2. Dr. Priya Bhave Chittawar
MBBS 1999( Gandhi Medical College, Bhopal): with distinction in 8 subjects and 15
gold medals. Awarded 'Dr.Vishal Vikram Singh Award' for highest marks in MBBS
(1994-1999). President of India Dr. Shankar Dayal Sharma Award for the Best
Outgoing student MBBS (1994-1999).
Served in various capacities in the Students Union and awarded " Dr. Suresh Kak
Memorial Award for best All Rounder MBBS 1994-1999)
Fellowship in Reproductive Medicine (Christian Medical College, Vellore) 2008-
2010 : passed with distinction
Awarded by the Chief Minister Shri Shivraj Singh Chouhan in June 2008 for
exemplary work in emergency Obstetrics
Best Paper award for thesis on Role of GnRH antagonists in IUI- ISAR 2010
Best Paper award in ISAR 2012 for paper on “ Hysteroscopic Management of
adenomyotic myometrial cysts”
Author of Cochrane review ( Menstrual disorder and
subfertility group)
Author of Cochrane sexually transmitted infections group.
3. Nagpur Obs Gyne society
Dr. D. K. Tank Foundation
AOFOG
Merck Serono
Thanks!
4. The stories that end badly are sad, sadder still
are the ones that never began….
5.
6. What we know: KNOWN KNOWN
What we know we do not know:
KNOWN UNKNOWN
What we know but do not do:
UNKNOWN KNOWN
What we do not know that we do
not know
UNKNOWN UNKNOWN
OUTLINE….
9. Three or more consecutive
miscarriages
Risk of miscarriage in is 30% after 2
losses, 33% after 3 losses among
patients without a history of a live
birth.
15% sporadic miscarriage
By chance alone 1 in 300 couples
What?
10. Age
Genetic : embryonic and parental
Immune: autoimmune/alloimmune
Anatomic
Endocrine
Others
Why?
12. Nondisjunction during meiosis
Autosomal trisomy, monosomy X,
triplody, tetraploidy, translocations
Incidence increases with maternal
age
60% of conceptus
Genetic: Embryonic
13. Carriers of balanced chromosomal
abnormalities
3-5% of RPL couples
Risk of severely handicapped child
due to aneuploidy
Chances of miscarriage greater than
those of RPL couples who are not
carriers ( 49% vs. 30%).
(Franssen,BMJ;2006)
Genetic: paternal
16. Antiphospholipid antibody
syndrome: 15% women with RPL vs
2% with low risk Obs. hist
ACA, LA , anti beta2 glycoprotein 1
antibody
Trophoblast function, activation
complement at fetal maternal
interface, thrombosis at placental villi
Without heparin, LBR<10%
Alloimmune
17. Septum: partial, complete
Bicornuate, unicornuate uteri
Poor vascularity of the septum,
disordered myometrial
contractions
1.8-37% of RPL couples
Anatomic
19. History including family history of
miscarriages, Toxin exposure
Age, BMI,Examination; Ultrasound
TSH, HbA1c, VDRL, ACA, LAC,
Anti Beta 1 glycoprotein
Karyotyping
Karyotyping of products of
conception
Workup
25. Not a valid cause of infertility or
RPL
Reflection of an inadequate
follicular phase or an incompetent
pregnancy (Bukulmez,
OGClinNA,2004)
Luteal Phase defect
26. Similar rate of aneuploidy of products
of conception (Lathi, JARG,2007,24;
Munoz, FS,2007,94:7)
Type of aneuploidy might differ
(viable autosomal trisomies( 9,13,21)
and monosomy X significantly lower
when no fetal pole seen
Early embryonic demise is similar
event occurring earlier temporally.
Early fetal demise vs. early
embryonic demise
27. Recommended in third miscarriage ( Greentop
no 17)
Maternal tissue contamination (
Jarret,AJOG,2001)
Failure to grow ( 20-30%)
Failure to look for other causes
Abnormal embryonic dev reported with
normal karyotype ( dimorphic embryos) with
embryoscopy.
Villi have to separated from maternal tissue
Microsatellite analysis: differentiate from
maternal tissue
Karyotyping of POC
28. Only if karyotyping of POC reveals unbalanced
numerical defects ( Greentop)
In all cases of RPL ( ASRM)
In couples at high risk of being carriers (
risk=>2.2%) (ESHRE)
Parental Karyotyping
29. Low maternal age at second miscarriage,
A history of three or more miscarriages
A history of two or more miscarriages in a
brother or sister
A history of two or more miscarriages in the
parents of either partner
increase the probability of carrier status(
Jauniaux, HR,2006)
Parental Karyotyping
30.
31. 1. Normal karyotype in the conceptus
2. Carrier status of same balanced structural
abnormality
3. Unbalanced structural abnormality1% (
Miscarriage, Stillbirth, child with handicap)
chances of having a healthy child are as high as
for non-carrier couples (over 80%)
Chances of subsequent miscarriage higher
(50%) compared to non carrier couples with
RPL (30%)
(Franssen,BMJ;2006)
Consequences of carrier state
32. LBR in PGD group 31%
LBR in natural conception 55.5%
Miscarriage rate in PGD group 0-
50% ( median 0%)
Miscarriage rate in natural
conception 34%
( Franssen, HR,2011)
PGD for carrier couples
33. Cochrane: A statistically significant
benefit in using hCG (risk ratio
(RR) 0.51, 95% confidence interval
(CI) 0.32 to 0.81; five studies, 302
women ( Jan 2013)
HCG for RPL
35. High heterogeneity ( 39%)
After excluding data from poorly
designed studies, revised RR 0.74
(CI 0.44 to 1.23).
Small numbers
Chromosomal analysis not carried
out
HCG for RPL
36.
37. PROMISE trial underway
760 women randomised
Immunomodulatory action:
upregulate TGF-β secretion in
response to trophoblast, blocks Thl
immunity to trophoblast.
Upregulates STAR
Myometrial relaxation
Progesterone for RPL
38. Three small non randomized trials
(Stray-Pederson, Liddel 1991,
Clifford 1997)
Control groups not matched and
small
No testing for APS
Livebirth rates claimed to increase
by 50% for groups receiving TLC
Tender loving care…
39. Combined aspirin/heparin
treatment versus placebo in women
with unexplained RM (
Kaandorp2010, NEJM)
NO difference in LBR
Significant side effects in treatment
group
Anticoagulation for
unexplained RPL
40. HepASA trial: no difference in LBR
between ASA alone versus ASA
and heparin (Laskin, Journal of
Rheumatology,2009)
Trial stopped prematurely due to
equivalent LBR in both groups.
Anticoagulation for RPL with
ANA/thrombophilia
44. Luteal phase defect
Early fetal demise and early embryonic
demise
Karyotying of POC
Parental karyotyping
HCG and progesterone for RPL
TLC
Anticoagulation for unexplained RPL
Anticoagulation for ANA/thrombophilia
45. Type 1 unexplained RPL: occurring by
chance
Type 2 unexplained RPL: due to an
underlying pathology that is not
currently identified by routine clinical
investigations or due to significant
environmental and lifestyle risk
factors. Younger women, higher order
miscarriages
(Saravelos, HR2012)
Unexplained RPL
47. Think septum!
A good 2D TVS.
HSG/office hysteroscopy
LBR 85% after septal resection.
Doing what we know…
48. Pool our knowledge and patient
base
Well designed RCT looking at
treatments for RPL
Multicentric
Trying to know the
unknown..
49. When you know something, to hold
that you know it. When you do not
know a thing, to allow that you do
not know it, this is knowledge
Confuscious
THANKS !!!
