ࡢࣜࢽ࢔ࣉࣟ

࣮ࣈࡀ௜ᒓࡋࡓ⤒┤⭠㉸㡢Ἴ⏬ീデ᩿⿦⨨㸦MyLab five㸹Esaote SpA㸪Genoa㸪

(46)

㸦MyLab five㸹Esaote SpA㸪Genoa㸪Italy㸧ࢆ⏝࠸࡚ color-flow Doppler mapping mode ࡟ࡼࡾほᐹࢆ⾜ࡗࡓࠋ㯤య┤ᚄࡀ᭱኱࡟࡞ࡿࡼ࠺࡞㟼Ṇ⏬ࢆグ㘓ࡋ㸪BFA ࢆ ⟬ฟࡋࡓࠋ  㯤య㠃✚㸪㯤యෆ⭍㠃✚㸪୺ᖍ༸⬊㠃✚࠾ࡼࡧBFA ࡣ㸪Image J ࢆ⏝࠸࡚⟬ฟࡋ ࡓࠋ㯤య⤌⧊㠃✚ࡣ㸪㯤య㠃✚࠿ࡽ㯤యෆ⭍㠃✚ࢆᕪࡋᘬ࠸࡚⟬ฟࡋࡓࠋ  ༸ᕢື⬦࠿ࡽศᒱࡋ༸ᕢᐇ㉁ෆࢆ㉮⾜ࡍࡿࡽࡏࢇື⬦ࡢ㯤యഃᇶ㒊ࡢ⾑ὶ㏿ᗘ ࢆ ᐃࡋ㸪TAMV ࢆ⟬ฟࡋࡓࠋ ⾑₢P4⃰ᗘࡢ ᐃ  Day 14 ࡟ 21G ᥇⾑㔪࡜࣊ࣃࣜࣥຍ┿✵᥇⾑⟶㸦࣋ࣀࢪ࢙ࢡࢺϩ┿✵᥇⾑⟶㸪 TERUMO㸪ᮾி㸪᪥ᮏ㸧ࢆ⏝࠸㸪ᑿ㟼⬦ࡼࡾ 10ml ࡢ᥇⾑ࢆ⾜ࡗࡓࠋ᥇⾑ᚋ┤ࡕ࡟ ị෭ࡋ㸪30 ศ௨ෆ࡟ 3,000g㸪15 ศ㛫㐲ᚰศ㞳ᚋ㸪P4 ᐃࡲ࡛㸫30Υ࡛෾⤖ಖᏑࡋ ࡓࠋ ᐃ┤๓࡟ᐊ ࡟࡚⼥ゎࡋ㸪➨1-2. ❶࡜ྠᵝ࡟ EIA ἲ࡟ࡼࡾ⾑₢ P4⃰ᗘࢆ  ᐃࡋࡓࠋ ⤫ィฎ⌮  ⤖ᯝࡣࡍ࡭࡚ᖹᆒ್ s ᶆ‽ㄗᕪ࡛♧ࡋࡓࠋཷ⫾⩌࡜୙ཷ⫾⩌࡟࠾࠸࡚㸪㯤య㠃

✚㸪㯤య⤌⧊㠃✚㸪୺ᖍ༸⬊㠃✚㸪BFA㸪TAMV㸪Day 7 ࢆᇶ‽࡜ࡋࡓ BFA ࡜ TAMV

ࡢ┦ᑐⓗኚ໬࠾ࡼࡧ⾑₢P4⃰ᗘࡢᖹᆒ್ࢆẚ㍑ࡍࡿࡓࡵ㸪Student ࡢ t ᳨ᐃࢆ⾜ࡗ

ࡓࠋ⤫ィฎ⌮࡟ࡣ⤫ィฎ⌮ࢯࣇࢺ࢙࢘࢔SPSS 13㸦SPSS Japan㸪ᮾி㸪᪥ᮏ㸧 ࢆ

(47)

