nav emailalert searchbtn searchbox tablepage yinyongbenwen piczone journalimg journalInfo journalinfonormal searchdiv searchzone qikanlogo popupnotification paper paperNew
2025, 11, v.34 1457-1465
黄体生成素添加对子宫内膜异位症患者拮抗剂方案促排卵结局的影响
基金项目(Foundation):
邮箱(Email):
DOI:
摘要:

目的 探究子宫内膜异位症(EMs)对拮抗剂方案促排卵结局的影响,以及黄体生成素(LH)添加对EMs患者拮抗剂方案促排卵结局的影响。方法 回顾性分析2021年1月至2024年6月在我院行拮抗剂方案促排卵体外受精/卵胞浆内单精子注射(IVF/ICSI)助孕治疗患者的临床资料。根据不孕因素分为EMs组和非EMs组,使用倾向性评分匹配法(PSM)按照1∶1的比例进行匹配,最终两组各纳入421个周期,分别比较两组患者的基础情况及促排卵结局。此外,在两组内进一步根据促排卵期间是否添加LH分为添加LH亚组及不添加LH亚组,使用PSM按照1∶1的比例进行匹配,最终EMs组中添加/不添加LH亚组各纳入145个周期,非EMs组中添加/不添加LH亚组各纳入851个周期,分别比较两亚组间患者的基础情况及促排卵结局。结果 PSM匹配后EMs组、非EMs组两组间患者年龄、体质量指数(BMI)、基础性激素水平、抗苗勒管激素(AMH)水平、基础窦卵泡数(AFC)和IVF/ICSI周期比例等基础情况比较均无显著性差异(P>0.05),两组间促性腺激素(Gn)总量及天数、获卵数、成熟卵率(MⅡ卵率)、受精率、正常受精率、可用胚胎率和囊胚形成率等比较均无显著性差异(P>0.05)。EMs组中添加与不添加LH亚组间患者年龄、BMI、基础性激素水平、AMH水平、AFC和IVF/ICSI周期比例等基础情况比较均无显著性差异(P>0.05),亚组间获卵数、MⅡ卵率、受精率及正常受精率比较亦无显著性差异(P>0.05),但添加LH亚组可用胚胎率(57.34%vs. 51.90%)以及囊胚形成率(75.44%vs. 68.56%)显著高于不添加LH亚组(P<0.05);非EMs组中添加与不添加LH亚组间患者基线资料以及获卵数、MⅡ卵率、受精率、可用胚胎率和囊胚形成率比较均无显著性差异(P>0.05)。此外,PSM匹配后EMs组、非EMs组两组间的累积妊娠率比较无显著性差异(P>0.05),EMs组中添加LH亚组与不添加LH亚组的累积妊娠率比较亦无显著性差异(P>0.05)。结论 EMs并未降低拮抗剂方案促排卵助孕周期的卵子成熟率、正常受精率、可用胚胎率以及囊胚形成率;在EMs人群中,使用拮抗剂方案促排卵时添加LH能够明显增加可用胚胎率和囊胚形成率,提示LH添加可能改善EMs患者拮抗剂方案促排卵的卵母细胞质量。

Abstract:

