卵巢低反应人群用药技巧
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摘要
卵巢低反应(POR)即在控制性促排卵中卵巢对外源性促性腺素刺激反应不良的状态,在临床中极为常见。目前临床上POR诊断常采用博洛尼亚标准,但该标准仍然具有局限性。本文介绍了目前文献报道常用的POR人群用药方案与相关的辅助治疗,但现有POR相关的研究仍普遍存在纳入标准不一、样本量小等问题,因此尚未有一种受到学界广泛认可的干预措施可改善POR患者的妊娠结局。未来需要在完善、细化博洛尼亚标准的前提下,进行大样本、多中心的随机对照实验及合理、严谨的大数据荟萃分析,以求获得可有效地改善POR患者生育结局的干预手段。
Poor ovarian response(POR)is a status of decreased ovarian reservation and presented as a substantial minority of patients' poor response to the exogenous gonadotropins.Bologna criteria have been used to diagnose the poor ovarian responders.While the content of Bologna criteria is still under controversial and is need to be updated in the future.We reviewed the popular controlled ovarian hyperstimulation regiments and alternative approaches applied in POR patients in the past two decades.However,the POR-related studies are still prevalent in the different inclusion criteria,small sample size etc.,so there is not yet a widely accepted intervention by the academy to improve the pregnancy outcome of POR patients.To achieve the optimal assisted fertilization managements of POR patients,it is necessary to carry out randomized controlled tests with large sample size and appropriated added-on Bologna criteria in the future.
Poor ovarian response(POR)is a status of decreased ovarian reservation and presented as a substantial minority of patients' poor response to the exogenous gonadotropins.Bologna criteria have been used to diagnose the poor ovarian responders.While the content of Bologna criteria is still under controversial and is need to be updated in the future.We reviewed the popular controlled ovarian hyperstimulation regiments and alternative approaches applied in POR patients in the past two decades.However,the POR-related studies are still prevalent in the different inclusion criteria,small sample size etc.,so there is not yet a widely accepted intervention by the academy to improve the pregnancy outcome of POR patients.To achieve the optimal assisted fertilization managements of POR patients,it is necessary to carry out randomized controlled tests with large sample size and appropriated added-on Bologna criteria in the future.
引文
[1]Tarlatzis B,Zepiridis L,Grimbizis G,et al.Clinical management of low ovarian response to stimulation for IVF:a systematic review[J].Hum Reprod Update,2003,9:61-76.
[2]Ubaldi F,Vaiarelli A,D’Anna R,et al.Management of poor responders in IVF:is there anything new?[J].Biomed Res Int,2014,2014:352098.DOI:1155/2014/352098
[3]Ferraretti A,La Marca A,Fauser B,et al.ESHRE consensus on the definition of‘poor response’to ovarian stimulation for in vitro fertilization:the Bologna criteria[J].Hum reprod,2011,26:1616-1624.
[4]Soto N,I1iguez G,López P,et al.Anti-Müllerian hormone and inhibin B levels as markers of premature ovarian aging and transition to menopause in type 1diabetes mellitus[J].Hum Reprod,2009,24:2838-2844.
[5]Al-Rimawi H,Jallad M,Amarin Z,et al.Hypothalamicpituitary-gonadal function in adolescent females with betathalassemia major[J].Int J Gynecol Obstet,2005,90:44-47.
[6]Amato P,Roberts AC.Transient ovarian failure:a complication of uterine artery embolization[J].Fertil Steril,2001,75:438-439.
[7]Ferraretti AP,Gianaroli L.The Bologna criteria for the definition of poor ovarian responders:is there a need for revision?[J].Hum Reprod,2014,29:1842-1845.
[8]Polyzos N,Sunkara S.Sub-optimal responders following controlled ovarian stimulation:an overlooked group?[J].Hum Reprod,2015,30:2005-2008.
[9]Owen E,West C,Mason B,et al.Co-treatment with growth hormone of sub-optimal responders in IVF-ET[J].Hum Reprod,1991,6:524-528.
[10]Papathanasiou A,Searle BJ,King NM,et al.Trends in‘poor responder’research:lessons learned from RCTs in assisted conception[J].Hum Reprod Update,2016,22:306-319.
[11]Broekmans F,Kwee J,Hendriks D,et al.A systematic review of tests predicting ovarian reserve and IVF outcome[J].Hum Reprod Update,2006,12:685-718.
[12]Broer SL,Broekmans FJ,Laven JS,et al.Anti-Müllerian hormone:ovarian reserve testing and its potential clinical implications[J].Hum Reprod Update,2014,20:688-701.
[13]Wei LH,Ma WH,Tang N,et al.Luteal-phase ovarian stimulation is a feasible method for poor ovarian responders undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer treatment compared to a GnRH antagonist protocol:A retrospective study[J].Taiwan J Obstet Gynecol,2016,55:50-54.
