Leuprolide Research Articles

The effect of antiangiogenic agent aflibercept on surgically induced endometriosis in a rat model.

The aim of the study is to show for the first time how aflibercept affects endometriosis lesions. Surgically induced endometriosis in Wistar albino female rats. Rats with endometriosis were randomly divided into three groups: control (Co), aflibercept (Af), and leuprolide acetate (Le). Then, Af, aflibercept, and Le received leuprolide acetate. The control group was not treated. The weights and changes in intra-abdominal adhesions of the rats before and after treatment were recorded according to the Blauer adhesion score. Blood extracted for sacrifice was analyzed. Endometriotic lesions were evaluated for size, volume, histology, and immunohistochemistry (vascular endothelial growth factor [VEGF] and CD31). Significance level was accepted as p < 0.05. Aflibercept significantly reduced endometrial implant volume (p = 0.002). The explant epithelial histological score showed a significant difference between aflibercept and leuprolide acetate (p = 0.006) and between aflibercept and control groups (p = 0.002). Aflibercept decreased VEGF-H and CD31 expression (p = 0.001) more than leuprolide acetate. Aflibercept improved adhesions (p = 0.006). Aflibercept is more successful than leuprolide acetate in the treatment of endometriosis.

Efficacy and Safety of Radiotherapy Plus Relugolix in Men With Localized or Advanced Prostate Cancer

Combination androgen deprivation therapy (ADT) with radiotherapy is commonly used for patients with localized and advanced prostate cancer. To assess the efficacy and safety of the oral gonadotropin-releasing hormone antagonist relugolix with radiotherapy for treating prostate cancer. This multicenter post hoc analysis of patients with localized and advanced prostate cancer receiving radiotherapy in 2 randomized clinical trials (a phase 2 trial of relugolix vs degarelix, and a subset of the phase 3 HERO trial of relugolix vs leuprolide acetate) included men who were receiving radiotherapy and short-term (24 weeks) ADT (n = 103) from 2014 to 2015 and men receiving radiotherapy and longer-term (48 weeks) ADT (n = 157) from 2017 to 2019. The data were analyzed in November 2022. Patients receiving short-term ADT received relugolix, 120 mg, orally once daily (320-mg loading dose) or degarelix, 80 mg, 4-week depot (240-mg loading dose) for 24 weeks with 12 weeks of follow-up. Patients receiving longer-term ADT received relugolix, 120 mg, orally once daily (360-mg loading dose) or leuprolide acetate injections every 12 weeks for 48 weeks, with up to 90 days of follow-up. Castration rate (testosterone level <50 ng/dL [to convert to nmol/L, multiply by 0.0347) at all scheduled visits between weeks 5 and 25 for patients receiving short-term ADT and weeks 5 and 49 for patients receiving longer-term ADT. Of 260 patients (38 Asian [14.6%], 23 Black or African American [8.8%], 21 Hispanic [8.1%], and 188 White [72.3%] individuals), 164 (63.1%) received relugolix. Relugolix achieved castration rates of 95% (95% CI, 87.1%-99.0%) and 97% (95% CI, 90.6%-99.0%) among patients receiving short-term and longer-term ADT, respectively. Twelve weeks post-short-term relugolix, 34 (52%) achieved testosterone levels to baseline or more than 280 ng/dL. Ninety days post longer-term ADT, mean (SD) testosterone levels were 310.5 (122.4) (106.7) ng/dL (relugolix; n = 15) vs 53.0 ng/dL (leuprolide acetate; n = 8) among the subset assessed for testosterone recovery. Castration resistance-free survival was not statistically different between the relugolix and leuprolide acetate cohorts (hazard ratio, 0.97; 95% CI, 0.35-2.72; P = .62). Adverse events grade 3 or greater for short-term or longer-term relugolix (headache, hypertension, and atrial fibrillation) were uncommon (less than 5%). The results of these 2 randomized clinical trials suggest that relugolix rapidly achieves sustained castration in patients with localized and advanced prostate cancer receiving radiotherapy. No new safety concerns were identified when relugolix was used with radiotherapy.

Outcomes of men with high-risk biochemically recurrent prostate cancer who suspended enzalutamide monotherapy treatment in the phase 3 EMBARK study.

