DANH GIA HIEU QUA CUA PHU0NG PHAP HO TRff PHOI THOAT MANG BANG TIA LASER TREN BENH NHAN LOTN TUOI
N G U Y I N THj L I E N HaONG - Bpnh vi$n Php San Trung IfOng N G U Y I N TH! BINH - TrUdng D^i hpc Y Hi Ndi TOM T A T
Ky thuit hd trg phdi thoit mang (assisted hatching-AH) bing tia laser bit diu dugc thuc hiin t^i Viet Nam vao nim 2009. Hiin tai, ehua cd nghiin citu nao danh gta vi phuang phip vi hiiu qui cCia ky thuat nay trin benh nhin > 38 tuii. Mijc tiiu: Dinh gii hieu qui cda phuang phip hi trg phdi thoit mang bhng tia laser trin binh nhan > 38 tuii. Thiit ki nghien cUu: tiin cdu, can thiep. Dii tugng: 130 binh nhan chuyin phdi tuai > 38 tuii chia 2 nhdm: nhdm 1:
58 binh nhin khdng lam AH; nhdm 2: 72 binh nhan cd lim AH trudc khi chuyin phii. Kit qui: Ty li cd thai (PR) nhdm 1 thip han nhdm 2 khdng ed y nghTa thdng ki: 17.14% & 22,22% (p=0,2); Ty li lam ti (IR) nhdm 1 thip ban nhdm 2 khdng ed y nghTa thing ki (p=0,84). Kit luin: Hi trg phdi thoit ming bing tia laser khdng cii thien ty li cd thai trin benh nhin thu tinh ing nghiim > 38 tuii.
Tdkhda: hd trg phdi thoit ming, tia laser, binh nhan > 38 tuii.
SUMMARY
Laser assisted hatching- LAH began fo be implemented in Vietnam In 2009. Currently, no study has evaluated the effectiveness of this technique on embryos ofwomens > 38 years of age.
Objective: To assess the ef^ctlveness of LAH on embryos of womens > 38 years of age.
Study design: prospective, intervention.
Subjects: 130 embryo transfer cycles of womens >
38 years o/d were allocated into two gmups: group 1:
58 cycles without LAH; group 2: 72 cycles with LAH before embryo transfer.
Results: The pregnancy rate (PR)of group 1 lower than group 2 (no statistieally significant):
17.14% & 22.22% (p = 0.2); implantation rate (IR) of group 1 lower than group 2 (no statistically significant, p = 0.84).
Conclusion: LAH did not improve the pregnancy rate in IVF womens > 38 years of age.
Keywords: embryo assisted hatching, laser, womens > 38 years of age.
BAjy/Kuoi
TJ le ldm td trong ky thudt thu tinh trong dng nghiem van cdn chua cao (10-25%), Nhieu ky thuit hfl trp ad ra ddi d l nang cao tJ l i ndy. Ky thuit ho trp phoi thoat mdng (assisted hatching-AH) la mdt trong cac kJ thuit dd, Gan day, phudng phap hd trp phdi thoat ming bang tia laser da bat d i u dupc thue hien tai Viet Nam vdo nam 2009. Hiin tai, chua cd nghien cCfu nao danh gia v l phUdng phdp va hieu qua cda ky thuat nay tren benh n h i n > 38 tuoi. Do vay, nghien cCfu nay dudc thirc h i i n vdi muc tieu: Danh gid hieu
quS cda phUdng p h i p hd trp phdi thoit m i n g bang tia laser tren b i n h nhan > 38 tuoi.
0 6 l TUgNG VA PHaONG P H A P NGHieN ClJU 1. Dd'l tupng: benh nhdn chuyen phdi tUdi > 38 tudi chia 2 nhdm: nhdm 1: khdng l i m AH; nhdm 2: cd idm AH trudc khi chuyin phdi.
2. Thiet ke nghien cCTu: Nghien cdu tiln cdu can thiep,
3. Dja diem nghien cdfu: Trung t i m HP trd sinh san- Benh vien Phu san Trung Udng, Bd mdn Md phdi TrUdng Dai hpc Y Hd Ndi.
