A Study of Cooperative Network of Diagnosis and Treatment of Uterine Adenomyosis.
Conditions: Dysmenorrhea, Metrorrhagia, Infertility, Female, Pathology, Ultrasonography, Radiography
Sponsor: Peking Union Medical College Hospital

Cooperative	  Adenomyosis	  Network	   （CAN）	  
Version	  2（June,2017）	  

CONTENTS	  
	  
	  
A.   OBJECT	  
B.   STUDY	  METHOD	  AND	  DESIGN	  
C.   TECHNICAL	  ROUTE	  
D.   STATISTICS	  ANALYSIS	  
E.   QUALITY	  CONTROL	  MEASUREMENT	  AND	  RESULT	  
PUBLICATION	  
F.   SOURCE(S)	  OF	  FUNDING	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  
	  

	  
	  
	  
A.   OBJECT	  
	   	   5000	   women	   diagnosed	   of	   Adenomyosis(AM)	   with	   pathology	   or	   magnetic	  
resonance	  image	  (MRI)	  will	  be	  enrolled	  from	  nationwide	  multicenter.	  Each	  center	  
should	  recruite	  at	  least	  200	  patients.	  
	  
－PATHOLOGY	   :Adenomyosis	   can	   be	   present	   diffusely	   throughout	   the	  
myometrium,	   or	   confined	   to	   a	   discrete	   area.	   Upon	   sectioning	   the	   uterus,	   the	  
myometrial	   wall	   appears	   thickened	   and	   often	   contains	   small	   hemorrhagic	   or	  
chocolate	  colored	  areas	  representing	  islands	  of	  endometrial	  bleeding.	  The	  term	  
cystic	  is	  used	  to	  describe	  either	  diffuse	  adenomyosis	  or	  adenomyomas	  for	  which	  
with	  cysts	  >5	  mm	  in	  diameter.	  
	  
-­‐‑TRANSVAGINAL	  SONOGRAPHY:	  
1.   Uterine	  enlargement—Globular	  uterine	  enlargement	  that	  is	  generally	  up	  to	  12	  
cm	  in	  uterine	  length	  and	  that	  is	  not	  explained	  by	  the	  presence	  of	  leiomyomata	  
is	  a	  characteristic	  finding.	  
2.   Cystic	   anechoic	   spaces	   or	   lakes	   in	   the	   myometrium—The	   cystic	   anechoic	  
spaces	  within	  the	  myometrium	  are	  variable	  in	  size	  and	  can	  occur	  throughout	  
the	   myometrium.	   The	   cystic	   changes	   in	   the	   outer	   myometrium	   may	   on	  
occasion	   represent	   small	   arcuate	   veins	   rather	   than	   adenomyomas.	   The	  
application	  of	  color	  Doppler	  imaging	  at	  low	  velocity	  scales	  may	  help	  in	  this	  
differentiation.	  
3.   Uterine	  
wall	  
thickening—The	  
uterine	  
wall	  
thickening	  
can	  
show	  
anteroposterior	  asymmetry,	  especially	  when	  the	  disease	  is	  focal.	  
4.   Subendometrial	   echogenic	   linear	   striations—Invasion	   of	   the	   endometrial	  
glands	  into	  the	  subendometrial	  tissue	  induces	  a	  hyperplastic	  reaction,	  which	  
appears	  as	  echogenic	  linear	  striations	  fanning	  out	  from	  the	  endometrial	  layer.	  
5.   Heterogeneous	   echo	   texture—There	   is	   a	   lack	   of	   homogeneity	   within	   the	  
myometrium	  with	  evidence	  of	  architectural	  disturbance.	  This	  finding	  has	  been	  
shown	  to	  be	  the	  most	  predictive	  of	  adenomyosis.	  
6.   Obscure	   endometrial/myometrial	   border—Invasion	   of	   the	   myometrium	   by	  
the	   glands	   also	   obscures	   the	   normally	   distinct	   endometrial/myometrial	  
border.	  
7.   Thickening	   of	   the	   transition	   zone—This	   zone	   is	   a	   layer	   that	   appears	   as	   a	  
hypoechoic	  halo	  surrounding	  the	  endometrial	  layer.	  A	  thickness	  of	  12	  mm	  or	  
greater	  has	  been	  shown	  to	  be	  associated	  with	  adenomyosis.	  
	  

