gia tri cac xet nghiem amh, fsh va afc du doan dap ung buong trung trong thu tinh ong nghiem

DAI HOC Y DUOC THANH PHO HO CHI MINH

LUAN AN TIEN SI Y HOC

GIA TRI CAC XET NGHIEM AMH, FSH VA AFC DU DOAN DAP UNGBUONG TRUNG TRONG THU TINH ONG NGHIEM

CHUYEN NGANH: SAN PHU KHOA - MA SO: 62720131

NCS VUONG THI NGOC LAN - HDKH PGS. TS. VO MINH TUAN

Kich thich buong trung (KTBT) La mot cong doan quan trong va duoc ap dung thuong quy trong quy trinh thu tinh ong nghiem (TTON). KTBT lam tang so luong noan thu duoc, la dieu kien can de chuan bi tot nhat cho cac buoc tiep theo nhu tao phoi va chon lua phoi chuyen vao buong tu cung nham gia tang co hoi co thai cho chu ky dieu tri. Dap ung cua buong trung voi KTBT duoc the hien bang so luong noan thu duoc. So luong noan phu hop giup tao duoc mot so luong phoi tot, mang lai co hoi co thai cao ma ti le qua kich buong trung thap.

Ngoai ra, so luong phoi thua con duoc tru lanh de su dung cho cac lan chuyen phoi sau, giup tang ti le co thai cong don cua mot chu ky KTBT. So luong noan qua nhieu khong lam tang co hoi thanh cong nhung tang nguy co qua kich buong trung va giam ti le lam to cua phoi. Nguoc lai, so luong noan qua it co lien quan voi ti le thai lam sang thap tang ti le huy chu ky do khong du noan de thu tinh, tang chi phi vat chat va ganh nang tinh than cho benh nhan.

Du doan dap ung BT co y nghia lon, la co so de tu van truoc dieu tri cho benh nhan ve cac nguy co cua KTBT va xac suat thanh cong cua thu tinh ong nghiem (TTON). Dua tren ket qua du doan dap ung buong trung, cac bac si lam sang dua ra quyet dinh phu hop trong viec chon lua phuong phap dieu tri, phac do KTBT va lieu thuoc KTBT. Du doan dap ung buong trung thuong thong qua cac dac diem lam sang cua benh nhan hay cac xet nghiem khao sat du tru buong trung.

Follicle Stimulating Hormone (FSH) Co ban la loai xet nghiem da duoc su dung tu lau, gan day, Anti-Mullerian Hormone (AMH), Antral Follicle Count (AFC) Cung duoc phat trien va dua vao ap dung lam sang. Nhieu nghien cuu da duoc thuc hien nham khao sat gia tri cua AMH, FSH va AFC de du doan cac dap ung buong trung bat thuong, tuy nhien, da so cac nghien cuu co co mau nho, tieu chuan chan doan dap ung buong trung bat thuong khac nhau, cac loai xet nghiem va phuong phap do luong khac nhau. Co 2 phan tich gop duoc thuc hien nham so sanh gia tri cua AMH, FSH va AFC de du doan dap ung buong trung kem va cua AMH voi AFC de du doan dap ung buong trung nhieu nhung cac nghien cuu duoc chon vao phan tich khong dong chat nen van chua the dua ra gia tri nguong thong nhat cua cac xet nghiem de su dung trong lam sang. Ngoai ra, gia tri cac xet nghiem duoc ghi nhan la khac nhau giua cac chung toc, bi tac dong boi cac dac diem lam sang va loi song cua benh nhan, do do, can thuc hien nghien cuu trong nhieu nhom dan so khac nhau de tim gia tri nguong dac hieu cho dan so truoc khi ung dung vao lam sang.

Tai Viet Nam, ky thuat thu tinh ong nghiem (TTON) ngay cang pho bien voi so chu ky dieu tri tang qua tung nam. KTBT duoc ap dung thuong quy cho hau nhu tat ca cac chu ky dieu tri. Truoc day, chi co FSH co ban la xet nghiem duoc dung de khao sat du tru va dap ung buong trung, sau do co them AFC va chi moi khoang 3 nam gan day, AMH duoc su dung rat pho bien o cac trung tam TTON. Mot so van de duoc ghi nhan tu viec su dung cac xet nghiem tren trong du doan dap ung buong trung la:

