Vol XXX[V n 4 2007 ISS O)(J ()o03

crnieal and Experimental Obs etries ampGynecology

EdIted 11)

A ONNJ S

IRoG CAN~DA INC WV w imgl1et

Contents Clinical and Experimental Obstetrics amp Gynel~ology - VoL XXXIV n 4 2007

IEDITORIAL ARTICLES I

Treatment of male iniertility HI Check - Camden NJ (USA) Subnormal semen specimens may be treated by medical llItaos with low gonadotropins andor testosterone intrauterine inseminatiun IVF-Ei with or without intracytoplasmic sperm injection with the least effective varicocelectomy

201

Evidence that progesterone receptor antagonists may help in the treatment of a variety of cancers by locally suppressing natulal killcr cell activity

JJ-l Check L Sansoucie 1 Chern N Amadi M Srivastava K Larece - Camden NJ (US) Evidence is provided that mifepristone may belp tu inhibit malilIlant tumor progression through immune suppression hy supshypressing a progesterone-illduleu ulllllllllomodulalU1Y pmteill

207

I ORIGINAL ARTICLES I

Reproductive Biology Sectioll

Successful full-term pregnancies with assisted reproduction supported with prednisolone acetylsalicylic acid and high progesterone doses in a lupus patient

E Trakakis C Loghis D Laggas G Simeonides V Vaggopoulos C Chrelias G Lambos D Kassanos -Athens GREECE

I young wuman suffering from lupus erythematosus had two successful full-term pregnancies with assisted reproduction after receivi ng prednisolone acetylsalicylic acid ami prugcsterone in high doses

212

General Section

Laparoscopic resection or sonography-guided vaginal aspiJation of elldometliomas prior to ICSI-ET does not WOlsen treatment outcomes

T Cirpan F Akercan RN Tavmergen Gokcr E OZYlJIek R Levi E Tavmergen - Bursa TURKEY

Laparascopic resection or sonography-guided aspiratioll of endometrioma prior to IRT treatment does Ilot worsen treatmcnt outcomes

215

Cervical neoplasia after diagnosis and follow-up of women with atypical s(uamous cells of undetershymined significance

EFC MUlta CS Da Silva 1B Vieira KM Khabbaz SJ Adad - Gerais BRAZIL

eliof or invasive lesions frequently occur ill women diagnosed with ASCUS

219

In vitro effects of ritodrine magnesium sulfatc and their combination on spontaneous contractions of myometrial strips of pregnant rat uted

S HacivchogJu T Cirpan M Cosan Terek 1 Kanit M Kazandi K Oztekin - IzmiJ TURKEY

Ritodrine is a more effedive tocolytil drug thun magnesium sulfate

223

Evaluation ofVEGF in placental bed biopsies from preeclamptic women by immunohistochemistry T Cirpan F AklfCan Me Terek M Kazandi IIT Ozcakir G Giray S Sagol -lvlunisl TURKEY VEGF expressiun of Uw plaCental bed is significantly lower in patients with preedumpsia

228

Comenr 199

Morphological and biochemical appruisul of the liver and rellul effects of indinuvir Oil rut pregnuncy MP Quintino RS Simoes FHM Oliveira RM Oliveira-Filho MJ Simoes ML Nakamura L Kulay Jr - Sao Paulo (SP) B~1ZlL Matcrnal and fctal effccts of indinavir on rat pregnancy arc examined

232

Combined inherited thrombophilia and adverse pregnancy outcome G Androutsopouos A Mougiou M Karakantza G Sakellaropoulos G KOluounis G Decavalas - Riol1 GREECE The associubon bel ween combined inherited thrombophilia and poor pregnancy olltcome in the South-Western Greek populashytion was investigatec1_

236

Role of lipid peroxidation and enzymatic antioxidants in pregnancy-induced hypertension SB Patil MV Kodliwadmath SM Kodliwadlllath - Begaum KARMAlAKA

Elevateti levels of lipid peroxidation (malondialdehyde) dne to a decline in the efficacy of antioxidant defenses may predispo~e individuals to preeclampsia

239

Gynecological screening for HPV infection R Idotta MT Fiorino P Surace F Arena I Scopclllti - Reggio Calabria l1ALY

242

Effect of different types of textiles on pregnancy A Shafik - Cairo EGYPT lhe different cffcds of textiles on pngnuncy wcrt studied in iiv( groups of patients one control group and fOllr experimental groups

244

ICASE REPORTS I

Episceritis as a possible complication of lymphocyte immunotherapy - case report B Katsoff JH Check 1 Devlin - Camden NJ (USA) Episcleritis after lymphocyte imrnullOlhcrapy before embryo transfer could be a complication

247

Cholecystitis during pregnancy A case report and brief review of the literature C Chloptsios V Karanasiou G Dias N Kavouras K Stamatiou F Lebren - Thebes GREECE A case of cholecystitis during pregnancy with a good outcome after treatment with antibiotic therapy is described_

250

Spontaneous heterotopic pregnancy a successful outcome AA Seoud MM Saleh AH Yassin - Lancashire UK A case of heterotopic pregnancy with a successful outcome after treatment of the ectopic elemcllt 13paroscopically is reported

252

Murkcd improvement of intractable arthritic pain in a woman with rheumatoid arthritis with sympathshyomimetic amine treatment despite previolls failure with standard therapy and possible implications for last trimester unexplained fetal demise - case report

P Boimel J H_Check - Camden NJ (USA) Sympathomimetic alllines effectively treated intractable rheumatoid aIthritis in a woman with unexplained last trimester fetal

dcmise

254

Leiomyoma of the utelus and retroperitoneal angioleiomyoma case report G Lazovic S Milicevic J Alanackovic V Milosevic T Bofunovic M Gojnic - Belgrade SERB1A

A rare case of retroperitoneal angioleiomyoma diagnosed during surgical intervention for uterine myoma is desl-Tibed

257

Pregnancy achieved following IVF -ET after surgery tor infertility with perforate transverse vaginal sepshytum and incomplete septate uterus case repOlt

N Koyama K Hasuda A Hayashi T Hasuda - Kumamoto IAFAN

In a patient with transverse vaginal septum IVF-ET after surgery achieved pregnancy

259

Index vol XXXIV 2007 263

Index uf Authors vol XXXIV 2007 267

Combined inherited thrombophilia and adverse pregnancy outcome

G Aodroutsopoulosl A MOUllouZ M Karakantza1bull G SakellaropouJosJ

G Kouruunj~i G Decavalasl

(DtpttrtllMIII of ObnttrlcY QlNt GplMCnt I ~~Il t1llkmDl tldiciIk Dfi5iorf ttlH~M itaI Ph)$ l~ Ultfi~ ric of I JrlerlKJJi 1tcJoI ampRt fG-

Summary

Inherited lbrombophill twl ~n AlJiCSltd as a Ible condition rUMrea$ed ~pubilily ll) IIh rsa ptegtUnCy OUloomlU In OW p~iVc olud)bull ~e ille5Ji~ soclauoo cwee laquoml ned inhtriled lh rol1lbophil nntl(I regn~ Il~-Y out(Otn( n Ibe SOuthWestml Greek population