－PELVIC	  MRI:	  
1.   Thickening	  of	  the	  junctional	  zone(JZ)	  ≥	  12	  mm	  
2.   Greatest	   JZ	   thickness	   to	   total	   myometrium	   ratio	  >	  40–50%	   (connected	   to	  
muscular	  hypertrophy).	  
3.   Foci	  of	  high	  signal	  intensity	  running	  alongside	  the	  endometrium	  on	  T2	  and	  
sometimes	  also	  T1-­‐‑weighted	  images	  that	  persist	  on	  Fat-­‐‑Sat	  (FS)	  
B.   STUDY	  DESIGN	  AND	  METHOD	  
－STUDY	  DESIGN:	  A	  Prospective	  Multicenter	  Observational	  Cohort	  Study	  
－METHODS:	  
Period:3	   years,	   including	   6	   months	   for	   building	   up	   Network	   platform	   and	  
database, 30	  months	  for	  the	  follow-­‐‑up	  with	  an	  interval	  of	  at	  least	  once	  every	  6	  
months	  done	  for	  every	  patient	  and	  updating	  the	  database	  timely.	  
C.   TECHNICAL	  ROUTE	  
1.   Build	   up	   database	   basing	   on	   the	   Network	   platform. Licensed	   research	  
centers	   recruite	   patients	   according	   to	   the	   consistent	   universal	   diagnostic	  
criteria，and	   then	   extract	   and	   register	   clinical	   pathologic	   data	   from	   their	  
medical	  records	  system	  after	  getting	  their	  informed	  consent	  .Limited	  sharing	  
platform	   for	   the	   database	   entry	   would	   be	   built	   by	   expert	   network	   firms,	  
making	   it	   available	   for	   sub-­‐‑centers	   to	   access	   the	   database	   and	   download	  
relevant	  data. Ultimately, on the premise of research	  results	  sharing，we	  could	  
carry	  out	  clinical	  scientific	  research	  development	  and	  summary	  nationwide.
［Picture	  1.］	  
Clinical	  pathologic	  data:	  
1). Characteristics	   of	   epidemiology	   (Age,	   reproductive	   history，menstrual	  
history，body	  parameters)	  
2). Diagnostic	  criteria	  (pathology,	  transvaginal	  ultrasonography	  or	  magnetic	  
resonance	  image)	  
3) Semeiology	  and	  evaluative	  criteria(vision	  algetic	  standard（VAS）；pictorial	  
blood	  loss	  assessment	  chart(PBAC))	  
4)	  Surgical	  approach	  and	  perioperative	  reproductive	  techniques	  program	  
5) Medical	  treatment	  
6) Reproductive choices and fertility	  outcomes	  
7) Symptom	  improvement，quality	  and	  satisfaction	  of	  Life	  
8) Malignant	  transformation	  
9)	  Menopausal	  symptoms	  and	  Hormone	  therapy	  
10)	  Systematic	  assessment	  of	  the	  side	  effects	   	  

	  
2.  
Based	  on	  the	  database	  imformations, 30-­‐‑month	  follow-­‐‑up	  will	  be	  done	  for	  
every	   patient,	   trying	   to	   analyze	   the	   problems	   below：1）The	   diagnostic	  
strategies	  for	  AM;2) Selection	  of	  therapeutic	  scheme;3) Etiology	  of	  AM	  and	  
endometriosis;4)The	  study	  of	  histology、molecular	  and	  genetics	  about	  AM	  
and	  endometrial	  receptivity.	  
	  
3.  
The	   Follow-­‐‑up	   visits	   is	   standardized,	   and	   the	   contents	   include：1)	   The	  
therapeutic	  
efficacy,	  
complication	  
and	  
side-­‐‑effect	  
of	  
different	  
treatments;2)The	  fertility	  outcomes	  of	  different	  reproductive	  choices;3)	  AM	  
&menopausal	  symptoms	  and	  hormone	  therapy；4)	  Relevant	  issues	  among	  
malignant	  transformation	  of	  AM.	  
	  
