R}SXARCN-HS?E

Efferts of using the analgesir tramadnl inmice undergaing embryo transfer $urgeryf;Jr{# ,{oufrt:li, f,A?"J'J, F*rrl ,{le"rdJi*s, 1,.{T'1, /,*rh*r{as Hrrlqcrzrrrf$, I}l,'$'lJ, Irsns Svnr*o*, J,A?'J':,f;rurlgeltrs Snirrlirs, LdfJ, Ctrrr;'sri fir;r1dg:'t gr, J)l",H, p}rfJ" gF.\tkcrlrlers }i.ttslurrifsopou/gs, I)1',V, /'ltllr

[mbryu transfer is a surgical technique that is widely used in reproductivebiotechnolngy. Despite the ethical abligation to relieve animals' post-operat'ive pain,analgesia is not routinely provided after embryo transfer surgery because it has beensuggested that analgesic$ may be detrimental to embryo Eurvival. Studies :uggest,however, that the pntential for adverse effects varies dependins on the typr ofanalgesic used and the timing of its administration. The authsrs carried out a studyto determine whether pre-CIperatively administered trarnadol. a synthetic anatogue ofcodeins, inftuenced birth rate, litter survival ar the post-operative body weights ofsurrogate dams. Compared with controls that were not given any analgesic, surrogatedams given tramadst had sirniLar birth rates and sirni|'ar body weights at atl tim*points. The tramadol-treated surrogate dams showed a statistica[[y significant increasein the numb*r uf affspring that survived to weaning. The authsrs conclude thatpre-operativety administered tramadot does not harm the success rate of embryotransf*r surgr,ry and even may imprnve litter survival.

li"rr"rbrv* lran*lbr is u r*'it{el,v useti tec'hniqu* in repro-ductiye biutexhnr:lugy fi:r pr*dnction of grneticalll'engin*rrrd mice, for rrr titrti fertiliealion, lirr intrae pr:-plasmic sperm ini*ctir;ln, tbr re-clerir.ution xnd reconiiti-tut ion oim*use li ner after r:mhr1.* cry opre$enxl icn, andlirr re-est;rblishnr*nt *lgratlr*grn-lr** $trl{hs *f mice l'1.

A n i rna I r','el f;rr* reg u I ati r:n s ;r nd gu idrl i nes rrqui reths us* *i analgesigg 1'r-rr procer{r,rr*s th*t "rr}av {fiusem*rr thgn nronlrntcry t: lr t l ight pain r:r *Jistr*ss"'3^Ilecrusr it is nr;lu, rer:*gnixctl thct r*mparable p;rins*nsing meEh*niunr* exist in r*rientx *ntl humans'{- itshr:uld be *ssurneti that any. procxdure thai ciruses painin humnns alsr: cau.\es pii in in aninrals uniess dem*n-ctrated *fherrtie*5. AnirnalE becume xtrrssrt"l and dis-trsssr"d rr,hcn their pain ir ntrt tre*ted, iinri untreatrclp* in ean r ic lay w*ul td heal ing and rnrpr* i r inrnrun*xe tir,iry&-$. In m*re sei-ere case.\. unr{:liel,erJ pairt n:a!'caus{ a r*sFilnsr ta an *th*rrvise n*n-p*inful *timulrrsduc tn central pr in s*nsi t ix t t i *n {al lodyni i r }v }0.

Derpite thr ethical *bligxtiun to pr*vid* anxlg**i;rin order to relirve ptrst-$perative prin$. unalgericsare nnt rautinely administered alter ennbryo tr&n*-fer surgery, eitller becaust trhev are n*l{ ccnrirtrererinrrrtsart' or h*t*us* it is t**r*tl that th* *rullgericc*ulrl h*rnr embrl',: implalrt; lt ion *nrJ u1o1ri111rl ' l ' I t

Rrporrs ln:nr lrr:th *ninrrl experirnents rr"rrl r l irr ical*Lrsrrvati i lns have e*tablishrd that lhe plarenta ir itprnetrxbk bnrrie r that d*es n{}f frr{lte{t th* f*tus linrnrxposurs to drugs fhat ;1rc llkcn h,v cr adminisr*rrd tofh* nlt:thrr. Rath*r, rlm*st all rncdiriltions *r!.uinrr-tt:rcd t$ Fresnant mothnrs rs*rh the fetus, uprin rvhiththey rnay r.t iert adverse et'fects:l^'"t. Opiuids, a widelr,usqd cl*s* of an*lge*i{$. {an *lra indirecti;";t lfe';t th*fr:tns hv:l ltr:ring thc m*th*r' l i nrinuK vr-nti l i l f i*n itrtt iut*rin(' f*n*l{,

'I'h* pu*rible Elf€cts *f * drug r}r'r .}r"!

embry* *r fetus tary depending un the stage of lstalder,*lnFrnenl. For *x*mple, drugs adrninister*d lothr m*ther rluring lerti l izarian *r during rhe eilr lv

l I. 'ah0r"rt$r1';1nlnralf;tr:t}it icl,Xi*rnrdicg|Ilrsu*lr*i:}tltnt{*|irrn+ftlu.{caE{trnv.uf-Atirtn*.Atitrnr,Lirctcr.

