Objective:For the first time, this study aimed to investigate the potential protective effects of L-carnitine and moderate-intensity exercise training (MIET), both individually and in combination, against varicocele (VCL)-induced impairment of spermatogonial stem cell (SSC) self-renewal. Materials and Methods:In this experimental study, a total of 36 male Wistar rats (200 ± 20 g) were divided into the following groups: control, VCL (3-month and 5-month), and treatment groups receiving either Lcarnitine (100 mg/kg/day, orally) or MIET for two months, starting three months after VCL induction. After three months of VCL induction, the condition was confirmed by measuring serum testosterone levels and sperm count. The animals in the treatment groups were then subjected to L-carnitine, MIET, or their combination for an additional two months. The expression of key markers involved in SSC self-renewal, including glial cell line-derived neurotrophic factor (Gdnf), its receptors C-ret and Gfrα1, and target genes Etv5 and Bcl6b, was assessed and compared between groups. Results:The VCL-sole groups exhibited significant reductions in serum testosterone, sperm counts, and the numbers of Gdnf+, Gfrα1+, and C-ret+ spermatogonia and spermatocytes compared to controls (P=0.001). Lcarnitine and MIET, both individually and in combination, significantly increased Gdnf, Gfrα1, and C-ret expression at mRNA and protein levels, enhanced the numbers of Gdnf+, Gfrα1+, C-ret+, Etv5+, Bcl6b+, and Nanog+ cells per seminiferous tubule, and improved SSC repopulation index (RI). Conclusion:MIET, particularly in combination with L-carnitine, enhances SSC self-renewal by upregulating the Gdnf/C-ret/Gfrα1 signaling pathway and activating downstream target genes, such as Etv5 and Bcl6b.
Objective:Infertility arises from diverse etiologies, with polycystic ovarian syndrome (PCOS) being a leading cause among women, while male factors account for approximately 50% of cases. Selecting the most appropriate assisted reproductive technology (ART) for each couple is crucial. This study aimed to develop a dynamic mathematical model to predict ART success rates based on infertility etiology, laboratory tests, and clinical findings. Materials and Methods:In this retrospective study, data from 1,374 cases were reviewed, and a sample of 502 couples from the Yazd Research and Clinical Center for Infertility, Yazd, Iran, was analyzed (April 2016-February 2017). Participants were evaluated according to body mass index (BMI), anti-Müllerian hormone (AMH) levels, number of transferred embryos, and infertility etiology of (PCOS, male factor, or both). Couples were categorized into eight classes based on infertility susceptibility, embryo quality (A, B, C), positive beta human chorionic gonadotropin (β-hCG), clinical pregnancy outcomes, and fertility status. Results:The model estimated ART success rates within subgroups considering all relevant factors. Higher BMI (>30 kg/m²) and lower AMH (<3.5 ng/mL) were associated with reduced success rates. Intracytoplasmic sperm injection (ICSI) showed higher predicted success across all etiologies. Mathematical analysis indicated system stability, and backward bifurcation highlighted the importance of increasing recovery rates (positive clinical pregnancy) to reduce the primary reproduction number (R₀) below one and control infertility. No Hopf bifurcation was observed, indicating the absence of periodic fluctuations in treatment outcomes. Conclusion:This dynamic model provides a framework to predict ART success and understand the interactions between clinical and biological factors in infertile couples. It may assist clinicians in optimizing individualized treatment strategies based on patient-specific characteristics.
