Hormone Antagonist Research Articles

Dual trigger versus human chorionic gonadotropin trigger for blastocyst quality and cumulative live birth.

To evaluate the difference in the number of euploid blastocysts and cumulative live birth rate (LBR) between dual and human chorionic gonadotropin (hCG) triggers in poor and normal ovarian responders undergoing preimplantation genetic testing (PGT) cycles. This retrospective cohort study was enrolled from July 2018 to December 2021 and followed up until June 2024 at a single reproductive medical center. Overall, 1040 in vitro fertilization (IVF)-PGT and 784 frozen-thawed embryo transfer (FET) cycles were assessed. Dual (triptorelin acetate 0.2 mg and recombinant hCG [rhCG] 250 µg) or hCG (rhCG 250 µg) trigger was used for oocyte maturation in the gonadotropin-releasing hormone antagonist protocol and PGT cycles. We assessed the embryo outcomes and FET cumulative pregnancy outcomes. The number of oocytes retrieved (10.17 ± 5.22 vs 10.27 ± 5.14, P = 0.789), MII oocytes (8.24 ± 4.26 vs 8.28 ± 4.05, P = 0.888), blastocysts (2.16 ± 1.50 vs 2.12 ± 1.49, P = 0.729), euploid blastocysts (1.06 ± 1.14 vs 1.09 ± 1.23, P = 0.726), and the rate of cumulative LBR (24.9% vs 24.9%, P = 1.000) in the dual trigger group were comparable with those in the hCG group. The trigger method was not correlated with higher LBR based on logistic regression analysis (odds ratio[OR] = 1.040 [0.778-1.392], P = 0.790). For poor and normal ovarian responders, the dual trigger, compared with the hCG trigger, did not improve the PGT embryo outcomes and FET cumulative pregnancy outcomes.

Efficacy and safety of neoadjuvant chemohormonal therapy for high-risk prostate cancer treated with robot-assisted laparoscopic radical prostatectomy: a propensity score-matched analysis (the MSUG94 group).

The optimal neoadjuvant regimen before radical prostatectomy (RP) in patients with high-risk (HR) prostate cancer (PCa) remains to be determined. This retrospective multicenter cohort study assessed the effectiveness and safety of neoadjuvant chemohormonal therapy (NCHT) in patients with HR-PCa undergoing robot-assisted laparoscopic radical prostatectomy (RALP). We reviewed the datasets of 1023 subjects who underwent RALP at nine Japanese facilities between September 2012 and October 2023. The enrolled patients were divided into two groups using propensity score matching: a RALP-alone group and those who underwent NCHT followed by RALP (NCHT group). The NCHT regimen consisted of a luteinizing hormone-releasing hormone antagonist and tegafur-uracil for at least 3months before RALP. The primary endpoint was biochemical recurrence (BCR) after RALP. The secondary endpoint was the surgical specimen pathology findings. Propensity score matching identified 139 individuals for each group. Median follow-up was 18.2months. During follow-up, BCR was observed in 41 patients (29.5%) in the RALP-alone group and 22 patients (15.8%) in the NCHT group (p = 0.010). Pathological results showed significantly more organ-confined PCa and significantly fewer positive surgical margins or lymphovascular invasion in the NCHT group than in the RALP-alone group. The 2-yr biochemical recurrence-free survival (BRFS) was 72.7% and 74.7% in the RALP-alone and NCHT groups, respectively (p = 0.086). Two patients (1.4%) experienced grade 3 liver disorder as an NCHT-related adverse event. The results suggest that NCHT can safely treat HR-PCa and may reduce the incidence of BCR when combined with RALP.

Optimizing in vitro fertilization outcomes: Long-acting gonadotrophin releasing hormone agonist versus gonadotrophin releasing hormone antagonist protocol in Poseidon groups 3 and 4

Optimizing in vitro fertilization outcomes: Long-acting gonadotrophin releasing hormone agonist versus gonadotrophin releasing hormone antagonist protocol in Poseidon groups 3 and 4

Astaxanthin improves assisted reproductive technology outcomes in poor ovarian responders through alleviating oxidative stress, inflammation, and apoptosis: a randomized clinical trial

