International Journal of Fertility & Sterility最新文献

Background: Limited data exist regarding the outcomes of frozen-thawed cleavage-stage embryos that undergo extended culture to reach the blastocyst stage. This study aimed to compare the pregnancy outcomes between two approaches: transferring blastocysts derived from frozen-thawed cleavage embryos (D3-5 group) and frozen-thawed blastocysts (D5 group).

Materials and methods: This retrospective observational cohort analysis was conducted at Hung Vuong Hospital (CS/HV/24/23) from January 2022 to December 2023. The D3-5 group comprised 167 patients who underwent embryo transfer with frozen-thawed cleavage embryos, which were subsequently cultured for 2 days before being transferred as blastocysts. The D5 group included 342 patients who received frozen-thawed blastocysts. Positive human chorionic gonadotropin (hCG) rate, clinical pregnancy rate, ongoing pregnancy rate, live birth rate, pregnancy failure rate and cancellation rate were compared between the two groups.

Results: In the D3-5 group, a significant proportion of cycles (65.3%) were cancelled, primarily due to the absence of developed blastocysts for transfer (85.3%), while the remaining 14.7% of cancellations were attributed to other reasons. Patients in the D3-5 group demonstrated comparable pregnancy outcomes to those in the D5 group: positive hCG rate (52 vs. 53%, P=0.898), clinical pregnancy rate (45 vs. 48%, P=0.785), ongoing pregnancy rate (34 vs. 33%, P=0.873), live birth rate (31 vs. 29%, P=0.839), and pregnancy failure rate (21 vs. 24%, P=0.656).

Conclusion: The strategy of culturing frozen-thawed cleavage embryos for two days and transferring them as blastocysts is not inferior to the transfer of frozen-thawed blastocysts. It increases workload for embryologists and poses a risk of cycle cancellation. We propose that the use of frozen-thawed blastocysts may be a more efficient and patient-friendly option.

Background: The study was conducted to investigate the effect of dual trigger with gonadotropin-releasing hormone agonist (GnRH-a) and standard dose human chorionic gonadotropin (hCG) on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes in patients with a history of suboptimal ovarian response.

Materials and methods: In this randomized clinical trial, 52 infertile women who were referred to Royan Institute from November 2019 to November 2022 for a second treatment with IVF/ICSI cycles, and had a suboptimal ovarian response [the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) classification group I] in their previous cycle were evaluated. Ovulation stimulation was performed in all patients with the standard antagonist protocol. At the point of the final ovarian stimulation, patients were randomly assigned into two groups using the permuted block randomization method. In the dual trigger group, 0.2 mg of GnRH-a and two ampoules of recombinant hCG subcutaneously were administered to the patients at the same time. In control group, only two ampoules of recombinant hCG were injected subcutaneously. The ovarian stimulation outcomes and pregnancy rates were compared between groups utilizing appropriate statistical methods.

Results: The two groups were homogeneous in terms of baseline characteristics. The statistical differences were found between groups in terms of, the total number of retrieved oocytes and the number of metaphase II (MII) oocytes as well as the number of obtained and frozen embryos in the dual trigger group were significantly more than those of in the control group (P=0.001, P=0.022, P=0.01, and P=0.035, respectively). The clinical pregnancy and live birth rates in the dual group were higher than those of the control group; nevertheless, the differences were not statistically significant (40.9 vs. 25% and 40.9 vs. 20%, P=0.275 and P=0.143, respectively).

Conclusion: By virtue of these findings, dual trigger significantly improved the ovarian stimulation outcomes in the patients with a history of unexpected poor response. To validate the current findings, further clinical trials with larger sample sizes are required (registration number: NCT04549649).

Background: Celiac disease (CD) is one of the most prevalent chronic digestive disorders, often presenting with intestinal symptoms as well beyond. These symptoms may include reproductive complications. To gain a deeper understanding of a women's fertility potential, medical professionals employ sonographic and laboratory techniques to predict the ovarian reserve. The aim of this study was to explore the ovarian reserve in women affected by CD in comparison to healthy women in their reproductive years, this study aimed to find the relationship between CD and ovarian reserve.

