1 (gonadotropin, Gn) -,, : - (IVF-ET); (COH); ; : R711.6 : A : X(2014)

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1 34 10 Vol.34 No Oct Reproduction & Contraception doi: /j.issn X ( ) - : - (IVF-ET); (COH); ; : R711.6 : A : X(2014) %~ 10% - (in vitro fertilizationembryo transfer IVF-ET) (controlled ovarian hyperstimulation COH) IVF-ET (poor ovarian responders s) 10%~20% [1] 2010 (ESHRE) (the Bologna criteria) (poor ovarian response ) [2] 3 2 : ( 40 ) ; ( 3 ) ; [ (AFC)5~7 (AMH) 0.5~1.1 ng/ml] Vollenhoven [3] 9%~26% (No ) (No.12JC ) : ; Tel: ; Fax: ; syun163@163.com (gonadotropin ) COH IVF : (follicle stimulating hormone FSH) 300~450 IU/d ; FSH FSH ; (human menopausal gonadotropin hmg) FSH hmg

2 Wei [4] s 225 IU/d 14 d IVF [4] Chuang [5] s 14 d IVF 2 (gonadotropin releasing hormone agonist RHa) RH FSH (luteal hormone LH) COH RH (flare up) / / COH LH COH s LH Olivennes [6] 0.5 mg/d mg/d IVF flare up IVF LH Wang [7] 0.5 mg/d /2 COH 1/2 Spandorfer [8] 2 1 mg/d mg/d IVF 20.4% 3 3 / 2 >2 3 / 2 IVF ~80 μg/d flare up LH Demirol [9] s 3 40 μg bid Karimzadeh [10] 3 859

3 50 μg bid d 3 hcg flare up Orviet [11] 4 (OHSS) [14] (CC) (LE) [15] [10] Karimzadeh s CC 3 (gonadotropin releasing hormone antagonist RH- A) 1997 COH 2000 IVF RH 2 5~6 hcg 1 14 mm 600 pg/ml LH 10 IU/L hcg 2 LH [12] 1999 IVF [13] 2011 Pu Meta 14 [16] [17] LH RH- A 20% [18] LH Edward IVF-ET 16~18 mm LH hcg 24~36 h IVF OHSS 1999 Bassil [19] %

4 Morgia [20] LH FSH(75~100 IU) LH Elizur [21] COH FSH [22] FSH 21 2~4 mg/d 3 d Frattarelli [23] Shastri [24] (oral contraception OC) IVF 6.2 OC COH OC LH OC 2~5 OC 1 21 d OC FSH FSH [25] IVF Kim [26] OC [27] OC (intracytoplasmic sperm injection ICSI) OC 6.3 FSH -1 (insulinlike growth factors IGF-1) COH 15~21 d 10~12.5 mg/d IVF 1 [28] 2012 Bosdou Meta 163 [29] ~25 3 mg/d 0.25 mg/d 4~7 d LH FSH LH FSH Fanchin [30] Humaidan [31] IVF (growth hormone GH) GH GH 861

5 GH (IGF) IGF GH DNA s GH [32] [33] GH de Ziegler 3 ART GH [34] COH GH COH Kolibianakis 6 RCT Meta [35] GH GH RCT [36] GH s GH GH IVF 7.2 LH - FSH LH LH LH LH FSH LH LH (ceiling) LH LH ceiling COH LH LH LH LH IVF LH Revelli [37] 7 LH [38] FSH>12 U/L AFC 5 35~41 5 LH LH (DHEA) DHEA DHEA DHEA IGF-1 Gleicher 1 [39] DHEA IVF/ICSI DHEA DHEA 2010 Wiser 1 DHEA [40] IVF DHEA hcg DHEA - 9 (growth differentiation factor-9 GDF-9) [4142] 8 (in vitro maturation IVM) COH Cha [43] IVM IVM IVM IVM [44]

