Progestogens in obstetrics: Which type and route????

1. Progestogens in obstetrics:
Which type and route????
Aboubakr Elnashar
Benha university, Egypt
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2. CONTENTS
1. PROGESTAGEN USED DURING PREGNANCY
2. ABSORPTION
3. VAGINAL PROGESTAGEN AND 17 HP
4. USES OF PROGESTAGENS IN OBSTETRICS
 CONCLUSION
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3. I. Progestagen used during pregnancy
Progesterone
Secreted by:
Corpus luteum
Placenta
Adrenal cortex
Adrenal cortex: progesterone is an intermediate product in the formation
of cortisol.
Adrenal cortex and ovary:
progesterone can be converted to androgens and oestrogens
Metabolised: rapidly by the liver
Excreted: 20% in the urine as sodium pregnanediol
glucuronide.
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4. Progestogen
Compound with progesterone-like action
Produces progestational changes in an oestrogen-primed
endometrium.
Transform a proliferative into a secretory endometrium to
support pregnancy.
Natural
Synthetic.
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5. Natural progestagens
Synthesized from: plant sources: soybeans and
Mexican yam roots
occasionally from: animal ovaries.
The hormone is not available from any natural source without extraction and
synthesis
Chemically and structurally identical to human
progesterone: “bioidentical” or “natural”.
Forms:
1. Oral
2. Intravaginal
3. Injectable
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6. Synthetic Progestogens= Progestins
synthetically produced and differs in structure from
progesterone.
Progesterone derivatives:
17α-oH progesterone caproate
Stereoisomers of progesterone
Dydrogesterone
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7. II. ABSORBTION
Transvaginal Progesterone.
:uterine effects with minimal systemic side effects
(Fanchin et al, 1997).
One hour after application Four hours after application
Endometrial Diffusion: Targeted delivery: Micronised Vaginal Progesterone
Progressive diffusion of progesterone from the cervix to the fundus of the uterus
(Bulletti et al. Hum Reprod. 1997)
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8. Vaginal progesterone increases endometrial tissue levels
(Fert.Steril, 2012)
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9. IM progesterone is associated with the highest
serum levels
(Fert.Steril, 2012)
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10. III. DIFFERENCE BETWEEN NATURAL
PROGESTAGEN AND 17HP
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11. IV. USES IN OBSTETRICS
1.THREATENED MISCARRIAGES
2.RECURRENT MISCARRIAGES
3.PREVENTION OF PTL IN SINGLETON
PREGNANCY
4.PREVENTION OF PTL IN TWIN PREGNANCY
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12. 1. THREATENED MISCARRIAGES
 Cochrane Database Syst Rev. 2011:
4 studies (421)
Pandian
2009
El-Zibdeh
2009
Palagiano
2004
Gerhard
1987
(n=191)(n=146)(n=50)(n=64)
initial 40 mg
oral
dydrogesterone
followed by 10
mg twice/d
continued until
16 w
90 mg
progesterone
(Crinone
8%) vaginal
sups once
daily
for 5d
oral
dydrogesterone
10 mg twice/d
continued for
1 w after
bleeding
stopped
25mg;
progesterone;
twice/d vaginal
sups
continued for
14 d after
bleeding stopped
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13.  Use of progestogens is effective in the tt of
threatened miscarriage
Reduced the risk of miscarriage by 47% (with a
confidence interval consistent with a risk reduction of 21% to 65%).
Significant reduction in the mean pain score
(Palagiano 2004)
Only in a subgroup of women who were treated
with vaginal progesterone was the tt not
statistically effective in reducing miscarriage
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14. No statistically significant difference in the number
of congenital abnormalities, pregnancy-induced
hypertension nor antepartum hge between the
women who received progestogens and those who
did not.
 Limitation of MA:
1. poor methodological quality of studies
2. small number of the participants
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15. Carp, 2012, MA
335 women
13% miscarriage rate after dydrogesterone vs
24% in control women [odds ratio for miscarriage 0.47, (CI = 0.31–0.7),
11% absolute reduction in the miscarriage rate.
significant reduction of 47% in the odds for
miscarriage when dydrogesterone is compared to
standard care
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16. 2. RECURRENT MISCARRIAGES
Cochrane Database Syst Rev. 2013
4 trials, 225 women
El-Zibdeh
2005
Goldzieher 1964Le Vine
1964
Swyer
1953
1805456113
10 mg bid oral
Dydrogesterone,
5000 IU IM
hCG/4d
Duration: 12th w
10 mg/d oral
Dydrogesterone,
Duration: not
stated.
500 mg/w
IM
17 oh PC
Duration:
until 36 w
6 x 25 mg
progesterone
pellets
Duration: unclear.
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17.  3 or more consecutive miscarriages
Progestogen tt:
significant decrease in miscarriage rate compared
to placebo or no tt
(Peto OR 0.39; 95% CI 0.21 to 0.72).
2 prior miscarriages.
a trend but not a significant reduction in miscarriage
rates
(Peto OR 0.68; 95% CI 0.43 to 1.07).
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18. Subgroup analysis by method of administration
(oral, IM or vaginal): no statistically significant
difference between progestogen and placebo
groups.
Limitations of MA:
these 4 trials were of poorer methodological quality.
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19. Carp et al, 2015, SR and MA
509 women
10.5% miscarriage rate after dydrogesterone
administration vs 23.5% in control women (odds ratio for
miscarriage 0.29 [confidenceinterval 0.13–0.65] and
13% absolute reduction in the miscarriage rate
significant reduction of 29% in the odds for
miscarriage when dydrogesterone is compared to
standard care
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20. 3. PREVENTION OF PRETERM LABOUR IN
SINGLETON PREGNANCY
Cochrane Database Syst Rev.2014
Progestational agents:
reduction of PTL
reduce the frequency of uterine contractions
attenuate the shortening of cervical length.
prolong pregnancy
increase in birth weight.
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21. Limitation of MA
relatively small number of available studies.
varying types, dosages and routes of
administration of progesterone
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22. Short cervix
Vaginal progesterone reduced the incidence of
PTL
(Fonseca et al, 2007; Hassan et al, 2011)
17a OH P C did not.
(Grobman et al, 2012)
Prior PTL
17a OH P C reduced the incidence of PTL
(Meis et al, 2003)
Vaginal progesterone did not.
(O’Brien et al, 2007)
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23. AboubakrElnashar

24. AboubakrElnashar

25. Universal CL screening of singleton gestations
without prior PTB for the prevention of PTB remains
an object of debate.
cannot yet be universally mandated.
 reasonable, and can be considered by individual
practitioners, following strict guidelines.
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26. 4. PREVENTION OF PTL IN TWIN PREGNANCY
13 trials included 3768 women
(Schuit et al, 2014, MA)
Neither 17Pc (250 mg/w) nor
vaginal progesterone **
reduced the incidence of PTL
**Pessary: 200-400 mg
Gel: 90 mg
Sups: 100 -400 mg
Caps: 200 mg
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27. In a subgroup of women with a cervical length of
≤25 mm:
vaginal progesterone reduced PTL when cervical
length was measured
at randomisation (15/56 vs 22/60; RR 0.57; 95% CI 0.47–0.70) or
before 24 w of gestation (14/52 vs 21/56; RR 0.56;95% CI
0.42–0.75).
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28. CONCLUSION
1. T M: Oral or IM
2. RM: Oral, vaginal or IM
3. PTL in Singleton:
Short cx: vaginal
Previous PTL: IM
4. PTL in Twin:
Short cx: vaginal
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29. Invitation
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