15 Background: In the 3-arm EMBARK trial, enzalutamide (enza) + leuprolide acetate (leuprolide) and enza monotherapy (mono) showed statistically superior and clinically meaningful improvements in metastasis-free survival (MFS) vs placebo + leuprolide (alone) in patients (pts) with high-risk biochemically recurrent (BCR) prostate cancer. Based on serum prostate-specific antigen (PSA) response, treatment (tx) was suspended at week 37 in 304 (85.9%) pts in the enza mono arm and 240 (67.8%) in the leuprolide-alone arm; pts who did not meet suspension criteria continued tx. Outcomes with enza mono vs leuprolide alone by tx suspension status are presented. Methods: EMBARK is a double-blind phase 3 study of pts with high-risk BCR (i.e., PSA doubling time (PSADT) ≤9 months and PSA ≥2 ng/mL above nadir post-radiotherapy [RT] or ≥1 ng/mL after radical prostatectomy [RP] ± postoperative RT). Pts were randomized (1:1) to enza mono (160 mg/day, open-label) or leuprolide alone (22.5 mg every 12 weeks). PSA &lt;0.2 ng/mL at week 36 triggered tx suspension at week 37; tx restarted when PSA reached ≥2 ng/mL or ≥5 ng/mL for pts with or without primary RP, respectively. The proportion of pts with undetectable PSA 2 years after tx suspension was a secondary endpoint. MFS (by blinded independent central review) was analyzed descriptively in each tx arm by suspension status. P-values were nominal. Results: In the suspension group, the 3-year MFS rate (95% CI) was 88.1% (83.8–91.4%) for enza mono and 90.0% (85.3–93.2%) for leuprolide alone; there was no difference in MFS (hazard ratio [HR] 0.840, 95% CI 0.575–1.226; P=0.3659). In the no suspension group, 3-year MFS rates were 88.5% (68.5–96.2%) and 66.9% (55.4–76.1%), respectively; MFS was longer with enza mono vs leuprolide alone (HR 0.340, 95% CI 0.118–0.985; P=0.0378). In the suspension group vs the no suspension group, a greater proportion had received prior RP (enza mono: 78.9 vs 41.9%; leuprolide alone: 78.3 vs 52.2%) or RP and RT (enza mono: 50.7 vs 16.1%; leuprolide alone: 55.0 vs 38.0%), while baseline median PSADT was similar (enza mono: 4.9 vs 5.9 months; leuprolide alone: 5.0 vs 4.8 months). The proportion (95% CI) of pts with undetectable PSA 2 years after tx suspension was 4.6% (2.5–7.6%) for enza mono and 9.6% (6.2–14.0%) for leuprolide alone ( P=0.0326). Conclusions: In pts with high-risk BCR who suspended tx, the tx effect on MFS with enza mono was not different compared with leuprolide alone, though more pts reached tx suspension criteria with enza mono. However, in the no suspension group, enza mono prolonged MFS vs leuprolide alone, though the number of MFS events was limited (n=4). Pts with prior RP were also more likely to reach the PSA threshold for tx suspension. Few pts who suspended tx had undetectable PSA after 2 years, regardless of tx. Clinical trial information: NCT02319837 .

6-month Formulations of Androgen Deprivation Therapy for Advanced Prostate Cancer: Effectiveness and Rationale for Extended Dosing

Background: Luteinizing hormone-releasing hormone (LHRH) agonists and GnRH antagonists are the most widely used androgen deprivation therapy to achieve castration levels of serum testosterone (T). Adherence to dosing schedules is important to avoid treatment failure. A recent analysis found a high non-adherence rate of 84% for LHRH agonist injections based on dosing schedules used in pivotal trials. Method: Narrative review of LHRH therapy and evaluation of which offers optimal efficacy, safety, and practicality. Results: 6-month LHRH agonist formulations require fewer appointments for injections than shorter-acting formulations. Therefore, the frequency of late/missed doses and overall non-adherence may be reduced compared to options requiring frequent dosing (e.g., oral therapies and shorter-acting injections). This flexibility may be preferable for patients who live in multiple locations throughout the year, live long distances from clinics, and/or lack access to reliable transportation. 6-month formulations may also have cost benefits compared to shorter-acting doses. Despite similar levels of T suppression during the labeled dosing period, individual 6-month LHRH agonist formulations appear to have unique profiles, e.g., 6-month subcutaneous leuprolide acetate (LA) results in lower T escape rates compared to 6-month intramuscular LA, if dosing is late. Conclusion: The efficacy and practicality offered by 6-month LHRH formulations suggest these could reduce opportunities for late injections by requiring fewer office visits and provide greater confidence that efficacy will be maintained should there be extenuating circumstances leading to delays in therapy administration, as experienced during the recent pandemic.

Deep reinforcement learning identifies personalized intermittent androgen deprivation therapy for prostate cancer.

