rpl2 report

7/26/2019 RPL2 Report

1/66

RecurrentRecurrent

Pregnancy LossPregnancy Loss


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Defnition

of 3 or more spontaneous andconsecutive pregnancies

RCOG Guideline No. 17, May !!3

of or 3 or more consecutive pregnancylosses

"COG #ractice $ulletin No. %, &e' !!1


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Incidence

1( to !)

*+e most idely accepted rate of loss for a

-single spontaneous a'ortion

/!) 0% in ( of spontaneous a'ortions

occur in t+e first trimester of pregnancy

R#2 affects %) of reproductive age

couples4tep+enson M, 5utte+ 6. 8valuation and management of recurrent

early pregnancy loss. Clin O'stet Gynecol !!7


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Number o Patients with RPLUP-PGH, High Risk Clinic

January-March 2011


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RiskFactors

M"9OR R:45 &"C*OR4

Gestational age of t+e pregnancy

Maternal age #ast o'stetrical +istory


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RiskFactors

G84*"*:ON"2 "G8

;"'normalities present in< 70% 1sttrimester losses

5.6% 2ndand 3rdtrimester losses


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RPL based on Gestational ageUP-PGH, High Risk Clinic

January-March 2011


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RiskFactors

M"*8RN"2 "G8 R#2 rate

; =nder 3!y>o 1% )

;"'ove %!y>o %!)

*+e #ractice Committee of t+e "merican 4ociety for Reproductive Medicine.

"ging and infertility in omen. &ertil 4teril !!?


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Maternal ageUP-PGH, High Risk Clinic

January-March 2011

N@ 17


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RiskFactors

#"4* O$4*8*R:C"2 :4*ORA

; #rimigravid %()

; #oor O$ istory %)


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GraviditUP-PGH, High Risk Clinic

January-March 2011

N@17


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Genetic Factors


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GeneticFactors

(?) *risomy 1?, and 1(!) #olypoid

1/) Monosomic for c+romosome B

%) =n'alanced translocations


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!auses o RPL

ACOG

Couples i!h RP" shoul# $e !es!e# %or paren!al $alance#chro&oso&e a$nor&ali!ies

"e'el C

Recommendations#arental 5aryotyping

RCOG

All couples i!h a his!ory o% RP" shoul# ha'e peripheral $loo#karyo!yping per%or&e# an# a ()* %in#ing shoul# pro&p! re%erral !oa clinical gene!icis!

"e'el + gra#e C


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!auses o RPL

RecommendationsCytogenetic analysis of the products of conception

RCOG

In all couples with a history of RPL, cytogeneticanalysis of the products of conception should be

performed if the next pregnancy fails

Level IV grade C


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"natomical Factors


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!ongenital uterine anomalies

unicornuate and bicornuate uteri

Fundal flling deects or intrauterineabnormalities in the u##er two$thirdso the uterine cavit

fbroids and polyps greater than 1.0 cm

septa greater than 1.0 cm wide and 1.0 cmdeep

Ashermans syndrome adhesions.

"natomical

Factors

iagnostic factors identified in 1!! omen it+ vs 3 or more recurrent pregnancy losses

9aslo, Carney, 5utte+ M et al, &ertility and 4terility Dol. E3, No. %, Marc+ 1, !1!!1! "merican 4ociety for Reproductive Medicine, #u'lis+ed 'y 8lsevier :nc.


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"natomicalFactors

iagnostics

; ysterosalpingogram 04G

; pelvic ultrasound F> 4ono+ysterograp+y

; 3 =ltrasound

; 2aparoscopy

; ysteroscopy


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!auses o RPL

Recommendations

Anatomical Factors

All women with RPL should have a pelvic

ultrasound to assess uterine anatomy and

morphology

Women with RPL and a uterine septum should

undergo hysteroscopic evaluation and resection


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%ormonal "bnormalities


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%ormonal

"bnormalities Generally considered luteal p+ase defects

Result from inadeuate progesteroneeffect on t+e uterine endometrial lining

PCOS

3? ; (?) of R#2 H levels of androgen No Inon t+erapy in decreasing t+e risI of pregnancy loss in

