复发性流产的免疫治疗效果分析

目的了解采用淋巴细胞对复发性流产进行主动免疫的疗效。方法采用丈夫外周血淋巴细胞治疗复发性流产,454例患者疗程结束并成功随访,妊娠至20周后者为治愈。结果 116（25.55%）例足月分娩,治愈率70.48%（未包括已孕20周内）。其间1例孕20周诊断无脑儿,1例孕26周超声示胎儿先天性左心发育不良,畸形率0.44%。结论免疫治疗是安全、有效的治疗复发性流产的方法之一,能确实解决病患实际问题。     

Allogenic Lymphocyte Immunotherapy for Unexplained Recurrent Spontaneous Abortion: A Meta‐Analysis

Allogenic lymphocyte immunotherapy (LIT) as a treatment for unexplained recurrent spontaneous abortion (URSA) is still controversial due to the lack of enough controls to evaluate its effectiveness. Eighteen randomized, placebo‐controlled trials with LIT for URSA were included in the meta‐analysis. Live birth rates for each group were extracted, and the overall odds ratio (OR) for LIT was calculated. The success rate of treatment group was significantly higher (OR 3.74, 95% CI 3.07 ~ 4.57). LIT performed before and during pregnancy had dramatically improved the live birth rate in women with URSA (OR 4.67, 95% CI 3.70 ~ 5.90). The overall OR was 5.25 (95% CI 4.16 ~ 6.64), which supports a low dose of lymphocytes for treating URSA. Our results indicate that LIT provides a significantly beneficial effect over placebo for URSA. LIT given before and during pregnancy is superior to LIT given only before pregnancy, and the lower doses per treatment (less than 100 × 10⁶ lymphocytes or 100 mL peripheral blood) achieved a better outcome.     

Suppression of Natural Killer Cell Activity by Monocytes Following Immunotherapy for Recurrent Spontaneous Aborters

PROBLEM : Natural killer (NK) cell activity has previously been shown to decrease in normal pregnancy as compared with the nonpregnancy state. The purpose of this study was to determine NK cell activity in recurrent aborters and to investigate the kinetics of NK cell activity following immunotherapy. METHODS : Recurrent aborters (N = 17) were immunized with husbands' mononuclear cells (1 × 10⁸) twice during the early stage of current pregnancy. NK cell activity of recurrent aborters as well as that of normal pregnant (N = 12) and nonpregnant (N = 6) women (controls) was determined by ⁵¹Cr release assay. Monocytes were depleted from the mononuclear cell fraction and its effect on the NK cell activity was determined as well. RESULTS : At around 5 wk of gestation, NK cell activity in recurrent aborters before treatment was significantly higher (28.0 ± 5.1%) than that in normal pregnancy (18.9 ± 4.3%) (P < 0.01). Following immunotherapy, NK cell activity of recurrent aborters (N = 13) who maintained their pregnancy decreased significantly (21.7 ± 8.9%) (P < 0.05). In contrast, NK cell activity of recurrent aborters (N = 4) who aborted their current pregnancy did not decrease. Depletion of monocytes resulted in a significant increase in NK cell activity (P < 0.05). CONCLUSIONS : This study suggests that the immunotherapy induces suppression of NK cell activity which may contribute for the maintenance of pregnancy. Moreover, monocytes may be involved in this suppression.     

The Influence of Intravenous Immunoglobulin Treatment on Maternal Immunity in Women With Unexplained Recurrent Miscarriage

PROBLEM: Recently the protective value of high-dose intravenous immunoglobulin (IVIG) in the treatment of unexplained recurrent miscarriage has been reported to be similar to that of conventional immunotherapy with paternal leukocytes. We examined the effect of IVIG treatment on the cellular and humoral level of maternal immunity to demonstrate the possible mechanism by which IVIG might act to prevent recurrence of pregnancy loss. METHOD: Eight patients were treated with a 20- to 25-g dose of IVIG every 2 to 3 wk during their first-trimester pregnancies. The development of anti-idiotypic autoantibodies against maternal T-cell receptors, maternal anti-paternal lymphocyte antibodies detected by flow cytometric crossmatch, and changes of maternal lymphocyte subpopulations were monitored before pregnancy and then weekly during IVIG treatment. RESULTS: Five of eight patients gave birth successfully after IVIG treatment given during the first trimester of pregnancy (success rate: 62.5%). Although we could not demonstrate a general immunological effect of IVIG on maternal immunity in vivo, a few significant changes of immunological parameters were found in some patients. CONCLUSION: Our results suggest that the effect of IVIG on maternal immunity is not a passive increase of blocking antibody including anti-HLA antibody or modification of maternal T-cell subsets but, more likely, a passive increase of anti-idiotypic antibody against anti-HLA antibody or soluble HLA antigens. However, whether the immunomodulating effect of IVIG is related to its possible mechanism to prevent abortion remains unestablished.     

