35 2 Vol.35 No.2 2015 2 Feb. 2015 Reproduction & Contraception doi: 10.7669/j.issn.0253-357X.2015.02.0099 E-mail: randc_journal@163.com (FSH) - Meta FSH ( 400010) : (IVF) (ICSI) (rfsh) (ufsh) (COS) : PubMed EMBASE Cochrane CNKI rfsh 2013.09 rfsh ufsh IVF ICSI RevMan 5.2 IVF ICSI FSH (OHSS) Meta : 21 6 496 rfsh ufsh FSH ; rfsh ufsh : rfsh ufsh COS : (rfsh); (ufsh); (IVF); (ICSI); ; Meta : R711.6 : A : 0253-357X(2015)02-0099-10 : hmg( FSH LH) [ufsh (ufsh-p) (ufsh-hp)] (rfsh) [1] 80 rfsh 90 : rfsh FSH FSH : ; Tel: +86-13983180200; Fax: +86-23-63813374; E-mail: yehongmed@163.com [2] ufsh rfsh FSH Meta rfsh ufsh [3] FSH FSH ; FSH / [4] Meta rfsh(rfshα rfshβ) ufsh (ufsh-p ufsh-hp) (IVF) (ICSI) FSH (OHSS) 99
1 1.1 : PubMed EMBASE Cochrane (CNKI) rfsh 1995 2013.09 FSH (recombinant) (urinary) (gonadotrophin) (purify/purified) PubMed (FSH or Follicle Stimulating Hormone) and (recombinant and Urinary) or (rfsh* and ufsh*) and gonadotrophin 1.2 1.2.1 : rfsh ufsh IVF (RCT); : GnRH ; : FSH ; : OHSS FSH 1.2.2 ; ; 1.3 2 Cochrane RCT : RCT A B C 3 A : ; B : ; C : 1.4 2 ( ) ( / FSH OHSS ) 3 ; FSH 1.5 I 2 P<0.05 (I 2 50%) OHSS (odds ratio OR) ( ) (mean difference MD) ; MD OR 95% (confidence interval CI) P<0.05 RevMan5.2 Meta ( Mantel-Haenszel ) 2 2.1 266 21 ( 1) 2 : ufsh-p ufsh-hp 1 2.2 2.2.1 Corcoran A B 2.2.2 ( 2A 2B) 2.3 Meta 2.3.1 10 [341011141518-21] 10 I 2 =76% P<0.001 100
Identification (n=266) Records identified through database searching (n=0) Additional records identified through other sources Screening (n=213) Records excluded after initial screening of titles and abstracts Eligibility Records screened (n=47) (n=26) Full-text articles excluded with reasons (n=21) Included Studies included in quantitative synthesis (meta-analysis) 1 Figure 1 Flow chart of literature search 1 Table 1 Characteristics of included studies ( ) No. of cycles (n) Reference No. of cases age (year) Total rfsh ufsh Protocol Comparison [3] 1 027 IVF <4 prior OR age 18~39 981 585 396 GnRH-a long rfsh vs ufsh [5] 731 IVF <4 prior OR age 21~37 NR NR NR GnRH-a long rfsh vs ufsh/-hp [6] 280 IVF/ICSI no prior OR age 18~37 NR NR NR GnRH-a long rfsh vs ufsh/-hp [7] 781 IVF/ICSI <4 prior OR age 23~36 2 1 1 GnRH-a long rfsh vs ufsh/-hp [8] 629 IVF/ICSI prior OR NR age 18~39 NR NR NR GnRH-a long rfsh vs ufsh/-hp [9] 100 IVF 3 prior OR age 18~37 NR NR NR GnRH-a long rfsh vs ufsh/-hp [10] 152 IVF <3 prior OR age 18~39 152 76 76 GnRH-a short rfshα vs ufsh/-hp [11] 235 IVF <4 prior OR age 18~38 233 119 114 GnRH-a long rfshα vs ufsh/-hp [12] 241 IVF <4 prior OR age 25~40 254 131 123 GnRH-a short rfshβ vs ufsh/-hp [13] 120 IVF prior OR NR age 18~39 238 118 120 GnRH-a rfshβ vs ufsh/-hp [14] 120 ICSI 120 60 60 GnRH-a long rfshα vs ufsh HP [14] 168 IVF no prior OR age 18~38 155 80 75 GnRH-a long rfshα vs ufsh HP [15] 278 IVF <4 prior OR age 18~38 278 139 139 GnRH-a long rfshα vs ufsh/-hp [16] 169 IVF <3 prior OR age 18~39 165 83 82 GnRH-a long rfshβ vs ufsh/-hp [17] 88 IVF prior OR NR age 18~38 52 22 30 GnRH-a short rfshα rfshβ vs ufsh/-hp [18] 257 IVF prior OR NR age 39 2 1 1 GnRH-a long rfshα vs ufsh/-hp [19] 496 IVF/ICSI <3 prior OR age 18~38 496 247 249 GnRH-a long rfshα vs ufsh/-hp [20] 267 IVF/ICSI no prior OR age 18~38 267 134 133 GnRH-a long rfshα vs ufsh/-hp [21] 99 IVF <4 prior OR age 18~39 99 60 39 GnRH-a long rfshβ vs ufsh [22] 131 IVF prior OR NR age NR 131 70 61 FSH individual rfshβ vs ufsh [23] 127 IVF <4 prior OR age 18~38 123 60 63 GnRH-a long rfsh vs ufsh prior OR: prior oocyte retrieval NR: not reported MD 1.40 95%CI=0.79~2.02(Z=4.46 P< 0.001) 2 : ufsh-p ufsh-hp MD 1.81(95%CI=1.11~2.51) 1.31 (95%CI=0.19~2.43) 3 rfsh ufsh 101
