International Journal of Fertility & Sterility
Year:2020 | Volume:13 | Issue:4|Papers Count:14

Chronic endometritis (CE) is a poorly investigated pathology which has been related to adverse reproductive outcomes, such as implantation failure and recurrent miscarriage. In this paper, we aim to provide an overview of diagnosis, etiology, pathophysiology and treatment of CE, its impact on endometrial microenvironment and its association with infertility. We present a narrative review of the current literatures, synthesizing the findings retrieved from searches of computerized databases. CE is more prevalent in infertile patients. Effective antibiotic treatment of CE seems to improve the pregnancy and live birth rate in patients with unexplained recurrent pregnancy loss (RPL), and increase ongoing pregnancy rate in patients with recurrent implantation failure. In order to increase the diagnostic accuracy, immunohistochemistry is recommended besides the conventional histology. In addition, hysteroscopy could be considered as gold standard tool for diagnosis, considering its high correlation with histological findings. CE, as the chronic inflammation of endometrium, is usually asymptomatic and probably underestimated. Interaction of bacteria with endometrial microenvironment promotes changes in leukocyte population, cytokine production and growth factors which support its negative impact on endometrial receptivity. Nevertheless, standardization of the criteria for histopathological diagnosis and immunohistochemistry technique needs to be defined.

Polycystic ovary syndrome (PCOS) is a common, complex condition that affects up to 18% of reproductiveaged women, causing reproductive, metabolic and psychological dysfunctions. We performed an overview and appraisal of methodological quality of systematic reviews that assessed medical and surgical treatments for reproductive outcomes in women with PCOS. Databases (MEDLINE, EMBASE, CINAHL PLUS and PROSPERO) were searched on the 15th of September 2017. We included any systematic review that assessed the effect of medical or surgical management of PCOS on reproductive, pregnancy and neonatal outcomes. Eligibility assessment, data extraction and quality assessment by the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool were performed in duplicate. We identified 53 reviews comprising 44 reviews included in this overview; the majority were moderate to high quality. In unselected women with PCOS, letrozole was associated with a higher live birth rate than clomiphene citrate (CC), while CC was better than metformin or placebo. In women with CC-resistant PCOS, gonadotrophins were associated with a higher live birth rate than CC plus metformin, which was better than laparoscopic ovarian drilling (LOD). LOD was associated with lower multiple pregnancy rates than other medical treatments. In women with PCOS undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), the addition of metformin to gonadotrophins resulted in less ovarian hyperstimulation syndrome (OHSS), and higher pregnancy and live birth rates than gonadotrophins alone. Gonadotrophin releasing hormone (GnRH) antagonist was associated with less OHSS, gonadotrophin units and shorter stimulation length than GnRH agonist. Letrozole appears to be a good first line treatment and gonadotrophins, as a second line treatment, for anovulatory women with PCOS. LOD results in lower multiple pregnancy rates. However, due to the heterogeneous nature of the included populations of women with PCOS, further larger scale trials are needed with more precise assessment of treatments according to heterogeneous variants of PCOS.

Background: Infertility affects different aspects of life including the quality of life (QOL) in infertile couples. Many infertile couples conceive via using assisted reproductive technology (ART). However, the effect of pregnancy and childbearing on QOL is not known in these couples. This study aimed to evaluate QOL and general health during pregnancy and after successful treatment of infertility, in women conceived with ART. Materials and Methods: In this case-control study, QOL and general heath were evaluated in 40 women conceived with ART and 40 women who conceived spontaneously and served as the control group. WHO quality of life-BREF (WHOQOL-BREF) inventory was used to evaluate QOL and General Health Questionnaire-28 (GHQ-28) was applied to evaluate general health. These two questionnaires were completed in the first and second trimester of pregnancy and results were compared between the two groups. Results: Mean age of women was 29. 4 ± 4. 4 and 29. 6 ± 5 years in ART and control group, respectively. QOL in women conceived with ART was similar to QOL in the control group in the first and second trimester of pregnancy while general health score (distress level) in women conceived with ART was significantly higher than that of the control group in both trimesters. Although distress level decreased in the second trimester in ART group, but yet, it was higher than that recorded for the control group. Conclusion: After pregnancy, QOL in women conceived with ART is similar to women conceived spontaneously. However, these women experience higher distress level in the first and second trimester of pregnancy compared to women conceived spontaneously.