㯤య⤌⧊㠃✚㸪BFA㸪TAMV ࠾ࡼࡧ⾑₢ P4⃰ᗘ㸧ࢆ⏝࠸ࡓࠋ

ᚑ᮶࠿ࡽ⏝࠸ࡽࢀ࡚࠸ࡿ3 ࡘࡢዷፎண ᅉᏊ㸦㯤య㠃✚㸪㯤య⤌⧊㠃✚࠾ࡼࡧ⾑

₢ P4⃰ᗘ㸧࡜᪂ࡋ࠸ᅉᏊ㸦BFA ࠾ࡼࡧ TAMV㸧ࡢዷፎண ⢭ᗘࡢẚ㍑࡜࢝ࢵࢺ࢜

ࣇ್ࢆ⟬ฟࡍࡿࡓࡵ࡟㸪ROC ゎᯒࢆ⾜ࡗࡓࠋROC ᭤⥺ࢆసᡂᚋ㸪Perkins ࡽ㸦61㸧

ࡢሗ࿌࡟ᇶ࡙ࡁឤᗘ࡜≉␗ᗘࡀ 100%࡛࠶ࡿᕥୖ㝮࡜ࡢ㊥㞳ࢆゎᯒࡋ㸪ࡑࡢ㊥㞳ࡀ

᭱ᑠ࡜࡞ࡿⅬࢆ᭱㐺࡞࢝ࢵࢺ࢜ࣇ್࡜Ỵᐃࡋࡓࠋ 

2-3. ⤖ᯝ

㯤య⾑ὶ㔞ࡢẚ㍑

BFA ࡢẚ㍑ࢆ Fig. 2-2. A ࡟♧ࡋࡓࠋDay 14 ࡟࠾ࡅࡿ BFA ࡣཷ⫾⩌ࡀ୙ཷ⫾⩌

࡟ẚ㍑ࡋ࡚᭷ព࡟㧗࠸್ࢆ♧ࡋࡓ㸦P < 0.01㸧ࠋ

TAMV ࡢẚ㍑ࢆ Fig. 2-2. B ࡟♧ࡋࡓࠋDay 14 ࡟࠾ࡅࡿ TAMV ࡣཷ⫾⩌ࡀ୙ཷ

⫾⩌࡟ẚ㍑ࡋ࡚᭷ព࡟㧗࠸್ࢆ♧ࡋࡓ㸦P < 0.01㸧ࠋ

Day 7 ࢆᇶ‽࡜ࡋࡓ BFA ࡜ TAMV ࡢ┦ᑐⓗኚ໬ࢆ Fig. 2-3.࡟♧ࡋࡓࠋBFA ࡣ୧

⩌㛫࡛᭷ព࡞ᕪࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋTAMV ࡣཷ⫾⩌ࡀ୙ཷ⫾⩌ẚ㍑ࡋ࡚㧗࠸ഴྥ ࢆ♧ࡋࡓ㸦P < 0.1㸧ࠋ 㯤య㠃✚ࠊ୺ᖍ༸⬊㠃✚࠾ࡼࡧ⾑₢P4⃰ᗘࡢẚ㍑  ཷ⫾⩌࠾ࡼࡧ୙ཷ⫾⩌࡟࠾ࡅࡿ㸪㯤య㠃✚㸪㯤య⤌⧊㠃✚㸪୺ᖍ༸⬊㠃✚࠾ࡼࡧ ⾑₢ P4⃰ᗘࡢẚ㍑ࢆ Fig. 2-4.࡟♧ࡋࡓࠋཷ⫾⩌࠾ࡼࡧ୙ཷ⫾⩌࡛඲࡚ࡢ㡯┠࡟᭷ ព࡞ᕪࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ

(48)