I.al:rr>raturir. 'r,Frtuhr'.*{.| lea|tharrdt..*rirrgsfr*nhj hr rddr*rt'd t* N, K^ i nkr.rrt*rn r9'hi*.u{,rrlrrrr!,, gr ) .

t*E AI.JIf'tAL Vn lune 43 , H* . 5 I F { *Y :S14 16 t

Rg$xas.cH sgrs

rt*gcx *f *nrbry*nir c*l l r i i l . isitn r*dl eau$e ;rpr*pttr-s i* r . r r int*r l*re wi th **11 r . i iv i* i r in{"1i . ln l ight r : l ' thes*r*l:r)rts\ th* concern fif scientistr r*g*rding ths usetrf *nrrlgursi* *ttt*r enhr3'* tr*nrfir srirsrrv is uniJcrxtand*lri*. ln ,.:*nrrust, hrlwer,i ir, * I ir:r it*t i rrulnhs:r *l 'studie:* r:r";rluating the eitccti r i l" r 'ari*us i lnalgexirs..tuch ax met*mixt-rl, i lunixin an* buprent:rrplrine, andaf nruifirnadal analge.rin- uring rr elrrnhinali*n qrf {:;}r-g'rrr 'rt*rt .rnd buprennrphinr. rln rjrrir lus nrf;trures *fenrhrvu surl'iv*l ;rnd p*st eip*r*f ir.'tl pain in surrrlgatrrJ;lm* h*l 'e t*und th*t past-ap*rativ*l l. irdministEred*nalg*ti* is ntl detrimentsl t* embrlrr: turtir,al afir:rt"mbryi"r lransi"er surgrryl'i' t ti"

' l i i lma*Jr:l i* * *ynthrtir *nxkrguc i:f cndein* that

il{tr ctnlrall.r* *ncl rvith crtrnprlrahle *n.rIg*sic eil'it":ai!'anrJ p*tr:n{! ' ir: ct"rd*inull ' ' l t . l t is a r;rue*riu r:rixturci*nsis.Iin6 nf twn enantr*nrers th*f lurrutir.rn in a cum-plementilrf firirrl rlr'rl{1. A It lrnugh t rirrnati*l's afli n itI'tirr th* Xr *pioid rr:r:{Fr{}r i* lt-exk, ix r,ifrrr xnrt animrlstudies htvr dr'nr*nstr:*lfr lrJ t lrat trrrmildol als* $ynsr-gi:t irally inhilr its the renptak* sf norrpir:ephrixe and*ert:rf*nin and stimulate* l lre pre-svnaptir relcals *fssrr^rirrn i n J I -:+. plot*r)r'er, $* rn *ti*l - i nclucrd anul gesi ai* n*t rntagr:nired by nak:x*n*, the npi*te antag*ni*t:i.' l 'hs*e

i inrl ingri sugS{$t thirt nr*l:hani*m *l tr.rmad*la*tir:n is n:ult inr*d*1, its :rnalgesic el ' l*ct$ n'rrdiut*rih,v it.l opi*id ;ind monc;rrnin*rgir pre-rpertir*l:. "I^he

*nalge*ic *lftctivenetrn *l ' t irt drug in rnir:e is dnse andstfir in drpsndsnt:6.' l 'he inridsncrs trf re*Pi ratr:rr" *ncl{a rd iil {i detrr ret*i* n ir ss*r.- i trt*d r*' i t h t rilnr;ltl t:1- *s rv* I Ias its ahu*e F*trfit i ir l- are lu$-qr th*n thirt r:f opirit lan*lg*.l icsJi: '3$^'1't**arJol is nr*tahr:l ired rnnr* rup-irlh' in rntl*nls than in hunranr; f l 're ternrinal elinrinir-t i*n half-l i l ir g{"trrrrnathr} is *"1 h in ri}ts, **hrrexs itis 5 .tr h in hun*nrl". lt har *l*r h*en r*;rr:rted tlr*ttram;rd*l ri*cs nol rxcrt ter*trtssnir cr cmbrl'fitux.tcrttsrts in nricu, rats and rah,hits .rnel t irat q:nlr, dr-rresthat *r* nratcrnallr* r$xir" itrr p*ril*us it'rr tlre emhryore^tl*l lertiv*l1'" th*s* l indings inrl ie*tr: fhat tr"rrnr*J*l **nbe sxlrlv u.\ed in rnic*"

Numert:us stutlies huve iienrurr*tr;rted th{t et'tb{-tive bl*thade *f n*xit"ru* stimuli hel'ore s$rgrrr- {an*nnsiderahly nr in inr ixe the intrnsi l . - r ane{ sever i ty r : i

l lasf -$perilt ir,r Fain bl 'hlt ickirl{[ lhr upr*gulatit:n itfesrrtral pain prure*sing puthl+.rv*{'1rl 11. }{err we pr*"*p*ratir"ely irrinrinirteretl tr;rrnadt:l {as an anulg**icre6in'r*n) trl surrogsfc d*nr$ pri*r fa rmhry* tran*fersurgery an*i rontpared their reproductrve r lutct)mesrlnri wtl lh*ing with th*te *l surr*g*tc damr that ha*in*t heet: a*lnrinir*t*rerl pr*-*pe r*tive an.l lgt:xii l . I l irthr*te {nunrb*r nf'Fre;;nilni: iss c.lrrierJ tr: terttt}. [ i ttersir-* and litter survivol {nuntber r;f 'r* 'ean*tl *f{ 'springper rJamlrvere us*ct t* evaiu*t* re;xarisil i l"e s$rre$s,rnd brr:rl.r weights reec,r{.le{i inrnredi*telr. J4 }r *nti .{S hilftcr *firhryrt Iransler sursrrt ' $-rrr usrid aE inti i i*tur**l ' t he dam:i' wellh*irrgi: ' :r,

168 Vcl lum* 41. I ' le) , S I MAY ?*tq

J:

HTTHOBgAll prrurr:etiurm r"*er* rnrri*tl rut in th* l*L,r:r*t.lrr illtrrnul tarilities r:f the $i*rnsdieal Research Founil*ti*nrif the ,{r:arie m} of Atlrens" "l"h* rxpe rimenlai irrt-rt*r:t:lr!'a $ illtlrrr:t'r:d Lrt' I h* re^r nr p*t* nl r*trri na r \,,] u I I r *r r 1 r' * I racc*rd*n":r wrth the i lreek kgixlxti*n tn ihe lxrrltcrIi*n *i ltnintals uE*d l irr r:xperirnental purpr.rres,

' l 'hr

nri i:* usr:d in the rtudl, 'were h*ug*ri anrJ maintrrnr'din *;r-nrtirnc* wilh the F"ur*trrcxn Il irr 'c{irr* l{}l{ l i f i}

t re l . 34J {*r the pr*t* i t i *n * f tn inr"r l : *rcd l*r scir"r ttifir purpussl; atrrJ the {irriris.Jiir llrr' Lrrrt' rrnef Lj,ir r.rJLri tr* rr:l {lrr,t, ".{ nirn*rlst.

