Letrozole Group Research Articles

Effect of a single dose of letrozole on ejaculation time, semen quality, and testicular hemodynamics in goat bucks subjected to heat stress.

Letrozole (LTZ) is an aromatase inhibitor that limits estrogen (E2) production and increases testosterone (T) levels. This research aimed to examine the impact of a single dose of LTZ on testicular hemodynamics, ejaculation time, and semen quality in goats under heat stress (HS). Therefore, Doppler examination and semen evaluation were performed on twelve mature bucks for two weeks (W-1, W-2) as pre-heat stress control during winter. Then during summer HS bucks were subjected to Doppler examination, semen evaluation, and hormonal analysis (T, E2, and LH) at 0h. Afterward, bucks were assigned into two groups and subcutaneously injected with physiological saline (n = 6; CON) or LTZ (0.25mg/kg BW; n = 6; LTZ). Both groups were subjected to Doppler scanning and hormonal analysis at 2, 4, 24, 48, 72, 96,144, and 168h. Semen evaluation was performed at 48 and 168h. The LTZ group showed increasing (P < 0.05) in semen volume, sperm motility, and viability and decreasing (P < 0.05) in ejaculation time and sperm abnormalities compared to CON group at 48h. Additionally, T concentrations increased (P < 0.01) at 2, 24, and 48h, E2 decreased (P < 0.01) from 2 to 48h, and LH raised (P < 0.01) at 2 and 72h in LTZ group compared to CON one. Doppler indices reduced (P < 0.05) at 96h in LTZ group. semen pH and scrotal circumference were not affected by LTZ. In conclusion, LTZ administration shortened ejaculation time and enhanced semen quality in bucks during HS.

The Effectiveness of Letrozole Alone or in Combination with Methotrexate in the Management of Ectopic Pregnancy, A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to investigate the effect of letrozole alone or in combination with Methotrexate on the management of ectopic pregnancy. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were applied for reporting. The EMBASE, PubMed, Scopus, and Web of Science databases were searched for relevant studies focused on women diagnosed with ectopic pregnancy and managed non-surgically with letrozole alone or in combination with methotrexate (MTX) until April 2024. The success rate, laboratory findings, and complications were analyzed and reported. Meta-analysis was done using RevMan 5.4.1 software. Out of 129 unique studies obtained, 7 of them were found eligible for final review; of which, 3 were nonrandomized prospective cohort studies, 2 were randomized clinical trials, and 2 study were case studies. In 5 studies letrozole was used as monotherapy. While in another study letrozole was used with MTX. The meta-analysis showed a significantly lower level of β-HCG in the letrozole group compared to MTX, 7days after initiation of treatment (Fixed effect model, MD = -92.22, 95%CI: [-159.39, -25.04], P = 0.007, I2 = 0%). There was no significant difference in the level of anti-mullerian hormone (AMH) between groups (Fixed effect model, MD = 0.18, 95%CI: [-0.09, 0.45], P = 0.20, I2 = 0%). Success rate, platelet count, and level of liver enzymes seemed to be better or similar among patients receiving Letrozole compared to patients receiving Methotrexate. Letrozole exhibits potential as a therapeutic option for ectopic pregnancies; however, further randomized clinical trials are necessary to establish strong evidence.

Effects of Letrozole And Metformin Versus Metformin alone on incretin in Iraqi patients with PCOS

I Background: The emergence of numerous novel therapeutic agents for managing T2DM has expanded the assortment of tailored therapies available for PCOS sick. One illustration of these is the incretin-based therapeutic agents. Patients and methods:The extanttrainingcomprised 75 sickthrough an age extent of 18 to less than 40 years. Patients were categorized into three groups: metformin group (positive control group) and they received metformin as 500 mg per-oral (bid); letrozole group who were treated using 2.5 mg per-oral (bid), and combination groups who received both agents with similar doses as above. Each group included 25 females. Informationalmost age and body mass index (BMI) stayed included in the study. Serum measurement of incretin (GLP-1) was done before treatment and 90 days after treatment using Enzyme-Linked Immunosorbent Assay. Results: There stayed no importantvariance in mean age (p = 0.981) betweentraining groups and means of age were 29.24 ± 6.10 years, 29.56 ± 5.50 years and 29.44± 5.83 years, respectively and the range of age was between 18 and 40 years. In addition, in this training, there stayed no importantalteration in mean BMI (p = 0.534) among study groups and means of BMI were 28.80 ±2.72 kg/m2, 27.53 ±1.95 kg/m2 and 27.07 ±1.99 kg/m2, respectively and the range of BMI was between 21.07 and 31.18 kg/m2. Serum incretin (GLP-1) level showed no significant variation among study groups, the mean levels were in the range of 10.87 -13.79 ng/ml and the range of values was from 9.56 -14.49 ng/ml. Changes in BMI are shown in. Metformin alone caused in more important weight decrease; nevertheless, adding of letrozole caused significant reduction in body mass index, letrozole alone also affect body weight significantly. It was observed that combined use of either drug resulted in more significant change of GLP-1 level at (p ≤ 0.001). Conclusion: Combined treatment with letrozole and metformin is safe and efficient in femalesby PCOS resultant in weight decrease, improved insulin

Application of small animal ultrasound imaging technology for identification of polycystic ovary syndrome in a mouse model