Objective:Oocyte activation deficiency remains a significant obstacle in assisted reproductive technologies. Intracytoplasmic sperm injection combined with artificial oocyte activation (ICSI-AOA) has been introduced as a promising strategy to enhance fertilization efficiency and clinical outcomes. This study aimed to provide a comprehensive analysis of clinical results from 1,300 ICSI-AOA cycles and to assess the health status of the resulting offspring. Materials and Methods:This retrospective study analyzed 1,300 ICSI-AOA cycles performed between 2018 and 2020. Follow-up assessments were conducted after live birth to evaluate child health. Fertilization outcomes, embryo development parameters, pregnancy results, and offspring health status were examined using imaging, molecular, and biochemical approaches to ensure a comprehensive evaluation. Results:Across the 1,300 ICSI-AOA cycles, the failed fertilization rate was 4.54% and 20.16% of cycles were cancelled, while 91.06% proceeded to embryo transfer. Of 14,522 retrieved cumulus-oocyte complexes, 85.38% reached maturation. Mature oocytes showed a fertilization rate of 59.69% and a cleavage rate of 96.93%, producing 7,180 day-three embryos. Fresh transfers (n=571) resulted in chemical and clinical pregnancy rates of 24.6% and 20.82%. In addition, 3,270 embryos were cryopreserved, and thawed transfers achieved chemical and clinical pregnancy rates of 22.55% and 21.61%. Among 3,018 non-frozen embryos, 447 formed blastocysts, and 44 fresh blastocyst transfers yielded pregnancy rates of 21.87% (chemical) and 9.38% (clinical). Thawed blastocyst transfers achieved chemical and clinical pregnancy rates of 23.67% and 22.11%. Overall, 266 live births were obtained from 1,317 transfers, corresponding to a 14.19% implantation rate and a 20.20% per-cycle live birth rate, with anomalies detected in 1.5% of offspring. Conclusion:ICSI-AOA provides favorable fertilization, pregnancy, and live birth outcomes, and no major health concerns were observed in the resulting children, consistent with previous ICSI reports.
Objective:Antiphospholipid antibodies (aPL) may contribute to recurrent implantation failure (RIF) in women undergoing in vitro fertilization (IVF). These antibodies may impair endometrial receptivity and placentation, though evidence remains contradictory due to incomplete aPL data, nonstandardized testing, and inconsistent outcome definitions. To evaluate associations between aPL and pregnancy outcomes in women with RIF following IVF. Materials and Methods:In this retrospective cohort study, we analyzed women with 2 or more unexplained implantation failures following IVF. All participants underwent repeated aPL testing-lupus anticoagulant (LA), anticardiolipin (aCL) IgG/IgM, and anti-beta2-glycoprotein I (anti-β2GPI) IgG/IgM-at ≥ 12 weeks intervals. The primary endpoint was the cumulative live birth rate across the first 6 embryo-transfer (ET) cycles. The secondary endpoint comprised per-cycle obstetric outcomes and the influence of prophylactic low-molecular-weight heparin (LMWH). Results:Among 125 women, 26 (20.8%) tested positive for aPL. LA positivity was the most common (59.3%). Across 327 embryo transfer cycles, the live birth rates were comparable between aPL-negative and aPL-positive groups (7.0 vs 7.8%, respectively). Only anti-β2GPI IgM-positive women achieved live births among aPL-positive patients. Cumulative live birth rates after 6 ET cycles reached 38% (95% CI: 15-56) for aPL-negative and 25% (95% CI: 0-46) for aPL-positive women. aPL positivity showed no significant association with live birth (adjusted hazard ratio 0.89, 95% CI: 0.32-2.45, P=0.821). Prophylactic LMWH demonstrated no significant improvements in live birth rates [crude risk ratio (RR) 2.20, 95% CI: 0.73-6.62, P=0.163]. Conclusion:Live birth rates were similar between anti-β2GPI IgM-positive and aPL-negative women. No births occurred among LA-positive or aCL-positive patients. LMWH showed no statistically significant benefit. Prospective studies are warranted to confirm these findings (registration number: TCTR20231003007).
Objective:Human papillomavirus (HPV) is a prevalent sexually transmitted virus hypothesised to contribute to unexplained male infertility that potentially affects sperm quality. The current research looks at the impact of HPV infections on sperm quality. Materials and Methods:Web of Science, PubMed, Cochrane Library, Medline, and Embase databases were searched on August 24, 2024 for reviews that examined the relationship between sperm quality and HPV infection, which were published between 1996 and 2024. PRISMA guidelines were followed for this study. The AMSTAR tool was used to assess the risk of bias. Evaluation of heterogeneity was conducted by the Q test and I² statistics. Pooled effect sizes were expressed as the standardised mean difference (SMD) with a 95% confidence interval (95% CI). These were synthesised using fixed-effect or random effects models as appropriate. Results:Out of 537 initially identified articles, 16 systematic reviews and meta-analyses were eligible for inclusion. Our umbrella review results showed that HPV infection in semen significantly reduced progressive motility (SMD = -0.48, 95% CI: -0.75, - 0.21), total motility (SMD = -0.59, 95% CI: -0.82, -0.35), sperm count (SMD = -0.27, 95% CI: -0.43, -0.10), viability (SMD = -0.38, 95% CI: -0.62, -0.14), and morphology (SMD = -0.32, 95% CI: -0.53, -0.10). Conclusion:HPV infections in semen may be a significant factor in the reduction of sperm quality, as observed in HPV-positive relative to HPV-negative individuals.