[14]Chuang M,Zapantis A,Taylor M,et al.Prolonged gonadotropin stimulation is associated with decreased ART success[J].J Assist Reprod Genet,2010,27:711-717.
[15]Berkkanoglu M,Ozgur K.What is the optimum maximal gonadotropin dosage used in microdose flare-up cycles in poor responders?[J].Fertil Steril,2010,94:662-665.
[16]Polyzos NP,DeVos M,Humaidan P,et al.Corifollitropin alfa followed by rFSH in a GnRH antagonist protocol for poor ovarian responder patients:an observational pilot study[J].Fertil Steril,2013,99:422-426.
[17]Ubaldi FM,Capalbo A,Vaiarelli A,et al.Follicular versus luteal phase ovarian stimulation during the same menstrual cycle(DuoStim)in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate:new insight in ovarian reserve exploitation[J].Fertil Steril,2016,105:1488-1495.
[18]Ubaldi F,Rienzi L,Baroni E,et al.Hopes and facts about mild ovarian stimulation[J/OL].Reprod Biomed Online,2007,14:675-681.
[19]Polyzos N,Blockeel C,Verpoest W,et al.Live birth rates following natural cycle IVF in women with poor ovarian response according to the Bologna criteria[J].Hum Reprod,2012,27:3481-3486.
[20]Schimberni M,Morgia F,Colabianchi J,et al.Natural-cycle in vitro fertilization in poor responder patients:a survey of500consecutive cycles[J].Fertil Steril,2009,92:1297-1301.
[21]Wang PT,Lee RKK,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].J Assist Reprod Genet,2002,19:1-6.
[22]Kyrou D,Kolibianakis EM,Venetis CA,et al.How to improve the probability of pregnancy in poor responders undergoing in vitro fertilization:a systematic review and metaanalysis[J].Fertil Steril,2009,91:749-766.
[23]de Ziegler D,Streuli I,Meldrum DR,et al.The value of growth hormone supplements in ART for poor ovarian responders[J].Fertil Steril,2011,96:1069-1076.
[24]Kolibianakis E,Venetis C,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[J].Hum Reprod Update,2009,15:613-622.
[25]Reynolds KA,Omurtag KR,Jimenez PT,et al.Cycle cancellation and pregnancy after luteal estradiol priming in women defined as poor responders:a systematic review and meta-analysis[J].Hum Reprod,2013,28:2981-2989.
[26]de Ziegler D,Fanchin R,de Moustier B,et al.The hormonal control of endometrial receptivity:estrogen(E2)and progesterone[J].J Reprod Immunol,1998,39:149-166.
[27]Sunkara SK,Pundir J,Khalaf Y.Effect of androgen supplementation or modulation on ovarian stimulation outcome in poor responders:a meta-analysis[J/OL].Reprod Biomed Online,2011,22:545-555.
[28]Barad D,Gleicher N.Effect of dehydroepiandrosterone on oocyte and embryo yields,embryo grade and cell number in IVF[J].Hum Reprod,2006,21:2845-2849.
[29]Zhang M,Niu W,Wang Y,et al.Dehydroepiandrosterone treatment in women with poor ovarian response undergoing IVF or ICSI:a systematic review and meta-analysis[J].J Assist Reprod Genet,2016,33:981-991.
[30]González-Comadran M,Durán M,SolàI,et al.Effects of transdermal testosterone in poor responders undergoing IVF:systematic review and meta-analysis[J/OL].Reprod Biomed Online,2012,25:450-459.
[31]Fischer R.Understanding the role of LH:myths and facts[J/OL].Reprod Biomed Online,2007,15:468-477.
[32]Lehert P,Kolibianakis EM,Venetis CA,et al.Recombinant human follicle-stimulating hormone(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.
[2]Ubaldi F,Vaiarelli A,D’Anna R,et al.Management of poor responders in IVF:is there anything new?[J].Biomed Res Int,2014,2014:352098.DOI:1155/2014/352098
[3]Ferraretti A,La Marca A,Fauser B,et al.ESHRE consensus on the definition of‘poor response’to ovarian stimulation for in vitro fertilization:the Bologna criteria[J].Hum reprod,2011,26:1616-1624.
[4]Soto N,I1iguez G,López P,et al.Anti-Müllerian hormone and inhibin B levels as markers of premature ovarian aging and transition to menopause in type 1diabetes mellitus[J].Hum Reprod,2009,24:2838-2844.
[5]Al-Rimawi H,Jallad M,Amarin Z,et al.Hypothalamicpituitary-gonadal function in adolescent females with betathalassemia major[J].Int J Gynecol Obstet,2005,90:44-47.
[6]Amato P,Roberts AC.Transient ovarian failure:a complication of uterine artery embolization[J].Fertil Steril,2001,75:438-439.
[7]Ferraretti AP,Gianaroli L.The Bologna criteria for the definition of poor ovarian responders:is there a need for revision?[J].Hum Reprod,2014,29:1842-1845.
