自身抗体与不孕及自发性流产关系的探讨

目的检测抗心磷脂抗体(ACA)和抗精子抗体(AsAb)两种自身抗体在不孕及自发性流产患者中存在的情况,并观察应用阿司匹林治疗ACA阳性反复流产患者的临床效果。方法应用酶联免疫吸附(ELISA)法检测150例原发或继发不孕患者(不孕组)、198例自发性流产或有胚胎停育史患者(流产组)及40例正常对照组血清中的ACA及AsAb抗体。对其中53例ACA阳性反复流产患者在孕前一个月或孕早期采用低剂量阿司匹林治疗。结果不孕组及流产组ACA总阳性率分别为48.00%和50.51%,与对照组(7.50%)相比有非常显著性差异(P<0.001);不孕组及流产组AsAb阳性率分别为31.33%和25.25%,与对照组(10.00%)比较亦有显著性差异(P<0.05)。53例经治疗患者活产婴儿48例,妊娠成功率为90.57%。结论ACA和AsAb等自身抗体是导致不孕及自发性流产的免疫学因素之一,应用低剂量阿司匹林治疗ACA阳性反复流产患者是保证其妊娠成功的有效方法。     

不孕及反复自然流产患者血清抗精子抗体分析

目的：探讨不孕及反复自然流产与抗精子抗体（AsAb）的关系。方法：用金标法检测有反复自然流产史患者245例（流产组）、原发或继发不孕患者164例（不孕组）及正常妇女40例（对照组）血清中的AsAb。结果：不孕组AsAb总阳性率52.44%,流产组总阳性率48.57%,与对照组比较差异均有统计学意义（P〈0.05）。结论：AsAb与不孕及反复自然流产有着密切关系。     

Human chorionic gonadotrophin-beta gene sequences in women with disorders of HCG production

Women with recurrent abortion, primary unexplained infertility, and gestational trophoblastic neoplasia (GTN) manifest disordered human chorionic gonadotrophin (HCG) secretion. Mutations in the HCG beta/luteinizing hormone (LH) beta gene complex could cause aberrant HCG production in these disorders. The purpose of this study was to determine whether HCG beta gene deletions occur in women with recurrent abortion or primary unexplained infertility, and whether HCG beta gene duplications are present in women with GTN. DNA was extracted from 10 patients with unexplained recurrent abortion, 10 patients with unexplained primary infertility, 12 patients with GTN, three partners of women with GTN, and 30 controls. Southern blots were constructed and hybridized with DNA probes for HCG beta-5 and the LH beta gene. No gene deletions were identified in patients with recurrent abortion or primary unexplained infertility. Likewise, no gene duplications were identified in women with GTN. A previously described Mbol restriction fragment length polymorphism (RFLP) was identified in both patients and controls. A new Pstl RFLP was also characterized, but was present in patients and controls. Deletion/duplication mutations in the HCG beta/LH beta gene complex do not appear to be common causes of aberrant HCG production in humans with these disorders.      

Association between infertility and spontaneous abortion.

Women experiencing recurrent spontaneous abortion have a higher frequency of infertility than that expected in the general population. To further define the relationships between infertility and spontaneous abortion, the obstetrical histories of 43 women with unexplained secondary infertility were evaluated for the frequency of spontaneous abortion. Of the 88 pregnancies studied, 39 (44%) resulted in spontaneous abortion. Women with unexplained secondary infertility experienced a three-fold increase (P less than 0.0001) in the frequency of spontaneous abortions and half the number of live births (P less than 0.0001) compared with the general population. We conclude that the association between infertility and spontaneous abortion includes a higher frequency of spontaneous abortion among infertile couples as well as a higher prevalence of infertility among recurrent spontaneous aborters compared with the general population.     