6 ICSI IVF IVF 8 IVF COH IVF COH [1] Lamazou F Fuchs F Grynberg M et al. Cancellation of IVF- ET cycles: poor prognosis poor responder or variability of the response to controlled ovarian hyperstimualtion? An analysis of 142 cancellations. J Gynecol Obstet Biol Reprod (Paris) (1):41-7. [2] Ferraretti AP La Marca A Fauser BC. ESHRE consensus on the definition of poor response to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod (7): [3] Vollenhoven B Osianlis T Catt J. Is there an ideal stimulation regimen for IVF for poor responders and does it change with age? J Assist Reprod Genet (11-12): [4] Wei Z Cheng X Li H. Effects of prolonging administration gonadotropin on unexpectedly poor ovarian responders undergoing in vitro fertilization. Reprod Biol Endocrinol :26. [5] Chuang M Zapantis A Taylor M et al. Prolonged gonadotropin stimulation is associated with decreased ART success. J Assist Reprod Genet (12): [6] Olivennes F Righini C Fanchin R et al. A protocol using a low dose of gonadotrophin-releasing hormone agonist might be the best protocol for patients with high follicle-stimulating hormone concentrations on day 3. Hum Reprod (6): [7] Wang PT Lee RK Su JT et al. Cessation of low-dose gonadotropin releasing hormone agonist therapy followed by high-dose gonadotropin stimulation yields a favorable ovarian response in poor responders. J Assist Reprod Genet (1):1-6. [8] Spandorfer S Navarro J Kump LMet al. Co-Flare stimulation in the poor responder patient: predictive value of the flare response. J Assist Reprod Genet (12): [9] Demirol A Gurgan T. Comparison of microdose flare-up and antagonist multiple-dose protocols for poor-responder patients: a randomized study. Fertil Steril (2): [10] Karimzadeh MA et al. Comparison of mild and microdose RH agonist flare protocols on IVF outcome in poor responders. Arch Gynecol Obstet (5): [11] Orvieto R Kruchkovich J Rabinson J et al. Ultrashort gonadotropin-releasing hormone agonist combined with flexible multidose gonadotropin-releasing hormone antagonist for poor responders in in vitro fertilization/embryo transfer programs. Fertil Steril (1): [12] Kolibianakis EM Venetis CA Kalogeropoulou L et al. Fixed versus flexible gonadotropin-releasing hormone antagonist administration in in vitro fertilization: a randomized controlled trial. Fertil Steril (2): [13] Pu D Wu J Liu J. Comparisons of RH antagonist versus RH agonist protocol in poor ovarian responders undergoing IVF. Hum Reprod (10): [14] Mohsen IA El Din RE. Minimal stimulation protocol using letrozole versus microdose flare up RH agonist protocol in women with poor ovarian response undergoing ICSI. Gynecol Endocrinol (2): [15] Davar R Oskouian H Ahmadi S et al. RH antagonist/ letrozole versus microdose RH agonist flare protocol in poor responders undergoing in vitro fertilization. Taiwan J Obstet Gynecol (3): [16] (12): [17]. IVF/ICSI (4): [18] Engel JB Ludwig M Felberbaum R et al. Use of cetrorelix in combination with clomiphene citrate and gonadotrophins: a suitable approach to friendly IVF? Hum Reprod (8): [19] Bassil S Godin PA Donnez J. Outcome of in-vitro fertilization through natural cycles in poor responders. Hum Reprod (5): [20] Morgia F Sbracia M Schimberni M et al. A controlled trial of natural cycle versus microdose gonadotropin-releasing hormone analog flare cycles in poor responders undergoing in vitro fertilization. Fertil Steril (6): [21] Elizur SE Aslan D Shulman A et al. Modified natural cycle using RH antagonist can be an optional treatment in poor responders undergoing IVF. J Assist Reprod Genet (2):

7 [22]. IVF-ET (20): [23] Frattarelli JL Hill MJ McWilliams GD et al. A luteal estradiol protocol for expected poor-responders improves embryo number and quality. Fertil Steril (5): [24] Shastri SM Barbieri E Kligman I et al. Stimulation of the young poor responder: comparison of the luteal estradiol/ gonadotropin-releasing hormone antagonist priming protocol versus oral contraceptive microdose leuprolide. Fertil Steril (2): [25] Keltz MD Gera PS Skorupski J et al. Comparison of FSH flare with and without pretreatment with oral contraceptive pills in poor responders undergoing in vitro fertilization. Fertil Steril (2): [26] Kim CH You RM Kang HJ et al. RH antagonist multiple dose protocol with oral contraceptive pill pretreatment in poor responders undergoing IVF/ICSI. Clin Exp Reprod Med (4): [27] Duvan CI Berker B Turhan NO et al. Oral contraceptive pretreatment does not improve outcome in microdose gonadotrophin-releasing hormone agonist protocol among poor responder intracytoplasmic sperm injection patients. J Assist Reprod Genet (2-3): [28] Fabregues F Penarrubia J Creus M et al. Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized clinical trial. Hum Reprod (2): [29] Bosdou JK Venetis CA Kolibianakis EM et al. The use of androgens or androgen-modulating agents in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis. Hum Reprod Update (2): [30] Fanchin R Castelo Branco A Kadoch IJ et al. Premenstrual administration of gonadotropin-releasing hormone antagonist coordinates early antral follicle sizes and sets up the basis for an innovative concept of controlled ovarian hyperstimulation. Fertil Steril (6): [31] Humaidan P Bungum L Bungum M et al. Reproductive outcome using a RH antagonist (cetrorelix) for luteolysis and follicular synchronization in poor responder IVF/ICSI patients treated with a flexible RH antagonist protocol. Reprod Biomed Online (6): [32] (2): [33] Pereira GR Lorenzo PL Carneiro GF et al. The effect of growth hormone (GH) and insulinlike growth factor I (IGFI) on in vitro maturation of equine oocytes. Zygote: Cambridge University Press 2011:1-8. [34] de Ziegler D Streuli I Meldrum DR et al. The value of growth hormone supplements in ART for poor ovarian responders. Fertil Steril (5): [35] Kolibianakis EM Venetis CA Diedrich K et al. Addition of growth hormone to gonadotrophins in ovarian stimulation of poor responders treated by in-vitro fertilization: a systematic review and meta-analysis. Hum Reprod Update (6): [36] Liu H Bravata DM Olkin I et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med (2): [37] Revelli A Chiado A Guidetti D. Outcome of in vitro fertilization in patients with proven poor ovarian responsiveness after early vs. mid-follicular LH exposure: a prospective randomized controlled study. Assist Reprod Genet (9): [38] Musters AM van Wely M Mastenbroek S et al. The effect of recombinant LH on embryo quality: a randomized controlled trial in women with poor ovarian reserve. Hum Reprod (1): [39] Gleicher N Weghofer A Barad DH. Improvement in diminished ovarian reserve after dehydroepiandrosterone supplementation. Reprod Biomed Online (3): [40] Wiser A Gonen O Ghetler Y et al. Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective study. Hum Reprod (10): [41] (4): [42].. / (6): [43] Cha KY Koo JJ Ko JJ et al. Pregnancy after in vitro fertilization of human follicular oocytes collected from nonstimulated cycles their culture in vitro and their transfer in a donor oocyte program. Fertil Steril (1): [44] Lim KS Chae SJ Choo CW et al. In vitro maturation: clinical applications. Clin Exp Reprod Med (4): ( ) ( 874 refer to p874) 864