h{icc wrre Lr*us*ri jn inelividrrxl}l r,enl i l*te<ilngr$ t "l'rcni pl*rt, Ru gn ggi at*, It*ly ) u n tl er spc:r.: i fir:pirthngen^ fr*e { Sl}[r] r"*ndil i*ns. Rtlrrnts ltrre nr;in -

tainc{i on ir I l-h; I l"h l ightrdarh cv*}* {l i*rn ?:tl{! a.lrrto i: l l{} p.rn.) rvith tenrperatur*r r:f Jl t J "{l xnri r*la-rir,r hr.lrnitlirl' n; 4 5 * I {lryn,

.l'he rnicn u.*re led irr*rir-

tred pell*r:r {19 I lt "l"*klad d}l*baI I i]$:{, I}r*tein Rr:de neI.list, l'larlarr I-* brorat*rier, I ntl i.rin aptl ig, I N ] "r nri h.rr.ia{ies5 til t*!:r lriiter {iEJ Jiflilurn. {iag*s werr lined *,11}rcorncnb b*dr l ing tRehct i " r , l . Ret lennrai*r & St ihne,R*s*nh*rg, (ierrnsn,vl, *ntl the cag*s irnci hrddrngrverc" changecl *nct'p*r wr*ek. "l"h* h*alth *t 'all nricr:in the tuuil it,r, war nrrxrit*rud in ace ,rrdalrce n'lth lht'F*deratitrn uf [,ur*pean l-ab*rat*ry Anim*l $*irn*eAss*ciati*nr' rrcrl lnmendati*ns35. $,l ice rvrr* f{lundtci b* l-re* nf a wid* r&nfic *i p:*tht-rg*nr inclur,lingminute t, irus r:i nire. mr)rl.\s hep*tit i5 r, irr,rs, SentJaiv i rux" grn*unl fn ia vtrur of 'n l t ic , rsor, i rus t i 'p"rr I l l ,rntru$e snc{phalorny*lit is rirus, epiit*ulic dixrr}r*atl l ' infanl nri{e, nrrtus* pxrv*virur, l1,mph*cvtic ehei-ri*meningitir virus, l{ irntan r"irus. *cironrelia r. ' iru$,m{} tt*r} r:yt{}nleg;} I *t'i r tts, rit$ t3:if *rl*nt)r, i r u$ l, nleiu s{atl*n*r,iru* J, polvrtnta !'intrg, I{"r,itrtts, j}*rsir:frr/Jii

lrr*rtcfr is*rpt i* rt, {- if rtl&il cl sr rr;de:n I f urx. (., ics J rirjilrrrlprfif*rure, L'srl n*&rlclgritrtr ftrul$dft*"ri, l{rfir*r&rtrfers pp., $'.|1'i'np{sewl fi p u Jrn t: n f s, Frl stru rr/l+t {:{"'{r d" Sslf *r * ru trifr r*Ff)., Sfrtrgftr&xifJ$s xlErurfl i / irrrni. i, I l-hsnt*luliu)it f{ptoe $ (:* i, .5 f rr:pf ar e{:*r} pner.{rtt r}r} id tj. } r: rsi rrr rr s p p..hlcllsi*l&l *pg:., lur mites and pinlvurrus.

Obtaining smbryss frr transferl{e sel*r:fed firrt-gen*rati*n {.w*ek *kJ i*rn.ri*n{i l l : l j l , tt lr l rnii:* {brt:cl frr nr,r {]5?$l.i{,r lr:nr*l* arrrla t.)gr1;3 lx*le) xr emlrrv* rl*n*rs l irr t-rur studier,hr*caure they pr*du*e s liirg* numi:*r i;f rggs rrft*r*rtprr*vulatinn.

'l'wiw p*r lveek, lve irrriure*J suprrr-

ruv*latirrn in ten f{rrfr;Flltlr lemgle mice r'vi{h *n irrfrapr*ritun*al {i,p.} inl*cli*n t}l-5 ILJ pregn*nt n};Irr **rtj}}]gun* il*f rr:pi n { }}}t 5t i l S rrll igc, n, I ntsrr.rt, Br:iu;**u l*,FraneeJ- ftrl l*wed 4$*.'{ l} h later with an i.p. inier":"f iu l r * f 5 lU human ch*r i r :n i r g*nad*trerpin { i ' { t . t i ;{lh* rul *n, I n f r n'et, lleruc*ur-e, I"'rxnr."* }, I nr nrt:tl iat eh',rfter th* I '{ l: i l inj**tittn, lr"tv nral*d ttr*:ur*ruvuIalr '. in:ice rvith {:- t* I $-rnr.rnth rld Sf-tl l} l j I l t .r rrralu rturir

wrv*, *lh.l tl i rrlfi {. t tlrt"

NASEARC}I HNTE

(rl pri l l 'rr l [r"rt i l i t l ' { I lenraLl:l maie} ;rnrJ rtraintirirrtds:ach hrt"rrdirrg pair irr irrt l iviriual cag*s.

Th* tnli*wing dilv. u'* rlrecks{l rhe iemales lorcopruiatnrl ' plugs. 1{'* humurr*lv kil lcd femaleri thathad ptugs bv r:ervical ri i t l*cati*n in i lcc*rri*nee **ithrhe "{VI,{A gnidrl ines inr the *ulhana*ra of'anrnralsi*.tr{r **l leEted the cviducts in ;r ,15-nrnt culture ,Jishrontaiuing 2 mi l l '1J culturc nrEdiun^r { Si I si | " $igmrAIdrich, l i t. !-cruis, i l{ i l l . Alier lerl lcrtiun. lvr' tttns-ferr*d *ar l r ovidnct l r r a drsh ccl t ta in ing I ml r \12nteti iunr {.! igma-Aldrich, "tr- I '*nis- hl{^11 anri 75 flln 'a lur*nid; lse { l0 mg/ml; Signta"Aleir ic l r . $t" I "*uis,LI{}}. Then we *}xrred the ;rmpull* t* r*lrr*se tltr*{lcr'1ri, trt'e w;*shrd th* oo(:w*s thrre tim*r *'irh {"reshh{3 medir:rrr and then rinrrd thtm with fim]rryomtxt\$ClS.{ rn*dium {l\Ierr:k I{i l l ipor*, Bil leric;.r, SlAl.11'e then collectrd thr r:ne^rell xtage eggs *nd plac*dthe ru in live 20-pl micr*drops r-rf fimbrrl,crna$ KS{}hlnt*diunr, s*verrd th*n^r with ern['rrl.*- f*rit*d miner*l* i l { l \ lSJl0, Signra Ahlr ich, $t . L*uis, \ l t } } .urd ine uhratrd th*m ilt 3? ot. n l1,r r:-lrhcn di*sit lr f*r l-1 lr s*thr l ,cuuld devclup intn fx 'o-rel l st*ge eggr.

