A simple and practical approach to elective egg freezing to control costs and expand access to care.

Social elective egg freezing (EEF) is now widely used globally but in many countries is unaffordable to many women because of high costs and lacking insurance coverage. Efforts to reduce costs, therefore, are of importance. Surprisingly, a simple, well-defined and practical approach ensuring optimal outcomes for EEF has, however, so-far not been published. We, therefore, conducted a narrative review of the literature for relevant articles regarding the different steps of ovarian stimulation (OS) in the EEF process, in order to define such a standard protocol. This review revealed that in order to maximize oocyte yields with minimal number of OS cycles - while ensuring patient safety - a multiple-dose GnRH antagonist protocol with a daily gonadotropin dose of 300 IU appears best, unless patients demonstrate a polycystic ovarian phenotype, suggestive of likely high responses. The initial gonadotropin should be recFSH, while LH supplementation should be co-administered with the addition of GnRH antagonist. Final follicular maturation should be triggered by GnRH agonist trigger, with a dual trigger (1000-1500 IU hCG) considered for suboptimal responders to GnRH agonist trigger, optionally with Cabergoline to mitigate ovarian hyperstimulation syndrome (OHSS) in high responders.

Dual trigger or hCG alone: A retrospective analysis on patients with diminished ovarian reserve under in vitro fertilization and embryo transfer (IVF-ET) treatment.

OBJECTIVE: With remarkable deficiency in both oocyte stock and competence, the prognosis of IVF-ET in diminished ovarian reserve (DOR) is obstinately poor, underscoring warranted optimization to current procedures. We compared the efficacy of dual-trigger (hCG plus GnRH-a) and hCG alone on the outcomes for DOR patients. STUDY DESIGN: A total of 381 couples and 857 controlled ovarian stimulation (COS) cycles, and 222 couples and 366 frozen embryo transfer (FET) ones were included. The intermediate outcomes during oocyte retrieval and in vitro culture were compared based on COS dataset, while outcomes after embryo transfer analyzed based on FET dataset. The marginal effect of all study factors and covariates were evaluated with a cluster-weighted GEE model. RESULTS AND CONCLUSION: Neither the intermediate nor implantation outcomes were improved by dual-trigger. The OR values were 1.08 (95 % CI: 0.41-2.78) for retrieval cancellation, 1.33 (95 % CI: 0.89-2.00) for oocyte harvest, 1.04(95 %CI: 0.94-1.15) for viable embryo and 1.03(95 %CI: 0.88-1.19) for top-quality embryo. Similarly, the ORs were 0.90 (95 %CI: 0.62-1.30) for implantation and 0.97 (95 %CI: 0.56-1.69) for clinical pregnancy. This equivalence remained unchanged after adjusting for the covariates such as age, BMI, controlled ovarian stimulation protocols, etc. Thus, dual-trigger cannot provide significant advantage over hCG in related to immediate or clinical outcomes of IVF-ET treatments in DOR patients.

GnRH agonist pretreatment for frozen embryo transfer among women with polycystic ovary syndrome: a narrow systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Frozen embryo transfer (FET) is usually recommended for women with polycystic ovary syndrome (PCOS) undergoing In vitro fertilization (IVF). While there is no consensus as to the optimal protocol of endometrial preparation for FET. The effect of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment for FET among women with PCOS remains controversial. PURPOSE: We intend to explore whether GnRH-a pretreatment could improve clinical outcomes for women with PCOS undergoing FET. METHODS: PubMed, Embase, ClinicalTrials.gov, Cochrane Library, and Web of Science were searched up to May 16, 2024. Eligible studies involved patients with PCOS undergoing FET and receiving GnRH-a pretreatment for endometrial preparation, with artificial cycle (AC) as the control therapy. Only randomized controlled trials (RCTs) published in Chinese and English were included. Data extraction was performed independently by two authors. Effect was quantified using odd ratios (ORs) with 95% confidence intervals (CIs) using random-effect models with the Mantel-Hansel (M-H) method in Revman software. Quality of outcomes was evaluated using the GRADEpro system. Primary outcomes contained the clinical pregnancy rate, miscarriage rate, and live birth rate. Secondary outcomes included the incidence of preterm labor and gestational diabetes mellitus (GDM). RESULTS: Ninety-seven records were initially retrieved, with 21 duplicates and 65 articles excluded after title and abstract screening. Seven studies were excluded due to retrospective design, leaving three RCTs with 709 participants. Among them, 353 received GnRH-a pretreatment as the intervention group and 356 received AC as the control group. No significant differences were observed in the clinical pregnancy rate (OR 1.09, 95% CI 0.75 to 1.56, P = 0.66), miscarriage rate (OR 0.73, 95% CI 0.28 to 1.90, P = 0.52), live birth rate (OR 0.87, 95% CI 0.61 to 1.25, P = 0.46), and the risk of preterm labor (OR 1.45, 95% CI 0.79 to 2.65, P = 0.23) and GDM (OR 0.73, 95% CI 0.37 to 1.48, P = 0.39) between the two groups. CONCLUSIONS: In this meta-analysis, GnRH-a pretreatment does not confer any advantages and appears unnecessary for women with PCOS undergoing FET. Additional RCTs should focus on maternal complications and the health of offspring.

