Immunogenicity and safety of RAZI recombinant spike protein vaccine (RCP) as a booster dose after priming with BBIBP-CorV: a parallel two groups, randomized, double blind trial.

BACKGROUND: The immunity induced by primary vaccination is effective against COVID-19; however, booster vaccines are needed to maintain vaccine-induced immunity and improve protection against emerging variants. Heterologous boosting is believed to result in more robust immune responses. This study investigated the safety and immunogenicity of the Razi Cov Pars vaccine (RCP) as a heterologous booster dose in people primed with Beijing Bio-Institute of Biological Products Coronavirus Vaccine (BBIBP-CorV). METHODS: We conducted a randomized, double-blind, active-controlled trial in adults aged 18 and over primarily vaccinated with BBIBP-CorV, an inactivated SARS-CoV-2 vaccine. Eligible participants were randomly assigned (1:1) to receive a booster dose of RCP or BBIBP-CorV vaccines. The primary outcome was neutralizing antibody activity measured by a conventional virus neutralization test (cVNT). The secondary efficacy outcomes included specific IgG antibodies against SARS-CoV-2 spike (S1 and receptor-binding domain, RBD) antigens and cell-mediated immunity. We measured humoral antibody responses at 2 weeks (in all participants) and 3 and 6 months (a subgroup of 101 participants) after the booster dose injection. The secondary safety outcomes were solicited and unsolicited immediate, local, and systemic adverse reactions. RESULTS: We recruited 483 eligible participants between December 7, 2021, and January 13, 2022. The mean age was 51.9 years, and 68.1% were men. Neutralizing antibody titers increased about 3 (geometric mean fold increase, GMFI = 2.77, 95% CI 2.26-3.39) and 21 (GMFI = 21.51, 95% CI 16.35-28.32) times compared to the baseline in the BBIBP-CorV and the RCP vaccine groups. Geometric mean ratios (GMR) and 95% CI for serum neutralizing antibody titers for RCP compared with BBIBP-CorV on days 14, 90, and 180 were 6.81 (5.32-8.72), 1.77 (1.15-2.72), and 2.37 (1.62-3.47) respectively. We observed a similar pattern for specific antibody responses against S1 and RBD. We detected a rise in gamma interferon (IFN-γ), tumor necrosis factor (TNF-α), and interleukin 2 (IL-2) following stimulation with S antigen, particularly in the RCP group, and the flow cytometry examination showed an increase in the percentage of CD3 + /CD8 + lymphocytes. RCP and BBIBP-CorV had similar safety profiles; we identified no vaccine-related or unrelated deaths. CONCLUSIONS: BBIBP-CorV and RCP vaccines as booster doses are safe and provide a strong immune response that is more robust when the RCP vaccine is used. Heterologous vaccines are preferred as booster doses. TRIAL REGISTRATION: This study was registered with the Iranian Registry of Clinical Trial at www.irct.ir , IRCT20201214049709N4. Registered 29 November 2021.

Histological Evaluation of Products of Conception, Who Benefits from It?

Background: Histopathological evaluation of the first trimester pregnancy loss has always been controversial. Although it is recommended, it is not a part of guidelines.Methods: Six hundred eighty-six samples in a referral infertility clinic were evaluated microscopically and categorized. Two hundred ninety-five cases were evaluated by genetic methods (Multiplex Ligation-dependent Probe Amplification).Results: From 569 samples with chorionic villi, 361 cases had history of three or more abortions. 18.3% of this group showed chronic intervillous of unknown etiology (CIUE) and 8.3% revealed intervilli fibrin deposition, both pathologies with a high risk of recurrence. History of a live child was significantly higher in CIUE group. 29% of genetically evaluated cases had a chromosomal abnormality.Conclusion: Histological evaluation of recurrent pregnancy loss could illuminate the cause of abortion in relatively acceptable percentage of cases, especially in mothers with higher number of previous abortion, mothers with a history of live child and in referral centers.

Investigation of risk factors for tunneled hemodialysis catheters dysfunction: competing risk analysis of a tertiary center data.

