2. Recurrent miscarriage
@ Habitual abortion
@ Recurrent pregnancy loss
Definition : 3 or more consecutive miscarriage
3. Epidemiology
1% of all women
Spontaneous abortion: 10-15% of all clinically recognised
pregnancies
2 consecutive miscarriage : 2%
Theoretical risk of 3 consecutive miscarriage:
0.15 x 0.15 x 0.15 = 0.3%
Probable underlying problem leading to recurrent
miscarriage
The reason why need to investigate further if recurrent
miscarriage
4. Recurrent miscarriage
What about 2 consecutive miscarriage?
American Society of reproductive medicine (ASRM 2008)
Define as 2 consecutive miscarriage
Royal college of O&G, UK (RCOG 2011)
Define as 3 consecutive miscarriage
Different practices between O&G specialist
Local practice – usually take 3 consecutive miscarriage
Earlier investigation/referral should be considered for
special cases:
Advanced maternal age (? How old)
Bad obstetric history (e.g. ectopic, IUD)
History of infertility
Patient request due to social reasons
7. Polycystic ovary syndrome (PCOS)
Criteria for diagnosis (Revised 2003 international
consensus)
Presence of at least 2 of the following 3 criteria:
Polycystic ovaries
≥ 12 follicles in each ovary (<10 mm (2-9 mm in diameter))
and/or
Ovarian volume > 10 cm3
Oligomenorrhea and/or anovulation
Clinical and/or biochemical hyperandrogenism
8. Antiphospholipid syndrome (APS)
Most important treatable cause of recurrent
miscarriage
Diagnosed by Revised Sapporo classification (2006):
At least one clinical criteria and one laboratory criteriaClinical Laboratory
Thrombosis ≥1 documented episodes of:
Arterial
Venous and/or
Small vessel thrombosis
ACA ACA of IgG and/or IgM
isotype in medium/high titre
(> 40 IU) or >99th percentile
Pregnancy
morbidity
≥1 unexplained fetal deaths of ≥ 10
weeks POA
(morphologically normal fetus)
LA Detected
≥1 premature births of ≤ 34th week
POA d/t:
Severe PE or
Placental insufficiency (IUGR)
(morphologically normal neonate)
Anti-
beta2-
glycopr
otein
>99th percentile
≥3 unexplained consecutive
spontaneous abortions < 10 week POA
* On 2 or more occasions
At least 12 weeks apart
12. Endocrine factors
Usually DM or thyroid disease
Well-controlled DM and treated thyroid dysfunction
are not risk factors for recurrent miscarriage
16. Cervical incompetence
Diagnosis is clinical, usually based on history
Miscarriage
2nd-trimester miscarriage
Subsequent miscarriages are usually earlier
Preceded by spontaneous rupture of membranes
Bulging membranes through the cervix prior to onset of labour
Painless and progressive cervical dilatation
Fetus alive during miscarriage
History of cervical surgery (cone biopsy, LLETZ)
No satisfactory objective test
18. Bacterial vaginosis
Presence of BV in the first trimester
Reported as a risk factor for 2nd-trimester miscarriage or
preterm delivery.
A RCT reported that treatment of BV early in the 2nd-
trimester with oral clindamycin significantly reduces
the incidence of second-trimester miscarriage and
preterm birth in the general population.
No data to assess the role of antibiotic therapy in
women with a previous second-trimester
miscarriage.
19. Management
Emotional aspect
Lost of pregnancy – can be a devastating
traumatic experience
Can lead to anxiety, stress & depression
Instead of getting sympathy and support,
often made to feel that it is somehow her fault
Under intense pressure to provide a child for
the family
May even lead to family problem @ divorce
Sensitivity is required in assessing and
counselling couples
Approach with sympathy and understanding
DO NOT blame, scold or make her feel at
fault
20. Management
Should refer to hospital with specialist for further
management.
Preliminary management that can be done in district
hospital/clinics:
History
Examination
21. History
Full history including:
Complete obstetric history
Year of miscarriage
Gestation
How was the pregnancy confirmed?
UPT? Ultrasound?
Assumed pregnant as missed menses?
Spontaneous, D&C or termination?
Life embryo at miscarriage?
Any complications
If 2nd timester loss, ask for features of cervical
incompetence
22. History
Any surgical history esp uterine instrumentation,
cervical surgery
Any medical illnesses
Consanguinity?
