International Journal of Fertility & Sterility is a peer review and quarterly English publication of Royan Institute. The aim of the journal is to disseminate information through publishing the most recent scientific research studies on Fertility and Sterility and other related topics. Int J Fertil Steril has been certified by Ministry of Culture and Islamic Guidance in 2007 and was accredited as a scientific and research journal by HBI (Health and Biomedical Information) Journal Accreditation Commission in 2008. Int J Fertil Steril is an Open Access journal. Phone: +9821-22510895 Address: 5th Floor, No 9, Royan Institute Cell Therapy Center, East Shaghayegh Alley, Bani Hashem Sq, Bani Hashem St, Resalat Highway, Tehran, Iran.
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Papers by international journal of fertility and sterility Int J Fertil Steril
Background: Severe oligoasthenoteratozoospermia (OAT), characterized by a reduced sperm count, mo... more Background: Severe oligoasthenoteratozoospermia (OAT), characterized by a reduced sperm count, motility, and altered morphology, presents a significant challenge in the field of male infertility. Platelet-rich plasma (PRP), renowned for its regenerative capabilities, emerges as a potential intervention for this condition. This study aims to explore the impact of PRP on male infertility, focusing specifically on individuals with severe OAT. Materials and Methods: The clinical trial study involved 88 infertile men diagnosed with OAT and devoid of underlying diseases. These participants were referred to the infertility center and subsequently divided into two cohorts: a control (44 individuals) and an intervention group (44 individuals). Patients in the intervention group received 2 cc of PRP in each testicle, prepared by centrifuging the patients autologous blood samples. Sperm parameters and DNA fragmentation index (DFI) of the patients were measured before and after the procedure. Statistical analysis used SPSS version 16 software, with a significance level set at less than 5%. Results: The statistical analysis revealed a significant difference in concentration (11.32 ± 8.44 vs. 16.06 ± 15.16, P=0.030), progressive motility (8.86 ± 7.79 vs. 11.97 ± 11.82%, P=0.014) and DNA fragmentation (25.62 ± 12.84 vs. 17.23 ± 9.15%, P<0.001) between the control and intervention groups after PRP injection. However, no significant difference was found in normal morphology (1.63 ± 1.44 vs. 1.81 ± 3.68%, P=0.628) and volume (2.13 ± 0.82 vs. 2.24 ± 1.43, P=0.663) between the control and intervention groups after PRP injection. Conclusion: This study demonstrates the effectiveness of PRP treatment in increasing sperm concentration and motility, while also reducing sperm DNA fragmentation. However, further studies are needed to validate these findings (registration number: IRCT20220317054318N2).
Background: In this phase I clinical trial, our primary objective was to develop an innovative th... more Background: In this phase I clinical trial, our primary objective was to develop an innovative therapeutic approach utilizing autologous bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) for the treatment of nonobstructive azoospermia (NOA). Additionally, we aimed to assess the feasibility and safety of this approach. Materials and Methods: We recruited 80 participants in this non-randomized, open-label clinical trial, including patients undergoing NOA treatment using autologous BM-MSCs (n=40) and those receiving hormone therapy as a control group (n=40). Detailed participant characteristics, such as age, baseline hormonal profiles, etiology of NOA, and medical history, were thoroughly documented. Autotransplantation of BM-MSCs into the testicular network was achieved using microsurgical testicular sperm extraction (microTESE). Semen analysis and hormonal assessments were performed both before and six months after treatment. Additionally, we conducted an in-silico analysis to explore potential protein-protein interactions between exosomes secreted from BM-MSCs and receptors present in human seminiferous tubule cells. Results: Our results revealed significant improvements following treatment, including increased testosterone and inhibin B levels, elevated sperm concentration, and reduced levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin. Notably, in nine patients (22.5%) previously diagnosed with secondary infertility and exhibiting azoospermia before treatment, the proposed approach yielded successful outcomes, as indicated by hormonal profile changes over six months. Importantly, these improvements were achieved without complications. Additionally, our in-silico analysis identified potential binding interactions between the protein content of BM-MSC-derived exosomes and receptors integral to spermatogenesis. Conclusion: Autotransplantation of BM-MSCs into the testicular network using microTESE in NOA patients led to the regeneration of seminiferous tubules and the regulation of hormonal profiles governing spermatogenesis. Our findings support the safety and effectiveness of autologous BM-MSCs as a promising treatment modality for NOA, with a particular focus on the achieved outcomes in patients with secondary infertility (registration number: IRCT20190519043634N1).
Background: A low progesterone level on the embryo transfer (ET) day significantly reduces the pr... more Background: A low progesterone level on the embryo transfer (ET) day significantly reduces the pregnancy rate. Therefore, the present study aims to investigate the effect of adding daily 50 mg intramuscular progesterone to a total of 800 mg progesterone suppository on the in vitro fertilization (IVF) success rate in women with low progesterone levels. Materials and Methods: This parallel open-label clinical trial was performed on 218 IVF candidate infertile women who had <9.2 ng/ml progesterone levels on the ET day. These women were randomised to the intervention or control group using the randomisation allocation rule. In the intervention group, 50 mg progesterone was prescribed intramuscularly once daily in addition to 400 mg of progesterone suppository every 12 hours from the day of ET. The control group received only 400 mg of progesterone suppositories every 12 hours. In the case of pregnancy, the drugs above were continued until 12 weeks after the ET. Results: Clinical pregnancy occurred in 54 (50.0%) women in the intervention group and in 39 (36.8%) women in the control group, which was significantly different (P=0.035). Ongoing pregnancy occurred in 47 (43.5%) women in the intervention group, and 33 (31.1%) women in the control group, which was significantly different (P=0.042). There were no significant differences in terms of abortion and multiple pregnancy rates between the two groups. Conclusion: Intramuscular injection of 50 mg progesterone significantly increases the clinical and ongoing pregnancy rates (registration number: IRCT20150105020558N6).
Background: There is an ongoing debate about the optimal dosage of gonadotropin-releasing hormone... more Background: There is an ongoing debate about the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for oocyte triggering in polycystic ovarian syndrome (PCOS) patients at risk for ovarian hyperstimulation syndrome (OHSS). In this study, we intend to ascertain whether the use of repeated doses of a GnRH agonist for oocyte triggering in these patients can enhance the outcomes of controlled ovarian stimulation (COS) for in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. Materials and Methods: This randomised clinical trial enrolled 70 PCOS women candidates for IVF/ICSI with the standard antagonist protocol at Royan Institute (Tehran, Iran) from May 2020 to June 2022. Patients at risk of OHSS with oestradiol (E2) levels >3000 pg/ml on the day of trigger were randomly assigned to a control or experimental group. Group A (control group) patients received 0.2 mg triptorelin (Decapeptyl ®) for final oocyte maturation. Group B (experimental group) patients received a second dose of 0.1 mg Decapeptyl ® 12 hours after their first dose, for a total dose of 0.3 mg. IVF/ICSI outcomes were compared between the groups. Results: Ultimately, 35 women from the study group and 33 from the control group completed the treatment cycle. Both groups were comparable in terms of demographic characteristics, baseline hormonal profiles, and PCOS phenotypes. The dosage of gonadotropin, stimulation duration, number of retrieved oocytes, oocyte maturation rate, and oocyte recovery ratio did not significantly differ between the groups. No significant differences were found in terms of the number of blastocyst and cleavage embryos, nor the quality of obtained embryos between the groups. The mild to moderate OHSS rate was significantly lower in the study group (P=0.038). Conclusion: A second dose of GnRH agonist 12 hours after the first dose did not improve the number and maturity of oocytes, or pregnancy outcomes in PCOS patients (registration number: NCT04600986).
Background: A bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa, DLBS3233, has... more Background: A bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa, DLBS3233, has recently been used for type-2-diabetes treatment due to its favorable effect on insulin sensitivity. The insulin resistance leading to metabolic syndrome is closely linked to hyperandrogenemia in polycystic ovary syndrome (PCOS). This study evaluated the metabolic and reproductive efficacy and safety of DLBS3233 in insulin-resistant PCOS women. Materials and Methods: This was a 2-arm, randomized, double-blind, controlled, noninferiority clinical study over a 6-month therapy with DLBS3233 100-mg daily in comparison to metformin-XR 750 mg twice daily, involving 124 PCOS women with insulin resistance. The primary efficacy endpoint was the improvement of Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). Secondary endpoints were improvements in other metabolic and reproductive parameters. Safety endpoints were based on blood pressure, heart rate, electrocardiogram findings, liver and renal function, and adverse events. Results: After 6 months, HOMA-IR improvement in DLBS3233-treated group (-1.03 ± 0.50) and metformin-XR (-1.19 ± 0.50) were comparable, with a between-group difference fell within the pre-set non-inferiority margin (0.16; 95% confidence interval (CI): -1.24, 1.56; P=0.3168). The HOMA-IR in both groups were significantly improved from baseline. On all secondary endpoints, both groups showed comparable effects. Markedly fewer adverse events occurred in the DLBS3233 treated group than in the Metformin-XR-treated group and most were mild clinically and had been resolved by the end of the study. Conclusion: Treatment with DLBS3233 100-mg daily in PCOS women demonstrated comparable efficacy to metformin- XR 750-mg twice daily in improving insulin resistance. However, the non-inferiority of DLBS3233 to metformin- XR remains inconclusive. DLBS3233 was more tolerable than metformin-XR (registration number: NCT01733459).