Immunity to Cytomegalovirus in Women With Unexplained Recurrent Spontaneous Abortion

ABSTRACT: Humoral and cellular immunity to cytomegalovirus (CMV) has been assessed in women suffering unexplained recurrent spontaneous abortions (RSA). A significantly lower prevalence of serum anti-CMV antibodies was observed for RSA women compared with either their male partners or age-matched female controls, unlike for serum antibodies to Herpes simplex virus. In addition, there was a markedly impaired lymphocyte proliferative response to CMV for CMV-sero-positive RSA women compared with CMV-seropositive controls. These results indicate that women with unexplained RSA have difficulty in responding to CMV, and are of significance when considering leukocyte transfusion immunotherapy.     

不明原因习惯性流产患者主动免疫治疗前后Th1/Th2型细胞因子水平的变化

为探讨主动免疫治疗对不明原因习惯性流产 (UHA )患者Th1/Th2型细胞因子水平的影响。采用酶联免疫吸附法检测15例正常非妊娠妇女、 35例UHA患者淋巴细胞主动免疫治疗前后经滋养细胞抗原刺激的外周血单个核细胞 (PBMC )培养上清液中IL 2、IFN γ、IL 4、IL 10的水平。结果发现 :(1)在最佳诱导时间下 ,UHA组治疗前PBMC产生IL 2、IFN γ的水平明显高于正常对照组 (P <0 0 5 ) ,IL 4、IL 10水平明显低于正常对照组 (P <0 0 5 )。UHA组治疗后PBMC产生IL 2、IFN γ的水平较治疗前明显降低 (P <0 0 5 ) ,IL 4、IL 10水平较治疗前明显升高 (P <0 0 5 )。UHA组治疗后PBMC产生各细胞因子的水平与正常对照组比较 ,差异均无显著性 (P >0 0 5 ) ;(2 )UHA组 35例患者主动免疫治疗后半年内 2 8例妊娠 ,其中 9例又出现自然流产。 9例自然流产者治疗后IL 2、IFN γ水平未明显下降 ,IL 10水平未明显上升。 19例妊娠成功者治疗后IL 2、IFN γ水平较治疗前明显下降 (P <0 0 5 ) ,IL 4、IL 10水平明显上升 (P <0 0 5 )。以上结果表明UHA患者对滋养细胞抗原产生以Th1型反应为主的免疫应答 ,产生大量Th1型细胞因子 ,主动免疫治疗有助于上调Th2型细胞因子及下调Th1型细胞因子 ,利于UHA患者妊娠成功。     

Is an Additional Vaccination Necessary for a Successful Second Pregnancy in Unexplained Recurrent Aborters Who Were Successfully Immunized With Their Husband's Lymphocytes Before the First Pregnancy?

PROBLEM: Is an additional immunotherapy necessary or not for patients who have obtained successful results after initial immunotherapy? METHODS: The successive pregnancy outcome was analyzed in 22 patients out of 29 unexplained recurrent aborters who had undergone immunotherapy with their husband's lymphocytes according to our previously reported protocol (Takakuwa et al., Am J Reprod Immunol Microbiol. 10:1–9, 1986; Takakuwa et al., Am J Reprod Immunol. 23:37–41, 1990) and had obtained successful outcome between January 1983 and December 1989. In addition, the alteration of blocking antibodies (BAbs), which was evaluated by a one-way mixed lymphocyte culture reaction (MLR) blocking assay between the spouses, was analyzed in 26 patients out of 29. RESULTS: None of the 22 patients underwent further immunotherapy because a significantly high titer of MLR-BAbs had been detected before the new pregnancy. In 19 out of the 21 patients (90.5%), pregnancy was successful. CONCLUSION: Additional immunotherapy is not necessary for patients who have obtained successful results after the initial immunotherapy and are positive for MLR-BAbs after their first delivery.     

