Infertility treatments and risk of breast benign diseases: a case‒control study.

BACKGROUND: Theoretically, endocrine fluctuations occurring during infertility treatments, including ovulation induction (OI) and assisted reproductive techniques (ART), could be associated with an increased risk of benign breast diseases (BBDs). To date, no studies have been conducted on this association. Therefore, the present study investigated the association between different types of infertility treatments and BBDs. METHODS: This case‒control study was conducted in Arash Women's Hospital, Tehran, Iran. The case group included infertile women diagnosed with BBDs without atypia, and the control group included infertile women without breast disease. Breast imaging studies (mammography/ultrasound) were performed for BBD screening, and the diagnosis was confirmed by histopathological examination. Study variables were collected retrospectively from medical records, hospital databases, and questionnaires. RESULTS: Finally, 154 infertile women, including 50 cases (BBDs) and 104 controls (no BBDs), were compared. Our data showed that 66% of cases and 61.4% of controls had undergone at least one course of infertility treatment. There was no association between BBD risk and previous infertility treatments (OR = 1.21; 95% CI = 0.59-2.46), ART (OR = 1.14; 95% CI = 0.90-1.44), or OI cycles (OR = 1.13; 95% CI = 0.98-1.32). Stratification by confounding variables did not change these results. CONCLUSIONS: It seems that there is no association between BBDs in infertile women and the type, duration, or number of prior infertility treatments; however, considering the small sample size of the study, the clinical significance of this finding should not be neglected. Therefore, we consider it essential to carry out more extensive, detailed, and prospective studies to distinguish the association of BBDs with different infertility treatments and medications.

Efficacy and safety of celecoxib for treatment of mild to moderate postpartum depression: a randomized, double-blind, placebo-controlled trial.

PURPOSE: Evidence has demonstrated the roles of inflammatory processes in pathogenesis of depression. We aim to assess the effects of adjunctive celecoxib with cognitive behavioral therapy (CBT), an anti-inflammatory agent, in treatment of postpartum depression and on levels of Brain-derived neurotrophic factor (BDNF) and inflammatory cytokines. METHODS: This was a randomized, double-blind, placebo-controlled trial to investigate the effects of adjunctive celecoxib with CBT on postpartum depression. Fifty outpatient women with postpartum depression, participated in this study. Patients randomly received either a celecoxib capsule twice a day or a placebo capsule twice a day for 6 weeks. Patients were assessed using the Hamilton Depression Rating Scale (HDRS) and the adverse event checklist at baseline and weeks 2, 4, and 6. RESULTS: Patients in the celecoxib group showed a greater decline in HDRS scores from baseline to all three study time points compared to the placebo group (p = 0.12 for week 2, p = 0.001 for week 4, p < 0.001 for week 6). Rate of response to treatment was significantly higher in the celecoxib group compared to the placebo group at week 4 (60 vs 24%, p = 0.010) and week 6 (96 vs 44%, p < 0.001). Rate of remission was significantly higher in the celecoxib group compared to the placebo group at week 4 (52 vs 20%, p = 0.018) and week 6 (96 vs 36%, p < 0.001). Levels of most inflammatory markers were significantly lower in the celecoxib group compared to the placebo group at week 6. Levels of BDNF were significantly higher in the celecoxib group compared to the placebo group at week 6 (p < 0.001). CONCLUSIONS: Findings suggest adjunctive celecoxib is an effective treatment for the improvement of postpartum depressive symptoms.

Astaxanthin treatment decreases pro-inflammatory cytokines and improves reproductive outcomes in patients with polycystic ovary syndrome undergoing assisted reproductive technology: A randomized clinical trial.

