激素替代方案准备内膜的冻胚移植前雌激素治疗时间对新生儿体质量的影响

doi:10.6040/j.issn.1671-7554.0.2024.1447

摘要/Abstract

摘要： 目的探讨激素替代方案(hormone replacement therapy, HRT)准备子宫内膜的冻融胚胎移植(frozen embryo transfer, FET)周期中,胚胎移植前较为理想的雌激素用药时间。方法回顾性分析2012年2月至2020年2月期间以激素替代方案准备子宫内膜、行单囊胚FET并获得单胎活产的患者,共有4 577个周期被纳入分析。根据冻融胚胎移植前雌激素治疗天数分为3组:12~16 d 组(n=1 078)、17~20 d 组(n=2 924)、21~31 d 组(n=575)。主要分析指标为新生儿体质量,次要分析指标包括早产、妊娠期糖尿病、妊娠期高血压、子痫前期、剖宫产、胎膜早破、胎盘早剥、胎盘前置、产后出血、新生儿性别。结果经回归校正混杂因素后,三组间新生儿体质量、小于胎龄儿、大于胎龄儿、巨大儿发生率差异无统计学意义。胚胎移植前雌激素治疗时间21~31 d 与12~16 d 组相比低出生体质量儿发生率显著升高(aOR=1.780,95%CI: 1.055~3.003,P=0.031)。其他妊娠并发症及新生儿结局如早产、妊娠期糖尿病、妊娠期高血压、子痫前期、剖宫产、胎盘早剥、前置胎盘、产后出血、新生儿性别的差异也无统计学意义(P>0.05)。结论在单囊胚冻融胚胎移植周期中,三组间新生儿体质量差异无统计学意义, 但与雌激素使用时间12~16 d 组相比,21~31 d 组的雌激素治疗会增加低出生体质量儿的发生率,差异有统计学意义。雌激素使用时间在21 d 内不会对新生儿体质量以及母婴并发症产生负面影响,在临床上需结合患者实际情况合理安排时间。

关键词: 胚胎冷冻, 胚胎移植, 雌二醇, 治疗时间, 妊娠结局

Abstract: Objective To investigate the optimal estrogen exposure duration prior to embryo transfer in frozen embryo transfer(FET)cycles with hormone replacement therapy(HRT)for endometrial preparation. Methods This was a retrospective cohort study. Patients who underwent HRT regimen for endometrial preparation before FET and single blastocyst transfer and achieved singleton live birth between 2012 and 2020 were included in the analysis. Overall, 4,577 FET cycles were included for analyses. According to the duration of estrogen treatment before embryo transfer, we divided the cycles into three groups: 12-16 days group(n=1,078), 17-20 days group(n=2,924), and 21-31 days group(n=575). The main outcome measures were neonatal birthweight, and secondary outcomes were gestational diabetes mellitus(GDM), gestational hypertension(HDP), preeclampsia, cesarean section, premature abruption, placenta previa, postpartum hemorrhage, sex of neonates, preterm delivery, small-for-gestational age(SGA), large-for-gestational age(LGA), low birth weight(LBW)and macrosomia. Results There was no significant difference in neonatal birthweight, SGA, LGA, macrosomia among the three groups. The rate of LBW was higher in the 21-31 days group than the 12-16 days group(aOR=1.780, 95%CI: 1.055-3.003, P=0.031). The rates of other pregnancy and neonatal outcomes such as preterm delivery, GDM, HDP, preeclampsia, cesarean section, premature abruption, placenta previa, and postpartum hemorrhage, neonatal outcomes, including sex of neonates were also comparable among the three groups(P>0.05). Conclusion There is no significant difference in birthweight among the three groups, but longer estrogen treatment duration before embryo transfer is associated with a higher rate of LBW in HRT regimen for endometrial preparation before FET. These findings suggest that clinical protocols should individualize estrogen exposure duration based on patient characteristics.

