Andrology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Hum Reprod. 2020 Jun 1;35(6):1288-1295. doi: 10.1093/humrep/deaa070.
What is the relationship between the degree of sperm autoimmunisation, as assessed by IgG-mixed antiglobulin reaction (MAR) test, and natural and intrauterine insemination (IUI)-assisted live births?
Compared with a lower degree of positivity (50-99%), a 100%-positive MAR test was associated with a much lower occurrence of natural live births in infertile couples, who could be successfully treated with IUI, as first-line treatment.
The World Health Organization (WHO) has recommended screening for antisperm antibodies, through either the IgG-MAR test or an immunobead-binding test, as an integral part of semen analysis, with 50% antibody-coated motile spermatozoa considered to be the clinically relevant threshold. However, the predictive value of the degree of positivity of the MAR test above such a cut-off on the occurrence of natural pregnancies remains largely undetermined. Furthermore, the effectiveness of IUI in cases of strong sperm autoimmunisation is not yet well-established.
STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study on 108 men with a ≥50%-positive MAR test, where the couple had attended a university/hospital andrology/infertility clinic for the management of infertility from March 1994 to September 2017.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The IgG-MAR test was carried out as an integral part of semen analysis. The patients were divided into two groups: 100% and 50%-99%-positive MAR test. The post-coital test (PCT) was performed in all the couples, and IUI was offered as the first-line treatment. Laboratory and other clinical data were retrieved from a computerised database. Data on subsequent pregnancies were obtained by contacting patients over the telephone.
A total of 84 men (77.8%) were successfully contacted by telephone, and they agreed to participate. Of these, 44 men belonged to the group with a 100%-positive MAR test, while 40 showed lower MAR test positivity. The couples with a 100%-positive MAR test showed a natural live birth rate per couple (LBR) that was considerably lower than that observed with a lower degree of positivity (4.5% vs. 30.0%; P = 0.00001). Among the clinical variables, a significant difference between the two groups was observed only for the PCT outcome, which was poor in the 100%-positive MAR test group. Better PCT outcomes (categorised as negative, subnormal and good) were positively associated with the occurrence of natural live births (6.3, 21.7 and 46.2%, respectively; P = 0.0005 for trend), for which the sole independent negative predictor was the degree of sperm autoimmunisation. IUI was performed as the first-line treatment in 38 out of 44 couples with a 100%-positive MAR test, yielding 14 live births (36.8%). In couples with lower MAR test positivity, the LBR after IUI (26.9%) was similar to the natural LBR in this group (30.0%).
LIMITATIONS, REASONS FOR CAUTION: Given the retrospective nature of the study, we cannot exclude uncontrolled variables that may have affected natural pregnancies during the follow up or a selection bias from the comparison of natural live births with those after IUI.
The routine use of the IgG-MAR test in the basic fertility workup is justified as it influences decision making. A 100%-positive IgG-MAR test can represent the sole cause of a couple's infertility, which could be successfully treated with IUI. On the other hand, a lower degree of positivity may only represent a contributing factor to a couple's infertility, and so the decision to treat or wait also depends on the evaluation of conventional prognostic factors including the PCT outcome.
STUDY FUNDING, COMPETING INTEREST(S): This study was supported by PRIN 2017, Ministero dell'Università e della Ricerca Scientifica (MIUR), Italy. On behalf of all authors, the corresponding author states that there is no conflict of interest.
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抗精子自身免疫程度（通过 IgG-混合抗球蛋白反应 (MAR) 试验评估）与自然妊娠和宫腔内人工授精 (IUI) 辅助活产之间的关系如何？
与较低的阳性度（50-99%）相比，100%阳性的 MAR 试验与不孕夫妇自然活产的发生率低得多相关，这些夫妇可以成功地接受 IUI 作为一线治疗。
世界卫生组织 (WHO) 建议通过 IgG-MAR 试验或免疫珠结合试验筛查抗精子抗体，作为精液分析的一个组成部分，将 50%抗体包被的活动精子被认为是具有临床意义的临界值。然而，MAR 试验阳性度高于该临界值对自然妊娠发生率的预测价值在很大程度上仍未确定。此外，强烈的精子自身免疫在 IUI 中的有效性尚不清楚。
研究设计、大小、持续时间：这是一项回顾性队列研究，纳入了 108 名 MAR 试验阳性度≥50%的男性，这些夫妇于 1994 年 3 月至 2017 年 9 月在一所大学/医院男科/不孕不育诊所接受治疗。
参与者/材料、设置、方法：进行 IgG-MAR 试验作为精液分析的一个组成部分。将患者分为两组：100%和 50%-99%MAR 试验阳性。对所有夫妇进行后性交试验 (PCT)，并提供 IUI 作为一线治疗。从计算机化数据库中检索实验室和其他临床数据。通过电话联系患者获得后续妊娠数据。
共有 84 名男性（77.8%）成功通过电话联系并同意参与。其中，44 名男性属于 100%MAR 试验阳性组，而 40 名男性显示 MAR 试验阳性度较低。100%MAR 试验阳性组的自然活产率（LBR）明显低于较低阳性度组（4.5% vs. 30.0%；P=0.00001）。在临床变量中，仅 PCT 结果存在显著差异，100%MAR 试验阳性组的 PCT 结果较差。更好的 PCT 结果（分类为阴性、亚正常和良好）与自然活产的发生呈正相关（分别为 6.3%、21.7%和 46.2%；趋势 P=0.0005），唯一的独立负预测因子是精子自身免疫程度。在 44 名 100%MAR 试验阳性的夫妇中，有 38 对接受了 IUI 作为一线治疗，共产生了 14 例活产。在 MAR 试验阳性度较低的夫妇中，IUI 后的 LBR（26.9%）与该组的自然 LBR（30.0%）相似。
局限性、谨慎的原因：由于研究的回顾性性质，我们不能排除在随访期间自然妊娠过程中可能存在的不可控变量或从 IUI 后自然活产的比较中存在选择偏倚。
在基本生育评估中常规使用 IgG-MAR 试验是合理的，因为它会影响决策。100%阳性的 IgG-MAR 试验可以成为夫妇不孕的唯一原因，可以通过 IUI 成功治疗。另一方面，较低的阳性度可能仅代表夫妇不孕的一个促成因素，因此治疗或等待的决定也取决于包括 PCT 结果在内的常规预后因素的评估。
研究资金、利益冲突：这项研究得到了 PRIN 2017、意大利大学和科学研究部（MIUR）的支持。代表所有作者，通讯作者表示没有利益冲突。
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