curs5+6_tradus_engleza

8/17/2019 curs5+6_tradus_engleza

1/53

Fertility preservation

Asist. Univ. Dr. Tulin RalucaEndocrinology/ Embryology Specialist

UMF “Carol Davila” – Embryology department,

Anatomy discipline


2/53

Fertility Preservation

• Storage of gametes (eggs or sperm)

or gonadic tissue (ovarian ortesticular) through medical proceduresfor a period of time in individuals atrisk of sterility at a reproductive age.


3/53

Gametes or gonadic tissue

preservation


4/53

Ice/ Liquid itrogen !"#$%&'(


5/53


Indications)#. Delaying mot*er*ood " social reasons!TR+D,-(

. e0ore initiating radiot*erapy treatments / surgery /

antineoplastic agents 0or autoimmune or ot*erdiseases!1T*erapeutic 2an3ing4( 5 medical reasons

6. e0ore adne7ectomy !R'A"*ig* ris3(

8. Genetic diseases associated 9it* accelerated loss o0

0ertility!:dr. Turner; :dr


6/53


Reasons• >omen !social and medical(

• ?en !social and medical(

•

Prepu2ertal c*ildren and adolescents!medical(


7/53

>*y@

"medical reasons•# " B$. ne9 cases o0 cancer in 9omen !:iegel R #;

U:A(; #C in 9omen at a non"reproductive age!8= yrs(

•

#C o0 total cancer cases is in c*ildren. EC o0 c*ildren 9it*cancer survive

•# in = people survive cancer !latt #$$$(. :urvival rate is

rising.

IF+RTILIT, is one o0 t*e maor issues in survivors


8/53

'ure rate can ac*ieve $C 0or some 0orms o0

cancer

UTFertility rate post cancer #C


9/53


10/53


11/53

80% of children diagnosed with cancer

survive


12/53

varian Reserve


13/53

vogenesis

•

ogenesis 2egins 2e0ore 2irt* ! primary oocytes o0every 9oman are 1older4 t*an t*emselves (

• >omen are 2orn 9it* all t*e primary eggs already

0ormed• ocyte depletion occurs t*roug* apoptosis ! $$ C

undergo apoptosis 2y pu2erty(

•

nly 8 oocytes are ovulated during li0e


14/53

varian Reserve

• >omen are 2orn 9it* a 0inite num2er o0ovarian 0ollicles! Hu3erman; #$=#(

Johnson, illy et al! "##$, "##%! &erm line stem cellsArticle

Nature $"'; #8="#= !## ?arc* 8( doi)#.#6E/nature6#%J Received ## :eptem2er 6J Accepted 6 Decem2er 6 / ovarian

germline stem cells !G:'s(

&ermline stem cells and (ollic)lar rene*al in the postnatal mammalian ovary

Kos*ua Ko*nson#;; Kacqueline 'anning#;; Tomo3o


15/53

>*y@

"social reasons"

• 1iology does not 9ait 0or social or

pro0essional ac*ievement4• Lac3 o0 partner 5 during reproductive stage


16/53

:ocial reasons


• >omen in t*eir 6Os 9it*out a partner


17/53

?edical Reasons

Fertility preservation in 9omen

• eoplastic disease;

prior t*erapy

• Autoimmune disease

2e0ore t*erapy – Lupus eryt*ematous

systemic

– e*cet disease

– Glomerulonep*ritisautoimmune

– '*ron disease

– Ulcerative colitis

Gonado toxicity is almost irreversible


18/53

on neoplastic 1situations4 9it* *ig* ris3 o0

premature ovarian 0ailure


19/53

• Destroys gro9t* 0ollicles

• Destroys primordial 0ollicles

• "nduces follicle atrophy

#. '*emot*erapy


20/53

Primordial follicles⇩⇩⇩

Ovarian reserve⇩⇩⇩

Early Menopa)se + ac)te ovary (ail)re in(ertility


21/53


22/53

APOPTOSI

S

Vascular CORTICAL

FIBROSIS

#. '*emot*erapy

Direct and indirect e00ects

cortex

medulla

(Meirow et al. Hum Reprod 2007)


23/53

• T*e e00ect o0 c*emot*erapy on ovarian 0unction doesnOt

apply 2ased on all or not*ing1 la9

•T*e num2er o0 primordial 0ollicles t*at survive

c*emot*erapy is inversely proportional to dose and age"

dependent.

