International Journal Of Fertility and Sterility
Volume:15 Issue: 3, Jul-Sep 2021

Semen analysis is usually the first step in the assessment of male fertility. Although analyzes provide valuable information about male fertility, success of cytoplasmic sperm injection using this method is not predictable. In the recent years, studies have shown that sperm quality assessment helps clinicians predict male fertility status based on the expression of biomarkers. To write this article, a comprehensive study was conducted on several RNA transcripts by searching related words on medical information databases by 2018. According to the literature, spermatogenesis based disorders in male infertility have a significant relationship with the expression level of some RNA molecules (like DAZ and PRM1/PRM2 ratio) in semen and testicular tissue. Thus, they might be used as predictor biomarkersto evaluate success rate of testicular sperm extraction (TESE) procedure, but confirmation of this hypothesis requires more extensive research. By comparing the number of RNAs attributed to each fertility disorder in men, it is possible to trace the causes of disease or return fertility to some infertile patients by regulating the mentioned molecules. Further researches can provide a better understanding of the use of RNA expression profiles in the diagnosis and treatment of male infertility.

Prior to chemotherapy interventions, in vitro maturation (IVM) of folliclesthrough vitrification can be used to help young people conserve their fertility.   This experimental study was conducted on immature female BALB/c mice (12-14 days). Follicles were gathered mechanically and placed in α-Minimal Essential Medium (α-MEM) containing 5% fetal bovine serum (FBS). Some pre-antral follicles were frozen. The fresh and vitrified follicles were cultured in different concentrations of sodium alginate (0.25%, 0.5%, and 1%) and two dimensional (2D) medium for 12 days. The samples were evaluated for viability percentage, the number of MII-phase oocytes and reactive oxygen specious (ROS) level. Additionally, Gdf9, Bmp15, Bmp7, Bmp4, Gpx, mnSOD and Gcs gene expressions were assessed in the samples.  The highest and lowest percentages of follicle viability and maturation in the fresh and vitrified groups were respectively 0.5% concentration and 2D culture. There was no significant difference among the concentrations of 0.25% and 1%. Viability and maturation of follicles showed a significant increase in the fresh groups in comparison with the vitrified groups. ROS levels in the both fresh and vitrified groups with different concentrations of alginate showed a significant decrease compared to the control group. ROS levels in follicles showed a significant decrease in the fresh groups in comparison with the vitrified groups (P≤0.0001). The highest gene expression levels were observed in the 0.5% alginate (P≤0.0001). Moreover, the viability percentage, follicle maturation, and gene expression levels were higher in the fresh groupsthan the vitrified groups (P≤0.0001).   Alginate hydrogel at a proper concentration of 5%, not only helps follicle get mature, but also promotes the expression of developmental genes and reducesthe level of intracellular ROS. Follicular vitrification decreases quality of the follicles, which are partially compensated using a three dimensional (3D) cell culture medium.

Premature ovarian failure (POF) can be found in 1% of women at the age of 35-40, mostly due to unknown causes. PI3K-Akt signaling is associated with both ovarian function and growth of primordial follicles. In this study, we examined the effects of autologous in vitro ovarian activation with stem cells and autologous growth factors on reproductive and endocrine function in patients with ovarian impairment. The longitudinal prospective observational study included 50 patients (between 30 and 50 years) with a diagnosis of POF and infertility. This multicenter study was performed at Jevremova Special Hospital in Belgrade, Saint James Hospital (Malta), and Remedica Skoplje Hospital, between 2015 and 2018. All patients went through numerous laboratory testings, including hormonal status. The autologous bone marrow mesenchymal stem cells (BMSCs) and growth factors were used in combination for activation of ovarian tissue before its re-transplantation. The software package SPSS 20.0 was used for statistical analysis of the results. Differences in follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (PG) hormone concentrations before and after 3, 6, and 12 months post-transplantation were tested in correlation with the volume of transplanted ovarian tissue. A significant correlation (P=0.029) was found between the change in E2 level after 3 months and the volume of re-transplanted tissues. Also after re-transplantation, 64% of the patients had follicles resulting in aspiration of oocytes in 25% of positive women with follicles.   The SEGOVA method could potentially solve many human reproductive problems in the future due to the large number of patients diagnosed with POF, as well asthe possibility of delaying menopause, thus improving the quality of life and general health (Registration number: NCT04009473).

