Sperm DNA

1. FE
RTILITY PRESE
R
VATION
DR. J. HOLLE
TT
-CAINE
S M.D. FRCSC, G.R.E
.I. (AWC)
ASSOCIATEPROFE
SSOR
DEPT
. OBSTE
TR
ICS AND GYNE
COLOGY
DIVISION OF REPRODUCTIVEENDOCRINOLOGY AND INFERTILITY
WESTE
RN UNIVER
SITY

3. FE
RTILITYTHR
E
ATE
NING THERAPIES
• OVE
R100,000 INDIVIDUALS< 45 YE
AR
SOF AGEAR
EDIAGNOSE
DWITH
CANCERANNUALL
Y IN USA
• ADVANCEMENTS IN CHEMOTHERAPEUTICSHAVELEDTO DRAMATIC
IMPR
OVEMENTSIN SURVIVAL
• REPRODUCTIVERISKSOF CANCERTHERAPIESAND IMPROVED LONG-
TE
R
M SUR
VIVALHAVELE
D TO E
XP
ANDING INTE
R
E
STIN FE
R
TILITY
PR
E
SE
R
VATION FOR CANCERP
ATIE
NTS

4. AMERICAN SOCIE
TYOF
CLINICAL ONCOLOGY
• 2006 – PUBLISHEDRECOMMENDATIONSON FERTILITYPRESERVATION
ST
ATING THAT
• “ ASP
AR
TOF EDUCATION AND INFORMEDCONSENTBEFOR
E
CHEMOTHERAPY,ONCOLOGISTSSHOULDADDRESSTHEPOSSIBILITYOF
INFERTILITYWITHP
ATIENTSTR
E
ATEDDUR
ING THE
IRR
E
PR
ODUCTIVEYEARS
ANDB
EPREPAREDTO DISCUSSPOSSIBLEFERTILITYPRESERVATION
OPTIONS OR R
E
F
E
RP
ATIENTSTO R
E
PR
ODUCTIVESPECIALISTS
.”

5. FE
RTILITY P
R
E
S
ER
VATION S
E
R
VICES
AREUNDERUTILIZED
• IN ORDERT
O E
XP
AND R
E
PR
ODUCTIVEOPTIONSOF P
ATIE
NTS, NE
E
D:
• IMPR
OVED MULTIDISCIPLINARY COLLABORATION BE
TWEE
N
ONCOLOGISTSAND R
E
PR
ODUCTIVESPE
CIALISTS
• WIDESPREADAVAILABILITYOF FERTILITYPRESERVATION SERVICES

6. R
E
QUIRE
MENTSFORA
FE
R
TILITY P
R
E
S
E
R
VATION
PROGRAM
• R
APIDACCE
SS
• INTE
R
DISCIPLINAR
YME
DICALTE
AM
• EXPERIENCEDASSISTEDREPRODUCTIVETECHNOLOGY PROGRAM
• COUNSELORS:MENTALHEALTH,GENETIC, FINANCIAL
• INTE
R
DISCIPLINAR
YCOLLABOR
ATION

7. CURRENTL
YAVAILABLESTRATE
GIE
S-
FEMALE
• EMBR
YO CR
YOPR
ESE
R
VATION
• MATUREOOCYTECR
YOPR
ESE
R
VATION
• OVARIAN TR
ANSPOSITION
• OVARIAN TISSUECR
YOPR
E
SE
R
VATION
• IN VITR
O MATURATION
• GNR
H/LHRHAGONISTS

8. CURRENTL
YAVAILABLESTRATE
GIE
S-
MALE
• E
JACULATE
D SPE
R
M CR
YOPR
E
SE
R
VATION
• E
XTRACTE
D SPE
R
M CR
YOPR
E
SE
R
VATION
• CRYOPRESERVATION OF TESTICULAR TISSUEIN PREPUBERTALBOYS

10. EMBR
YO CR
YOPRESER
VATION
• FOR POST
-PUBE
R
T
AL FE
MALE
S
• HAVEA COMMITTED PARTNEROR WISH TO USEDONOR SPERM
• UNDERGO OVARIAN STIMULATION WITH GONADOTROPINS FORIN
VITR
O FE
R
TILIZATION (+/ - ICSI)
• GOAL OF R
E
TR
IE
VING 8-10 OOCYTE
S
• FR
E
E
ZEE
MBR
YOS – BE
STSUCCESSR
ATEFOR PR
E
GNANCY

11. MATUREOOCYTE CRYOPRESERVATION
• FOR POSTPUBE
R
T
AL FE
MALE
S
• WITHOUT A COMMITTED PARTNEROR WHO DO NOT WISH TO USE
DONOR SPE
R
M
• UNDERGO OVARIAN STIMULATION WITH GONADOTROPINS FORIN
VITR
O FE
R
TILIZATION
• GOAL OF R
E
TR
IE
VING 8-10 OOCYTE
S
• FR
E
E
ZEOOCYTE
S(CUR
R
E
NTSUCCESSR
ATE
S8-20%)

