PowerPoint Presentation · PDF file29-4-2017 1 Adenomyose: Epidemiologie & impact op fertiliteit 24 april 2017 V. Mijatovic, MD PhD Endometriosis Center VUmc

29-4-2017

1

Adenomyose:

Epidemiologie & impact op fertiliteit

https://questa-studie.nl/adenomyose-symposium

24 april 2017

V. Mijatovic, MD PhD

Endometriosis Center VUmc

Department of Reproductive Medicine

VU university medical center

Amsterdam

www.endometriosecentrum.vumc.nl

Disclosure

Geen financiële belangenverstrengeling van de spreker


Topics of my Lecture

1. Achtergronden & epidemiologie van

adenomyose

2. Adenomyose: een infertiliteits factor ?

3. Effecten van Adenomyose op voortplanting:

na spontane conceptiena IVFna endometriose chirurgie

4. Hoe dit te verklaren ?

5. Take home messages


Adenomyose: historisch perspectief

1860 Rokitansky “cystosarcoma adenoides uterinum”

1887 Chiari “salpingitis isthmica nodosa”

1908 Cullen diffuse - en focale adenomyose

Benign invasion of endometrium into the myometrium

producing an enlarged uterus with endometrial glands & stroma

surrounded by hypertrophic myometrium

Adenomyose van nu

Bird et al, Am J Obstet Gynecol 1972


Diepte criterium van Ferenczy

Invasie tot minimaal 25 % van het myometrium

Doel: 1. onderscheid maken met (fysiologische) invaginatie(s) van

het endometrium in het myometrium

2. verkrijgen van meer realistische prevalenties


https://questa-studie.nl/adenomyose-symposium

http://www.kgu.de/zmorph/histopatho/patho/data/wg/de/JA1_010_a.html

http://www.kgu.de/zmorph/histopatho/patho/data/wg/de/JA1_010_a.html

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Variatie in prevalenties van adenomyose

Tussen pathologen: 10 - 80 %

Bij obducties: 20 - 67 %

Na hysterectomie obv aantal doorsneden:

3 doorsneden 31%

6 doorsneden 61 %

Bergeron et al, Best Practise & Research Clinical Obst Gynecol 2006


Non-symptomatisch (30%)

Menorraghie (50%)

Metrorraghie (20%)

Dysmenorroe (30%)

Diepe dyspareunie (20%)

Chronische buikpijn (10-20%)

Dyschezie (10%)

Wat zijn de klachten van Adenomyose ?

Overlap met

symptomatologie

myomen &

endometriose

Bergeron et al, Best Practise & Research Clinical Obst Gynecol 2006

Adenomyose: gelijktijdig voorkomen met

andere pathologie


Bird et al, Am J Obstet Gynecol 1972

Adenomyose: epidemiologie pre-imaging era

o.b.v. hysterectomie studies


Epidemiological data by Imaging

15-20 % of adenomyosis cases are reported in 2nd & 3rd decade

17-20 % of women with deep endometriosis concomitantly show

adenomyosis on MRI.Ferrero et al, 2009

Darai et al, 2010

Garcia & Isaacson, 2011

Stepniewska et al, 2011


Adenomyose op MRI (2015)

Prevalentie: 18%

adenomyose bij diepe

endometriose op MRI


http://www.google.nl/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=1onaGjs-F6YhCM&tbnid=lSmMfqYuJouY8M:&ved=&url=http%3A%2F%2Fwww.lumc.nl%2Fcon%2F3040%2F130813%2F90629033535221%2F90706035926185%2F&ei=W61qUfOuDums0QWMj4HwDw&bvm=bv.45175338,d.d2k&psig=AFQjCNFYbd20cp8abrNXgA2v2uZX95rqOQ&ust=1366032091765635

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Major developments in time

Endometriosis

Adenomyosis1921

1927

1960’s

Laparoscopic surgery

1990’s

MRI & TVSHysterectomy


Mijatovic et al, NTOG 2010

Adenomyosis: an infertility factor?

Prevalentie van adenomyose in relatie tot subfertiliteit in

een prospectief cohort patienten met chirurgisch bewezen

onbegrepen sufertiliteit


Imaging studies on adenomyosis in infertile patients with proven

endometriosis versus infertile controls without endometriosis:

Prevalence

79%

Kunz et al, Hum Reprod 2005

27%

Bazot et al, Hum Reprod 2006

27%

Mijatovic et al, Eur J Obstet Gynecol Reprod Biol 2010

Adenomyosis: an infertility factor?

