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Damage Female infertility & Premature ovarian failure0`ZZZZ %Proven Fertility Preservation OptionsC Conservative surgery Oophoropexy Embryo Cryopreservation for IVFF" " -"  -  +Experimental Fertility Preservation OptionsO Ovarian suppression Oocytes cryopreservation Ovarian tissue cryopreservation.O " O$Ovarian tissue harvestingYBENEFITS: No delay Pre-pubertal Any stage menstrual cycle Store large number of gametes @ <P GRISKS/PROBLEMS: Surgical procedure In vitro maturation not yet possible4880Experimental use of cryopreserved ovarian tissue11(*Allografting  3 live births to date (Demeestere 2006, Meirow 2005, Donnez 2004) Xenogenic transplantation In-vitro culture of ovarian follicles% " . "  "  "  " & " %.  &"Ovarian harvesting -ConsiderationsPractical Consent issues Cost issues Increased risk cancer in offspring? Risk of reintroducing malignancy Related health issues e.g. cardiac toxicityB ZZsZ s  In summaryNot all girls/women become infertile Fertility preservation options limited particularly in the young Ovarian tissue cryopreservation  provides exciting experimental techniques for young women  ReferencesAmerican Society of Clinical Oncology Recommendations on Fertility Preservation in cancer patients, S.J. Lee et al. Journal of Clinical Oncolgy, 2006. Ovarian tissue banking for cancer patients: is ovarian cortex cryopreservation presently justified?, Ariel Revel & Joseph Shenker. Human Reproduction, Vol 19, No. 1, pages 14-19, 2004 Ovarian function and spontaneous pregnancy after combined heterotopic and orthotopic cryopreserved ovarian tissue transplantation in a patient previously treated with bone marrow transplantation: Case report, I. Demeestere et al. Human Reproduction, April 3, 2006. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy, Meirow et al. New England Journal of Medicine 353,318-321, 2005. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue, Donnez et al. Lancet 364, 1405-1410, 2004. nPm / . 0` r77f3/Ʊ` fff` KfxP` 7_/U<ff` HghXs3q̙` WXcklugti~^ӤO` ־3f3f` 33^` J%xiff3>?" dd@,?nFd@  d nF@ d`nF n?" dd@   @@``PP   @ ` ` p>> P(  6 T ~  "~  c B@CW DEF"d@ W @W @W W @`".~  c B,CW DEF"d@ W ,W ,@`". \ ~  "~  c B CDEF"@   @`"(4  c B C DEF"d@ @`"(W4  c BtC DEF"d@t t tt@`"~   c B CDEF"@ @`"([4W   c B CDEF"d@ @`"(4   c B CDEF"2@  @`"(4[   c BC DEF"d@ @`"_   c BC DEF"@ @`"  c BC DEF"@  @`"\  BxH{ ?"0F { T Click to edit Master title style! !$  0dK{ "0 { RClick to edit Master text styles Second level Third level Fourth level Fifth level!     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S 0 6  O  v X*  0 6    v Z* H 0 0whg ? 3380___PPT10. } (0  f(  r  S 3v v r  S vp v |  S ,A leedsf i( J0   S fA >lthtLeeds Teaching Hospitals Trustv )  J0H  0޽h ? 33___PPT10i.mOk+D=' = @B + '0 0 0(   x  c $e0F   x  c $Hf0  H  0޽h ? 33___PPT10u..m }+D=' = @B + '0 8@(  8x 8 c ${0F    8 S T  "p`PpH 8 0޽h ? 33___PPT10u..1}#\+D=' = @B + '0 DF(  Dx D c $p-0F    D c $Xev0  "p`PpH D 0޽h ? 33___PPT10u..3}F+D=' = @B + '0 P(  x  c $p{0F  { x  c $${  { r  S 8{m  { H  0޽h ? 33___PPT10u..m-~+D=' = @B +  '0 p (  x  c ${dF  {   c $[m0< { "p`PpX   C 0Awhitemouse c H  0޽h ? 33___PPT10u..m~+D=' = @B +E '0 PH`(  x  c $0F   x  c $     c $(   < H  0޽h ? 33___PPT10u..m`^~+D=' = @B + '0  0(   x  c $v0F  v x  c $tv< v H  0޽h ? 33___PPT10u..mpԼ~+D=' = @B +* '0 $*(  $x $ c $0F   r $ S 7`  H $ 0޽h ? 