13. J CLIN ONCOL. 2008] JUN 1;26(16):
2630-5.
• AZIM AA1, COSTANTINI-FERRANDOM, OKTAY K.
• GOAL WAS TO DETERMINE THE EFFECTOF CONTROLLED OVARIAN
STIMULATION (COS) USING A COMBINATION OF LETROZOLE WITH
STANDARD FERTILITY MEDICATIONS ON DISEASE-FREE SURVIVAL IN
WOMEN UNDERGOING EMBRYOOR OOCYTE CRYOPRESERVATION
BE
FOREADJUVANTCHE
MOTHER
APY

14. J CLIN ONCOL. 2008] JUN 1;26(16):
2630-5.
• OF 215 WOMEN WITH BR
E
ASTCANCERWER
E
PR
OSPE
CTIVE
L
Y EVALUATEDFORFERTILITYPRESERVATION
BEFOREADJUVANT CHEMOTHERAPY.
• N = 79 E
LE
CTE
D T
O UNDER
GO COS WITH LE
TR
OZOLEAND
GONADOTROPINS FOREMBRYOOR OOCYTE CRYOPRESERVATION.
• N = 136 P
ATIE
NTSUNDER
WENTNO FE
R
TILITY-PR
E
SE
R
VING
PR
OCEDUR
EAND SE
R
VED AS CONTR
OLS.

15. J CLIN ONCOL. 2008] JUN 1;26(16):
2630-5.
• TIMEBE
TWEE
N SUR
GER
YAND CHE
MOTHE
R
APY WASLONGERFOR IVF
P
ATIE
NTS(45.08 VS33.46 DAYS; P< .01).
• PE
AK E
STR
ADIOL LE
VELS: 1,486.76 +/ - 942.13 PMOL/ LIN COS P
ATIE
NTS.
• THEME
DIAN FOLLOW-UPAFTE
RCHE
MOTHE
R
APY WAS23.4 MONTHS
(R
ANGE, 7.5 TO 63.6 MONTHS) IN THECOS GROUPAND33.05 MONTHS
(R
ANGE, 4.5 TO 63.6) IN THECONTR
OL GROUP
.
• THEHAZAR
DR
ATIO FOR R
E
CUR
R
E
NCEAFTE
RIVFWAS0.56 (95% CI, 0.17
TO 1.9), HOWEVE
R
, THESUR
VIVALWASNOTCOMPR
OMISE
D
COMP
ARE
DWITH CONTR
OLS.

16. FE
RTILSTERIL2012 OCT
;98(4):957-60.
• ALMOG B1, AZE
M F
, GORDON D, P
AUZNE
RD, AMITA, BARKAN G,
LE
VIN I.
• EVALUATETHEEFFECTSOF CANCER ON OVARIAN RESPONSEIN
CONTROLLEDOVARIAN HYPERSTIMULATION(COH).
• COMPARED81 CANCERPATIENTSUNDERGOINGCOHCYCLESFOR
FERTILITYPRESERVATIONWITH AGE- AND DATE-MATCHEDCONTROLS
UNDERGOINGCOHFORINVITROFERTILIZATION(IVF)FORMALE
F
ACTOR INFE
R
TILITY
.

17. FE
RTILSTERIL2012 OCT
;98(4):957-60.
• NUMBEROF DOMINANT FOLLICLESAND OOCYTES ASPIRATEDOF THE
STUDYGROUPAND CONTR
OL WER
ECOMP
ARABLE
• 8.8 ± 5.3 VS. 9.7 ± 4.9, AND 11.93 ± 8.3 VS. 12.3 ± 7.9, RESPECTIVELY.
• TOTALDOSEOFGONADOTROPINSUSED(2,250 IU)ANDNUMBEROF
STIMULATION DAYS(9.5) OF THESTUDYGROUP WEREALSO SIMILAR TO
THECONTR
OLS(2,100 IUAND10 DAYS).
• COMPARISONBETWEENFOURSUBGROUPSOFCANCER:BREAST
CANCER, SOFTTISSUESARCOMA, HEMATOLOGIC MALIGNANCIES, AND
GASTR
OINTE
STINALTR
ACTCANCE
R
S
• SHOWEDNO DIFFERENCEIN THEIROVARIANRESPONSEINDEXES.

