International Journal Of Fertility and Sterility
Volume:13 Issue: 4, Jan-Mar 2020

Chronic endometritis (CE) is a poorly investigated pathology that has been related to adverse reproductive outcomes, such as implantation failure and recurrent miscarriage. In this paper we aim to provide an overview about diagnosis, etiology, pathophysiology and treatment of CE, its impact on endometrial microenvironment and how it may be associated with infertility.

Narrative review of the current literature, 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 per pregnancy live birth rate in patients with unexplained recurrent pregnancy loss, and increase ongoing pregnancy rate in patients with recurrent implantation failure. In order to increase the diagnostic accuracy, immunohistochemistry is recommended besides conventional histology. In addition, hysteroscopy could be considered the gold standard tool for the diagnosis, considering its high correlation with histological findings.

CE is the chronic inflammation of the endometrium, usually asymptomatic and probably underestimated. Interaction between bacteria and 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 and complex condition affecting up to 18% of reproductive-aged women with reproductive, metabolic and psychological dysfunction. We performed an overview and appraisal of methodological quality of systematic reviews assessing medical and surgical treatments for reproductive outcomes in women with PCOS.

This was an overview of systematic reviews. Databases (MEDLINE, EMBASE, CINAHL PLUS and PROSPERO) were searched on the 15th of September 2017. We included any systematic review assessing the effect of medical or surgical management of PCOS on reproductive, pregnancy and neonatal outcomes. Eligibility assessment, data extraction and quality assessment (by the AMSTAR tool) were performed in duplicate.

We identified 53 reviews comprising 44 reviews included in this overview; the majority being 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 again 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 / intra-cytoplasmic sperm injection (IVF/ICSI), adding metformin to gonadotrophins resulted in less ovarian hyperstimulation syndrome (OHSS), higher pregnancy and live birth rate than gonadotrophins alone. Gonadotrophin releasing hormone (GnRH) antagonist was associated with less OHSS, gonadotrophins units and shorter stimulation length than GnRH agonist.

Letrozole appears to be a good first line treatment and gonadotrophins as second line treatment for anovulatory women with PCOS. LOD results in lower multiple pregnancy rates. However, due to the heterogeneous nature of included populations of women with PCOS, further larger scale trials are needed with more precise assessment of treatments according to heterogeneous variants of PCOS.

Infertility affects different aspects of life as well as quality of life (QOL) in infertile couples. Many infertile couples conceive via using Assisted Reproduction Technologies (ART). However, the effect of pregnancy and childbearing on QOL is not known in these couples. This study aim was to evaluate quality of life and general health during pregnancy and after successful treatment of infertility in women conceived by ART.

In a case-control study quality of life and general heath were evaluated in 40 women conceived by ART and 40 women conceived spontaneously as control group. WHO quality of life- BREF (WHOQOL-BREF) inventory was used to evaluate quality of life and General Health Questionnaire–28 (GHQ-28) was applied to evaluate general health. These two questionnaires were completed in first and second trimester of pregnancy and compared between the two groups.

Mean age of women was 29.4±4.4 and 29.6± 5 years in ART and control group, respectively. Quality of life in women conceived by ART was similar to control group in first and second trimester of pregnancy while general health score (distress level) in women conceived by ART was significantly higher than control group in both trimesters. Although distress level decreased in second trimester in ART group but yet, it was higher than control group.

After pregnancy, quality of life in women conceived by ART is similar to women conceived spontaneously. However, these women experience higher distress level in first and second trimester of pregnancy compared to women conceived spontaneously.

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 conceiving via ART in comparison with mothers naturally conceiving, using Edinburgh Postnatal Depression Scale (EPDS).

This historical cohort study investigated 406 mothers with infants aged 3-9 months. Three hundred and eight women with natural pregnancies were selected as control group, among mothers who referred to Tehran healthcare centres for infant vaccination. Ninety-eight women who conceived via ART at the Royan Institute were selected as ART group. A general questionnaire, including education, occupation, number of children, delivery method, history of infant hospitalization, breastfeeding, mothers’ and infants’ ages, cause of infertility (in the case of ART group only), and history of depression, was used. It has to be pointed out that a validated Persian version of the EPDS was used to measure depressive symptoms.