0

500

000

500

!000

!500

0 !0 50 "500m#$%#

&ose ofC clo )os )amide

N u m * e

r o f P + F , s

-( . 0/000

(Meirow et.al. Hum Reprod 1999)


24/53

# '*emot*erapy su2stances• Al3ylating agents

• 'yclop*osp*amide ; i0os0amide ; c*loram2ucil; melp*alan ;

2usul0an

– T*e greatest ris3 0or ovarian 0ailure !small cell

speci0icity acts in all p*ases o0 t*e cell cycle(

• -ar)ri de platina

– 'isplatin; car2oplatin; o7aliplatin

• medium ris3

•

Antimetabolites. – ?et*otre7ate ; 2leomycin ; = "0luorouracil ; actinomycin ;

vincristine; mercaptopurine ; *ydro7yurea

– Decreased ris3 o0 ovarian 0ailure !active meta2olically

active cells(


25/53

• Normone medication used in 2reast cancer

!tamo7i0en ; ovarian suppressors( does not induce

amenorr*ea / early menopause

/U

• Long term use !9it* contraindication o0

pregnancy during treatment(


26/53

#. '*emot*erapy

• >omen over 8 years " $ C s*o9 amenorr*ea 0ollo9ingcom2ined c*emot*erapy

• ,oung 9omen) C " $C s*o9 amenorr*ea 0ollo9ingcom2ined c*emot*erapy

• All patients e7posed to c*emot*erapy s*o9s lo9 ovarianreserve

• It is estimated t*e pro2a2ility o0 ovarian 0ailure a0terc*emot*erapy as at least = C 2y t*e age o0 6years!Letourneau ; 'ancer ##(


27/53

. Radiot*erapy

• vary is directly a00ected

• A00ects t*e *ypot*alamic 5 pituitary

• A00ects" dependant o0 0ull dose and o0 0ractioned dose

• Dependant on age

• Dependant on t*e irradiated 0ield !pituitary damage leads

to endocrine disorders(

• It can also a00ect t*e 0unction / structure o0 t*e uterus!perinatal complications(


28/53

. Radiot*erapy

•

T*e younger t*ey are; premature 0ailure occurs later !0ora given dose(• :teriliQing dose decreases as t*e patient is older

– 6 Gy 2irt* – #E8 Gy # yrs – #%= Gy yrs – #86 Gy 6 yrs

• Transposition o0 ovary !medial or lateral " 2e*ind t*e

uterus( " irradiation to reduce to ="#=C• It is recommended to postpone mot*er*ood more t*an #

year a0ter t*e end o0 radiot*erapy• !> Namis* >allace; Lancet 2005, International Journal of Radiation

Oncology!iology"#ysics 2005(


29/53

Fertility post c*emo/radiot*erapy

• In *umans; it 9as not demonstrated t*at t*ere is an increased ris3

0or 2irt* de0ects or c*romosomal a2normalities 0or patients 9*o

are cancer survivorsJ i0 conception is occurred a0ter more t*an #

year a0ter stopping t*erapy• $%int#er J& 20'', Genetic (isease in t#e )#ildren of (anis# *urvivors of )#ild#ood and +dolescent

)ancer, Journal of )linical Oncology


30/53

Fertility Preservation Plan

Includes)• PatientOs age; ovarian reserve

• ase disease

• Planned treatment !Radio/'*emo T*erapy(

• Availa2le time !possi2ility o0 postponing treatment(

• Presence/Lac o0 partner !social status(

• eoplastic type !metastasis possi2ility((Holzer Tan 2005)