18. FE
RTILSTERIL2010 FE
B;93(3):865-8.
• QUINTE
R
O R
B1, HELMERA, HUANG JQ, WESTPHALLM.
• EVALUATECONTROLLED OVARIAN HYPERSTIMULATION (COH) IN
WOMEN WITH CANCERCOMPAREDWITH HEALTHY WOMEN
• FIFTYWOMEN UNDERGOING OOCYTE RETRIEVALBEFORECANCER
TR
E
ATMENTAND 50 AGE-MAT
CHE
D CONTR
OLS

19. FE
RTILSTERIL2010 FE
B;93(3):865-8.
• THEREWERENO SIGNIFICANT DIFFERENCES IN
• NUMBE
ROF OOCYTE
SR
E
TR
IEVED(13 VS. 11.5)
• NUMBEROF MATUREDOOCYTESRETRIEVED(9.7 VS. 9.6)
• NUMBEROF OOCYTES FERTILIZED(7.4 VS. 6.8).
HOWEVER, THEPATIENTSWITH CANCERHAD A LONGER DURATION OF
STIMULATION (10.5 VS. 9.0 DAYS)AND HIGHERTOTALDOSEOF
GONADOTR
OPINS (4,174 IUVS. 3,416 IU).

21. OVARIAN TRANSPOSITION
• FORPATIENTSREQUIRING LOCAL PELVIC RADIATION THERAPY
• TRANSPOSE THEOVARIES TO SITESAWAY FROM MAXIMAL RADIATION
EXPOSURE
• MAY PREVENTFUTURETRANSVAGINAL OOCYTE RETRIEVAL IF IVF IS
REQUIRED

23. OVARIAN TISSUECR
YOPRESER
VATION
• STILLCONSIDE
R
E
D E
XPE
R
IME
NT
AL
• THEORE
TICALL
Y COULD PR
E
SE
R
VETHOUSANDSOF OVAR
IAN FOLLICLE
S
ATONE TIME
• E
SPE
CIALLY IMPORT
ANTFOR PR
E
PUBE
R
T
AL GIRLSOR FOR THOSE
WHO CANNOT DELAYCANCERTREATMENTIN ORDERTO UNDERGO
COH AND OOCYTER
E
TR
IE
VAL
• TO DATENO LIVE BIRTHSHAVE BEENREPORTEDIN FEMALESWHO
CR
YOPR
E
SE
R
VED TISSUEBE
FOREPUBE
R
TY

24. OVARIAN TISSUECR
YOPRESER
VATION
• INVOLVESOBT
AINING OVARIAN COR
TICAL TISSUEBY LAP
AROSCOPY
OR LAP
AROT
OMY
• 1) DISSECTTHISTISSUEINTO SMALLFRAGMENTSAND CRYOPRESERVEIT
OR
• 2) WHOLEOVAR
YCR
YOPR
E
SE
R
VATION
• CHALLE
NGE
SOFCR
YOPR
E
SE
R
VING THEE
NTIR
EOVAR
Y

25. OVARIAN TISSUECR
YOPRESER
VATION
• MAY POSSIBL
YR
E
INTR
ODUCECANCE
RCE
LLSTHATR
E
MAIN IN THE
OVAR
IAN ME
DULLAR
Y TISSUE(L
YMPHOMA) ORBLOOD VE
SSE
LS
(LEUKEMIA)
• SYSTEMATICREVIEWOF AUTO TRANSPLANTATION OF OVARIAN TISSUE
FROM289 PATIENTSWITHLEUKEMIA,LYMPHOMA,EWINGSARCOMA,
COLORE
CTAL, BR
E
AST
, GASTR
IC, E
NDOMETR
IALAND CE
R
VICALCANCE
R
• METASTASESWERECOMMON IN PATIENTSWITH LEUKEMIA, LESSCOMMON
IN OTHER CANCERS, AND NOT SEENWITH LYMPHOMA OR BREASTCANCER
PATIENTS

26. SAFE
TY CONCERNS
• GIVEN THEUNCER
T
AINTIE
S R
E
GAR
DING TR
ANSMISSION OF DISE
ASE
,
OVARIANTISSUETRANSPLANTATIONISNOTRECOMMENDEDFOR
P
ATIE
NTSWITH
• BLOOD-BORNECANCER
S
• MALIGNANCIE
S THATMET
AST
ASIZET
O THEOVARY
• AN INHERENTPREDISPOSITIONTO OVARIAN CANCER

27. OVARIAN TISSUE
TRANSPLANTATION AND
OUT
COMES
• AUTOLOGOUSOVARIAN TISSUETR
ANSPLANT
ATION HASBE
E
N
APPLIE
D SUCCESSFULLY
• DEMONSTR
ATER
E
ST
ORATION OF OVARIAN FUNCTION BY
• ENDOGENOUS HORMONEPR
ODUCTION
• ACHIEVEMENT OF PR
EGNANCY
• INVOLVESATT
ACHING VIABL
E CORTICAL OVARIAN TISSUET
O
• PE
L
VIC SITE(ORTHOTOPIC)
• EXTRA-PELVICSITE(HETEROTOPIC) – FOREARM/ABDOMINAL WALL