Objective:Since the complications associated with endometriosis during pregnancy are rare, there is not enough evidence to indicate that this disease has major detrimental effects on pregnancy outcome. Therefore, the present study was conducted with the aim of investigating pregnancy complications related to endometriosis in pregnant women. Materials and Methods:This case-control study was conducted on pregnant women referred to the Obstetrics and Gynecology Clinic at Amiralmomenin Hospital (Zabol, Iran) from 2021 to 2023 to evaluate obstetric complications in those with endometriosis. Fifty pregnant women with endometriosis were compared to fifty pregnant women without endometriosis in terms of pregnancy complications and outcomes. The significance level was considered less than 0.05. Results:The mean age of the participants was 28.8 ± 5.3 years. The youngest and oldest women were 16 and 43 years old, respectively. 47% of all women had at least one pregnancy complication (54% in the endometriosis group and 40% in the normal group (P=0.161). Women with endometriosis had significantly hagher rates of abortion than the control group (P=0.046), but other complications related to pregnancy were not significantly different between the two groups. Conclusion:In this study, abortion was more frequent among pregnant women with endometriosis than among controls. However, no statistically significant between-group differences were observed for the other assessed obstetric complications.
Objective:The primary objective of this study was to develop an artificial ovary made of polylactic acid (PLA) material, which could potentially be used for fertility preservation. This scaffold was used to carry umbilical cord mesenchymal stem cells (UCMSCs) for xenotransplantation to study follicular growth, viability, and angiogenesis. Materials and Methods:The experimental study involved transplanting human ovarian cortical pieces into 3Dprinted baskets, with or without human UCMSCs. Four groups were considered as control: vitrified-warmed ovarian tissue (OT), OT transplantation without 3D-printed baskets without UCMSCs, OT+D; OT transplantation with 3D-printed baskets and without UCMSCs, and OT+D+C; OT transplantation with 3D-printed baskets and UCMSCs. Eighteen rats were divided into three transplantation groups, with grafts implanted into their back muscles. After one week, comparisons were made between OT, OT+D, and OT+D+C with control groups. Histological evaluations and gene expression analyses, including CX37, CX43, KL, GDF9, and VEGF, were conducted to evaluate factors such as angiogenesis, cell proliferation, and follicle development. Results:The results revealed that OT+D had the highest follicular growth (99.3%) and transition rate (74.08%). OT+D+C indicated increased follicular survival, reduced mortality (P<0.0001), and a higher percentage of primordial follicles (59.1%) compared to OT and OT+D groups. UCMSCs' paracrine secretions likely preserved the follicular reserve. Additionally, OT+D+C exhibited significantly increased blood vessel number and diameter (P<0.0001) compared to other groups. Conclusion:This study underscores the significance of utilizing a three-dimensional basket scaffold to enhance the development of ovarian follicles and facilitate angiogenesis. The integration of stem cells with the scaffold demonstrated a noteworthy synergistic effect, resulting in improved preservation and viability of the follicles and Reduced fibrosis. These findings illuminate the promising potential of scaffold-based strategies in advancing reproductive therapies and tissue engineering, thereby offering prospects for innovative treatments in the future.