Health-related quality of life of patients with prostate cancer initiating GnRH agonist therapy: the PRISME study.

OBJECTIVES: To compare the evolution of health-related quality of life (HRQoL) over 6 months of GnRH agonist (GnRHa) therapy among age groups for patients with prostate cancer (PCa). PATIENTS AND METHODS: PRISME (NCT03516110) was a non-interventional, prospective study conducted in France in patients aged ≥60 years with PCa initiating GnRHa therapy within routine care. HRQoL was evaluated at baseline and after 6 months using the EORTC quality of life in ELDerly cancer patients 14 items (QLQ-ELD14) questionnaire. Cognitive status was assessed using the Mini Mental State Examination (MMSE). Analyses of covariance compared the evolution of the change from baseline of the QLQ-ELD14 scores among age groups. RESULTS: 814 patients were enrolled (245, 60-70 years; 314, 70-75 years; 252, ≥75 years). Slight or no changes were observed in each QLQ-ELD14 dimension between baseline and 6 months, overall and by age. In the primary effectiveness analysis, there was no difference among age groups in the change from baseline in QLQ-ELD14 scores. Baseline cognitive status was lower in the oldest age group, but there were no changes in all age groups. As expected, sexual function declined in all age groups. CONCLUSION: GnRHa therapy influence on HRQoL, cognition and sexuality appeared independent of age.

Prostate cancer that has spread to other parts of the body is called "advanced prostate cancer." Hormone therapy is a common treatment for high risk localized and advanced prostate cancer. It works by lowering hormone levels, causing prostate cancers to grow more slowly or shrink. But, side effects from this kind of treatment can affect a patient's quality of life. Common side effects of hormone therapy include a loss of sex drive, erectile dysfunction, bone weakening, hot flushes, or mood disorders. Most patients with prostate cancer are over the age of 60 years, but elderly patients are often excluded from clinical trials, meaning that we lack data about them. This study assessed if there was a link between age and health-related quality of life in men with advanced prostate cancer treated with hormone therapy. The study included 814 men with advanced prostate cancer who were over 60 years old and had started a type of hormone therapy called gonadotropin-releasing hormone agonist (GnRHa) therapy. The results showed that health-related quality of life was similar after 6 months of hormone therapy, in the overall group of patients and in the different age groups (60­70, 70­75, and over 75 years of age). Cognitive impairment occurred about twice as often in patients aged over 75 years than among younger patients, before initiation of hormone therapy. Cognitive impairment was likely caused by ageing and was not associated with hormone therapy treatment. Sexual function decreased in all age groups, particularly in patients aged 60­70 years. This study did not reveal any major impact of hormone therapy on health-related quality of life in older men with advanced prostate cancer, after a 6-month period and the use of routine questionnaires.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Use of puberty-blocking hormones for gender dysphoria in New Zealand: descriptive analysis and international comparisons.

