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Abstract Background A decrease in HOXA11 expression in eutopic mid-secretory endometrium has been found in women with endometriosis-associated infertility. Methods Using Real-time quantitative PCR (RQ-PCR) and western blotting analysis we studied the HOXA11 transcript and protein levels in mid-luteal eutopic endometrium from eighteen infertile women with minimal endometriosis, sixteen healthy fertile women and sixteen infertile women with fallopian tubal occlusion from the Polish population. We also evaluated transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in these groups of women. Results There were significantly lower levels of HOXA11 transcripts (p = 0.003, p = 0.041) and protein (p = 0.004, p = 0.001) in women with endometriosis as compared to fertile women and infertile women with tubal occlusion. Moreover, we found significantly higher methylation levels of the CpG region in the first exon of HOXA11 in infertile women with endometriosis compared with fertile women (p < 0.001) and infertile women with tubal occlusion (p < 0.001). We also observed significantly increased levels of DNMT3A transcript in women with endometriosis than fertile women (p = 0.044) and infertile women with tubal occlusion (p = 0.047). However, we did not observe significant differences in DNMT1 and DNMT3B transcript levels between these investigated groups of women. Conclusions We confirmed that reduced HOXA11 expression may contribute to endometriosis-associated infertility. Moreover, we found that DNA hypermethylation can be one of the possible molecular mechanisms causing a decrease in HOXA11 expression in the eutopic mid-secretory endometrium in infertile women with endometriosis.

Objective: To determine the frequency of chromosomal aberrations in chorions after a miscarriage. The second was to examine selected euploid chorions using a next-generation sequencing (NGS) panel designed to assess 43 genes associated with pregnancy loss., Materials and Methods: The 1244 chorions were tested by targeted quantitative fluorescent PCR (QF-PCR, 827 chorions) and microarray-based comparative genomic hybridization (aCGH, 417 chorions). Then, 9 euploid chorions were examined using a designed NGS panel., Results: Trisomies were the most common chromosomal aberration identified in the spontaneous miscarriage samples. The second chromosomal abnormality in the aCGH group and the third most common in the QF-PCR group was monosomy X. Structural aberrations were the third most common aberration in the samples screened by aCGH (7.7% of chorions). In 19% of 647 couples who submitted chorions for analysis after pregnancy loss, the chromosomal abnormality in the chorion originated from a woman with a balanced chromosomal rearrangement. This discovery was statistically significant compared to patients with normal chorions. Using the designed NGS panel, we identified a potentially pathogenic de novo variant in the F5 gene in two euploid chorions. Additionally, among the patients who experienced miscarriages and were screened using the NGS panel, we identified variants in the MDM , ACE , and NLRP2 genes that could be associated with a predisposition to pregnancy loss., Conclusion: Numerical aberrations are the most common cause of miscarriages, but structural chromosomal aberrations also account for a significant proportion of abnormal results. Our findings indicate that couples with structural chromosomal abnormalities in material post-miscarriage are at increased risk of carrying balanced chromosomal abnormalities. Moreover, NGS-based analyses can uncover previously unidentified causes of miscarriages in the chorionic villi.

Sexual and gender minority (SGM) medical students and physicians are exposed to bias in professional contexts. One strategy for promoting SGM visibility and inclusion within medicine is the development of institutional OutLists, which are online, opt-in lists of SGM-identified individuals affiliated with an academic institution. We present the first quantitative evaluation of publicly accessible OutLists at medical institutions in the United States, Canada, and Europe. Nineteen OutLists were identified in the United States; no OutLists were identified in other countries. All OutLists in the United States were identified at allopathic institutions with no institutional religious affiliation. Clinicians in high-prestige specialties and more senior clinicians were underrepresented on OutLists. A state-level measure of SGM equality predicted presence of OutLists within the state (odds ratio 1.429, p = .047) but was not associated with the total number of individuals on OutLists. Future research would benefit from incorporating qualitative methodologies to explore the effectiveness of OutLists and the individual experiences of participants in these lists.