The evolution of drug resistance leads to treatment failure and tumor progression. Intermittent androgen deprivation therapy (IADT) helps responsive cancer cells compete with resistant cancer cells in intratumoral competition. However, conventional IADT is population-based, ignoring the heterogeneity of patients and cancer. Additionally, existing IADT relies on pre-determined thresholds of prostate-specific antigen to pause and resume treatment, which is not optimized for individual patients. To address these challenges, we framed a data-driven method in two steps. First, we developed a time-varied, mixed-effect and generative Lotka-Volterra (tM-GLV) model to account for the heterogeneity of the evolution mechanism and the pharmacokinetics of two ADT drugs Cyproterone acetate and Leuprolide acetate for individual patients. Then, we proposed a reinforcement-learning-enabled individualized IADT framework, namely, I$^{2}$ADT, to learn the patient-specific tumor dynamics and derive the optimal drug administration policy. Experiments with clinical trial data demonstrated that the proposed I$^{2}$ADT can significantly prolong the time to progression of prostate cancer patients with reduced cumulative drug dosage. We further validated the efficacy of the proposed methods with a recent pilot clinical trial data. Moreover, the adaptability of I$^{2}$ADT makes it a promising tool for other cancers with the availability of clinical data, where treatment regimens might need to be individualized based on patient characteristics and disease dynamics. Our research elucidates the application of deep reinforcement learning to identify personalized adaptive cancer therapy.

Effects of different treatment methods on clinical efficacy and fertility outcomes of patients with adenomyosis

ObjectiveThis trial was to investigate the effect of different treatment methods on the clinical efficacy and fertility outcome of patients with adenomyosis.MethodsIn total, 140 patients with adenomyosis were evenly and randomly allocated into group A (laparoscopic surgery), group B (laparoscopic surgery combined with gonadotropin-releasing hormone analogs [GnRH-a]), group C (ultrasound-guided percutaneous radiofrequency ablation), and group D (ultrasound-guided percutaneous radiofrequency ablation combined with GnRH-a). On the 3rd day after surgery, patients in group B and group D were subcutaneously injected with GnRH-a (Leuprorelin Acetate SR for Injection) at 3.75 mg/time, once every 4 weeks, for a total of 3 months. The therapeutic effects of the 4 groups were compared, including menstrual volume, dysmenorrhea score, uterine volume, clinical efficacy, luteinizing hormone (LH), estradiol (E2), and follicle-stimulating hormone (FSH) levels, CA125 levels, recurrence, pregnancy status, and pregnancy outcomes.ResultsAfter treatment, the menstrual volume of 4 groups was lowered, dysmenorrhea, Visual Analog Scale (VAS) score, LH, FSH, E2, and CA125 levels were reduced, and uterine volume was decreased. The menstrual volume, VAS score, levels of LH, FSH, E2, and CA125, and uterine volume were reduced in groups B, C, and D compared with group A, and the decrease was more significant in group D. The total effective rate of group D was 100.00%, which was higher than that of group A (71.43%), group B (80.00%), and group C (82.86%). After one year of drug withdrawal, the recurrence of hypermenorrhea, dysmenorrhea, uterine enlargement, and excessive CA125 in group D was significantly lower than that in groups A, B and C, and the recurrence in groups B and C was significantly lower than that in group A (P < 0.05). Compared with groups A, B, and C, group D had a higher pregnancy rate, natural pregnancy rate, and lower in vitro fertilization-embryo transfer rate (P < 0.05), but showed no significant difference in pregnancy outcomes.ConclusionUltrasound-guided percutaneous radiofrequency ablation combined with Leuprorelin Acetate is effective in the treatment of adenomyosis, which can effectively relieve clinical symptoms, protect postoperative ovarian function, reduce recurrence rate, alleviate pain, and improve quality of life.

Systemic therapies for salivary gland carcinomas: an overview of published clinical trials.

There is no consensus about effective systemic therapy for salivary gland carcinomas (sgcs). Our aim was summarized the clinical trials assessing the systemic therapies (ST) on sgcs. Electronic searches were carried out through MEDLINE/pubmed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases, and gray literature. Seventeen different drugs were evaluated, and the most frequent histological subtype was adenoid cystic carcinoma (n=195, 45.5%). Stable disease, observed in 11 ST, achieved the highest rate in adenoid cystic carcinoma treated with sunitinib. The highest complete (11.1%) and partial response (30.5%) rates were seen in androgen receptor-positive tumors treated with leuprorelin acetate. Despite all the advances in this field, there is yet no effective evidence-based regimen of ST, with all the clinical trials identified showing low rates of complete and partial responses. Further, translational studies are urgently required to characterize molecular targets and effective ST.