3380___PPT10.m/~L0   4\ (  4^ 4 S 0po   v  4 c $I0e .1  v R  EVER INCREASING SURVIVAL RATES - A GREATER EMPHASIS ON EVALUATING LONG TERM EFFECTS OF TREATMENT. RISKS OF CHEMOTHERAPY + RADIOTHERAPY SHOULD BE EXPLAINED TO EACH PATIENTS AT THE TIME OF TREATMENT INCLUDING THE IMPACT ON FUTURE FERTILITY. EFFECTS OF TREATMENT ON FERTILITY can be DETERMINED BY size & location of radiation field, dosage radiation dosage chemotherapy method of administration (iv/oral) type of disease age of the patient PATIENT SEX FEMALES = DISADVANTAGED  UNLIKE MALES, WOMEN HAVE A FIXED GAMETE POOL BIRTH - 2 million primordial follicles DECLINES TO around 1000 AT MENOPAUSE. (Ref Lancet oncology 2005, H Wallace). ALKYLATING AGENTS, RADIOTHERAPY,DAMAGE TO THE UTERUS/OVARIES FROM SURGERY, DAMAGE TO THE HYPOTHATLAM-PITIUTARY AXIS NOT ALL TREATMENT LAEADS TO INFERTILITY  AROUND 20% OF PATIENTS BECOME INFERTILE AFTER TREATMENT. Current research shows that patients do consider infertility to be important when considering appropriate treatment. Surveys of cancer survivors have shown an increased risk of emotional distress in those who become infertile secondary to treatment for their cancer. There is also some evidence that patients may chose a less effective treatment at providing cure to avoid some long term complications. (Ref ASCO Recommendations on Fertility Preservation, May 2006) psychological impact of infertility + physical impact on general health in POF due to loss of protective hormonal function on bone metabolism and cardiovascular disease. x*PPPPXPPd H 4 0whg ? 3380___PPT10. } oV R 0 <b(  <^ < S 0po    < c $l0e .1  rj___PPT9LD PROVEN FERTILITY PRESERVATION OPTIONS AVAILABLE FOR GIRLS AND YOUNG WOMEN ARE LIMITED AT PRESENT THERE ARE THE 3 MAIN PROVEN METHODS LISTED HERE: CONSERVATIVE SURGERY includes TRACHELECTOMY = surgical removal of the cervix in cases of cervical cancer whilst preserving the uterus. ONLY POSSIBLE IN EARLY STAGES OF THE CANCER (the literature shows no evidence of increased relapse). OOPHOROPEXY is the SURGICAL REPOSITIONING OF THE OVARIES AWAY FORM A RADIATION FEILD. IT IS NOT WITHOUT COMPLICATION AND HAS ONLY A 50% SUCCESS RATE IN MAINTAINING FERTILITY can be problems with altered ovarian blood flow, scattered irradiation and ovarian migration after the procedure. Patients may need repositioning of the ovaries after treatment or IVF to achieve conception EMBRYO CRYOPRESERVATION FOR LATER IMPLANATATION This is the most established technique for fertility preservation in women (Ref ASOC). POSSIBLE IF: SEXUALLY MATURE, HAS A LIFE PARTNER WILLING TO PARTICIPATE In a teenager or young woman this is not a common circumstance. INVOLVES A DELAY IN STARTING CANCER TREATMENT TO ALLOW FOR OVARIAN STIMULATION AT THE START OF A NEW MENSTRUAL CYCLE TO PRODUCE OOCYTES FOR HARVESTING ( 2 to 6 weeks). Such a delay may not be possible or desirable. There is additionally the requirement for an outpatient surgical procedure for harvest the oocytes. Religious beliefs may limit this as a viable option due to the possibility of future destruction of unused embryos. .PC" P" PXPP1" PYP;PPD ' 1   > xH < 0whg ? 