Marron Kevin, Harrity Conor
Reprod Fertil. 2025 Jan 11;6(1). doi: 10.1530/RAF-24-0034. Print 2025 Jan 1.
Blood lymphocyte reference ranges in non-pregnant females are established, but changes in pregnancy are less well understood. The early identification of immunological markers that could suggest an increased risk of early pregnancy loss may allow for timely intervention to improve outcomes. A lymphocytic immunophenotype provides a broad assessment of important immune parameters and potential indicators, which may be of relevance to pregnancy outcome. Comparison of immunophenotype results on the day of a positive hCG after embryo transfer between successful and failed pregnancies allows for this assessment. Baseline non-pregnant lymphocyte percentage and cell/µL profiles were established with a comprehensive panel on 93 age-matched male factor controls. Sixty-five in-vitro fertilisation (IVF) patients had an immunophenotype assessment on the day of a positive hCG, followed by further hCG tests and ultrasound monitoring as required to ultimately evaluate success (live birth) or failure (miscarriage). Thirty-one pregnancies were viable, leading to a live birth, while 34 ended in miscarriage. Total CD56, pNK, NKT, CD4 and CD8 levels were equivalent between all groups. Regardless of the outcome, B lymphocytes increased in pregnancy compared to controls. Of interest, in the later miscarriage cohort, pNK-specific CD69 was reduced (1.6 vs 5.4%, P = 0.02), while CD57+ cells were increased (45.4 vs 38.9%, P = 0.025). Corresponding changes were observed in cell/µL concentrations. Low level CD69 activation and elevated CD56dim and CD57+ NK cells were identified as markers that could potentially identify a pregnancy at risk of miscarriage, with further study needed to explore whether these changes represent cause or effect.
Unexplained infertility remains a difficult issue for patients and physicians alike, but despite recent diagnostic strides and innovative methods, there are no clear solutions on the horizon. Pregnancies can still occur in these challenging populations, either spontaneously or by interventions such as IVF. The early identification of various immune markers by blood sampling that may correlate with the subsequent outcome could be beneficial in identifying pregnancies at increased risk of miscarriage and perhaps allowing for timely and effective interventions.
非妊娠女性的血液淋巴细胞参考范围已确定，但孕期的变化尚不太清楚。早期识别可能提示早期流产风险增加的免疫标志物，或许能及时进行干预以改善结局。淋巴细胞免疫表型可对重要免疫参数和潜在指标进行全面评估，这可能与妊娠结局相关。通过比较胚胎移植后hCG阳性当天成功妊娠和失败妊娠的免疫表型结果，可进行此项评估。利用一个综合检测板对93名年龄匹配的男性因素对照者建立了非妊娠基线淋巴细胞百分比和细胞/µL图谱。65名体外受精（IVF）患者在hCG阳性当天进行了免疫表型评估，随后根据需要进行进一步的hCG检测和超声监测，以最终评估成功（活产）或失败（流产）情况。31例妊娠成功并活产，34例以流产告终。所有组的总CD56、pNK、NKT、CD4和CD8水平相当。无论结局如何，与对照组相比，孕期B淋巴细胞均增加。有趣的是，在晚期流产队列中，pNK特异性CD69降低（1.6%对5.4%，P = 0.02），而CD57 +细胞增加（45.4%对38.9%，P = 0.025）。在细胞/µL浓度方面也观察到了相应变化。低水平的CD69激活以及CD56dim和CD57 + NK细胞升高被确定为可能识别有流产风险妊娠的标志物，还需要进一步研究来探讨这些变化是原因还是结果。
不明原因的不孕症对患者和医生来说仍然是个难题，但尽管近期在诊断方面取得了进展并采用了创新方法，目前仍没有明确的解决方案。在这些具有挑战性的人群中，妊娠仍可能自然发生或通过IVF等干预措施实现。通过血液采样早期识别各种可能与后续结局相关的免疫标志物，可能有助于识别流产风险增加的妊娠，并可能允许及时进行有效干预。
