控制性促排卵中特殊人群添加重组人黄体生成素的临床应用
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摘要
成功的辅助生殖结局与适宜的卵巢刺激紧密相关。FSH和LH在卵泡发生和激素合成过程中扮演协同作用。LH是E2生成、卵泡最适发育、排卵和黄素化的必须因素。多数学者认为1.2U/L≤LH≤5.0U/L是卵泡发育和卵母细胞成熟的治疗窗。控制性促排卵(COH)中低LH是否需要添加重组人黄体生成素(r-hLH)一直广受争议。本文就COH中可能通过添加r-hLH获益的特殊人群及添加的剂量和时机进行综述。
Successful assisted reproductive outcome is closely related to appropriate ovarian stimulation.FSH and LH play a synergistic role in folliculogenesis and steroidogenesis.LH is critical for E2 synthesis,optimal follicle development,ovulation and luteinization.It is well accepted that 1.2 U/L≤LH≤5.0 U/L is the therapeutic window for follicular development and oocyte maturation.Recombinant human luteinizing hormone(r-hLH)supplementation in low LH patients in controlled ovarian hyperstimulation(COH)remains controversial.Here we aim to review the subgroup population to whom and when exogenous luteinizing hormone supplementation in controlled ovarian stimulation is needed.
Successful assisted reproductive outcome is closely related to appropriate ovarian stimulation.FSH and LH play a synergistic role in folliculogenesis and steroidogenesis.LH is critical for E2 synthesis,optimal follicle development,ovulation and luteinization.It is well accepted that 1.2 U/L≤LH≤5.0 U/L is the therapeutic window for follicular development and oocyte maturation.Recombinant human luteinizing hormone(r-hLH)supplementation in low LH patients in controlled ovarian hyperstimulation(COH)remains controversial.Here we aim to review the subgroup population to whom and when exogenous luteinizing hormone supplementation in controlled ovarian stimulation is needed.
引文
[1] Balasch J,Fabregues F.Is luteinizing hormone needed for optimal ovulation induction?[J].Curr Opin Obstet Gynecol,2002,14:265-274.
[2] Shoham Z.The clinical therapeutic window for luteinizing hormone in controlled ovarian stimulation[J].Fertil Steril,2002,77:1170-1177.
[3] Alviggi C,Conforti A,Esteves SC,et al.Recombinant luteinizing hormone supplementation in assisted reproductive technology:a systematic review[J].Fertil Steril,2018,109:644-664.
[4] Maher JY,Segars J.When is recombinant luteinizing hormone supplementation beneficial during ovarian stimulation?[J].Fertil Steril,2018,109:611-612.
[5] Younis JS,Laufer N.Recombinant luteinizing hormone supplementation to recombinant follicle stimulating hormone therapy in gonadotropin releasing hormone analogue cycles:what is the evidence?[J].Curr Med Res Opin,2018,34:881-886.
[6] Ferraretti AP,Gianaroli L,Magli MC,et al.Exogenous luteinizing hormone in controlled ovarian hyperstimulation for assisted reproduction techniques[J].Fertil Steril,2004,82:1521-1526.
[7] De Placido G,Alviggi C,Perino A,et al.Recombinant human LH supplementation versus recombinant human FSH(rFSH)step-up protocol during controlled ovarian stimulation in normogonadotrophic women with initial inadequate ovarian response to rFSH.A multicentre,prospective,randomized controlled trial[J].Hum Reprod,2005,20:390-396.
[8] Ruvolo G,Bosco L,Pane A,et al.Lower apoptosis rate in human cumulus cells after administration of recombinant luteinizing hormone to women undergoing ovarian stimulation for in vitro fertilization procedures[J].Fertil Steril,2007,87:542-546.
[9]中华医学会生殖医学分会.辅助生殖促排卵药物治疗专家共识[J].生殖与避孕,2015,35:211-223.
[10] De Placido G,Alviggi C,Mollo A,et al.Effects of recombinant LH(rLH)supplementation during controlled ovarian hyperstimulation(COH)in normogonadotrophic women with an initial inadequate response to recombinant FSH(rFSH)after pituitary downregulation[J].Clin Endocrinol(Oxf),2004,60:637-643.
[11] Yazici Yilmaz F,Gorkemli H,Colakoglu MC,et al.The evaluation of recombinant LH supplementation in patients with suboptimal response to recombinant FSH undergoing IVF treatment with GnRH agonist down-regulation[J].Gynecol Endocrinol,2015,31:141-144.