31/53

?et*ods o0 preserving 0ertility in

9omen

#. +m2ryo cryopreservation

. ocyte cryopreservation6. varian tissue cryopreservation

8. varian transposition !protection(

=. T*e use o0 GnRN agonists !protection(


32/53

ptions" ovarian preservation

#. +m2ryo cryopreservation

• As part o0 IMF procedures ! over 6 years(

• T*e success rate o0 S = C !depending on your age and

t*e time to *arvest oocytes(

• T*e only standardiQed procedure 0or 0ertility preservation

• Post "pu2erty

• Requires partner

• R Donor

-#e first c#ild born

after free.e / t#aembryo 1'34


33/53

T*e 0irst 2irt* a0ter cryopreserved oocytes !slo9 0reeQing ( #$E% "t9ins!'*en et al; Australia(.

UT)

• ocytes are more vulnera2le

• Intracellular ice crystal 0ormation

• Impaired plasma mem2rane ; t*e cytos3eleton and spindle or

• DA#$E%"#$$B = pregnancies

•

#$E%" $

E pregnancies

ptions 5 ovarian preservation

. ocyte cryopreservation

/y "##% 0 cryopreserved oocytes pregnancy rate 0"123 AFE4 "##% 0 5"1% 3


34/53

'ow concentrations ofcryoprotectives'onger eposure Technically easy to perform

Elevated concentrations ofcryoprotectivesShort eposure

revents ice crystal formation


35/53

'ryopreservation o0 oocytes / em2ryosa0ter ovarian stimulation

− Requires a period o0 "% 9ee3s

− Time is not availa2le at times 0or cancer patients

− varian stimulation is associated 9it* increased levels o0estrogen !not 2ene0icial 0or patients 9it* 2reast cancer or

ot*er *ormone" sensitive tumours (− +strogen *as indirect mitogen e00ect !Gupta P %(


36/53


6. varian tissue cryopreservation

#.Transplant o0 ovarian tissue !ort*otropic and *eterotopic( .

Intact ovary transplant 9it* vascular pedicle !e7perimental ;

only in animals( >ang et al Nature J Im*o0 et al %J edai9y et al B

– Tec*nical " di00icult !requires in0usion cryoprotector

– T*eoretically --- Ris3 o0 spreading neoplastic cells


37/53


6. varian tissue cryopreservation

• :uita2le 0or patients pre / post pu2erty• Nundreds or t*ousands o0 primordial 0ollicles can 2e stored• ot involve delays

• >it*out ovarian stimulation• It does not require a partner• T*e only option 0or prepu2escent girls

• Involves t9o surgical procedures ! IMF(• Anaest*etic ris3• T*eoretically "T*e ris3 o0 recurrent neoplastic and

neoplastic cell transplant !especially in *aematologicalcancers (


38/53

="#%

• "##% " First 2a2y !girl( a0ter autologous ovarian cortical tissue in t*e ovary

outstanding 9it* IMF . +LGIU?

• Tissue 0roQen / t*a9ed / autologous a0ter t9o years in one patient o0 E years

!early menopause a0ter c*emot*erapy 0or 6on0 7odg8in lymphoma( . $ mont*s

a0ter t*e ovarian tissue transplantation "9:F )nstim)lated cycle pregnancy!?eiro9 =; Pregnancy a0ter Transplantation o0 'ryopreserved varian Tissue in a Patient 9it*

varian Failure a0ter '*emot*erapy; +ngl K ?ed(

• "#;;0 T*e 0irst 2irt* in Germany a0ter autologous tissue and IMF ovarian cortical

•"#;" " T*e 0irst 2irt* in Italy a0ter autologous ovarian cortical tissue 9it*out IMF! ATURAL (

– Tissue 0roQen / t*a9ed / autologous a0ter seven years in one patient o0 E

years ! early menopause a0ter c*emot*erapy 0or 2one marro9 transplant #

years(. #= mont*s a0ter transplantation o0 ovarian tissue " spontaneous

pregnancy


39/53

• "#;% 5 First 2irt* a0ter ovarian tissue transplant autologous 0roQen in c*ild*ood

!aged #6 " % pieces o0 ovarian tissue ( and t*a9ed in B years " spontaneo)s

pregnancy . +LGIU?