Objective:Embryo transfer is a complex process that often fails due to poor endometrial growth. Pelvic floor physiotherapy improves endometrial thickness by enhancing pelvic blood circulation and stimulating uterine muscle with varied frequency flows, consequently boosting embryo implantation and pregnancy success rates. The present study aimed to assess the effectiveness of pelvic floor physiotherapy on endometrial thickness during embryo transfer. Materials and Methods:We systematically reviewed databases with no time restriction (out of 574 retrieved records, 8 studies were meta-analysed). This study analyzed randomized controlled trials (RCTs) assessing pelvic floor physiotherapy effects on endometrial thickness in infertile women, compared to routine treatments such as estradiol valerate tablets with vaginal progesterone gel, and oral Progynova. Participants were infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) or frozen ET (FET). Outcomes included endometrial thickness (primary outcome), arterial resistance index (RI), pulsatility index (PI), and pregnancy rate (secondary outcomes). Results:A total of 8 studies were meta-analyzed and we found that electrical physiotherapy combined with routine treatments, may increase the endometrial thickness versus controls [mean difference (MD)=0.93, 95% confidence interval (CI): 0.30 to 1.55; 7 trials, P=0.004; low-certainty evidence], but does not affect RI (MD=-0.03, 95% CI: -0.14 to 0.07; 4 trials, P=0.570; very low-certainty evidence) and PI (MD=-0.16, 95% CI: -0.41 to 0.09; 3 trials, P=0.210; very low-certainty evidence). However, physiotherapy with routine treatments may increase pregnancy rates with low-quality evidence (OR=2.72, 95% CI: 1.87 to 3.95; 6 trials, P<0.001; low-certainty evidence). Conclusion:Our study suggests that combining pelvic floor physiotherapy with standard infertility treatments may enhance endometrial thickness and boost fertility rates compared to standard treatments alone. Critically, this conclusion is based on low to very low-quality evidence, limiting confidence in the observed benefits. Furthermore, the effect of physiotherapy on uterine arterial resistance and pulsatility indices is currently undetermined due to insufficient data (Prospero ID: CRD42023442310).
The sharp decline in fertility in Iran represents one of the country’s most pressing demographic challenges. This trendhas led policymakers to promote childbearing to mitigate further population aging and structural imbalance. Thisstudy uses data from the 2017-2018 Iranian National Marriage and Divorce Survey conducted by the Civil RegistryOrganization, based on a sample of 8,341 individuals preparing for the first marriage, addressing the question: “Howmany children would you like to have after marriage?” The findings showed that the vast majority of respondents(97.9%) intend to have children, with a mean ideal family size of approximately two children. Gender differences areevident, with women tending to prefer one to two children, while men are more likely to report preferences for three ormore. Significant variation is observed across socioeconomic and demographic groups, including education, income,place of residence, and ethnic-religious identity. Rural residents and individuals from larger families report higherfamility ideals, whereas urban residents and those with higher education and income tend to prefer smaller families.Overall, the mean ideal number of children is approximately 2.1, corresponding to replacement-level fertility intentions.The finding suggests that the decline in actual fertility below replacement level is primarily driven by economicand structural constraints rather than a substantial shift in fertility preferences. Accordingly, rather than promotinghigher fertility per se, policies should focus on enabling young couples to realize their existing childbearing intentions,particularly during the early years of marriage.
Objective:Infertility remains a multifactorial disorder influenced by both genetic and environmental factors, yet the molecular interplay between these two dimensions is poorly understood. The Brca1 gene, classically known for its tumor-suppressive role in mammary tissue, also plays a crucial role in maintaining oocyte quality and ovarian reserve. Mutations or dysregulation of Brca1 may therefore link mammary toxicity to reproductive failure. This study investigated the impact of environmental exposure to the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA), in conjunction with selected trace elements [cadmium (Cd), cobalt (Co), and zinc (Zn)], on fertility, oxidative balance, and Brca1 expression in female rats. Materials and Methods:In this experimental study, female Wistar rats were treated with DMBA alone or combined with Cd, Co, or Zn for 20 weeks. Serum oxidative stress biomarkers [malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT)] and mammary gland immunohistochemistry for Brca1, apoptosis, and necrosis were evaluated. Fertility outcomes and cell viability [evaluated using the (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) (MTT) assay] were examined to correlate systemic redox imbalance with reproductive performance. Results:Co- or Cd-combined exposure to DMBA markedly increased oxidative stress and mammary apoptosis, resulting in the lowest fertility rates. In contrast, Zn-co-treatment partially restored antioxidant capacity and reduced cell death, suggesting a modulatory rather than strictly protective role. Dysregulated Brca1 expression across all treatment groups supports a mechanistic link between mammary genotoxicity and impaired fertility. Conclusion:This study integrated genetic susceptibility (Brca1) with environmental metal co-exposure to explain infertility through oxidative and apoptotic mechanisms. The findings showed that trace elements differentially affected reproductive outcomes in Brca1-compromised females, highlighting the reproductive risks posed by Cd and Co and the more nuanced role of zinc. By demonstrating the combined toxicogenetic interaction between DMBA and metal exposure, this work outlined a mechanistic model linking oxidative damage in the mammary gland to declining fertility.