[12] Lisi F,Rinaldi L,Fishel S,et al.Use of recombinant LH in a group of unselected IVF patients[J/OL].Reprod Biomed Online,2002,5:104-108.
[13] Alviggi C,Clarizia R,Pettersson K,et al.Suboptimal response to GnRHa long protocol is associated with a common LH polymorphism[J/OL].Reprod Biomed Online,2009,18:9-14.
[14] Alviggi C,Conforti A,Santi D,et al.Clinical relevance of genetic variants of gonadotrophins and their receptors in controlled ovarian stimulation:a systematic review and metaanalysis[J].Hum Reprod Update,2018,24:599-614.
[15] G AR,Cheemakurthi R,Prathigudupu K,et al.Role of Lh polymorphisms and r-hLh supplementation in GnRh agonist treated ART cycles:A cross sectional study[J].Eur J Obstet Gynecol Reprod Biol,2018,222:119-125.
[16]田莉峰,伍琼芳,谭俊,等.早卵泡期长方案血清LH低的患者添加r-LH的临床结局分析[J].生殖医学杂志,2018,27:310-315.
[17] Pezzuto A,Ferrari B,Coppola F,et al.LH supplementation in down-regulated women undergoing assisted reproduction with baseline low serum LH levels[J].Gynecol Endocrinol,2010,26:118-124.
[18] Lahoud R,Ryan J,Illingworth P,et al.Recombinant LH supplementation in patients with a relative reduction in LH levels during IVF/ICSI cycles:A prospective randomized controlled trial[J].Eur J Obstet Gynecol Reprod Biol,2017,210:300-305.
[19] Konig TE,van der Houwen LE,Overbeek A,et al.Recombinant LH supplementation to a standard GnRH antagonist protocol in women of 35years or older undergoing IVF/ICSI:a randomized controlled multicentre study[J].Hum Reprod,2013,28:2804-2812.
[20] Raju GA,Chavan R,Deenadayal M,et al.Luteinizing hormone and follicle stimulating hormone synergy:A review of role in controlled ovarian hyper-stimulation[J].J Hum Reprod Sci,2013,6:227-234.
[21] Bosch E,Labarta E,Crespo J,et al.Impact of luteinizing hormone administration on gonadotropin-releasing hormone antagonist cycles:an age-adjusted analysis[J].Fertil Steril,2011,95:1031-1036.
[22] Matorras R,Prieto B,Exposito A,et al.Mid-follicular LH supplementation in women aged 35-39years undergoing ICSI cycles:a randomized controlled study[J].Reprod Biomed Online,2009,19:879-887.
[23]邓宇,尹敏娜,梁佩玲,等.长方案添加黄体生成素对体外受精-胚胎移植结局的影响[J].南方医科大学学报,2017,37:1501-1505.
[24] Younis JS,Izhaki I,Ben-Ami M.The effect of LH supplementation to the GnRH antagonist protocol in advanced reproductive ageing women:aprospective randomized controlled study[J].Clin Endocrinol(Oxf),2016,84:99-106.
[25] He W,Lin H,Lu J,et al.The impact of luteinizing hormone supplementation in gonadotropin-releasing hormone antagonist cycles:a retrospective cohort study[J].Gynecol Endocrinol,2018,34:513-517.
[26] Lehert P,Kolibianakis EM,Venetis CA,et al.Recombinant humanfollicle-stimulatinghormone(r-hFSH)plus recombinant luteinizing hormone versus r-hFSH alone for ovarian stimulation during assisted reproductive technology:systematic review and meta-analysis[J].Reprod Biol Endocrinol,2014,12:17.
[27]农璎琦,刘文娟,黄倩文,等.拮抗剂方案中卵泡期促黄体生成素水平对不同卵巢反应者体外受精-胚胎移植结局的影响[J].中华生殖与避孕杂志,2018,38:192-199.
[28] Gizzo S,Andrisani A,Noventa M,et al.Recombinant LH supplementation during IVF cycles with a GnRH-antagonist in estimated poor responders:A cross-matched pilot investigation of the optimal daily dose and timing[J].Mol Med Rep,2015,12:4219-4229.
[29] Humaidan P,Chin W,Rogoff D,et al.Efficacy and safety of follitropin alfa/lutropin alfa in ART:a randomized controlled trial in poor ovarian responders[J].Hum Reprod,2017,32:544-555.