Objectives:To investigate whether endometriosis(EMs) affects the outcomes of ovarian stimulation using a gonadotropin releasing hormone(GnRH) antagonist protocol, and to evaluate the effect of luteinizing hormone(LH) supplementation on the outcomes of ovarian stimulation with GnRH antagonist protocol in patients with EMs.Methods:A retrospective analysis was conducted on the clinical data of patients who underwent in vitro fertilization/intra-cytoplasmic sperm injection(IVF/ICSI) assisted reproduction using a GnRH antagonist protocol at Nanjing Drum Tower Hospital from January 2021 to June 2024. According to infertility factors, patients were divided into an EMs group and a non-EMs group. Propensity score matching(PSM) was performed at a 1∶1 ratio, with 421 cycles included in each group. Baseline characteristics and ovarian stimulation outcomes were compared between the two groups. Furthermore, within each group, patients were subdivided into an LH supplementation subgroup and a non-LH supplementation subgroup based on whether LH was added during ovarian stimulation. PSM was again applied at a 1∶1 ratio. Ultimately, 145 cycles were included in both the LH supplementation and non-supplementation subgroups within the EMs group, respectively. While 851 cycles were included in each corresponding subgroup within the non-EMs group. Baseline characteristics and ovarian stimulation outcomes were compared among the subgroups.Results:After PSM,there were no significant differences in baseline characteristics between the EMs and non-EMs groups, including age, body mass index(BMI),baseline sex hormone levels, anti-Müllerian hormone(AMH) level, antral follicle count(AFC),and the proportion of IVF/ICSI cycles(P>0.05). Additionally, there were no significant differences between the two groups in total dosage and duration of gonadotropin used, number of oocytes retrieved, oocyte maturation rate(MⅡ rate),fertilization rate, normal fertilization rate, available embryo rate and blastocyst formation rate(P>0.05). In the EMs group, there were no significant differences in baseline characteristics in terms of age, BMI,baseline sex hormone levels, AMH level, AFC and the proportion of IVF/ICSI cycles between the LH supplementation and non-supplementation subgroups(P>0.05). The number of oocytes retrieved, MⅡ rate, fertilization rate, and normal fertilization rate were also comparable between the two subgroups(P>0.05). However, the available embryo rate(57.34% vs. 51.90%) and blastocyst formation rate(75.44% vs. 68.56%) were significantly higher in the LH supplementation subgroup than those in the non-supplementation subgroup(P<0.05). In the non-EMs group, there were no significant differences in baseline characteristics, number of oocytes retrieved, MⅡ rate, fertilization rate, available embryo rate and blastocyst formation rate between the LH supplementation and non-supplementation subgroups(P>0.05). Additionally, after PSM,no significant difference was observed in cumulative pregnancy rate between the EMs and non-EMs groups(P>0.05),nor between the LH supplementation and non-supplementation subgroups within the EMs group(P>0.05).Conclusions:EMs does not reduce oocyte maturation rate, normal fertilization rate, available embryo rate and blastocyst formation rate in ovarian stimulation cycles of GnRH antagonist protocol. In patients with EMs, LH supplementation during ovarian stimulation with an GnRH antagonist protocol can significantly improve available embryo rate and blastocyst formation rate, suggesting that LH supplementation may enhance oocyte quality in EMs patients undergoing GnRH antagonist protocol.

参考文献

[1] Bonavina G,Taylor HS.Endometriosis-associated infertility:From pathophysiology to tailored treatment[J].Front Endocrinol (Lausanne),2022,13:1020827.

[2] Clower L,Fleshman T,Geldenhuys WJ,et al.Targeting oxidative stress involved in endometriosis and its pain[J].Biomolecules,2022,12:1055.

[3] Shebl O,Sifferlinger I,Habelsberger A,et al.Oocyte competence in in vitro fertilization and intracytoplasmic sperm injection patients suffering from endometriosis and its possible association with subsequent treatment outcome:a matched case-control study[J].Acta Obstet Gynecol Scand,2017,96:736-744.

[4] Gayete-Lafuente S,Vilà Famada A,Albayrak N,et al.Indirect markers of oocyte quality in patients with ovarian endometriosis undergoing IVF/ICSI:a systematic review and meta-analysis[J/OL].Reprod Biomed Online,2024,49:104075.

[5] Orvieto R.HMG versus recombinant FSH plus recombinant LH in ovarian stimulation for IVF:does the source of LH preparation matter?[J/OL].Reprod Biomed Online,2019,39:1001-1006.

[6] Yu EH,Joo JK.Commentary on the new 2022 European Society of Human Reproduction and Embryology (ESHRE) endometriosis guidelines[J].Clin Exp Reprod Med,2022,49:219-224.

[7] Wang X,Zhang M,Jiang L,et al.Exosomal AFAP1-AS1 binds to microRNA-15a-5p to promote the proliferation,migration,and invasion of ectopic endometrial stromal cells in endometriosis[J].Reprod Biol Endocrinol,2022,20:77.

[8] Poirier D,Nyachieo A,Romano A,et al.An irreversible inhibitor of 17β-hydroxysteroid dehydrogenase type 1 inhibits estradiol synthesis in human endometriosis lesions and induces regression of the non-human primate endometriosis[J].J Steroid Biochem Mol Biol,2022,222:106136.

[9] Han SJ,Jung SY,Wu SP,et al.Estrogen receptor β modulates apoptosis complexes and the inflammasome to drive the pathogenesis of endometriosis[J].Cell,2015,163:960-974.

