Comparative study between vaginal vs intramuscular progesterone for prevention of threatened PTL predicted by TV US

3. L/O/G/O
A thesis Submitted in Partial Fulfillment of the Requirements for (M.D.) in
Obstetrics & Gynecology By Moataz Gamal Taha Abu-Shahba (2014)
Specialist of Obstetrics &Gynecology Al-Galaa Teaching Hospital

4. • Praise be to Allah, who exalted in knowledge
whom he wills; but above those that have
knowledge, there is one more knowing; to
Him is the goal and to Him is the return of all.
• Supervising Professors
Especially Professor Fawzy Abel Aziz,
Professor Mohamed Sherif El-Sayes and
Dr. Mohamed Ibrahim Mostafa
• My Family (Mother, brothers, wife, children).
Acknowledgments

5. INTRODUCTION

6. Preterm labor
 Birth of a baby of less than 37 weeks gestational age.
 The cause is elusive and unknown.
 The reduction of PTL is a challenging proposition.
 PTB vs. premature birth.
 PTB is among the top causes of death in infants
worldwide.

7. Epidemiology & Magnitude of The Problem
 In Europe, PTB is generally 5-9% and in USA it has been
risen to 12-13% in the last decades.(Goldenberg,2008).
 It is estimated that one-third of LBW deliveries are due to
preterm delivery.
 PTB is a significant cost factor in healthcare including long
term care for disabilities .
 550.000 PTB each year in USA , run up 26$ billion ,
mostly related to NICU.

8. Etiology (Risk
F.)

9. Diagnosis
Symptoms
signs
Initial
Evaluation
• Gestational age
• ROM
• Infection
• In Labor
• T/V U/S&/or FFN
Assess
ROM
• Speculum ex. (sample for FFN, ,
alkalinity, nitrazine paper test
Assess for
infection
• Urine sample(bacteriuria, &P.N.)
• RectoVaginal culture(GBS)
• Gonorrhea,B.V.,&T.V.

10. Diagnosis
True labor
• Regular Uterine contra.+dilat. &effeac. +descent
(3cm,80%,ROM& V.Bl.)
FFN
• -ve predictive value 99%
• +ve predictive value 13-30%
Aminosure® • One step immuno chromatographic assay.(PAMG-1)
T/VU/S&F
FN. • More accurate than either test alone.

11. Complications
Mortality&
Morbidity
Specific risks
for PTB
neonate
• Shorter the term the
greater the risk.
• PT-premature ,is at risk
of death in 1st year of
life(infant)& mostly in 1st
month(neonatal)
• Neurological
• CVS
• Respiratory
• GIT &Metabolic
• Hematological
• Infection

12. Management

13. Progesterone & PTL
• Progesterone known as P4 (pregn-4-ene-3,20-dione) is
a C -21 steroid hormone involved in the female menstrual
cycle, pregnancy support and embryogenesis of humans.
• Progesterone consists of 4 interconnected cyclic
hydrocarbons .It contains ketone and oxygenated
functional groups ,as well as 2 methyl branches.

14. Medical applications
• Progesterone was approved by FDA as vaginal gel on July
1997, an oral capsule on May 1998 , injection form on April
2001 and as vaginal insert on June 2007.
• Other specific uses for progesterone
 L. Ph. Support in ART.
 Control persistent unovulatory Bl.
 Progesterone Withdrawal Bl.
 TTT multiple sclerosis.
 Has a role in skin elasticity & bone strength.
 Prevent conception or inducing abortion progest. receptor
antag. or SPRMs (RU486).
 Male behavior.
 a component of HRT for ttt of gender dysphoria.

15. Prevention of PTB; Vaginal progesterone
in women with a short cervix .
• Indeed PTL. & term labor share a common terminal
pathway , defined as anatomic, endocrinologic,
biochemical, and clinical events.
• An important diff. between term & PTL. is that the former
“physiologic activation of the common pathway, while the
later ( pathologic activation that extemporaneously activates
components of the common pathway).

16. Prevention of PTB; Vaginal progesterone
in women with a short cervix .
• The activation of UT. Components of the common pathway
may be synchronous or asynchronous.
 Synchronous clinical PTL
 Asynchronous diff. clinical presentation
(PPROM,Cx.insuff.,PT. Ut.contr.)

17. The preterm parturition syndrome
• The mechanisms of PTL shown in this figure, It is noted that
more than one mechanism may be operative in one patient.

18. Short Cervix
• A short cervix is syndromic in nature and can be caused by
multiple etiologies:

19. Technique for sonographic examination
of the uterine cervix
• Trans abdominal examination(not recommended )
due to:
o Requires distended bladder.
o A distended bladder compresses & artificially lengthen
Ut.cervix.
o A waiting room with patients having full bladder.
o The image quality.
o 45% of Patients with cx. Legnth ≤ 25mm would be missed.

20. Technique for sonographic examination
of the uterine cervix
• Tans abdominal examination(not recommended)
due to:
o Requires distended bladder.
o A distended bladder compresses & artificially lengthen
Ut.cervix.
o A waiting room with patients having full bladder.
o The image quality.
o 45% of Patients with cx. Legnth ≤ 25mm would be missed.

21. Technique for sonographic examination
of the uterine cervix
• Transabdominal sonogram performed in a patient with a full
bladder. The bladder is causing compression and artificial
lengthening of the uterine cervix (Adopted from: Romero et
al., 2013).
• Same patient but with the bladder emptied and transvaginal
sonography performed. Note that the true cervical length is
short (15.5 mm) (Adopted from: Romero et al., 2013).

22. Technique for sonographic examination
of the uterine cervix
• Transabdominal ultrasound when the fetus is in a vertex
presentation. Note that the image quality of the uterine
cervix is poor, which is due to the greater distance
between the probe and the cervix, and shadowing from
the fetal head (Adopted from: Romero et al., 2013).

