Prognostic models for high and low ovarian responses in controlled ovarian stimulation using a GnRH antagonist protocol.
Prognostic models for high and low ovarian responses in controlled ovarian stimulation using a GnRH antagonist protocol.
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使用 GnRH 拮抗剂方案进行受控卵巢刺激时卵巢反应高低的预后模型。
DOI：
10.1093/humrep/deu090
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Witjes H
中科院分区：
文献类型：
--
作者：
Broekmans FJ;Verweij PJ;Eijkemans MJ;Mannaerts BM;Witjes H
在接受GnRH拮抗剂方案的控制性卵巢刺激（COS）的患者中，能否确定低和高卵巢反应的预测因素？卵巢高反应和低反应的常见预后因素是女性年龄、窦卵泡计数（AFC）和基础血清FSH和LH。卵巢反应的预测因子已在GnRH激动剂方案中确定。随着在COS期间引入GnRH拮抗剂以防止LH过早升高，以及使用长GnRH激动剂逐渐转变为短GnRH拮抗剂方案，需要关于GnRH拮抗剂周期中卵巢反应可预测性的数据。Engage试验数据的回顾性分析和Xpect试验的验证。构建高（>18个卵母细胞获得）和低（<6个卵母细胞获得）卵巢反应的预后模型。模型构建基于Engage试验的重组FSH（rFSH）组（n = 747）。以逐步方式构建多变量logistic回归模型（P < 0.15）。在Xpect试验中，对接受等效治疗的患者（n = 199）进行了基于校准的验证。IVF前有COS适应症的不孕女性。Engage和Xpect试验包括来自北美和欧洲的相似种族的患者，他们有规律的月经周期。男性因素、输卵管因素、子宫内膜异位症是导致不孕的主要原因。在Engage试验中，18.3%的患者卵巢反应性高，12.7%的患者卵巢反应性低。年龄、AFC、刺激第1天的血清FSH和血清LH是高和低卵巢反应的预后因素。较高的AFC和LH与卵巢高反应的机会增加有关。年龄较大和较高的FSH与卵巢低反应的机会增加相关。区域（北美/欧洲）和BMI是高卵巢反应的预后因素，刺激第1天的血清雌二醇与低卵巢反应相关。高卵巢反应模型的受试者工作特征（ROC）曲线下面积（AUC）为0.82。敏感性和特异性分别为0.82和0.73;阳性和阴性预测值分别为0.40和0.95。低卵巢反应模型的AUC为0.80。敏感性和特异性分别为0.77和0.73，阳性和阴性预测值分别为0.29和0.96。在Xpect中，19.1%的患者为卵巢高应答者，16.1%为卵巢低应答者。高和低卵巢反应的校准线斜率分别为0.81和1.35，均与1.0无统计学差异。总之，卵巢高反应和低反应的常见预后因素是女性年龄、AFC和基础血清FSH和LH。简单的多变量模型能够预测接受GnRH拮抗剂方案和每日rFSH治疗的患者的卵巢反应过低或过高。抗苗勒管激素未纳入预测模型。这一发现将有助于识别卵巢反应性过高或过低的患者，并有助于COS治疗的个体化。本研究和编辑工作的财政支持由Merck，Sharp & Dohme Corp.（MSD）提供，该公司是Merck & Co. Inc.的子公司，美国新泽西州怀特豪斯站。F.J.B.收到了CVZ给他的机构的赠款; P. J. M. V.和H.W.是默沙东和B.M.J.L.M.的雇员是默沙东的员工在开发这个手稿的时候。NCT 00696800和NCT 00778999。
Can predictors of low and high ovarian responses be identified in patients undergoing controlled ovarian stimulation (COS) in a GnRH antagonist protocol? Common prognostic factors for high and low ovarian responses were female age, antral follicle count (AFC) and basal serum FSH and LH. Predictors of ovarian response have been identified in GnRH agonist protocols. With the introduction of GnRH antagonists to prevent premature LH rises during COS, and the gradual shift in use of long GnRH agonist to short GnRH antagonist protocols, there is a need for data on the predictability of ovarian response in GnRH antagonist cycles. A retrospective analysis of data from the Engage trial and validation with the Xpect trial. Prognostic models were constructed for high (>18 oocytes retrieved) and low (<6 oocytes retrieved) ovarian response. Model building was based on the recombinant FSH (rFSH) arm (n = 747) of the Engage trial. Multivariable logistic regression models were constructed in a stepwise fashion (P < 0.15 for entry). Validation based on calibration was performed in patients with equivalent treatment (n = 199) in the Xpect trial. Infertile women with an indication for COS prior to IVF. The Engage and Xpect trials included patients of similar