Luteal Phase Support

DAMAS CUS UNI VE RS I T Y

Marwan&Alhalabi&&MD&PhD&Professor&in&Reproduc7ve&Medicine&Faculty&of&Medicine&&Damascus&University&&&Clinical&Medical&Director&&Orient&Hospital&&Assisted&Reproduc7on&Center&&Damascus,&Syria.&


•  Is&luteal&phase&support&necessary&?&•  If&so…&Progesterone&or&HCG&?&•  Are&they&equally&effec7ve&?&•  Which&progesterone&to&use&?&•  By&which&route&–&oral,&IM&or&vaginal&?&•  Are&there&pa7ent&preferences&?&

DAMAS CUS UNI VE RS I T Y 6


7


&

&&


•  Progesterone)was) independently& discovered&by) four) research) groups) in&1933.))

•  The) name) PROGESTERONE) derived) from& PROGEsta:onal) STERoidal)ketONE.)

•  The)molecular&weight&of)progesterone)is)100)x)π)=)314)dalt.)

•  Like) other) steroids,) progesterone) consists) of& four& interconnected& cyclic&hydrocarbons.&&

•  Progesterone)contains&ketone&and)oxygenated)func:onal)groups,)as)well)as)two)methyl&branches.)

•  Like)all)steroid)hormones,)it)is)hydrophobic.&


Exerts& its& ac7on& primarily& through& the& intracellular& membrane& bound&progesterone&receptor&&

•  Reproduc7ve&system&&o  Endometrium&o  Cervical)endothelium)and)mucus))o  Immune&system&during&implanta7on&and&early&pregnancy&o  Decreases&contrac7lity&of&the&uterine&smooth&muscles&&o  Inhibits)lacta:on))o  Drop& in& progesterone& levels& is& possibly& one& step& that& facilitates&

the&onset&of&labor.&&

•  Regula7ng&the&effects&of&estrogen.&&


Exerts& its& ac7on& primarily& through& the& intracellular& membrane& bound&progesterone&receptor&&

•  The& fetus& metabolises& placental& progesterone& in& the&produc7on&of&adrenal&mineraloW&and&glucosteroids.&

•  Nervous&System&o  Neuroprotec7ve&o  ?&Memory&and&cogni7ve&ability.&

•  Other&systems:&&o  Core&temperature&&o  Reduces&spasm&and&relaxes&smooth&muscle&&o  Prevent&endometrial&cancer&by&regula7ng&the&effects&of&estrogen&

(as&in&PCOS).&&


•  Control&anovulatory&bleeding&•  In&infer7lity&therapy&&

•  To&support&early&pregnancy&(?)&

•  Pa7ents& with& recurrent& pregnancy& loss& due& to& inadequate&progesterone&produc7on&

•  Hormone&replacement&therapy&&

•  Preterm&Labor&

•  Progesterone& receptor& antagonists,& or& selec7ve& progesterone&receptor&modulators&(SPRM)s&&

•  Hormonal& contracep7on& do& not& contain& progesterone& but& a&proges7n&&&&

•  Trea7ng&mul7ple&sclerosis&??&

•  Aging&??&

•  Brain&Damage&&???&&


•  P& induces&a&secretory&transforma7on&of& the&endometrium…&

…&Which&improves&endometrial&recep7vity&…&

…&Which&allows&blastocyst&impanta7on.&

•  P&also&causes&local&endometrial&vasodila7on.&

•  P& reduces& the& contrac7lity& of& uterine&muscle.&


2

2.5

3

3.5

4

4.5

Day 15 Day 16 Day 17 Day 18 Day 19 Day 20

(De Ziegler et al. J Soc Gynecol Invest 1996;3(2):141A)

UC F

requ

ency

/M

in

Crinone 8% administered every other day (EOD) in women with ovarian premature failure


0%5%10%

15%20%25%

<3.0 3.1-4.0 4.1-5.0 >5.0

(Fanchin et al. Human Reprod 1998;13(7):1968-74)

P <0.0001,ANOVA UC/Min

Impl

anta

tion

Rate


•  Studies&with&Progesterone&vs.&no&supplementa7on& PR&are&higher&with&P&supplementa7on&

