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Analysis of serum and endometrial progesterone in determining endometrial receptivity
Human Reproduction ( IF 6.1 ) Pub Date : 2021-08-04 , DOI: 10.1093/humrep/deab184
E Labarta 1, 2 , P Sebastian-Leon 2 , A Devesa-Peiro 2, 3 , P Celada 1 , C Vidal 1, 2 , J Giles 1, 2 , C Rodriguez-Varela 2 , E Bosch 1, 2 , P Diaz-Gimeno 2
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STUDY QUESTION Is there a relationship between serum and endometrial progesterone (P4) levels, including P4 and metabolites (oestrone, oestradiol and 17α-hydroxyprogesterone), and endometrial receptivity? SUMMARY ANSWER Serum P4 levels were not correlated with endometrial P4, nor associated with endometrial receptivity as determined by the ERA® test; however, endometrial P4 and 17α-hydroxyprogesterone levels were positively correlated and related to endometrial receptivity by ERA. WHAT IS KNOWN ALREADY Acquisition of endometrial receptivity is governed by P4, which induces secretory transformation. A close relationship between serum P4 and pregnancy outcome is reported for hormone replacement therapy (HRT) cycles. However, the relationship between serum and uterine P4 levels has not been described, and it is unknown whether uterine receptivity depends more on serum or uterine P4 levels. STUDY DESIGN, SIZE, DURATION A prospective cohort study was performed during March 2018–2019 in 85 IVF patients undergoing an evaluation-only HRT cycle with oestradiol valerate (6 mg/day) and micronised vaginal progesterone (400 mg/12 h). PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were under 50 years of age, had undergone at least one failed IVF cycle, had no uterine pathology, and had adequate endometrial thickness (> 6.5 mm). The study was conducted at IVI Valencia and IVI Foundation. An endometrial biopsy and a blood sample were collected after 5 days of P4 vaginal treatment. Measures included serum P4 levels, ERA®-based evaluation of endometrial receptivity, and endometrial P4 levels along with metabolites (oestrone, oestradiol and 17α-hydroxyprogesterone) measured by ultra-performance liquid chromatography–tandem mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE Seventy-nine women were included (mean age: 39.9 ± 4.6, BMI: 24.2 ± 3.9 kg/m2, endometrial thickness: 8.2 ± 1.4 mm). The percentage of endometria indicated as receptive by ERA® was 40.5%. When comparing receptive versus non-receptive groups, no differences were observed in baseline characteristics nor in steroid hormones levels in serum or endometrium. No association between serum P4 and endometrial steroid levels or ERA result was found (P < 0.05). When the population was stratified according to metabolite concentration levels, endometrial P4 and 17α-hydroxyprogesterone were significantly associated with endometrial receptivity (P < 0.05). A higher proportion of receptive endometria by ERA was observed when endometrial P4 levels were higher than 40.07 µg/ml (relative maximum) and a lower proportion of receptive endometria was associated with endometrial 17α-hydroxyprogesterone lower than 0.35 ng/ml (first quartile). A positive correlation R2 = 0.67, P < 0.001 was observed between endometrial P4 and 17α-hydroxyprogesterone levels. LIMITATIONS, REASONS FOR CAUTION This study did not analyse pregnancy outcomes. Further, the findings can only be extrapolated to HRT cycles with micronised vaginal progesterone for luteal phase support. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest that the combined benefits of different routes of progesterone administration for luteal phase support could be leveraged to ensure an adequate concentration of progesterone both in the uterus and in the bloodstream. Further studies will confirm whether this method can optimise both endometrial receptivity and live birth rate. Additionally, targeted treatment to increase P4 endometrial levels may normalise the timing of the window of implantation without needing to modify the progesterone administration day. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the IVI-RMA Valencia (1706-VLC-051-EL) and Consellería d’Educació, Investigació, Cultura, i esport Generalitat Valenciana (Valencian Government, Spain, GV/2018//151). Almudena Devesa-Peiro (FPU/15/01398) and Cristina Rodriguez-Varela (FPU18/01657) were supported by the FPU program fellowship from the Ministry of Science, Innovation and Universities (Spanish Government). P.D.-G. is co-inventor on the ERA patent, with non-economic benefits. The other authors have no competing interests. TRIAL REGISTRATION NUMBER NCT03456375.