3380___PPT10.2}Pe 0 ^VL(  L^ L S 0po   P L c $<0e .1    OVARIAN SUPRESSION IS A CONTROVERSIAL TECHNIQUE SOME STUDIES SHOW A BENEFIT, OTHERS SHOW NONE  THE JURY IS STILL OUT IT IS ACHIEVED BY ADMINISTERING A Gonadotrophin releasing hormone (GnRH) AGONIST OR ANTAGONIST DURING TREATMETN TO EFFECTIVELY SWITCH OFF THE OVARIES AND REDUCE THE TOXIC DAMAGE TO THEM.. TRIALS are ONGOING at present in AMERICA AND GERMANY patients with BREAST CANCER & HODGKIN S LYMPHOMA aiming to further determine what benefits there are to the use of GnRH analogues in preserving fertility. The use of this technique is recommended only in a clinical trial setting (Ref ASCO). Interestingly there are some observational studies which show that the OCP may have some benefit in preservation of ovarian function. OOCYTE CRYOPRESERVATION is an alternative to those patients who have UDERGONE PUBERTY and are unable or not willing to undertake embryo cryopreservation. This still REQUIRES OVARIAN STIMULATION and TO PROVIDE OOCYTES FOR HARVESTING = SAME 2 to 4 WEEK DELAY in starting treatment needed The consideration of short term exposure to high hormonal levels also apply E.G. BREAST CANCER. Current research shows that UNFERTILISED OOCYTES are MORE PRONE TO DAMAGE FROM CRYOPRESERVATION than embryos (Ref ASCO). Therefore the PREGNANCY RATE = LOWER from this technique with only a 2% success rate per frozen oocyte cycle. So far there have been around 120 DELIVERIES FROM THIS TECHNIQUE WORLD WIDE. With improving cryopreservation success rates should improve as time goes on. FINALLY THERE IS THE VERY EXCITING AREA OF OVARIAN TISSUE CRYOPRESERVATION. This technique involves the removal of ovarian tissue laparoscopically under GA (takes about 1 hour) and its cryopreservation for use at a later. >PPPPP H L 0whg ? 3380___PPT10.;}@)  0 T L P(  P^ P S 0po   F P c $0e .1   vMANY CONSIDERATIONS when considering undertaking ovarian tissue harvesting for cryopreservation. SOME ALREADY MENTIONED Not to forget  ethical/moral Consent issues - Discussion at a time of great stress and worry are inevitably difficult child/parent relationship experimental treatment  uncertain benefits, no guarantees of success. risks of procedure What to do with the tissue if the patient dies unknown = the likelihood of negative health impact on progeny from IVF using cryo-preserved tissue stored for long periods of time  e.g. in a child of 10 who may not want children for 20 years or so. LIKELIHOOD OF ADEQUATE FUTURE HEALTH TO SUSTAIN A PREGNANCY E.G. cardiotoxic chemotherapy MOST IMPORTANTLY = RE-INTORDUCTION OF THE MALIGNANCY MUST BE AVOIDED. In patients with ovarian cancer/blood bourne malignancy ALLOGRAFTING IS NOT A VIABLE OPTION (currently the only proven experimental method of cryopreserved ovarian tissue use in humansH& H P 0whg ? 3380___PPT10.>}x]kE0  TU(  T^ T S 0po    T c $0e .1   K7There are many benefits to this technique when compared with oocyte or embryo cryopreservation including the absence of the need for ovarian stimulation, that it can be done in those who are pre-pubertal and that a large number of gametes are stored. However the use of the stored tissue is still experimental.H T 0whg ? 3380___PPT10.?