&&&&&&&&&&(Leeton&et&al.,&1985,&BelaischWAllart&et&al.,&1987,&Yovich&et&al.,&1985)&

•  Studies&with&hCG&vs.&no&supplementa7on&& PR&are&higher&with&supplementa7on&

&&&&&&&(Smith&et&al.,&1989,&BelaischWAllart&et&al.,&1990,&Herman&et&al.,&1990)&

•  MetaWanalysis:&&&Progesterone&or&hCG&improved&the&pregnancy&rates&in&IVF&cycles&&&&&&&&&&&

Supports&rou7ne&use&of&luteal&phase&support&in&IVF&cycles&(Soliman&et&al.,&1994)&


in&IVF/ICSI&cycles:&*&live&birth&rate&was&significantly&higher&with&progesterone&for&luteal&phase&support.&

• Linden et al, Human Reproduction Update, Vol.18, No.5 p. 473, 2012. ** Erdem et al, Fertility and Sterility Vol. 91, No. 6, June 2009.

in&IUI&cycles:&**&live&birth&rate&was&significantly&higher&with&progesterone&for&luteal&phase&&


•  Con7nued&downWregula7on&by&GnRHa&!&LH&↓&

•  Induc7on&of&mul7ple&follicles&per$se$

•  Removal&of&large&quan77es&of&granulosa&cells&at&oocyte&retrieval&

•  Supraphysiological&E2/P4&in&early&luteal&phase&!&nega7ve&feedback&!&LH&↓&&

•  hCG&LH&suppression&


LH FSH

Progesterone

Oestrogen


22


•  Effec7ve&•  Physiological&

serum&levels&•  Painful&(long,&

thick,&needles)&•  Occasional&

sterile&abscess&•  Occasional&

allergic&reac7on&(oil&vehicle)&

•  Needs&to&be&administered&by&nurse&

•  Ineffec7ve&

•  Low&bioavailability&

•  High&rate&of&metabolites&

•  Minimal&endometrial&effect&

•  High&rate&of&side&effects&(somnolence)&

•  Effec7ve&•  Convenient&

(selfWadministra7on)&

•  First&uterine&pass&effect&/&targeted&delivery&

•  Can&be&messy&

•  Might&require&mul7ple&dosing&/&day&

DAMAS CUS UNI VE RS I T Y (Cocrane Rev., 2004)

DAMAS CUS UNI VE RS I T Y (Cocrane&Rev.,&2004)&


(Textbook of ART, 2nd Ed., 2004; Cocrane Rev., 2004)


(Cocrane&Rev.,&2004)&


•  Serum&levels&of&progesterone&vs.&local&levels.&

•  Recommend& star7ng& vaginal& P& on& oocyte&collec7on&day&or&next&day&(day&before&ET).&

•  ‘’first&pass&effect’’&•  Low& serum& levels& do& not& equate& to& uterine&concentra7ons.&

•  Also& a& beneficial& effect& on& reducing& uterine&contrac7ons.&


•  There& is& 14x& the& concentra7on& of& progesterone&in& the& uterus& compared& with& the& serum& levels&following& vaginal& administra7on,& whereas& the&ra7o&is&1:1&with&IM&progesterone.&

•  Direct&transport&of&progesterone&from&the&vagina&to&the&uterus.&

Cincinelli&E.&et$al.$2000&


•  There&con7nues&to&be&controversy&about&the&benefit&of&intramuscular&over&

vaginal&use.&

It)is)also)interes:ng)to)note)that)IM)progesterone)is)not)licensed)for)use)in)IVF)/)ART)by)the)FDA)in)

the)United)States!)


•  More& consistent& uterine& absorp7on& and&u7liza7on&of&progesterone&

•  “first&pass&effect”&•  Targeted&to&the&uterus&specifically&

•  Preferable&to&IM&progesterone&

• Much&more&“pa7ent&friendly”&


Conclusion:&The) luteal) phase) support) in) ART) cycles) with) Utrogest)200mg.)Capsules)(three):mes)per)day))or)vaginal)gel)8%)(two) :mes) per) day)) by) the) vaginal) route) resulted) in)similar)outcomes)with) respect) to) implanta:on,)ongoing)pregnancy,) and) abor:on) rates.) The) two) recommended)regimens) of) P) supplementa:on) in) ART) proved) to) be)equivalent&and&safe.)

