International Journal of Fertility & Sterility最新文献

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).

Background: Cynodon dactylon traditionally employed or treating hormonal problems in women. Therefore, this study aimed to assess the effect of C. dactylon hydroalcoholic extract of on letrozole-induced polycystic ovary syndrome (PCOS) in adult rats.

Materials and methods: In this experimental study, hydroalcoholic extract was prepared from the whole plant except the root. Then, 16 female Sprague-Dawley rats were divided into four groups. In the control group, the PCOS model was not induced and no treatment was performed. The PCOS-induced groups received 1 mg/kg of body-weight letrozole daily by gavage for 21 days. In the PCOS-induced groups two groups were orally treated with 250 mg/kg body weight daily metformin or 500 mg/kg body weight daily C. dactylon extract, 28 days after PCOS induction. Hormonal, histopathologic, and histomorphometric analyses were performed. Molecular docking also done to evaluate effect of C. dactylon extract on receptors involved in the pathophysiology of PCOS.

Results: C. dactylon had a remarkable positive effect on estrous cycles and also led to a significant reduction in the weight of PCOS rats. Moreover, C. dactylon extract mitigates PCOS-induced hormonal imbalances including a significant decrease in testosterone and estrogen levels, as well as increased progesterone levels. Ovarian and uterine structures were improved including reducing theca layer thickness, enhancing antral follicular areas, and a significant decrease in the luminal area of the perimetrial layer, endometrial glands, and the total uterine area when compared to the PCOS group. Besides, molecular docking analysis showed that Ar-tumerone, Tumerone, Tricyclo[6.3.0.0(1,5)] undec-2-en-4-one, 2,3,5,9- tetramethyl, Curlone, and 3-Tert-butyl-4-hydroxyanisole showed the most binding affinity to the receptors that play crucial role in the pathophysiology of PCOS.

Conclusion: C. dactylon extract could display positive effects on both the ovary and uterus of letrozole-induced PCOS rats. Therefore, C. dactylon had therapeutic effects on the ovary and uterus of PCOS-induced rat models.

Background: This research delves into exploring the nexus between lipid profiles and pro-inflammatory cytokines in both blood and follicular fluid (FF). It examines their impact on assisted reproductive technology (ART) outcomes and the propensity for ovarian hyperstimulation syndrome (OHSS) in non-obese polycystic ovary syndrome (PCOS) patients.

Materials and methods: One hundred and thirty-one PCOS patients with intracytoplasmic sperm injection (ICSI) indication, participated in this cross-sectional study. Based on plasma fasting lipids, patients were divided into two groups, dyslipidemia group (n=79) was defined as patients with triglyceride (TG) ≥150 mg/dl or/and total cholesterol (TC) ≥200 mg/dl. Patients with lower levels of lipids were included in the normal lipid group (n=51). All patients underwent the antagonist protocol to stimulate ovulation for ICSI. Blood and FF samples collected on the ovum pick-up (OPU) day. The concentrations of lipids in serum and FF, including TC and TG using Colorometry method, and also, high-density lipoprotein (HDL) using turbidimetric method. The lowdensity lipoprotein (LDL) level was calculated by the formula: LDL= TC-TG/5- HDL. Serum tumor necrosis factor-alpha (TNF-α) and interleukin-18 (IL-18) were measured with ELISA kit. ART outcomes encompassed retrieved oocytes, metaphase II oocytes (MII), and rates of fertilization, cleavage, blastocyst development, and chemical and clinical pregnancy.

Results: FF level of LDL-C in the dyslipidemia group was markedly higher than the normal lipid group (P=0.007). Serum TNFα levels (P<0.001) and FF levels of TNF-α and IL-18 were significantly elevated in the dyslipidemia group (P=0.005, P<0.001, respectively). A robust correlation between FF inflammatory cytokines and ART outcomes emerged in PCOS patients, independent of lipid status. Notably, the normal lipid group exhibited a significantly higher risk of OHSS than the dyslipidemia group (P=0.034).

Conclusion: The present study underscored the association between lipid metabolic disorders in PCOS and heightened inflammatory cytokine levels, correlating with ART outcomes but not with OHSS risk.

Background: Hormone replacement therapy (HRT) is the preferred protocol for endometrial preparation. Progesterone is important for successful implantation and the outcome of assisted reproductive techniques (ART). The impact of serum progesterone concentration on pregnancy outcomes has been extensively studied; however, there are conflicting results for dosage and route of administration. This study investigates the association between serum progesterone levels on embryo transfer day and assisted reproductive technique outcomes in frozen-thawed embryo transfer (FET).

Materials and methods: This prospective cohort study was conducted on women who underwent FET. Participants received HRT with 6 mg of oestradiol valerate and 400 mg of micronized vaginal progesterone, along with 50 mg of intramuscular (IM) progesterone for endometrial preparation. Serum progesterone was assessed before embryo transfer. The primary outcome was live birth rate (LBR).

Results: Overall, 190 infertile women underwent cleavage FET and were categorised according to the presence (group I: n=38) or absence (group II: n=152) of live birth. Group I women had significantly higher progesterone levels on the transfer day (34.48 ± 8.95 ng/ml) compared to group II women (29.83 ± 11.076 ng/ml, P=0.008). We divided the serum progesterone values into quartiles and observed significantly lower clinical pregnancy rates in the Q1 quartile (progesterone ≤23.84 ng/ml). Receiver operating characteristic (ROC) curve analysis indicated a significant threshold for progesterone level on the day of embryo transfer in terms of LBR, with an area under the curve (AUC) of 0.64 [95% confidence interval (CI): 0.54-0.73, P<0.001]. The estimated threshold was 26.95 ng/ml, with a sensitivity of 82% and a specificity of 43%.

Conclusion: The present study showed a significant positive association between serum progesterone levels on transfer day and LBR in FET cycles after patients received a combination of vaginal and IM progesterone supplements. Monitoring of serum progesterone in FET cycles are recommended.

Background: This study aimed to investigate whether uterine cavity flushing combined with antibiotic administration, improves the outcomes of assisted reproductive technology for patients with thin endometrium (<7 mm) associated with chronic endometritis.

Materials and methods: A retrospective cohort study was conducted, including 202 patients. Subsequently, a single frozen-thawed embryo of high morphological quality (≥4AB) was transferred either in an artificial cycle or on day 7 after the luteinizing hormone (LH) peak in the natural cycle. The parameters measured included the number of CD138-positive plasma cells in the endometrial stroma, endometrial thickness on the day of embryo transfer, clinical pregnancy rate (CPR), and live birth rate (LBR).

Results: Following treatment with endometrial flushing and antibiotics (group 1), there was a significant increase in endometrial thickness compared to antibiotics alone (group 2): 9.93 ± 1.37 mm vs. 8.2 ± 0.4 mm (P<0.001). Additionally, there was a significant reduction in the number of CD138-positive plasma cells in the endometrial stroma: 0.4 ± 0.8 vs. 4.1 ± 5.2 (P<0.001). The CPR with high-quality ET was 68.6 vs. 48%, respectively (P=0.016). The take-home baby rate was 60.8 vs. 39%, respectively (P=0.002).

Conclusion: Therapy for chronic endometritis, which includes uterine flushing along with antibacterial treatment, when compared with the standard treatment method, resulted in a significant reduction in the clinical symptoms of chronic endometritis (CE) and can enhance the effectiveness of assisted reproductive technology treatments.