血清维生素D水平对卵巢功能减退患者体外受精-胚胎移植助孕结局的影响

目的分析卵巢功能减退(diminished ovarian reserve,DOR)患者的血清维生素D水平与其体外受精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)助孕结局的关系,探讨维生素D对DOR人群卵泡生长、胚胎发育及妊娠结局的影响。方法回顾性分析2014年1月1日至2017年12月31日于海军军医大学附属长征医院生殖医学中心行IVF-ET助孕的DOR患者,共纳入204对夫妇,新鲜周期486个,复苏周期270个。根据血清25(OH)D水平分为3组:<20μg/L为缺乏组;20~30μg/L为不足组;≥30μg/L为充足组。观察指标:促性腺激素(gonadotropins,Gn)使用剂量、Gn天数、获卵数、D3可移植胚胎率、D3优质胚胎率、临床妊娠率、流产率及累积妊娠率。统计学方法采用非参数KruskalWallis秩和检验、Bonferroni校正法和χ^2检验。结果维生素D缺乏组、不足组、充足组的Gn剂量分别为(1353±811)、(1191±784)、(1131±661)IU,Gn天数分别为(8.7±3.1)、(8.0±3.2)、(7.8±2.4)d,缺乏组的Gn剂量和Gn天数均高于不足组和充足组(P<0.05),而不足组与充足组的Gn剂量和Gn天数比较,差异无统计学意义(P>0.05)。3组患者的获卵数[(3.9±4.1)、(3.4±3.0)、(3.1±2.4)个]、D3可移植胚胎率[82.8%(313/378)、82.4%(416/505)、82.9%(223/269)]、D3优质胚胎率[60.0%(204/340)、53.4%(242/453)、52.7%(127/241)]比较,差异均无统计学意义(P>0.05)。维生素D充足组无新鲜周期移植的患者;缺乏组与不足组新鲜周期的临床妊娠率[71.4%(5/7)与66.7%(4/6)]和流产率[0.0%(0/5)与0.0%(0/4)]比较、3组复苏周期的临床妊娠率[44.3%(35/79)、42.7%(50/117)、35.7%(25/70)]和流产率[25.7%(9/35)、20.0%(10/50)、16.0%(4/25)]比较,差异均无统计学意义(P>0.05);3组的累积妊娠率分别为73.6%(39/53)、65.4%(53/81)、60.5%(23/38),差异也无统计学意义(χ^2=1.844,P=0.398)。结论维生素D缺乏的DOR患者在IVF-ET助孕中需要更多剂量的Gn和更长的Gn时间来促进卵泡发育,但不影响胚胎发育和妊娠结局。

The effect of serum vitamin D on the clinical outcomes of patients with diminished ovarian reserve undergoing IVF-ET

Objective To analyze the relationship of serum vitamin D level and the outcomes of patients with diminished ovarian reserve(DOR) undergoing in vitro fertilization-embryo transfer(IVF-ET), and to discuss the effect of vitamin D on follicular growth, embryo development and pregnancy outcomes in patients with DOR. Methods From January 1, 2014 to December 31, 2017, among patients with DOR who received IVF-ET therapy in Reproductive Medicine Center, Changzheng Hospital, Naval Military Medical University of the PLA, 204 couples were included in the study, including 486 fresh cycles and 270 frozenthawed cycles. According to the level of serum 25(OH)D, the patients were divided into three groups: deficiency group(<20 μg/L), insufficiency group(20-30 μg/L) and sufficiency group( ≥ 30 μg/L). The observation indexes were retrospectively analyzed: dose of gonadotropins(Gn), days of ovarian hyperstimulation, number of oocytes achieved, rate of D3 transferable embryos, rate of D3 embryos of good quality, clinical pregnancy rate, miscarriage rate and cumulative pregnancy rate. Nonparametric Kruskal Wallis test, Bonferroni correction and χ^2 test were used for statistics. Results The dosage of Gn in vitamin D deficiency group, insufficiency group and sufficieny group were(1 353±811),(1 191±784) and(1 131±661) IU. The days of Gn treatment were(8.7±3.1),(8.0±3.2) and(7.8±2.4) d, respectively. The Gn dosage and Gn days of deficiency group were higher than those of insufficiency group and sufficiency group(P<0.05), but there were no significant differences between insufficiency group and sufficiency group(P>0.05). There were no significant differences among the three groups in the number of oocytes obtained [(3.9±4.1),(3.4±3.0) and(3.1±2.4)], the rate of D3 transferable embryos [82.8%(313/378), 82.4%(416/505) and 82.9%(223/269)], the rate of D3 embryos of good quality [60.0%(204/340), 53.4%(242/453) and 52.7%(127/241)](P>0.05). In fresh embryo transfer cycles, there was no tansfer in sufficiency group. The clinical pregnancy rate [71.4%(5/7) vs 66.7%(4/6)] and abortion rate [0.0%(0/5) vs 0.0%(0/4)] had no significant differences between the deficiency group and insufficiency group(P>0.05). In frozen-thawed embryo transfer cycles, the clinical pregnancy rate [44.3%(35/79), 42.7%(50/117) and 35.7%(25/70)] and abortion rate [25.7%(9/35), 20.0%(10/50) and 16.0%(4/25)] had no significant differences among the three groups(P>0.05). The cumulative pregnancy rates of the three groups were 73.6%(39/53), 65.4%(53/81) and 60.5%(23/38) respectively(χ^2 =1.844, P=0.398). Conclusion Patients with vitamin D deficiency need more Gn dosage and longer Gn days to promote follicular development in the IVF-ET treatment, but it does not affect embryo development and pregnancy outcomes.