International Journal Of Fertility and Sterility
Volume:12 Issue: 4, Jan-Mar 2019

Calcium (Ca) is a significant element that acts as an intracellular second messenger. It is necessary for many physi- ological processes in spermatozoa including spermatogenesis, sperm motility, capacitation, acrosome reaction and fertilization. Although influences of Ca deficiency on sperm function and male infertility have been widely studied, mechanisms for these abnormalities are not well considered. Poor sperm motility, impairment of chemotaxis, capaci- tation, acrosome reaction and steroidogenesis are the major mechanisms by which Ca deficiency induces male infertil- ity. Therefore, an optimal seminal Ca concentration is required to strengthen sperm function and all steps leading to successful fertilization. Furthermore, identification of these mechanisms provides valuable information regarding the mechanisms of Ca deficiency on male reproductive system and the way for developing a better clinical approach. In this review, we aim to discuss the proposed cellular and molecular mechanisms of Ca deficiency on male reproductive system, sperm function and male fertility. Also we will discuss the valuable information currently available for the roles of Ca in male reproduction.

Acrosome plays an integral role during fertilization and its absence in individuals with globozoospermia leads to failure of in vitro fertilization (IVF) and oocyte activation post-intracytoplasmic sperm injection (ICSI). A variety of processes, organelles and structures are involved in acrosome biogenesis including, trans-golgi network (TGN), acroplaxome and cellular trafficking. This review aims to explain roles of related signals and molecules involved in this process and also describe how their absence in form of mutation, deletion and knockout model may lead to phe- nomenon referred to globozoospermia.

Infertile women are at a higher risk of sexual dysfunction compared to fertile women. Infertility is a major source of stress, anxiety, and depression, which strongly affects sexual health. The aim of this study is to estimate the prevalence of female sexual dysfunction (FSD) among infertile Iranian women. We searched the main international databases (Web of Science, PubMed, Medline, and Scopus) and national databases (Scientific Information Database, Magiran, and IranMedex) from their inception until April, 2017. Due to heterogeneity between the studies, the extracted data were pooled using a random-effects model by Stata software. Out of 313 retrieved studies, we included 18 studies of 3419 infertile women in the meta-analysis. The pooled prevalence of FSD was 64.3% [95% confidence interval (CI): 53.3-75.3]. Our findings revealed that sexual desire (59.9%, 95% CI: 38.7-81.2) was the most prevalent disorder and vaginismus (19.2%, 95% CI: 11.3-27.2) was the least prevalent among infertile women. The results of our meta- analysis suggested that more than 64% of infertile Iranian women reported sexual dysfunction, which was meaning- fully high. This study also showed that sexual desire was significantly more common than other sexual dysfunction dimensions and the prevalence of vaginismus was the least common.

Background: Multiple studies have been carried out examining the association of tumor necrosis factor-α gene (TNF-α) promoter region polymorphisms with recurrent pregnancy loss (RPL) risk. However, the results remain con- troversial and incomplete. Hence, we performed a meta-analysis to evaluate the association of the TNF-α -308G>A and -238G>A polymorphisms with RPL risk.
Materials and Methods: In this meta-analysis, a comprehensive search of PubMed, Web of Knowledge and EM- BASE was performed to identify relevant studies published until December 1, 2017. The associations were assessed by odds ratio (OR) and its corresponding 95% confidence interval (CI).
Results: A total of 29 case-control studies, comprising 20 studies on TNF-α -308G>A (3,461 cases and 3,895 con- trols) and nine studies on TNF-α -238G>A (2,589 cases and 2,664 controls), were included in the meta-analysis. Over- all, we found TNF-α -308G>A to be associated with an increase in RPL risk under the homozygote (OR=1.716, 95% CI: 1.210-2.433, P=0.002) and the recessive (OR=1.554, 95% CI: 1.100-2.196, P=0.012) models. TNF-α -238G>A was also significantly associated with increased risk of RPL under the allele model (OR=1.554, 95% CI: 1.100-2.196, P=0.012). Stratified analysis revealed a more significant association between the TNF-α -308G>A polymorphism and increased RPL risk in Asians under the homozygote (OR=2.190, 95% CI: 1.465-3.274, P≤0.001), the dominant (OR=1.642, 95% CI: 1.269-2.125, P≤0.001) and the recessive (OR=1.456, 95% CI: 1.039-2.040, P=0.029) models, but not in Caucasians. A non-significant association was, however, identified between TNF-α -238G>A and RPL risk based on ethnicity. Moreover, TNF-α -308G>A and -238G>A polymorphisms were significantly associated with in- creased risk of RPL in high quality studies and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) subgroups.
Conclusion: The present meta-analysis demonstrates that TNF-α -308G>A and -238G>A polymorphisms are associ- ated with an increased risk of RPL.