28. ORTHOTOPICTRANSPLANTATION
OF CORTICAL TISSUE
• ATT
ACH T
O MEDULLAR
Y PORTION OF R
E
MAINING OVARY OR T
O
PE
R
ITONE
UM OF THEOVARIAN FOSSA
• ADVANTAGE: POSSIBILITYOF NATUR
ALCONCE
PTION
• DISADVANTAGE: INVASIVE PROCEDUREAND LIMIT TO # OF FRAGMENTS
THATCAN BETR
ANSPLANTED
• RESUMPTIONOF MENSESOCCURS 4-9 MONTHS AFTER
TRANSPLANTATION
• VARIABILITYIN GRAFTSURVIVAL AND OVARIAN FUNCTION
• SEVERALMONTHSTO 7 YEARS

29. P
R
E
GNANCYOUT
COMEAFTER
ORTHOTOPIC TRANSPLANTATION
• 24 BIR
THSWORLDWIDEAFTE
R10 YEARS
• CONFOUNDER
• MOSTSUR
GERIE
SDID NOTINVOLVETHER
EMOVALOF BOTHOVAR
IE
S
• THUSSITEOF OVULATION NOTCONFIR
MED (NATIVER
EMAINING OVAR
Y
OR THETR
ANSPLANTEDTISSUE)
• PR
EGNANCY COULDHAVEBEENTHER
E
SUL
TOF OVULATION FR
OM THE
NATIVEOVARY AND NOT FROM THETRANSPLANTEDTISSUE

30. HETE
ROTOPICTRANSPLANTATION
OF CORTICAL TISSUE
• REPORTSOF RESTORATIONOF OVARIAN FUNCTION AND FOLLICULAR
DEVELOPMENT
• PR
E
GNANCY CAN ONL
Y BEACHIE
VED THROUGH IVF
• DISADVANTAGE:
• NO LIVEBIR
THSYE
TR
ECORDED
• ADVANTAGE:
• EASIE
RSUR
GER
Y
• EASIERFOLLICULARMONITORING AND RETRIEVAL

31. WHOLEOVAR
YTRANSPLANTATION
• DECRE
ASE
S R
ISK OF TISSUEISCHE
MIA
• DECRE
ASE
S R
ISK OF LIMITE
D SURVIVAL OF THEGRAFT
• NO R
E
PORTOF A SUCCESSFUL TR
ANSPLANT
ATION OF A PR
E
VIOUSL
Y
CR
YOPR
E
SE
R
VED WHOLE OVARY IN HUMANS
• FRESHWHOLE OVARY TRANSPLANTATION BETWEENA LIVE DONOR
T
O A R
E
CIPIE
NTHASBE
E
N SUCCESSFUL IN HUMANS
• ONE STUDY SHOWED A LIVEBIR
TH

32. CR
YOPRES
E
R
VATION OF OVARIAN
TISSUE
• METHODST
O CR
YOPR
E
SE
R
VEOVARIAN TISSUE
• SLOW FR
E
E
ZING
• VITRIFICATION (NO PREGNANCIESRECORDEDWITH THISPROCESSYET)
• OVARIAN TISSUECRYOPRESERVATIONIS STILLCONSIDERED
EXPERIMENTAL

34. IN VITRO MATUR
ATION
• ALTE
R
NATIVET
O TR
ANSPLANT
ATION OF THEHAR
VESTE
D OVARIAN
TISSUE
• MATURATIONIN CULTUREOF IMMATURE OOCYTES
• IMMATURE OOCYTES PROGRESSFROMPROPHASEI STAGE THROUGH
MEIOSISI T
O R
E
ACH MET
APHASEII
• CRYOPRESERVEMATUREOOCYTES OR EMBRYOS

35. IN VITRO MATUR
ATION
• PATIENTSNEED TO B
EAWARE THATIMPLANTATION AND PREGNANCY
R
ATE
SARESIGNIFICANTL
Y LOWERTHAN WITH ST
ANDARD IVF
• PR
EGNANCY R
ATES5.5 – 21%
• STILLCONSIDEREDAN EXPERIMENTAL PROCEDURE

37. GNRH/LHRHAGONISTS
• STILLCONTR
OVER
SIAL
• “THEE
FFICACY OF GNR
H AGONISTSIN R
E
DUCING THER
ISK OF
OVARIANFAILURE,ASSOCIATED WITH THEUSEOF CHEMOTHERAPY,
IN PREMENOPAUSALWOMEN IS STILLCONSIDEREDUNCERTAINAND
ITSUSEISNOTCONSIDEREDASSTANDARDOFCARETOP
RE
S
E
RVE
FERTILITY”
• GYNE: ASR
M, CFAS, E
SHR
E
• ONC: ASCO, E
SMO

