Kop Petronella Al, Mochtar Monique H, O'Brien Paul A, Van der Veen Fulco, van Wely Madelon
Obstetrics and Gynaecology, Center for Reproductive Medicine, Academic Medical Centre, Meibergdreef 9, Amsterdam, Netherlands, 1105 AZ.
Cochrane Database Syst Rev. 2018 Jan 25;1(1):CD000317. doi: 10.1002/14651858.CD000317.pub4.
The first-line treatment in donor sperm treatment consists of inseminations that can be done by intrauterine insemination (IUI) or by intracervical insemination (ICI).
To compare the effectiveness and safety of intrauterine insemination (IUI) and intracervical insemination (ICI) in women who start donor sperm treatment.
We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL in October 2016, checked references of relevant studies, and contacted study authors and experts in the field to identify additional studies. We searched PubMed, Google Scholar, the Grey literature, and five trials registers on 15 December 2017.
We included randomised controlled trials (RCTs) reporting on IUI versus ICI in natural cycles or with ovarian stimulation, and RCTs comparing different cointerventions in IUI and ICI. We included cross-over studies if pre-cross-over data were available.
We used standard methodological procedures recommended by Cochrane. We collected data on primary outcomes of live birth and multiple pregnancy rates, and on secondary outcomes of clinical pregnancy, miscarriage, and cancellation rates.
We included six RCTs (708 women analysed) on ICI and IUI in donor sperm treatment. Two studies compared IUI and ICI in natural cycles, two studies compared IUI and ICI in gonadotrophin-stimulated cycles, and two studies compared timing of IUI and ICI. There was very low-quality evidence; the main limitations were risk of bias due to poor reporting of study methods, and serious imprecision.IUI versus ICI in natural cyclesThere was insufficient evidence to determine whether there was any clear difference in live birth rate between IUI and ICI in natural cycles (odds ratio (OR) 3.24, 95% confidence interval (CI) 0.12 to 87.13; 1 RCT, 26 women; very low-quality evidence). There was only one live birth in this study (in the IUI group). IUI resulted in higher clinical pregnancy rates (OR 6.18, 95% CI 1.91 to 20.03; 2 RCTs, 76 women; I² = 48%; very low-quality evidence).No multiple pregnancies or miscarriages occurred in this study.IUI versus ICI in gonadotrophin-stimulated cyclesThere was insufficient evidence to determine whether there was any clear difference in live birth rate between IUI and ICI in gonadotrophin-stimulated cycles (OR 2.55, 95% CI 0.72 to 8.96; 1 RCT, 43 women; very low-quality evidence). This suggested that if the chance of a live birth following ICI in gonadotrophin-stimulated cycles was assumed to be 30%, the chance following IUI in gonadotrophin-stimulated cycles would be between 24% and 80%. IUI may result in higher clinical pregnancy rates than ICI (OR 2.83, 95% CI 1.38 to 5.78; 2 RCTs, 131 women; I² = 0%; very low-quality evidence). IUI may be associated with higher multiple pregnancy rates than ICI (OR 2.77, 95% CI 1.00 to 7.69; 2 RCTs, 131 women; I² = 0%; very low-quality evidence). This suggested that if the risk of multiple pregnancy following ICI in gonadotrophin-stimulated cycles was assumed to be 10%, the risk following IUI would be between 10% and 46%.We found insufficient evidence to determine whether there was any clear difference between the groups in miscarriage rates in gonadotrophin-stimulated cycles (OR 1.97, 95% CI 0.43 to 9.04; 2 RCTs, overall 67 pregnancies; I² = 50%; very low-quality evidence).Timing of IUI and ICIWe found no studies that reported on live birth rates.We found a higher clinical pregnancy rate when IUI was timed one day after a rise in blood levels of luteinising hormone (LH) compared to IUI two days after a rise in blood levels of LH (OR 2.00, 95% CI 1.14 to 3.53; 1 RCT, 351 women; low-quality evidence). We found insufficient evidence to determine whether there was any clear difference in clinical pregnancy rates between ICI timed after a rise in urinary levels of LH versus a rise in basal temperature plus cervical mucus scores (OR 1.31, 95% CI 0.42 to 4.11; 1 RCT, 56 women; very low-quality evidence).Neither of these studies reported multiple pregnancy or miscarriage rates as outcomes.
