Recurrent Pregnancy Loss

apa yang dapat kita lakukan?

Kanadi Sumapraja
kanadisuma@yahoo.com

Divisi Imunoendokrinologi Reproduksi

Departemen Obstetri & Ginekologi
FKUI-RS Dr Cipto Mangunkusumo
Apa yang diharapkan pasien keguguran berulang ?

Diagnosis penyebab
Prognosis kehamilan selanjutnya
Tindakan pengobatan bila tersedia
 Definisi
Recurrent Miscarriage (RM) = Recurrent Pregnancy Loss (RPL) ?
NO CONSENSUS !
Patient with two losses at 27, 29 weeks vs. Patient with three losses of blighted ova ~
do we have similar problem?

Miscarriage (Keguguran)
… kehamilan yang gagal berlanjut, berakibat pada kematian dan
dikeluarkannya embrio atau janin dari dalam … 500 g or less ~ 20 weeks
(WHO)

Keguguran berulang
… tiga kali kejadian keguguran berturut-turut …
 Angka kejadian ?

• Angka kejadian "single spontaneous abortion" adalah 15-20%

(1 di antara 6 pasangan) dari kehamilan yang "clinically detected"

• Angka kejadian RPL berkisar antara 0.6-2.3%

• RPL bukan suatu kejadian kebetulan  kejadian melebihi 1%

(0.143=0.27%) (3 dari 4 kasus RPL – disebabkan bukan karena
faktor kebetulan)
 TRIMESTER 1 TRIMESTER 2 TRIMESTER 3

Keguguran berulang sebaiknya didefinisikan dengan lebih baik sebelum

direncanakan untuk dilakukan tindakan investigasi atau pengobatan
Farquhar
Bagaimana mengetahui kehamilan ?

5 weeks 7 weeks
Dawood F et al. Curr Obstet Gynecol 2004;14:247-53
Classification of Recurrent Miscarriages
Type of loss Typical gestation Fetal heart US findings b hCG level
(weeks) activity

Biochemical loss <6 Never Pregnancy not Low then fall

(Pregnancy of unknown (0-6) located on US
location)

Early pregnancy loss 6-8 Never Empty sac or Initial rise than
(4-6) large sac with fall
minimal
structures, with
no FH activity

Late pregnancy loss >12 Lost CRL and FH Rise than static
(10-20) activity or fall
previously
identified
ESHRE Special Interest Group for Early Pregnancy (SIGEP), 2005
 Subgroups of RPL

The primary RPL

The secondary RPL

The tertiary RPL

PREGNANCY PREGNANCY LOSS

The two major clinically important
categories of causes for spontaneous
miscarriages

• Fetal causes
– The genetic composition of the fetus

• Maternal causes
– Abnormalities in the environment which the embryo and fetus
develops
Porter TF., Scott JR. Best Pract Res Clin Obstet Gynecol 2005;19:85-101
Panduan Keguguran Berulang 2010
PENYEBAB KEGUGURAN BERULANG

Gangguan hormon Gangguan anatomik

10% 10%

Kelainan kromosom
15%
Tidak diketahui
50%
APS
15%

Carp HJA, 2007

Recurrent pregnancy loss or recurrent miscarriage as a
HOMOGENOUS CONDITION

Otherwise its HETEROGENOUS

and has DIFFERENT PROGNOSIS
 Mono etiological thinking vs. Multifactorial thinking

RM RM

Threshold for Threshold for

miscarriage miscarriage

Christiansen OB., et al. Fertil Steril 2005;83:821-39

Christiansen OB., et al. Fertil Steril 2005;83:821-39
INVESTIGATIONS RCOG ACOG ESHRE

Genetics
Parental karyotyping Recommended Recommended Recommended
Fetal karyotyping Recommended Insufficient evidence Trial required
Anatomic
Uterine cavity Recommended Recommended Recommended
assessment
Coagulation/Immunity
Hereditary thrombophilia Insufficient evidence Insufficient evidence Recommended
(advanced investigation)
APS assessment Recommended Recommended Recommended
Alloimmune testing Not recommended Not recommended Not recommended
Endocrine
Luteal phase - Insufficient evidence Insufficient evidence
Thyroid function Not recommended Not recommended Recommended
Glucose challenge test Not recommended Not recommended Recommended
Infections
TORCH testing Not recommended Not recommended Not recommended
Bacterial vaginosis Insufficient evidence Not recommended -
Carp HJA, 2007
 Rencana investigasi recurrent miscarriage

Keguguran berulang

Gaya hidup Anamnesis – Pemeriksaan fisik

Karyotype Anatomi Endokrin Koagulasi Imunitas Infeksi

Ultrasonografi Faktor pembekuan Swab vagina

HSG Fibrinogen, D-dimer,
Histeroskopi Agregasi trombosit,
Pemeriksaan busi Hormon metabolik Homosistein
Tiroid, Pankreas
Orang tua Hormon reproduksi APS
Jaringan abortus LH, prolaktin, progesteron

Panduan Keguguran Berulang 2010

 Kegunaan apabila mendefinisikan suatu recurrent miscarriage
Type of miscarriage
Pre-embryonic and embryonic
Fetal (early and late)
Spontaneous mid-trimester loss
Associated conditions
Karyotype abnormalities
Endocrine abnormalities
Endometrium abnormalities
Immunological disorders
APS
Thrombophilia
Anatomical
Cervical weakness
Bacterial vaginosis
Dawood F et al. Curr Obstet Gynecol 2004;14:247-53
Investigations
Karyotype: parental, miscarried
tissue
Day 21 P4, FSH, LH, Pelvic US
Endometrial sampling
ACA, LA
ACA, LA
Protein C, Protein S,
hyperhomocysteinemia, Factor
V Leiden, Prothrombin gene
mutation
Pelvic US, hysteroscopy, SIS
Swab for microorganisms
Panduan Keguguran Berulang 2010
Panduan Keguguran Berulang 2010
Panduan Keguguran Berulang 2010
 Keguguran berulang

Anamnesis – Pemeriksaan fisik

Karyotype Anatomi Endokrin Koagulasi Imunitas Infeksi BV

Uterus Metabolik
Kelainan numerik Hiperkoagulabel APS Antibiotika
Kelainan morfologik
Koreksi Konsul ke
bedah TS IPD
Serviks Antikoagulan
Konseling Antiagregasi
PGD
Skrining LPD PCOS Hiperprolaktinemia
Sirklase
pranatal
Stimulasi ovarium Dopamine
Panduan Keguguran Berulang 2010 Luteal support agonists
 Idiopatik ?

prednisone (20 mg/d) and progesterone 90

(20 mg/d) for the first 12 weeks of 80
gestation, aspirin (100 mg/d) for 38 70
weeks of gestation, and folate (5 mg 60
every second day) throughout their 50
pregnancies 40 Treated
Control
30
20
10
0
Tempfer CB., et al. Fertil Steril 2006;86:145-8 Live birth 1st trim Ab 2nd trim Ab
rate
 Panduan untuk menentukan prognosis

Good prognosis Medium prognosis Poor prognosis

Jumlah keguguran 2, 3 4 5, 6, 7, 8, 9

Usia 20s 30s 40s

Karyotype jaringan Aberrant Normal Normal

abortus
Primary/Secondary/Tert Secondary Primary/Tertiary Primary/Tertiary
iary aborter
Keguguran dini/lanjut Early Early Late

Fertilitas Normal fertility Infertility

Antibodi antifosfolipid Positive Negative Negative

NK cells Normal High

Carp HJA, 2007