Tbree hllndred and nlnetysix healthy Greek women with tipontaneou~ pregnancies were investigaud for Qmbin ILl) of thl thIcc commoiiclillhromOOphili~ IYu[lltions (Fact 1 II G2021OA ~act()r V lcilkn and MJHFR C671T~ Ilnd rolowed ror 1dC6e pIqshynancy outtomes Stnililical ilnalyW WII5 performed by i~middots cbi-squa ~l(

Four worlWln (t~) had the FV lcidenIMTHFR 16m dwhll geOOl)-pt and lyenill middot men WSk) ad Ult AI G20Z IOAIMTHFR T611T double cnotype Although me mamplJ munber of la5CS of combined inherited lhrombophilia it IIj rms that Ihe p~srncc of fV leiclenfMTHfR T677T 46Uble ttenl)IYpe in~se lh rifi~ for plll~ntid abruptiofl

Key words Filclor U G20210A Factor V lelden MTHFR C677T CGmbinM inbcriled Ihmmbopluha Pngnancy 001(1

latrodutdon Inherited thrombophilia the principal risk factor for

maternal thrllmboemboli middotm has been SUsatSlcil as Dposshysible CQwilioD of increased sUlceplibilily to ad HSe p~gnancy OUIpoundOmes Sutre5sful preatallcy ouComQ is dependent Il the development and maintenance or deshyquate placcnrat circullllon AbnormaHties of placeneal vasculatu re may result in a num~ f of geStailonai pathologic including early and late ~ lQS1i pJashyceruaJ abruption intrautaine grou-lh tCtZlordation (lUQR) intrauterine fctal dealb (IUFD) and Ilre~clampslD (le) 11] All these outcomes complicate up III 02middot3 of prea nancics and Ilre the lelldin causes of perinatal morbidity DOd monaJit 12J

The prm-encr o f acquired or inherited thrombophilic (actor-s increases the risk of Ihrornlgtocmbolic disea~ in the motner while these fuc~Qrs hae also been implicOlled In the development of gesl tional ~ompl icati0D5l15SOC shywd IQ pluentul -aiClllopaIby (3) In OW pm -pective stud) we investigated the i-Slgtoci ll

~ i()n between combined Illherited thmmbophilia ana ad verse pregnancy outcome in the Southmiddot Western Gmk population

Material a Methods Between Jallu~ry 2004 and J~lnUElry 2006 ~96 WQm~n witmiddot

lIpontaoeous pregrutndes II-en rdcrrcd to the Outpatien CI nle ot rhe Obstelrk Itod Gynxlr)IOS) Dcparunent i the rnh~rshy

I) of IltIlrn MIdictI School II women ~ ili ga~ed II lite mree laquoJ moq~SI tbrumb pbJLic mutatiuns (f actor II Ol0210A Factor V Lciden und M1HFR C677r tod foll17wtld

n pound 1 Ozo amp Gft XXXIV n ~ trII

for Ildverse pregmmcy GUlCOmlt- Women wirb known inherited mrom)xlphilia pre xioling 3ntlphapbolipifl S)1IdJome (APS) and aDllpbospboljpd lDb~ we~ ~Iuded fro I 1M 1IUdy The ~tly was Jppnl ed b~ the ElhkJl Committe( Qf the hosshypi tal Wrillen informed cunsenl was obtained flom each womlln All women were starteu Ill sUfJSllementr (11 folate 3fld iron lhe 13 wed of iCSliltion

Blood satnpks ill h l)T ~ eN Ollccled from I womeD 00 Ihcit rim i~ 10 dr Ouqwiefll Cbnll laquo()S weeks of gcmtion) M Ilaquobr diagn is amp$ performed a(t~r DNA illLlltticm polyshymer I chwn reaction IPCR) ampliliu(lUon anu hybridization of amplifillHiQn prolt C~8 lsin 3Jlclc specific Qlli on uclilotidc probe for the detection of factor II CUooIOA FaaorV C506A aId MTHFR C617T nonna mil muW~ Ie ia Gene Muwion Ass y Kit Vienna L bullAP~uia

Ad1lISC ))regnanlY outcomes we~ cf)nsidercd for all fetid los~c~ (spontmeous ubortl()n and inlrwtmne deillh ) al well ~ gc5latirll1al compliclltlon~ with relomllcmal circulMcHy rtisturshy~(P~[3) abfuptlOn ialnDldinc IfOWlh mrdmon and ~psil)

Intll1ulenne dcalh (I ) WitS dcfil)cd as fel1 I ()s~ after 24 wecks gClitation

Pla~cntoJ abrupuml lKIa of hePAl was defjned is he pliil-=flIamp from its sit~ of implmmtioo Ixfixt the dlJIay q ~ fetus 1-1

InIIa1lla1De ~lh IIUdDrton (ItlCiR was defined w II bir1h wcighl below me 5ih percentile for geK1atiQnaJ age [~l

Pree clampsia WF1 wn defined Ity II blilOO pre~)lUlC above 14090 mrn( Ig a~ 20 ~L~ glaquos13l iltw ptOOin~agt JCJ) maf14 hours or pmisreDI 30 mgd) 11+ dipstitir in nmdnm wiDe sampII1Iampei The reno ~ pncclamji~i i$ ~cd IIfbcn bllaquogtd prrrStU abovr 1601110 mmHg is ncDrdrd al fClaBt si x hours part lind prot~jnWia ur more than 5 i rLing 14 It fJOICUB (6)

Suuiullll analyses crc performed us in the SPS5- ll f(lr w mdm t he chi~qUlm test AS ustd mess 1M bull beOCD aom arilbIH

Contents Clinical and Experimental Obstetrics amp Gynel~ology - VoL XXXIV n 4 2007

IEDITORIAL ARTICLES I

Treatment of male iniertility HI Check - Camden NJ (USA) Subnormal semen specimens may be treated by medical llItaos with low gonadotropins andor testosterone intrauterine inseminatiun IVF-Ei with or without intracytoplasmic sperm injection with the least effective varicocelectomy

201

Evidence that progesterone receptor antagonists may help in the treatment of a variety of cancers by locally suppressing natulal killcr cell activity

JJ-l Check L Sansoucie 1 Chern N Amadi M Srivastava K Larece - Camden NJ (US) Evidence is provided that mifepristone may belp tu inhibit malilIlant tumor progression through immune suppression hy supshypressing a progesterone-illduleu ulllllllllomodulalU1Y pmteill

207

I ORIGINAL ARTICLES I

Reproductive Biology Sectioll

Successful full-term pregnancies with assisted reproduction supported with prednisolone acetylsalicylic acid and high progesterone doses in a lupus patient

E Trakakis C Loghis D Laggas G Simeonides V Vaggopoulos C Chrelias G Lambos D Kassanos -Athens GREECE

I young wuman suffering from lupus erythematosus had two successful full-term pregnancies with assisted reproduction after receivi ng prednisolone acetylsalicylic acid ami prugcsterone in high doses