Background and AimsPolycystic ovary syndrome (PCOS) is a hormonal disorder common among women of reproductive age, characterized by irregular menstrual periods, elevated levels of androgens, and polycystic ovaries, leading to various symptoms and complications such as infertility, metabolic issues, and increased risk of diabetes and heart disease. This study aimed to compare traditional histological methods and ultrasound imaging for consistency in identifying PCOS in a mouse model. The shortest time to construct the PCOS model using letrozole was determined. MethodsFemale C57/BL mice were randomly divided into three groups: Group A received normal saline and a regular diet; Group B received 1 mg/kg/day of letrozole with a regular diet; and Group C received 1 mg/kg/day of letrozole with a high-fat diet. All mice were administered letrozole by intragastric gavage daily for five weeks. The traditional identification method included measuring body weight, examining vaginal smears, monitoring the estrous cycle, measuring serum androgen levels, and performing H&E staining of ovarian tissues. The PCOS model was evaluated using ultrasound imaging to identify and monitor follicles. The significance of the difference between the traditional identification method and the ultrasonic method was calculated using the nonparametric McNemar test, and consistency between the two methods was assessed with the kappa-coefficient test. On this basis, the ultrasound imaging technology was used to monitor the model-making process for 2, 3 and 4 weeks, and to monitor the parameters of the ovary and follicles to judge the shortest time that gavage letrozole caused the appearance of vesicular follicles in the mouse ovary. ResultsThe traditional identification method showed no PCOS phenotype in group A mice, while groups B and C showed multiple ovarian cystic follicles, indicating successful model induction. The ultrasound imaging results were consistent with the traditional method, showing no PCOS in group A and multiple cystic follicles in groups B and C. The McNemar test revealed no significant difference between the traditional and ultrasonic identification methods. The kappa-coefficient test assessed consistency, yielding a value of 0.903, indicating strong agreement between the methods. The ovarian area, diameter, and the number and diameter of cystic follicles were not significantly changed at two weeks in the letrozole group compared with the control group. At three weeks, there were significant increases in the number and in the diameter of vesicular follicles compared with control cells. At four weeks, the number and diameter, the maximum cross-sectional area and diameter of the ovary were significantly increased compared with the control group. ConclusionsThe ultrasound and traditional methods provide consistent results for identifying PCOS in a mouse model. Construction of the PCOS model by letrozole gavage takes at least three weeks.

Letrozole co-treatment in an antagonist protocol for overweight women undergoing IVF treatment: a retrospective study

BackgroundOverweight women undergoing IVF treatment have lower success rates. Letrozole, an aromatase inhibitor, has been used as an adjunct for IVF treatment, but its specific effects in overweight women have not been investigated. This study was to explore the effects of letrozole co-treatment in an antagonist protocol for overweight infertile women undergoing IVF treatment.MethodsThis retrospective cohort study included overweight infertile women who underwent IVF/ICSI treatment and fresh embryo transfer (ET), with or without letrozole co-treatment in an antagonist protocol, from 2007 to 2021 at Shanghai Ninth People’s Hospital (Shanghai, China). A total of 704 overweight infertile women were included: 585 women were in the antagonist group, and 119 women were in the letrozole co-treatment group. The primary outcome was the live birth rate after fresh ET. Propensity score-based patient-matching was employed to balance the covariates between the groups. Multivariate logistic regression analysis was also performed to estimate odds ratio (OR) and 95% confidence interval (CI) for association of letrozole co-treatment and the live birth outcome.ResultsLetrozole co-treatment induced significant changes in hormonal profile on the trigger day. The letrozole group exhibited a decrease in the total number of follicles compared to the antagonist group, but a higher proportion of large follicles at oocyte retrieval (P < 0.05). The quantity and quality of embryos were comparable between the two groups (P > 0.05). The letrozole co-treatment group had a significantly higher live birth rate than the control group (38.7% vs. 22.6%, P = 0.026). With multivariate logistic regression analysis, letrozole co-treatment was associated with higher odds of live birth after adjusting for potential confounding factors (adjusted OR = 2.00, 95% CI = 1.17–3.39, P = 0.011). Letrozole presented no significant associations with obstetrical or neonatal complications (P > 0.05).ConclusionLetrozole co-treatment in an antagonist protocol may offer potential benefits for overweight infertile women undergoing IVF treatment. Further research is warranted to validate these findings and explore the broader implications for letrozole co-treatment.

Evaluation of birth outcomes, congenital anomalies and neonatal complications of singletons born to infertile women treated with letrozole: A retrospective cohort study.

At present, safety of letrozole administration as an ovulation-inducing drug still remains controversial. Investigation of the safety of letrozole use for the induction of ovulation in the Chinese population is scant. The present study aimed to fill this gap. Data concerning mothers using letrozole and birth outcomes of their singleton offspring were collected as the letrozole group (n=194), equivalent data from mothers using non-letrozole drugs and their singleton offspring were included as the non-letrozole group (control, n=154). Birth outcomes, congenital anomalies and neonatal complications were compared and analyzed between the two groups. Univariate analysis, Spearman's rank correlation analysis and the logistic regression model were utilized. For birth outcomes, the percentage of caesarean section deliveries in the letrozole group was lower than the non-letrozole group (43.8 vs. 56.4%, P=0.019). For congenital anomalies, no significant difference was found between the two groups (all P>0.05). The statistical P-value for the correlation between the maternal use of letrozole and neonatal complications was marginal (P=0.051). Results from the logistic regression analysis confirmed that maternal use of letrozole was not a significant contributor for neonatal complications, independent of statistical adjustment [crude odds ratio (OR), 1.436; 95% confidence interval (CI), 0.803-2.569; P=0.223 vs. adjusted OR, 1.406; 95% CI, 0.748-2.643; P=0.290). The results of the present study suggested that maternal use of letrozole for ovulation induction does not associate with poorer birth outcomes or increased risk of congenital anomalies and neonatal complications.