Background Preterm premature rupture of membranes (pPROM) is associated with a high risk of prematurity and complications of fetal inflammatory response syndrome (FIRS). The aim of the study is to determine any correlations between the concentration of selected cytokines contained in the cervicovaginal secretion eluates and in the umbilical cord plasma in patients with pPROM and to find the noninvasive markers of FIRS in order to pinpoint the optimal time of the delivery. Methods The study included 80 patients with pPROM between the 24th and 34th week of gestation. The cervicovaginal fluid and umbilical cord blood were collected. Interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 19 (IL-19) and tumor necrosis factor-α (TNF-α) concentrations were measured in both materials. For the statistical analysis, SigmaStat3.5 software was used. Results There was no direct association in levels of IL-6, TNF-α, IL-10 and IL-19 between the cord blood and cervicovaginal secretions within the studied group. The cut-off point of IL-6 of 26.8 pg/mL in the vaginal fluid had high sensitivity and specificity in order to discriminate between newborns with and without FIRS (81.08%; 76.74%). Conclusion Further studies are needed on a larger group of participants to demonstrate that an elevated concentration of IL-6 above 26.8 pg/mL in the cervicovaginal secretion eluate is an indirect noninvasive marker of FIRS.

Purpose: To present antenatal management and use of ex utero intrapartum treatment (EXIT) in different fetal neck and high airway anomalies., Material and Methods: We have presented four different cases of fetal neck or airway pathology which were indications for EXIT, at our department., Results: In three cases of fetal neck tumors, the primary precise antenatal diagnoses of tumors were confirmed after birth. The airways of all three fetuses were properly secured during EXIT by laryngologist. All these newborns survived. In the fourth case, a primary, antenatal diagnosis of congenital high airway obstruction syndrome due to severe trachea obstruction was not confirmed after birth. Finally, due to complete trachea dysgenesis, neither tracheoscopy nor tracheostomy was done during EXIT and the baby died., Conclusion: Despite a failure of intrapartum treatment in the fourth case, we strongly recommend this procedure for deliveries of fetuses with a suspicion of airway obstruction.

Purpose: Endometriosis is considered to be an estrogen-related chronic inflammatory disease. The 17β-hydroxysteroid dehydrogenase 1 (HSD17B1) converts estrone to 17β estradiol. The role of HSD17B1 937 A>G (rs605059) single nucleotide polymorphism (SNP) in development of endometriosis is still disputable. This study evaluated the association of the HSD17B1 937 A>G (rs605059) SNP with infertile women affected by endometriosis from Polish Caucasian population., Methods: The genotyping of cases (n = 290) and fertile women (n = 410) was conducted by high-resolution melting curve analysis., Results: Statistical analysis demonstrated that the HSD17B1 937 A>G SNP is associated with endometriosis in stages I and II. The p trend and p allelic values calculated for the HSD17B1 937 A>G polymorphism were statistically significant and were equal to 0.001 and 0.0009, respectively. There was a significant association for the dominant model: (AG + GG vs AA) OR = 1.973 (95% CI = 1.178-3.304), p = 0.009, and for the recessive model: (GG vs AG + AA) OR = 1.806 (95% CI = 1.178-2.770), p = 0.006. However, we did not find statistical association of HSD17B1 937 A>G polymorphism with all infertile women with endometriosis or infertile women with endometriosis in stages III and IV., Conclusion: Our genetic study demonstrated HSD17B1 937 G variant as a risk factor for infertility in women with stage I and II endometriosis in Polish Caucasian patients.

In this review article we describe the ante- and perinatal management of fetal neck tumors. Although there are rare congenital anomalies, the clinical consequences for the fetus may be fatal and include airways obstruction, heart insufficiency, pulmonary hypoplasia and cosmetic effect. The right management allows to decrease the fetal and neonatal mortality and morbidity associated with the disease. It includes intrauterine therapy in some cases, mostly in a goitrus hypothyroidism of the fetus, but firstly, an assessment of the fetal airways patency with a subsequent, eventual Ex-Utero Intrapartum Treatment (EXIT).

