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DR.KALPANA M.D (O.G) F.N.B (reproductive medicine). LPD. Luteal phase is defined as the period between ovulation and either the establishment of a pregnancy or menstruation Luteal phase of a natural cycle is characterized by the formation of a corpus luteum which secretes E2, P4 - PowerPoint PPT Presentation
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DR.KALPANA M.D (O.G) F.N.B (reproductive medicine)
LPDLuteal phase is defined as the period between
ovulation and either the establishment of a pregnancy or menstruation
Luteal phase of a natural cycle is characterized by the formation of a corpus luteum which secretes E2, P4
After implantation, blastocyst secretes HCGRole of HCG produced by the embryo is to
maintain the C.L
NATURAL CYCLEProgesterone Secretion peaks 4th day of
ovulation.Peak persist for 7th days then falls.Menstruation starts 4 days after the fall.In pregnancy placental progesterone starts
around 7 weeks.
IVFIVF is not the first line of treatment for all
patients with infertilityNational guidelines for IVF focus on
diagnosis & indications for IVF.
IVFIVF was initially designed to overcome tubal
infertilityNow it is the treatment of choice for
unexplained infertility, male infertility, endometriosis ,an ovulation .
Introduction of ICSI for severe forms of male infertility has widened the scope of IVF
DENUDED OOCYTES
2 PN EMBRYO
D2 & D3 EMBRYO
BLASTOCYST
LPD PREVALENCELuteal phase of all stimulated IVF cycles is
abnormal Edward
et al 1980.
AETIOLOGY OF LPDRemoval of granulose cells during OR results
in reduced P4
OR in natural cycle did not reduce P4 secretion and did not shorten the luteal phase.
Kerin et al 1981
AETIOLOGY OF LPDProlonged effect of GnRH agonist prevents
LH rise results in LPD Smitz et al 1992.Antag cycles also resulted in short luteal
phase and reduced PR Albanoct al 1998.
AETIOLOGY OF LPDHCG used as a trigger suppress LH
production .Miyake et al 1979.HCG in unstimulated cycles did not reduce
LH level Tavaniotou Derroey et al 2003.
AETIOLOGYSupra physiological levels of steroids
produced by multiple C.L which inhibit LH Secretion from the pituitary .
Fauser and Devroey 2003.
IVF CYCLEE2,P4 levels are supra physiological because
of multiple corpus luteum, Results in decreased in I.R
Duration of steroid production is 1-3 days shorter than normal cycle.
Abrupt fall is E2,P4 compared to natural cycle.
IUI
mild male factor infertility unexplained infertilityminimal to mild endometriosis
COHNatural Cycles CCCC+HMGCC+FSHHMGFSH (Urinary, Pure, Rec)HMG+FSHGnRHa + HMGGnRHa + FSHGnRHa +HMG + FSH
Number of trials of IUI ?
Pregnancies resulting from IUI occur during early treatment cycles.
Eighty-eight percent of pregnancies occur in the first three cycles of IUI and 95.5% within the first four cycles (Morshedi M et al, 2003).
Continued IUI beyond four trials
is not recommended
CC-|U|No positive effect of P4 was found in CC
cycles montivlle et al 2009.
CC|U|
In normo ovualatory patients stimulated with CC for |U| P4 did not increase PR [8.7 Vs 9.3%]
This is the first RCT analyzing the effect of P4, in CC stimulated cycle.
D.kyrou et al H.R 2010.Vol:25 issue:10
CC
Occupies E2, receptor in hypo thalamus stimulates GnRH secretion.
Increase the pituitary sensitivity to GnRHFSH,LH secretions are increased .LH is
responsible for the maintenance of C.LDirect effect on the ovary makes the granulosa
cells more sensitive to Gn So E2,P4 levels are increased
CC occupies hypo thalamic E2 receptor for a longer period than E2, this is the resaon for the greater luteal LH concetration.
Summary:
luteal phase P4 support did not increase PR in normo ovulatory women <37,years and stimulated with CC for |U|.
This was the first RCT to test the need for luteal support in |U| cycles and it was under powered .
Further studies are needed. Ky rou
et al H.R 2010 Vol:25
Gn-IUIRCT by erdem etal in 2009 concluded a
beneficial effect (PR) of p4 in IUI cycles stimulated with Gn in patients with unexplained infertility
Pcos-Letrozole
P4 increase PR in Pcos patients stimulated with letrozole montville et al 2009
Should luteal phase support be introduced in ovarian stimulation/IUI programmes? It is recommended to apply luteal phase support in
stimulated IUI cycles only when proven cost-effective.
Further trials are mandatory to investigate both endometrial and hormonal profile changes in the luteal phase after mild ovarian stimulation, and the cost-effectiveness of luteal support in IUI programmes
Fertility and SterilityVolume 91, Issue 6 , Pages 2508-2513, June 2009
LPSLPS is used to describe the administration of
medication which support the implantation process.
Different doses, duration and types of treatment have been evaluated.
How ever, there is no agreement regarding the optimal supplementation scheme (Fatem et al 2006)
ROLE OF P4 IN THE LUTEAL PHASEP4 causes Secretary change of the endo
metrium. Improves endo metrial receptivity.Causes local vaso dilatation.Induce nitric oxide synthesis in the decidua
and makes the uterus quie scent. Kolibiankis and devroey 2002.
