The effect of intrauterine contraceptive devices on the endometrium

Insertion of an IUD into the uterine cavity is associated with an inflammatory cellular response of the endometrium, which initially is common to all IUDs as the endometrial tissue reacts to the presence of a foreign body. Other types of morphologic modifications specific to different types of IUDs are then observed and may be important in understanding the mode of action of the device and in explaining bleeding patterns associated with IUDs. The endometrial response to inert and copper IUDs is quite similar. The part of the endometrial surface in contact with an inert or copper IUD loses its outer layer of epithelial tissue, exposing the lower layer of basal membrane. The rest of the epithelium in contact with the IUD appears flattened, and some epithelial cells lose their microvilli. Ultrastructural studies have demonstrated a reduction in number of ciliated cells and an alteration of the secretory activity of the surface epithelium and to a lesser degree of the glandular epithelium in reaction to the IUD. Diffuse interstitial bleeding with migration of erythrocytes between the interepithelial spaces has frequently been seen. Ultrastructural studies clearly show that inert IUDs induce lesions and later secondary modifications of the surface epithelium, the superficial vascular epithelium, the glandular epithelium, and to a lesser extent other endometrial cells. With copper IUDs, surface erosions of endometrial epithelium are seen, with much more cellular destruction and signs of bleeding in the part in contact with the copper. As with inert IUDs, the adjacent basal membrane is usually intact. A notable finding in the endometrium is the existence of microthrombosis of stromal capillaries, especially in the portion exposed to the copper. There appears to be a direct relationship between the amount of copper and the degree of ultrastructural modification. The effects of progesterone-releasing IUDs on the surface epithelium, the glands, the stroma, and the vascularization vary as a function of the dose and type of progestin, the proximity of the tissue and the part of the IUD treated, and the time elapsed since insertion.     

生长激素在子宫内膜发育不良中的作用

目的:探讨辅助生殖技术中生长激素(growth hormone,GH)对子宫内膜的影响及作用。方法:回顾分析2005年1月～2007年12月因子宫内膜发育不良致体外受精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)治疗失败66例的临床资料。再次IVF-ET治疗中,以加用GH治疗的41例为研究组,未用GH治疗的25例为对照组。结果:人绒毛膜促性腺激素(human chorionic gonadotropin,HCG)注射日研究组子宫内膜的厚度较对照组明显增加,差异有统计学意义(P<0.05),内膜的类型无明显改变。两组的Gn用量、平均获卵数、受精率、卵裂率及优质胚胎率无统计学差异(P>0.05)。HCG注射日雌二醇(estradiol,E2)水平无明显变化(P>0.05)。研究组妊娠率高于对照组(P<0.05)。结论:生长激素有助于促进子宫内膜发育,对内膜类型无明显影响。生长激素对卵子质量无显著影响,可能通过改善子宫内膜的容受性提高了妊娠率。     

放置宫内节育器对子宫内膜血管内皮生长因子及其激酶受体表达及微血管密度变化的影响

目的探讨放置固定式带铜宫内节育器(FCu-IUD)和含吲哚美辛FCu-IUD(FICu-IUD),对子宫内膜组织中血管内皮生长因子(VEGF)及其激酶受体(KDR)表达以及微血管密度(MVD)变化的影响及意义.方法采用免疫组化法及原位杂交法,检测放置FCu-IUD妇女(10例,FCu-IUD组)及放置FICu-IUD妇女(10例,FICu-IUD组)放置IUD前后子宫内膜VEGF、VEGF mRNA及KDR的表达,并计数子宫内膜MVD.结果 FCu-IUD组放置IUD后,VEGF及KDR蛋白为0.568±0.027,0.244±0.022,均高于放置IUD前的0.357±0.032,0.215±0.029,放置IUD前后比较,差异有显著性(P<0.05).FCu-IUD组放置IUD前VEGF mRNA表达为0.359±0.022,低于放置IUD后的0.425±0.019,放置IUD前后比较,差异有显著性(P<0.05).FICu-IUD组放置IUD前后VEGF、KDR蛋白及VEGF mRNA表达比较,差异无显著性(P>0.05). FCu-IUD组放置IUD后MVD为19.8±4.8,明显高于放置IUD前的15.4±2.8,且与VEGF蛋白的表达呈正相关关系(r=0.847,P<0.01).FICu-IUD组放置IUD前后MVD比较,差异无明显性(P>0.05).结论放置FCu-IUD可促进子宫内膜VEGF及KDR的表达,FICu-IUD可抑制子宫内膜VEGF及KDR的生成.VEGF及KDR可能参与了FCu-IUD 及FICu-IUD所引起的子宫内膜微血管结构和功能的改变.     