Background: Osteopontin (Opn) is one of the co-factors involved in cell adhesion and invasion during the implanta- tion process. Several reports have shown Opn expression changes in diabetic condition in several tissues. In addition, an increased incidence of spontaneous abortion is reported in diabetic women. We, therefore, designed a study to eval- uate the effects of diabetes on Opn expression at implantation time after treatment with metformin and pioglitazone. Materials and Methods: In this interventional and experimental study, 28 rats were randomly divided into four groups, namely control, diabetic, pioglitazone-treated diabetic rats and metformin-treated diabetic rats. Streptozo- tocin (STZ) and nicotinamide (NA) were used to induce type 2 diabetes (T2D). During the implantation window, the endometrium was removed and the expression of Opn was analysed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results: Opn expression was significantly higher (30.70 fold-changes) in the diabetic group in comparison with the control group (P=0.04). Furthermore, the expression of Opn was significantly lower in the diabetic group treated with pioglitazone when compared with the diabetic group (P=0.04).
Conclusion: According to the high Opn expression and the possibility of increased adhesion of endometrial epithelial cells, the invasion of blastocyst may be affected and thus reduced. As pioglitazone significantly reversed the upregula- tion of Opn in diabetic rats, it may be considered as a therapeutic compound for treating T2D.

Background: Microdeletions of the Yq chromosome are among the most frequent genetic etiological factor of male infertility which spans the azoospermia factor regions (AZFa, AZFb and AZFc). Microdeletions are mostly seen in the AZFc region and usually cover genes actively involved in spermatogenesis. Partial AZFc microdeletions may also occur with various spans, namely gr/gr, b2/b3 and b1/b3. It is known that the outcome of microtesticular sperm extraction (TESE), the surgical process for sperm retrieval from the testis in infertile azoospermic men, may be pre- dicted based on the type of AZF microdeletion. We therefore aimed to evaluate the correlation between partial AZFc microdeletions and microTESE results. Materials and Methods: In this cross-sectional study, 200 infertile azoospermic men referred to the Royan Institute were examined for the presence of partial AZFc microdeletions before undergoing microTESE. Partial AZFc micro- deletions were detected by multiplex polymerase chain reaction (PCR) of seven different sequence-tagged site (STS) markers. The data were analyzed with the Chi-square test. Results: Among the 90 patients (45%) with a positive microTESE outcome, 9 (10%) showed a partial microdeletion in AZFc region. Of the 110 (55%) patients with a negative microTESE outcome, 7 (6.3%) had an AZFc partial micro- deletion. With respect to the span of the microdeletions, among the 200 patients, 11 (5.5%) were gr/gr and 5 (2.5%) were b2/b3. Statistical analysis showed no significant difference between the patients with and without partial AZFc microdeletions with respect to microTESE outcome. Conclusion: Partial AZFc microdeletions is not a predictor of microTESE outcome in azoospermic men.

