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Adenomyosis is a commonly encountered pathology in women of reproductive age and frequently coexists with infertility. The effect of adenomyosis on fertility, particularly on in vitro fertilisation and intracytoplasmic sperm injection outcomes, is not well understood. Various pretreatment modalities have been used to improve pregnancy rates and live birth outcomes; however, because of a lack of high-quality evidence, there is no clear consensus on the best pretreatment option. This review was conducted through a PubMed search aiming to highlight the relationship between pretreatment and fertility in women with adenomyosis. Medical, ablative surgical, and non-surgical therapies were reviewed. According to the current literature, gonadotropin-releasing hormone agonist therapy and placement of a levonorgestrel intrauterine system are two suitable medical pretreatment strategies that can improve the clinical pregnancy rates of patients with adenomyosis. Surgical ablation of adenomyosis can also be beneficial, although surgical management can be challenging. Non-surgical thermal techniques, including high-intensity focused ultrasound ablation, percutaneous microwave ablation, and radiofrequency ablation, are much less invasive techniques that have shown effectiveness in improving fertility. Although evidence remains limited, all these procedures have demonstrated a favourable safety profile. Further studies are needed to better develop these techniques and demonstrate their effectiveness. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Design Setting Population Methods Main Outcome Measures Results Conclusions To investigate the effect of gonadotropin‐releasing hormone agonist (GnRHa) pre‐treatment on the clinical outcomes of fresh and frozen embryo transfers (ETs and FETs, respectively) in infertile patients with adenomyosis.Retrospective cohort study with literature review.Peking University First Hospital.We analysed 413 cycles of 369 women with adenomyosis who underwent ETs or FETs.We performed logistic regression analysis and meta‐analysis to assess the association of GnRHa pre‐treatment with the clinical outcomes of ETs and FETs.The live birth rate (LBR) was compared between patients with and without GnRHa pre‐treatment.The LBR was higher in the GnRHa pre‐treatment group than in the non‐GnRHa pre‐treatment group in ETs (41.27% vs. 24.32%, p = 0.034) and FETs (40.36% vs. 20.75%, p = 0.008). The odds of achieving a live birth of women with GnRHa pre‐treatment were 2.65 times higher than that of those without (95% CI: 1.19–5.92, p = 0.017) after adjusting for confounders in ETs. Similarly, the adjusted odds ratio (OR) was 2.43 (95% CI: 1.10–5.40, p = 0.029) in FETs. For the meta‐analysis, eight studies met the inclusion criteria; however, only six reported the adjusted ORs. Combination of these six adjusted ORs with our results revealed that the GnRHa pre‐treatment group had higher LBRs than the non‐GnRHa pre‐treatment group (ET: OR 1.71, 95% CI: 1.30–2.26, FET: OR 2.61, 95% CI: 1.52–4.49).In women with adenomyosis, GnRHa pre‐treatment may be beneficial for LBRs following both ETs and FETs. [ABSTRACT FROM AUTHOR]

Aim: To investigate the efficacy and safety of long‐term adjusted low‐dose gonadotropin‐releasing hormone agonist therapy (GnRH agonist drawback therapy) with nafarelin acetate in patients with uterine fibroids and/or adenomyosis with menstrual symptoms. Methods: This single‐center, retrospective, observational study initially included 118 patients with uterine fibroids and/or adenomyosis with menstrual symptoms who had received GnRH agonist (nafarelin acetate) drawback therapy for at least 7 months between 2010 and 2020. Blood hemoglobin level, maximum fibroid diameter, area of the corpus uteri, blood estradiol level, daily dosage of nafarelin acetate, and bone density in the lumbar spine and femoral neck were assessed before and after the treatment initiation. Results: The median treatment period was 28 months. Menstruation had ceased in all patients. The median hemoglobin level significantly increased from 8.6 to 13.2 g/dL before treatment and at 12 months after the treatment initiation in patients with fibroids and from 8.8 to 13.3 g/dL in patients with adenomyosis, respectively. Although the treatment did not exert a significant shrinking effect on the fibroids and adenomyosis, an increase in their size was not observed in any patient. The initial dose of nafarelin acetate was 400 μg/day and was lowered to 130 μg/day at 12 months. Only 29 patients (25%) had an estradiol level <30 pg/mL. The average rate of bone density change over 6 months was −1.23% in the lumbar spine and −1.12% in the femoral neck in patients with fibroids and −1.06% in the lumbar spine and −0.14% in the femoral neck in patients with adenomyosis, which were lower than the previously reported rates. Conclusions: GnRH agonist drawback therapy was found to be useful for the long‐term conservative treatment of uterine fibroids and adenomyosis. The treatment was safely and inexpensively performed with few adverse events. [ABSTRACT FROM AUTHOR]

Background: Conservative surgery for adenomyosis has been shown to be effective. However, risk factors for postoperative recurrence have yet to be clarified. In this study, we aimed to determine the recurrence rate after conservative surgery for adenomyosis and identify the risk factors for recurrence. Methods: This retrospective study was conducted in a tertiary hospital. Patients who underwent conservative surgery for adenomyosis between January 2013 and April 2023 were identified. Eligible patients were assigned to either the recurrent or non-recurrent group. Continuous and categorical variables were compared between the two groups using the Mann–Whitney U test or chi-squared test. Risk factors for recurrence were identified by Cox proportional risk analysis. Results: Data for 133 eligible patients who underwent conservative surgery for adenomyosis were analyzed. The mean follow-up duration was 52 months. The recurrence rate after conservative surgery was 39.1% (52/133). Cox proportional risk analysis identified adenomyosis involving the posterior uterine wall (hazard ratio [HR] 6.505, P = 0.018), two or more adenomyotic lesions (HR 6.310, P = 0.030), laparotomy (HR 2.490, P = 0.029), and concomitant endometriosis (HR 2.313, P = 0.036) to be risk factors for recurrence after conservative surgery. Postoperative combined progestogen therapy (HR 0.126, P < 0.001) or treatment with a gonadotropin-releasing hormone agonist (GnRHa) (HR 0.237, P = 0.004) prevented recurrence of adenomyosis. Conclusion: Adenomyosis continues to have a relatively high long-term recurrence rate after conservative surgery. Patients with adenomyosis involving the posterior wall of the uterus, those with two or more adenomyotic lesions, and those with concomitant endometriosis are at high risk for recurrence after conservative surgery. Postoperative progestogen or GnRHa therapy may reduce the risk of recurrence of adenomyosis. Considering the retrospective nature of this study and its small sample size, larger prospective studies are needed to confirm its findings. [ABSTRACT FROM AUTHOR]

There are known sex differences in cardiorespiratory fitness (CRF). Little is known about the impact of pubertal blockade with a gonadotropin-releasing hormone agonist (GnRHa) followed by hormone therapy on CRF for transgender adolescents. We aimed to 1) determine the effect of GnRHa monotherapy on CRF and mitochondrial function and associations with metabolomic profiles and 2) evaluate changes after 1 and 12 mo of testosterone therapy among transgender adolescents. Participants assigned female at birth (n = 19, baseline age of 15.0 ± 1.0 yr) from two groups: GnRHa+ (n = 8) and GnRHa− (n = 11) were examined at baseline and 1- and 12-mo post-testosterone therapy in a longitudinal observational study to assess cardiorespiratory fitness, mitochondrial respiration, and metabolic profile. Fasted morning labs included assessment of metabolomics and peripheral blood mononuclear cell mitochondrial respiration and degree of mitochondrial coupling (respiratory control ratio, RCR). A graded cycle ergometer test was performed. Baseline differences were evaluated between groups. Changes were compared with mixed linear regression models evaluating time (baseline, 1 mo, and 12 mo), group (GnRHa treatment yes/no), and their interaction. At baseline GnRHa+ individuals had higher relative V̇ o 2peak (30.1 ± 4.83 vs. 25.24 ± 4.47 mL/kg/min, P = 0.042) than GnRHa− individuals. In regression models, GnRHa+ individuals had a significant increase in peak watts (P = 0.011) and total exercise time (P = 0.005) after 12 mo of testosterone (P = 0.012) but not GnRHa− individuals. GnRHa+ individuals have significantly higher RCR under carbohydrate (P = 0.0007) and lipid (P = 0.0002) conditions than GnRHa+ individuals. Pretreatment with GnRHa positively influences peak CRF and mitochondrial respiration in adolescent transgender males undergoing testosterone therapy. NEW & NOTEWORTHY: This study demonstrates differences in exercise capacity and mitochondrial respiration at baseline based on whether or not individuals had feminizing puberty blocked. Individuals who had puberty blocked had greater improvements in cardiopulmonary exercise testing parameters after 12 mo of testosterone than those who went through feminizing puberty. [ABSTRACT FROM AUTHOR]