Enhancement of the Expression of Progesterone Receptor on Progesterone-Treated Lymphocytes After Immunotherapy in Unexplained Recurrent Spontaneous Abortion

PROBLEM: The immunological mechanism of an effective immunotherapy with paternal lymphocytes for unexplained recurrent spontaneous abortion (RSA) is not yet clear. Previous studies revealed that progesterone plays an important role in maintaining normal pregnancy and lower expression of progesterone receptor (PGR) on lymphocytes was found in RSA. Therefore, it was of interest to investigate whether immunotherapy for RSA would be able to enhance the expression of PGR on lymphocytes of RSA. METHOD: PGR expression on lymphocytes was analyzed with indirect immunofluorescence using flow cytometry. RESULTS: There was no change of PGR expression on PBL of RSA between pre- and post-immunotherapy (P > 0.05), while in the presence of 10.0 ug/ml progesterone for 24 h, PGR expressed on PBL on post-immunotherapy was increased significantly as compared with that of pre-immunotherapy in successful cases (P < 0.05) and decreased in abortive cases (P < 0.05). Most PGR was expressed on both CD4⁺ and CD8⁺ lymphocyte subsets. In successful cases, CD8⁺PGR⁺ subset of post-immunotherapy was found to be increased significantly (P < 0.05) in comparison with that of pre-immunotherapy. CONCLUSION: The data in the present study suggest that immunotherapy for RSA induced a higher expression of PGR on progesterone-treated lymphocytes, which may be involved in successful pregnancy.     

Intralipid as Treatment for Recurrent Unexplained Abortion?

PROBLEM: Safe, effective, and inexpensive alternatives to partner leukocyte immunotherapy are being sought. Psychotherapy may be effective but it is uncertain what constitutes effective treatment and the form of treatment tested in cohort controlled trials is expensive. IVIG also appears effective, but is expensive. METHOD: A published double blind randomized controlled trial in which Intralipid (Kabi Vitrum, Toronto, Ontario) was used as a control versus trophoblast membrane vesicles was reviewed. A prediction made from this data was then tested using the DBA/2-mated CBA/ J mouse model of recurrent spontaneous abortion. RESULTS: It can be hypothesized from the human clinical trial data that Intralipid even in small doses could be an effective antiabortion treatment. The number of patients in the published study is too small for the required degree of precision. Intralipid was highly effective in preventing abortion in mice, and protection was prolonged. This may be explained by previous data in the literature showing that Intralipid affects the reticuloendothelial system of the recipient. CONCLUSIONS: The evidence suggests that Intralipid might be an effective treatment for human recurrent miscarriages, and injection into women who may become pregnant has been found ethically acceptable at one university center. Comparison of Intralipid to partner leukocyte immunotherapy or IVIG would be worthwhile. For adequate statistical power, this would require a large, multicenter, prognostically stratified randomized controlled trial and could be accomplished via the Recurrent Miscarriage Immunotherapy Trialists Group network.     

Variation in Antisperm Antibody Results Using Different Assays

PROBLEM: The detection of various types of antisperm antibodies (ASA) in the serum varies among different assays. This variation may influence the diagnosis and management of infertile couples who are tested for such immunologic factors. This prospective study was conducted to determine the variation in the results of ASA as measured by the sperm immobilization (SI), sperm agglutination (SA), and the indirect immunobead (IB) assays. METHOD: The sera of 79 patients that tested positive for ASA by at least one of the assays listed above were concurrently tested with all three assays. RESULTS: Using an individual ASA assay, 66 (84%), 26 (33%) or 36 (46%) of sera tested positive by the SA, SI, or IB assays, respectively. However, using a combination of assays, 67 (85%), 78 (99%) or 40 (51%) of sera tested positive using either the SA+SI, SA+IB or SI+IB assays, respectively. CONCLUSION: These findings suggest that the utilization of different assays to detect ASA may detect sera that are positive for ASA with more reliability than single assay testing.     

The Effectiveness of Allogeneic Leukocyte Immunization in Unexplained Primary Recurrent Spontaneous Abortion