Materials and methods: This case-control study included a total of 27 patients diagnosed with CD, alongside an agematched group of 27 women without CD. A comprehensive checklist for demographic information was completed for each participant. During days 2-4 of the menstrual cycle, blood samples were collected to measure the levels of follicular stimulating hormones (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), anti-mullerin hormone (AMH), and prolactin. Simultaneously, pelvic ultrasound was conducted to assess the number of antral follicles count (AFC) and ovarian volume on the same day.

Results: There was no significant difference in age, pregnancy history, spontaneous abortion, stillbirth, premature births, and low birth weight babies between the case and control groups (P>0.05). However, there were significant variations in mean weight, body mass index, and menarche age between the two groups (P<0.05). Moreover, the serum levels of FSH and AFC of the right and left ovaries also showed significant differences between the two groups (P<0.05). However, no significant difference was observed regarding AMH, LH, TSH, prolactin, and ovarian volumes (P>0.05).

Conclusion: The present study showed that women with CD have significantly higher AFC and serum FSH levels than healthy women.

Background: The important roles of aberrant DNA methylation on semen abnormality have been demonstrated. Alternatively, 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a vital enzyme to regulate the sperm DNA methylation patterns. This study aimed to investigate the methylation of MTHFR at differentially methylated regions (DMR) and the correlation between sperm DNA methylation patterns with semen quality parameters for assessing reproductive health and fertility status.

Materials and methods: In this case-control study, semen samples were collected from 30 infertile (asthenospermia and oligoasthenoteratospermia), and 15 healthy men. Following the modification of DNAs by sodium bisulfite treatment, the methylation status of the MTHFR gene at MDRs was evaluated by the quantitative methylation specific PCR (qMSP) method.

Results: Men with oligoasthenoteratospermia showed a statistically significant difference in mean MTHFR-DMR methylation levels compared to controls (P=0.047) and asthenospermia (P=0.034). Moreover, significant trends of decreasing values were observed in all parameters of the ejaculate (sperm concentration, their overall motility or vitality, and morphology) in men with asthenospermia and oligoasthenoteratospermia. These findings suggest a potential association between increased MTHFR-DMR methylation and reduced semen quality such as spermatozoa count (P=0.002), spermatozoa concentration (P=0.003), progressive (P=0.019), and normal morphology (P=0.003).

Conclusion: We found that abnormal DNA methylation of MTHFR at DMR region was correlated with decreased sperm parameters and therefore male infertility. Further research is needed to explore the mechanisms affecting of MTHFR methylation on male infertility.

Background: Ifosfamide (IFO) is a widely used chemotherapeutic agent that exerts cytotoxic effects through various mechanisms, including the induction of apoptosis and oxidative stress. However, its use is associated with detrimental effects on male reproductive health, including mitochondrial dysfunction and oxidative stress-induced damage. Mitophagy, a selective autophagic process, plays a crucial role in maintaining mitochondrial homeostasis during spermatogenesis. This study aimed to investigate the potential protective effect of lycopene against IFO-induced mitophagy in testicular tissue. We evaluated the expression levels of key mitophagy regulators Pink1, Parkin, and LC3-I/ II in testicular tissue of rats treated with IFO alone or in combination with lycopene.

Materials and methods: In this experimental study, 24 mature male Wistar rats (250 g ± 25) were divided into control (received normal saline), IFO-sole (received 250 mg/kg, single dose, ip), lycopene (25 mg/kg, orally), and IFO+lycopene groups. Following 60 days, the rats were euthanized and the testicles were dissected out. The expression levels of Pink1, Parkin, and LC3-I/II were evaluated using qRT-PCR and immunohistochemistry (IHC) techniques.

Results: Our findings demonstrated that IFO significantly upregulated Pink1, Parkin,, and LC3-I/II expression at both mRNA and protein levels compared to controls. Conversely, lycopene administration mitigated these increases induced by IFO, suggesting its potential to attenuate IFO-induced mitophagy. Immunohistochemistry analysis confirmed the protective effect of lycopene, showing reduced expression levels of Pink1, Parkin,, and LC3-I/II in the presence of lycopene following IFO treatment.

Conclusion: These results underscore lycopene's role as a potent protective agent that can mitigate IFO-induced mitophagy in testicular tissue. Further research into the underlying mechanisms of lycopene's protective effects will be crucial for developing therapeutic strategies to preserve male fertility during IFO treatment.