omen it+ R#2


22/66

!auses o RPL

ACOG

"n association 'eteen t+e luteal p+ase defect and R#2 is controversial. 2# s+ould 'e

confirmed 'y endometrial 'iopsy

2uteal p+ase support it+ progesterone is of unproven efficacy

Level B

Recommendations

Hormonal Abnormalities

RCOG #olycystic ovary morp+ology itself does not predict an increased risI of future pregnancy

loss among ovulatory omen it+ a +istory of R#2 +o conceive spontaneously

Level III grade B

#repregnancy suppression of +ig+ 2 concentration among ovulatory omen it+ R#2and #CO4 does not improve t+e live 'irt+ rate Level Ib grade A

*+ere is insufficient evidence to evaluate t+e effect of progesterone supplementation in

pregnancy to prevent a miscarriage Level Ia grade A

*+ere is insufficient evidence to evaluate t+e effect of +CG in pregnancy to prevent amiscarriage Level Ib grade A


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Metabolic "bnormalities


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Metabolic "bnormalities

*+yroid disease

) of omen it+ midtrimester loss ere

+ypot+yroid

ia'etes mellitus

if ellcontrolled, it is NO* associated it+

recurrent pregnancy loss


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!auses o RPL

"COG

es!s %or glucose in!olerance, !hyroi# a$nor&ali!ies an# an!i-!hyroi#an!i$o#ies are no! reco&&en#e# in !he e'alua!ion o% o!herise

nor&al o&en i!h RP"

"e'el C

Recommendations

Meta'olic isorders

RCOG Rou!ine screening %or occul! .M an# !hyroi# #isease i!h oral glucose

!olerance !es! an# !hyroi# %unc!ion !es!s in asy&p!o&a!ic o&enpresen!ing i!h RP" is unin%or&a!i'e

Rou!ine screening %or !hyroi# #isease in o&en i!h RP" is no!reco&&en#e#

"e'el +++ gra#e /


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Inectious Diseases


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"ntip+osp+olipid syndrome 0"#4J 6+ere does it come fromK

4+erer, $lanI, 4+oenfeld et al, !!7 8lsevier 2td.


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Inectious!auses

Microbial inection Positive cervicalcultures

; !hlamdia trachomatis; Mco#lasma hominis

; &rea#lasma urealticum

iagnostic factors identified in 1!! omen it+ vs 3 or more recurrent pregnancy losses

9aslo, Carney, 5utte+ M et al, &ertility and 4terility Dol. E3, No. %, Marc+ 1, !1!

!1! "merican 4ociety for Reproductive Medicine, #u'lis+ed 'y 8lsevier :nc.


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!auses o RPL

$acterial Daginosis

a risI factor for ndtrimester miscarriage and preterm delivery

association it+ 1sttrimester miscarriage is inconsistent

For women with history of previos preterm birth!

dete"tion and treatment of B# in early pregnan"y may

prevent a frther preterm birth

Co"hrane review $%%% Level &A grade A


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%ematologic cause

*+rom'op+ilia

&actor D 2eiden gene mutation

deficiency of protein C, protein 4 and

antit+rom'in :::


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Immunologic !auses


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Re#roductive Immune Failure'ndrome

!"()G*R+ I , "lloimmune

!"()G*R+ II , "P"'

!"()G*R+ III , "N" Positive

!"()G*R+ I- , "ntis#ermantibodies

!"()G*R+ - , Natural kiler cellsand embroto.ic ctokines/ organs#ecifc antibodies


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"nti#hos#holi#id"ntibod 'ndrome


34/66

"nti#hos#holi#id "ntibod

'ndrome most common acuired cause of

+ypercoagula'ility

associated it+ J; fetal loss

; thrombosis

; atoimmne thrombo"ytopenia

; elevated levels of antiphospholipidantibodies


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"nti#hos#holi#id "ntibod

'ndrome Considered as t+e autoimmune cause of R#2

:nvolves to anti'odiesJ

2upus anticoagulant 02"C 7)