Objective:Polycystic ovary syndrome (PCOS) is a multifactorial, polygenic endocrinopathy with an incompletely understood aetiology that accounts for approximately 80% of female anovulatory infertility. Both genetic and environmental factors contribute significantly to its pathogenesis. This study is the first to investigate the association of DENN/MADD domain-containing 1A (DENND1A rs2479106 and rs10986105), luteinising hormone/choriogonadotropin receptor (LHCGR rs13405728), follicle-stimulating hormone receptor (FSHR rs6166), thyroid adenomaassociated protein I (THADA rs13429458), and cytochrome P450 17A1 (CYP17A1 rs743572) gene polymorphisms with PCOS-related anovulatory infertility in Malay women. Materials and Methods:In this case-control study, 96 participants were recruited - 48 anovulatory infertile-PCOS patients and 48 infertile non-PCOS controls. Single nucleotide polymorphisms (SNPs) were detected using highresolution melting (HRM) analysis, with sequencing performed for validation. Results:The LHCGR rs13405728 polymorphism was strongly associated with an increased risk of PCOS-related anovulatory infertility, with each minor G allele conferring an odds ratio (OR) of 2.63 and 95% confidence interval (95% CI) of 1.11-6.27, P= 0.020). Conversely, the THADA rs7568365 T allele exhibited a protective effect, reducing the risk by 72% (OR=0.28; 95% CI: 0.08-0.90; P=0.020). No significant associations were observed for DENND1A rs2479106 and rs10986105, FSHR rs6166, THADA rs13429458, or CYP17A1 rs743572. Haplotype analysis revealed that the A-T (rs13429458-rs1317772225-rs7568365) and ATA and ACA (rs13405728-rs6166-rs13429458) haplotypes were protective, with ORs of 0.13, 0.19, and 0.30, respectively (P<0.05). Conclusion:The LHCGR rs13405728 polymorphism is significantly associated with the risk of PCOS-related anovulatory infertility in Malay women and may serve as a potential early prognostic biomarker for the development of PCOS-related infertility.
Objective:Sperm freeze-thaw is a crucial technique in assisted reproductive technologies (ART), but it induces oxidative stress in sperm. Melatonin, a powerful antioxidant, reduces oxidative stress by penetrating mitochondria and neutralising free radicals. However, its protective role in the sperm of asthenozoospermic men during freeze-thaw remains poorly understood. This study examines the in vitro effects of melatonin on sperm quality in asthenozoospermic men during the freeze-thaw process. Materials and Methods:In this experimental study, semen samples were collected from 30 asthenozoospermic men and divided into three groups: control group, freeze group, and freeze+melatonin (1 mM) group. Sperm parameters including mitochondrial membrane potential (MMP), plasma membrane integrity, acrosomal reaction, and DNA fragmentation were assessed. The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH), total antioxidant capacity (TAC), malondialdehyde (MDA), reactive oxygen species (ROS), tumour necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) were estimated. Expressions of apoptosis-related genes and proteins, BAX and BCL-2, were also analysed. Results:There was a significant decrease (P=0.004) in sperm parameters, MMP, plasma membrane and acrosome integrity, TAC, GSH, SOD, IL-10 levels, and Bcl-2 expression in the freeze group compared to the control group. Conversely, MDA, ROS, TNF-α, DNA fragmentation, and BAX expression significantly increased (P=0.010). However, all these parameters showed significant improvements in the freeze+melatonin group compared to the freeze group (P=0.019). Conclusion:Melatonin may improve sperm quality during freeze-thaw by increasing antioxidant defence, reducing inflammation via TNF-α/IL-10 modulation, inhibition of apoptosis through BAX/BCL-2 regulation, and preservation of acrosome integrity. These findings suggest that melatonin may have potential as a cryoprotectant in ART.
