Fertile Control Subjects Research Articles

Implications of dysregulated endogenous cannabinoid family members in the pathophysiology of endometriosis

To determine the involvement of the endocannabinoid (EC) family member in the pathophysiology of endometriosis (EMS). Mass spectrometry analysis of plasma and tissue samples from patients with EMS, controls, and a mouse model of EMS and messenger RNA and immunohistochemistry analysis of the samples from patients with EMS and controls. Academic teaching hospital and university. Patients with EMS and healthy fertile control subjects. None. Endocannabinoid analysis in patient plasma, EMS lesions, and healthy endometrial samples. Circulating ECs were detected in the plasma samples, whereas no significant changes were observed in patients with EMS compared with healthy fertile controls. However, the palmitoylethanolamide levels were significantly higher in the EMS lesions than in the endometrium from patients with EMS. Similarly, genes involved in the EC signaling pathways were differentially expressed in the EMS lesions. Analysis of cannabinoid 1 and 2 receptors in the EMS lesions revealed a significantly lower cannabinoid 2 receptor expression, whereas no significant changes were observed in cannabinoid 1 receptor expression compared with those in the endometrium from both patients with EMS and healthy fertile controls. The palmitoylethanolamide levels were significantly elevated in plasma from EMS mice compared with that from sham controls and in EMS lesions compared with uterine samples. Together, we provide evidence toward dysregulation of members of the ECs in both patients with EMS and the mouse model of EMS. These findings will advance the knowledge of the role of ECs in EMS and their potential implications as therapeutic targets.

Genome-wide expression analysis of endometrium before and after endometrioma surgery

ObjectiveThis study was planned to investigate possible alteration in the number of differentially expressed genes (DEGs) in eutopic endometrium before and after laparoscopic removal of the ovarian endometrioma. Study designSix infertile women with ovarian endometrioma who underwent laparoscopic endometrioma cystectomy and six fertile control subjects who underwent tubal sterilization were included the study. Endometrial samples were collected before and 3 months after surgery throughout the mid-luteal phase. Genome-wide expression profiling was performed with Illumina Human HT-12V4 microchip, a high density silica bead-based microarray which utilizing more than 47.000 probs. Illumina microsequence system was used to assess detection of p value for each probe in every sample. Probes revealing significant assessment (p < .05) were selected for comparative analysis. ResultsWe have detected 1478 DEGs in the comparison between endometrium of women with endometrioma and fertile controls. 118 out of 1478 genes (7.9 %) were significantly increased or decreased more than 1.5-fold in their expression. When the preoperative values of the control and patient groups are compared the number of DEGs was 243 (7.5 %). In 9 out of 243 genes, the fold change was found to be 1.5 and more (3.7 %). Comparison of the number of DEGs after endometrioma surgery and tubal ligation revealed that expression patterns of 1036 genes (33.7 %) were changed in endometrioma group. In 105 out of 1036 genes, the fold change was found to be 1.5 and above (10 %). A comparison using 2706 probes revealed changes in the expression patterns of 106 different genes (3.9 %) after endometrioma resection. In 4 out of 106 genes, the fold change was found to be 1.5 and above (3.7 %). The comparison using 6035 probes revealed changes in the expression patterns of 93 genes (1.5 %) after tubal ligation. None of the 93 genes had a fold change of 1.5 or higher. The number of DEGs in endometrioma groups after surgery was approximately 3-fold higher than control group. ConclusionsEndometrium of women with endometrioma displayed abnormal expression of genes associated with implantation, immunological, endocrine and neuracrine functions. Positive alteration of the expression pattern of DEGs and signal transduction pathways following endometrioma surgery can improve the receptive capacity and implantation rates of eutopic endometrium.