[10] Juhasz-B?ss I,Fischer C,Lattrich C,et al.Endometrial expression of estrogen receptor β and its splice variants in patients with and without endometriosis[J].Arch Gynecol Obstet,2011,284:885-891.

[11] Matsuzaki S,Pouly JL,Canis M.Dose-dependent pro- or anti-fibrotic responses of endometriotic stromal cells to interleukin-1β and tumor necrosis factor α[J].Sci Rep,2020,10:9467.

[12] Zubrzycka A,Migdalska-S?k M,J?drzejczyk S,et al.The expression of TGF-β1,SMAD3,ILK and miRNA-21 in the ectopic and eutopic endometrium of women with endometriosis[J].Int J Mol Sci,2023,24:2453.

[13] Check JH.What role does decreased ovarian reserve play in the aetiology of infertility related to endometriosis?[J].Hum Reprod,2003,18:653-655.

[14] Dolmans MM,Martinez-Madrid B,Gadisseux E,et al.Short-term transplantation of isolated human ovarian follicles and cortical tissue into nude mice[J].Reproduction,2007,134:253-262.

[15] David A,Van Langendonckt A,Gilliaux S,et al.Effect of cryopreservation and transplantation on the expression of kit ligand and anti-Mullerian hormone in human ovarian tissue[J].Hum Reprod,2012,27:1088-1095.

[16] Horton J,Sterrenburg M,Lane S,et al.Reproductive,obstetric,and perinatal outcomes of women with adenomyosis and endometriosis:a systematic review and meta-analysis[J].Hum Reprod Update,2019,25:592-632.

[17] Zhou L,Wang L,Geng Q,et al.Endometriosis is associated with a lowered cumulative live birth rate:A retrospective matched cohort study including 3071 in vitro fertilization cycles[J].J Reprod Immunol,2022,151:103631.

[18] Hillier SG.Current concepts of the roles of follicle stimulating hormone and luteinizing hormone in folliculogenesis[J].Hum Reprod,1994,9:188-191.

[19] Hugues JN.Impact of ‘LH activity’ supplementation on serum progesterone levels during controlled ovarian stimulation:a systematic review[J].Hum Reprod,2012,27:232-243.

[20] Smitz J,Andersen AN,Devroey P,et al.Endocrine profile in serum and follicular fluid differs after ovarian stimulation with HP-hMG or recombinant FSH in IVF patients[J].Hum Reprod,2007,22:676-687.

[21] Hillier SG.Gonadotropic control of ovarian follicular growth and development[J].Mol Cell Endocrinol,2001,179:39-46.

[22] Revelli A,Chiado A,Guidetti D,et al.Outcome of in vitro fertilization in patients with proven poor ovarian responsiveness after early vs.mid-follicular LH exposure:a prospective,randomized,controlled study[J].J Assist Reprod Genet,2012,29:869-875.

[23] He W,Lin H,Lv J,et al.The impact of luteinizing hormone supplementation in gonadotropin-releasing hormone antagonist cycles:a retrospective cohort study[J].Gynecol Endocrinol,2018,34:513-517.

[24] Hill MJ,Levy G,Levens ED.Does exogenous LH in ovarian stimulation improve assisted reproduction success?An appraisal of the literature[J/OL].Reprod Biomed Online,2012,24:261-271.

[25] Cahill DJ,Wardle PG,Maile LA,et al.Pituitary-ovarian dysfunction as a cause for endometriosis-associated and unexplained infertility[J].Hum Reprod,1995,10:3142-3146.

[26] R?nnberg L,Kauppila A,Rajaniemi H.Luteinizing hormone receptor disorder in endometriosis[J].Fertil Steril,1984,42:64-68.

[27] Cahill DJ,Harlow CR,Wardle PG.Pre-ovulatory granulosa cells of infertile women with endometriosis are less sensitive to luteinizing hormone[J].Am J Reprod Immunol,2003,49:66-69.

基本信息:

中图分类号:R711.71

引用信息:

[1]晏媛,梅洁,沈晓月,等.黄体生成素添加对子宫内膜异位症患者拮抗剂方案促排卵结局的影响[J].生殖医学杂志,2025,34(11):1457-1465.

检 索 高级检索

引用

GB/T 7714-2015 格式引文
MLA格式引文
APA格式引文