BackgroundPoor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR.MethodsIn this randomized, triple-blind, placebo-controlled trial, 60 infertile POR patients from POSEIDON Group 4 (the poorest prognosis category, age > 35 and poor ovarian reserve (anti-müllerian hormone < 1.2 ng/ml or antral follicle count < 5) undergoing intracytoplasmic sperm injection were enrolled. Patients were assigned to receive either 12 mg/day AST or placebo for eight weeks. All patients underwent a gonadotropin-releasing hormone antagonist regimen for COS. ART outcomes were compared between groups. Blood serum and follicular fluid (FF) were analyzed for OS markers (superoxide dismutase [SOD], total antioxidant capacity [TAC], and malondialdehyde [MDA]), and pro-inflammatory cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) via enzyme-linked immunosorbent assay kits, and cell-free DNA [cfDNA] (apoptotic marker) via ALU quantitative polymerase chain reaction.ResultsAfter the intervention, the AST group exhibited a significant elevation in serum (P = 0.013) and TAC (P = 0.030), accompanied by a significant reduction in serum MDA (P = 0.005). No significant differences between AST and placebo groups were observed in OS markers in FF. AST group showed significant reductions in the serum IL-6 (P < 0.001), IL-8 (P = 0.001), and VEGF (P = 0.002) levels following AST therapy. In the AST group, FF levels of IL-6 (P = 0 < 001), IL-8 (P = 0.036), VEGF (P = 0.006), and cfDNA (P < 0.001) were significantly lower than in the placebo group. Between-group comparisons showed significant differences in the alterations of serum SOD (P = 0.027), IL-6 (P < 0.001), and IL-8 (P = 0.035) levels between AST and placebo groups. The AST group showed significant increases in the number of retrieved oocytes (P = 0.003), MII oocytes (P = 0.004), frozen embryos (P = 0.037), and high-quality embryos (P = 0.014) compared to the placebo group.ConclusionAST shows promise as a COS adjuvant therapy, potentially enhancing some ART outcomes in POR through alleviating OS, inflammation, and apoptosis.Trial registrationClinical trial registration number: IRCT20230223057510N1, URL: https://irct.behdasht.gov.ir/trial/68870, registration date: 2023 March 16.Graphical

Regression and growth rates in androgen deprivation therapy for advanced castration-sensitive prostate cancer.

No study has compared cancer regression (d) and growth (g) rates in patients with advanced castration-sensitive prostate cancer (CSPC) treated with androgen deprivation therapy. The comparison of d and g rates provides insight into the differential impact of ADT regimens on tumor dynamics, potentially guiding more personalized treatment strategies. Therefore, we aimed to estimate these rates and evaluate their impact on survival outcomes. Sequential prostate-specific antigen (PSA) data was obtained from the KYUCOG-1401 trial including patients with advanced CSPC randomized to gonadotropin-releasing hormone (GnRH) antagonist (group A) and GnRH agonist plus bicalutamide (group B). d and g rates were estimated by applying mathematical models and were compared in subgroups. PSA-progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) were compared by lower and higher than the median of these rates. Patients with higher PSA and higher extent of disease score at enrollment presented higher d rates (0.03965 vs. 0.03546, p = 0.0006) and (0.03947 vs. 0.03587, p = 0.0113) for groups A and B, respectively. The median d rate was lower for group A than group B (0.03306 vs. 0.039965, respectively [p = 0.0002]). The median g rate was higher for group A than group B (0.00016 vs. 0.00002, respectively [p = 0.0014]). The g rate, but not the d rate discriminated PSA-PFS, rPFS, and OS. Our results suggest that GnRH agonist plus bicalutamide reduced PSA level faster and suppressed PSA rising longer than GnRH antagonist. Moreover, measuring the g rate can predict PSA-PFS, rPFS, and OS in patients with advanced CPSC treated with androgen deprivation therapy. These findings suggest that incorporating g rate measurements into clinical practice could improve prognostic accuracy and guide treatment decisions in advanced CSPC.

Clinical evaluation and outcome in patients with heart failure receiving chemotherapy with different anti-cancer agents