Background: Repeated implantation failure (RIF) refers to the condition where high quality embryo... more Background: Repeated implantation failure (RIF) refers to the condition where high quality embryos are unable to successfully implant after multiple cycles of in vitro fertilization (IVF) treatment. The aim of this study is to investigate the impact of intrauterine granulocyte colony-stimulating factor (G-CSF) and platelet-rich plasma (PRP) on pregnancy rate in patients with RIF. Materials and Methods: The present randomised clinical trial study was conducted at the IVF Centre of Mehr Medical Institute in Rasht, Iran, from 2020 to 2022. The research consisted of 200 individuals who had experienced multiple failed cycles. These patients were randomised into two groups: intrauterine infusion of 1 ml of G-CSF and intrauterine infusion of 1 ml autologous PRP at least 48 hours before embryo transfer (ET). The groups were compared in terms of implantation rate, and chemical, clinical, and ongoing pregnancy. Results: The implantation rate was significantly higher in patients who received PRP (P=0.016). Chemical pregnancy in the PRP group was significantly higher than G-CSF group (P=0.003). Both clinical pregnancy and ongoing pregnancy rates were significantly higher in the PRP group (P=0.001) compared to the G-CSF group (P=0.02). Conclusion: The utilisation of PRP via intrauterine infusion is considerably more successful than G-CSF in enhancing pregnancy and live birth rates among patients with RIF. (registration number: IRCT20180528039878N3).
Background: Embryo transfer (ET) is an important step in assisted reproductive technology. Uterin... more Background: Embryo transfer (ET) is an important step in assisted reproductive technology. Uterine length measurement before ET (ULMbET) enables the determination of catheter length and anatomical variation before the ET. Therefore, in this study, we aim to compare ULMbET and transabdominal ultrasound-guided ET (TAUGET). Materials and Methods: This open-label randomised clinical trial enrolled 264 women who were scheduled for frozen-thawed ET (FET) cycles. The women were randomised to the ULMbET or TAUGET group for ET. The primary outcome of this study was clinical pregnancy. Results: A total of 132 women were randomly assigned to the ULMbET group and 132 women to the TAUGET group. However, four women in the ULMbET group did not receive the allocated method after randomisation. Finally, 128 women from the ULMbET group and 132 women from the TAUGET group were assessed. No statistically significant differences existed in chemical pregnancy rate (31.3 vs. 36.4%, P=0.384), clinical pregnancy rate (23.4 vs. 28%, P=0.397), and implantation rate (15 vs. 17.8%, P=0.401) between the ULMbET and TAUGET groups, respectively. Conclusion: The results of this clinical trial show no differences in pregnancy outcomes in FET cycles following ULMbET and TAUGET (registration number: IRCT20110509006420N240).
Background: Blastocyst stage transfer appears to improve pregnancy outcomes. The aim of this stud... more Background: Blastocyst stage transfer appears to improve pregnancy outcomes. The aim of this study is to evaluate the pregnancy results between fresh cycle blastocyst stage embryo transfer and cleavage stage embryo transfer in patients who undergo intracytoplasmic sperm injection (ICSI). Materials and Methods: This randomised clinical trial study was conducted at the Infertility Research Centre of Milad Hospital in Mashhad, Iran from 2018 to 2020 on 240 infertile women who presented for their first ICSI procedure. These patients were assigned to receive either cleavage embryo transfer (n=112) or blastocyst stage transfer (n=107). Pregnancy outcomes were measured in both groups. Results: There were no differences regarding age, body mass index (BMI), serum follicle-stimulating hormone (FSH), duration of infertility, and aetiology of infertility between the groups (P>0.05). There were more follicles, total oocytes, and metaphase II (M2) oocytes in the blastocyst stage group. Considerably more cleavage stage embryos were transferred compared to the number of transferred blastocysts (P=0.001). The blastocyst group had more vitrified embryos than the cleavage group (P=0.000). The rates of implantation (P=0.332), chemical pregnancy (P=0.165), clinical pregnancy (P=0.694), and live births (P=0.727) were higher in the blastocyst group, but they were not significantly different. The rate of abortion was also not significantly higher in the blastocyst group (P=0.296). Conclusion: Blastocysts transferred in the fresh cycle of an ICSI procedure may be more advantageous compared to cleavage stage embryo transfer (registration number: IRCT20181030041503N1).
Background: Endometrial scratching (ES) remains controversial regarding its potential effectivene... more Background: Endometrial scratching (ES) remains controversial regarding its potential effectiveness in improving pregnancy rates. The objective of the present study was to assess the impact of endometrial fundal incision (EFI) during hysteroscopy on reproductive outcomes in a population of oocyte recipients. Materials and Methods: A randomized controlled trial was conducted between 2020 and 2023 at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki and “Assisting Nature Centre of Reproduction and Genetics”. The study population consisted of women who underwent hysteroscopy randomly assigned in a 1:1 ratio to either EFI (one to three months before embryotransfer with donor oocytes) or no intervention throughout office hysteroscopy. Clinical pregnancy and live birth rates were the primary outcomes. Results: After the exclusion of patients with intraoperative diagnosed endometrial pathology, a total of 124 women underwent randomization. The pregnancy test was positive in 79% (n=49/62) of the women in the EFI compared to 59.7% (n=37/62) in the hysteroscopy-only group (P=0.019), while the live birth rates did not differ between the two groups (58.1%, n=36/62 vs. 51.6%, n=32/62, P=0.470). Conclusion: EFI during hysteroscopy seems to improve pregnancy rates in oocyte recipients without intrauterine pathology, while live birth rates are not affected by the EFI. These results should be interpreted with caution before the implementation of EFI in the routine in vitro fertilization (IVF) practice (registration number: NCT04580056).
In the ever-evolving landscape of infertility science,
clinical trials emerge as the cornerstone ... more In the ever-evolving landscape of infertility science, clinical trials emerge as the cornerstone of progress. These trials, propelled by the unwavering dedication of scientific pioneers, serve as the bedrock for innovation and discovery in reproductive health. Through rigorous experimentation and meticulous analysis, they illuminate the path towards novel solutions for the complex challenges of infertility.
Int J Fertil Steril, Vol 18, No 3, July-September , 2024
An artificial ovary based on the alginate (ALG) hydrogel has been widely implemented to preserve ... more An artificial ovary based on the alginate (ALG) hydrogel has been widely implemented to preserve prepubertal female fertility. However, this platform is not fully capable of successful an ovary microenvironment simulation for follicle development, holding great potential for its improvement. Therefore, this experimental study aimed to evaluate the effect of an amniotic membrane extract (AME)-loaded hydrogel on the mouse preantral follicles in vitro development. In order to have better follicle development, first, the impact of different concentrations of follicle-stimulating hormone (FSH) was evaluated on the mouse preantral follicles encapsulated in ALG. Later, the appropriate dose was adjusted for the follicles encapsulated in the ALG-AME hydrogel. Results demonstrated that 100 mIU/ml FSH showed a significant follicle survival rate compared with 10 mIU/ml FSH (P=0.005). According to MTT assay finding, the rate of weight loss, and rheology evaluations, ALG containing 1 mg/ml AME was identified as an optimal sample of follicle culture instead of other AME concentrations. Follicle diameter significantly increased in the ALG-AME 1 hydrogel compared with the ALG control group without AME (P=0.027). The storage modulus of ALG-AME 1 was 773 Pa and retained the follicle morphology for 13 days. No statistically substantial difference was seen in survival, antrum cavity formation, and competent oocyte in terms of the normal chromosomal arrangement and meiotic spindle rate in comparison with the control group. It can be concluded that ALG-AME 1 could not significantly impact the mouse preantral follicle.
Int J Fertil Steril, Vol 18, No 3, July-September , 2024
Background: The aim of this study is to investigate the co-culture effects of human endometrial m... more Background: The aim of this study is to investigate the co-culture effects of human endometrial mesenchymal stem cells (EnMSCs) with mouse oocytes to enhance their maturation and development by using the hanging drop and sodium alginate hydrogel methods. Materials and Methods: In this experimental study, we prepared human EnMSCs (2.5×10 5 cells/mL) and co-cultured them with partially denuded mouse oocytes by the hanging drop (n=120) and sodium alginate hydrogel (n=120) methods. Control oocytes (n=230, total) were cultured in both systems in the absence of human EnMSCs for 18 hours. Both survival and maturation rates of the oocytes were analysed morphologically. After insemination with capacitated sperm, the fertiliza tion and development of the embryos up to the blastocyst stage were assessed and compared statistically for all of the study groups via one-way ANOVA and the t tests. Results: Oocytes cultured in the hanging drop method had a significantly higher survival rate than their control group (92.60 ± 4.36% vs. 84.20 ± 3.12%, P=0.018). There were no significant differences between the two experimental groups in terms of survival. The mean percent of oocytes that reached the metaphase II (MII) stage was 64.35 ± 3.19% and fertilised was 62.25 ± 4.43% in the hanging drop method; these rates were 63.43 ± 1.92% and 58.14 ± 4.14 in sodium alginate hydrogel method, respectively. These rates were higher than their controls (P<0.050), but there were no statistical differences between the two experimental groups (P>0.050). Among the studied groups, the highest significant blastocyst rate (32.55 ± 2.18%) was observed in the hanging drop experimental group (P=0.0017). Conclusion: The results of this study show that human EnMSCs improve the survival, maturation, and development rates of oocytes and they could have future clinical applications.
Int J Fertil Steril, Vol 18, No 3, July-September , 2024
Background: Prenatal and postnatal depression (PND) is associated with adverse outcomes for mothe... more Background: Prenatal and postnatal depression (PND) is associated with adverse outcomes for mother, fetus, and child. The aim of study was to examine the prevalence and risk factors of prenatal and postnatal depressive symptoms. Materials and Methods: This was a cross-sectional and hospital-based survey of 2305 pregnant women and post-partum women (18-48 years) that was registered in the Babol Pregnancy Mental Health Registry (BPMHR) database from June 2020 to March 2021. Two questionnaires, including demographics and depression, were analyzed in this study. Also, the Edinburg Postnatal Depression Scale (EPDS) was used to assess the depressive symptoms. Independent t test and the analysis of variance were used to compare the means. Multiple logistic regressions were used to determine risk factors for depressive symptoms. Results: According to the EPDS scale, the prevalence of depressive symptoms was 19.8% in the pregnant woman group in comparison with the postpartum period (11.6%). Risk factors for antenatal depressive symptoms were parity (women with parity ≥ 4 vs. 1 parity, ß=1.808, P=0.020), two groups of gestational age (gestational age ≤12 weeks vs. 28 weeks, ß=1.562 P=0.030) as well as (gestational age 21-27 weeks vs. 28 weeks (ß=1.586, P=0.033), and high-risk pregnancy (high-risk vs. low-risk pregnancy, ß=1.457, P=0.003). For postnatal depressive symptoms, none of the factors were a significant risk. Conclusion: Prenatal and postnatal depressive symptoms should be screened, particularly for women in the first and second trimesters, with high parity, and those with a high-risk pregnancy, as recommended by the present study.