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 and 20.4% among the control and ART groups, respectively. The difference in occurrence of PPD was not statistically significant between the control and ART groups (P =0.26).

The occurrence of PPD in mothers who conceived via ART was similar to those who naturally conceived.

This study was performed to compare the success level of laparoscopic ovarian drillind by means of standard and dose-adjusted (on the basis of ovarian volume) treatment methods among infertile clomiphene resistant PCO women.

This randomized clinical trial was conducted on infertile clomiphene citrate resistant PCOS women in the Gynecology department of Imam Reza Hospital between 2016 and 2017. The patients were randomly divided into two groups based on the ovarian cautery

group A (standard method) and group B (cautery on the basis of ovarian volume). The two groups were examined and compared regarding the antral follicles, serum level of AMH and androgens and midluteal progesterone one month after the operation. Regularity of cycles, ovulation and pregnancy were examined monthly up to 6 months of the operation. The significance level was set at P<0.05.

In total 60 women received bilateral LOD (n=30 per group). The level of AMH, testosterone and DHEAS was not significantly different at study entrance (P= 0.73, 0.91 and 0.16, respectively). The same result was obtained after one month of ovarian cautery (P= 0.94, 0.46 and 0.12, respectively) and also for postoperative midluteal progesterone (P = 0.31). Regarding intragroup comparisons, the decrease in the number of antral follicles and testosterone in group A (P = 0.02) and AMH level in group B (P = 0.04) was statistically significant. During the 6 months after treatment, the two groups had no meaningful difference in the cycles regularity, ovulation and pregnancy (P= 0.22, 0.11 and 0.40, respectively)

According to the results of this study, none of the two methods of ovarian cautery has priority to the other with regard to establishing cycles’ regularity and ovulation, but both methods are highly effective in establishing regular cycles. Moreover, the standard treatment was effective on decreasing the numbers of antral follicles and testosterone level whereas the dose-adjusted method significantly affected the decrease in AMH level. Therefore conducting similar studies with a larger samples size is highly recommended.

The aim of this study was to investigate the effects of vaginal sildenafil on the outcome of patients with at least two times of unsuccessful IVF / ICSI.

Method and Material(s): A total of 66 infertile women aged ≤ 38 years, with a history of normal ovarian reserve, two prior consecutive failed IVF/ICSI attempts, hCG day endometrial thickness <7 mm in all prior IVF/ICSI cycles, normal endometrial appearance in hysteroscopy or hysterosonography or hysterosalpingography were studied. The conventional GnRH protocol was used for ovarian stimulation. The patients were randomly divided into three groups: vaginal sildenafil (100 mg/daily), a combination of placebo (vaginal supp.) and vaginal Sildenafil (100 mg/daily), and placebo alone (vaginal sup.). All patients underwent color Doppler ultrasound (day 14 previous cycle) to investigate any abnormality in uterus and adnexa, and endometrial parameters including 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.

There was no significant difference between three groups in endometrial thickness on hCG injection day. The chemical and clinical pregnancy in women who received sildenafil (alone or in combination with placebo) showed a two-fold increase in comparison to those who just used placebo. This increase was clinically meaningful, but according to sample size, it was statistically non-significant. The results of our study showed that the implantation is also higher in women who received placebo + sildenafil compared than those in two other groups. Abortion rate was not statistically significant among the groups.

It seems that vaginal sildenafil may, conceivably, improve chemical and clinical pregnancy rates in repeated IVF failure patients. Further randomized clinical trials using oral or vaginal sildenafil with higher sample size are recommended.

The aim of this study is to evaluate the relationship between phytoestrogen intake with endometriosis risk.

A case-control study was conducted on 78 women with a laparoscopically confirmed diagnosis of endometriosis and on 78 normal pelvis women (as the control group). Common dietary intake was collected by a validated 147-item semi-quantitative FFQ. Calculation type of phytoestrogen of each dietary item was computed by the database from the USDA. A logistic regression model was used to determine the association between phytoestrogen intake with endometriosis risk.

