Unexplained Recurrent Spontaneous Abortion Research Articles

Enoxaparin for prevention of unexplained recurrent miscarriage: a multicenter randomized double-blind placebo-controlled trial

AbstractIt is common practice in many centers to offer antithrombotic medications to women with unexplained recurrent miscarriage, in the presence or absence of inherited thrombophilia. Although no benefit of aspirin vs placebo has been clearly demonstrated, a double-blind placebo-controlled trial on the effect of low-molecular-weight heparin is lacking. We enrolled 258 pregnant women with a history of unexplained recurrent miscarriage (≥2 consecutive miscarriages before 15 weeks' gestation) and a negative thrombophilia workup. They were randomly assigned to receive one daily subcutaneous injection of enoxaparin 40 mg or placebo until 35 weeks' gestation. We included 256 women (mean age 32 years, ≥3 miscarriages: 72%; mean gestational age 39 days of amenorrhea) in the intention-to-treat analysis; 66.6% of 138 who received enoxaparin had a live birth vs 72.9% of 118 who received placebo. The absolute difference was −6% (95% CI, −17.1 to 5.1), excluding a 10% increase in the rate of live-birth on enoxaparin (P = .34). In this first randomized, double-blind, placebo-controlled trial, enoxaparin (40 mg once daily) did not improve the chance of a live birth in nonthrombophilic women with unexplained recurrent miscarriage. This trial is registered at www.ClinicalTrials.gov as #NCT00740545 and the French National Health and Drug Safety Agency (EudraCT #2006-003350-18).

Novel missense mutation in WNT6 in 100 couples with unexplained recurrent miscarriage.

Do mutations and/or polymorphisms in coding sequences in Wingless-Type MMTV Integration Site Family, Member 6 (WNT6) play a role in unexplained recurrent miscarriage (unexplained RM) in Chinese couples? We found four mutations in the coding sequences of WNT6 which appear to exist in a small proportion of Chinese women with unexplained RM. WNT6 has been proved to be essential for stromal cell proliferation during decidualization in mice, but in humans WNT6 has not been studied in recurrent miscarriage populations. For this study, 100 couples with unexplained RM (at least three or more unexplained spontaneous miscarriages), and 100 ethnically matched fertile couples (at least one live birth and no history of pregnancy pathologies) were recruited. All the participants were chosen over a 7-year period from the National Research Center for Assisted Reproductive Technology and Reproductive Genetics at Shandong University, Jinan, China. Patients were recruited following extensive clinical studies. Genomic DNA was isolated from peripheral blood. Mutation analysis in the coding regions of WNT6 was performed by PCR amplification and DNA sequences testing in all participants. Functional effects of missense variants were predicted using Polyphen-2 and sorting intolerant from tolerant (SIFT). Four rare novel mutations, including one missense mutation, were found in intron 1, exon 3 and the 3' untranslated region of WNT6 in four women with unexplained RM. Gene software predictions showed that the missense mutation in exon 3 could alter the function of WNT6. No mutations or polymorphisms were detected in the male partners of the unexplained RM patients or in the fertile controls. To further validate the findings, we continued to screen this missense mutation site in another 100 peripheral blood samples of normal fertile females, and there was still no positive result. There is no direct evidence to validate whether these novel mutations discovered in the present research are related to unexplained RM. Further studies are warranted to investigate the role of WNT6 in unexplained RM, including larger studies in an independent group. These results provide evidence to suggest the importance of WNT6 in reproductive failure and may support the hypothesis that WNT6 is essential for stromal cell proliferation during decidualization. This work was supported by Science and Technology Development Planning of Shandong (2013GGE27001), the National Natural Science Foundation of China (81300459), the Science Projection of Bureau of Public Health in Weifang (2012044) and the Science Research Foundation Item of No-earnings Health Vocation. The authors have no competing interests to declare.

Effect of Prednisolone Administration on Patients with Unexplained Recurrent Miscarriage and in Routine Intracytoplasmic Sperm Injection: A Meta-Analysis.