Int J Fertil Steril, Vol 18, No 3, July-September , 2024
Background: Spermatogenic maturation arrest is thought to be caused by epigenetic defects, specif... more Background: Spermatogenic maturation arrest is thought to be caused by epigenetic defects, specifically in chromatin remodeling and histone modification. This study evaluated the status of chromatin remodeling chromodomain helicase DNA binding protein 5 (CHD5) and histone modifications histone 4 lys-12 acetylation (H4K12ac) and histone 3 lys-9 trimethylation (H3K9me3) in human testicular biopsies, based on maturation arrest type. Materials and Methods: The cross-sectional study utilized 18 Bouin-fixed paraffin-embedded (BFPE) specimens prepared from residual tissue from routine laboratory tests of infertile patients. The expression of CHD5, H4K12ac, and H3K9me3 was examined through immunohistochemistry (IHC). The intensity was measured using ImageJ with IHC Profiler and StarDist plugins. Statistical analysis was performed using Python with Scipy.Stats module. The data were tested with Shapiro– Wilk for normality and Levene test for homogeneity. The differences in the intensity of spermatogenic cells were assessed using Kruskal-Wallis and Mann-Whitney tests. A difference was considered statistically significant if P<0.05. Results: We found three types of maturation arrest, including Sertoli cell only (n=5), spermatocyte arrest (n=4), and spermatid arrest (n=9). CHD5 was positive in spermatogonia and round spermatids but absent in spermatocytes. The mean grey value (MGV) of CHD5 in spermatogonia was generally weak in spermatocyte arrest (157.4 ± 16.6) and spermatid arrest (155.3 ± 16.8), and there was no significant difference between them [P=0.49, 95% confidence interval (CI): (-4.3, 6), effect size (r): 0.02]. Although there was a significant difference in the expression of H3K9me3 and H4K12ac (P<0.001), both histone modifications were found in all observed spermatogenic cells. Conclusion: The expressions of CHD5, H3K9me3, and H4K12ac in different spermatogenic cell types produce similar results, indicating that they cannot be used as markers to determine the type of spermatogenic maturation arrest in humans. The significant finding in this research is the expression of CHD5 in human spermatogonia cells, which requires further study for elaboration.
Int J Fertil Steril, Vol 18, No 3, July-September , 2024
Background: The dilation and torsion of testicular veins in the plexus pampiniformis causes Varic... more Background: The dilation and torsion of testicular veins in the plexus pampiniformis causes Varicocele, which is a surgically repairable cause of male infertility. This study assessed the impact of varicocelectomy on semen characteristics, total motile sperm count (TMSC) and sperm DNA integrity in patients with severe oligoasthenoteratozoospermia (OAT). Materials and Methods: In this prospective study, semen samples of 360 men with severe OAT who underwent varicocelectomy according to World Health Organization (WHO) criteria 2021 were studied (pre-operatively and at 6, 12, and 18 months post-operatively). Results: The average age of our patients was 38.5 years. The mean spermatozoa concentration was found to be 1.60 ± 0.83 million/ml pre-operatively, while the mean post-operative concentration was 5.17 ± 1.23 million/ml at 6 months, 8.32 ± 0.98 million/ml at 12 months, and 13.51 ± 1.48 million/ml at 18 months (P<0.0001). The mean percentage of A+B motile spermatozoa was 2.92 ± 1.17% pre-operatively, 6.10 ± 1.51% at six months, 9.58 ± 1.49% at 12 months and 13.92 ± 1.88% at 18 months postoperatively (P<0.0001). The mean Modified David's morphology score was 3.80 ± 1.43% pre-operatively, 5.95 ± 1.23% at 6 months, 7.94 ± 1.18% at 12 months, and 10.82 ± 1.91% at 18 months post-operatively (P<0.0001). The mean of total motile sperm count (TMSC) was statistically improved after varicocelectomy (P<0.001). The mean of DNA fragmentation index (DFI) of the spermatozoa was 31.40 ± 0.52% pre-operatively, and post-operatively at 28.20 ± 0.32% at 6 months, 25.90 ± 0.31% at 12 months and 20.50 ± 0.40% at 18 months (P<0.001). Conclusion: Varicocelectomy was associated with significant improvement of sperm parameters and DNA fragmentation resulting in significant improvement of spermatogenesis quality. We believe that universalization in the routinely used sperm dispersion chromatin (SDC) test could be beneficial in the treatment of infertility.
Int J Fertil Steril, Vol 18, No 3, July-September , 2024
Background: Age, smoking, sleep duration, sleep quality, and obesity are risk factors that can af... more Background: Age, smoking, sleep duration, sleep quality, and obesity are risk factors that can affect the amount of sperm concentration, morphology, and motility. The aim of this study is to assess the lifestyle effects: of age, smoking, sleep duration, sleep quality, and obesity on the amount of concentration, morphology, and motility of sperm. Materials and Methods: The study utilized an analytical observational approach with a cross-sectional design. The study subjects comprised 70 male partners of infertile couples admitted to the Sekar Fertility Clinic at the Dr. Moewardi General Hospital between March and August 2022. The study assessed variables including age, body mass index (BMI), smoking status, sleep duration, sleep quality, sperm concentration, sperm morphology, and sperm motility. Furthermore, the data were analyzed using univariate, bivariate, and multivariate methods with SPSS 25 software. Results: The research findings demonstrate that obesity is significantly associated with abnormal sperm concentration [odds ratio (OR)=40.07, confidence interval (CI)=3.90-411.67, P=0.002]. Furthermore, moderate or heavy smoking is significantly associated with abnormal sperm concentration (OR=17.45, CI=1.83-166.15, P=0.013) and sleep quality with severe disorders (OR=5.73, CI=1.12-29.21, P=0.036). Moreover, obesity is significantly associated with abnormal sperm motility (OR=12.97, CI=2.66-63.15, P=0.002), while moderate or heavy smoking (OR=5.89, CI=1.23-28.20, P=0.026) and poor sleep duration (OR=6.21, CI=1.43-26.92, P=0.015) also exhibit significant associations with abnormal sperm motility. However, no significant findings were observed regarding sperm morphology. Conclusion: The findings of this study indicate that obesity, moderate or heavy smoking, and sleep quality have statistically significant effects on sperm concentration, while obesity, moderate or heavy smoking, and sleep duration have statistically significant effects on sperm motility. However, no statistically significant influence was observed on sperm morphology. Further research with larger sample sizes and more diverse populations is needed to validate these findings and explore other potential factors that may impact male fertility.
Int J Fertil Steril, Vol 18, No 3, July-September , 2024
Background: Selecting embryos with the highest implantation potential is crucial for in vitro fer... more Background: Selecting embryos with the highest implantation potential is crucial for in vitro fertilization (IVF) success. Both the timing of blastulation, day 5 (D5) or D6, and the embryo quality have been suggested as influential factors in determining the clinical outcome of single euploid blastocyst transfers. However, evidence supporting the superiority of D5 over D6 blastocysts remains inconclusive. The aim of this study was to compare clinical outcomes following the transfer of euploid blastocysts with different quality and timing of blastulation. Materials and Methods: A retrospective cohort study was conducted at our Assisted Reproductive Center, analyzing the outcome of 774 transfers with D5 euploids and 155 transfers with D6 euploids performed between January 2019 and February 2022. Results: The live birth rate was significantly lower in the euploid D6 group compared to the euploid D5 group (38.71vs. 55.04%, P=0.001). The outcome was significantly influenced by the quality of the embryos. Live birth rates were 62.14 and 53.61% following transfers of D5 and D6 excellent embryos respectively, 45.18 and 32.21% following transfer of D5 and D6 good embryos but only 28.64 and 19.32% following transfer of D5 and D6 fair embryos. The outcome difference was statistically significant across embryo quality categories (P=0.001). The adjusted risk ratios (RR) of clinical outcomes indicated that excellent euploid D5 embryos consistently outperformed other types of embryo quality. Conclusion: The timing of blastulation and embryo quality are crucial factors in determining the success of single euploid blastocyst transfers. Excellent euploid D5 transfers yielded superior clinical outcomes, providing valuable insights for IVF teams and patients when selecting embryos to be transferred.
Int J Fertil Steril, Vol 18, No 3, July-September , 2024
Background: Central nervous system damage in multiple sclerosis (MS) leads to severe physical dis... more Background: Central nervous system damage in multiple sclerosis (MS) leads to severe physical disability and neurological defects. Sexual dysfunction and infertility in patients with MS have often been neglected in previous studies. Aerobic exercise is suggested to improve circulating testosterone levels and sexual function. Therefore, the purpose of this study was to investigate the effect of aerobic exercise on sex hormone levels in a cuprizone rat model of MS. Materials and Methods: In this experimental study, 30 male rats (aged 70 days, 154.55 ± 18.1 g) were randomly divided into five groups: MS, exercise-MS (EX-MS), MS-EX, EX-MS-EX, and normal control (control). MS was induced by feeding cuprizone pellets (0.2%) to the rats for six weeks. The exercise groups performed an aerobic exercise protocol on a treadmill five days/week for six weeks before and during the induction of the MS model. Serum testosterone, follicle stimulating hormone (FSH), and luteinising hormone (LH) levels were measured using the ELISA method with standard kits (ZellBio Germany). Luxol fast blue staining (LFB) of the corpora collosa were performed. Results: The results showed a significant decrease in the serum levels of testosterone, FSH, and LH in the MS groups compared to the control group (P<0.05). There was a significant increase in the serum levels of testosterone, FSH, and LH in the EX-MS-EX, and EX-MS groups compared to the MS group (P<0.05). Conclusion: Aerobic exercise could improve the level of sex hormones in the cuprizone rat model of MS and may be used to attenuate sexual dysfunction in patients with MS.