AIM: To investigate use of puberty-blocking hormones (gonadotropin-releasing hormone analogues [GnRHa]) for gender dysphoria in New Zealand. Specifically, to describe demographic characteristics and time trends in the prevalence and incidence of prescribing, and to calculate cumulative incidence (proportion) of first prescribing of GnRHa for gender dysphoria in order to make valid international comparisons. METHOD: The national Pharmaceutical Collection was used to identify all dispensing from 2006 to 2023 to those aged <18, by sex/gender and age. Cumulative incidence of first prescriptions between ages 12 and 17 (which largely excludes prescribing for other indications) was calculated and compared with the Netherlands and England and Wales. RESULTS: In New Zealand, prescription of GnRHa for gender dysphoria started around 2011; prevalence of use increased to 2014, then more steeply to 2022, followed by a decline. Incidence data show the decline started from 2021. New Zealand, compared to the Netherlands (which started prescribing in the 1990s), had 1.7 times the cumulative incidence of first prescriptions by 2018. Compared to England and Wales up to 2020, New Zealand had 3.5-6.9 times the cumulative incidence. CONCLUSION: The high rate of prescribing for probable gender dysphoria in New Zealand, and the decline after 2021, require further investigation.

GnRH agonist-only trigger, compared to dual trigger, reduces oocyte retrieval rate in high responders without affecting cumulative live birth rate.

Introduction: This study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). Materials and methods: A retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR. Results: We analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p <0.05), while fertilization rates, blastocyst formation rates, and cumulative LBR were comparable. Notably, no OHSS cases had been reported in the GnRH agonist-only group, compared with 7 cases in the dual trigger group. Conclusion: GnRH agonist-only triggers resulted in a lower oocyte retrieval rate compared to dual triggers but did not significantly affect cumulative LBR in high responders. This approach effectively reduces OHSS risk without compromising pregnancy outcomes, making it a preferable option in freeze-all strategies, despite a longer oocyte pick-up duration and a medium cost. GnRH agonist-only trigger, however, may not be suitable for fresh embryo transfers or patients with low serum LH levels on trigger day.

GnRH-a-based fertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients: a multicenter, open-label, randomized designed clinical trial protocol.

BACKGROUND: Around 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes. METHODS: This study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence. ETHICS AND DISSEMINATION: The protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association's Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal. CONCLUSIONS: Prospective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.

Effects of pretreatment with long-acting gonadotropin-releasing hormone agonists on pregnancy outcomes in patients with minimal and mild peritoneal endometriosis: A retrospective study of 274 frozen-thawed embryo transfer cycles.

To investigate the effects of pretreatment with long-acting gonadotropin-releasing hormone agonist (GnRH-a) before frozen-thawed embryo transfer (FET) on pregnancy outcomes in patients after minimal-mild (stages I-II) peritoneal endometriosis surgery. A retrospective cohort study was performed from March 2018 to May 2019. Overall, 274 patients met inclusion criteria of undergoing FET after minimal/mild peritoneal endometriosis surgery. For the FET protocol, patients were divided into 2 groups: GnRH-a plus hormone replacement therapy (HRT) (group A, n = 154) and HRT-only (group B, n = 120), with the former divided into 2 subgroups receiving 1 (group A1, n = 80) or 2 doses (group A2, n = 74) of GnRH-a. Basic characteristics and pregnancy outcomes of groups A and B and groups A1 and A2 were compared. Clinical pregnancy rate (CPR) and live birth rate (LBR) were the primary outcomes and logistic regression was used to analyze independent correlation factors. The CPR and LBR in group A were 58.4% and 50.0%, respectively, and were not significantly higher than in group B (49.2% and 40.0%; respectively, χ2 = 2.339, P = .126 and χ2 = 2.719, P = .099, respectively). CPR and LBR in group A1 were not significantly lower than those in group A2 (52.5% and 45.0% vs 64.9% and 55.4%, respectively; χ2 = 2.420, P = .120 and χ2 = 1.665, P = .197, respectively). However, group A2's CPR and LBR were significantly higher than group B's (64.9% and 55.4% vs 49.2% and 40.0%, respectively; χ2 = 4.560, P = .023 and χ2 = 4.375, P = .026, respectively). Logistic regression analysis showed that GnRH-a pretreatment (1 or 2 doses) had no significant effect on CPR and LBR compared with the HRT-only group. Patients with minimal-mild (stages I-II) peritoneal endometriosis surgery may not require GnRH-a pretreatment before FET.

Severe ovarian hyperstimulation syndrome following sole gonadotropin-releasing hormone (GnRH) agonist trigger: a case series and literature review.