23. Examination
Features of PCOS
Features of SLE
Speculum
Any features of genital tract infection
24. Investigations
PCOS screen
Se testosterone
SHBG
Antiphospholipid antibodies
Anticardiolipin antibodies (ACA) & Lupus anticoagulant
Anti-beta2 glycoprotein – if available
Karyotyping (both couples)
To detect chromosomal abnormalities i.e. balanced
translocations
Should be performed on POC of the 3rd and subsequent
consecutive miscarriages
Parenteral karyotyping of both partners should be performed
when testing of POC reports an unbalanced structural
chormosomal abnormality.
25. If karyotype of the miscarried pregnancy is
abnormal, there is a better prognosis for the next
pregnancy
Risk of miscarriage as a result of fetal aneuploidy
decreases with an increasing number of pregnancy loss
26. Pelvic ultrasound – assess uterine anatomy
HSG can also be used as an initial screening test
Suspected uterine anomalies may require further
investigations to confirm diagnosis:
Hysteroscopy
Laparoscopy
3D ultrasound
Thrombophilia screen – for 2nd trimester miscarriage
27.
28.
29. Screening for diabetes, thyroid disorders is only
indicated if there is clinical suspicion. Not
recommended as a routine test.
However, as subclinical hypothyroidism increases risk of
miscarriage, some authors recommend doing TFT
TORCHES – Not useful
30. Investigations
Routine cervical cultures for Chlamydia sp. Or
mycoplasma sp. and vaginal evaluation for bacterial
vaginosis are not useful among healthy women.
31. Management – Unexplained RM
Good prognosis for future pregnancy outcome
75% chance of a eventual live birth in subsequent
pregnancy
However, prognosis worsens with:
Increasing maternal age
Number of previous miscarriages
Maternal age and number of previous miscarriage
are two independent risk factors for a further
miscarriage.
Advancing maternal age is associated with a decline in
the number and quality of the remaining oocytes.
32. Management – Unexplained RM
Unexplained recurrent miscarriage (idiopathic)
Role of progesterone
Role of aspirin
33. Efficacy of progestogens in recurrent miscarriage
33
Haas & Ramsey 2008; Swyer & Daley 1953;
Goldzieher 1964; LeVine 1964; El-Zibdeh 2005
Study or Progestogen Placebo Peto Odds Ratio Weight Peto Odds Ratio
subgroup n/N n/N Peto Fixed 95% CI Peto Fixed 95% CI
El-Zibdeh 2005 11/82 14/48 46.9% 0.37 [0.15, 0.90]
Goldzieher 1964 1/6 4/10 8.5% 0.36 [0.04, 2.99]
Le Vine 1964 4/15 8/15 18.4% 0.34 [0.08, 1.44]
Swyer 1953 7/27 9/20 26.1% 0.44 [0.13, 1.46]
Total (95% CI) 130 93 100.0% 0.38 [0.20, 0.70]
Total events 23 (Progestogen), 35 (Placebo)
Heterogenety: Chi2 = 0.08, df = 3 (P = 0.99) i2 = 0.0%
Test for overall effect: Z = 3.10 (P = 0.0020)
0.1 10
Favours progestogen Favours placebo
34. Management – Unexplained RM
Role of aspirin
Usually prescribed for women with unexplained recurrent
miscarriage
Alone or in combination with heparin
2 recent RCTs – neither treatment improves live birth
rate among these women.
Use of this empirical treatment is unnecessary and should
be resisted (RCOG, UK April 2011)
35. Management
Idiopathic or not investigated
Start when pregnancy confirmed:
T. Duphaston 10mg od/bd till 20/52 POA
Insufficient evidence to evaluate the effect of progesterone
supplementation in pregnancy (RCOG, UK April 2011)
Lifestyle modification – can increase fertility potential
Stop smoking
Reduce alcohol intake
Reduce BMI (for obese women)
36. Cervical incompetence
2 options in the next pregnancy
Cervical surveillance
Start at 14-16 weeks
Every 2 weeks as long as cervical length >30mm
Increase frequency to weekly if 25-29mm
If <25mm before 24 weeks, consider cerclage
Cervical cerclage at 12-14 weeks POA
37. Management - APS
Low-dose aspirin and heparin until 36 weeks of
pregnancy
38. PCOS
Role of Metformin
Previously prescribed to reduce risk of recurrent
miscarriage
Insufficient evidence to evaluate the effect of metformin
supplementation
Recent meta-analysis of 17 RCTs - metformin has no
effect on sporadic miscarriage risk
Uncontrolled small studies (no RCTs) – associated with
reduction in miscarriage rate in women with recurrent
miscarriage
39. Endocrine
Optimize disease
Should be stable for around 6 months
Refer Prepregnancy Clinic when plan to embark on
pregnancy
Counselling
Drug adjustment – minimize, safe