212

General Section

Laparoscopic resection or sonography-guided vaginal aspiJation of elldometliomas prior to ICSI-ET does not WOlsen treatment outcomes

T Cirpan F Akercan RN Tavmergen Gokcr E OZYlJIek R Levi E Tavmergen - Bursa TURKEY

Laparascopic resection or sonography-guided aspiratioll of endometrioma prior to IRT treatment does Ilot worsen treatmcnt outcomes

215

Cervical neoplasia after diagnosis and follow-up of women with atypical s(uamous cells of undetershymined significance

EFC MUlta CS Da Silva 1B Vieira KM Khabbaz SJ Adad - Gerais BRAZIL

eliof or invasive lesions frequently occur ill women diagnosed with ASCUS

219

In vitro effects of ritodrine magnesium sulfatc and their combination on spontaneous contractions of myometrial strips of pregnant rat uted

S HacivchogJu T Cirpan M Cosan Terek 1 Kanit M Kazandi K Oztekin - IzmiJ TURKEY

Ritodrine is a more effedive tocolytil drug thun magnesium sulfate

223

Evaluation ofVEGF in placental bed biopsies from preeclamptic women by immunohistochemistry T Cirpan F AklfCan Me Terek M Kazandi IIT Ozcakir G Giray S Sagol -lvlunisl TURKEY VEGF expressiun of Uw plaCental bed is significantly lower in patients with preedumpsia

228

Comenr 199

Morphological and biochemical appruisul of the liver and rellul effects of indinuvir Oil rut pregnuncy MP Quintino RS Simoes FHM Oliveira RM Oliveira-Filho MJ Simoes ML Nakamura L Kulay Jr - Sao Paulo (SP) B~1ZlL Matcrnal and fctal effccts of indinavir on rat pregnancy arc examined

232

Combined inherited thrombophilia and adverse pregnancy outcome G Androutsopouos A Mougiou M Karakantza G Sakellaropoulos G KOluounis G Decavalas - Riol1 GREECE The associubon bel ween combined inherited thrombophilia and poor pregnancy olltcome in the South-Western Greek populashytion was investigatec1_

236

Role of lipid peroxidation and enzymatic antioxidants in pregnancy-induced hypertension SB Patil MV Kodliwadmath SM Kodliwadlllath - Begaum KARMAlAKA

Elevateti levels of lipid peroxidation (malondialdehyde) dne to a decline in the efficacy of antioxidant defenses may predispo~e individuals to preeclampsia

239

Gynecological screening for HPV infection R Idotta MT Fiorino P Surace F Arena I Scopclllti - Reggio Calabria l1ALY

242

Effect of different types of textiles on pregnancy A Shafik - Cairo EGYPT lhe different cffcds of textiles on pngnuncy wcrt studied in iiv( groups of patients one control group and fOllr experimental groups

244

ICASE REPORTS I

Episceritis as a possible complication of lymphocyte immunotherapy - case report B Katsoff JH Check 1 Devlin - Camden NJ (USA) Episcleritis after lymphocyte imrnullOlhcrapy before embryo transfer could be a complication

247

Cholecystitis during pregnancy A case report and brief review of the literature C Chloptsios V Karanasiou G Dias N Kavouras K Stamatiou F Lebren - Thebes GREECE A case of cholecystitis during pregnancy with a good outcome after treatment with antibiotic therapy is described_

250

Spontaneous heterotopic pregnancy a successful outcome AA Seoud MM Saleh AH Yassin - Lancashire UK A case of heterotopic pregnancy with a successful outcome after treatment of the ectopic elemcllt 13paroscopically is reported

252

Murkcd improvement of intractable arthritic pain in a woman with rheumatoid arthritis with sympathshyomimetic amine treatment despite previolls failure with standard therapy and possible implications for last trimester unexplained fetal demise - case report

P Boimel J H_Check - Camden NJ (USA) Sympathomimetic alllines effectively treated intractable rheumatoid aIthritis in a woman with unexplained last trimester fetal

dcmise

254

Leiomyoma of the utelus and retroperitoneal angioleiomyoma case report G Lazovic S Milicevic J Alanackovic V Milosevic T Bofunovic M Gojnic - Belgrade SERB1A

A rare case of retroperitoneal angioleiomyoma diagnosed during surgical intervention for uterine myoma is desl-Tibed

257

Pregnancy achieved following IVF -ET after surgery tor infertility with perforate transverse vaginal sepshytum and incomplete septate uterus case repOlt

N Koyama K Hasuda A Hayashi T Hasuda - Kumamoto IAFAN

In a patient with transverse vaginal septum IVF-ET after surgery achieved pregnancy

259

Index vol XXXIV 2007 263

Index uf Authors vol XXXIV 2007 267

Combined inherited thrombophilia and adverse pregnancy outcome

G Aodroutsopoulosl A MOUllouZ M Karakantza1bull G SakellaropouJosJ

G Kouruunj~i G Decavalasl

(DtpttrtllMIII of ObnttrlcY QlNt GplMCnt I ~~Il t1llkmDl tldiciIk Dfi5iorf ttlH~M itaI Ph)$ l~ Ultfi~ ric of I JrlerlKJJi 1tcJoI ampRt fG-

Summary

Inherited lbrombophill twl ~n AlJiCSltd as a Ible condition rUMrea$ed ~pubilily ll) IIh rsa ptegtUnCy OUloomlU In OW p~iVc olud)bull ~e ille5Ji~ soclauoo cwee laquoml ned inhtriled lh rol1lbophil nntl(I regn~ Il~-Y out(Otn( n Ibe SOuthWestml Greek population

Tbree hllndred and nlnetysix healthy Greek women with tipontaneou~ pregnancies were investigaud for Qmbin ILl) of thl thIcc commoiiclillhromOOphili~ IYu[lltions (Fact 1 II G2021OA ~act()r V lcilkn and MJHFR C671T~ Ilnd rolowed ror 1dC6e pIqshynancy outtomes Stnililical ilnalyW WII5 performed by i~middots cbi-squa ~l(

Four worlWln (t~) had the FV lcidenIMTHFR 16m dwhll geOOl)-pt and lyenill middot men WSk) ad Ult AI G20Z IOAIMTHFR T611T double cnotype Although me mamplJ munber of la5CS of combined inherited lhrombophilia it IIj rms that Ihe p~srncc of fV leiclenfMTHfR T677T 46Uble ttenl)IYpe in~se lh rifi~ for plll~ntid abruptiofl

Key words Filclor U G20210A Factor V lelden MTHFR C677T CGmbinM inbcriled Ihmmbopluha Pngnancy 001(1

latrodutdon Inherited thrombophilia the principal risk factor for

maternal thrllmboemboli middotm has been SUsatSlcil as Dposshysible CQwilioD of increased sUlceplibilily to ad HSe p~gnancy OUIpoundOmes Sutre5sful preatallcy ouComQ is dependent Il the development and maintenance or deshyquate placcnrat circullllon AbnormaHties of placeneal vasculatu re may result in a num~ f of geStailonai pathologic including early and late ~ lQS1i pJashyceruaJ abruption intrautaine grou-lh tCtZlordation (lUQR) intrauterine fctal dealb (IUFD) and Ilre~clampslD (le) 11] All these outcomes complicate up III 02middot3 of prea nancics and Ilre the lelldin causes of perinatal morbidity DOd monaJit 12J