  Infertility stigma is a phenomenon associated with various psychological and social tensions especially for women. The stigma is associated with a feeling of shame and secrecy. The present study was aimed to explore the concept of infertility stigma based on the experiences and perceptions of infertile women. This qualitative conventional content analysis study was conducted in Isfahan Fertility and Infertility Center, Iran. Data were collected through in-depth interviews with 17 women who had primary infertility. All the interviews were recorded, transcribed and analyzed according to the steps suggested by Graneheim and Lundman. The Standards for Reporting Qualitative Research (SRQR) checklist was followed for this research. Eight hundred thirty-six initial codes were extracted from the interviews and divided into 25 sub-categories, 10 categories, and four themes. The themes included “stigma profile, self-stigma, defensive mechanism and balancing”. Stigma profile was perceived in the form of verbal, social and same sex stigma. Self-stigma was experienced as negative feelings and devaluation. Defensive mechanism was formed from three categories of escaping from the stigma, acceptance and infertility behind the mask. Two categories; empowered women and pressure levers, created a balancing theme against the infertility stigma.   Infertile women face social and self-stigma which threatenstheir psychosocial wellbeing and self-esteem. They use defensive response mechanisms and social support to mitigate these effects. Education focused on coping strategies might be helpful against infertility stigma.

Polycystic ovary syndrome (PCOS) is considered to be one of the most common endocrine disorders in women of reproductive age. Zinc, a vital trace element in the body, plays a key role in maintaining health, especially due to its antioxidant role. On the other hand, lack of antioxidants and oxidative stress can adversely affect oocytes quality and consequently fertility rate. The available studiesthat report the effect of follicular fluid (FF) zinc in terms of the number and quality of the oocytes in infertile women with PCOS, are few and not consistent. We decided to investigate this issue.

In this cross-sectional study, from the women with PCOS referring to Omolbanin Hospital, Dezful, Iran (February to December 2019), a total of 90 samples (follicular fluid, oocytes, and embryos) were collected from those who had undergone in vitro fertilization (IVF). To measure zinc level in follicular fluid, high performance liquid chromatograpy (HPLC) was utilized. Also, oocytes maturity and embryos quality evaluation was performed using inverted optical microscopy. One-way ANOVA and Fisher’s least significant difference (LSD) were used for data analysis.

The amount of FF zinc was not associated with any significant differences in the number of oocytes and metaphase I (MI) and germinal vesicle (GV) oocytes, but a significant decrease was observed in the number of metaphase II (MII) oocytes at zinc values lessthan 35 μg/dL. The FF zinc levels lessthan 35 μg/dL were also significantlyassociated with decreased embryo quality.

A significant relationship was found between the level of FF zinc and the quality and the number of oocytes taken from the ovaries of infertile patients with PCOS history who were candidates for IVF treatment as well as the number of high quality embryos.

Gonadotropin-releasing hormone (GnRH) analogues have been extensively utilized in the ovarian stimulation cycle for suppression of endogenous rapid enhancement of luteinizing hormone (LH surge). Exclusive properties and functional mechanisms of GnRH analogues in in vitro fertilization (IVF) cycles are clearly described. This randomized clinical trial was performed to evaluate clinical and molecular impacts of the GnRH agonist and antagonist protocols in IVF cycles. For this purpose, gene expression of cumulus cells (CCs) as well as clinical and embryological parameters were evaluated and compared between two groups (GnRH agonist and antagonist) during the IVF cycle. Twenty-one infertile individuals were enrolled in this double-blind randomized clinical study. Subjects were randomly allocated into two groups of GnRH agonist (n=10) treated patients and GnRH antagonist (n=11) treated individuals. The defined clinical embryological parameters were compared between the two groups. Expression of BAX, BCL-2, SURVIVIN, ALCAM, and VCAN genes were assessed in the CCs of the participants using the real-time polymerase chain reaction (PCR) technique. The mean number of cumulus oocyte complex (COC), percentage of metaphase II (MII) oocytes, grade A embryo and clinical parameters did not show noticeable differences between the two groups. BAX gene expression in the CCs of the group treated with GnRH agonist was remarkably higher than those received GnRH antagonist treatment (p <0.001). The mRNA expression of BCL-2 and ALCM genes were considerably greater in the CCs of patients who underwent antagonist protocol in comparison to the group that received agonist protocol (p <0.001). Despite no considerable difference in the oocyte quality, embryo development, and clinical outcomes between the group treated with GnRH agonist and the one treated with antagonist protocol, the GnRH antagonist protocol was slightly more favorable. However, further clinical studies using molecular assessments are required to elucidate this controversial subject (Registration number: IRCT20101115005181N16).