0viductal smbryo tranrfer1$* wsrd 3S 8- t* 1{J-week"*ld allr intr (.rl:t l t} l { i( lRifemaie nric* m embrvo reciprerris in *r.lr .rtudiex.l,fe grr:up-haused the nric* with x nlaumum r,rt 'six

rtt ict per cage in orrler lu gvnclrr*nizr t lteir rstruscv*:lt:r. trte indu*rd pseudoprsgnafi{,v by rnating thr.tem*lt" nrice with t{ nr*nth-*}d varect*nriztt l nt;ih'*of t lr i: $ilm* slrainl earlr nlale was nratEtl rqit ir fH'*ternal*s" The foll*wing morning thrfore l*:t lt] a.nt.],rl'r rh*cked th* 3[ mir:e itrr cnpulat*rv pls1g5- and wefrrund that 16 *l thenr harl plugl. Therie 3S tem*l*srn'cre rundslmh'divideri into two *irauils rrf l3 mic*"

An rxperiencrri surgeon carrivl *ut all surgi**lpr*r**lurrs unrler sseFti{ ccrrr,lilianx in a design;trdtlEF$-l ' i l terud *perlf ing rronl luri ltetl insitk th*.$lrF laii l i t,v, l\ ie w*ighed all surrt:gxtc dtnrs u*ing rdigit;rl halance {n$\tf l${}b" nl Delnrac lnstrunrrnts,Atht"ns, firerce ). The hal.rnre rt'ilt calil"rr.rteti nn *;tchmr;l*rrrement d[! ' using kns]rr'n r*eigl 'rts *f tf l* g,i g and I g. Fiiteen rninutes prirr to the inrJucti*n of'an*tthesial?, ttn* grod5) *l"surrt:rg*i* i i irms we re sul:-cul*ne*u*lv injrc.teri rv-ith lfr mF Frr kg L.rndy weight*t tr*tr:adul hvdru*:lrl*ride t^l 'rxnlal, {-ir i inenthal,Aachen, Gerr:ta:r1). Nr analg*sics n*re irdn:inistercdtt the tlth*r grouft ul surr*g;ltE dxrns b*f*rr *r xlierenrhr yqr lr;rnsler: .rrtrgtry.

Ftrr th* e nrbrl'rt tr;rnribr $urgely" w* *rl*sthelirrrdirl l mice rrith an i.p. injection oi 100 mg per kg bodvn'*ight ketantinr {Inralgen*, Llerial, Fr;lnce} ;rnrl ll} tng

fler hg bndv w*ight xylirzine (Rornpun, l layrr,l,everkusrn, tj*rnrasyJ. 1,1"* uted CIphfhalnric t"rint-mrnt *ont*ining cartrnnter tThih.gel i l .3tl i , AlronLab*rtt*riet Hellx* 5.",t." hlaroussi, {lrter:e} to prrvent

{txtlrli{l dr,vilrg during thr: sp1g1't.r'. \{rhvn tite r:'l{tuf*rras unr{ipxtttt i l t 'nrsr to pinchrng ol'thr parr", rvr rtk'riorirr.ed tht left antl right otarv ant{ nvi<lur:t by nrxkirrg lrr 'n l-cnr dorsal incisians thr*ngh the skin *neinrus*ks *n either rir le oithe v*rtrhri l l u*inrnn brinr*'the {evel *f rhe last rih. l{ ith t}rr ait l *i;r rlrnr*lt insrn ic r*scope, rr.e i nt rt)riurqd ! {} tr+'* - *el I stag* en't br r vt:tint i l the infur: t l iLrulum r: l . the r ight *nd kt t cvi t lur ts

{te rt e *tbr.virli Frr {rlldurt } uxing * glilt* pipe tt*. Lip*nrrintprlgliqln *l ' thc tranrfer, wr' inff rittr irt ' t l t l :c t. ir '" lr ier and *r"idur:l$ *ul **lured th* nb$ttsnin.ri nr*srlerand skin usrng i rhs*rhable 5"{} s i lk Eurur*s {} fsrs i lk ,l i thicnn Ins., N*rritrxierlt, t lernranyi.

Furt-operativ* tareAfter the surgerv. rve t ranslerred ;r l l surrog- l te dai t t rto * temperati lrf-{{lntrolled rr,arming p*d, n'heret l rey were v ixual ly mcni turer i unt i l thel ' r* te iveredlr*rn anesthesia. itr$ rl$se$$ed Lrv tlre fetilrr1 *l nt]rnrxlnrohiIit,t.. lrnnrediatrl} tfttr r{l{r}vrr.$, rr{ trl(135ur*d th*bildv wt",igh* *f th* $urr*gi*t{ rJants. lt'e lh*n plae*rithe surnrgat* danrs in indivit iuui r:u$r$ atd plarrd ;lsingle FeFrr tow*l in tach cage irrr nrst bniltJing. \{teagain rneasured the h*<lv weightr oinlldirms l4 h and"ls h afte r the xurgerv.

trVe chetkcd sll mice tlaib' l irr signs ol'prggtt*^.*'\then litters $ere hCIr$, rl'{ tr*{(}rrietl th* nunbsr rifpupr borrr tt: cach surrcgul*.nnth*r. \t 'e rn,.: lutic{.i inthe anah.sis anv surrogrte rn*tht*r* Ihat lxilq"ti li) r:.1n'vtlrc *nrhrT*s t*r thr sntire duritt itrn *f 't l i t" presnanr v(lr sFlfinl$neQusly ah*rtrd tluring thr: pr*gnxn{T; thtsrl itters wrre rrc*rdtd as h*ving rrr* pufr* "rt birt ir.

