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1 33 11 Vol.33 No Nov Reproduction & Contraception doi: /j.issn X IVF-ET ( ) ( ) : (COH) (premature luteinization ) IVF-ET : GnRH-a IVF-ET hcg (P)/ (E2) >1 : P/E ; : P/E2< COH : GnRH-a IVF-ET 2.68% (BMI) E2(bE2) blh bfsh Gn hmg hmg hcg LH (P>0.05) Gn Gn (P<0.05) hcg >15 mm MII (P<0.05) : GnRH-a IVF-ET 2.68% Gn Gn Gn Gn : IVF-ET; (); (COH) : R711.6 : A : X(2013) (premature luteinization ) (controlled ovarian hyperstimulation COH) hcg (P) 13%~71% GnRH-a IVF-ET ( : 2012Y ) : ; Tel: ; ljq88gz@163.com IVF-ET ~ GnRH-a IVF-ET : 20~45 ; ; (artificial insemination with husband sperm AIH) ; IVF- 749

2 ET ; 1.3 mg ; ; (PCOS) (EMs) ; 1.2 COH : 1 ( 19~21 ) ( Ipsen )1.0 mg 2 bfsh blh be2 ( <10 mm <5 mm FSH<5 miu/ml LH< 5 miu/ml E2<50 pg/ml 183 pmol/l) FSH(Gonal-F Merck Serono ) / (hmg ) Gn bfsh E2 2~ 3 18 mm FSH hmg hcg( )4 000~ IU hcg( Merck Serono)250 μg 34~36 h G5 ( Vitrolife) 4~6 h 16~20 h (2PN) 48 h 72 h : 2 3 < 20%; 3 6 <20% ( )40 mg/d ~3 FSH LH E2 P (T) (PRL) hcg 8 00~10 00 LH E 2 P i2000sr 1.4 hcg P/E2 hcg P/E2 1 hcg P/E2<1 P/E2 P(nmol/L) 1 000/E2 (pmol/l) (x s) (%) SPSS 18.0 t χ P< IVF-ET % 15.28%(11/72) 2.03%(22/1 086) (P<0.05) (BMI) E2(bE2) blh bfsh (P>0.05)( 1) 2.2 COH Gn Gn (P<0.05) hcg >15 mm MII (P<0.05) Gn hmg hmg hcg LH (P> 0.05) Schoolcraft [2] IVF IVF : ; [1-46] 750

3 1 (x s %) Table1 Comparison of baseline characteristics Item group non- group P n ( ) Female age (year) ( ) Male age (year) BMI Female BMI (kg/m 2 ) be2 (pmol/l) blh (U/L) bfsh (U/L) Duration of infertility (a) No. of cycles (n) hcg (mm) Endometrial thickness on hcg injection day Fertility rate (%) Pregnancy rate (%) (12/24) (551/1 061) COH (x s %) Table 2 Comparison of COH parameters Parameter group non- group P n Gn Dosage of Gn started (IU) Gn Days of Gn stimulation (d) Gn Amount of Gn used (IU) hmg Total dosage of hmg used (IU) hmg Days of hmg used (d) hcg >15 mm (n) No. of follicles with diameter >15 mm on the hcg injection day hcg LH (U/L) LH level on the hcg injection day MII No. of MII oocytes (n) IVF-ET Ozçakir [6] P GnRH (GnRH-a) Bosch [7] GnRH (GnRH-A)+ rfsh ( hcg P>1.5 ng/ml) COH hcg P 0.8~2 ng/ml( 2.5~6.4 nmol/l) P [8] P/E2 > 1 P [4] P/E2 > 1 13%~71% P/E % hcg 751

4 LH LH [4] GnRH-a 95%~98% LH hcg LH Younis hcg LH hcg LH hcg LH (P>0.05) hcg LH Younis Gn hcg/lh Copperman GnRH-a+hMG IVF hcg [5] hcg hmg hcg/lh hmg hcg/lh rfsh ufsh(lh ) GnRH-a+rFSH [16] hmg hmg [7910] FSH LH FSH P (PR) Papanikolaou [11] IVF hcg PR P ( ) (ER) Bosch [7] GnRH-A+IVF-ET LH FSH Ubaldi GnRHa+rFSH/uFSH IVF-ET [12] P FSH LH FSH Elnashar [13] LH FSH E2 FSH P Gn (P<0.05) FSH P/E2 COH 3 FSH hcg >14 mm [3] LH Lidor [4] >37 hcg >15 mm MII [15] [1516] -9 (GDF-9) 15(BMP15) ( ) GDF-9 (StAR) P450 (P450 scc) P450 [1718] (suppression subtraction hybridization SSH) StAR ACC(acetyl-CoA carboxylase) P450 scc PHLDA1(pleckstrin homology-like domain family A member 1 PHLDA1) [9] GDF-9 [1920] FSH IGF-1 PKA FSH IGF-1 Gn 8~15 hcg P 752