Testosterone Recovery for Relugolix Versus Leuprolide in Men with Advanced Prostate Cancer: Results from the Phase 3 HERO Study

BackgroundIn the HERO study, relugolix demonstrated sustained testosterone suppression superior to that of leuprolide acetate (97% vs 89%; difference 7.9% [95% confidence interval, 4.1–12%; p < 0.001]). ObjectiveTo analyze testosterone recovery in a prespecified subset of men from the HERO study not indicated to continue androgen deprivation therapy. Design, setting, and participantsMen (N = 934) were randomized (2:1) to receive relugolix 120 mg orally daily or leuprolide acetate injections every 12 wk for 48 wk. Outcome measurements and statistical analysisTestosterone recovery was assessed in 184 men who completed 48 wk of treatment. During the 90-d recovery period, assessments included time to testosterone recovery (>280 ng/dl; ≥80% of baseline testosterone), serum levels of prostate-specific antigen and pituitary hormones, and adverse events. Results and limitationsThe cumulative incidence rate of testosterone recovery to >280 ng/dl at 90 d following drug discontinuation was significantly higher in the relugolix cohort (n = 137) than in the leuprolide acetate cohort (n = 47; 54% vs 3.2%; nominal p = 0.002). The median time to testosterone recovery was faster following relugolix treatment than with leuprolide acetate treatment (86.0 d vs 112.0 d). Compared with leuprolide acetate, more men treated with relugolix achieved ≥80% of baseline testosterone levels (39% vs 2.1%). Men ≤65 yr and those with baseline testosterone greater than the median had a higher incident rate of testosterone recovery. Adverse events were generally similar between treatment groups. One limitation is the short testosterone recovery follow-up period. ConclusionsOral relugolix had faster and more complete recovery of testosterone to normal levels after treatment discontinuation than leuprolide acetate in a subset of men from the HERO study. The clinical implications of a faster testosterone recovery with relugolix may be significant for men being treated with androgen deprivation therapy and influence treatment decisions. Patient summaryThe male hormone testosterone is reduced during androgen deprivation therapy for prostate cancer. Reduced testosterone levels cause side effects, impacting patient quality of life. When treatment is stopped, the side effects lessen over time as the levels of testosterone come back to pretreatment range (testosterone recovery). In this study, we found that the time to testosterone recovery was faster with relugolix than with leuprolide acetate.

A Computational Exploration: Docking Analysis of Compounds from Foeniculum vulgare as Potential Aromatase Inhibitors for Endometriosis Candidate Therapy

Aromatase inhibitors (AI) have controlling symptoms and size of endometriotic implants, making them a promising second-line therapy for endometriosis treatment.pretreatment with letrozole, an AI, combined with leuprolide acetate and resveratrol has been found to improve in vitro fertilization (IVF) outcomes in women mild endometriosis.in this study we screening and analysis of ten phenolic compounds from Foeniculum vulgare using molecular docking with Mcole server.from this results showed that three phenolic trans resveratrol (TR), caempherol coumaril (CC) have low gibbs energy compare with resveratrol (R). The binding modalities of compound TR and compound R were hydrogen-bonding between the hydroxyl and oxygen atom and Thr310 and hydrophobic interactions with Phe187, Ala272, Asp275, Ala189.and compound R exhibited cation-π interactions between Val336 as binding activity from aromatase.aromatase inhibitors and resveratrolfrom fennel lies in the potential of resveratrol to modulate hormonal pathways, including aromatase inhibition.

Analysis of hippocampus in rats with acute brain ischemia-reperfusion injury treated with leuprolide acetate, an agonist of GnRH.

The hippocampus is highly vulnerable to damage in the brain ischemia-reperfusion injury model. Leuprolide acetate has been shown to promote neurological recovery after injury in various regions of the central nervous system. The objective of this study was to assess the histology of the hippocampus and the expression of neuronal recovery markers, specifically the 200 kDa neurofilaments and the myelin basic protein, in rats with brain ischemia-reperfusion injury treated with leuprolide acetate. The rats were divided into three groups: Sham, ischemia-reperfusion with saline solution, and ischemia-reperfusion treated with leuprolide acetate. Coronal brain slices were obtained and stained with hematoxylin-eosin. The histological analysis involved quantifying the number of neurons in the hippocampal regions CA1, CA3 and DG. The myelin basic protein and neurofilaments were quantified using western blot. The number of neurons in CA1 and DG was significantly higher in the leuprolide acetate group compared to the untreated group. Additionally, the expression of neurofilament and myelin basic protein markers was significantly increased in rats treated with leuprolide acetate compared to the untreated rats. Leuprolide acetate promotes the recovery of hippocampal neurons in an acute brain ischemia-reperfusion injury model. These findings suggest that leuprolide acetate could be a potential therapeutic intervention for reversing damage in hippocampal ischemic lesions.