Cisplatin is an effective antineoplastic drug that is used to treat varioustypes of cancers. However, it causes side effects on the male reproductive system. The present study aimed to investigate the possible protective effects of Aloe vera gel (known as an antioxidant plant) on cisplatin-induced changes in rat spermparameters, testicular structure, and oxidative stress markers.

In this experimental study, forty-eight adult male rats were divided into 6 groups including: control, cisplatin (CIS), A. vera (AL), metformin (MET), cisplatin+A. vera (CIS-AL), and cisplatin+metformin (CIS-MET). Cisplatin was used intraperitoneally at a dose of 5 mg/kg on days 7, 14, 21, and 28 of the experiment. A. vera gel (400 mg/kg per day) and metformin (200 mg/kg per day) were administered orally for 35 days (started one week before the beginning of the experiment). Testes weight and dimensions, and morphometrical and histological alterations, activities of antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GPx), serum testosterone concentration, lipid peroxidation level, and sperm parameters were examined.  

Cisplatin caused a significant decrease (p <0.05) in relative weight and dimension of the testis, germinal epithelium thickness and diameter of seminiferoustubules, the numbers of testicular cells, and spermatogenesis indexes.The malondialdehyde (MDA) levels increased and antioxidant enzymes activities decreased in the CIS group compared to the control group (p <0.05). Additionally, sperm parameters (concentration, viability, motility, and normal morphology), and testosterone levels reduced significantly in cisplatin-treated rats (p <0.05). Also, cisplatin induced histopathological damages including disorganization, desquamation, atrophy, and vacuolation in the testis. However, administration of A. vera gel to cisplatin-treated rats attenuated the cisplatin-induced alterations, mitigated testicular oxidative stress and increased testosterone concentration.  

The results suggest that A. vera as a potential antioxidant plant and due to free radicals scavenging activities, has a protective effect against cisplatin-induced testicular alterations.

Because of the widespread use of organophosphate (OP) pesticides in agriculture, they are major environmental contaminants in developing countries. OP pesticides decrease sperm concentration and affect its quality, viability, and motility. Studies have demonstrated the association between abnormal semen analysis and OP pesticides exposure among the high-risk population. Asthere is limited data on the percentage of OP pesticides exposure, the study aimed to determine the OP pesticides exposure in Southern Indian men with idiopathic abnormal semen analysis and find the possible source of their OP pesticides exposure.  

 In this cross-sectional pilot study, fifty men with idiopathic abnormal semen analysis as cases and fifty men with normal semen analysis as controls were recruited. Detailed history wastaken and general and systemic examinations were carried out. OP pesticides exposure was determined by assessment of pseudocholinesterase and acetylcholinesterase levels and urinary OP pesticides metabolites dialkyl phosphate (DAP) consisting of dimethyl phosphate (DMP), diethyl thiophosphate (DETP), and diethyl dithiophosphate (DEDTP).  