[30] Caserta D,Lisi F,Marci R,et al.Does supplementation with recombinant luteinizing hormone prevent ovarian hyperstimulation syndrome in down regulated patients undergoing recombinant follicle stimulating hormone multiple follicular stimulation for IVF/ET and reduces cancellation rate for high risk of hyperstimulation?[J].Gynecol Endocrinol,2011,27:862-866.
[31]李元,龚斐.重组人黄体生成素能改善改良超长方案多囊卵巢综合征患者IVF/ICSI妊娠结局[J].生殖医学杂志,2015,24:21-25.
[32] Santi D,Casarini L,Alviggi C,et al.Efficacy of folliclestimulating hormone(FSH)alone,FSH+luteinizing hormone,human menopausal gonadotropin or FSH+human chorionic gonadotropin on assisted reproductive technology outcomes in the"personalized"medicine era:a Meta-analysis[J].Front Endocrinol(Lausanne),2017,8:114.
[2] Shoham Z.The clinical therapeutic window for luteinizing hormone in controlled ovarian stimulation[J].Fertil Steril,2002,77:1170-1177.
[3] Alviggi C,Conforti A,Esteves SC,et al.Recombinant luteinizing hormone supplementation in assisted reproductive technology:a systematic review[J].Fertil Steril,2018,109:644-664.
[4] Maher JY,Segars J.When is recombinant luteinizing hormone supplementation beneficial during ovarian stimulation?[J].Fertil Steril,2018,109:611-612.
[5] Younis JS,Laufer N.Recombinant luteinizing hormone supplementation to recombinant follicle stimulating hormone therapy in gonadotropin releasing hormone analogue cycles:what is the evidence?[J].Curr Med Res Opin,2018,34:881-886.
[6] Ferraretti AP,Gianaroli L,Magli MC,et al.Exogenous luteinizing hormone in controlled ovarian hyperstimulation for assisted reproduction techniques[J].Fertil Steril,2004,82:1521-1526.
[7] De Placido G,Alviggi C,Perino A,et al.Recombinant human LH supplementation versus recombinant human FSH(rFSH)step-up protocol during controlled ovarian stimulation in normogonadotrophic women with initial inadequate ovarian response to rFSH.A multicentre,prospective,randomized controlled trial[J].Hum Reprod,2005,20:390-396.
[8] Ruvolo G,Bosco L,Pane A,et al.Lower apoptosis rate in human cumulus cells after administration of recombinant luteinizing hormone to women undergoing ovarian stimulation for in vitro fertilization procedures[J].Fertil Steril,2007,87:542-546.
[9]中华医学会生殖医学分会.辅助生殖促排卵药物治疗专家共识[J].生殖与避孕,2015,35:211-223.
[10] De Placido G,Alviggi C,Mollo A,et al.Effects of recombinant LH(rLH)supplementation during controlled ovarian hyperstimulation(COH)in normogonadotrophic women with an initial inadequate response to recombinant FSH(rFSH)after pituitary downregulation[J].Clin Endocrinol(Oxf),2004,60:637-643.
[11] Yazici Yilmaz F,Gorkemli H,Colakoglu MC,et al.The evaluation of recombinant LH supplementation in patients with suboptimal response to recombinant FSH undergoing IVF treatment with GnRH agonist down-regulation[J].Gynecol Endocrinol,2015,31:141-144.
[12] Lisi F,Rinaldi L,Fishel S,et al.Use of recombinant LH in a group of unselected IVF patients[J/OL].Reprod Biomed Online,2002,5:104-108.
[13] Alviggi C,Clarizia R,Pettersson K,et al.Suboptimal response to GnRHa long protocol is associated with a common LH polymorphism[J/OL].Reprod Biomed Online,2009,18:9-14.
[14] Alviggi C,Conforti A,Santi D,et al.Clinical relevance of genetic variants of gonadotrophins and their receptors in controlled ovarian stimulation:a systematic review and metaanalysis[J].Hum Reprod Update,2018,24:599-614.
[15] G AR,Cheemakurthi R,Prathigudupu K,et al.Role of Lh polymorphisms and r-hLh supplementation in GnRh agonist treated ART cycles:A cross sectional study[J].Eur J Obstet Gynecol Reprod Biol,2018,222:119-125.
