Glucocorticoid supplementation improves reproductive outcomes in infertile women with antithyroid autoimmunity undergoing ART: A meta-analysis.

BACKGROUND: Thyroid autoimmune disease (TAI) has been verified to be related to multiple adverse pregnancy outcomes. A growing number of evidences highlight the protective roles of glucocorticoid on the treatments of TAI. This meta-analysis aimed to study whether it is beneficial to add glucocorticoid treatment in infertile women with TAI when they are undergoing assisted reproductive technology (ART). METHODS: We conducted a systematic search in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang database, Weipu China Science and Technology Journal Databases (VIP database) up to September 10, 2020. The Revman 5.3 software was utilized for data statistics. We used a random-effects model to analyze data and the odds ratio (OR) combining with 95% confidence interval (95% CI) were employed to reveal the results. RESULTS: Three publications with 237 antithyroid antibody (ATA)-positive and 384 ATA-negative women were included in the final analysis. Overall, glucocorticoid therapy showed satisfying effects on improving clinical pregnancy rate (OR = 4.63, 95% CI [2.23, 9.58], I2 = 0.0%, P < .0001) and live birth rate (OR = 3.19, 95% CI [1.13, 9.04], I2 = 0.0%, P = .03) of ATA-positive women compared with control group. However, it seems that glucocorticoid showed no significant difference in the abortion rate (OR = 0.62, 95% CI [0.09, 4.32], I2 = 35%, P = .64) and oocyte recovery (OR = 2.26, 95% CI [-1.46, 5.99], I2 = 79%, P < .0001) between the 2 groups. CONCLUSIONS: Glucocorticoid may improve the pregnancy outcomes of ART women with ATA positive, but there is no significant reduction in the risk of miscarriage. Due to the limited enrolled references, glucocorticoid adjuvant therapy should be applied after more randomized controlled trials.

Increasing number of implantation failures and pregnancy losses associated with elevated Th1/Th2 cell ratio.

PROBLEM: We aimed to assess whether an imbalance of T-helper (Th) 1 and Th2 cells contributes to implantation failure and pregnancy loss. METHOD OF STUDY: In this cross-sectional study, 197 consecutive patients with a history of repeated implantation failure (RIF) after three or more embryo transfer (ET) cycles and/or recurrent pregnancy loss (RPL) after two or more clinical pregnancy losses underwent Th cell testing. After excluding 42 women aged ≥44 and 9 with vitamin D supplementation, we recruited 146 women including 79 with RIF and 81 with RPL. Fourteen women had a history of both RIF and RPL. We also recruited 45 fertile women and 40 general infertile women without a history of in vitro fertilization treatment. This study was approved by the local ethics committee. RESULTS: There was no significant difference in IFN-γ-producing Th1 and IL-4-producing Th2 cell levels between the fertile and general infertile women, but Th1 cell levels and the Th1/Th2 cell ratio were significantly higher in the women with ≥4 ET cycles and ≥2 pregnancy losses than in the fertile and general infertile women. In the general infertile women, the total livebirth rates including natural conception after two ET cycles in the normal and high Th1/Th2 groups (Th1/Th2 <11.8 and ≥11.8, respectively) were 66.7% and 87.5%, respectively (p = .395). CONCLUSIONS: A high Th1/Th2 cell ratio was linked to ≥4 implantation failure cycles and ≥2 pregnancy losses but not to general infertility.

Chinese herbal medicine for immune infertility: A protocol for systematic review and meta-analysis.