Statirtical rnalysis\fe te*ted thr dat* firr normalitv h*i*re slatistir*l *nal-vsis using a mudilied Shapiro-l't illi test" f ir: *igniliriutt leyiatiuns l 'rorn normality tttr* loun{. !\ 'e carrtcdnul eompilrisons *f bcd,v weight*, l i trcr nrr,: arrd titter rurvival brelwt:t 'n the t**** grou$]li usirrg Sturie nt'tirrd*pen*"lerlI $ilmFies f "te$ts lvith Ltr"*nt-l1 trstr l i trcqrull i t l ' *f r,rlr iane t*. C*rnparisr:n r:rf tht" numh*r cl-prrgnant srrrngate danrs thct carried rh*ir l i ftrrs t*-lterm wiis cilrrietl tut using Firherk ex*rt 1*st r*therth*n lleursotrlr;: r:n'ing to the snrall tntal r*rnpl* size,All xtatistical lnalysss wf,rr e arried rtut uritrg, d r(lnr-putrri**rl statirt ical *qll ' t**are Fr{}$iram {5p55 I v.t},SPSS lnc., (.hicago, ILi, []ata arc dirplar'*d ds mr{nwith ritilnti*rd rleviati*n { s.rj. } lvith a signifir.l*ee lsl'elqrf F.r i l .{.}5.

RESIJLTS\4'r did n*t f in* anv nignitic*nr rtrit"trtrrrrie* itt thr

hadv rveight: of the tw* grnups of surr*gut* rJarnt

messurxd hrf 'are entbrvr: trtnsfer surgrrv {F = ff. l5Siur mearurrd i rnmediatr lv (F x 0.2 t .+ j ,21h {P = * .1091and 4l t l r { I } * 0. .135i af t r r the rurger\ ' { ' Iable l i

LAS AHIT$L Volurnr 43, f i r . 5 I rdAY e$ l1 169

RHSH{RIIT }{*.T$.

Immrdi*lily rS rrqpry

tF.S * 3"$

lS.9 * [.S

3* q#.Tfffi .1,,,,.f1?t"& srqqy

4il#:*,8,S t$.s* 3.Xl*a analgcrfr

fnn-apantiv* tn*ffiSd

Ftior tn *urypry

t}-$ * .8.S

*$;S * S,sf

B**ly r+eights *f cni{e in the u.nt.re*t.*d *n*i tranr*dol-

{reated grsuF$ {S }r aft*r surgery {}8.0 * }.1 S 6nd3$-$ * 3"3 &, r**6:e*firr*lyl *lid n,ct elx*nge xignificnntlyfrcn: pre-$p*rativ* b*dy w*ight* {3?.S * ?.9 S and

?9.* * t.57 g- respxctive$y)"A greater nu,rfiher mf trlnrrrJ*tr-trr*teci dnms *nr-

rkd thrir pregnaxcien to tern tttan did dsrns nrtprevirted arr*lg**irl, *lth*uglr the *trfi*r*nfs wss nstxignific*nt {p * S"}3; Tt*blx 3}. The numb*r of c'ff-spring pr*duc*r$ byth* tri*o grnnp* *f surrogat* d*.ms

did nst diff,er cignifir*ntl,r {p * *,34$}" How*v*r, thcnurnbersf f I-d"*ld affnpr:ing rvsaned frsm tL$ re,ma.-tJol^tre*t d surr*g*te dams wru *iglli$ic**fly gteafer

{F * 0.SI9i than the nurnb*r sf otlbFrins w*ari*S fror*the uxtreateet xurr*g*tr darns {Ttblt 3}.

III.${HS5IS}*?hr use uf anxlg*si* i* xn ethir:xl, *cientifir and regu-lat*ry crblig*tirn in all irrt*rnati*nal guitlelines f,rr

x*israls that untl*rgu surtival *wrg*ry, Tht adr$in-istration of analgesicx f*ll*wing *rrlhr.vo transferswrstrry h*s n*t treen r*mftlon! hcwtr,'an b*c*u** itw*n nqrt ccn*i*Jered nec*ssar3. *r b*cause it tryan fe*ffdthat *lr*lgeni*$ enuid harm emtrryer implantation andv,iabilityl't, In tl.li* -rtudy, rv'* xSministered trarnsdml.t5 rnin prior tt erntrryc) tr*nrfsr $ilrgery t* ane *ftw* Sr${rp* *f surr*g*te dam*, -tlth*ugh i{ has beenptev'i*unly rxperrt*S thnt *urg*ry tra"nni*n*y de*reeresp*st-*per*t[v* fu*d int,ak* md b*Sy *'*ig]tt3']fi,nn .weight ltma rry** rre*rded pfttt-frHryery in mine mf

eithcr Sroup, Tk** rnsult *uggcrt* that th* intc'n*i$*r *ev*rity cf n*"rt-*perntiv* p*in did **t prtv*nt thxsnin:*ls frsrlr e,atins and drinhing"