Strong Early Impact of Letrozole on Ovulation Induction Outperforms Clomiphene Citrate in Polycystic Ovary Syndrome.

Polycystic ovary syndrome is a common endocrine disorder, characterized by hyperandrogenism and/or chronic oligo/anovulation, which leads to infertility. The aim of this systematic review and meta-analysis was to explore the efficacy of letrozole compared with clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome. The study protocol has been registered with PROSPERO (registration number CRD42022376611). The literature search included randomized clinical trials. We conducted our systematic literature search across three medical databases: MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase. The data synthesis employed a random effects model. Out of the 1994 articles screened, 25 studies fulfilled the inclusion criteria. The letrozole group exhibited a significant increase in endometrial thickness (mean difference = 1.70, confidence interval: 0.55-2.86; I2 = 97%, p-value = 0.008). The odds of ovulation (odds ratio = 1.8, confidence interval: 1.21-2.69; I2 = 51%, p-value = 0.010) and pregnancy (odds ratio = 1.96, confidence interval: 1.37-2.81; I2 = 32%, p-value = 0.002) were significantly higher. The resistance index of the subendometrial arteries showed a significant decrease (mean difference = -0.15, confidence interval: -0.27 to -0.04; I2 = 92%, p-value = 0.030). Women diagnosed with polycystic ovarian syndrome and treated with letrozole for ovulation induction had increased ovulation and pregnancy rates and increased endometrial thickness. The lower resistance index of subendometrial arteries can enhance intrauterine circulation, creating more favorable conditions for embryo implantation and development.

P-586 Mild ovarian stimulation using the aromatase inhibitor letrozole (LTZ) is an effective stimulation protocol to obtain euploid blastocysts for women of an advanced maternal age

Abstract Study question Does MOS with LTZ produce higher numbers of good-quality blastocysts compared with the use of clomiphene citrate (CC) for women of an advanced maternal age? Summary answer MOS using LTZ is a good ovarian stimulation protocol for a higher number of good-quality blastocysts for women of an advanced maternal age (AMA) What is known already The clinical pregnancy rate with a good blastocyst should be 40% or more among younger women, but about 35% for AMA women (≥40 years). Therefore, high-dose gonadotropins are usually used for AMA women. However, the best efforts for both patients and clinicians are sometimes in vain. Many AMA women show a lower ovarian reserve where ovarian stimulation with a lessened dose of gonadotropins is preferred. Taking CC or LTZ with MOS can reduce the amount of gonadotropins used, but it remains uncertain whether it is better to administer LTZ or CC together for MOS. Study design, size, duration This retrospective study was conducted between January 2020 and April 2021. A total of 288 women received MOS. Of course, 153 used CC (CC group) and 133 used LTZ (LTZ group). The ART outcomes were compared between these two groups. Among them, the women who were ≥40 years old were divided into two groups: CC-O40 (n = 61) and LTZ-O40 (n = 54). The ART outcomes were compared between the two groups. Participants/materials, setting, methods All women took either 100 mg of CC or 5 mg of LTZ daily for 7 days between menstrual cycle 3 (MC3) and MC9, and 225 IU of recombinant-FSH were administered on MC3, MC5, MC7 and MC9. On MC 10, when 3 or more well-developed follicles (≥ 20 mm in diameter) were confirmed, a dual-maturation trigger was performed using rec-hCG and GnRH agonist nasal spray, and then oocyte-pick up (OPU) was performed 35-36 hours afterward. Main results and the role of chance The number of retrieved oocytes in the CC group averaged 7.5 ± 5.3 (mean ± S.D.), which was significantly higher than that in the LTZ group (6.3 ± 4.7; p &amp;lt; 0.05). The average number of blastocysts and morphologically good blastocysts was comparable in the CC and LTZ groups (CC group; 2.8 ± 3.0 and 1.8 ± 2.4; LTZ group; 2.4 ± 2.7 and 1.4 ± 2.0, respectively, [P=NS]). For AMA women, the average number of blastocysts in the CC-O40 group was 1.7 ± 1.8, which was similar to that in the LTZ-O40 group (1.7 ± 1.8, P=NS). The blastocyst formation rate in the LTZ-O40 group was 58.5%, which was significantly higher than that in the CC-O40 group (46.6%; P &amp;lt; 0.05), but the rate for good blastocysts in the LTZ-O40 group (30.8%) was comparable to that in the CC-O40 group (23.3%, P=NS). The euploid rates in the LTZ group was 53.4%, which was significantly higher than that in the CC group (38.0%; P &amp;lt; 0.05), and the difference was significant even for AMA women (LTZ-O40; 40.5%, CC-O40; 16.7%, respectively, p &amp;lt; 0.05). Limitations, reasons for caution The study was a controlled trial with a limited number in the study population. Additionally, all cases had not received a trophectoderm (TE) biopsy. Further study is needed to determine the effect that an aromatase inhibitor exerts on obtaining either morphologically good blastocysts or euploid blastocysts. Wider implications of the findings AMA women showed blastocyst formation rates from LTZ with MOS significantly higher than that of the CC group, and euploid rates in the LTZ group were also significantly higher. The characteristics of an LTZ such as aromatase inhibitor enhanced the development of embryos. Trial registration number not applicable

