Infertility Of Unknown Etiology Research Articles

Relationship between Serum 25-Hydroxyvitamin D Levels and Hormonal Status in Infertile Women: A Retrospective Study.

(1) Background: Infertility is a prevalent issue that affects 10-18% of couples worldwide, and up to 30% in Eastern Europe. Infertility of unknown etiology is one of the most challenging forms of infertility. Vitamin D has recently been extensively studied and researchers are investigating its possible role in ovulation and pregnancy. While the evidence suggests a positive association between vitamin D and ovulation, more research is needed to understand the role that vitamin D plays in ovulation. (2) Methods: In this study, 86 infertile patients were studied retrospectively in a single center by analyzing their anthropometric (body mass index), biochemical (total cholesterol, insulin resistance) and hormonal data in correlation with their vitamin D status. (3) Results: It was found that the mid-luteal progesterone level was significantly related to the 25-hydroxy vitamin D level in a multivariate linear regression model. An analysis of subgroups of ovulatory and anovulatory patients suggests that serum 25-hydroxy vitamin D levels of approximately 20 ng/mL may be necessary to trigger ovulation or to support progesterone secretion. (4) Conclusions: Vitamin D deficiency should be considered when infertility of unknown etiology and progesterone-related disorders occur.

Correlation of Estrogen Receptor Alpha Serum Level with Gene Polymorphism and Its Effect on Women with Unexplained Infertility, Basra, Iraq.

Infertility of unknown etiology is considered a significant medical and health problem. This study focused on the role of the estrogen receptor alpha (ESRα) gene polymorphism, PvuII (rs2234693), and its effect on the amount of ESRα in the blood of women who cannot get pregnant for unknown reasons. A total of 184 females were evaluated, including 102 with unexplained infertility (UI) and 82 age-matched control females (with at least one living child and no history of infertility). Blood samples were collected, genomic DNA was isolated from blood samples, and the genotyping of the ESRα gene was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). ESRα expression levels were assessed by the ELISA. The study revealed that the mean serum level of ESRα was significantly higher in the case group than in the control group (P<0.05). Furthermore, the genotypes (TT, TC, and CC) and alleles (T and C) significantly influenced the plasma level of ESRα in the study population. Moreover, the presence of the C allele was considered a risk factor, and the polymorphism had a significant effect on ESRα expression level in women with UI.

Endometriosis as an Infectious Disease: Association with Chronic Endometritis

Objectives: Recent studies focus on immunological, infectious, and inflammatory aspects of endometriosis. Meanwhile, chronic endometritis (CE) is an immunological, infectious, and inflammatory disorder of the eutopic endometrium with unusual stromal plasmacyte infiltration. Mechanism: In this review article, we aimed to gain a better understanding of the relationships between endometriosis and CE. Findings in Brief: Accumulating evidence supports the idea that CE is associated with infertility of unknown etiology, repeated implantation failure in an in vitro fertilization-embryo transfer program, recurrent pregnancy loss, as well as several perinatal/neonatal complications. Endometrial biopsy/histopathologic examinations and/or hysteroscopy are required to make a definitive diagnosis of CE. Conclusions: While endometriosis has been long considered a cause of infertility, CE is also an emerging issue that may reduce fecundity in women of reproductive age. Endometriosis and CE share characteristics of endometrial proliferative nature. The potential relationships between these two diseases of the uterine lining warrant future studies.

Challenges in Clinical Diagnosis and Management of Chronic Endometritis.

Chronic endometritis (CE) is a local mucosal infectious and inflammatory disorder characterized by unusual filtration of CD138(+) endometrial stromal plasmacytes. CE is attracting attention due to its potential association with infertility of unknown etiology, repeated implantation failure, recurrent pregnancy loss, and several maternal/neonatal complications. Due to the variance in study design among researchers, universal diagnostic criteria remain to be established for the clinical diagnosis and management of CE. This review article aims to summarize current knowledge and provide insights into unsolved questions on CE to establish clinical guidelines for the disease from the viewpoint of human reproduction.