Abstract Background Conservative surgery for adenomyosis has been shown to be effective. However, risk factors for postoperative recurrence have yet to be clarified. In this study, we aimed to determine the recurrence rate after conservative surgery for adenomyosis and identify the risk factors for recurrence. Methods This retrospective study was conducted in a tertiary hospital. Patients who underwent conservative surgery for adenomyosis between January 2013 and April 2023 were identified. Eligible patients were assigned to either the recurrent or non-recurrent group. Continuous and categorical variables were compared between the two groups using the Mann–Whitney U test or chi-squared test. Risk factors for recurrence were identified by Cox proportional risk analysis. Results Data for 133 eligible patients who underwent conservative surgery for adenomyosis were analyzed. The mean follow-up duration was 52 months. The recurrence rate after conservative surgery was 39.1% (52/133). Cox proportional risk analysis identified adenomyosis involving the posterior uterine wall (hazard ratio [HR] 6.505, P = 0.018), two or more adenomyotic lesions (HR 6.310, P = 0.030), laparotomy (HR 2.490, P = 0.029), and concomitant endometriosis (HR 2.313, P = 0.036) to be risk factors for recurrence after conservative surgery. Postoperative combined progestogen therapy (HR 0.126, P

Objective：To investigate the effect of gonadotropin ⁃ releasing hormone agonist（GnRH ⁃ a）trigger on the laboratory technical indicators of embryos during natural cycle in vitro fertilization（IVF）in patients with diminished ovarian reserve（DOR). Methods：A retrospective study was conducted to analyze the data of patients with DOR who underwent natural IVF cycles in the Reproductive Medicine Center of the Affiliated Obstetrics and Gynaecology Hospital of Nanjing Medical University from January 1, 2018 to April 30, 2023. According to whether the GnRH⁃a trigger was used, the patients were divided into the trigger group and the non⁃trigger group, with 300 cycles in the trigger group and 47 cycles in the non⁃trigger group. A 1∶3 propensity score matching（PSM） was performed to compare the total number of oocytes retrieved, transferable embryos, high⁃quality embryos normal fertilization rate, oocyte utilization rate, high⁃quality embryos rate, and non⁃retrieved oocytes rate between the two groups. Results：A total of 165 cycles were included the（46 cycles in the non⁃trigger group and 119 cycles in the trigger group）after PSM, and the high⁃quality embryo rate in the trigger group was higher than that in the non⁃trigger group（61.1% vs. 35.0%, P=0.045). There were no significant differences in the total number of oocytes retrieved, the number of transferable embryos, the number of high⁃quality embryos, the normal fertilization rate, the oocyte utilization rate, and the non⁃retrieved oocyte rate between the two groups（all P > 0.05). Conclusion：The use of GnRH⁃a trigger during the natural cycle can improve the rate of high⁃quality embryos in patients with DOR. [ABSTRACT FROM AUTHOR]

Purpose of reviewThe purpose of this review is to summarize the scientific evidence on bone health in transgender and gender diverse (TGD) youth.Recent findingsGender-affirming medical therapies may be introduced during a key window of skeletal development in TGD adolescents. Before treatment, low bone density for age is more prevalent than expected in TGD youth. Bone mineral density Z-scores decrease with gonadotropin-releasing hormone agonists and differentially respond to subsequent estradiol or testosterone. Risk factors for low bone density in this population include low body mass index, low physical activity, male sex designated at birth, and vitamin D deficiency. Peak bone mass attainment and implications for future fracture risk are not yet known. TGD youth have higher than expected rates of low bone density prior to initiation of gender-affirming medical therapy. More studies are needed to understand the skeletal trajectories of TGD youth receiving medical interventions during puberty.

Adenomyosis is a commonly encountered pathology in women of reproductive age and frequently coexists with infertility. The effect of adenomyosis on fertility, particularly on in vitro fertilisation and intracytoplasmic sperm injection outcomes, is not well understood. Various pretreatment modalities have been used to improve pregnancy rates and live birth outcomes; however, because of a lack of high-quality evidence, there is no clear consensus on the best pretreatment option. This review was conducted through a PubMed search aiming to highlight the relationship between pretreatment and fertility in women with adenomyosis. Medical, ablative surgical, and non-surgical therapies were reviewed. According to the current literature, gonadotropin-releasing hormone agonist therapy and placement of a levonorgestrel intrauterine system are two suitable medical pretreatment strategies that can improve the clinical pregnancy rates of patients with adenomyosis. Surgical ablation of adenomyosis can also be beneficial, although surgical management can be challenging. Non-surgical thermal techniques, including high-intensity focused ultrasound ablation, percutaneous microwave ablation, and radiofrequency ablation, are much less invasive techniques that have shown effectiveness in improving fertility. Although evidence remains limited, all these procedures have demonstrated a favourable safety profile. Further studies are needed to better develop these techniques and demonstrate their effectiveness.

ContextTreatment options for central precocious puberty (CPP) are important for individualization of therapy.ObjectiveWe evaluated the efficacy and safety of 6-month 45-mg leuprolide acetate (LA) depot with intramuscular administration.MethodsLA depot was administered at weeks 0 and 24 to treatment-naïve (n = 27) or previously treated (n = 18) children with CPP in a phase 3, multicenter, single-arm, open-label study (NCT03695237). Week 24 peak-stimulated luteinizing hormone (LH) suppression (

Background: There is an ongoing debate about the optimal dosage of gonadotropin-releasing hormone (GnRH)agonist for oocyte triggering in polycystic ovarian syndrome (PCOS) patients at risk for ovarian hyperstimulation syndrome(OHSS). In this study, we intend to ascertain whether the use of repeated doses of a GnRH agonist for oocytetriggering in these patients can enhance the outcomes of controlled ovarian stimulation (COS) for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.Materials and Methods: This randomised clinical trial enrolled 70 PCOS women candidates for IVF/ICSI with thestandard antagonist protocol at Royan Institute (Tehran, Iran) from May 2020 to June 2022. Patients at risk of OHSSwith oestradiol (E2) levels >3000 pg/ml on the day of trigger were randomly assigned to a control or experimentalgroup. Group A (control group) patients received 0.2 mg triptorelin (Decapeptyl®) for final oocyte maturation. GroupB (experimental group) patients received a second dose of 0.1 mg Decapeptyl®12 hours after their first dose, for a totaldose of 0.3 mg. IVF/ICSI outcomes were compared between the groups.Results: Ultimately, 35 women from the study group and 33 from the control group completed the treatment cycle. Bothgroups were comparable in terms of demographic characteristics, baseline hormonal profiles, and PCOS phenotypes.The dosage of gonadotropin, stimulation duration, number of retrieved oocytes, oocyte maturation rate, and oocyte recoveryratio did not significantly differ between the groups. No significant differences were found in terms of the numberof blastocyst and cleavage embryos, nor the quality of obtained embryos between the groups. The mild to moderateOHSS rate was significantly lower in the study group (P=0.038).Conclusion: A second dose of GnRH agonist 12 hours after the first dose did not improve the number and maturity ofoocytes, or pregnancy outcomes in PCOS patients (registration number: NCT04600986).

Background: There is an ongoing debate about the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for oocyte triggering in polycystic ovarian syndrome (PCOS) patients at risk for ovarian hyperstimulation syndrome (OHSS). In this study, we intend to ascertain whether the use of repeated doses of a GnRH agonist for oocyte triggering in these patients can enhance the outcomes of controlled ovarian stimulation (COS) for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Materials and Methods: This randomised clinical trial enrolled 70 PCOS women candidates for IVF/ICSI with the standard antagonist protocol at Royan Institute (Tehran, Iran) from May 2020 to June 2022. Patients at risk of OHSS with oestradiol (E2) levels >3000 pg/ml on the day of trigger were randomly assigned to a control or experimental group. Group A (control group) patients received 0.2 mg triptorelin (Decapeptyl®) for final oocyte maturation. Group B (experimental group) patients received a second dose of 0.1 mg Decapeptyl®12 hours after their first dose, for a total dose of 0.3 mg. IVF/ICSI outcomes were compared between the groups. Results: Ultimately, 35 women from the study group and 33 from the control group completed the treatment cycle. Both groups were comparable in terms of demographic characteristics, baseline hormonal profiles, and PCOS phenotypes. The dosage of gonadotropin, stimulation duration, number of retrieved oocytes, oocyte maturation rate, and oocyte recovery ratio did not significantly differ between the groups. No significant differences were found in terms of the number of blastocyst and cleavage embryos, nor the quality of obtained embryos between the groups. The mild to moderate OHSS rate was significantly lower in the study group (P=0.038). Conclusion: A second dose of GnRH agonist 12 hours after the first dose did not improve the number and maturity of oocytes, or pregnancy outcomes in PCOS patients (registration number: NCT04600986). [ABSTRACT FROM AUTHOR]

