IOF POI. hypergonadotropic hypogonadism primary ovarian insufficiency POI /premature ovarian failure POF. Van Kasteren. Coulam POI FSH E.

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1 hypergonadotropic hypogonadism primary ovarian insufficiency POI /premature ovarian failure POF Coulam POI Turner Fragile X premutation FSHR NOBOX FOXL etc POI FSH miu/ml AMH AMH AMH FSH / Knauff POI IOF TOF AMH AMH POI POI AMH POI Van Kasteren POI Tartagni POI FSH E E Clomiphene citrate CC Gonadotropins HMG Estrogens E Oral contraceptives E CC E HMG GnRHa GnRHa HMG IVF-ICSI GnRHa HMG E GnRH GnRHa HMG Corticosteroids E Hypophysectomy HMG/E/CC Total

2 POI negative feedback FSH FSH FSH FSH FSH FSH FSH POI EBM POI POI EBM / JISART POI POI XX SD POI P FSH E POI FSHIU/L Epg /ml POI POI POI E FSH E pg/ml E pg/ml ROC pg/ml POI E pg/ml area under curve POI Bidet POI

3 Case Case Case Case Age of POI onset Age of menarche Age at initial visit to our outpatient clinic Pregnancy history G P G G G Serm FSH at initial diagnosis by our hospital Serum E at initial diagnosis by hospital Age at initiation of FM Karyotype XX XX XX XX Other laboratory data none mild leukopenia, SSB-Ab mildly elevated ACA- anti-nuclear Ab and elevated CH Ab TPO-Ab Months of FDCs after initiation of FM Duration of FM months Number of FM cycles FDCs NFDCs Initial serum FSH in FDCs MEAN SD a Initial serum FSH in NFDCs MEAN SD a Initial serum E in FDCs MEAN±SD b c Initial serum E in NFDCs MEAN±SD not tested b c Treatments : FDCs/total FM cyclesfdcs no treatment / / / / estrogen alone / / / / clo iphene alone / / / / hmg alone / / / / GnRHa alone / / / / estrogen+hmg / / / / clomiphene+hmg / / / / GnRHa+hMG / / / / predonisolone / / / / Methods for insemination TSI IUI IVF ICSI A pregnancy achievement cycle Age at achievement of pregnancy Initial serum FSH in the pregnancy achievement cycle day day day day Initial serum E in the pregnancy achievement cycle day day day day Treatment for follicle development none none estrogen therapy estrogen therapy Method for pregnancy TSI day IUI day IUI day IUI day hcg for ovulation Luteal support Pregnancy outcome NSD wk, female NSD wk, female NSD wk, female NSD wk, male g g g g Pregnancy course uneventful uneventful uneventful uneventful a, P b, P c, P Ab, antibody ; ACA, anti-cardiolipin ; FDCs, follicle development cycles ; FM, follicle monitoring ; ICSI, intracytoplasmic sperm injection ; IVF, in vitro fertilization ; IUI, intrauterine insemination ; NFDCs, Non-follicle development cycle ; NSD, normal spontaneous delivery ; TSI, timed sexual intercourse ; SSB, Sjogren syndrome type B antigen ; TPO, Thyroperoxidase

4 Bidetetal.JCEM, unpublished POI FSH mlu/ml or or FSHmlU/mL HRT E and E mm POI POI B E POI FSH FSH E FSH POI White DDX POI Kawamura POI POI Akt Akt POI POI Faddy MJFollicle dynamics during ovarian ageing. MolCellEndocrinol, -. Coulam CB, Adamson SC, Annegers JFIncidence of premature ovarian failure. Obstet Gynecol, -. Nelson LMClinical practice. Primary ovarian insufficiency. N Engl J Med, -. VisserJA,deJongFH,LavenJS,ThemmenAPAnti -Mullerian hormone : a new marker for ovarian function. Reproduction, -. Knauff EA, Eijkemans MJ, Lambalk CB, ten Kate-Booij MJ, Hoek A, et alanti-mullerian hormone, inhibin B, and antral follicle count in young women with ovarian failure. J Clin Endocrinol Metab, -. Bidet M, Bachelot A, Bissauge E, Golmard JL, Gricourt S, et alresumption of ovarian function and pregnancies

5 in patients with premature ovarian failure. J Clin Endocrinol Metab, -., -. van Kasteren YM, Schoemaker JPremature ovarian failure : a systematic review on therapeutic interventions to restore ovarian function and achieve pregnancy. Hum Reprod Update, -. Tartagni M, Cicinelli E, De Pergola G, De Salvia MA, Lavopa C, et aleffects of pretreatment with estrogens on ovarian stimulation with gonadotropins in women with premature ovarian failure : a randomized, placebo-controlled trial. Fertil Steril, -. Ireland JJ, Richards JSAcute effects of estradiol and follicle-stimulating hormone on specific binding of human I iodofollicle-stimulating hormone to rat ovarian granulosa cells in vivo and in vitro. Endocrinology, -. van Kasteren YM, Hoek A, Schoemaker JOvulation induction in premature ovarian failure : a placebo-controlled randomized trial combining pituitary suppression with gonadotropin stimulation. Fertil Steril, -., -. Awwad JT, Ghazeeri GS, Hannoun A, Isaacson K, Abou- Abdallah M, et alan investigational ovarian stimulation protocol increased significantly the psychological burden in women with premature ovarian failure. Acta Obstet Gynecol Scand, -. Silber SJ, Gosden RGOvarian transplantation in a series of monozygotic twins discordant for ovarian failure. N Engl J Med, -. Maruyama T, Miyazaki K, Uchida H, Uchida S, Masuda H, et alachievement of pregnancies in women with primary ovarian insufficiency using close monitoring of follicle development : case reports. Endocr J, -. White YA, Woods DC, Takai Y, Ishihara O, Seki H, et al Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med, -. Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, et alhippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A, -.