38. WHY ISTHE
R
ECONTROVERSY?
• CONFLICTINGRESULTSOFPREVIOUSLYPUBLISHEDTRIALSAND
METHODOLOGY OF PR
E
VIOUS SYSTE
MATIC R
E
VIE
WS WITH MET
A-
ANALYSES
• 2 RECENTMETA-ANALYSES MAY PUTTHIS CONTROVERSY TO RE
S
T

39. LUCIA DELMAESTRO E
TAL,
CANCERT
R
E
ATMENTREVIEWS 2014
JUN; 40(5):675-683
• ITALIAN STUDY R
E
LE
ASE
D 2014
• SYSTEMATICREVIEWANDMETA-ANALYSISOFRANDOMIZEDTRIALS
EVALUATINGTHEEFFICACYOF GNRH AGONISTS GIVEN BEFOREAND
DUR
ING CHE
MOTHER
APY FOR THEPR
E
VENTION OF PR
E
MATURE
OVARIAN FAILURE(POF) IN PREMENOPAUSALWOMEN

40. LUCIA DELMAESTRO E
TAL,
CANCERT
R
E
ATMENTREVIEWS 2014
JUN; 40(5):675-683
• 501 STUDIE
SIDE
NTIFIE
D
• ONL
Y 9 INCLUDE
D
• SE
LE
CTION CRITE
R
IA:
• ENGLISHLANGUAGE
• RANDOMIZEDTRIALDESIGNED TO COMPAREGNRH AGONISTS AND
CHEMOTHERAPYWITH CHEMOTHERAPYALONEIN TERMSOF
• R
E
SUMPTION OFME
NSTR
UALACTIVITYOR
• OCCURRENCEOF POF IN PREMENOPAUSAL CANCERPATIENTS
• ODDS RATIOFORPOF HADTO BEREPORTEDOR COULD BECOMPUTED
FR
OM THEDATA PR
ESENTE
D

41. LUCIA DELMAESTRO E
TAL,
CANCERT
R
E
ATMENTREVIEWS 2014
JUN; 40(5):675-683
• THEEFFECTOF TREATMENTWAS EVALUATEDIN TERMSOF AN ODDS
RATIO(OR)COMPUTEDASTHEODDSOFPOFINTHEGNRHAPLUS
CHEMOARMDIVIDEDBYTHEODDS OF POF IN THESTANDARD
CHE
MO ALONEARM
• ODDS RATIO < 1 FAVOURSTHEGNRH A PLUSCHEMO TREATMENT
ARM

42. LUCIA DELMAESTRO E
TAL,
CANCERT
R
E
ATMENTREVIEWS 2014
JUN; 40(5):675-683
• TYPE
SOF CANCERINCLUDE
D IN THESTUDIE
S
• OVAR
IAN – 1
• BR
EAST– 6
• HODGKIN’S/ NON HODGKIN’SL
YMPHOMA – 2
• DUR
ATION OF FOLLOW UP: 6-36 MONTHS
• MEDIAN AGE
• CHEMO PLUSGNRHA: 21-45 YEARS
• CHEMO ALONE: 22-45 YEARS

43. RESULTS
• OVERALL 225 EVENTS OF POF WERERECORDEDIN 765 PATIENTS
• 89 IN 401 P
ATIENTSTR
EA
TE
D WITHGNRHA (22%)
• 136 IN 364 CONTROLS (37%)
• OVER
ALL POOLED ODDSR
ATIO FOUND A HIGHLY
SIGNIFICANT REDUCTIONIN THERISKOFPOFINPTSRECEIVING
GNRHAIN ADDITION T
O CHE
MO
• OR = 0.43
• 95% CI: 0.22 – 0.84
• P= 0.013

44. RESULTSOF SUBGROUPANAL
YSIS
• SIGNIFICANTINTERACTIONSEENBETWEENTHETREATMENTARMAND
THETYPEOF CANCER(P= 0.028)
• E
FFE
CT OF GNR
H A IN THE3 TUMOURTYPE
SWAS HETE
R
OGENE
OUS
• NO PR
OTE
CTIVEE
FFE
CTOBSE
R
VEDIN L
YMPHOMA P
ATIENTS(2 STUDIE
S)
• OR= 1.02, 95% CI: 0.39 – 2.6
• PR
OTE
CTIVEE
FFE
CTFORBR
EASTCANCE
R(8 STUDIE
S)
• OR= 0.39, 95% CI: 0.19 – 0.84)
• PR
OTE
CTIVEE
FFE
CTFOROVAR
IAN CANCE
R(1 STUDY)
• OR= 0.06, 95% CI: 0.00 – 1.24