4. Thdi gian nghien cdu: tCr thing 6 /2009 d i n thing 6/2012.
5. Cd mdu: Phu nCf > 38 tuoi sau khi ed phdi nhd ky thudt IVF/lCSl ngiu nhien dupc chia Idm 2 nhdm nhd.
+ Nhdm 1: 72 benh n h i n phdi dupe hd trp thodt mang (AH).
+ Nhdm 2: 58 benh nhdn khdng lam hd trp phdi thodt ming.
6. Tieu chuan chpn vao m l u nghien curu - Ddng ^ tham gia nghien cdu.
- Cdc benh nhan chuyen phdi tudi > 38 tuoi cd > 1 phdi rat tdt (TQE), niem mac tCr cung > 8mm. chuyin phdi d l . khdng ed m i u cd t h i dupc chon vao mdu nghiin eCfu.
7. PhUdng phap nghien cdu 7.1 Ky thuit thu tinh ing nghiim - Phac dd kich thfch budng IrCfng v i theo ddi siiu dm nang noan
Cdc binh nhdn deu duoc kich thich nang noan, sieu i m nang noan theo phac dd chuan eda Trung tim, Phdc dd ddi dung GnRH ddng van. khoang 13- 14 ngay. Sau dd thCf lai ndi t i l t (FSH, LH, E2), khi thay FSH « 2 lU/l, LH »2 lU/l, E2 < 50 (pmol/l) v i sieu i m khdng thay nang cd ndng > 20 mm thi chuyin sang ddng thulc kich thich nang noan (FSH). Phdc dd ngan chi dung 1 lan t i i m GnRH ddi van vao ngdy thCf 2 cda chu ky. Thudc kich thich nang noan tiem trong khoang 8-13 ngay, khi sieu dm ed > 3 nang noan kich thudc > 16 mm thi eho thude mng tomg HCG (Pregnyl 5000 hodc 10 000 ddn vi). Choc hut trCrng sau t i i m HCG 34-36 gid.
- Qui trinh chgc hot trdng vi nudi dy phdi:
+ Noan sau chpc hut dUpc d trong tu cdy 3-6h trudc khi cho thu tinh vdi tmh trung da dupc chuan bi bang cich cay vdi mat dd 150-200 ngan tinh tomg/
mdt gieng 2 -3 noan hodc t i i m tinh trdng vao bao tuong noan (ICSI-intra cytoplasmic sperm mjection'i
Y HOC THUC HANH (848) - SO 11/2012
Ddnh gia thu tinh 14-18h sau ICSI, 18-20h sau IVF.
Danh gia c h i t lupng phdi n g i y 2 de chpn phdi t i t . Danh gia c h i t iirong phdi n g i y 3 de chpn phdi chuyin. N l u phdi tdt cd t h i nudi t i l p d l chuyin phdi ngiy 5. Tomg dUpc ddnh gid thu tinh sau khi cho t i l p xdc vdi tinh trung 12-14 gid ddi vdl ICSI va 16-18 gid ddi vdi IVF don t h u i n . Ddnh gid c h i t lUdng p
+ Ddnh g i i phdi tuoi tn;dc chuyin: c h i t lupng phdi chia 4 dp: phdi dd 4 phdi r i t tdt (TQE-top embryo quality).
+ Chuyin phdi.
•*• Theo ddi thai sinh hda: thijf jJhCG sau 14 ngdy chuyen phdi > 501U.
Theo ddi thai ldm s i n g : t h i y tdi di trong lit cung, d i m sdtdi di,
7.2. Qui trinh lim hS trp phii thoit ming - Chuin bj dTa Idm AH: Nhd 4 giot Gamete (Vitrolife- Thuy" Diln) l i n dia Petri nhd 35 (Vitrolife- Thuy Diln). t h i tich m i l gipt = 20 \i\. D i n h s l thCf t u cdc gipt trudc dd d m i l sau dTa Petri. Phd kin d i u Ovoii (Vitrolife- Thuy Diln) ldn dia, d l vdo td c l y (37''C, 5%C02) 30 phdt tn/dc khi sdr dung (hinh 2,1).