Background: It is thought that mothers who conceive via assisted reproductive technology (ART) may be at greater risk of postpartum depression (PPD) because of the problems and psychological stresses associated with ART treatment. The aim of the present study is to determine the occurrence of PPD among mothers who conceive by ART in comparison with those who naturally conceive. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess PPD. Materials and Methods: This historical cohort study investigated 406 mothers with infants aged 3-9 months. Three hundred and eight women with natural pregnancies were selected as the control group from mothers who referred to Tehran healthcare centres for infant vaccinations. The ART group consisted of 98 women who conceived via ART at Royan Institute. Participants completed a general questionnaire that asked about education, occupation, number of children, delivery method, history of infant hospitalization, breastfeeding, mothers’ and infants’ ages, cause of infertility (ART group), and history of depression. A validated Persian version of the EPDS was used to measure depressive symptoms. Results: The mean EPDS score in mothers who naturally conceived was 8. 38 ± 0. 35 in comparison with mothers who conceived via ART (7. 59 ± 0. 63). The proportions of women who reported PPD were 26. 0% for the control group and 20. 4% for the ART group. There was no statistically significant difference in PPD between the control and ART groups (P=0. 26). Conclusion: The occurrence of PPD in mothers who conceived via ART was similar to those who conceived naturally.

Background: One of the treatment methods for increasing the ovarian response to ovulation induction in polycystic ovary syndrome (PCOS) is laparoscopic ovarian drilling (LOD). The optimal amount of the electrosurgical energy discharged in the ovaries to achieve maximum treatment response with minimal follicle injury is unknown. This study was performed to compare the success level of LOD by means of standard and dose-adjusted treatment methods among infertile clomiphene-resistant PCOS women. Materials and Methods: This randomized clinical trial was conducted on infertile clomiphene citrate-resistant PCOS women in the Gynaecology Department of Imam Reza Hospital between 2016 and 2017. The patients were randomly divided into two groups based on the ovarian cautery method. The two groups were examined and compared regarding the antral follicles, the serum levels of anti-Mü llerian hormone (AMH), androgens, and mid-luteal progesterone one month after surgery. The regularity of cycles, ovulation, and pregnancy were examined monthly up to six months after surgery. Results: In total, 60 women received bilateral LOD (n=30 per group). The level of AMH (P=0. 73), testosterone (P=0. 91), and dehydroepiandrosterone sulphate (DHEAS, P=0. 16) did not differ at study entrance and one month after ovarian cautery [P=0. 94 (AMH), P=0. 46 (testosterone), and P=0. 12 (DHEAS)] and for postoperative mid-luteal progesterone (P=0. 31). Intragroup comparisons showed a statistically significant difference in the decrease in the number of antral follicles and testosterone in the standard group (P=0. 02) and AMH level in the cautionary dose-adjusted group (P=0. 04). We observed no difference in cycle regularity (P=0. 22), ovulation (P=0. 11), and pregnancy (P=0. 40) between the two groups after six months. Conclusion: The results indicated that there was no difference between the two methods of ovarian cautery with regards to establishing cycle regularity and ovulation. The standard treatment was effective in decreasing the numbers of antral follicles and testosterone levels, whereas the dose-adjusted method significantly affected the decrease in AMH levels (Registration Number: IRCT20171210037820N1).

Background: The aim of this study was to investigate the effects of vaginal sildenafil on the outcome of patients with at least two unsuccessful in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) attempts. Materials and Methods: In this randomized placebo-controlled trial study, a total of 66 infertile women aged ≤ 38 years, with a history of normal ovarian reserve, two prior consecutive failed IVF/ICSI attempts, human chorionic gonadotropin (hCG) day endometrial thickness <7 mm in all prior IVF/ICSI cycles, normal endometrial appearance by either hysteroscopy, hysterosonography, or hysterosalpingography enrolled in this study. The conventional gonadotropin-releasing hormone (GnRH) protocol was used for ovarian stimulation. The patients were randomly divided into three groups: vaginal sildenafil (suppository-100 mg/daily), vaginal placebo/sildenafil (suppository-100 mg/daily), and vaginal placebo (suppository). Each patient underwent colour Doppler ultrasound on day 14 of their previous cycle to investigate any abnormalities in the uterus and adnexa. Endometrial thickness, echo pattern, uterine artery resistance, and pulsatility indices were recorded pre-and post-treatment. The primary outcome measures were implantation, chemical and clinical pregnancy rates. For data analysis, SPSS version 20 software was used. In all tests, the significance level was considered less than 0. 05. Results: There was no significant difference between three groups in endometrial thickness on the hCG injection day. The chemical pregnancy in women who received sildenafil (alone or in combination with placebo) showed a two-fold increase in comparison to the placebo group. This increase was clinically meaningful, but according to sample size, it was statistically non-significant. The results of our study showed that the implantation was higher in women who received placebo/sildenafil compared to the other groups. The abortion rate was not statistically significant among the groups. Conclusion: Vaginal sildenafil may conceivably improve chemical pregnancy rates in repeated IVF failure patients. Further randomized clinical trials using oral or vaginal sildenafil with higher sample size are recommended (Registration number: NCT03192709).

