Treatment with plasma exchange of a pregnant woman with anti-PP1Pk alloimmunization: A case report.

The histo-blood group antigens P, P1 and Pk are a closely related set of glycosphingolipid structures expressed by red blood cells and other tissues. None of these three characters is expressed on p cells, a null phenotype that arises in the context of homozygous mutation of the A4GALT gene. Subjects with p phenotype spontaneously develop a natural alloantibody named anti-PP1Pk, which is a mixture of IgG and IgM against P1, P and Pk. While anti-P1 is a weak cold antibody with poor clinical significance, anti-P and anti-Pk antibodies are potent haemolysins responsible for severe hemolytic transfusion reactions. The rare anti-PP1Pk alloantibodies are associated with recurrent spontaneous abortion in the first trimester of gestation. P and Pk antigens are expressed at high levels on the placenta and antibodies directed against both these structures are deleterious to placental trophoblasts. Here we describe the use of plasma exchange (PEX) in a nulliparous 39-year-old woman with anti-PP1Pk antibodies and a history of repeated spontaneous early abortions and hypofertility. The patient underwent apheresis starting from the third week throughout the pregnancy and a healthy child was delivered by cesarean section at 35 WG. The newborn required only phototherapy within a few days of life. We can state that an early treatment with the only PEX has proven to be effective and safe in the management of a fetomaternal P-incompatibility caused by a high anti-PP1Pk titer (256).

Altered profile of plasma phospholipids in woman with recurrent pregnancy loss and recurrent implantation failure treated with lipid emulsion therapy.

BACKGROUND: Recurrent Pregnancy Loss (RPL) and Recurrent Implantation Failure (RIF) are highly heterogeneous condition and many of the mechanisms involved still require elucidation. The aim was to analyze the lipidomic profile in plasma of women with RPL and RIF before and after receiving the Lipid Emulsion Therapy (LET) containing 10% fish oil (SMOFlipid® 20%). METHODS: This study included twenty-six women with RPL or RIF from immunological or inflammatory causes, with elevated natural killer cell levels and divided into a Pregnancy Loss or a Live Birth group according to the outcome. The women received intravenous LET and sample collecting was done before the first, third and fifth dose of LET in the pregnant women. Ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF MS) and multivariate statistical methods were performed to evaluate the profile of phospholipids present in the women's plasma. RESULTS: An increase of phosphatidylcholines (PC) 40:8 and 36:5 levels with predominance of n6 polyunsaturated fatty acids (PUFA) was observed in plasma lipids of the Pregnancy Loss Group compared to Live Birth Group. We also observed an increase in the relative abundance of n3 PUFA-PC species (42:10 and 36:6) and LysoPC 15:0 with the long term use of LET. CONCLUSION: The greater availability of n3 PUFA in plasma of the pregnant women stemming from LET use can be considered advantageous regarding the alteration of the phospholipid profile and its postulated anti-inflammatory and immunomodulatory role.

Low molecular weight heparin monotherapy for recurrent abortion with antiphospholipid system: A protocol of a systematic review.

BACKGROUND: Previous clinical studies reported low molecular weight heparin (LMWH) monotherpay has been utilized for the treatment of recurrent abortion (RCA) with antiphospholipid system (APS). However, its efficacy is still inconclusive. This systematic review aims to assess its efficacy and safety for patients with RCA and APS. METHODS: A systematic literature search for article up to February 2019 will be conducted in 9 databases: Cochrane Library, EMBASE, MEDILINE, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data. Inclusion criteria are randomized control trials of LMWH monotherpay for patients with RCA and APS. The Cochrane risk of bias tool will be used to evaluate the methodological quality for each qualified study. The summary results will be showed by using fixed-effects and random-effects models for pooling the data based on the heterogeneity of included studies. RESULTS: This systematic review will assess the clinical efficacy and safety of LMWH monotherpay in treating RCA with APS. The primary outcome is pregnancy loss. The secondary outcomes include frequency of preterm delivery, live birth rates, maternal and fetal complications, as well as adverse events. CONCLUSION: The findings of this study will summarize the present evidence to judge whether LMWH monotherpay is an effective therapy for patients with RCA and APS. DISSEMINATION AND ETHICS: The findings of this study will be published by through peer-reviewed journals. This study does not needs ethic documents, because it will not analyze individual patient data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019121064.

The role and mechanism of vitamin D-mediated regulation of Treg/Th17 balance in recurrent pregnancy loss.