A homozygous RPL10L missense mutation associated with male factor infertility and severe oligozoospermia

To identify the genetic cause of male factor infertility characterized by severe oligozoospermia. Genetic studies. Medical university. Two infertile brothers with severe oligozoospermia in a consanguineous Han Chinese family, 414 additional patients with oligo-/azoospermia, and 223 fertile (control) subjects. None. Genetic analyses using whole-exome and Sanger sequencing were performed for two brothers with severe oligozoospermia. The effects of an identified candidate causative mutation were investigated in silico and invitro. Whole-exome sequencing screening for the candidate mutation was conducted in 414 patients with oligo-/azoospermia and 223 fertile subjects. A homozygous missense variant (NM_080746:c.A257C: p.H86P) in RPL10L was identified in the two affected brothers and shown to cosegregate with the severe oligozoospermia phenotype. The mutation was absent in public databases, including the 1000 Genomes Project and the Exome Aggregation Consortium. All queried databases predicted the mutation to be damaging, consistent with the fact that it decreased protein levels invitro. Subsequent mutation screening identified three additional heterozygous RPL10L mutations in three of 414 subjects with oligo-/azoospermia, but no RPL10L mutations among 223 fertile subjects. Our findings implicate RPL10L as a novel candidate gene in the pathogenesis of human male factor infertility and severe oligozoospermia.

Proteomic sift through serum and endometrium profiles unraveled signature proteins associated with subdued fertility and dampened endometrial receptivity in women with polycystic ovary syndrome.

The objective of this study is to discern the proteomic differences responsible for hampering the receptivity of endometrium and subduing the fertility of females with polycystic ovary syndrome in analogy to healthy fertile females. This study was designed in collaboration with Hakeem Abdul Hameed Centenary Hospital affiliated to Jamia Hamdard, New Delhi, India. Serum samples were taken from infertile PCOS subjects (n = 6) and fertile control subjects (n = 6) whereas endometrial tissue samples were recruited from ovulatory PCOS (n = 4), anovulatory PCOS (n = 4) and normal healthy fertile control subjects (n = 4) for proteomic studies. Additionally, endometrial biopsies from healthy fertile control (n = 8), PCOS with infertility (n = 6), unexplained infertility (n = 3) and endometrial hyperplasia (n = 3) were taken for validation studies. Anthropometric, biochemical and hormonal evaluation was done for all the subjects enrolled in this study. Protein profiles were generated through 2D-PAGE and differential proteins analyzed with PD-QUEST software followed by identification with MALDI-TOF MS protein mass fingerprinting. Validation of identified proteins was done through RT-PCR relative expression analysis. Protein profiling of serum revealed differential expression of proteins involved in transcriptional regulation, embryogenesis, DNA repair, decidual cell ploidy, immunomodulation, intracellular trafficking and degradation processes. Proteins involved in cell cycle regulation, cellular transport and signaling, DNA repair, apoptotic processes and mitochondrial metabolism were found to be differentially expressed in endometrium. The findings of this study revealed proteins that hold strong candidature as potential drug targets to regulate the cellular processes implicating infertility and reduced receptivity of endometrium in women with polycystic ovary syndrome.

Characterizing the gut microbiota in females with infertility and preliminary results of a water-soluble dietary fiber intervention study.

Despite the advances in assisted reproductive technology, approximately 8–12% of the individuals worldwide who are willing to conceive are unable to do so. Fertility depends on a receptive state of the endometrium and hormonal adaptations as well as the immune system. Local and systemic immunities are greatly influenced by the microbiota. The aim of the present study was to compare the gut microbiota in female patients with that in infertility with fertile control subjects and to evaluate the effect of prebiotic partially hydrolyzed guar gum supplementation on gut dysbiosis and the outcome of pregnancy in patients treated with assisted reproductive technology. Dietary fiber can reconstitute the host intestinal microbiota and modify the immune function; however, clinical data regarding the effect of dietary fiber treatment on the success of assisted reproductive technology is lacking. To investigate the gut microbiota in fertile and infertile females, we conducted 16S metagenomic analysis of fecal samples. In total 18 fertile female subjects and 18 patients with infertility matched by age were recruited, and fecal samples were obtained to analyze the gut microbiome using 16S rRNA V3–V4 sequencing. The unweighted and weighted principal coordinate analyses showed a trend indicating microbial structural differences in β-diversity between these two groups. The abundance of the phylum Verrucomicrobia was higher in patients with infertility. At the genus level, a decrease in the abundance of the genera Stenotrophomonas, Streptococcus, and Roseburia and an increase in the abundance of the genera Unclassified [Barnesiellaceae] and Phascolarctobacterium was observed in patients with infertility. Twelve patients agreed to receive the combined therapy comprising embryo transfer by assisted reproductive technology and oral supplementation with partially hydrolyzed guar gum. The success of pregnancy by this combined therapy was 58.3% (7/12), and the failure was 41.7% (5/12). Predictive factors for pregnancy before treatment were characterized by a decrease in the abundance of Paraprevotella and Blautia and an increase in the abundance of Bifidobacterium. Predictive factors for pregnancy before treatment were characterized by a decrease in the abundance of Paraprevotella and Blautia and an increase tendency in the abundance of Bifidobacterium. In conclusion, the present study showed differences in the abundance of gut microbiota between fertile and infertile groups; moreover, partially hydrolyzed guar gum supplementation helped improve gut dysbiosis and the success of pregnancy in females with infertility.