Differential Vaginal Microbiota Profiling in Lactic-Acid-Producing Bacteria between Infertile Women with and without Chronic Endometritis

Purpose: Chronic endometritis (CE) is an infectious and inflammatory disorder associated with infertility of unknown etiology, repeated implantation failure, and recurrent pregnancy loss. In the current clinical practice, intrauterine interventions such as endometrial biopsy/histopathologic examinations and/or hysteroscopy are required for the diagnosis of CE. In this study, we analyzed the microbiota in vaginal secretions (VS) as a potential prediction tool for CE in infertile women. Methods: Using next-generation sequencing analysis, we compared the VS and endometrial fluid (EF) microbiota in infertile women with (n = 20) or without CE (n = 103). Results: The detection rate of Streptococcus and Enterococcus as well as the bacterial abundance of Atopobium and Bifidobacterium in the VS microbiota was significantly lower in the CE group than in the non-CE group. Meanwhile, the detection rate and bacterial abundance of Lactobacillus in the EF and VS microbiota were at similar levels between the two groups. Conclusion: These findings suggest that VS microbiota in infertile women with CE is characterized by the reduction in Bifidobacterium and lactic-acid-producing bacteria other than Lactobacillus. Our results hold promise for the prediction of CE, not by somewhat interventional intrauterine procedures, but by less invasive VS sampling. TRIAL REGISTRATION NUMBER: UMIN000029449 (registration date 6 October 2017).

Association of Vitamin D Status with Semen Parameters and Male Reproductive Hormones in Egyptian Infertile Men

Background: Although vitamin D receptor (VDR) is expressed in human sperm, little is known about the role of vitamin D (Vit. D) in male reproduction. Our objective was to assess Vit. D levels both in serum and seminal fluid and to establish the relation between serum and seminal Vit. D levels, semen parameters, male sex hormones and serum calcium level in Egyptian infertile men. Patients and Methods: We conducted a prospective case control study including 30 healthy fertile males as a control group and 60 male patients with infertility of unknown etiology. Semen samples were collected and semen parameters were evaluated. Also, seminal Vit. D level was measured. Blood samples were taken as serum levels of Vit. D, calcium, testosterone, Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) were estimated. Results: There was significant decrease of both serum and seminal Vit. D level in groups of male infertility compared to control group. A significant positive correlation was found between serum and seminal Vit. D levels in different study groups. Also, significant positive correlation between serum Vit. D level and non-progressive sperm motility. Conclusion: Our results support the role of Vit. D in semen parameters and male fertility status.

Relationship between endogenous plasma adrenocorticotropic hormone concentration and reproductive performance in Thoroughbred broodmares.

BackgroundPituitary pars intermedia dysfunction (PPID) is an endocrine disorder the clinical signs of which include infertility, but few reports have examined the relationship between PPID and reproductive performance in broodmares.Hypothesis/ObjectiveBroodmares with infertility of unknown etiology were screened for PPID using baseline endogenous plasma ACTH concentrations, and its relationship with subsequent reproductive performance was analyzed.AnimalsSixty‐seven Thoroughbred broodmares.MethodsAdrenocorticotropic hormone concentrations were measured in autumn. The broodmares were divided into 3 groups based on endogenous plasma ACTH concentration (low, <50 pg/mL; intermediate 50‐100 pg/mL; and high >100 pg/mL) as recommended by the Equine Endocrinology Group. We compared these results with those of other blood tests, clinical examinations, subsequent conception, and frequency of normal delivery.ResultsThe numbers of horses per group (percentage) were 22 (32.8%), 20 (29.9%), and 25 (37.3%). The mean ± SD ages (years) were 11.1 ± 3.4, 12.1 ± 4.5, and 13.0 ± 4.3, with no significant difference among groups. Mean ± SD plasma cortisol concentrations (μg/dL) were 4.0 ± 1.6, 7.1 ± 1.4, and 7.6 ± 1.9, with the intermediate and high ACTH groups having significantly higher results than the low ACTH group (P < .001). Conception rates were 77.3%, 89.5%, and 56.5% and normal delivery rates were 77.2%, 84.2%, and 43.5% with the percentage of each significantly lower in the high ACTH group (P = .02, P = .008, respectively).Conclusions and Clinical ImportanceThe study group of infertile broodmares may include horses with PPID. The reproductive performance of the high ACTH group was significantly lower than the other groups. Early diagnosis and treatment of infertile broodmares by screening plasma ACTH concentrations could help improve reproductive performance.