Background: Endometriosis is an important gynecologic disease affecting reproductive-age women. Based on the effect of phytoestrogens on inflammatory, immunological and hormonal factors, limited studies have suggested that phytoestrogen consumption could probably modulate endometriosis risk. The aim of this study was to evaluate the relationship between phytoestrogen intake and endometriosis risk. Materials and Methods: In the present case-control study, 78 women with a laparoscopically confirmed endometriosis and 78 normal pelvis women (as the control group), were recruited. Common dietary intake was recorded by a validated 147-item semi-quantitative food frequency questionnaire (FFQ). Type of phytoestrogen in each dietary item was analyzed by the database from the United States Department of Agriculture (USDA). A logistic regression model was used to determine the association between phytoestrogen intake and endometriosis risk. Results: Higher intake of total phytoestrogen (P-trend=0. 01), total isoflavones (P-trend=0. 002) specially formononetin (P-trend=0. 04) and glycitein (P-trend=0. 04), total lignan (P-trend=0. 01) specially secoisolariciresinol (P-trend=0. 01) and lariciresinol (P-trend=0. 02) and matairesinol (P-trend=0. 003), and total coumestrol [third quartile odds ratios (OR): 0. 38; 95% confidence intervals (CI): 0. 15-0. 96; P-trend=0. 1] was related to reduced endometriosis risk. Among food groups, only isoflavin (OR: 0. 48; 95% CI: 0. 44-0. 63), lignan (OR: 0. 66; 95% CI: 0. 62-0. 94), coumestrol (OR: 0. 64; 95% CI: 0. 51-0. 99), phytoestrogen (OR: 0. 46; 95% CI: 0. 38-0. 83) in dairy products and coumestrol in fruits (OR: 0. 69; 95% CI: 0. 03-0. 77) were negatively associated with endometriosis risk. Conclusion: Phytoestrogens have a major impact on the level of hormones, and immune and inflammatory markers; thus, it can play an important role in the control and prevention of many diseases. Due to the inflammatory nature of endometriosis and the effect of hormones on the progression of the disease, the role of phytoestrogens consumption in the progression and regression of the disease should be assessed in future works.

Background: The aim of this study was to investigate two enkephalin-degrading enzymes, aminopeptidase N (APN/ CD13) and endopeptidase (NEP/CD10), gene and protein expression levels in sperm samples of fertile and heroinaddicted men, and the correlation between their expressions and semen quality. Materials and Methods: In this case-controlled study, semen was collected from 24 normozoospermic healthy (as a control group) and 24 heroin-addicted men donors (as case or addiction group). Sperm cells isolated by Cook Medical gradient (40-80%) and followed up by swim-up techniques were used for real-time quantitative polymerase chain reaction (qPCR) and flow cytometry techniques to assess APN/CD13 and NEP/CD10 genes and proteins subsequently. Semen parameters were analyzed by computer-assisted sperm analysis. Results: The findings revealed that there were significant differences in sperm total motility (41. 07 ± 3. 63 vs. 63. 03 ± 3. 31 %, P=0. 0001), progressive motility (35. 21 ± 2. 64 vs. 20. 93 ± 3. 22%, P=0. 001) and viability (69. 9 ± 4. 69 vs. 86. 81 ± 1. 26 %, P=0. 002) in the addicted group vs. control ones. APN and NEP gene expression levels in the addicted group decreased compared with the control ones (1. 00 ± 0. 67 vs. 0. 36 ± 0. 13, P= 0. 008 and 1. 07 ± 0. 11 vs. 0. 52 ± 0. 12 0. 002, respectively). Flow cytometry analysis showed that the average percent of APN/CD13 in heroin consumers significantly decreased compared with the healthy ones, while NEP/CD10 rate between two groups was similar. We also observed that duration of drug dependence is correlated with sperm viability (r=-0. 627, P=0. 016) and motility (r=-0. 410, P=0. 05), NEP (r=-0. 434, P= 0. 049), and APN (r=-0. 641, P=0. 002) gene expression levels. Conclusion: We conclude that semen quality and enkephalin-degrading enzymes were altered in heroin-addicted men. other confirming the internal validity of our estimates.