Int J Fertil Steril, Vol 18, No 3, July-September , 2024
Background: Ovarian reserve is one of the most important factors that influences the success of a... more Background: Ovarian reserve is one of the most important factors that influences the success of assisted reproductive technology (ART). Recently, the role of anti-müllerian hormone (AMH) in ART has been investigated as a marker for the prediction of ovarian response. We aim to examine this relationship within a large Iranian population. Materials and Methods: In this cross-sectional study, we obtained data from 1000 infertile couples who referred to the Research and Clinical Centre of Yazd Infertility Clinic for in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Serum AMH levels, oocyte count, numbers of fertilised oocytes, endometrial thickness, and percentage of mature oocytes were measured. The relationship between AMH serum levels and the number and quality of oocytes and embryos in ART cycles was analysed. Results: In the linear regression model, the log of the variables total dose of gonadotropin, two pronuclei (2PN), log oestradiol, total embryos, duration of stimulation, number of embryos transferred, protocol, and cause of infertility were significant predictors of log AMH. Conclusion: There appears to be a relationship between serum AMH levels in the early follicular phase and ovarian reserve. Higher serum AMH levels were also associated with shorter ART cycles.
Int J Fertil Steril, Vol 18, No 3, July-September, 2024
Background: Middle-aged working women represent most patients attending fertility clinics for in ... more Background: Middle-aged working women represent most patients attending fertility clinics for in vitro fertilization (IVF) treatment. In this study, we aimed to identify the association of women's working status with clinical pregnancy and miscarriage in the first trimester after IVF treatment. Materials and Methods: In this single-centre cross-sectional study at a private clinic in Kazakhstan, we reviewed electronic medical records of all IVF with intracytoplasmic sperm injection (ICSI) and fresh embryo transfer (ET) cycles from January 2018 to December 2019 (n=654). 300 cycles in patients with normal ovarian reserve and registered working status of a female partner in the medical records were selected for the analysis. The study's primary outcome measures were clinical pregnancy rates and clinical miscarriage in the first trimester. Results: 204 women were employed, while 96 were not employed before the start of treatment. The mean age of all patients was 32.2 ± 4.8 years, ranging from 23 to 46 years. Two-thirds of working women had office-based occupations employed as doctors, school and university teachers, accountants, clerks, and managers. One-third of the study participants had manual labor jobs, including service positions and plant workers. There was no association between women's working status and clinical pregnancy rate adjusted for age, antral follicle count, history of pelvic adhesiolysis, and embryo development stage at embryo transfer. However, working women had almost five times the risk of the first trimester miscarriage compared to non-working women [adjusted odds ratio (aOR) 4.56, 95% confidence interval (CI): 0.52 to 4.96] adjusted for age and number of retrieved oocytes. Conclusion: Women who work before commencing IVF treatment can be reassured of having equal chances of conception following the treatment compared to non-working women. The observed risk of first trimester miscarriage in working women necessitates further research before drawing any conclusions from medical and public health points.
Background: Severe oligoasthenoteratozoospermia (OAT), characterized by a reduced sperm count, mo... more Background: Severe oligoasthenoteratozoospermia (OAT), characterized by a reduced sperm count, motility, and altered morphology, presents a significant challenge in the field of male infertility. Platelet-rich plasma (PRP), renowned for its regenerative capabilities, emerges as a potential intervention for this condition. This study aims to explore the impact of PRP on male infertility, focusing specifically on individuals with severe OAT. Materials and Methods: The clinical trial study involved 88 infertile men diagnosed with OAT and devoid of underlying diseases. These participants were referred to the infertility center and subsequently divided into two cohorts: a control (44 individuals) and an intervention group (44 individuals). Patients in the intervention group received 2 cc of PRP in each testicle, prepared by centrifuging the patients autologous blood samples. Sperm parameters and DNA fragmentation index (DFI) of the patients were measured before and after the procedure. Statistical analysis used SPSS version 16 software, with a significance level set at less than 5%. Results: The statistical analysis revealed a significant difference in concentration (11.32 ± 8.44 vs. 16.06 ± 15.16, P=0.030), progressive motility (8.86 ± 7.79 vs. 11.97 ± 11.82%, P=0.014) and DNA fragmentation (25.62 ± 12.84 vs. 17.23 ± 9.15%, P<0.001) between the control and intervention groups after PRP injection. However, no significant difference was found in normal morphology (1.63 ± 1.44 vs. 1.81 ± 3.68%, P=0.628) and volume (2.13 ± 0.82 vs. 2.24 ± 1.43, P=0.663) between the control and intervention groups after PRP injection. Conclusion: This study demonstrates the effectiveness of PRP treatment in increasing sperm concentration and motility, while also reducing sperm DNA fragmentation. However, further studies are needed to validate these findings (registration number: IRCT20220317054318N2).
Background: In this phase I clinical trial, our primary objective was to develop an innovative th... more Background: In this phase I clinical trial, our primary objective was to develop an innovative therapeutic approach utilizing autologous bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) for the treatment of nonobstructive azoospermia (NOA). Additionally, we aimed to assess the feasibility and safety of this approach. Materials and Methods: We recruited 80 participants in this non-randomized, open-label clinical trial, including patients undergoing NOA treatment using autologous BM-MSCs (n=40) and those receiving hormone therapy as a control group (n=40). Detailed participant characteristics, such as age, baseline hormonal profiles, etiology of NOA, and medical history, were thoroughly documented. Autotransplantation of BM-MSCs into the testicular network was achieved using microsurgical testicular sperm extraction (microTESE). Semen analysis and hormonal assessments were performed both before and six months after treatment. Additionally, we conducted an in-silico analysis to explore potential protein-protein interactions between exosomes secreted from BM-MSCs and receptors present in human seminiferous tubule cells. Results: Our results revealed significant improvements following treatment, including increased testosterone and inhibin B levels, elevated sperm concentration, and reduced levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin. Notably, in nine patients (22.5%) previously diagnosed with secondary infertility and exhibiting azoospermia before treatment, the proposed approach yielded successful outcomes, as indicated by hormonal profile changes over six months. Importantly, these improvements were achieved without complications. Additionally, our in-silico analysis identified potential binding interactions between the protein content of BM-MSC-derived exosomes and receptors integral to spermatogenesis. Conclusion: Autotransplantation of BM-MSCs into the testicular network using microTESE in NOA patients led to the regeneration of seminiferous tubules and the regulation of hormonal profiles governing spermatogenesis. Our findings support the safety and effectiveness of autologous BM-MSCs as a promising treatment modality for NOA, with a particular focus on the achieved outcomes in patients with secondary infertility (registration number: IRCT20190519043634N1).
Background: A low progesterone level on the embryo transfer (ET) day significantly reduces the pr... more Background: A low progesterone level on the embryo transfer (ET) day significantly reduces the pregnancy rate. Therefore, the present study aims to investigate the effect of adding daily 50 mg intramuscular progesterone to a total of 800 mg progesterone suppository on the in vitro fertilization (IVF) success rate in women with low progesterone levels. Materials and Methods: This parallel open-label clinical trial was performed on 218 IVF candidate infertile women who had <9.2 ng/ml progesterone levels on the ET day. These women were randomised to the intervention or control group using the randomisation allocation rule. In the intervention group, 50 mg progesterone was prescribed intramuscularly once daily in addition to 400 mg of progesterone suppository every 12 hours from the day of ET. The control group received only 400 mg of progesterone suppositories every 12 hours. In the case of pregnancy, the drugs above were continued until 12 weeks after the ET. Results: Clinical pregnancy occurred in 54 (50.0%) women in the intervention group and in 39 (36.8%) women in the control group, which was significantly different (P=0.035). Ongoing pregnancy occurred in 47 (43.5%) women in the intervention group, and 33 (31.1%) women in the control group, which was significantly different (P=0.042). There were no significant differences in terms of abortion and multiple pregnancy rates between the two groups. Conclusion: Intramuscular injection of 50 mg progesterone significantly increases the clinical and ongoing pregnancy rates (registration number: IRCT20150105020558N6).
Background: There is an ongoing debate about the optimal dosage of gonadotropin-releasing hormone... more Background: There is an ongoing debate about the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for oocyte triggering in polycystic ovarian syndrome (PCOS) patients at risk for ovarian hyperstimulation syndrome (OHSS). In this study, we intend to ascertain whether the use of repeated doses of a GnRH agonist for oocyte triggering in these patients can enhance the outcomes of controlled ovarian stimulation (COS) for in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. Materials and Methods: This randomised clinical trial enrolled 70 PCOS women candidates for IVF/ICSI with the standard antagonist protocol at Royan Institute (Tehran, Iran) from May 2020 to June 2022. Patients at risk of OHSS with oestradiol (E2) levels >3000 pg/ml on the day of trigger were randomly assigned to a control or experimental group. Group A (control group) patients received 0.2 mg triptorelin (Decapeptyl ®) for final oocyte maturation. Group B (experimental group) patients received a second dose of 0.1 mg Decapeptyl ® 12 hours after their first dose, for a total dose of 0.3 mg. IVF/ICSI outcomes were compared between the groups. Results: Ultimately, 35 women from the study group and 33 from the control group completed the treatment cycle. Both groups were comparable in terms of demographic characteristics, baseline hormonal profiles, and PCOS phenotypes. The dosage of gonadotropin, stimulation duration, number of retrieved oocytes, oocyte maturation rate, and oocyte recovery ratio did not significantly differ between the groups. No significant differences were found in terms of the number of blastocyst and cleavage embryos, nor the quality of obtained embryos between the groups. The mild to moderate OHSS rate was significantly lower in the study group (P=0.038). Conclusion: A second dose of GnRH agonist 12 hours after the first dose did not improve the number and maturity of oocytes, or pregnancy outcomes in PCOS patients (registration number: NCT04600986).