ethnic origins from North America and Europe who had regular menstrual cycles. The main causes of infertility were male factor, tubal factor and endometriosis. In the Engage trial, 18.3% of patients had a high and 12.7% had a low ovarian response. Age, AFC, serum FSH and serum LH at stimulation Day 1 were prognostic for both high and low ovarian responses. Higher AFC and LH were associated with an increased chance of high ovarian response. Older age and higher FSH correlated with an increased chance of low ovarian response. Region (North America/Europe) and BMI were prognostic for high ovarian response, and serum estradiol at stimulation Day 1 was associated with low ovarian response. The area under the receiver operating characteristic (ROC) curve (AUC) for the model for a high ovarian response was 0.82. Sensitivity and specificity were 0.82 and 0.73; positive and negative predictive values were 0.40 and 0.95, respectively. The AUC for the model for a low ovarian response was 0.80. Sensitivity and specificity were 0.77 and 0.73, respectively; positive and negative predictive values were 0.29 and 0.96, respectively. In Xpect, 19.1% of patients were high ovarian responders and 16.1% were low ovarian responders. The slope of the calibration line was 0.81 and 1.35 for high and low ovarian responses, respectively, both not statistically different from 1.0. In summary, common prognostic factors for high and low ovarian responses were female age, AFC and basal serum FSH and LH. Simple multivariable models are presented that are able to predict both a too low or too high ovarian response in patients treated with a GnRH antagonist protocol and daily rFSH. Anti-Müllerian hormone was not included in the prediction modelling. The findings will help with the identification of patients at risk of a too high or too low ovarian response and individualization of COS treatment. Financial support for this study and the editorial work was provided by Merck, Sharp & Dohme Corp. (MSD), a subsidiary of Merck & Co. Inc., Whitehouse Station, NJ, USA. F.J.B. received a grant from CVZ to his institution; P.J.M.V. and H.W. are employees of MSD, and B.M.J.L.M. was an employee of MSD at the time of development of this manuscript. NCT 00696800 and NCT00778999.
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影响因子：
5.8
作者：
Hehenkamp, Wouter J. K.;Looman, Caspar W. N.;Broekmans, Frank J. M.
通讯作者：
Broekmans, Frank J. M.
影响因子：
6.7
作者：
Mukherjee, T;Copperman, AB;Grunfeld, L
通讯作者：
Grunfeld, L
影响因子：
13.3
作者：
Leushuis, Esther;van der Steeg, Jan Willem;Hompes, Peter G. A.
通讯作者：
Hompes, Peter G. A.
DOI：
10.1093/humrep/dep291
发表时间：
2009-12
期刊：
Human reproduction (Oxford, England)
影响因子：
--
作者：
Devroey P;Boostanfar R;Koper NP;Mannaerts BM;Ijzerman-Boon PC;Fauser BC;ENGAGE Investigators
通讯作者：
ENGAGE Investigators
影响因子：
6.7
作者：
Jayaprakasan, Kannamannadiar;Chan, YeeYin;Raine-Fenning, Nick
通讯作者：
Raine-Fenning, Nick