P-644 Effect of Letrozole co-stimulation with gonadotropin in women with normal ovarian reserve on oocyte maturation: a Randomized controlled trial

Abstract Study question To define whether letrozole co-stimulation with gonadotropin in normal-ovarian reserve women will improve the number of oocyte maturation. Summary answer Letrozole co-stimulation in normal ovarian reserve resulted in a reduced number of MII. What is known already Letrozole functions as an aromatase inhibitor. By inhibiting this enzyme, letrozole effectively lowers estrogen levels. Thus, letrozole prevents the estrogen-negative feedback to the HPO axis, which can increase the secretion of gonadotropins from the pituitary gland to promote folliculogenesis. The application of letrozole co-stimulation in women with a normal ovarian reserve is still debated. Study design, size, duration This study is an open-labeled, randomized controlled trial. Letrozole co-stimulation with gonadotropin in women with normal ovarian reserve. The RCT was conducted at the Fertility and Reproductive Biology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Siriraj Hospital in Thailand, from March 2023 to October 2023. Participants/materials, setting, methods One hundred forty-four infertile women 18-40 years old with normal ovarian reserve (AMH 1.2-7 ng/ml, AFC ≥ 5) were random to gonadotropin co-stimulation with letrozole 5 mg once daily (n = 72) and gonadotropin alone (n = 72). The number of MII oocytes, follicle-to-oocyte index, GDF-9 and BMP-15 in follicular fluid were assessed. Main results and the role of chance Letrozole co-stimulation resulted in a significantly reduced number of MII [8 (4,12) vs 9 (5, 15.8), p = 0.042] and the rate of MII [ 71.7(60, 83.8) vs 80 (66.7, 90), p = 0.013]. However, the number of retrieved oocytes [12 (6,16.8) vs. 12 (6,16), p = 0.335] and FOI [85.7 (57.4,107.5) vs 84.2 [61.8, 112.5], p = 0.396] remained unchanged. The total dose of gonadotropin in the letrozole group was no different from the control group [1,350 (1,200, 1,650) vs 1,500 (1,350, 1,718.8) I.U., p = 0.137]. The duration of ovarian stimulation was shortened in the letrozole group compared to the control group [9 (8, 10) vs 9 (8.3, 10) days, p = 0.027]. The letrozole and control group had a similar level of GDF-9 (0.036 ± 0.003 A.U. vs. 0.028 ± 0.004 A.U., p = 0.119, letrozole and control group, respectively) and BMP-15 (0.034 ± 0.002 A.U. vs. 0.033 ± 0.004 A.U., p = 0.923, letrozole and control group respectively) in follicular fluid. Limitations, reasons for caution This study was open-label, with limited generalizability due to 91% of ovarian stimulation being strict to the research protocol (r-FSH and antagonist protocol) and no pregnancy outcome. Wider implications of the findings The study showed no benefit of letrozole co-stimulation in women with normal ovarian reserve. Trial registration number TCTR20221125002

P-367 Letrozole or Tamoxifen co-administration during fertility preservation of breast cancer patients: a retrospective cohort study

Abstract Study question How do fertility preservation (FP) outcomes differ between breast cancer patients stimulated with FSH and Tamoxifen versus FSH and Letrozole? Summary answer Letrozole and Tamoxifen co-administration yielded similar number of retrieved and cryopreserved oocytes/embryos, as well as similar oocyte maturation and fertilization and rates. What is known already Oocyte/embryo cryopreservation is recommended before initiation of chemotherapy in cancer patients. The co-administration of Tamoxifen, a selective estrogen receptor modulator, or Letrozole, an aromatase inhibitor, during ovarian stimulation with gonadotropins, are used to limit the potentially harmful effects of a supra-physiological rise in estrogen levels on hormone-sensitive cancers. However, the optimal choice between the two is still unclear and with no sound evidence. Study design, size, duration Retrospective cohort study of all FP treatments of newly diagnosed breast cancer patients in two tertiary centers between 2000-2022. Collected data included 354 FP cycles of 290 patients and compared treatment parameters and outcomes of Tamoxifen or Letrozole co-administration. Participants/materials, setting, methods Breast cancer patients who underwent FP before chemotherapy were included. Patients with a history of radiation or gonadotoxic treatment, as well as those undergoing other fertility preservation treatments, such as ovarian tissue cryopreservation were excluded. Main results and the role of chance Overall, 215 Letrozole and 139 Tamoxifen treatment cycles were compared, with no significant demographic differences. Treatments with Letrozole had higher FSH dosages (3970IU vs. 2839IU, p &amp;lt; 0.001) but shorter duration (9.7 vs. 10.5 days, p &amp;lt; 0.001). The Letrozole group achieved lower peak E2 levels and endometrial thickness (1508pmol/L, 8.1mm vs. 8760pmol/L, 9.5mm, p &amp;lt; 0.001). The mean number of retrieved oocytes was comparable between the groups (13.6 with Letrozole vs 14.7 with Tamoxifen, p = 0.06). In 122 Letrozole and 46 Tamoxifen patients that underwent strictly oocytes cryopreservation the mean number of cryopreserved oocytes was comparable (11 vs. 12.1, p = 0.21). Moreover, in embryo cryopreservation cycles of 71 patients treated with Letrozole compared to 76 patients with Tamoxifen, no difference was observed in the number of cryopreserved embryos (6.2 vs. 7.0, p = 0.12). Oocyte maturation rate among strictly oocyte preservation cycles was comparable (86% with Letrozole vs. 83% with Tamoxifen, p = 0.80), as were fertilization rates in embryo cryopreservation cycles (62% vs. 63%, p = 0.8 and 71% vs. 76%, p = 0.3 in IVF and ICSI with Letrozole and Tamoxifen, respectively). Multivariate analysis, controlling for potential confounders showed no significant correlations between Tamoxifen or Letrozole co-administration and the number of retrieved oocytes or oocyte maturation rate. Limitations, reasons for caution The primary limitation of our study is its retrospective design and the variation in treatment duration and gonadotrophin dosages among groups. Wider implications of the findings This study provides reassurance that both Tamoxifen and Letrozole are equally effective options when co-administered in FP treatments of breast cancer patients. Trial registration number not applicable