Abstract Background Over the last few decades, advances in cancer therapy have prolonged the life expectancies of patients diagnosed with malignancies. Although traditional cytotoxic chemotherapy, molecularly targeted therapy, and immunotherapy have improved survival rates, off-target adverse effects such as complications of the cardiovascular system require attention. The optimal strategy for modern chemotherapy should be based on a comprehensive approach for patients with cancer and cardiovascular diseases. Therefore, cardio-oncology has received increasing attention owing to the cardiotoxic effects of anti-cancer therapies. Purpose To assess the clinical characteristics and outcomes of patients with heart failure (HF) who received chemotherapy compared with those of a matched cohort with HF who did not receive chemotherapy, using real-world HF data. Methods This study used the Diagnosis Procedure Combination database of the Japanese Registry of All Cardiac and Vascular Disease. We identified 1,328,113 patients hospitalized for HF between April 2012 and March 2021. We excluded 14,043 patients with unknown outcomes, non-emergency admissions, and unknown chemotherapy data. The primary endpoint was readmission. Thus, our study included 5,774 patients who received chemotherapy and 39,412 patients who did not. The propensity score (PS) was estimated using a logistic regression model, with chemotherapy as the dependent variable, and clinically score-matched analysis of 11,532 patients with HF with or without chemotherapy. Results Colon, lung, breast, and prostate cancers accounted for &amp;gt; 60% of all cancer types. After PS matching, 62.5% and 19.5% of patients with HF had prostate and breast cancer, respectively. After PS matching, readmission was more frequently observed in patients undergoing chemotherapy than those not undergoing chemotherapy (odds ratio [OR], 1.26; 95% confidence interval [CI] 1.17–1.36, p&amp;lt;0.0001). Treatment with genomic epidermal growth factor receptor tyrosine kinase inhibitors (OR, 1.69; 95% CI 1.39–2.07), taxane (OR, 2.95; 95% CI 2.11–4.12), anthracyclines (OR, 1.86; 95% CI 1.19–2.90), and fluorouracil agents (OR, 1.65; 95% CI 1.18–2.30) resulted in a significant risk of readmission. Moreover, patients treated with endocrine therapy before hospitalization had significantly higher readmission rates than the matched patients who did not receive chemotherapy (aromatase inhibitors: OR, 1.40; 95% CI 1.19–1.65: anti-androgens: OR, 1.39; 95% CI 1.27–1.52: luteinizing hormone-releasing hormone agonists: OR, 1.18; 95% CI 1.08–1.30 and gonadotropin-releasing hormone antagonists: OR, 2.17; 95% CI 1.68–2.79). Conclusions Medical providers need to monitor and follow-up patients with HF, depending on the characteristics of the anticancer agents and types of cancer. Furthermore, close collaboration among oncologists, cardiologists, and healthcare professionals will ensure the delivery of optimal care for patients with HF undergoing chemotherapy.

The Effect of Androgen Deprivation Therapy on the Cardiovascular System in Advanced Prostate Cancer

Androgen deprivation therapy (ADT) is a mainstay treatment for metastatic prostate cancer, improving progression-free survival. ADT suppresses the production of testosterone and reduces circulating levels of the hormone. Luteinizing hormone-releasing hormone (LH-RH) agonists are the most commonly used ADT modality. They can be given alone or in combination with androgen synthesis inhibitors or androgen receptor antagonists. An estimated 40% of prostate cancer patients will receive ADT as part of their therapy during their lifetime. However, ADT has numerous adverse effects, including an increased cardiovascular risk that impacts quality of life. Relugolix is an alternative form of ADT. It is the only oral gonadotropin-releasing hormone antagonist, circumventing injection site reactions, making it easier for patients to take, and thus increasing compliance. Testosterone suppression with relugolix is excellent and testosterone recovery after discontinuation is rapid. This paper reviews the ADT and anti-androgen treatment options for men with prostate cancer and the cardiovascular effects of these therapies. There is accumulating evidence that cardiovascular risk with relugolix is lower than with other ADT medications and also lower than with androgen synthesis inhibitors and androgen receptor antagonists. This paper provides insight into the use of different ADT regimens based on the cardiovascular status and circumstances. It explores strategies to mitigate negative cardiovascular consequences and highlights the need for further study.

A novel approach for the treatment of AML, through GHRH antagonism: MIA-602.

Acute myeloid leukemia (AML) is the most aggressive and prevalent form of leukemia in adults. The gold-standard intervention revolves around the use of chemotherapy, and in some cases hematopoietic stem cell transplantation. Drug resistance is a frequent complication resulting from treatment, as it stands there are limited clinical measures available for refractory AML besides palliative care. The goal of this review is to renew interest in a novel targeted hormone therapy in the treatment of AML utilizing growth hormone-releasing hormone (GHRH) antagonism, given it may provide a potential solution for current barriers to achieving complete remission post-therapy. Recapitulating pre-clinical evidence, GHRH antagonists (GHRH-Ant) have significant anti-cancer activity across experimental human AML cell lines in vitro and in vivo and demonstrate significant inhibition of cancer in drug resistant analogs of leukemic cell lines as well. GHRH-Ant act in manners that are orthogonal to anthracyclines and when administered in combination synergize to produce a more potent anti-neoplastic effect. Considering the adversities associated with standard AML therapies and the developing issue of drug resistance, MIA-602 represents a novel approach worth further investigation.

Fixed versus flexible gonadotropin releasing hormone antagonist protocol in women with polycystic ovary syndrome undergoing in vitro fertilization: An RCT.

