Effect of omega-3 supplements or diets on fertility in women: A meta-analysis.

Objective: This study aimed to assess the effect of increased omega-3 consumption on fertilization rates and the probability of women getting pregnant. This study is needed because different perspectives exist regarding the use of omega-3 fatty acids in enhancing fertility among women with reproductive issues, and information for those planning a spontaneous pregnancy is limited. Methods: PubMed, Clinical Trials, CINAHL/EBSCO, Medline Complete, Cochrane Library, and Google Scholar were searched for articles published until April 2021, and the search was limited to articles in English language. The search strategy included the following key words: "in-vitro fertilization (IVF)," "intracytoplasmic sperm injection techniques (ICSI)," "pregnancy," "omega-3 fatty acid," "alpha-linolenic acid," "eicosapentaenoic acid," "docosahexaenoic acid," "n-3 polyunsaturated fatty acid," and "fish oil and seafood." Studies reporting female fertility occurring naturally or IVF/ICSI concurrent with omega-3 intake were included. Retrospective studies, studies including postmenopausal women, and unevenly matched control and study groups were excluded. To assess bias, we used the Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0. To synthesize the findings from the studies included in this review, a meta-analysis was conducted using calculated or extracted odds ratios (OR) of clinical pregnancies and fertilization rates for each group in each study. Results: We included six trials involving 1789 women who received fertility treatment, four trials involving 2607 women who conceived naturally, and three trials involving 1725 oocytes for fertility rates. Aggregated ORs for the effects of omega-3 on pregnancies were 1.74, 1.36, and 2.14 for women who received fertility treatment, those who conceived naturally, and fertilization rate, respectively. All these results were significant (p ≤ 0.01), although they had high heterogeneity I2>68 %. Conclusion: This systematic review and meta-analysis suggest that omega-3 intake significantly improves women's pregnancy and fertilization rates; however, the high heterogeneity in this review somewhat limits its interpretation. Therefore, further prospective randomized studies are necessary to better understand this relationship.

Timing of midstream urine culture before endourological procedure-can we do better?-A comparative study.

Endourological procedures are the mainstay of treatment for stone disease in the upper urinary system. Infection is a common complication, and urine cultures (UC) are often obtained preoperatively. In this study, we sought to investigate the role of positive UC in the 90 days prior to surgery (90PreOp) in predicting postoperative infectious complications in comparison to a single positive preoperative UC (PreOP). We compared the correlation between positive PreOp UCs and positive 90PreOp UCs with postoperative urosepsis, and a positive UC obtain proximal to obstruction (Prox UC) during percutaneous nephrolithotomy, ureteroscopy and a placement of nephrostomy tube or ureteral stent. Data from 140 consecutive patients were collected. PreOp UCs were positive in 15 (11%) of patients versus 31 of 140 (22%) positive 90PreOp UCs. All six sepsis events had a positive 90PreOp UC, and five had a positive PreOp UC. Fourteen (93.3%) out of 15 positive Prox UC had a positive 90PreOp UC, whereas only 7 (38.9%) had a positive 90PreOp UC. Positive 90PreOp UC outperformed PreOp UC in predicting positive Prox UC, OR = 12.8 (95% CI 3.70-44.30, p < 0.001), versus OR of 88.9 (95% CI 11.0-720.7, p < 0.001); sensitivity 93%(95% CI 68-100%) versus 47%(95% CI 21-73%); as well as area under the ROC curve(AUC), 0.90 (CI 0.80-0.95) for 90PreOp versus 0.70 (CI 0.56-0.82) for positive Prox UC. Uropathogen persistence was better identified when using 90PreOp UC (27%) than using PreOp UC (12%). We suggest reviewing UCs taken within 90 days preoperatively as this was found superior to a single preoperative midstream UCs in predicting postoperative infectious sequela after stone procedure.

Omega-3 Intake Improves Clinical Pregnancy Rate in Polycystic Ovary Syndrome Patients: A Double-Blind, Randomized Study.