(i) Chua co gia tri tham khao cua nguoi Viet Nam,
(ii) Chua biet xet nghiem nao (trong dieu kien thuc hien tai Viet Nam) Co gia tri tot hon de dua vao do ma ra quyet dinh lam sang, nhat la trong truong hop ket qua cac xet nghiem khong thong nhat, va
(iii) Hien nay, co nhieu trung tam dang thuc hien ca 3 loai xet nghiem cho moi benh nhan, neu co mot hay cac xet nghiem nao duoc chung minh co gia tri tot hon, co the giam so xet nghiem can thuc hien, tiet kiem chi phi va thoi gian cho benh nhan. Nghien cuu ve du doan dap ung buong trung o benh nhan nguoi Viet Nam chua nhieu. Nguyen Xuan Hoi va cong su (2009) Ghi nhan FSH co ban va nong do estradiol la 2 yeu to tien luong doc lap cua dap ung buong trung kem. Cac nghien cuu khac ghi nhan AMH co tuong quan tot voi so luong noan thu duoc o benh nhan TTON va AMH co gia tri du bao nguy co qua kich buong trung. Tuy nhien, mot so nghien cuu co co mau nho, dieu kien bao quan mau xet nghiem chua dam bao va tieu chuan chan doan dap ung buong trung kem hoac nhieu cung khac nhau. Chua co nghien cuu so sanh gia tri cua cac xet nghiem AMH, FSH va AFC de du doan dap ung buong trung.

Chung toi thuc hien de tai nham tra loi cau hoi nghien cuu nhu sau:

1. Trong so cac xet nghiem AMH, FSH va AFC, xet nghiem nao co gia tri tot nhat de du doan dap ung buong trung kem hoac nhieu?

2. Gia tri nguong nao cua cac xet nghiem AMH, FSH va AFC de du doan dap ung buong trung kem hoac nhieu?





MUC LUC

Danh muc cac ky hieu, cac chu viet tat

Danh muc doi chieu Anh – Viet

Danh muc cac bang

Danh muc cac hinh, so do, bieu do

DAT VAN DE MUC TIEU NGHIEN CUU

Chuong 1. TONG QUAN TAI LIEU

1.1. Kich thich buong trung

1.2. Dap ung buong trung

1.3. Cac xet nghiem du doan dap ung buong trung dang duocsu dung pho bien

1.4. So sanh gia tri cac xet nghiem AMH, FSH va AFC trong dudoan dap ung buong trung

1.5. Mo hinh du doan dap ung buong trung

1.6. Nghien cuu ve du doan dap ung buong trung tai Viet Nam

1.7. Tong hop cac van de lien quan den de tai nghien cuu

Chuong 2. DOI TUONG VA PHUONG PHAP NGHIEN CUU

2.1. Thiet ke nghien cuu

2.2. Doi tuong nghien cuu

2.3. Co mau

2.4. Cach chon mau

2.5. Dia diem va thoi gian tien hanh nghien cuu

2.6. Phuong phap tien hanh

2.7. Phuong phap phan tich so lieu

2.8. Dao duc nghien cuu

Chuong 3. KET QUA NGHIEN CUU

3.1. Cac dac diem cua doi tuong nghien cuu

3.2. So sanh gia tri du doan va xac dinh gia tri nguong cua cac xetnghiem AMH, FSH va AFC de du doan dap ung buong trung

3.3. Mo hinh du doan dap ung buong trung

Chuong 4. BAN LUAN

4.1. Tinh cap thiet cua de tai nghien cuu

4.2. Phuong phap nghien cuu

4.3. Ket qua nghien cuu

4.4. Diem manh va han che cua nghien cuu

4.5. Ung dung ket qua nghien cuu vao lam sang

4.6. Y nghia khoa hoc cua de tai nghien cuu

KET LUAN

KIEN NGHI

DANH MUC CAC CONG TRINH LIEN QUAN DEN LUAN AN

TAI LIEU THAM KHAO

PHU LUC

Phu luc 1. Phuong phap dinh luong AMH

Phu luc 2. Phuong phap dinh luong FSH

Phu luc 3. Bang xac suat du doan dap ung buong trung kem dua tren AMH va AFC

Phu luc 4. Bang xac suat du doan dap ung buong trung nhieu dua tren AMH va AFC

Phu luc 5. Quyet dinh cua Hoi dong Dao duc cho phep thuc hien nghien cuu

Phu luc 6. Quyet dinh cho phep thu thap so lieu cua benh vien An Sinh

Phu luc 7. Bang thu thap so lieu

Phu luc 8. Phieu thong tin cho benh nhan ve nghien cuu

Phu luc 9. Ban cam ket tham gia nghien cuu

Phu luc 10. Danh sach benh nhan tham gia nghien cuu

DANH MUC CAC KY HIEU, CAC CHU VIET TAT

AMH Anti-Mullerian Hormone

AFC Antral Follicle Count

AIC Akaike Information Criterion

AUC Area Under Curve

BMI Body Mass Index

CRP C-Reactive Protein

FSH Follicle Stimulating Hormone

FTI Free Testosterone Index

GnRH Gonadotropin Releasing Hormone

GnRHa Gonadotropin Releasing Hormone Agonist

GnRHanta Gonadotropin Releasing Hormone AntagonisthCG human Chorionic Gonadotropin