Comparison of laparoscopic findings with tuberculosis polymerase chain reaction in the diagnosis of genital tuberculosis among subfertile women

Background: Female genital tuberculosis (FGTB) is an important cause of infertility. The Fallopian tubes are involved in almost 90% of the cases. Materials and Methods: All 50 participants were women with complaints of infertility to whom FGTB was suspected as a cause of infertility or women with infertility of unknown etiology. After selecting the patient according to inclusion criteria, women were posted for diagnostic laparoscopy and endometrial aspirate/biopsy was sent for TB polymerase chain reaction (TB PCR). Results: In our study, infertile women who had clinical and hysterosalpingography findings suggestive of genital TB underwent endometrial biopsy for TB PCR and hysterolaparoscopy for further evaluation. Among them, 7 (14%) endometrial TB PCR-positive cases were found in the study. Clinical and hysterolaparoscopy findings in these cases were carefully reviewed, although laparoscopic findings were suggestive of TB in 9 (18%) women. Conclusion: Direct visualization of the female genital tract by laparoscopy is most confirmatory and should be considered for starting the antitubercular treatment on the basis of laparoscopic findings.

Role of natural killer cells in reproductive failure

Reproductive losses are quite frequent in the modern world. They include: infertility, infertility of unknown etiology, multiple losses when IVF, recurrent implantation failure, miscarriage, recurrent miscarriage, both in the natural cycle and after ART management. It is important to note that the classification of some of these categories are not established yet. The etiology of reproductive losses is extremely diverse. Successful development of pregnancy at early terms is determined by genetic and immunological factors. Among the reproductive failures of unclear etiology, immunological causes are 50-80%. Over the past 20 years there are already known many different immunological factors that play role in the processes of fertilization. In this case, the evidence base on the role of each of them in the pathogenesis of reproductive failures is only being formed. Currently, the immunological relationship between mother and fetus is considered as a two-way communication process: the presentation of fetal antigens on the one hand, and on the other – the recognition and response to these antigens of the maternal immune system. Implantation of the embryo is accompanied by an increase in the production of proinflammatory cytokines followed by a sharp change in the cellular composition in the decidualizing endometrium, and the main population is NK cells. That is why this type of cells have a significant role in the normal development of pregnancy. The properties of NK cells in the uterus and peripheral blood are significantly different. To predict the onset and prolongation of pregnancy, peripheral blood NK (activity and quantity) is used. Evaluation of endometrial NK is often performed for the diagnosis of chronic endometritis. Currently, the definition of NK cells in peripheral blood in many clinics is proposed as a useful diagnostic test to address the issue of further appointment of immunoglobulins and evaluating the effectiveness of this therapy in patients with reproductive losses.

Enzymatic toxicity induced by lead acetate and its possible reversal by

Objective: An important part of male infertility of unknown etiology may be attributed to various environmental and occupational exposures to toxic substances, such as lead. Lead is the known environmental contaminant adversely affecting the male reproductive system in human and experimental animals. The cytotoxic effects of lead on male reproductive system involve the production of reactive oxygen species (ROS) and oxidative damage in tissue. The higher quantities of ROS in testicular tissue detrimentally affected enzymatic activities so as to produce verities of biochemical abnormalities and finally reduced sperm count. Methods: Adult male mice were divided into three groups: control, treated with lead acetated (1.25 mg/kg/day) and recovery group lead acetated (1.25 mg/kg/day) with vitamin E (2 mg/kg/day). Treatments were administered by daily gavage for 45 days. After treatment testis and epididymal weights were recorded and testis was used for the biochemical analysis (acid phosphatase (ACPase), alkaline phosphatase (ALKPase), and glutathione (GSH) and epididymal was used to count sperm. Results: Administration of lead acetate at a dose of 1.25mg/kg body weight for 45 days decreased the activities of all above parameters. Lead exposure resulted in oxidative stress and this was well extrapolated from the increase in lipid peroxidation products (LPP). Coadministration of vitamin E (2 mg/kg/day) with lead acetate restored all the parameters cited above to near the control values. Conclusions: This concludes that vitamin E has beneficial effects against lead acetate induced enzymatic toxicity in testicular tissue of mice.

