猕猴子宫腺肌病模型建立及经皮微波消融治疗对生育影响研究

Adenomyosis is of high incidence among women of reproductive age. Except for causing progressive dysmenorrhea and anemia, adenomyosis could also cause infertility， abortion and decrease of assistant conception rate. Traditional therapy for adenomyosis is hysterectomy which is invasive，leads to the loss of fertility and influences the function of ovaries. As the marriage age and fertility age are getting later, the drawbacks of hysterectomy is more outstanding. It has reached a consensus that conservative therapeis should be the first choices for uterine benign diseases. The conversion of this treatment concept promoted the devepment of minimally invasive treatment techniques. However, uterine conservation is not equal to the improvement of fertility, for example, the clinical live birth rate after medicine and lesion removal is only 8%-32%. At the same time, the influence of ablation in situ and UAE on fertility is still not clear. Therapy for adenomyosis which can improve fertility rate is the focus of current research. Percutanous microwave ablation（PMWA） is of little invasion, convenient, safe and highly efficient, can also obviously shrink the uterus, relieve the symptom.Some of the treated patients were pregnant, but the effect of ablation on the uterine structure and the ability of fertility is still not clear in general. At the same time, it is not suitable to perform in clinical. The model of adenomyosis in only seen in mice, and there is still no primate model similar to human beings existed which makes it diffult to research on interventional treatment. We plan to build adenomyosis model of macaque and study the influence of PMWA on endometrium, ovaries and prognosis of pregnancy, thereby we can supply detail evidence for the establishment of conservative treatment for unfertile patients.

子宫腺肌病是育龄妇女高发病，除引起进行性痛经、贫血，还造成不孕、流产和辅助生殖受孕率降低。传统子宫切除治疗创伤大，使患者失去生育能力，且影响卵巢功能。近年由于女性婚育年龄增高，子宫切除的弊端更显突出。对子宫良性病首先应保守治疗已成共识，治疗理念的转变促进了微创治疗技术的发展。但保留子宫的治疗不意味不影响生育能力，如药物和病灶剔除治疗后临床活产率仅为8%-32%，原位消融和UAE对生育的影响尚不清楚，改善生育能力的治疗技术研究成当前焦点。超声引导经皮微波消融（PMWA）治疗创伤微小、操作方便、安全、有效缩小子宫、缓解症状，治疗后患者已有怀孕，但消融对子宫结构及生育的整体影响尚不清楚，也不宜在临床研究。子宫腺肌病模型仅见于小鼠，无与人类相似的灵长类模型给介入治疗研究造成困难，本项目拟建立猕猴子宫腺肌病模型并研究PMWA对子宫内膜、卵巢及妊娠预后的影响，为建立适于未育患者的保守治疗方法提供依据。

子宫腺肌病是育龄妇女高发病，除引起进行性痛经、贫血，还造成不孕、流产和辅助生殖受孕率降低。传统子宫切除治疗创伤大，使患者失去生育能力，且影响卵巢功能。近年由于女性婚育年龄增高，子宫切除的弊端更显突出。对子宫良性病首先应保守治疗已成共识，治疗理念的转变促进了微创治疗技术的发展。但保留子宫的治疗不意味不影响生育能力，如药物和病灶剔除治疗后临床活产率仅为8%-32%，原位消融和UAE对生育的影响尚不清楚，改善生育能力的治疗技术研究成当前焦点。超声引导经皮微波消融（UPMWA）治疗创伤微小、操作方便、安全、有效缩小子宫、缓解症状，治疗后患者已有怀孕，但消融对子宫结构及生育的整体影响尚不清楚，也不宜在临床研究。子宫腺肌病模型仅见于小鼠，无与人类相似的灵长类模型给介入治疗研究造成困难。灵长类动物猕猴的子宫与人类最相似，有同人类相似的月经周期，目前猕猴子宫内膜异位模型已较成熟，子宫腺肌病的模型尚未形成。本研究首先通过研究应用自体内膜种植法建立Wistar大鼠子宫腺肌病动物模型的可行性，为猕猴子宫腺肌病建模奠定实验方法基础；而后应用子宫内膜种植法成功建立猕猴子宫腺肌病动物模型，并通过MRI检查、超声检查、相关实验室检查及组织病理检查加以评价，弥补目前没有适宜的大动物子宫腺肌病模型的空白，为临床子宫腺肌病治疗研究提供与人类子宫腺肌病最相似的灵长类动物模型，对临床子宫腺肌病微创或无创治疗的基础研究及治疗技术对生育影响的研究起到巨大的推动作用。建模成功后进行UPMWA治疗，而后对治疗后猕猴进行混笼饲养，观察自然受孕情况及妊娠预后，通过对超声引导经皮微波消融治疗子宫腺肌病对生育的影响进行模拟临床的系列试验研究，为建立可安全、有效地用于有生育要求的症状性子宫腺肌病患者的微创治疗方法提供实验依据。临床基础研究部分通过随访UPMWA治疗子宫肌层良性病变后患者的无计划妊娠情况，并观察妊娠结局、持续妊娠过程及相关产科并发症来探讨UPMWA对患者自然妊娠的影响，积累临床经验和证据，为研究UPMWA治疗对生育功能的影响提供临床依据。