The Efficacy of Letrozole Co-Treatment in an Antagonist Protocol for Women with Polycystic Ovary Syndrome Undergoing IVF: A Retrospective Study.

Our objective was to investigate the efficacy of letrozole co-treatment in an antagonist protocol for infertile women with polycystic ovary syndrome (PCOS). This retrospective cohort study included infertile women with PCOS undergoing IVF/ICSI with and without letrozole co-treatment in an antagonist protocol from 2007-2021 at Shanghai Ninth People's Hospital (Shanghai, China). A total of 1559 participants were enrolled, with 1227 women in the antagonist group and 332 women in the letrozole co-treatment group. Propensity score-based patient-matching model was conducted to balance covariates between the groups. The primary outcome was the number of retrieved oocytes, with secondary outcomes including endocrine parameters, ovarian stimulation outcomes, pregnancy outcomes, and obstetrical and neonatal complications. Letrozole co-treatment induced significant changes in hormonal regulation, increased the percentage of large follicles, and resulted in fewer retrieved oocytes (P < 0.05). However, there was no negative impact on the number of usable embryos or good-quality embryos (P > 0.05). The live birth rates following fresh embryo transfer were comparable between the letrozole and control groups (single embryo transfer: 28.9% vs 29.7%, P > 0.05; double embryo transfer: 37.3% vs 45.6%, P > 0.05). Additionally, there were no significant differences between the two groups in the live birth rate per patient after frozen embryo transfer and the cumulative live birth rate (P > 0.05). No significant differences in obstetrical and neonatal complications were observed between the groups (P > 0.05). The addition of letrozole to the antagonist protocol for women with PCOS undergoing IVF induces a higher percentage of large follicles during oocyte retrieval, while reducing the overall number of retrieved oocytes. Moreover, the use of letrozole demonstrates comparable clinical outcomes following embryo transfers. These findings highlight the potential application of letrozole in an antagonist protocol for women with PCOS.

Cytoarchitectural differences in reproductive organs of some polycystic ovary-like induced animal models

Polycystic ovary syndrome (PCOS) is the most common gynaecological, endocrine disorder that occurs during reproductive age and is a significant cause of anovulatory infertility. Letrozole is an aromatase inhibitor which negates the action of the aromatase enzyme, which results in the buildup of male hormones (testosterone) in the females, causing hyperandrogenism, which is a hallmark of Polycystic Ovarian Syndrome. Mifepristone (RU486) is a progestin antagonist that acts to arrest the actions of the progesterone hormone, resulting in follicular atresia and anovulation. DHEA is an androgen which was also administered in a bid to cause hyperandrogenism in the rats.This study aimed to evaluate the effects of these hormones on the cytoarchitecture of the ovaries and uterus to assess their various PCOS-like histological features.Animals were grouped mainly into three: Letrozole, Mifepristone and DHEA groups, which were further divided into two subgroups each, administered low and high doses of letrozole orally, Mifepristone and Dehydroepiandosterone (DHEA) subcutaneously. Each of the subgroups also had a comparison control group. Following the completion of administration, the Wistar rats were euthanized, and their ovaries and uterus were collected for histological analysis.Increased proliferation of ovarian follicles was noted in the treated groups compared to control, as well as thickening of the endometrial layer.

Comparing the effectiveness of letrozole versus methotrexate for treatment of ectopic pregnancy: A randomized controlled trial