Background: Endometriosis is a prevalent women's health disorder that lacks a definitive cure. Numerous studies have been conducted to identify the underlying causes of this disease and select the most effective pharmaceutical intervention. ISL LIM homeobox 2 (ISL2) plays a significant role in promoting angiogenesis. Contemporary investigations strongly suggest that inhibiting angiogenesis could lead to the modulation of endometriosis and reduce associated symptoms. This study aims to repurpose drugs to target ISL2 for endometriosis treatment.

Materials and methods: In this computational study, we sought to confirm that ISL2 is an appropriate target for this study by evaluating its expression in the endometrial tissues of patients diagnosed with endometriosis, as well as in tissues from a control group of healthy women. Subsequently, we used computational techniques to select the best inhibitor for ISL2 from among select food and drug administration (FDA)-approved drugs.

Results: There was a significant increase ISL2 gene expression in the tissues of women with endometriosis. Therefore, we selected the ISL2 protein as a target for drug repurposing. Initial docking results revealed that, out of 2471 FDAapproved drugs, six (Dactinomycin, Paritaprevir, Ivermectin, Ergotamine, Alectinib, and Simeprevir) exhibited the most favourable binding energy (ΔG ≤-8 kcal/mol) with ISL2. Molecular dynamics (MD) simulations of these six complexes showed that Ivermectin displayed the lowest root mean square fluctuation (RMSF) and root mean square deviation (RMSD), as well as the highest count of hydrogen bonds and number of contacts, which indicated a more stable formation of this complex with ISL2.

Conclusion: Although these six drugs appear to be promising candidates for modulating endometriosis, Ivermectin is more likely to effectively inhibit ISL2.

Background: Pre-eclampsia is a serious medical condition characterised by high blood pressure and signs of organ damage that is associated with adverse pregnancy outcomes, including low birth weight. Selenoprotein P (SELENOP) and vascular endothelial growth factor B (VEGF-B) are antioxidants that can improve the condition of this disease. This study aims to investigate the placental levels of SELENOP and VEGF-B, and their association with birth weight in pregnant women with pre-eclampsia compared to healthy pregnant women.

Materials and methods: This case-control study enrolled 30 pregnant women with pre-eclampsia as the case group and 30 healthy pregnant women as the control group. Demographic information and anthropometric indices were collected and recorded in forms. Placental levels of SELENOP and VEGF-B were assessed by a commercial human kit and based on enzyme-linked immunosorbent assay (ELISA). P<0.05 indicated statistical significance.

Results: The mean placental level of VEGF-B in pregnant women with pre-eclampsia was lower than the healthy group (P=0.001) as was the mean placental level of SELENOP compared to the healthy group (P=0.048). No significant correlation existed between placental levels of SELENOP (r=0.253, P=0.051) and VEGF-B (r=0.671, P=0.056) with birth weight.

Conclusion: Our findings showed that pregnant women with pre-eclampsia had lower levels of VEGF-B and SELENOP compared to healthy pregnant women. The findings may assist with pre-eclampsia diagnosis, management, and prediction, and benefit mothers and babies.

Background: Endometriosis is a complex, heterogeneous disease with several genetic and non-genetic pathogenic factors. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway may influence both progression and different stages of endometriosis. This study aims to investigate the effects of the PIK3CA, AKT1, and mTOR single nucleotide polymorphisms (SNP) with endometriosis risk in an Iranian cohort.

Materials and methods: In this case-control study, samples from 127 patients and 125 controls were examined using allelespecific polymerase chain reaction (AS-PCR) polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: The PIK3CA rs2230461 and AKT1 rs1130233 had a more than 2.5-fold significant increase in disease risk in a homozygous mutation [95% confidence interval (CI): 1.119 -5.985; 95% CI: 1.093-7.535, respectively]. However, the risk was reduced by half or less than half in carriers of the mutant alleles for mTOR rs2295080 (95% CI: 0.108- 0.927, P=0.036). We confirmed that moderate/severe endometriosis was approximately five times more common in patients with the PIK3CA mutant genotype [odds ratio (OR): 4.800, 95% CI: 2.171-10.611, P<0.001], and over two times more frequent in patients with the AKT1 mutant variant (OR: 2.674, 95% CI: 1.261-5.670, P=0.010). The mutant allele for mTOR rs2295080 was more frequent in patients with stages I and II endometriosis (P=0.022).