Background: Assessing the net-results of microsurgical varicocelectomy in infertile men with non-obstructive azoosper- mic (NOA) and clinical varicocele in five years at Royan Institute. Materials and Methods: This is a descriptive retrospective cohort study. A backward-looking review of patients treated for NOA and varicocele from march 2011 to march 2016 was performed. In addition, MDTESE results of 57 patients with NOA and clinical varicocele, with 537 NOA patients without varicocele were compared. Results: Of 57 patients who underwent varicocelectomy, eight patients (14%) had sperm on sperm analysis post-opera- tively. One of the eight patients was single, and one of them had spontaneous pregnancy (1/7) 14%, and one had a child by microinjection (1/7) 14%. Out of these 8 patients, 6 had hypospermatogenesis pathology. Of 38 patients who under- went MDTESE, 14 patients (36%) had sperm on their testis tissues, but one of them had no egg fertilization. Therefore, the fertilization rate was (92%). Of the remaining 13 patients, 3 had live child birth (3/13) 23%. Sperm retrieval rate (SRR) in NOA men without clinical varicocele was lower from those who had varicocele and NOA (22 vs. 36%). Also live birth rate in NOA men with varicocelectomy was higher than NOA men without varicocele (23 vs. 11%). Conclusion: Microsurgical varicocelectomy in NOA men may have positive effects on post-operative sperm in ejacu- late and natural or assisted pregnancies, but it seems that the effect is more significant on MDTESE results and follow- ing successful microinjection. Meanwhile, SRR and live birth rate was higher in our patients compare to NOA men without clinical varicocele.

Background: Human papillomavirus (HPV) is a DNA virus that causes sexually transmitted infections (STI). Recent reports suggest that HPV may affect sperm parameters and lead to male infertility. This study aims to evaluate the cor- relation between seminal high-risk HPV infection and impairment of sperm quality in infertile Iranian men. Materials and Methods: In this case-control study, we collected fresh semen samples from 70 fertile men and 70 confirmed infertile men who referred to Yazd Infertility Centre in 2015. Semen analyses were performed according to the World Health Organization (WHO) guidelines. High-risk HPV DNA was detected by real-time polymerase chain reaction (PCR). Results: A total of 140 subjects participated in the current study. Among 70 confirmed infertile males, only 8 (11.43%) cases tested positive for high-risk HPV and all fertile men were HPV-negative. This data revealed a significant asso- ciation between high-risk HPV and male infertility (P=0.03). The percentage of normal sperm morphology and sperm motility rate significantly declined in men infected with HPV (P<0.001). Conclusion: There was a significantly higher prevalence of high-risk HPV in infertile men than fertile men. HPV infection seemed to be a risk factor for male infertility. Additional, larger studies should be conducted to confirm the impact of HPV on male infertility.

Background: The objective of this study was to describe the association between luteinizing hormone (LH)/ follicle-stimulating hormone (FSH) ratio and demographic variables and maturation stage of oocytes in insulin- resistant and insulin-sensitive patients with polycystic ovary syndrome (PCOS) in comparison with control group. Materials and Methods: In this case-control study, 60 patients with in vitro fertilization (IVF)/intracytoplas- mic sperm injection (ICSI) indication were subdivided into 3 groups as follow: 20 subjects were assigned to control (fertile women with male infertility history) group, 20 subjects with PCOS were insulin resistant (IR) and 20 subjects with PCOS were insulin sensitive (IS). After puncture, retrieved oocytes were classified into metaphase II (MII) as mature and in metaphase I (MI) or germinal vesicle stage (GV) as immature. Regres- sion analyses were used to explore the association between MII oocyte number and demographic and clinical variables. Results: LH/FSH ratio was significantly higher in PCOS-IR women compared to controls but not significantly dif- ferent from that of PCOS-IS group. PCOS-IR women had lower MII oocyte number compared with that of controls. According to multiple regression analysis, the number of previous assisted reproductive technology (ART) cycles was negatively associated with the number of MII oocytes. Conclusion: Insulin resistance can be associated with reductions in MII oocyte number in patients with PCOS.