RESEARCH QUESTION: In a randomized, triple-blind, placebo-controlled clinical trial (RCT), we investigated the effect of astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and assisted reproductive technology (ART) outcomes in 44 infertile Polycystic Ovary Syndrome (PCOS) patients. DESIGN: Patients with PCOS were randomly divided into two groups. The intervention group received 6 mg AST, and the control group received placebo daily for 8 weeks. Blood samples were obtained from all patients before and after intervention and follicular fluid (FF) was collected during the ART procedure. Interleukin (IL) -6, IL-1ß were evaluated from serum samples and FF and OS markers (malondialdehyde [MDA], catalase [CAT], superoxide dismutase [SOD], and reactive oxygen species [ROS]) were measured from FF. The groups were compared for ART outcomes as well. RESULTS: A significant decrease in IL-6 and IL-1ß concentrations (both, P = < 0.01) serum levels was found following AST treatment. FF cytokine levels and OS markers did not differ significantly between the groups. Reproductive outcomes, including the number of oocytes retrieved (P = 0.01), the MII oocyte count (P = 0.007), oocyte maturity rate (MII %) (P = 0.02) and number of frozen embryos (P = 0.03) significantly improved after intervention. No significant differences were found in chemical, clinical and multiple pregnancies between the groups. CONCLUSIONS: AST pretreatment may modify inflammation and improve ART outcomes in PCOS infertile patients. Further investigations are recommended to verify these findings.

Antioxidant supplementations ameliorate PCOS complications: a review of RCTs and insights into the underlying mechanisms.

Polycystic ovary syndrome (PCOS) is one of the most important gynecological disorders of women in the age of reproduction. Different hormonal and inflammatory cross-talks may play in the appearance of its eventual complications as a leading cause of infertility. Excessive production of reactive oxygen species over the power of the antioxidant system as oxidative stress is known to contribute to a variety of diseases like PCOS. Thus, the utilization of antioxidants can be efficient in preventing or assistant in treating these diseases. In this review, we describe the clinical trial studies that have examined the efficiency of antioxidant strategies against PCOS and the possible underlying mechanisms. The investigations presented here lead us to consider that targeting oxidative stress pathways is probably a powerful promising therapeutic approach towards PCOS. There is preparatory evidence of the effectiveness of antioxidant interventions in ameliorating some of the PCOS complications, including metabolic and hormonal disorders. Due to limited data and relatively few clinical trials, many of these interventions need further investigation before they can be considered effective agents for routine clinical use.

The effect of letrozole versus artificial hormonal endometrial preparation on pregnancy outcome after frozen-thawed embryos transfer cycles: a randomized clinical trial.

BACKGROUND: Considering that clinical trial studies are limited in polycystic ovary syndrome (PCOS) patients, and there is no consensus on an optimum endometrial preparation protocol for frozen embryo transfer (FET), the present study was designed as a randomized clinical trial to compare the reproductive outcomes following stimulated cycles with letrozole plus human menopausal gonadotropin (HMG) for endometrial preparation compared with routine AC-FET. METHODS: This randomized controlled trial was carried out on infertile PCOS patients who underwent IVF/ICSI and FET cycles in Arash Women's Hospital affiliated to Tehran University of Medical Sciences between September 2018 and January 2020. PCOS diagnosis was based on the Rotterdam criteria. Eligible patients were randomly allocated into two groups: stimulated cycle with letrozole plus (HMG) (intervention group) and routine artificial hormonal endometrial preparation (control group). RESULTS: One hundred seventy-seven infertile patients were recruited for participation in the study. Of these, 57 women were excluded due to non-eligibility for entering the study, and a total of 120 patients were randomly assigned to two study groups. After follow up, the cycle outcomes of 57 patients in the intervention group and 59 patients in the control group were compared. The data analysis showed that the two groups did not have significant differences in fundamental and demographic characteristics. After the intervention, there were no significant differences in implantation rate, chemical, ectopic, and clinical pregnancy rates between groups. Moreover, the rates of miscarriage and ongoing pregnancy were similar between groups (P > 0.05). CONCLUSIONS: We found similar pregnancy outcomes with two endometrial preparation methods. Noting that each treatment centre should select the most beneficial and cost-effective method with the least adverse effects for patients, letrozole preparations for FET could be incorporated into possible options; however, establishing this approach as first-line treatment is premature in light of current evidence, and future randomized clinical trials with larger sample sizes are required for widespread application. TRIAL REGISTRATION: The study was also registered in the Iranian Registry of Clinical Trials on March 20th, 2020. ( IRCT20090526001952N12 at www.irct.ir , registered retrospectively).