PROBLEM: Vitamin D has a pivotal role in regulating immune responses in women with recurrent pregnancy loss (RPL), but the underlying mechanism has not been completely clarified. This study aimed to determine the correlation between vitamin D and Treg/Th17 and the effects of vitamin D supplementation on Treg/Th17 balance in RPL patients. METHODS OF STUDY: The level of vitamin D was determined in women with normal pregnancy and RPL by electrochemiluminescence. The percentages of CD4+ Foxp3+ Treg, CD4+ IL-17+ Th17, and CD4+ Foxp3+ IL-17+ T cells were determined by flow cytometry before and after vitamin D supplementation. Changes about Treg/Th17 balance after culturing with active vitamin D in vitro were determined. Vitamin D metabolic activity of peripheral blood mononuclear cells was also detected by RT-PCR. RESULTS: Compared with normal pregnancy, both the level of vitamin D and the Treg/Th17 ratio were significantly decreased in women with RPL. There was a positive correlation between the level of vitamin D and the Treg/Th17 ratio in the RPL group. Within the RPL group, those who received 2 months of vitamin D supplementation showed a significantly increased Treg/Th17 ratio compared with those without vitamin D supplementation. In vitro analysis showed that adding different concentrations of active vitamin D increased the Treg/Th17 ratio, also the mRNA levels of the vitamin D receptor and the metabolic enzyme CYP24A1 increased significantly. CONCLUSION: The occurrence of RPL may be related to vitamin D insufficiency and Treg/Th17 imbalance. The Treg/Th17 imbalance seen in women with RPL can be restored by vitamin D supplementation both in vivo and in vitro. The effects of vitamin D on the immune regulation of RPL indicate that vitamin D might be used as an alternative therapy in the future.

[Male factors and countermeasures for recurrent spontaneous abortion].

Recurrent spontaneous abortion (RSA) has a very complicated pathogenesis and male factors for this condition should not to be ignored, which are mainly related to genetics, immunology, infection, sperm quality, and others. In case of RSA, an etiological screening ought to be performed for the husband, which involves general, genetic and immunological examinations and infection detection. According to specific etiological factors, such measures as genetic consultation, immunotherapy, and traditional Chinese medication can be taken, which may contribute to the outcome of pregnancy.

The YY1/MMP2 axis promotes trophoblast invasion at the maternal-fetal interface.

YY1 is a sequence-specific DNA-binding transcription factor that has many important biological roles. However, its function in trophoblasts at the maternal-fetal interface remains to be elucidated. In this study, we used an mRNA microarray and reverse transcription qPCR and compared the YY1 mRNA expression level in trophoblasts between patients with recurrent miscarriage (RM) and healthy control subjects. Our results revealed that YY1 mRNA expression was significantly lower in the trophoblasts of the RM group compared with the healthy control group. Furthermore, immunofluorescence and immunohistochemical data showed that YY1 was highly expressed in human placental villi during early pregnancy, especially in cytotrophoblast cells and invasive extravillous trophoblasts, and it was expressed at a much lower level in the placental villi of term pregnancy. YY1 overexpression enhanced, and knockdown repressed, the invasion and proliferation of trophoblasts. Antibody array screening revealed that YY1 significantly promoted MMP2 expression in trophoblasts. Bioinformatics analysis identified three YY1-binding sites in the MMP2 promoter region, and chromatin immunoprecipitation analysis verified that YY1 binds directly to its promoter region. Importantly, inhibition of YY1 by siRNA clearly decreased trophoblast invasion in an ex vivo explant culture model. Overall, our findings revealed a new regulatory pathway of YY1/MMP2 in trophoblast cell invasion during early pregnancy and indicated that YY1 may be involved in the pathogenesis of RM.

[Early recurrent miscarriage: Evaluation and management]. / Fausses couches précoces « à répétition ¼ : bilan et prise en charge.