The prm-encr o f acquired or inherited thrombophilic (actor-s increases the risk of Ihrornlgtocmbolic disea~ in the motner while these fuc~Qrs hae also been implicOlled In the development of gesl tional ~ompl icati0D5l15SOC shywd IQ pluentul -aiClllopaIby (3) In OW pm -pective stud) we investigated the i-Slgtoci ll

~ i()n between combined Illherited thmmbophilia ana ad verse pregnancy outcome in the Southmiddot Western Gmk population

Material a Methods Between Jallu~ry 2004 and J~lnUElry 2006 ~96 WQm~n witmiddot

lIpontaoeous pregrutndes II-en rdcrrcd to the Outpatien CI nle ot rhe Obstelrk Itod Gynxlr)IOS) Dcparunent i the rnh~rshy

I) of IltIlrn MIdictI School II women ~ ili ga~ed II lite mree laquoJ moq~SI tbrumb pbJLic mutatiuns (f actor II Ol0210A Factor V Lciden und M1HFR C677r tod foll17wtld

n pound 1 Ozo amp Gft XXXIV n ~ trII

for Ildverse pregmmcy GUlCOmlt- Women wirb known inherited mrom)xlphilia pre xioling 3ntlphapbolipifl S)1IdJome (APS) and aDllpbospboljpd lDb~ we~ ~Iuded fro I 1M 1IUdy The ~tly was Jppnl ed b~ the ElhkJl Committe( Qf the hosshypi tal Wrillen informed cunsenl was obtained flom each womlln All women were starteu Ill sUfJSllementr (11 folate 3fld iron lhe 13 wed of iCSliltion

Blood satnpks ill h l)T ~ eN Ollccled from I womeD 00 Ihcit rim i~ 10 dr Ouqwiefll Cbnll laquo()S weeks of gcmtion) M Ilaquobr diagn is amp$ performed a(t~r DNA illLlltticm polyshymer I chwn reaction IPCR) ampliliu(lUon anu hybridization of amplifillHiQn prolt C~8 lsin 3Jlclc specific Qlli on uclilotidc probe for the detection of factor II CUooIOA FaaorV C506A aId MTHFR C617T nonna mil muW~ Ie ia Gene Muwion Ass y Kit Vienna L bullAP~uia

Ad1lISC ))regnanlY outcomes we~ cf)nsidercd for all fetid los~c~ (spontmeous ubortl()n and inlrwtmne deillh ) al well ~ gc5latirll1al compliclltlon~ with relomllcmal circulMcHy rtisturshy~(P~[3) abfuptlOn ialnDldinc IfOWlh mrdmon and ~psil)

Intll1ulenne dcalh (I ) WitS dcfil)cd as fel1 I ()s~ after 24 wecks gClitation

Pla~cntoJ abrupuml lKIa of hePAl was defjned is he pliil-=flIamp from its sit~ of implmmtioo Ixfixt the dlJIay q ~ fetus 1-1

InIIa1lla1De ~lh IIUdDrton (ItlCiR was defined w II bir1h wcighl below me 5ih percentile for geK1atiQnaJ age [~l

Pree clampsia WF1 wn defined Ity II blilOO pre~)lUlC above 14090 mrn( Ig a~ 20 ~L~ glaquos13l iltw ptOOin~agt JCJ) maf14 hours or pmisreDI 30 mgd) 11+ dipstitir in nmdnm wiDe sampII1Iampei The reno ~ pncclamji~i i$ ~cd IIfbcn bllaquogtd prrrStU abovr 1601110 mmHg is ncDrdrd al fClaBt si x hours part lind prot~jnWia ur more than 5 i rLing 14 It fJOICUB (6)

Suuiullll analyses crc performed us in the SPS5- ll f(lr w mdm t he chi~qUlm test AS ustd mess 1M bull beOCD aom arilbIH

Comenr 199

Morphological and biochemical appruisul of the liver and rellul effects of indinuvir Oil rut pregnuncy MP Quintino RS Simoes FHM Oliveira RM Oliveira-Filho MJ Simoes ML Nakamura L Kulay Jr - Sao Paulo (SP) B~1ZlL Matcrnal and fctal effccts of indinavir on rat pregnancy arc examined

232

Combined inherited thrombophilia and adverse pregnancy outcome G Androutsopouos A Mougiou M Karakantza G Sakellaropoulos G KOluounis G Decavalas - Riol1 GREECE The associubon bel ween combined inherited thrombophilia and poor pregnancy olltcome in the South-Western Greek populashytion was investigatec1_

236

Role of lipid peroxidation and enzymatic antioxidants in pregnancy-induced hypertension SB Patil MV Kodliwadmath SM Kodliwadlllath - Begaum KARMAlAKA

Elevateti levels of lipid peroxidation (malondialdehyde) dne to a decline in the efficacy of antioxidant defenses may predispo~e individuals to preeclampsia

239

Gynecological screening for HPV infection R Idotta MT Fiorino P Surace F Arena I Scopclllti - Reggio Calabria l1ALY

242

Effect of different types of textiles on pregnancy A Shafik - Cairo EGYPT lhe different cffcds of textiles on pngnuncy wcrt studied in iiv( groups of patients one control group and fOllr experimental groups

244

ICASE REPORTS I

Episceritis as a possible complication of lymphocyte immunotherapy - case report B Katsoff JH Check 1 Devlin - Camden NJ (USA) Episcleritis after lymphocyte imrnullOlhcrapy before embryo transfer could be a complication

247

Cholecystitis during pregnancy A case report and brief review of the literature C Chloptsios V Karanasiou G Dias N Kavouras K Stamatiou F Lebren - Thebes GREECE A case of cholecystitis during pregnancy with a good outcome after treatment with antibiotic therapy is described_

250

Spontaneous heterotopic pregnancy a successful outcome AA Seoud MM Saleh AH Yassin - Lancashire UK A case of heterotopic pregnancy with a successful outcome after treatment of the ectopic elemcllt 13paroscopically is reported

252

Murkcd improvement of intractable arthritic pain in a woman with rheumatoid arthritis with sympathshyomimetic amine treatment despite previolls failure with standard therapy and possible implications for last trimester unexplained fetal demise - case report

P Boimel J H_Check - Camden NJ (USA) Sympathomimetic alllines effectively treated intractable rheumatoid aIthritis in a woman with unexplained last trimester fetal

dcmise

254

Leiomyoma of the utelus and retroperitoneal angioleiomyoma case report G Lazovic S Milicevic J Alanackovic V Milosevic T Bofunovic M Gojnic - Belgrade SERB1A

A rare case of retroperitoneal angioleiomyoma diagnosed during surgical intervention for uterine myoma is desl-Tibed