Hinh 1. OTa Petri phd dau chuin bj lim AH - Chuan bj he thdng laser: sit dung he thdng laser Hamilton Thom ed gan may anh ky thuat sd, chUdng trinh Ziios de dieu khien he thdng laser,
- K i l m tra cac thdng sd vd chuan hda t i i u d i l m : Chpn tan sd va n i n g luong can thilt cho viec thao tdc ban laser, d djnh dang d i l u chinh chpn l i l u lUdng xung la 300|im v i ndng lupng Id 100% d l tdc kich.
Trong tnrdng hpp mdng trong sudt eda phdi qua ddy, d l an t o i n cho phdi, chl t i n g iilu lUdng xung len t l i da la 500Mm de ban thdng. Trong trudng hpp mdng trong sudt mdng hdn, ed the giam l i l u lupng xung xudng den 200 nm d l han c h l lac ddng cua nhiit dp md vdn ban thdng muc tieu,
- Thue hien ho trd phdi thodt mdng: Trade chuyin phdi 30 phut, nhdt phdi chuan b; cho chuyin phdi vdo dia AH, 01 phdi/ 1^ gipt. D i t dTa AH len dia am 37°C trin kfnh hien vi dao ngupc Nikon. Dinh vj phdi, D i l u chmh 6c vi d p sao eho thay rd phdi. Chinh ddng tieu diem c i n ban tren m i n g trong sudt cda phdi, Chd y chpn lua vj tri ban tia laser d ndi cd khoang PVS (khoang quang noan = khoang quanh phdi b i o ) (perivitelline space) rdng nhd't hodc vj tri cd nhilu manh vd (fragment), Lam mdng 50% mang trong sudt Iren 1/4 chu vl mang. Ban lU ngoai vao trong. Ludn ddt vdng tron dfch sao eho vdng trdn ngoii eung klidng cham vdo phdi bao.
Hinh 2. Phfll ngiy 3, \km mdng 50% ming trong i\i6l tren 1/4 chu vl ming
- Phdi sau khi thuc h i i n hd trp phdi thoat mdng dupc rdia qua mdi trudng nudi c l y rdi nhdt cdc phdi ti^
dTa AH sang dTa c h u i n bj chuyen phdi. nudi cay tiep trong td c l y . Chuyin phdi sau khi thUc hidn ho tro phdi t h o i t m i n g 30 phdt ( t i t nhit) d i n tdi da 1 h.
7.3. Ky thu$t thu thip s6U$u
C i c sd l i i u ve mdu nghiin cCfu dUpc nhdp tn/c t i l p v i l i i n tue v i o chUdng trinh SPSS, cdc dCf lieu ve chat luong phdi. ma benh nhdn dude ghi trong nhdt ky lab thu tinh dng nghiem.
K^T QuA
1. D$c diem mau nghien c d u . Bang 1. Nguyin n h i n vd sinh Nguyen nhdn vd sinh
TScvOilnJnq KhOng rfi nguydn nhdn
Do ch6nq LNMTC BT da nang Nguyen nhdn phtii hop
Do cS 2 vd ch6nci KhSc T6nq
Kh0nqAH(n=5e) n 32 4 10 0 1 4 6 1 58
55.17
%
6.89 17.24 0 1.72
6.9 10.35 1.72 100
AH (n=72) n 30 6 26 2 0 2 6 0 72
41,66
%
8.33 36,11 2.78 0 2.78 8.33 0 100 N h i n xet: T } le nguydn nhdn v d sinh do tac vdi o nhdm khdng idm A H cao hdn nhdm cd lam AH"
55.17% so vdi 4 1 , 7 % (tuy nhien p > 0.05); T j l i vd sinh do chdng d nhdm lam A H cao hdn nhdm khdng Idm A H : 36,08%so vdi 17,24%, s u khde b i i t n i y eung khdng cd y nghTa thdng ke (p>0,05).