#100 : Can the Dual Trigger be Effective in Improving Oocyte Maturation and Embryo Quality Compared to the HCG Trigger or the GnRH-a Trigger?

Background and Aims: HCG was the standard trigger of final oocyte maturation in IVF cycles. An alternative trigger with gonadotropin releasing hormone agonist (GnRH-a) was effective in reducing OHSS. But GnRH-a trigger induced increased luteal insufficiency and cycle cancellation. A dual trigger (HCG with GnRH-a) was introduced to reduce OHSS, luteal insufficiency and cycle cancellation. This study was designed to compare the effect of dual trigger on final oocyte maturation n embryo quality with conventional HCG trigger and GnRH-a trigger. Method: We conducted this retrospective cohort study of patients who underwent IVF antagonist cycles from Jan. 2020 to Dec. 2022. Patients undergoing their oocyte retrieval 36 hours after trigger with only HCG 10,000 units, or only leuprolide acetate 40 units, or a dual trigger of HCG 5000 units with leuprolide acetate 40 units. Male factor infertility and oocyte donor cycle were excluded. The main outcomes were retrieved mature oocyte rate and fertilization rate. Secondary outcomes include implantation rate and pregnancy rate. Results: Total 3266 patients were included. Dual trigger was in 2279, GnRH-a in 282 and HCG in 705 cycles. Patients using GnRH-a were younger (33.7± 4.0 years) compared to those receiving dual trigger (37.8±2.3 years) and HCG only (37.2±3.2 years) (p&lt;0.01). Because GnRH-a groups were younger, despite low total gonadotropin dose, the larger number of oocytes were retrieved. Dual trigger resulted in no difference in mature oocyte ratio, compared to HCG trigger and GnRH-a trigger (63.0%, 58.3%, 62.8% p: 0.074). Analysis did not show any statistical differences in fertilization rate between the types of triggering methods. Cycel cancellation due to no oocyte recovered from multiple follicles aspirated was shown only in GnRH-a cycle (6 cases. 2.1%). Conclusion: Compared to HCG trigger and GnRH-a trigger, the dual trigger showed no difference in mature oocyte rate and fertilization rate. To reduce OHSS and cycle cancellations, dual trigger could be considered the standard care in IVF without decreasing oocyte quality.

#334 : Tackling Complex Infertility Patient: A Case Report

Background: Infertility is a common problem presented in women with endometriosis especially as it is often associated with poor quality of life. Therefore, surgical Intervention has been considered as the first-line treatment of choice. On the other hand, surgery itself has detrimental effects on ovarian reserve and is associated with ovarian failure. Case Report: We present a case of a 39-year-old woman para 1 with multiple myoma uteri, bilateral endometriosis cyst, left hydrosalpinx, deep infiltrating endometriosis (DIE), and adhesion (Figure 1). She comes with a history of heavy abnormal uterine bleeding, lower abdominal pain, and unable to conceive 11 years after their first child despite adequate unprotected intercourse. The patient was anemic (Hemoglobin 7.30 g/dL) with low Anti Mullerian Hormone (AMH; 0.26 mg/ml). We decided to perform laparoscopic uterine myoma with multiple bilateral endometrial cysts, left salpingectomy, and adhesiolysis (Figure 2). Patient then underwent an ultra-long protocol with three cycles of leuprolide acetate 3.75 mg. Ovum pick-up was performed and we retrieved five M-II oocytes and from embryo culture, two embryos with good and moderate quality were collected for vitrification procedure. Prior frozen embryo transfer, extra acetylsalicylic acid 80 mg once a day and estradiol valerate 4 mg thrice a day were given for 18 days. The patient soon became pregnant after a few weeks of embryo transfer with βHCG of 185 mIU/m. Conclusion: Individualized treatment plans based on the patient’s symptoms and respective reproductive goals are important points to be discussed in endometriosis-associated infertility patients. Surgical intervention before IVF/ICSI is deemed as necessary to preserve ovarian reserve and to restore normal anatomy to increase the success rate of embryo implantation.