257

Pregnancy achieved following IVF -ET after surgery tor infertility with perforate transverse vaginal sepshytum and incomplete septate uterus case repOlt

N Koyama K Hasuda A Hayashi T Hasuda - Kumamoto IAFAN

In a patient with transverse vaginal septum IVF-ET after surgery achieved pregnancy

259

Index vol XXXIV 2007 263

Index uf Authors vol XXXIV 2007 267

Combined inherited thrombophilia and adverse pregnancy outcome

G Aodroutsopoulosl A MOUllouZ M Karakantza1bull G SakellaropouJosJ

G Kouruunj~i G Decavalasl

(DtpttrtllMIII of ObnttrlcY QlNt GplMCnt I ~~Il t1llkmDl tldiciIk Dfi5iorf ttlH~M itaI Ph)$ l~ Ultfi~ ric of I JrlerlKJJi 1tcJoI ampRt fG-

Summary

Inherited lbrombophill twl ~n AlJiCSltd as a Ible condition rUMrea$ed ~pubilily ll) IIh rsa ptegtUnCy OUloomlU In OW p~iVc olud)bull ~e ille5Ji~ soclauoo cwee laquoml ned inhtriled lh rol1lbophil nntl(I regn~ Il~-Y out(Otn( n Ibe SOuthWestml Greek population

Tbree hllndred and nlnetysix healthy Greek women with tipontaneou~ pregnancies were investigaud for Qmbin ILl) of thl thIcc commoiiclillhromOOphili~ IYu[lltions (Fact 1 II G2021OA ~act()r V lcilkn and MJHFR C671T~ Ilnd rolowed ror 1dC6e pIqshynancy outtomes Stnililical ilnalyW WII5 performed by i~middots cbi-squa ~l(

Four worlWln (t~) had the FV lcidenIMTHFR 16m dwhll geOOl)-pt and lyenill middot men WSk) ad Ult AI G20Z IOAIMTHFR T611T double cnotype Although me mamplJ munber of la5CS of combined inherited lhrombophilia it IIj rms that Ihe p~srncc of fV leiclenfMTHfR T677T 46Uble ttenl)IYpe in~se lh rifi~ for plll~ntid abruptiofl

Key words Filclor U G20210A Factor V lelden MTHFR C677T CGmbinM inbcriled Ihmmbopluha Pngnancy 001(1

latrodutdon Inherited thrombophilia the principal risk factor for

maternal thrllmboemboli middotm has been SUsatSlcil as Dposshysible CQwilioD of increased sUlceplibilily to ad HSe p~gnancy OUIpoundOmes Sutre5sful preatallcy ouComQ is dependent Il the development and maintenance or deshyquate placcnrat circullllon AbnormaHties of placeneal vasculatu re may result in a num~ f of geStailonai pathologic including early and late ~ lQS1i pJashyceruaJ abruption intrautaine grou-lh tCtZlordation (lUQR) intrauterine fctal dealb (IUFD) and Ilre~clampslD (le) 11] All these outcomes complicate up III 02middot3 of prea nancics and Ilre the lelldin causes of perinatal morbidity DOd monaJit 12J

The prm-encr o f acquired or inherited thrombophilic (actor-s increases the risk of Ihrornlgtocmbolic disea~ in the motner while these fuc~Qrs hae also been implicOlled In the development of gesl tional ~ompl icati0D5l15SOC shywd IQ pluentul -aiClllopaIby (3) In OW pm -pective stud) we investigated the i-Slgtoci ll

~ i()n between combined Illherited thmmbophilia ana ad verse pregnancy outcome in the Southmiddot Western Gmk population

Material a Methods Between Jallu~ry 2004 and J~lnUElry 2006 ~96 WQm~n witmiddot

lIpontaoeous pregrutndes II-en rdcrrcd to the Outpatien CI nle ot rhe Obstelrk Itod Gynxlr)IOS) Dcparunent i the rnh~rshy

I) of IltIlrn MIdictI School II women ~ ili ga~ed II lite mree laquoJ moq~SI tbrumb pbJLic mutatiuns (f actor II Ol0210A Factor V Lciden und M1HFR C677r tod foll17wtld

n pound 1 Ozo amp Gft XXXIV n ~ trII

for Ildverse pregmmcy GUlCOmlt- Women wirb known inherited mrom)xlphilia pre xioling 3ntlphapbolipifl S)1IdJome (APS) and aDllpbospboljpd lDb~ we~ ~Iuded fro I 1M 1IUdy The ~tly was Jppnl ed b~ the ElhkJl Committe( Qf the hosshypi tal Wrillen informed cunsenl was obtained flom each womlln All women were starteu Ill sUfJSllementr (11 folate 3fld iron lhe 13 wed of iCSliltion

Blood satnpks ill h l)T ~ eN Ollccled from I womeD 00 Ihcit rim i~ 10 dr Ouqwiefll Cbnll laquo()S weeks of gcmtion) M Ilaquobr diagn is amp$ performed a(t~r DNA illLlltticm polyshymer I chwn reaction IPCR) ampliliu(lUon anu hybridization of amplifillHiQn prolt C~8 lsin 3Jlclc specific Qlli on uclilotidc probe for the detection of factor II CUooIOA FaaorV C506A aId MTHFR C617T nonna mil muW~ Ie ia Gene Muwion Ass y Kit Vienna L bullAP~uia

Ad1lISC ))regnanlY outcomes we~ cf)nsidercd for all fetid los~c~ (spontmeous ubortl()n and inlrwtmne deillh ) al well ~ gc5latirll1al compliclltlon~ with relomllcmal circulMcHy rtisturshy~(P~[3) abfuptlOn ialnDldinc IfOWlh mrdmon and ~psil)

Intll1ulenne dcalh (I ) WitS dcfil)cd as fel1 I ()s~ after 24 wecks gClitation

Pla~cntoJ abrupuml lKIa of hePAl was defjned is he pliil-=flIamp from its sit~ of implmmtioo Ixfixt the dlJIay q ~ fetus 1-1

InIIa1lla1De ~lh IIUdDrton (ItlCiR was defined w II bir1h wcighl below me 5ih percentile for geK1atiQnaJ age [~l

Pree clampsia WF1 wn defined Ity II blilOO pre~)lUlC above 14090 mrn( Ig a~ 20 ~L~ glaquos13l iltw ptOOin~agt JCJ) maf14 hours or pmisreDI 30 mgd) 11+ dipstitir in nmdnm wiDe sampII1Iampei The reno ~ pncclamji~i i$ ~cd IIfbcn bllaquogtd prrrStU abovr 1601110 mmHg is ncDrdrd al fClaBt si x hours part lind prot~jnWia ur more than 5 i rLing 14 It fJOICUB (6)

Suuiullll analyses crc performed us in the SPS5- ll f(lr w mdm t he chi~qUlm test AS ustd mess 1M bull beOCD aom arilbIH