BACKGROUND: Omega-3 fatty acids promote fertility in males and females and constitute an important factor in the normal development of the fetus. OBJECTIVES: We investigated the effect of omega-3 supplements during ovulation induction treatment in women with polycystic ovary syndrome (PCOS)-related infertility. METHODS: A randomized, double-blind study was conducted for 60 treatment cycles in 34 women with PCOS-related oligo/anovulation referred to the fertility clinic at the Bikur Cholim/Shaare Zedek Medical Center in Jerusalem, who underwent ovulation induction with clomiphene citrate (50 mg). Seventeen women (mean age 33.9 ± 0.9 years) received omega-3 supplements (3 × 600 mg/day) and 17 received placebo capsules (mean age 32.7 ± 0.9 years) for a maximum of two cycles. We recorded their characteristics and data from their serial hormonal blood tests and ultrasound examinations. We also conducted both univariate and multivariate analyses. The primary endpoint was conception. RESULTS: There were clinical pregnancies in 8/30 (26.7%) treatment cycles for women receiving omega-3 supplements versus 4/30 (13.3%) cycles with placebo. Among overweight/obese women (body mass index [BMI] 25-35), there were clinical pregnancies in 8/27 cycles (29.6%) versus 1/19 (5.3%) with placebo (P < 0.04). For overweight/obese PCOS women, omega-3, lower BMI rates, and higher values of the endometrium's thickness increased the odds of becoming pregnant. No harmful side effects from the omega-3 treatment were reported. CONCLUSIONS: Omega-3 supplements demonstrated beneficial effects for fertility in women diagnosed with PCOS. Among the overweight/obese participants, the increased clinical pregnancy rate was significant.

Reversal of prenatal heroin-induced alterations in hippocampal gene expression via transplantation of mesenchymal stem cells during adulthood.

Neurobehavioral teratology is the study of typically subtle neurobehavioral birth defects. Our previously described mouse model demonstrated septohippocampal cholinergic innervation-related molecular and behavioral deficits after prenatal exposure to heroin. Since the alterations are below malformation level, they are likely to represent consequences of regulatory processes, feasibly gene expression. Consequently, in the present study pregnant mice were injected with heroin on gestation days 9-18 and were transplanted with mesenchymal stem cells (MSC) on postnatal day (PD) 105. The hippocampi of the offspring were analyzed on PD120 for the expression of the pertinent genes. Heroin induced global gender-dependent statistically significant changes in the expression of several genes. Significant Treatment X Sex interaction occurred in D1 and SOX2 genes (p < 0.01). Transplantation of MSC reversed the prenatal heroin-induced alterations in approximately 80% of the genes. The reversal index (RI), shifting the score of the heroin-exposed offspring by transplantation back toward the control level, was 0.61 ± 0.10 for the difference from RI = 0 (p < 0.001), confirming the validity of the effect of the neuroteratogens across variations among different genes. The present study suggests that neurobehavioral defects induced by prenatal heroin exposure are likely to be a consequence of regulatory changes. This study on prenatal exposure to insults with subsequent MSC therapy provides a model for elucidating the mechanisms of both the neuroteratogenicity and the therapy, steps that are critical for progress toward therapeutic applications.

Genome-wide characterization of copy number variations in the host genome in genetic resistance to Marek's disease using next generation sequencing.

BACKGROUND: Marek's disease (MD) is a highly neoplastic disease primarily affecting chickens, and remains as a chronic infectious disease that threatens the poultry industry. Copy number variation (CNV) has been examined in many species and is recognized as a major source of genetic variation that directly contributes to phenotypic variation such as resistance to infectious diseases. Two highly inbred chicken lines, 63 (MD-resistant) and 72 (MD-susceptible), as well as their F1 generation and six recombinant congenic strains (RCSs) with varied susceptibility to MD, are considered as ideal models to identify the complex mechanisms of genetic and molecular resistance to MD. RESULTS: In the present study, to unravel the potential genetic mechanisms underlying resistance to MD, we performed a genome-wide CNV detection using next generation sequencing on the inbred chicken lines with the assistance of CNVnator. As a result, a total of 1649 CNV regions (CNVRs) were successfully identified after merging all the nine datasets, of which 90 CNVRs were overlapped across all the chicken lines. Within these shared regions, 1360 harbored genes were identified. In addition, 55 and 44 CNVRs with 62 and 57 harbored genes were specifically identified in line 63 and 72, respectively. Bioinformatics analysis showed that the nearby genes were significantly enriched in 36 GO terms and 6 KEGG pathways including JAK/STAT signaling pathway. Ten CNVRs (nine deletions and one duplication) involved in 10 disease-related genes were selected for validation by using quantitative real-time PCR (qPCR), all of which were successfully confirmed. Finally, qPCR was also used to validate two deletion events in line 72 that were definitely normal in line 63. One high-confidence gene, IRF2 was identified as the most promising candidate gene underlying resistance and susceptibility to MD in view of its function and overlaps with data from previous study. CONCLUSIONS: Our findings provide valuable insights for understanding the genetic mechanism of resistance to MD and the identified gene and pathway could be considered as the subject of further functional characterization.

