Progestogens are used during pregnancy for threatened miscarriage, recurrent miscarriage, and prevention of preterm labor. Vaginal administration of progesterone results in targeted uterine delivery with minimal systemic effects. It increases endometrial tissue levels more than oral or injectable routes. Progestogen treatment reduces miscarriage risk by 47% for threatened miscarriage and 29% for recurrent miscarriage. For preterm labor prevention in singletons, vaginal progesterone reduces risk with a short cervix while injectable 17-OH PC works for prior preterm labor. In twins, vaginal progesterone only helps if the cervix is short.

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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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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