Advances in early cancer diagnosis and treatment have significantly improved survival rates. However, as awarenessgrows about the adverse effects of cytotoxic therapies on ovarian function and fertility, an increasing number of patientsare seeking fertility preservation before undergoing anti-cancer treatments. Embryo cryopreservation remainsthe gold standard for fertility preservation when there is sufficient time for ovarian stimulation and oocyte retrieval.For single women, oocyte freezing offers a viable alternative, allowing them to preserve their eggs for future use. Forprepubertal girls and women who cannot delay treatment, ovarian tissue cryopreservation is currently the only feasiblemethod of fertility preservation. Between 2000 to 2010, researchers at Royan Institute conducted a wide rangeof investigations on ovarian tissue cryopreservation, providing a structured and evidence-based fertility preservationprotocol for cancer patients candidates for this service. In 2010, the Royan Institute established the Royan HumanOvarian Tissue Bank (OTB) as a subgroup of the Embryology Department. After obtaining ISO 9001:2015 certification,the OTB was officially transferred to the Royan Infertility Clinic. This article presents the Royan OTB guidelinesfor cryopreserving ovarian tissue in prepubertal girls and women with cancer, described step by step.
Objective:Spermatogenesis is a tightly regulated process that involves an orchestrated transcriptional and translational event across the seminiferous epithelium. While individual regulators of this process have been studied, the network-level dynamics underlying the transition from spermatogonial stem cells (SSCs) to round spermatids (RSs) remain poorly understood. The dynamic molecular transitions between SSCs and RSs have not been fully characterised, particularly at the network level. Therefore, this study aimed to characterise the molecular and network-level dynamics underlying the transition from SSCs to RSs by integrating transcriptomic profiling, protein-protein interaction network analysis, functional enrichment, and immunohistochemical validation. Materials and Methods:In this experimental study, we evaluated the gene expression dynamics from SSCs to RSs. We analysed publicly available microarray datasets (GEO) comprising four biological replicates for RSs and three biological replicates for SSCs. Differentially expressed genes (DEGs) were identified and mapped onto proteinprotein interaction (PPI) networks, followed by prioritisation of central regulators. Functional enrichment analysis was performed to characterise biological pathways. Immunohistochemistry (IHC) for SOX9, n-MYC, VASA, SOX2, and DAZL was conducted to examine spatial and developmental protein expressions across the seminiferous tubules. Results:A set of 3598 DEGs was identified between SSCs and RSs. This analysis highlighted central genes, Actb, Kras, Pten, Jun, Cdc42, and Gart, that act as central nodes in spermatogenic networks. These genes were associated with pathways that govern cell cycle regulation, chromatin organisation, and signal transduction, consistent with their established roles in germline development. Protein-level localisation confirmed stage-specific expression patterns within the seminiferous tubules. SOX9 localised to Sertoli cells, n-MYC and VASA were activated in differentiating germ cells, DAZL was restricted to early progenitors, and SOX2 appeared only in late-stage subsets. Conclusion:This study used transcriptomic profiling with network analysis and molecular experiments to reveal novel regulatory connections that underlie the SSC-RS transition. These findings provide a systems-level framework for understanding male germline development and may facilitate future research on infertility and reproductive health.
Objective:Gestational trophoblastic disease (GTD) is characterized genetically by an excess paternal genome and maternal chromosome loss. Intracytoplasmic sperm injection (ICSI) and ICSI with preimplantation genetic screening (PGS) enhance the selection of viable embryos by ensuring that only those with the appropriate genetic makeup are implanted. We aimed to evaluate the pregnancy outcome following ICSI and ICSI/PGS in infertile women with a history of GTDs. Materials and Methods:In this retrospective study, we recruited couples who were referred to the Royan Institute with infertility complaints with GTD history from 2010 to 2022. GTD had been confirmed by serial β-human chorionic gonadotrophin (β-hCG) titer, ultrasonography, and histopathology assessment of the evacuated uterine contents. The fluorescent in situ hybridization (FISH) probes were specific for the chromosomes 13, 18, 21, X, and Y. Results:A total of 69 cycles of ICSI (n=41) and ICSI/PGS (n=28) were analyzed. The two treatment groups were comparable in terms of patients' demographic characteristics. The mean number of total retrieved oocytes, MII oocytes, and obtained embryos in the ICSI/PGS cycle was higher compared to the ICSI cycle (P<0.001 for all). Also, a statistically significant difference between groups in the mean number of poor embryos (P=0.004) was found. No statistically significant difference was observed in clinical pregnancy, miscarriage, and live birth rates per embryo transfer (ET) between groups. The findings indicate that 27.2% of embryos exhibited genetic normalcy in the ICSI/PGS group. Conclusion:Despite achieving more embryos in ICSI/PGS cycles, the success rates of pregnancy in both groups are approximately the same. Both of these methods can be effective in the management of women with the previous GTD. Considering the high costs and the necessity to eliminate 46XX embryos during PGS procedures, it is advisable to restrict this method to cases with a significant risk of recurrent GTD.