Despite the extensive use of the gonadotropin-releasing hormone (GnRH) antagonist protocol in treating infertile women, particularly those with polycystic ovary syndrome (PCOS), there have not been sufficient evidence to compare the flexible and fixed variants in in vitro fertilization (IVF) cycles. This study aims to assess the treatment outcomes of flexible and fixed types of GnRH-antagonist protocol for IVF in women with PCOS. In this randomized clinical trial, 150 infertile women with PCOS, who were candidates for IVF, and referred to the Yazd Research and Clinical Center for Infertility, Yazd, Iran between October 2023 and February 2024 were included. Participants were divided into 2 groups (n = 75/each) based on the type of antagonist protocol (fixed or flexible). GnRH antagonist administration started on the 5 day of gonadotropin treatment in the fixed group. In the flexible group when there was at least one follicle 12-14 mm, GnRH antagonist was started. Finally, the number of metaphase II oocyte, the quality of embryos, the duration of the stimulation cycle, the dose of gonadotropin, the number of GnRH-antagonist, and the rate of ovarian hyperstimulation syndrome were evaluated. No statistically significant difference was observed in terms of cycle length and the total dose of gonadotropin between groups. Nevertheless, a notable distinction was observed in the total number of oocytes (17.84 vs. 15.5, p = 0.023) and mature oocytes (13.64 vs. 11.83, p = 0.019) in the flexible group compared to the fixed group. In conclusion, the IVF outcomes are more favorable in women with PCOS undergoing the flexible GnRH-antagonist protocol compared to the fixed protocol.

Bleeding vs Thrombosis: Treatment Strategy for Women Having Large Uterine Fibroids and DVT

Large uterine fibroids (UFs) are clonal neoplasms of the uterus that form during the mid and late-aged women. Such women generally consume oral contraceptive pills, tranexamic acid, or NSAIDS to manage heavy menstrual bleeding (HMB) and associated complications while waiting for a conclusive procedure or avoiding hysterectomy. The procoagulant effect of these medicinal agents can result in venous stasis of the lower limbs, leading to deep vein thrombosis (DVT), a challenging complication with HMB. We examine the complicated state of heavy bleeding with thrombosis and explore better management options. It has been seen that women with hypothyroidism have an increased risk of getting DVT due to an alteration in the coagulation system. These incidences are mostly associated with higher uterine weight, which is related to the extrinsic compression of the inferior vena cava. In such cases, the occurrence of postoperative thrombosis is riskier if hysterectomy/myomectomy is the only option. Utilization of appropriate anticoagulants with modification of the steroid-hormone system using hormone agonists or antagonists (e.g., levonorgestrel intrauterine system, high-dose progestin-only therapy, danazol, aromatase inhibitors, Vitamin-D supplements or selective estrogen receptor modulators) could be an effective technique, but adverse consequences of continued use should be monitored. More research is needed into the basic biology associated with the role of growth factors and genetic alterations in these malignancies. The development of new leiomyomas following conservative therapy is also a significant issue.

Effect of progesterone concentration on hCG trigger day on clinical outcomes after high-quality single blastocyst transfer in GnRH antagonist cycles.

To investigate whether progesterone levels on the human chorionic gonadotropin (hCG) trigger day are associated with clinical outcomes in fresh cycles and the first frozen-thawed cycles (the freeze-all strategy) following the transfer of a high-quality single blastocyst. This single-center retrospective analysis was conducted on patients undergoing in vitro fertilization with the gonadotropin-releasing hormone (GnRH) antagonist protocol from January 2017 to December 2023. The study included the first and second oocyte retrieval cycles with progesterone levels ≤2 ng/ml on hCG trigger day. Clinical pregnancy rates and early miscarriage rates were compared among groups using curve fitting, threshold effect analysis, and multivariable regression. When progesterone levels were between 1 and 2 ng/ml, the pregnancy rate in fresh cycles was only 51% of that in cycles with progesterone levels ≤1 ng/ml (95% CI: 0.33, 0.79, p = 0.0028). And the pregnancy rate decreased by 25% (95% CI: 0.51, 1.09) for frozen cycles, although there was no statistically significant (p = 0.1273). When cycle types were used as a binary variable in multivariate regression analysis, it was found that the clinical pregnancy rate in frozen cycles was 1.84 times higher than in fresh cycles (OR = 1.84, 95% CI: 1.38-2.47). For progesterone levels between 1 and 2 ng/ml, the clinical pregnancy rate in frozen cycles was 2.90 times that of fresh cycles (OR = 2.90, 95% CI: 1.59, 5.29, p = 0.0015). Progesterone levels on hCG day had no impact on the clinical pregnancy rate in thaw cycles, nor did they affect miscarriage rates in fresh or thaw cycles (p > 0.05). When progesterone levels on hCG trigger day were between 1 and 2 ng/ml, the clinical pregnancy rate for frozen-thawed cycles of high-quality single blastocyst transfer using an GnRH antagonist protocol significantly surpasses that of fresh cycles, thus elective frozen embryo transfer after the freeze-all strategy is recommended.