㯤య⾑ὶ㔞࡟ࡼࡿዷፎண 

 ཷ⫾ࡢᡂྰࢆᚑᒓኚᩘ㸪10 ᅉᏊ㸦ᖺ㱋㸪⏘Ṕ㸪ศፔᚋ᪥ᩘ㸪BCS㸪୺ᖍ༸⬊㠃✚㸪

㯤య㠃✚㸪㯤య⤌⧊㠃✚㸪BFA㸪TAMV ࠾ࡼࡧ⾑₢ P4⃰ᗘ㸧ࢆ⊂❧ኚᩘ࡜ࡋࡓ㸪

512 ㏻ࡾࡢࣟࢪࢫࢸ࢕ࢵࢡᅇᖐᘧࢆẚ㍑ࡋ㸪࣋࢖ࢬ᝟ሗ㔞ᇶ‽ࡀ᭱ᑠࡢࡶࡢࢆ Table

2-1.࡟♧ࡋࡓࠋDay 14 ࡟࠾࠸࡚ BFA㸦P < 0.001㸧࡜ TAMV㸦P = 0.002㸧ࡀඃࢀ

ࡓዷፎண ᅉᏊ࡛࠶ࡿࡇ࡜ࡀศ࠿ࡗࡓࠋᚑ᮶࠿ࡽ⏝࠸ࡽࢀ࡚ࡁࡓ㯤య㠃✚㸪㯤య⤌

⧊㠃✚࠾ࡼࡧ⾑₢P4⃰ᗘࡣዷፎண ࡟᭷⏝࡛ࡣ࡞ࡃ㸪Day 14 ࡟࠾ࡅࡿ P್ࡣࡑࢀ

ࡒࢀ0.807㸪0.230 ࠾ࡼࡧ 0.758 ࡛࠶ࡗࡓࠋ

 ROC ゎᯒࡢ⤖ᯝࢆ Fig. 2-5.࡟♧ࡋࡓࠋDay 7 ࡜ྠᵝ࡟㸪Day 14 ࡟࠾࠸࡚ࡶ༢୍

ᅉᏊ࡛ዷፎண ࢆ⾜࠺ሙྜ࡟ࡣ BFA ࡀ᭱ࡶඃࢀࡓᅉᏊ࡛࠶ࡿࡇ࡜ࡀศ࠿ࡗࡓࠋࡲ ࡓ㸪࣋࢖ࢬ᝟ሗ㔞つ‽࡛ホ౯ࡋࡓሙྜ㸪Day 14 ࡟࠾࠸࡚ࡣ㸪BFA ࡢࡳࢆ౑⏝ࡍࡿ ࡼࡾࡶBFA ࡜ TAMV ࡢ 2 ᅉᏊࢆ⪃៖ࡋࡓ㔜ᅇᖐᘧ࡟ࡼࡿዷፎண ࡀ᭱ࡶඃࢀ࡚࠸ ࡓࠋ Day 14 ࡟࠾ࡅࡿዷፎண ࡢࡓࡵࡢ࢝ࢵࢺ࢜ࣇ್ࡢẚ㍑ࢆ Table 2-2.࡟♧ࡋࡓࠋ BFA ࡢ࢝ࢵࢺ࢜ࣇ್ࢆ 0.56 cm2࡟タᐃࡍࡿࡇ࡜࡛㸪㧗࠸ឤᗘ㸦88.2%㸧࡜≉␗ᗘ 㸦79.2%㸧ࢆྠ᫬࡟ᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡲࡓ㸪BFA ࡜ TAMV ࢆ⤌ࡳྜࢃࡏࡓሙྜ㸪 ࣟࢪࢫࢸ࢕ࢵࢡᅇᖐᘧ࠿ࡽண ࡉࢀࡿዷፎ☜⋡ࡀ 60%࡛࠶ࡿ BFA 0.63 cm2 ࠿ࡘ TAMV 50.60 cm/s ࢆ࢝ࢵࢺ࢜ࣇ್࡟タᐃࡍࡿࡇ࡜࡛ࡉࡽ࡟㧗࠸ឤᗘ㸦85.3%㸧࡜≉ ␗ᗘ㸦91.7%㸧ࢆྠ᫬࡟ᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋ 2-4. ⪃ᐹ