5 [7] hcg FSH/hMG hcg(200 IU/d) FSH/hMG [21] IVF/ICSI : 1 >14 mm; >600 pg/ml; LH >10 IU/L; LH [22] IVF P>1.0 ng/ml [12] hcg: P hcg IVF 40 mg [22] COH Gn Gn Gn Gn Younis JS Matilsky M Radin O et al. Increased progesterone/ estradiol ratio in the late follicular phase could be related to low ovarian reserve in in vitro fertilization-embryo transfer cycles with a long gonadotropin-releasing hormone agonist. Fertil Steril (2): [2] Schoolcraft W Sinton E Schlenker T et al. Lower pregnancy rate with premature luteinization during pituitary suppression with leuprolide acetate. Fertil Steril (3): [3] Ou YC Lan KC Chang SY et al. Increased progesterone/ estradiol ratio on the day of hcg administration adversely affects success of in vitro fertilization-embryo transfer in patients stimulated with gonadotropin-releasing hormone agonist and recombinant follicle-stimulating hormone. J Obstet Gynecol (2): [4] Lidor AL Cohen SB Seidman DS et al. Preferred treatment of infertile women older than 37 years of age who demonstrate premature luteinization in the first evaluation cycle. Fertil Steril (2): [5] Copperman AB Horowitz GM Kaplan P et al. Relationship between circulating human chorionic gonadotropin levels and premature luteinization in cycles of controlled ovarian hyperstimulation. Fertil Steril (6): [6] Ozçakir HT Levi R Tavmergen E et al. Premature luteinization defined as progesterone estradiol ratio >1 on hcg administration day seems to adversely affect clinical outcome in long gonadotropin-releasing hormone agonist cycles. J Obstet Gynaecol Res (2): [7] Bosch E Valencia I Escudero E et al. Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome. Fertil Steril (6): [8] Younis JS Simon A Laufer N. Endometrial preparation: lessons from oocyte donation. Fertil Steril (6): [9] Filicori M Cognigni GE Pocognoli P et al. Modulation of folliculogenesis and steroidogenesis in women by graded menotrophin administration. Hum Reprod (8): [10] Long X Peng C Lu G. Isolation and identification of genes differentially expressed in premature luteinization granulosa cell during controlled ovarian hyperstimulation. Fertil Steril (5): [11] Papanikolaou EG Bourgain C Kolibianakis E et al. Steroid receptor expression in late follicular phase endometrium in GnRH antagonist IVF cycles is already altered indicating initiation of early luteal phase transformation in the absence of secretory changes. Hum Reprod (6): [12] Ubaldi F Camus M Smitz J et al. Premature luteinization in in vitro fertilization cycles using gonadotropin-releasing hormone agonist (GnRH-a) and recombinant follicle-stimulating hormone (FSH) and GnRH-a and urinary FSH. Fertil Steril (2): [13] Elnashar AM. Progesterone rise on the day of hcg administration (premature luteinization) in IVF: an overdue update. J Assist Reprod Genet (4): [14] Hussein MR. Apoptosis in the ovary: molecular mechanisms. Hum Reprod Update (2): [15] Chand L Ponnampalam P Harris E et al. Mutational analysis of BMP15 and GDF9 as candidate genes for premature ovarian failure. Fertil Steril (4): [16] Di Pasquale E Rossetti R Marozzi A et al. Identification of new variants of human BMP15 gene in a large cohort of women with premature ovarian failure. J Clin Endocrinol Metab (5): [17] Yamamoto N Christenson LK McAllister JM et al. Growth differentiation factor-9 inhibits 3'5'-adenosine monophosphate-stimulated steroidogenesis in human granulosa and theca cells. J Clin Endocrinol Metab (6): [18] Spicer LJ Aad PY Allen DT et al. Growth differentiation factor-9 (GDF9) stimulates proliferation and inhibits steroidogenesis by bovine theca cells: influence of follicle size on responses to GDF9. Biol Reprod (2):

6 [19] Richards JS. New signalling pathways for hormones and cyclic adenosine 3-5-monophosphate action in endocrine cells. Mol Endocrinol (2): [20] Richards JS Rusell DL Ochsner S et al. Novel signalling pathways that control ovarian follicular development ovulation and luteinization. Recent Prog Horm Res : [21] Filicori M Cognigni GE Gamberini E et al. Efficacy of lowdose human chorionic gonadotropin alone to complete controlled ovarian stimulation. Fertil Steril (2): [22] Escudero EL Boerrigter PJ Bennink HJ et al. Mifepristone is an effective oral alternative for the prevention of premature luteinizing hormone surges and/or premature luteinization in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. J Clin Endocrinol Metab (4): ( ) Potential Causes of Premature Luteinization during the Treatment of in vitro Fertilization-embryo Transfer (IVF-ET) Xiao-qiao GUO 1 Xiao-fang SUN 2 Sha-sha SI 1 Zi-xin MAI 1 Ming LEI 1 Jia-wei LING 1 Jian-qiao LIU 1 (1. Department of Reproductive Medicine Center the Third Affiliated Hospital of Guangzhou Medical University Guangzhou ) (2. Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institues the Third Affiliated Hospital of Guangzhou Medical University Guangzhou ) ABSTRACT Objective: To investigate how to avoid premature luteinization () during controlled ovarian hyperstimulation (COH) and improve pregnancy rate. Methods: A total of cycles who had undergone IVF-ET for infertility treatment were enrolled into the respective study. group consisted of the patients with of which P/E2 ratio on human chorionic gonadotropin (hcg) administration day was 1 (n=63) and non- group consisted of the patients whose P/E2 ratio was <1 (n=2 292). The differences between the two groups in clinical parameters were compared. Results: The incidence rate of was 2.68%. The differences had no statistical significance between the two groups in the female age male age woman s body mass index (BMI) the basic levels of E2 LH FSH the duration of infertility treatment cycles initial dasages of gonadotropin (Gn) total dosages of hmg used duration of hmg stimulation serum LH level on the day of hcg injection (P>0.05). But the total dosages of Gn used and duration of Gn used in group were significantly higher than those in non- group (P<0.05). The number of follicles with the diameter>15 mm on the hcg injection day and the number of MII egg in group were less than those in non- group (P<0.05). Conclusion: The total dosages of Gn used the duration of Gn used poor ovarian response may be relate to the. To reduce the incidence of we had better decrease the total dosages of Gn used and the dosage of Gn started. Key words: IVF-ET; premature luteinization (); controlled ovarian hyperstimulation (COH) 754