Vortioxetine effects on quality of life of irritable bowel syndrome patients: A randomized, double-blind, placebo-controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Irritable bowel syndrome (IBS) is a functional gastrointestinal disease causing a substantial productivity loss with no definite treatment. Our study investigates the effects of vortioxetine vs placebo in enhancing the IBS patients' quality of life. METHODS: In a double-blinded, placebo-controlled, randomized trial, adults with IBS, according to the ROME IV criteria, were randomized to placebo and vortioxetine for 6 weeks. Participants were visited every two weeks to fill IBS quality of life, hospital anxiety and depression scale, and adverse effect questionnaires. RESULTS: Eighty patients were randomized, and seventy-two finished the trial. Baseline characteristics of groups were similar. Both placebo and vortioxetine significantly increased the quality of life during course of the study (both P-values < .001), whereas vortioxetine demonstrated a greater increase (P-value < .001). According to the analysis of covariances, this enhancement was irrespective of depression or anxiety score changes (P-value = .002). Adverse effect profile was similar between the groups and can increase IBS patients' quality of life superior to placebo. Vortioxetine effects in our study were observed irrespective of the depression and anxiety levels.

Vitamin E and ginseng supplementation to enhance female sexual function: a randomized, double-blind, placebo-controlled, clinical trial.

Female sexual disorders (FSD) are a spectrum of disorders common among women, especially in their middle age, which can reduce the female quality of life substantially. We aimed to evaluate the effects of a combined vitamin E and ginseng supplement on amelioration of female sexual dysfunction. In a 6-week, double-blind, randomized, placebo-controlled clinical trial, participants, suffering from sexual dysfunction based on the female sexual function index (FSFI) questionnaire, were randomly allocated to receive the supplement (100 IU vitamin E, 67 mg Korean ginseng, and 40 mg Siberian ginseng) or placebo daily. The primary outcome in our trial was the change in the FSFI total score. Sixty-nine participants were enrolled, but only 31 in each group completed the trial. Changes in the FSFI total score and its domain scores were significant during the trial course within each group. However, the supplement only ameliorated desire and satisfaction domains superior to the placebo. In case of the total score and other domains, the changes were insignificantly different between the treatment groups. Although our study could not find additional benefits for the vitamin E and ginseng supplement over placebo in enhancing sexual function overall, the supplement worked better in enhancing sexual desire and satisfaction.

Safety and efficacy of allogenic placental mesenchymal stem cells for treating knee osteoarthritis: a pilot study.

OBJECTIVE: Knee osteoarthritis (OA) is a common skeletal impairment that can cause many limitations in normal life activities. Stem cell therapy has been studied for decades for its regenerative potency in various diseases. We investigated the safety and efficacy of intra-articular injection of placental mesenchymal stem cells (MSCs) in knee OA healing. METHODS: In this double-blind, placebo-controlled clinical trial, 20 patients with symptomatic knee OA were randomly divided into two groups to receive intra-articular injection of either 0.5-0.6 × 108 allogenic placenta-derived MSCs or normal saline. The visual analogue scale, Knee OA Outcome Score (KOOS) questionnaire, knee flexion range of motion (ROM) and magnetic resonance arthrography were evaluated for 24 weeks post-treatment. Blood laboratory tests were performed before and 2 weeks after treatment. RESULTS: Four patients in the MSC group showed mild effusion and increased local pain, which resolved safely within 48-72 h. In 2 weeks post-injection there was no serious adverse effect and all of the laboratory test results were unchanged. Early after treatment, there was a significant knee ROM improvement and pain reduction (effect size, 1.4). Significant improvements were seen in quality of life, activity of daily living, sport/recreational activity and decreased OA symptoms in the MSC-injected group until 8 weeks (P < 0.05). These clinical improvements were also noted in 24 weeks post-treatment but were not statistically significant. Chondral thickness was improved in about 10% of the total knee joint area in the intervention group in 24 weeks (effect size, 0.3). There was no significant healing in the medial/lateral meniscus or anterior cruciate ligament. There was no internal organ impairment at 24 weeks follow-up. CONCLUSION: Single intra-articular allogenic placental MSC injection in knee OA is safe and can result in clinical improvements in 24 weeks follow-up. TRIAL REGISTRATION NUMBER: IRCT2015101823298N.

