Effects of Estrogen Application Duration in HRT-FET on Pregnancy Outcomes
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摘要:
目的 探讨雌激素应用天数对使用激素替代疗法冻融胚胎移植（hormone replacement therapy-frozen thawed embryo transfer，HRT-FET）育龄期女性妊娠结局的影响。 方法 采用病例对照研究，回顾性分析2017年01月至2020年12月在昆明医科大学第二附属医院生殖医学科接受HRT-FET的1 348个周期患者临床资料，根据患者内膜转化前雌激素应用天数分为4组：A组（≤12 d），B组（13～16 d），C组（17～20 d），D组（> 20 d），比较4组患者的一般临床特征和妊娠结局。统计学分析，计量资料的多组间比较采用单因素方差分析，计数资料采用χ2检验。 结果 4组患者子宫内膜转化日的内膜厚度、雌激素（E2）比较，A组的子宫内膜厚度最高，其他组依次递减，A组的E2水平最低，其他组依次递增，差异具有统计学意义（P < 0.05）。4组患者一般临床特征比较，不孕年限、取卵年龄、抗缪勒管激素（AMH）、体重指数（BMI）、子宫内膜转化日孕酮（P）水平比较均无显著性差异（P > 0.05）。4组患者妊娠结局比较，HCG阳性率、临床妊娠率、异位妊娠率、早期流产率、活产率、单胎早产率、单胎低出生体重儿率，差异无统计学意义（P > 0.05）。 结论 对于HRT-FET周期的患者，延长雌激素应用时长或许可以改善子宫内膜增长不良患者的内膜厚度，虽然其内膜厚度较正常患者相比仍有差异，但可获得与正常子宫内膜患者相似的妊娠结局。 Abstract:Objective To investigate the effect of estrogen application duration on pregnancy outcomes in women of childbearing age during hormone replacement therapy frozen-thawed embryo transfer （HRT-FET）. Methods A case-control study was conducted to retrospectively analyze the clinical data of 1, 348 patients who underwent HRT-FET at the Reproductive Medicine Department of the Second Affiliated Hospital of Kunming Medical University from January 2017 to December 2020. The patients were divided into four groups based on the number of days of estrogen application before endometrial transformation: Group A （≤12 days）, Group B （13-16 days）, Group C （17-20 days）, and Group D （> 20 days）. The general clinical characteristics and pregnancy outcomes of the four groups of patients were compared. Statistical analysis included one-way analysis of variance for continuous variables and chi-square test for categorical variables. Results The endometrial thickness and estradiol （E2） levels on the day of endometrial transformation were compared among four groups of patients. Group A had the highest endometrial thickness, while the other groups showed a decreasing trend. Group A had the lowest E2 level, while the other groups showed an increasing trend. The differences were statistically significant （P < 0.05）. General clinical characteristics, including infertility duration, age at oocyte retrieval, anti-Mullerian hormone （AMH） levels, body mass index （BMI）, and progesterone （P） levels on the day of endometrial transformation, showed no significant differences among the four groups （P > 0.05）. Comparison of pregnancy outcomes among the four groups of patients, including HCG positive rate, clinical pregnancy rate, ectopic pregnancy rate, early miscarriage rate, live birth rate, singleton preterm birth rate, and singleton low birth weight rate, showed no statistically significant differences （P > 0.05）. Conclusion For patients with HRT-FET cycles, extending the duration of estrogen application may improve the endometrial thickness of patients with inadequate endometrial growth. Although there are still differences in endometrial thickness compared to normal patients, similar pregnancy outcomes as normal endometrial patients can be achieved. -
