recurrent miscarriage is a real clinical problem with different aetioogies. However, recent observations pointed to vascular dysfunction as a main underlying factor: how ? this talk may help in illustrating this

1. RPL
Role of endometrial vascularity
HESHAM AL-INANY
PROF. OB. & GYN.
CAIRO UNIVERSITY

2.  Trilaminar endometrium as seen
at the end of the follicular
phase;
 luteal endometrium as seen at
about the time that
implantation would normally
occur.
 This is what we know

3. Endometrial
&subendometrial
flow
 This is what we want
to talk about

4. OBJECTIVES
 Understand the problem
 Understand the emerging concept

5. The problem
 RPL
 ?underlying pathology

6. Definition : Updated
 ACOG : Two or more :
Because the risk of a recurrent loss is fairly
high after 2 losses (26%), we have to start
work-up after 2 losses.

7. MATERNAL AGE- RPL
Maternal age Clinical Preclinical
< 20 y 12.2 % 20 %
20-24 14.3 29
25-29 13.7 30
30-34 15.5 35
35-39 18.7 40
40-44 33.8 45
> 44 53.8 65

8. 50 %
chromosomal
10-15 %
Anatomic
17- 20 %
10-15 %
Coagulation/
Immunity
Endocrine

9. APAS
Antiph. antibodies:
1- Lupus anticoagulant { IgG – IgM }
2- Anticardiolipin (aCL) antibodies
{IgG – IgM}
 NB : Definite APS is diagnosed when AB levels are
repeatedly >20 units & levels <20 units are of uncertain
significance

10. Vascular dysfunction
 studies suggest that APAS is associated
with arterial and venous thrombosis,
thrombocytopenia, and livedo reticularis
(Nayak & Komatireddy et al., 2002).

11. Another observation
 Premature atherosclerosis is a clinical and
histological feature of with primary APAS
(Ames et al., 2009).

12. More Importantly
 The live birth rate of women with RPL increased to
40% when they are treated with low-dose aspirin
only
 It is significantly improved to 70% when they are
treated with low-dose aspirin in combination with
low-dose heparin.
 corticosteroids are not used anymore
RCOG May 2003

13. Another underlying
pathology :Thrombophilia
Associated with:
 Recurrent miscarriage
 Pre eclampsia
 IUGR
 Placental abruption
 Still birth

14. Thrombophilia
 Mechanism: Microthrombosis in the placenta
 Causes:
1. Activated protein C resistance {Factor V Leiden
mutation} : the most prevalent cause
2. Prothrombin gene mutation
3. Antithrombin III deficiency
4. Protein C deficiency
5. Protein S deficiency.

15. Thrombophilia
Treatment :
studies have suggested that heparin therapy may
improve the live birth rate for these women..

16. Another cause for RPL :
Hyperhomocysteinemia
 It is an inborn error of metabolism
 Elevated levels of homocysteine in the
bloodstream can irritate the blood vessels, which
may eventually lead to hardening of the arteries
 Treatment:
1. Oral administration of vit B6 & folate
2. Monthly injection of vit B12 (Mishell,2002).
3. SC heparin to reduce the risk of Venou thrombosis

17. Interestingly : Septate uterus
 Is the most frequent
anatomic abnormality
associated with RPL.
Suggested Mechanism:
 Impaired vascularization
of pregnancy

18. Recent data
 Spontaneous RPL (>3) is associated with
about five times higher risk of myocardial
infarction later in life (Kharazmi et al.,
2011)

19. The problem
 RPL
 Endometrial vascular dysfunction

20. Emerging concept
 A considerable number of RPL
could be due to endometrial
vascular dysfunction whatever the
underlying pathology

21. Can this vascular
dysfunction be evaluated?
 brachial-ankle PWV (baPWV)
measurement can be performed easily by
simultaneous oscillometric measurement of
pulse waves in all four extremities
 It is a promising technique to assess
vascular dysfunction in women with RPL