 Cases had statistically significantly lower levels of pseudocholinesterase (5792.07 ± 1969.89 vs. 10267.01 ± 3258.58 IU/L) (P=0.006) and acetylcholinesterase [102.90 (45.88-262.74) vs. 570.31 (200.24-975.30) IU/L] (P=0.001) as compared to controls. Cases had a statistically significantly higher percentage of urinary DAP positivity as compared to controls (80 vs. 38%) (p <0.0001). Hence, cases had a significantly higher percentage of OP pesticides exposure as compared to controls (20 vs. 4 %) (P=0.015). OP-exposed cases had significantly higher urinary DETP and DEDTP levels as compared to OP non-exposed cases. Also, urinary DETP and DEDTP levels were significantly negatively associated with sperm concentration, motility, and normal morphology among OP-exposed cases.

Southern Indian men with idiopathic abnormal semen analysis had a significantly higher percentage of OP pesticides exposure as compared to men with a normal semen analysis.

We aimed to compare the effects of using high-fat (HF) and advanced glycation end-products (AGEs) containing dietsto induce obesity and diabetes on sperm function in mice.  

 In this experimental study, twenty-five 4-week old C57BL/6 mice were divided into 5 groups and were fed with control, 45% HF, 60% HF, 45% AGEs-HF, or 60% AGEs-HF diet. After 28 weeks, fast blood sugar, glucose intolerance, insulin concentration, homeostatic model assessments (HOMA) for insulin resistance (IR) and HOMA for beta cells (HOMA beta) from systematic blood were assessed. In addition, body weight, morphometric characteristics of testes, sperm parameters, DNA damage (AO), protamine deficiency (CMAA3), and sperm membrane (DCFH-DA) and intracellular (BODIPY) lipid peroxidation were measured.  

 Body mass and fasting blood sugar increased significantly in all experimental groups compared to the control group. Insulin concentration, glucose intolerance, HOMA IR, and HOMA beta were also increased significantly with higher levels of fat and AGEs in all four diets (p <0.05). The changes in the 60% HF-AGEs group, however, were more significant (p <0.001). Morphometric characteristics of the testis, sperm concentration, and sperm morphology in the diet groups did not significantly differ from the control group, while sperm motility and DNA damage in the 45%HF were significantly low. Although for protamine deficiency, both 60% HF-AGEs and 45% HF showed a significant increase compared to the control, the mean of sperm lipid in the 45% HF group and intracellular peroxidation in the 60% HF-AGEs group had the highest and the lowest increases, respectively.  

Our results, interestingly, showed that isthe negative effects of a diet containing AGEs on examined parameters are lessthan those in HF diets. One possible reason is detoxification through the activation of the protective glyoxalase pathway asthe result of the chronic AGEs increase in the body.

 Total fertility rate (TFR) in Iran decreased from the year 2000 and recently Iran has experienced fertility rates below replacement level. Birth interval is one of the most important determinants of fertility levels and plays a vital role in population growth rate. Due to the importance of this subject, the aim of this study was analyzing three birth intervals using three Survival Recurrent Event (SRE) models.   In a 2017 cross-sectional fertility survey in Tehran, 610 married women, age 15-49 years, were selected by multi-stage stratified random sampling and interviewed using a structured questionnaire. The effects of selected covariates on first, second and third birth intervals were fitted to the data using the Prentice-Williams- Peterson-Gap Time (PWP-GT) SRE model in SAS 9.4.   Calendar-period had a significant effect on all three birth intervals (p <0.01). The Hazard Rate (HR) for a short birth interval for women in the most recent calendar-period (2007-2017) was lower than for the other calendarperiods. Women’s migration influenced second (P=0.044) and third birth intervals (P=0.031). The HR for both birth intervals in migrant women was 1.298 and 1.404 times shorter, respectively than non-migrant women. Women’s employment (P=0.008) and place of residence (p <0.05) also had significant effects on second birth interval; employed women and those living in developed, completely-developed and semi-developed areas, compared to unemployed women and those living in developing regions, had longer second birth intervals. Older age at marriage age increased the HR for a short third birth interval (p <0.01).    The analysis of birth interval patterns using an appropriate statistical method provides important information for health policymakers. Based on the results of this study, younger women delayed their childbearing more than older women. Migrant women, unemployed women and women who live in developing regions gave birth to their second child sooner than non-migrant employed women, and women who lived in more developed regions. The implementation of policies which change the economic and social conditions of families could prevent increasing birth intervals and influence the fertility rate.