Some transgender youth are treated with gonadotropin-releasing hormone agonists (GnRHa) followed by testosterone or estradiol, which may impact bone mineral density (BMD). This cross-sectional study of transgender youth (n = 56, aged 10.4-19.8 years, 53% assigned female at birth [AFAB]) utilized total body dual-energy x-ray absorptiometry to evaluate BMD Z-scores, and associations between GnRHa duration, body mass index (BMI), and BMD. Participants on GnRHa alone (n = 19, 14 assigned male at birth [AMAB], 5 AFAB) at the time of the study visit were 13.8 [12.8, 15.3] (median [IQR]) years old, had been on GnRHa for 10 [5.5, 19.5] months, and began GnRHa at age 12 [10.4, 12.6] years. Total body BMD Z-score for individuals on GnRHa monotherapy was −0.10 [−0.8, 0.4] (AFAB, female norms) and −0.65 [−1.4, 0.22] (AMAB, male norms). AFAB participants (n = 21) on testosterone were age 16.7 [15.9, 17.8] years, had been on testosterone for 11 [7.3, 14.5] months, and started testosterone at age 16 [14.8, 16.8] years; total body BMD Z-score −0.2 [−0.5, 0] (male norms) and 0.4 [−0.2, 0.7] (female norms). AMAB participants (n = 16) were age 16.2 [15.1, 17.4] years, had been on estradiol for 11 [5.6, 13.7] months, and started estradiol at age 16 [14.4, 16.7] years; total body BMD Z-score −0.4 [−1.1, 0.3] (male norms) and −0.2 [−0.7, 0.6] (female norms). BMD Z-score was negatively correlated with GnRHa duration (male norms: r = −0.5, P =.005; female norms: r = −0.4, P =.029) and positively correlated with BMI (male norms: r = 0.4, P =.003; female norms: r = 0.4, P =.004). In this cross-sectional cohort, total body BMD Z-scores were slightly below average, but lowest in the AMAB group on GnRHa monotherapy. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of GnRH agonist (GnRH-a) down-regulation prior to hormone replacement treatment (HRT) to prepare the endometrium in frozen embryo transfer (FET) cycles in women of different ages. Methods: This was a retrospective study, and after excluding patients with adenomyosis, endometriosis, severe endometrial adhesions, polycystic ovary syndrome (PCOS), and repeated embryo implantation failures, a total of 4,091 HRT cycles were collected. Patients were divided into group A (<35 years old) and group B (≥35 years old), and each group was further divided into HRT and GnRHa-HRT groups. The clinical outcomes were compared between groups. Results: There was no statistically significant difference in clinical outcomes between the HRT and GnRHa-HRT groups among women aged <35 years. In women of advanced age, higher rates of clinical pregnancy and live birth were seen in the GnRHa-HRT group. Logistic regression analysis showed that female age and number of embryos transferred influenced the live birth rate in FET cycles, and in women aged ≥ 35 years, the use of GnRH-a down-regulation prior to HRT improved pregnancy outcomes. Conclusions: In elderly woman without adenomyosis, endometriosis, PCOS, severe uterine adhesions, and RIF, hormone replacement treatment with GnRH agonist for pituitary suppression can improve the live birth rate of FET cycles. [ABSTRACT FROM AUTHOR]

This study investigates the effect of GnRHa pretreatment on pregnancy outcomes in artificial endometrial preparation for frozen–thawed embryo transfer (AC-FET) cycles. A systematic review of English language studies published before 1 September 2022, was conducted, excluding conference papers and preprints. Forty-one studies involving 43,021 participants were analyzed using meta-analysis, with a sensitivity analysis ensuring result robustness. The study found that GnRHa pretreatment generally improved the clinical pregnancy rate (CPR), implantation rate (IR), and live birth rate (LBR). However, discrepancies existed between randomized controlled trials (RCTs) and observational studies; RCTs showed no significant differences in outcomes for GnRHa-treated cycles. Depot GnRHa protocols outperformed daily regimens in LBR. Extended GnRHa pretreatment (two to five cycles) significantly improved CPR and IR compared to shorter treatment. Women with polycystic ovary syndrome (PCOS) saw substantial benefits from GnRHa pretreatment, including improved CPR and LBR and reduced miscarriage rates. In contrast, no significant benefits were observed in women with regular menstruation. More rigorous research is needed to solidify these findings. [ABSTRACT FROM AUTHOR]

Objective: To compare the reproductive pregnancy outcomes of pretreatment with long-acting gonadotropin-releasing hormone agonist (GnRH-a) plus hormone replacement therapy (HRT) with HRT-only cycles, and investigate differences between single polypectomy and multiple polypectomies, and between one or two doses of GnRH-a. Materials and methods: This was a retrospective cohort study on patients undergoing polypectomy who underwent frozen–thawed embryo transfer (FET) from March 2018 to May 2019. They were divided into GnRH-a pretreatment and HRT-only groups. Each group was divided into single polypectomy or multiple polypectomies (in a single hysteroscopic session) subgroups. Clinical pregnancy rate and live birth rate (LBR) were the main outcomes. The effect of GnRH-a dosage was further analysed. Results: There were 212 GnRH-a pretreatment cases (45 single and 167 multiple polyps) and 448 HRT-only cases (228 single and 220 multiple polyps). The LBR of the GnRH-a pretreatment group (53.3%) was significantly higher than the HRT group (43.3%; P = 0.016). Logistic regression analysis showed that GnRH-a pretreatment significantly affected the LBR (odds ratio, OR 1.470, 95% confidence interval, Cl 1.046–2.065; P = 0.026). In the multiple polypectomy subgroup, the LBR with GnRH-a pretreatment was higher than with HRT-only (54.5% vs 43.6%; P = 0.034). However, the LBR was not different between the respective single polypectomy subgroups (48.9% vs 43.0%; P = 0.466). For patients with multiple polyps, two GnRH-a pretreatments produced a higher LBR than a single GnRH-a pretreatment (62.7% vs 47.8%), but without significant difference (P = 0.055). Conclusion: GnRH-a pretreatment improved the LBR for FET cycles after hysteroscopic multiple polypectomies, independent of dose.

Introduction: Superovulation is a critical step in assisted reproductive technology, but the use of human chorionic gonadotropin (hCG) as a trigger for superovulation can result in ovarian hyperstimulation. Thus, the use of Gonadotropin-releasing hormone agonist (GnRHa) trigger has been increasingly adopted, although it has been associated with a higher rate of pregnancy failure compared to natural cycles. This study aimed to investigate the effect of GnRHa trigger on embryo implantation in a mouse model. Methods: Mice in the superovulation (PG) group were administered 7.5 IU of PMSG, followed by the injection of 3.5 mg of GnRHa (Leuprorelin) 48 h later, whilemice in the control group (CTR) mated naturally. We compared the number of oocytes, blastocysts, and corpus luteum between the two groups and the implantation sites after the transfer of natural blastocysts. Ovaries, uterus, and serum 2 and 4 days after mating were collected for qRT-PCR, transcriptome sequencing, and hormone assays. Results: The PG group had more oocytes, blastocysts, and corpus luteum after superovulation than the CTR group. However, the mRNA expression of leukemia inhibitory factor (Lif) and the number of implantation sites were reduced in the PG group. The ELISA assay revealed that superovulation increased ovarian estrogen secretion. The transcriptome analysis showed that superphysiological estrogen led to a response of the uterus to a high estrogen signal, resulting in abnormal endometrium and extracellular matrix remodeling and up-regulation of ion transport and inflammation-related genes. Conclusion: Our findings suggest that a combination of PMSG and GnRHa trigger impaired embryo implantation in mice, as the excessive uterine response to superphysiological estrogen levels can lead to the change of gene expression related to endometrial remodeling, abnormal expression of uterine ion transport genes and excessive immune-related genes. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of GnRH agonist (GnRH-a) down-regulation prior to hormone replacement treatment (HRT) to prepare the endometrium in frozen embryo transfer (FET) cycles in women of different ages. Methods This was a retrospective study, and after excluding patients with adenomyosis, endometriosis, severe endometrial adhesions, polycystic ovary syndrome (PCOS), and repeated embryo implantation failures, a total of 4,091 HRT cycles were collected. Patients were divided into group A (

Abstract Background Diphereline is a Gonadotropin-Releasing Hormone agonist commonly used in patients with breast cancer. This study aimed to compare the efficacy and safety of one-month and three-month Microrelin injections produced by Homa Pharmed Company with three-month Diphereline injections manufactured by IPSEN, France. Methods The study was a non-inferiority randomized clinical trial conducted between 2019 and 2023 on premenopausal women candidates for endocrine therapy. The participants were randomly assigned in blocks of six to one of three groups named A (Diphereline 11.25 mg), B (Microrelin 11.25 mg), and C (Microrelin 3.75 mg). The participants’ menopausal symptoms, estradiol, and FSH serum levels were recorded in three-month intervals for one year. The efficacy of each medication and its side effects were compared among the three groups by statistical analysis during the one-year follow-up. Results The study included 133 patients with breast cancer. A decreasing trend in the serum levels of FSH and estradiol and an increasing trend of menopausal symptoms were recorded during the study. No specific side effects leading to drug disruption, hospitalization, or exclusion from the study were observed. Adjusting the effect of study group and time showed no significant changes in estradiol levels between groups B (p = 0.506) and C (p = 0.607) and group A. Also, serum FSH changes between groups B (p = 0.132) and C (p = 0.104) compared to group A were not significant. Moreover, the menopausal symptoms during the one-year follow-up did not significantly increase in group B (p = 0.108) and C (p = 0.113) compared to group A. Conclusions It can be concluded that injections of both Microrelin 11.25 mg and 3.75 mg, produced by Homa Pharmed, Iran, are non-inferior in terms of effectiveness and incidence of menopausal symptoms compared to Diphereline, manufactured by IPSEN, France. Trial registration IRCT.ir, IRCT20201227049847N1; Registered on 09/01/2021.