Key words: Frozen embryo, Embryo transfer, Estradiol, Duration of treatment, Pregnancy outcomes

中图分类号:

R714.8

韩馨玮,牛月,魏代敏. 激素替代方案准备内膜的冻胚移植前雌激素治疗时间对新生儿体质量的影响[J]. 山东大学学报 (医学版), 2025, 63(11): 46-52.

HAN Xinwei, NIU Yue, WEI Daimin. Influence of the duration of estrogen treatment prior to frozen embryo transfer in hormone replacement protocols in endometrial preparation on neonatal birth weight[J]. Journal of Shandong University (Health Sciences), 2025, 63(11): 46-52.

参考文献

[1] Glujovsky D, Pesce R, Sueldo C, et al. Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes[J]. Cochrane Database Syst Rev, 2020, 10(10): CD006359. doi: 10.1002/14651858.CD006359.pub3
[2] 赵娟, 邹奕洁, 谈勇, 等. 3种不同内膜准备方案对行冻融胚胎移植周期多囊卵巢综合征患者子宫内膜容受性及妊娠结局影响[J]. 临床军医杂志, 2025, 53(2): 181-183, 187.
[3] Zhang JW, Du MZ, Wang ZK, et al. The duration of estrogen treatment before progesterone application does not affect neonatal and perinatal outcomes in frozen embryo transfer cycles[J]. Front Endocrinol, 2023, 14: 988398. doi: 10.3389/fendo.2023.988398
[4] Li XF, Shi WH, Gao YE, et al. Is duration of estrogen supplementation associated with clinical outcomes in frozen-thawed autologous single-blastocyst transfer cycles?[J]. J Assist Reprod Genet, 2022, 39(5): 1087-1094.
[5] 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. YAN Yani, ZHANG Jian, YANG Na, et al. Prolonged estrogen(E2)treatment prior to frozen-blastocyst transfer decreases the live birth rate[J]. Chinese Journal of Birth Health & Heredity, 2020, 28(7): 891-894.
[6] 邢雅纯, 苏雁, 赵纯, 等. 降调节激素替代方案中雌激素启动时机对冻融胚胎移植妊娠结局的影响[J]. 国际生殖健康/计划生育杂志, 2021, 40(2): 89-92. XING Yachun, SU Yan, ZHAO Chun, et al. Effect of estrogen starting time on the outcome of frozen-thawed embryo transfer in hormone replacement treatment after GnRHa down regulation[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(2): 89-92.
[7] Ganer Herman H, Volodarsky-Perel A, Nu TNT, et al. The effect of oestrogen dose and duration in programmed frozen cycles on obstetric outcomes and placental findings[J]. Reprod Biomed Online, 2023, 46(4): 760-766.
[8] Chen Z-J, Shi YH, Sun Y, et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome[J]. N Engl J Med, 2016, 375(6): 523-533.
[9] Wei DM, Liu JY, Sun Y, et al. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial[J]. Lancet, 2019, 393(10178): 1310-1318.
[10] Shi YH, Sun Y, Hao CF, et al. Transfer of fresh versus frozen embryos in ovulatory women[J]. N Engl J Med, 2018, 378(2): 126-136.
[11] Zegers-Hochschild F, Adamson GD, Dyer S, et al. The international glossary on infertility and fertility care, 2017[J]. Hum Reprod, 2017, 32(9): 1786-1801.
[12] Dai L, Deng CF, Li YH, et al. Birth weight reference percentiles for Chinese[J]. PLoS One, 2014, 9(8): e104779. doi: 10.1371/journal.pone.0104779
[13] Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment[J]. Nat Rev Endocrinol, 2018, 14(5): 270-284.
[14] Bahri Khomami M, Joham AE, Boyle JA, et al. Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity: a systematic review, meta-analysis, and meta-regression[J]. Obes Rev, 2019, 20(5): 659-674.
[15] Carson SA, Kallen AN. Diagnosis and management of infertility: a review[J]. JAMA, 2021, 326(1): 65-76.