BACKGROUND: Infertility is a reproductive disorder caused by multiple causes and is an adverse event of reproductive health for couples in the reproductive period. Women who do not avoid sex for at least 12 months and are not pregnant are said to be infertile. 10% to 20% of infertility is caused by immune factors. At present, there is no unified diagnostic standard for immunological infertility. Clinically, it is considered that abnormal ovulation and reproductive system function of women are excluded, and no obvious pathogenic factors occur; routine examination of male semen is normal, but there is evidence of anti-reproductive immunity, thus causing infertility is immunological infertility. Traditional Chinese medicine (TCM) has a long history of treating infertility and has remarkable curative effect. It plays an important role in the treatment of gynecological and obstetrical diseases in China. The purpose of this study is to evaluate the efficacy and safety of traditional Chinese medicine for the treatment of immune infertility. METHOD: we searched the literature from following databases: Cochrane Library, PubMed, China Biomedical Literature Database (CB), EMBASE, Chinese Journal of Science and Technology (VIP), China National Knowledge Infrastructure Database (CNKI) and Wanfang Database were searched. All the databases mentioned above will be searched from the start date to the latest version. A manual search of all references to the included trials, published randomized controlled trials (RCTs) whether blind or unblind, any languages and length of follow up were included. Treatments included Chinese medicinal herbs (single or compound). Controlls were placebo and western medicine, or no intervention. Key outcomes will include pregnancy rates, the efficiency of Chinese herbal medicine (at least one negative antibody for infertility), birth rates (the ratio of the number of pregnant women giving birth to their babies normally after herbal treatment to the total number of patients treated), recurrence rate and safety index. Two evaluators independently retrieved and extracted data and import it into Endnote X8. Then they conduct methodological evaluation on the quality of the included studies, and meta-analysis was conducted with RevMan 5.3 and Stata 13.0 software. We will use the Cochrane risk analysis tool to assess the risk of bias. Differences will be resolved by consensus or through the participation of third parties. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The purpose of this study is to evaluate the efficacy and safety of traditional Chinese herb medicine in the treatment of immune infertility. CONCLUSION: This meta-analysis can provide evidence for clinicians to help patients make better choices. TRIAL REGISTRATION NUMBER: INPLASY2020120073.

Poor ovarian response is associated with serum vitamin D levels and pro-inflammatory immune responses in women undergoing in-vitro fertilization.

Poor ovarian response (POR1) limits the success of infertility treatment modality. In this study, we aim to investigate if POR is associated with serum 25(OH) vitamin D (VD2) levels and pro-inflammatory immune responses in infertile women with a history of in-vitro fertilization and embryo transfer failures. A retrospective cross-sectional study included 157 women with IVF failures. Study patients were divided into four groups based on serum 25(OH)VD level and ovarian responses during the most recent IVF cycle; low VD (LVD3) with POR, LVD with normal ovarian response (NOR4), normal VD (NVD5) with POR, and NVD with NOR. Serum 25(OH)VD level, cellular- and auto-immunity, and metabolic parameters, including homocysteine and plasminogen activator inhibitor-1 were investigated. Peripheral blood CD56+ NK cell levels (%) and NK cytotoxicity were significantly higher in POR-LVD when compared to the other groups (P < 0.05, respectively). CD19 + B and CD19+/5+ B-1 cell levels were significantly higher in women with POR-LVD as compared with those of NOR-LVD and POR-NVD (P < 0.05, respectively). TNF-α/IL-10 producing Th1/Th2 cell ratio of POR-LVD was significantly higher than those of POR-NVD and NOR-NVD (P < 0.05 respectively). Peripheral blood homocysteine level of POR-LVD was significantly higher than those of NOR-LVD and POR-NVD (P < 0.05 respectively). We conclude that assessment of cellular and autoimmune abnormalities and metabolic factors, such as homocysteine should be considered in women with POR and LVD. VD and folic acid supplementation may be explored further as a possible therapeutic option for POR with immune and metabolic etiologies.

Vitamin D Regulates Maternal T-Helper Cytokine Production in Infertile Women.

Vitamin D (VD) deficiency is associated with reproductive failure. However, the relationship between VD and maternal immunity remains unclear. We investigated the clinical efficacy of VD in maternal T-helper (Th) cytokines in 276 infertile women and examined for Th1 and Th2 cells based on the deficient, insufficient, and sufficient serum 25-hydroxyvitamin D3 (25[OH]VD) levels (<12, 12⁻30, and >30 ng/mL, respectively). Most infertile women had a low-level of VD (87.3%). Immunological tests of pre-/post-VD supplementation were performed in patients who were deficient and insufficient in VD. Of 23 patients, 11 (47.8%) exhibited sufficient VD levels after supplementation. Th1/Th2 cell ratio in patients with insufficient VD was significantly decreased after supplementation (p = 0.004). After supplementation, serum 25(OH)VD levels of the patients: 11 in the sufficient group showed significant decreases in Th1 cell level and Th1/Th2 cell ratio (p = 0.032 and 0.010, respectively), whereas no significant differences in Th1/Th2 cell ratio were recognized in the insufficient group. Furthermore, mid-luteal endometrial biopsies (n = 18) were processed for primary cultures and measured interferon [IFN]-γ and interleukin [IL]-4 in condition media. Decidualizing cultures with 1,25-dihydroxvitamin D3 (1,25[OH]2VD) decreased IFN-γ. Sufficient VD supplementation in women with insufficient VD may optimize maternal T-helper cytokines during pregnancy via rebalancing the Th1/Th2 cell ratio.