Kleinstein J Luteal phase study group

Fer:l)Steril.)2005;83(6):1641Z9.)


Paul)W.)Zarutskie)and)James)A.)Phillips)

MetaWanalysis&of&progesterone&luteal&support&

&

Conclusion:&

Administra7on&of&vaginal&P&is&comparable&to&administra7on&of&IM&P&for&luteal&phase&support&in&assisted&reproduc7ve&technology.&

Fer:l)Steril)2009;92:163Z9.)


•  Pa7ent&inconvenience&(painful&injec7ons)&

•  Higher&risk&of&OHSS&(Soliman&et&al.,&1994)&

  Poten7ally&lifeWthreatening&complica7on&

  Risk&of&thrombo&embolism&

  Risk&of&myocardial&infarc7on&

  Long&hospital&stay&

•  No&uterineWrelaxant&proper7es&as&vaginal&P&

“There& no& longer& seems& to& be& place& for& hCG& supplementa7on&during&the&luteal&phase”&

$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$Ludwig$M$et$al,$Eur$J$Obstet$Gynecol$Reprod$Biol$2002;103:48E52$


Oral&Progesterone&

Reduced&bioavailability&1&

Significantly&lower&rates&of&implanta7on&and&pregnancy&rates&2,3&

Higher&incidence&of&side&effects&3&

Oral&Dydrogesterone&(DG)&

Incomplete&secretory&transforma7on&of&the&endometrium,&suppor7ng&reduced&efficacy&of&this&formula7on&4&

Endometrium&fails&to&present&the&op7mal&condi7ons&for&the&implanta7on&of&human&embryos&4&

Vaginal&micronized&progesterone&was&significantly&more&effec7ve&than&oral&DG&in&crea7ng&an&“in&phase”&secretory&endometrium&1&

1- Fatemi HM et al, Hum Reprod Update 2007;13:581–90.

2- Penzias AS et al, Reprod Biomed Online 2003; 6: 287–95.

3- Lan VTN, Reprod Biomed Online 2008; 17: 318–234.

4- Fatemi HM et al, Hum Reprod 2007;22:1260–1263.

“Oral administration is not appropriate for luteal support”


•  CRINONE&is&a&bioWadhesive&vaginal&gel&which&contains&micronized&progesterone&

•  CRINONE&preWfilled&vaginal&applicator&•  Accurate&delivery&of&90mg&progesterone&in&1.125g&of&gel&

•  CRINONE&is&based&on&a&vaginal&moisturising&formula&•  White&to&offWwhite&gel&


&Progesterone&supplementa7on&or&replacement&as&part&of&an&assisted&reproduc7ve&technology&(ART)&treatment&&

&for&infer7le&women&with&progesterone&deficiency*&

•  Once&daily&for&supplementa7on&&&

•  Twice&daily&as&replacement&&&&&&&

Preferable&to&applied&in&the&morning&

&

* FDA Approval


Polycarbophil&•  Bioadhesive&waterW

insoluble&polymer&

•  Stays&anached&to&the&vaginal&epithelial&cells&un7l&they&turn&over&

•  Not&absorbed&

&Allows&sustained&

&release&of&progesterone&

Emulsion$system&•  The&carrier&vehicle&is&an&oilW

inW&water&emulsion&containing&the&polycarbophil&

•  The&progesterone&(P)&is&par7ally&soluble&in&both&the&oil&and&water&phases&of&the&vehicle&with&the&majority&of&progesterone&exis7ng&as&a&suspension&&Ensures&controlled&release&of&P&

+!