"nticardiolipin anti'ody 0"C" 1()


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"nti#hos#holi#id"ntibod

'ndromeLAC + ACALAC + ACALAC + ACALAC + ACA

FETAL LOSSFETAL LOSS

THROMBOSISTHROMBOSISTHROMBOSISTHROMBOSIS


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Diagnosis o "P"'1. Clinical Criteria

Recurrent Dascular *+rom'osis; arterial, venous, or small vessel t+rom'osis in any tissue or organ confirmed 'yJ

imaging, doppler studies, +istopat+ology

1 uneLplained deat+ 1!t+ eeI "OG

1 premature 'irt+ 3%t+ eeI of gestation 'ecause ofJ; 4evere preeclampsia or eclampsia

; 4evere placental insufficiency

3 consecutive spontaneous a'ortions

1!t+ eeI of gestation eLcluding t+e folloing as causesJ; Maternal anatomic or +ormonal a'normalities

; Maternal and paternal c+romosomal a'normalities

Sapporo, 1998


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Anticardiolipin Antibodies0"C" >aC2; "C" :gG or :gM 'y 82:4"; medium to +ig+ titers 0 i.e %! G#2 or %! M#2 or EEt+

percentile on to or more occasions at least 12eeIs apart'y

and / or

Lupus Anticoagulant02"C or 2"J

p+osp+olipid dependent coagulation tests F occasions at least 12eeIs apart

; 5aolin Clotting *ime 05C*,; ilute Russel Diper Denom *ime 0RDD*; activated #artial *+rom'oplastin *ime 0a#**

. 2a'oratory Criteria

11t+:nternational Congress on "#"4, 4ydney "ustralia, Nov. !!%

"P"'


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"P"' screenUP-PGH, High Risk Clinic

January-March 2011


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2a'oratory Criteria

An!i-2 glycopro!ein-1 an!i$o#y +gG an#

or +gM iso!ype in seru& or plas&a

( in !i!er !hcen!ile* presen! on !o or

&ore occasions a! leas! 12 eeks apar!

&easure# $y "+3A accor#ing !o

reco&&en#e# proce#ures4

11t+:nternational Congress on "#"4, 4ydney "ustralia, Nov. !!%


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"nti$01 GP2

"nti G#1 anti'odies are independent risI

factors for

;*+rom'osis 0 8vidence level ::

; #regnancy complications 0 8vidence level :

:n 31!) of "#4 patients, "nti G#1 may 'e

t+e only test positive 0 8vidence level 1


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"nti#hos#holi#id"ntibod

'ndrome efinite "ntip+osp+olipid "nti'ody4yndrome s+ould fulfill

; 1 clinical and

; 1 la'oratory criteria


43/66


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RPL

eneticenetic AnatomicAnatomic !"rombop"ilia!"rombop"ilia #mmunologic#mmunologic

$arotping$arotping

eneticenetic

counsellingcounselling

&ptions 'or&ptions 'or

adoptionadoption

()*()*"steroscop"steroscop

+!,* -R#+!,* -R#

)urgical)urgical

correctioncorrection

AP) screenAP) screen

omanagedomanaged

#mmunolgist#mmunolgist(ematologist(ematologist

A)A (eparinA)A (eparin

#' postie#' postie

ie (eparinie (eparin

ndocrinendocrine #n'ectious#n'ectious

!)( screen i'!)( screen i'

smptomaticsmptomatic

P&)P&)