Dehydroepiandrosterone supplementation in women undergoing assisted reproductive technology with poor ovarian response. A prospective case-control study.

Objective The effects of dehydroepiandrosterone (DHEA) supplementation in Saudi Arabian women with poor ovarian response (POR) is presently unknown. The present study aimed to assess the benefits of DHEA supplementation in women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Methods This was a prospective case-control study involving 62 women who were diagnosed with POR and underwent IVF/ICSI between January 2012 and June 2016. The positive influence of DHEA in 34 women, compared with 28 women without supplementation, was defined as improvements in the number of oocytes retrieved, the fertilization rate, the number of grade I embryos generated and the pregnancy rate. Results Both groups were evenly matched for age, body mass index and laboratory test parameters. There were statistically significant differences between the groups with and without DHEA supplementation for oocyte yield (6.35 ± 2.41 versus 3.98 ± 3.2), Grade I embryos generated (55% versus 30%), positive pregnancy rate (21/34 versus 10/28), and live birth rate (18/34 versus 4/28). Conclusion DHEA supplementation in women with POR had a positive effect on hormonal profiles, the quality of the endometrium, the number of oocytes retrieved, the quality of embryos, and the pregnancy and live birth rates.

Chinese medicine as complementary therapy for female infertility.

Chinese medicine (CM) has been used in clinical treatment for thousands of years in China, Japan, Korea, and other countries. CM is at present attracting many attentions around the world for reproductive health care and disease prevention, including treatment of female infertility. This review focuses on the CM treatment for female infertility patients, and supplies a summary on the efficacy, safety, and mechanism of some Chinese herbal medicines, herbal medicine-derived active compounds, and acupuncture. A large number of researches have reported that CM could alleviate or even cure female infertility by regulating hormone, improving reproductive outcome of in vivo fertilization, affecting embryonic implantation, curing polycystic ovarian syndrome, endometriosis, pelvic inflammatory disease, relieving mental stress, and regulating immune system. Meanwhile, a few studies claimed that there was little adverse reaction of CM in randomized controlled trials. However, up to present there is a lack of adequate evidences with molecular mechanistic researches and randomized controlled trials to prove the CM as an effective and safe treatment for infertility. Thus, utility of CM as a complementary medicine will be a feasible method to improve the outcome of female infertility treatment.

Neonatal phytoestrogen exposure alters oviduct mucosal immune response to pregnancy and affects preimplantation embryo development in the mouse.

Treatment of neonatal mice with the phytoestrogen genistein (50 mg/kg/day) results in complete female infertility caused in part by preimplantation embryo loss in the oviduct between Days 2 and 3 of pregnancy. We previously demonstrated that oviducts of genistein-treated mice are "posteriorized" as compared to control mouse oviducts because they express numerous genes normally restricted to posterior regions of the female reproductive tract (FRT), the cervix and vagina. We report here that neonatal genistein treatment resulted in substantial changes in oviduct expression of genes important for the FRT mucosal immune response, including immunoglobulins, antimicrobials, and chemokines. Some of the altered immune response genes were chronically altered beginning at the time of neonatal genistein treatment, indicating that these alterations were a result of the posteriorization phenotype. Other alterations in oviduct gene expression were observed only in early pregnancy, immediately after the FRT was exposed to inflammatory or antigenic stimuli from ovulation and mating. The oviduct changes affected development of the surviving embryos by increasing the rate of cleavage and decreasing the trophectoderm-to-inner cell mass cell ratio at the blastocyst stage. We conclude that both altered immune responses to pregnancy and deficits in oviduct support for preimplantation embryo development in the neonatal genistein model are likely to contribute to infertility phenotype.

[Study on changes in cytokines of infertile women with mycoplasma infection and intervention with traditional Chinese medicines].

