Progestogens in obstetrics:

Which type and route???? Aboubakr Elnashar

Benha university, Egypt

Aboubakr Elnashar

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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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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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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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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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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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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Vaginal progesterone increases endometrial tissue levels

(Fert.Steril, 2012)

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IM progesterone is associated with the highest

serum levels (Fert.Steril, 2012)

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III. DIFFERENCE BETWEEN NATURAL

PROGESTAGEN AND 17HP

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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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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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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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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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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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2. RECURRENT MISCARRIAGES

Cochrane Database Syst Rev. 2013

4 trials, 225 women

El-Zibdeh

2005

Goldzieher 1964 Le Vine

1964

Swyer

1953

180 54 56 113

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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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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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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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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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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Limitation of MA

relatively small number of available studies.

varying types, dosages and routes of

administration of progesterone

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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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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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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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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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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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Invitation

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