Effects of Combined Laparoscopic Cystectomy and Leuprolide Acetate Therapy on Anti-Mullerian Hormone Level and Antral Follicle Count Profile in Endometriosis

Objective: This study examines the effectiveness of combined laparoscopic cystectomy and leuprolide acetate therapy on AMH level and AFC profile in endometriosis. Method: This study is a randomized controlled clinical trial with open label form. The subjects were divided into control and therapy groups, with the therapy group receiving leuprolide acetate injection following laparoscopic cystectomy. In both groups, the AMH levels and AFC were examined prior to the surgery and six weeks after before they were compared. Results: There were significant pre-post differences of AMH levels(p = 0.000) and AFC (p = 0.000) in the therapy group but not in the control group. In the therapy group, the mean increases of AMH level and AFC were 0.94 (95% CI: 0.63-1.25) and 9.53 (95% CI: 6.83-12.24), respectively. Linear regression model found that AFC level prior to intervention was a significant predictor of endometriosis ASRM grade (p = 0.001) with an R-value of 0.633, suggesting strong correlation. Conclusion: The combined therapy of laparoscopic cystectomy and leuprolide acetate injection for endometriosis provided better outcome concerning ovarian reserve, as opposed to the therapy with laparoscopic cystectomy alone.

Effects of Combined Laparoscopic Cystectomy and Leuprolide Acetate Therapy on Anti-Mullerian Hormone Level and Antral Follicle Count Profile in Endometriosis

Objective: This study examines the effectiveness of combined laparoscopic cystectomy and leuprolide acetate therapy on AMH level and AFC profile in endometriosis.Method: This study is a randomized controlled clinical trial with open label form. The subjects were divided into control and therapy groups, with the therapy group receiving leuprolide acetate injection following laparoscopic cystectomy. In both groups, the AMH levels and AFC were examined prior to the surgery and six weeks after before they were compared.Results: There were significant pre-post differences of AMH levels(p = 0.000) and AFC (p = 0.000) in the therapy group but not in the control group. In the therapy group, the mean increases of AMH level and AFC were 0.94 (95% CI: 0.63-1.25) and 9.53 (95% CI: 6.83-12.24), respectively. Linear regression model found that AFC level prior to intervention was a significant predictor of endometriosis ASRM grade (p = 0.001) with an R-value of 0.633, suggesting strong correlation.Conclusion: The combined therapy of laparoscopic cystectomy and leuprolide acetate injection for endometriosis provided better outcome concerning ovarian reserve, as opposed to the therapy with laparoscopic cystectomy alone. Peran Kombinasi Laparoskopi Kistektomi dan Terapi Leuprolide Asetat Terhadap Kadar Hormon Anti-Mullerian dan Profil Jumlah Folikel Antral pada Penderita EndometriosisAbstrakTujuan:Studi ini bertujuan menguji keefektifan kombinasi kistektomi laparoskopi dan terapi leuprolide acetate terhadap kadar AMH dan profil AFC pasien endometriosis.Metode: Penelitian ini merupakan uji klinis terkontrol acak dengan bentuk open label. Subjek dibagi menjadi kelompok kontrol dan terapi, dengan kelompok terapi menerima injeksi leuprolide acetate setelah kistektomi laparoskopi. Pada kedua kelompok, kadar AMH dan AFC diperiksa sebelum pembedahan dan enam minggu setelahnya sebelum kemudian dibandingkan.Hasil: Terdapat perbedaan bermakna kadar AMH (p = 0,000) dan AFC (p = 0,000) sebelum dan sesudah pada kelompok terapi tetapi tidak pada kelompok kontrol. Pada kelompok terapi, rata-rata peningkatan kadar AMH dan AFC adalah masing-masing 0,94 (95% CI: 0,63-1,25) dan 9,53 (95% CI: 6,83-12,24). Model regresi linier menemukan bahwa kadar AFC sebelum intervensi merupakan prediktor signifikan derajat endometriosis sesuai ASRM (p = 0,001) dengan nilai R sebesar 0,633 yang menunjukkan korelasi yang kuat.Kesimpulan: Terapi kombinasi kistektomi laparoskopi dan injeksi leuprolide acetate untuk endometriosis memberikan hasil yang lebih baik terhadap cadangan ovarium, dibandingkan dengan terapi dengan kistektomi laparoskopi saja.Kata kunci: endometriosis; leuprolide acetate; kistektomi; hormon anti-mullerian; jumlah folikel antral

Efficacy and safety of leuprorelin 3-month depot (11.25 mg) for idiopathic central precocious puberty treatment of Chinese girls: a single-center retrospective study.