OBJECTIVE: To investigate the changes in cytokines (IL-1beta, IL-2, TNF-alpha) of peripheral blood and cervical mucous of infertile women with mycoplasma infection and the effect of intervention of traditional Chinese medicines (TCMs). METHOD: According to the results of culture of mycoplasma from genital tracts, 72 patients with positive mycoplasma were randomly divided into the TCM group (38 cases) and the western medicine group (34 cases). The western medicine group was treated with 0.5 g azithromycin for 3 days and consecutively treated for six courses of treatment, each course of treatment of 4 days. The TCM group were treated with Xiaozhi decoction twice every day for 6 weeks. The IL-1beta, IL-2 and TNF-alpha levels of the peripheral blood and cervical mucous of the two groups were measured by the Ria testing before and after the treatment, and the mycoplasma culture (-) of 32 infertile women as set for control. RESULT: Before the treatment, TNF-alpha and IL-1beta in levels of the two treatment groups were higher than those of the control group (P < 0.01). In the TCM group, TNF-alpha and IL-1beta levels showed significant differences compared with those before the treatment (P < 0.05) and those of the western group after the treatment (P < 0.01); and IL-2 level didn't have significant change before and after the treatment. The cytokines in peripheral blood of the two treatment groups showed notable difference compared with those of the control group (P < 0.01). In TCM group, IL-2 level had remarkable difference compared with that before the treatment (P < 0.01) and compared with the control group after the treatment (P < 0.01). CONCLUSION: Cytokines (IL-1beta, IL-2, TNF-alpha) in the peripheral blood and cervical mucous increase in infertile women with the mycoplasma infection, suggesting that TCMs can effectively inhibit the levels of IL-1beta, IL-2, TNF-alpha in the peripheral blood and IL-1beta, TNF-alpha in cervical mucous. It is proved that Xiaozhi decoction can be used to treat infertile women with mycoplasma infection.

[Exploration into rules of combined Chinese and Western medical treatment on immune infertility].

In order to explore the rules of combined Chinese and Western medical treatment on immune infertility, the study was carried out by searching relative primary documents from databases and 26 articles (dealing with 5865 cases) were screened out. Excel was used to perform the frequency analysis on the Western drugs and 27 Chinese recipes emerging in the documents separately. It was discovered that the combined use of Chinese and Western medicines has its superiority. Low dose glucocorticoids together with vitamine is the main Western treatment used, and dexamethasone is the most frequently used preparation of glucocorticoids. Among the 72 Chinese drugs presented in the 27 Chinese recipes, 13 appeared for more than 1800 times, they were Angelica sinensis, Salvia miltiorrhiza, Radix Paeoniae Rubra, Radix Astragali, Poria, Carthamus tinctorius, Phellodendron amurense, Scutellaria baicalensis, Anemarrhena asphodeloides, Rehmannia glutinosa, Cuscuta chinensis, Radix Paeoniae Alba and Radix Glycyrrhiza.

Clinical observation on treatment of 2,062 cases of immune infertility with integration of traditional Chinese medicine and western medicine.

To study the therapeutic effect of integrated traditional Chinese medicine and western medicine on female immune infertility. 3,496 women suffering from primary or secondary infertility had their ASAb, EMAb, AOAb and ACAb level tested, with the positive rate of 23.11%, 34.95%, 20.77% and 30.41% respectively. 2,062 positive cases were periodically treated with the Chinese drug Xiaokangwan plus dexamethasone, vitamin E and vitamin C for 2 periods as a course of treatment. At the end of a treatment course, the rate for the antibodies to turn negative reached over 85% and the average pregnant rate reached 36.66%. The treatment of immune infertility with the integrated approach can reduce or eliminate the influence of antibodies in the serum of patients on various links of pregnancy, thus reaching the goal of curing infertility.

[Evidence of antibodies against the chlamydial heat shock protein (cHSP60) in women from "in vitro" fertilization program]. / Prukaz protilátek proti proteinu tepelného soku chlamydií (cHSP60) u zen zarazených do in vitro fertilizacního programu.