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), total coumestrol (third quartile OR: 0.38; %95CI: 0.15-0.96; P-trend=0.15) is related to reduce endometriosis risk. Among food groups, only isoflavin (OR: 0.48; %95CI: 0.44-0.63), lignan (OR: 0.66; %95CI: 0.62-0.94), coumestrol (OR: 0.64; %95CI: 0.51-0.99) and phytoestrogen (OR: 0.46; %95CI: 0.38-0.83) in dairy product and Coumestrol in fruit (OR: 0.69; %95CI: 0.03-0.77) is associated with endometriosis risk.

Due to the inflammatory nature of endometriosis and the effect of hormones on the progression of the disease, the role of phytoestrogen consumption in the regression of the disease should be more determined.

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 heroin-addicted men, and the correlation between their expressions and semen quality.

This case-control study, semen 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 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.

The findings revealed that sperm total motility (41.07 ±3.63 vs. 63.03 ± 3.31 %, p = 0.0001) and 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) were significant differences in 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.

We concluded that semen quality and enkephalin-degrading enzymes were altered in heroin-addicted men.

Paraquat (PQ) is a herbicide and is genotoxic and cytotoxic poison for male germ cells. Therefore, in this study, the protective role of Crocin (Cr) against the destructive effects of Paraquat on sperm quality and in-vitro fertilization results Paraquat was investigated.

Twenty-eight male mice (20-25g) were used in four groups. The control group received 0.1ml of the normal saline intraperitonealy (IP) per day, and the sham control group (PQ group) received Paraquat 5mg/kg/day, IP, the experimental group (PQ+Cr group) received PQ along with Crocin (Cr) (200mg/kg/day, IP), and positive control group received only Cr (200mg/kg/day, IP). 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 and prepared for evaluation of sperm parameters and in-vitro fertilization (IVF).

In PQ+Cr group Crocin caused a significant increase in the average number of sperms and mean percentage of motile and viable sperms and a significant decrease in the mean number of immature and DNA-damaged sperms compared to sham control group (p<0.001). In addition, IVF evaluation in the PQ+Cr group showed that the mean percentage of fertilization, two- and four-cell embryos and blastocysts and hatched embryos significantly increased. Moreover, Crocin caused a significant decrease in the mean percentage of the arrested embryos compared to the sham control group (p<0.001). However, Crocin in the Cr group does not have any toxic effects on sperm quality or IVF results.

The findings of this study showed that Crocin, due to its effective and potent antioxidant properties, can reduce or suppress the destructive effects on sperm parameters and IVF caused by Paraquat.

Uric acid (UA) is crucial for sperm metabolism; it protects seminal plasma against oxidative damage. Zinc, too, plays a central role in sperm metabolism. The current study was designed to investigate the role of zinc supplementation on the qualitative and quantitative properties of seminal fluid, in parallel with the UA level and urate pathway enzymes in the semen of patients with asthenozoospermia.

The study design is a randomized controlled trial of 60 asthenozoospermic subfertile men. The current study, which was conducted for a 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 patients and healthy groups.

UA levels (P = 0.034) and 5'-NU activity (P = 0.046) were significantly lower and ADA (P = 0.05) and XO (P = 0.015) activities were significantly higher in infertile men than in healthy men. In addition to inducing an increase in UA (P = 0.001) level and 5'-NU activity (P = 0.001), treatment with zinc sulfate stimulated the decrease of ADA (P = 0.016) and XO (P = 0.05) activities.

Zinc supplementation restores UA levels and the activities of enzymes involved in the urate pathway (xanthine oxidase and adenosine deaminase) 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.

Imbalance between production of reactive oxygen species (ROS) and total antioxidant capacity in testis, epididymis, and seminal fluid can eventually lead to subfertility and infertility. Abnormal chromatin packaging, and DNA fragmentation is considered as the main underlying causes. In this regard, 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 ICSI cycle.

In this observational study, semen samples were collected from infertile men with at least one failed ICSI cycle (N=20). Sperm parameters, DNA damage, protamine deficiency, persistent histones, and lipid peroxidation were assessed using CASA system, SCSA and TUNEL assays, chromomycin A3, aniline blue, and BODIPY C11 staining, respectively.