OBJECTIVE: The aim of this study was to report three cases of early severe ovarian hyperstimulation syndrome (OHSS) in patients undergoing a GnRH antagonist protocol triggered with GnRH agonist (GnRH-a), leading to hospitalization and the need for peritoneal drainage. Additionally, a review of the existing literature on this topic is provided. DESIGN: This is a retrospective case series and a literature review. SETTING: This study was conducted at obstetrics and gynecology department of tertiary academic referral hospitals, Israel. PARTICIPANTS: This study included three patients presented with severe OHSS symptoms, including abdominal distension, ascites, and hemoconcentration. MAIN OUTCOME MEASURES: The main focus of the treatment was to address the symptoms and prevent any further complications. The outcome was the complete recovery of the patients. RESULTS: The presented cases detail instances of severe OHSS following oocyte retrieval, utilizing GnRH-a for triggering. Case 1 involved a 33-year-old patient with a history of polycystic ovary syndrome (PCOS), Case 2 featured a 22-year-old patient with familial adenomatous polyposis (FAP), and Case 3 included a 41-year-old patient with a history of depressive disorder. All patients receiving supportive care, including infusions and medications, exhibited gradual improvement during hospitalization, with complete resolution observed during the 20-day post-hospitalization check-up. CONCLUSIONS: These three cases highlight the occurrence of severe early OHSS following a GnRH antagonist protocol triggered with GnRH-a in the absence of human chorionic gonadotropin (hCG) administration for trigger or luteal-phase support. Clinicians must be aware that a GnRH-a trigger followed by a freeze-all approach does not guarantee the complete elimination of OHSS in all patients.

Clinical pharmacology in adolescent transgender medicine.

Adolescent transgender medicine is a growing clinical field. Gender-affirming medications for transgender youth may include gonadotropin-releasing hormone (GnRH) agonists, gender-affirming hormones or both. To evaluate the potential effects of GnRH agonists (puberty suppression) on pharmacokinetic processes for transgender youth, we searched PubMed from inception to May 2024 for publications on the effects of GnRH agonists on drug absorption, distribution, metabolism or excretion for transgender adolescents or effects on hormones (including gonadotropins, adrenal androgens, sex steroids) that are associated with changes in drug metabolism during puberty in the general adolescent population. No publications discussed the effects of GnRH agonist treatment on pharmacokinetic processes for adolescent transgender people. Sixteen publications observed marked decreases in gonadotropins and sex steroids for both adolescent transgender men and adolescent transgender women and slight effects on adrenal androgens. During GnRH agonist treatment, changes in body composition and body shape were greater for adolescent transgender people than for cisgender adolescent people. Further research is needed to better understand the effects of GnRH agonists on drug metabolism and other pharmacokinetic processes for transgender adolescents receiving GnRH agonists and other gender-affirming medications.

Economic evaluation of GnRH-agonist long protocol and GnRH-antagonist protocol in IVT/ICSI among the Chinese population: using pharmacoeconomic models.

OBJECTIVE: This paper uses health economics methods to discuss the cost-effectiveness value of long protocol and antagonist protocol for in vitro fertilisation and embryo transfer (ET) in the Chinese population. DESIGN: Health economic evaluation study. SETTING: The data needed to construct the model for this study were derived from published studies and other secondary sources in China. PARTICIPANTS: No patients participated in the study. MEASURES: The main outcomes were live birth rate (LBR) and cost. From the societal perspective, we considered the direct and indirect costs over the course of the treatment cycles. A cost-effectiveness was measured using the incremental cost-effectiveness ratio and the probability that a protocol has higher net monetary benefit. Sensitivity analysis was carried out to verify the reliability of the simulation results. RESULTS: For the Chinese population, the long protocol resulted in a higher LBR than the antagonist protocol (29.33% vs 20.39%), but at the same time, it was more expensive (ï¿¥29 146.26 (US$4333.17) vs ï¿¥23 343.70 (US$3470.51)), in the case of considering only one fresh ET cycle. It was the same when considering subsequent frozen ET (FET) cycles (51.78% vs 42.81%; ï¿¥30 703.02 (US$4564.62) vs ï¿¥24 740.95 (US$3678.24)). The results of most subgroups were consistent with the results of the basic analysis. However, for certain populations, the long protocol was the inferior protocol (less effective and more expensive). CONCLUSION: For the Chinese population, when the monetary value per live birth was greater than ï¿¥65 420 (US$9726) and ï¿¥66 400 (US$9872), respectively, considering only one fresh cycle and considering subsequent frozen cycles, the long protocol is the preferred protocol. This threshold also varies for women of different ages and ovarian response capacities. For women in POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) group 2, group 3 and group 4, antagonist protocol is recommended as the preferred protocol. The results of this study need to be verified by further large-scale randomised controlled trials.