OBJECTIVE: A contribution to the role of chlamydial heat shock protein in women from the IVF program. DESIGN: A serological study proving the antibodies against the chlamydial heat shock protein. SETTING: Veterinary Research Institute, Brno, Department of Clinical Microbiology, and Centrum of Reproductive Medicine, Faculty Hospital Brno. METHODS: The IgG antibodies against the chlamydial heat shock protein (cHSP60) and the IgA and IgG antibodies against species specific chlamydial major outer membrane protein (cMOMP) of Chlamydia trachomatis (C. trachomatis) and Chlamydophila pneumoniae (C. pneumoniae) in the blood serum of 70 females being in the fertilization program due to fertility disorders (Group 1) have been estimated and the results compared with those obtained in 50 females suffering from pelvic inflammation disease (PID) (Group 2) and in 51 female blood donors (Group 3) respectively. RESULTS: The anti-cHSP60 antibodies have been ascertained as follows: in 26 women from the first group (37.1%), in 16 of the second group (32.0%) and in 12 (23.5%) of female blood donors. The anti cHSP60-antibody-occurrence and mean index of positivity as well, found in the groups examined, was statistically insignificant. Similarly no difference has been found in the occurrence of the species specific anti-cMOMP antibodies C. trachomatis and C. pneumoniae in the groups examined. The anti-cMOMP antibodies against C. trachomatis and simultaneously against C. pneumoniae have been detected in 21 from 171 women of all groups (12.3%), only against C. trachomatis in 9 (5.3%) and against C. pneumoniae in 73 of them (42.7%). There was considerably higher occurrence of the specific antibodies against C. trachomatis in women with a positive finding of antibodies against the cHSP60, especially in women suffering from gynecological disorders, than in women without such antibodies. CONCLUSION: C. trachomatis has a significant impact on the production of antibodies against the cHSP60. This fact can be documented by considerably higher occurrence of the specific antibodies against C. trachomatis in women with a positive finding of antibodies against the cHSP60, than in women without such antibodies. Preceding infection C. trachomatis and following sensitization with chlamydial heat shock protein indicate an unfavourable prognosis of the reproductive outcome and impairs the perspective of a successful in vitro fertilization. The proof of antibodies against the chlamydial HSP60 can be recommended as a further auxiliary criterion in women suffering from fertility disorders.

[Exploration on the relationship between positive antisperm antibody and nitric oxide level of infertile patients and on integrative Chinese and Western medicine treatment].

OBJECTIVE: To study the relationship between the positive antisperm antibody (AsAb) and nitric oxide (NO) content in blood of infertile patients and the therapeutic effect of integrative Chinese and western medicine (ICWM) treatment on the disease. METHODS: Infertile patients, 75 of AsAb positive and 68 of AsAb negative were selected to observe the mature partuient rate and abortion rate. Serum NO level were measured before treatment to observe the relationship between NO and positive AsAb. Patients were treated with ICWM and followed-up for five years. RESULTS: Mean value of serum NO in patients with positive AsAb was significantly higher than that in fertile women, and there was no significant difference between patients with negative AsAb and fertile women (P < 0.01). In the 5 years after treatment, the mature partuient rate between the two groups showed insignificant difference (P > 0.05). CONCLUSION: AsAb positive and NO level abnormal may interfere mutually, to intervent the reproductive process. ICWM therapy could effectively regulate auto-immunity and endocrine function, and make the infertile patients obtain satisfactory efficacy.

Application of traditional Chinese medicine in the treatment of infertility.

The philosophy and practice of traditional Chinese medicine (TCM) have been evolving for thousands of years in China, Japan and other Asian countries. TCM is now generating popular interest worldwide for reproductive health care and disease prevention, including applications for treating infertility and improving sexual function. This review focuses on the application of TCM for infertility patients, and provides a critical reflection on the efficacy and safety of selected Chinese herbal formulas. It has been claimed that some formulas produce high clinical pregnancy rates with few or no side effects, as well as improving the general well-being of patients. The need for randomized control trials and research into possible mechanisms of action, effective doses, contra-indications and toxicity is self-evident. However, the task is enormous in view of the number of herbal products currently available on the market; yet among these products are undoubtedly some that will prove to be safe and beneficial.

[Clinical observation on effect of zhenqi zhuanyin decoction combined with intrauterine insemination in treating spleen-kidney deficiency type patients of sterility with positive anti-sperm antibody].

