Transcript Hysterectomy

Max Brinsmead MB BS PhD
May 2015
RECURRENT
MISCARRIAGE
A summary of...
 RCOG Green-top Guideline number 17 April 2011
 “The Investigation and Treatment of Couples with
Recurrent First-trimester and Second-trimester
Miscarriage”
 RCOG Scientific Advisory Committee Opinion
Paper 26 June 2011
 “The Use of Antithrombotics in the Prevention of
Recurrent Pregnancy Loss”
 Plus some empiric recommendations based on
my own personal experience
Definition of Recurrent Miscarriage (RM)
 Loss of three or more consecutive pregnancies at
<20 (24) weeks gestation
 Some distinguish between primary and secondary RM
 Without or with prior live birth
 Incidence:
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Overall 15% of clinical pregnancies end in miscarriage
5% of couples will experience two consecutive losses
1 – 2% will experience three consecutive losses
But thereafter the chance of successful livebirth is ≈ 40%
Factors Associated with Miscarriage
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Maternal age
(Paternal age)
Alcohol abuse
Smoking
Excessive caffeine consumption
Maternal obesity
Anaesthetic gases – data incomplete
Visual Display Units - no effect
Maternal Age and Risk of Miscarriage
 12 – 19 years
 13%
 20 – 24 years
 11%
 25 – 29 years
 12%
 30 – 34 years
 15%
 35 – 39 years
 25%
 40 – 45 years
 51%
 >45 years
 93%
Possible Causes of Recurrent
Miscarriage
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Antiphospholipid Syndrome
Parental Chromosome Rearrangement
Uterine Abnormalities
Cervical Incompetence
Endocrine abnormalities in the mother
Infective agents
Immune factors
Inherited Thrombophilias
Idiopathic/Unknown
 >50%
Antiphospholipid Syndrome
 Found in ≈ 15% couples
 Characterised by the identification of lupus
anticoagulant and/or anticardiolipin antibodies
 May or may not be associated with clinical
maternal autoimmune disease
 Responds to a combination of Aspirin and
Heparin
 But not aspirin alone
 Either unfractionated heparin or LMW heparin in non
heparinising doses
 Pregnancies remain at risk of pre eclampsia, IUGR and
pre term delivery
Parental Chromosomal Rearrangements
 1-2% of couples will have a balanced
translocation of chromosomes
 Best identified by screening the
chromosomes of the 3rd spontaneous
miscarriage
 Because of the high cost of chromosome analysis
 A medical geneticist can provide a risk of
recurrence
 Management options include
 Use of donor gametes
 IVF and pre implantation genetic diagnosis
Uterine Abnormalities
 Can be found in 1 – 5% of all women
 And 2 – 35% of couples with recurrent miscarriage
 Thus their aetiological roles is controversial
 Probably associated with 2nd-trimester loss
 And some of these are due to associated cervical
incompetence
 Reconstructive surgery carries risks of secondary
adhesions and uterine rupture in any subsequent
pregnancy
 But there is a role for the hysteroscopic resection
of uterine septa
 And fibroids that distort the uterine cavity
Cervical Incompetence
 Associated with recurrent , painless second
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trimester losses
The diagnosis is easy with a classical history
But there may be a spectrum of disorder
And there is no gold standard for nonpregnant diagnosis
Consensus is to insert a cervical suture if
there is a suggestive history and the cervix is
<25 mm in length before 24 weeks
But some patients will miscarry despite
surveillance
Infective Agents
 Untreated Syphilis and HIV no question
 But Toxoplasmosis, Herpes, CMV and Listeria
fail Koch’s postulates
 There is an association between recurrent
pregnancy loss/pre term labour and bacterial
vaginosis (BV)
 And a RCT of treatment BV with oral
Clindamycin suggests benefit
 So screening for BV is worthwhile
Endocrine Causes
 Meticulous control of blood sugars reduces
the risk of miscarriage & congenital
malformations in known diabetics
 But any role for Metformin in patients with
suspected insulin resistance e.g. PCO, obesity
or gestational diabetes is unproven
 There is a weak association with thyroid
disorder but screen & treat only hypo or
hyperthyroidism
 Any role for Progesterone Support or HCG
therapy remains unproven
Immune Factors
 The role of HLA-compatibility (or incompatibility)
between partners remains unproven
 So immunomodulation with paternal/donor
leukocyte/trophoblast immunisation is not indicated
 There may be role played by uterine Natural Killer
(uNK) cells
 There may also be a relative deficiency of anti
inflammatory cytokines (Interleukin 4, 6 and 10)
 But empiric therapies with corticosteroids have
proved disappointing
Inherited Thrombophilias
Abnormality
↑RR of Miscarriage Stillbirth
 Factor V Leiden
 2-fold
 Activated Protein C resist.
 3.5-fold
 Protein S deficiency
 14-fold
 Protein C deficiency
 Not ↑
 Antithrombin III deficiency
 Not ↑
 Homocysteinuria
 ?
 Prothrombin gene
 2.3-fold
mutations
8-fold
7-fold
?
2.3-fold
Recommended Investigations for RM
 HIV and Syphilis serology
 Lupus anticoagulant (Russell Viper inhibition)
and anticardiolipin antibodies (EIA) ± ANA
 Karyotyping miscarriage tissue number 3
 Ultrasound of the uterus (or HSG)
 Follow up with hysteroscopy ± Laparoscopy
 3-D ultrasound or MRI
 Thrombophilia screen
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Factor V Leiden
Protein S deficiency
Prothrombin gene mutation only
(others if there is a history of thromboembolism)
Management of Unexplained RM
 There is no place for empiric low-dose aspirin
 May actually ↑risk of miscarriage
 RCT’s of antithrombotic therapy show no
benefit
 And make no sense because there is no
intervillous blood flow before 10 – 12 w
 Non RCT’s of “close supportive care” have a
75% live birth rate
 This can be done with early monitoring of S.
Progesterone and vaginal Progesterone
support for <30 nmol/L
 Plus early ultrasound for encouragement
ANY QUESTIONS
OR COMMENTS?
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