Ting Deng, Yin Lin, Li Chen, Jun-Ying Jiang Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, People’s Republic of ChinaCorrespondence: Jun-Ying Jiang, Email 1057851146@qq.comObjective: To compare the spontaneous pregnancy rates between dydrogesterone and Gonadotropin-releasing hormone agonist (GnRH-a) treatments in patients with endometriosis stage III and IV after laparoscopy.Methods: The clinical data of patients with endometriosis stage III and IV administered laparoscopic surgery in our hospital from January 2018 to March 2020 were retrospectively analyzed. Totally 151 cases were divided into two groups according to postoperative medication, including the study (70 cases) and control (81 cases) groups treated with dydrogesterone and GnRH-a, respectively. The spontaneous pregnancy and subsequent pregnancy outcomes were assessed within 12 months.Results: Totally 49 patients had spontaneous pregnancy. Among them, there were 31 cases in the dydrogesterone group (spontaneous pregnancy rate of 44.3%, 31/70), including 25 live birth cases (35.7%, 25/70), 4 miscarriage cases, and 2 ectopic pregnancy cases. The time to conception was 1– 10 months (median value of 5 months). Totally 18 cases in the GnRH-a group had spontaneous pregnancy (22.2%, 18/81), including 16 live birth cases (19.8%, 16/81). 81) and 2 miscarriage cases; the time to conception was 3– 11 months (median value of 6 months). There were significant differences in spontaneous pregnancy rate and cumulative spontaneous pregnancy rate between the two groups (P = 0.005 and 0.003, respectively).Conclusion: Dydrogesterone after laparoscopic surgery in patients with endometriosis stage III and IV improved the natural pregnancy rate.Keywords: endometriosis, laparoscopic surgery, dydrogesterone, gonadotropin-releasing hormone agonist, spontaneous pregnancy

Purpose: There are no definite guidelines on the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for treatment of central precocious puberty (CPP). We compared growth outcomes of GnRH agonist at different dosages in girls with idiopathic CPP to assess the optimal dosage. Methods: This retrospective study included 86 girls with idiopathic CPP who had been treated with GnRH agonist for at least one year and had attained their final adult height. Leuprolide was given as fixed dosage (3.75 mg every 4 weeks in body weight >20 kg, n=72) or weight-based dosage (60-85 μg/kg every 4 weeks, n=14). We compared suppression of advanced puberty and treatment response between the 2 groups. Results: Peak estradiol and luteinizing hormone and bone age (BA)/chronological age after injection of GnRH agonist were effectively suppressed in both groups. In both groups, the height standard deviation score (SDS) for BA increased after treatment. Final adult height (FAH) (fixed dosage group,160.8±4.1 cm and weight-based dosage group, 161.2±4.4 cm) was significantly higher than the initial predicted adult height (PAH) (155.5±3.3 and 156.1±3.6 cm, respectively) (both P<0.001) and similar to midparental height (159.8±3.3 and 160.6±3.7 cm, respectively). There were no differences in gain in height SDS for BA and gain in height (FAH-PAH at the start) between the 2 groups. Conclusion: There were no differences in treatment outcome between fixed dosage (3.75 mg/4 wk) and weight-based dosage (60-85 μg/kg/4wk) of GnRH agonist. Therefore, a fixed dosage of GnRH agonist can be used more conveniently for CPP treatment without growth oversuppression. [ABSTRACT FROM AUTHOR]

Aim: The aim of this systematic review was to assess the effects on psychosocial and mental health, cognition, body composition, and metabolic markers of hormone treatment in children with gender dysphoria. Methods: Systematic review essentially follows PRISMA. We searched PubMed, EMBASE and thirteen other databases until 9 November 2021 for English‐language studies of hormone therapy in children with gender dysphoria. Of 9934 potential studies identified with abstracts reviewed, 195 were assessed in full text, and 24 were relevant. Results: In 21 studies, adolescents were given gonadotropin‐releasing hormone analogues (GnRHa) treatment. In three studies, cross‐sex hormone treatment (CSHT) was given without previous GnRHa treatment. No randomised controlled trials were identified. The few longitudinal observational studies were hampered by small numbers and high attrition rates. Hence, the long‐term effects of hormone therapy on psychosocial health could not be evaluated. Concerning bone health, GnRHa treatment delays bone maturation and bone mineral density gain, which, however, was found to partially recover during CSHT when studied at age 22 years. Conclusion: Evidence to assess the effects of hormone treatment on the above fields in children with gender dysphoria is insufficient. To improve future research, we present the GENDHOR checklist, a checklist for studies in gender dysphoria. [ABSTRACT FROM AUTHOR]

Gonadotropin-releasing hormone agonist (GnRHa) has been used for central precocious puberty (CPP) or early and fast puberty. It was aimed to assess changes in body mass index (BMI), polycystic ovary syndrome (PCOS) frequency, and anti-Müllerian hormone (AMH) in girls who had been treated with GnRHa. Fifty-eight adolescent girls treated with GnRHa for CPP or early and fast puberty (3.75 mg/28 days), between 2011 and 2015, were re-evaluated in 2020–2022 at least 2 years after menstruation. Hormonal analyses were compared with 51 healthy adolescents. In the GnRHa-treated group, a statistically significant increase was observed when the BMI standard deviation score (SDS) at the beginning of the treatment was compared with the BMI SDS at the end of the treatment (p=0.038). A statistically significant decrease was observed when the BMI SDS at the end of the treatment was compared with the BMI SDS in late adolescence (p=0.012). When the BMI SDS at the beginning of the treatment was compared with the BMI SDS in late adolescence, it was observed that there was no statistically significant difference (p=0.196). Of the 58 girls in the GnRHa-treated group, 8 (14 %) had PCOS. Serum AMH levels did not differ between the GnRHa-treated and the control group. GnRHa treatment causes no adverse effect on BMI, at least in late adolescence. Girls treated with GnRHa were not found to be prone to developing PCOS. AMH levels were similar in the GnRHa-treated group as in the control group. [ABSTRACT FROM AUTHOR]

To explore the use duration of a gonadotropin-releasing hormone agonists (GnRHa) plus add-back in adolescents with laparoscopically confirmed endometriosis and the treatment course before and after GnRHa therapy. Retrospective cohort study. We identified 51 subjects with laparoscopically confirmed endometriosis who had participated in a randomized trial of a GnRHa plus add-back as adolescents between 2008 and 2012. Electronic medical records were reviewed to obtain demographic data, clinical characteristics, and treatment outcomes after trial completion. The study was deemed IRB exempt. The average age of participants during trial enrollment was 17.9 ± 1.7 years. Thirty-three participants had stage I endometriosis (65%). The most common treatments trialed before GnRHa therapy were combined oral contraceptives (n = 47, 92%) and progestin-only pills (n = 23, 45%). The average duration of GnRHa use during the trial was 9.5 ± 3.5 months; 34 subjects (67%) completed the 1-year trial. After trial completion, 23 subjects (45%) continued to use a GnRHa with add-back therapy. The mean duration of additional GnRHa use was 31.7 ± 28.6 months, and the longest identified duration was an additional 96 months. Twenty-four subjects switched to other hormonal treatments after trial participation, most commonly oral progestins (n = 15) or combined oral contraceptives (n = 6). Thirteen participants (25%) returned to a therapy that had been trialed before GnRHa use. Almost half the participants in this cohort continued to use a GnRHa with add-back for treatment of endometriosis beyond the 12-month recommended duration. Treatment varied widely after discontinuation of GnRHa, with many participants returning to previously trialed medical therapies. [ABSTRACT FROM AUTHOR]

Objective: To provide perspectives on preoperative diagnosis and conservative treatment for diffuse uterine leiomyomatosis (DUL). Methods: The clinical characteristics, management, and outcome of the five cases diagnosed with DUL receiving surgical treatment at Peking Union Medical College Hospital between January 2010 and December 2021 were retrospectively analyzed. Results: DUL is a diagnosis based on histopathology. It is a subtype of uterine leiomyoma, characterized by innumerable, poorly circumscribed hypercellular nodules of bland smooth muscle cells with no cytologic atypia diffusely involving the myometrium. Clinical manifestations, including menorrhagia, anemia, and infertility, are similar to those of typical uterine leiomyomas, making a definitive preoperative diagnosis difficult. Magnetic resonance imaging plays an important role in the pre‐treatment mapping. Conservative surgery can reduce the uterine volume and improve the contour of the uterine cavity, thereby relieving symptoms of menorrhagia and improving the chance of conception. Gonadotropin‐releasing hormone (GnRH) agonist therapy is of great significance for controlling vaginal bleeding, reducing uterine volume, and delaying postoperative recurrence, and can be used alone or as postoperative adjuvant therapy for conservative surgery. Conclusion: The treatment goal for DUL patients with fertility‐sparing request should not aim at complete fibroid removal. A successful pregnancy can be achieved following conservative surgery and/or GnRH agonist therapy. SYNOPSIS: The treatment goal for diffuse uterine leiomyomatosis should not be complete fibroid removal; a successful pregnancy can be achieved following conservative surgery and/or GnRH agonist therapy. [ABSTRACT FROM AUTHOR]