抗子宫内膜抗体和抗精子抗体在临床中的价值探讨

目的探讨抗精子抗体和抗子宫内膜抗体在临床上检测原发性不孕和复发性自然流产的价值。方法回顾性分析2018年1月至2018年12月在复旦大学附属妇产科医院诊治的原发性不孕患者及复发性自然流产患者病史,以同期进行常规检查的孕妇作为对照,对比研究对象抗子宫内膜抗体、抗精子抗体的水平,分析抗子宫内膜抗体、抗精子抗体在原发性不孕和复发性自然流产中可能的相关性。结果收集到原发性不孕患者170例及复发性自然流产患者238例病史资料,以同期进行常规检查的孕妇208例作为对照组。原发性不孕患者抗精子抗体检测阳性例数显著高于对照组,但抗子宫内膜抗体并无显著改变;复发性自然流产患者抗子宫内膜抗体检测阳性率显著高于对照组,但抗精子抗体并无明显不同;早孕期流产患者抗精子抗体检测阳性率显著高于对照组;发生复发性自然流产在4次以上的病人,其体内抗子宫内膜抗体和抗精子抗体的水平均显著高于对照组。结论抗子宫内膜抗体和抗精子抗体检测在复发性自然流产和原发性不孕患者中具有相关的临床价值,应加强备孕人群的筛查工作,及早干预。     

南宁地区41例平衡易位携带者的细胞遗传学分析

目的通过对2856例反复流产、不良孕产史、不孕不育等患者进行染色体结果调查,探讨染色体平衡易位携带者的临床效应。方法采用外周血淋巴细胞染色体培养技术,G显带,核型分析。结果41例染色体平衡易位携带者中,男性21例,女性20例,常一常染色体易位39例,其中包括3例罗伯逊易位;性一常染色体易位2例。主要临床表现为女性反复自然流产、不良孕产史等;男性少弱精子症及不育等。结论染色体平衡易位是导致反复流产、不良孕产史、男性少弱精子症、不育等的重要因素之一。对于这些有反复流产史、不良妊娠史、不孕不育的临床患者,进行外周血染色体核型分析十分必要。     

NK Cells,Autoantibodies, and Immunologic Infertility: A Complex Interplay

Infertility and recurrent spontaneous abortion (RSA) are heterogeneous conditions that have been frequently explained with an immunological pathomechanism. A deeper insight into apparently unexplained infertility and RSA shows increasing evidences supporting both alloimmune and autoimmune mechanisms, in which natural killer (NK) cells and autoantibodies seem to play a relevant role. Successful pregnancy is considered as Th1–Th2 cooperation phenomenon, with a predominantly Th2-type lymphocytes response, together with the emerging role of interleukin (IL)-12, IL-15, and IL-18 and of other unidentified soluble factors dependent on NK cells. Uterine NK cells comprise the largest population at implantation site, and their activity, characteristics, and abundance suggest that they participate at the “decidualization” process that, vice versa, induces NK activation and recruitment in each menstrual cycle. However, NK cell alteration may be associated with impaired pregnancy, and the modulation in the number of circulating NK cells is most likely to be a primary event rather than an active inflammation/drug administration consequence during an inflammatory/autoimmune process, thus playing an important role in the pathogenesis of immunological infertility. Relationships within immunological infertility, recurrent spontaneous abortion, autoantibodies, and NK cells will be reviewed herein.     

精子抗原对RSA者和不孕症患者外周血单个核细胞产生IgE的影响

探讨精子抗原(SAg)对反复自然流产(RSA)者和不孕症患者外周血单个核细胞(PBMC)产生IgE的影响。用ELISA法分别测定36例RSA者,34例不孕症患者和22名正常妊娠者血清IgE和PBMC与SAg培养液中IgE水平。结果表明,血清IgE水平大于150 IU/mL的RSA者和不孕症患者与血清IgE水平≤150 IU/mL患者及早孕对照者相比,PBMC经SAg刺激后,培养液中IgE水平显著升高,提示SAg可诱导部分RSA和不孕症患者产生特异性IgE,这可能在RSA者和不孕症的发病机理中起一定作用。     

Distributions of endometrial NK cells,B cells,T cells,and Th2/Tc2 cells fail to predict pregnancy outcome following recurrent abortion