BACKGROUND: Hemodialysis tunneled catheters are prone to failure due to infection or thrombosis. Prediction of catheter dysfunction chance and finding the predisposing risk factors might help clinicians to prolong proper catheter function. The multidimensional mechanism of failures following infection or thrombosis needs a multivariable and comprehensive analytic approach. METHODS: A longitudinal cross-sectional study was implemented on 1048 patients admitted for the first hemodialysis tunneled catheterization attempt between 2013 and 2019 in Shahid Hasheminejdad hospital, Tehran, Iran. Patients' information was extracted from digital and also paper records. Based on their criteria, single and multiple variable analyses were done separately in patients with catheter dysfunction due to thrombosis and infection. T-test and Chi-square test were performed in quantitative and categorical variables, respectively. Competing risk regression was performed under the assumption of proportionality for infection and thrombosis, and the sub-distributional hazard ratios (SHR) were calculated. All statistical inferences were made with a significance level of 0.05. RESULTS: Four hundred sixty-six patients were enrolled in the analysis based on study criteria. Samples' mean (SD) age was 54(15.54), and 322 (69.1%) patients were female. Three hundred sixty-five catheter dysfunction cases were observed due to thrombosis 123(26.4%) and infection 242(52%). The Median (range) time to catheter dysfunction event was 243(36-1131) days. Single variable analysis showed a statistically significant higher proportion of thrombosis in females (OR = 2.66, 95% CI: 1.77-4.00) and younger patients, respectively. Multivariate competing risk regression showed a statistically significant higher risk of thrombosis in females (Sub-distributional hazard (SHR) = 1.81), hypertensive (SHR = 1.82), and more obese patients (BMI SHR = 1.037). A higher risk of infection was calculated in younger (Age SHR = 0.98) and diabetic (SHR = 1.63) patients using the same method. CONCLUSION: Female and hypertensive patients are considerably at higher risk of catheter thrombosis, whereas diabetes is the most critical risk factor for infectious catheter dysfunction. Competing risk regression analysis showed a comprehensive result in the assessment of risk factors of catheter dysfunction.

The effect of low-molecular-weight heparin on live birth rate of patients with unexplained early recurrent pregnancy loss: A two-arm randomized clinical trial.

Background: The effect of anticoagulant medication in unexplained early recurrent pregnancy loss (RPL) patients is controversial. This clinical trial evaluated the effect of low-molecular-weight heparin (LMWH) on pregnancy outcomes in these patients. Materials and Methods: The study was performed as a single-blind randomized clinical trial between 2016 and 2018. Samples were selected from patients who were referred to Avicenna RPL clinic with a history of at least two previously happened early unexplained miscarriages. The eligibility was defined strictly to select unexplained RPL patients homogenously. One hundred and seventy-three patients who got pregnant recently were allocated randomly into two groups LMWH plus low-dose aspirin treatment (Group A = 85) and low-dose aspirin treatment only (Group B = 88)) and were followed up till their pregnancy termination (delivery/abortion). A per-protocol analysis was carried out and all statistical tests were two-sided with a P < 0.05 significance level. Results: The live birth rates (LBRs) in Groups A and B were 78% and 77.1%, respectively, which did not show any statistically significant difference between the two groups, neither in rates nor in time of abortion. In subgroup analysis for polycystic ovary syndrome (PCOS) patients, the odds ratio for study outcome (intervention/control) was 2.25 (95% confidence interval: 0.65-7.73). There was no major adverse event whereas minor bleeding was observed in 18% of patients in Group A. Conclusion: LMWH does not improve the LBR in unexplained RPL patients, however, it is recommended to evaluate its effect separately in PCOS patients.

Investigating the factors affecting the survival rate in patients with COVID-19: A retrospective cohort study.

Background: As hospitalized patients with COVID-19, especially those who are admitted to ICU or die afterwards, generally have comorbidities, the aim of this study was to determine the factors affecting the survival rate of COVID-19 patients in Iran using a retrospective cohort. Methods: This retrospective cohort study was conducted on patients with COVID-19 who referred to medical centers under the supervision of Iran University of Medical Sciences, Tehran, Iran, from February 22 to March 25, 2020. The final date of follow-up was April 19, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study. Clinical laboratory, radiological, treatment, and demographic data were collected and analyzed. The associations among gender, immune disease, diabetes, liver disease, cardiovascular disease, kidney disease, chronic pulmonary disease, cancer, chronic nervous disease, type of treatment, and risk of death were analyzed. The Kaplan-Meier and Log-rank tests were used to estimate survival rate and compare survival rates, respectively. Results: The total number of deaths or desired event in the study was 329 (10.3%).The risk of death in the age groups of 50-60 years, 60-70 years, and >70 years compared to the 30-40 age group was 2.17 (95% CI: 1.03, 4.55; p: 0.040); 3.72 (95 % CI: 1.80, 7.68; p: 0.001) and 5.09 (95 % CI: 2.49, 10.40; p: 0.001), respectively. The results showed men had 11.5% more risk of deaths than women (HR: 1.11; 95 % CI: 0.89, 1.39; p: 0.341). Kidney disease increased the risk of death by 52.3% in these patients, which was not statistically significant (HR: 1.78; 95 % CI: 1.04, 3.04; p: 0.035). Also, chronic pulmonary diseases and diabetes increased the risk of death in COVID-19 patients by 89.5% and 41.3% compared to COVID-19 patients without chronic pulmonary diseases and diabetes [(HR: 1.89; 95 % CI: 1.17, 3.04; p: 0.008), (HR: 1.41; 95 % CI: 1.01, 1.96; p: 0.038)]. Conclusion: Based on the results of this study, more attention and care should be paid to COVID-19 patients with underlying diseases, such as chronic obstructive pulmonary disease, diabetes, and kidney disease to reduce the number of deaths.

