Mendes MC[12]等对超排卵后卵巢过度刺激的病例进行研究,发现血浆中PRL的浓度在取卵前达到最高值, PRL升高的程度与基础PRL水平相比大于两倍组,其大卵泡数(直径>=12mm),卵子成熟率和IVF成功率均高于升高程度小于或等于两倍组,推测暂时性的高催乳素血症与IVF结局有关.
Doldi N[14]等对将进行ICSI治疗存在暂时性高催乳素血症的病人分两组,其中一组服用卡麦角林或溴隐亭使PRL水平下降,另一组安慰剂对照;在IVF周期中,对照组使用FSH总量少、优质胚胎较多、受精率较高、平均移植胚胎数较多。提示:暂时性高催乳素血症与ICSI周期结局成正相关,尤其在卵子质量和受精率方面。
我们的研究结论与上述不全相同:HCG日PRL水平与受精率无关;HCG日PRL>30~≤60ng/ml(B组)种植率和妊娠率最高;而PRL过高,>90ng/ml(D组),将明显影响妊娠结局。
过高的PRL水平可能通过影响下丘脑-垂体-性腺轴功能、黄体功能、子宫内膜的容受性、免疫耐受等方面影响妊娠结局。
高PRL血症对下丘脑-垂体-性腺轴内的各级水平有多种影响:高水平的PRL通过对GT1下丘脑神经元细胞系上表达的PRL受体的一种作用抑制GnRH从该细胞系的释放,通过降低脉冲振幅和频率抑制LH脉冲性分泌。
PRL对大鼠黄体功能有营养作用,因此有“黄体营养激素”之称。McNatty等[16]的研究表明,生理性低水平PRL是人颗粒细胞合成PRL的孕酮所必需的,而体外研究显示,高水平PRL表现为抑制性作用。Feltus FA等的研究显示PRL可以激活Ⅱ型3β-羟甾脱氢酶的表达,该酶是孕酮生物合成过程中最后的酶。国外有报道,给正常妇女口服溴隐亭,致使血浆PRL水平低于正常,则黄体期孕酮水平也显著下降,子宫内膜活检也出现黄体功能不全的表现,说明正常水平的PRL对维持黄体功能是必需的。但高PRL血症可引起颗粒膜细胞功能障碍,使甾体激素产生减少,影响卵泡的发育。Polissceni等通过大鼠实验证实:高催乳素水平(4.6~9.1 nmol/L)可明显减少由hCG诱导的成熟及排卵,可以调控卵巢的局部的β-内啡肽及前列腺素E2(PGE2)的释放,从而干扰外源性Gn诱导排卵的过程。
在胚胎种植期,子宫内膜合成PRL并通过内膜上的PRL-R为胚泡提供适宜的微环境,维持子宫内膜的容受性,而高催乳素则会抑制黄体颗粒细胞增生和黄体功能,使黄体期变短,孕酮不足,孕酮不足会导致植入及早期胚胎发育异常[17]。
PRL不仅是泌乳激素,同时也是淋巴细胞存活、激活和增生的免疫调节因子,过高的PRL水平可能通过其免疫功能影响母体对胚胎种植的免疫耐受。PRL对受TCR刺激的Th1型细胞的成熟发挥作用,并参与T细胞的分化,调节Th1/Th2平衡向Th1方向偏移。而正常妊娠中存在Th1/Th2型细胞因子之间的平衡向远离Th1型细胞因子的方向移动,Th1型细胞因子分泌增多,细胞免疫增强,影响胚胎种植的免疫耐受,损害妊娠,导致流产[18]。
因此,促排卵后PRL水平过高对IVF结局有不利的影响。体外受精与胚胎移植中HCG日PRL维持在适当的水平(>30~≤60ng/ml)种植率和妊娠率最高,当PRL水平明显升高时(PRL> 90ng/ml),种植率及临床妊娠率明显下降。建议对COS过程中催乳素水平异常的病人给予严密的监测和适当的干预,有助于提高临床妊娠率。
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