Department of Pathology, Erlangen University Hospital, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
Kaufbeuren-Ravensburg Institute of Pathology, Ravensburg, Germany.
Am J Reprod Immunol. 2022 Nov;88(5):e13620. doi: 10.1111/aji.13620. Epub 2022 Sep 23.
It is important to evaluate the dynamics of uterine natural killer (uNK) cells in hormone replacement therapy (HRT) cycles, given their potential role in implantation and the common usage of HRT cycles with in vitro fertilization (IVF).
A total of 132 subfertile patients were evaluated during the secretory phase of either natural ovulation (OV) or HRT cycles, with two biopsies taken on approximately days 5 and 10 after ovulation/progesterone administration in a single menstrual cycle. Immunohistochemical Personal Endometrial Maturation Analysis (PEMA) was used to better quantify secretory-phase endometrial development, in combination with subsequent evaluation of uNK cell density.
uNK cell density increased rapidly from the early to mid-secretory phase, with mean uNK densities of 113 and 117 per mm in first biopsies and 315 and 387 per mm in second biopsies for OV and HRT cycles, respectively. After reassessment of endometrial development with PEMA, the first and second biopsies in HRT and OV cycles were histologically dated to developmental ranges between days 15-20 (first biopsy) and days 19-25 (second biopsy).
Subfertile women showed variable endometrial development in PEMA assessment, with uNK cell density correlating with the dating results. Overall, comparable levels of uNK cell density were observed in OV and HRT cycles. Importantly, uNK cell density depends on the histological maturation stage, with similar low coefficients of determination. This observation suggests that aberrant uNK cell results more likely reflect displaced endometrial maturation, rather than an intrinsic anomaly in uNK cell trafficking.
考虑到自然杀伤（uNK）细胞在着床中的潜在作用以及激素替代疗法（HRT）与体外受精（IVF）联合应用的普遍性，评估其在 HRT 周期中的动态变化非常重要。
在自然排卵（OV）或 HRT 周期的分泌期，共评估了 132 名生育力低下的患者，在单个月经周期中，大约在排卵/孕酮给药后第 5 天和第 10 天进行两次活检。使用免疫组织化学个人子宫内膜成熟分析（PEMA）来更好地量化分泌期子宫内膜的发育情况，并随后评估 uNK 细胞密度。
uNK 细胞密度从早期到中期分泌期迅速增加，OV 和 HRT 周期的第一次活检中 uNK 细胞密度的平均值分别为 113 和 117 个/mm，第二次活检中分别为 315 和 387 个/mm。通过 PEMA 重新评估子宫内膜发育后，HRT 和 OV 周期的第一次和第二次活检在组织学上分别被标记为第 15-20 天（第一次活检）和第 19-25 天（第二次活检）。
在 PEMA 评估中，生育力低下的女性表现出不同的子宫内膜发育，uNK 细胞密度与发育结果相关。总体而言，OV 和 HRT 周期中观察到类似水平的 uNK 细胞密度。重要的是，uNK 细胞密度取决于组织学成熟阶段，具有相似的低决定系数。这一观察结果表明，uNK 细胞的异常结果更可能反映了子宫内膜成熟的移位，而不是 uNK 细胞迁移的内在异常。
