PDF(Pubmed)
Abstract：
OBJECTIVE: What is the relationship between late follicular phase progesterone levels and clinic pregnancy and live birth rates in couples with unexplained infertility undergoing ovarian stimulation with IUI (OS-IUI)?
CONCLUSIONS: Late follicular progesterone levels between 1.0 and <1.5 ng/ml were associated with higher live birth and clinical pregnancy rates while the outcomes in groups with higher progesterone levels did not differ appreciably from the <1.0 ng/ml reference group.
BACKGROUND: Elevated late follicular progesterone levels have been associated with lower live birth rates after fresh embryo transfer following controlled ovarian stimulation and egg retrieval, but less is known about whether an association exists with outcomes in OS-IUI cycles. Existing studies are few and have been limited to ovarian stimulation with gonadotrophins, but the use of oral agents, such as clomiphene citrate and letrozole, is common with these treatments and has not been well studied.
METHODS: The study was a prospective cohort analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial. Frozen serum was available for evaluation from 2121 cycles in 828 AMIGOS participants. The primary pregnancy outcome was live birth per cycle, and the secondary pregnancy outcome was clinical pregnancy rate per cycle.
METHODS: Couples with unexplained infertility in the AMIGOS trial, for whom female serum from day of trigger with hCG was available in at least one cycle of treatment, were included. Stored frozen serum samples from day of hCG trigger during treatment with OS-IUI were evaluated for serum progesterone level. Progesterone level <1.0 ng/ml was the reference group for comparison with progesterone categorized in increments of 0.5 ng/ml up to ≥3.0 ng/ml. Unadjusted and adjusted risk ratios (RR) and 95% CI were estimated using cluster-weighted generalized estimating equations to estimate modified Poisson regression models with robust standard errors.
RESULTS: Compared to the reference group with 110/1363 live births (8.07%), live birth rates were significantly increased in cycles with progesterone 1.0 to <1.5 ng/ml (49/401 live births, 12.22%) in both the unadjusted (RR 1.56, 95% CI 1.14, 2.13) and treatment-adjusted models (RR 1.51, 95% CI 1.10, 2.06). Clinical pregnancy rates were also higher in this group (55/401 clinical pregnancies, 13.72%) compared to reference group with 130/1363 (9.54%) (unadjusted RR 1.46, 95% CI 1.10, 1.94 and adjusted RR 1.42, 95% CI 1.07, 1.89). In cycles with progesterone 1.5 ng/ml and above, there was no evidence of a difference in clinical pregnancy or live birth rates relative to the reference group. This pattern remained when stratified by ovarian stimulation treatment group but was only statistically significant in letrozole cycles.
CONCLUSIONS: The AMIGOS trial was not designed to answer this clinical question, and with small numbers in some progesterone categories our analyses were underpowered to detect differences between some groups. Inclusion of cycles with progesterone values above 3.0 ng/ml may have included those wherein ovulation had already occurred at the time the IUI was performed. These cycles would be expected to experience a lower success rate but pregnancy may have occurred with intercourse in the same cycle.
CONCLUSIONS: Compared to previous literature focusing primarily on OS-IUI cycles using gonadotrophins, these data include patients using oral agents and therefore may be generalizable to the wider population of infertility patients undergoing IUI treatments. Because live births were significantly higher when progesterone ranged from 1.0 to <1.5 ng/ml, further study is needed to clarify whether this progesterone range may truly represent a prognostic indicator in OS-IUI cycles.
BACKGROUND: Oklahoma Shared Clinical and Translational Resources (U54GM104938) National Institute of General Medical Sciences (NIGMS). AMIGOS was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, and U10HD055925. Research made possible by the funding by American Recovery and Reinvestment Act. Dr Burks has disclosed that she is a member of the Board of Directors of the Pacific Coast Reproductive Society. Dr Hansen has disclosed that he is the recipient of NIH grants unrelated to the present work, and contracts with Ferring International Pharmascience Center US and with May Health unrelated to the present work, as well as consulting fees with May Health also unrelated to the present work. Dr Diamond has disclosed that he is a stockholder and a member of the Board of Directors of Advanced Reproductive Care, Inc., and that he has a patent pending for the administration of progesterone to trigger ovulation. Dr Anderson, Dr Gavrizi, and Dr Peck do not have conflicts of interest to disclose.