Bang 2, Cdc ddc diem khae
S6 nang noan SS phOi chuyen tmnq binh 56 phdi 181 tnjnq binh
AH (n=72) Mm
1 Max
18 TB 5.78*3.3
3.34±1.21 2.56±1.50
KhOnqAH(n=58) Min
2 Max
18 TB 7.93±4,02
4.04±0.98
2.37±1.31 Nhan xet: Lieu dung F S H v a tong iieu F S H . n6ng 36 E2 n g i y tiem hCG giBa 2 nhom l<liac biet I<h6ng CO i ngliTa thong ks (p >0.05). S d nang noan trung binh d nh6m t<h6ng lam A H cao hdn n h o m c 6 lam AH:
7.93 +.4.02 so v6i 5,78 ± 3,3. T u y nhien sir Ichac biet
Y HOC THUC HANH (848). s 6 11/2012
nay khdng ed y nghTa thdng ke (p >0,05). Sd phdi chuyin trung binh d nhdm khdng Idm AH cao hdn nhdm cd lam AH: 3,34 +1,21 so vdi 4,04 + 0.98 (khac biet khdng cd y nghTa thdng ke p >0.05), Sd phdi chuyen tdt trung binh 2 nhdm la tudng duong nhau:
2,56±1,50;2,37±1,31, 2. Ty le cd thai vd lam to Bang 3. K i t qua cd thai vd ldm t l
Ket qui Itiai Kit quS iaml^
Cdlhai Ktldnq cd thai
Tdng Ldm Id KhOnqidmtd
Tdng
AH (n=70) N 12 58 70 20 214 234
17.14
%
82.86 too 8.55 91,45 100
Khdng AH N 12 42 54 20 198 218
(n=54)
%
22.22 77.78 too 9.17 91.83 100
P
0.2
0,87
Nhin xet: T j l i cd thai d ea 2 nhdm Id luong auong, su khac biel khdng cd y nghTa thdng ke (p=0,2). TJ Id l i m td d ca 2 nhdm l i tUdng dUdng, sU khac biet khdng cd y nghTa thing k i (p=0,87).
BAN LUAN y/i H 6 T R P P H 6 I THOAT MANG Tinh dong nhat git}a hai nhom nghien cUu.
Hai nhdm nghien eCfu cda chdng tdi dUpe lUa chon ngdu nhiin de dam bao tfnh dong nhat cda mdu nghien cCfu. Nguyen nhdn vd smh, chi djnh thu linh ong nghiem, sd phdi t i t trung blnh, sd phdi chuyin tmng binh, niem mac tCf eung, each thd'c chuyen phdi giifei 2 nhdm chdng vd nhdm lam AH eu khac biet khong cd y nghTa thong ke,
K^T QUA NGHIEN CQU
Nghien edru cda chung tdi dupc thuc hien tren 130 benh nhdn, dupe chia lam 2 nhdm. Nhdm 1 gom 58 benh nhdn khdng l i m LAH, nhdm 2 gdm 72 benh nhan lam LAH. K i t qua eho thay cd 12/70 binh n h i n CO thai d nhdm Idm AH, (ed 2 benh nhdn khdng lien iac dupc nen khdng b i l l k i t qua cd thai hay khdng), tj le cd thai cda nhdm ndy la 17,14%. Nhdm churng ciing cd 12/54 benh nhdn cd thai (cd 4 benh n h i n khong lien lac dUOe de biet k i t qua ed thai), ty l i cd thai l i 22,22%. 6 nhdm l i m AH cd 20 tdi di tren 234 phoi chuyen. tJ ie lam td Id 9,2%. Nhdm chCfng cd 20 tlii oi tren 218 phdi chuyen, ty" le lam td ia 9.4%, Ty le CO thai vd ty le lam td giCfa 2 nhdm khic biet khdng cd J nghTa thdng k i (p> 0.05).
Kll qua trong nghiin cCru cda chdng tdi eung tuyng duong vdi mdt sd bdo cao trudc ddy, Nghien cQU cCia Horng vd cs, (2001) tren 120 chu ky IVF/ICSI cl nhiing phu nur > 37 tudi, chia lam 2 nhdm. Nhdm 1 khong ldm hd trd phdi thodt mdng, nhdm 2 lam AH mh 16 20^m tren mang trong sudt. K i t qua eho thay ty ie iam td (IR) cda nhdm 1 va nhdm 2 khac biet khdng CO J nghTa thdng k i : 7,3 % va 6,7%, p= 0,89; ty le cd thai (PR) cda 2 nhdm Id 16,3% va 17,5%, p= 0,86, Tac gia cda nghien cCru d i ket ludn LAH khdng cai Wen dupe tJ Id Idm to cung nhU tJ le cd thai cda nhom phu nQ'> 37 tuoi [2],
Nghien eCru cda Blder D v i cs. (1997), Susan E.
