Management of fertility preservation in young patients with Turner syndrome
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1 Maagemet of fertility preservatio i youg patiets with Turer sydrome Clémece Berjoeau 1, Aurélie Rives 1, Géraldie Jolly-Hélas 2, Ariae Cuy 3, Mireille Castaet 3, Maria Letailleur 4, Agès Liard 5, Clavier Brigitte 4, Frace Verhaeghe 1,Nathalie Rives 1 1 EA 4308 «Gamétogeèse et Qualité du Gamète», IRIB, Laboratoire de Biologie de la Reproductio-CECOS, ART ceter, CHU de Roue Normadie, Uiversité de Roue 2 Laboratoire de Cytogéétique, CHU de Roue Normadie 3 Service de pédiatrie, CHU de Roue Normadie 4 ART ceter, CHU de Roue Normadie 5 Chirurgie ifatile, CHU de Roue Normadie Clémece Berjoeau, MD Professor Nathalie Rives, MD, phd Roue Uiversity Hospital, Roue, Frace Maagemet of fertility preservatio i youg patiets with Turer sydrome Nothig to declare 1
2 Turer sydrome diagosis 1/2500 / 1/3000 female ewbors 10-20% spotaeous abortio <1% of 45,X viable Mostly preatal diagosis or childhood (~12 years) ~ 50% before 12 years Short stature / Ovaria isufficiecy (puberty retardatio) [Stocholm al., Trovo de Marqui et al., Silvia D Ippolito et al., Cule et al., Gravholt et al., 2017] Puberty / Fertility Spotaeous puberty ~40-50% (mosaic form +++) [Hadott, 2011] Spotaeous mearche 10% [Hov atta, Welt, Hadott, Hewitt, 2013] 45,X/46,XX Xp distal deletio (>Xp11. 1, Xp21.1, Xp ) 45,X Xq deletio Xq (Xq13.2, Xq26, Xq27) Chromosome X rig Y chromosome material Premature ovaria failure 29.3 years (TS mosaic) [Reidalo RH, 1996] 1.8 to 7.6 % of spotaeous pregacy [Hov atta, Hadott, Chak htoura, Hewitt et al., 2013] Birth rate 3 à 40% Age at pregacy [22;24] years [Reyaud, Lachla, Kamma, Kavoussi, Purushothama, Mercier et al., Berard et al;, 2016] 2
3 Natural history of TS ovary developmet From preatal life to puberty Decreased umber of oogoia Accelerated degeeratio of primordial follicles ~ 18 Weeks Follicular loss depedig o chromosome abormality 45,X Chromosome X rig Xp21 / Xp11.1 Xq26 / Xq28 [Weiss, Pasquio et al., Hreisso et al., Reyaud et al., Kammou et al., Kavoussi et al., Borgström et al., Lachla et al., Mercer et al., 2013 ] Natural history of TS ovary developmet From preatal life to puberty Decreased umber of oogoia Accelerated degeeratio of primordial follicles ~ 18 Weeks Follicular loss depedig o chromosome abormality 45,X Chromosome X rig Xp21 / Xp11.1 Xq26 / Xq28 [Weiss, Pasquio et al., Hreisso et al., Reyaud et al., Kammou et al., Kavoussi et al., Borgström et al., Lachla et al., Mercer et al., 2013 ] Fertility preservatio? 3
4 Ovaria tissue Mature oocyte Before or afterpuberty? After puberty? I vitro maturatio? Retrospective cohort study Roue Uiversity Hospital Parets & pre-pubertal girls (>2 years / 10 years / 11 years / 12 years / 13 years ) * FSH, LH, Estradiol, AMH, Ihibi B * Ovaria ultra-soud examiatio * Iformatio o future fertility * Alterative procedures to mother Paediatricia edocriologist Geeral follow-up / puberty sigs Parets & pubertal adolescets ** Absece of mestrual cycles *FSH, LH, Estradiol, AMH, Ihibi B *Ovaria ultra-soud examiatio ** Presece of mestrual cycles *FSH, LH, E/T, AMH, Ihibi B o day 3 *Atral follicle cout o day 3 * Iformatio o future fertility * Alterative procedures to mother * Psychologist * If mestrual cycles, mature oocyte cryopreservatio 4