BACKGROUND: N/A.
CONCLUSIONS: Late follicular progesterone levels between 1.0 and <1.5 ng/ml were associated with higher live birth and clinical pregnancy rates while the outcomes in groups with higher progesterone levels did not differ appreciably from the <1.0 ng/ml reference group.
BACKGROUND: Elevated late follicular progesterone levels have been associated with lower live birth rates after fresh embryo transfer following controlled ovarian stimulation and egg retrieval, but less is known about whether an association exists with outcomes in OS-IUI cycles. Existing studies are few and have been limited to ovarian stimulation with gonadotrophins, but the use of oral agents, such as clomiphene citrate and letrozole, is common with these treatments and has not been well studied.
METHODS: The study was a prospective cohort analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial. Frozen serum was available for evaluation from 2121 cycles in 828 AMIGOS participants. The primary pregnancy outcome was live birth per cycle, and the secondary pregnancy outcome was clinical pregnancy rate per cycle.
METHODS: Couples with unexplained infertility in the AMIGOS trial, for whom female serum from day of trigger with hCG was available in at least one cycle of treatment, were included. Stored frozen serum samples from day of hCG trigger during treatment with OS-IUI were evaluated for serum progesterone level. Progesterone level <1.0 ng/ml was the reference group for comparison with progesterone categorized in increments of 0.5 ng/ml up to ≥3.0 ng/ml. Unadjusted and adjusted risk ratios (RR) and 95% CI were estimated using cluster-weighted generalized estimating equations to estimate modified Poisson regression models with robust standard errors.
RESULTS: Compared to the reference group with 110/1363 live births (8.07%), live birth rates were significantly increased in cycles with progesterone 1.0 to <1.5 ng/ml (49/401 live births, 12.22%) in both the unadjusted (RR 1.56, 95% CI 1.14, 2.13) and treatment-adjusted models (RR 1.51, 95% CI 1.10, 2.06). Clinical pregnancy rates were also higher in this group (55/401 clinical pregnancies, 13.72%) compared to reference group with 130/1363 (9.54%) (unadjusted RR 1.46, 95% CI 1.10, 1.94 and adjusted RR 1.42, 95% CI 1.07, 1.89). In cycles with progesterone 1.5 ng/ml and above, there was no evidence of a difference in clinical pregnancy or live birth rates relative to the reference group. This pattern remained when stratified by ovarian stimulation treatment group but was only statistically significant in letrozole cycles.
CONCLUSIONS: The AMIGOS trial was not designed to answer this clinical question, and with small numbers in some progesterone categories our analyses were underpowered to detect differences between some groups. Inclusion of cycles with progesterone values above 3.0 ng/ml may have included those wherein ovulation had already occurred at the time the IUI was performed. These cycles would be expected to experience a lower success rate but pregnancy may have occurred with intercourse in the same cycle.
CONCLUSIONS: Compared to previous literature focusing primarily on OS-IUI cycles using gonadotrophins, these data include patients using oral agents and therefore may be generalizable to the wider population of infertility patients undergoing IUI treatments. Because live births were significantly higher when progesterone ranged from 1.0 to <1.5 ng/ml, further study is needed to clarify whether this progesterone range may truly represent a prognostic indicator in OS-IUI cycles.
BACKGROUND: Oklahoma Shared Clinical and Translational Resources (U54GM104938) National Institute of General Medical Sciences (NIGMS). AMIGOS was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, and U10HD055925. Research made possible by the funding by American Recovery and Reinvestment Act. Dr Burks has disclosed that she is a member of the Board of Directors of the Pacific Coast Reproductive Society. Dr Hansen has disclosed that he is the recipient of NIH grants unrelated to the present work, and contracts with Ferring International Pharmascience Center US and with May Health unrelated to the present work, as well as consulting fees with May Health also unrelated to the present work. Dr Diamond has disclosed that he is a stockholder and a member of the Board of Directors of Advanced Reproductive Care, Inc., and that he has a patent pending for the administration of progesterone to trigger ovulation. Dr Anderson, Dr Gavrizi, and Dr Peck do not have conflicts of interest to disclose.