This study aimed to evaluate the efficacy and safety of 3-month leuprorelin acetate (3-month LA, 11.25 mg) for the treatment of idiopathic central precocious puberty (ICPP) in Chinese girls. We conducted a single-center retrospective study in China on 28 girls with ICPP who received at least one year of 3-month LA treatment. Data from anthropometry, biochemistry, bone age (BA), and pelvic ultrasonography were assessed before and every 6months during medication. At CPP diagnosis, the mean chronological age (CA) was 7.8±0.8 years, with bone age advancement (BA-CA) of 1.5±0.8 years. After treatment initiation, growth velocity decreased significantly from 8.5±1.6 cm/year to 5.8±1.1 cm/year at month 12 (p<0.001). GnRH-stimulated peak LH≤3IU/L, the primary efficacy criterion, was observed in 27 out of 28 (96.4 %) children at month 3. Basal estradiol <20 pg/mL was achieved by all 28 girls (100 %) at month 6 and remained stable at month 12. Basal follicle-stimulating hormone (FSH) decreased from 4.1±3.5 to 1.7±0.9 (p<0.001), and basal LH was also significantly reduced from 3.3±6.5 to 0.7±0.8 (p=0.035) at month 12. The mean predicted adult height (PAH) at treatment initiation was 152.7±5.8 cm, it increased significantly to 157.5±5.5 cm (p=0.007) after one-year treatment. Pubertal development was slowed in most patients, and in some cases, it was even reversed. Only one patient (3.6 %) reported local intolerance. Three-month leuprorelin acetate is a safe and effective treatment for suppressing the pituitary-gonadal axis and restoring impaired adult height in Chinese girls.

Novel Approaches to Possible Targeted Therapies and Prophylaxis of Uterine Fibroids.

Uterine leiomyomas are the most common benign tumors in women of childbearing age. They may lead to problems of conception or complications during the gestational period. The methods of treatment include surgical (myomectomy and hysterectomy, embolization of arteries) and therapeutic treatment (ulipristal acetate, leuprolide acetate, cetrorelix, goserelin, mifepristone). Both approaches are efficient but incompatible with pregnancy planning. Therefore, there is a call for medical practice to develop therapeutical means of preventing leiomyoma onset in patients planning on becoming pregnant. Based on the analysis of GWAS data on the search for mononucleotide polymorphisms associated with the risk of leiomyoma, in meta-transcriptomic and meta-methylomic studies, target proteins have been proposed. Prospective therapeutic treatments of leiomyoma may be based on chemical compounds, humanized recombinant antibodies, vaccines based on markers of the uterine leiomyoma cells that are absent in the adult organism, or DNA and RNA preparations. Three different nosological forms of the disease associated with driver mutations in the MED12, HMGA2, and FH genes should be considered when developing or prescribing drugs. For example, synthetic inhibitors and vaccines based on matrix metalloproteinases MMP11 and MMP16 are expected to be effective only for the prevention of the occurrence of MED12-dependent nodules.

The Role of Reproductive Surgeons/Surgery has Got Rekindled with Plateauing of IVF Results and Advances in Technology: A Comprehensive Narrative Review

Earlier we have reviewed the role of surgery in need for fibroids removal prior to IVF in improving success rates, management of inoperable recurrent endometrioma presenting as severe incapacitating pain following leuprolide acetate depot by aspiration, recurring again at 2 years subsequently for sclerosing therapy presented as a case report updated advances in classification along with re¬productive surgeries in mullerian anomalies. Updated management of oncofertility-does the use of vsels appear practical in the near future in human malignancies replacing cortical tissue and testicular tissue, autologous Platelet Rich Plasma (PRP) probability of it becoming a revolutionary therapy in the field of gynaecology and reproductive endocrinology and infertility, role of surgery in endometriomas and endometriosis, adenomyomas, tubal surgery. Here we have tried to outline how prior to the invention of In Vitro Fertilization (IVF), reproductive surgeries which were believed to be fertility sparing were properly acknowledged, role of reproductive surgeons became obsolete. With the plateauing of IVF result interest has got rekindled with considerable advantages of reproductive surgeries is this field. Additionally, newer instrumentation as well as along with surgical procedure has evoked and made it attractivefor reproductive surgeons for improvementof their expertise with regards to conservation of future fertility as well as train future Reproductive Endocrinology and Infertility specialist (REI) in view of solidifying this field of yielding pregnancies to maximum of infertile cases even in patients having cancer surgeries or earlier cryopreservation of oocytes in say patients with turners syndrome etc.