8208 Unexpected And Significant Rise In TSH In The Setting Of Relugolix Use

Abstract Disclosure: A.Y. Groysman: None. A. Poloju: None. P. Majety: None. T. Abraham: None. Background: Relugolix is a gonadotropin-releasing hormone antagonist used as androgen deprivation therapy for metastatic and nonmetastatic castration-resistant prostate cancer that was FDA-approved in December 2020. Common side effects include hot flashes, increased glucose and triglycerides, and decreased hemoglobin. We report a case of Relugolix interference with the absorption of levothyroxine, which has not been reported in the literature. Case: A 79-year-old white man with high-risk, Gleason 9 prostate cancer and Hashimoto’s hypothyroidism presented for evaluation of elevated thyroid stimulating hormone (TSH) level- 52.87 mIU/L (0.28-4.10 mIU/L). He did not have cold intolerance, constipation, fatigue, or weight gain. He was diagnosed with hypothyroidism in 1998 and was on a stable dose of levothyroxine 88mcg daily from 2016 until the time of this presentation. He is adherent and reports following a routine of having breakfast with coffee soon after taking levothyroxine for many years. In June 2022, his TSH was 4.48 mIU/L. In July 2022, he started taking Relugolix along with levothyroxine. Following this, his TSH levels increased to 30.08 mIU/L (FT4: 0.67 ng/dL), 35.43 mIU/L (FT4: 0.57 ng/dL), 52.87 mIU/L (FT4: 0.48 ng/dL) on 2/24/23, 3/3/23, and 3/14/23, respectively. No new medications were reported. His other medications were atorvastatin, tamsulosin, and vitamin D, which he took at night. He did not take calcium or biotin supplements. He had gradual weight gain (8 lbs) over the last 9 months. Levothyroxine dose was increased from 88 to 125 mcg daily and he was instructed to separate Relugolix from levothyroxine so he started taking Relugolix at bedtime. Repeat TSH was low at 0.12 mIU/L. The levothyroxine dose was eventually titrated back to 88 mcg daily and TSH was 5.2 (appropriate for age). Conclusion: Several medications are known to interfere with the absorption of levothyroxine. Our case suggests that Relugolix may be one of them. The significant rise in TSH and levothyroxine requirements months after starting Relugolix and the ability to return to the previous dose of levothyroxine only by separating Relugolix from levothyroxine strongly suggests that there is an interference between these medications that has not been reported. Presentation: 6/2/2024

GnRH antagonist protocol with hCG triggering ameliorates fertilization defect caused by failure of cumulus cell pentraxin-3 expression in unilateral endometriomas.

The aim of the study was to determine the expression pattern of long pentraxin 3 (PTX3) mRNA in cumulus cells (CCs) isolated from metaphase II oocytes of women with unilateral endometrioma undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone antagonist (GnRHa) protocol. A total of 60 CC samples, 30 from the affected ovary and 30 from the contralateral ovary, were collected from 12 patients with unilateral endometrioma who underwent flexible GnRHa protocol with recombinant human chorionic gonadotropin (rhCG) trigger. Thirty CC samples collected from the left ovary of 12 women with male factor infertility were used as external controls. Long PTX3 mRNA expression in each group was analyzed by real-time polymerase chain reaction (RT-PCR). Relative gene expression (fold-change) was calculated according to the 2-ΔΔCt equation. Fertilization rates after intracytoplasmic sperm injection (ICSI) were recorded for each group. CC-PTX3 mRNA expression in the unilateral endometrioma group was significantly lower than the mRNA expression of the disease-free ovary (0.90±0.01 vs. 0.25±0.02, p<0.01). CC-PTX3 mRNA expression of MII oocytes of the disease-free ovary was found to be similar to the control group (1.02±0.03 vs. 0.90±0.01, p=0.107). A significant 3.6-fold downregulation was observed in the CC-PTX3 mRNA expression of the endometrioma group compared to the CC-PTX3 mRNA expression in the contralateral ovary. CC-PTX3 mRNA expression in the endometrioma group was downregulated 4.08-fold compared to the CC-PTX3 mRNA expression of the control group (1.02±0.03 vs. 0.25±0.02, p<0.001). The cumulus morphologies of the endometrioma group with low CC-PTX3 expression and the groups with normal CC-PTX3 levels were similar. Fertilization rates of the endometrioma group were similar to the contralateral ovary and control groups. Unilateral endometrioma reduces CC-PTX3 expression but does not affect disease-free ovaries. The GnRHa protocol improved the fertilization rates, suggesting that failed CC-PTX3 expression is an in vivo pathology.

Childhood growth of singletons conceived following intracytoplasmic sperm injection - irrelevance of gonadotropin stimulation.