45. RESULTSOF SUBGROUPANAL
YSIS
• NO SIGNIFICANT INTERACTION BETWEENTHETREATMENT ARM WAS
SE
E
N WHEN COMP
ARE
• P
ATIENTSAGE(< / 35 AND >35)
• TIMING OF POF ASSE
SSMENT(< / 12 MONTHSAND > 12 MONTHS)

46. M. LAMB
ER
TINI E
TAL,
ANNALSOF ONCOLOGY 2015 DEC;
26(12): 2408 - 2419
• ITALIAN STUDY (2015) META-ANAL
YSISOFR
ANDOMIZE
D CONTR
OLLE
D
TRIALS
• INCLUDEDBR
EASTCANCERP
ATIENTSONL
Y (PR
EMENOP
AUSAL)
• INVE
STIGATEWHE
THE
RTE
MPORAR
YOVAR
IAN SUPPR
E
SSION WITH LHRH
AGONISTDUR
ING CHE
MO, IN PR
E
MENOP
AUSALBR
E
ASTCANCER
P
ATIE
NTS, AFFE
CTS
• R
ATEOF TR
EA
TMENTR
E
LATE
DPOF
• PR
EGNANCYR
ATE
• DISEASEFR
E
ESURVIVAL(DFS)

47. M. LAMB
ER
TINI E
TAL,
ANNALSOF ONCOLOGY 2015 DEC;
26(12): 2408 - 2419
• SE
LE
CTION CRITE
R
IA FOR ARTICLE
S
• R
ANDOMIZEDTR
IALS
• CONDUCTEDINEARLYSTAGEPREMENOPAUSALBREASTCANCER
P
ATIENTSWHO WERECANDIDATE
SFORNEO-ADJUVANT AND/ OR
ADJUVANT CHEMO
• THEODDSR
ATIO (OR) FORPOF AND/ OR PR
EGNANCYHAD TO BE
REPORTEDOR COULD B
ECOMPUTED FROM THEDATAPRESENTEDIN THE
SE
LECTEDSTUDIE
S
• NO LANGUAGE R
E
STR
ICTIONS

48. M. LAMB
ER
TINI E
TAL,
ANNALSOF ONCOLOGY 2015 DEC;
26(12): 2408 - 2419
• 676 STUDIE
SIDE
NTIFIE
D
• ONL
Y 12 P
APE
R
SINCLUDE
D
• 2 STUDIESPATIENTSRECEIVED OTHER FORMSOF ENDOCRINE AGENTS
IN ADDITION TO CHEMO WITH OR WITHOUT CONCURRENTLHRHA
• TAMOXIFE
N OR LHRH ANTAGONIST
• OCCUR
R
E
NCEOF POF WAS DIAGNOSE
D BY E
ITHER
• NO R
E
SUMPTION OF MENSE
SAND/ OR
• MENOP
AUSALLEVELSOF FSHAND E
STR
ADIOL

49. M. LAMB
ER
TINI E
TAL,
ANNALSOF ONCOLOGY 2015 DEC;
26(12): 2408 - 2419
• P
ATIE
NTAGEIN 12 STUDIE
S
• LHRH A PLUSCHEMO: 29 – 45
• CHEMO ALONE: 30 – 46
• TIMING OF ASSE
SSMENTOF POF
• R
ANGE OF 6 – 36 MONTHS

50. M. LAMB
ER
TINI E
TAL,
ANNALSOF ONCOLOGY 2015 DEC;
26(12): 2408 - 2419
• ODDSR
ATIO (OR) FOR PR
E
GNANCYWASCALCULATE
D ASTHEODDSOF
PATIENTSWITH PREGNANCY INTHELHRH AAND CHEMO GROUP
DIVIDE
D BYTHEODDSOF P
ATIE
NTSPR
E
GNANTIN THECONTR
OL GROUP
(CHE
MO ALONE
)
• AN OR > 1 INDICATESTHATTHEUSEOF LHRHA INCREASEDTHEPROBABILITY
OF SUBSEQUENTPR
EGNANCIES
• HAZARD R
ATIO (HR) WAS CALCULATE
D FOR THEE
FFE
CTOF LHRH A
VE
R
SUSCHE
MO ALONEFOR DFS
• AHR< 1 INDICATESTHEUSEOFLHRHAREDUCEDTHEPROBABILITYOF
DEVELOPING DFS

51. RESULTS
• 320 POF E
VE
NTSR
E
CORDE
D IN 1231 P
ATIE
NTS
• 114 OF 616 PATIENTSTREATEDWITH LHRHA DURINGCHEMO(18.5%)
• 206 OF615 P
ATIENTSUNDERGOING CHEMO ALONE(33.5%)
• SIGNIFICANT RISKREDUCTION OF POF IN PATIENTSRECEIVINGLHRHA
DUR
ING CHE
MO
• OR = 0.36
• 95% CI: 0.23 – 0.57
• P, 0.001