Tr*nrsd*l me*fn-tcnt had n* signifr*tnt effect rnrkx pregnsnry ret* *r *r* th* litter cixe* nf th* s$rro-gate dnm*- tlt*:,aryh dums sd:ffiinister*d pre-o5t#r*tiissnrxrlgesia rrrre slightly mors lik*,ly rs {*rry their

lS.S * l.'$ t$;S * *.S

pregnnncie* t*l t*rm" Thtse findirrge suggest that tra-

m*deil h*s n* detrirnental effec* nrr ernbryo impliw"tstion and E*:rl,ivsl. Furth€rnrstr€, we fsund thst th*

nu:tlber *t pup* wua*lsd ft*rn tr*n**d*l-ffe*ted sus-

rogate dun* r*xs,stgn *ficantly g,restsr th,a* ths, mtlrnb*r

*f gh*se weaned lirom untrestsd *firrsgste dEnns, kk

sussest that thh Frcneficial effect of tr*madol on pup

sxryil'al may betht reault sf aiievi*ling the surr*gat*damr' p*-st-*pxr*tir"e pain" It h*s been estatriish*d

thst f*md* rsde.nt* tend ta be nrare ssnsttiv* t* pain-

f$i stimrcti than males, rnsst lik*ty *r+'ing tqr the e*-

mctiulstisn of upioid recept*m by g*xadnl xtersic{h*rrnernerirs, Mscl*ren and !*iqhiffsll were the first lslahow thtt tht r€ssrp{isn ratr sf tr,&nsferred *rnhry,**incre*n*d xrhen $rrrogalf, dsms un:d*n+ent * tr*at-r&*ti ruqgi**I prn*edmr*. "tlth**gh thxir *nBerir*entwae *lesigned .t* d*| ibe rately t raurnx{lce th* $urs*Sat*dnrns ch;rring *rnbry* trsns&r stirsexyb sursesns {an-not alweyx cpxtr*I the nm*unt *f p,ain caussd tq th*

animd. Theref*rer prs*op*rstive *n*lg*si* *auld be

viexud *$ s pr*ysntiv* mrs$urc t* minitxie* pai* *xdh* n*Cicip lly i n fl'rre n ce re p rod ucti ve aut**rn r* "

Siol*gical differences h*tr*een th* nurrogate darns*s"$ Ideltr &$ rirleriy s{lrsr fsct*r* t}r*f can contr}bufe rcr

tls suceess *f eseh step of embrl'rr tr*nsf*r e$rgtrryimay havr inf'lue*crd sur rcslrlf*. Sur experiert*e r+:jfh

exrbrX'o lrensfer in mice hss sf.!CIrtnr,l fhat succe*sful

rnnbry* trans d*pends sn !${ny fastoss, in*ludi*g

the :r*spnns* ef w*,,ryn dsns-r fsfln,sles t* st4r*r*rrnli*-ti*n; the strain* tht h*dy weiglt *ndthe reprnttuctivecapability af the embryo danor f*males and ree ipient

mnthers; th* qu*lity a*d nurnber tf implanted €gS$;

the qua$itp' $,f ctrlt$rr rnsditlr'n, that,is u*ed f*r embrvctde:r*l*prnxn* thc *rgeriens* *f the $$rg*jsn; tke k'CIu*-

ing *cntiiti€ns sf th* anirnals; thc anesthetlc$ that ar€

used in the ernhry* trensfer $urgsry; and the po$t"

operative care *f tht mimal$4t-&5. fn this rtrr*fy, we

$ied to minimirE the infiu*nc* pf thuse fectors thet

arc kncrryn t* sdvsrcely influen{e sil{{essful *mhsrytr

tran*fer rnd thnr inter{ere tsitk the experim*n{al

trindlngs. Fnr ixst*r*e*, dsn*r embr.rn*x unr*srx'*nt

*Xuality chrcks b*,th hefurssnd efter their rultir"ttittn,snd th*se egg,s with a r,norphol*gical artq,ntalt' sn*l"r

as p*h'sperm,y {)r cvtnpl*sm*c fr*grn*ntiittnn, or fhat

wrr* undergi:ing c*ll divi$irrr rrer* discard**$ and

nnt used f*r enrtrnlt* transtbrss. Nelxrth*less" f"rrrthnr

studies using x lxrger numb*r *f turr*6*tc darn* sn{t

cliff*r*n.t d*xe* *f tramxct*l *re needeti tc c*n$irm th*

l'rlidiry *f u,ur r*sults.

t{crt * r"&lt*l*r of !lc*n r *d. smrbrr

prprlretw numbcr af cf PtrylwriGd to Fupe pcr mmcd prr

"$ry $lqry @r ,f*o a*rlg*tlc 10

Fr,p.aptret{m 13tnm# ' ,

43 . l {a . S I HAY 4014

$.$ * *-F 4*S *,.{

S.1 *.*"6 S.I * &.$

1 f $ V * { u m * wwv* lablntrne{, c*nn

RESEARCH HOTE

In *$r t * l$r i { }n , I t r tu rpe-ra t i r ' * adn l in is t f t i t i r :n er f

l nrn:;rrlol at a tL:sr r:f lti mfi frcr k,g bnrlv r'r'*ight tltrr:r

nul hrrm thc srtcr*ss rales *t 'emhrv* tr. ln*f"er 5urgt"rv.

Arl t i i t i*nal studirs arf, nr 'rrsi*r l ' l r) t i l r th*r inl '* t t !-

g;rte u,hetlr*r tral l l {d*l ha* x pr*: i t ivr rnfJuctter: $n {hr

tt t t *t i :cr ul" pspl rt 'e"rnf t l .

(*irPnnfi 6 rril*nrr*t IirxRtsTSihe aulhr:r; d*tlare *B r:0mpe'.irg f,rrtrrrial i i l iefetis^

R*cciv*d 23 OttobEr 2Sl3: rcc*ptcd ? f.larrh I014Publirhed *nline at http :llw*r. laheninat.c*rn/

l. i-rcul*ing. D.R. ef uf. ihr *ff*rtl *f perro;r*r*tive *nalg*:t*

*q i i t t * r r i l * in { r l : {S1{ l { { i n i t : t utdarqi . } r r lg d i t : rnrYt)tr*nrfer. J. 4,qry. .4:s**. l**. {pirn. ki. 4}. 4l.i-4?S {f*1*1.

i. P*rl:*r, J.lt4., Au*il:, J., 'r l i lkt.s*rt. j,,S larb*lrr, r- [f iects nf,nuliinrr:r1li ,xl*tq*fi-r *l the ${t{{ei\ c{ nr{irrt* €rnitrya f i*rfEre.ur$sry, i. Iw {rr*r. lo$. drrirn. "{c'r. 50, 4***4?CI {?*:1}.