In conventional, gonadotropin stimulated, in vitro fertilization or intracytoplasmic sperm injection (c-IVF/ICSI) growth and development of multiple follicles is induced by gonadotropins, combined with gonadotropin-releasing hormone agonist or antagonist. In recent studies, singletons conceived after c-IVF/ICSI cycles had lower birth weight not only than spontaneously conceived children but also children born after unstimulated natural IVF/ICSI cycles (NC-IVF/ICSI). Lower birth weight is associated with a catch-up growth within the first years of life. Following the Barker hypothesis accelerated growth has been associated with a higher risk of cardiovascular diseases later in life. The aim of the study is to assess, if children conceived with NC-IVF/ICSI have a higher birthweight and therefore do not show a catch-up growth within the first two years. Therefore, we assume that children born after NC-IVF/ICSI have a better long-term cardiometabolic risk profile. Whether the weight- and height gain is comparable to spontaneously conceived children is unknown, since to our knowledge we are the first study to investigate the longitudinal growth of children born after unstimulated natural cycle ICSI (NC-ICSI). We conducted a single-center, prospective cohort study (2010-2017) including children (n = 139) born after NC-ICSI or c-ICSI treatment. Growth parameters up to 24 months were collected. Standard deviation scores based on growth references were calculated. The study included 98 children in the NC-ICSI and 41 children in the c-ICSI group. The median birth weight in NC-ICSI children was 3.4 kg [0.1 standard deviation score (SDS)] compared to 3.3 kg (-0.3 SDS) in c-ICSI children (p = 0.61). Median length at birth was 50 cm in both groups (NC-ICSI (-0.5 SDS), c-ICSI children (-0.8 SDS), p = 0.48). At age 24 months, median weight in NC-ICSI children was 12.2 kg (0.3 SDS) versus 12.2 kg (0.2 SDS) in c-ICSI children (p = 0.82) and median length 87.5 cm (0.1 SDS) versus 88.0 cm (0.4 SDS) (p = 0.43). We found no difference in growth between children conceived after stimulated and unstimulated ICSI. Growth parameters of both treatment groups did not differ from Swiss national growth references (N = 8500). One of the main limitations of our study was the small sample size (N = 139) of complete data sets over time and the high drop-out rate of 49% (68/139). Nevertheless, with the increasing number of children born after IVF/ICSI every year it is of immense importance to search for possibilities to reduce their long-term cardiometabolic risk and we want our data to contribute to this discussion.

Abstract A075: Racial and ethnic inequities in receipt of degarelix among patients diagnosed with advanced prostate cancer in United States

Abstract Background: Prostate cancer (CaP) is the most commonly diagnosed non-cutaneous cancer among men in the United States (US). Limited data currently exists regarding inequities in access to androgen deprivation therapy (ADT) which is the backbone of systemic treatment in management of advanced CaP. Gonadotropin-releasing hormone (GnRH) antagonists, first approved in 2008, represent a novel class of ADT drugs with faster onset of action and without initial testosterone surge or symptom flare when compared to GnRH agonists. There is also some evidence that GnRH antagonists, compared to GnRH agonists, may be associated with lower cardiovascular complications. Thus, in this study, we assessed inequities in access to GnRH antagonist (degarelix) by examining the associations of race and ethnicity with initiation of this drug among patients diagnosed with distant CaP. Methods: Using the Surveillance, Epidemiology and End Results (SEER) data linked to Medicare fee-for-service (Parts A, B, and D), we identified a cohort of patients, at least 66 years of age, who were diagnosed with distant CaP between 2008 and 2019 with follow-up through 2020. We defined treatment initiation with a GnRH antagonist (degarelix) or GnRH agonists (leuprolide, goserelin, histrelin, or triptorelin) as starting treatment with the study drug within one year after diagnosis. Poisson regression models were used to estimate adjusted rate ratios (aRR) and 95% confidence intervals (CI) for the association between race and ethnicity and degarelix treatment initiation (vs GnRH agonists, no treatment). All models were adjusted for age and Gleason score and compared Non-Hispanic Black (NHB), Hispanic, Non-Hispanic Asian American and Pacific Islander (NHAAPI), and Non-Hispanic American Indian and Alaska Native (NHAIAN) with Non-Hispanic White (NHW) patients. Results: There were 25,277 patients diagnosed with CaP in our analytic cohort, 3,033 (12.0%) initiated degarelix, and 14,045 (55.6%) initiated GnRH agonists over the study period. Mean (SD) age in the study population was 77.8 (7.8). Among all patients, 19,231 (76.1%) were NHW, 3,013 (11.9%) were NHB, 2,075 (8.2%) were Hispanic, 770 (3.0%) were NHAAPI, and 119 (0.5%) were NHAIAN. In the primary analysis, NHB (aRR: 0.58, 95% CI: 0.51-0.66), Hispanic (aRR: 0.59, 95% CI: 0.51-0.69), NHAIAN (aRR: 0.85, 95% CI: 0.49-1.47), and NHAAPI (aRR: 0.75, 95% CI: 0.59-0.94) were less likely to initiate degarelix compared with NHW patients. Discussion: In this US population-based study of patients diagnosed with distant CaP, we observed lower rates of treatment initiation with degarelix among patients of all other racial and ethnic groups compared to NHW patients, which may suggest lower access to these new class of ADT in these groups. Additional research is needed to elucidate health systems, provider, and patient access barriers that contribute to these inequities. Citation Format: Farzin Khosrow-Khavar, Mingchao He, Elizabeth Handorf, Tina Mayer, Thomas Jang, Saum Ghodoussipour, David Golombos, Biren Saraiya, Elisa V. Bandera, Hari S. Iyer. Racial and ethnic inequities in receipt of degarelix among patients diagnosed with advanced prostate cancer in United States [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A075.