Laparoscopic excision of deeply infiltrating endometriosis: a prospective observational study assessing perioperative complications in 244 patients.

PURPOSE: To examine peri-operative complications in patients undergoing laparoscopic excision of deeply infiltrating endometriosis (DIE). METHODS: This was a prospective study of a case series of women having laparoscopic excision of deeply infiltrating endometriosis from September 2013 through August 2016 in a tertiary referral center for endometriosis and minimally invasive gynaecological surgery in Iran. Data collected included demographics, baseline characteristics, intraoperative and postoperative data up to 1 month following surgery. RESULTS: We analysed data from 244 consecutive patients, who underwent radical laparoscopic excision of all visible DIE. Major postoperative complications occurred in 3 (1.2%) and minor complications in 27 (11.1%) of patients. 80.3% of our patient group had Stage IV endometriosis. Segmental bowel resection was performed in 34 (13.9%), disc resection in 7 (2.9%), rectal shave in 53 (21.7%). Joint operating between a gynaecologist and colorectal and/or urological colleague was required in 29.6% of cases. The mean operating time was 223.8 min (± 80.7 standard deviation, range 60-440 min) and mean hospital stay was 2.9 days (± 1.5 standard deviation, range 1-11). The conversion to laparotomy rate was 1.6%. CONCLUSIONS: A combination of different laparoscopic surgical techniques to completely excise all visible DIE, within the context of a tertiary referral center offering multi-disciplinary approach, produces safe outcomes with low complication rates.

Comparison of Embryological Results of Microinjection in Two Groups of Men with and without Requesting Sperm DNA Fragmentation Index Measurement.

Introduction: The sperm DNA fragmentation index (DFI) is considered a valuable measure to assess male fertility, but the predictive value of DFI for the outcomes in assisted reproductive technology (ART) is still controversial. Therefore, this study is aimed at investigating the effect of requesting a DFI test or performing ART without DFI on the results observed in the embryology laboratory (number of embryos, fertilization rate, and embryo quality) after intracytoplasmic sperm injection (ICSI). Methods: This retrospective study was conducted on infertile men who underwent ICSI and were referred to the Avicenna Infertility and Recurrent Abortion Treatment Center in Tehran from 2019 to 2022. The samples were categorized into two groups: a case group with DFI measurement and a control group without DFI measurement. We conducted a comparative analysis of the embryology results between the two groups, focusing on parameters such as fertilization rate, number of embryos, and embryo quality. t-tests and Mann-Whitney U tests were used to conduct single variable analysis. Potential confounding effects were adjusted to use the multivariate linear and logistic regression. Results: Data analysis showed no significant statistical difference between the case group and the control group in terms of the number of embryos (95% confidence interval for the regression coefficient (ß) = -0.257-0.123), and embryo quality (95% confidence interval for ß = -0.199-0.114). There was no significant statistical difference between the two groups due to the fertilization rate (95% confidence interval for ß = -3.42-3.42), except for the variables of woman's age and sperm count after ICSI, as determined by adjusted linear regression. Conclusions: Although DFI measurement is used to assess male infertility, its importance as a predictor for the embryology outcomes after ICSI requires further evaluation and the determination of a cut-off point for predicting results. This study was based on retrospectively collected DFI data, and prospective studies confirming the superiority of ICSI outcomes are necessary.

Investigating the relationship between spermogram parameters and sexual desire in infertile men: a cross-sectional study from a tertiary centre in Iran.