[16] Qin JB, Sheng XQ, Wu D, et al. Worldwide prevalence of adverse pregnancy outcomes among singleton pregnancies after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis[J]. Arch Gynecol Obstet, 2017, 295(2): 285-301.
[17] Cavoretto P, Candiani M, Giorgione V, et al. Risk of spontaneous preterm birth in singleton pregnancies conceived after IVF/ICSI treatment: meta-analysis of cohort studies[J]. Ultrasound Obstet & Gyne, 2018, 51(1): 43-53.
[18] Lang MN, Zhou MY, Lei RB, et al. Comparison of pregnancy outcomes between IVF-ET pregnancies and spontaneous pregnancies in women of advanced maternal age[J]. J Matern Fetal Neonatal Med, 2023, 36: 2183761. doi: 10.1080/14767058.2023.2183761
[19] Pinborg A, Wennerholm UB, Romundstad LB, et al. Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? Systematic review and meta-analysis[J]. Hum Reprod Update, 2013, 19(2): 87-104.
[20] Farhi J, Ben-Haroush A, Andrawus N, et al. High serum oestradiol concentrations in IVF cycles increase the risk of pregnancy complications related to abnormal placentation[J]. Reprod Biomed Online, 2010, 21(3): 331-337.
[21] Zhang JW, Du MZ, Sun LJ. Supraphysiological estradiol levels on the hCG trigger day are associated with SGA for singletons born from fresh embryo transfer[J]. J Dev Orig Health Dis, 2022, 13(2): 244-251.
[22] Pereira N, Elias RT, Christos PJ, et al. Supraphysiologic estradiol is an independent predictor of low birth weight in full-term singletons born after fresh embryo transfer[J]. Hum Reprod, 2017, 32(7): 1410-1417.
[23] Huang JL, Lu XF, Lin JY, et al. Association between peak serum estradiol level during controlled ovarian stimulation and neonatal birthweight in freeze-all cycles: a retrospective study of 8501 singleton live births[J]. Hum Reprod, 2020, 35(2): 424-433.
[24] Yang XY, Zhang J, Wu JY, et al. Association between the number of oocytes retrieved and neonatal outcomes after freeze-all IVF cycles[J]. Hum Reprod, 2019, 34(10): 1937-1947.
[25] 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.
[26] Ma W-G, Song H, Das SK, et al. Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation[J]. Proc Natl Acad Sci U S A, 2003, 100(5): 2963-2968.
[27] Sekhon L, Feuerstein J, Pan S, et al. Endometrial preparation before the transfer of single, vitrified-warmed, euploid blastocysts: does the duration of estradiol treatment influence clinical outcome?[J]. Fertil Steril, 2019, 111(6): 1177-1185.
[28] Mouhayar Y, Franasiak JM, Sharara FI. Obstetrical complications of thin endometrium in assisted reproductive technologies: a systematic review[J]. J Assist Reprod Genet, 2019, 36(4): 607-611.
[29] Moffat R, Beutler S, Schötzau A, et al. Endometrial thickness influences neonatal birth weight in pregnancies with obstetric complications achieved after fresh IVF-ICSI cycles[J]. Arch Gynecol Obstet, 2017, 296(1): 115-122.
[30] Guo ZZ, Xu XX, Zhang L, et al. Endometrial thickness is associated with incidence of small-for-gestational-age infants in fresh in vitro fertilization-intracytoplasmic sperm injection and embryo transfer cycles[J]. Fertil Steril, 2020, 113(4): 745-752.
[31] Zhang J, Liu HF, Mao XY, et al. Effect of endometrial thickness on birthweight in frozen embryo transfer cycles: an analysis including 6,181 singleton newborns[J]. Hum Reprod, 2019, 34(9): 1707-1715.

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