A Pharmacological Overview of Degarelix and Relugolix in Advanced Prostate Cancer

Prostate cancer (PCa) ranks the second most diagnosed cancers among men globally and the sixth leading cause of cancer-related deaths. Advanced prostate cancer can be defined as the recurrence after definitive therapies (radical prostatectomy or external beam radiotherapy) and de novo metastasis (metastasis without prior treatment). Advanced PCa can be categorized as metastatic hormone sensitive prostate cancer (mHSPC), non-metastatic castration resistant prostate cancer (nmCRPC), and metastatic castration resistant prostate cancer (mCRPC). Management of advanced PCa often involves castration to reduce testosterone levels, which can be achieved by gonadotropin releasing hormone antagonists such as degarelix and relugolix. Degarelix is injectable while relugolix is an orally administered form of GnRH antagonist. This review aims to explore the latest pharmacological aspects of these drugs to inform treatment decisions for advanced PCa.

Effectiveness of surgical castration by bilateral subcapsular orchiectomy as monotherapy for the treatment of advanced prostate cancer.

Prostate cancer is the most common malignancy in men and the second cause of death due to cancer [1]. Treatment of prostate cancer has been a field of many progresses, but the discovery of the role of androgen in the genesis of prostate cancer by Hugins and Hodges is really a milestone in the treatment of advanced prostate cancer [2]. In patients with advanced prostate cancer, options for androgen ablation include bilateral orchiectomy, therapy with luteinizing hormone-releasing hormone (LHRH) analogues and antagonists, and combined androgen blockade (typically a LHRH analogue plus a first-generation anti-androgen). Although orchiectomy remains the historical gold standard for androgen ablation, LHRH therapy is considered to be equivalent therapeutically. Medical castration has the advantage to induce less psychological effects comparatively to the surgery, reason why in developed countries patients are managed with medical therapy [3]. However, LHRH agonists cannot induce a complete castration levels of testosterone in some patients [4]. Instead, surgical castration can completely eliminate remaining testosterone produced by the Leydig cells in testes [5]. According to the latest recommendations of the European Association of Urology (EAU), androgen deprivation therapy (ADT) is the firstline indication in patients with advanced and metastatic PCa [6]. This first line is made of LHRH agonists, surgical castration representing the second line [7] And Several techniques of surgical castration have been described with comparable results in terms of patient survival and quality of life, but the sub-capsular technique of preserving testicular albuginea and epididymis is the most commonly used [8]. The relatively high cost of chemical castration is a constraint in the therapeutic choice in developing countries [9]. Therefore, surgical castration is an interesting alternative because of its simplicity and affordability in patients, most of whom have no health insurance. In Togo, most patients diagnosed with prostate cancer are at the metastasis stage, and surgical castration is often used as first-line treatment [10]. The aim of this study was to assess the biological and clinical effectiveness of surgical castration as the sole treatment in patients with advanced prostate cancer.

Significance of FSHR and LHCGR gene polymorphisms on clinical outcomes in gonadotropin-releasing hormone antagonist protocol with freeze-all strategy: A case-control study.

Follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor (LHCGR) are integral to ovarian function, facilitating follicle development and maturation through their respective hormonal interactions. The influence of receptor polymorphisms on the outcomes of freeze-all cycles remains unclear. This study investigates the impact of FSHR N680S and LHCGR N312S polymorphisms on clinical outcomes in freeze-all cycles. Women undergoing controlled ovarian stimulation for assisted reproductive technology participated in this study. They were administered a gonadotropin-releasing hormone antagonist protocol, with recombinant follicle-stimulating hormone (rFSH) dosages adjusted according to age, body mass index, antral follicle count, and individual hormonal responses. Additionally, human menopausal gonadotropin dosages were tailored based on the LHCGR N312S genetic variant. Analysis revealed no significant differences in age, body mass index, antral follicle count, or marital status across the genotypes of FSHR N680S and LHCGR N312S. However, notable differences were observed in the rFSH dosage required daily and in total among the FSHR polymorphism genotypes. Genotypes of the LHCGR polymorphism correlated with fewer stimulation days. A significant interaction was observed between the 2 polymorphisms concerning total rFSH dosage. The presence of serine in the FSHR polymorphism was associated with higher rFSH dosage requirements. Both FSHR N680S and LHCGR N312S polymorphisms significantly influenced clinical pregnancy and live birth outcomes in freeze-all cycles, underscoring the potential of a pharmacogenomic approach to optimize hormone supplementation in controlled ovarian stimulation protocols during assisted reproductive technology treatments.