Among the most prevalent yet poorly understood female health issues is uterine leiomyomas. In order to preserve fertility and avoid or delay surgical intervention, medical treatments are typically considered first-line. Therapeutic benefits of GnRH antagonists, aromatase inhibitors, progestin, and selective progesterone receptor modulators have been studied for the treatment of irregular uterine bleeding and the reduction of fibroid volume. To compare the effect of gonadotropin-releasing hormone agonist (leuprolide acetate) vs. Aromatase inhibitor (Letrozole) on volume of uterine leiomyoma in pre-menopausal women with leiomyomas. Randomized Controlled Trial. The study was conducted at Obstretrics and Gynaecolocy Department of Tertiary Care Hospital of Lahore i.e, Lady Willingdon Hospital Lahore. The study duration was six months. Patients were split into two groups of 31 using a lottery system; Group-A and Group-B. Group-A received aromatase inhibitor (letrozole) tablets and long-acting GnRHa (leuprolide acetate) injections (Group-B). The Aromatase Inhibitor (Tab letrozole). Every participant was given a set of standard measurements. All ultrasound examinations and analyses were carried out by a trained sonologist, who most often used a transvaginal probe. Once the myoma was located, its volume was determined utilising a step-by-step planimetry approach and a unified piece of software. Mean values were determined from measurements taken at the beginning of treatment and again at weeks 4, 8, and 12. Statistical analysis showed no significant difference among Leuprolide acetate treatments after 12 weeks of administration, (10.42 vs. Letrazole's 9.95, p=0.626) and Letrazole (22.44 vs. Letrazole's 22.95, p=0.692) in terms of myoma volume reduction. Both groups had a drop in volume, but there were no statistically significant differences between treatments. Results of this study demonstrate no significant difference for leuprolide acetate and Letrozole on volume reduction of uterine leiomyoma in pre-menopausal women.

Purpose: Gonadotropin-releasing hormone agonist (GnRHa) before artificial cycle (AC) is expected to improve pregnancy outcomes in frozen-thawed embryo transfer (FET). Many studies have explored the impact of GnRHa pretreatment of AC in FET, but the results were inconsistent. This meta-analysis was performed to systematically evaluate the effect of GnRHa pretreatment on AC in FET. Methods: The last search was January 31, 2022. Randomized controlled trials and cohort studies aiming to assess the effect of GnRHa as the pretreatment of AC for endometrial preparation in FET were included. GnRHa was used before AC in the treatment group. In the control group, no pretreatment was used before AC. The eligible studies included at least one of the following outcomes: implantation, clinical pregnancy, and live birth. We calculated the odds ratio (OR) or mean difference (MD) and 95% confidence interval (CI) for each study and used a random-effects or fixed model to estimate the results. Results: 27 articles (10 RCTs and 17 non-RCTs) and 14152 patients were included. AC + GnRHa improved the implantation rate (OR = 1.31, 95% CI 1.03–1.66, I2 = 79%), clinical pregnancy rate (OR = 1.27, 95% CI 1.10–1.45, I2 = 53%), and live birth rate (OR = 1.16, 95% CI 1.05–1.29, I2 = 39%). We also found that AC + GnRHa increased the implantation rate (OR = 1.35, 95% CI 1.07–1.69, I2 = 53%) and clinical pregnancy rate (OR = 1.50, 95% CI 1.12–2.01, I2 = 50%) in repeated implantation failure. In addition, AC + GnRHa was positively associated with preterm birth (OR = 1.5, 95% CI 1.15–1.94, I2 = 0%). Conclusions: GnRHa pretreatment in FET can improve implantation, clinical pregnancy, and live birth rates, especially in patients with repeated implantation failure. GnRHa pretreatment seems to improve FET outcomes, though with a higher preterm birth rate. [ABSTRACT FROM AUTHOR]

Background: Frozen embryo transfer (FET) has become a widely used technique in assisted reproductive technology (ART) cycles. Various protocols have been developed to optimize outcomes, including hormone replacement therapy followed by frozen embryo transfer (HRT FET) cycles and non-stimulated FET (NC-FET) protocols. Additionally, the use of gonadotropinreleasing hormone analogues (GnRH-a) in combination with FET has been explored. However, comparative studies evaluating the effectiveness of these protocols on clinical pregnancy and live birth rates are limited. This study aimed to assess the efficacy of addition of GnRH-a during luteal support in FET different on clinical pregnancy and live birth. Methods: A retrospective cohort analysis was conducted on 3,515 data from patients undergoing FET cycles at the reproductive center of the Hospital of Zhengzhou University between February 2018 and December 2,021. Patients were divided into two groups based on the FET protocol utilized: GnRH-a (Triptorelin +existing treatment) group (1,033 patients) and non-GnRH-a group (existing treatment without Triptorelin) (2,458 patients) group. Clinical pregnancy rates and live birth rates were compared between these groups using appropriate statistical analyses. Results: The study revealed significantly enhanced clinical pregnancy rates (58.0% vs. 48.4%; p=0.003) and live birth rates (52.7% vs. 45.6%; p=0.001) specifically for HRT-FET cycles compared to controls. However, no significant differences were observed between NC-FET groups. Similarly, no statistical difference emerged when comparing GnRH-a plus HRT-FET or stimulation-FET cycles to their respective controls regarding both clinical pregnancy rates and live birth rates. Notably, within the GnRH-a group, a 47% increase in clinical pregnancy rates and a 33% rise in live birth rates were noted. Conclusion: Our findings suggest that HRT-FET cycles may be associated with improved clinical pregnancy and live birth rates compared to standard FET protocols. However, further studies are warranted to validate these results and explore the mechanisms underlying the observed differences in outcomes among different FET protocols. Additionally, the potential benefits of GnRH-a use in FET cycles warrant further investigation. [ABSTRACT FROM AUTHOR]

Gonadotropin-releasing hormone agonists (GnRHa) are used as an alternative to human chorionic gonadotropin (hCG) to trigger ovulation and decrease the risk of ovarian hyperstimulation syndrome. GnRHa is less potent at inducing ovarian vascular endothelial growth factor (VEGF), but may also affect endometrial angiogenesis and early placental development. In this study, we explore the effect of superovulation on endometrial angiogenesis during critical periods of gestation in a mouse model. We assigned female mice to three groups: natural mating or mating following injection with equine chorionic gonadotropin and trigger with GnRHa or hCG trigger. Females were killed prior to implantation (E3.5), post-implantation (E7.5), and at midgestation (E10.5), and maternal serum, uterus, and ovaries were collected. During peri-implantation, endometrial Vegfr1 and Vegfr2 mRNA were significantly increased in the GnRHa trigger group (P

Purpose The aim of this study was to examine whether gonadotropin-releasing hormone (GnRH) agonist treatment is effective in preserving final height in patients with central precocious puberty (CPP) or early puberty (EP). Methods The medical records of 40 patients with CPP and 206 patients with EP who completed GnRH agonist treatment following diagnosis were analyzed retrospectively. Height and height standard deviation (height SDS) scores based on bone age (BA) were measured and calculated at baseline, after treatment completion, and at final follow-up to compare changes within and between groups. Predicted adult height (PAH) was estimated by the height corresponding to height SDS for BA in girls at 18 years 11 months of age based on the growth chart. Results PAH at baseline did not differ significantly between the CPP group (153.67±4.95) and the EP group (154.77±3.72). In the CPP group, PAH significantly increased at treatment completion (156.01±4.61) and at final follow-up (158.52±6.04) compared to baseline. In the EP group, PAH significantly increased at treatment completion (157.7±3.60) and at final follow-up (159.31±4.26) compared to baseline. The increase in PAH at all timepoints compared to baseline did not significantly differ between the CPP and EP groups. Conclusions Both CPP and EP groups had significantly greater PAH after treatment, with no difference in the amount of increase between groups. These results show that GnRH agonist treatment can help increase final height even in patients diagnosed with EP after the age of 8 years.

Objective To investigate the clinical efficacy of combined gonadotropin-releasing hormone agonist(GnRH-a) therapy in patients with ovarian endometrioma after conservative surgery. Methods Using a retrospective cohort study analysis, 206 patients who underwent conservative surgery for ovarian endometriosis cysts at the Department of Gynecology, Affiliated Hospital of Nanjing University of Chinese Medicine from December 2014 to December 2018 were selected and divided into 138 cases in the observation group(postoperative combined GnRH-a use for 6 months) and 68 cases in the control group(postoperative with no drug). Recurrence between two groups and the scores of dysmenorrhea, pain during in tercouse（PDI）, and chronic pelvic pain were compared between two groups at different times in 2 years after surgery. Results In the 2 years follow-up, the observation group was superior with statistical significance in the comparison of chronic pelvic pain and dysmenorrhea scores between the two groups and time points(P＜0.05). There was no significant difference in intergroup effect and time effect of sexual intercourse pain (P>0.05). The recurrence rate of patients in the observation group was lower than that of the control group in the first year after surgery(3.62% vs 11.77%, P＜0.05), while no significant difference in recurrence rate of two groups was found in the second year after surgery (P>0.05), but the 2-year cumulative recurrence rate in the observation group was lower than that in the control group (13.24% vs 25.00%, PConclusion GnRH-a can be a choice for postoperative pain management and recurrence prevention in endometriosis.