The effects of prednisolone on pregnancy outcome are open to debate. This meta-analysis was performed to evaluate the efficiency of prednisolone administration on unexplained recurrent miscarriage (RM) and the process of assisted reproductive technology (ART). Relevant publications were searched from databases and the included randomized controlled trials (RCTs) investigated effects of prednisolone administration in women with unexplained RM or during ART. The outcomes in our analysis were measured in terms of risk ratios (RRs) with 95% confidence intervals (CI) using random effect models. This meta-analysis was performed based on pregnancy outcomes following prednisolone treatment. This meta-analysis provides evidence that prednisolone therapy improves pregnancy outcomes in women with idiopathic RM (live birth rate: RR 1.58, 95% CI 1.23-2.02; successful pregnancy outcome: RR 7.63, 95% CI 3.71-15.69; miscarriage rate: RR 0.42, 95% CI 0.28-0.61). Our meta-analysis revealed a non-significant effect of prednisolone on pregnancy outcome during intracytoplasmic sperm injection (ICSI) cycles (pregnancy rate: RR 1.02, 95% CI 0.84-1.24; clinical pregnancy rate: RR 1.01, 95% CI 0.82-1.24; implantation rate: RR 1.04, 95% CI 0.85-1.28). Prednisolone administration may improve pregnancy outcomes in women with idiopathic RM; its efficacy in women undergoing ICSI is not significant.

Platelet function in patients with a history of unexplained recurrent miscarriage who subsequently miscarry again

ObjectiveThis study was designed to evaluate platelet aggregation in pregnant women with a history of unexplained recurrent miscarriage (RM) and to compare platelet function in such patients who go on to have either another subsequent miscarriage or a successful pregnancy. Study designA prospective longitudinal study was performed to evaluate platelet function in a cohort of patients with a history of unexplained RM. Platelet reactivity testing was performed at 4–7 weeks gestation, to compare platelet aggregation between those with a subsequent miscarriage and those who had successful live birth outcomes. Platelet aggregation was calculated using a modified assay of light transmission aggregometry with multiple agonists at different concentrations. ResultsIn a cohort of 39 patients with a history of RM, 30 had a successful pregnancy outcome while nine had a subsequent miscarriage again. Women with subsequent miscarriage had reduced platelet aggregation in response to adenosine diphosphate (P value 0.0012) and thrombin receptor activating peptide (P value 0.0334) when compared to those with successful pregnancies. Women with subsequent miscarriages also had a trend towards reduced platelet aggregation in response to epinephrine (P value 0.0568). ConclusionPatients with a background history of unexplained RM demonstrate reduced platelet function if they have a subsequent miscarriage compared to those who go on to have a successful pregnancy.

Changes and clinical significance of peripheral blood helper T lymphocyte and natural killer (NK) cells in unexplained recurrent spontaneous abortion (URSA) patients after abortion and successful pregnancy

Objective: This study aims to investigate the number changes and the clinical significance of the peripheral blood T lymphocyte subsets and NK (natural killer) cells in unexplained recurrent spontaneous abortion (URSA) patients before and after abortion, as well as after successful pregnancy. Materials and Methods: Thirty-nine URSA patients (URSA-abortion group), among who 22 patients were followed up until the final successful parturition (URSA-pregnancy group), 31 normal-pregnancy (NP) cases and 25 normal non-pregnancy (NNP) control cases in which the peripheral blood T lymphocytes and subsets, B cells, and NK cells were assessed flow cytometry. Results: Compared with the URSA-pregnancy group and the NP group, the Th cells and NK cells of the URSA-abortion group increased (p Conclusion: The abnormal numbers of the peripheral blood T cell subsets and NK cells were related with the occurrence of URSA.

Gene expression analysis of VEGF and its receptors and assessment of its serum level in unexplained recurrent spontaneous abortion.