Do body esteem and quality of life scores change with puberty signs or precocious puberty treatment?

OBJECTIVES: Body esteem (BE) and quality of life (QOL) of girls aged 9-11 years may change depending on their puberty. We aimed to examine The Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) and the Body Esteem for Adolescents and Adults Scale (BESAA) for children. METHODS: The groups were determined as those whose puberty signs had not yet started (Group 1), those having with breast development stage 3 and/or larger (Group 2), and those who had received gonadotropin-releasing hormone agonist (GnRHa) treatment for at least 6 months (Group 3). RESULTS: A total of 145 girls (Group 1: 41, Group 2: 56, Group 3: 48), were included. The PedsQL scores of the Group 1 was higher than Group 2 (78.5 ± 10.3 vs. 70.1 ± 14.2; p=0.008). The PedsQL scores of the Group 1 was higher but not statistically different from Group 3 (78.5 ± 10.3 vs. 74.2 ± 14.3; p=0.401). The PedsQL scores of Group 2 was not statistically different from Group 3 (p=0.354). There was no statistical difference in BESAA scores between groups (p=0.291). Group 1's PedsQL Health and Activity subscale score was higher than Group 2 (p=0.002). CONCLUSION: The QOL of the girls with PP was found to be lower than their healthy peers. Health and Activity-related QOL scores were found to be lower in the untreated group, indicating that girls with PP were probably significantly disturbed by their puberty-related physical development at the onset of the disease.

Neurological recovery in rats with portocaval anastomosis-induced hepatic encephalopathy treated with leuprolide acetate, a GnRH agonist.

Hepatic encephalopathy (HE) is a neuropsychiatric complication of acute liver failure or chronic liver injury. Liver dysfunction impairs ammonia detoxification, allowing it to cross the blood-brain barrier (BBB) and disrupt brain function. The hippocampus becomes a crucial target during elevated ammonia levels, causing spatial memory impairment and decreased learning ability. Leuprolide acetate (LA), a GnRH agonist, has been implicated in neuroprotection and neuroregeneration in several regions of the central nervous system (CNS) including hippocampus. In this study, we aim to evaluate the effects of LA treatment on hippocampus of rats with HE induced by portocaval anastomosis (PCA) trough cognitive tests, histology analysis and expression of neuronal recovery marker proteins, such as neurofilament (NF200) and neurabin II, and astrocyte marker glial fibrillary acidic protein (GFAP). Rats were divided into three groups: SHAM, portocaval anastomosis with saline solution (PCA + SS) and portocaval anastomosis treated with LA (PCA + LA). To evaluate learning and spatial memory elevated T-maze (ETM) and Y-maze test (YMT) were respectively used. Results indicated that LA-treated rats performed significantly better in ETM and YMT than untreated rats. Histological analysis of hippocampus showed increased neuron density, nuclear area, and layer thickness in dentate gyrus of PCA + LA group compared to PCA + SS. Additionally, neurabin II and NF200 expression were higher in LA-treated rats, while GFAP expression was elevated in the PCA + SS group compared to control and PCA + LA groups. In conclusion, LA enhances hippocampal neuron recovery and reduces astrogliosis, suggesting its potential as a therapeutic intervention for attenuating hippocampal damage during HE.

Peripheral administration of a κ-opioid receptor agonist nalfurafine inactivates gonadotropin-releasing hormone pulse generator activity in goats.

Neurons co-expressing kisspeptin, neurokinin B, and dynorphin A (KNDy neurons), located in the arcuate nucleus (ARC) of the hypothalamus, are indicated to be the gonadotropin-releasing hormone (GnRH) pulse generator. Dynorphin A is reported to suppress GnRH pulse generator activity. Nalfurafine is a selective agonist of the κ-opioid receptor (KOR), a receptor for dynorphin A, clinically used as an anti-pruritic drug. This study aimed to evaluate the effects of nalfurafine on GnRH pulse generator activity and luteinizing hormone (LH) pulses using female goats. Nalfurafine (0, 2, 4, 8, or 16 µg/head) was intravenously injected into ovariectomized Shiba goats. The multiple unit activity (MUA) in the ARC area was recorded, and plasma LH concentrations were measured 2 and 48 h before and after injection, respectively. The MUA volley interval during 0-2 h after injection was significantly increased in the nalfurafine 8 and 16 µg groups compared with the vehicle group. In 0-2 h after injection, the number of LH pulses was significantly decreased in the nalfurafine 8 and 16 µg groups, and the mean and baseline LH were significantly decreased in all nalfurafine-treated groups (2, 4, 8, and 16 µg) compared with the vehicle group. These results suggest that nalfurafine inhibits the activity of the GnRH pulse generator in the ARC, thus suppressing pulsatile LH secretion. Therefore, nalfurafine could be used as a reproductive inhibitor in mammals.