2 (A) (B) Figure 2 Funnel plot of birth rate of each cycle (A) and clinical pregnancy (B) 3 rfsh ufsh Figure 3 Comparison of oocytes retrieved numbers between rfsh and ufsh rfsh 2.3.2 FSH 8 [341113-1621] FSH 8 P<0.001 MD 222.56 95%CI= 383.24 61.88(Z=2.71 P=0.007) 2 : rfsh ufsh-p rfsh ufsh-hp MD 87.02 95%CI= 247.09~ 73.06 419.74 95%CI= 719.31~ 120.18 4 FSH rfsh ufsh-p rfsh FSH 2.3.3 16 [34810-23] 16 I 2 =8.29 P=0.73 OR 0.96 95%CI=0.86~1.08(Z= 0.66 P=0.51) 2 : rfsh ufsh-p rfsh ufsh-hp OR 1.22(95%CI= 0.92~1.60) 1.02(95%CI=0.85~1.22) 5 102
4 rfsh ufsh FSH Figure 4 Comparison of FSH dosage between rfsh and ufsh 5 rfsh ufsh Figure 5 Comparison of birth rate between rfsh and ufsh 103
6 rfsh ufsh Figure 6 Comparison of clinical pregnancy rate between rfsh and ufsh rfsh ufsh-p 2.3.4 16 [48-23] 16 (I 2 =18.53 P=0.73) OR 0.93 95%CI=0.83~1.04(Z=1.35 P= 0.18) rfsh ufsh-p rfsh ufsh-hp OR 1.25(95%CI=0.76~2.06) 1.02 (95%CI=0.83~1.04) 6 rfsh ufsh-p 2.3.5 5 [38111521] 5 I 2 =7.63 P=0.47 OR 1.01 95%CI=0.87~1.17(Z=0.11 P=0.90) rfsh ufsh-p rfsh ufsh- HP OR 1.24(95%CI=0.94~1.63) 0.98(95%CI=0.71~1.36) 7 rfsh ufsh-p 2.3.6 OHSS 10 OHSS [3481113151819-21] 10 I 2 =13.83 P=0.61 OR 1.27 95%CI=0.91~1.79(Z= 1.39 P=0.17) rfsh ufsh-p rfsh ufsh- HP OR 1.24(95%CI=0.94~1.63) 0.98(95%CI=0.71~1.36) 8 OHSS rfsh ufsh-p 104
7 rfsh ufsh Figure 7 Comparison of ongoing pregnancy rate between rfsh and ufsh 8 rfsh ufsh Figure 8 Comparison of OHSS between rfsh and ufsh 105
3 rfsh ufsh 6 496 IVF/ICSI Meta FSH 2 rfsh OHSS rfsh ufsh FSH DNA rfsh ufsh rfsh IVF ( FSH ) [424] rfsh [25] IVF [26] Meta rfsh ufsh 40 IVF [27] : 10% 4% rfsh rfsh ufsh ( 25%~30%) [29] Meta rfsh FSH ufsh rfsh ; Meta rfsh rfsh [28] rfsh rfsh Meta rfsh ufsh Meta [1] Zwart-van Rijkom JE Broekmans FJ Leufkens HG. From HMG through purified urinary FSH preparations to recombinant FSH: a substitution study. Hum Reprod 2002 17 (4):857-65. [2] Lispi M Bassett R Crisci C et al. Comparative assessment of the consistency and quality of a highly purified FSH extracted from human urine (urofollitropin) and a recombinant human FSH (follitropin α). Reprod Biomed Online 2006 13 (2):179-93. [3] Out HJ Mannaerts BM Driessen SG et al. A prospective randomized assessor-blind multicentre study comparing recombinant and urinary follicle stimulating hormone (Puregon versus Metrodin) in in-vitro fertilization. Hum Reprod 1995 10(10):2534-40. [4] Lenton E Soltan A Hewitt J et al. Induction of ovulation in women undergoing assisted reproductive techniques: recombinant human FSH (follitropin alpha) versus highly purified urinary FSH (urofollitropin HP). Hum Reprod 2000 15(5): 1021-7. [5] Andersen AN Devroey P Arce JC. Clinical outcome following stimulation with highly purified hmg or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial. Hum Reprod 2006 21(12):3217-27. [6] Bosch E Vidal C Labarta E et al. Highly purified hmg versus recombinant FSH in ovarian hyperstimulation with GnRH antagonists a randomized study. Hum Reprod 2008 23 (10):2346-51. [7] Diedrich K Devroey P Engels S et al. Efficacy and safety of highly purified menotropin versus recombinant follicle-stimulating hormone in in vitro fertilization/intracytoplasmic sperm injection cycles: a randomized comparative trial. Fertil Steril 2002 78(3):520-8. [8] Dickey RP Thornton M Nichols J et al. Comparison of the efficacy and safety of a highly purified human follicle-stimu- 106