PROBLEM: To evaluate the ability of immunophenotypes of endometrial leukocytes from patients with histories of recurrent abortion to predict outcome of subsequent pregnancy. METHODS OF STUDY: Seventeen women with two successive spontaneous abortions with normal karyotype in the conceptus and 15 women with male-factor infertility were studied. Subsequent pregnancy outcomes in 17 recurrent abortion patients were noted; 11 had live birth, while six aborted in the first trimester. All of 15 women with male-factor infertility became pregnant after therapy, resulting in live birth in all cases. Endometrium was sampled during the peri-implantation period before subsequent pregnancy. We immunostained paraffin-embedded sections for lymphocyte markers including natural killer (NK) cell markers, CD56 and CD16, a B-cell marker CD20, T-cell markers CD3 and CD8, and a specific T-helper(Th)2 and T-cytotoxic (Tc)2 marker termed 'chemoattractant receptor-homologous molecule expressed on Th2 cells' (CRTH2). Immunoreactive cells for these antigens were counted and positivity ratios to CD45- or CD3-positive cells were calculated. These parameter were compared between 17 patients with histories of recurrent abortion and 15 control women and also compared between 11 patients whose subsequent pregnancy was successful and six patients whose subsequent pregnancy was a failure. RESULTS: Numbers of CD45+, CD56+, CD16+, CD20+, CD3+, CD8+, and CRTH2+ cells in recurrent abortion patients resembled those in controls. No significant difference in lymphocyte subset numbers or ratios was noted between patients whose subsequent pregnancy was successful and those who again aborted. CONCLUSION: We could not predict pregnancy outcome by immunophenotypic analysis of endometrium in women with recurrent abortion.     

抗生殖免疫抗体与不明原因反复自然流产的关系

目的：为探讨抗生殖免疫抗体与不明原因反复自然流产的关系。方法：采用ELISA法检测52例不明原因反复自然流产(流产组)血清抗精子抗体(AsAb)、抗子宫内膜抗体(EmAb)、抗卵巢抗体(AovAb)、抗心磷脂抗体(AcAb)和抗绒毛膜促性腺激素抗体(AhcGAb)的含量。结果：流产组AsAb阳性26．92％,EmAb阳性42．30％,AovAb阳性30．76％,AcA阳性46．15％和AhcGAb阳性48．07％;流产组的各项抗生殖免疫抗体检出率均明显高于对照组。结论：以上5种抗生殖免疫抗体可干扰卵的发育成熟、排卵、受精、胚泡着床和胚胎发育等过程。抗生殖免疫抗体与不明原因反复自然流产关系十分密切。     

No evidence for a decreased fertilizing potential after in-vitro fertilization using spermatozoa from polyzoospermic men

Polyzoospermia is generally recognized as a male factor contributing to infertility and/or recurrent abortion. Although a reduced spermatozoal fertilizing capacity is assumed to be involved, so far there is no conclusive explanation for the assumed reduced reproductive performance in these patients, and data on the fertilizing capacity of spermatozoa from polyzoospermic men are lacking. The present study therefore aimed at analysing the outcome after in-vitro fertilization (IVF)-embryo transfer in polyzoospermic patients. Retrospective analysis showed that only 0.5% out of 7863 IVF cycles were performed with spermatozoa from polyzoospermic men. The outcome of these IVF cycles shows neither a reduction in spermatozoal fertilizing capacity nor an increase in pregnancy wastage in cycles in which a pregnancy was obtained. These results may suggest a normal reproductive potential in polyzoospermic patients and therefore the question may be raised whether polyzoospermia represents a real pathological entity leading to infertility.      

Controversies in reproductive immunology.

Nine areas of current controversy in the field of immunology of reproduction have been selected for discussion: (1) do antisperm antibodies cause infertility; (2) does cell mediated immunity cause infertility; (3) do antibodies cause spontaneous abortion; (4) is abortion due to rejection of the "fetal allograft"; (5) is altered antigen expression crucial for survival of the "fetal allograft"; (6) is abortion mediated by graft rejection mechanisms; (7) does locoregional suppression prevent abortion; (8) does immunization to prevent abortion and promote pregnancy act via immunotropism and cytokine cross-talk; (9) do immune responses prevent spontaneous abortion in humans? The reasons for debate and uncertainty are reviewed and current data considered in an attempt to arrive at the most likely answer to each question. Directions for future research are proposed where appropriate.     

