International Journal of Fertility & Sterility最新文献

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: 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: 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).

Background: Endometriosis is an estrogen-dependent disease. Cytochrome P450 aromatase which encoded by CYP19A1 is a key enzyme in the pathway of estrogen biosynthesis. cAMP response element (CRE) binding protein (CREB) and cAMP response element modulator (CREM), two members of the CREB family have important roles in the regulation of steroidogenic gene expression. CREB and CREM form homo and heterodimers for binding to the CRE sequence in the promoter of the CYP19A1 gene and regulate its expression. CREB regulated transcription coactivator 2 (CRTC2) is a CREB coactivator and regulates aromatase gene expression via binding to the CREB. Inducible cAMP early repressor (ICER) is one of CREM inhibitory isoforms that represses cAMP-induced transcription. Therefore, in this study, we decided to examine the expression levels of CREB, CREM, and CRTC2 genes and also the binding of ICER to the promoter II of the aromatase gene in endometriosis.

Materials and methods: In this case-control study, ectopic and eutopic endometrial tissues of women with endometriosis and endometrial control samples were collected. Real-time polymerase chain reaction (PCR) technique was used for quantitative gene expression of CREB, CREM, and CRTC2. For protein-DNA interaction analysis, soluble chromatin was extracted, and chromatin immunoprecipitation (ChIP) coupled with real-time PCR was performed to quantify the binding of ICER to CYP19A1 promoter II.

Results: Gene expression levels of CREB, CREM, and CRTC2 were significantly increased in ectopic lesions compared with control endometrial samples. In addition, the binding of ICER to CYP19A1 promoter II was significantly decreased in ectopic and eutopic samples compared to the controls.

Conclusion: The overexpression of CREB, CREM, and CRTC2 in the endometriotic tissue samples and decreased binding of ICER to the CYP19A1 prompter II in ectopic and eutopic samples may contribute to the pathogenesis of endometriosis via their regulatory role in the expression of estrogen biosynthesis enzymes.

Background: Due to the high prevalence of intrauterine pathologies, postmenopausal women are more eligible for hysteroscopy procedure. Cervical dilatation is always a major challenge for performing hysteroscopy. The present study aimed to determine the efficacy of vaginal Hyoscine N-butylbromide (HBB) on cervical dilatation prior to hysteroscopy in postmenopausal women.

Materials and methods: This open-label randomized controlled trial was conducted on postmenopausal women who were scheduled for hysteroscopy. Eligible patients were randomly assigned with a ratio of 1:1 to the intervention (received 20 mg HBB vaginally two hours prior to hysteroscopy) and control (did not receive HBB) groups. As the study outcomes, pre-hysteroscopy cervical dilatation (based on the passage of the dilator number 4 through the cervical canal) and the adverse event consequences were compared between the two groups.

Results: Overall, 128 postmenopausal women who were eligible for hysteroscopy were included in the study, with 64 individuals in each group. The percentage of cervical dilatation in the intervention group was significantly higher than the control group (100 vs. 70.3%, P<0.001). Furthermore, none of the adverse event consequences differed significantly between the intervention and control groups: bleeding (3.1 vs. 3.1%, P>0.999), nausea and vomiting (4.7 vs. 0%, P=0.244), dry mouth (3.1 vs. 0%, P=0.496), dizziness (0 vs. 0%), and headache (0 vs. 0%).

Conclusion: Based on the findings, vaginal HBB is effective without any significant side effects in cervical dilation of postmenopausal women (registration number: IRCT20220822055772N1).

Background: This study aims to determine the effect of laparoscopic surgery for advanced endometriosis on spontaneous pregnancy rates and assisted reproductive techniques (ARTs) in patients with endometriosis.

Materials and methods: This retrospective study included 74 reproductive-aged patients who were diagnosed with deep infiltrating endometriosis (DIE), desired to conceive, and underwent resection surgery at the Arash Women's Hospital, Tehran, Iran between March 2017 and March 2021. Patients with any plausible infertility factors or abnormalities in their partner's semen analysis were excluded. At least 6 months after surgery, the patients were contacted by phone to evaluate the success rate of pregnancy in patients and by which approach they were convinced, i.e., naturally, ovulation induction, or using ARTs. Besides, the impact of patients's factors on pregnancy success was evaluated.

Results: During 3 years after surgery, 37 patients (50%) became pregnant. Out of the 37 pregnancies, 16 patients (43.2%) conceived spontaneously, while 21 patients (56.8%) used ARTs. The mean age of women who became pregnant was significantly lower than those who did not conceive. These two groups do not show any significant differences in terms of endometriosis stage, the maximum size of the cyst, DIE nodule type, and the number and anatomical places of nodules. Additionally, patients who benefit from ART are more likely to have adenomyosis.

Conclusion: DIE surgery is associated with a considerable fertility rate. It is also important to note that patient age plays a significant role in the pregnancy rate of this population. Further randomized clinical trials are required to validate the obtained results.