Objective:Various studies have reported aberrant function of the immune system in endometriosis. This highly prevalent disease can initiate and progress by numerous genetic and epigenetic alterations that affect immune system functions. Regulatory T cells (Treg) play an important role in controlling and prevention of endometriosis through regulating immune responses. Treg cells are regulated by the forkhead box P3 (FOXP3) gene. The aim of this study is to monitor any changes in gene expression and epigenetic profile of FOXP3) in endometriosis. Materials and Methods:In the current case-control study, endometriotic tissues of women diagnosed with endometriosis (n=20) were compared with non-endometriotic women (n=20). Parallel to expression of this gene, chromatin immunoprecipitation (ChIP) coupled with real-time polymerase chain reaction (PCR) was used to quantify the incorporated levels of the epigenetic activating/repressing markers of H3K9ac/me2 into the FOXP3 promoter (n=6 in each group). Results:There was a significant reduction of FOXP3 in endometriotic tissues compared to the control group (P=0.001). Additionally, changes in the incorporated H3K9ac/me2 epigenetic markers were consistent with the expression results and supported the findings of this study. Conclusion:Downregulation of FOXP3 expression may be involved in the pathogenesis of endometriosis beyond its critical role in Treg responses. In addition, histone modifications of H3K9ac/me2 in the FOXP3 promoter may regulate gene expression in endometriosis.
Objective:Repeated implantation failure (RIF) is a major challenge in in vitro fertilization (IVF). Insufficient uterine blood flow and reduced endometrial thickness are important factors contributing to implantation failure. Pelvic physiotherapy, including electrotherapy, manual therapy, and exercise therapy, has shown potential to enhance endometrial thickness and improve local blood flow through pelvic floor exercises. Transfer of Energy Capacitive and Resistive (TECAR) therapy, a novel physiotherapy modality, promotes vasodilation, tissue oxygenation, and blood circulation. This study presents a clinical trial protocol designed to evaluate the effect of pelvic physiotherapy, comprising electrotherapy, exercise therapy, and TECAR therapy, on uterine blood supply in infertile women with RIF. Materials and Methods:Eligibility criteria include women with a history of at least two RIF events and inadequate uterine blood flow (pulsatility index (PI)> 1.95). The primary aim of this protocol is to evaluate uterine blood flow, endometrial thickness, and endometrial pattern, while secondary outcomes will include sexual function, depression, quality of life, pregnancy and implantation rates, fetal growth up to 12 weeks of gestation, ectopic pregnancy, and miscarriage. Following approval from the relevant ethics committee, this protocol will initially be implemented in a pilot phase involving 22 participants at Al-Zahra Hospital, Tabriz University of Medical Sciences. Results:As of the protocol submission date, the pilot phase is planned but not yet completed. No participant data have been analyzed. Therefore, no results on uterine blood flow, endometrial thickness, implantation rates, or secondary outcomes are available at this stage. Upon completion of the pilot phase and subsequent full-scale trial, the findings will be reported separately. Conclusion:The findings of the forthcoming trial are expected to contribute to establishing evidence-based physiotherapy approaches for improving uterine perfusion and implantation outcomes in infertile women with RIF (registration number: IRCT20230206057338N1).
Objective:Over the past few decades, a marked decline in human semen quality has been observed, with evidence suggesting that dietary factors may account for 50-60% of this decline. The present randomized clinical trial aimed to evaluate the effects of a fertility diet (FD) on sperm parameters in infertile men. Materials and Methods:In this randomized clinical trial study, 70 infertile men were randomly assigned to two groups: the intervention group, which followed the FD plan, and the control group, which kept a healthy diet (HD) for 12 weeks. Anthropometric measurements, semen analysis, DNA fragmentation index (DFI), malondialdehyde (MDA) levels, and sex hormone profiles were assessed before and after the intervention. Dietary intake was monitored throughout the study. Results:Compared to the HD group, the FD group showed significant improvements in total sperm count (P=0.016), sperm concentration (P=0.003), total motility (P=0.024), progressive motility (P=0.048), and normal morphology (P=0.023). Participants in the FD group showed an increase in the intake of total fat, monounsaturated fatty acids, polyunsaturated fatty acids, omega-3 fatty acids and fiber during the intervention (P<0.05). Additionally, the FD group consumed higher amounts of key fertility-related micronutrients including magnesium, calcium, phosphorous, potassium, zinc, selenium, vitamin C, and lycopene. Notably, a significant reduction in DFI (P=0.010) and MDA (P<0.001) was also observed in the FD group compared to the HD group. No significant differences were found in sex hormone levels or anthropometric parameters between the groups. Conclusion:These findings suggest the potential of a FD to improve sperm parameters and reduce DFI and oxidative stress. However, further studies with larger sample sizes and longer durations are needed to confirm these effects (registration number: IRCT20230514058181N1).