The modulating effects of Resveratrol on the expression of MMP-2 and MMP-9 in endometriosis women: a randomized exploratory trial.

Endometriosis is an inflammatory disease; the hallmark of inflammation is over-activation of matrix metalloproteinases (MMPs). The regulatory effects of Resveratrol on MMPs were formerly depicted in other cell lines. This study aimed at investigating the effects of Resveratrol on expression of MMP-2 and -9 in endometriosis patients. This trial was carried out on endometriosis patients (n = 34) who were randomly divided into treatment (i = 17) and control (n = 17) groups. Alongside the routine protocol, the control and treatment groups took placebo and Resveratrol (400 mg), respectively, for 12-14 weeks. Endometrial tissue and fluid as well as blood sampling from both groups were done before and after the intervention. The level of mRNA and protein of both MMP-2 and -9 reduced in the endometrium of treatment group following intervention. Also, the serum and the endometrial fluid concentration of them lowered within the treatment group. Moreover, the serum and endometrial fluid levels of MMP-2 as well as MMP-9 were also diminished following the surgical removal of endometritic lesions. We showed that Resveratrol can modify the inflammation process in the endometrium of women with endometriosis at least in the level of MMP-2 and -9 expressions. The therapeutic potency of Resveratrol in endometriosis needs more clinical studies.

Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder associated with post-menopausal hot flashes: a double-blind, randomized, placebo-controlled trial.

PURPOSE: Due to concerns regarding the side effects of hormone therapy, many studies have focused on the development of non-hormonal agents for treatment of hot flashes. The aim of this study was to evaluate the efficacy and safety of saffron (stigma of Crocus sativus) in treatment of major depressive disorder associated with post-menopausal hot flashes. METHODS: Sixty women with post-menopausal hot flashes participated in this study. The patients randomly received either saffron (30 mg/day, 15 mg twice per day) or placebo for 6 weeks. The patients were assessed using the Hot Flash-Related Daily Interference Scale (HFRDIS), Hamilton Depression Rating Scale (HDRS) and the adverse event checklist at baseline and also at the second, fourth, and sixth weeks of the study. RESULTS: Fifty-six patients completed the trial. Baseline characteristics of the participants did not differ significantly between the two groups. General linear model repeated measures demonstrated significant effect for time × treatment interaction on the HFRDIS score [F (3, 162) = 10.41, p = 0.0001] and HDRS score [F (3, 162) = 5.48, p = 0.001]. Frequency of adverse events was not significantly different between the two groups. CONCLUSIONS: Results from this study revealed that saffron is a safe and effective treatment in improving hot flashes and depressive symptoms in post-menopausal healthy women. On the other hand, saffron, with fewer side effects, may provide a non-hormonal and alternative herbal medicine option in treatment of women with hot flashes.

The role of information therapy in reducing anxiety in patients undergoing in vitro fertilisation treatment.

This article is the first in the feature to come from Iran. The lead author, Sara Ahmadizadeh, manages the Library at Arash Women's Hospital and was awarded an MA in Information Science and Knowledge and Librarianship from Tehran Azad University in July 2015. Her MA dissertation was innovative and ambitious in that it looked at the impact of information therapy on levels of anxiety amongst women undergoing IVF treatment. Her study demonstrated that quality information sessions, delivered in a structured way, can have a positive impact on patients' awareness of their condition and can reduce anxiety. A. M.

Celecoxib Versus Diclofenac in Mild to Moderate Depression Management Among Breast Cancer Patients: A Double-Blind, Placebo-Controlled, Randomized Trial.