52. RESULTS
• THEREWAS SIGNIFICANT HETEROGENEITY BETWEENSTUDIES
• THEESTIMATEDODDS RATIO COMPUTED EXCLUDING EACHSTUDYAT
A TIME
, R
ANGED FR
OM 0.33 T
O 0.41, WITH ALL R
E
SULTSSHOWING
ST
ATISTICAL SIGNIFICANCE

53. AMENOR
R
H
EA (POF)1 YEARAFTE
R
THECOMPLETION OF CHEMO
• 8 STUDIES
• 326 E
VE
NTSR
E
CORDE
D IN 882 P
ATIE
NTS
• 136 OF 439 P
ATIENTSTR
EA
TE
DWITHLHRHA DURING CHEMO(31%)
• 190 OF443 UNDERGOING CHEMO ALONE(42.9%)
• SIGNIFICANT REDUCTION IN THERISKOF AMENORRHEA 1 YEARAFTER
THEE
ND OF CHE
MO WITHUSEOF LHRH A
• OR = 0.55
• 95% CI: 0.41 – 0.75
• P< 0.001

54. P
R
E
GNANCY
• 5 STUDIES
• OF 359 P
ATIE
NTSTR
E
ATE
DWITH LHRH A DUR
ING CHE
MO, 33 WER
E
PR
E
GNANT(9.2%)
• 19 OF 347 WOMEN PREGNANTWHO HAD CHEMO ALONE (5.5%)
• HIGHER CHANCE OF BECOMING PREGNANTIF PATIENTTREATEDWITH
LHR
H A DUR
ING CHE
MO
• OR = 1.83
• 95% CI: 1.02 – 3.28
• P= 0.041

55. DISEAS
EF
R
E
ESURVIVAL(DFS)
• 3 STUDIES
• 1 STUDY (LI E
TAL) - ALLP
ATIENTSHAD HORMONER
ECEPTOR POSITIVE
DISEASE
• POEMS-SWOG SO230 – ALLPATIENTSHAD HORMONE RECEPTOR
NEGATIVEDISEASE
• PROMISE– 80.4% OF PATIENTSHAD HORMONE RECEPTORPOSITIVE
DISEASE
• FOLLOW UPRANGEDFROM35.6 MONTHS TO 7.3 YEARS

56. DFS
• P
ATIE
NTSTR
E
ATE
D WITH LHRH A AND CHE
MO:
• 60 DFSEVENTSIN 307 P
ATIENTS(19.5%)
• P
ATIE
NTSTR
E
ATE
D WITH CHE
MO ONL
Y:
• 60 DFSEVENTSIN 319 P
ATIENTS(18.8%)
• THUSNO DIFFE
R
E
NCE AND USEOF LHRH A DOESNOTWORSE
N DFS
• HAZAR
D R
ATIO (HR
) = 1.00
• 95% CI: 0.49 – 2.04
• P= 0.939

58. SPECIALCLINICALCONSIDE
R
ATIONS -
FE
MALEP
ATIENTS
• BR
E
ASTCANCER
• BR
CA MUTATIONS
• HEMAT
OLOGIC MALIGNANCIE
S
• CHILDR
E
N AND ADOLESCENTS

59. SPECIALCLINICALCONSIDE
R
ATIONS
FE
MALEP
ATIENTS– BREASTCANCER
• POTE
NTIALIMP
ACT OF COH R
E
LATE
D HYPE
R
E
STR
OGENE
MIA
• USECO-ADMINISTR
ATION OF AROMAT
ASEINHIBITORST
O MINIMIZE
CIR
CULATING E
STR
OGEN LE
VELS

60. SPECIALCLINICALCONSIDE
R
ATIONS
FE
MALEP
ATIENTS– BRCAMUTATIONS
• MAY BEOFFEREDBILATERALSALPINGO-OOPHORECTOMY AS A RISK
R
E
DUCTION STR
ATE
GY
• USUALL
Y PE
R
FORMED AFTE
RCHILDBE
AR
ING COMPLE
TE
D
• MAY WISHTO INSTE
AD CR
YOPR
E
SE
R
VEE
MBR
YOS OR OOCYTE
SWITH
PRE-IMPLANTATIONGENETICDIAGNOSIS(PGD)OFBRCAMUTATIONS
PR
IOR TO E
MBR
YO TR
ANSFE
ROR IVM OF HAR
VE
STE
D TISSUEFR
OM BSO