An Overview of Long-Acting GnRH Agonists in Premenopausal Breast Cancer Patients: Survivorship Challenges and Management.

Managing breast cancer in premenopausal women poses unique challenges due to its considerable effect on both morbidity and mortality. Goserelin, a gonadotropin-releasing hormone agonist, has emerged among the various modalities as a preferred option for ovarian function suppression, owing to its efficacy in reducing ovarian estrogen production in premenopausal women with hormone receptor-positive breast cancer. Recent studies have affirmed the efficacy and safety of long-acting (LA) goserelin 10.8 mg every 12 weeks, offering comparable outcomes to monthly injections. This flexibility enables personalized treatment approaches, potentially enhancing patient satisfaction. Off-label utilization of goserelin LA surged during the coronavirus disease pandemic, prompting initiatives to broaden its use for breast cancer treatment. Switching to goserelin LA can streamline treatment, boost adherence, and optimize resource utilization. With the recent approval of goserelin 10.8 mg LA by Health Canada on 6 May 2024, for use in breast cancer, Canada is the latest to join over 60 countries worldwide to expand the accepted indications for goserelin LA and ensure its availability to potentially enhance healthcare delivery, patient care, and breast cancer outcomes. Goserelin LA offers premenopausal patients a means to more effectively manage the constraints imposed by breast cancer treatment and its impact on survivorship.

Medical management of endometriosis.

PURPOSE OF REVIEW: While laparoscopic surgery plays a key role in the management of endometriosis, symptoms commonly recur, and repeat surgery comes with increased risk. Medical management, including hormonal and nonhormonal treatment, is vital in managing painful symptoms. This review summarizes recent evidence regarding various medical management options available to treat pelvic pain associated with endometriosis. RECENT FINDINGS: Efficacy of dienogest vs. combined oral contraceptive on pain associated with endometriosis: randomized clinical trial.Once daily oral relugolix combination therapy vs. placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2).A randomized, double-blind, placebo-controlled pilot study of the comparative effects of dienogest and the combined oral contraceptive pill in women with endometriosis.Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study. SUMMARY: All symptomatic women with suspected endometriosis who are not desiring immediate fertility can be offered suppressive treatment to control symptoms and slow the progression of disease. First-line treatments include the combined oral contraceptive pill and progestogens. Second-line treatments include gonadotropin-releasing hormone agonists and antagonists but current guidelines recommend that these should be reserved for people whose symptoms fail to be controlled by first-line agents. The use of complementary and alternative medicines is also increasing in both volume and number of agents used.

The effectiveness of prolonged downregulation with gonadotrophin-releasing hormone analogue (GnRHa) treatment in women with adenomyosis undergoing IVF/ICSI: A systematic review and meta-analysis.