Background: Hydrosalpinx is a recognized condition affecting the fallopian tubes, which decreases the embryo implantation rate and success in in vitro fertilization (IVF) outcomes. It can manifest detrimental effects through inflammatory conditions in the uterine endometrium that may lead to alterations in the expression of transcription factors and cytokines such as; Interleukin-6 (IL-6), Glycodelin A (GdA), and Heparin-binding epidermal growth factor (HB-EGF) involved in endometrial receptivity (ER) and embryo implantation. The alterations of these markers in the endometrium of patients with hydrosalpinx have not been investigated. Therefore, we aimed to evaluate the mRNA expression level of IL-6, HB-EGF, and GdA in the endometrium of women exposed to hydrosalpinx fluid (HF) compared to the fertile group.

Materials and methods: In this case-control study, 30 subjects were enrolled for this study: fifteen patients with communicating hydrosalpinx (aged between 20-37 years old) were compared with 15 fertile aged-matched egg donor women as the control group. All subjects underwent uterine endometrial sampling by Pipple on days 19-24 of the menstrual cycle. Gene expression was quantitatively analyzed using a real-time polymerase chain reaction (PCR) technique. Data analysis was conducted using the Wilcoxon rank test.

Results: The mRNA expression level of IL-6 showed a significant increase in patients with hydrosalpinx compared to the control group (P=0.022). HB-EGF gene expression was significantly reduced in the hydrosalpinx group compared to fertile women (P=0.007). There was an insignificant decrease in GdA mRNA expression level compared to healthy fertile controls (P=0.419).

Conclusion: The presence of hydrosalpinx led to an alteration in the expression of endometrial IL-6, HB-EGF, and GdA mRNA levels in the implantation window, which may explain the reduced implantation rate and success in IVF outcome.

Background: The endometrial microbiome, its composition, and the quantity of some bacteria could be predictors of successful implantation in vitro fertilisation (IVF) treatment. The presence of Lactobacillus, which negatively correlates with pathogenic bacteria, could be a contributing factor to endometrial ecosystem stability. The study aimed to determine whether the quantity of Lactobacillus spp and Gardnerella vaginalis in the endometrium depends on estrogen levels. A secondary aim was to determine whether the decreased number of Lactobacillus spp leads to increased pathogenic bacteria such as Gardnerella vaginalis in the endometrial cavity.

Materials and methods: This prospective study was conducted in a private IVF center in Tuzla, Bosnia and Herzegovina. Participants were recruited from February 2023 to December 2023. The tip of a double-lumen catheter was used to collect samples from the endometrium. QIAamp DNA Mini Kit was used for DNA isolation. A commercial real-time polymerase chain reaction (RT-PCR) kit was used to detect Lactobacillus spp and Gardnerella vaginalis quantitatively.

Results: In total, 92 participants were included in the study, 57 in the fresh cycle and 35 in the frozen cycle of IVF. The youngest participant was 18 years old, and the oldest was 45 years old. The mean age of participants was 34.3 years with a standard deviation of 5.7. After RT-PCR, 90 participants had positive tests on Lactobacillus spp, Gardnerella vaginalis was positive in 31 participants.

Conclusion: Supraphysiological estrogen levels do not significantly change the quantity of Lactobacillus spp and Gardnerella vaginalis in the endometrial cavity. Decreasing the number of Lactobacillus spp increased the number of pathogenic bacteria Gardnerella vaginalis in the endometrial cavity.

Background: There is evidence that pomegranate juice and sildenafil can be effective supplements especially in pregnancy. Therefore; this study aimed to compare the effect of pomegranate juice and sildenafil on Doppler ultrasound findings, Apgar score and fetal estimated weight (FEW) in cases with intrauterine growth retardation (IUGR).

Materials and methods: This randomized clinical trial conducted on a population of naturally pregnant women with IUGR in Arak city (Arak, Iran) during October 2021 to January 2022. Participants were randomly divided into two equal groups (n=27) that received pomegranate juice (230 ml daily dose for 6 weeks, Narnoosh, Arak, Iran) and sildenafil (25 mg, three times a day for 6 weeks, Marham Daru Co., Tehran, Iran). Doppler ultrasound evaluation, including umbilical artery pulsatility index (PI), uterine artery PI and FEW were assessed by a gynecologic resident along with a radiologist immediately after intervention, and birth weight and 1- and 5-minute Apgar scores were registered by a neonatologist.

Results: Twenty-one cases in pomegranate juice group and 23 cases in sildenafil group were included in the analysis. The mean age and weight of participants were 27.1 ± 4.7 year and 68.5 ± 11.5 kg, respectively. The results showed that there was no significant difference between the two groups in terms of mean Apgar score of 1 minute (P=0.631), 5 minutes (P=0.323) and birth weight (P=0.580). No significant difference was observed between two groups in terms of uterine artery PI (P=0.301) and umbilical artery PI (P=0.168), but the EFW changes in the sildenafil group were significantly greater than the pomegranate group (P=0.009).

Conclusion: The results of our study showed that pomegranate juice has a similar effect of sildenafil in IUGR. Therefore, it is recommended to design more studies to achieve results that are more valid (registration number: IRCT20210730052014N1).