Background: Infertility is one of the most common challenges that women in reproductive age would encounter today. The maternal nutritional status could be a determinant of oocyte quality and embryonic growth. This study was conducted to assess the relationship between dietary patterns and reproductive outcomes in infertile women. Materials and Methods: This prospective cohort study was conducted on 140 women with primary infertility who had referred to Isfahan Fertility and Infertility center, Isfahan, Iran. The average number of total oocytes and metaphase II oocytes, the fertilization rate, the ratio of good and bad quality embryo and biochemical and clinical pregnancy were considered as the outcomes of assisted reproductive techniques (ART). A 168-item food frequency questionnaire was used for estimating the dietary intakes during the last year. Factor analysis was used for identifying the dietary patterns and analysis of variance (ANOVA), analysis of covariance (ANCOVA), chi-square, and logistic regression analysis were used for assessing the relation between dietary patterns and ART’s outcomes. Results: Three major dietary patterns (the healthy, western and unhealthy diet) were identified. Women with high adherence to the “healthy diet” had a higher educational level and were employed. There was a significant increase in the average number of total oocytes (P-trend=0.009) and metaphase II oocytes (P-trend=0.006) in the third tertile of “healthy diet” compared to the first tertile. Also, women with high adherence to the second tertile of “unhealthy” diet compared to the first tertile, had a significantly lower chance of getting pregnant [odds ratio (OR): 0.14, 95% confidence interval (CI): 0.3-0.7]. Conclusion: Nutrition status could affect infertility treatment outcomes. Greater adherence to the healthy diet may enhance oocyte quality and quantity. Unhealthy diet could adversely affect the chance of getting pregnant.

Background: Potentially modifiable factors, such as the appropriate informing process given to infertile patients, can affect their infertility knowledge and information. This study aims to assess infertility information provided to Irani- ans who undergo assisted reproductive treatment. Materials and Methods: In this cross-sectional study, participants recruited were a convenience sample of all infer- tile patients who received assisted reproductive treatments from Royan Institute, Tehran, Iran. Inclusion criteria con- sisted of: patient’s first time visit, no previous infertility treatment failures, and referral to the centre between January and March 2015. A 20-item tool designed by researchers measured patient satisfaction with the infertility informing process. This tool included cause of infertility, type of recommended treatment, diagnostic procedures, approximate treatment duration, success rate of the treatment, approximate cost of treatment, and non-therapeutic factors in treat- ment success. Results: A total of 235 infertile patients were invited to participate in the study, from which 200 (100 men and 100 women) participants completely responded to the questionnaire with a response rate of approximately 85%. The mean age of participants was 30.93 ± 5.56 years. In terms of satisfaction with information provided about the cause of in- fertility, male responders reported the lowest mean score of 3.59 ± 1.05 compared to female responders (3.82 ± 0.85, P=0.078). Infertile women had a greater mean score of 3.85 ± 0.78 than infertile men (3.58 ± 1.29) in satisfaction with information provided about the type of recommended treatment (P=0.037). There was a statistically significant difference between males (3.26 ± 1.04) and females (3.58 ± 0.93) in satisfaction with approximate treatment duration (P=0.031). Conclusion: According to the results, most infertile patients were satisfied with the informing process related to the cause of infertility and recommended therapies. Information about infertility should be provided more systemati- cally to all treated patients by medical staff, especially in terms of success rate of treatment and financial cost of therapy.