PCR检测沙眼衣原体与习惯性流产和女性不孕相关性研究

本文应用聚合酶链反应技术（ＰＣＲ），对１２０例不孕和１００例查体妇女的宫颈内膜标本进行沙眼衣原体检测，以了解女性沙眼衣原体感染与自发流产的关系，并与一般细胞培养法进行了比较。结果：不孕妇女中沙眼衣原体感染率为１８．３％，显著高于对照组（８％Ｐ＜０．０５），并且自发流产３次、４次的妇女沙眼衣原体阳性率明显高于对照组（Ｐ＜０．０１）．敏感性也较一般培养法高（Ｐ＜０．０１）。本研究提示：沙眼衣原体感染与自发性习惯性流产关系十分密切，而且ＰＣＲ法在检测沙眼衣原体感染方面较一般培养法更敏感、快速，是早期诊断生殖道沙眼衣原体感染的一项有价值的方法。     

Mouse is the new woman? Translational research in reproductive immunology

In an outbred mating typical of human reproduction, the embryo and feto-placental unit express paternal antigens to which the mother’s immune system can react. However, the embryo and feto-placental unit can engineer the maternal immune defense system towards helpful rather than harmful reactions. Indeed, this begins with the prospective mother’s exposure to paternal seminal plasma. In this review, the pregnancy complications of implantation failure (infertility), recurrent spontaneous abortion, pre-eclampsia and intrauterine growth restriction, and premature labor are examined to determine the degree of similarity between events in women and events in lab mouse models. The artificially induced model of endometriosis (which contributes to infertility) is also compared to what occurs in women. One may conclude that the female mouse provides a good analog of the human female. Nevertheless, it is always important to validate mouse data with human studies. The discussion focuses on the intrauterine interface between embryonic and placental tissues and maternal uterine tissues and the dialogue that is referred to as cross-talk. Issues relating to bidirectional transplacental traffic of immune system cells are not discussed as there is very little relevant data.     

Fertility outcomes following myomectomy in an urban hospital setting

OBJECTIVE: Infertility is rarely a consequence of myomas. However, a causal relationship may be suspected when other causes of infertility have been excluded. Uterine myomas have been reported in 27% of infertile women; 50% of women with unexplained infertility become pregnant after myomectomy. The objective of this study was to establish the impact of the surgical removal of myomas on fertility outcomes in women experiencing recurrent pregnancy loss or unexplained infertility. Fallopian tube, anovulatory disorders and male fertility factors had been appropriately excluded. DESIGN: This was a retrospective study in which we compiled data from the medical records of eight patients from 2003-2004 who underwent abdominal myomectomy for infertility or recurrent pregnancy loss. We calculated rates for subsequent spontaneous abortion, preterm delivery, cesarean delivery, malpresentation and postpartum hemorrhage. RESULTS: There were two patients who were nulliparous premyomectomy, and six had recurrent pregnancy losses. There was a cumulative success rate of 75% (six live births in eight patients) following myomectomy. One had two subsequent pregnancies. There were no spontaneous abortions. Three (37.5%) patients failed to conceive postmyomectomy, one of which was found to have bilateral tubal occlusion. Of the six pregnancies achieved, two (33%, 95% CI 2.06, 3.14) were preterm deliveries, six (100%, 95% CI 1.74, 3.50) were delivered by cesarean section and three (50%, 95% CI 3.50, 1.73) were malpresentations (two breech, one transverse lie). One patient (16%, 95% CI 2.06, 3.30) had abruptio placentae and two patients (33%, 95% CI 2.06, 3.14) experienced postpartum hemorrhage. CONCLUSION: This study suggests that there may be a beneficial effect of surgical removal of myomas on enhancing fertility and successful pregnancy outcome. However, the sample was too small to achieve statistical significance.     

Recurrent heterotopic pregnancy after repeated in-vitro fertilization treatment

We report a rare clinical case of recurrent heterotopic pregnancy in the same patient following in-vitro fertilization treatments. A 27 year old woman, who suffered from infertility for the last 4 years due to male factor, was being treated by intracytoplasmic sperm injection which resulted in two episodes of combined intrauterine and tubal pregnancy, in a 1 year period. The first ended in emergency salpingectomy by laparotomy and missed intrauterine abortion. The second was managed by laparoscopic salpingectomy and the synchronous pregnancy ended in the delivery of twins. The possibility of heterotopic pregnancy and recurrent heterotopic pregnancy, though rare, should be considered by every gynaecologist, especially those who use infertility treatment on patients.      