Development and validation of a risk prediction model to diagnose Barrett's oesophagus (MARK-BE): a case-control machine learning approach.

Background: Screening for Barrett's Oesophagus (BE) relies on endoscopy which is invasive and has a low yield. This study aimed to develop and externally validate a simple symptom and risk-factor questionnaire to screen for patients with BE. Methods: Questionnaires from 1299 patients in the BEST2 case-controlled study were analysed: 880 had BE including 40 with invasive oesophageal adenocarcinoma (OAC) and 419 were controls. This was randomly split into a training cohort of 776 patients and an internal validation cohort of 523 patients. External validation included 398 patients from the BOOST case-controlled study: 198 with BE (23 with OAC) and 200 controls. Identification of independently important diagnostic features was undertaken using machine learning techniques information gain (IG) and correlation based feature selection (CFS). Multiple classification tools were assessed to create a multi-variable risk prediction model. Internal validation was followed by external validation in the independent dataset. Findings: The BEST2 study included 40 features. Of these, 24 added IG but following CFS, only 8 demonstrated independent diagnostic value including age, gender, smoking, waist circumference, frequency of stomach pain, duration of heartburn and acid taste and taking of acid suppression medicines. Logistic regression offered the highest prediction quality with AUC (area under the receiver operator curve) of 0.87. In the internal validation set, AUC was 0.86. In the BOOST external validation set, AUC was 0.81. Interpretation: The diagnostic model offers valid predictions of diagnosis of BE in patients with symptomatic gastroesophageal reflux, assisting in identifying who should go forward to invasive testing. Overweight men who have been taking stomach medicines for a long time may merit particular consideration for further testing. The risk prediction tool is quick and simple to administer but will need further calibration and validation in a prospective study in primary care. Funding: Charles Wolfson Trust and Guts UK.

Factors Predicting Operating Room Time in Ureteroscopy and Ureterorenoscopy.

BACKGROUNDS/AIMS: Operation room (OR) time is of great value affecting surgical outcome, complications and the daily surgical program with financial implications. METHODS: We retrospectively evaluated 570 consecutive patients submitted to ureteroscopy or ureterorenoscopy for the treatment of ureteral or renal stones. Demographic parameters, patient's stones characteristics, type of ureteroscope, surgeon experience and surgical theater characteristics were analyzed. OR time was calculated from the initiation of anesthesia to patient extubation. Multivariate analysis was conducted using a linear regression test with multiple parameters to identify predictors of OR time. RESULTS: Eight factors were identified as significant. These include total stones volume, ureteroscope used, stone number, nurses experience, radio-opacity of the stone on kidney-ureter-bladder X-ray, main surgeon experience, operating room type, and having a nephrostomy tube prior to surgery. CONCLUSIONS: The surgical team experience and familiarity with endourological procedure, and the surgical room characteristics has a crucial impact on OR time and effectiveness.

Variations in biochemical values for common laboratory tests: a comparison among multi-ethnic Israeli women cohort.

BACKGROUND: Biochemical laboratory values are an essential tool in medical diagnosis, treatment, and follow-up; however, they are known to vary between populations. Establishment of ethnicity-adjusted reference values is recommended by health organizations. AIM: To investigate the ethnicity element in biochemical lab values studying women of different ethnic groups. METHODS: Biochemical lab values (n = 27) of 503 adult Israeli women of three ethnicities (Jewish Ashkenazi, Jewish Sephardic, and Bedouin Arab) attending a single medical center were analyzed. Biochemical data were extracted from medical center records. Ethnic differences of laboratory biochemicals were studied using ANCOVA to analyze the center of the distribution as well as quartile regression analysis to analyze the upper and lower limits, both done with an adjustment for age. RESULTS: Significant ethnic differences were found in almost half (n = 12) of the biochemical laboratory tests. Ashkenazi Jews exhibited significantly higher mean values compared to Bedouins in most of the biochemical tests, including albumin, alkaline phosphatase, calcium, cholesterol, cholesterol LDL and HDL, cholesterol LDL calc., folic acid, globulin, and iron saturation, while the Bedouins exhibited the highest mean values in the creatinine and triglycerides. For most of these tests, Sephardic Jews exhibited biochemical mean levels in between the two other groups. Compared to Ashkenazi Jews, Sephardic Jews had a significant shift to lower values in cholesterol LDL. CONCLUSIONS: Ethnic subpopulations have distinct distributions in biochemical laboratory test values, which should be taken into consideration in medical practice enabling precision medicine.