ObjectiveTo evaluate the efficacy of two different regimens of Letrozole, an aromatase inhibitor, in the management of ectopic pregnancy compared to methotrexate. Study DesignThis randomized controlled trial was conducted on 88 women diagnosed with ectopic pregnancy with a baseline level of serum beta-human chorionic gonadotropin under 3000 mIU/mL between June 30, 2023, and December 30, 2023, at the Department of Obstetrics and Gynecology of the Vali-e-Asr Hospital affiliated with Tehran University of Medical Sciences. Participants were allocated into either methotrexate (n = 43), 5-day course Letrozole (n = 24), or 10-day course Letrozole (n = 21) treatments. The methotrexate group received a single dose of 50 mg/m2 dosage intramuscular methotrexate. The 5-day Letrozole group received a 2.5 mg Letrozole tablet three times daily for 5 days, whereas the 10-day Letrozole group received a 2.5 mg Letrozole tablet twice daily for 10 days. The primary outcome was the treatment response, defined as the achievement of a negative serum beta-human chorionic level without the need for additional methotrexate treatment or surgery. The secondary outcomes were the need for additional methotrexate dose or laparoscopic surgery intervention. The trial protocol was prospectively registered in ClinicalTrials.gov with code NCT05918718. ResultsThe treatment response rates in methotrexate, 5-day Letrozole, and 10-day Letrozole groups were 76.7 %, 75.0 %, and 90.5 %, respectively, with no significant differences between the groups (P-value = 0.358). A total of 10 (23.3 %) patients from the methotrexate group, 3 (12.5 %) from the 5-day Letrozole group, and 2 (9.5 %) from the 10-day Letrozole group required an additional methotrexate dose, with no significant differences between the groups (P-value = 0.307). Furthermore, only 3 (12.5 %) patients, all from the 5-day Letrozole group, were suspected of tubal rupture and underwent surgery (P-value = 0.016). ConclusionOur findings suggest Letrozole as a safe alternative to methotrexate in treating stable ectopic pregnancies, with a favorable treatment response rate. However, there is still a need for future larger studies to determine the applicability of Letrozole in the EP management. Also, the non-significant higher effectiveness of the 10-day Letrozole regimen than the 5-day Letrozole group underscores the need for future research to determine the optimal Letrozole regimen for the management of ectopic pregnancy.

Letrozole and ovarian hyperstimulation syndrome: Retrospective cross-sectional study.

Recently, letrozole has been used to prevent moderate to severe ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology cycles due to its estrogen-reducing and androgen-increasing effects on the ovaries, affecting granulosa cells, and reducing vascular endothelial growth factor production. This study aimed to investigate the impact of letrozole consumption in preventing OHSS in infertile women with polycystic ovarian syndrome undergoing in vitro fertilization. In this cross-sectional study, among 1743 medical records of infertile women who were scheduled for oocyte retrieval at Research and Clinical Center for Infertility, Yazd, Iran. Data of 343 women with polycystic ovarian syndrome diagnosis and at risk of OHSS was extracted from March 2022-2023. The stimulation was carried out using a flexible gonadotropin releasing hormone (GnRH) antagonist protocol. Women were divided into 2 groups based on whether they received letrozole or not. In the letrozole group, 2.5 mg letrozole twice daily was continued from the trigger day, while in the control group, women did not receive letrozole. The parameters of OHSS severity, hospitalization rates, and the need for albumin prescription were analyzed. 89 women in the letrozole and 254 women in the control group were examined. There was no statistically significant difference between groups in terms of age and body mass index; however, anti-Mullerian hormone was significantly higher than control group (7.53 4.61 vs. 5.47 3.63, p 0.001). The parameters of OHSS severity, hospitalization rates, and the need for albumin prescription showed no significant differences between the groups. Recent study indicates that incorporating letrozole into the treatment of GnRH antagonists and cabergoline does not reduce the OHSS severity.

The effect of letrozole on liver function and some biochemical parameters in rats

Letrozole (LTZ), is an aromatase inhibitor, that has been widely used in a variety of diseases such as polycystic ovary syndrome, endometriosis, and breast cancer. LTZ is received via the oral route and metabolized in the liver. Therefore, LTZ may have toxic effects like other drugs metabolized in the liver. Based on this, our study aimed to investigate the effect of LTZ on liver function and biochemical parameters. For this purpose, 16 Wistar albino female rats were divided into two groups (n=8): Control and LTZ respectively. The rats in the letrozole group were administered with 2 mL/kg LTZ by oral gavage once a day for 21 days. The Control group received the vehicle once a day for 21 days. Blood samples were collected on the 22nd day of the experiment. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), albumin (ALB), alkaline phosphatase (ALP), direct bilirubin and total bilirubin were measured. Biochemical analysis indicated that ALT, AST, LDH, ALP, and total bilirubin levels were significantly higher in the LTZ administrated group compared to the Control. ALB levels decreased in the LTZ group. In conclusion, it was determined that LTZ has toxic and detrimental effects on the liver. We suggested that long-term LTZ administrated patients should be under control against liver damage and may have liver supporting adjuvant therapies for robust liver functions.

Gedatolisib in combination with palbociclib and endocrine therapy in women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the dose expansion groups of an open-label, phase 1b study