•  CRINONE&contains&micronized&progesterone&in&an&‘oilWinWwater’&emulsion&

&

•  The&majority&of&progesterone&exists&as&a&lipophilic&suspension&•  a&lipid&(oil)&reservoir&

•  The&aqueous&(water)&por7on&releases&progesterone&

&into&the&cellular&7ssue&and&is&replenished&from&the&&

lipid&reservoir& aqueous

Lipid`

tissue


•  Direct&delivery&from&vagina&to&uterus&&

•  FirstWpass&uterine&effect&


1&hour&

3&hours&

2&hours&

4 hours&

Radioactive test substances

Radioactive reference substances

Time

Bulletti C et al, Hum Reprod 1997; 12: 1073–9

Direct&delivery&from&vagina&to&uterus&&FirstWpass&uterine&effect&

Time-dependent diffusion of progesterone from the cervix to the fundus of the uterus


Endometrial levels

11.5

1.40

2

4

6

8

10

12

14

Vaginal P IM P

ng P/mg proteinSerum levels

11.9

69.8

0

10

20

30

40

50

60

70

80

Vaginal P IM P

ng/mL

P < 0.05 P < 0.05

Miles RA et al. Fertil Steril 1994;62:485–90

“IM Progesterone in not recommended as a first choice luteal phase support” Fatemi HM et al, Hum Reprod Update 2007;13:581–90


•  First&uterine&pass&effect&avoiding&firstWpass&hepa7c&metabolism&1&

•  Greater&bioavailability&in&the&uterus&2&•  Maximum&uterine&effect&and&minimum&systemic&levels&and&

side&effects&3&

“Vaginal progesterone should be the standard choice for luteal phase support”

Ludwig M, Diedrich K et al. Acta Obstet Gynecol Scand 2001;80:452–466.

1- Bulletti C et al: the first uterine pass effect. Hum Reprod 1997; 12: 1073–9. 2- Penzias AS, et al. Reprod Biomed Online 2003; 6: 287–95. 3- Fatemi HM et al,Hum Reprod 2007;22:1260–1263.


43

23

46.3

47

39

47.6

0 5 10 15 20 25 30 35 40 45 50

Coutifaris et al.

Williams et al

Yanushopolsky et al

Pregnancy % (P= NS)

IM Progesterone Crinone

Comparable pregnancy rates to IM Progesterone

&Significantly&&lower&rate&of&miscarriage&with&vaginal&progesterone&compared&to&&IM&progesterone&&&Paul&W.&Zarutski&et&al&:Fer7l&Steril.2009;92:163&Yanushpolsky et al : Fertil Steril 2008;89:485-7 ,Williams et al :Fertil Steril.2000;74(suppl 1):S209.Abstract P 363 \,Coutifaris et al : Fertilk Sterli.2000;74(suppl 1)S205.Abstract p 350


is not true at all!

is absolutely true!

18.9

30

30.9

28

28.8

39

33.1

31

0 5 10 15 20 25 30 35 40 45 50

Ludwig and Diedrich

Williams et al

Simunic et al

Lan et al

Pregnancy % (P= NS)

Progesterone susppositories Crinone

Comparable&pregnancy&rates&to&&Progesterone&suppositories&

Williams et al :Fertil Steril.2000;74(suppl 1):S209.Abstract P 363

,Ludwig et al : Acta Obstet Gynecol Scand 2001;80:452-466 Lan VTN et al : Reprod Biomed Online 2008;17:318-23

,Simunic V et al :Fertil Steril 2007;87:83-87


•  The&aim:&evaluate&the&outcome&in&pa7ents&receiving&frozenWthawed&embryo&transfer&arer&doubling&the&vaginal&P&gel&supplementa7on.&

•  FrozenWthawed&embryo&transfer&cycles&priming&with&oestradiol&and&vaginal&progesterone&gel&were&included.&

•  The& vaginal& progesterone& dose&was& changed& from& 90mg& (Crinone)& once& a&day&to&twice&a&day&

•  The& pregnancy& rate& increased& significantly& arer& doubling& of& the&progesterone&dose&(26.7%&(90mg))&versus&38.4%&(180mg);&P=0.021).&

•  The&early&pregnancy& loss& rate&decreased& significantly& (67.4%&versus&43.7%&respec7vely;&P=0.014),&which&significantly&increased&the&delivery&rate&(8.7%&versus&20.5%,&respec7vely;&P=0.002).$