"Stoneless" or Negative Ureteroscopy: A Reality in the Endourologic Routine or Avoidable Source of Frustration? Estimating the Risk Factors for a Negative Ureteroscopy.

INTRODUCTION: A "Negative" ureteroscopy (URS) is defined as a URS in which no stone is found during the procedure. It may occur when the stone has already been passed spontaneously or when it is located outside the collecting system. The aim of the study was to outline risk factors for Negative-URS. MATERIALS AND METHODS: We retrospectively analyzed the possible risk factors for Negative-URS from a database of 341 URS cases. In every case where presumptive ureteral stone was not found, a formal nephroscopy as well as a whole collecting system revision was completed. The Negative-URS group was compared with the non-Negative-URS group, in terms of patient and stone characteristics. RESULTS: The database of 341 URS cases included 448 different stone instances, of which 17 (3.8%) were negative and 431 (96.2%) were therapeutic. There was no statistical significant difference between the two groups concerning age, body mass index, stone location in the ureter, stone laterality, and whether the patient was prestented. The stepwise multiple logistic regression revealed three important risk factors, namely CT stone surface area (p < 0.0001), radiopacity of the stone at kidney, ureter, and bladder radiograph (KUB; p = 0.0004), and gender (p = 0.0011) with an area under the curve of 0.91. Women were found to have more possibilities to have a negative procedure by four- to sevenfold than men depending on the model. A nonradio-opaque stone at KUB is more likely to be correlated with a Negative-URS by 9.5- to 11-fold more than a radiopaque stone at KUB. For each increase of 1 U in CT stone surface area, there is an increase of 10%-12% to be non-negative. CONCLUSIONS: Female gender, a nonradio-opaque stone at KUB, and a smaller stone surface were statistically significantly different in the Negative-URS population.

Hormonal levels of estradiol, testosterone, and progesterone at entry into lay of year 1980 vs. 2000 broiler breeder females under fast and slow release from feed restriction.

In the mid-1960s egg production, fertility, and hatchability of broiler breeder females dropped precipitously. Due to disrupted follicle hierarchies and development of the erratic oviposition and defective eggs (EODES) syndrome. EODES was controlled by restricting feed. In the 1990s, another set of problems arose at entry of broiler breeders into lay and characterized by high mortality followed by lower peak lay and reduction in egg and chick production. These problems are induced by even slight over-feeding, and hence we termed it the "Over Feeding Complex" (OFC). We have speculated that OFC is a quasi-EODES condition, induced by the intense selection for increased breast proportion. To test this, we compared, under fast (FF) and slow (SF) release from feed restriction, body composition and reproductive performance of a broiler breeder from year 1980 (B1980) and kept without selection for performance traits since then, to a line hatched in 2000 (B2000). During the first 16 d of lay, feeding treatment had little effect on egg mass or Laying % for the B1980 birds, while for the B2000 birds, SF treatment resulted in significantly greater egg mass and Laying % compared to FF, showing that the OFC indeed manifested in this experiment. However, contrary to hypothesis, follicle hierarchies were normal for both lines under both feeding treatments. To gain further insight into the OFC syndrome, we here report levels of estradiol, testosterone, and progesterone for these line and treatment groups in the time period leading up to and into lay. A significant line × feeding treatment interaction effect was found for estradiol and testosterone, to a lesser extent for progesterone. For all 3 hormones, for B1980 levels 2 to 3 wk post entry into lay were similar and intermediate under FF and SF, but differed significantly for B2000, being much greater under SF than under FF. Thus, the hormonal effects were parallel and may explain the egg mass and Laying % effects of FF and SF in the 2 genetic types.

Targeted Recombinant Progeny: a design for ultra-high resolution mapping of Quantitative Trait Loci in crosses between inbred or pure lines.