PREPERATIONOralI.MVaginal
ORAL10% of oral dose circulates (Liver first pass
mechanism).Increasing dose results in Somnolescence.Lower I.R, P.R Increased Abortion rate.
I . MAdvantage – No first pass mechanism.Disadvantage Painful
Needs some one to give.AbscessAllergic reaction
IM P4Dose Vary between 25 to 100 mg/day with
out any Significant difference in outcome. (Pritts and Atwood et al 2002)
VAGINALAdvantage
Self administered.Easily tolerated.Allergic reaction-rareTargeted delivery even thoughP4 level is low
. Efficacy – equal to I.M.
VAGINAL P4There is recent evidence in the literature that
vaginal P4 is at least as effective as I M P4 in stimulate cycle
Simunic et al 2007.300 – 600 mg of natural micronized P4 is
divided in 2-3 dosesTavaniotou et al 2000Further prospective RCT are essential to
define the necessary dose of Vaginal P4 for LPS in IVF.
CRINONE 8% GELPreparation contains 90mg micronized P4 in
emulsion.It adheres to vaginal epithelium.Advantage
- long half life - Patient to patient variability in
absorption is less
. 8% gel = 200mg tid - Vaginal capsule
17 Hydroxy progesterone Caproate. Twice a week. PR, IR – Similar to daily IM injection.
HCGHCG was found to be superior to P4. Meta analysis by No sarka et al 2005
Contra Indicated in OHSS
Dydro gesteroneDydro gesterone and P4 were associated with
similar PR. Chakravarty el al
2005.Vaginal P4 was more effective than oral
Dydro gesterone in Creating in phase endometrium .
Fatemi et al 2007.
E2 SUPPLEMENTATIONImproves PR.Stimulates P4 receptors E2 and P4 better PR than P4 alone.
E2E2 6mg/day significantly improved the PR in
long protocol. Lukaszuk et al 2005No improvement in short GnRH agonist antag
protocol.
GnRH AGONITSActs on the pituitary and increase LH Secretion.Acts on the endo metrium pirard et al 2005Acts on the embryo Trsarih et al 2006Triptorelin 0.1mg given 6 days after ICSIHCG, E2, P4 levels increased Despite this encouraging results, Great concern exists
about the possible adverse effect on Oocyte, embryos Lambalk, Homburg et al
2006 Larger RCT needed.
LPSP4 and ascorbic acid.P4 and prednisolone.P4 and asprin.
ONSET OF LPSTiming of LPS is debatable 3 days after OR - Williams et al 2001No difference between OR day and ET days - Baruffi et al 2003Should not be later than 3days after OR as
5day after HCGHCG covers a maximum of 8 days
SUMMARYLPS with HCG or progesterone results in increased
PRVaginal and I.M. have comparable resultsE2 addition is beneficial in long GnRH agonist
protocol., but not in short GnRH agonist and antag protocol
It is too early to recommend the use of GnRH agonist in LPS
Since the cause of LPD in IVF is related to the supra physiological levels of steroids milder stimulation protocols should be used to eliminate LPD.
SUMMARYWith a growing tendency towards the
transfer of a reduced number of embryos (fauser, Devroey et al 2003) with an increasing number of European investigators advocating SET (Papanikolaou et al 2006) attitude should shift towards milder Stimulation protocol to eliminate LPD
Patient selectionCOHFollicular studyIUI
IUI
mild male factor infertility unexplained infertilityminimal to mild endometriosis
COHNatural Cycles CCCC+HMGCC+FSHHMGFSH (Urinary, Pure, Rec)HMG+FSHGnRHa + HMGGnRHa + FSHGnRHa +HMG + FSH
Number of trials of IUI ?
Pregnancies resulting from IUI occur during early treatment cycles.
Eighty-eight percent of pregnancies occur in the first three cycles of IUI and 95.5% within the first four cycles (Morshedi M et al, 2003).
Continued IUI beyond four trials
is not recommended
DENUDED OOCYTES
2 PN EMBRYO
D2 & D3 EMBRYO
BLASTOCYST
Success doesn’t mean the absence of failures. It means the attainment of the ultimate objective. It means winning the war not just the battle
IVF CYCLEGn RH antag with Gn RH a as a frigger most
affected.HCG in hibits pituifary LH Result in LPD.
ADVANTAGE OF P4Quietening effect on uterus .No dys synchrony between gland and stroma.E.T. During 2 nd 4 th day of p4 support
improves I.R.
SUMMARYTill 7 weeks Ovarian production of hormones
is Critical.Vaginal route has promising results.
IM Vs VAGINAL P4Meta analysis published in 2002 by pritts and
At wood included 5 RCT.PR, delivery rates were significantly higher in
I.M Progesterone.Despite the conclusion of pritts analysis,
Vaginal P4 has a viable alternative to I.M injection which is associated with high side effects.
IUI CYCLERagni et al in 2001 analysed luteal phase
hormone profile in Gn stimulated cycles with or with out antag.
No adverse effect of antag on luteal phase P4 level or the duration of the luteal phase.
Gn-IUI