Unexplained recurrent spontaneous abortion (URSA) is one of the main complications of pregnancy which is usually defined as three or more consecutive pregnancy losses before the 20(th) week of gestation without a known cause. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor and shown, along with its receptors (VEGFR1, 2), to play important roles in several physiologic processes including reproduction. The aim of the present study was to analyze gene expression of VEGF and VEGF receptors in endometrium of patients with a history of URSA compared with normal fertile women. In addition, serum VEGF concentration was assessed and compared between the two groups at the same time. In this case control study, endometrial and blood samples were obtained between day 19(th)and 24(th) of menstrual cycle (window of implantation) from 10 women with a history of URSA (case group) and 6 fertile women who had at least one successful pregnancy (control group). Expression of VEGF and VEGFRs was studied by reverse transcription- polymerase chain reaction (RT-PCR) and then quantified by real time PCR. Normalization of expression levels was done by comparison with beta-actin expression level as an internal control. Relative VEGF, VEGFR1 and VEGFR2 expression quantities were compared between the two groups. Enzyme linked immunosorbent assay (ELISA) was used for serum VEGF assay. VEGF, VEGFR1 and VEGFR2 gene expression was detected in endometrial samples of both groups. The mean relative expression of VEGF gene was lower in the case group compared with control women, however, both VEGF receptors were expressed higher in endometrium of the case group. In addition, the serum level of VEGF was significantly higher in the case group compared with the controls. Alteration in gene expression of VEGF and its receptors in endometrium and changes of serum VEGF might play important roles in pathogenesis of unexplained RSA.

M2/ANXA5 haplotype as a predisposition factor in Malay women and couples experiencing recurrent spontaneous abortion: a pilot study

Recurrent spontaneous abortion (RSA) is a prevalent condition among the Malay population of Malaysia, where carriage risk of conventional hereditary thrombophilia factors has been generally ruled out. The contribution of M2/ANXA5, a common haplotype in the annexin A5 gene promoter, was evalauted for RSA in Malay. Seventy-seven women who had experienced two or more unexplained RSA and 41 available male partners were selected for study, with 360 population controls recruited from healthy Malay individuals. Incidence of M2 carriage and odds ratios were calculated between control and patient groups, and clinically defined subgroups and RSA risk was evaluated. M2/ANXA5, found in 42.2% of the general Malay population, was associated with greater risks for women with primary and secondary RSA with early (gestational week 5–15) losses. The risk was somewhat higher in Malay couples when both partners were carriers and a trend of higher prevalence was seen for the male partners patients who had experienced RSA. M2 carriage seems to be a risk factor with unusually high incidence in Malay women and couples with primary and secondary RSA with ‘early’ spontaneous abortions. The associated male partner risk confirms the proposed role of M2/ANXA5 as a genetic trait impeding embryonic anticoagulation.

Thrombophilic Mutations and Folate Gene Polymorphisms and Plasminogen Activator Inhibitor-1 in Russian Women with Unexplained Recurrent Early Spontaneous Abortion