}~ 0 0X(  X^ X S 0po   ~ X c $쇹0e .1   RE-IMPLANTATION OF OVARIAN TISSUE OR ALLOGRAFTING  Technique has been USED FOR LESS THATN A DECADE  the FIRST REPORT OF TRANSPLANTATION was PUBLISHED in 2000. Ovarian tissue can be RE-IMPLANTED ORTHOTOPICALLY to the PELVIS or HETEROTOPICALLY to areas such as the foream/lower abdomen. This TISSUE can THEN be STIMULATED to PRODUCE OOCYTES for HARVESTING and SUBSEQUENT IVF. 2 REPORTS OF LIVE BIRTHS following ORTHOTOPIC TRANSPLANTATION of ovarian tissue IN HUMANS (2004 and 2005). ONE child was CONCIEVED NATURALLY and the OTHER FROM IVF. However these case reports have been subject to some doubt as both patients had transplantation to the old ovary site and it is thought possible that resumption of the original ovary function may have been the reason from pregnancy. There has additionally been ONE FURTHER CASE REPORT in the literature in APRIL 2006 of a live birth following COMBINED HETEROTOPIC AND ORTHOTOPIC cryopreserved ovarian tissue re-implantation. The difficulties  more than 25% of the tissue s follicles die after re-implantation due to inadequate vascularisation/blood supply. Therefore in an adult usually a whole ovary is taken to allow for the best chance of success of this technique. However, this will reduce the likelihood of pregnancy and adequate ovarian function resuming naturally after treatment ends. This is AN AREA which is STILL IN NEED of FURTHER DEVELOPMENT and study. Another POSSIBLE TECHNIQUE  BUT ILLEGAL IN HUMANS, is the transplantation of human ovarian tissue on to an animal (mouse) i.e. XENOGENIC TRANSPLANTATION. This tissue is again subject to hormonal stimulation allowing oocyte production for harvesting and IVF. Currently this is a technique which has only been successful producing pregnancy in animals (mouse, 2002, Snow et al.) FOR THE FUTURE: The IDEAL SITUATION would be to USE FROZEN-THAWED OVARIAN CORTEX to PRODUCE MATURE OOCYTES FROM IMMATURE GERM CELLS in the laboratory. THESE ARE NUMEROUS IN THE HARVESTED CORTEX. Oocyte in-vitro maturation is currently only possible in mature follicles which are in the latest stages of development as has been done in patients with PCOS (Cha, Chain 1998) in fresh ovarian tissue. The use of cryopreserved tissue will have a lower capacity for oocyte maturation. Primordial follicles are more numerous in ovarian cortex than those in the late stages of development. To develop these into mature oocytes would allow a greater chance of pregnancy from IVF using cryopreserved ovarian tissue. In-vitro development of primordial follicles is extremely difficult especially in the human. Pregnancy from in-vitro maturation of primordial follicles has been achieved in animals (mouse, Eppig & O Brien, 1996), but as yet has not been possible in humans. XPPP+Q*( ,#/ // #  $"W0H X 0whg ? 3380___PPT10.@}c0 0((  X  C 0po   (  S y0e .1   IN SUMMARY  I WOULD LIKE TO OFFER THE CONSIDERATIONS UP FOR DEBATE AND QUESTIONING AND TO ASK - Should we be offering ovarian harvesting to all girls & young women at diagnosis as part of a multi-center clinical trial? Considerations  Moral/ethical Consent Practical = cost (240 per year for storage) removal of tissue|H  0whg ? 3380___PPT10. O0 kc@ (   X   C 0po   c   S `0e .1   THANK YOU FOR GIVING ME THIS OPPORTUNITY SPEAK TO YOU TODAY I AM TO PROVIDE YOU WITH A SHORT OVERVIEW OF CURRENT FERTILITY PRESERVATION OPTIONS available to YOUNG WOMEN. I will focus on the exiting area of ovarian tissue harvesting.H   0whg ? 3380___PPT10.^Drd 2ORZ a ^md gI?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~Root EntrydO)Pictures ;Current UserSummaryInformation(UPowerPoint Document(HDocumentSummaryInformation8