Background: A bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa, DLBS3233, has... more Background: A bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa, DLBS3233, has recently been used for type-2-diabetes treatment due to its favorable effect on insulin sensitivity. The insulin resistance leading to metabolic syndrome is closely linked to hyperandrogenemia in polycystic ovary syndrome (PCOS). This study evaluated the metabolic and reproductive efficacy and safety of DLBS3233 in insulin-resistant PCOS women. Materials and Methods: This was a 2-arm, randomized, double-blind, controlled, noninferiority clinical study over a 6-month therapy with DLBS3233 100-mg daily in comparison to metformin-XR 750 mg twice daily, involving 124 PCOS women with insulin resistance. The primary efficacy endpoint was the improvement of Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). Secondary endpoints were improvements in other metabolic and reproductive parameters. Safety endpoints were based on blood pressure, heart rate, electrocardiogram findings, liver and renal function, and adverse events. Results: After 6 months, HOMA-IR improvement in DLBS3233-treated group (-1.03 ± 0.50) and metformin-XR (-1.19 ± 0.50) were comparable, with a between-group difference fell within the pre-set non-inferiority margin (0.16; 95% confidence interval (CI): -1.24, 1.56; P=0.3168). The HOMA-IR in both groups were significantly improved from baseline. On all secondary endpoints, both groups showed comparable effects. Markedly fewer adverse events occurred in the DLBS3233 treated group than in the Metformin-XR-treated group and most were mild clinically and had been resolved by the end of the study. Conclusion: Treatment with DLBS3233 100-mg daily in PCOS women demonstrated comparable efficacy to metformin- XR 750-mg twice daily in improving insulin resistance. However, the non-inferiority of DLBS3233 to metformin- XR remains inconclusive. DLBS3233 was more tolerable than metformin-XR (registration number: NCT01733459).
Background: Repeated implantation failure (RIF) refers to the condition where high quality embryo... more Background: Repeated implantation failure (RIF) refers to the condition where high quality embryos are unable to successfully implant after multiple cycles of in vitro fertilization (IVF) treatment. The aim of this study is to investigate the impact of intrauterine granulocyte colony-stimulating factor (G-CSF) and platelet-rich plasma (PRP) on pregnancy rate in patients with RIF. Materials and Methods: The present randomised clinical trial study was conducted at the IVF Centre of Mehr Medical Institute in Rasht, Iran, from 2020 to 2022. The research consisted of 200 individuals who had experienced multiple failed cycles. These patients were randomised into two groups: intrauterine infusion of 1 ml of G-CSF and intrauterine infusion of 1 ml autologous PRP at least 48 hours before embryo transfer (ET). The groups were compared in terms of implantation rate, and chemical, clinical, and ongoing pregnancy. Results: The implantation rate was significantly higher in patients who received PRP (P=0.016). Chemical pregnancy in the PRP group was significantly higher than G-CSF group (P=0.003). Both clinical pregnancy and ongoing pregnancy rates were significantly higher in the PRP group (P=0.001) compared to the G-CSF group (P=0.02). Conclusion: The utilisation of PRP via intrauterine infusion is considerably more successful than G-CSF in enhancing pregnancy and live birth rates among patients with RIF. (registration number: IRCT20180528039878N3).
Background: Embryo transfer (ET) is an important step in assisted reproductive technology. Uterin... more Background: Embryo transfer (ET) is an important step in assisted reproductive technology. Uterine length measurement before ET (ULMbET) enables the determination of catheter length and anatomical variation before the ET. Therefore, in this study, we aim to compare ULMbET and transabdominal ultrasound-guided ET (TAUGET). Materials and Methods: This open-label randomised clinical trial enrolled 264 women who were scheduled for frozen-thawed ET (FET) cycles. The women were randomised to the ULMbET or TAUGET group for ET. The primary outcome of this study was clinical pregnancy. Results: A total of 132 women were randomly assigned to the ULMbET group and 132 women to the TAUGET group. However, four women in the ULMbET group did not receive the allocated method after randomisation. Finally, 128 women from the ULMbET group and 132 women from the TAUGET group were assessed. No statistically significant differences existed in chemical pregnancy rate (31.3 vs. 36.4%, P=0.384), clinical pregnancy rate (23.4 vs. 28%, P=0.397), and implantation rate (15 vs. 17.8%, P=0.401) between the ULMbET and TAUGET groups, respectively. Conclusion: The results of this clinical trial show no differences in pregnancy outcomes in FET cycles following ULMbET and TAUGET (registration number: IRCT20110509006420N240).
Background: Blastocyst stage transfer appears to improve pregnancy outcomes. The aim of this stud... more Background: Blastocyst stage transfer appears to improve pregnancy outcomes. The aim of this study is to evaluate the pregnancy results between fresh cycle blastocyst stage embryo transfer and cleavage stage embryo transfer in patients who undergo intracytoplasmic sperm injection (ICSI). Materials and Methods: This randomised clinical trial study was conducted at the Infertility Research Centre of Milad Hospital in Mashhad, Iran from 2018 to 2020 on 240 infertile women who presented for their first ICSI procedure. These patients were assigned to receive either cleavage embryo transfer (n=112) or blastocyst stage transfer (n=107). Pregnancy outcomes were measured in both groups. Results: There were no differences regarding age, body mass index (BMI), serum follicle-stimulating hormone (FSH), duration of infertility, and aetiology of infertility between the groups (P>0.05). There were more follicles, total oocytes, and metaphase II (M2) oocytes in the blastocyst stage group. Considerably more cleavage stage embryos were transferred compared to the number of transferred blastocysts (P=0.001). The blastocyst group had more vitrified embryos than the cleavage group (P=0.000). The rates of implantation (P=0.332), chemical pregnancy (P=0.165), clinical pregnancy (P=0.694), and live births (P=0.727) were higher in the blastocyst group, but they were not significantly different. The rate of abortion was also not significantly higher in the blastocyst group (P=0.296). Conclusion: Blastocysts transferred in the fresh cycle of an ICSI procedure may be more advantageous compared to cleavage stage embryo transfer (registration number: IRCT20181030041503N1).
Background: Endometrial scratching (ES) remains controversial regarding its potential effectivene... more Background: Endometrial scratching (ES) remains controversial regarding its potential effectiveness in improving pregnancy rates. The objective of the present study was to assess the impact of endometrial fundal incision (EFI) during hysteroscopy on reproductive outcomes in a population of oocyte recipients. Materials and Methods: A randomized controlled trial was conducted between 2020 and 2023 at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki and “Assisting Nature Centre of Reproduction and Genetics”. The study population consisted of women who underwent hysteroscopy randomly assigned in a 1:1 ratio to either EFI (one to three months before embryotransfer with donor oocytes) or no intervention throughout office hysteroscopy. Clinical pregnancy and live birth rates were the primary outcomes. Results: After the exclusion of patients with intraoperative diagnosed endometrial pathology, a total of 124 women underwent randomization. The pregnancy test was positive in 79% (n=49/62) of the women in the EFI compared to 59.7% (n=37/62) in the hysteroscopy-only group (P=0.019), while the live birth rates did not differ between the two groups (58.1%, n=36/62 vs. 51.6%, n=32/62, P=0.470). Conclusion: EFI during hysteroscopy seems to improve pregnancy rates in oocyte recipients without intrauterine pathology, while live birth rates are not affected by the EFI. These results should be interpreted with caution before the implementation of EFI in the routine in vitro fertilization (IVF) practice (registration number: NCT04580056).
In the ever-evolving landscape of infertility science,
clinical trials emerge as the cornerstone ... more In the ever-evolving landscape of infertility science, clinical trials emerge as the cornerstone of progress. These trials, propelled by the unwavering dedication of scientific pioneers, serve as the bedrock for innovation and discovery in reproductive health. Through rigorous experimentation and meticulous analysis, they illuminate the path towards novel solutions for the complex challenges of infertility.
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An artificial ovary based on the alginate (ALG) hydrogel has been widely implemented to preserve ... more An artificial ovary based on the alginate (ALG) hydrogel has been widely implemented to preserve prepubertal female fertility. However, this platform is not fully capable of successful an ovary microenvironment simulation for follicle development, holding great potential for its improvement. Therefore, this experimental study aimed to evaluate the effect of an amniotic membrane extract (AME)-loaded hydrogel on the mouse preantral follicles in vitro development. In order to have better follicle development, first, the impact of different concentrations of follicle-stimulating hormone (FSH) was evaluated on the mouse preantral follicles encapsulated in ALG. Later, the appropriate dose was adjusted for the follicles encapsulated in the ALG-AME hydrogel. Results demonstrated that 100 mIU/ml FSH showed a significant follicle survival rate compared with 10 mIU/ml FSH (P=0.005). According to MTT assay finding, the rate of weight loss, and rheology evaluations, ALG containing 1 mg/ml AME was identified as an optimal sample of follicle culture instead of other AME concentrations. Follicle diameter significantly increased in the ALG-AME 1 hydrogel compared with the ALG control group without AME (P=0.027). The storage modulus of ALG-AME 1 was 773 Pa and retained the follicle morphology for 13 days. No statistically substantial difference was seen in survival, antrum cavity formation, and competent oocyte in terms of the normal chromosomal arrangement and meiotic spindle rate in comparison with the control group. It can be concluded that ALG-AME 1 could not significantly impact the mouse preantral follicle.