Hct Hematocrit

KTC Khoang tin cay

KTBT Kich thich buong trung

LH Luteinizing Hormone

LR Likelihood Ratio

NPV Negative Predictive Value

OR Odds ratio

PPV Positive Predictive Value

ROC Receiver Operating Characteristic

TTON Thu tinh ong nghiem

DANH MUC DOI CHIEU ANH – VIET

American Society for Reproductive Medicine ASRM Hiep Hoi Y hoc sinh san Hoa Ky

Asia Pacific Initiative on Reproduction ASPIRE Hiep Hoi Y hoc sinh san Chau A Thai Binh Duong

Basic Fibroblast Growth Factor b_FGF Yeu to tang truong nguyen baosoi co ban

Bioassays Xet nghiem sinh hoc

Diagnostic System Lab DSL Phuong phap xet nghiem DSL

Electrochemilunescence Mien dich dien hoa phat quang

Enzyme Linked Immunosorbent Assay ELISA Mien dich gan ket men

Epidermal Growth Factor EGF Yeu to tang truong ngoai bi

European Society of Human Reproduction and Embryology ESHRE Hiep Hoi Y hoc sinh san Nguoiva Phoi hoc chau Au

International Committee for Monitoring Assisted Reproductive Technologies ICMART Uy ban giam sat cac ky thuat hotro sinh san

Intracytoplasmic Sperm Injection ICSI Tiem tinh trung vao bao tuongnoan

In-vitro Maturation IVM Truong thanh noan trong ongnghiem

Immunoassays Xet nghiem mien dich

Insulin-like growth factor IGF-1 Yeu to tang truong giong insulinnhom

Interferons IFNs Khang the duoc tao ra va giaiphong boi te bao ky chu

Immunotech IOT Phuong phap xet nghiem IOT

Lithium heparin plasma Li-heparinplasma

Huyet thanh chua trong ongnghiem trang voi muoi Lithiumcua Heparin

Metaphase II MII Pha trung ky cua giam phan II

Physicochemical assays Xet nghiem hoa ly

Power Do manh kiem dinh

Recombinant human Chorionic

GonadotropinrhCG hCG tai to hop

Recombinant Follicle Stimulating HormonerFSH FSH tai to hop

Statistical Package for the Social Sciences SPSS Phan mem thong ke cho khoahoc xa hoi

Transforming Growth Factor a TGF-a Yeu to tang truong bien doialpha

Transforming Growth Factor a TGF-a Yeu to tang truong bien doi beta

Tumor Necrosis Factor TNF Yeu to hoai tu u

Tumor Necrosis Factor Binding Protein I TNF_BP I Protein gan ket yeu to hoai tu uloai I

Vascular Epithelial Growth Factor VEGF Yeu to tang truong noi mo machmau

World Health Organization WHO To chuc Y te the gioi

World Health Organization 2nd WHO 2nd

International Reference Preparation IRP

Chuan tham khao quoc te ve xetnghiem cua To chuc Y te the gioiphien ban II

DANH MUC CAC BANG

Bang 1.1. Dac diem cac loai xet nghiem AMH hien dang su dung vanghien cuu

Bang 1.2. Gia tri nguong cua AMH du doan dap ung buong trung kem

Bang 1.3. Gia tri nguong cua AMH du doan dap ung buong trung nhieu

Bang 1.4. Gia tri nguong cua AFC du doan dap ung buong trung kemhoac nhieu

Bang 1.5. Nghien cuu so sanh gia tri cac xet nghiem AMH, FSH va AFCdu doan so noan choc hut duoc

Bang 1.6. Mo hinh don bien va da bien du doan dap ung buong trung kem

Bang 1.7. Tom luoc cac mo hinh du doan dap ung kem hoac nhieu (phantich lai tu cac thu nghiem lam sang co nhom chung)

Bang 2.1. Co mau can thiet de phat hien su khac biet giua 2 dien tich duoiduong cong ROC AUC1 (f1) Va AUC2 (f2)

Bang 2.2. Dien tich duoi duong cong ROC du doan dap ung kem hoacnhieu cua cac xet nghiem AMH, FSH va AFC