lating hormone (Bravelle) and recombinant follitropin-β for in vitro fertilization: a prospective randomized study. Fertil Steril 2002 77(4):1202-8. [9] Nardo LG Bellanca SA Burrello N et al. Concentrations of insulin-like growth factor (IGF)-I and IGF binding protein-3 in the follicular fluid of women undergoing ovarian hyperstimulation with different gonadotropin preparations. Gynecol Endocrinol 2001 15(6):413-20. [10] Baker VL Fujimoto VY Kettel LM et al. Clinical efficacy of highly purified urinary FSH versus recombinant FSH in volunteers undergoing controlled ovarian stimulation for in vitro fertilization: a randomized multicenter investigator-blind trial. Fertil Steril 2009 91(4):1005-11. [11] Bergh C Howles C Borg K et al. Recombinant human follicle stimulating hormone (r-hfsh; Gonal-F) versus highly purified urinary FSH (Metrodin HP): results of a randomized comparative study in women undergoing assisted reproductive techniques. Hum Reprod 1997 12(10):2133-9. [12] Cheon KW Byun HK Yang KM et al. Efficacy of recombinant human follicle-stimulating hormone in improving oocyte quality in assisted reproductive techniques. J Reprod Med 2004 49(9):733-8. [13] Dickey RP Nichols JE Steinkampf MP et al. Highly purified human-derived follicle-stimulating hormone (Bravelle) has equivalent efficacy to follitropin-beta (Follistim) in infertile women undergoing in vitro fertilization. Reprod Biol Endocrinol 2003 1(1):63. [14] Franco J Baruffi R Coelho J et al. A prospective and randomized study of ovarian stimulation for ICSI with recombinant FSH versus highly purified urinary FSH. Gynecol Endocrinol 2000 14(1):5-10. [15] Frydman R Howles C Truong F. A double-blind randomized study to compare recombinant human follicle stimulating hormone (FSH; Gonal-F) with highly purified urinary FSH (Metrodin-HP) in women undergoing assisted reproductive techniques including intracytoplasmic sperm injection. Hum Reprod 2000 15(3):520-5. [16] Hoomans EH Andersen AN Loft A et al. A prospective randomized clinical trial comparing 150 IU recombinant follicle stimulating hormone (Puregon) and 225 IU highly purified urinary follicle stimulating hormone (Metrodin-HP) in a fixed-dose regimen in women undergoing ovarian stimulation. Hum Reprod 1999 14(10):2442-7. [17] Hugues JN Bstandig B Bry-Gauillard H et al. Comparison of the effectiveness of recombinant and urinary FSH preparations in the achievement of follicular selection in chronic anovulation. Reprod Biomed Online 2001 3(3):195-8. [18] Mohamed MA Sbracia M Pacchiarotti A et al. Urinary follicle-stimulating hormone (FSH) is more effective than recombinant FSH in older women in a controlled randomized study. Fertil Steril 2006 85(5):1398-403. [19] Schats R De Sutter P Bassil S et al. Ovarian stimulation during assisted reproduction treatment: a comparison of recombinant and highly purified urinary human FSH. Hum Reprod 2000 15(8):1691-7. [20] Selman HA De Santo M Sterzik K et al. Effect of highly purified urinary follicle-stimulating