PROBLEM: Unexplained primary recurrent spontaneous abortion (RSA) can be viewed as a partner-specific problem for which immunization with allogeneic leukocytes is being offered as therapy. Published data from randomized controlled trials have produced conflicting results regarding treatment effectiveness. The aim of this study was to perform a subgroup analysis of the data from a recent worldwide collaborative meta-analysis using the raw data for patients with primary RSA entered into randomized controlled trials of immunotherapy. METHODS: Data from randomized controlled trials in eight centers were included in this analysis. Individual patients were included only if they had had three or more spontaneous abortions, no previous pregnancy beyond 20 weeks' gestation, no identifiable cause for the abortions, and no evidence of antipaternal antibodies. Meta-analysis by centre and logistic regression analysis were performed to determine the overall effect of treatment in achieving live birth and to identify variables that affect the prognosis for a successful outcome. RESULTS: In the meta-analysis by center, immunotherapy significantly improved the live birth rate (common odds ratio = 1.94, 95% confidence interval (CI) = 1.20 to 3.12). In the analysis by patient, the likelihood of a successful outcome was also significantly better with treatment (relative risk = 1.46, 95% CI 1.19 to 1.69). The absolute treatment effect was 16.3% producing a number needed to treat of 6. The number of previous abortions had a significant negative correlation with live birth rate, such that for each additional pregnancy loss beyond three, the likelihood of live birth was reduced by 23%. CONCLUSION: Allogeneic leukocyte immunization is an effective treatment for unexplained primary RSA when pretreatment antipaternal antibodies are absent. Better diagnostic tests are required to identify patients who may derive maximal benefit from this therapeutic approach.     

Correlation Between Regional Specificity of Antisperm Antibodies to the Spermatozoan Surface and Complement-Mediated Sperm Immobilization

ABSTRACT: Sera from men at risk for immunity to spermatozoa were screened for antisperm antibodies by immunobead binding following passive antibody transfer to antibody-free sperm of fertile donors. The percent motile sperm after incubation in diluted antibody positive serum in the presence of complement was compared with the regional distribution of immunoglobulins bound to the sperm surface. The extent of complement-mediated sperm immobilization varied with immunoglobulin class and with the location of antibody bound to the sperm surface. Tests utilizing complement-mediated immobilization of sperm are insensitive to the presence of antibodies of IgG and IgA classes that are directed against the head, the distal one-fifth of the sperm tail principal piece, or the tail end piece. A high degree of immobilization was found only when IgG binding occurred on the distal two-fifths to three-fifths of the principal piece of the tail or when IgM bound to the sperm tail end piece.     

Production of Blocking Antibodies by Vaccination With Husband's Lymphocytes in Unexplained Recurrent Aborters: The Role in Successful Pregnancy

ABSTRACT: To elucidate an immunological mechanism in terms of the effectiveness of vaccination of the unexplained habitual aborters with their husband's lymphocytes, 20 patients were selected as the experimental group, and 10 fertile couples were selected as the control group. Subjects were studied by mixed lymphocyte reaction-blocking assay so as to determine whether they had blocking antibodies (BAbs) in their sera. In the experimental group, BAb levels were found to be significantly lower as compared to the ten control multiparous wives; 17 cases (85%) of them were proved not to have sufficient BAbs. Significant sharing of HLA-D/DR antigens was observed in experimental couples. Then, 10 out of 17 patients with evidence of no produced BAbs were vaccinated with their husband's lymphocytes, and all of them were observed to produce BAbs within three vaccinations. After vaccination, seven out of ten patients have so far become pregnant, five of these pregnancies have been successful, with evidence of continuing production of BAbs. In conclusion, vaccination of the patients with husband's lymphocytes was found to stimulate a production of BAbs, and it was thus strongly suggested that this may lead to their production in a subsequent pregnancy, which would allow its success.     

Worldwide Collaborative Observational Study and Meta-Analysis on Allogenic Leukocyte Immunotherapy for Recurrent Spontaneous Abortion1