(49)

ࡣ㯤య㠃✚ࡸ⾑₢ P4⃰ᗘ࡜ẚ㍑ࡋ࡚ BFA ࡜ TAMV ࡀዷፎண ࡟᭷⏝࡛࠶ࡾ㸪ࣟ

ࢪࢫࢸ࢕ࢵࢡᅇᖐᘧ࠿ࡽண ࡉࢀࡿዷፎ☜⋡ࡀ 60%࡛࠶ࡿ BFA 0.63 cm2 ࠿ࡘ

TAMV 50.60 cm/s ࢆ࢝ࢵࢺ࢜ࣇ್࡟タᐃࡍࡿࡇ࡜࡛᭱ࡶ㧗࠸ឤᗘ㸦85.3%㸧࡜≉␗

ᗘ㸦91.7%㸧ࢆྠ᫬࡟ᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋᚑࡗ࡚㸪࣮࢝ࣛࢻࣉࣛἲ࡟ࡼࡿ BFA ࡜

TAMV ࡢ ᐃࡣཷ⬇∵ࡢ㉸᪩ᮇዷፎデ᩿࡟᭷⏝࡛࠶ࡿ࡜⪃࠼ࡽࢀࡓࠋ

ཷ⫾⩌࡛ࡣ୙ཷ⫾⩌࡟ẚ㍑ࡋ࡚㸪Day 14 ࡟࠾ࡅࡿ BFA ࡜ TAMV ࡀ᭷ព࡟㧗࠸

ࡇ࡜ࡀ♧ࡉࢀࡓࠋࡉࡽ࡟㸪ࣟࢪࢫࢸ࢕ࢵࢡᅇᖐศᯒࡢ⤖ᯝ࠿ࡽࡶ㸪ཷ⫾࡟ᙳ㡪ࢆཬ

ࡰࡍᅉᏊࡣ BFA ࡜ TAMV ࡛࠶ࡾ㸪㯤య㠃✚ࡸ⾑₢ P4⃰ᗘࡣᅇᖐᘧ࡟ྵࡲࢀ࡞࠸

ࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋࡇࢀࡽࡢࡇ࡜࠿ࡽ㸪ET ᚋࡢ㯤యࡢ㇏ᐩ࡞⾑⟶ᙧᡂࡸ㯤య