5 Chromosome abormalities q 25 patiets [3;27] yrs Media : 12±5 yrs q Chromosome abormalities Fertility progosis 45,X (3) 46,X,i(X)(q) (2) 45,X/46,X i(x)(q) (2) 45,X/46,X r(x ) (1) 45,X/46,X i(y) (2) 45,X/46,XX,del(X)(p) (1) 46, XX,del(X)(q) (1) 45,X/46,X,+marY (1) 13/25 (52%) 45,X/46,XX (9) 45,X/47,XXX (1) 45,X/46,XX /47,XXX (1) 46,XX,del(X)(p) (1) 12/25 (48%) Cliical features Cotext of diagosis Preatal diagosis 10 (40%) Growth retardatio 12 (48%) No pubertal developmet 1 POF/ Growth retardatio 2 Malformatios Heart 5 Kidey 6 Learig disorder 10 (40%) Psychosocial problem (Emotioal immaturatio) 25 5
6 Puberty Pre-pubertal 52% (13/25 4/25) Spotaeous 48% (10/21) [11;15] yrs Spotaeous mearche 48% (10/21) [11;15] yrs POF 44% (11/25) Fertility preservatio Authors/Patiets Stimulatio Karyotype Age of spotaeous mearche Cotexte of diagosis FSH D3 (IU/l) AMH D3 (IU/l) AFC Age stimulatio (years) Protocol Froze oocytes matures Froze ovaria tissue Histological aalysis (follicles/mm 2) P1 1 45,X/46,XX 12 Preatal diagosis atagoist 14 2 atagoist 11 LO 80 P7 1 45,X/46,XX 15 Short stature atagoist 6 P ,X/46,XX 13 Short sature agoist 2 LO P ,XX,delXp 15 Preatal diagosis atagoist 5 P ,X/46,XX 13 Short stature atagoist 12 P ,XX/47,XXX 15 Short stature atagoist 3 2 atagoist 4 Mature oocyte freezig 6 patiets with at least oe oocyte bakig cycle 2 patiets awaitig fertility preservatio [45,X ; 45,X/47,XXX] 2 patiet refusals [parets, «fear» of the patiet] 6
7 Fertility preservatio Authors/Patiets Stimulatio Karyotype Age of spotaeous mearche Cotexte of diagosis FSH D3 (IU/l) AMH D3 (IU/l) AFC Age stimulatio (years) Protocol Froze oocytes matures Froze ovaria tissue Histological aalysis (follicles/mm 2) P1 1 45,X/46,XX 12 Preatal diagosis atagoist 14 2 atagoist 11 LO 80 P7 1 45,X/46,XX 15 Short stature atagoist 6 P ,X/46,XX 13 Short sature agoist 2 LO P ,XX,delXp 15 Preatal diagosis atagoist 5 P ,X/46,XX 13 Short stature atagoist 12 P ,XX/47,XXX 15 Short stature atagoist 3 2 atagoist 4 Ovaria tissue bakig 2 patiets i additio to oocyte bakig 1 patiet with POF (10 yrs) 3 patiets with bilateral goadectomy (Y chromosome material) 1 with goadoblastoma (3 yrs) Parets poit of view Preset [ 23/25 ; 2 patiets > 25 yrs] Complete agreemet with the procedure (21/23) The sydrome was too preset They feeled guilty ad were ot completely objective No questio o future sexuality of their daughter Experimetal ature of the procedure 7
8 Patiets poit of view 24 patiets (>3 yrs) Future fertility was a high priority for 20/24 patiets 5 patiets did ot have ay kowledge about TS ad fertility 4 patiets expressed some hesitatios about fertility preservatio with two refusals Absolute ecessity to discuss the possibility of POF Absolute ecessity to discuss alterative procedure to mother (adoptio oocyte doatio livig without childre) 12 patiets did ot have ay kowledge o oocyte doatio 3 patiets talked spotaeously about oocyte doatio 4 patiets talked spotaeously about adoptio We impose the ecessity of parethood to childre? Iformed coset? 8
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