[8]Polyzos N,Sunkara S.Sub-optimal responders following controlled ovarian stimulation:an overlooked group?[J].Hum Reprod,2015,30:2005-2008.
[9]Owen E,West C,Mason B,et al.Co-treatment with growth hormone of sub-optimal responders in IVF-ET[J].Hum Reprod,1991,6:524-528.
[10]Papathanasiou A,Searle BJ,King NM,et al.Trends in‘poor responder’research:lessons learned from RCTs in assisted conception[J].Hum Reprod Update,2016,22:306-319.
[11]Broekmans F,Kwee J,Hendriks D,et al.A systematic review of tests predicting ovarian reserve and IVF outcome[J].Hum Reprod Update,2006,12:685-718.
[12]Broer SL,Broekmans FJ,Laven JS,et al.Anti-Müllerian hormone:ovarian reserve testing and its potential clinical implications[J].Hum Reprod Update,2014,20:688-701.
[13]Wei LH,Ma WH,Tang N,et al.Luteal-phase ovarian stimulation is a feasible method for poor ovarian responders undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer treatment compared to a GnRH antagonist protocol:A retrospective study[J].Taiwan J Obstet Gynecol,2016,55:50-54.
[14]Chuang M,Zapantis A,Taylor M,et al.Prolonged gonadotropin stimulation is associated with decreased ART success[J].J Assist Reprod Genet,2010,27:711-717.
[15]Berkkanoglu M,Ozgur K.What is the optimum maximal gonadotropin dosage used in microdose flare-up cycles in poor responders?[J].Fertil Steril,2010,94:662-665.
[16]Polyzos NP,DeVos M,Humaidan P,et al.Corifollitropin alfa followed by rFSH in a GnRH antagonist protocol for poor ovarian responder patients:an observational pilot study[J].Fertil Steril,2013,99:422-426.
[17]Ubaldi FM,Capalbo A,Vaiarelli A,et al.Follicular versus luteal phase ovarian stimulation during the same menstrual cycle(DuoStim)in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate:new insight in ovarian reserve exploitation[J].Fertil Steril,2016,105:1488-1495.
[18]Ubaldi F,Rienzi L,Baroni E,et al.Hopes and facts about mild ovarian stimulation[J/OL].Reprod Biomed Online,2007,14:675-681.
[19]Polyzos N,Blockeel C,Verpoest W,et al.Live birth rates following natural cycle IVF in women with poor ovarian response according to the Bologna criteria[J].Hum Reprod,2012,27:3481-3486.
[20]Schimberni M,Morgia F,Colabianchi J,et al.Natural-cycle in vitro fertilization in poor responder patients:a survey of500consecutive cycles[J].Fertil Steril,2009,92:1297-1301.
[21]Wang PT,Lee RKK,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].J Assist Reprod Genet,2002,19:1-6.
[22]Kyrou D,Kolibianakis EM,Venetis CA,et al.How to improve the probability of pregnancy in poor responders undergoing in vitro fertilization:a systematic review and metaanalysis[J].Fertil Steril,2009,91:749-766.
[23]de Ziegler D,Streuli I,Meldrum DR,et al.The value of growth hormone supplements in ART for poor ovarian responders[J].Fertil Steril,2011,96:1069-1076.
[24]Kolibianakis E,Venetis C,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[J].Hum Reprod Update,2009,15:613-622.
[25]Reynolds KA,Omurtag KR,Jimenez PT,et al.Cycle cancellation and pregnancy after luteal estradiol priming in women defined as poor responders:a systematic review and meta-analysis[J].Hum Reprod,2013,28:2981-2989.
[26]de Ziegler D,Fanchin R,de Moustier B,et al.The hormonal control of endometrial receptivity:estrogen(E2)and progesterone[J].J Reprod Immunol,1998,39:149-166.
[27]Sunkara SK,Pundir J,Khalaf Y.Effect of androgen supplementation or modulation on ovarian stimulation outcome in poor responders:a meta-analysis[J/OL].Reprod Biomed Online,2011,22:545-555.
[28]Barad D,Gleicher N.Effect of dehydroepiandrosterone on oocyte and embryo yields,embryo grade and cell number in IVF[J].Hum Reprod,2006,21:2845-2849.
[29]Zhang M,Niu W,Wang Y,et al.Dehydroepiandrosterone treatment in women with poor ovarian response undergoing IVF or ICSI:a systematic review and meta-analysis[J].J Assist Reprod Genet,2016,33:981-991.
[30]González-Comadran M,Durán M,SolàI,et al.Effects of transdermal testosterone in poor responders undergoing IVF:systematic review and meta-analysis[J/OL].Reprod Biomed Online,2012,25:450-459.
[31]Fischer R.Understanding the role of LH:myths and facts[J/OL].Reprod Biomed Online,2007,15:468-477.
[32]Lehert P,Kolibianakis EM,Venetis CA,et al.Recombinant human follicle-stimulating hormone(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.