࡟⾑ᾮࢆ౪⤥ࡋ࡚࠸ࡿࡽࡏࢇື⬦ࡢ㧗㏿࡞⾑ὶࡀཷ⫾࡟ᙉ࠸ᙳ㡪ࢆཬࡰࡋ࡚࠸ࡿ

ࡶࡢ࡜⪃࠼ࡽࢀࡓࠋཷ⫾⩌࡛Day 14 ࡟࠾ࡅࡿ BFA ࡜ TAMV ࡀ㧗࠸ཎᅉ࡜ࡋ࡚㸪

Day 7 ࡟࠾࠸࡚⾑⟶ᙧᡂࡢከ࠸㯤యࡀࡑࡢᚋࡶᏳᐃࡋ࡚⾑⟶ᙧᡂࢆቑຍࡋࡓࡇ࡜ࡀ ⪃࠼ࡽࢀࡿࠋࡲࡓ㸪Interferon tau㸦IFNτ㸧ࡢࡼ࠺࡞⬇࠿ࡽࡢࢩࢢࢼࣝ࡟ࡼࡗ࡚⾑ ὶ㔞ࡀቑຍࡋࡓྍ⬟ᛶࡶ⪃࠼ࡽࢀࡿࠋDay 7 ࢆᇶ‽࡜ࡋࡓ┦ᑐⓗኚ໬ࡣ㸪BFA ࡟᭷ ព࡞ᕪࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࡀ㸪TAMV ࡣཷ⫾⩌ࡀ୙ཷ⫾⩌࡟ẚ㍑ࡋ࡚㧗࠸ഴྥࢆ♧ ࡋࡓࠋࡇࡢࡇ࡜࠿ࡽ㸪୧⪅࡜ࡶ࡟㯤య⾑ὶ㔞ቑຍࡢཎᅉ࡜࡞ࡗ࡚࠸ࡿ࡜᥎ ࡋࡓࠋ ࣄࢶࢪ࡟࠾࠸࡚ዷፎ 12 ᪥┠௨๓㸪࢘ࢩ࡟࠾࠸࡚ࡣ 13 ᪥࠿ࡽ 14 ᪥┠࡟Ꮚᐑ࠿ࡽ⬇ ࢆ㝖ཤࡍࡿ࡜㯤యࡀ㏥⾜ࡋⓎ᝟ࡀᅇᖐࡍࡿࡀ㸪13 ᪥┠௨㝆ࡢ㝖ཤ࡛ࡣ㯤యࡢᑑ࿨ࡀ ᘏ㛗ࡉࢀࡿ㸦53㸧ࠋࡲࡓ㸪ࣄࢶࢪ࡟ዷፎ 14 ᪥࠿ࡽ 16 ᪥┠ࡢࣄࢶࢪ⬇ᢳฟ≀ࢆᏊᐑ ෆᢞ୚ࡍࡿ࡜㸪㯤యࡢ㏥⾜ࡀᢚไࡉࢀࡿ㸦48㸧ࠋࡇࢀࡽࡢࡇ࡜࠿ࡽ㸪ࡇࡢ᫬ᮇࡀẕయ ࡢዷፎㄆ㆑᫬ᮇ࡜ࡉࢀ㸪⬇ࡢᰤ㣴⭷⣽⬊࠿ࡽ⏘⏕ࡉࢀࡿ IFNτ ࡀዷፎㄆ㆑≀㉁࡜ࡋ

(50)