A negative significant correlation was observed between sperm concentration with percentage of sperm persistent histones (r= -0.56; p=0.02), while positive significant correlations were found between percentage of sperm persistent histones with percentage of abnormal morphology (r= 0.54; p=0.02), CMA3-positive spermatozoa (r=o.6; p=0.008) and intensity of lipid peroxidation (r=0.6; p=0.01). In addition, significant correlation was observed between sperm DNA damage with intensity and percentage of lipid peroxidation (r=0.62; p=0.009). Correlation between CMA3-positive spermatozoa and intensity of lipid peroxidation (r=0.5; p=0.03) were also significant.

Observed significant correlations between sperm functional tests in infertile men with at least one failed ICSI cycle, indicated that the reduction of oxidative stress by antioxidant supplementation may be considered as one therapy approach that can improve sperm function and increase the chance of successful clinical outcomes in next assisted reproductive cycle.

In the present study, the effects of alginate (ALG) concentration and ovarian cells (OCs) on the development and function of follicles were simultaneously evaluated.

In the first step, preantral follicles (100-130 µm in diameter) were mechanically isolated from the ovaries of 2-week-old NMRI 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 follicles and the maturation of oocytes were evaluated during culture. In the second step, preantral follicles were cultured in the best ALG concentration (determined in the first step), in the absence or presence of OCs. Afterward, the amount of DNA fragmentation, connexin 37 and connexin 43 proteins expression and estradiol, progesterone and androstenedione secretions by the follicles and the quality of mature (MII) oocytes were assessed.

Our data revealed that in the absence of OCs, follicles of 0.5% group showed a higher survival rate than 0.75 and 1% groups (71.87 vs. 52.52 and 40%; P < 0.05); nonetheless, the antrum formation rate of 1% group was higher and its oocytes degeneration rate was lower than other groups. Furthermore, it was shown that co-culture of follicles with OCs relatively increased the follicles diameter, survival, antrum formation, and GV to GVBD/MII transition rates. At last, the comparison of 0.5%-OCs and 0.5%+OCs groups indicated that 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 oocyte’s cortical granules abnormalities (100 vs. 40% for 0.5%-OCs and 0.5%+OCs groups).

The present study revealed that 0.5% ALG hydrogel is relatively more suited to preantral follicles culture and in the presence of OCs mimics the ovarian condition better than 0.75 and 1% ALG hydrogels.

Aspirated ovarian follicular fluids (FF) contain luteal granulosa cells (LGC) and other contaminating cell types. Several strategies such as the antibody binding methods, the flask method, the cell strainer, and the positive selection of granulosa aggregates after density gradient centrifugation, were tested as LGCs purification methods. Each of these strategies has its own advantages and disadvantages. The positive selection of granulosa aggregates after density gradient centrifugation is simple, rapid, and efficient in terms of LGC recovery. However, it results in a low purity. Here we aimed to test if modifying the traditional protocol by collecting the aggregates, from the follicular fluid, before the density gradient centrifugation could decrease the percentage of contaminating cells.

In the present prospective study, 32 FF, from 32 women,were randomly assigned into one of the two purification techniques: The positive selection of granulosa aggregates after density gradient centrifugation (DG/Agg) (n=16)or the positive selection of granulosa aggregates from the FF before density gradient centrifugation (Agg/DG) (n=16). At the end of each procedure the cell count, vitality, morphology, and the purity of the cell suspension were evaluated.

No significant difference was detected in the total number of granulosa cells between DG/Agg and Agg/DG (p>0.05). However, a higher percentage of granulosa cells 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.

Here we showed that the positive selection of granulosa aggregates from the FF prior to density gradient technique had a higher purity compared to the traditional protocol. Thus, it could be a method of choice to prepare granulosa cells 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 apoptosis. Some factors hasten such depletion such as chemo- and radiotherapy. Others have been investigated in trials to preserve the OR including gonadotropins, cytokines, growth hormones, nitric oxide and reorganization of the actin cytoskeleton. The loss of ovarian reserve occurs normally at the menopausal age, a stage called menopausal ovarian senescence. At some periods, there are other sources for ovarian hormones away from the ovary such as during use of contraceptive pills and at pregnancy after the formation of the placenta. Future trials to preserve the ovarian follicles at these periods might postpone the onset of the menopause and hence lengthen the fertile female age.