Pathological diagnosis of thoracic endometriosis.

A 26-year-old woman, who underwent abdominal surgery because of pelvic endometriosis, suffered from upper abdominal pain, fever and dyspnoea 2 days postoperatively. Paralytic ileus and right-sided pneumothorax were revealed. Treatment with a chest drain was not successful and, thus, a video-assisted thoracoscopic surgery was performed, revealing endometriosis-like lesions. Basic histopathology did not confirm the visual diagnosis, but additional immunohistochemical staining for oestrogen and progesterone receptors showed positive reaction in epithelial lung cells, thus proved the diagnosis thoracic endometriosis. A resection of the apex of the right upper lobe and pleurodesis by talc poudrage was performed after which a mesh graft was applied on the diaphragm. After 5 years of follow-up, no recurrent pneumothorax occurred.

Optimization of microRNA Acquirement from Seminal Plasma and Identification of Diminished Seminal microRNA-34b as Indicator of Low Semen Concentration.

About 10-15% of couples who want to conceive suffer from subfertility, while in 30% of these cases, a male factor plays a role. Levels of particular microRNAs in seminal plasma, including those involved in spermatogenesis, may serve as an indicative parameter for subfertility. We first optimized a protocol for acquiring microRNAs from seminal plasma. Next, using a test-validation strategy in a male cohort, we aimed to identify microRNAs of which the levels are related to semen motility and concentration. By qPCR, 742 microRNAs were profiled in three normozoospermic samples, three seminal samples with a low semen motility (asthenozoospermia), and three with a low semen concentration (oligozoospermia). MicroRNAs showing significant differences between groups were further validated in a second cohort consisting of 40 samples with normozoospermia (control group), 47 samples with asthenozoospermia, and 19 samples with oligozoospermia (of which 74% also low motility). Highest microRNA yields were obtained with the Biofluids RNA extraction kit, with inclusion of MS2 RNA carrier and proteinase K treatment to the protocol, and when 50 µL of seminal plasma was used as input. Exosome isolation prior to RNA extraction did not lead to enhanced yields. In the test cohort, 236 microRNAs could be detected, of which 54 microRNAs showed a difference between groups. Five microRNAs were analyzed in the validation cohort. MiR-34b-5p levels in the control group were significantly higher compared to the asthenozoospermia group (p < 0.05) and compared to the oligozoospermia group (p < 0.001). We optimized microRNA acquirement from seminal plasma and identified microRNA levels in relation to semen concentration and motility. As recent human and mouse studies show that the miR-34 family is a marker of low semen concentration and is crucial in spermatogenesis, seminal plasma miR-34b-5p may represent a suitable candidate to study further as a marker of male subfertility.

Soluble HLA-G levels in seminal plasma are associated with HLA-G 3'UTR genotypes and haplotypes.

Soluble HLA-G (sHLA-G) levels in human seminal plasma (SP) can be diverse and may affect the establishment of maternal-fetal tolerance and thereby the outcome of pregnancy. We investigated whether sHLA-G levels in SP are associated with polymorphisms in the 3'-untranslated region (UTR) and UTR haplotypes of the HLA-G gene. Furthermore, we compared the HLA-G genotype distribution and sHLA-G levels between men, whose partner experienced unexplained recurrent miscarriage (RM), and controls. Soluble HLA-G levels (n = 156) and HLA-G genotyping (n = 176) were determined in SP samples. The concentration of sHLA-G was significantly associated with several single-nucleotide polymorphisms (SNPs): the 14 base pair (bp) insertion/deletion (indel), +3010, +3142, +3187, +3196, and + 3509. High levels of sHLA-G were associated with UTR-1 and low levels with UTR-2, UTR-4, and UTR-7 (P < .0001). HLA-G genotype distribution and sHLA-G levels in SP were not significantly different between the RM group (n = 44) and controls (n = 31). In conclusion, seminal sHLA-G levels are associated with both singular SNPs and 3UTR haplotypes. HLA-G genotype and sHLA-G levels in SP are not different between men whose partner experienced RM and controls, indicating that miscarriages are not solely the result of low sHLA-G levels in SP. Instead, it is more likely that these miscarriages are the result of a multifactorial immunologic mechanism, whereby the HLA-G 3'UTR 14 bp ins/ins genotype plays a role in a proportion of the cases. Future studies should look into the functions of sHLA-G in SP and the consequences of low or high levels on the chance to conceive.