Association of seminal plasma cadmium levels with semen quality in non-occupationally exposed infertile Nigerian males

Aim: Male infertility of unknown etiology may be attributed to various environmental exposures to toxic substances such as metals. Very few human studies have evaluated the relationship between male reproductive function and toxic metal concentrations in seminal plasma in Nigeria. The objective of this study was to evaluate the levels of cadmium in seminal plasma of non-occupationally exposed infertile Nigerian males and correlate their levels with semen quality. Materials and Methods: A total of 80 subjects were enrolled, which includes 60 infertile males on a routine visit to the University of Benin Teaching Hospital, Benin City and 20 fertile males (controls). The concentration of cadmium in seminal plasma was measured using atomic absorption spectrophotometer. Semen analyses were performed according to World Health Organization standard. Results: Mean seminal plasma cadmium level was significantly higher (P < 0.001) in infertile males compared with controls. The toxic metal correlated negatively (P

Withania somnifera Improves Semen Quality in Stress-Related Male Fertility.

Stress has been reported to be a causative factor for male infertility. Withania somnifera has been documented in Ayurveda and Unani medicine system for its stress-combating properties. However, limited scientific literature is available on this aspect of W. somnifera. We undertook the present study to understand the role of stress in male infertility, and to test the ability of W. somnifera to combat stress and treat male infertility. We selected normozoospermic but infertile individuals (N = 60), further categorized in three groups: normozoospermic heavy smokers (N = 20), normozoospermics under psychological stress (N = 20) and normozoospermics with infertility of unknown etiology (N = 20). Normozoospermic fertile men (N = 60) were recruited as controls. The subjects were given root powder of W. somnifera at a rate of 5 g/day for 3 months. Measuring various biochemical and stress parameters before and after treatment, suggested a definite role of stress in male infertility and the ability of W. somnifera to treat stress-related infertility. Treatment resulted in a decrease in stress, improved the level of anti-oxidants and improved overall semen quality in a significant number of individuals. The treatment resulted in pregnancy in the partners of 14% of the patients.

Value of semen culture in the diagnosis of chronic bacterial prostatitis: A simplified method

To investigate the role of semen cultures versus segmented urine cultures for the diagnosis of bacterial chronic prostatitis. We retrospectively examined 895 patients (age range 17-67 years) who met the consensus criteria for clinical chronic prostatitis/chronic pelvic pain syndrome, 50.1% of whom had dysuria and/or perineal discomfort, 37.4% infertility of unknown etiology and 12.5% erectile dysfunction. Segmented urine cultures, including expressed prostatic secretions (EPSs) and semen culture, were performed in all patients. Of the 895 patients, 182 had significant positive cultures for Gram-negative microorganisms (Escherichia coli was the commonest specimen isolated: 70.4% of cases) and 283 had significant positive cultures for Gram-positive microorganisms. We compared the culture yield in EPS and/or the urine voided after prostatic massage (VB3) sample (four-glass method) with that of the semen sample. In the Gram-negative group, 32 patients were diagnosed by means of semen culture (negative EPS and/or VB3 sample) and in only five cases was a positive diagnosis made despite a negative semen culture (positive EPS and/or VB3 sample). In the remaining subjects, diagnosis was performed with the aid of both EPS/VB3 sample and semen (both of which were positive). In the Gram-positive group, there was significant growth of such microorganisms in semen in every case considered positive, but in only 46 cases was diagnosis achieved via EPS and/or VB3 sample. A diagnosis of chronic prostatitis by Gram-positive microorganisms in these patients was only considered when the same microorganism was retrieved in repeated cultures without previous treatment. Only three cases met such criteria (all of whom had negative EPSs). To evaluate the diagnostic efficiency of the semen and EPS samples, we analyzed their sensitivity and specificity, obtaining higher sensitivity in semen than EPS samples for significant Gram-negative cultures: 97% vs 82.4%. In significant Gram-positive cultures, the sensitivity of semen samples was 100%, compared to only 16.1% for EPS. A semen sample has higher sensitivity than an EPS for the diagnosis of bacterial chronic prostatitis. In our clinical work-up, first-void urine and a semen culture are considered the only tests necessary to diagnose chronic prostatitis.