22. Why not to hit the target?
 Our target is the uterus
 Specifically the endometrial and
subendometrial vascularity

23. This concept has to be
tested
 Recent technology could help
 3 D Doppler study for subendometrial blood flow

24. Anatomical Factors
CONGENITAL :
Septate . 60%
Arcuate.
Bicornuate.
Unicornuate. 44 %
Didelphic. 36 %
DES Exposure – T shaped uterus

25. Endometrial volume and blood flow Subendometrial shell volume and blood flow

26. gives physiologic data,
rather than anatomic
information alone.

28. Endometrial volume calculation by using the VOCAL software after
3D.

29. Uterine Artery “PI”
uterine artery Doppler (PI=3.16). uterine artery Doppler (PI=1.15).

31. The Histogram
 The Vascularization Index (VI),in %, measures the
number of the blood vessels within the tissue.
 The Flow Index (FI) represents average colour
intensity.
 And the Vascular-Flow Index (VFI) represents both
blood flow and vascularization

32. Determination of the subendometrial area volume by using the
"shell" facility. In this case 5 mm has been chosen.

33. Vascularization of the subendometrial area by 3D-Power
Doppler. VI, FI and VFI refers to the shell area, not the
endometrium.

34. A proof of concept study
 only one study on 40 women with unexplained
RPL showing that 3D vascularisation indices could
be affected in these women (Vaquero et al ,
Ultrasound Obstet Gynecol. ; 32:262–266)

35. Objective:
 to evaluate subendometrial blood flow in
women with a history of recurrent
unexplained abortion compared to
women who had at least 1 live child and
no history of spontaneous abortions

36. Participants & Methods
 Women with RPL were compared to women with
no history of abortion and at least 1 child born at
term.

37. Transvaginal 3D power
Doppler
 Subendometrial area to detect subendometrial
blood flow presented by the indices:-
vascularisation index (VI),
 flow index (FI),
 and vascular flow index (VFI). (Accuvix XQ,
Medison, Korea)

38. Investigations done
 activated partial thromboplastin time
 antinuclear antibodies
 lupus anticoagulant antibodies
 Anticardioliplin abs
 Thyroid : TSH, free T3, T4
 Karyotyping
 HSG

39. Results
 Mean uterine artery pulsatility index(M UAPI) was
higher in case group(2.319±0.5309)than in control
group(1.689±0.4832) which was statistically
significant (p value 0.000).
 Vascularity index(VI) was higher in case group
(2.726±3.0482)than in control group (2.29±3.03)
which was statistically insignificant (p value 0.29).

40. Flow Index
 flow index (FI) was higher in control group
(23.975±4.1716) than in case
group(19.138±6.9013) which was
statistically significant(p value 0.002).

41. vascular flow index(VFI)
 was higher in control (1.20±1.11)than in case
group(0.71±0.65) which was statistically
significant(p value 0.048).

42. How accurate it is !!

43. This means
PI < 3
FI > 20%
VFI > 20 %

44. Follow Up
 patients who got pregnant and reached
the third trimester had higher three
subendometrial indices compared to
those who aborted

45. Recent evidence
 Decreased endometrial vascularity
in patients with antiphospholipid
antibodies-associated recurrent
miscarriage during midluteal phase
Chen et al, 2012 Fertil Steril

46. Limitations
 no cut off values could be established
 Should be conducted in tertiary centers with
advanced facilities

47. Advantages
 Non invasive
 Relatively available
 Relatively not so expensive

48. then how to manage :
 Isosorbide mononitrite significantly
decreased uterine artery and increased
sub-endometrial blood flow indices (p <
0.001). abdelrazek et al, 2014
 Follow up for pregnancy is ongoing

49. In conclusion,
 vascular dysfunction may be the
key to the pathophysiology of RPL.
 3D vascular indices should be
applied routinely for women with
RPL

50. THANK YOU