Background: Paraquat (PQ) is an herbicide that is genotoxic and cytotoxic for male germ cells. In this study, we investigated the protective role of crocin (Cr) against the destructive effects of PQ on sperm quality and in vitro fertilization (IVF) outcomes. Materials and Methods: In this experimental study, a total of 28 male mice (20-25 g) were divided into four groups: control, which received intraperitoneal (IP) injections of 0. 1 ml normal saline per day; PQ group received IP injections of PQ (5 mg/kg/day); experimental (PQ+Cr group) received PQ along with IP injections of Cr (200 mg/kg/day); and positive control (Cr) received IP injections of Cr (200 mg/kg/day). In the last two weeks of the treatment period (35 days of treatment), 16 non-pregnant mice were stimulated to receive adult oocytes. At the end of the treatment period, after euthanizing the mice, the sperms were extracted from the epididymis of each mouse and prepared for evaluation of sperm parameters and IVF. Results: In the PQ+Cr group, Cr caused a significant increase in the average number of sperms and the mean percentage of motile and viable sperms. There was a significant decrease in the mean number of immature and DNA-damaged sperms compared to the PQ group (P<0. 001). IVF evaluation in the PQ+Cr group showed that the mean percentage of fertilization, two-and four-cell embryos, blastocysts, and hatched embryos significantly increased. Cr caused a significant decrease in the mean percentage of the arrested embryos compared to the PQ group (P<0. 001). However, the Cr group did not have any toxic effects on sperm quality or IVF results. Conclusion: The findings of this study showed that Cr, due to its effective and potent antioxidant properties, could reduce or suppress the destructive effects on sperm parameters and IVF caused by PQ.

Background: Uric acid (UA) is crucial for sperm metabolism as it protects seminal plasma against oxidative damage. Zinc also plays a central role in sperm metabolism. The current study was designed to investigate the role of zinc supplementation on qualitative and quantitative properties of seminal fluid, in parallel with the UA level and urate pathway enzymes in the semen of patients with asthenozoospermia. Materials and Methods: The study was designed as a randomized clinical trial of 60 asthenozoospermic subfertile men. The current study, which was conducted during one year, involved 60 fertile and 60 asthenozoospermic subfertile men belonging to Hilla City, Iraq. Semen samples were obtained from the participants before and after treatment with zinc supplements. The levels of UA, xanthine oxidase (XO), adenosine deaminase (ADA) and 5'-nucleotidase (5'-NU) activities were determined in spermatozoa and seminal plasma of both groups. Results: UA levels (P=0. 034) and 5'-NU activity (P=0. 046) were significantly lower but ADA (P=0. 05) and XO (P=0. 015) activities were significantly higher in infertile men than in healthy men. Treatment with zinc sulfate induced an increase in UA (P=0. 001) level and 5'-NU activity (P=0. 001), but a decrease in ADA (P=0. 016) and XO (P=0. 05) activities. Conclusion: Zinc supplementation restores UA levels and the activities of enzymes involved in the urate pathway (XO and ADA) in the seminal plasma and spermatozoa of patients with asthenozoospermia, to reference values. Supplementation of Zn compounds enhances the qualitative and quantitative properties of semen (Registration number: NCT03361618).

Background: Imbalance between production of reactive oxygen species (ROS) and total antioxidant capacity in testis, epididymis, and seminal fluid can eventually lead to infertility. Abnormal sperm chromatin packaging, and DNA fragmentation is considered as the main underlying causes of infertility. Therefore, we aimed to assess relationship between sperm parameters with DNA damage, protamine deficiency, persistent histones, and lipid peroxidation in infertile men with at least one failed cycle after intracytoplasmic sperm injection (ICSI). Materials and Methods: In this experimental study, semen samples were collected from infertile men with at least one failed cycle after ICSI (n=20). Sperm parameters, DNA damage, protamine deficiency, persistent histones, and lipid peroxidation were assessed using computer-assisted sperm analysis (CASA) system, sperm chromatin structure assay (SCSA) and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, chromomycin A3, aniline blue, and BODIPY C11 staining, respectively. Results: A negative significant correlation was observed between sperm concentration with percentage of sperm persistent histone (r=-0. 56, P=0. 02), while positive significant correlations were found between percentage of sperm persistent histones with abnormal sperm morphology (r=0. 54, P=0. 02), CMA3-positive spermatozoa (r=0. 6, P=0. 008) and intensity of lipid peroxidation (r=0. 6, P=0. 01). In addition, a significant correlation was observed between sperm DNA damage with intensity and percentage of lipid peroxidation (r=0. 62, P=0. 009, r=0. 77, P=0. 007). Correlation between CMA3-positive spermatozoa and intensity of lipid peroxidation (r=0. 5, P=0. 03) were also significant. Conclusion: Observed significant correlations between sperm functional tests in infertile men with at least one failed cycle after ICSI, indicated that the reduction of oxidative stress by antioxidant supplementation may be considered as one therapy approach for improvement of sperm function and increase the chance of successful clinical outcomes in next assisted reproductive cycle.