淋巴细胞主动免疫治疗母-胎免疫识别低下型反复性流产疗效分析

目的分析淋巴细胞主动免疫疗法治疗母-胎免疫识别低下型反复性流产（RSA）的临床疗效和作用机制。方法以临床筛查封闭抗体确诊为母-胎免疫识别低下型RSA未孕患者86例为研究对象,采用淋巴细胞主动免疫疗法治疗,将妊娠患者与同期不明原因反复性自然流产（URSA）已孕患者治疗情况对比观察疗效,对母-胎免疫识别低下型RSA患者治疗后不同归向原因进行对比分析该方法的作用机制。结果治疗后妊娠56例,妊娠成功51例,成功率91.07%,与对照组比较P〈0.01,主动免疫治疗疗效与患者年龄、反复流产次数有相关性,与注射淋巴细胞密度无相关性。结论母-胎免疫低下型RSA患者宜早期治疗,淋巴细胞主动免疫疗法是治疗母-胎免疫识别低下型RSA的有效方法。     

9号染色体臂间倒位的遗传效应探讨

目的 研究人类9号染色体臂间倒位的遗传效应,分析9号染色体臂间倒位与自然流产、不育、不孕的关系.方法 采取患者外周血进行淋巴细胞培养,按常规方法制备染色体,应用G显带和C显带技术进行核型分析;对3组患者分别与正常对照组进行比较.结果 在3117例受检患者中,共检出9号染色体臂间倒位66例,发生率为2.1%,其中自然流产组为2.1%,不育组为2.6%,不孕组为2.0%,正常对照组为0.9%,经统计学分析几组之间差异存在统计学意义.结论 9号染色体臂间倒位可导致异常生育.     

Association of maternal HLA haplotypes with recurrent spontaneous abortions

Histocompatibility typing was done on 63 women with idiopathic, recurrent abortions (greater than or equal to 3 consecutive, spontaneous abortions; summarized abortion rate: 92.8%), 112 of their full siblings and 101 parents. The distribution of full sisters sharing 2, 1 and 0 of the probands' haplotypes diverged from expected Mendelian segregation (p less than 0.05). Sisters sharing both the probands' haplotypes had an abortion rate of 59.1%, haploidentical sisters had an abortion rate of 25.0% whereas 6.3% of the pregnancies of the 0 haploidentical sisters had ended in miscarriage. The probands' HLA haplotypes included a significant (p less than 0.02) excess of HLA-A, B haplotypes which have previously been shown to exhibit features of positive linkage disequilibrium in Danes. Analysis of abortion rates among the probands and their siblings indicate that the idiopathic recurrent abortion syndrome and probably also the tendency to some sporadic abortions are inherited conditions determined by genes in the HLA region. The presented data may be compatible with an additive polygenic mode of inheritance with exclusive or predominant phenotypic expression in females controlled by an HLA linked spontaneous abortion susceptibility region (SASR).     

Hypothesis on the role of sub-clinical bacteria of the endometrium (bacteria endometrialis) in gynaecological and obstetric enigmas.

Unexplained infertility, recurrent abortion, dysfunctional uterine bleeding, pelvic pain, premenstrual syndrome, premature labour, placental insufficiency and pre-eclampsia are examples of common obstetric and gynaecological problems that frequently defy adequate explanation. Bacterial vaginosis, a non-inflammatory condition, is associated with premature labour, but antibiotics administered topically provide less effective prophylaxis than those administered orally. This would indicate that bacterial vaginosis might be a marker for significant genital tract bacteria, but some pathology is dependent on micro-organisms ascending out of reach of topical antibiotics. The author was led to consider the hypothesis that micro-organisms, possibly those associated with bacterial vaginosis, surreptitiously inhabit the uterine cavity (bacteria endometrialis) where they are culprits of some common gynaecological and obstetric enigmas. The objective of this review is to provide an initial theoretical examination of this hypothesis. Bacteria in the endometrium have been associated with infertility. Antiphospholipids have been linked to recurrent miscarriage and pre-eclampsia and with infections including Mycoplasma. Pre-eclampsia might be explained by an exaggerated host response to intrauterine micro-organisms or bacterial toxins. The hypothesis that one common factor, bacteria endometrialis, could provide a plausible explanation for a variety of obstetric and gynaecological mysteries is particularly intriguing. There is sufficient evidence to justify further investigation.