OBJECTIVE: To compare the effect of combined therapy of Zhenqi Zhuanyin Decoction (ZQZYD) and timely intrauterine insemination (IUI) with that of using ZQZYD and IUI separately in treating patients of sterility with positive anti-sperm antibody (AsAb). METHODS: One hundred and three patients were randomly divided into 3 groups, 34 patients in Group A treated with combined ZQZYD and IUI, 34 in Group B treated with ZQZYD alone and 35 in Group C treated with IUI alone. The negative conversion rate of AsAb, pregnancy rate in patients, pregnancy rate in AsAb converted patients, as well as changes of TCM Syndrome and T-lymphocyte subsets were observed. RESULTS: (1) The negative conversion rate of AsAb in the 3 groups was 76.47% (26/34), 82.35% (28/34) and 8.57% (3/35) respectively. (2) In Group A, the pregnancy rate was 41.18% (14/34), pregnancy rate in AsAb negative converted patients was 50.0% (13/26); in Group B, the respective criteria was 20.59% (7/34) and 21.43% (6/28) respectively; and in Group C, the pregnancy rate was 11.43% (4/35). The pregnancy rate in Group A was significantly higher than that in Group B or C (P < 0.01). (3) The effective rate on TCM Syndrome in Group A and B was 88.23% and 91.18% respectively (P > 0.05). (4) In Group A and B, CD4 decreased, CD8 increased and CD4/CD8 ratio decreased after treatment, which were significantly different from those before treatment and in Group C after treatment (P < 0.05). CONCLUSION: Combined therapy of ZQZYD and IUAI shows a better effect in treating infertility with positive AsAb than that by ZQXYD or IUI alone.

[An experimental study on inhibitory effect of Chinese medicine tai-bao on antisperm antibody].

OBJECTIVE: To investigate whether Chinese medicine Tai-bao could inhibit antisperm antibody in experimental mice. METHODS: The experimental immunoinfertility mice were due to antisperm antibody induced by injection of human sperm membrane antigens. The experimental immuno-infertile mice used in the present study were divided into four groups including Tai-bao high dose group (46.8 g.kg-1.d-1), Tai-bao low dose group (31.2 g.kg-1.d-1), prednisone group and normal saline group. The enzyme linked immune sorbent assay (ELISA) and microcytotoxic assay were used for detection of antisperm antibody. The change of levels of antisperm antibody before and after treatment, pregnant rate, and the number of implantation were investigated in tested mice. RESULTS: The pregnant rates in normal saline group, prednisone group, Tai-bao high dose group and low dose were 38.89%, 47.06%, 70.00% and 75.00% respectively. The rate of pregnancy in Tai-bao low dose group was significantly higher as compared with normal saline group (P < 0.05). The rate of implantation in Tai-bao low dose group was significantly higher than that in prednisone group (P < 0.05). The results of detection of the cytotoxic antibody to sperm showed that cytotoxic percentages in Tai-bao high dose group (63.0 +/- 10.3%) and prednisone group (56.3 +/- 13.7%) were significantly lower (P < 0.05 and P < 0.01) than that in normal saline group (72.84 +/- 5.05%). CONCLUSION: Chinese medicine Tai-bao possesses regulatory effect on reproductive immune function, inhibitory effect on antisperm cytotoxic antibody, and promoting effect on pregnancy.

Immunohistochemical identification of porcine reproductive and respiratory syndrome virus (PRRSV) antigen in the heart and lymphoid system of three-week-old colostrum-deprived pigs.

Porcine reproductive and respiratory syndrome virus (PRRSV) antigens were detected by a streptavidin-biotin complex technique in tissues of 3-week-old colostrum-deprived pigs that had been inoculated intranasally with PRRSV and had developed moderate respiratory disease. Moderate, multifocal, tan-colored consolidation of the lungs and severe enlargement of the lymph nodes were noted at necropsy. Severe interstitial pneumonia characterized by type 2 pneumocyte proliferation, septal infiltration with mononuclear cells, and accumulation of macrophages and necrotic cells in alveolar spaces was observed at 4 and 9 days postinoculation. Moderate multifocal perivascular lymphohistiocytic myocarditis was observed at 9 days postinoculation. Marked lymphoid follicular hyperplasia and follicular necrosis in the tonsil, spleen, and lymph nodes was observed. A monoclonal antibody that recognizes a conserved epitope of PRRSV nucleocapsid protein was used as primary antibody for immunohistochemistry. Antigen was readily detected in alveolar macrophages in the lung and in endothelial cells and macrophages in the heart. Macrophages and cells resembling dendritic cells in tonsil, lymph nodes, thymus, and spleen also stained intensely positive for viral antigen. PRRSV appears to replicate primarily within macrophages in the respiratory and lymphoid systems of the pig.