BACKGROUND: Male factor infertility can affect spermatogenesis, sexual desire, and thus the quality of life of couples. The present study was conducted to investigate the relationship between spermogram parameters, and the score of sexual desire in infertile men. METHODS: This cross-sectional study was conducted on 315 infertile men referred to the Avicenna Infertility Center of Tehran (March 2022 to March 2023). The participants were selected based on the results of previous spermogram and hormonal tests recorded in their medical records. Eligible men completed the demographic information questionnaire and Hurlbert Index of Sexual Desire. A multivariable linear regression model was used to adjust the effect of variables on Hurlbert's score. RESULTS: There was no significant relationship among sperm parameters (count, morphology, motility, vitality, concentration and DNA Fragmentation Index) and with sexual desire of infertile men. Education level, age of men and their partners, the duration of the marriage and duration of infertility did not have a statistically significant effect on sexual desire. However, economic status had an inverse effect on men's sexual desire, with regression coefficients of 7.37 and 7.78 for medium and low socioeconomic levels compared with high (p<0.05). CONCLUSION: Male sexual desire is primarily influenced by social factors rather than organic ones. Further multicentre prospective studies are recommended for more accurate results.

Study on the comparison between Bosentan and Macitentan in the treatment of persistent pulmonary hypertension of the newborns, simultaneously on sildenafil: A randomized double-blinded non-inferiority parallel clinical trial.

BACKGROUND: Persistent Pulmonary Hypertension of the newborn (PPHN) is characterized by sustained elevated Pulmonary Artery Pressure (PAP). Drug resistance and the adverse effects of current therapeutic agents warrant investigation of other targeted therapies. Bosentan has shown benefits in affected neonates. However, trials reported the association with unwanted effects. Thus, in this study, we assess another agent in the same family, Macitentan. However, its efficacy in the treatment of PPHN is not yet reported. Hence, this study evaluated the effect of Macitentan compared to Bosentan in terms of efficacy and safety in the treatment of PPHN. METHODS: This randomized, double-blinded non-inferiority clinical trial was conducted in Shahid Akbar Abadi hospital, Tehran, Iran. Sixty clinically stable neonates with signs suggestive of PPHN were randomly allocated into two groups (n = 30 in each group) and they received either Bosentan 1 mg/kg/dose BD (twice daily) or Macitentan 1 mg/kg/dose BD simultaneously with sildenafil. The echocardiographic and laboratory indices of efficacy and safety were compared between groups. SPAP (systolic pulmonary artery pressure) was used to assess the non-inferiority of the Macitentan compared to the Bosentan in their respective doses used in the study. RESULTS: Participants' mean (SD) age was 3.53 (1.21) days, and 55% were female. No mortality case occurred. SPAP was reduced in both Bosentan and Macitenan groups with the mean difference in SPAP of 9 (95% CI: 7.34-10.65) in Bosentan and SPAP mean difference of 14 (95% CI: 12.12-15.86) in Macitentan group. Categorical comparison of primary outcome improvement showed that Macitentan was superior to Bosentan with a 10% non-inferiority margin. Similar results were obtained in other echocardiographic indices. Also, no significant alterations were observed in laboratory safety parameters. CONCLUSION: Macitentan 1 mg/kg/dose BD (twice daily) is non-inferior to Bosentan 1 mg/kg/dose BD in improving echo outcomes of PPHN and it was even more effective in improving some of these. Also, it is non-inferior to Bosentan in terms of safety. TRIAL REGISTRY NUMBER: (IRCT20160120026115N9).

Comparison of the Effect of Fenugreek and Metformin on Clinical and Metabolic Status of Cases with Polycystic Ovary Syndrome: A Randomized Trial.