Aims: To assess the association between FVL G1691A, FII G20210A, MTHFR A1298C, C677T and PAI-1 5G/675/4G gene polymorphisms among women with unexplained recurrent early spontaneous abortion (URESA) Materials and Methods: This study included two groups of Russian women: 50 currently nonpregnant women with a history of 2-5 unexplained recurrent early spontaneous abortion and unknown causes of miscarriages (URESA group), and 50 currently non-pregnant women with a Original Research Article Belokrinitskaya et al.; BJMMR, 5(5): 626-632, 2015; Article no.BJMMR.2015.067 627 history of having given birth to at least one live baby and without a history of spontaneous abortion, prematurity, stillbirth, eclampsia and other pregnancy complications (control group). Gene polymorphisms were detected by the technique of polymerase chain reaction-real time (PCR-RT). We have analyzed the frequencies, χ2 test, odds ratio (OR) and its 95% confidence interval (CI), Hardy-Weinberg equilibrium. Results: Significant association between heterozygotes genotype FVL 1691G/A and URESA was found (OR=3.1). Heterozygous genotype FII20210G/A was associated mainly with recurrent spontaneous abortions (4% vs 0%). The PAI-1 5G/4G genotype was significantly associated with URESA (OR=2.3). Heterozygotes with MTHFR 677C/T genotype had high risk of early recurrent pregnancy loss (OR=4.6). Heterozygotes with MTHFR 1298A/C genotype showed low association with pregnancy loss (OR=1.2). We did not observe increased risk of early pregnancy loss in mutant homozygotes with MTHFR 677C/C and 1298C/C genotypes (OR=1.0). The presence of the PAI-1 gene 5G/4G genotype together with the MTHFR 677C/T or MTHFR 1298A/C or FVL 1691G/A genotypes was found to be a risk factor for URESA (OR=4.5; OR=2.3, respectively). Combined PAI-1 5G/4G// FVL 1691G/A genotypes was detected only in patients (2% vs 0%). Women carrying combined PAI-1 5G/4G//MTHFR 677C/T//MTHFR 1298A/C genotypes had an increased frequency of recurrent early spontaneous abortion (OR=1.4). Conclusion: The genetic polymorphisms of FVL 1691G/A, FII 20210G/A, MTHFR 677C/T, MTHFR 1298A/C, and PAI-1 4G/4G, and the PAI-1 5G/4G genotypes are associated with URESA. The patients carrying combined heterozygous genotypes PAI-1 5G/4G//MTHFR 677C/T or PAI-1 5G/4G//MTHFR 1298A/C or PAI-1 5G/4G//FVL 1691G/A or PAI-1 5G/4G//MTHFR 677C/T//MTHFR 1298A/C have higher risks of URESA. These results might indicate a genetic influence on pathogenesis of URESA.

Polymorphisms in the methylene tetrahydrofolate reductase and methionine synthase reductase genes and their correlation with unexplained recurrent spontaneous abortion susceptibility.

We aimed to explore the correlation between unexplained recurrent spontaneous abortion and polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes. A case control study was conducted in 118 patients with unexplained recurrent spontaneous abortion (abortion group) and 174 healthy women (control group). The genetic material was extracted from the oral mucosal epithelial cells obtained from all subjects. The samples were subjected to fluorescence quantitative PCR to detect the single nucleotide polymorphisms (SNPs) in the MTHFR (C677T and A1298C) and MTRR (A66G) gene loci. The distribution frequency (18/118, 15.3%) of the MTHFR 677TT genotype was significantly higher in the abortion group (χ2 = 11.006, P = 0.004) than in the control group (2/174, 1.1%); on the other hand, the distribution frequency of the MTHFR A1298C genotype did not significantly differ between the abortion and control groups (χ(2) = 0.441, P = 0.507). The distribution frequency of the MTRR A66G genotype was also significantly higher in the abortion group (14/118, 11.9%; χ(2) = 10.503, P = 0.005) than in the control group (8/174, 4.6%). The MTHFR C677T and MTRR A66G polymorphisms are significantly correlated with the occurrence of spontaneous abortion.

Increased CD56(+) NK cells and enhanced Th1 responses in human unexplained recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA) is reported to be associated with immune imbalance at the maternal-fetal interface. Immune cells in the decidual tissue are involved in maintaining immune tolerance during pregnancy; however, whether natural killer (NK) and T cells are altered in unexplained RSA (URSA) remains unknown. In this study, we compared the number and percentage of CD56(+) NK cells, CD4(+) T cells and CD8(+) T cells by flow cytometry in 30 URSA patients and 30 normal pregnant controls. We found that there are a higher proportion of CD4(+) T cells and CD16(+)CD56(+) NK cells and a lower number of CD8(+) T cells in the decidual tissue of URSA patients compared to normal controls. In addition, the number of T helper type 1 (Th1) cells and the Th1/Th2 ratio were higher in URSA patients compared to normal pregnant controls. In conclusion, our results indicate that the changes in the proportion of local T lymphocyte subsets, NK and Th1 cells, in the maternal-fetal interface may be related to occurrence of URSA.

A Comparison of Pattern of Pregnancy Loss in Women with Infertility Undergoing IVF and Women with Unexplained Recurrent Miscarriages Who Conceive Spontaneously.

