Rodriguez-Purata Jorge, Latre Laura, Ballester Marta, González-Llagostera Clara, Rodríguez Ignacio, Gonzalez-Foruria Iñaki, Buxaderas Rosario, Martinez Francisca, Barri Pedro N, Coroleu Buenaventura
Reproductive Medicine Service, Institut Universitari Dexeus, Gran Via de Carles III, 71-75, Barcelona 08022, Spain.
Hum Reprod Open. 2018 Feb 15;2018(2):hoy002. doi: 10.1093/hropen/hoy002. eCollection 2018.
What is the impact on live birth rates (LBR) when a donor IUI (dIUI) cycle is performed with an insemination volume of 0.5 mL versus the usual 0.2 mL?
LBR after a dIUI cycle is no different when performed with 0.5 versus 0.2 mL.
An IUI has an important role in the treatment of severe male infertility, and is often used in same-sex female couples and single parents. Different variables have been studied to determine factors correlated with clinical outcomes (IUI scheduling, ovarian stimulation, sperm parameters) but little is known about the inseminated volume. The use of conical bottom test tubes could contribute substantially to the loss of inseminated spermatozoa because it precludes the total recovery of the sample. Additionally, the insemination catheter could uphold this reduction causing sperm adhesion on the inner walls of the insemination catheter, decreasing even more the total inseminated volume. It is expected that utilizing an IUI approach that increases sperm volume in the fallopian tubes (0.5 mL rather than 0.2 mL) at the time of ovulation will lead to higher LBRs. To avoid bias related to sperm quality, the study population was restricted to dIUI cycles.
A parallel-group, double-blinded, RCT, including patients undergoing natural or stimulated dIUI, was performed between March 2013 and April 2015. dIUI cycles ( = 293) were randomized through a computer-generated list to undergo insemination with 0.2 mL (control group) or 0.5 mL (study group), of which 24 were excluded (protocol deviation) and 269 received the allocated intervention. Patients with the presence of tubal factor infertility, grades III-IV endometriosis, >3 previous dIUI cycles or with ≥3 follicles >14 mm were excluded. The study was designed with 80% power to detect a 5% difference in LBR with a reference of 15% and a two-tailed 5% significance level. The required sample size was 118 per group.
PARTICIPANTS/MATERIALS SETTING AND METHOD: There were 143 cycles (0.2 mL group) and 126 cycles (0.5 mL group). The primary end-point of the trial was LBR per dIUI cycle in both treatment groups. Clinical pregnancy rate and miscarriage rate were evaluated as secondary outcomes.
No adverse events were reported during the study trial. Study groups (0.2 versus 0.5 mL, respectively) were similar in age (35.8 ± 3.9 versus 35.4 ± 4.0 years: mean±SD), and had similar anti-Mullerian hormone levels (2.2 ± 1.8 versus 2.0 ± 1.5 ng/mL), basal antral follicle count (13.2 ± 6.4 versus 13.6 ± 6.0), BMI (23.5 ± 3.9 versus 23.7 ± 4.1 kg/m), number of follicles >17 mm (1.1 ± 0.5 versus 1.1 ± 0.5), total gonadotrophin dose (553.1 ± 366.3 versus 494.6 ± 237.1 IU), and total motile sperm count (8.22 ± 7.1 versus 7.7 ± 5.7 million). Similar clinical pregnancy rates (18.9% (27/143) versus 19.8% (25/126), NS), LBRs (15.4% (22/143) versus 19.0% (24/126), NS) and miscarriage rates (18.5% (5/27) versus 4.0% (1/25), NS) were observed between groups.
The study was not powered to detect differences in the secondary outcomes, clinical pregnancy and miscarriage rates. The randomization was performed at the dIUI cycle level, therefore, the results are reported as success rate per dIUI cycle rather than per patient.
This is the first RCT to show that the inseminated volume is not correlated with the probability of a live birth. The miscarriage rate was higher in the 0.2 mL group, although this difference was not statistically significant. If the lower miscarriage rate observed in the 0.5 mL group is confirmed, this could be related to the presence of uterine contractions similar of those generated during sexual intercourse, which may be implicated in the inception of early biochemical embryo-endometrium communication.