OBJECTIVE: To establish recommendations for early recurrent miscarriages (≥3 miscarriages before 14weeks of amenorrhea). MATERIALS AND METHODS: Literature review, establishing levels of evidence and recommendations for grades of clinical practice. RESULTS: Women evaluation includes the search for a diabetes (grade A), an antiphospholipid syndrome (APS) (grade A), a thyroid dysfunction (grade A), a hyperprolactinemia (grade B), a vitamin deficiency and a hyperhomocysteinemia (grade C), a uterine abnormality (grade C), an altered ovarian reserve (grade C), and a couple chromosome analysis (grade A). For unexplained early recurrent miscarriages, treatment includes folic acid and progesterone supplementation, and a reinsurance policy in the first quarter (grade C). It is recommended to prescribe the combination of aspirin and low-molecular-weight heparin when APS (grade A), glycemic control in diabetes (grade A), L-Thyroxine in case of hypothyroidism (grade A) or the presence of thyroid antibodies (grade B), bromocriptine if hyperprolactinemia (grade B), a substitution for vitamin deficiency or hyperhomocysteinemia (grade C), sectionning a uterine septum (grade C) and treating an uterine acquired abnormality (grade C). CONCLUSION: These recommendations should improve the management of couples faced with early recurrent miscarriages.

Office diagnostic and operative hysteroscopy using local anesthesia only: an analysis of patient reported pain and other procedural outcomes.

STUDY OBJECTIVE: To evaluate the effectiveness of a multimodality local anesthetic protocol for office diagnostic and operative hysteroscopy. DESIGN: Retrospective cohort study (Canadian Task Force classification II-3). SETTING: Academic community-based institution. PATIENTS: Five hundred sixty-nine women undergoing 639 office-based diagnostic or operative hysteroscopic procedures. INTERVENTIONS: Multimodality local anesthetic protocol addressing vagina, cervix, paracervical region, and endometrial cavity. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were numeric pain scores and rate of premature termination because of pain. Secondary outcomes included procedure pain and parity, delivery route, menopausal status, procedure type, and cost effect on procedure delivery. The overall mean (SD) pain score across 535 evaluable procedures was 3.7 (2.5). Patients undergoing operative hysteroscopy had a higher mean maximum pain score than did those who underwent diagnostic hysteroscopy only (4.1 vs 3.2; p < .001). There was no difference among women in different age groups; however, those with both cesarean section and vaginal delivery had scores higher than the mean (4.7 [0.4]; p < .001). The estimated cost savings was almost $2 million. CONCLUSION: Using a multimodality approach to local anesthesia, a broad spectrum of diagnostic and operative procedures can be performed successfully, comfortably, and inexpensively in the context of an office procedure room, without the need for procedural sedation.

Vitamin D deficiency may be a risk factor for recurrent pregnancy losses by increasing cellular immunity and autoimmunity.