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Background: The aim of this study is to investigate the co-culture effects of human endometrial m... more Background: The aim of this study is to investigate the co-culture effects of human endometrial mesenchymal stem cells (EnMSCs) with mouse oocytes to enhance their maturation and development by using the hanging drop and sodium alginate hydrogel methods. Materials and Methods: In this experimental study, we prepared human EnMSCs (2.5×10 5 cells/mL) and co-cultured them with partially denuded mouse oocytes by the hanging drop (n=120) and sodium alginate hydrogel (n=120) methods. Control oocytes (n=230, total) were cultured in both systems in the absence of human EnMSCs for 18 hours. Both survival and maturation rates of the oocytes were analysed morphologically. After insemination with capacitated sperm, the fertiliza tion and development of the embryos up to the blastocyst stage were assessed and compared statistically for all of the study groups via one-way ANOVA and the t tests. Results: Oocytes cultured in the hanging drop method had a significantly higher survival rate than their control group (92.60 ± 4.36% vs. 84.20 ± 3.12%, P=0.018). There were no significant differences between the two experimental groups in terms of survival. The mean percent of oocytes that reached the metaphase II (MII) stage was 64.35 ± 3.19% and fertilised was 62.25 ± 4.43% in the hanging drop method; these rates were 63.43 ± 1.92% and 58.14 ± 4.14 in sodium alginate hydrogel method, respectively. These rates were higher than their controls (P<0.050), but there were no statistical differences between the two experimental groups (P>0.050). Among the studied groups, the highest significant blastocyst rate (32.55 ± 2.18%) was observed in the hanging drop experimental group (P=0.0017). Conclusion: The results of this study show that human EnMSCs improve the survival, maturation, and development rates of oocytes and they could have future clinical applications.
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Background: Prenatal and postnatal depression (PND) is associated with adverse outcomes for mothe... more Background: Prenatal and postnatal depression (PND) is associated with adverse outcomes for mother, fetus, and child. The aim of study was to examine the prevalence and risk factors of prenatal and postnatal depressive symptoms. Materials and Methods: This was a cross-sectional and hospital-based survey of 2305 pregnant women and post-partum women (18-48 years) that was registered in the Babol Pregnancy Mental Health Registry (BPMHR) database from June 2020 to March 2021. Two questionnaires, including demographics and depression, were analyzed in this study. Also, the Edinburg Postnatal Depression Scale (EPDS) was used to assess the depressive symptoms. Independent t test and the analysis of variance were used to compare the means. Multiple logistic regressions were used to determine risk factors for depressive symptoms. Results: According to the EPDS scale, the prevalence of depressive symptoms was 19.8% in the pregnant woman group in comparison with the postpartum period (11.6%). Risk factors for antenatal depressive symptoms were parity (women with parity ≥ 4 vs. 1 parity, ß=1.808, P=0.020), two groups of gestational age (gestational age ≤12 weeks vs. 28 weeks, ß=1.562 P=0.030) as well as (gestational age 21-27 weeks vs. 28 weeks (ß=1.586, P=0.033), and high-risk pregnancy (high-risk vs. low-risk pregnancy, ß=1.457, P=0.003). For postnatal depressive symptoms, none of the factors were a significant risk. Conclusion: Prenatal and postnatal depressive symptoms should be screened, particularly for women in the first and second trimesters, with high parity, and those with a high-risk pregnancy, as recommended by the present study.
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Background: Spermatogenic maturation arrest is thought to be caused by epigenetic defects, specif... more Background: Spermatogenic maturation arrest is thought to be caused by epigenetic defects, specifically in chromatin remodeling and histone modification. This study evaluated the status of chromatin remodeling chromodomain helicase DNA binding protein 5 (CHD5) and histone modifications histone 4 lys-12 acetylation (H4K12ac) and histone 3 lys-9 trimethylation (H3K9me3) in human testicular biopsies, based on maturation arrest type. Materials and Methods: The cross-sectional study utilized 18 Bouin-fixed paraffin-embedded (BFPE) specimens prepared from residual tissue from routine laboratory tests of infertile patients. The expression of CHD5, H4K12ac, and H3K9me3 was examined through immunohistochemistry (IHC). The intensity was measured using ImageJ with IHC Profiler and StarDist plugins. Statistical analysis was performed using Python with Scipy.Stats module. The data were tested with Shapiro– Wilk for normality and Levene test for homogeneity. The differences in the intensity of spermatogenic cells were assessed using Kruskal-Wallis and Mann-Whitney tests. A difference was considered statistically significant if P<0.05. Results: We found three types of maturation arrest, including Sertoli cell only (n=5), spermatocyte arrest (n=4), and spermatid arrest (n=9). CHD5 was positive in spermatogonia and round spermatids but absent in spermatocytes. The mean grey value (MGV) of CHD5 in spermatogonia was generally weak in spermatocyte arrest (157.4 ± 16.6) and spermatid arrest (155.3 ± 16.8), and there was no significant difference between them [P=0.49, 95% confidence interval (CI): (-4.3, 6), effect size (r): 0.02]. Although there was a significant difference in the expression of H3K9me3 and H4K12ac (P<0.001), both histone modifications were found in all observed spermatogenic cells. Conclusion: The expressions of CHD5, H3K9me3, and H4K12ac in different spermatogenic cell types produce similar results, indicating that they cannot be used as markers to determine the type of spermatogenic maturation arrest in humans. The significant finding in this research is the expression of CHD5 in human spermatogonia cells, which requires further study for elaboration.
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Background: The dilation and torsion of testicular veins in the plexus pampiniformis causes Varic... more Background: The dilation and torsion of testicular veins in the plexus pampiniformis causes Varicocele, which is a surgically repairable cause of male infertility. This study assessed the impact of varicocelectomy on semen characteristics, total motile sperm count (TMSC) and sperm DNA integrity in patients with severe oligoasthenoteratozoospermia (OAT). Materials and Methods: In this prospective study, semen samples of 360 men with severe OAT who underwent varicocelectomy according to World Health Organization (WHO) criteria 2021 were studied (pre-operatively and at 6, 12, and 18 months post-operatively). Results: The average age of our patients was 38.5 years. The mean spermatozoa concentration was found to be 1.60 ± 0.83 million/ml pre-operatively, while the mean post-operative concentration was 5.17 ± 1.23 million/ml at 6 months, 8.32 ± 0.98 million/ml at 12 months, and 13.51 ± 1.48 million/ml at 18 months (P<0.0001). The mean percentage of A+B motile spermatozoa was 2.92 ± 1.17% pre-operatively, 6.10 ± 1.51% at six months, 9.58 ± 1.49% at 12 months and 13.92 ± 1.88% at 18 months postoperatively (P<0.0001). The mean Modified David's morphology score was 3.80 ± 1.43% pre-operatively, 5.95 ± 1.23% at 6 months, 7.94 ± 1.18% at 12 months, and 10.82 ± 1.91% at 18 months post-operatively (P<0.0001). The mean of total motile sperm count (TMSC) was statistically improved after varicocelectomy (P<0.001). The mean of DNA fragmentation index (DFI) of the spermatozoa was 31.40 ± 0.52% pre-operatively, and post-operatively at 28.20 ± 0.32% at 6 months, 25.90 ± 0.31% at 12 months and 20.50 ± 0.40% at 18 months (P<0.001). Conclusion: Varicocelectomy was associated with significant improvement of sperm parameters and DNA fragmentation resulting in significant improvement of spermatogenesis quality. We believe that universalization in the routinely used sperm dispersion chromatin (SDC) test could be beneficial in the treatment of infertility.
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Background: Age, smoking, sleep duration, sleep quality, and obesity are risk factors that can af... more Background: Age, smoking, sleep duration, sleep quality, and obesity are risk factors that can affect the amount of sperm concentration, morphology, and motility. The aim of this study is to assess the lifestyle effects: of age, smoking, sleep duration, sleep quality, and obesity on the amount of concentration, morphology, and motility of sperm. Materials and Methods: The study utilized an analytical observational approach with a cross-sectional design. The study subjects comprised 70 male partners of infertile couples admitted to the Sekar Fertility Clinic at the Dr. Moewardi General Hospital between March and August 2022. The study assessed variables including age, body mass index (BMI), smoking status, sleep duration, sleep quality, sperm concentration, sperm morphology, and sperm motility. Furthermore, the data were analyzed using univariate, bivariate, and multivariate methods with SPSS 25 software. Results: The research findings demonstrate that obesity is significantly associated with abnormal sperm concentration [odds ratio (OR)=40.07, confidence interval (CI)=3.90-411.67, P=0.002]. Furthermore, moderate or heavy smoking is significantly associated with abnormal sperm concentration (OR=17.45, CI=1.83-166.15, P=0.013) and sleep quality with severe disorders (OR=5.73, CI=1.12-29.21, P=0.036). Moreover, obesity is significantly associated with abnormal sperm motility (OR=12.97, CI=2.66-63.15, P=0.002), while moderate or heavy smoking (OR=5.89, CI=1.23-28.20, P=0.026) and poor sleep duration (OR=6.21, CI=1.43-26.92, P=0.015) also exhibit significant associations with abnormal sperm motility. However, no significant findings were observed regarding sperm morphology. Conclusion: The findings of this study indicate that obesity, moderate or heavy smoking, and sleep quality have statistically significant effects on sperm concentration, while obesity, moderate or heavy smoking, and sleep duration have statistically significant effects on sperm motility. However, no statistically significant influence was observed on sperm morphology. Further research with larger sample sizes and more diverse populations is needed to validate these findings and explore other potential factors that may impact male fertility.
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Background: Selecting embryos with the highest implantation potential is crucial for in vitro fer... more Background: Selecting embryos with the highest implantation potential is crucial for in vitro fertilization (IVF) success. Both the timing of blastulation, day 5 (D5) or D6, and the embryo quality have been suggested as influential factors in determining the clinical outcome of single euploid blastocyst transfers. However, evidence supporting the superiority of D5 over D6 blastocysts remains inconclusive. The aim of this study was to compare clinical outcomes following the transfer of euploid blastocysts with different quality and timing of blastulation. Materials and Methods: A retrospective cohort study was conducted at our Assisted Reproductive Center, analyzing the outcome of 774 transfers with D5 euploids and 155 transfers with D6 euploids performed between January 2019 and February 2022. Results: The live birth rate was significantly lower in the euploid D6 group compared to the euploid D5 group (38.71vs. 55.04%, P=0.001). The outcome was significantly influenced by the quality of the embryos. Live birth rates were 62.14 and 53.61% following transfers of D5 and D6 excellent embryos respectively, 45.18 and 32.21% following transfer of D5 and D6 good embryos but only 28.64 and 19.32% following transfer of D5 and D6 fair embryos. The outcome difference was statistically significant across embryo quality categories (P=0.001). The adjusted risk ratios (RR) of clinical outcomes indicated that excellent euploid D5 embryos consistently outperformed other types of embryo quality. Conclusion: The timing of blastulation and embryo quality are crucial factors in determining the success of single euploid blastocyst transfers. Excellent euploid D5 transfers yielded superior clinical outcomes, providing valuable insights for IVF teams and patients when selecting embryos to be transferred.