PROBLEM: Recurrent spontaneous abortion (RSA) is a common complication of pregnancy for which there is no known cure. Therefore, effective treatment is needed. Published results from controlled clinical trials of allogeneic leukocyte immunization of women suffering from RSA have given conflicting results. To address this controversy, the international raw data of all patients who had been entered into clinical trials that included a control group were collected and analyzed. The primary question to be answered was whether alloimmune stimulation of the female partner improves the subsequent live birth rate. METHODS: Fifteen clinical centers were identified worldwide because they controlled appropriate raw data. Consequently, nine randomized trials (seven double-blinded) were evaluated independently by two separate data analysis teams to assure conclusions were robust. One team also compared randomized trials to the results of six nonrandomized cohort-controlled studies to test for bias in nonrandomized trials. Factors predicting successful live births among couples with RSA were evaluated by logistic regression. RESULTS: Although the two independent analyses made use of different definitions and utilized different statistical methods, the results of both were similar. The live birth ratios (ratio of live births in treatment and control groups) with 95% confidence intervals (CI) were 1.16 (CI, 1.01-1.34, P = 0.031) and 1.21 (CI, 1.04-1.37, P = 0.024), respectively. The absolute differences in live birth rates between treatment and control groups were 8% and 10% in respective analyses. Results in randomized and nonrandomized trials were surprisingly similar despite significant differences in composition of control and treatment groups. Live birth rates were lower with older female partners, more than five abortions, with a positive ANA or with positive anticardiolipin antibodies. Live birth rates were higher if the female partner had prior to treatment serum antibodies to paternal leukocytes or converted from negative to positive with immunization. Approximately 0.5% of controls and 2.1% of treated patients experience side effects for a 1.6% treatment related effect. There was no evidence of an increased risk of adverse effects on the fetus. CONCLUSIONS: Two independent analyses of worldwide data on allogeneic leukocyte immunization for treatment of RSA suggest that alloimmunization may be an effective treatment. The treatment effect appears, however, to be small, and the data indicate that immunotherapy helps only 8% to 10% of affected couples. A current lack of diagnostic tests defining patients who most likely would benefit from immunotherapy, precludes the identification of a patient population that would benefit most from such treatment. The efficacy of treatment in such a subgroup could be expected to increase and could be of sufficient magnitude to allow the determination of more effective immunization protocols. This study does not exclude the possibility of a partial correction of a widely prevalent immunology defect by immunotherapy. The presence of such a defect would indicate a need for more effective therapy. The unexplained variation in pregnancy success rates of control groups among centers continues to present a statistical problem, limiting the statistical evaluation of retroactively obtained data.     

抗独特型疫苗在肿瘤免疫治疗中的研究现状及前景

恶性肿瘤的治疗已有很多进展,但微小残留病灶仍难以被现行的化疗、放疗、手术等方案彻底清除。如果应用肿瘤免疫治疗激发机体免疫监视系统,消灭残存肿瘤细胞,有可能彻底治愈肿瘤。肿瘤特异性主动免疫治疗研究已有几十年历史,其中抗独特型抗体由于能模拟肿瘤抗原打破机体对肿瘤的免疫耐受而越来越受到人们的重视,成为肿瘤免疫治疗的新途径。     

母-胎免疫识别低下型反复自然流产配偶淋巴细胞免疫疗法的改进

比较配偶淋巴细胞诱生后与非诱生免疫疗法 ,对于母 胎免疫识别低下型反复自然流产 (RSA )的临床疗效 ,并分析其疗效机制。 194例母 胎免疫识别低下型RSA患者随机分成 2组 ,分别采用经体外诱生的或未经体外诱生的配偶淋巴细胞对其进行皮内多点注射免疫治疗。分别观察随后的妊娠结局、封闭抗体水平。经配偶淋巴细胞免疫后 ,体外诱生的淋巴细胞免疫组妊娠成功率为 90 0 % ;未经体外诱生的淋巴细胞免疫组妊娠成功率为 84 8%。对于封闭抗体各项指标分析结果显示 ,配偶淋巴细胞皮内免疫能有效促进RSA患者封闭抗体及其抗独特型抗体水平的升高 ;经体外诱生的配偶淋巴细胞免疫疗法能显著提高RSA患者外周血抗CD3 BE的水平。配偶淋巴细胞皮内免疫疗法通过刺激封闭抗体的产生 ,改善随后的妊娠预后 ,配偶淋巴细胞经体外诱生后作为免疫原 ,通过升高抗CD3封闭抗体水平 ,有助于改善妊娠预后。     

淋巴细胞免疫治疗不明原因复发性流产不同疗程临床效果分析

目的 探讨本院生殖门诊患者淋巴细胞主动免疫治疗对原因不明性复发性流产不同疗程的疗效.方法 选取本院患者200例,治疗组:提取其丈夫淋巴细胞进行主动免疫,孕前及孕后均4次.对照组:同样进行淋巴细胞主动免疫,孕前4次,孕后只注射1～2次.自孕前免疫治疗4次疗程完成时开始,18个月后对其封闭抗体转阳率、妊娠成功率等进行比较.结果 2组比较对照组封闭抗体转阳率、妊娠成功率均低于治疗组,差异有统计学意义(P＜0.05).结论 淋巴细胞提取治疗免疫原因引起的复发性流产,微创,操作简单,安全经济,疗效满意,值得临床推广.     