᥋╔ࢆ㛤ጞࡍࡿ㸦ዷፎ18 ࠿ࡽ 20 ᪥㡭㸧࡜ࡑࡢ⏘⏕ࡣῶᑡࡍࡿ㸦6㸪22㸧ࠋࡑࡢస⏝ ࡣ㸪╔ᗋ๓ᚋࡢ༸ᕢᶵ⬟ࡢไᚚ㸪⬇ࡢⓎ⫱ࡸఙ㛗㸪Ꮚᐑෆ⭷ࡢᶵ⬟ࡢㄪ⠇࡛࠶ࡿ㸦19㸧ࠋ ዷፎㄆ㆑᫬ᮇ࡟Ꮚᐑෆ࡟ IFNτ ࡀᏑᅾࡍࡿࡇ࡜࡛㸪Ꮚᐑෆ⭷ୖ⓶ୖࡢ࢜࢟ࢩࢺࢩࣥ ࣞࢭࣉࢱ࣮ࡢⓎ⌧ࡀᢚไࡉࢀ㸪㯤య㏥⾜ࡀ㜼ᐖࡉࢀࡿ㸦29㸪66㸪88㸧ࠋᮏ❶࡟࠾࠸ ࡚ヨ㦂ࢆ⾜ࡗࡓ Day 14 ࡣ IFNτ ⏘⏕㔞ࡀᛴቑࡍࡿ᫬ᮇ࡛࠶ࡿࡇ࡜࠿ࡽ㸪ཷ⫾⩌࡟ ࠾ࡅࡿ㯤యࡢ㇏ᐩ࡞⾑⟶ᙧᡂ࡜㧗㏿࡞⾑ὶࡣ⬇࠿ࡽ⏘⏕ࡉࢀࡓ IFNτ ࡟ࡼࡿᙳ㡪ࡶ ࠶ࡿ࡜᥎ ࡉࢀࡓࠋࡇࡢάⓎ࡞⾑ὶࡀ㸪㯤య࡬ࡢᰤ㣴ࡸ P4 ࡢᇶ㉁ࡢ౪⤥ࢆቑຍࡉ ࡏ㸪P4⏘⏕࡜ศἪࡢቑຍࢆࡶࡓࡽࡋࡓࡢ࡛ࡣ࡞࠸࠿࡜⪃࠼ࡓࠋࡋ࠿ࡋ㸪ᮏ❶࡟࠾࠸ ࡚㸪ཷ⫾⩌࡜୙ཷ⫾⩌࡛Day 14 ࡢ⾑₢ P4⃰ᗘ࡟᭷ព࡞ᕪࡣㄆࡵࡽࢀ࡞࠿ࡗࡓࠋ㯤 యࡢ࠶ࡿ༸ᕢ࡜ྠഃࡢ༸⟶ࡸᏊᐑゅࡢP4⃰ᗘࡣᑐഃ࡟ẚ㍑ࡋ࡚㧗ࡃ㸦95㸪96㸧㸪༸ ᕢ࡜Ꮚᐑ㛫࡛ᒁᡤᚠ⎔ࡍࡿP4ࡀᏑᅾࡍࡿ࡜⪃࠼ࡽࢀ࡚࠸ࡿ㸦95㸪96㸧ࠋᚑࡗ࡚㸪ά Ⓨ࡞⾑⟶ᙧᡂ࡟క࠺ P4ࡢ⏘⏕࡜ศἪࡢቑຍࡣ㸪ᮎᲈ⾑୰ࡢ P4⃰ᗘ࡟ࡣᙳ㡪ࢆ୚࠼ ࡞࠸ࡀ㸪㯤య࡜ྠഃࡢᏊᐑゅෆࡢP4⃰ᗘࢆቑຍࡉࡏࡿࡢ࡛ࡣ࡞࠸࠿࡜⪃࠼ࡽࢀࡓࠋ ࡉࡽ࡟㸪ẕయࡢ P4⃰ᗘࡣ⬇ࡢⓎ⫱࡜⬇࠿ࡽࡢ IFNτ ⏘⏕࡟ᙳ㡪ࢆ୚࠼㸪ẕయࡢ P4 ⃰ᗘࡀ㧗࠸࡜IFNτ ࡢ⏘⏕ࡀቑຍࡍࡿࡇ࡜ࡀ♧၀ࡉࢀ࡚࠸ࡿ㸦37㸧ࠋᚑࡗ࡚㸪Ꮚᐑෆ ࡢP4⃰ᗘࡀ㧗࠸ࡇ࡜ࡀ⬇ࡢⓎ⫱ࢆಁࡋ㸪IFNτ ⏘⏕㔞ࡀቑຍࡋ㸪ࡉࡽ࡟⬇ࡢⓎ⫱࡜ ╔ᗋ࡟㐺ࡋࡓ⎔ቃ࡜࡞ࡗࡓࡢ࡛ࡣ࡞࠸࠿࡜᥎ ࡉࢀࡓࠋ ㏆ᖺ㸪ᦠᖏᆺ㉸㡢Ἴデ᩿⿦⨨ࢆ⏝࠸ࡓAI ᚋ 25㸫29 ᪥௨㝆ࡢ᪩ᮇዷፎデ᩿ࡀ୍⯡ ⓗ࡟⾜ࢃࢀ࡚࠸ࡿ㸦26㸪87㸧ࠋࡉࡽ࡟㸪㉸㡢Ἴࢻࣉࣛἲࢆ⏝࠸ࡓ᪩ᮇዷፎデ᩿ࡀヨࡳ ࡽࢀ࡚࠸ࡿ㸦77㸪89㸧ࠋAI ᚋ 20 ࠾ࡼࡧ 21 ᪥࡟࠾࠸࡚㸪ཷ⫾∵࡛ࡣ୙ཷ⫾∵࡟ẚ㍑ ࡋ࡚㯤య⾑ὶ㔞ࡀከࡃ㸪㯤య⾑ὶ㔞ࡢどぬⓗホ౯ࡣ᪩ᮇዷፎデ᩿㸪≉࡟୙ཷ⫾∵ࡢ