Prostate Specific Antigen and Prostate Cancer in Gender Affirming Hormone Therapy for Transgender or Nonbinary Individuals.

The effects of gender affirming hormone therapy on prostate specific antigen (PSA) and prostate cancer incidence in transgender or non-binary individuals (TGNB) born with prostate glands remains uncharacterized. The cohort included 1,024 self-identified TGNB individuals assigned male at birth who received PSA testing in the VA Healthcare System, matched by birth year to cisgender men. PSA changes were measuring using linear-mixed effects modeling accounting for repeated measured and matching. Non-gonadotrophin releasing hormone agonist or antagonist (GnRH) therapy was associated with 1.30 ng/mL lower PSA (95% confidence interval (CI) 1.14-1.46, p < 0.001) and GnRH therapy was associated with 1.08 ng/mL lower PSA (95% CI 0.60-1.55, p < 0.001) compared with cisgender men. Among 450 TGNB individuals who had PSA testing before and after initiation of hormone therapy, non-GnRH and GnRH therapies resulted in 0.49 ng/mL decrease (95% CI 0.35-0.62, p<0.001) and 0.73 ng/mL decrease (95% CI 0.43-1.02, p<0.001), respectively, from median baseline of 0.70 ng/mL. From time of age 50, TGNB prostate cancer incidence was 1.79 per 1,000 patient-years versus 4.02 per 1,000 patient-years in cisgender men. Gender affirming hormone therapies are associated with significant decreases in PSA, and TGNB individuals assigned male at birth remain at risk for prostate cancer. Future work should establish if a lower threshold for biopsy should be used in these contexts and if the decreased incidence is a result of ascertainment bias or hormone therapy resulting in a true decrease in the incidence of prostate cancer.

Increasing dominant follicular proportion was associated with adverse IVF/ICSI outcomes in low-prognosis women undergoing GnRH antagonist protocol: a retrospective cohort study

PurposeThis study aimed to examine the correlation between different dominant follicle proportions (DFPs) and outcomes of in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) among patients classified under POSEIDON Groups 3 and 4, who underwent gonadotropin-releasing hormone antagonist (GnRH-ant) protocols. Additionally, it sought to determine the optimal DFP threshold for trigger timing.MethodsA retrospective analysis was performed on patients classified under POSEIDON Groups 3 (n = 593) and 4 (n = 563) who underwent GnRH-ant protocols for controlled ovarian hyperstimulation (COH) between 2016 and 2022. These patients were categorized into two groups based on their DFPs, defined as the ratio of ≥ 18-mm dominant follicles to ≥ 12-mm follicles on the trigger day (DFP ≤ 40% and DFP ≥ 40%). Statistical analyses, including restricted cubic spline (RCS) and multivariate logistic regression, were employed to assess the relationship between DFP and IVF/ICSI outcomes.ResultsDemographic characteristics of patients were similar across groups. In POSEIDON Groups 3 and 4, DFP > 40 was associated with a significant decrease in the number (No.) of oocytes retrieved, cleaved embryos, and available embryos. Moreover, following the GnRH-ant cycle, the clinical pregnancy and live birth rates in fresh embryo transfer (ET) were notably reduced in the DFP > 40 group compared with the DFP ≤ 40 group, whereas no significant differences were observed in the pregnancy outcomes of the first frozen-thawed embryo transfer (FET) between the groups. In POSEIDON Group 3, the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLRB) were significantly higher in the DFP ≤ 40 subgroup than in the DFP > 40 subgroup, with a notable decrease in CLRB observed with increasing DFP levels. However, in POSEIDON Group 4, no significant differences in CCPR and CLRB were found between the groups. Logistic regression analysis identified age and the No. of oocytes retrieved as pivotal factors influencing CLRB in Group 4.ConclusionFor patients in POSEIDON Group 3, maintaining a DFP ≤ 40 mm is crucial to achieve optimal laboratory and pregnancy outcomes by avoiding delayed triggering. However, for patients in POSEIDON Group 4, age remains a critical factor influencing CLRB regardless of DFP, although a higher No. of oocytes retrieved and available embryos with DFP ≤ 40 is beneficial.