&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&RBM&online&February&2013&

&


Leakage and messiness are complaints commonly

associated with the use of vaginal micronized

progesterone

Lan VTN et al : Reprod Biomed Online 2008;17:318-23


Ernest et al :Eur J Obstet Gynecol Reprod Biol 2003;111:50-55


Ernest et al :Eur J Obstet Gynecol Reprod Biol 2003;111:50-55

Significantly&more&pa7ents&using&micronized&progesterone&suppositories&versus&Crinone&graded&:&&&W&Inconvenience&of&administra7on&&W&leaking&out&&&W&Interference&with&coitus&&

as Moderate&or&Severe&


Levin et al :Fertil Steril 2000;74:836-837


Easier& Preferable&94%&of&pa7ents&found&Crinone® easier

to use vs IM progesterone&84%&of&pa7ents&preferred&Crinone®

over IM progesterone&

Some&pa7ents&do&prefer&injec7ons&as&they&believe&they&must&“work&bener”&if&the&are&painful&


Simunic V et al :Fertil Steril 2007;87:83-87


•  Vaginal&progesterone&•  Allergy&•  ?effec7ve&if&bleeding&•  “messy”(?)&

•  IM&progesterone&•  Allergy&•  Abcess&•  Pulmonary&


Pa7ents& receiving& vaginal& progesterone&should& be& counselled& that& early& bleeding&may&occur,&and&that&this&is&a&consequence&of&their&not&being&pregnant&–&not&the&reason&or&cause&for&failure&to&achieve&pregnancy.&


ART Procedure Crinone 8% (90mg) – once daily

IVF-ET From day of egg retrieval

Oocyte donation After estrogen priming (around day 15)

Frozen egg cycles As for oocyte donation *

IUI From insemination (36h after hCG) *

OI 12-24 hours after hCG

Luteal phase defect On day following LH surge


•  Target&Progesterone&Delivery&to&the&Uterus&&&&&&&&High&endometrial&levels,&low&serum&levels&2&

•  Effec7ve&Luteal&Phase&Support&3&&&&&&&&&Comparable&PR&to&IM&progesterone&and&suppositories&2W9&

•  Significantly&Higher&Pa7ent&Preference&3&Z  Less&messy,&no&lying&down&arer&applica7on&4&

Z  Less&interference&with&Coitus&2&

Z  More&convenient&and&easier&to&use&10&1- Bulletti C et al. Hum Reprod 1997. 2- Ernest HY Ng et al, Eur J Obstet Gynecol Reprod Biol 2003. 3- Penzias AS et al, Reprod Biomed Online 2003. 4- Lan VTN et al, Reprod Biomed Online 2008. 5- Paul W et al, Fertil Steril 2008. 6- Yanushpolsky E et al, Fertil Steril 2008. 7- Williams SC et al, Fertil Steril. 2000 (Data on file). 8- Coutifaris C et al. A preliminary report. Fertil Steril. 2000 (Data on file). 9- Simunic V et al. Fertil Steril 2007. 10- Penzais AS. Fertil Sterl. 2002.


The&addi7on&of&E2&to&progesterone&in&the&luteal&phase&&does&not&enhance&the&probability&of&pregnancy.&


•  Further& research& is& needed& to& assess& the&efficacy& of& adjuvant& luteal& phase& support&treatments& such& as& lowWdose& aspirin,&heparin,& prednisolone,& immuglobulins& and&fat&emulsions.&

•  These&interven7ons&are&star7ng&to&be&used&in& clinical& prac7ce& in& the& absence& of& any&RCT& evidence& of& benefit,& and& even& where&there&is&RCT&evidence&of&no&benefit.&


•  Inadvertent&GnRHa&administra7on&in&the&luteal&phase&does&not&compromise&pregnancy&but&rather&seems&to&improve&implanta7on&

•  GnRH&receptor&is&expressed&in&the&human&preimplanta7on&embryos,&endometrium,&and&corpus&luteum,&implica7ng&a&direct&effect&of&GnRHa&on&the&these&targets&

•  GnRHa&has&been&shown&to&s7mulate&trophoblast&produc7on&of&hCG.&


Oocytes)from)each)donor)were)shared)by)two)recipients,)one)of)whom))received)a&single&dose&of&GnRHa&(0.1&mg&triptorelin)&6&days&arer&ICSI,))and)the)other)received)placebo)at)the)same):me.)Recipient:)pituitary)downZregula:on)by)GnRHa)!)oral)E2)valerate)!))))))))))))))))))oral)E2)valerate)+)vaginal)utrogestan)(±)GnRHa)6)days)ader)ICSI))

GnRH&agonist)administra:on)at&the&7me&of&implanta7on)enhances)embryo)developmental)poten:al,)probably)by)a)direct&effect&on&the&embryo.)

