www.smso.

net
Benha University Hospital, Egypt
Delta (Mansura)& Benha fertility
centers
Email: elnashar53@hotmail.com

www.smso.net
There are a large number of protocols
for LPS in ART.
LPS has consisted of HCG; P; P plus
HCG, E, ascorbic acid, aspirin or
prednisolone.
Different combinations, doses,
durations & formulations are used, but
the best dose, duration or formulation of
treatment remains controversial.
www.smso.net
Objective
To review RCTs & meta-analyses
concerning LPS in ART
Materials & methods
An electronic search of the
Cochrane library, Pub Med for RCT
& meta-analyses concerning LPS
from 1990 to 2004.

www.smso.net
Results
Five meta-analyses,
41 RCT &
no Cochrane systematic review
were found.
Studies were classified into long,
short, ultra-short & direct
protocol studies.
www.smso.net
LPS in the long protocol
using P, HCG or P plus
HCG or E was analyzed.
P support was reviewed as
regard the type, dose, route
of administration, when to
start & when to stop.
www.smso.net
www.smso.net


1. Progesterone alone
Progesterone Vs no treatment:
a significantly higher PR in
groups treated with IM or oral P
compared with no treatment (8
RCTs,Soliman et al, 1994)
www.smso.net
I. Route of administration:
1.IM Vs oral:
IM P conferred the most benefit
compared with oral P (meta-analysis, Prittis & Atwood, 2002)
IM P (50 mg/day) resulted in significantly
higher IR, CPR compared with oral P (600
mg/day) (Casini et al,2003).
4/30 women discontinued treatment
because of their inability to administer IM
P.
www.smso.net
2. IM Vs vaginal:
Vaginal P is as effective as the IM P
& is associated with fewer side effects
& greater patient adherence &
satisfaction (10 RCT,Felicia et al ,2003).
Adequate tissue levels of P after
vaginal P is attributed to uterine first-
pass effect.

www.smso.net
3. Oral Vs vaginal:
The C & OPR were significantly lower with the
oral formulation (Pouly et al, 1996; Frieder et al,
1999, Sucedo et al, 2000). These studies
strongly suggest the inferiority of oral P for
LPS.
1. The vaginal administration of P results in a
greater bioavailability with less relative variability
than oral P (Levine & Watson, 2000).
2. Oral P is subjected to first-pass pre-hepatic &
hepatic metabolism.

www.smso.net
II. Dose:
1. Oral:
Micronized P at doses of 400 & 600
mg. No differences in CPR (Chanson
et al,1996).
2. IM:
25 mg IM P was compared with 100
mg P. No difference in CPR (Check et
al,1991)..
www.smso.net
III. Type (formulation):
1. Vaginal:
Pezino et al (2004) compared
Gel (Crinone 8%, 90 mg/day),
Capsules (Uterogestan 200 mg twice daily) &
Suppositories (cyclogest 200 mg daily).
No differences in CPR.
Cost & minor side effects (perineal irritation,
leaking out, interference with coitus) may limit the gel
in favor of capsules & suppositories.
www.smso.net
2. IM:
50 mg/d of IM P Vs 341 mg
/3 days (Costabile et al,2001) or
once weekly (Abte et al,1997)
of IM 17 OH progesterone
caproate
No differences in CPR or
OPR.
www.smso.net
IV. When to start:
Day 6 Vs day 3 after OR:
PRs are significantly decreased
by starting on day 6 compared to
day 3 (Williams et al,2001).
Day of OR Vs day of ET:
No difference (Baruffi et
al,2002).
www.smso.net
V. When to stop:
At the time of pregnancy test
(Stelling et al, 1999;
Penzias,2002; Jacobs &
Balen,2003).
At 8 W (Costabile et al, 2001)
At 10-12 W (Check et al, 1991).
www.smso.net
Most treatment protocols advocate
the use of P throughout the first
trimester, based on the findings of
Shamma et al, who used 17-OH P
as a marker to demonstrate
ongoing corpus luteum activity up
to week 10 of pregnancy.

www.smso.net
Stelling et al (1999) found no difference
in the CPR, OPR, spontaneous abortion
between stop or continuing luteal
support after positive pregnancy test.
LPS beyond the pregnancy test
may not be indicated
(Penzias,2002; Jacobs &
Balen,2003).

