Department of Obstetrics and Gynecology, University of Oklahoma College of Medicine, Oklahoma City, OK 73104, USA.
Department of Biostatistics and Epidemiology, University of Oklahoma College of Public Health, Oklahoma City, OK 73104, USA.
Hum Reprod. 2020 Jun 1;35(6):1296-1305. doi: 10.1093/humrep/deaa027.
Are intrauterine insemination (IUI) performance characteristics and post-processing total motile sperm count (TMC) related to live birth rate in couples with unexplained infertility?
Patient discomfort with IUI and lower inseminate TMC were associated with a reduced live birth rate, while time from hCG injection to IUI, sperm preparation method and ultrasound guidance for IUI were not associated with live birth success.
We previously determined that some baseline characteristics of couples with unexplained infertility, including female age, duration of infertility, history of prior loss and income, were related to live birth rate across a course of ovarian stimulation and IUI treatment. However, the relationship between treatment outcomes and per-cycle characteristics, including ultrasound guidance for IUI, timing of IUI relative to hCG injection, difficult or painful IUI and inseminate TMC, are controversial, and most prior investigations have not evaluated live birth outcome.
STUDY DESIGN, SIZE, DURATION: This was a secondary analyses of 2462 cycles from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. This prospective, randomised, multicentre clinical trial determined live birth rates following IUI after ovarian stimulation with clomiphene citrate, letrozole or gonadotropins in 854 couples with unexplained infertility. It was conducted between 2011 and 2014, and couples could undergo up to four consecutive treatment cycles.
PARTICIPANTS/MATERIALS, SETTING, METHODS: AMIGOS was an NIH-sponsored Reproductive Medicine Network trial conducted at 12 clinical sites. Participants were women with unexplained infertility who were between 18 and 40 years of age. Cluster-weighted generalised estimating equations (GEE), which account for informative clustering of multiple IUI treatment cycles within the same patient, were used to determine associations between IUI performance characteristics, including inseminate TMC, and live birth rate. Efficiency curves were also generated to examine the relationship between inseminate TMC and live birth rate.
After adjustment for treatment group and baseline factors previously associated with live birth across a course of OS-IUI treatment, patient discomfort during the IUI procedure was associated with a reduction in live birth rate (aRR 0.40 (0.16-0.96)). Time from hCG trigger injection to IUI was not significantly associated with outcome. Higher TMC was associated with greater live birth rate (TMC 15.1-20.0 million (14.8%) compared to ≤5 million (5.5%)) (aRR 2.09 (1.31-3.33)). However, live births did occur with TMC ≤ 1 million (5.1%).
LIMITATIONS, REASONS FOR CAUTION: This investigation is a secondary analysis, and AMIGOS was not designed to address the present question. Since timed intercourse was allowed as part of the AMIGOS trial, we cannot rule out the possibility that any given pregnancy resulted from intercourse rather than IUI.
Most factors associated with the performance of IUI were not significantly related to obtaining live birth. Our findings suggest that higher TMC inseminated leads to an increase in live birth rate up to TMC ~20 million. However, there may be no reasonable threshold below which live birth is not possible with IUI.
STUDY FUNDING/COMPETING INTEREST(S): Funding was received through grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936 and U10 HD055925. This research was made possible by funding by the American Recovery and Reinvestment Act. Dr Hansen reports grants from NIH/NICHD and Yale University during the conduct of the study, grants from Roche Diagnostics and grants from Ferring International Pharmascience Center US outside the submitted work. Dr Peck reports support from Ferring Pharmaceuticals outside the submitted work. Dr Coward has nothing to disclose. Dr Wild reports grants from NICHD during the conduct of the study. Dr Trussell has nothing to disclose. Dr Krawetz reports grants from NICHD during the conduct of the study, grants from Merck and support from Taylor and Frances and from Springer, outside the submitted work. Dr Diamond reports grants from NIH/NICHD, Yale University, during the conduct of the study and support from Advanced Reproductive Care AbbVie, Bayer and ObsEva, outside the submitted work. Dr Legro reports support from Bayer, Kindex, Odega, Millendo and AbbVie and grants and support from Ferring, outside the submitted work. Dr Coutifaris reports grants from NICHD/NIH and personal fees from American Society for Reproductive Medicine, outside the submitted work. Dr Alvero has nothing to disclose. Dr Robinson reports grants from NIH during the conduct of the study. Dr Casson has nothing to disclose. Dr Christman reports grants from NICHD during the conduct of the study. Dr Santoro reports grants from NIH during the conduct of the study. Dr Zhang reports grants from NIH during the conduct of the study and support from Shangdong University outside the submitted work.