BACKGROUND: Depression is a well-known complication of breast cancer, which is known to adversely affect quality of life, prognosis, and survival in breast cancer patients. Celecoxib, a nonsteroidal anti-inflammatory drug, which acts via the selective inhibition of cyclo-oxygenase (COX)-2, has been shown to have antidepressive effects. OBJECTIVES: Here, we aimed to compare the efficacy and safety of celecoxib, a selective inhibitor of COX-2, with diclofenac, a nonselective inhibitor of both COX-1 and COX-2 in reducing depressive symptoms and pain in breast cancer patients. METHODS: A total of 52 outpatients with breast cancer with mild to moderate depression, who suffered from pain and needed analgesics, participated in the trial and underwent 6 weeks of treatment with either celecoxib (200 mg twice daily) or diclofenac (50 mg twice daily). Participants were investigated using the Hamilton Depression Rating Scale (HDRS). The primary outcome measure was to compare the antidepressant effects of celecoxib and diclofenac. RESULTS: Repeated-measures analysis demonstrated significant effect for Time × Treatment interaction on the HDRS scores: F(1.76, 87.85) = 9.66; P < 0.001. By study conclusion, greater improvement was observed in the HDRS score of the celecoxib group compared with the diclofenac group (P = 0.002). No one experienced remission (HDRS ≤ 7) in either group. Frequencies of adverse events were not significantly different between groups. CONCLUSION: Celecoxib seems to possess superior antidepressive effects compared with diclofenac in breast cancer patients with mild to moderate depression.

Outcomes of female reproductive performance with assisted reproductive techniques after recent mild to moderate COVID-19 infections: An observational study.

OBJECTIVE: The purpose of this study was to evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on clinical outcomes among high-risk patients. METHODS: This retrospective study involved 1,368 patients and the same number of cycles, including 520 cycles with PGT-A and 848 cycles without PGT-A. The study participants comprised women of advanced maternal age (AMA) and those affected by recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or severe male factor infertility (SMF). RESULTS: PGT-A was associated with significant improvements in the implantation rate (IR) and the ongoing pregnancy rate/live birth rate (OPR/LBR) per embryo transfer cycle in the AMA (39.3% vs. 16.2% [p<0.001] and 42.0% vs. 21.8% [p<0.001], respectively), RIF (41.7% vs. 22.0% [p<0.001] and 47.0% vs. 28.6% [p<0.001], respectively), and RPL (45.6% vs. 19.5% [p<0.001] and 49.1% vs. 24.2% [p<0.001], respectively) groups, as well as the IR in the SMF group (43.3% vs. 26.5%, p=0.011). Additionally, PGT-A was associated with lower overall incidence rates of pregnancy loss in the AMA (16.7% vs. 34.3%, p=0.001) and RPL (16.7% vs. 50.0%, p<0.001) groups. However, the OPR/LBR per total cycle across all PGT-A groups did not significantly exceed that for the control groups. CONCLUSION: PGT-A demonstrated beneficial effects in high-risk patients. However, our findings indicate that these benefits are more pronounced in carefully selected candidates than in the entire high-risk patient population.

Saffron for treatment of fluoxetine-induced sexual dysfunction in women: randomized double-blind placebo-controlled study.

OBJECTIVE: Saffron (Crocus sativus L.) has shown beneficial aphrodisiac effects in some animal and human studies. The aim of the present study was to assess the safety and efficacy of saffron on selective serotonin reuptake inhibitor-induced sexual dysfunction in women. METHODS: This was a randomized double-blind placebo-controlled study. Thirty-eight women with major depression who were stabilized on fluoxetine 40 mg/day for a minimum of 6 weeks and had experienced subjective feeling of sexual dysfunction entered the study. The patients were randomly assigned to saffron (30 mg/daily) or placebo for 4 weeks. Measurement was performed at baseline, week 2, and week 4 using the Female Sexual Function Index (FSFI). Side effects were systematically recorded. RESULTS: Thirty-four women had at least one post-baseline measurement and completed the study. Two-factor repeated measure analysis of variance showed significant effect of time × treatment interaction [Greenhouse-Geisser's corrected: F(1.580, 50.567) = 5.366, p = 0.012] and treatment for FSFI total score [F(1, 32) = 4.243, p = 0.048]. At the end of the fourth week, patients in the saffron group had experienced significantly more improvement in total FSFI (p < 0.001), arousal (p = 0.028), lubrication (p = 0.035), and pain (p = 0.016) domains of FSFI but not in desire (p = 0.196), satisfaction (p = 0.206), and orgasm (p = 0.354) domains. Frequency of side effects was similar between the two groups. CONCLUSIONS: It seems saffron may safely and effectively improve some of the fluoxetine-induced sexual problems including arousal, lubrication, and pain.

Change in frequency of acute and subacute effects of ecstasy in a group of novice users after 6 months of regular use.