Development of a depot formulation with an in situ non-lamellar liquid crystal-forming system with phospholipids

Non-lamellar liquid crystal (NLLC) structures have gained increasing attention for the controlled release of entrapped drugs. In the present study, an in situ NLLC structure-forming depot formulation through contact with water was developed using a ternary mixture system of soya phosphatidyl choline (SPC), 1, 2-dioleoyl-sn-glycero-3-phosphoglycerol sodium salt (DOPG), and sorbitan trioleate (Span 85), and the long-term release of an entrapped model drug, leuprolide acetate (LA), was investigated using evaluation of in vitro release and in vivo blood concentration–time profiles. Polarized images and small angle X-ray scattering analysis were used to confirm the presence of NLLC structures by contacting the prepared formulation with water. In addition, LA release and blood concentration–time profiles were investigated using in vitro and in vivo experiments, respectively. In situ NLLC constructed formulations by contacting water were achieved using a ternary mixture of SPC, DOPG, and Span 85. In particular, negative curvature was increased with an increase in the amount of Span 85 in the formulation, and an Fd3m structure was obtained with a sustained release of LA. A maintained blood concentration of LA over 21 days was confirmed by subcutaneous (s.c.) administration of the formulation. No retained administered formulation at the injection site was confirmed 28 days after administration without any signs of irritation, inflammation, or other apparent toxicity confirmed by visual observation. This result may be helpful for the development of a lipid-based formulation of peptides and proteins with sustained drug release.

Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in Men with High-Risk Biochemically Recurrent Prostate Cancer and Prior Radiotherapy: EMBARK Subgroup Analysis

Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in Men with High-Risk Biochemically Recurrent Prostate Cancer and Prior Radiotherapy: EMBARK Subgroup Analysis

SAT336 A Successful Ovulation Induction And Embryo Generation In A Woman With P450-oxidoreductase Deficiency From Mutation G539R, Which Preferentially Impairs 17,20-lyase Activity

Abstract Disclosure: S. Charoensri: None. M. Thakur: None. R.J. Auchus: None. Introduction: Cytochrome P450 oxidoreductase (POR) deficiency is an autosomal recessive disorder causing decreased activity of several P450 enzymes, including CYP21A2, CYP17A1, and CYP19A1 that are essential for steroidogenesis in the adrenals and gonads. Female POR deficiency patients are typically manifested with genital ambiguity, abnormal menstruation, and infertility. Very few pregnancies have been documented from these patients. Case presentation: During an evaluation for infertility, a 35-year-old woman with late menarche, irregular cycles, and unruptured ovarian follicles was diagnosed with POR deficiency due to compound heterozygous pathogenic variant c.1615G&amp;gt;C (G539R) and a large deletion c.1669+5_1669+32del in the POR gene. Because mutation G539R preferentially impairs the 17,20-lyase activity of CYP17A1, she underwent in-vitro fertilization (IVF) with the protocol that has been used successfully to achieve pregnancy in incomplete 17-hydroxylase deficiency. Oral dexamethasone of 0.5 mg/day was given to suppress the adrenal-derived progesterone. After one menstrual cycle induced with estradiol and progesterone priming, leuprolide acetate was used to down-regulate endogenous gonadotropin secretion, then the oocyte maturation was induced with recombinant follicle-stimulating hormone (rFSH) and highly purified menotrophin. In the first cycle, 6 eggs were retrieved, 2 that were mature and fertilized with intracytoplasmic sperm injection (ICSI); however, none advanced to the blastocyst stage. She underwent the same protocol in a second IVF cycle with higher rFSH dosing. Despite increasing dexamethasone to 1.5 mg/day, progesterone rose to 4.9 ng/mL, while estradiol peaked at 120 pg/mL, consistent with progesterone accumulation in the developing ovarian follicles due to POR deficiency. From 6 eggs retrieved, 5 eggs were mature and all fertilized, and 3 developed past day 3. On day 6, one embryo (grading 5BB) was biopsied for preimplantation genetic testing and frozen. The second phase of the treatment plan is to lower adrenal-derived progesterone with a combination of hydrocortisone and prednisolone, prepare the endometrium with estradiol followed by progesterone, and perform embryo transfer. Conclusions: Very few examples of pregnancy in women with POR deficiency have been reported, and we describe the first example of successful ovulation induction and embryo generation in a woman with POR deficiency caused by the G539R mutation, which preferentially impairs 17,20-lyase activity. The complex array of steroid excess and deficiencies, from both adrenal and ovarian origin, must be systematically managed during assisted reproduction treatment for these women. Presentation: Saturday, June 17, 2023