Background: Antenatal anxiety or maternal stress is a prevalent chronic mental disorder in pregnant women. We have assessed the effect of maternal stress from positive aneuploidy screening results on the changes in uterine artery blood flow. Materials and Methods: We performed a prospective cohort (one sample) pilot study at a hospital in Tehran, Iran. A total of 60 pregnant women who were candidates for amniocentesis due to abnormal sequential screening test results entered the study. We conducted 2 standard psychological tests, the Spielberger’s State-Trait Anxiety Inventory and the Beck Anxiety Inventory, to determine anxiety levels in the participants before amniocentesis and two weeks after amniocentesis. The uterine artery resistance index was also measured before and two weeks after amniocentesis. The level of maternal stress was compared with the uterine artery resistance index. Results: Patients had a mean State Trait Anxiety Inventory score before amniocentesis of greater than 40, which meant that the mothers experienced high anxiety. There were no correlations between both inventories’ anxiety scores and uterine artery blood flow before amniocentesis. However, two weeks after amniocentesis, we observed significant negative correlations between the State Anxiety (P=0.0041) and Trait Anxiety (P=0.010) Inventory scores and the uterine artery resistance indexes. Also, there was an association between the decreased right uterine artery resistance index and State Anxiety scores (P=0.036). There were significant correlations between State and Trait Anxiety scores and second trimester analytes of β-human chorionic gonadotropin (β-hCG, P<0.001), α-fetoprotein (P<0.001), and unconjugated estriol (P=0.048). Conclusion: Maternal anxiety because of positive aneuploidy screening serum analytes and amniocentesis can af- fect perinatal outcomes via mood-based alterations in blood flow of the uterine arteries and the screening markers β-hCG,unconjugated estriol, and α-fetoprotein.

Energy balance is regulated by ghrelin which is a neuroendocrine modulator. Ghrelin is expressed in repro- ductive organs. However, the role of ghrelin during in vitro maturation (IVM) and bovine preimplantational development is limited. The purpose of this study was to measure the expression of ghrelin (GHRL) and its receptor growth hormone secretagogue receptor 1A (GHS-R1A) mRNA, and determine cumulus oocyte complex (COC) viability after IVM with 0, 20, 40 and 60 pM of ghrelin. Also, pronuclear formation was recorded after in vitro fertilization (IVF). GHRL and GHS-R1A mRNA expression in oocyte and cumu- lus cells (CCs) was assessed using reverse transcription-polymerase chain reaction (PCR). Oocyte and CC viability were analyzed with the fluorescein diacetate fluorochrome-trypan blue technique. Pronuclear formation was determined 18 hours after IVF with Hoechst 33342. The results demonstrated that ghrelin mRNA is present in oocyte and CCs before and after 24 hours IVM with all treatments. Ghrelin receptor, GHS-R1A, was only detected in oocytes and CCs after 24 hours IVM with 20, 40 and 60 pM of ghrelin. Oocyte viability was not significantly different (P=0.77) among treatments. However, CC viability was significantly lower (P=0.04) when COCs were matured with ghrelin (77.65, 72.10, 66.32 and 46.86% for 0, 20, 40, and 60 pM of ghrelin, respectively). The chance of two pronuclei forming were higher (P=0.03) when ghrelin was not be added to the IVM medium. We found that ghrelin negatively impacts CC viability and pronuclear formation.

The efficacy of in vitro fertilization (IVF) for treating human infertility has only one final efficacy index and that is the achievement of a delivery. However, with the evolution of the freeze-all strategy, a new problem is arising for evaluating the performance of an embryological team. The aim of the study was to present a new representative index, combining fresh and frozen embryo transfer success rates. In this opinion article, apart from the effectiveness of managing fresh gametes and embryos, we wish to evaluate the efficacy of the processes of both freezing and thawing of the produced embryos. The reporting of pregnancy rates of an IVF unit in the past was primarily laying in the fresh embryo transfer (ET) pregnancy rates. Now with the most frequent utilization of freeze-all strategy, it does not seem logical to report only on poor prognosis patients as all the good cases are postponed for thawed cycles. Ongoing implementation of the freeze-all strategy has indicated the need to establish a new representative index that may combine the success of both fresh and frozen cycles performed in the same woman; an index that may not be biased by the policy of an IVF center towards or against the freeze-all strategy. This newly proposed index, which is referred to as COMFFETI (Combined Fresh & Frozen Embryo Transfers per Individual), describes the optimal way to report final reproductive outcomes in the present opinion article.