www.smso.net
The optimal length of treatment
remains unsolved at present & further
trials are needed before clear
recommended.
The assumption that high serum P
levels are required to achieve biological
efficacy in the endometrium appears to
be incorrect (Penzias,2000)

www.smso.net
2. Progesterone plus
estrogen
The oral estrogen doses: 2 to
6 mg /d
1. No advantage
(Lewin et al, 1994; Smitz et al,1993;Tay
& Lenton, 2003; Rashidi et al,2004).
www.smso.net
2. Beneficial effect on IR & PR
(Farhi et al,2000; Gorkemli et
al,2003).
3. Beneficial effect on PR in
patients with profound E2
decline (E2 on day of HCG/ E2
of ET >50%) (Lakkis et al,2002;
Gleicher et al,2000).
www.smso.net
3. Progesterone plus HCG
HCG
5000 IU/3d: no statistically
significant differences in CPR
(Ludwig et al,2001).
2500 IU midluteal. No affect on
PR, but it helps to preserve corpus
luteum function & avoids the need
for further supplementation during
early pregnancy (Herman et al,1996)
www.smso.net
4. Progesterone
plus ascorbic acid
No benefit
(Griesinger et al, 2002)
www.smso.net
5. Progesterone plus
Prednisolone
Prednisolone (15 mg daily following
ET) does not improve the clinical
pregnancy or implantation rates
(Ezzeldin et al, 2003).
The sample size of this study was
small.
www.smso.net
6. Progesterone plus
Prednisolone & Low dose
aspirin
No benefit on PR , but it may
reduce the rate of
spontaneous pregnancy loss
(Mollo et al,2003)
www.smso.net


1. HCG Vs no treatment:
HCG 1000-5000 s.c. every 2-5 days
A significantly higher PR (Meta-analysis
of 5 RCTs, Soliman et al, 1994)
Many clinics have now stopped
giving HCG because OHSS is not
always easy to predict (Jacobs
&Balen,2003).
www.smso.net
2. HCG Vs IM P:
CPR & OPR were not
different (Albert & Pfeifer,
1991, Claman et al,1992;
Araujo et al,1994; Artini et
al,1995; Loh & Leong,1996;
Claman et al,1992; Artni et
al,1995).
www.smso.net
3. HCG Vs vaginal P:
No differences in CPR,
OPR or SAB
(Artini et al,1995; Martinez
et al,2000; Ludwig et
al,2001; Ugur et al,2001).
www.smso.net
4. HCG Vs oral P:
CPR & OPR were not
significantly different (Buvat et
al,1990).
5. HCG Vs IM P plus
oestrogen: There were no
significant differences (Pritts &
Atwood,2002)
www.smso.net
www.smso.net
1. Oral Progesterone VS
HCG:
When using IM HCG the CPR,
OPR & IR were significantly higher
(Buvat et al,1990).
The poor results obtained with
oral P is related to its poor
bioavailability
www.smso.net
2. Vaginal Progesterone Vs P
plus estrogen:
No differences in CPR or IR
(Farhi et al, 2000). The power of
this study was low.
3. Vaginal Progesterone Vs P
plus HCG:
No differences in CPR or SAB
(Ugur et al,2001).

www.smso.net
www.smso.net
1. IM progesterone Vs HCG :
In a single very small study, there
were no significant differences in
CPR or DR (Golan et al,1993).
2. Vag Progesterone VS P plus
HCG:
Vaginal P alone provides sufficient
luteal phase support (Mochtar et al,1996).
www.smso.net
www.smso.net
A.Progesterone
1. Vaginal P Vs placebo:
No difference in PR (Polson et
al,1992)
2. IM P Vs no treatment:
PR was similar (Steirteghem et al,1988;
Leeton et al,1985).
P LPS is unlikely to have a significant
effect on increasing PR.
www.smso.net
B. HCG
1.HCG Vs no treatment:
HCG support of the luteal phase is not
routinely warranted in hMG-stimulated
cycles (Keenan & Moghissi,1992)
2. Oral P, HCG or placebo:
No differences (Kupfemrminc et al,1990).
No necessity of P supplementation in
the luteal phase if GnRH agonists
were not used (Daya,1988).
www.smso.net
www.smso.net
I. In long protocol:
IM P is more effective than oral
P.
Vag P is more effective than oral
P.
Addition of oral E to P improves
IR&PR in patients with profound
E2 decline.
www.smso.net
No significant differences in
fertility outcomes when
comparing:
1. IM P with vag P;
2. different doses of P;
3. different forms of vag or IM P;
4. start of P at oocyte retrieval
with start at ET
www.smso.net
Addition of
ascorbic acid,
prednisolone,
aspirin to P has no
benefit.
www.smso.net
II. In direct protocol:
No need of P
supplementation in
the luteal phase
www.smso.net
Benha University Hospital
Delta (Mansura)& Benha fertility centers
Email: elnashar53@hotmail.com