Purpose: This randomised clinical pilot study evaluated the effect of the midluteal additional single dose of gonadotropin-releasing hormone agonist (GnRHa) on the clinical outcome of the females subjected to artificial cycle frozenthawed embryo transfer (AC-FET). Methods: A total of 129 females were randomised into two groups (70 in the control group and 59 in the intervention group). Both groups received standard luteal support. The intervention group was given an extra dose of 0.1 mg GnRH-a in the luteal phase. The live birth rate served as the primary endpoint. The secondary endpoints were the positivity of pregnancy tests, the clinical pregnancy rate, the miscarriage rate, the implantation rate, and the multiple pregnancy rate. Results: There were more positive pregnancy tests, clinical pregnancies, live births, and twinning pregnancies, and fewer miscarriages observed in the intervention arm compared to the controls, though no statistical significance was concluded. No difference was found in the number of macrosomia in the two groups. There was no congenital abnormality newborn. Conclusion: Overall, the difference of 12.1 percentage points in the live births rate (40.7% vs 28.6%) between the two groups, however, is statistically insignificant. the improvement of the pregnancy outcome supports the noninferiority of GnRH-a added during the luteal phase in AC-FET. Larger-scale clinical trials are required to further establish the positive benefits. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the therapeutic efficacy of gonadotropin-releasing hormone agonist (GnRHa) plus levonorgestrel-releasing intrauterine system (LNG-IUS) for moderate and severe endometriosis (EMS). Methods: 94 patients with EMS were randomized into experimental and control groups. Patients in the experimental group (EG) received LNG-IUS + GnRHa while those in the control group (CG) received GnRHa. Pre- and post-treatment estradiol (E2), folliclestimulating hormone (FSH), luteinizing hormone (LH), interleukin (IL)-2, IL-4, and interferon-γ (INF-γ) levels in serum were measured, and alterations in antral follicle count (AFC), ovarian stroma (OS) and peak systolic velocity (PSV) were observed using an ultrasonic tester. Patients were followed up for one-year during which the severity of dysmenorrhea was determined with the Visual Analogue Scale (VAS), and the clinical efficacy was evaluated at the last follow-up while the recurrence of EMS was counted. Results: EG patients had lower FSH, E2, LH and IL-2 levels than CG patients after treatment, with higher AFC, PSV, IL-4 and INF-γ (p<0.05). The prognostic follow-up showed a continuous decrease in VAS in both groups, with a lower score among EG patients (p<0.05). No statistical difference was identified in the recurrence rate of EMS between EG and CG patients (p>0.05) even though the overall response rate was higher among EG patients (p<0.05). Conclusion: LNG-IUS + GnRHa has better, stable and long-term efficacy against moderate and severe EMS, and higher efficacy in improving patients' ovarian function. [ABSTRACT FROM AUTHOR]

Leuprolide acetate, a gonadotropin-releasing hormone agonist, is used in the treatment of central precocious puberty. Besides local reactions, systemic hypersensitivity reactions have been reported in the literature during GnRH analog therapy. A case which has developed angioedema after 7th and 8th doses of the treatment while receiving leuprolide acetate treatment for central precocious puberty is presented in this article. Clinicians should be aware of allergic reactions that occur with GnRH analog therapy and injections must be administered in the hospital setting after appropriate precautions have been taken. [ABSTRACT FROM AUTHOR]

Objective: To compare the recurrence rate and risk factors between conservative surgery followed by medical treatments and conservative surgery‐only in patients with focal adenomyosis. Methods: This retrospective study was conducted in a single teaching hospital from May 2011 to October 2016. All eligible patients were identified into three groups: surgery‐only group, surgery combined with gonadotropin‐releasing hormone agonist (GnRHa), and a levonorgestrel‐releasing intrauterine system (LNG‐IUS) group. The recurrence rate and risk factors were compared among groups using Kaplan–Meier and Cox proportional hazards analyses. Receiver operating characteristic (ROC) curve analysis was applied to determine a cut‐off value for identifying recurrence‐related risk factors. Results: A total of 249 postoperative patients with adenomyosis were included in the final analysis with a mean of 41 months of follow up. The recurrence rate at the long‐term follow up was significantly lower in intervention groups than in the surgery‐only group (P = 0.011). The Cox proportional hazards and ROC analyses showed that a menstrual cycle longer than 26 days (P = 0.026), diameter of lesions <6 cm (P = 0.030), and combination treatment using GnRHa (P = 0.039) or LNG‐IUS (P = 0.007) were protective against relapse. The risk of recurrence was lower in patients with anterior (P = 0.034) or fundus (P = 0.038) adenomyosis. Conclusion: Postoperative therapy using GnRHa or LNG‐IUS decreases the long‐term relapse rate in women undergoing conservative surgery. Synopsis: Postoperative therapy using GnRH agonist or levonorgestrel‐releasing intrauterine system decreases the long‐term relapse rate in women undergoing conservative surgery. [ABSTRACT FROM AUTHOR]

Background and objectives: Teverelix drug product (DP) is a gonadotropin-releasing hormone antagonist in development for the treatment of patients with prostate cancer in whom androgen deprivation therapy is indicated. The aim of this paper is to present the results of five Phase 2 studies that assessed the pharmacokinetics, pharmacodynamics, efficacy and safety of different loading dose regimens of teverelix DP. Methods: Five single-arm, uncontrolled clinical trials were conducted in patients with advanced prostate cancer. The five different loading dose regimens of teverelix DP tested were (a) a single 90 mg subcutaneous (SC) injection of teverelix DP given on 3 consecutive days (Days 0, 1 and 2); (b) a single 90 mg intramuscular (IM) injection of teverelix DP given 7 days apart (Days 0 and 7); (c) a single 120 mg SC injection of teverelix DP given on 2 consecutive days (Days 0 and 1); (d) 2 × 60 mg SC injections of teverelix DP given on 3 consecutive days (Days 0, 1 and 2), and (e) 2 × 90 mg SC injections of teverelix DP given on 3 consecutive days (Days 0, 1 and 2). The primary efficacy parameter was the duration of action of an initial loading dose regimen in terms of suppression of testosterone to below the castration level (0.5 ng/mL). Results: Eighty-two patients were treated with teverelix DP. Two regimens (90 mg and 180 mg SC on 3 consecutive days) had a mean duration of castration of 55.32 days and 68.95 days with >90% of patients having testosterone levels < 0.5 ng/mL at Day 28. The mean onset of castration for the SC regimens ranged from 1.10 to 1.77 days, while it was slower (2.4 days) with IM administration. The most common adverse event (AE) was injection site reaction. No AEs of severe intensity were reported. Conclusions: Teverelix DP is safe and well tolerated. Castrate levels of testosterone can be rapidly achieved following the subcutaneous injection of teverelix DP on 3 consecutive days. Streamlining of the administration of the loading dose and identifying a suitable maintenance dose will be investigated in future trials. [ABSTRACT FROM AUTHOR]

This study investigates the effect of GnRHa pretreatment on pregnancy outcomes in artificial endometrial preparation for frozen–thawed embryo transfer (AC-FET) cycles. A systematic review of English language studies published before 1 September 2022, was conducted, excluding conference papers and preprints. Forty-one studies involving 43,021 participants were analyzed using meta-analysis, with a sensitivity analysis ensuring result robustness. The study found that GnRHa pretreatment generally improved the clinical pregnancy rate (CPR), implantation rate (IR), and live birth rate (LBR). However, discrepancies existed between randomized controlled trials (RCTs) and observational studies; RCTs showed no significant differences in outcomes for GnRHa-treated cycles. Depot GnRHa protocols outperformed daily regimens in LBR. Extended GnRHa pretreatment (two to five cycles) significantly improved CPR and IR compared to shorter treatment. Women with polycystic ovary syndrome (PCOS) saw substantial benefits from GnRHa pretreatment, including improved CPR and LBR and reduced miscarriage rates. In contrast, no significant benefits were observed in women with regular menstruation. More rigorous research is needed to solidify these findings.

PurposeSubstantial evidence indicates that men with prostate cancer are at an increased risk for cardiovascular disease, and medical and surgical androgen deprivation therapy is associated with further increased cardiovascular risk. There are conflicting reports of differences in cardiovascular safety between gonadotropin-releasing hormone (GnRH) agonists and antagonists. The purpose of this narrative review is to compare data on the cardiovascular risks and safety outcomes associated with different hormonal treatment options in prostate cancer patients and to provide guidance on how to manage the increased risk associated with the condition.MethodsA PubMed search was conducted for papers published in the last 15 years using the following MeSH terms: “prostate neoplasms,” “gonadotropin-releasing hormone,” “androgen agonist,” “androgen antagonists,” “cardiovascular disease,” “epidemiology.”ResultsEvidence regarding the risk of cardiovascular events during treatment with GnRH agonists and antagonists is conflicting. Some retrospective studies have shown that agonists are associated with a greater risk of cardiovascular disease and cardiovascular mortality and morbidity, and a similar risk with agonists and combined androgen blockade. Some studies have reported that antagonists are associated with a decreased risk of cardiovascular mortality and morbidity compared with agonists. With respect to coronary heart disease, ischemic heart disease, myocardial infarction, stroke, or sudden cardiac death, current evidence has failed to demonstrate a significant difference between antagonists and agonists. Cardiovascular risks in patients should be mitigated by regular monitoring of blood pressure, blood glucose, and lipids, as well as counseling patients to abstain from alcohol and improve their diet and exercise. Statins, metformin, and aspirin should also be considered.