Objective. Women with infertility and recurrent miscarriages may have an overlapping etiology. The aim of this study was to compare the pregnancy loss in pregnancies after IVF treatment with spontaneous pregnancies in women with recurrent miscarriages and to assess differences related to cause of infertility. Methods. The outcome from 1220 IVF pregnancies (Group I) was compared with 611 spontaneous pregnancies (Group II) in women with recurrent miscarriages. Subgroup analysis was performed in Group I based on cause of infertility: tubal factor (392 pregnancies); male factor (610 pregnancies); and unexplained infertility (218 pregnancies). Results. The clinical pregnancy loss rate in Group I (14.3%) was significantly lower than that of Group II (25.8%, p < 0.001) and this was independent of the cause of infertility. However the timing of pregnancy loss was similar between Groups I and II. The clinical pregnancy loss rate in Group I was similar in different causes of infertility. Conclusions. The clinical pregnancy loss rate following IVF treatment is lower than that of women with unexplained recurrent miscarriages who conceived spontaneously. This difference persists whether the infertility is secondary to tubal factors, male factors, or unexplained cause.

Regulation of CD4⁺FOXP3⁺ T cells by CCL20/CCR6 axis in early unexplained recurrent miscarriage patients.

Expression and function of CCR6/CCL20 in CD4(+)FOXP3(+) regulatory T cells (Tregs) was investigated in unexplained recurrent miscarriage (URM) patients. Flow cytometry, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, western blots, and Transwell migration assays were used to analyze the expression and function of regulatory T cells in peripheral blood (PB) and decidual samples of women with URM and of healthy controls. Proportions of CD4(+)FOXP3(+) T cells and CCR6(+)CD4(+)FOXP3(+) T cells were lower in URM patients than in healthy controls for both PB lymphocytes and decidual samples (P < 0.05). Expression levels of FOXP3 and CCR6 mRNA were lower in URM patients than in control subjects for PB and decidual samples (P < 0.05). CCL20 protein levels were lower in URM patients than in controls (P < 0.05). An effect of Treg migration was significantly blocked (by 89.13%) using a neutralizing anti-CCL20 antibody in vitro. Furthermore, CCL20-stimulated Tregs exhibited a 3.21-fold increase in migration and this was blocked using a neutralizing anti-CCL20 antibody. IL-10 concentration in culture supernatants of CD4(+)CD25(+)CD127(dim/-) Tregs of URM patients was significantly lower than that in controls. Anti-CCL20 antibody inhibited IL-10 and IL-4 expression but increased IFN-r and IL-17 levels when there was cell-cell contact between PB CD4(+)CD25(+) T cells and CD4(+)CD25(-) T cells. No difference was detected when cell-cell contact was prevented by a semi-permeable Transwell membrane. CCL20-CCR6 could drive immune activity of CD4(+)FOXP3(+) Tregs, followed by their migration to the feto-maternal microenvironment. These results elucidated the mechanism by which Tregs exert this suppressive effect.

Uterine blood flow indices, antinuclear autoantibodies and unexplained recurrent miscarriage.

ObjectiveTo study the correlation between 2D and 3D uterine flow indexes and the presence or the absence of antinuclear antibodies (ANA) in women with unexplained recurrent miscarriage (uRM).MethodsFifty-two subjects (26 uRM and 26 control women) underwent 2D Doppler measurement of pulsatility index and resistance index of the uterine arteries in both the follicular and midluteal phase of the cycle. Additionally, 3D ultrasonography determination of vascularisation index, flow index, and vascularisation flow index was carried out with the aid of the VOCAL technique. Serum assay for the presence of ANA was performed in all women.ResultsPulsatility index of ANA+ uRM women was higher than that of ANA- uRM women and control ANA+ and ANAwomen, both in the follicular and in the midluteal phase of the cycle. Vascularisation index in ANA- uRM women was significantly higher than that in ANA+ control women. Flow index in uRM ANA+ women was significantly lower than that of each of the other groups.ConclusionANA might be involved in uRM by determining an impairment in uterine blood flow hemodynamic, particularly in uterine blood flow intensity and uterine artery impedance.