Combined inherited thrombophilia and adverse pregnancy outcome

G Aodroutsopoulosl A MOUllouZ M Karakantza1bull G SakellaropouJosJ

G Kouruunj~i G Decavalasl

(DtpttrtllMIII of ObnttrlcY QlNt GplMCnt I ~~Il t1llkmDl tldiciIk Dfi5iorf ttlH~M itaI Ph)$ l~ Ultfi~ ric of I JrlerlKJJi 1tcJoI ampRt fG-

Summary

Inherited lbrombophill twl ~n AlJiCSltd as a Ible condition rUMrea$ed ~pubilily ll) IIh rsa ptegtUnCy OUloomlU In OW p~iVc olud)bull ~e ille5Ji~ soclauoo cwee laquoml ned inhtriled lh rol1lbophil nntl(I regn~ Il~-Y out(Otn( n Ibe SOuthWestml Greek population

Tbree hllndred and nlnetysix healthy Greek women with tipontaneou~ pregnancies were investigaud for Qmbin ILl) of thl thIcc commoiiclillhromOOphili~ IYu[lltions (Fact 1 II G2021OA ~act()r V lcilkn and MJHFR C671T~ Ilnd rolowed ror 1dC6e pIqshynancy outtomes Stnililical ilnalyW WII5 performed by i~middots cbi-squa ~l(

Four worlWln (t~) had the FV lcidenIMTHFR 16m dwhll geOOl)-pt and lyenill middot men WSk) ad Ult AI G20Z IOAIMTHFR T611T double cnotype Although me mamplJ munber of la5CS of combined inherited lhrombophilia it IIj rms that Ihe p~srncc of fV leiclenfMTHfR T677T 46Uble ttenl)IYpe in~se lh rifi~ for plll~ntid abruptiofl

Key words Filclor U G20210A Factor V lelden MTHFR C677T CGmbinM inbcriled Ihmmbopluha Pngnancy 001(1

latrodutdon Inherited thrombophilia the principal risk factor for

maternal thrllmboemboli middotm has been SUsatSlcil as Dposshysible CQwilioD of increased sUlceplibilily to ad HSe p~gnancy OUIpoundOmes Sutre5sful preatallcy ouComQ is dependent Il the development and maintenance or deshyquate placcnrat circullllon AbnormaHties of placeneal vasculatu re may result in a num~ f of geStailonai pathologic including early and late ~ lQS1i pJashyceruaJ abruption intrautaine grou-lh tCtZlordation (lUQR) intrauterine fctal dealb (IUFD) and Ilre~clampslD (le) 11] All these outcomes complicate up III 02middot3 of prea nancics and Ilre the lelldin causes of perinatal morbidity DOd monaJit 12J

The prm-encr o f acquired or inherited thrombophilic (actor-s increases the risk of Ihrornlgtocmbolic disea~ in the motner while these fuc~Qrs hae also been implicOlled In the development of gesl tional ~ompl icati0D5l15SOC shywd IQ pluentul -aiClllopaIby (3) In OW pm -pective stud) we investigated the i-Slgtoci ll

~ i()n between combined Illherited thmmbophilia ana ad verse pregnancy outcome in the Southmiddot Western Gmk population

Material a Methods Between Jallu~ry 2004 and J~lnUElry 2006 ~96 WQm~n witmiddot

lIpontaoeous pregrutndes II-en rdcrrcd to the Outpatien CI nle ot rhe Obstelrk Itod Gynxlr)IOS) Dcparunent i the rnh~rshy

I) of IltIlrn MIdictI School II women ~ ili ga~ed II lite mree laquoJ moq~SI tbrumb pbJLic mutatiuns (f actor II Ol0210A Factor V Lciden und M1HFR C677r tod foll17wtld

n pound 1 Ozo amp Gft XXXIV n ~ trII

for Ildverse pregmmcy GUlCOmlt- Women wirb known inherited mrom)xlphilia pre xioling 3ntlphapbolipifl S)1IdJome (APS) and aDllpbospboljpd lDb~ we~ ~Iuded fro I 1M 1IUdy The ~tly was Jppnl ed b~ the ElhkJl Committe( Qf the hosshypi tal Wrillen informed cunsenl was obtained flom each womlln All women were starteu Ill sUfJSllementr (11 folate 3fld iron lhe 13 wed of iCSliltion

Blood satnpks ill h l)T ~ eN Ollccled from I womeD 00 Ihcit rim i~ 10 dr Ouqwiefll Cbnll laquo()S weeks of gcmtion) M Ilaquobr diagn is amp$ performed a(t~r DNA illLlltticm polyshymer I chwn reaction IPCR) ampliliu(lUon anu hybridization of amplifillHiQn prolt C~8 lsin 3Jlclc specific Qlli on uclilotidc probe for the detection of factor II CUooIOA FaaorV C506A aId MTHFR C617T nonna mil muW~ Ie ia Gene Muwion Ass y Kit Vienna L bullAP~uia

Ad1lISC ))regnanlY outcomes we~ cf)nsidercd for all fetid los~c~ (spontmeous ubortl()n and inlrwtmne deillh ) al well ~ gc5latirll1al compliclltlon~ with relomllcmal circulMcHy rtisturshy~(P~[3) abfuptlOn ialnDldinc IfOWlh mrdmon and ~psil)

Intll1ulenne dcalh (I ) WitS dcfil)cd as fel1 I ()s~ after 24 wecks gClitation

Pla~cntoJ abrupuml lKIa of hePAl was defjned is he pliil-=flIamp from its sit~ of implmmtioo Ixfixt the dlJIay q ~ fetus 1-1

InIIa1lla1De ~lh IIUdDrton (ItlCiR was defined w II bir1h wcighl below me 5ih percentile for geK1atiQnaJ age [~l

Pree clampsia WF1 wn defined Ity II blilOO pre~)lUlC above 14090 mrn( Ig a~ 20 ~L~ glaquos13l iltw ptOOin~agt JCJ) maf14 hours or pmisreDI 30 mgd) 11+ dipstitir in nmdnm wiDe sampII1Iampei The reno ~ pncclamji~i i$ ~cd IIfbcn bllaquogtd prrrStU abovr 1601110 mmHg is ncDrdrd al fClaBt si x hours part lind prot~jnWia ur more than 5 i rLing 14 It fJOICUB (6)

Suuiullll analyses crc performed us in the SPS5- ll f(lr w mdm t he chi~qUlm test AS ustd mess 1M bull beOCD aom arilbIH

237

Results

From lie 396 wOmen included in the stud four WOmen (1S() had the FV Lciden 1tTHFR T6i7Tdoubl gen~gttypc und two omen I 05 (~ ) had Ib~ f11 G202IOAfMTHFR T677T double genmype Th~ dernflshygraphiCS of Wl)men ~rrh (lOlltJle (hT(Irnb~)philic genotypes fU~ sh)wn in Tab-Ie L

From the six women irh dOLlN~ lruomoopbilic gelloshytype$ three (5Mi otveloped ge uniQl1al compilcations dming (he follow-up o( their current pregnancy

None of the omen wirh double rhrombophilk genoshytypes developed thromboembolic comp~ication~ (jur ing pregnancy