BACKGROUND: Recent studies have reported higher risks of adverse maternal and neonatal outcomes, such as hypertensive disorders of pregnancy, after programmed frozen embryo transfer, especially in cycles with gonadotropin-releasing hormone agonist pretreatment. It remains unclear if GnRH agonist pretreatment before programmed frozen embryo transfer further increases the risk for obstetrical complications among women with polycystic ovary syndrome. OBJECTIVE: This study aimed to compare the obstetrical and neonatal complications of singleton and twin pregnancies after programmed frozen embryo transfer with or without gonadotropin-releasing hormone-a pretreatment among women with polycystic ovary syndrome. STUDY DESIGN: This was a secondary analysis of a single-center, randomized controlled trial comparing the live birth rate and cost-effectiveness of programmed cycle-prepared frozen embryo transfers with or without gonadotropin-releasing hormone agonist pretreatment among women with polycystic ovary syndrome. The analysis was restricted to women with polycystic ovary syndrome, aged 24 to 40 years, who delivered live neonates after frozen-thawed blastocyst transfer. The obstetrical and neonatal outcomes were compared between programmed cycles with and those without gonadotropin-releasing hormone agonist pretreatment. The adjusted odds ratios with 95% confidence intervals were calculated and adjustments were made for relevant confounders. RESULTS: The maternal and neonatal complications associated with 177 live single births and 38 twin births (253 newborns in total) were analyzed. There were no significant differences in the frequencies of obstetrical complications, including hypertensive disorders of pregnancy, between the gonadotropin-releasing hormone agonist pretreatment and no pretreatment group for both singleton and twin pregnancies. However, there was a significantly greater incidence of having a low birthweight neonate among singleton infants born after gonadotropin-releasing hormone agonist pretreatment when compared with no pretreatment (10.2% vs 1.3%; P=0.042), and a low birthweight among singleton infants was still more likely after adjusting for confounders (relative ratio, 3.85; 95% confidence interval, 1.13−7.11; P=.024). Other neonatal complications were all comparable between the pretreatment and no pretreatment groups for both singleton and twin pregnancies. CONCLUSION: For women with polycystic ovary syndrome, programmed frozen embryo transfer cycles with gonadotropin-releasing hormone agonist pretreatment could lead to a greater risk of having a low birthweight singleton neonate.

Background Twenty years ago, the Dutch Protocol—consisting of a gonadotropin-releasing hormone agonist (GnRHa) to halt puberty and subsequent gender-affirming hormones (GAHs)—was implemented to treat adolescents with gender dysphoria. Aim To study trends in trajectories in children and adolescents who were referred for evaluation of gender dysphoria and/or treated following the Dutch Protocol. Methods The current study is based on a retrospective cohort of 1766 children and adolescents in the Amsterdam Cohort of Gender Dysphoria. Outcomes Outcomes included trends in number of intakes, ratio of assigned sex at birth, age at intake, age at start of GnRHa and GAH, puberty stage at start of GnRHa, proportions of adolescents starting and stopping GnRHa, reasons for refraining from GnRHa, and proportions of people undergoing gender-affirming surgery. Results A steep increase in referrals was observed over the years. A change in the AMAB:AFAB ratio (assigned male at birth to assigned female at birth) was seen over time, tipping the balance toward AFAB. Age at intake and at start of GnRHa has increased over time. Of possibly eligible adolescents who had their first visit before age 10 years, nearly half started GnRHa vs around two-thirds who had their first visit at or after age 10 years. The proportion starting GnRHa rose only for those first visiting before age 10. Puberty stage at start of GnRHa fluctuated over time. Absence of gender dysphoria diagnosis was the main reason for not starting GnRHa. Very few stopped GnRHa (1.4%), mostly because of remission of gender dysphoria. Age at start of GAH has increased mainly in the most recent years. When a change in law was made in July 2014 no longer requiring gonadectomy to change legal sex, percentages of people undergoing gonadectomy decreased in AMAB and AFAB. Clinical Implications A substantial number of adolescents did not start medical treatment. In the ones who did, risk for retransitioning was very low, providing ongoing support for medical interventions in comprehensively assessed gender diverse adolescents. Strengths and Limitations Important topics on transgender health care for children and adolescents were studied in a large cohort over an unprecedented time span, limited by the retrospective design. Conclusion Trajectories in diagnostic evaluation and medical treatment in children and adolescents referred for gender dysphoria are diverse. Initiating medical treatment and need for surgical procedures depends on not only personal characteristics but societal and legal factors as well. [ABSTRACT FROM AUTHOR]

Objective: To evaluate two different gonadotropin‐releasing (pituitary downregulating) hormones used in in vitro fertilization (IVF) on the live birth rate in young patients with low body mass index (BMI) undergoing their first IVF cycle. Methods: In a retrospective study in a single public medical center, 555 long gonadotropin‐releasing hormone agonist (GnRH‐a) protocols were compared with 431 prolonged GnRH‐a protocols between 2016 and 2018. All analyses were performed using the SPSS version 22.0. The primary measured outcome was live birth rate. Results: Compared with the long protocol, the prolonged protocol required more doses of gonadotropin and a longer duration of ovarian stimulation. Lower levels of serum luteinizing hormone and serum estrogen were detected on the day of chorionic gonadotropin administration, and a lower fertilization rate was found in the prolonged protocol. Although more oocytes were retrieved and more frozen embryos were recorded in the prolonged protocol, the live birth rate per fresh cycle was comparable between the two protocols (P = 0.057). The incidence of ovarian hyperstimulation syndrome was higher in the prolonged protocol group. In the subgroup of women with antral follicle count (AFC) of 12 or less, there was no difference in the live birth rate between the two protocols (P = 0.688). However, for women with AFC > greater than 12, the prolonged protocol was still a positive predictor of live birth rate. The odds ratio was 1.73 (95% confidence interval 1.04–2.89). Conclusion: The prolonged protocol might not increase the live birth rate in women with low BMI who are undergoing their first IVF cycle. However, for women with AFC greater than 12, a prolonged protocol could be a good choice to improve the live birth rate. Synopsis: Prolonged protocols were a positive predictor of live birth rate in young patients with antral follicle count below 12 and low BMI. [ABSTRACT FROM AUTHOR]

Purpose: To analyze whether response to the GnRH test is a predictor of empty follicle syndrome (EFS) and to analyze independent risk factors for EFS. Methods: The GnRH test results of 3765 patients from 2016 to 2018 were used to define the reference range of the GnRH test. Risk factors for EFS were estimated by multivariate logistic analysis of 5282 cycles (5247 oocyte‐retrieved cycles with GnRH agonist trigger and 35 cycles of EFS) conducted from 2016 to 2019. Results: GnRH testing showed basal hormone values as follows: median LH 5.2 (95 percentile; 1.3–12.6) mIU/mL, LH 30 min 22.0 (6.8–57.1), basal FSH 7.3 (3.0–20.5), FSH 30 min 11.5 (5.1–30.4) and FSH/LH ratio 1.5 (0.6–4.1). Independent risk factors for EFS were antral follicle count (adjusted odds ratio; 0.94, 95% CI; 0.89–0.99), basal LH (0.78, 0.66–0.90), and days duration of ovarian stimulation (1.41, 1.21–1. 60). The respective thresholds were 8 for AFC, 5.0 for basal LH, and 16 days for duration. Conclusions: LH 30 min values of the GnRH test did not predict EFS. Independent risk factors for EFS were AFC, basal LH and days duration of ovarian stimulation. [ABSTRACT FROM AUTHOR]

Background: Adenomyosis is a gynecological benign lesion caused by the invasion of endometrium and stroma into normal myometrium. To further improve the treatment of adenomyosis, the objective of this study was to investigate the clinical effect of levonorgestrel-releasing intrauterine system, combined with gonadotropin-releasing hormone agonist (GnRH-a) drug-assisted focused ultrasound ablation, in the treatment of adenomyosis and its effect on phosphatidylinositol 3 kinase/phosphatase and tensin homolog (PI3K/PTEN) signal pathway. Methods: A study was conducted in subjects aged 28–54 years with adenomyosis, treated in our hospital. A total of 87 subjects were assigned to a control group (n = 41), which was given focused ultrasound ablation, and a study group (n = 46), which was given focused ultrasound ablation + GnRH-a + levonorgestrel-releasing intrauterine system, depending on the different treatment methods. The follow-up time was 12 months, and the treatment effect, adverse reaction, and PI3K/PTEN signal pathway related protein level were compared between the two groups. Results: After 12 months intervention, it was corroborated significant difference between focused ultrasound ablation group and the focused ultrasound ablation + GnRH-a + levonorgestrel group in uterine volume, visual analogue scale (VAS) score, pictorial blood loss assessment chart (PBAC) score, and serum cancer antigen 125 (CA125) levels. In terms of proteins level in the eutopic endometrial tissue, it was observed notably higher levels of PTEN and notably lower levels of protein kinase B (AKT) and p-AKT in the study group versus control group, 12 months after treatment. Conclusions: Levonorgestrel-releasing intrauterine system combined with GnRH-a drug-assisted focused ultrasound ablation is more effective in the treatment of adenomyosis, and its mechanism may be related to the regulation of the expression of molecules related to PI3K/PTEN signal pathway.