4.  
According	   to	   the	   data	   above,	   intensive	   training	   courses	   about	   AM	   will	   be	  
organized	  regularly，finally	  propeling	  the	  formation	  of	  Expert	  Consensus	  and	  
Clinical	  Guidelines	  about	  AM	  which	  suitable	  to	  chinese	  conditions. 	  
	  
	  
D.   STATISTICS	  ANALYSIS	  
	   Categorical	  data	  is	  analyzed	  by	  Chi-­‐‑square	  test,	  and	  continuous	  data	  is	  analyzed	  
by	  T	  test.	  If	  the	  baseline	  characteristics	  are	  similar,	  the	  chi-­‐‑square	  test	  can	  be	  used	  
directly	  to	  compare	  the	  incidence	  rates	  between	  the	  group	  of	  exposure	  and	  the	  
group	  of	  non-­‐‑exposure,	  to	  conclude	  if	  there	  is	  a	  correlation	  between	  the	  exposure	  
factor	   and	   outcome.	   In	   a	   meanwhile,	   calculate	   the	   relative	   risk	   and	   95%	  
confidence	   interval	   in	   order	   to	   further	   illustrate	   the	   degree	   of	   correlation.	   In	  
contrast,	  if	  the	  baseline	  characteristics	  of	  exposure	  group	  and	  non-­‐‑exposure	  group	  
are	   different,	   multiple	   factor	   linear	   regression	   should	   be	   used	   to	   control	   the	  
PI	  unit	  
NP	  and	  database development	  
sub-­‐‑centers 
database	  buildting 
Major	  objective	  :	  diagnostic  
criteria,epidemiology of the 
semeiology	  
Minor	  objective:	  
sub-­‐‑projects 
Super	  control&	  
Full	  access	  
Part	  control	  &	  
access	  
research	  
agreement	  
Data	  access	  
&	  Authorize	  
Picture1.	  Network	  platform(NP)	  and	  database	  Building 

mixing	  factors.	  If	  there	  is	  no	  time	  variation	  in	  the	  data,	  logistic	  linear	  regression	  
can	  be	  used	  to	  adjust	  the	  baseline	  characteristics	  of	  the	  groups	  which	  are	  different	  
in	  the	  model.	  If	  there	  are	  time	  variations	  in	  the	  data,	  Cox	  linear	  regression	  should	  
be	  used	  to	  adjust	  the	  baseline	  characteristics	  of	  the	  groups	  which	  are	  different	  in	  
the	  model.	  
	  
E.   QUALITY	   CONTROL	   MEASUREMENT	   AND	   RESULT	  
PUBLICATION	  
1.   Every	  center	  of	  the	  research	  possesses	  the	  competence	  of	  scientific	  research	  
to	   conduct	   clinical	   studies. Special	   people	   from	   each	   center	   will	   be	   put	   in	  
charge	  of	  the	  research	  and	  monitoring	  the	  whole	  procedure.The	  rights	  and	  
interests，responsibility	  and obligation	  of	  all	  centers	  will	  be	  standardized	  with	  
the	  research	  agreement.	  
2.   The	  maintenance,	  secrecy	  and	  safety	  of	  Network	  platform	  and	  database	  will	  be	  
guaranteed	  by	  Department	  of	  Obsterics	  and	  Gynecology,	  Peking	  Union	  Medical	  
College	  Hospital.	  
3.   Every	  center	  is	  responsible	  for	  the	  database	  building，and	  required	  to	  finish	  
the	  prospective follow	  up	  for	  200	  patients	  at	  least.	  
4.   The	  researchers'	  findings	  will	  be	  released	  in	  a	  paper	  published	  online.	  
	  
F.   SOURCE(S)	  OF	  FUNDING	  
1.  
This study does not charge any fee to any patients. 
2.  
The major cost of the study, a total of 300000 RMB, comes from the special 
financial funds set up by Chinese Medical Doctor Association Division of 
Gynecologic Endocrinology and Chinese Maternal and Child Health Association 
Division of Gynecologic Endocrinology.