Evaluation of Oxidative Stress Markers and Hormonal Profiles in Women Diagnosed with Infertility in Port Harcourt

Aim: The study evaluates the contribution of oxidative stress and fertility hormones to female infertility in Port Harcourt.&#x0D; Methodology: A total of 140 women aged 15 – 49 years consisting 70 apparently healthy infertile women who are attending diagnostic fertility clinics in Port Harcourt as test subjects and 70 age-matched healthy fertile women as control were recruited. Subjects were recruited using structured questionnaires after given their informed consent. The levels of Malondialdehyde, total antioxidant capacity, lipid peroxidation index, follicle stimulating hormone, luteinizing hormone, prolactin, progesterone and estrogen of infertile and the fertile (control) subjects were determined by standard procedures.&#x0D; Results: There was statistically significant increase in lipid peroxidation index in the test subjects than in the fertile group (p&lt;0.05). Total antioxidant capacity showed a statistically reduced value in the test subjects than in the control at p&lt;0.05. Lipid peroxidation index was significantly increased in test subjects exposed to oxidant agents like alcohol, infections and ulcer than their counterparts who were not exposed to any of the agents (p&lt;0.05). Also significantly elevated lipid peroxidation was observed in test subjects with normal hormone levels compared to those with hormone imbalance (p&lt;0.05).&#x0D; Conclusion: The outcome of this study suggests that the infertility being experienced by some of the infertile women in Port Harcourt are due not only to endocrine dysfunction, but some order conditions that induce oxidative stress. Thus investigation of oxidative parameters is highly suggested as an adjunct for effective management of unexplained infertility in women. Further studies on estimation of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GHR) are recommended to validate reliability.

Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-based method

To systematically compare the endometrial microbiota in infertile women with and without chronic endometritis (CE), as diagnosed by a quantitative and reference range-based method. Case-control observational study. University-affiliated hospital. One hundred and thirty infertile women. Endometrial biopsy and fluid (uterine lavage, UL) collected precisely 7days after LH surge, with plasma cell density (PCD) determined based on Syndecan-1 (CD138)-positive cells in the entire biopsy section and culture-independent massively parallel sequencing of the 16S ribosomal RNA gene performed on both the CE and non-CE endometrial fluid samples. Relative abundance of bacterial taxa. Chronic endometritis was diagnosed if the PCD was above the 95th percentile (>5.15cells per 10mm2) of the reference range in fertile control subjects. With this stringent diagnostic criterion, 12 women (9%) were diagnosed with CE. Sequencing was successfully performed on all endometrial samples obtained by UL) (CE, n = 12; non-CE, n = 118). The median relative abundance of Lactobacillus was 1.89% and 80.7% in the CE and non-CE microbiotas, respectively. Lactobacillus crispatus was less abundant in the CE microbiota (fold-change, range: 2.10-2.30). Eighteen non-Lactobacillus taxa including Dialister, Bifidobacterium, Prevotella, Gardnerella, and Anaerococcus were more abundant in the CE microbiota (fold-change, 2.10-18.9). Of these, Anaerococcus and Gardnerella were negatively correlated in relative abundance with Lactobacillus (SparCC correlation magnitude, range: 0.142-0.177). Chronic endometritis was associated with a statistically significantly higher abundance of 18 bacterial taxa in the endometrial cavity. ChiCTR-IOC-16007882.

The correlation between mammalian target of rapamycin (mTOR) gene expression and sperm DNA damage among infertile patients with and without varicocele.

