PCOS: PCO S: Diagnosis, Approaches to

Therapy and Implications for IVF Prof. Dr. Basil C. Tarlatzis Unit for Human Reproduction 1st Dept. of OB/GYN, School of Medicine Aristotle University of Thessaloniki, Greece

PCOS Prevalence  

5-10% general female population Up to 30% of infertility population

Polycystic Ovary Syndrome

Diagnostic Dilemmas

Clinical abnormalities • hirsutism hi ti • obesity • oligo/amenorrhea • infertility

Polycystic ovaries • ultrasound • other

Endocrine features

• hyperandrogenemia • elevated LH • insulin resistance

PCOS Diagnostic Criteria

1990 NIH concensus

Both criteria  Chronic anovulation  Hyperandrogenism H d i (clinical or biochemical) Exclusion of other etiologies Dunaif A. PCOS. Blackwell Scientific, 1992

ESHRE/ASRM PCOS Consensus Meeting

Rotterdam, 2003

ESHRE / ASRM PCOS Concensus Meeting, Rotterdam, The Netherlands Sci Com: Chang, Azziz, Legro, Dewailly, Franks, Tarlatzis, Fauser Congress Chair; Tarlatzis, Fauser

Azziz Laven Bouchard Dewailly Legro L

Organon sponsored

Nestler Diamanti Pasquali Ibanez B l Balen

Dahlgren Homburg Wild Norman Franks F k

Wild Tan Dunaif Devoto strauss

Taylor Pugeat Filicori Magoffin

Rotterdam, May 2003

ESHRE/ASRM PCOS Consensus Paper

Concensus on PCOS Nomenclature

Rotterdam 2003

 





Syndrome of ovarian dysfunction Cardinal features hyperandrogenism polycystic ovary morphology Clinical manifestation menstrual irregularities, signs of androgen excess, obesity Associated with increased risk type 2 diabetes ESHRE/ASRM PCOS Consensus, Hum Reprod & Fertil Steril, 2004

PCOS Revised Diagnostic Criteria

Rotterdam 2003



2 out of 3 criteria must be fulfilled:  Oligo and/or anovulation  Hyperandrogenism clinical or biochemical evidence  Polycystic y y ovaries 

Exclusion of other conditions, such as congenital adrenal hyperplasia or androgen-secreting tumors



Thorough documentation of applied diagnostic criteria in research papers for future evaluation ESHRE/ASRM PCOS Consensus, Hum Reprod & Fertil Steril, 2004

PCOS Diagnosis - 1990 NIH Consensus -

PCOS

Hyperandrogenemia yp g

Oligo/anovulation

PCOS Diagnosis

- 2003 Rotterdam Consensus -

PCOS

PCO

Hyperandrogenemia yp g

Oligo/anovulation

PCOS Phenotypes According to the Rotterdam 2003 Criteria 







chronic anovulation, hyperandrogenism (only biochemical or only clinical) and polycystic ovaries. chronic anovulation and hyperandrogenism (only biochemical or only clinical), but normal ovaries. hyperandrogenism (only biochemical or only clinical) and polycystic ovaries, but regular confirmed ovulation. chronic anovulation and polycystic ovaries, but no biochemical or clinical hyperandrogenism.

Diagnosing g g PCOS: Still Controversial?

Controversies 





Polycystic ovaries with regular cycles and hyperandrogenism (HA) Polycystic ovaries with irregular cycles and without HA Polycystic ovaries and no overt symptoms of PCOS

AES Diagnostic Criteria for PCOS, 2009

PCOS Phenotypes According to the NIH, Rotterdam and AES Criteria   

NIH 8.7% AES 10.2% (increase 17.2%) Rotterdam 11 11.9% 9% (increase 36 36.8 8 & 16 16.7%) 7%)

March et al, Hum Reprod, 25:544 2010

PCOS Phenotypes: Challenges for

the Future







To identify the most accurate tests and the cutoff values for the diagnostic criteria. To study the prevalence, prevalence pathophysiology and genetics of the aforementioned phenotypes and subphenotypes. To explore the metabolic and long-term health risks that the different phenotypes and subphenotypes carry.

ESHRE/ASRM Consensus, Thessaloniki 2007

The Thessaloniki ESHRE/ASRM Consensus Paper, 2008

PCOS: Management     

Life-style changes LifeOvulation induction Metformin and other insulininsulinsensitising drugs Laparoscopic ovarian surgery In Vitro Fertilization

PCOS: Management 

Life-style changes LifeDiet Exercise

Weight Loss in PCOS: Results of RCT C o n tr o l

I n te r v e n tio n

(n = 8 4 )

W e ig h t lo s s (k g ) P r e g n a n c ie i s a t 1 8 m o n th s

4 .7 (0 .3 ) *

1 8 (2 1 .4 4% )

5 3 (6 1 % ) *

3 (1 6 .6 % )

M is c a r r ia g e A R T p r e g n a n c ie s S p o n ta n e o u s p r e g n a n c ie s

(n = 8 7 )

1 .3 (0 .2 )

6 (1 1 .3 % )

9%

37% *

11%

24% * Moran et al, 2003

* p16 mm

225 IU / d

150 IU / d

increased by 75 IU every 3-7 days

Step up protocols

Starting dose

Scan d7

HCG 5000 IU leadfoll lead foll =>16 mm

“ Low dose protocol “

Low (37.5 - 75 IU/d) FSH dose 37.5 - 75 IU / d

Increase dose by 5050-100%

increased by 5050-100 % every 7 days

Scan d 21 Starting dose

Scan d7

37.5 - 75 IU / d

Scan d 14

HCG 5000 IU leadfoll lead foll =>16 mm

Increase dose Increase dose by 50% by 50%

“ Chronic Low dose protocol “

Low (37.5 - 75 IU/d) FSH dose increased by 50% after 14 days

Step down protocols Scan d 44- 5

Starting dose

Foll > 9 mm

“ Step - down protocol “

Scan d8

HCG 5000 IU lead foll follll ≥16 mm

Loading FSH dose (112.5 to 187.5 0 IU/d) decreased byy 37.5 IU

112.5 to 187.5 IU / d

Decrease by 37.5 IU

Decrease by 37.5 IU

every 33-5 days

Scan d 21 Starting dose

Scan d7

Foll =14 mm HCG 5000 IU leadfoll lead foll ≥ 16 mm

Scan d 14

“ Sequential protocol “

FSH threshold dose

37.5 - 75 IU / d

Increase dose Increase dose Decrease dose by 50% by 50% by 50%

decreased by 50% when leading follicle reaches 14 mm diameter

Step-Up Step-Down ( 85) (n=85) ( 72) (n=72) Duration stimulation Total amount rFSH Monofoll. Cycles (%) E2 day hCG Rate hCG Rate hyperstimulation Pregnancy rate

15.2 951 68 454 85 2.3 19

9.7 967 32 849 62 11 16

P