Key words:
- Freeze-thaw embryo transfer /
- Hormone replacement cycle /
- Estrogen /
- Pregnancy outcome
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表 1 4组患者的基线资料（
$\bar x \pm s $ ）Table 1. Baseline characteristics of the four groups patients （
$\bar x \pm s $ ）分组 n 取卵年龄（岁） 不孕年限（a） BMI（kg/m2） AMH （ng/mL） ≤12 d组 165 32.69 ± 3.95 4.01 ± 3.37 22.29 ± 3.12 4.78 ± 3.51 13～16 d组 672 32.55 ± 4.01 4.05 ± 3.00 22.70 ± 2.88 5.35 ± 4.17 17～20 d组 430 32.02 ± 3.97 3.70 ± 2.91 22.74 ± 3.03 5.26 ± 3.43 >20 d组 81 32.44 ± 4.30 4.06 ± 2.75 22.71 ± 3.15 4.94 ± 2.32 P 0.129 0.266 0.388 0.325 
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表 2 4组移植情况的比较（
$\bar x \pm s $ ）Table 2. Embryo parameters of the four groups patients （
$\bar x \pm s $ ）分组 n 补佳乐总剂量（mg） 转化日子宫内膜厚度（mm） 内膜转化日E2（pg/mL） 内膜转化日（ng/mL） ≤12 d组 165 62.66 ± 12.79 9.30 ± 1.66 239.69 ± 146.25 0.27 ± 0.25 13～16 d组 672 83.84 ± 14.93 9.01 ± 1.66 278.53 ± 307.89 0.31 ± 0.64 17～20 d组 430 116.03 ± 113.66 8.65 ± 1.75 410.84 ± 533.39 0.40 ± 2.89 >20 d组 81 143.01 ± 21.91 8.38 ± 2.02 580.30 ± 718.50 0.26 ± 0.19 P <0.0001* 0.0001* 0.0001* 0.780 *P < 0.05。
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表 3 4组妊娠结局的比较（%）（1）
Table 3. Clinical outcomes of the four groups （%）（1）
分组 n HCG阳性率 临床妊娠率 异位妊娠率 早期流产率 ≤12 d组 165 52.73（87/165） 46.06
（76/165）1.21
（2/27）6.06
（10/76）13～16 d组 672 55.65（374/672） 47.62
（320/672）0.74
（5/320）6.10（41/320） 17～20 d组 430 60.47（260/430） 53.02
（228/430）1.16
（5/228）5.35（23/228） >20 d组 81 59.26（48/81） 44.44
（36/81）0.00
（0/36）4.94
（4/36）P 0.261 0.209 0.157 0.777
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表 3 4组妊娠结局的比较（%）（2）
Table 3. Clinical outcomes of the four groups patients （%）（2）
分组 n 活产率 单胎早产率 单胎低出生体重儿率 ≤12 d组 165 35.76（59/165） 0.53（4/381） 5.26（2/38） 13～16 d组 672 37.50（252/672） 12.35（21/170） 12.94（22/170） 17～20d组 430 43.95（189/430） 8.87（11/124） 5.65（7/124） >20 d组 81 37.04（30/81） 13.64（3/22） 18.18（4/22） P 0.119 0.778 0.075 *P < 0.05。
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[1] Mackens S,Santos-Ribeiro S,van de Vijver A,et al. Frozen embryo transfer: A review on the optimal endometrial preparation and timing[J]. Hum Reprod,2017,32(11):2234-2242. doi: 10.1093/humrep/dex285 [2] Vinsonneau L,Labrosse J,Porcu-Buisson G,et al. Impact of endometrial preparation on early pregnancy loss and live birth rate after frozen embryo transfer:A large multicenter cohort study (14 421 frozen cycles)[J]. Hum Reprod Open,2022,(2):7. [3] 王丽燕,符晓倩,罗宇迪,等. 超生理剂量雌激素方案对内膜薄患者子宫内膜厚度及FET妊娠结局的影响[J]. 生殖医学杂志,2022,31(1):63-69. [4] Alyasin A,Agha-Hosseini M,Kabirinasab M,et al. Serum progesterone levels greater than 32.5 ng/ml on the day of embryo transfer are associated with lower live birth rate after artificial endometrial preparation:A prospective study[J]. Reprod Biol Endocrinol,2021,19(1):24. doi: 10.1186/s12958-021-00703-6 [5] 李红真. 雌、孕激素暴露时间及其血清浓度对人工周期冻融胚胎移植结局的影响[J]. 中华生殖与避孕杂志,2021,41(3):257-263. [6] 张欣,王琇,魏学聪等. 