STUDY FUNDING/COMPETING INTERESTS: All authors declare having no conflict of interest with regard to this trial. No funding was received for this study. This research was performed under the auspices of 'Càtedra d'Investigació en Obstetrícia I Ginecologia' of the Department of Obstetrics, Gynaecology and Reproductive Medicine, Hospital Universitari Quiron-Dexeus, Universitat Autònoma de Barcelona.
The trial was registered at clinicaltrials.gov (Identifier: NCT03006523).
与常规的0.2mL授精体积相比，供体宫腔内人工授精（dIUI）周期采用0.5mL授精体积时对活产率（LBR）有何影响？
dIUI周期采用0.5mL与0.2mL授精体积时的LBR没有差异。
宫腔内人工授精在严重男性不育症治疗中具有重要作用，常用于同性女性伴侣和单亲家庭。人们已经研究了不同变量以确定与临床结局相关的因素（宫腔内人工授精的时间安排、卵巢刺激、精子参数），但对授精体积了解甚少。使用锥形底试管可能会导致大量授精精子的损失，因为无法完全回收样本。此外，授精导管可能会加剧这种减少，导致精子粘附在授精导管内壁，进一步减少总授精体积。预计在排卵时采用能增加输卵管内精子体积（0.5mL而非0.2mL）的宫腔内人工授精方法会带来更高的LBR。为避免与精子质量相关的偏倚，研究人群仅限于dIUI周期。
研究设计、规模与持续时间：一项平行组、双盲、随机对照试验，纳入接受自然或刺激dIUI的患者，于2013年3月至2015年4月进行。通过计算机生成的列表将dIUI周期（n = 293）随机分为接受0.2mL授精（对照组）或0.5mL授精（研究组），其中24个周期被排除（方案偏差），269个周期接受了分配的干预。排除存在输卵管因素不孕、III-IV级子宫内膜异位症、既往有>3个dIUI周期或有≥3个直径>14mm卵泡的患者。该研究设计的检验效能为80%，以检测LBR有5%的差异，参考值为15%，双侧显著性水平为5%。每组所需样本量为118个周期。
参与者/材料、设置与方法：0.2mL组有143个周期，0.5mL组有126个周期。试验的主要终点是两个治疗组每个dIUI周期的LBR。临床妊娠率和流产率作为次要结局进行评估。
研究试验期间未报告不良事件。研究组（分别为0.2mL与0.5mL）在年龄（35.8±3.9岁与35.4±4.0岁：均值±标准差）、抗苗勒管激素水平（2.2±1.8ng/mL与2.0±1.5ng/mL）、基础窦卵泡计数（13.2±6.4与13.6±6.0）、体重指数（23.5±3.9kg/m²与23.7±4.1kg/m²）、直径>17mm的卵泡数量（1.1±0.5与1.1±0.5）、总促性腺激素剂量（553.1±366.3IU与494.6±237.1IU）以及总活动精子计数（8.22±7.1与7.7±5.7百万）方面相似。两组间观察到相似的临床妊娠率（18.9%（27/143）与19.8%（25/126），无显著性差异）、LBR（15.4%（(22/143）与19.0%（24/126），无显著性差异）和流产率（18.5%（5/27）与4.0%（1/25），无显著性差异）。
局限性、谨慎的原因：该研究的检验效能不足以检测次要结局（临床妊娠和流产率）的差异。随机化是在dIUI周期水平进行的，因此，结果报告为每个dIUI周期的成功率而非每位患者的成功率。
这是第一项随机对照试验表明授精体积与活产概率无关。0.2mL组的流产率较高，尽管这种差异无统计学意义。如果在0.5mL组观察到的较低流产率得到证实，这可能与类似于性交时产生的子宫收缩有关，子宫收缩可能参与早期生化胚胎-子宫内膜通讯的起始过程。
研究资金/利益冲突：所有作者声明在本试验中不存在利益冲突。本研究未获得资金支持。本研究是在巴塞罗那自治大学基隆-德克塞斯大学医院妇产科与生殖医学系的“妇产科研究讲座”的支持下进行的。
该试验在clinicaltrials.gov注册（标识符：NCT03006523）。