Background: In the present study, the effects of alginate (ALG) concentration and ovarian cells (OCs) on the development and function of follicles were simultaneously evaluated. Materials and Methods: In the first step of this experimental study, preantral follicles were isolated from the ovaries of 2-week-old mice, encapsulated in the absence or presence of OCs in 0. 5, 0. 75 and 1% ALG hydrogels, and cultured for 14 days. The morphology, diameter, survival and antrum formation rates of the follicles and the maturation of the oocytes were evaluated during culture. In the second step, preantral follicles were cultured in the best chosen ALG concentration, in both the absence and presence of OCs. Following these steps, the amount of DNA fragmentation, the expression levels of connexin 37 and connexin 43 proteins, the secretion levels of estradiol, progesterone and androstenedione by the follicles and the quality of mature (MII) oocytes were assessed. Results: Our data revealed that in the absence of OCs, follicles of 0. 5% group showed a higher survival rate than the 0. 75 and 1% groups (71. 87 vs. 52. 52 and 40%, respectively, P<0. 05). Nonetheless, the antrum formation rate of the 1% group was higher and its oocyte degeneration rate was lower than that in the other groups. Furthermore, it was observed that co-culture of follicles with OCs relatively increased the follicle diameter, survival, antrum formation, and germinal vesicle (GV) to GV break down (GVBD)/MII transition rates. At last, the comparison of 0. 5%-OCs and 0. 5%+OCs groups indicated that the co-culture condition resulted in more progesterone production (1. 8 ± 0. 2 vs. 3. 2 ± 0. 4 ng/ml, respectively, P<0. 05) and also decreased oocytes’ cortical granule abnormalities (100 vs. 40% for 0. 5%-OCs and 0. 5%+OCs groups, respectively). Conclusion: The present study revealed that 0. 5% ALG hydrogel is relatively suitable for preantral follicle culture, and in the presence of OCs, it mimics the natural ovarian condition better than the higher concentrations of ALG hydrogel.

Background: Aspirated ovarian follicular fluids (FF) contain luteal granulosa cells (LGCs) and other contaminating cell types. Several strategies, such as the antibody binding methods, the flask method, the cell strainer and positive selection of granulosa aggregates after density gradient (DG) centrifugation, were tested as LGC purification methods. Each of these strategies has its own advantages and disadvantages. Positive selection of granulosa aggregates after DG centrifugation is simple, rapid and efficient in terms of LGC recovery. However, it results in a low purity. Here, we aimed to test whether modifying the traditional protocol by collecting the aggregates from the FF, before the DG centrifugation could decrease the percentage of contaminating cells. Materials and Methods: In the present prospective study, 32 FF, from 32 women, were randomly assigned into one of the two purification techniques: positive selection of granulosa aggregates from the FF, after DG centrifugation (DG/ Agg, n=16) or positive selection of granulosa aggregates from the FF, before DG centrifugation (Agg/DG, n=16). At the end of each procedure cell count, vitality, morphology and purity of the cell suspension were evaluated. Results: No significant difference was detected in the total number of GCs between DG/Agg and Agg/DG (P>0. 05). However, higher percentage of GCs with normal morphology was detected in Agg/DG compared to DG/Agg (P<0. 001). Moreover, lower percentages of white blood cells (P<0. 01), red blood cells (P<0. 001) and epithelial cells (P<0. 01) were identified in Agg/DG compared to DG/Agg. Conclusion: Here we showed that positive selection of granulosa aggregates from the FF prior to DG technique had a higher purity compared to the traditional protocol. Thus, it could be a method of choice to prepare GCs for research purposes in clinical in vitro fertilization settings.

The ovarian reserve (OR) gradually decreases throughout the female fertile life. This continuous depletion in OR is irreversible. This occurs through a programmed cell death, known as apoptosis. Some factors hasten such depletion, such as chemo-and radio-therapy. Others have been investigated in trials to preserve the OR including gonadotropins, cytokines, growth hormones, nitric oxide and reorganization of the actin cytoskeleton. Loss of OR occurs normally at the menopausal age, a stage called menopausal ovarian senescence. At some periods, there are other sources for ovarian hormones that are away from the ovary, like during use of contraceptive pills and at pregnancy after formation of placenta. Future trials to preserve ovarian follicles at these periods might postpone the onset of menopause and hence lengthen the fertile female age.