Background: It is hypothesized that fenugreek seeds are a rich source of fiber with anti-diabetic effects, which can help to lower blood glucose in patients with polycystic ovary syndrome (PCOS). In this study, the clinical and metabolic effects of fenugreek were compared to those of metformin in women with PCOS aged 16-40 years. Methods: In a randomized, triple-blind, parallel clinical trial, the efficacy of fenugreek 333 mg (n=55) was compared with metformin 500 mg (n=55), both administered three times a day in women with PCOS of reproductive age. Changes in some clinical outcomes and metabolic laboratory profile outcomes were evaluated at baseline and two months after the study. Results: By the end of the intervention period, all investigated factors improved significantly in patients of both groups (p<0.05). Reduction in biometric indices (body mass index and waist-hip ratio), fasting blood sugar (FBS), and insulin resistance was significantly higher after metformin consumption (p<0.001). Metformin also significantly improved irregular menstruation (p=0.02). In contrast, fenugreek significantly improved patients' lipid profiles, including low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) compared to metformin (p<0.001). Both interventions improved the patient's hair loss and hirsutism. Conclusion: Fenugreek cannot substitute metformin in PCOS treatment. However, regarding its lipid-lowering ability and low frequency of adverse effects, it can be used as an adjuvant treatment in PCOS, especially in PCOS patients with hyper-lipidemia and severe hair loss.

Comparison of luteal phase stimulation with follicular phase stimulation in poor ovarian response: a single-blinded randomized controlled trial.

BACKGROUND: In the last decade, luteal-phase ovarian stimulation (LPOS) has been suggested as an alternative controlled ovarian stimulation (COS) protocol for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles mainly in women with a history of poor ovarian response (POR). The present randomized controlled trial study aimed to compare the outcomes of follicular phase ovarian stimulation (FPOS) and LPOS protocols in POR cases undergoing ICSI cycles. METHODS: Seventy-eight POR patients who met the Bologna criteria and underwent an ICSI cycle were included. In this study, 39 POR cases were allocated to the FPOS group, and 39 POR cases were allocated to the LPOS group. The primary outcome was the number of metaphase II (MII) oocytes. In addition, the total number of oocytes, number of top-quality day 3 embryo, day 3 embryo development rate, chemical pregnancy and clinical pregnancy rates were defined as secondary outcomes. RESULTS: The obtained results demonstrated that the number of MII oocytes significantly increased in the LPOS group compared to the FPOS group (P = 0.007). However, there was no significant difference between the two groups regarding the number of GV and MI oocytes, number of top-quality day 3 embryos and day 3 embryo development rate among both categories of patients. Also, the number of total and MII oocytes was significantly higher in the LPOS group (P = 0.016). CONCLUSION: These results suggest that LPOS protocol effectively increases the number of mature oocytes in women with a history of POR. TRIAL REGISTRATION: IRCT20210405050852N1 (Registered at Iranian registry of clinical trials; available at https://en.irct.ir/trial/55402 ).

Pregnancy-related complications in patients with endometriosis in different stages.

BACKGROUND: Endometriosis is one of the most common and costly diseases among women. This study was carried out to investigate pregnancy outcomes in women with endometriosis because of the high prevalence of endometriosis in reproductive ages and its effect on pregnancy-related complications outcomes. METHODS: This was a cross-sectional study performed on 379 pregnant women with endometriosis who were referred to the endometriosis clinic of the Avicenna Infertility Treatment Center from 2014 to 2020. Maternal and neonatal outcomes were assessed for the endometriosis group and healthy mothers. The group with endometriosis was further divided into two groups: those who underwent surgery and those who either received medication alone or were left untreated before becoming pregnant. The analysis of the data was done using SPSS 18. RESULTS: The mean age of the patients was 33.65 ± 7.9 years. The frequency of endometriosis stage (P = 0.622) and surgery (P = 0.400) in different age groups were not statistically significant. The highest rates of RIF and infertility were in stages 3 (N = 46, 17.2%) (P = 0.067), and 4 (N = 129, 48.3%) (P = 0.073), respectively, but these differences were not statistically different, and the highest rate of pregnancy with ART/spontaneous pregnancy was observed in stage 4 without significant differences (P = 0.259). Besides, the frequency of clinical/ectopic pregnancy and cesarean section was not statistically different across stages (P > 0.05). There is no significant relationship between endometriosis surgery and infertility (P = 0.089) and RIF (P = 0.232). Most of the people who had endometriosis surgery with assisted reproductive methods got pregnant, and this relationship was statistically significant (P = 0.002) in which 77.1% (N = 138) of ART and 63% (N = 264) of spontaneous pregnancies were reported in patients with endometriosis surgery. The rate of live births (59.4%) was not statistically significant for different endometriosis stages (P = 0.638). There was no stillbirth or neonatal death in this study. All cases with preeclampsia (N = 5) were reported in stage 4. 66.7% (N = 8) of the preterm labor was in stage 4 and 33.3% (N = 4) was in stage 3 (P = 0.005). Antepartum bleeding, antepartum hospital admission, preterm labor, gestational diabetes, gestational hypertension, abortion, placental complications and NICU admission were higher in stage 4, but this difference had no statistical difference. CONCLUSION: Endometriosis is significantly correlated with infertility. The highest rates of RIF and infertility are observed in stages 3 and 4 of endometriosis. The rate of pregnancy with ART/spontaneous pregnancy, preterm labor, preeclampsia and pregnancy-related complications is higher in stage 4. Most of the people who had endometriosis surgery with assisted reproductive methods got significantly pregnant. Clinical/ectopic pregnancy, cesarean sections, and live birth were not affected by the endometriosis stages.