STUDY QUESTION: Do women with recurrent pregnancy losses (RPL) and low vitamin D have increased prevalence of auto- and cellular immune abnormalities when compared with women with RPL who have normal vitamin D, and does vitamin D have any effect on cellular immunity in vitro? SUMMARY ANSWER: A high proportion of women with RPL have vitamin D deficiency and the risk of auto- and cellular immune abnormalities is increased in women with RPL and vitamin D deficiency. WHAT IS KNOWN ALREADY: Vitamin D deficiency in pregnant women is associated with increased risk of obstetrical complications such as pre-eclampsia, bacterial vaginosis associated preterm delivery, gestational diabetes mellitus and small-for-gestational age births. STUDY DESIGN, SIZE, DURATION: A retrospective cross-sectional study of 133 women with RPL who were enrolled in a 2-year period, together with laboratory experiments. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with three or more consecutive spontaneous abortions prior to 20 weeks of gestation who were enrolled at the University clinic. Serum vitamin D level, cellular activity and autoimmune parameters in vivo and in vitro were measured. MAIN RESULTS AND THE ROLE OF CHANCE: Sixty-three out of 133 women (47.4%) had low vitamin D (<30 ng/ml). The prevalence of antiphospholipid antibody (APA) was significantly higher in low vitamin D group (VDlow) (39.7%) than in the normal vitamin D group (VDnl) (22.9%) (P< 0.05) and the adjusted odds ratio (OR) for APA in VDlow was 2.22 with the 95% confidence interval (CI) of 1.0-4.7. The prevalence of antinuclear antigen antibody (VDlow versus VDnl; 23.8% versus 10.0%, OR 2.81, 95% CI 1.1-7.4), anti-ssDNA (19.0% versus 5.7%, OR 3.76, 95% CI 1.1-12.4) and thyroperoxidase antibody (33.3% versus 15.7%, OR 2.68, 95% CI 1.2-6.1) was significantly higher in VDlow than those of VDnl (P < 0.05 each). Peripheral blood CD19(+) B and CD56(+) NK cell levels and NK cytotoxicity at effector to target cell (E:T) ratio of 25:1 were significantly higher in VDlow when compared with those of VDnl (P < 0.05 each). Reduction (%) of NK cytotoxicity (at E:T ratio of 50:1 and 25:1) by IgG (12.5 mg/dl) was significantly lower in VDlow than those of VDnl (P < 0.05, P < 0.01, respectively). There were no differences in Th1/Th2 ratios between VDlow and VDnl. When vitamin D3 was added in NK cytotoxicity assay in vitro, NK cytotoxicity at E:T ratio of 50:1 was significantly suppressed with 10 nMol/L (nM) (11.9 ± 3.3%) and 100 nM (10.9 ± 3.7%) of vitamin D3 when compared with controls (15.3 ± 4.7%) (P < 0.01 each). TNF-α/IL-10 expressing CD3(+)/4(+) cell ratios were significantly decreased with 100 nM of vitamin D3 (31.3 ± 9.4, P < 0.05) when compared with controls (40.4 ± 11.3) in vitro. Additionally, INF-γ/IL-10 expressing CD3(+)/4(+) cell ratio was significantly decreased with 100 nM of vitamin D3 (12.1 ± 4.0, P < 0.05) when compared with controls (14.8 ± 4.6). IFN-γ and TNF-α secretion from NK cells were significantly decreased (P < 0.01 each), and IL-10, IL-1ß, vascular endothelial growth factor and granulocyte colony stimulating factor levels were significantly increased (P < 0.01 each) with vitamin D3 100 nM when compared with those of controls. LIMITATIONS, REASONS FOR CAUTION: The prevalence of vitamin D deficiency in women with RPL in this study is open to a possible type I error since women with vitamin D supplementation were excluded from this study. WIDER IMPLICATIONS OF THE FINDINGS: Assessment of vitamin D level is recommended in women with RPL. Vitamin D supplementation should be explored further as a possible therapeutic option for RPL. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the intramural funding from Department of Microbiology and Immunology, Chicago Medical School at Rosalind Franklin University of Medicine and Science. None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Palatal tremor, focal seizures, repeated miscarriages and elevated anti-thyroid antibodies.

Neurological manifestations of thyroid autoimmunity are heterogeneous and nonspecific. The most frequently adopted name for this entity is Hashimoto's encephalopathy although this eponym has been recently contested. In the absence of specific clinical features, diagnosis is suggested by the presence of elevated levels of anti-thyroid antibodies in the appropriate clinical context. We describe a patient with recurrent focal seizures, palatal tremor and elevated anti-thyroid antibodies but no encephalopathy. Her past medical history was marked by recurrent miscarriages. The markedly elevated thyroid antibodies, the temporal relationship between neurological symptoms and hypothyroidism, and the absence of another explanation to her symptoms suggest a causal role of thyroid autoimmunity. In the clinical setting of recurrent spontaneous miscarriages, elevated levels of anti-thyroid antibodies and neurological deficits not attributed to another disease entity, Hashimoto's encephalopathy should be suspected.

[Hypothyroidism: from the desire for pregnancy to delivery]. / Hypothyroïdie: du désir de grossesse à l'accouchement.

The link between hypothyroidism and infertility is still a matter of debate. Hypothyroidism can result in cycle disturbances, such as oligomennorhea and functional bleeding. Additionally, several studies have shown that thyroid autoimmunity (detection of anti peroxydase antibodies) may account for the occurrence of repetitive miscarriages. In infertility work-up, screening thyroid function should be specifically recommended for women with clinical hypothyroidism, with a personal, familial history of thyroid or other auto immune diseases (such as type I diabetes) as well as for women with unexplained anovulation or functional bleeding. Moreover, detection of thyroid antibody seems to be worthwhile for the assessment of recurrent miscarriages, due to the potential benefit of thyroid supplementation. In pregnant women, assessment of thyroid function seems specifically crucial to ensure adequate foetal development. Indeed, it has been well established that untreated maternal hypothyroidism may be associated with disturbances of brain development and low intellectual quotient. Additionally, other foetal (growth deficiency, premature birth, low birth weight) as well as maternal (gestational hypertension, pre-eclampsia...) complications have been also reported in pregnant women with untreated hypothyroidism. Consequently, screening of thyroid function should be performed in every woman at risk of thyroid disease. Recent studies even advocate that thyroid screening should be extended to the overall pregnant population. The objective is to adjust L-thyroxin supplementation to maintain serum TSH concentrations below the threshold of 2.5 mUI/l. Finally, iodine deficiency, currently observed in pregnant women, should be prevented by iodine supply prior to conception, during pregnancy and during breast feeding as well.

