recurrent miscarriage ppt gynae seminar
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Recurrent miscarriage
Dr. Kang Marcus
O&G Consultant
Hospital Sibu
Recurrent miscarriage @ Habitual abortion @ Recurrent pregnancy loss
Definition : 3 or more consecutive miscarriage
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
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
Causes Idiopathic in 40-50% of cases
Easier to divide into 1st or 2nd trimester losses 1st trimester losses (PACE U)
PCOS (Polycystic ovary syndrome) APS (Antiphospholipid syndrome) Chromosomal abnormalities Endocrine disorders (untreated DM, thyroid
disease) Uterine abnormalities
Submucous fibroid Subseptate uterus
2nd trimester losses (CABUT) Cervical incompetence Asherman syndrome (intrauterine synechiae) Bacterial vaginosis Uterine abnormalities
Congenital – bicornuate, septate, subseptate, hypoplasia
Myomas Thrombophilias
Others – SLE, hyperprolactinaemia
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
Antiphospholipid syndrome (APS) Most important treatable cause of recurrent
miscarriage Diagnosed by Revised Sapporo classification
(2006): At least one clinical criteria and one laboratory
criteria
Clinical LaboratoryThrombosis ≥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-glycoprotein
>99th percentile
≥3 unexplained consecutive spontaneous abortions < 10 week POA
* On 2 or more occasionsAt least 12 weeks apart
Chromosomal abnormalities - Karyotyping
Chromosomal abnormalities Balanced translocation
Reciprocal or Robertsonian
Chromosomal abnormalities
Endocrine factors Usually DM or thyroid disease
Well-controlled DM and treated thyroid dysfunction are not risk factors for recurrent miscarriage
Uterine abnormalities
Uterine abnormalities
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
Asherman syndrome
Normal uterus
• Usually caused by pregnancy-related D&C
Intrauterine synechiae
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.
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
Management Should refer to hospital with specialist for
further management. Preliminary management that can be done in
district hospital/clinics: History Examination
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
History Any surgical history esp uterine
instrumentation, cervical surgery Any medical illnesses Consanguinity?
Examination Features of PCOS Features of SLE Speculum
Any features of genital tract infection
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.
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
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
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
Investigations Routine cervical cultures for Chlamydia sp. Or
mycoplasma sp. and vaginal evaluation for bacterial vaginosis are not useful among healthy women.
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.
Management – Unexplained RM Unexplained recurrent miscarriage (idiopathic)
Role of progesterone Role of aspirin
Efficacy of progestogens in recurrent miscarriage
33Haas & 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
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)
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)
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
Management - APS Low-dose aspirin and heparin until 36 weeks
of pregnancy
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
Endocrine Optimize disease
Should be stable for around 6 months Refer Prepregnancy Clinic when plan to
embark on pregnancy Counselling Drug adjustment – minimize, safe