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宫腔内人工授精（IUI）的性能特征和处理后的总活动精子计数（TMC）与不明原因不孕夫妇的活产率相关吗？
患者对 IUI 的不适和较低的授精 TMC 与活产率降低相关，而 hCG 注射到 IUI 的时间、精子制备方法和 IUI 的超声引导与活产成功无关。
我们之前确定了一些不明原因不孕夫妇的基线特征，包括女性年龄、不孕持续时间、既往流产史和收入，与卵巢刺激和 IUI 治疗过程中的活产率有关。然而，治疗结果与每周期特征的关系，包括 IUI 的超声引导、相对于 hCG 注射的 IUI 时间、困难或疼痛的 IUI 和授精 TMC 等，存在争议，并且大多数先前的研究并未评估活产结局。
研究设计、大小和持续时间：这是来自卵巢刺激（AMIGOS）临床试验的多次宫内妊娠评估的二次分析。这项前瞻性、随机、多中心临床试验确定了在 854 对不明原因不孕夫妇中，使用克罗米芬、来曲唑或促性腺激素进行卵巢刺激后 IUI 后的活产率。该试验于 2011 年至 2014 年进行，夫妇可以进行多达四次连续的治疗周期。
参与者/材料、设置、方法：AMIGOS 是由美国国立卫生研究院（NIH）赞助的生殖医学网络试验，在 12 个临床地点进行。参与者是年龄在 18 至 40 岁之间的不明原因不孕的女性。使用群集加权广义估计方程（GEE），可以对同一患者的多个 IUI 治疗周期进行信息聚类，以确定 IUI 性能特征（包括授精 TMC）与活产率之间的关联。还生成了效率曲线，以检查授精 TMC 与活产率之间的关系。
在调整了治疗组和与卵巢刺激-IUI 治疗过程中活产率相关的基线因素后，IUI 过程中患者的不适与活产率降低相关（ARR 0.40（0.16-0.96））。hCG 触发注射到 IUI 的时间与结果无显著相关性。较高的 TMC 与较高的活产率相关（TMC 15.1-20.0 百万（14.8%）比 ≤5 百万（5.5%））（ARR 2.09（1.31-3.33））。然而，TMC≤1 百万（5.1%）也发生了活产。
局限性、谨慎的原因：这项研究是二次分析，AMIGOS 并非专门用于解决当前的问题。由于 AMIGOS 试验允许定时性交，因此我们不能排除任何给定的妊娠是由性交而不是 IUI 引起的。
与 IUI 性能相关的大多数因素与获得活产无关。我们的研究结果表明，较高的 TMC 授精会导致活产率增加，直到 TMC~20 百万。然而，可能不存在低于该水平就不可能通过 IUI 获得活产的合理阈值。
研究资金/利益冲突：该研究得到了美国国立卫生研究院儿童健康与人类发育研究所（NICHD）的资助：U10 HD077680、U10 HD39005、U10 HD38992、U10 HD27049、U10 HD38998、U10 HD055442、HD055444、U10 HD055436 和 U10 HD055425。这项研究得益于美国复苏和再投资法案的资金支持。Hansen 博士在研究期间报告了与 NICHD 和耶鲁大学有关的资助、罗氏诊断公司的资助以及费森尤斯国际制药中心美国公司的资助，这些都与正在进行的工作无关。Peck 博士报告说，在研究期间，从费雷尔制药公司获得了支持，从罗氏诊断公司获得了支持，从费雷尔国际制药中心美国公司获得了支持。考沃德博士没有什么可披露的。特拉斯勒博士报告说，在研究期间，从 NICHD 获得了资助。特鲁塞尔博士没有什么可披露的。克拉维茨博士报告说，在研究期间，从 NICHD 获得了资助，从默克公司获得了资助，并从泰勒和弗朗西斯公司以及施普林格公司获得了支持，这些都与正在进行的工作无关。戴蒙德博士报告说，从 NICHD、耶鲁大学获得了资助，从拜耳公司、Kindex、Odega、Millendo 和 AbbVie 获得了支持，并从 Bayer 和 ObsEva 获得了支持，这些都与正在进行的工作无关。莱格罗博士报告说，从拜耳公司、Kindex、Odega、Millendo 和 AbbVie 获得了支持，从费雷尔生殖医学公司获得了支持，并从美国生殖医学协会获得了报酬，这些都与正在进行的工作无关。考特里斯博士报告说，从 NICHD 获得了资助，从美国生殖医学协会获得了报酬，并从生殖医学公司获得了报酬，这些都与正在进行的工作无关。阿罗尔博士没有什么可披露的。罗宾逊博士报告说，在研究期间从 NIH 获得了资助。卡森博士没有什么可披露的。克里斯塔曼博士报告说，在研究期间从 NICHD 获得了资助。桑托罗博士报告说，在研究期间从 NIH 获得了资助。张博士报告说，在研究期间从 NIH 获得了资助，并从山东大学获得了资助，这些都与正在进行的工作无关。
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