hormone on oocyte and embryo quality. Fertil Steril 2002 78(5):1061-7. [21] Hedon B Out H Hugues J et al. Efficacy and safety of recombinant follicle stimulating hormone (Puregon) in infertile women pituitary-suppressed with triptorelin undergoing in-vitro fertilization: a prospective randomized assessorblind multicentre trial. Hum Reprod 1995 10(12):3102-6. [22] Meden-Vrtovec H Mocnik-Roznik S Tomazevic T et al. Recombinant FSH vs. urinary FSH for ovarian stimulation in in vitro fertilization. J Reprod Med 2003 48(10):799-803. [23] Recombinant Human F. Study Group. Clinical assessment of recombinant human follicle-stimulating hormone in stimulating ovarian follicular development before in vitro fertilization. Fertil Steril 1995 63(1):77-86. [24]. (rfsh). 2014 34(1):17-26. [25] Out HJ Mannaerts BM Driessen SG et al. Recombinant follicle stimulating hormone (rfsh; Puregon) in assisted reproduction: more oocytes more pregnancies. Results from five comparative studies. Hum Reprod Update 1996 2(2): 162-71. [26] Al-Inany H Aboulghar M Mansour R et al. Meta-analysis of recombinant versus urinary-derived FSH: an update. Hum Reprod 2003 18(2):305-13. [27] Sunkara SK Rittenberg V Raine-Fenning N et al. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod 2011 26(7):1768-74. [28] Bayram N Van Wely M van Der Veen F. Recombinant FSH versus urinary gonadotrophins or recombinant FSH for ovulation induction in subfertility associated with polycystic ovary syndrome. Cochrane Database Syst Rev 2001 2(2): CD002121. [29].. 2003 12(5):275-8. (2014 9 11 ) 107
Application of recombinant human FSH and urinary FSH in IVF-ET: a Meta analysis Hong YE Guo-ning HUANG (Chongqing Health Center for Women and Children Chongqing 400010) ABSTRACT Objective: To evaluate the role and efficacy in controlled ovarian stimulation (COS) of recombinant FSH (rfsh) and urinary FSH (ufsh) during in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) therapy. Methods: Prospectively randomized controlled studies of the use of rfsh and ufsh in IVF and ICSI treatment were enrolled in this study from PubMed EMBASE Cochrane CNKI and Data Base of Wanfang. After quality assessment and data extraction Meta analysis was conducted under the assessment of odds ratio (OR) and mean difference (MD) by RevMan 5.2 software. Results: A total of 21 randomized controlled trail (RCT) studies were enrolled in this study after excluding poor quality and repeat published studies. The patients were further divided into 3 subgroups according to the types of ufsh. There was a significant difference in oocytes retrieved numbers between the two groups rfsh was more effective [MD=1.40 95%CI=0.79 2.02 (Z=4.46 P<0.000 01)]. There was a significant difference in FSH dosage between the two groups rfsh needed less total dosage of FSH [MD= 222.56 95%CI= 383.24 61.88 (Z=2.71 P=0.007)]. There was no significant difference in the birth rate of cycle clinical pregnancy rate. Conclusions: rfsh is more effective than ufsh in COS during assiting reproduction. Key words: recombinant FSH (rfsh); urinary FSH (ufsh); in vitro fertilization (IVF); intracytoplasmic sperm injection (ICSI); reproduction; Meta analysis &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& 2015.05.08~2015.05.10 ; ; : ; : http://www.cnphars.org/view.asp?ar_id=1085&anclassid=7&nclassid= 108