This study aimed to assess the possible correlation between mammalian target of rapamycin (mTOR) gene expression and sperm DNA damage among infertile patients with and without varicocele. The study included sixty infertile males and fifty fertile males as controls. The infertile group was subdivided into the following subgroups: thirty males with varicocele and thirty males without varicocele. All subjects underwent medical history collection, clinical examination, semen analysis, sperm DNA integrity assessment, mTOR gene expression assessment and scrotal colour Doppler ultrasound. The mean mTOR gene expression in infertile patients with varicocele (23.52±14.65) was significantly higher than that in infertile patients without varicocele (12.24±12.44) and fertile control subjects (3.92±3.26; p=0.003 and p<0.001 respectively). In the infertile varicocele-positive group, mTOR gene expression showed a significant negative correlation with sperm count (p=0.028, r=-0.400) and progressive sperm motility (p=0.038, r=-0.381), as well as a significant positive correlation with the sperm DNA fragmentation index (DFI; p=0.001, r=0.578). In the infertile varicocele-negative group, mTOR gene expression showed a significant negative correlation with progressive sperm motility (p=0.018, r=-0.429) and a significant positive correlation with sperm DFI (p<0.001, r=0.673). In conclusion, according to these results, there is a significant positive correlation between mTOR gene expression and sperm DFI among infertile patients with and without varicocele.

Evaluation of Kisspeptin Level in Non Obstructive Azoospermic Patients

AbstractBackground: Non-obstructive azoospermia is characterized by the complete absence of sperm in the ejaculate due to testicular failure. One of the genetic causes of non-obstructive azoospermia is the mutations in kisspeptin hormone and the kisspeptin hormone receptor (Kiss1r) genes. The level of kisspeptin hormone has been investigated in patients with non-obstructive azoospermia.Aim of Study: The aim of the study was to evaluate the level of kisspeptin hormone (KISS1) in the serum of non-obstructive azoospermic males and its relation to fertility hormones (Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Testosterone and Prolactin).Patients and Methods: This case control study was done from August 2017 to August 2018 & included 25 non-obstructive azoospermic patients & 25 cases of age matched healthy fertile control subjects. After full history taking and general and local examination, Kisspeptin level was measured using ELISA. Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Testosterone (T) and Prolactin hormone (PRL) were also measured.Results: The mean value of kisspeptin hormone was significantly lower in cases (6.30±2.07ng/ml) than controls (36.70±9.64ng/ml). The patients had significant high level of FSH (p-value <0.001), high level of LH (p-value=0.001) and low level of Testosterone (p-value=0.022). No correlation was found between plasma kisspeptin levels and (FSH, LH, Testosterone & Prolactin).Conclusion: Kisspeptin level is lower in non-obstructive azoospermic infertile males than the fertile controls, so it might be used as a diagnostic tool for infertility and treatment of infertility disorders in patients proved to have a low level of kisspeptin hormone.

DHEA supplementation improves endometrial HOXA-10 mRNA expression in poor responders.

Objective:The study was planned to investigate whether DHEA supplementation had an impact on endometrial receptivity in women who were poor responders (POR).Material and Methods:Twenty-eight POR women who were undergoing hysteroscopy and five fertile control subjects were included. The POR women were equally subdivided into two separate groups as patients who were currently using DHEA and those who were not. Endometrial samples of the subjects were obtained during hysteroscopy at the late follicular phase. Expression levels of endometrial HOXA-10, HOXA-11, and LIF mRNA were measured with the using real-time polymerase chain reaction. Spontaneous clinical pregnancy rates were also noted.Results:Compared with POR women who were not given DHEA, upregulated endometrial HOXA-10 (7.33-fold) and HOXA-11 (2.39-fold) mRNA expression were detected in POR women on DHEA. The increase in HOXA-10 mRNA was significant (p<0.03). The fold increase in HOXA-11 mRNA was found as 2.39, which indicated a positive upregulation. However, this fold increment was insignificant (p<0.45). An insignificant increase in spontaneous clinical pregnancy rates in POR women on DHEA (53.3%) was observed compared with POR women who were not given DHEA (43.8%).Conclusion:Oral DHEA supplementation in POR upregulates endometrial HOXA-10 mRNA expression, which is known to positively modulate endometrial receptivity.