The PI3K-mTOR pathway is frequently dysregulated in breast cancer. Combining an inhibitor targeting all class I PI3K isoforms and mTOR complex 1 (mTORC1)-mTOR complex 2 (mTORC2) with endocrine therapy and a CDK4/6 inhibitor might provide more effective tumour control than standard-of-care therapy. To evaluate this hypothesis, gedatolisib, a pan-PI3K-mTOR inhibitor, was assessed in a phase 1b trial combined with palbociclib and endocrine therapy in patients with hormone receptor-positive, HER2-negative, advanced breast cancer. Results from the dose expansion portion of this trial are reported herein. This multicentre, open-label, phase 1b study recruited female patients aged at least 18 years from 17 sites across the USA with hormone-receptor-positive, HER2-negative, advanced breast cancer and an Eastern Cooperative Oncology Group performance status of 0-1. Four patient groups were studied in the dose expansion portion of the study: treatment-naive in the advanced setting (first line; group A), progression on 1-2 lines of endocrine therapy but CDK4/6 inhibitor-naive (group B); and one or more previous lines (second-line and higher) of therapy, including a CDK4/6 inhibitor (groups C and D). Gedatolisib 180 mg was administered intravenously weekly in 28-day treatment cycles for groups A-C, and on days 1, 8, and 15 for group D. Letrozole (group A), fulvestrant (groups B-D), and palbociclib (all groups) were administered at standard doses and schedules. The primary endpoint was investigator-assessed objective response rate per RECIST version 1.1 in the evaluable analysis set. This trial is completed and registered with ClinicalTrials.gov, NCT02684032. Between Dec 19, 2017, and June 19, 2019, 103 female participants were enrolled in the dose expansion groups A (n=31), B (n=13), C (n=32), and D (n=27). Median follow-up was 16·6 months (IQR 5·7-48·4) for group A, 11·0 months (7·6-16·9) for group B, 3·6 months (1·8-7·5) for group C, and 9·4 months (5·3-16·7) for group D for the primary endpoint. Gedatolisib, palbociclib, and endocrine therapy induced an objective response in 23 (85·2%; 90% CI 69·2-94·8) of 27 evaluable first-line participants (group A). In the second-line and higher setting, an objective response was observed in eight (61·5%; 90% CI 35·5-83·4) of 13 evaluable group B participants, seven (25·0%; 12·4-41·9) of 28 evaluable group C participants, and 15 (55·6%; 38·2-72·0) of 27 evaluable group D participants; this included participants with both wild-type and mutated PIK3CA tumours. The most common grade 3-4 treatment-related adverse events were neutropenia (65 [63%] of 103), stomatitis (28 [27%]), and rash (21 [20%]). Grade 3-4 hyperglycaemia was reported in six (6%) participants. 23 (22%) of 103 participants had a treatment-related serious adverse event, and there were no treatment-related deaths. Nine (9%) participants discontinued treatment because of a treatment-emergent adverse event. Gedatolisib plus palbociclib and endocrine therapy showed a promising objective response rate compared with the published results for standard-of-care therapies and had an acceptable safety profile. Pfizer and Celcuity.

What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles among anovulatory women? A retrospective cohort study

ObjectiveDifferent endometrial preparation protocols are used prior to frozen-thawed embryo transfer (FET). It is not clear whether letrozole-stimulated cycles are beneficial for anovulatory women compared to artificial cycles (AC) in anovulatory women. Our objective was to investigate whether clinical outcomes following frozen-thawed embryo transfer in letrozole-stimulated cycles differ from artificial cycles in anovulatory women.Study design: This is a retrospective cohort study conducted in a public fertility center in China comparing letrozole-stimulated and artificial cycles during FET. A total of 5,322 anovulatory women undergoing the first cycle of FET between January 2020 and December 2021. The primary outcome was the live birth rate. The secondary outcomes included biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage, and ectopic pregnancy. ResultsThe live birth rates were significantly higher in the letrozole compared with AC (49.57 % vs. 45.22 %) both in the crude (odds ratio [OR] 1.19, 95 % confidence interval [CI] 1.01–1.40) and adjusted analysis (aOR 1.27, 95 %CI 1.08–1.50). After controlling for potential covariates, the adjusted probability of biochemical pregnancy (65.71 % vs. 63.25 %, aOR 1.20, 95 %CI: 1.01–1.43), clinical pregnancy (61.53 % vs. 58.79 %, aOR 1.20, 95 %CI: 1.02–1.43), and ongoing pregnancy (50.14 % vs. 45.66 %, aOR 1.28, 95 %CI: 1.08–1.51) were higher among those using letrozole-stimulated cycles than among those undergoing artificial cycles. The miscarriage rate was lower following letrozole compared with artificial cycles (aOR 0.59, 95 %CI: 0.43–0.80). The ectopic pregnancy in the letrozole group was similar to that in the artificial cycles. ConclusionsLetrozole-stimulated FET was significantly associated with higher rates of biochemical pregnancy, clinical pregnancy, ongoing pregnancy and live birth, and with a lower rate of miscarriage, compared with artificial cycles.

Reassessing the impact of letrozole co-administration in controlled ovarian hyperstimulation: findings from a single-center repeated measures study.

To explore whether letrozole improved outcomes in subsequent controlled ovarian hyperstimulation (COH) cycles. This was a retrospective repeated measures cohort study examining COH cycles. Patients were included if they underwent two cycles for unexplained infertility, male factor infertility, or planned oocyte/embryo cryopreservation. The first cycles for all patients implemented a non-letrozole, conventional gonadotropin protocol. Second cycles for the study group included letrozole (2.5-7.5 mg for 5 days) with no medication change to second cycles amongst controls. Our primary objective was to compare oocyte yield. Cohorts were then subdivided by pursuit of oocyte (OC) or embryo (IVF) cryopreservation. Secondary outcome amongst the OC subgroup was oocyte maturation index (metaphase II (MII)/total oocytes). Secondary outcomes amongst the IVF subgroup were normal fertilization rate (2-pronuclear zygotes (2PN)/oocytes exposed to sperm), blastocyst formation rate (blastocysts/2PNs), and embryo ploidy (%euploid and aneuploid). Fifty-four cycles (n = 27) were included in letrozole and 108 cycles (n = 54) were included in control. Oocyte yield was higher in second cycles (p < 0.008) in the letrozole group but similar in second cycles (p = 0.26) amongst controls. Addition of letrozole did not impact MII index (p = 0.90); however, MII index improved in second cycles amongst controls (p < 0.001). Both groups had similar rates of normal fertilization (letrozole: p = 0.52; control: p = 0.61), blast formation (letrozole: p = 0.61; control: p = 0.84), euploid (letrozole: p = 0.29; control: p = 0.47), and aneuploid embryos (letrozole: p = 0.17; control: p = 0.78) between cycles. Despite improved oocyte yield, letrozole did not yield any difference in oocyte maturation or embryo outcomes.