vd cs. (1998) cOng cho k i t qua tUdng tU. Phai chang l i nhiJmg nguyin nhdn khac (tuoi, chat lUdng phdi, c h i t lupng nodn, not liet ) anh hudng d i n t f l i cd thai eda nhufng d6\ tupng bdnh nhdn nay hOn l i yeu td dnh hudng tir m i n g trong sudt eda phdt [1], [5],
Nghien cCru cda Saima v i cs. (2006) cd k i t qua khac nghidn cdu eda chdng tdi. Nghidn edu ndy gdm 168 bdnh nhdn chia lam 2 nhdm: nhdm chCfng ed 85 benh n h i n , nhdm can thiep cd 83 binh n h i n dupc Idm AH bang AT. K i t q u i id tJ l i l i m td (IR) eda nhdm ^ 35 t u l i Idm AH cao hOn cd y nghTa thdng ke so vdi nhdm chCmg: 16% vd 8%, p=0,006. Thai sinh hda, thai ldm sdng vd qua trinh thai nghin d hai nhdm cung khac biet khdng ed y nghTa thdng k i , mdc du sd ludng say thai vd chCfa ngodi tCrcung tren thiic te cao hOn d nhdm ldm AH [3], TrUdc dd, nghien cCfu cda Schoolcraft v i cs. (1995) cung khing dinh PR, IR cda nhdm AH cao hdn cd y nghTa thdng ke [4], Tuy n h i i n , d ea hai nghiin culi cda t i e gia ndy, nhdm chCfng dUpc chuyin phdi n g i y 2, sau chuyen phdi khdng dupc dung khdng sinh va thude npi tilt, Trong khi dd, nhdm can thiep lai chuyen phdi n g i y 3 v i ngoai lam AH dupc dung them khing sinh va thudc npi t i l t sau chuyin phdi, Dd cd the la iy do l i m ty l i l i m to va tJ le ed thai cua nhdm can thiep cao hdn vi phdc dd d i l u tri v i each thd'c chpn phdi chuyen cung nhu ngdy chuyen phdi anh hudng khdng nho d i n nhuTig ty i i n i y .
KET LUAN
Nghien cCiU t i l n h i n h hd trp phdi thoai mdng bang tia laser dUa tren gia thuyei mdng trong suol d benh nhdn ldn tudi cd the anh hudng den ty le cd thai cung nhu ty ie lam to trong thu tinh trong dng nghiem. Tuy nhien, nghien cCfu budc dau cda chung tdi cd the k i t luan rang hd tro phdi thoat mdng bang tia laser khdng eai thien dupc ty Id lam td eung nhu ty le cd thai tren nhCfng phu nu" > 38 tuoi. Do vdy, cd t h i hudng tdi nhilu nguyin nhdn khdc anh hudng den ty Id thdnh cdng cda nhutig dor tuong ndy,
T A I L I E U THAM KHAO
1 Bider D, Livshits A, Yonish M, et al. Assisted hatching by zona drilling of human embryos in women of advanced age. Hum Reprod 1997; 12: 317-20
2. Homg SG et al. (2002). Laser - assisted hatching of embryos in women of advanced age after in vitro fertiiizalion: a preliminary report. Chang Gung Med J.
2002Aug;25(8):531-7.
3. Sai fwla et al (2006) impact of assisted hatching on the outcome of intracytoplasmic sperm injection' a prospective, randomized clinical Iriai and pregnancy follow-up Fertility and Steriiity Volume 85, Issue 4,
Pages 895-900, April 2006http7/www,fertstert org/articie/SOOl 5-
0282%2805%2904104-X/abstract - article-footnote-1.
4. Schoolcraft WB et ai, (1995), in vitro fertilization in women age 40 and older: the impact of assisted hatching, J Assist Reprod Genet. 1995 Oct;12(9):581-4.
5. Susan E.et al. 2010. A prospective, randomized, double-biinded study of assisted hatching in women younger than 38 years undergoing in viim fertiiizalion.
Fertility and Sterility voi. 93, no, 2, pp, 586-591.
YHOC THUC HANH (848) - S 6 11/2012