Endometriosis is considered to be an epigenetic disease. It has previously been reported that the DNA methyltransferase 3-like (DNMT3L) rs8129776 single nucleotide polymorphism (SNP) contributes to endometrioma. In the present study, high‑resolution melting curve analysis was used to investigate the risks associated with the DNMT3L c.910‑635A/G (rs8129776), c.832C/T (rs7354779), c.812C/T (rs113593938) and c.344+62C/T (rs2276248) SNPs on stage I‑II endometriosis‑associated infertility. Included in the present study were patients presenting with stage I‑II endometriosis‑associated infertility (n=154) and a control cohort of healthy patients with confirmed fertility (n=383). No significant association between the above‑listed DNMT3L SNPs and the development of endometriosis‑associated infertility was identified. The lowest P‑values generated from trend analysis were observed in the DNMT3L c.832C/T (rs7354779) SNP (Ptrend=0.114). Furthermore, haplotype analyses of the DNMT3L SNPs failed to reveal any risk association between the development of endometriosis‑associated infertility and the above‑listed polymorphisms, even when the SNPs were present in combinations. Finally, a meta‑analysis was performed to examine the association between the DNMT3L rs8129776 SNP and the development of endometrioma, from which no association between the two was identified. On the basis of these results, the present study has demonstrated that variations in the DNMT3L gene do not contribute to stage I-II endometriosis-associated infertility.

It has recently been reported that vitamin D blood plasma levels are associated with reduced risk of endometriosis. The present study aimed to investigate whether the vitamin D binding protein (GC), vitamin D receptor (VDR), and retinoid X receptor (RXR) gene variants may be genetic risk factors for endometriosis‑associated infertility. The subjects consisted of 154 women with endometriosis‑associated infertility and 347 controls. Using polymerase chain reaction restriction fragment length polymorphism and high resolution melt techniques, the GC rs1155563, rs2298849 and rs7041; RXRA rs10881578, rs10776909 and rs749759; VDR BsmI rs1544410; and FokI rs2228570 single nucleotide polymorphisms (SNPs) were investigated in the patients with endometriosis and the healthy controls. The results indicated that no significant differences were observed between the genotype and allele frequencies of all experimental SNPs in the vitamin D signaling pathway genes in women with endometriosis-associated infertility and controls. However, a significant association was present between the A‑T haplotype, consisting of VDR rs1544410 and rs222857 minor alleles, and endometriosis-associated infertility [OR=1.659 (1.122‑2.453), P=0.011]. The results of the present study suggested that VDR gene variants act as genetic risk factors for endometriosis‑associated infertility.

The article is a review of the literature on the use and clinical applicability of Doppler examination in the second half of pregnancy Nowadays, despite its accessibility Doppler ultrasound in pregnancy is often contraindicated. At the same time, the is no evidence of clinical utility of Doppler studies in a low-risk pregnancy The main indications for Doppler examinations in pregnancy include intrauterine growth restriction (IUGR), suspicion of fetal anemia, and complications of monochorionic twin pregnancy As far as IUGR is concerned, Doppler allows to diagnose IUGR associated with placental insufficiency and to differentiate IUGR from small for gestational age fetuses (SGA). Doppler is also very useful in making the decision about the time of delivery of IUGR fetuses. The assessment of the peak systolic velocity in the middle cerebral artery (PSV-MVA) reduced the rate of invasive procedures due to fetal anemia by approximately 70%. Complications of the second half of pregnancy which are indications for Doppler ultrasound include selective IUGR, TTTS and TAPS. Similarly to the first trimester, the mid-trimester assessment of the blood flow in the uterine arteries plays an important role in the prediction of preeclampsia and IUGR, especially early-onset forms of these complications.

Data suggests that dopamine receptor DRD2 gene variants may contribute to hyperprolactinemia and that they may be risk factors for endometriosis-related infertility. The purpose of the present study was to determine whether nucleotide variants of the DRD2 gene may be associated with infertility related to endometriosis. Five DRD2 SNPs, rs1800497, rs6277, rs2283265, rs4245146 and rs4648317, which are located in different blocks of linkage disequilibrium, were studied in 151 cases and 381 controls. No significant differences between DRD2 rs1800497, rs6277, rs2283265, rs4245146 and rs4648317 genotype, allele nor haplotype frequencies were observed in women with endometriosis-related infertility compared with the control group. The present results did not confirm DRD2 gene variants to be genetic risk factors for endometriosis-related infertility.