ProgesteroneProgesterone

ericalerical

culturescultures


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Management

Reerred to Immunolog


46/66

Reerred to ImmunologUP-PGH, High Risk Clinic

January-March 2011


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Management23 Medical treatment includes he#arin/

low$dose as#irin/ andimmunoglobulins

13 "ctive attem#t to search or othercauses o RPL

43 Management o RPL should also

include e.tensive counseling or the#atient and her amil


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(hera#eutics

"nticoagulation alone ma besu5cient in most cases3

; "s#irin

; %e#arin


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(hera#eutics

"s#irin; 'tart "s#irin 67$277 mg dail at least a month

#rior to conce#tion and throughout #regnanconce #regnanc test is #ositive3

; "'" given #reconce#tion is an inde#endentand signifcant #rognostic actor associatedwith a good outcome 3

; !ontinued #ost deliver as #rimar

#ro#hla.is i the #atient is not breasteeding3

Carmona F et al Am J Reprod Immunol 2001; 46: 24!2"


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(hera#eutics

%e#arin

; "dded once #regnanc test is #ositive/ or#ositive or a etal heartbeat at

#ro#hlactic doses3; Discontinued once the #atient is in labor3

)#idural anesthesia is avoided i he#arinand "'" are still being given together

because o the risk o bleeding3; Resumed 21 hours ater deliver and

maintained u# to 1 weeks #ost#artum

! l i i h


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!orrelation o treatment with*utcomes

(R)"(M)N( LI-) 8IR(% R"() "n treatment overall 9:37;

None 2439;

"s#irin alone :637;

Prednisone alone 4237;

%e#arin alone


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(reatmentUP-PGH, High Risk Clinic

January-March 2011


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ABomen considering#regnanc should be

counseled regarding thecourse o the disease and its

com#lications3C


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Bork u# 2st(rimester

8aseline !8!/ #latelet count/ bloodt#ing and urinalsis

Platelet count weekl 4./ then evertrimester

)ncourage anti$stasis e.ercises/regular walks

Bork u# 1nd and 4rd


55/66

Bork$u# 1ndand 4rd(rimester

8iometr ever 1$@ weeks or intervalgrowth rom 1nd trimester onwardsand observe or

; I&GR; 'igns o abru#tio #lacenta

; 'ubchorionic hemorrhages

; Placental inarctions; *ligohdramnios

; Premature aging o the #lacenta

Monitoring 1nd and 4rd


56/66

Monitoring 1ndand 4rd(rimester

Do##ler -elocimetr o uterine andumbilical arteries at 17 weeks andmonthl thereater

; "n abnormal umbilical and uterine arterdo##ler velocit waveorm is aninde#endent #rognostic actor #redictive o

adverse outcome

!armona F et al "m E Re#rod Immunol 1772 @9 1:@$1:77 mg with -itamin D dail

; 8one densitometr at 9th month %#eracidit/ rom "s#irin/ Prednisone; Ma give antacids


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Plan and Mode o Deliver

Prevent e.cessive bleeding duringdeliver

; Discontinue "'" two weeks #rior to

deliver e3g3 4@ or 4> weeks; I on Low molecular weight he#arin/ shit

to unractionated he#arin a week beore

deliver term Juncertain wash$oH timeK; Discontinue unractionated he#arin 9 to21 hours beore !'


61/66

Plan and Mode o Deliver

!o$manage with Immunologist and %ematologist

I deliver is urgent but #atient still on "'" andull he#arini?ation #re#are the ollowing

; Platelets; Fresh ro?en #lasma; Packed R8!; (ransuse #latelets and FFP beore giving anesthesia or

!' or during labor; )valuate need to reverse he#arin eHect with #rotamine

sulate

Minimi?e risk o thrombosis during labor JD-(/Pulmonar embolism/ MIK

Route o deliver


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Route o deliverUP-PGH, High Risk Clinic

January-March 2011


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Post #artum Management

%e#arin 21 hours #ost#artumu# to @ weeks #ost#artum3


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Post Partum !are

Goals

Prevent thrombosis

!ounsel or the ne.t #regnanc !ounseling or uture risk othrombosis reassess need or

anticoagulation


65/66

!ounseling or Ne.t

Pregnanc No oral contrace#tives whichare thrombogenic

"dvise #re$conce#tionalanticoagulant treatment


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(he )nd

rpl2 report

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