Recurrent miscarriage

1. Recurrent miscarriage
(RM)
DR NOOR ASIKIN MOHD SAKRI

2. Madam N.S
• 39 yo G9P3+5 at 17 weeks POA
• Regular menses
• Dating scan at 12 wks, FH present, confirmed EDD
• MOGTT x 1 normal, Hb booking 11.1g/dL-latest 11.4g/d, previous
pregnancy(10-11g/dL)
• Unplanned pregnancy, on coitus interruptus
• Consanguine marriage, married with cousin’s son
• Hx 5 times complete miscarriage with 3 consecutives , not
investigated earlier
• 2009, 6/52
• 2010, 5/52
• 2011, 8/52
• 2012 FTSVD 3.2kg
• 2016, FTSVD 2.96kg
• 2018, FTSVD 3.2 kg
• 2020, 12/52, HPE confirmed POC
• Jan 2021, 6/52, HPE confirmed POC
• All pregnancy confirmed by UPT and TAS, then had complete
miscarriage

3. • No hx GDM/PIH/PE in previous pregnancy, no IUGR
• Last seen by us in Feb this year, post miscarriage,
planned for APLS screening today & TCA on
8/6/2020
• Patient is housewife
• One husband, husband has stable HPT, smoker,
work as lecturer at Ump, no exposure to chemical
• Mother has HPT, grandmother has DM, no family hx
of blood disorder, no family hx of congenital
anomalies (CHD) or aneuploid (trisomy 21,18,13), no
other family member has recurrent miscarriage
• Presented with pv spotting yesterday at 2pm,
minimal amount, no abdominal pain, no passing out
POC, no hx of trauma
• O/e not pale
• PA : soft uterus at 16 weeks
• TAS: singleton fetus, no FH activity, CRL 82.2mm,
~14weeks, edematous, placenta posterior not low,
2cm thickness
• Opted for expectant management, TCA in 1/52
• Ix: FBC/ Coag profile/ TORCHES/ PVB19/ FBP/ FBS
• APL antibodies/TFT-to be taken later

4. Definitions
• Miscarriage definitions
• The expulsion or extraction of a fetus weighing <500g or 22 completed weeks
gestation (WHO)
• Spontaneous loss of pregnancy before the fetus reaches viability or termination prior
to 24 completed weeks of gestation (RCOG)
• RM/RPL definitions
• 3 or more consecutive pregnancy losses, affects 1% of couples trying to conceive
(RCOG)
• 2 or more consecutive pregnancy losses, affects 5% of couples (ASRM & ESHRE)

5. Risk factors for RM (RCOG)
• Epidemiology- maternal age, no of
miscarriage
• Anti-phospholipid syndrome
• Genetic factors 80% in 1st trimester loss
• Parental chromosome rearrangements
• Embryonic chromosomal abnormalities
• Anatomical factors
• Congenital uterine malformation, adhesion,
leiomyoma
• Cervical weakness
• Endocrine-failure of proper progesterone
concentration, thyroid hormone
• Immune –thyroid autoimmunity
• Infection –BV, toxoplasmosis, listeriosis,
chlamydia, gonorrhea, rubella
• Thrombophilia defects-inherited
• *Unexplained

6. APLS
• Refers to the association between antiphospholipid antibodies (lupus
anticoagulant, anticardiolipin antibodies and anti-B2 glycoprotein-I antibodies)
and adverse pregnancy outcome or vascular thrombosis.
• 15% of women with recurrent miscarriage
• Adverse pregnancy outcomes include:
• three or more consecutive miscarriages before 10 weeks of gestation
• one or more morphologically normal fetal losses after the 10th week of gestation
• one or more preterm births before the 34th week of gestation owing to placental
disease-severe pre-eclampsia/IUGR

7. History
• Gestational age of loss, chromosome and endorine earlier than anatomical or immunological causes
• Irregular menses or galactorrhea suggestive possible endocrine dysfunction/hyperprolactinemia
• Consanguinity/family hx of congenital abnormalities/early losses-possible genetic cause
• Uterine instrumentation-possible intrauterine adhesions
• Exposure to radiation, chemotherapeutic agents, chemicals
• Alcohol and caffeine-in dose-dependent manner
• Cigarette smoking
• H/o thrombosis/PCOS
• Any previous investigation taken-lab/pathology/imaging

8. Physical examinations
• General signs of endocrinopathy-hirsutism, galactorrhea, thyroid
• Systemic
• TVS

9. Investigations
Risk factors Recommendation
APLS Lupus anticoagulant,
anticardiolipin antibodies
and anti-B2 glycoprotein-I
antibodies
-Two positive tests at least 12
weeks apart
-Medium or high titre over
40 g/l or ml/l,or above the
99th percentile
Genetic Karyotype parental and POC -Not advice for routine (cost)
-Selective parental
karyotyping may be more
appropriate when an
unbalanced chromosome
abnormality is identified in
the POC.

10. Risk factors Recommendation
Anatomical Pelvic USG
Two –dimensional/three-
dimensional USG and HSG
If required for hysteroscopy,
laposcopy, or MRI
Endocrine Thyroid-TSH, antibodies
HbA1c, prolactin
Immune ANA
Infection Chlamydia, Endometrial
biopsy and culture
Thrombophilia defects Acquired APLS-SLE Inherited
Male factor Sperm DNA fragmentation ASRM-not indicated
routinely as weak evidence
ESHRE-can be done to
provide explaination to RM

11. Treatment
APLS Low dose Aspirin and
heparin in pregnancy and up
to 6 weeks postpartum-
improve live birth rate
LMWH safer
Corticosteroids or
intravenous immunoglobulin
therapy, provoke significant
maternal and fetal morbidity
Genetic The finding of an abnormal
parental karyotype should
prompt referral to a clinical
geneticist
Referral for genetic
counselling
Preimplantation genetic
screening with in vitro
fertilisation treatment in
women with unexplained
recurrent miscarriage does
not improve live birth rates.

12. Anatomical Uterine abnormal
-Insufficient evidence to assess
the effect of uterine septum
resection
Cervical weakness/insufficiency
-Cervical cerclage if hx of one
second trimester loss (CL
<25mm)
Pt who not undergone a history-
indicated cerclage, need for
cervical surveillance
Endocrine Insufficient evidence to evaluate
the effect of progesterone
supplementation
Human chorionic
gonadotrophin supplementation
–multicenter placebo control
failed to show any benefit in
pregnancy outcome
PCOS-metformin reduce of
miscarriage rate-insufficient of
RCT

13. Immunotherapy Paternal cell immunisation,
third-party donor leucocytes,
trophoblast membranes and
intravenous immunoglobulin
Does not improve the live
birth rate
Inherited thrombophilias Heparin therapy increased
live birth rate of women with
second-trimester miscarriage
Unexplained recurrent
miscarriage
Support care-TLC
Aspirin+/-heparin
-empirical treatment is
necessary –need to
individualised
75% successful future
pregnancy

14. References
• The Investigation and Treatment of Couples with Recurrent Firsttrimester and
Second-trimester Miscarriage, GTG No. 17, Royal College of Obstetricians and
Gynaecologists (RCOG)
• Evaluation and treatment of recurrent pregnancy loss: a committee opinion,
American Society of Reproductive Medicine (ASRM) guideline
• European Society of Human Reproduction and Embryology (ESHRE) guideline