BACKGROUND: Recent research trends are to specify the relation between patterns of ecstasy use and side effects, possibility of dependency, tolerance and long term neurocognitive damage. The objective of this study was to assess the impact of regular ecstasy use on its acute and subacute effects. SUBJECTS AND METHODS: At the first stage, we recruited 120 subjects. If participants continued regular use of ecstasy in this period, they were asked to participate in the second stage of the research 6 months later. Thirty-five subjects attended the second stage of the study, 5 of which were excluded because they had less than 5 drug experiences during the last 6 months. At last, we recruited 30 novice ecstasy users by means of the snowball technique in Tehran, Iran. The pattern of use and experienced effects of ecstasy was documented at the beginning and after 6 months of regular consumption with a self administered questionnaire. RESULTS: Little or no change was observed in acute effects. Those subacute effects that had considerable increase in frequency were anxiety, depression, aggression, memory impairment, poor concentration and learning problems. CONCLUSION: Small change in acute effects suggests low possibility of tolerance after at least 6 months of regular use. Our results support long term neurocognitive damage and mood impairment with ecstasy use.

Effects of Antidepressant Medication on Brain-derived Neurotrophic Factor Concentration and Neuroplasticity in Depression: A Review of Preclinical and Clinical Studies.

Depression is the most prevalent and debilitating disease with great impact on societies. Evidence suggests Brain-Derived Neurotrophic Factor (BDNF) plays an important role in pathophysiology of depression. Depression is associated with altered synaptic plasticity and neurogenesis. BDNF is the main regulatory protein that affects neuronal plasticity in the hippocampus. A wealth of evidence shows decreased levels of BDNF in depressed patients. Important literature demonstrated that BDNF-TrkB signaling plays a key role in therapeutic action of antidepressants. Numerous studies have reported anti-depressant effects on serum/plasma levels of BDNF and neuroplasticity which may be related to improvement of depressive symptoms. Most of the evidence suggested increased levels of BDNF after antidepressant treatment. This review will summarize recent findings on the association between BDNF, neuroplasticity, and antidepressant response in depression. Also, we will review recent studies that evaluate the association between postpartum depression as a subtype of depression and BDNF levels in postpartum women.

Celecoxib in Treatment of Postpartum Depression: A Case Report.

Postpartum depression (PPD) impairs mother-infant interaction and has negative effects on the child's emotional, behavioral, and cognitive skills. There is considerable evidence to suggest that inflammation plays a role in the pathogenesis of depression. Controlled trials indicate that celecoxib has antidepressant effects in patients with major depressive disorder. A 34-year-old woman with mild to moderate PPD received a celecoxib capsule twice a day. This treatment has not been reported in previous studies and is novel in clinical practice. The patient was assessed using the Hamilton Depression Rating Scale (HDRS). Moreover, levels of brain-derived neurotrophic factor (BDNF) and inflammatory cytokines were measured at baseline and at the end of celecoxib therapy. This case suggests that celecoxib can improve depressive symptoms in patients with mild to moderate PPD. No adverse effects occurred during follow-up.

Pregnancy outcomes in women with adenomyosis, undergoing artificial endometrial preparation with and without gonadotropin-releasing hormone agonist pretreatment in frozen embryo transfer cycles: An RCT.

Background: Selecting a suitable and preferable method for endometrial preparation in frozen embryo transfer (FET) cycles for women with adenomyosis is still challenging in infertility treatment. Objective: To compare 2 artificial endometrial preparation regimens with and without gonadotropin-releasing hormone agonist (GnRHa) pretreatment in women with adenomyosis undergoing FET cycles. Materials and Methods: This randomized clinical trial study was conducted on 140 adenomyosis cases who underwent FET cycles at Arash Women's hospital, Tehran, Iran from May 2020 to March 2021. Participants were randomly allocated into hormonal replacement therapy (HRT) and HRT+GnRHa pretreatment groups (n = 70/each). Endometrial preparation with 2-6 mg daily estradiol was started in the HRT+GnRHa group, taking after down-regulation with the GnRHa. Within the HRT group, the same dose of estradiol was commenced within the early follicular stage. The main (chemical and clinical pregnancy rates) and auxiliary results (twin pregnancy, miscarriage, and live birth rates) were compared between groups. Results: The demographic characteristics and severity of adenomyosis, endometrial thickness, and pattern at starting progesterone administration were similar in the 2 groups, and triple-line endometrium was found to be the dominant pattern in both groups (p = 0.65). No significant differences were observed in chemical, clinical, and twin pregnancy rates as well as miscarriage and live birth rates between groups (p = 0.71, p = 0.81, p = 0.11, and p = 0.84, respectively). However, the total estrogen dose and duration of estrogen consumption were significantly higher in the pretreatment group (p = 0.001, and p = 0.003). Conclusion: These results indicated that the hormonal endometrial preparation with estrogen and progestin for FET cycles is as efficacious as a protocol involving preceding pituitary suppression with a GnRHa. Further large randomized clinical studies are required to confirm these findings.