3. Amrrrcsn {ottege *f iaborstor? Ar:irn,ri }4edirtn*. {,stdsdrn*s

J*rr t*e A$:e.{lr$fnf dnd ,4r}*rfemxnf ql P*rn rr,r ff*drnl: un,i,trrfihil"r {F.rbtir ltrt*r,'r*nt. &{l Ail, tCIt7 }" r, hti ;.rr.iiwwvr,arltm"O'C,rC$nt*nt.Jfi lr:r 'f i{el:.Puhlic.."Ar t:v*,rpt::rfi*r Sa i n,roCeqt. ra ' I i t . pdf . .

t . Lr*"F*rrilr, |}, *r:atq*.si* f*r r*drnt e;<grl:rimrr.,tni tLi'q*rr-.&.r. i. Ye.r. ,{*rJ. S?, }"{ {}**}1.

i. 1r'rt*raqeacy Rr:,Ea:rh Animal {ammlttee. l i.J. $ovr,'nm€rtfirtgtip{e-t for ft* tffi/lzclir:* ond {lr:* o1 !'*',4tr,truf* dltltg&

{Js*d rn lhlting. fr-se*rr*. r:*d lr*inin-{ if}f{irt of 5rirruesrrd 1*rhrt*lpqy P*liey, lt 'arhinglar. P{" i! i8i}.

*. Yrntil, S., l{ay. &^ & i{alhr:lra" 5. dr:'itiggr*". .4.*segf,bc-vs s$dfrrign*rrry*: '{ frsrl:rtcj 6rr'r'#* ?ntJ ed*^ {{ar,rbrirlg* {lntv*rrilyFre:1. Ca'rhndge, tJX, ? i ]07).

;. {*na-S*uil. J.J., Sil ittt. A. & It*r:ry', [. i*mun*iugiu alp*ctl

*l v*t*rin,lry *nrltftt"l ia anrl "lr*lge'. 'a. J. Cllt, r '*l^ +lect.

dss* t . 12 f , , : 15 '3 *3 {eCt *5 } .8. 1'ls&uire. L. rt cj. fctn and w$and ht*l:r"g ir: lurgrc,l"

Fa[!urr*, .4,rn. S*lt$r... ,*f*d. 11, l65*:12 i3{JS6:^{, Inctit i^Jl* far l.**rrxtnry A*irnal R*r*'tr{h. dr"rirf*.yer Lirs f,r:r*

snd ilse rrsd {.*b*rrfs'qy Asirngis &lh erJr. {Nalicrt:i Ar.qdEmiesFr*g. fYa:hi t tgt** , 0{ . 301:J.

l{1. Jrshr, fi.n & 0qunrraiL*, B,i}. {tnr*qatrir*t *l i*aeirqu.rtepr'tst{:t*r'dt'iu* pai* rrfief and chrr:niq Bitrriltentpugl*ssr*live p*irt. 4reltttEsi*f^ {Jj.n. ftr:.4'! drt*rcs 2}.31 ] f i i?0{ j5 i .

i 1. Ihset* . 1, . {1. . tB! . in, 5.1. & }urJ lq{ , A^I . Inrpart t f,:nesth*lic; and analgeliu *n f*tal grcrvth in th,e m*ulei *n . 4n rm. 4? , 115 .1*3 { I f i l i } "

",? [hisn,tr. t.N. & le*. f .{^ {ndl.i Prtcrrl*l Srr.rg fxpss$rrjfii$afics cnd vy(ncrnirt, f,'f$,{ fss*r,'ri ,{*rr*grr:p* 5enr'l #60

{U.$, I}*fartmenl *f ri*.*lth *nd Hurrlr !srB!r*:, l lochv:[ie,

t4s . r985) .t . t . Simn*n*, R.* . , i , t i l t r r . R.{" S Xxi logg. [ . i { . Prerst- l l

diarepan: dittt ibti*.isn aFd r' 'retlbslism in F*ri$stit faie"

l* rEr l*Jr*y 28, 1XI* t$g {)** l } .lri. litilefard. l. ffferts nn tire fet*s "qnd zr*wborn *f rst*rnai

tn*lq*rir an{ awrthEtia: a reuiew. lrn^ .,,'. rtr.rr*lf.}" 51,5&6-**9 tf0{j/ i}.

15. farbn*:inEh. "1, Th* *ffer:tr cri n:**icrtjcr: durin{ ntegnati":y,f*s. .Fsrn. Ptuysirir.n 3?, i0i)*101: {19e.1J.

tS. 0*r';rh. M.*1., i l l t$, t" & F.**drieh. 11.J. S*el 'reoFrrstiverrjnir;i l lrrtion sf ryelarxiru{ {t{*ralgi', I *f$xct poltt:Frrairvil

hady iteiqht and duratist *f rerovrry fru,t !*krxirte-

ryiafin€ a*a**fh*ia in mice u*d*rgcing *mbryt trtrrtfpr: *pr*tir:rir ',*ry r*psrt. [rS. doin" ]S, 4{*{9 i}i l{ l{i^

1) . Val l* , M,. [arr ldt . l , { .J . . Pt t*n, J. } t , , {* [ r " 'e, R. *lrrrr:uniz, l. i. Fh *s'rnare kin*tic-phar rr:ara dyrtam irnadrli i l{ t l the antinoticeslrve effer:tt of at*ir: acti 'r*mi:tsbciit*: cf trarn.rt*1, q*]-{J",felmetngltr*wtdr:l

al:eJ i*J-*-i l*r*:ethyitran*Sttl, in t{it. .7. Ph$rm*lGf.tup. I ' ler. :S3, b40'651 {r$ff}i.

II. t iurr.qn*1. I. $a fl, Ar:*l ',r:tpt'. nl analg*ll: l i l {11iittr: trdrr:i{l+itr^rrtrotinc feir,*i* lcrqul"l r:,. l inrn.tdsi gtrrd,r: rl itttn',u{a:it ir '.