Objectives: The aim of the study was to analyze the levels of pro-inflammatory interleukins in cervical secretions of women with PROM, depending on Ureaplasma spp. infection and the time elapsed since the rupture of the membranes, and to correlate their concentration in cervical secretions and in cord blood of the newborns., Material and Methods: The study included 30 women with PROM between 24 and 33+6 weeks of gestation. Cervical swabs from women with confirmed rupture of membranes taken at certain intervals and umbilical cord blood of their newborns constituted the study material. Cervical secretions were evaluated microbiologically and by the PCR method. Concentrations of IL-6, IL-19, IL-10 and TNF-α were analyzed by ELISA., Results: Ureaplasma spp. were the most frequently isolated microorganisms in cervical secretions of women with PROM. Secretion of interleukins in the cervix was not influenced by time elapsed since the PROM. Comparison of interleukin levels in cord blood of newborns born to mothers with and without Ureaplasma spp infection revealed significantly higher levels of IL-6 in the case of Ureaplasma spp. A positive correlation between IL-6 and TNF-α levels in cervical secretions and in cord blood of mothers with PROM and Ureaplasma spp. was detected., Conclusions: 1. Cervical culture method appears to be sufficient for detecting Ureaplasma spp. 2. Pro-inflammatory interleukins, especially IL-6, obtained by non-invasive methods can be used to predict fetal inflammatory response.

There are inconsistent data on the contribution of vascular endothelial growth factor ( VEGF ) -460 C/T (rs833061), +405 G/C (rs2010963) and +936 C/T (rs3025039) single-nucleotide polymorphisms (SNPs) to endometriosis in different ethnicities. Therefore, using high-resolution melting curve analysis, the present study examined the distribution of these SNPs in females with endometriosis-related infertility and a control group. None of the three VEGF SNPs were associated with endometriosis-related infertility in the dominant and recessive models. The lowest P-values of the trend were observed for the VEGF +936 C/T (rs3025039) SNP in endometriosis-related infertility (P trend =0.149). Similarly, haplotype analyses of VEGF SNPs did not demonstrate any SNP combination as a risk for endometriosis-related infertility, and the lowest overall P-values, P=0.141 and P corr =0.395, were observed for a haplotype (TGT) of the above SNPs. Taken together, these results did not demonstrate the contribution of VEGF C/T, +405 G/C and +936 C/T SNPs to endometriosis-related infertility.

Objective: The aim of the study was a long-term follow-up of children with prenatally found increased nuchal translucency (NT) and normal karyotype., Material and Methods: The study was conducted among 147 pregnant women who underwent amniocentesis due to increased fetal NT with or without other structural anomalies in the fetus. The final analysis concerned children with prenatally found increased NT and normal karyotype who were at least 2 years of age. A questionnaire was sent to all patients who underwent amniocentesis in order to assess the development of the children., Results: Normal karyotype was found in 101 (68.7%) fetuses with increased NT Complete information on the outcome of pregnancy and further development of the children was submitted by 70 patients (69.3%). An abnormal outcome of pregnancy congenital structural anomalies and abnormal development was found finally in 17.1% of the children. In case of normal result of the second-trimester fetal ultrasound scan, normal further development was found in 93% of the children., Conclusions: 1. Further development of the children with prenatally found increased NT and normal karyotype is usually normal. 2. The degree of NT increase and the result of the second-trimester fetal anatomy scan seem to play the key role in the prognosis of further, postnatal outcome of the fetuses with increased NT 3. Normal karyotype in fetuses with increased NT does not exclude the possibility of an existing genetic syndrome.

Objective: To answer the question as to whether the markers of thrombophilia in pregnant women, whose pregnancies ended in success, are reflected in the level of inflammation in the blood of the umbilical cord of the newborn., Materials and Methods: Umbilical cord blood and placenta after childbirth were secured from 16 patients with inherited (n = 7), acquired (n = 9) thrombophilia, and control group (n = 20). The concentrations of cytokines IL1β, IL10, TNFα, C5a anaphylatoxin, and granzyme A were assessed. decay accelerating factor (DAF) and membrane cofactor protein (MCP) levels were determined in the placentas, and the incidence of thrombotic changes was evaluated., Results: Higher levels of anaphylatoxin C5a (P = 0.041), TNFα (P = 0.016), and IL1β (P = 0.037) were observed in the study group compared to the control group. In the study group, C5a levels correlated with the levels of TNFα (P = 0.018) and IL1β (P = 0.012). Higher levels of DAF and MCP proteins in study group were found in the control group (P < 0.001). In placentas from study group, there was a more frequent occurrence of incidences of thrombotic changes., Conclusion: The observed, increased levels of pro-inflammatory factors in the cord blood of newborns of mothers with thrombophilia may result from a reaction of the prothrombotic and pro-inflammatory markers of thrombophilia present in maternal blood., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)