Safety and Efficacy of 2.5 mg and 1.25 mg Nebulized Salbutamol Compared with Placebo on Transient Tachypnea of the Newborns: A Triple-Blind Phase II/III Parallel Randomized Controlled Trial.

Background: To evaluate the safety and efficacy of 2.5 and 1.25 mg nebulized salbutamol on Transient Tachypnea of the Newborn (TTN) compared with placebo. Methods: We conducted a triple-blind, phase II/III parallel randomized controlled trial in two university-affiliated hospitals with neonatal intensive care units. Newborns with a confirmed diagnosis of TTN, with gestational age >35 weeks and gestational weight >2 kg were included. Cases of asphyxia, meconium aspiration syndrome, and persistent pulmonary hypertension were excluded. Ninety eligible patients were randomly allocated in three intervention groups (2.5 mg salbutamol, 1.25 mg salbutamol, and placebo), and a single-dose nebulized product was prescribed 6 hours after the birth. Safety outcomes included postintervention tachycardia, hyperglycemia, hypokalemia, and changes in blood pressure. To evaluate the efficacy, the duration of postintervention tachypnea, TTN clinical score, and clinical and paraclinical respiratory indices were assessed. Parents, Outcome assessors, and data analyzer were blind to the intervention. Results: There was no adverse reaction, including tachycardia, hypokalemia, and jitteriness. Both groups of salbutamol recipients showed significant improvement regarding respiratory rate, TTN clinical score, and oxygenation indices compared with the placebo (p-values <0.001). Nonstatistically significant higher hospital stay was observed in the placebo group. Single 2.5 mg salbutamol nebulization showed a little better outcome than the dose of 1.25 mg, although we could not find statistical superiority. Conclusion: The newly applied single high dose of 2.5 mg nebulized salbutamol is safe in treating TTN and leads to notable faster improvement of respiratory status without any considerable adverse reaction. Registry code: IRCT20190328043133N1.

Safety and efficacy of RCP recombinant spike protein covid-19 vaccine compared to Sinopharm BBIBP: A phase III, non-inferiority trial.

Background: We conducted a phase III, non-inferiority trial comparing safety and efficacy of RCP recombinant spike protein Covid-19 vaccine to BBIBP (Sinopharm). Methods: Adult Iranian population received RCP or BBIBP in a randomized, double blind and an additional non-randomized open labeled trial arms. Eligible participants signed a written informed consent and received two intramuscular injections three weeks apart. In the randomized arm, an intranasal dose of vaccine or adjuvant-only preparation were given to the RCP and BBIBP recipients at day 51 respectively. Participants were actively followed for up to 4 months for safety and efficacy outcomes. Primary outcome was PCR + symptomatic Covid-19 disease two weeks after the second dose. The non-inferiority margin was 10% of reported BBIBP vaccine efficacy (HR = 1.36). Results: We recruited 23,110 participants (7224 in the randomized and 15,886 in the non-randomized arm). We observed 604 primary outcome events during 4 months of active follow-up including 121 and 133 in the randomized and 157 and 193 cases in the non-randomized arms among recipients of RCP and BBIBP respectively. Adjusted hazard ratios for the primary outcome in those receiving RCP compared with BBIBP interval were 0.91 (0.71-1.16) and 0.62 (0.49-0.77) in the randomized and non-randomized arms respectively. The upper boundary of 99.1% confidence interval of HR = 0.91 (0.67-1.22) remained below the margin of non-inferiority in the randomized arm after observing the early stopping rules using O'Brien Fleming method. Conclusion: Our study showed that the RCP efficacy is non-inferior and its safety profile is comparable to the BBIBP.

Effect of Endometrial Ablation by Thermal Balloon vs. Hysteroscopy Ablation on Amenorrhea Rates in Patients with Abnormal Uterine Bleeding: A Randomized Clinical Trial.