MRI

TVS

Does Adenomyosis have an influence

on spontaneous conception ?

Case-control studie: natuurlijke conceptie bij vrouwen met

en zonder adenomyose bij verder geen andere infertiliteits

factoren


Adenomyosis & spontaneous

conceptionPapio Anubis Study

1986-2002

Population N=3827

Cases: 37

Controls: 37

Barrier et al, Fertil Steril 2004

Two strong associations were found:

1. An association between adenomyosis &

endometriosis, (OR 31, P< 0.001)

2. An association between adenomyosis & life

long infertility, (OR 21, P< 0.001)


Adenomyosis & IVF

Inclusion: 9 observational studies

Publication date: 1999-2012

Total population: N= 1865

Retrospective Cohort Studies: 5 (N=1200)

Prospective Cohort Studies: 4 (N=665)


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Adenomyosis & IVF

Age: 36.0 ± 2.6 yrs

Adenomyosis Prevalence: 21.9 ± 8.8 %

Imaging modality: MRI (2/9) TVS (7/9)

Concomitent Endometriosis: 100% in 2 studies

8-35% in 6 studies

IVF protocols: Long GnRH protocol 2/9 st.

Short protocol 4/9 st.

Unknown 2/9 st.

Antagonist protocol 1/9 st.

Results


Adenomyosis & IVFClinical pregnancy rates

28 % reductie


Adenomyosis & IVFRisk of miscarriage


Adenomyosis & IVF

Additional results

Meta-regression: no association observed between

prevalence of endometriosis & clinical pregnancy

No dose-response effect could be established


Adenomyosis & IVF

Critical appraisal

A meta-analysis of observational studies

with high qualitative & quantitative hetrogenity

Only available evidence to guide us !


5 observationele studies, N= 309, diagnose adenomyose

middes TVE/ MRI (prevalentie 17-20%)

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Doorgaand zwanger na diepe endometriose chirurgie:

Met adenomyose 11,9% (7/59)

Zonder adenomyose 43% (74/172)

68% reductie in doorgaande

zwangerschappen

Geen info over miskramen !


Pathophysiology of adenomyosis-associated

infertility

1. Altered myometrial peristaltic activity ?Kunz et al, Hum Reprod 2005

Kissler et al, Br J Obstet Gynaecol 2006

2. Impaired implantation ?

3. Altered decidualization ?

Campo S et al, RBM on line 2012Martinez-Conjero et al, Fertil Steril 2011

Tremellen et al, Aust NZ J Obstet Gynecol 2011

Quinn et al, J Obstet Gynaecol 2007

Brosens et al, Endocrinology 1999Minici et al, Hum Reprod 2008

Mehasseb et al, fertil steril 2011



infertility

Campo et al, RBM online 2012


infertility3. Imapired implantation by hostile Endometrial

immune environment ?

Immunostain of CD163+ macrophages in

endometrial stroma Tremellen & Russel, J Reprod Imunol 2012



infertility3. Altered Endometrial immune environment by

GnRH agonists

Khan K et al, Hum Reprod 2010

Adenomyosis & IVFLong-term GnRH agonist prior to IVF

Clinical Pregnacy Miscarriage


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Retrospectieve studie (Korea)

N= 241

IVF cycli: 295

Periode: 2006-2012

Diagnose adenomyose: TVE

3 groepen: A. verse ET zonder GnRH agonist (147 c/ 116 vr)

B. verse ET met GnRH agnist (105 c/ 87 vr)

C. cryo ET met GnRH agonist (43 c/ 38 vr)

www.endometriosecentrum.vumc.nl www.endometriosecentrum.vumc.nl


Adverse reproductive outcomes in adenomyosis after deep

endometriosis surgery (68% lower CP rates)

Take home messages

Available information is insufficient for establishing cause-

effect relationship adenomyosis & infertility

Confounding: strong association with endometriosis

Adenomyosis is associated with various

pathophysiological mechanisms. Some are shared with

endometriosis

Long-term GnRH agonist prior to IVF may correct the

adverse outcomes in adenomyosis

In IVF: 28% lower CP rates and 2-fold increase in miscarriages


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PowerPoint Presentation · PDF file29-4-2017 1 Adenomyose: Epidemiologie & impact op fertiliteit 24 april 2017 V. Mijatovic, MD PhD Endometriosis Center VUmc