Bang 2.3. Lieu FSH trung binh/ ngay va lieu dau FSH duoc chon theo cacnhom tuoi

Bang 2.4. Cac bien so nghien cuu can thu thap

Bang 3.1. Dac diem dan so - xa hoi cua doi tuong nghien cuu

Bang 3.2. Dac diem lam sang cua doi tuong nghien cuu

Bang 3.3. Gia tri cac xet nghiem AMH, FSH va AFC truoc kich thichbuong trung cua doi tuong nghien cuu

Bang 3.4. Dac diem kich thich buong trung cua doi tuong nghien cuu

Bang 3.5. Ket qua choc hut noan va nuoi cay phoi

Bang 3.6. Ket qua chuyen phoi va bien chung cua thu tinh ong nghiem

Bang 3.7. So sanh gia tri cac xet nghiem AMH, FSH va AFC du doan dap ung kem

Bang 3.8. Gia tri nguong cac xet nghiem AMH, FSH va AFC du doan dap ung kem

Bang 3.9. So sanh gia tri cac xet nghiem AMH, FSH va AFC du doan dap ung nhieu

Bang 3.10. Gia tri nguong AMH, FSH va AFC du doan dap ung nhieu

Bang 3.11. Phan tich don bien cac dac diem cua doi tuong nghien cuu voidap ung kem

Bang 3.12. Phan tich da bien cac dac diem cua doi tuong nghien cuu voidap ung kem

Bang 3.13. So sanh dien tich duoi duong cong ROC cua cac mo hinh dudoan dap ung kem

Bang 3.14. Phan tich don bien cac dac diem cua doi tuong nghien cuu voidap ung nhieu

Bang 3.15. Phan tich da bien cac dac diem cua doi tuong nghien cuu voidap ung nhieu

Bang 3.16. So sanh dien tich duoi duong cong ROC cua cac mo hinh dudoan dap ung nhieu

Bang 4.1. So sanh ket qua kich thich buong trung giua cac nghien cuu

Bang 4.2. Cac nghien cuu so sanh gia tri cua cac xet nghiem AMH, FSHva AFC du doan dap ung kem

Bang 4.3. So sanh gia tri nguong cua cac xet nghiem AMH, FSH va AFCdu doan dap ung kem

Bang 4.4. So sanh gia tri nguong cua AMH du doan dap ung nhieu

Bang 4.5. Dien tich duoi duong cong ROC cua cac mo hinh du doan dap ung kem hoac nhieu

Bang 4.6. Tom tat cac dac diem cua xet nghiem du doan dap ung buong trung

DANH MUC CAC HINH

Hinh 1.1. Phac do dai phoi hop GnRH dong van va FSH

Hinh 1.2. Phac do phoi hop GnRH doi van va FSH

Hinh 1.3. Phac do ngan phoi hop GnRH dong van va FSH

Hinh 1.4. Su che tiet AMH trong buong trung

Hinh 2.1. Cach thuc hien AFC

Hinh 4.1. Cac yeu to tac dong len dap ung buong trung

DANH MUC CAC SO DO

So do 2.1. Qui trinh kich thich buong trung va theo doi su phat triennang noan

So do 2.2. Tom tat cac buoc thu thap so lieu

So do 3.1. So benh nhan tham gia cac cong doan cua qui trinh nghien cuu 67

DANH MUC CAC BIEU DO

Bieu do 1.1. Su thay doi nong do AMH trong suot doi song nguoi phu nu

Bieu do 1.2. Nong do AMH theo tuoi (sau tuoi 25)

Bieu do 1.3. Gia tri AFC theo tuoi o bach phan vi thu 3,10,25,50,75,90,97

Bieu do 1.4. So sanh gia tri AMH, FSH, inhibin va AFC du doan dap ungkem va nhieu o hai nhom benh nhan su dung HP-hMG va rFSH

Bieu do 1.5. So sanh AMH va AFC du doan dap ung nhieu

Bieu do 3.1. Muc do dap ung buong trung

Bieu do 3.2. Duong cong ROC cua AMH, FSH va AFC du doan dap ung kem

Bieu do 3.3. Duong cong ROC cua AMH, FSH va AFC du doan dap ungnhieu

Bieu do 3.4. Duong cong ROC cua 3 mo hinh du doan dap ung kem

Bieu do 3.5. Kiem dinh cua mo hinh AMH+ AFC du doan dap ung kem

Bieu do 3.6. Duong cong ROC cua 3 mo hinh du doan dap ung nhieu

Bieu do 3.7. Kiem dinh cua mo hinh AMH+ AFC du doan dap ung nhieu

 DANH MUC CAC CONG TRINH LIEN QUAN DEN LUAN AN

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