中文翻译:

测定子宫内膜容受性的血清和子宫内膜黄体酮分析

研究问题 血清和子宫内膜孕酮 (P4) 水平(包括 P4 和代谢物(雌酮、雌二醇和 17α-羟基孕酮))与子宫内膜容受性之间是否存在关系?总结 答案 血清 P4 水平与子宫内膜 P4 无关,也与 ERA® 测试确定的子宫内膜容受性无关;然而,子宫内膜 P4 和 17α-羟孕酮水平与 ERA 的子宫内膜容受性呈正相关并相关。已知情况 子宫内膜容受性的获得受 P4 控制,它诱导分泌转化。据报道,激素替代疗法 (HRT) 周期的血清 P4 与妊娠结局之间存在密切关系。然而,尚未描述血清和子宫 P4 水平之间的关系,并且尚不清楚子宫容受性是否更多地取决于血清或子宫 P4 水平。研究设 参与者/材料、设置、方法 患者年龄在 50 岁以下,经历了至少一个失败的 IVF 周期,没有子宫病变,并且具有足够的子宫内膜厚度(>6.5 mm)。该研究在 IVI Valencia 和 IVI 基金会进行。在 P4 阴道治疗 5 天后收集子宫内膜活检和血样。测量包括血清 P4 水平、基于 ERA® 的子宫内膜容受性评估、子宫内膜 P4 水平以及代谢物(雌酮、通过超高效液相色谱-串联质谱法测量雌二醇和 17α-羟基孕酮。主要结果和机会的作用 包括 79 名女性(平均年龄:39.9 ± 4.6,BMI:24.2 ± 3.9 kg/m2,子宫内膜厚度:8.2 ± 1.4 mm)。ERA® 指示接受的子宫内膜的百分比为 40.5%。在比较接受组与非接受组时,基线特征和血清或子宫内膜中的类固醇激素水平均未观察到差异。未发现血清 P4 与子宫内膜类固醇水平或 ERA 结果之间存在关联(P < 0.05)。当根据代谢物浓度水平对人群进行分层时,子宫内膜 P4 和 17α-羟基孕酮与子宫内膜容受性显着相关(P < 0.05)。当子宫内膜 P4 水平高于 40.07 µg/ml(相对最大值)时,ERA 观察到较高比例的接受性子宫内膜,而接受性子宫内膜的较低比例与低于 0.35 ng/ml(第一四分位数)的子宫内膜 17α-羟基孕酮相关。正相关 R2 = 0.67,P<在子宫内膜 P4 和 17α-羟基孕酮水平之间观察到 0.001。限制,谨慎的原因 本研究没有分析妊娠结局。此外,这些发现只能外推到使用微粉化阴道黄体酮支持黄体期的 HRT 周期。研究结果的更广泛意义 我们的研究结果表明,黄体期支持的不同黄体酮给药途径的综合益处可以用来确保子宫和血流中的黄体酮浓度足够。进一步的研究将证实这种方法是否可以优化子宫内膜容受性和活产率。此外,增加 P4 子宫内膜水平的靶向治疗可以使植入窗口的时间正常化,而无需修改孕酮给药日。研究资金/竞争利益 本研究得到了 IVI-RMA Valencia (1706-VLC-051-EL) 和 Consellería d'Educació, Investigació, Cultura, i esport Generalitat Valenciana(瓦伦西亚政府,西班牙,GV/2018)的支持//151)。Almudena Devesa-Peiro (FPU/15/01398) 和 Cristina Rodriguez-Varela (FPU18/01657) 得到了科学、创新和大学部(西班牙政府)的 FPU 计划奖学金的支持。PD-G。是 ERA 专利的共同发明人,具有非经济利益。其他作者没有竞争利益。试用注册号 NCT03456375。
更新日期:2021-08-04
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