Association of microRNA-related gene polymorphisms and idiopathic azoospermia in a south-east Turkey population

ABSTRACTMicroRNAs (miRNAs) are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression. Although it is reported in many studies that there are associations between alterations of miRNA homeostasis and pathological conditions such as cancer, psychiatric and neurological diseases, cardiovascular disease and autoimmune disease, the effects of common genetic variants of these genes on male infertility are unclear. To better understand this effect, we performed a case-control study including a total of 108 infertile men with idiopathic azoospermia and 125 fertile control subjects. Real-time polymerase chain reaction was used to genotype six single-nucleotide polymorphisms (SNPs) of microRNA biogenesis pathway genes and the associations between individual and combined genotypes and idiopathic azoospermia were analysed. The results showed significant difference between the individual AA genotype frequency of the GEMIN3 (rs197388) gene in the patient and control groups, indicating that the AA genotype may be considered as indicative of a higher predisposition to idiopathic azoospermia. The combined genotype analysis, including six SNPs, revealed statistically significant differences between the patients and control subjects for some combinations. For example, the frequency of genotype distributions of the AA\\CA-CC-TT-AT genotype combination for the XPO5-RAN-DICER1-GEMIN3 combined loci was significantly different, and it may be considered a predisposition to idiopathic azoospermia. According to the obtained results, both individual and combined genotypes of SNPs from miRNA genes may be used to predict the risk of male infertility with idiopathic azoospermia.

Cancer risk in first- and second-degree relatives of men with poor semen quality

To further characterize the association of male infertility with health risks by evaluating semen quality and cancer risk in family members. Retrospective, cohort study. Not applicable. A total of 12,889 men undergoing SA and 12,889 fertile control subjects that had first-degree relative (FDR) data (n = 130,689) and 8,032 men with SA and 8,032 fertile control subjects with complete second-degree relative (SDR) data (n = 247,204) were identified through the UPDB. An equal number of fertile population control subjects were matched. None. Adult all-site, testicular, thyroid, breast, prostate, melanoma, bladder, ovarian, and kidney cancer diagnoses in FDRs and SDRs. The FDRs of men with SA had a 52% increased risk of testicular cancer compared with the FDRs of fertile population control subjects. There was no significant difference in testicular cancer risk for the SDRs based on any of the semen parameters. The FDRs and SDRs of azoospermic men had a significantly increased risk of thyroid cancer compared with fertile population control subjects. These data suggest a link between male infertility and selected cancer risk in relatives. This highlights the possibilities of shared biologic mechanisms between the two diseases, exposure to environmental factors, and an increased level of genetic and/or epigenetic burden in subfertile men and their relatives that may be associated with risk of cancer.

Patients with multiple morphological abnormalities of the sperm flagella due to DNAH1 mutations have a good prognosis following intracytoplasmic sperm injection.