• T*e patient su00ered 0rom sic3le cell anaemia and *ad 2one marro9 transplant at#= years old !premature ovarian 0ailure( "sabelle *emeestere et al& 'ive birth afterautograft of ovarian tissue cryopreserved during childhood& Human Reproduction, -une#$. *O"

• #% " appro7 % pregnancies a0ter

0reeQing / t*a9ing ovarian tissue• conceived naturally J IMF


40/53

Pre"pu2erty 0ertility preservation

• '*ild*ood and adolescence are recogniQed as periods

o0 emotional and psyc*ological insta2ility !topics

related to se7uality and 0ertility are o0 particular

importance(• T*e loss o0 gonadoto7ic oocytes a0ter treatment is

directly related to ovarian reserve

• ,oung patients *ave more oocytes " t*eir loss

appears to 2e less severe t*an in older patients


41/53

Pre"pu2erty 0ertility preservation

• T*e incidence o0 premature ovarian 0ailure in patients

surviving c*ild*ood cancer is %.6 C "# C!a33er; 8(

•

T*e met*od o0 c*oice " cryopreservation o0 ovarian tissue• 6etastases

One ovary as surgically removed from 47 8atients aged '

mont# 1 '4 years9 Ovarian fragments ere cryo8reserved 9

None #ad visible signs of tumor infiltration$"oirot 2007


42/53

ptions" varian protection

#. vary protection) – :*ielding ovary

– varian transposition 2e0ore initiating radiot*erapy

• Reduces radiation to ="#= C• Patients 8 years

• Laparoscopic

• T*e location is c*osen according to t*e irradiated area .

•Does not protects during c*emot*erapy

(Tulandi 200)


43/53


. GnRN agonists " protects t*e gonads duringc*emot*erapy 2y 3eeping t*em in a less active cellcycle; t*ere2y decreasing sensitivity toc*emot*erapy.!lumen0eld B ;Nuser E(


44/53


meta analyses published 0

• GnRNa " are use0ul in ovarian preservation

and reduce post"c*emot*erapy amenorr*ea!'lo9se $; en A*aron #(

• GnRNa " Provides greater c*ance o0 restoring ovarian

cycle !menstruation and ovulation(; 2ut 9it*out

improvements in pregnancy rate !edai9y #(


45/53

Fertility preservation in men

• :ocial reasons@@@


46/53

Impaired 0ertility in men

• '*emot*erapy

– mainly a00ects spermatogenetic

cells

– Less a00ected are Leydig cells

se7ualisation is normal

– testosterone 9it*in t*e normal

range

– Leydig cell damage TD: !no

se7(in0ertility

– 'umulative dose 5 very

important


47/53

Radiot*erapy

• Mery *arm0ul• Testicular direct irradiation or 9*ole 2ody radiation

! prior 2one marro9 transplant or neoplastic in0iltration o0

leu3aemia( aQoospermia

• 'ranial irradiation a00ects *ypot*alamic"pituitary a7is

• Leydig cells are less a00ected !Gy( t*an spermatogenesis

line

– .# Gy 5transitory aQoospermia

– ver % Gy 5 irreversi2le aQoospermia

• Vulnerability of the human Leydig cell to radiation damage is dependent upon age. *#alet *6 ' ,