Recurrent miscarriage associated with antiphospholipid antibodies: prophylactic treatment with low-dose aspirin and fish oil derivates.

PROBLEM: The aim of this study was to evaluate the effects of two different prophylactic protocols, low-dose aspirin and fish oil derivates, in the treatment of patients with recurrent pregnancy loss associated with antiphospholipid antibodies (APA) syndrome. METHODS: A prospective study included 30 patients who were alternately assigned to treatment. Each patient had had at least two consecutive spontaneous abortions, positive antiphospholipid antibodies on two occasions, and a complete evaluation. RESULTS: Among patients treated with low-dose aspirin, 12 out of the 15 (80%) pregnancies ended in live births. In the fish oil derivate group 11 out of the 15 (73.3%) ended in live births (p > 0.05). There were no significant differences between the low-dose aspirin and the fish oil derivates groups with respect to gestational age at delivery (39.9 +/- 0.4 vs 39 +/- 1.5 weeks), fetal birth weight (3290 +/- 200g vs 3560 +/- 100 g), number of cesarean sections (25% vs 18%), or complications. CONCLUSION: There were no significant differences in terms of pregnancy outcome between women with recurrent pregnancy loss associated with APA syndrome treated with low-dose aspirin or fish oil derivates.

Low Vitamin B(12) level as a risk factor for very early recurrent abortion.

OBJECTIVE: To examine the relationship between Vitamin B(12) deficiency and early recurrent abortion (ERA) or very early recurrent abortion (VERA) abortion around 5 weeks of amenorrhea. STUDY DESIGN: Serum B(12), folate and homocysteine levels were carried out in 110 consecutive women with unexplained ERA or VERA and in 96 women with one or more children and no abortion history. RESULTS: Ten women were found to have low serum B(12) levels versus one in the control group. A total of 50% of these had raised homocysteine. No difference was noticed between cases and controls for folate. Among women with low serum B(12) level and ERA, 87.5% of the abortions were VERA. Vitamin B(12) supplementation led to four normal pregnancies in five women who became pregnant again. In a statistical analysis performed on five studies in which serum B(12) was assayed in ERA, including ours, a significant relationship was found between ERA and Vitamin B(12) deficiency. CONCLUSION: Vitamin B(12) deficiency may be involved in ERA. Vitamin B(12) assay should be done in ERA women whether or not hematological abnormalities are present.

The selenium status of women with a history of recurrent miscarriage.

OBJECTIVE: To assess the relationship between selenium levels in human blood and hair, and the risk of recurrent miscarriages. DESIGN: Case-control study. PARTICIPANTS: Two groups of non-pregnant women: 18 women with one or more successful pregnancies and no history of miscarriage (control group); 26 women with a history of recurrent miscarriage (> or = 3) with no subsequent successful pregnancies (study group). METHODS: Samples of venous blood and scalp hair were collected and the selenium content analysed by inductively coupled plasma mass spectrometry. RESULTS: No significance difference was found between the level of selenium in the blood samples of the women in each group. There was a significant reduction in the mean hair selenium level in the recurrent miscarriage group compared with the control group (0.14 microg/g vs 0.34 microg/g). Further analysis of the recurrent miscarriage group revealed no relationship between levels of serum or hair selenium with parity. There was a significantly greater proportion of women in the control group who ate cereals, vitamin supplements, and liver or kidney. CONCLUSION: There was evidence of selenium deficiency in women with recurrent miscarriages compared with a control group of women with a good reproductive performance. This difference was seen in hair samples but not serum samples and therefore may not represent a simple nutritional deficiency. The importance of selenium deficiency in miscarriage has still not been determined.

Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis.