Does DNAH1 status influence intracytoplasmic sperm injection (ICSI) outcomes for patients with multiple morphological abnormalities of the sperm flagella (MMAF)? Despite a highly abnormal morphology, sperm from MMAF patients with DNAH1 mutations have a low aneuploidy rate and good nuclear quality, leading to good embryonic development following ICSI and a high pregnancy rate. Teratozoospermia represents a heterogeneous group including a wide range of phenotypes. Among all these qualitative defects, a flagellar phenotype called MMAF is characterized by a mosaic of morphological abnormalities of the flagellum, including coiled, bent, irregular, short or/and absent flagella, mainly due to the absence of the axonemal central pair microtubules. We previously demonstrated that homozygous mutations in the DNAH1 gene, encoding an inner arm heavy chain dynein, are frequently found in patients with MMAF (28% of the patients from the initial cohort). Numerous studies have reported an increased rate of aneuploidy and a poor sperm nuclear quality related to sperm flagellar abnormalities, which could impede ICSI outcome. Moreover, success rates after ICSI may be influenced by the type of ultrastructural flagellar defects and/or by the gene defects carried by the patients. This retrospective cohort study included 6 infertile males with MMAF due to deleterious homozygous DNAH1 mutations and their respective spouses, who underwent 9 ISCI cycles, with 16 embryos being transferred. ICSI results were compared with two control populations of 13 MMAF men without DNAH1 mutations and an aged-matched control group of 1431 non-MMAF couples. All ICSI attempts took place between 2000 and 2012. Clinical and biological data were collected from patients treated for infertility at the CPSR les Jasmins in Tunis (Tunisia). We compared the ICSI outcomes obtained with couples including DNAH1 mutated and nonmutated patients and non-MMAF couples. For the analysis of the chromosomal status, fluorescence in situ hybridization (FISH) analyses were performed on sperm cells from 3 DNAH1-mutated patients and from 29 fertile control subjects. Sperm chromatin condensation and DNA fragmentation were evaluated using aniline blue staining and TUNEL assays, respectively, on sperm cells from 3 DNAH1-mutated men and 6 fertile controls. There was a significantly increased proportion of disomy XY and 18 in sperm from DNAH1 mutated patients compared with fertile controls (1.52 versus 0.28%, P = 0.0001 and 0.64 versus 0.09%, P = 0.0001). However, there were no statistically significant differences among sperm from the two groups in their frequencies of either 13, 21, XX or YY disomy or diploidy. Measures of DNA compaction and fragmentation demonstrated a good nuclear sperm quality among DNAH1 mutated men. The overall fertilization, pregnancy and delivery rates of couples including DNAH1 mutated men were of 70.8, 50.0 and 37.5%, respectively. There were no statistically significant differences in any of these parameters compared with the two control groups (P > 0.05). A limitation of this study is the small number of DNAH1-mutated patients available and the low number of genes identified in MMAF. Further genetic studies are warranted to identify other MMAF-inducing genes to better characterize the genetic etiology of the MMAF phenotype and to improve the management of patients diagnosed with flagellar defects. MMAF patients with DNAH1 mutations have low aneuploidy rates and good nuclear sperm quality, explaining the high pregnancy rate obtained with these patients. Good ICSI results were obtained for both MMAF groups (DNAH1 mutated and nonmutated), suggesting that patients presenting with asthenozoospermia due to flagellar defects have a good ICSI prognosis irrespective of their genotype. The majority of MMAF cases currently remain idiopathic with no genetic cause yet identified. In depth genetic analysis of these patients using next generation sequencing should reveal new causal genes. Subsequent genotype phenotype analyses could improve advice and care provided to MMAF patients. None of the authors have any competing interest. This work is part of the project 'Identification and Characterization of Genes Involved in Infertility (ICG2I)', funded by the program GENOPAT 2009 from the French Research Agency (ANR) and the MAS-Flagella project, financed by the French ANR and the Direction Générale de l'Offre de Soins (DGOS).

Subfertility increases risk of testicular cancer: evidence from population-based semen samples

To further understand the association between semen quality and cancer risk by means of well defined semen parameters. Retrospective cohort study. Not applicable. A total of 20,433 men who underwent semen analysis (SA) and a sample of 20,433 fertile control subjects matched by age and birth year. None. Risk of all cancers as well as site-specific results for prostate cancer, testicular cancer, and melanoma. Compared with fertile men, men with SA had an increased risk of testicular cancer (hazard rate [HR] 3.3). When the characterization of infertility was refined using individual semen parameters, we found that oligozoospermic men had an increased risk of cancer compared with fertile control subjects. This association was particularly strong for testicular cancer, with increased risk in men with oligozoospermia based on concentration (HR 11.9) and on sperm count (HR 10.3). Men in the in the lowest quartile of motility (HR 4.1), viability (HR 6.6), morphology (HR 4.2), or total motile count (HR 6.9) had higher risk of testicular cancer compared with fertile men. Men with sperm concentration and count in the 90th percentiles of the distribution (≥178 and ≥579 × 10(6)/mL, respectively), as well as total motile count, had an increased risk of melanoma (HRs 2.1, 2.7, and 2.0, respectively). We found no differences in cancer risk between azoospermic and fertile men. Men with SA had an increased risk of testicular cancer which varied by semen quality. Unlike earlier work, we did not find an association between azoospermia and increased cancer risk.