BACKGROUND: High-resolution mapping of the loci (QTN) responsible for genetic variation in quantitative traits is essential for positional cloning of candidate genes, and for effective marker assisted selection. The confidence interval (QTL) flanking the point estimate of QTN-location is proportional to the number of individuals in the mapping population carrying chromosomes recombinant in the given interval. Consequently, many designs for high resolution QTN mapping are based on increasing the proportion of recombinants in the mapping population. The "Targeted Recombinant Progeny" (TRP) design is a new design for high resolution mapping of a target QTN in crosses between pure, or inbred lines. It is a three-generation procedure generating a large number of recombinant individuals within a QTL previously shown to contain a QTN. This is achieved by having individuals that carry chromosomes recombinant across the target QTL interval as parents of a large mapping population; most of whom will therefore carry recombinant chromosomes targeted to the given QTL. The TRP design is particularly useful for high resolution mapping of QTN that differentiate inbred or pure lines, and hence are not amenable to high resolution mapping by genome-wide association tests. RESULTS: In the absence of residual polygenic variation, population sizes required for achieving given mapping resolution by the TRP-F2 design relative to a standard F2 design ranged from 0.289 for a QTN with standardized allele substitution effect = 0.2, mapped to an initial QTL of 0.2 Morgan to 0.041 for equivalent QTN mapped to an initial QTL of 0.02 M. In the presence of residual polygenic variation, the relative effectiveness of the TRP design ranges from 1.068 to 0.151 for the same initial QTL intervals and QTN effect. Thus even in the presence of polygenic variation, the TRP can still provide major savings. Simulation showed that mapping by TRP should be based on 30-50 markers spanning the initial interval; and on at least 50 or more G2 families representing this number of recombination points,. CONCLUSIONS: The TRP design can be an effective procedure for achieving high and ultra-high mapping resolution of a target QTN previously mapped to a known confidence interval (QTL).

MTHFR C677T polymorphism affects normotensive diastolic blood pressure independently of blood lipids.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism was found to be associated with hypertension. High blood pressure (BP) is a major risk factor for cardiovascular disease, gestational hypertension, and high-risk pregnancy. BP is a complex trait strongly associated with blood lipid parameters. However, studies of the effect of MTHFR C677T polymorphism on BP levels independently of blood lipids are scarce. Our objective was to analyze and quantify the effect of MTHFR C677T polymorphism on normotensive BP independently of blood lipids. METHODS: MTHFR C677T genotyping was done for 151 Israeli women attending the genetics clinic at Soroka Medical Center. Biochemical (blood lipids) and BP data were extracted from Soroka Medical Center records. BP was regarded as a continuous parameter using analysis of covariance and post hoc Tukey's HSD (honestly significant difference) analysis. RESULTS: The frequencies of genotypes CC, TT, and CT were 41%, 12%, and 47%, respectively. A significant (P < 0.0001) association was found between genotype and diastolic BP (DBP) when adjusted to body mass index and age. Mean DBP was significantly lower for CC than for TT genotypes (71.2 vs. 78.7 mm Hg); however the difference between the heterozygotes (73.9 mm Hg) and the other 2 genotypes was not significant. Cholesterol, LDLcalc (LDLcalculaed), and homocysteine blood levels significantly contributed to the effect of MTHFR C677T polymorphism on the DBP trait. There was also significant association between genotype and folic acid levels. CONCLUSIONS: MTHFR C677T polymorphism significantly affects DBP in Israeli women, independently of blood lipids. Each C to T substitution is associated with a mean 3.4-mm Hg increase in DBP.

Mapping QTL affecting resistance to Marek's disease in an F6 advanced intercross population of commercial layer chickens.

BACKGROUND: Marek's disease (MD) is a T-cell lymphoma of chickens caused by the Marek's disease virus (MDV), an oncogenic avian herpesvirus. MD is a major cause of economic loss to the poultry industry and the most serious and persistent infectious disease concern. A full-sib intercross population, consisting of five independent families was generated by crossing and repeated intercrossing of two partially inbred commercial White Leghorn layer lines known to differ in genetic resistance to MD. At the F6 generation, a total of 1615 chicks were produced (98 to 248 per family) and phenotyped for MD resistance measured as survival time in days after challenge with a very virulent plus (vv+) strain of MDV. RESULTS: QTL affecting MD resistance were identified by selective DNA pooling using a panel of 15 SNPs and 217 microsatellite markers. Since MHC blood type (BT) is known to affect MD resistance, a total of 18 independent pool pairs were constructed according to family x BT combination, with some combinations represented twice for technical reasons. Twenty-one QTL regions (QTLR) affecting post-challenge survival time were identified, distributed among 11 chromosomes (GGA1, 2, 3, 4, 5, 8, 9, 15, 18, 26 and Z), with about two-thirds of the MD resistance alleles derived from the more MD resistant parental line. Eight of the QTLR associated with MD resistance, were previously identified in a backcross (BC) mapping study with the same parental lines. Of these, 7 originated from the more resistant line, and one from the less resistant line. CONCLUSION: There was considerable evidence suggesting that MD resistance alleles tend to be recessive. The width of the QTLR for these QTL appeared to be reduced about two-fold in the F6 as compared to that found in the previous BC study. These results provide a firm basis for high-resolution linkage disequilibrium mapping and positional cloning of the resistance genes.