Paternal HLA-C is a risk factor in unexplained recurrent miscarriage.

PROBLEM: HLA-C is the only classical HLA-I antigen expressed on trophoblast. We hypothesized that the alloimmune response to paternal HLA-C plays a role in unexplained recurrent miscarriage. METHOD OF STUDY: In a case-control design, we included 100 women with at least three unexplained consecutive miscarriages along with their partners and children. For the first control group, we included 90 women with an uneventful singleton pregnancy without pregnancy complications in their history along with their children. The second control group consisted of 425 families. HLA-C*07 and HLA-C*17 frequencies, which are the most immunogenic HLA-C antigens, along with HLA-C mismatches, and the presence of specific HLA antibodies in the mother were determined. RESULTS: HLA-C and HLA-C*07 mismatches were significantly increased in couples with recurrent miscarriage compared to control subjects (P = .016, P = .008, respectively). The incidence of child-specific HLA-C*07/HLA-C*17 antibodies was increased in women with recurrent miscarriage (P = .007). CONCLUSION: The results show that HLA-C incompatibility between couples is significantly associated with unexplained recurrent miscarriage.

Increased complement C4d deposition at the maternal-fetal interface in unexplained recurrent miscarriage.

C4d is a footprint of antibody-mediated classical complement activation, and has evolved as a useful diagnostic marker of antibody-mediated rejection. It is unknown if complement activation, as reflected by C4d deposition plays a role in unexplained recurrent miscarriage. In a case-control study products of conception of 35 women with three or more unexplained consecutive miscarriages within 20 weeks of gestation with the same partner (case group), 22 women with one spontaneous sporadic miscarriage and no history of complicated pregnancy(ies) (control group 1), and 40 women who underwent an elective abortion for psychosocial reasons (control group 2) were included. Immunohistochemical staining for C4d was performed on products of conception. Positivity for C4d was scored semi-quantitatively. C4d deposition was present in products of conception of 14 out of 35 women with unexplained recurrent miscarriage (40.0%), compared to 6 out of 22 women with a sporadic miscarriage (27.3%), and 4 out of 40 women with an elective abortion (10.0%) (p=0.020). C4d is increased at the maternal-fetal interface in women with unexplained recurrent miscarriage, which may reflect an aberrant anti-fetal immunity in these women. Further knowledge of the specific pathogenic mechanism may lead to the development of new treatment strategies for this group of women.

HLA associations and HLA sharing in recurrent miscarriage: A systematic review and meta-analysis.

PROBLEM: The aim of this meta-analysis was to evaluate whether specific maternal HLA alleles and HLA sharing of couples are associated with the occurrence of recurrent miscarriage (RM). METHOD OF STUDY: A systematic literature search was performed for studies that evaluated the association between HLA alleles, HLA sharing and RM. RM was defined as three or more consecutive unexplained miscarriages and a control group was included of women with at least one live birth and no miscarriages in their history. Meta-analyses were performed and the pooled odds ratio (OR) was calculated. RESULTS: We included 41 studies. Selection bias was present in 40 studies and information bias in all studies. Meta-analyses showed an increased risk of RM in mothers carrying a HLA-DRB1*4 (OR 1.41, 95% CI 1.05-1.90), HLA-DRB1*15 (OR 1.57, 95% CI 1.15-2.14), or a HLA-E*01:01 allele (OR 1.47, 95% CI 0.20-1.81), and a decreased risk with HLA-DRB1*13 (OR 0.63, 95% CI 0.45-0.89) or HLA-DRB1*14 (OR 0.54, 95% CI 0.31-0.94). Pooling results for HLA sharing showed that HLA-B sharing (OR 1.39, 95% CI 1.11-1.75) and HLA-DR sharing (OR 1.57, 95% CI 1.10-1.25) were both associated with the occurrence of RM. CONCLUSION: Although the present systematic review and meta-analysis demonstrates that specific HLA alleles and HLA sharing are associated with RM, a high degree of bias was present and therefore observed results should be interpreted carefully.

The optimal treatment of severe hypertension in pregnancy: update of the role of nicardipine.