Antisperm Antibody Detection: 2. Clinical,Biological, and Statistical Correlation Between Methods

PROBLEM: In clinical andrology, the detection of antisperm antibodies (ASA) is regarded as one of the most important steps in the study of male infertility. This practice is generally accepted even though there is still some disagreement about the true meaning of antisperm immunity, and there remains a good deal of controversy about the test regarded as the most suitable for the detection of antibodies directed against sperm antigens. International Workshops have tried to standardize universally accepted protocols. A panel of three or four methods is generally advised to provide a correct and complete screening of patients with antisperm immunity. The aim of the present paper is to report our studies on the correlation between direct methods (IBT, MAR test) and indirect methods (gelatin agglutination test [GAT], and tray agglutination test [TAT]) and to establish whether biological models can explain the antibody tests results. An attempt was also made to establish a “predictive threshold” to explain even apparently discordant direct and indirect results.     

Immunotherapy for Recurrent Pregnancy Loss: Analysis of Results From Clinical Trials

PROBLEM: Up to 80% of unexplained recurrent spontaneous abortions (RS A) are thought to have an immunologic mechanism. Yet clinical trials using immunotherapy to treat women experiencing RSA have low treatment effects. The present study was undertaken to explain the low treatment effects. METHODS: Results of clinical trials using allogeneic leukocyte immunization and intravenous (IV) immunoglobulin (Ig) are compared. The mechanisms of pregnancy loss are reviewed in light of data on frequency of karyotype abnormalities in trophoblast of failing pregnancies. RESULTS: Results of two independent analyses using allogeneic leukocyte immunization as immunotherapy for all women with RSA revealed live birth ratios of 1.16 (P = 0.03) and 1.21 (P = 0.02). When the analysis was limited to primary aborters, the live birth ratio increased to 1.46 (P = 0.006). Live birth ratio after immunotherapy for all RSA using IVIg was 1.88 (P = 0.04). Because of low treatment effects, confounders to treatment success of maternal age and number of previous abortions were studied. Chromosomal abnormalities have been identified in 55% of concepti from RSA. The frequency of chromosomal abnormalities remained constant for up to six pregnancy losses. Women with a history of primary compared to secondary RSA had a higher frequency of karyotypically abnormal concepti (χ² = 4.54, P < 0.05). Risk factors for RSA also include number of previous losses. CONCLUSION: Chromosomal abnormalities are a significant confounder when evaluating efficacy of immunotherapy for treatment of RSA. Some women with RSA have a high risk of recurrent chromosomal problems.     

Cell-Surface CD200 May Predict Efficacy of Paternal Mononuclear Leukocyte Immunotherapy in Treatment of Human Recurrent Pregnancy Loss

Problem The allogeneic leukocytes in transfused blood can modulate the recipient’s immune system so as to induce TGF‐β‐producing suppressor cells, and the cell‐surface CD200 tolerance‐signaling molecule on mononuclear dendritic cells is required for this effect. A subset of couples with unexplained recurrent pregnancy loss appears to benefit from transfusion of allogeneic paternal blood leukocytes (LIT), and considerable effort has been devoted to characterizing those who may benefit. Some data has been accumulated for LIT as sole therapy in patients with classical spontaneous abortions with respect to dose–response, duration of protection, need for boosting, excluding patients with autoimmunity, and inefficacy of paternal mononuclear cells stored at 4°C overnight before use which causes loss of cell‐surface CD200. Recent data emphasize an important role of expression of the CD200 tolerance‐signaling molecule on cells used to prevent abortions both in mice and humans. Method of study An observational study of outcome as a function of the number of CD200⁺ paternal mononuclear cells was performed. Fourteen patients constituted the pilot group. Patients with autoimmunity who had failed inspite of treatment with IVIG + Heparin + Aspirin ± Prednisone were allowed to have paternal mononuclear cells added to their therapy. CD200 on purified paternal blood mononuclear cells was measured by flow cytometry. Results The number of CD200⁺ cells administered was significantly greater in women achieving pregnancy (39.2 × 10⁶ versus 20.8 × 10⁶, P < 0.025) and in those who achieved a live birth (50.2 × 10⁶ versus 20.8 × 10⁶, P < 0.005) compared to those who did not achieve pregnancy, and % of paternal cells that were CD200⁺ was greater (11–12.5% versus 5.6%, P < 0.01). Amongst those achieving pregnancy which failed, the CD200⁺ cell dose was not significantly different from the non‐pregnant group (30.5 × 10⁶ versus 20.8 × 10⁶). Conclusion The number of CD200⁺ paternal mononuclear leukocytes may be an important determinant of subsequent reproductive outcome in a subset of patients. A lower % CD200⁺ cell number may also reflect hitherto unappreciated paternal factors bearing on reproductive success. It is feasible to recruit women to enter observational studies and to obtain useful data as a foundation for further studies. More complete patient characterization in a larger study is needed.