$u.. J. tlir,.;, Pl;*rrr{}ffrj. 51, 3tr-3fi { 1{t-q6i.19. itrrand*. f '{ .t. $ Pinar*r, &, ,&rrtitccir:r;rt1**. trl i i{r,l ir '-e, attd

prtyli i. l i *eFfn{:eni:r r t:rnf;srit,: jrt t}r! '**lttr 1'g'1 1i'tt ' . ' lr ' .,;

tr;rnadcl. P,lcrrearoi. $r*rh*rr- Ssro'B 61. 15; -1s0 il{q8}.iS, teth*rdt, 6.f- & 5c'rnidt, I i. l. ierJ:.i fctvli*trio', i i$ {}f Fsi";

Jrrl pd,rr^ {Sprilger. Nt*,* v$rk, tf l*IJ^?i. t1rnrier. . l.t '{ . friderirhr. f. & trht:*i,Je{. .}. R*;.r.pllr ::r-di"ul

ar:at{*sir ,lr:d trtitei:rve Filtpnil- rf trlrrocoi" ,tl.i c:1.herwl*.r.t ld oprcir3*. 4.'z**irnrffg{.k!.:dfi$nt 38, 817 $U0 llq$gl

il, Q*{f*. ft.*. & }rrd*rirhl, {. ihe b.rl ic re isrrrr d!pe{.t t:ff

ir*rnsdri hy*r*r:hinride, Fsin $pr,. 3, 349."r?1 i:9Q6).2j. ft*ffa, R.$. *t *J. l l l ioid snd ne:r-orisi{ isrrrpfnr*i.!

irt*ep*rrdsntty r*ririhutr: t{":, fc}s !Tr{hitrr\$ *f atirc.rn *ftgarradci, ar

'*typical' *p'l*id snaic**ir. "r, Ffi*rms{rti. frpIher ?60, U i r i *A$* {1S9}} ,

?/i.. Bstrriglrade" ].A.. 0avidl*n. {.. trngfr:r,i. f i.1'1. i i Siant{*r*,l ,A. At t i l .nr * f t ran*d*t , i ts e n*nt innf r6 n,1c ar i , r< ,sr t ,

w*talolite, *-drl$ethyltgamad*l trn :"*r*t.tnin { 5-l{iJ *ft:rv

and ustahs tl th* rat d*rsa{ r*phu riucls$r^ Sr. ,i. 4rhtE:ffi.

7 1 . 3 5 J - ] t * i l 9 ? i l "?E, Gr*nrJ, 5. & Sabictzki , &. e l in i ra l phrr*rernbca ni t ranrt lo i .

{irr" Ph;rro*rofrr$el. 43. I}!*q2i i}lt l14I^l&" lyr"n*nrr, {. e; *{. f r*i*,.ri ion r:f lh* "t*'rlg(sic rrffrr:t t:f

tr;rnadni in lwn diff*r*rrt ttrairl *f rnic*. lr*r**ciirqi t:f f hr

35th Srierti l ir Icrferrrre rf t l",* Hell*nir 5*iretv f*:&ir:{u!rcal it i*nr^e {lt lafpi,u, Greei"* /3-J9 l '1*y /tl:Jj.

i7. f*etl*e, J,f. S '",*r !f igql{:frtnh*rq. x. 1f"}m$drl i}t nr{trl i i t 'r '*adfii 'rrirtered dunng aFeraii i,: 'n: d rluri:{ rl innr*di*ix

-iilitripersh vc eff'*r t s aher abct"Jni n*l hylttrur Ltrcy.S r - i . dn r :w f# .81 , I3? - ;4 I { l t c | I ) .

78. H*iJ$1*i. f i."1. et cl. fff irsry *nc srf*ty *f trarn'tdol I 'ets"rr

r:lcrpFrne fr-lr t. loderate drlc i*ve:e lclta$erati ';e grarn wtlr

:pru..iai r*gaed to tel.sir*t#ty rjesrtvlti$n. $r*:l ls. 4r:*!,; 74,

510 ' 11 , : {199? i "?9. lrlatif i ierel, 1., l!,:hrmann. l ',. lt i*gal. f.P- & {lragg. tl .

1f',e erF*rirteilt*l isri{*l*gy *l tr*ma$Bi; ar t '.ttvi<tw'I*,i lrr:/. Lstr. r$, 63 11 {l{tel.

30. , {anharsn.5." Srse[ey. H. , l {unrar, A. I t Ra; : . i . l i t * s f fer t*f srpenftr** rnalgelrs t* Fcsitrseraliue pair ruIj*f*

* prclp*tiivr rJ*uftle-nlind rtnr{*r.rit*d :ttdy" P*rt ,*{erf. 10,/*s*r3 {?m{}"{issin. I^ Preemptive ,rn*tge:ra at lhe cr*55rc*d. 4:txsts.4nslg 100. :1^1-:56 {2**51,*aumani. V. $rir. 'nl*': lac*'d asletsnntlt *lf anima' rt*[t.:rr:

labcra:*ry'-l*in"lsis. f,pv irr. ,?clt, 34, 5*l-511 ir '-*[:iSrc *n, *" 1.1. A*i m,.r I x*l{.lre: { *Fdipi}. * 1tJ .'tt*,1 }iJ r*rnt'tri''

. . i . t r ,nr f f . 5r t . [ { . 416] / ,1?1 { l l l t l i .3:rertrve i01*J'63/:i j cf tfe [ur-*Featl Parli.rnrri *r:c *i th*

lnurrri l sf 2? 5*pipfib*r ?*li l ffr, lhr pltttt(tt*r1 gtl , lrrifrt.{l 'o

uterJ f*r *cj*ptifrc purp*ter^ t?.r{ii:ull "i$;,r*$i {V il*- f:i;rri$i}i;frf fn io* ?7S, )3-?f ie$lS).t{rrhtai. Itt. el sJ. terornmerdatianr fcr t\e hea[thnqxi'{orirg *f rt:derrt a*t3 'tttbil c*l*,tt i*l in br*t"dlnrl *n,"j

*,cllrriu",*rrf*t urits. i*r}. 4mrn. 10, e!)-i;f {2C*aJ.*medcarr V*tsdrrry !{edi{{[ As5*rirti*r, $utdsttnts J6r lh*

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