添加来曲唑的拮抗剂方案对卵巢储备正常不孕患者内分泌和治疗结局的影响

Effect of GnRH antagonist combined with letrozole regimen on endocrine and pregnancy outcomes of infertile patients with normal ovarian reserve function

目的探讨IVF-ET治疗中卵巢储备功能正常的不孕症患者应用添加来曲唑(LE)的拮抗剂方案进行控制性卵巢刺激(COS),对内分泌、卵泡发育及妊娠结局的影响。方法选取2021年9月至2023年10月于石家庄市第四医院生殖医学中心行IVF-ET助孕的163例卵巢储备功能正常的不孕症患者为研究对象。根据拮抗剂促排卵方案是否添加LE分为两组:添加1.25 mg/d LE,连续服用至最大卵泡直径达到14 mm时停药者为LE组(n=81);未添加LE者为非LE组(n=82)。比较两组患者在COS期间不同时间点(刺激第1日、刺激第4日、刺激第6日、扳机前3日、扳机前1日、扳机日)血清雌二醇(E 2)、孕酮、FSH、LH、17-羟基孕酮(17-OH-P)、抑制素B(Inh B)和脱氢表雄酮(DHEA)水平,取卵日卵泡液17-OH-P、Inh B和DHEA水平,促排卵情况及临床妊娠率。结果在COS期间,LE组除刺激第1日外,其他时间点血清E 2均显著低于非LE组(P<0.05),LE组刺激第4日、扳机前1日、扳机日血清LH水平均显著高于非LE组(P<0.05),LE组血清FSH水平仅在刺激第4日时显著高于非LE组(P<0.05),LE组扳机前1日、扳机日血清孕酮水平均显著高于非LE组(P<0.05);LE组血清17-OH-P水平仅在扳机前1日显著高于非LE组(P<0.05),LE组除刺激第1日外其他时间点血清Inh B水平均显著高于非LE组(P<0.05),两组间各个时间点血清DHEA水平比较均无显著差异(P>0.05)。LE组取卵日卵泡液17-OH-P、Inh B及DHEA水平均显著高于非LE组(P<0.001)。与非LE组比较,LE组Gn时间、Gn总剂量及中重度OHSS发生率均显著降低(P<0.05),MⅡ卵数和优质胚胎率均显著增加(P<0.05),两组间获卵数、受精率、2PN受精率、囊胚形成率和临床妊娠率比较无显著差异(P>0.05)。结论对卵巢储备功能正常的不孕症患者,在拮抗剂方案中添加改良的低剂量LE(1.25 mg/d)和缩短用药时间,能够获得比拮抗剂方案更高的MⅡ卵数和优质胚胎数,并显著降低Gn应用时间、Gn总剂量和中重度OHSS发生率。

Objective:To explore the effect of GnRH antagonist combined with letrozole(LE)regimen for controlled ovarian stimulation(COS)in IVF-ET on endocrine,follicular development and pregnancy outcomes in the infertile patients with normal ovarian reserve function.Methods:A total of 163 patients with normal ovarian reserve function who underwent IVF-ET in the Reproductive Medicine Center of Shijiazhuang fourth Hospital from September 2021 to October 2023 were recruited.The patients were divided into two groups according to whether LE was added to the antagonist regimen for ovulation stimulation.A daily dose of 1.25 mg of LE was added and continuously used until the maximum follicle diameter reached 14 mm In the LE group(n=81),and it was no use in the non-LE group(n=82).The serum levels of estradiol(E_(2)),progesterone,FSH,LH,17-hydroxyprogesterone(17-OH-P),inhibin B(Inh B)and dehydroepiandrosterone(DHEA)were compared between the two groups at different time points during COS regarding stimulation day 1,stimulation day 4,stimulation day 6,3 days before trigger day,1 day before trigger day and the trigger day).The levels of follicular fluid 17-OH-P,Inh B and DHEA on the day of oocyte retrieval,ovulation promotion and clinical pregnancy rate were compared between the two groups.Results:The serum level of E 2 in the LE group was significantly lower(P<0.05)and the serum level of LH was significantly higher(P<0.05)at other time points except on stimulation day 1 when comparing with the non-LE group during COS period.The serum levels of LH in the LE group were significantly higher than those in the non-LE group on stimulation day 4,or 1 day before trigger day and the trigger day(P<0.05).The serum level of FSH in LE group was significantly higher than that in non-LE group only on stimulation day 4(P<0.05).The serum levels of progesterone in the LE group were significantly higher than those in the non-LE group on 1 day before trigger and trigger day(P<0.05).The serum level of 17-OH-P in the LE group was significantly higher than that of the non-LE group only on the day before trigger(P<0.05).The serum levels of Inh B in the LE group were significantly higher than those of the non-LE group at other time points except on stimulation day 1(P<0.05).There were no significant differences in the serum levels of DHEA between the two groups at all time points(P>0.05).On the day of oocyte retrieval,the levels of 17-OH-P,Inh B and DHEA in follicular fluid in the LE group were significantly higher than those in the non-LE group(P<0.001).In the LE group,shorter duration of gonadotropin(Gn)use,less total dose of Gn and lower incidence of moderate and severe OHSS as well as less oocyte in MⅡand lower rate of high-quality embryos were found(P<0.05).There were no significant differences in total number of oocyte retrieval,the fertilization rate,2PN fertilization rate,blastocyst formation rate and clinical pregnancy rate between the two groups(P>0.05).Conclusions:The addition of modified low-dose of LE(1.25 mg/d)and shortening the duration of administration to the antagonist regimen can obtain a higher number of MⅡoocytes and high-quality embryos than the antagonist regimen,and significantly shorten the duration of Gn application,the total dose of Gn,and the incidence of moderate and severe OHSS for infertile patients with normal ovarian reserve function.