Evaluating γH2AX in spermatozoa from male infertility patients

To investigate whether γH2AX levels were different in the spermatozoa of healthy men compared with infertility patients, and to assess the possible correlations between γH2AX and conventional semen parameters and double-stranded breaks (DSBs) identified with the use of comet assay. Prospective study. Clinical laboratory. Semen from 100 male infertile patients and 100 healthy sperm donors. Human sperm samples were analyzed in terms of World Health Organization parameters. The γH2AX levels were detected by means of flow cytometry. DSBs of sperm were detected by means of comet assay. Morphology slides were made and the sperm morphology assessed according to strict criteria. Conventional semen analyses, γH2AX levels in sperm, DNA DSBs in sperm, and correlations among γH2AX, conventional semen analyses, and DSBs. Concentration, viability, motility, and normal sperm morphology were significantly lower in male infertility patients compared with healthy men. Also, γH2AX levels and the number of DSBs were significantly higher in the sperm of infertile subjects compared with healthy men. γH2AX levels correlated negatively with conventional semen parameters and positively with DSBs. A threshold γH2AX level of 18.55% was identified as a cutoff value to discriminate infertile subjects from fertile control subjects with a specificity of 86.0% and a sensitivity of 83.0%. The positive and negative predictive values of the 18.55% γH2AX threshold were high: 87.7% and 85.5%, respectively. γH2AX levels were higher in the sperm of male infertility patients than in healthy men. γH2AX levels in sperm, as evaluated with the use of flow cytometry, might be a useful biomarker for evaluating DSBs in human spermatozoa.

Laparoscopic endometrioma resection increases peri-implantation endometrial HOXA-10 and HOXA-11 mRNA expression

To determine whether laparoscopic endometrioma resection alters peri-implantation endometrial HOXA-10, HOXA-11, LIF, ITGB3 and ITGAV mRNA expression. Case-control study. Medical school. Twenty infertile patients with uni- or bilateral endometrioma, five infertile patients having nonendometriotic benign ovarian cyst, and five fertile control subjects. Mid-luteal-phase endometrial sampling was performed at the time of surgery. Second endometrial biopsies were obtained 3 months after laparoscopic endometrioma resection during the mid-luteal phase of the cycle. Endometrial HOXA-10, HOXA-11, LIF, ITGAV, and ITGB3 mRNA expressions were evaluated with the use of reverse-transcription polymerase chain reaction. Significantly decreased endometrial ITGAV mRNA expression was noted in biopsies obtained from endometrioma and nonendometriotic cyst groups before surgery. Trends toward decreased endometrial HOXA-10, HOXA-11, LIF, and ITGB3 mRNA expressions were noted in the endometrioma and nonendometriotic cyst groups before surgery compared with the fertile subjects. However, the differences failed to show statistical significance. Compared with preoperative values, significantly increased HOXA-10 (12.1-fold change) and HOXA-11 (17.2-fold change) mRNA expressions were noted in endometrial biopsies obtained from subjects who were undergoing endometrioma surgery. Fold change in endometrial ITGAV mRNA after endometrioma surgery was found to be 30.1 and indicated a positive regulation. However, this fold increase was statistically insignificant. Expressions of these endometrial receptivity markers did not change significantly after surgical removal of nonendometriotic benign ovarian cysts. Laparoscopic endometrioma resection increases peri-implantation endometrial HOXA-10 and HOXA-11 mRNA expression, suggesting an improvement in endometrial receptivity.

A Case-Control study of Body Mass Index and Infertility in Algerian Women (Sidi Bel Abbes, West of Algeria)

ABSTRACTIntroductionThe prevalence of obesity and female infertility in Algeria has increased in past decades, and recent study are showing a relationship between body mass index (BMI) and the risk of female infertility, suggesting that obesity is a risk factor for infertility. In order to evaluate the risk of infertility associated with BMI, we conducted a case-control study.Materials and methodsThe relationship between BMI and female infertility was investigated in a case-control study of 256 infertile cases and 326 fertile control subjects. The BMI of infertile women was compared with the BMI of the control fertile group. Odds ratios (ORs) was calculated as measures of relative risk of infertility associated with BMI.ResultsMultiple analyses showed significant association between various measures of BMI and female infertility in this population. An association between BMI and infertility was observed for the overweight (25.00–29.99 kg/m2; odds ratio = 2.23; p = 0.021; 95% confidence interval, 1.52–3.25) and obese group (&gt; 30 kg/m2; odds ratio = 3.26; p = 0.019; 95% confidence interval, 1.62–6.58) compared to the normal weight group. However, no association was found between underweight and infertility (BMI &lt; 20 Kg/m2, odds ratio = 0.96; p = 0.063; 95% confidence interval, 0.57–1.63).ConclusionThe present study confirms the results that the previously reported research have shown and affirm that an negative association exist between obesity and overweight with fertility, this association might be influenced by other factors, that's why larger and more research in the Algerian population are needed.How to cite this articleMAÏ HA, Demmouche A. A Case-Control study of Body Mass Index and Infertility in Algerian Women (Sidi Bel Abbes, West of Algeria). Int J Infertil Fetal Med 2015;6(3):103-107.