冻融胚胎移植中激素替代周期雌激素应用天数对妊娠结局的影响[J]. 中国计划生育学杂志,2021,29(1):33-37. [7] Mumusoglu S,Polat M,Ozbek IY,et al. Preparation of the endometrium for frozen embryo transfer: A systematic review[J]. Front Endocrinol (Lausanne),2021,12:688237. doi: 10.3389/fendo.2021.688237 [8] Madero S,Rodriguez A,Vassena R,et al. Endometrial preparation: effect of estrogen dose and administration route on reproductive outcomes in oocyte donation cycles with fresh embryo transfer[J]. Hum Reprod.,2016,31(8):1755-1764. doi: 10.1093/humrep/dew099 [9] 张平贵. 宫腔分泌蛋白谱评估促排卵周期内膜容受性的研究[D]. 上海: 上海交通大学, 2013. [10] 周建新,阮焱. 3484例高龄孕妇妊娠结局分析[J]. 中国医刊,2018,53(9):1015-1019. [11] Jiang W J,Song J Y,Sun Z G. Short (seven days) versus standard (fourteen days) oestrogen administration in a programmed frozen embryo transfer cycle: a retrospective cohort study[J]. J Ovarian Res,2022,15(1):36. doi: 10.1186/s13048-022-00967-5 [12] Younis J S,Mordel N,Lewin A,et al. Artificial endometrial preparation for oocyte donation: the effect of estrogen stimulation on clinical outcome[J]. J Assist Reprod Genet,1992,9(3):222-227. doi: 10.1007/BF01203817 [13] 练春静. 不同内膜准备方案对PCOS患者冻融胚胎移植妊娠结局的影响[D]. 桂林: 桂林医学院, 2022. [14] Chen H,Cai J,Liu L,et al. Roles of estradiol levels on the day of human chorionic gonadotrophin administration in the live birth of patients with frozen embryo transfer[J]. J Clin Lab Anal,2020,34(9):e23422. [15] 冯文娟. 雌激素阴道给药改善薄型子宫内膜容受性的研究[D]. 济南: 山东大学, 2022. [16] An J,Li L,Zhang X,et al. A clinical and basic study of optimal endometrial preparation protocols for patients with infertility undergoing frozen-thawed embryo transfer[J]. Exp Ther Med,2020,20(3):2191-2199. [17] Ying Y,Wu Y,Liu S,et al. The timing for initiating estrogen stimulation in artificial cycle for frozen-thawed embryo transfer can be flexible[J]. Reprod Health,2021,18(1):181. doi: 10.1186/s12978-021-01229-1 [18] Bourdon M,Santulli P,Kefelian F,et al. Prolonged estrogen (E2) treatment prior to frozen-blastocyst transfer decreases the live birth rate[J]. Hum Reprod,2018,33(5):905-913. doi: 10.1093/humrep/dey041 [19] 闫娅妮,张健,杨娜等. 人工周期中延长雌激素治疗时间可降低冻融胚胎移植的活产率[J]. 中国优生与遗传杂志,2020,28(7):891-894. [20] Hizkiyahu R,Suarthana E,Kadour Peero E,et al. Does increasing estrogen dose during frozen embryo transfer affect pregnancy rate?[J]. J Assist Reprod Genet,2022,39(5):1081-1085. doi: 10.1007/s10815-022-02470-8 [21] 马兰,镡颖,陈静思. 移植后补充戊酸雌二醇对IVF-ET妊娠结局的影响[J]. 昆明医科大学学报,2013(11):93-96. [22] Kong N,Liu J,Zhang C,et al. The relationship between serum oestrogen levels and clinical outcomes of hormone replacement therapy-frozen embryo transfer: a retrospective clinical study[J]. BMC Pregnancy Childbirth,2022,22(1):265. doi: 10.1186/s12884-022-04605-2 [23] 李林玲. 排卵日孕酮水平与自然周期冻胚移植结局关系分析[D]. 济南: 山东大学, 2022. [24] Boynukalin F K,Gultomruk M,Cavkaytar S,et al. Parameters impacting the live birth rate per transfer after frozen single euploid blastocyst transfer[J]. PLoS One,2020,15(1):e0227619. doi: 10.1371/journal.pone.0227619 -
