Role of progesterone in Pregnancy

1. Dr. Meenakshi Sharma
Specialist Obs & Gyne
Dr. Hedgewar Arogya Sansthan
Govt NCT, Delhi
2011

2.  Prepares endometrium for blastocyst
implantation
 Maintenance of early pregnancy
 Immunomodulating effect of progesterone
prevents fetal rejection
 Progesterone induced blocking factor (PIBF)
induces Th2- dominant cytokine response
which favours pregnancy
 Regulates HLA-G expression and NK cell
activity promote normal gestation

3.  3 or more consecutive miscarriage
 0.5-1% of couples
 50% - cause not known
 Higher no. of miscarriage, failure likely
maternal factors
 Prognosis better for secondary than primary
recurrent aborters
 Risk increases with no. of successive losses

4.  Early studies P supplementation improves
pregnancy outcome in treated
Tho et al, 1983, Daya et al, 1988
Two meta-analysis conflicting results
 Meta-analysis combined data from 15
heterogeneous studies on ‘high risk’ showed no
benefit of progesterone in maintaining early
pregnancies
Goldstein et al, 1989
 Meta-analysis by Daya et al in 1989 reported
significantly improved pregnancy outcome in
women with RM
Daya et al, 1989

5. Meta-analysis by Daya et al in 1989
 Significantly improved pregnancy outcome in
women with RM
 Includes three controlled trials of progesterone in
RM shown small but not statistically significant ,
increase in rates of pregnancies that cont beyond
20 wks. Pooling of results using principles of
metaanalysis resulted OR for pregnancies reaching
20 wks was 3.09(95% CI 1.28, 7.42)
Daya et al, 1989

6. Metanalysis by Oates-Whitehead in 2003
 14 trials (1988 women)
 No statistically significant difference in risk of
miscarriage between progesterone and placebo (OR
1.05, 95% CI 0.83,1.34) when all women irrespective
of gravidity and previous miscarriages were included
 Subgroup analysis of three trials (n-91with RM) P Rx
statistically significant decrease in miscarriage rate
compared with placebo or no treatment (OR 0.39,
95% CI0.17, 0.91)
Oates-Whitehead et al, 2003
 In all three metaanalysis same three trials were
included >40 yrs old

7.  Recent study El Zibdeh, 2005, 180 women
with RM randomised to dydrogesterone, IM
hCG or no treatment
 Miscarriages were significantly(p<0.05) less
common in dydrogesterone group (11/82,
13.4%) than in control group (14/48, 29%)
 No statistically significant difference between
hCG and control group

8.  15 trials (2118) women
 No diff in risk of miscarriage in Progesterone vs
placebo or no treatment ( OR 0.98, 95% CI 0.78,
1.24) in all women irrespective of gravidity and
age
 In subgroup analysis, statistically significant
decrease in miscarriage rate in women with RM
(OR 0.38, 95% CI, 0.20, 0.70)
 No significant difference in adverse effect to
mother or baby
 No difference in route of Progesterone
oral/IM/vaginal vs placebo or no treatment
Hass DM, Cochrane Database Syst Rev, 2008

9.  There is insufficient evidence to
evaluate the effect of progesterone
supplementation in pregnancy to
prevent a miscarriage in women with
recurrent miscarriage. Level B
RCOG, 2011
 Insufficient evidence to recommend
progesterone for treatment of
recurrent miscarriage
ACOG, 2002

10.  Luteal phase support necessary in GnRH
agonist cycles
 Need for Progesterone supplementation not
confirmed in ovarian stimulation protocols
other than GnRHa cycles
Daya S et al, Hum Reprod, 1988
 In a metaanalysis of RCT comparing diff luteal
support, it was suggested that hCG may be
superior to progesterone in GnRH stimulated
cycles
Soliman et al, Fertil Steril, 1994

11.  Oral Progesterone inefficient in comparision with hCG in
GnRHa cycles
Buvat et al, Fertil Steril, 1990
 Im hCG vs Vaginal progesterone conflicting result
 No diff in PR
Smitz et al,1988, Claman et al, 1992, Araujo et al,1994,Artini et al,1995
 Im hCG superior to vaginal progesterone
Golan et al,1993
 Im (50mg) vs vaginal Progesterone (600 mg) in a RCT in
GnRHa cycles significantly lower miscarriage and trend
towards higher implantation rate with lower serum
progesterone with vaginal Progesterone
Smitz et al, Hum Reprod,1992

12.  59 studies included
 Progesterone resulted in small but significant
improvement in pregnancy rate in trials with
or without GnRH were grouped together(OR
1.35, 95% CI, 1.01, 1.79)
 No effect on miscarriage rate
 No diff P vs hCG/ P vs P+hCG/ P vs P+E+hCG
but OR for OHSS doubled for treatment with
hCG (OR 3.06, 95%CI 1.59, 5.86)
 No diff in route of Progesterone
Daya S,Cochrane Database Syst Rev, 2004

13.  Favorable progesterone effect in threatened
abortion though not statistically significant
Omar et al,2005, Pandian et al, 2009

14.  Cochrane review, 2011, by Whabi et al,
 Two studies (n 84) included in meta-analysis
 No evidence of effectiveness with use of
vaginal Progesterone compared to placebo in
reducing risk of miscarriage (RR 0.47%, 95%
CI 0.17, 1.30)
 Scarce data, no evidence for routine use of
progesterone in treatment of threatened
abortion
 Large RCT are needed

15. Evidence Consenses
Recurrent
abortion
Cochrane Review 2008
evidence level1+
Progesterone
beneficial in RM
Level B RCOG,
2011
Threatened
abortion
Cochrane Review 2
011
Evidence level1
Some benefit need
large RCT
Luteal phase
support
Cochrane review 2004 Progesterone
beneficial in GnRH
agonist cycles
In other protocols
benefit not clear