A Life of PCOS A Life of PCOS Roy Homburg Roy Homburg Barzili Medical Centre, Ashkelon and Barzili Medical Centre, Ashkelon and Maccabi Medical Services, Israel Maccabi Medical Services, Israel Homerton Fertility Centre, London Homerton Fertility Centre, London
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A Life of PCOS Roy Homburg Barzili Medical Centre, Ashkelon and Maccabi Medical Services, Israel Homerton Fertility Centre, London.
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A Life of PCOSA Life of PCOS
Roy HomburgRoy Homburg
Barzili Medical Centre, Ashkelon and Maccabi Medical Barzili Medical Centre, Ashkelon and Maccabi Medical Services, IsraelServices, Israel
Homerton Fertility Centre, LondonHomerton Fertility Centre, London
PCOS – A typical case historyPCOS – A typical case history
A life in 25 minutes of ………..A life in 25 minutes of ………..
Polly SistikPolly Sistik
Polly SistikPolly Sistik
Age 16, schoolgirl.Age 16, schoolgirl.c/o irregular periods, acne, hirsutism.c/o irregular periods, acne, hirsutism.All symptoms started age 13.5 when had All symptoms started age 13.5 when had first period, since then 3-4 periods/year. first period, since then 3-4 periods/year.
o/e o/e Obese – BMI 31.5Obese – BMI 31.5Abdo circ. 92cmAbdo circ. 92cmAcne face and backAcne face and backMild hirsutismMild hirsutism
Anti-estrogen effect on endometriumAnti-estrogen effect on endometrium
• Endometrial thinning in 15-50% Endometrial thinning in 15-50%
(Gonen &Casper, 1990;Dickey et al, 1993)(Gonen &Casper, 1990;Dickey et al, 1993)
• Causes ER downregulation and depletion.Causes ER downregulation and depletion.• Suppresses pinopode formation Suppresses pinopode formation (Creus et al, 2003)(Creus et al, 2003)
• No pregnancies when endometrial thickness at midcycle No pregnancies when endometrial thickness at midcycle < 7mm< 7mm
• Not dose related and recurs in repeat cycles Not dose related and recurs in repeat cycles
(Homburg et al, 1999)(Homburg et al, 1999)
Aromatase Inhibitor Treatment:Aromatase Inhibitor Treatment:Day 3-7 of CycleDay 3-7 of Cycle
• Do not block estrogen receptorsDo not block estrogen receptors • No detrimental effect on endometrium No detrimental effect on endometrium or cervical mucusor cervical mucus • Negative feedback mechanism not Negative feedback mechanism not turned off—less chance of multiple turned off—less chance of multiple follicular development follicular development
• Better than CC for first-line treatment?Better than CC for first-line treatment?
• Safety?Safety?
Aromatase Inhibitors vs CCAromatase Inhibitors vs CC
• Meta-analysis, 4 RCTsMeta-analysis, 4 RCTs
• Clear superiority of aromatase inhibitors Clear superiority of aromatase inhibitors in pregnancy rates (OR 2.0) and in pregnancy rates (OR 2.0) and deliveries (OR 2.4)deliveries (OR 2.4)
Polyzos et al, Fertil Steril, 2008Polyzos et al, Fertil Steril, 2008
Letrozole vs CCLetrozole vs CC
• 911 newborns in 5 centers911 newborns in 5 centers
CC LetrozoleCC LetrozolePregnancies 397Pregnancies 397 514514
Aghssa et al, 2007 (PCOS, eds Allahbadia, Agrawal)Aghssa et al, 2007 (PCOS, eds Allahbadia, Agrawal)
Metformin for ovulation Metformin for ovulation induction?induction?
Live birth ratesLive birth rates
CCCC MetforminMetformin CC+metforminCC+metformin
22.5% 7.2% 26.8%22.5% 7.2% 26.8% Legro et al, NEJM, 2007Legro et al, NEJM, 2007
15.4% 7.9% 21.1%15.4% 7.9% 21.1%
Zain et al, Fertil Steril, 2009Zain et al, Fertil Steril, 2009
Insulin-sensitising drugs for women with Insulin-sensitising drugs for women with PCOS, oligo/amenorrhea and subfertilityPCOS, oligo/amenorrhea and subfertility
• Tang et al. Cochrane Database, 2009Tang et al. Cochrane Database, 2009
There is no evidence that metformin improves live There is no evidence that metformin improves live birth rates whether it is used alone or in birth rates whether it is used alone or in combination with clomiphene, or when compared combination with clomiphene, or when compared with clomiphene. with clomiphene.
Therefore, the use of metformin in improving Therefore, the use of metformin in improving reproductive outcomes in women with PCOS reproductive outcomes in women with PCOS appears to be limited.appears to be limited.
Maitake mushroomMaitake mushroomChen JT et al, J Altern Complement Med, 2010Chen JT et al, J Altern Complement Med, 2010
Updated from Homburg & Howles, 1999Updated from Homburg & Howles, 1999
Low-dose FSHLow-dose FSH
• Only a low-dose protocol should be used Only a low-dose protocol should be used for ovulation induction in PCOS.for ovulation induction in PCOS.
• Small starting and incremental dose Small starting and incremental dose increases recommended with no dose increases recommended with no dose change for 14 days.change for 14 days.
Duration of Initial Dose: 14 or 7 Days?Duration of Initial Dose: 14 or 7 Days? 14 days 14 days 7 days7 days
FSH required FSH required - Amps - Amps 22 1722 17- Days - Days 17.4 1317.4 13
1 large follicle/cycle 74% 60%1 large follicle/cycle 74% 60%
• With a starting dose of 75 IU FSH, With a starting dose of 75 IU FSH, unchanged for a minimum of 14 days, unchanged for a minimum of 14 days, 90% will get to the criteria for hCG90% will get to the criteria for hCGwithin 14 dayswithin 14 days
Homburg & Howles, 1999Homburg & Howles, 1999
Factors affecting outcome of LOD for PCOSFactors affecting outcome of LOD for PCOS
CCR: 54% after 12 monthsCCR: 54% after 12 months 75% after 30 months75% after 30 months
CC and low-dose FSH may be added if no ovulation after 3 CC and low-dose FSH may be added if no ovulation after 3 monthsmonths
One-off treatment with low multiple pregnancy rate and no OHSSOne-off treatment with low multiple pregnancy rate and no OHSS
Best if < 3 years infertility, thin and high LHBest if < 3 years infertility, thin and high LH
Maternal PCOS in pregnancyMaternal PCOS in pregnancy