The Factor VIII:C plasma activity level in females with primary unexplained infertility and recurrent miscarriage

The Factor VIII:C plasma activity level in females with primary unexplained infertility and recurrent miscarriage

Intravenous immunoglobulin treatment for secondary recurrent miscarriage: a randomised, double-blind, placebo-controlled trial.

To determine whether infusions with intravenous immunoglobulin (IVIg) during early pregnancy increase live birth rate in women with secondary recurrent miscarriage compared with placebo. A single-centre, randomised, double-blind, placebo-controlled trial. A tertiary centre for recurrent miscarriage in Copenhagen, Denmark. A group of 82 women with unexplained secondary recurrent miscarriage and at least four miscarriages. Women were randomly assigned to repeated infusions with IVIg or placebo (albumin) from the time of positive pregnancy test to gestational week 15 or pregnancy loss. Primary outcome was birth with neonatal survival in all randomised women. In the intention-to-treat analyses, live birth rates were 23/42 (54.8%) in the IVIg and 20/40 (50.0%) in the placebo group, relative risk 1.11 (95% CI 0.70-1.74). In a per protocol analysis, almost identical results were found. The median gestational length at delivery was higher in the IVIg than the placebo group (282 versus 272 days, P = 0.02) but the mean birthweight was not significantly increased. In this trial, which is the largest so far, IVIg did not increase the live birth rate in patients with secondary recurrent miscarriage and the treatment cannot be recommended in clinical practice.

Ultrastructure alteration of decidual natural killer cells in women with unexplained recurrent miscarriage: a possible association with impaired decidual vascular remodelling.

This study aimed to evaluate the extent of remodelling of intra-decidual segments of the spiral arteries in human deciduas between the 6th and 10th gestational weeks in women with unexplained recurrent miscarriages (RM) in comparison to gestational-matched controls. A possible association with the number, immunoexpressive behaviour and ultrastructural changes of decidual natural killer cells (dNKCs) was investigated. Decidual biopsies were obtained from RM cases (n = 40) and women with no history of spontaneous miscarriage and at least one live birth at term (n = 30). Staining was performed using PAS, anti-CD34 and anti-CD56 antibodies, using an avidin-biotin-peroxides technique. Analysis by means of light and transmission electron microscopy was employed. To determine the extent of remodelling of decidual vessels, a quantitative score was analysed using histological criteria of vascular transformation and then related to the number of CD56(+) dNKCs. In RM, dNKCs were distributed among decidual cells and around the vessels. They possessed numerous polyploidic protrusions on cell membranes crossing from one cell to another. The cells became more irregular and exhibited heterogeneous electron-dense granules in their cytoplasm compared to controls. The non-remodelling score and number of dNKCs were significantly increased in RM group (p < 0.001). The number of dNKCs was significantly correlated with the scores in both control (r = 0.491; p = 0.006) and RM (r = 0.852; p < 0.001) groups. It appears that dNKCs play a key role in impaired decidual artery remodelling that may be involved with early RM. This may be due to increased numbers of cells or impaired cellular interactions resulting from alterations to the ultrastructure.

Can Porphyromonas gingivalis be a novel aetiology for recurrent miscarriage?