Conclusion: The results show that PIK3CA rs2230461 and AKT1 rs1130233 SNPs are risk factors for endometriosis and the mTOR rs2295080 gene polymorphism is a protective factor for the development of endometriosis in an Iranian cohort. The PIK3CA rs2230461, AKT1 rs1130233, and mTOR rs2295080 gene polymorphisms should be further investigated as potential candidate SNPs for predicting endometriosis susceptibility.

Background: Oligo-asthenoteratozoospermia (OAT) is one of the causes of male subinfertility, and one of the treatment solutions is sperm cryopreservation. However, during the freezing-thawing process, sperm parameters decrease. It is important to find compounds that can prevent the reduction of sperm parameters. The aim of this study is to reduce male infertility through sperm preservation.

Materials and methods: In this experimental study, thirty OAT patients meeting the inclusion criteria were selected for the current research. Initially, the patients were studied by karyotyping, and all of them were normal 46 XY. After that, sperm samples were taken from them. Sperm parameters such as viability, concentration, motility and percentage of abnormal morphology were determined before cryopreservation. Then, the samples were divided into four aliquots and placed in cryopreservation medium supplemented with different concentrations of curcumin (0, 15, 20, and 25 μM). These samples were placed in a nitrogen tank. After 7 days, the samples were thawed, and sperm parameters were measured. In the next step, the content of malondialdehyde (MDA) and the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured by kits. Finally, after RNA extraction and cDNA synthesis, the expression levels of the BAD, B-cell lymphoma-extra large (BCL-XL) and microRNA-21 (MIR-21) genes were investigated using reverse transcription polymerase chain reaction (RT-PCR).

Results: Curcumin (20 μM) conserved OAT sperm motility after the freezing-thawing process. Additionally, this concentration of curcumin decreased MDA and improved SOD and GPx activities in cryopreserved sperm. The results of gene expression analysis showed downregulation of BAD and overexpression of both BCL-XL and MIR-21 in 20 μM curcumin-treated sperm after the freezing-thawing process.

Conclusion: It can be concluded that adding appropriate antioxidants to the sperm freezing medium can greatly reduce the destructive effects of oxidative stress and improve sperm motility.

Background: Phase I study to assess the effects of single oral doses of 100, 200, and 300 mg/day of sodium tungstate (OXO-001) in healthy women of childbearing age.

Materials and methods: A randomized, double-blind, dose-finding, and placebo-controlled phase I study was conducted in healthy weight (body mass index [BMI] 18.5-24.9 kg/m2) and overweight (BMI 25 to ≥30 kg/m2) volunteers who received OXO-001 or placebo during a menstrual cycle (maximum 28 days). Data recorded were adverse events (AEs), vital signs, electrocardiogram (ECG), laboratory tests, pharmacokinetics (PK) parameters, and transvaginal ultrasound.

Results: Thirty women were included in the safety analysis, and 29 completed the study. Thirty-eight treatment emergent adverse events (TEAEs) were reported by 20 participants (15 in the OXO-001 group and 5 in the placebo group). TEAEs were related to OXO-001 administration in 13.2, 10.5, and 15.8% of cases of the 100, 200, and 300 mg doses, respectively. None of the participants discontinued the study, and no serious AEs or deaths were recorded. Differences in TEAEs by BMI were not found. The PK profile showed a fast absorption rate and proportional increases of OXO-001 plasma concentration to increasing doses, suggesting linear PK, with higher concentrations in BMI <25 kg/m2 group higher than in the ≥25 kg/m2 group. There were no relevant changes in vital signs, ECG, ovarian follicle development, endometrial morphology, and laboratory tests before and after the administration of OXO-001 or placebo.

Conclusion: The administration of OXO-001 in volunteers of childbearing age was safe and well tolerated, with consistent PK linear profile within doses studied and without detrimental effect on endometrium or ovary-related variables, with similar effects in healthy weight and overweight participants. The maximum studied dose (300 mg/ day) was safe and well tolerated. These data are sufficient to support further clinical trials (registration number: 2016-001276-30).