(51)

Day 14 ࡟࠾ࡅࡿዷፎண ⢭ᗘࡢẚ㍑ࢆ⾜࠺ࡓࡵ࡟ ROC ゎᯒࢆ⾜ࡗࡓࠋࡑࡢ⤖ᯝ㸪 BFA ࡜ TAMV ࡢ 2 ᅉᏊࢆ⪃៖ࡋࡓ㔜ᅇᖐᘧ࡟ࡼࡿዷፎண ࡀ᭱ࡶඃࢀ࡚࠸ࡓࠋࡲ

ࡓ㸪ࣟࢪࢫࢸ࢕ࢵࢡᅇᖐᘧ࠿ࡽண ࡉࢀࡿዷፎ☜⋡ࡀ60%࡛࠶ࡿ BFA 0.63 cm2

ࡘTAMV 50.60 cm/s ࢆ࢝ࢵࢺ࢜ࣇ್࡟タᐃࡍࡿࡇ࡜࡛᭱ࡶ㧗࠸ឤᗘ࡜≉␗ᗘࢆྠ

᫬࡟ᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡇࢀࡽࡢࡇ࡜࠿ࡽ㸪Day 14 ࡟࠾ࡅࡿዷፎண ࡟ࡣ BFA ࡜

TAMV ࢆ⤌ࡳྜࢃࡏࡿ᪉ἲࡀ᭱㐺࡛࠶ࡿ࡜⪃࠼ࡽࢀࡓࠋᚑࡗ࡚㸪 Day 14 ࡟ BFA

༢⊂࡛ࡣ࡞ࡃBFA ࡜ TAMV ࢆホ౯ࡍࡿࡇ࡜࡛㸪㐣ཤࡢሗ࿌ࡼࡾࡶ᪩ᮇ࡛ᑦୟࡘ⢭ ᗘࡢ㧗࠸㉸᪩ᮇዷፎデ᩿ࡀྍ⬟࡜࡞ࡿࡇ࡜ࡀ᫂ࡽ࠿࡟࡞ࡗࡓࠋ ௨ୖࡢࡇ࡜࠿ࡽ㸪Day 14 ࡟࠾࠸࡚㸪ཷ⫾⩌࡜୙ཷ⫾⩌ࡢ㯤య㠃✚㸪㯤య⤌⧊㠃 ✚㸪୺ᖍ༸⬊㠃✚㸪BFA㸪TAMV ࠾ࡼࡧ⾑₢ P4⃰ᗘࢆẚ㍑ࡋ㸪ዷፎண ࡟᭷⏝࡞ ᅉᏊࢆゎᯒࡋࡓ࡜ࡇࢁ㸪ཷ⫾⩌ࡢBFA ࠾ࡼࡧ TAMV ࡀ୙ཷ⫾⩌࡟ẚ㍑ࡋ࡚㧗ࡃ㸪 BFA ࡜ TAMV ࡢ⤌ࡳྜࢃࡏࡀዷፎண ࡟᭱ࡶ᭷⏝࡛࠶ࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋ ࡲࡓ㸪BFA 0.63 cm2 ࠿ࡘ TAMV 50.60 cm/s ࢆ࢝ࢵࢺ࢜ࣇ್࡟タᐃࡍࡿࡇ࡜࡛㧗

࠸ឤᗘ࡜≉␗ᗘࢆྠ᫬࡟ᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋᚑࡗ࡚㸪Day 14 ࡟࠾ࡅࡿ BFA ࡜ TAMV

