Iranian Biomedical Journal

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Comparing Stair-Step Letrozole with Letrozole/Gonadotropin Combined Regimens for Ovulation Induction in Letrozole-Resistant Infertile PCOS Candidates of Intrauterine Insemination

Maliheh Afiat, Nayyereh Khadem Ghaebi, Farzaneh Joghatayi, Negar Morovatdar, Fahimeh Afzaljavan, Navid Pousti,
Volume 28, Issue 0 (Supplementary 2024)

Abstract

Introduction: Infertility is a severe challenge for most health systems. One of the medications recently used for ovulation induction is letrozole, applied either alone or in combination with gonadotropin. The present study was conducted to compare ovulation induction in infertile polycystic ovarian syndrome (PCOS) women candidates of intrauterine insemination (IUI) who were resistant to letrozole by two regimens: single-drug stair step letrozole vs. combined letrozole plus human menopausal gonadotropin.
Methods and Materials: In this parallel randomized clinical trial, 60 infertile women with PCOS, candidates for intrauterine insemination, admitted to Milad Infertility Center at Imam Reza Hospital, Mashhad, Iran, were randomly assigned into two groups. The intervention group received 5 mg of letrozole for five days from menstruation day 3 and 7.5 mg of letrozole for another five days if dominant follicles were not observed on days 14-19. Control cases received letrozole (5 mg) from day 3 of the cycle for five days plus Cinnal-f® (75 international units subcutaneously daily) on days 8 and 9. They received another dose of Cinnal-f® if the dominant follicle was not observed on days 10-12 of the cycle. In the case of detecting dominant follicles, 5000 units of intramuscular hCG were prescribed, and 36 hours later, the patients underwent IUI. The outcomes were considered, and data were analyzed using SPSS.
Results: Almost 70% of the stair-step letrozole group and 53.2% in the combined medication had a dominant follicle (p = 0.12), mainly observed after day 14 in the stair-step letrozole group and during days 10-14 in the letrozole/gonadotropin group (p = 0.001). The positive beta-hCG level was significantly higher in the stair-step letrozole group (23.3%) than in the letrozole/gonadotropin group (13.3%). The clinical pregnancy and gestations of 20 weeks or beyond (ongoing pregnancy) were 16.66% and 10% in the stair-step letrozole and letrozole/gonadotropin groups, respectively (p = 0.03).
Conclusion and Discussion: Our study found similar frequencies of dominant follicles between the stair-step letrozole and letrozole/ gonadotropin groups and a significantly higher frequency of chemical pregnancy (positive beta-hCG) and clinical and ongoing pregnancy in the stair-step letrozole group. As an easy and acceptable method for patients, this protocol can be a suitable alternative for ovulation induction.

Effects of Marrubium vulgare Extract on Hormonal Parameters and Clinical Findings in Polycystic Ovarian Syndrome: A Randomized, Placebo-Controlled, Triple-Blind Clinical Trial

Malihe Afiat, Fahimeh Afzaljavan, Shima Jelodar, Navid Pousti,
Volume 28, Issue 0 (Supplementary 2024)

Abstract

Introduction: Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders in women of reproductive age. Marrubium vulgare has long been used in traditional Persian medicine to treat symptoms related to PCOS. However, limited studies have investigated its effect in treating this condition. The present study evaluated the impact of a dry extract of Marrubium vulgare on hormonal parameters and clinical symptoms of PCOS.
Methods and Materials: In this randomized, placebo-controlled, triple-blind clinical trial, patients diagnosed with PCOS according to the Rotterdam criteria, who were referred to Imam Reza Hospital between 2019 and 2023, were enrolled and randomly assigned to either intervention or placebo groups. The intervention group received 250 mg of dry extract of the Marrubium vulgare (two capsules daily for three months), while the control group was administered a placebo. Body mass index (BMI), testosterone levels, estradiol, and progesterone hormones, and serum levels of cholesterol, triglycerides, and fasting blood sugar were evaluated in all patients at the beginning and after the completion of the three-month treatment period. The severity of acne, hirsutism, and irregularity in the menstrual period of the patients was also checked before and after the intervention. Data were analyzed using SPSS statistical software version 26.
Results: In the placebo group, none of the evaluated criteria at the end of the trial was significantly different from the beginning of the study (p = 0.05). In the intervention group, BMI, hirsutism score, fetal bovine serum (FBS), and testosterone levels significantly reduced at the end of the study. Also, at the end of the study, the hirsutism frequency, dysmenorrhea, and irregular menstruations in the intervention group were significantly lower than in the placebo group (p = 0.048, p = 0.022, and p = 0.047, respectively). The mean reduction in the hirsutism score, FBS, and testosterone levels was higher in the intervention group than in the placebo group (p = 0.030, p = 0.002, and p = 0.001, respectively).
Conclusion and Discussion: Our findings suggest that Marrubium vulgare could serve as an effective and safe treatment for PCOS.

Predicting Signaling Cascades of Inflammasome-Induced Inflammatory Cell Death Following SARS-Cov-2 Infection through A Bioinformatic Approach

Ali Sepehrinezhad, Sajad Sahab Negah, Navid Pousti, Sajjad Mollaei,
Volume 28, Issue 0 (Supplementary 2024)

Abstract

Introduction: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by respiratory failure, pneumonia, coagulation, and multiorgan failure due to deregulation of cytokine release. Inflammasome activation has been reported with tissue injury and increased disease severity. Here, we conducted a bioinformatic analysis to predict possible cellular and molecular mechanisms of inflammasome activation-induced cell injury/death in COVID-19.
Methods and Materials: All genes- associated with SARS-CoV-2 and inflammasome were extracted from GeneWeaver. Afterward, common genes were selected for further enrichment analysis. Common genes were uploaded into the ToppGene database to predict significant molecular functions, biological processes, Cellular components, signaling pathways, and microRNAs for both SARS-CoV2 and inflammasome. Cytoscape was also used to reconstruct the drug-genetic network for shared genes.
Results: Our results demonstrated that 62 genes were related to inflammasome, and 2379 genes were associated with SARS-CoV-2. Among these gene sets, nine genes such as tumor necrosis factor, cathepsin B, baculoviral IAP repeat containing 3, interleukin 6, absent in melanoma 2, leptin receptor, NLR family pyrin domain containing 1, nucleotide-binding oligomerization domain containing 1, and signal transducer and activator of transcription one were shared between inflammasome and COVID-19. NOD-like receptor signaling, nucleotide-binding domain leucine-rich repeat-containing receptor NLR signaling, TNF-related weak inducer of apoptosis TWEAK signaling, SARS-CoV2 innate immunity evasion and cell-specific immune, and toll-like receptor signaling were the most significant involved pathways in pyroptosis following COVID-19. The external side of the plasma membrane, membrane raft, ISGF3 complex, AIM2 inflammasome complex, and endolysosome lumen were the main cellular components that may disrupt following inflammasome activation in COVID-19.
Conclusion and Discussion: Notably, our findings predicted some microRNAs and revealed central signaling cascades following inflammasome activity, which may benefit future therapeutic targets in COVID-19.

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