Tabl-e I - Women s dem()~mJJlriLf rrr =61

No) of plegnallCi~ I tgt~ iIt~) I IB3rlt-1 I 13Jt~ 1 ~ 1 I~~~)ancils 1667- I 2 I 667ft 1

Age of women lts O (O~ ) o(I ~

~~-J5 1 Ll~ 2cc l 1 3J3~c

gt 35 2 1661t( ~(66ml

CompGi(Jllion~ in prciCRL prcenu1Ci~ No f6(i 7~) J (667~ I

~ 1031 ) I (333lt( ) SrnOking No I i3JJ~) l (53311

ie- 2(661-) 2 (667-) Oiabete~ RlclhfU$ No 3110lKd 3 ~ IOO~~ f

Yo orO~1 orQSH Gestalkmai diabetes No 3 IOIlk ) 3 (J(XJ( I

Ycpound j(yeni- ) (Jtlt )

Discussion

Normal pregnancy is an acquired fhrombopllilk condimiddot tion in which marked chang~s in hemostasis take place The neT effect of these prcgnallcy induc~d changes l~ to promote dot formation extension and stahilily These alterations protect pregnant middotQI1)O from ~cre haemorshyrhage during delivery but ehry ttlso predispose them to fhromhoembolic c~)mplic~[ions [7)

The ct)existcnc~ of other acquired or inhertted lhmmshybophilic fac tors increases the risk of thromboembolic di~ase in the mochel iIIrule thcse factors have al~ been implicated in (he demiddotcl(lpmcnt of gestational complicashytiQns associa(d witb placental vaampculoparhy 131

The pathogenetic mechanisms repongtihl~ for plflC~ntlt1 vascular pathologies itl Iomet with lbrQmbophilia have not been fully ei llcida(ed It i f yCt Lmkno n wh) only some women wtfh thrornbophilia express vascuar ge~lashytional palhologic5 while others do not It J5 pos~ibl thaI Ibis may relate to local factors affecTing cuagulation fib middot rinolysis and middot a~cu l~1i lQJlC tU the kvd of the placental esie-l~ (81 CQjnhritan~c of multiple rbromb(tphi lic defects rc

signifkanlly a~~ociated ith increased ri 5K of Venous thrombosis [9 111 The highc [ rish is ex~rlcd by tbe

simultaneous presence of FV Leiden ard r-nG202lOA (OR ~5198 1 fill 12] Simllarly MTHFR 677TT increlses the risk assoiatcd with fV Lciden or with FIJ G102 HlA [[3 ) The simultaneous presence of FV Leideo and MTHFR T677T may be manifeoted by ~r~ thromshybotic events [9 Pl ~n OUtmiddot srudy none or (he women with oQuble thtombophilic genotypes developed rhromboemshyboli( complications during pre2nanc)

T he iarge Ell rOJ)f ll tl Pro~pecti vc Cuhort Oll Thromshybopltilia sl1Jdy (EPCOT) revealed that FV Leidm comshybincu with other thmmbophilk defects had an incfeagted risk for fetal loss r151 AI5o Ule highest ()(U rali () for stillbirth (OR 143 95(k C1 24-86) as doctunenitltl in palient with combined [hrombophilic ddtds [15] In ltlflOther study ~onlbincd thrombopbilic defects were docshyum~nted in 2t of women with prepoundnanty 101 comshypared with 5j ~l of eOJUrol parients [1 til Idiopatbilt tecur~n( nli~canmiddotiagc appears to increase in frequency when O or more concomitant Lhrombophilic defects are pr~sem [J 5 In our ~UJdy one woman (2Yfu) With the FV LeidenlMTHFR T677T double ge(lotype had a SPOOlitshyneOU~ aoortion

In a r~cetll study a strong association between FV Ltiuen and FIl G202 WA mutation wa aenlollstnHcd with primary miscarriages tI 7J confirming previuus findingii II g t9J In ()lIT stlldy FV LcidcnlFII G20210A double genOI)pe wa~ not dctcrtcd

Vhcn thrombophilic factors were considered in comshybination the MTHH mutatIon seemed to ~ign ilicalll l) increase the risk of plegoaocywJSlllge (1 8 20] Simishylady CO Ill brn at ions of lhmmbuphili state may fllrther irJcreasc the risk fOr recurrent fctallogtgt [91- In the Nime~ Ob~tctriciu Lls and HaemaEo~ogi si S Study 5 ( OHA5) placental pathologic vascul~r tiltdings werc documented in 8~~middott of women with r~)rnbined thrombophi lia and in WO(i( of those with a combination of any [hr~)mbophlliCl and MTHFR T677T l2 1) In our study three worn~n (75~) with FV leidenlMi HFR T677T double genotype developed pfegn~ocy cOlpound1plilttions ( I spontaneous aborshytion Ilnd 2 ptacenrai abruptions)

Eitplana1tions offered for the increased ri~k of pregshynancy loss include both th1O(I1bosis of placcntul vesscls and embtl0toxicil) Methyleneletranyclrofolate reductase catalyzes lemeOly]mion uf hClmoeysteine to meth ionine Homozygous MTHFR C677T genemuwtiotl has b~ltn associated rith elevated level of iJoffiucytcirlc and ha~ been identified as a ri sk fa(t l1T for thrombosi [22] The emlwymoxic efleclgt hav been postulated to be related to tllt irliluenc of homocysteine on the proliierl1tion of rapidly diiding elllbryonic cdl~ p3J

Multiple tbrombopbilic factor~ carry a major additional ri~k for advetmiddotse matcmal and fetal outcomes and correshylate we~J wilh phtccnta[ maladaptation as indl21ted by uterine Doppler veloci meHY and 24 h blood prcssurc monitoring A lea~Ol1 10 this tlmlinli may be that tbe low pressure inten11lolls blood flow in th~ presence of a ll1ah~tl1al hyper(oagulable statc might trigger tibtiil deposhysiJion in the placenta and cau~e placcentn~ll ir farcts that might incite development or severe disensc 20J

In ur (tidy two women 150 ) with FV LcideniMTHFR T677T double gCDQry developed fllashycent I ubruptio-n It seems lhat tb~ lm nc uf FV ~id(nMTHFR T677T double gen lypc increases the

ri sk fyr plmell[4l1 abmplion Tbe main limitation of our study Wit) fhe ~nlAlI mlmbcr

of (ISC If CLllfJhmed inheJhed thr mbaphilia 1 hese data require ~DIlIrmulion in large esp~ci~ lly pr41oipC~live ~tutlic

Coadusioo

De pin dIe mall number of c~s of mbined inhershyited lh ttnbophHia it ~eem~ that 1he pre cnce of FV LcidcnIMTIiFR T677T double genotype inc ases the r ik Im pltlenlaJ abruption

RetercntlS 11 1Sluli M MlIilJrVK ~Zzi11lloJCbull I)pck f(~nku11)

S Vi nlJU ~( ~ AM fnitaUIlnne Jl1uvLl rc~II~ IIOII iJI infanu of Ie 11IIn Ih 11yIW (J wlaquo~smiddot gCSt3lro~ 455 -1JlI2Cd Itamp~ I ho-I reAuJ~~middot tJt 1 OiH(~ G~nBnl 199 17l 1~9