Objective To study the association between Porphyromonas gingivalis (P. gingivalis) infection and recurrent miscarriage.Methods This case control study included women with early pregnancy failure admitted for surgical evacuation of retained products of conception. Cases (group 1) included 50 women with unexplained recurrent early miscarriage whereas the control group (group 2) consisted of 50 women with no such history. The evacuated products of conception, subgingival plaques, cervicovaginal secretions and saliva of all participants were examined to detect P. gingivalis deoxyribonucleic acid (DNA) using a polymerase chain reaction.Results The prevalence of P. gingivalis DNA in the chorionic villous tissue samples of group 1 was significantly higher than in group 2 (8 [16%] vs. 1 [2%], respectively; p = 0.036, odds ratio [OR]: 9.3, 95% confidence interval [CI]: 1.1–76.9). The prevalence of P. gingivalis DNA was significantly higher in cervicovaginal secretions of group 1 than in group 2 (9 [18%] vs. 1 [2%], respectively; p = 0.02, OR: 10.8, 95% CI: 1.3–88.5). On the contrary, P. gingivalis DNA could not be detected in subgingival plaques and saliva samples of either group.Conclusion The current study found an association between P. gingivalis infection of the female genital tract and the occurrence of recurrent miscarriage.Chinese 摘要目的：研究牙龈卟啉单胞菌（P. gingivalis）感染与复发性流产的相关性。方法：这项病例对照研究纳入的研究对象为早期妊娠失败、并需手术清除妊娠残留物的患者。病例组（组1）包括50名不明原因复发性流产的患者，而对照组（组2）包括50名没有这种病史的女性。使用聚合酶链反应检测所有参与者抽吸的妊娠物、牙龈下菌斑、宫颈阴道分泌物和唾液中的牙龈卟啉单胞菌脱氧核糖核酸（DNA）。结果：组1的绒毛膜组织样本中牙龈卟啉单胞菌DNA的患病率明显高于组2（患病率分别为8 [ 16% ] vs 1 [ 2% ]，P = 0.036，OR：9.3，95%CI：1.1–76.9）。组1的宫颈阴道分泌物中牙龈卟啉单胞菌DNA的患病率明显高于组2（患病率分别为9 [18%]vs1 [ 2% ]，P = 0.02，OR：10.8，95%CI：1.3–88.5）。相反的，牙龈卟啉单胞菌DNA在两组的牙龈下菌斑和唾液样品中均未能检出。结论：目前的研究发现女性生殖道的牙龈卟啉单胞菌感染与复发性流产相关。

Adenomyosis and accompanying gynecological pathologies.

The aim of the present study is to determine the potential risk factors for adenomyosis and to investigate its relationship with accompanying gynecological pathologies and clinical characteristics. This study is a retrospective analysis of 945 patients who underwent hysterectomy between May 2005 and January 2013 at the Sifa University Medical Faculty Hospital, Clinic of Obstetrics and Gynecology. The study included 327 patients with adenomyosis and 618 patients without adenomyosis by histopathological examination of the uterus. There was a significant positive correlation between development of adenomyosis and presence of leiomyoma (p < 0.0001), history of previous abortion (p < 0.0001), history of previous pregnancy (p = 0.0002), and normal body mass index (p < 0.0001). However, no significant relationship existed between development of adenomyosis and smoking (p > 0.4300), normal delivery (p = 0.9600), cesarean delivery (p = 0.5705), endometrial hyperplasia (p = 0.1721), or ovarian endometriosis (p = 0.8595). Women who are multiparous have leiomyoma, a previous history of abortion, and a normal body mass index are at increased risk for development of adenomyosis. Adenomyosis might be one cause of unexplained recurrent spontaneous abortion during pregnancy.

Live birth rate and time to live birth in women with unexplained recurrent miscarriage with or without inherited thrombophilia

Live birth rate and time to live birth in women with unexplained recurrent miscarriage with or without inherited thrombophilia

Sympathomimetic amine therapy found effective for treatment of refractory chronic complex regional pain syndrome (reflex sympathetic dystrophy)

Purpose: To determine if treatment with sympathomimetic amines could improve the pain from complex regional pain disorder (CRPD) which was keeping a woman from trying to conceive her second child. Materials and Methods: Dextroamphetamine sulfate was prescribed. Results: Within a short length of time the woman’s wrist pain considerably improved to the point that she is ready to try in vitro fertilization once again to have a second baby. Conclusions: Though sympathomimetic amines are used by some reproductive endocrinologists for unexplained infertility and unexplained recurrent miscarriages, the most common use by the gynecologist is for pelvic pain. Despite the thought by some clinicians and researchers that the etiology for CRPD may be related to sympathetic nervous system hyperactivity (and thus sympathomimetic amines could theoretically exacerbate the symptoms), in fact, the treatment with dextroamphetamine sulfate may turn out to be a new and possibly the most effective, least risky, and least expensive treatment to date for CRPD.