BACKGROUND: N/A.
摘要：
目的：在IUI（OS-IUI）卵巢刺激的不明原因不孕症夫妇中，晚期卵泡期孕酮水平与临床妊娠和活产率之间有什么关系？
结论：1.0至<1.5ng/ml的晚期卵泡期孕酮水平与较高的活产和临床妊娠率相关，而孕酮水平较高的组的结局与<1.0ng/
背景：晚期卵泡孕酮水平升高与受控卵巢刺激和取卵后新鲜胚胎移植后活产率降低有关，但对OS-IUI周期中是否存在与结果的关联知之甚少。现有的研究很少，并且仅限于用促性腺激素刺激卵巢，但是使用口服药物，如柠檬酸氯米芬和来曲唑，是常见的这些治疗方法，并没有得到很好的研究。
方法：本研究是一项前瞻性队列分析，对卵巢刺激（AMIGOS）随机对照试验评估多次宫内妊娠。828名AMIGOS参与者的2121个周期的冷冻血清可用于评估。主要妊娠结局是每个周期的活产，次要妊娠结局是每个周期的临床妊娠率。
方法：在AMIGOS试验中患有无法解释的不孕症的夫妇，在至少一个治疗周期中，从hCG触发之日起的女性血清可用，包括在内。在用OS-IUI治疗期间从hCG触发当天起储存的冷冻血清样品评估血清孕酮水平。与以0.5ng/ml至≥3.0ng/ml的增量分类的孕酮相比，孕酮水平<1.0ng/ml是参考组。使用聚类加权广义估计方程估计未调整和调整的风险比（RR）和95％CI，以估计具有稳健标准误差的修正泊松回归模型。
结果：与110/1363例活产的参照组（8.07%）相比，孕酮1.0至<1.5ng/ml的周期活产率显着增加（49/401活产，12.22%)在未调整模型(RR1.56，95%CI1.14，2.13)和治疗调整模型(RR1.51，95%CI1.10，2.06)中。该组的临床妊娠率也较高（55/401例临床妊娠，13.72％）与130/1363（9.54％）的参考组相比（未调整RR1.46，95％CI1.10，1.94和调整RR1.42，95％CI1.07，1.89）。在孕酮1.5ng/ml及以上的周期中，没有证据表明相对于参照组,临床妊娠率或活产率存在差异.当按卵巢刺激治疗组分层时，这种模式仍然存在，但在来曲唑周期中仅具有统计学意义。
结论：AMIGOS试验并非旨在回答这个临床问题，并且在某些孕酮类别中的数量较少，我们的分析在检测某些组之间的差异方面的能力不足。包括孕酮值高于3.0ng/ml的周期可能包括那些在进行IUI时已经发生排卵的周期。预计这些周期将经历较低的成功率，但怀孕可能发生在同一周期的性交。
结论：与以前主要关注使用促性腺激素的OS-IUI周期的文献相比，这些数据包括使用口服药物的患者,因此可推广到接受IUI治疗的不孕症患者的更广泛人群.因为当孕酮范围从1.0到<1.5ng/ml时，活产婴儿明显更高，在OS-IUI周期中,这一孕酮范围是否可以真正代表预后指标,还需要进一步研究.