Human Menopausal Gonadotropins

Abstract Long-standing infertility of unknown etiology is currently an indication for in vitro fertilization. Because of the prolonged waiting time, expense, and operative risk, we have treated a group of women with empiric human menopausal gonadotropins/human chorionic gonadotropin before in vitro fertilization. A study group of 97 couples with well-documented, long-standing idiopathic infertility received up to four cycles of empiric human menopausal gonadotropin therapy before in vitro fertilization. This group was compared with a control group of 48 couples who did not receive human menopausal gonadotropin before in vitro fertilization. The 12 (12.4%) conceptions and eight (8.2%) term births resulting from empiric human menopausal gonadotropin therapy in the study group was significantly higher than the number of spontaneous conceptions and births (1%) in the study group (p

Hysterosalpingography with oil contrast medium enhances fertility in patients with infertility of unknown etiology

Previous studies have suggested increased fertility rates following hysterosalpingography (HSG) using oil as compared with aqueous contrast medium. To compare the possible fertility-enhancing effects of two agents used for HSG, this prospective randomized study evaluated the subsequent fertility rates in 121 patients who underwent HSG, in which either oil or aqueous contrast medium was used. After random assignment to either agent, patients were observed for four menstrual cycles after HSG without resorting to any therapy other than clomiphene citrate where indicated. The pregnancy rates for the four cycles after HSG were compared with chi-square analysis in the total study and in the diagnostic subgroups. The subgroup with infertility of unknown cause had a significantly higher pregnancy rate after HSG with oil than after HSG with aqueous contrast medium. No significant difference was seen for any other subgroup or for the overall cohort.

Abnormal ovarian cycles as diagnosed by ultrasound and serum estradiol levels

A significant portion of human infertility is presumably due to defective ovulation, including patients who fail to conceive despite medical induction of ovulation, those who fail despite repeated timely donor inseminations, and those with "infertility of unknown etiology". All point out the inadequacy of standard criteria for normal ovulation. This investigation correlates preovulatory serum estradiol and gonadotropin concentrations with dominant follicle growth measured ultrasonographically and serum progesterone levels. The data indicate a 35% incidence of cycles with significantly abnormal serum estradiol levels, decreased dominant follicle size, and abnormal progesterone levels despite biphasic basal body temperature curves and normal cycle length. If these cycles represent inadequate or abnormal ovulation, they can be distinguished from adequate cycles prior to follicle rupture and may benefit the treatment of human infertility.

T-Mycoplasmas and Human Infertility: Correlation of Infection with Alterations in Seminal Parameters

The presence of T-mycoplasmas in semen specimens from 625 men with infertility of unknown etiology was correlated with seminal cytologic findings. A change in the distribution toward higher ejaculate volumes and lower counts was demonstrated in the 246 patients with positive T-mycoplasma cultures, compared with the 379 patients with negative cultures. There was a significant increase in the number of tapering forms and spermatids in the T-mycoplasma-positive group. The increases in aberrant forms occurred at the expense of the oval and microcephalic forms. This change in the cytologic picture is consistent with the "stress" pattern seen in viral infections and allergic reactions, with the exception of the specific decrease in microcephalic forms. Relatively fewer patients with T-mycoplasmas in their semen had a high-level spermatozoal motility, compared with those lacking T-mycoplasmas. More than half again as many patients with T-mycoplasma infections had the poorest levels of spermatozoal motility. Infertile patients with T-mycoplasma infections had an over-all decrease in semen quality compared with those lacking demonstrable T-mycoplasmas.