Abstract Background In frozen embryo transfer (FET), there is limited consensus on the best means of endometrial preparation in terms of the reproductive outcomes in women with polycystic ovary syndrome (PCOS). The present study aimed to compare the pregnancy and neonatal outcomes following artificial cycle FET (AC-FET) with or without gonadotropin-releasing hormone agonist (GnRH-a) pretreatment among women with PCOS. Methods A total of 4503 FET cycles that satisfied the inclusion criteria were enrolled in this retrospective cohort study between 2015 and 2020. The GnRH-a group received GnRH-a pretreatment while the AC-FET group did not. Propensity score matching (PSM) method and multivariate logistic regression analysis were performed to adjust for potential confounding factors. Results After PSM, women in the GnRH-a group suffered a significantly lower miscarriage rate (11.2% vs. 17.1%, P = 0.033) and a higher live birth rate (LBR) compared with those in the AC-FET group (63.1% vs. 56.8%, P = 0.043). No differences were observed in the rates of biochemical pregnancy, clinical pregnancy and ectopic pregnancy between the two groups. A higher mean gestational age at birth was observed in the GnRH-a group than in the AC-FET group (39.80 ± 2.01 vs. 38.17 ± 2.13, P = 0.009). The incidence of neonatal preterm birth (PTB) in the GnRH-a group was lower than that in the AC-FET group (7.4% vs. 14.9%, P = 0.009). Singleton newborns conceived after GnRH-a group were more likely to be small for gestational age (SGA) than those born after AC-FET group (16.4% vs. 6.8%, P = 0.009). However, no significant differences were found between the two groups in terms of mean birthweight, apgar score, the rates of macrosomia, large for gestational age and low birth weight. Conclusion(s) In women with PCOS who underwent AC-FET, GnRH-a pretreatment was significantly associated with a higher live birth rate and a reduced risk of neonatal PTB. However, there was a concomitant increase in the risk of developing SGA babies.

Abstract Background To determine whether gonadotropin-releasing hormone (GnRH) agonist downregulation combined with hormone replacement therapy (HRT) can improve the reproductive outcomes in frozen–thawed embryo transfer cycles for older patients (aged 36–43 years) with idiopathic recurrent implantation failure (RIF). Methods This retrospective cohort study involved 549 older patients undergoing their third cleavage-stage embryo or blastocyst transfer over a 5-year period (January 2015–December 2020) at Northwest Women’s and Children’s Hospital after in vitro fertilization/intracytoplasmic sperm injection cycles. Patients with known endometriosis or adenomyosis were excluded from the study. The patients were divided into three groups according to the endometrial preparation protocol: the natural cycle (NC) group (n = 65), the HRT group (n = 194), and the GnRH agonist downregulation combined with HRT cycle (GnRH agonist–HRT) group (n = 290). The primary outcome was the live birth rate, and the secondary outcomes were the clinical pregnancy, miscarriage, and ongoing pregnancy rates. Results The live birth rate in the GnRH agonist–HRT group (36.55%) was higher than that in the HRT group (22.16%) and NC group (16.92%) (P

Abstract Background Adenomyosis is a chronic gynecological disease characterized by invasion of the uterine endometrium into the muscle layer. In assisted reproductive technology (ART), gonadotropin-releasing hormone agonist (GnRHa) is often used to improve pregnancy rates in patients with adenomyosis, but the underlying mechanisms are poorly understood. Methods Eutopic endometrial specimens were collected from patients with adenomyosis before and after GnRHa treatment in the midsecretory phase. RNA sequencing (RNA-Seq) of these specimens was performed for transcriptome analysis. The differentially expressed genes (DEGs) of interest were confirmed by real-time PCR and immunohistochemistry. Results A total of 132 DEGs were identified in the endometrium of patients with adenomyosis after GnRHa treatment compared with the control group. Bioinformatics analysis predicted that immune system-associated signal transduction changed significantly after GnRHa treatment. Chemokine (C-C motif) ligand 21 (CCL21) was found to be highly expressed in the eutopic endometrium after GnRHa treatment, which may be involved in the improvement of endometrial receptivity in adenomyosis. Conclusion This study suggests that molecular regulation related to immune system-associated signal transduction is an important mechanism of GnRHa treatment in adenomyosis. Immunoreactive CCL21 is thought to regulate inflammatory events and participate in endometrial receptivity in adenomyosis.

Abstract Purpose To analyze whether response to the GnRH test is a predictor of empty follicle syndrome (EFS) and to analyze independent risk factors for EFS. Methods The GnRH test results of 3765 patients from 2016 to 2018 were used to define the reference range of the GnRH test. Risk factors for EFS were estimated by multivariate logistic analysis of 5282 cycles (5247 oocyte‐retrieved cycles with GnRH agonist trigger and 35 cycles of EFS) conducted from 2016 to 2019. Results GnRH testing showed basal hormone values as follows: median LH 5.2 (95 percentile; 1.3–12.6) mIU/mL, LH 30 min 22.0 (6.8–57.1), basal FSH 7.3 (3.0–20.5), FSH 30 min 11.5 (5.1–30.4) and FSH/LH ratio 1.5 (0.6–4.1). Independent risk factors for EFS were antral follicle count (adjusted odds ratio; 0.94, 95% CI; 0.89–0.99), basal LH (0.78, 0.66–0.90), and days duration of ovarian stimulation (1.41, 1.21–1. 60). The respective thresholds were 8 for AFC, 5.0 for basal LH, and 16 days for duration. Conclusions LH 30 min values of the GnRH test did not predict EFS. Independent risk factors for EFS were AFC, basal LH and days duration of ovarian stimulation.

Purpose: We aimed to ascertain the effectiveness of gonadotropin-releasing hormone (GnRH) agonist co-therapy for the preservation of ovarian function in patients with ovarian malignancy who underwent unilateral salpingooophorectomy and platinum-based chemotherapy. Methods: We enrolled 158 patients with ovarian malignancy who underwent fertility preservation surgery and postoperative platinum-based chemotherapy between January 2018 and December 2020. Patients were divided into two groups based on the use of GnRH agonist (GnRHa) during chemotherapy. Two patients withdrew from the study. Laboratory tests (serum follicle-stimulating hormone [FSH], serum luteinizing hormone [LH], and serum anti-Müllerian hormone [AMH]) were performed pre-chemotherapy and one year postchemotherapy. Data on menstruation resumption, perimenopausal symptoms (modified Kupperman Menopausal Index [KMI]), health-related quality of life (Medical Outcomes Study Short Form-36 [MOS SF-36]), and obstetric outcomes were collected. Results: One year post-chemotherapy, the serum AMH level in the GnRHa group was higher than that in the control group (P<0.001), while the serum FSH and FSH/LH levels in the GnRHa group were lower than those in the control group (P<0.001). The mean period from last chemotherapy to menstrual resumption was 3.86 and 5.78 months in the GnRHa and control groups (P<0.001), respectively. The rate of menstrual resumption postchemotherapy was 93.5% and 82.3% in the GnRHa and control groups (P<0.05), respectively. GnRHa co-administration during chemotherapy reduced the likelihood of low AMH levels post-chemotherapy and was significant in the multivariate analysis (P<0.05). The modified KMI scores and MOS SF-36 scores were better in the GnRHa group than in the control group (both P<0.001). Conclusion: GnRHa protects ovarian function during platinum-based adjuvant chemotherapy in young patients with ovarian malignancy. This study provides a therapeutic reference for gynecologists, especially for those in economically and medically underdeveloped areas. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis of randomized controlled trials aimed to evaluate the effect of a single-dose gonadotropin-releasing hormone agonist administration in the frozen-thawed embryo transfer cycle on pregnancy outcomes. A literature search was strategically conducted using PubMed, EMBASE, and the Cochrane Controlled Trials Register. The primary outcome was the clinical pregnancy rate. The secondary outcomes combined chemical pregnancy rate, implantation rate, ongoing pregnancy rate, live birth rate, miscarriage rate, and extrauterine pregnancy rate. Out of the 1594 citations that were found, only six met the criteria for being included in the meta-analysis. The clinical pregnancy rate was higher in the treatment group than in the control group (52.05% vs. 47.29%; p=0.04; RR=1.09; 95% CI=1.00-1.18). According to subgroup analysis based on the natural cycle, the clinical pregnancy rate with the agonist administration is significantly higher (43.75% vs. 27.35%; p=0.01; RR=1.6; 95% CI=1.10-2.32). However, there was no difference between the groups in terms of artificial cycles (p=0.80; 95% CI=0.96-1.20). The secondary outcomes did not show significant differences. We concluded that supplementing with a single dose of gonadotrophin-releasing hormone agonist can marginally increase the clinical pregnancy rate, particularly in the natural cycle. Other pregnancy outcomes do not improve with the treatment.