(Hum. Reprod., 2004)


1 21 M C

2

FSH + HMG

H C G

GnRHa ICSI Placebo or

GnRHa

ICSI +

6 d

HCG ET

ICSI +

3 d E2 4 mg po + Utrogestan 400 mg Vag. qd

Beneficial&Effect&of&LutealWphase&GnRHa&on&Embryo&Implanta7on&in&GnRHaWtreated&Ovarian&S7mula7on&Cycles&


LutealWphase&GnRHa&&(Triptorelin&0.1&mg&6&d&arer&ICSI)&enhances&embryo&implanta7on&&and&live&birth&rates&


Beneficial&Effect&of&LutealWphase&GnRHa&on&Embryo&Implanta7on&in&GnRHantWtreated&Ovarian&S7mula7on&Cycles&

1 21 M C

2

FSH + HMG

H C G

GnRH ant ICSI

Placebo or GnRHa

ICSI +

6 d

HCG ET

ICSI +

3 d E2 4 mg po + Utrogestan 400 mg Vag. qd

6

Oral pill

LutealWphase&GnRHa&&(Triptorelin&0.1&mg&6&d&arer&ICSI)&enhances&embryo&implanta7on&&and&live&birth&rates&



•  Evidence&from&the&literature&supports&progesterone&supplementa7on&in&the&luteal&phase&of&IVF&cycles&

"  Un7l&the&pregnancy&test&"  Not&indicated&beyond&posi7ve&pregnancy&test&

•  Although& serum& progesterone& levels& are& higher&arer&the&IM&route&vs.&vaginal&route,&the&pregnancy&rates&are&comparable&

)))))))))))))))))))))))))))))))))))))))))))))))))))))))(Penzias)A.)Fer:l)Steril)2002))


Mochtar&el&al.,&(2006)&

385&pa7ents&randomized&into&three&groups:&

1.   LPS&start&on&HCG&day&2.   LPS&start&on&day&of&OR&3.   LPS&start&on&ET&day&


•  The&administra7on&of&progesterone&before&oocyte&retrieval&is&associated&with&a&lower&pregnancy&rate&than&the&administra7on&of&progesterone&arer&oocyte&retrieval&(Sohn&et&al.,&1999)&

•  Decrease&of&24%&was&seen&when&luteal&phase&support&was&delayed&un7l&6&days&arer&OR&compared&to&3&days&arer&OR&(Williams&et&al.,&2001)&

•  No&difference&was&found&when&luteal&phase&support&was&started&at&OR&compared&to&star7ng&at&ET&(Baruffi&et&al.,&2003)&


Nyboe&et&al.&(2002)&385&pa7ents&randomized&into&three&groups:&

1.   LPS&con7nued&un7l&posi7ve&pregnancy&test.&

2.   LPS&con7nued&for&three&weeks&into&pregnancy&

Pregnancy&rates&(1)  (n=153)&=&78.7%&delivered&

(2)  (n=150)&=&82.4%&delivered&(NS)&

Conclusion:&&prolonga7on&of&LPS&beyond&a&posi7ve&pregnancy&test&is&not&beneficial&


•  Progesterone&only&for&LP&support.&•  Vaginal&P&equivalent&to&IM&P.&

•  Do&not&rou7nely&use&HCG.&•  The&evidence&does&not&support&con7nuing&LPS&beyond&8&weeks&gesta7on.&


&…&IVF&using&GnRha&for&pituitary&downWregula7on&should& be& informed& that& luteal& support& using&human&chorionic&gonadotrophin&or&progesterone&improves&pregnancy&rates&

&&…rou7ne&use&of&human&chorionic&gonadotrophin&for& luteal& support& is& not& recommended& because&of& the& increased& l ikelihood& of& ovarian&hypers7mula7on&syndrome.&&