61. SPECIALCLINICAL CONSIDERATIONS
FE
MALEP
ATIENTS: HEMATOLOGIC
CANCERS
• USUALL
Y T
OO ILLATDIAGNOSIST
O BEE
LIGIBL
EFOR A DELAY IN
TREATMENTREQUIREDFORFERTILITYSPARING THERAPY
• ALSO, R
ISK WITH TISSUECR
YOPR
E
SE
R
VATION AND AUTOLOGOUS
TR
ANSPLANT
ATION R
E
SE
E
DING MALIGNANTCELLS
• ABNORMAL HEMATOLOGIC PARAMETERSMAY B
EATRISKFOR
SURGICALCOMPLICATIONS

62. CHILDRENAND ADOLESCENTS
• SEVERALFACTORSIMPAIR FERTILITYPRESERVATION
• LACK OF AVAILABL
EFE
R
TILITY-PR
E
SE
R
VATION PR
OGR
AMSATPEDIATR
IC
HEAL
THCAR
EFACILITIE
S
• LACK OF KNOWLEDGEOF THEVULNERABILITY OF THESEPATIENTSTO
CANCE
RTHE
R
APIE
S
• DISCOMFOR
TIN DISCUSSING R
E
PR
ODUCTIVEHEALTHISSUE
SWITH
THE
SEP
ATIENTSAND THE
IRP
AR
ENTS

63. MALE– EJACULATE
D
SPERM
CRYOPRESERVATION
• SE
MEN COLLE
CTE
D BY MASTURBATION PR
IORT
O ADMINISTR
ATION
OF CHEMO/R
ADIATION THER
APY
• FOR USEIN POSTPUBE
R
T
AL MALE
S
• IDEALLY2 – 3 EJACULATED SAMPLESSHOULD B
EOBTAINED

65. MALE– CR
YOPRES
E
R
VATION
OF SURGICALL
YEXTRACTED
SPERM
• AL
TE
R
NATIVESTR
ATE
GY FOR MALE
SWHO
• CANNOTEJACULATE
• HAVENO VIABLESPE
R
M IN EJACULATE
• HAVESEVEREOLIGOSPE
R
MIA IN EJACULATE
• CAN BEOBTAINEDVIA
• PERCUTANEOUSEPIDYDIMALSPERMASPIRATION(PESA)
• TE
STICULARSPE
R
M EXTR
ACTION (TE
SE)
• TESTICULARSPE
R
M ASPIR
ATION (TESA)
• MICROSURGICALEPIDYDIMALSPE
R
M ASPIR
ATION (MESA)

66. TE
STICULARTISSUECR
YOPRESER
VATION
• IN PR
E
PUBE
R
T
AL BOYS
• INVESTIGATIONAL – GERMINAL EPITHELIAL STEMCELLSISOLATED AND
CRYOPRESERVED
• TO DATEHAS NOT DEMONSTRATED EFFICACY IN HUMANS

67. GNRH AGONISTS
• EXPERIMENTAL
• ADMINISTE
RDUR
ING CHE
MOTHER
APY
• SOME ANIMALSTUDIE
SR
E
VEALED PR
OMISING R
E
SULTS
• T
O DATEHUMAN STUDIE
SHAVE F
AILE
D T
O DEMONSTR
ATEFE
R
TILITY
PRESERVATIONOR MORERAPIDRETURNOF SPERMATOGENESISAFTER
CHEMOTHERAPY

69. SPECIALCLINICALCONSIDE
R
ATIONS -
MALEP
ATIENTS
• TE
STICULAR CANCER
• CHILDR
E
N AND ADOLESCENTS

70. SPECIALCLINICALCONSIDE
R
ATIONS -
MALEP
ATIENTS
• TE
STICULARCANCER
• SOME OF THESEMEN WILL HAVEAZOOSPERMIA OR SEVERELYIMPAIRED
SEMENP
AR
AMETE
R
S
• MAY HAVESPERMEXTRACTION(PESAOR TESE)PRIORTO ORCHIECTOMY
OR ATTIMEOF ORCHIECTOMY (ONCO-TE
SE
)

71. SPECIALCLINICALCONSIDE
R
ATIONS -
MALEP
ATIENTS
• CHILDR
E
N AND ADOLESCENTS
• SEVERALFACTORSHAMPERFERTILITYPRESERVATION:
• LACKOF FERTILITYPRESERVATIONPROGRAMSATPEDIATRICHEALTHCARE
FACILITIES
• LACK OFKNOWLEDGEOFTHEVULNE
R
ABILITYOFTHE
SEINDIVIDUALSTO
CANCE
RTHE
R
APIE
S
• DISCOMFOR
TIN DISCUSSING R
E
PR
ODUCTIVEHE
AL
THISSUE
SWITH THE
SE
P
ATIE
NTSANDTHE
IRP
AR
E
NTS