OBJECTIVE: To quantify the risk of recurrent early pregnancy loss in the presence of elevated fasting or afterload homocysteine concentrations or homozygosity for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene (T/T genotype). DESIGN: Case-control studies published between January 1992 and November 1999 were identified with a MEDLINE-search. These studies were combined with a recent case-control study performed by our own research group. SETTING: Academic research environment. PATIENT(S): Studies published in the English language, concerning two or more pregnancy losses before 16 weeks' menstrual age were included. INTERVENTION(S): Meta-analysis of all of the studies included. MAIN OUTCOME MEASURE(S): The number of subjects with and without hyperhomocysteinemia or with the T/T genotype were derived, if necessary the study was supplemented by personal communication with the original authors. RESULT(S): Pooled risk estimates of 2.7 (1.4 to 5.2) and 4.2 (2.0 to 8.8) were calculated for fasting and afterload plasma homocysteine concentrations, respectively. For the MTHFR T/T genotype a pooled risk estimate of 1.4 (1.0 to 2.0) was found. CONCLUSION(S): These data support hyperhomocysteinemia as a risk factor for recurrent early pregnancy loss. Further research should be focused on the pathophysiology of this relationship and on the clinical efficacy of B vitamin supplementation.

Hyperhomocysteinemia and pregnancy--review of our present understanding and therapeutic implications.

Homocysteine results from the transmethylation of methionine. Its metabolism depends primarily on three enzymes and several vitamin cofactors. Genetic abnormality in these enzymes or deficiency of these vitamins lead to hyperhomocysteinemia (HHCh). HHCh is usually biologically defined by a fasting value >15 micromol/l. HHCh belongs among the congenital hypercoagulable states and is a long-known vascular disease risk factor. The discovery that HHCh may also be responsible for several pregnancy complications has only recently been made. Studies in this area are still scarce and report on limited numbers of patients. It nevertheless appears clear that HHCh is associated with the syndromes of repeated miscarriage, pre-eclampsia, placenta abruptio, thromboembolic events, neural tube defects, and perhaps with fetal death-in-utero and intra-uterine growth retardation. Supplementation with vitamin B9 can reduce plasma HC levels, and is thus recommended in patients with HHCh. The prevention of thromboembolic events during pregnancy by anticoagulant treatment is also desirable in these patients.

[Hyperhomocysteinemia and pregnancy: a dangerous association]. / Hyperhomocystéinémie et grossesse : une association dangereuse.

Homocysteine results from the demethylation of the essential amino acid methionine. Its metabolism depends primarily on three enzymes and several vitamin cofactors (vit. B6, B9 and B12). Genetic abnormality in these enzymes or deficiency of these vitamins lead to Hyperhomocysteinemia. Hyperhomocysteinemia belongs among the congenital thrombophilies and is a long-known vascular disease risk factor. The discovery that hyperhomocysteinemia may also be responsible for several pregnancy complications has only recently been made. Studies in this area are still scarce and report on limited numbers of patients. It nevertheless appears clear that HHCh is associated with the syndromes of repeated miscarriage, pre-eclampsia, placenta abruptio, thromboembolic events, neural tube defects, and perhaps with fetal death-in-utero and intra-uterine growth retardation. Supplementation with vitamin B9 can reduce plasma HC levels, and is thus recommended in patients with HHCh. The prevention of thromboembolic events during pregnancy by anticoagulant treatment is also desirable in these patients.

Association of reduced selenium status in the aetiology of recurrent miscarriage.

OBJECTIVE: To determine whether recurrent miscarriage is associated with reduced selenium status. DESIGN: Case-control study. SETTING: Department of Obstetrics and Gynaecology, Glasgow Royal Infirmary and Glasgow Royal Maternity Hospital. POPULATION: Twenty nonpregnant women with a history of unexplained recurrent miscarriage, and 47 nonpregnant parous women with a history of at least one successful pregnancy and no more than one miscarriage. METHODS: A 7 mL blood sample from each woman was collected into lithium heparin 'vacutainer' tubes. Samples were centrifuged at 3000 g for 15 minutes, and plasma was extracted and stored at -20 degrees C. Selenium concentrations were measured using a fluorescence spectrophotometer. The selenium concentrations in the two groups were compared and the differences examined using the Student's t test. MAIN OUTCOME MEASURES: Plasma selenium concentration (microg/L). RESULTS: The mean selenium concentration for women with a history of unexplained recurrent miscarriage was 67.7 microg/L (SD 16.4). The selenium level for the women with no history of recurrent miscarriage was 70.3 microg/L (SD 12.7). There was no difference in selenium concentrations between the two groups (P = 0.53). CONCLUSIONS: In this study there is no association between unexplained recurrent miscarriage and reduced selenium status, implying that reduced selenium status is not a factor in the pathogenesis of recurrent miscarriage. We can find no rationale for a trial of selenium therapy in women with a history of recurrent miscarriage.