ࡢ ᐃࡀ㉸᪩ᮇዷፎデ᩿࡟᭷⏝࡛࠶ࡿ࡜⪃࠼ࡽࢀࡓࠋࡲࡓ㸪ᚑ᮶ࡢ᪉ἲࡼࡾ᪩ᮇ࡛ ᑦୟࡘḟᅇⓎ᝟࿘ᮇ௨๓࡟ዷፎデ᩿ࢆ⾜࠺ࡇ࡜࡛㸪୙ཷ⫾∵ࡢḟᅇࡢⓎ᝟Ⓨぢ⋡࠾ ࡼࡧAI ⋡ࡲࡓࡣ ET ⋡ࡢྥୖ࡟⧅ࡀࡿࡶࡢ࡜⪃࠼ࡽࢀࡓࠋ 2-5. ᑠᣓ ET ࠿ࡽ 7 ᪥ᚋ࡟ཷ⬇∵ࡢ BFA ࠾ࡼࡧ TAMV ࢆホ౯ࡍࡿࡇ࡜ࡣ㉸᪩ᮇዷፎデ᩿ ࡟᭷⏝࡛࠶ࡿࡇ࡜ࡀ♧ࡉࢀࡓࠋࡲࡓ㸪ᚑ᮶࠿ࡽ⾜ࢃࢀ࡚࠸ࡿዷፎデ᩿ࡼࡾࡶ᪩ᮇ࡛ ḟᅇⓎ᝟࿘ᮇ௨๓࡟ᐇ᪋ࡍࡿࡇ࡜ࡀྍ⬟࡛࠶ࡿࡓࡵ㸪୙ཷ⫾ࡢሙྜ࡟ࡣⓎ᝟Ⓨぢ⋡

(52)

Fig. 2-1. Schematic views of treatments, ultrasound examinations, and sampling schedules. The day on which the recipient cow had been observed to be in standing estrus was considered to be Day 0. Ultrasound examination of ovaries and blood samplings (Ⴠ) were conducted on Day 14. Embryo transfer (ET) and pregnancy diagnosis (PD) were conducted on Day 7 and 30, respectively.

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(53)

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Non-pregnant













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Fig. 2-2. The blood flow area (BFA) of the corpus luteum (A) and the time-averaged maximum velocity (TAMV) of the spiral artery (B) on Day 14. Black bars represent the pregnant group (n = 34). White bars show the non-pregnant group (n = 24). Data points show the mean s SEM for each day. The BFA and TAMV of the pregnant group were significantly higher than those of the non-pregnant group on 14.

(54)

Fig. 2-3. Relative changes of the blood flow area (BFA) (A) and the time-averaged maximum velocity (TAMV) (B) (% of respective values on Day 7). Data points show the mean s SEM for each day. The relative change of BFA did not











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(55)

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(A)

DF area (cm 2) P4 (ng/ml)











































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(B)

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Fig. 2-4. The corpus luteum (CL) area (A), CL tissue area (B), dominant follicle

(DF) area (C), and plasma P4 concentrations (D) on Day 14. Black bars represent

the pregnant group (n = 34). White bars show the non-pregnant group (n = 24). Data points show the mean s SEM for each day. In both groups, these trait values did not differ between the groups.

(56)

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Sensitivity

False positive rate (1 – specificity)

Fig. 2-5. Receiver operating characteristic (ROC) curves of the five pregnancy predictors on Day 14. The horizontal and vertical axes are a false positive rate (1 - specificity) and sensitivity, respectively. Thus, the upper left corner is the ideal point of 100% sensitivity and 100% specificity. The paired BFA and TAMV were the most appropriate predictors among the other predictors.

Abbreviations: BFA; blood flow area, TAMV; time-averaged maximum velocity, CL; corpus luteum.

(58)

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Fig. 1-1. Schematic views of ultrasound examinations and sampling schedules.
Fig. 1-2. Schematic views of treatments for estrus synchronization. The estrus of cows in the spontaneous estrus group (n = 34) was detected without synchronization
Fig. 1-3. Image of the corpus luteum (CL) using color Doppler ultrasonography.
Fig. 1-4. Schematic model of the corpus luteum and the spiral artery in cows illustrated by according to Yamada et al
+7

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