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Background: Central nervous system damage in multiple sclerosis (MS) leads to severe physical dis... more Background: Central nervous system damage in multiple sclerosis (MS) leads to severe physical disability and neurological defects. Sexual dysfunction and infertility in patients with MS have often been neglected in previous studies. Aerobic exercise is suggested to improve circulating testosterone levels and sexual function. Therefore, the purpose of this study was to investigate the effect of aerobic exercise on sex hormone levels in a cuprizone rat model of MS. Materials and Methods: In this experimental study, 30 male rats (aged 70 days, 154.55 ± 18.1 g) were randomly divided into five groups: MS, exercise-MS (EX-MS), MS-EX, EX-MS-EX, and normal control (control). MS was induced by feeding cuprizone pellets (0.2%) to the rats for six weeks. The exercise groups performed an aerobic exercise protocol on a treadmill five days/week for six weeks before and during the induction of the MS model. Serum testosterone, follicle stimulating hormone (FSH), and luteinising hormone (LH) levels were measured using the ELISA method with standard kits (ZellBio Germany). Luxol fast blue staining (LFB) of the corpora collosa were performed. Results: The results showed a significant decrease in the serum levels of testosterone, FSH, and LH in the MS groups compared to the control group (P<0.05). There was a significant increase in the serum levels of testosterone, FSH, and LH in the EX-MS-EX, and EX-MS groups compared to the MS group (P<0.05). Conclusion: Aerobic exercise could improve the level of sex hormones in the cuprizone rat model of MS and may be used to attenuate sexual dysfunction in patients with MS.
Int J Fertil Steril, Vol 18, No 3, July-September , 2024
Background: Ovarian reserve is one of the most important factors that influences the success of a... more Background: Ovarian reserve is one of the most important factors that influences the success of assisted reproductive technology (ART). Recently, the role of anti-müllerian hormone (AMH) in ART has been investigated as a marker for the prediction of ovarian response. We aim to examine this relationship within a large Iranian population. Materials and Methods: In this cross-sectional study, we obtained data from 1000 infertile couples who referred to the Research and Clinical Centre of Yazd Infertility Clinic for in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Serum AMH levels, oocyte count, numbers of fertilised oocytes, endometrial thickness, and percentage of mature oocytes were measured. The relationship between AMH serum levels and the number and quality of oocytes and embryos in ART cycles was analysed. Results: In the linear regression model, the log of the variables total dose of gonadotropin, two pronuclei (2PN), log oestradiol, total embryos, duration of stimulation, number of embryos transferred, protocol, and cause of infertility were significant predictors of log AMH. Conclusion: There appears to be a relationship between serum AMH levels in the early follicular phase and ovarian reserve. Higher serum AMH levels were also associated with shorter ART cycles.
Int J Fertil Steril, Vol 18, No 3, July-September, 2024
Background: Middle-aged working women represent most patients attending fertility clinics for in ... more Background: Middle-aged working women represent most patients attending fertility clinics for in vitro fertilization (IVF) treatment. In this study, we aimed to identify the association of women's working status with clinical pregnancy and miscarriage in the first trimester after IVF treatment. Materials and Methods: In this single-centre cross-sectional study at a private clinic in Kazakhstan, we reviewed electronic medical records of all IVF with intracytoplasmic sperm injection (ICSI) and fresh embryo transfer (ET) cycles from January 2018 to December 2019 (n=654). 300 cycles in patients with normal ovarian reserve and registered working status of a female partner in the medical records were selected for the analysis. The study's primary outcome measures were clinical pregnancy rates and clinical miscarriage in the first trimester. Results: 204 women were employed, while 96 were not employed before the start of treatment. The mean age of all patients was 32.2 ± 4.8 years, ranging from 23 to 46 years. Two-thirds of working women had office-based occupations employed as doctors, school and university teachers, accountants, clerks, and managers. One-third of the study participants had manual labor jobs, including service positions and plant workers. There was no association between women's working status and clinical pregnancy rate adjusted for age, antral follicle count, history of pelvic adhesiolysis, and embryo development stage at embryo transfer. However, working women had almost five times the risk of the first trimester miscarriage compared to non-working women [adjusted odds ratio (aOR) 4.56, 95% confidence interval (CI): 0.52 to 4.96] adjusted for age and number of retrieved oocytes. Conclusion: Women who work before commencing IVF treatment can be reassured of having equal chances of conception following the treatment compared to non-working women. The observed risk of first trimester miscarriage in working women necessitates further research before drawing any conclusions from medical and public health points.
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Papers by international journal of fertility and sterility Int J Fertil Steril
been used for type-2-diabetes treatment due to its favorable effect on insulin sensitivity. The insulin resistance leading
to metabolic syndrome is closely linked to hyperandrogenemia in polycystic ovary syndrome (PCOS). This study
evaluated the metabolic and reproductive efficacy and safety of DLBS3233 in insulin-resistant PCOS women.
Materials and Methods: This was a 2-arm, randomized, double-blind, controlled, noninferiority clinical study over
a 6-month therapy with DLBS3233 100-mg daily in comparison to metformin-XR 750 mg twice daily, involving 124
PCOS women with insulin resistance. The primary efficacy endpoint was the improvement of Homeostasis Model
Assessment-Insulin Resistance (HOMA-IR). Secondary endpoints were improvements in other metabolic and reproductive
parameters. Safety endpoints were based on blood pressure, heart rate, electrocardiogram findings, liver and
renal function, and adverse events.
Results: After 6 months, HOMA-IR improvement in DLBS3233-treated group (-1.03 ± 0.50) and metformin-XR (-1.19
± 0.50) were comparable, with a between-group difference fell within the pre-set non-inferiority margin (0.16; 95% confidence
interval (CI): -1.24, 1.56; P=0.3168). The HOMA-IR in both groups were significantly improved from baseline.
On all secondary endpoints, both groups showed comparable effects. Markedly fewer adverse events occurred in the
DLBS3233 treated group than in the Metformin-XR-treated group and most were mild clinically and had been resolved
by the end of the study.
Conclusion: Treatment with DLBS3233 100-mg daily in PCOS women demonstrated comparable efficacy to metformin-
XR 750-mg twice daily in improving insulin resistance. However, the non-inferiority of DLBS3233 to metformin-
XR remains inconclusive. DLBS3233 was more tolerable than metformin-XR (registration number: NCT01733459).
successfully implant after multiple cycles of in vitro fertilization (IVF) treatment. The aim of this study is to investigate
the impact of intrauterine granulocyte colony-stimulating factor (G-CSF) and platelet-rich plasma (PRP) on
pregnancy rate in patients with RIF.
Materials and Methods: The present randomised clinical trial study was conducted at the IVF Centre of Mehr
Medical Institute in Rasht, Iran, from 2020 to 2022. The research consisted of 200 individuals who had experienced
multiple failed cycles. These patients were randomised into two groups: intrauterine infusion of 1 ml of G-CSF and
intrauterine infusion of 1 ml autologous PRP at least 48 hours before embryo transfer (ET). The groups were compared
in terms of implantation rate, and chemical, clinical, and ongoing pregnancy.
Results: The implantation rate was significantly higher in patients who received PRP (P=0.016). Chemical pregnancy in
the PRP group was significantly higher than G-CSF group (P=0.003). Both clinical pregnancy and ongoing pregnancy
rates were significantly higher in the PRP group (P=0.001) compared to the G-CSF group (P=0.02).
Conclusion: The utilisation of PRP via intrauterine infusion is considerably more successful than G-CSF in enhancing
pregnancy and live birth rates among patients with RIF. (registration number: IRCT20180528039878N3).
pregnancy rates. The objective of the present study was to assess the impact of endometrial fundal incision (EFI) during
hysteroscopy on reproductive outcomes in a population of oocyte recipients.
Materials and Methods: A randomized controlled trial was conducted between 2020 and 2023 at the Third Department
of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki
and “Assisting Nature Centre of Reproduction and Genetics”. The study population consisted of women who
underwent hysteroscopy randomly assigned in a 1:1 ratio to either EFI (one to three months before embryotransfer
with donor oocytes) or no intervention throughout office hysteroscopy. Clinical pregnancy and live birth rates were
the primary outcomes.
Results: After the exclusion of patients with intraoperative diagnosed endometrial pathology, a total of 124 women
underwent randomization. The pregnancy test was positive in 79% (n=49/62) of the women in the EFI compared to
59.7% (n=37/62) in the hysteroscopy-only group (P=0.019), while the live birth rates did not differ between the two
groups (58.1%, n=36/62 vs. 51.6%, n=32/62, P=0.470).
Conclusion: EFI during hysteroscopy seems to improve pregnancy rates in oocyte recipients without intrauterine
pathology, while live birth rates are not affected by the EFI. These results should be interpreted with caution before
the implementation of EFI in the routine in vitro fertilization (IVF) practice (registration number: NCT04580056).
clinical trials emerge as the cornerstone of progress. These
trials, propelled by the unwavering dedication of scientific
pioneers, serve as the bedrock for innovation and discovery
in reproductive health. Through rigorous experimentation
and meticulous analysis, they illuminate the path towards
novel solutions for the complex challenges of infertility.
remodeling and histone modification. This study evaluated the status of chromatin remodeling chromodomain helicase
DNA binding protein 5 (CHD5) and histone modifications histone 4 lys-12 acetylation (H4K12ac) and histone 3
lys-9 trimethylation (H3K9me3) in human testicular biopsies, based on maturation arrest type.