23. Technique for sonographic examination
of the uterine cervix
• Transvaginal ultrasound of the uterine cervix (cervical
length 39.8 mm). This is the “gold standard” for the
performance of cervical examinations during pregnancy.
Note that the visualization of cervical anatomy and
measurement of the cervical length is optimal (Adopted
from: Romero et al., 2013).

30. parameter Group1 (IM) Group2 (Vaginal) Group 3 (Placebo) p
No. % No. % No. %
22-31 35 70 38 67 34 68
32-42 15 30 12 24 16 32
Mean+_ SD 29.3 28.9+_3.8 29.6+_3.7
0.6
Median (IQR) 29(25-34) 29(26-31) 30(27-32)

31. arameter Group1 Group2 Group3 P
No. % No. % NO. %
Working 29 58 26 52 32 64
0.6
House-wife 21 42 24 48 18 36

32. Parameter Group1 Group2 Group3 P
No. % No. % No. %
28-30 25 50 15 30 23 46
31-34 25 50 35 70 27 54
Mean+_ 30.8+_2.3 31.4+_2 30.9+_2.1
0.2
Median
(IQR)
28(29-33) 32(30-33) 31(29-33)

33. Parameter Group1 Group2 Group3 P
No. % No. % No. %
≤1500 10 20 8 16 10 20
≤2500 40 80 42 84 40 80
Mean+_SD 2385.3+_
596.4
2302.2+_
526.6
2238.6+_
573.4 0.3
Median
(IQR)
2627
(2540-2746)
2384
(1907-2640)
2500
(1869-2716)

34. Parameter Group1 Grouo2 Group3 P
No. % No. % No. %
Parous (with
prev.PTB)
18 36 16 32 19 38
Parous
(without PTB)
6 12 7 14 9 18
0.8
Nulliparous 26 52 27 54 22 44

35. Parameter Group1 Group2 Group3 p
No. % No. % No. %
White 41 82 43 86 45 90
Black 5 10 6 12 3 6
0.7
Others 4 8 1 2 2 2

36. Parameter Group1 Group2 Group3 P
No. % No. % No. %
18.5-25(n.) 17 34 24 48 19 38
25.1-30(O.W) 33 66 24 48 48 21
30.1-35(mod.Obese 2 4 7 14
35.1-40(severeObese) 3 6
0.2
Mean+_SD 26.1+_2.5 25.6+_2.4 27+_3.7
Median(IQR) 25.8(24.4-28.3) 25(24-27) 26(24-29)

37. Parameter Group1 Group2 Group3 P
No. % NO. % No. %
Single 45 90 43 86 42 84
0.5
Twin 5 10 7 14 8 16

38. Parameter Group1(IM Group2(vag) Group3( placebo p
Mean+_SD 20.8+_ 3.2 20.3+_3.5 20.7+_3
Median(IQR 21(18-23) 20(17-24) 21(18-23)
0.7

39. Comparison between the studied groups as regard 1ry & 2ry outcomes.
Parameter Group1(IM Group2(vag) Group3(placebo) p
No. % No. % No. %
1ry outcom 11 22 10 20 22 44 0.01
Fetal death 4 8 3 6 3 6 0.3
Neonatal death 1 2 0 0 1 2 1
IVH 4 8 5 10 3 6 0.8
RDS 7 14 8 16 4 8 0.5
ROP 3 6 3 6 3 6 o.6
NICU admission 13 26 14 28 11 22 0.6
Ventilation 6 12 5 10 3 6 0.7

41. Comparison between the studied groups as regards progesterone side
effects.
Parameter Group1(IM Group2(vag) P
Bloating 2 4 1 2 1
Fluid retention 2 4 1 2 1
Breast tenderness 8 16 10 20 0.3
Excessive Wt.gain 4 8 1 2 1
Nausea 6 12 2 4 1
Headache 6 12 4 8 1
Dizziness; Drowsiness 4 8 3 6 1
Difficulty of sleeping 2 4 2 4 1
Depression 2 4 1 2 1
Itching, Rash, Allergic
reaction
14 28 5 10
0.04
Vaginal irritation 0 0 20 40 0.001

43. DISCUSSION

44.  Prevention of PTB should be one of ANC, intervention for
preventing & ttt. PTB includes bed rest, cx. cerclage, and
progesterone and AB.
(FuKuyama et al.,2012)
 In the contemporary study , the rate of PTB among women
receiving vaginal progesterone from 20-24w until delivery
was 20% and 27.5% with IM progesterone .
 indicating that progesterone either vaginally or IM is highly
effective for prevention of PTB
Fonseca et al.,2003 Macknezie.,2006 Cetingoz et al., 2011
Berghella &Mackeen, 2011)

45.  Recent clinical studies depicted that progesterone is
effective even in the case of short cx. , it exerts effects by
inhibiting production of PG. & pro-inflammatory
cytokines (IL-8&IL-1B).
(Berghellaet al.,2010; Facchinetti et al.,2009)
 The current study demonstrated that there is no diff. in
the reduction of PTB in women (Vag.) & those (IM.)
 In this contemporaneous trial, the rate of S/E related to
Vag. Progesterone was lower compared with IM
progesterone .

46. Conclusions and Recommendations

47. • Our trial of progesterone administration
to pregnant women at risk of PTB with
short Cx.(15-20mm), predicted by TV
U/S seems to be effective, safe with
tolerable side effects.
• Route of Progesterone administration :
 Vaginal discharge, pruritus &
nausea
 IM bruises at injection site,
nausea, vomiting &hot flushes (Allergic
reactions).

48. Lastly, we concluded that
the effectiveness of
vaginal progesterone was
the same as IM with less
adverse effects.