IMPORTANCE: Adenomyosis can reduce the chance of clinical pregnancy in women undergoing assisted conception. Treatment with prolonged gonadotrophin-releasing hormone analogue (GnRHa) downregulation prior to IVF/ICSI has been postulated to improve pregnancy outcomes. OBJECTIVE: We aimed to evaluate the effectiveness and safety of prolonged GnRHa treatment (minimum one month) versus no pre-treatment in women with adenomyosis undergoing IVF/ICSI using a systematic review and meta-analysis. DATA SOURCES: We searched electronic databases: Embase (OVID), MEDLINE® (OVID), APA PsycInfo (OVID), Maternity & Infant Care Database (MIDIRS (OVID), HMIC Health Management Information Consortium (OVID) and ClinicalTrials.gov from inception until 27th of March 2023. STUDY SELECTION AND SYNTHESIS: We included studies that reported on women with adenomyosis receiving GnRHa to down-regulate the hypothalamic-pituitary-ovarian axis for one to six months before IVF/ICSI. We pooled data using the Haensel-Mantel method and reported using Odds Ratio (OR) with 95 % confidence intervals (CI). We assessed the quality of included studies using the Newcastle-Ottowa Scale and confidence in evidence using the GRADE criteria. Bias analysis was conducted via the Cochrane recommended tool (RevMan Web, Academic License). MAIN OUTCOMES AND RESULTS: We screened 365 citations and eight retrospective studies were included in the meta-analysis (n = 2422 women). The median age was 34 years [IQR 31.95-35.05], median BMI 21.30 kg/m2 [IQR 21.05-23.55] and median duration of GnRHa downregulation was 2.5 months [Range 1-4; IQR 1.37-3]. Women with adenomyosis receiving prolonged GnRHa treatment had a higher implantation rate 1/OR 1.69 [95 % CI 1.09, 2.56], I2 = 81 %, (P = 0.02) and clinical pregnancy rate 1/OR 1.42 [95 % CI 1.03, 2.0], I2 70 %, P = 0.03. There was no overall difference in live birth rate 1/OR 1.12 [95 % CI 0.70, 1.79], I2 = 78 %, p = 0.63), miscarriage rate 1/OR 0.92 [95 % CI 0.63, 1.28, P = 0.61, I2 0 % or mean number of oocytes retrieved (10 oocytes [IQR 8.95; 11.15] vs. 9.28 [IQR 8; 10.20], p = 0.22) between groups. CONCLUSIONS AND RELEVANCE: The benefit of prolonged GnRHa treatment in women with adenomyosis undergoing assisted conception treatment is uncertain based on existing retrospective studies. Implantation and clinical pregnancy rates were higher following prolonged downregulation in this population, though there was no statistically significant difference in live birth and miscarriage rates. Given the limited, low-quality existing data, there is a need for a well-designed, prospective randomised controlled trial to precisely evaluate the effectiveness of prolonged GnRHa treatment in this population.

Ovarian hyperstimulation syndrome without gonadotropin stimulation: an unusual response to a GnRH agonist.

Ovarian hyperstimulation syndrome (OHSS) is a well-known iatrogenic complication of ovarian stimulation with gonadotropins. We present the case of a woman in her 30s who developed OHSS without the administration of gonadotropins. She was due to undergo intracytoplasmic sperm injection (ICSI) for primary subfertility. After taking a gonadotropin-releasing hormone (GnRH) receptor agonist for 3 weeks, she presented with abdominal pain, nausea and bloating. She was diagnosed with moderate to severe OHSS, requiring management as an inpatient.Investigations included a pelvic ultrasound scan showing an enlarged ovary, serum oestradiol >30 000 pmol/L and an MRI of the brain with an incidental finding of a 5 mm pituitary microadenoma.She recovered rapidly and was referred for endocrinology evaluation and multidisciplinary team discussion. The OHSS was felt to be explained by an unusual 'flare' response to a GnRH agonist. A further ICSI cycle with an antagonist protocol is planned.

Ovarian hyperthecosis in adolescent females: two case reports and a review of the literature.

OBJECTIVES: Ovarian hyperthecosis (OHT) is a rare cause of severe hyperandrogenism in the adolescent age group. We describe two case reports, and present an approach to management in this age group based on a review of the literature. CASE PRESENTATION: Patient A presented at age 13 years with a 2 year history of androphonia and hirsuitism. Her testosterone level was elevated at 8.3 nmol/L, and there was marked enlargement of her ovaries bilaterally. There were no focal adrenal or ovarian lesions identified on imaging. She was treated with a gonadotropin releasing hormone (GnRH) agonist and spironolactone with biochemical and clinical improvement. Patient B presented at age 14 years with secondary amenorrhoea, and a 2 year history of androphonia, hirsutism and androgenetic alopecia. Her testosterone level was 12 nmol/L, and a pelvic ultrasound revealed numerous follicles in each ovary which were otherwise normal in size. She was managed with GnRH agonist initially, and now continues on a combined oral contraceptive pill. CONCLUSIONS: Ovarian hyperthecosis needs to be considered in pre-menopausal women presenting with severe hyperandrogenism, after exclusion of androgen-producing adrenal and ovarian tumours. The principles of management in this age group are gonadotropin suppression and hormone replacement.