[16]田莉峰,伍琼芳,谭俊,等.早卵泡期长方案血清LH低的患者添加r-LH的临床结局分析[J].生殖医学杂志,2018,27:310-315.
[17] Pezzuto A,Ferrari B,Coppola F,et al.LH supplementation in down-regulated women undergoing assisted reproduction with baseline low serum LH levels[J].Gynecol Endocrinol,2010,26:118-124.
[18] Lahoud R,Ryan J,Illingworth P,et al.Recombinant LH supplementation in patients with a relative reduction in LH levels during IVF/ICSI cycles:A prospective randomized controlled trial[J].Eur J Obstet Gynecol Reprod Biol,2017,210:300-305.
[19] Konig TE,van der Houwen LE,Overbeek A,et al.Recombinant LH supplementation to a standard GnRH antagonist protocol in women of 35years or older undergoing IVF/ICSI:a randomized controlled multicentre study[J].Hum Reprod,2013,28:2804-2812.
[20] Raju GA,Chavan R,Deenadayal M,et al.Luteinizing hormone and follicle stimulating hormone synergy:A review of role in controlled ovarian hyper-stimulation[J].J Hum Reprod Sci,2013,6:227-234.
[21] Bosch E,Labarta E,Crespo J,et al.Impact of luteinizing hormone administration on gonadotropin-releasing hormone antagonist cycles:an age-adjusted analysis[J].Fertil Steril,2011,95:1031-1036.
[22] Matorras R,Prieto B,Exposito A,et al.Mid-follicular LH supplementation in women aged 35-39years undergoing ICSI cycles:a randomized controlled study[J].Reprod Biomed Online,2009,19:879-887.
[23]邓宇,尹敏娜,梁佩玲,等.长方案添加黄体生成素对体外受精-胚胎移植结局的影响[J].南方医科大学学报,2017,37:1501-1505.
[24] Younis JS,Izhaki I,Ben-Ami M.The effect of LH supplementation to the GnRH antagonist protocol in advanced reproductive ageing women:aprospective randomized controlled study[J].Clin Endocrinol(Oxf),2016,84:99-106.
[25] He W,Lin H,Lu J,et al.The impact of luteinizing hormone supplementation in gonadotropin-releasing hormone antagonist cycles:a retrospective cohort study[J].Gynecol Endocrinol,2018,34:513-517.
[26] Lehert P,Kolibianakis EM,Venetis CA,et al.Recombinant humanfollicle-stimulatinghormone(r-hFSH)plus recombinant luteinizing hormone versus r-hFSH alone for ovarian stimulation during assisted reproductive technology:systematic review and meta-analysis[J].Reprod Biol Endocrinol,2014,12:17.
[27]农璎琦,刘文娟,黄倩文,等.拮抗剂方案中卵泡期促黄体生成素水平对不同卵巢反应者体外受精-胚胎移植结局的影响[J].中华生殖与避孕杂志,2018,38:192-199.
[28] Gizzo S,Andrisani A,Noventa M,et al.Recombinant LH supplementation during IVF cycles with a GnRH-antagonist in estimated poor responders:A cross-matched pilot investigation of the optimal daily dose and timing[J].Mol Med Rep,2015,12:4219-4229.
[29] Humaidan P,Chin W,Rogoff D,et al.Efficacy and safety of follitropin alfa/lutropin alfa in ART:a randomized controlled trial in poor ovarian responders[J].Hum Reprod,2017,32:544-555.
[30] Caserta D,Lisi F,Marci R,et al.Does supplementation with recombinant luteinizing hormone prevent ovarian hyperstimulation syndrome in down regulated patients undergoing recombinant follicle stimulating hormone multiple follicular stimulation for IVF/ET and reduces cancellation rate for high risk of hyperstimulation?[J].Gynecol Endocrinol,2011,27:862-866.
[31]李元,龚斐.重组人黄体生成素能改善改良超长方案多囊卵巢综合征患者IVF/ICSI妊娠结局[J].生殖医学杂志,2015,24:21-25.
[32] Santi D,Casarini L,Alviggi C,et al.Efficacy of folliclestimulating hormone(FSH)alone,FSH+luteinizing hormone,human menopausal gonadotropin or FSH+human chorionic gonadotropin on assisted reproductive technology outcomes in the"personalized"medicine era:a Meta-analysis[J].Front Endocrinol(Lausanne),2017,8:114.