Objective:Experimental evidence suggests that the human endometrium expresses receptors for human chorionic gonadotropin (hCG), and activation of these receptors may enhance embryo implantation. Numerous studies have explored the effects of intrauterine hCG injection on embryo transfer (ET) outcomes; however, the impact of systemic hCG administration has been investigated in comparatively fewer studies. This study aimed to evaluate the effects of intramuscular administration of 5000 IU hCG on the outcomes of frozen-thawed ET in hormonal replacement cycles using a gonadotropin-releasing hormone (GnRH)-agonist protocol. Materials and Methods:This randomized controlled trial (RCT, registered April 22, 2021) was conducted at the ROYAN Institute, a tertiary referral center in Tehran, Iran, between July 2020 and August 2022. A total of 200 infertile women undergoing cleavage-stage frozen-thawed ET were enrolled. Inclusion criteria were age <40 years, body mass index <30 kg/m2, and the availability of at least three frozen embryos of good or excellent quality. Participants were randomly assigned to either an intervention group receiving intramuscular hCG (5000 IU administered three times: 72 hours before ET, on the day of ET, and 72 hours after ET) or a control group without hCG. Results:A total of 188 participants completed the trial (93 in the intervention group and 95 in the control group). No significant differences were observed in implantation rate (P=0.903), chemical pregnancy (P=0.912), clinical pregnancy (P=0.999), pregnancy complications (P=0.480), preterm labor (P=0.853), or live birth rate (P=0.233). However, the miscarriage rate was lower in the intervention group. This reduction approached significance per cycle (P=0.059) and reached statistical significance per pregnancy (P=0.011). Conclusion:Intramuscular hCG administration in hormonal replacement cycles with a GnRH-agonist does not significantly affect overall frozen-thawed ET outcomes at the cleavage stage but may be associated with a lower miscarriage rate among those who achieve pregnancy (registration number: NCT04855383).
Objective:Previous studies have shown that the level of oxidative stress in individuals with recurrent pregnancy loss (RPL) is significantly higher than in fertile individuals. Alpha-lipoic acid (ALA) has been considered an antioxidant that can improve male fertility. This study aimed to investigate the antioxidant effect of ALA on sperm parameters and DNA fragmentation index (DFI) in couples with a history of RPL. Materials and Methods:In this randomized, double-blind clinical trial, 64 couples with a history of RPL, who were referred to the Milad Infertility Center, Mashhad, Iran, between February 2021 and March 2022, initially enrolled. Of these, 40 couples completed the three-month follow-up and were included in the final analysis. The intervention group received ALA and folic acid for three months, while the control group received a placebo and folic acid for the same duration. Baseline sperm parameters, including concentration, motility, and morphology, were assessed alongside the sperm DFI before and three months after the intervention. Results:There were no significant differences in baseline characteristics between the two groups (P>0.05). After three months, however, sperm concentration, motility and morphology significantly improved in the intervention group. In contrast, while sperm concentration improved in the control group, no significant changes were observed in sperm motility or morphology. There were no significant differences between the two groups regarding sperm parameters before and after the intervention (P>0.05). DFI showed a significant reduction in the intervention group compared to the control group (P<0.05). Conclusion:ALA supplementation appears to positively influence sperm parameters and reduce DFI within individuals in couples with a history of RPL. While within-group improvements were noted, between-group differences in sperm concentration, motility, and morphology were not statistically significant. These findings suggest a potential role for antioxidant therapy in the management of male infertility, though further studies are needed to confirm efficacy (registration number: IRCT20181030041503N4).