Adenocarcinoma of the endometrium following prolonged use of an intrauterine device

An Extremely rare case with the endometrial carcinoma induced by the prolonged (for 20 years) use of IUD (Oota Ring) was reported. The patient was a 57-year-old woman who visited our clinic claiming spotting, and the cancer was revealed by a D & C examination. Since no high risk factors for endometrial carcinogenesis were noted in this patient, it was inferred that prolonged use of IUD played an important role as a cocarcinogen. In particular, the mechanical action of the inserted IUD was thought to be responsible for carcinogenesis. The inflammatory reactions observed in the tumor tissues were considered to be the secondary changes induced by carcinoma.     

Effect of copper intrauterine device vs. injectable contraceptive on serum hormone levels and cell mitotic activity in endometrium

AimsTo compare changes in serum estradiol and progesterone level, endometrium cell mitotic activity and Ki67 in women using copper intrauterine device (Cu-IUD) with DMPA users 9 months after use.MethodsOne hundred and fifty women having no contra indication to either IUD or injectable contraceptive were studied. Office Endometrial biopsies and serum samples for estradiol and progesterone levels were taken on the 7th day of the menstrual cycle at recruitment and after 9 months. The endometrial samples were subjected to cell mitotic study and Ki67 estimation using morphology and proliferative indices.ResultsThe mean glandular mitotic index was 1.69 ± (0.39) for IUD user vs. 1.1 ± (0.69) for Injectable contraceptive user at first visit respectively and it was 0.57 ± (0.34) vs. 0.25 ± (0.11) at second visit after 9 months respectively. Similarly, Ki-67 count in glands was 11.79 ± 1.59 for IUD user vs. 12.03 ± 0.58 for injectable contraceptive user at first visit and 4.20 ± (0.24) vs. 2.27 ± (0.65) at second visit respectively. In the stroma, Ki67 decreased from a mean of 0.85–0.05 in 9 months for IUD user vs. 0.92–0.02. For injectable users suggesting a statistically significant decrease in proliferative and mitotic indices in the endometrium of women using either injectable contraceptives or IUD for more than 9 months. Non significant changes were observed in serum hormone levels in IUD users, while injectable contraceptive users showed a significant increase in serum progesterone level with insignificant change in the serum estrogen level.ConclusionEither copper intrauterine device or injectable contraceptive usage for more than 9 months results in significant decrease in endometrial proliferative or cell mitotic activity. While copper IUD has no effect on serum estradiol or progesterone levels, DMPA usage increased serum progesterone level with no effect on serum estradiol.     

放置IUD后宫腔微生物及子宫内膜病理学研究

研究ＩＵＤ与盆腔感染及子宫内膜恶变或其他病理改变的关系,探讨 ＩＵＤ长期使用的安全性。方法：将 ８８例分为 Ａ、Ｂ、Ｃ、Ｄ ４组,Ａ组 ２０例使用带尾丝活性 ＩＵＤ;Ｂ组２４例使用惰性 ＩＵＤ;Ｃ组 ２４例为正常对照组;Ｄ组 ２０例为盆腔感染组。所有病例取宫腔冲洗液进行需氧菌、厌养菌、解脲支原体、沙眼衣原体等培养,并取子宫内膜进行病理学检查,结果：Ａ、Ｂ组主要表现为正常增生期、分泌期或月经期子宫内膜,部分是单纯性或腺囊性增生,与Ｃ组、Ｄ组差异无显著性（Ｐ＞０．０５）,４组均未见不典型增生及恶变。Ａ、Ｂ、Ｃ３组子宫内膜均无慢性炎症改变,Ｄ组８例存在慢性子宫内膜炎改变,与Ａ、Ｂ、Ｃ组差异有显著性（Ｐ＜０．０５）。Ａ、Ｂ、Ｃ组淋巴细胞、浆细胞、中性白细胞、纤维细胞计数差异无显著性（Ｐ＞０．０５）,Ｄ组淋巴细胞、浆细胞、中性白细胞计数较以上３组明显增加（Ｐ＜０．０５）,间质细胞及纤维细胞计数与以上３组差异无显著性（Ｐ＞０．０５）。Ａ、Ｂ、Ｃ组宫腔微生物检出率分别为３０．０％,２９．２％,２０．８％,与Ｄ组（７０．０％）差异有显著性（Ｐ＜０．０５）。结论：使用ＩＵＤ５－１４年未增加子宫内膜癌、癌前病变及慢性子宫内膜炎发生率。Ｉ     

The effect of intrauterine contraceptive device (IUD) on pregnancy in the rabbit

Rabbits were inserted with 10 cm of Silastic tubing in 1 uterine horn; blastocysts were collected from the control or treated horn on Pregnancy Day 5 and transferred to the opposite horn. 16 of 22 (72%) blastocysts implanted into an IUD horn failed to survive to Day 23. 10 of 16 (62.5%) blastocysts transferred to the control horn were found implanted on Day 12 and 9 pups were delivered. In other rabbits with su rgical anastomosis between the 2 horns, 99.5% of implantations survived from Day 12 to 23 in control horns, but only 20% in IUD horns. The leukocyte counts was markedly elevated in IUD horns and only moderately in control horns. These data indicate that the antifertility effect of the IUD is largely due to its direct contact with the developing embryos and the endometrium.