Evaluation of effectiveness of Letrozole in treatment of infertility in women with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disease, characterized by hyperandrogenism, oligomenorrhea, and polycystic ovaries. PCOS is one of the most causes that affect the women of childbearing age, and often leads to infertility. Various managements were proposed for infertile women with PCOS. However, the optimal management option has not been addressed satisfied. Although multiple treatments including weight reduction, clomiphene citrate, metformin, gonadotropins, and ovary cauterization have been reported to treat such condition, the efficacy still has insufficient evidence to support. Objectives: Purpose of this study was to evaluate the effectiveness of Letrozole in treatment of infertility in women with polycystic ovary syndrome. Materials &amp; method: This study was carried out to assess the effectiveness of letrozole and on pregnancy outcomes including the ovulation induction, pregnancy rate, and endometrial thickness in infertile women with polycystic ovarian syndrome (PCOS). Total 106 infertile PCOS patients were recruited and allocated in two groups, Group-L (received letrozole at 2.5 mg twice daily on the 3rd–5th days of menstrual cycle for 5 consecutive days), Group-G 75 U/d−1 gonadotropin through intramuscular injection for 5 days starting from the third day of menstrual cycle). All patient in both arm completed treatment and follow-up. Patients in both groups were treated up to 5 treatment cycles. During follow up, transvaginalultrasonogram (TVS) was performed to see the details of the follicles and the endometrium. Data was processed and analysed with the help of computer program SPSS and Microsoft excel. Quantitative data expressed as mean and standard deviation and qualitative data as frequency and percentage. Comparison was done by tabulation and graphical presentation in the form of tables, pie chart, graphs, bar diagrams, histogram &amp; charts etc. Result: Mean age of the patient was 26.3 ± 5.7 years in group-L and 25.9 ± 6.1 years in group-G. There were no statistical significant differences between the 2 groups regarding age, body weight, height, body mass index (BMI). Present study results showed that patients who received letrozole exert better outcomes in primary endpoint, including ovulation rate (86.7% in group-L &amp; 62.2% in group-G, P =0.004), endometrial thickness (9.3 ± 1.1 mm in group-L &amp; 8.5 ± 1.1 mm in group-G, P = 0.003) and pregnancy rate (64.1% in group-L &amp; 30.1% in group-G, P =0.005). Abortion rate (till the end of 12th week) and multiple pregnancy rate were higher in group-G, but result were non-significant in between groups. Live birth rate in the letrozole group was higher 29(54.7%) than group-G 14(26.4%), the difference was statistically significant (P &lt; .05). Conclusion: Patients who took Letrozole had significantly higher endometrial thickness than other group. Due to the higher pregnancy rate and lower incidence of abortion or multiple pregnancy, letrozole can be an effective for the treatment of anovulatory subfertility of the PCOS patients. Central Medical College Journal Vol 7 No 1 January 2023 Page: 13-19

Induction of abortion in the first trimester of pregnancy using letrozole and misoprostol combination versus misoprostol alone - A comparative observational study

Background: Medical abortion is safer than surgical abortion. Several studies have shown that combination of antiprogesterone drug mifepristone and prostaglandin misoprostol can increase complete abortion rate in medical management of first-trimester miscarriage compared to misoprostol alone. Letrozole, an aromatase inhibitor, has emerged as an alternative to mifepristone for induction of medical abortion as mifepristone is expensive and not registered in many countries. Aims and Objectives: The aim of the present study was to evaluate the safety and efficacy of combined regimen of letrozole and misoprostol in first-trimester medical abortion compared to misoprostol alone. Materials and Methods: It was a comparative observational study conducted at R. G. Kar Medical College, a tertiary care hospital in West Bengal, India. The study population was the antenatal mothers booked at antenatal clinic willing for termination of pregnancy at &lt;12 weeks of gestational age. Participants were allocated, 39 in each group in a non-randomized manner. Patients in one group (Group A) were posted for medical abortion with combination regimen of tablet letrozole (10 mg) once daily for 3 days followed by application of tablet misoprostol 800 mcg sublingually on day 4. In other group (Group B), patients were on misoprostol-only regimen with the application of tablet misoprostol 800 mcg sublingually. Results: Induction-abortion time was significantly less in the letrozole group (11±0.79 h) than the misoprostol group (13.23±0.81 h), P=0.0001. Complete abortion rate was significantly higher in the letrozole group compared to misoprostol group (84.62% and 64.10%, respectively, P=0.03). 15.38% patients in the letrozole group and 35.90% patients in the misoprostol group had excessive vaginal bleeding and the difference was statistically significant, P=0.03. The duration of vaginal bleeding was also significantly less in the letrozole group (2.45±0.29 days) than the misoprostol group (2.82±0.37 days), P&lt;0.0001. Incidence of side-effects was comparable and the severity of side-effects was not significantly different between the groups. Conclusion: Letrozole and misoprostol combination regimen leads to significant increase in complete abortion rate and also significant reduction of the duration of vaginal bleeding, induction-abortion time, and need for surgical intervention when compared to misoprostol regimen.