BACKGROUND: Abnormal uterine bleeding (AUB) that is any irregularity in menstrual cycles causes women to refer to clinics. This study aimed to compare the efficacy, safety, and complications of endometrial ablation by the thermal balloon (Cavaterm) method with the hysteroscopy loop resection method in the treatment of AUB. MATERIALS AND METHODS: The present study is an open-label, randomized clinical trial that was performed in the two hospitals, Shahid Akbarabadi and Hazrat Rasoul Akram, of Tehran, Iran, from December 2019 to October 2020. Patients were randomly allocated to the two groups of interventions by a simple randomization method. The proportion of amenorrhea (as primary outcome) and consequent hysterectomy and patient satisfaction (as secondary outcomes) was assessed using the Chi-square test and independent t test. RESULTS: There was no significant difference between the two groups in the baseline characteristics. The percentage of intervention failure was statistically higher in the hysteroscopy group (24%) in comparison with the Cavaterm group [8.2%, P=0.03, relative risk (RR)=1.63, 95% confidence interval (CI): 1.13-2.36]. Mean ± standard deviation of satisfaction based on the Likert score in the Cavaterm group and hysteroscopy group were 4.3 ± 1.21 and 3.7 ± 1.56, respectively, that showed a significant difference (P=0.04). Assessing the procedural complications, the rate of spotting, bloody discharge, and malodor discharge was significantly higher in the Cavaterm group. In contrast, postoperative dysmenorrhea is more common in the hysteroscopy group. CONCLUSION: Cavaterm ablation is accompanied by a higher success rate of amenorrhea and patients' satisfaction than hysteroscopy ablation (registration number: IRCT20220210053986N1).

Transvaginal sonography and surgical findings in the diagnosis of endometriosis individuals: A cross-sectional study.

Background: Endometriosis is a challenging gynecological disease and a debilitating condition that profoundly affects the individual's quality of life. Besides pathological confirmation, diagnostic laparoscopy has been internationally accepted as the standard method to identify the accurate mapping of endometriosis. Transvaginal sonography (TVS) is the first non-invasive imaging modality to estimate the severity of endometriosis. Objective: This study aimed to evaluate the accuracy of TVS in affected women compared with surgical findings. Materials and Methods: This retrospective cross-sectional study surveyed 170 women with deep infiltrating endometriosis (DIE) referred to the endometriosis part of the Avicenna Infertility Center, Tehran, Iran and they underwent TVS followed by laparoscopy. Recorded data of individuals under study in the medical database system were reviewed. Finally, the agreement rate was calculated for ultrasound reports and intraoperative (IO) findings regarding ovarian endometrium, ovarian adhesion, involvement of cul-de-sac, rectovaginal septum, and bowel and ureter. Results: 170 women with DIE entered the study. The agreement of TVS and IO findings were 86.76% for left ovarian endometriosis and 70.86% for right ovarian endometriosis, 93.90% for left ovarian adhesion, and 88.90% for right ovarian adhesion, 88.90% for a cul-de-sac, and 84.82% for bowel nodules. The findings, based on a laparoscopic assessment of the pelvic floor, were completely compatible with ultrasound reports (100%). Conclusion: TVS allows a preoperative evaluation in planning the surgical policy associated. TVS is beneficial for dedicated mapping of DIE; thus, an expert radiologist can aid the surgeon in preoperative evaluation and IO management.

Immunogenicity and Safety of a Combined Intramuscular/Intranasal Recombinant Spike Protein COVID-19 Vaccine (RCP) in Healthy Adults Aged 18 to 55 Years Old: A Randomized, Double-Blind, Placebo-Controlled, Phase I Trial.

Objectives: This study aimed to determine the safety and immunogenicity of a combined intramuscular/intranasal recombinant spike protein COVID-19 vaccine (RCP). Methods: We conducted a randomized, double-blind, placebo-controlled, phase I trial. Three vaccine strengths were compared with an adjuvant-only preparation. It included two intramuscular and a third intranasal dose. Eligible participants were followed for adverse reactions. Specific IgG, secretory IgA, neutralizing antibodies, and cell-mediated immunity were assessed. Results: A total of 153 participants were enrolled (13 sentinels, 120 randomized, 20 non-randomized open-labeled for IgA assessment). No related serious adverse event was observed. The geometric mean ratios (GMRs) and 95% CI for serum neutralizing antibodies compared with placebo two weeks after the second injection were 5.82 (1.46-23.13), 11.12 (2.74-45.09), and 20.70 (5.05-84.76) in 5, 10, and 20 µg vaccine groups, respectively. The GMR for anti-RBD IgA in mucosal fluid two weeks after the intranasal dose was 23.27 (21.27-25.45) in the 10 µg vaccine group. The humoral responses were sustained for up to five months. All vaccine strengths indicated a strong T-helper 1 response. Conclusion: RCP is safe and creates strong and durable humoral and cellular immunity and good mucosal immune response in its 10 µg /200 µL vaccine strengths. Trial registration: IRCT20201214049709N1.

