| Objective:1. To investigate the feasibility and the success rate of the establishment of adenomyosis model in Wistar rats induced by autologous endometrial transplantation. 2. To evaluate the feasibility and success rate of the establishment of adenomyosis model in rhesus monkey induced by autologous endometrial transplantation. And to observe the feasibility and safety of ultrasound-guided percutaneous microwave ablation (UPMWA) for the rhesus model of adenomyosis.3. To observe the incidence of unplanned pregnancies in these women after UPMWA treatment for utrine fibroids and adenomyosis in order to evaluate its effect on natural conception.Material and Methods:the first part:Experimental research of establishment of animal model of uterine adenomyosis:1. Twenty-eight adult nonfertile female Wistar rats were randomly allocated into an adenomyosis model group (n=18) and a control group (n=10). A surgical incision was made on the left uterus. Autologous endometrial tissue was scraped and transplanted into the right uterine myometrium in the adenomyosis model group. The control group was treated with the same laparotomy method, injecting of equivalent normal saline instead of planting the endometrium. Measure the thickness of the uterine pre-operation and 1 month and 2 months post-operation. The status of endometrial gland infiltration into the myometrium was microscopically observed, and the effect of establishment of the model evaluated.2. Six healthy mature female rhesus monkeys (5 of the experimental group and 1 of the blank control group) were included. For the experimental group, the endometrium was taken through laparotomy implanted into the anterior wall of the uterus. Ultrasound guided puncture biopsy was done for the pathological examination 9 months post-operation. Serum CA125. CA19-9 and serum prolactin (PRL) levels were monitored before operation and 1,3,6.9.12 months post-operation, and ultrasonograghy were examined. Pelvic MRI were examined pre-operation and 9 months post-operation. The control group wasn’t modeled surgery, the same period for the relevant examination. The second part:Experimental study of ultrasound-guided microwave ablation for rhesus model of adenomyosis:the UPMWA treatments were applied for the three rhesus model of adenomyosis 12 months after surgery. The output energy of microwave abaltion was 20W and lasted for 80-100s. Contrast-enhanced Ultrasound (CEUS) was done before and after treatment to evaluate the ablation range and ablation rate. The third part:Natural pregnancy after UPMWA for uterine benign lesions:the medical history and pregnancy outcomes of patients who got pregnant after UPMWA treatment for uterine fibroids and adenomyosis from June,2007 to September, 2015 in our hospital were recorded.Results:The first part:An adenomyosis model was successfully established (100% success rate) in Wistar rats.The thickness of the uterine increased after modeling, and the thickness two months after surgery was thicker than that of one month after surgery with statistical difference (P<0.05). Typical endometrial glands could be seen under microscope after HE staining. The range of the invasion of the endometrium increased along with the increase of modeling time. No endometrial glandular infiltration and significant changes were observed in the myometrium of the control group. Endometrium glands could be seen of four monkeys in the experimental group by histopathological examination. The success rate was 80%(4/5). No endemetrium could be seen in the anterior myometrium of the control group. The menstrual cycle, the change of vaginal smear, and the imaging features of the rhesus monkey were similar with human being. The serum CA125 and serum PRL levels increased after succeful modeling. The second part:All the three rhesus model of adenomyosis received a successful UPMWA treatment, without any serious complications and side effects. The ablated ranges evaluated by CEUS were 6.8x4.9×5.1mm,8.2x4.8x5.4mm, and 8.0x5.4x5.2mm respectively. The ablation rate was 91.6%,95.3%, and 100% respectively.The third part:Twenty-two natural pregnancies in 19 women occurred after UPMWA treatment, including 21 intrauterine pregnancies and 1 cervical pregnancy. Among the patients who got pregnant, eleven suffered from uterine fibroids and eight suffered from adenomyosis, with the total pregnancy number of 12 and 10 respectively. The mean time from treatment to conception was 14.5±6.3 months. Thirteen patients did not have reproductive needs, one case experienced spontaneous abortion, one suffered from embryo development at 48 days of gestation, and one patient of cervical pregnancy underwent induced abortion; the rest of the 13 patients were selected artificial or drug abortion. Among the 6 patients who continued pregnancy, five gave birth to a healthy term infant by cesarean delivery (two of them had been previously diagnosed as infertility), and the other one was lost to follow-up 26 weeks after pregnancy. None of the five patients had any serious obstetric complications.Conclusion:1. It was feasible to establish a rat adenomyosis model by autologous endometrial transplantation with a high success rate and a short induction time.2. The establishment of rhesus monkey adenomyosis model by endometrium planting method is feasible and effective. The individual difference among different monkeys was the key of the success of modeling. The MRI and ultrasound imaging of rhesus monkey were similar with human beings. After modeling, the serum CA125 and PRL levels had the trend to increase with was related to the occurrence and progression of endometrium, which is consistent with the clinical result. The serum CA125 and PRL levels can be the indicators for modeling and efficacy evaluation.3. UPMWA treatment for the rhesus monkey adenomyosis model is safe and effective, without any severe complications, and provides the experimental foundation for the study of influence on fertility. But it required high surgical skills due to the relatively small volume of the rhesus monke uterus. Real-time ultrasound monitoring is needed to prevent damage to the surrounding normal tissue.4. UPMWA treatment for uterine fibroids and adenomyosis did not show significant effect on their ability of fertility. The impact on the continued pregnancy and pregnancy outcome is worthy of further prospective study with a large sample. |
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