OBJECTIVE: Hypertensive disorders in pregnancy remain a major cause of maternal morbidity and mortality. Blood pressure control is essential for maternal and neonatal outcome. Therefore, we analyzed the potency and side effects of two treatment options (nicardipine compared to labetalol) in order to gain insight in improved treatment of severe hypertension during pregnancy and to evaluate the feasibility of a randomised controlled trial. STUDY DESIGN: A nested case control study in an inner city teaching hospital alongside a meta-analysis. Data from women who received nicardipine were compared with patients who received labetalol during pregnancy. Primary outcome measure was successful control of severe hypertension. Secondary outcome measures were maternal and neonatal side effects. These results were included in a meta-analysis. RESULTS: Only one previous study described nicardipine in comparison to labetalol during pregnancy. The combined results indicate a similar success-rate of treatment with nicardipine compared to labetalol during pregnancy. Women treated with nicardipine had more often tachycardia, headache and nausea compared to women treated with labetalol. Hypotension resulting in fetal distress was found more often in the labetalol group. CONCLUSION: Nicardipine is a potent drug to control hypertension during pregnancy with side effects including maternal headaches, nausea and tachycardia. Labetalol had more neonatal side effects including hypotension compared with nicardipine. These results support the justification and prove that it is safe to perform a randomized controlled trial comparing nicardipine to labetalol in the treatment of severe hypertension in pregnancy.

Adhesion awareness: a nationwide survey of gynaecologists.

OBJECTIVE: Adhesions and related complications lead to substantially increased morbidity and mortality which increase medical costs. We investigated the awareness of adhesions among Dutch gynaecologists and gynaecology residents. STUDY DESIGN: A survey, assessing knowledge and opinion about adhesions, was sent to a randomly selected group of 381 gynaecologists and 256 residents. In addition, the informed consent process and application of anti-adhesive agents were questioned. RESULTS: The response rate was 56.9%. Complications due to adhesions were highly underestimated, leading to low knowledge scores (mean score 35.1%). Of all respondents 73.8% agreed that adhesions exert a clinically relevant and negative effect, but only 51.2% expressed a positive opinion on adhesion prevention. This correlated with a stronger belief in the clinically relevant and negative effects of adhesions and the opinion that adhesion prevention belongs to standard care (ρ=0.212, p<0.001; ρ=0.495, p<0.001). Of all respondents 31.4% expressed a positive attitude towards anti-adhesive agents and 19.8% expressed a negative one. A negative attitude correlated with a negative view in terms of cost-benefits (ρ=0.245, p<0.001). Although 43.5% had used anti-adhesive agents in the past year, 20.9% had used them before but stopped using agents in the past year. Only 5.2% routinely included adhesions or related morbidity in the informed consent. CONCLUSIONS: Awareness of adhesions is limited and informed consent is provided inadequately. Implementing adhesion prevention is related with awareness of adhesions. These findings underline the need to embed adhesions, related morbidity and prevention in educational programmes.

Beneficial or harmful effect of antipaternal human leukocyte antibodies on pregnancy outcome? A systematic review and meta-analysis.

PROBLEM: During pregnancy, antibodies are induced that target the paternal human leukocyte antigens of the semi-allogeneic fetus. The level and presence of these antibodies have been reported increased as well as decreased for a variety of pregnancy complications; the clinical relevance and consequences of these antibodies are not very clear. Therefore, the objective of this review is to determine whether the presence of antipaternal antibodies influences pregnancy outcome. METHOD: We performed a systematic search of studies that described the effect of antipaternal antibodies on pregnancy complications. The primary outcome was the risk ratio for HLA class I and class II antibodies on pregnancy complications. Furthermore, we calculated the risk for first- and third-trimester complications. RESULTS: The seventeen studies that were selected for meta-analysis showed high level of statistical and clinical heterogeneity. In the meta-analysis, we found no significant effect of HLA class I or class II antibodies on pregnancy outcome. CONCLUSION: No consistent conclusions can be drawn from the meta-analysis. Discrepancies in the meta-analysis are the result of different screening techniques, varying time points of screening, and use of incorrect control groups. Furthermore, more detailed analyses of the characteristics and specificity of the antibodies involved are essential.

[A Zambian woman with vaginal bleeding]. / Een Zambiaanse vrouw met vaginaal bloedverlies.

A woman reported with vaginal bleeding and abdominal pain in a Zambian hospital. Examination with ultrasound showed an intact gravidity outside the cavum uteri and free abdominal fluid. Laparotomy revealed an ectopic gravidity in the right tube. Subsequently, a tubectomy was performed with success.