Phase II, Safety and Immunogenicity of RAZI Cov Pars (RCP) SARS Cov-2 Vaccine in Adults Aged 18-70 Years; A Randomized, Double-Blind Clinical Trial.

BACKGROUND: This study explores the safety and immunogenicity of the Razi-Cov-Pars (RCP) SARS Cov-2 recombinant spike protein vaccine. METHOD: In a randomized, double-blind, placebo-controlled trial, adults aged 18-70 were randomly allocated to receive selected 10 µg/200 µl vaccine strengths or placebo (adjuvant). It included two intramuscular injections at days 0 and 21, followed by an intranasal dose at day 51. Immediate and delayed solicited local and systemic adverse reactions after each dose up to a week, and specific IgG antibodies against SARS Cov-2 spike antigens two weeks after the 2nd dose were assessed as primary outcomes. Secondary safety outcomes were abnormal laboratory findings and medically attended adverse events (MAAE) over six months follow up. Secondary immunogenicity outcomes were neutralizing antibody activity and cell-mediated immune response. RESULT: Between May 27th and July 15th, 2021, 500 participants were enrolled. Participants' mean (SD) age was 37.8 (9.0), and 67.0 % were male. No immediate adverse reaction was observed following the intervention. All solicited local and systemic adverse events were moderate (Grade I-II). Specific IgG antibody response against S antigen in the vaccine group was 5.28 times (95 %CI: 4.02-6.94) the placebo group with a 75 % seroconversion rate. During six months of follow-up, 8 SAEs were reported, unrelated to the study intervention. The participants sustained their acquired humoral responses at the end of the sixth month. The vaccine predominantly resulted in T-helper 1 cell-mediated immunity, CD8+ cytotoxic T-cell increase, and no increase in inflammatory IL-6 cytokine. CONCLUSION: RCP vaccine is safe and creates strong and durable humoral and cellular immunity. TRIAL REGISTRATION: (IRCT20201214049709N2).

Risk Factors for Anti Mullerian Hormone Decline after Laparoscopic Excision of Endometrioma: A Prospective Study.

BACKGROUND: Laparoscopic excision of ovarian endometrioma is believed to decrease the ovarian reserve, but the risk factors of declining ovarian reserve are not well studied. This study aimed to determine the risk factors of anti mullerian hormone (AMH) decline after laparoscopic surgery of endometrioma.
Materials and Methods: This prospective study was recruited in Yas and Arash Hospitals affiliated to Tehran University of Medical Sciences from 2020 to 2021. Women between 18-45 years with ovarian endometriomas with a diameter greater than 3 centimeters who were candidates for laparoscopy were included. AMH, luteinizing hormone (LH),
and follicular stimulating hormone (FSH) as well as cancer antigen 125 (CA125) and cancer antigen 19-9 (CA19-9) were obtained and compared pre and postoperatively. Indeed, the relation of AMH decline rate and the demographic, symptoms and endometrioma characteristics were investigated either.
Results: In this study, 100 women were recruited. The mean ± SD age of the participants was 29.08 ± 4.6. AMH (P<0.000) and LH (P=0.013) declined significantly postoperatively. Whereas, no significant difference was observed between pre and postoperative FSH (P=0.520). AMH decline rate was 30.07 ± 2.30% and didn't have significant relation with the demographic characteristics, preoperative AMH, and the amount of CA125. Otherwise in the multivariate analysys, CA125 (P=0.160) and the grade of endometriosis (P=0.05) had significant correlation with AMH decline rate.
Conclusion: Ovarian reserve decline after laparoscopic excision of endometrioma. Otherwise, there may no specific risk factor to predict the degree of ovarian reserve decline. Therefore, the selection of patients for laparoscopic excision of endometrioma should be taken more cautiously as the ovarian reserve diminishes even in the patients with the lowest risks.