背景：俄克拉荷马州共享临床和转化资源（U54GM104938）国家普通医学科学研究所（NIGMS）。AMIGOS由EuniceKennedyShriver国家儿童健康与人类发展研究所资助：U10HD077680，U10HD39005，U10HD38992，U10HD27049，U10HD38998，U10HD055942，HD055944，U10HD055936和U10055925。美国复苏和再投资法案的资助使研究成为可能。Burks博士透露，她是太平洋海岸生殖协会董事会成员。汉森博士透露，他是与目前工作无关的NIH赠款的接受者，并与美国Ferring国际药学中心和与目前工作无关的MayHealth签订了合同，以及与MayHealth的咨询费也与目前的工作无关。戴蒙德博士透露，他是高级生殖保健的股东和董事会成员，Inc.,并且他有一项正在申请中的黄体酮引发排卵的专利。安德森博士,Gavrizi博士,Peck博士没有利益冲突要披露。
背景：不适用。
结论：1.0至<1.5ng/ml的晚期卵泡期孕酮水平与较高的活产和临床妊娠率相关，而孕酮水平较高的组的结局与<1.0ng/
背景：晚期卵泡孕酮水平升高与受控卵巢刺激和取卵后新鲜胚胎移植后活产率降低有关，但对OS-IUI周期中是否存在与结果的关联知之甚少。现有的研究很少，并且仅限于用促性腺激素刺激卵巢，但是使用口服药物，如柠檬酸氯米芬和来曲唑，是常见的这些治疗方法，并没有得到很好的研究。
方法：本研究是一项前瞻性队列分析，对卵巢刺激（AMIGOS）随机对照试验评估多次宫内妊娠。828名AMIGOS参与者的2121个周期的冷冻血清可用于评估。主要妊娠结局是每个周期的活产，次要妊娠结局是每个周期的临床妊娠率。
方法：在AMIGOS试验中患有无法解释的不孕症的夫妇，在至少一个治疗周期中，从hCG触发之日起的女性血清可用，包括在内。在用OS-IUI治疗期间从hCG触发当天起储存的冷冻血清样品评估血清孕酮水平。与以0.5ng/ml至≥3.0ng/ml的增量分类的孕酮相比，孕酮水平<1.0ng/ml是参考组。使用聚类加权广义估计方程估计未调整和调整的风险比（RR）和95％CI，以估计具有稳健标准误差的修正泊松回归模型。
结果：与110/1363例活产的参照组（8.07%）相比，孕酮1.0至<1.5ng/ml的周期活产率显着增加（49/401活产，12.22%)在未调整模型(RR1.56，95%CI1.14，2.13)和治疗调整模型(RR1.51，95%CI1.10，2.06)中。该组的临床妊娠率也较高（55/401例临床妊娠，13.72％）与130/1363（9.54％）的参考组相比（未调整RR1.46，95％CI1.10，1.94和调整RR1.42，95％CI1.07，1.89）。在孕酮1.5ng/ml及以上的周期中，没有证据表明相对于参照组,临床妊娠率或活产率存在差异.当按卵巢刺激治疗组分层时，这种模式仍然存在，但在来曲唑周期中仅具有统计学意义。
结论：AMIGOS试验并非旨在回答这个临床问题，并且在某些孕酮类别中的数量较少，我们的分析在检测某些组之间的差异方面的能力不足。包括孕酮值高于3.0ng/ml的周期可能包括那些在进行IUI时已经发生排卵的周期。预计这些周期将经历较低的成功率，但怀孕可能发生在同一周期的性交。
结论：与以前主要关注使用促性腺激素的OS-IUI周期的文献相比，这些数据包括使用口服药物的患者,因此可推广到接受IUI治疗的不孕症患者的更广泛人群.因为当孕酮范围从1.0到<1.5ng/ml时，活产婴儿明显更高，在OS-IUI周期中,这一孕酮范围是否可以真正代表预后指标,还需要进一步研究.
背景：俄克拉荷马州共享临床和转化资源（U54GM104938）国家普通医学科学研究所（NIGMS）。AMIGOS由EuniceKennedyShriver国家儿童健康与人类发展研究所资助：U10HD077680，U10HD39005，U10HD38992，U10HD27049，U10HD38998，U10HD055942，HD055944，U10HD055936和U10055925。美国复苏和再投资法案的资助使研究成为可能。Burks博士透露，她是太平洋海岸生殖协会董事会成员。汉森博士透露，他是与目前工作无关的NIH赠款的接受者，并与美国Ferring国际药学中心和与目前工作无关的MayHealth签订了合同，以及与MayHealth的咨询费也与目前的工作无关。戴蒙德博士透露，他是高级生殖保健的股东和董事会成员，Inc.,并且他有一项正在申请中的黄体酮引发排卵的专利。安德森博士,Gavrizi博士,Peck博士没有利益冲突要披露。
背景：不适用。