Circulating and Endometrial Profiles of miR-145, miR-155-5p, miR-224, MPP-5, and PECAM-1 Expression in Patients with Repeated Implantation Failure: A Case Control Study.

OBJECTIVE: An association between microRNAs (miRNAs) and adhesion proteins expression with repeated implantation failure (RIF) has been recently reported; however, these findings are controversial. This study aims to evaluate the endometrial and circulating expressions of miR-145, miR-155-5p, and miR-224 in addition to the endometrial expressions of membrane protein palmitoylated-5 (MPP-5) and endothelial cell adhesion molecule-1 (PECAM-1) in patients with RIF compared to control subjects. MATERIALS AND METHODS: This case-control study was carried out between June 2021-July 2022. Subjects included 17 patients with RIF and 17 control subjects, who had previous spontaneous term pregnancy with a live birth, who referred to the Medical Centre of Arash Hospital, Tehran, Iran. Endometrial tissue samples were obtained via hysteroscopy and Pipelle catheter in the RIF and control subjects, respectively. Plasma samples were collected after ovulation in all subjects. The expression levels of MPP5, PECAM-1, miR-224, miR-145, and miR-155-5p were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The student's t test, chi-square, Mann-Whitney U, and analysis of covariance (ANCOVA) were used for data analyses. RESULTS: RIF patients had less endometrial miR-155-5p expression, and higher endometrial and circulating expressions of miR-145 and miR-224 compared to control subjects. Endometrial PECAM-1 and MPP5 expression significantly decreased in patients with RIF compared to the control group. There was a positive correlation between circulating miR-224 and endometrial miR-155-5p, and between circulating miR-155-5p and endometrial PECAM-1 expression levels in patients with RIF. CONCLUSION: The present study suggests that circulating miR-224, endometrial miR-145, and PECAM-1 can be reliable, novel biomarkers for diagnosis of RIF.

Natural cycle versus modified natural cycle for endometrial preparation in women undergoing frozen-thawed embryo transfer: An RCT.

Background: Studies have evaluated different endometrial preparation methods, but the optimal frozen-thawed embryo transfer (FET) cycle strategy in terms of the in-vitro fertilization outcome is still debated. Objective: To compare the natural versus modified natural cycles for endometrial preparation in women undergoing FET. Materials and Methods: This study was designed as a randomized clinical trial, and it was performed at the Arash women's hospital between August 2016-2018. Hundred and forty eligible participants were enrolled in this study and were randomly divided into 2 groups by using the block randomization method, including true natural FET (n = 70) and modified natural FET (mNFET) (n = 70) cycles. Both groups were monitored for endometrial thickness and follicular size; simultaneously spontaneous luteinizing hormone surge using urinary luteinizing hormone testing kits. The mNFET group received 5000 IU of human chorionic gonadotropin injection to trigger final follicular maturation. Luteal support by vaginal progesterone (cyclogest 400 mg twice daily) was used in true natural FET from the day of transfer until the 10 th wk of pregnancy. Chemical and clinical pregnancy and abortion rates were considered as the primary outcomes. Results: There were no differences in the participants' baseline characteristics between groups. There was no difference in clinical pregnancy and abortion rate between groups, while the implantation rate was significantly higher in the mNFET group (29.2% vs. 17.6%; p = 0.036). Conclusion: The results demonstrated that both types of natural cycles were similar in pregnancy outcomes, while modified cycles might be associated with a higher implantation rate.