-satsoulis +, %#ite#ead : , Read G9

http://www.ncbi.nlm.nih.gov/pubmed/?term=Shalet%20SM%5BAuthor%5D&cauthor=true&cauthor_uid=2493061http://www.ncbi.nlm.nih.gov/pubmed/?term=Shalet%20SM%5BAuthor%5D&cauthor=true&cauthor_uid=2493061http://www.ncbi.nlm.nih.gov/pubmed/?term=Shalet%20SM%5BAuthor%5D&cauthor=true&cauthor_uid=2493061http://www.ncbi.nlm.nih.gov/pubmed/?term=Tsatsoulis%20A%5BAuthor%5D&cauthor=true&cauthor_uid=2493061http://www.ncbi.nlm.nih.gov/pubmed/?term=Tsatsoulis%20A%5BAuthor%5D&cauthor=true&cauthor_uid=2493061http://www.ncbi.nlm.nih.gov/pubmed/?term=Whitehead%20E%5BAuthor%5D&cauthor=true&cauthor_uid=2493061http://www.ncbi.nlm.nih.gov/pubmed/?term=Read%20G%5BAuthor%5D&cauthor=true&cauthor_uid=2493061http://www.ncbi.nlm.nih.gov/pubmed/?term=Read%20G%5BAuthor%5D&cauthor=true&cauthor_uid=2493061http://www.ncbi.nlm.nih.gov/pubmed/?term=Whitehead%20E%5BAuthor%5D&cauthor=true&cauthor_uid=2493061http://www.ncbi.nlm.nih.gov/pubmed/?term=Tsatsoulis%20A%5BAuthor%5D&cauthor=true&cauthor_uid=2493061http://www.ncbi.nlm.nih.gov/pubmed/?term=Tsatsoulis%20A%5BAuthor%5D&cauthor=true&cauthor_uid=2493061http://www.ncbi.nlm.nih.gov/pubmed/?term=Shalet%20SM%5BAuthor%5D&cauthor=true&cauthor_uid=2493061http://www.ncbi.nlm.nih.gov/pubmed/?term=Shalet%20SM%5BAuthor%5D&cauthor=true&cauthor_uid=2493061


48/53

Impaired 0ertility in men

• Retroperitoneal surgery !lymp* node

dissection involvesTD: nerve damage and /

or retrograde eaculation or aneaculation(

• one marro9 transplant !9orld9ide =;

cycles / yearJ more t*an *al0 reproductive age(

require c*emot*erapy or radiot*erapy 0or

previously impaired 0ertility/6 o0 patients• Fertility after allogeneic haematopoietic stem cell transplantation in childhood and adolescence.

!orgmann1*taudt +' , Rendtorff R , Reinmut# * , ;o#mann ),


49/53

?et*ods o0 0ertility preservation

#. :perm cryopreservation

– T*e standard met*od

– ot very di00icult tec*nically

– Good results

– Any amount o0 trials

– o matter *o9 long

– :uita2le 0or IMF / I':I ! depending on t*e quality o0 pre0roQen

proo0 eg testicular cancer or lymp*oma a00ects Nod3ig sample

pretreatment (

-#e oldest met#od of cryo8reservation it# t#e best results 9

*tandardi.ed


50/53

?et*ods o0 0ertility preservation

. Testicular tissue cryopreservation

o2tained 2y T+:+ / microT+:+

• Usa2le only in I':I procedures

•

Anaest*etic ris3• Ris3 o0 negative 2iopsy

• ?ore di00icult to 2e accepted 2y

t*e patient

•

T*e only variant pre "pu2ertalex8erimental


51/53


52/53

arriers to 0ertility preservation

• Lac3 o0 in0ormation

• Financial ! *ealt* insurance does not cover

t*ese procedures 2ecause it does not meet t*e

de0inition o0 in0ertility (

• +t*ical and psyc*ological

• Religious


53/53

T*an3 you-

Date post:	06-Jul-2018
Category:	Documents
Upload:	arina-chifulescu
View:	215 times
Download:	0 times

curs5+6_tradus_engleza

Documents