AUTHORS' CONCLUSIONS: There was insufficient evidence to determine whether there was a clear difference in live birth rates between IUI and ICI in natural or gonadotrophin-stimulated cycles in women who started with donor sperm treatment. There was insufficient evidence available for the effect of timing of IUI or ICI on live birth rates. Very low-quality data suggested that in gonadotrophin-stimulated cycles, ICI may be associated with a higher clinical pregnancy rate than IUI, but also with a higher risk of multiple pregnancy rate. We concluded that the current evidence was too limited to choose between IUI or ICI, in natural cycles or with ovarian stimulation, in donor sperm treatment.
供精治疗的一线治疗方法包括通过宫内授精（IUI）或宫颈内授精（ICI）进行的授精。
比较在开始供精治疗的女性中，宫内授精（IUI）和宫颈内授精（ICI）的有效性和安全性。
我们于2016年10月检索了Cochrane妇科与生育组试验注册库、CENTRAL、MEDLINE、Embase、PsycINFO、CINAHL，检查了相关研究的参考文献，并联系了研究作者和该领域的专家以识别其他研究。我们于2017年12月15日检索了PubMed、谷歌学术、灰色文献以及五个试验注册库。
我们纳入了报告自然周期或卵巢刺激下IUI与ICI对比的随机对照试验（RCT），以及比较IUI和ICI中不同联合干预措施的RCT。如果有交叉前数据，我们纳入交叉研究。
我们采用了Cochrane推荐的标准方法程序。我们收集了关于活产和多胎妊娠率等主要结局的数据，以及关于临床妊娠、流产和取消率等次要结局的数据。
我们纳入了六项关于供精治疗中ICI和IUI的RCT（共分析708名女性）。两项研究比较了自然周期中的IUI和ICI，两项研究比较了促性腺激素刺激周期中的IUI和ICI，两项研究比较了IUI和ICI的时机。证据质量极低；主要局限性在于研究方法报告不佳导致的偏倚风险以及严重的不精确性。
自然周期中IUI与ICI的比较：没有足够的证据确定自然周期中IUI和ICI的活产率是否存在明显差异（优势比（OR）3.24，95%置信区间（CI）0.12至87.13；1项RCT，26名女性；证据质量极低）。本研究中仅有一例活产（在IUI组）。IUI导致更高的临床妊娠率（OR 6.18，95%CI 1.91至20.03；2项RCT，76名女性；I² = 48%；证据质量极低）。本研究中未发生多胎妊娠或流产。
促性腺激素刺激周期中IUI与ICI的比较：没有足够的证据确定促性腺激素刺激周期中IUI和ICI的活产率是否存在明显差异（OR 2.55，95%CI 0.72至8.96；1项RCT，43名女性；证据质量极低）。这表明如果假设促性腺激素刺激周期中ICI后的活产机会为30%，那么促性腺激素刺激周期中IUI后的活产机会将在24%至80%之间。IUI可能导致比ICI更高的临床妊娠率（OR 2.83，95%CI 1.38至5.78；2项RCT，131名女性；I² = 0%；证据质量极低）。IUI可能比ICI与更高的多胎妊娠率相关（OR 2.77，95%CI 1.00至7.69；2项RCT，131名女性；I² = 0%；证据质量极低）。这表明如果假设促性腺激素刺激周期中ICI后的多胎妊娠风险为10%，那么IUI后的风险将在10%至46%之间。我们没有足够的证据确定两组在促性腺激素刺激周期中的流产率是否存在明显差异（OR 1.97，95%CI 0.43至9.04；2项RCT，共67例妊娠；I² = 50%；证据质量极低）。
IUI和ICI的时机：我们未发现报告活产率的研究。与在促黄体生成素（LH）血水平升高两天后进行IUI相比，在LH血水平升高一天后进行IUI时临床妊娠率更高（OR 2.00，95%CI 1.14至3.53；1项RCT，351名女性；证据质量低）。我们没有足够的证据确定在LH尿水平升高后进行ICI与在基础体温加宫颈黏液评分升高后进行ICI的临床妊娠率是否存在明显差异（OR 1.31，95%CI 0.42至4.11；1项RCT，56名女性；证据质量极低）。这两项研究均未将多胎妊娠或流产率作为结局报告。
没有足够的证据确定在开始供精治疗的女性中，自然周期或促性腺激素刺激周期中IUI和ICI的活产率是否存在明显差异。关于IUI或ICI的时机对活产率的影响，现有证据不足。质量极低的数据表明，在促性腺激素刺激周期中，ICI可能比IUI与更高的临床妊娠率相关，但也与更高的多胎妊娠风险相关。我们得出结论，目前的证据过于有限，无法在供精治疗的自然周期或卵巢刺激中在IUI和ICI之间做出选择。