Criteria 25,000 cycles 50,000 cycles

Vaginal cream/gel 34% 34%

Vaginal capsule 28% 30%

IM progesterone 10% 13%

hCG 7% 4%

Oral progesterone 1% 2%

Vaginal P + IM P 19% 15%

Vaginal + Oral P 1% 1%

hCG + any progesterone 0% 1%

The&result&represent&25,500&and&50,000&IVF&cycles&from&35&countries.&www.ivf-worldwide.com


http://www.ivf-worldwide.com


•  84& IVF& treatment& centers& from& 35& countries;& total& of& 51,155&IVF&cycles&per&year,&completed&the&survey.&

•  There& is& a& major& change& in& clinical& use& of& agents& or& luteal&support:&"  hCG&is&now&out&of&use.&"  The&use&of&IM&progesterone&has&declined&significantly.&"  There&is&an&increase&in&the&use&of&vaginal&progesterone&"  If& the& pa7ents& conceive,& the& use& of& progesterone& is& now&being&shortened.&

•  The& shir& in& the& clinical& prac7ce& of& progesterone& is&approaching&the&E.B.M.&published&in&the&field.&&

www.ivf-worldwide.com


&&

&Current&UK&prac7ce&in&ART&luteal&phase&support&


64.5

30.6

3.2 1.6

0

10

20

30

40

50

60

70

%

Very ImportantImportantOthers+DKNot Important


48.3

25.8

19.3

4.8

05

101520253035404550

%

Day ECDay ETDay EC+1Others


48.4

11.2

4.8

24.2

11.2

05

101520253035404550

%

12 weeks8 weeksFetal HeartPregnancy Testother


Summary&of&findings:&•  69&studies&included;&16,327&women.&

•  Significant&effect&in&favor&of&P&for&LPS.&•  Addi7on&of&E2&or&hCG&to&LPS&of&no&benefit.&•  Route&and&dura7on&of&administra7on&of&P&were&equivalent.&

•  Adding&hCG&to&P&for&LPS&associated&with&higher&risk&of&OHSS.&Use&of&hCG&should&be&avoided.&

•  Significant&benefit&to&addi7on&of&GnRH&agonist&to&P&for&LPS.&

Van&der&Linden&et&al.&

Van&de&Linden&M&et&al.&Hum.&Reprod.&Update&2012;18:473W473&&&Cochrane&Review&2011.&


Final&conclusions:&•  Evidence&for&a&significant&effect&in&favor&of&progesterone&for&

luteal&phase&support.&Best&result&with&synthe7c&progesterone.&•  Evidence&that&the&addi7on&of&othe&substances&such&as&

estrogen&or&hCG&doe&not&improve&outcomes.&•  Evidence&for&equivalence&of&IM&and&vaginal&routes&of&

administra7on.&Vaginal&route&is&best&tolerated&by&pa7ents.&•  hCG,&or&hCG&plus&progesterone,&was&associated&with&a&higher&

risk&of&OHSS.&The&use&of&hCG&should&therefore&be&avoided.&•  Evidence&showing&a&benefit&from&the&addi7on&of&GnRH&agonist&

to&progesterone&in&luteal&phase&support.&


1.&Wash&your&hands&with&soap&and&water.&&2.&Remove&the&applicator&from&wrapper.&&3.&Hold&the&applicator&at&the&flat&end.&&Shake&down&several&7mes&like&a&thermometer&to&ensure&the&contents&are&at&the&thin&end.&

4.&Hold&the&applicator&by&the&flat&sec7on&of&the&thick&end.&Twist&off&the&tab&at&the&thin&end&and&discard&the&tab.&Do&not&squeeze&the&bubble&while&twis7ng&off&the&tab.&


5.&&Carefully&insert&the&thin&end&of&the&applicator&well&into&the&vagina&while&you&are&in&a&siwng&posi7on,&or&when&lying&on&your&back&with&your&knees&bent.&

6.&Squeeze&the&bubble&of&the&applicator&firmly&to&release&the&gel&into&the&vagina.&Remove&and&discard&the&applicator.&&Some&gel&may&be&ler&in&the&applicator.&Do&not&worry,&the&correct&dose&will&have&been&delivered.&

Luteal Phase Support

Health & Medicine

Transcript of Luteal Phase Support