Association of decreased spermatozoa omega-3 fatty acid levels and increased oxidative DNA damage with varicocele in infertile men: a case control study.

Varicocele is commonly associated with male infertility because it impairs normal sperm morphology and activity. Polyunsaturated fatty acids (PUFA) are important determinants of sperm cell structure and function, but their relationship with varicocele remains unclear. The aim of the present study was to investigate the PUFA composition in spermatozoa of infertile men with varicocele and to evaluate the potential relationship between PUFA and varicocele. This case control study recruited 92 infertile men with varicocele, 99 infertile men without varicocele and 95 fertile male control subjects. Semen morphology and activity parameters were assessed and seminal plasma 8-hydroxy-2-deoxyguanosine (8-OHdG) content was determined by ELISA. Sperm concentrations of omega-3 and omega-6 fatty acids were measured by gas chromatography. Infertile men with varicocele had lower concentrations of omega-3 PUFA, higher omega-6:omega-3 PUFA ratios and greater oxidative DNA damage in spermatozoa compared with infertile men without varicocele and normal subjects. The degree of varicocele and DNA damage was associated with decreased omega-3 PUFA concentrations and semen quality in infertile men with varicocele. The findings suggest that omega-3 PUFA deficiency could be implicated in varicocele-associated infertility, and highlight the need for intervention trials to test the usefulness of omega-3 supplementation in reducing sperm abnormalities in infertile men with varicocele.

Seminal Tumour necrosis factor-related apoptosis-inducing ligand and its relationship to infertility in Egyptian patients with varicocele.

Germ cell apoptosis has been proposed as one of the mechanisms by which varicocele can influence fertility. The aim of this study was to investigate the relationship between seminal tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) levels and male infertility in patients with varicocele. This study included 112 males: 30 fertile males with varicocele, 44 infertile males with varicocele and 38 healthy fertile control subjects without varicocele. Semen analysis was performed, and serum levels of reproductive hormones were measured. Seminal TRAIL levels in the infertile varicocele group were significantly higher than in the fertile varicocele and the control groups (P = 0.014). A significant negative correlation was found between seminal TRAIL and progressive (P < 0.001) and total motility scores (P < 0.001) in the infertile varicocele group. A significant negative correlation was also detected between seminal TRAIL levels and normal sperm morphology in the fertile varicocele (P = 0.007) and infertile varicocele patients (P = 0.047). Seminal TRAIL was significantly correlated with varicocele grade whether the patients were fertile (P = 0.001) or infertile (P = 0.035). Seminal TRAIL may thus have a potential role in varicocele-associated male infertility through its negative effect on sperm motility and morphology.

Urinary metabolome identifies signatures of oligozoospermic infertile men

To identify the differential urinary metabolic pattern of oligozoospermic infertile men and to determine the potential biomarkers indicative of infertility. Observational study. University hospital. Totals of 158 fertile volunteers and 135 oligozoospermic infertile men. None. Urinary metabolic profiles were acquired with the use of liquid chromatography/mass spectrometry. Potential oligozoospermic biomarkers were screened from orthogonal projections to latent structures discriminant analysis and further evaluated by receiver operating characteristic analysis. The Spearman correlations between the individual sets of biomarkers and between biomarkers and sperm parameters were investigated. The disrupted biologic pathways which the biomarkers were involved in also were analyzed. Oligozoospermic infertile men could be differentiated from fertile control subjects based on altered urinary metabolic profiles. A total of ten potential biomarkers were screened and tentatively identified. Among those, decreased acylcarnitines, aspartic acid, and leucylproline and increased adenine and methylxanthine were strongly associated with oligozoospermic risk. Many biomarkers were associated with sperm concentration and amplitude of lateral head displacement. The combined pattern of acetylcarnitine, carnitine C3:1, and aspartic acid provided moderate diagnostic power. Urinary metabolomics identified unique metabolic pattern of oligozoospermic infertility. The potential biomarkers suggested that oligozoospermia may be tightly associated with energy consumption and antioxidant defenses in spermatogenesis.