Materials and Methods: The cross-sectional study utilized 18 Bouin-fixed paraffin-embedded (BFPE) specimens prepared
from residual tissue from routine laboratory tests of infertile patients. The expression of CHD5, H4K12ac, and H3K9me3
was examined through immunohistochemistry (IHC). The intensity was measured using ImageJ with IHC Profiler and
StarDist plugins. Statistical analysis was performed using Python with Scipy.Stats module. The data were tested with Shapiro–
Wilk for normality and Levene test for homogeneity. The differences in the intensity of spermatogenic cells were assessed
using Kruskal-Wallis and Mann-Whitney tests. A difference was considered statistically significant if P<0.05.
Results: We found three types of maturation arrest, including Sertoli cell only (n=5), spermatocyte arrest (n=4), and
spermatid arrest (n=9). CHD5 was positive in spermatogonia and round spermatids but absent in spermatocytes. The
mean grey value (MGV) of CHD5 in spermatogonia was generally weak in spermatocyte arrest (157.4 ± 16.6) and
spermatid arrest (155.3 ± 16.8), and there was no significant difference between them [P=0.49, 95% confidence interval
(CI): (-4.3, 6), effect size (r): 0.02]. Although there was a significant difference in the expression of H3K9me3 and
H4K12ac (P<0.001), both histone modifications were found in all observed spermatogenic cells.
Conclusion: The expressions of CHD5, H3K9me3, and H4K12ac in different spermatogenic cell types produce similar results,
indicating that they cannot be used as markers to determine the type of spermatogenic maturation arrest in humans. The significant
finding in this research is the expression of CHD5 in human spermatogonia cells, which requires further study for elaboration.
technology (ART). Recently, the role of anti-müllerian hormone (AMH) in ART has been investigated as a marker for
the prediction of ovarian response. We aim to examine this relationship within a large Iranian population.
Materials and Methods: In this cross-sectional study, we obtained data from 1000 infertile couples who referred to
the Research and Clinical Centre of Yazd Infertility Clinic for in vitro fertilisation (IVF) or intracytoplasmic sperm
injection (ICSI). Serum AMH levels, oocyte count, numbers of fertilised oocytes, endometrial thickness, and percentage
of mature oocytes were measured. The relationship between AMH serum levels and the number and quality of
oocytes and embryos in ART cycles was analysed.
Results: In the linear regression model, the log of the variables total dose of gonadotropin, two pronuclei (2PN), log
oestradiol, total embryos, duration of stimulation, number of embryos transferred, protocol, and cause of infertility
were significant predictors of log AMH.
Conclusion: There appears to be a relationship between serum AMH levels in the early follicular phase and ovarian
reserve. Higher serum AMH levels were also associated with shorter ART cycles.
been used for type-2-diabetes treatment due to its favorable effect on insulin sensitivity. The insulin resistance leading
to metabolic syndrome is closely linked to hyperandrogenemia in polycystic ovary syndrome (PCOS). This study
evaluated the metabolic and reproductive efficacy and safety of DLBS3233 in insulin-resistant PCOS women.
Materials and Methods: This was a 2-arm, randomized, double-blind, controlled, noninferiority clinical study over
a 6-month therapy with DLBS3233 100-mg daily in comparison to metformin-XR 750 mg twice daily, involving 124
PCOS women with insulin resistance. The primary efficacy endpoint was the improvement of Homeostasis Model
Assessment-Insulin Resistance (HOMA-IR). Secondary endpoints were improvements in other metabolic and reproductive
parameters. Safety endpoints were based on blood pressure, heart rate, electrocardiogram findings, liver and
renal function, and adverse events.
Results: After 6 months, HOMA-IR improvement in DLBS3233-treated group (-1.03 ± 0.50) and metformin-XR (-1.19
± 0.50) were comparable, with a between-group difference fell within the pre-set non-inferiority margin (0.16; 95% confidence
interval (CI): -1.24, 1.56; P=0.3168). The HOMA-IR in both groups were significantly improved from baseline.
On all secondary endpoints, both groups showed comparable effects. Markedly fewer adverse events occurred in the
DLBS3233 treated group than in the Metformin-XR-treated group and most were mild clinically and had been resolved
by the end of the study.
Conclusion: Treatment with DLBS3233 100-mg daily in PCOS women demonstrated comparable efficacy to metformin-
XR 750-mg twice daily in improving insulin resistance. However, the non-inferiority of DLBS3233 to metformin-
XR remains inconclusive. DLBS3233 was more tolerable than metformin-XR (registration number: NCT01733459).
successfully implant after multiple cycles of in vitro fertilization (IVF) treatment. The aim of this study is to investigate
the impact of intrauterine granulocyte colony-stimulating factor (G-CSF) and platelet-rich plasma (PRP) on
pregnancy rate in patients with RIF.
Materials and Methods: The present randomised clinical trial study was conducted at the IVF Centre of Mehr
Medical Institute in Rasht, Iran, from 2020 to 2022. The research consisted of 200 individuals who had experienced
multiple failed cycles. These patients were randomised into two groups: intrauterine infusion of 1 ml of G-CSF and
intrauterine infusion of 1 ml autologous PRP at least 48 hours before embryo transfer (ET). The groups were compared
in terms of implantation rate, and chemical, clinical, and ongoing pregnancy.
Results: The implantation rate was significantly higher in patients who received PRP (P=0.016). Chemical pregnancy in
the PRP group was significantly higher than G-CSF group (P=0.003). Both clinical pregnancy and ongoing pregnancy
rates were significantly higher in the PRP group (P=0.001) compared to the G-CSF group (P=0.02).
Conclusion: The utilisation of PRP via intrauterine infusion is considerably more successful than G-CSF in enhancing
pregnancy and live birth rates among patients with RIF. (registration number: IRCT20180528039878N3).
pregnancy rates. The objective of the present study was to assess the impact of endometrial fundal incision (EFI) during
hysteroscopy on reproductive outcomes in a population of oocyte recipients.
Materials and Methods: A randomized controlled trial was conducted between 2020 and 2023 at the Third Department
of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki
and “Assisting Nature Centre of Reproduction and Genetics”. The study population consisted of women who
underwent hysteroscopy randomly assigned in a 1:1 ratio to either EFI (one to three months before embryotransfer
with donor oocytes) or no intervention throughout office hysteroscopy. Clinical pregnancy and live birth rates were
the primary outcomes.
Results: After the exclusion of patients with intraoperative diagnosed endometrial pathology, a total of 124 women
underwent randomization. The pregnancy test was positive in 79% (n=49/62) of the women in the EFI compared to
59.7% (n=37/62) in the hysteroscopy-only group (P=0.019), while the live birth rates did not differ between the two
groups (58.1%, n=36/62 vs. 51.6%, n=32/62, P=0.470).
Conclusion: EFI during hysteroscopy seems to improve pregnancy rates in oocyte recipients without intrauterine
pathology, while live birth rates are not affected by the EFI. These results should be interpreted with caution before
the implementation of EFI in the routine in vitro fertilization (IVF) practice (registration number: NCT04580056).
clinical trials emerge as the cornerstone of progress. These
trials, propelled by the unwavering dedication of scientific
pioneers, serve as the bedrock for innovation and discovery
in reproductive health. Through rigorous experimentation
and meticulous analysis, they illuminate the path towards
novel solutions for the complex challenges of infertility.
remodeling and histone modification. This study evaluated the status of chromatin remodeling chromodomain helicase
DNA binding protein 5 (CHD5) and histone modifications histone 4 lys-12 acetylation (H4K12ac) and histone 3
lys-9 trimethylation (H3K9me3) in human testicular biopsies, based on maturation arrest type.
Materials and Methods: The cross-sectional study utilized 18 Bouin-fixed paraffin-embedded (BFPE) specimens prepared
from residual tissue from routine laboratory tests of infertile patients. The expression of CHD5, H4K12ac, and H3K9me3
was examined through immunohistochemistry (IHC). The intensity was measured using ImageJ with IHC Profiler and
StarDist plugins. Statistical analysis was performed using Python with Scipy.Stats module. The data were tested with Shapiro–
Wilk for normality and Levene test for homogeneity. The differences in the intensity of spermatogenic cells were assessed
using Kruskal-Wallis and Mann-Whitney tests. A difference was considered statistically significant if P<0.05.
Results: We found three types of maturation arrest, including Sertoli cell only (n=5), spermatocyte arrest (n=4), and
spermatid arrest (n=9). CHD5 was positive in spermatogonia and round spermatids but absent in spermatocytes. The
mean grey value (MGV) of CHD5 in spermatogonia was generally weak in spermatocyte arrest (157.4 ± 16.6) and
spermatid arrest (155.3 ± 16.8), and there was no significant difference between them [P=0.49, 95% confidence interval
(CI): (-4.3, 6), effect size (r): 0.02]. Although there was a significant difference in the expression of H3K9me3 and
H4K12ac (P<0.001), both histone modifications were found in all observed spermatogenic cells.
Conclusion: The expressions of CHD5, H3K9me3, and H4K12ac in different spermatogenic cell types produce similar results,
indicating that they cannot be used as markers to determine the type of spermatogenic maturation arrest in humans. The significant
finding in this research is the expression of CHD5 in human spermatogonia cells, which requires further study for elaboration.
technology (ART). Recently, the role of anti-müllerian hormone (AMH) in ART has been investigated as a marker for
the prediction of ovarian response. We aim to examine this relationship within a large Iranian population.
Materials and Methods: In this cross-sectional study, we obtained data from 1000 infertile couples who referred to
the Research and Clinical Centre of Yazd Infertility Clinic for in vitro fertilisation (IVF) or intracytoplasmic sperm
injection (ICSI). Serum AMH levels, oocyte count, numbers of fertilised oocytes, endometrial thickness, and percentage
of mature oocytes were measured. The relationship between AMH serum levels and the number and quality of
oocytes and embryos in ART cycles was analysed.
Results: In the linear regression model, the log of the variables total dose of gonadotropin, two pronuclei (2PN), log
oestradiol, total embryos, duration of stimulation, number of embryos transferred, protocol, and cause of infertility
were significant predictors of log AMH.
Conclusion: There appears to be a relationship between serum AMH levels in the early follicular phase and ovarian
reserve. Higher serum AMH levels were also associated with shorter ART cycles.