A b Ie R bull fi F (j~ ~Iru f h( I t Sit bl E Froi S Th bophtlias as risk ampcmcs rot d p (

ffUJ t1t ~ fu~fSioI fkg p AWl bull ZOO~ L 118 1OUt I 11romboj)-Jilia implkaJioni ~ pr~ l~ OUKomt-

nlomb RFI bull ~3 109 i 3 1 1Cunnmgh 1 ( i lemiddotttl K 13logtm S lIllUlb II nd~lI fl III (

Wcnifllm K WUliams Ob5lerric~ 2~ ldn NcC YLlr~ 1cOnlw Hill ~OOS 811

11 ScCd~ SW Jmpaired feal ~f1)wlh dfilllliflIlllld l in i~J di~middot n(lSIK 011 (Irl (vrlrltI 198~ 64 U)

111 ()IIII1lf~lrlJm G Le~eno K Bloom S luth J ( lll IriMp LII L Well ltum K Vitliln1s Qbslllr)IS 22 N Ii N~ Ill McGrawshyHili 20U~ 762

PI Brc nllnc KA Hlemosuticchm~ ifl r ce n 1 111 Pro r Ngt middotIm IIUlmIam ~OOJ 16 15J

L I Dtell bull BIbrombophi md p~pound ~ R~~ lOO2 I 191

191 I II ~ D~IlIyenf B B-rm L Rosell - J ~ C II I i ll~ i bredi rCln and lac or V 1dJcnlt eC1on rhrombosis- N in I J ~tl 1996 n 4 63

f lO] Urnmcr B Zicl - U 1 Noo GlrlnIIl I S Grilllll JH rlit 1111 t - emol~ IhrombocmbQli~m ~~ Qo llltd II jlh j()Jlb e heJJlJIIf)1l il fCl1 R5D6Q mutali()Il oi fmltlr V rtd lor T~98M gt11ul~Liml uf prol i ~ 1 ( in I~~ iltmlly 01 iI (lfClIIl1i ly tl~ribcd hOltl)y tt()lI~ pnltciJl C ddiciem rcwbom 1 llh li~Umiddott Ihmmoomiddot SIS HltI 199( 8~ 811

1111111 WY Tllmim H Kreidy R_ Tim~lIl Goo Rrul E bull il lsi M ~I ltII 0 Lns~ Olurol ~rxI) Olil Iho o1i blll or actor ((j 11 pNthrombil G1Q2LO~ and TorTHfK ( 61 DlI1JI m l) h i Gil ~pcibiJir) )( ~p C~ lllmm i middotmiddot l lhlampdl

mnI If ~005 19 amp9

l iZ Mlrlmd i JbullTwola EbullCetio I Maiooni A (~ VU Myen ltI Ill Muulljetll in cuagllblllon (aClur in ~ IIU11 whh bulln CI(

113inL(~ III I ctllJ 111~s N Eirgl 1 Moo 2000 M3 (JI bull III FtlJ1 RlIlf1 II KlIimrki Tbull Sak~la Too At l)oK1l i Jl K ~o Hbull

MoDlkIl M tr(J C(murnm C677f poiyrntnpltl$llI ~n dll1l1~lhmiddot ylt1cl~ l rlllLy~f()flhu~ Teductas~ gene inclcll5l- Ill ri ik Ilir d~p veill Ihnllllbolth iiI pilritn~ lhromh R~5 200() 9~middot I

[l-lJ RidktT PM Ilcnnckens CoHbull Sehub J Miltlldl I p M liouw MR SlImpI r MI rlfl~bIIIIJ1 o t hypcrbqnmcYW ilttmia fl(I() v I Icko nd hl of fllOIrt enaill t1l h nhullmshyC7rrr4ariQOI IOf 5 I 77

i15 Pr F 1It0CflllAl j R ~ UL Brilt( [ bull ~orp Conard J CI til -llJCIlasai feW toss w abtr lluollabofilah IAIIltf 1996 Ja 91

1l6] u bull Youn J S HQffll3ll R L nif Hlumtnl(ld L bull Bft r II iii i~ co llmill m~~11 Ilh Ll t lhc pnJ(nB ty It and h lI~rjatcG with ]010 PfeIl1IIl Wfl)lll e f mil Srelll ~()( ) 77 ~2

[17] Finan RIL (unm ll H Ameen G Sbrida HlL RIlHhld M AJJmrl Wy Pr(alcnc~ nf facrnr V G 1691 A (fltltlllJ4 VmiddotIcIden) alld prolhmillbi ll (D()~IOI g~ne InlltnliOM in II 1t1Hrcm Ili~car i~~ r lpllhll icm bullLItI JIlillk2lol 20027 AlG

IIRJ Brennen IL Siltif a Wei~r 7_ Youlis I 6 hl mtnJe ld z l aBir N I1tltJfIlt1rhi 11 pol ~morphismS arc comn~oll I W 1fI1 n wl~h ictul Ioi ~ 11 IIf aPFMeQl a~o- Th~jI ffr~ 1 ~ 6

[19 Souz) SJi hm lit PoDt~ AU Za- MA_ FIfIIII(tI RP F It V C1den md f or II GOO lOA ill n 1A1l1t Itt llil - flUB RqmJd 999 J bull La

1T 11 t ClilIUUlbtlo SR lkliT o ~ 0 B GI 1111 middotAd ~nc n~1m~ n l 11IIIt f)l ~- tur 1 Obil~I G~n~ro[ l(~lrud 111 _001 U 7 14J

l ll Gris l e Q IJc-l I MiJl1JY[1lx F M ITtI(T E Rir I1middotN~v(u Sbullbull Tail 1 M I ai e llsc comml study of the h -1 ll ny of thrombupllll~ lli ~lIHkll in ltollpie~ wih lmc rtl ~1 I(~ Im d no (hmlllhllli~ 1I11llCcd~nt - the Nimcs Obstetricians llnd HIIemal~ln middot ~ist5 SuuJy ~ ~NOHASI Tlrmmh Hm~lIrr~yr 1999 X il91

[lJ Klui 1mnlls LA IIn den Heuve LP Boc-r Gl I 1Lt lii1 P Slcven I ~I oAi~ OIlS BA ~l al Mo oulllor 1C~1)Cl 1111 1Y b In

mild hr~pc-rlJ ll1Q1 t Ciaclln io i lt1) I(ln nLlilalll ll 111 Ihe d ll)middotlmiddot i~trr )drorulill rtdumiddottll~ gi~ is a ~ mit( r ut ( do11Ku 1( lJm 1 HfDlL CJd~ I~

E231 i lHbu t LM 1 T CJ - The oumbn flI CttIK1lllIlll _~ b~ w c-ommon mIR

rr Rqrlid ~~ 15 2659

dd~s nprint rcq1lst~ (0 G ANDRO SOPOULOS M D An ug0Ilt45 Agbull mi I ~1 G~