Hyperandrogenic eumenorrheic NON-PCOS women versus women with PCOS after the GnRH-agonist stimulation test preceded by suppression of adrenal steroidogenesis with dexamethasone.

The subject of polycystic ovary syndrome (PCOS) has been extensively covered in the literature; however, there is a paucity of data regarding eumenorrheic women with hyperandrogenism and/or hyperandrogenemia without ultrasound evidence of PCO morphology (EuHyperA), and even less data on the comparison between PCOS and EuHyperA subjects. It has previously been shown that around half of PCOS women exhibit a hyper-response of serum 17-hydroxy-progesterone (17-OHP) to the stimulation by GnRH-agonists, also indicated as functional ovarian hyperandrogenism (FOH). Often, this stimulation test is preceded by suppression of the adrenal steroidogenesis with oral dexamethasone (Dex). FOH has been associated with an increase of the P450c17 activity in the ovaries driven by elevated insulin levels. Interestingly, treatment of women with PCOS with Dex suppression and GnRH-agonist stimulation (buserelin) highlighted the possible existence of two clusters of patients: hyper-responders (HR) and normal responders (NR). In this retrospective study, we included 15 hyper-responders (HR) EuHyperA, 34 normal responders (NR) EuHyperA, 62 HR-PCOS and 45 NR-PCOS. The demographic characteristics, glucose-metabolism indices, and the hormonal response to Dex or buserelin were analyzed, with both intra-group and inter-group comparisons performed. The rate of FOH was significantly greater in PCOS than EuHyperA women. Compared to HR-PCOS, HR-EuHyperA had [i.] significantly greater age at observation; [ii.] lower cortisol, 17-OHP, Δ4-androstenedione (Δ4-ASD), total testosterone (TT), LH, and buserelin-stimulated whole curve of dehydroepiandrosterone sulfate (DHEAS), 17-OHP, Δ4-ASD and TT. Compared to NR-PCOS, NR-EuHyperA had [i.] significantly greater FSH, and buserelin-stimulated whole curve of DHEAS; [ii.] significantly lower post-HD Dex Δ4-ASD, TT, buserelin-stimulated whole curve of 17-OHP, Δ4-ASD and TT. Compared to NR-PCOS, HR-PCOS had [i.] significantly greater body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA-IR), cortisol, DHEAS, Δ4-ASD, TT, FT, FAI, E2, and insulin AUC0-120min (area under the curve) at oral glucose tolerance test (OGTT); [ii] higher levels of post-LD and post-HD Dex 17-OHP, Δ4-ASD, TT, post-HD Dex DHEAS (with greater levels indicating weaker adrenal suppression), whole curve of DHEAS, 17-OHP, Δ4-ASD, TT and LH; [iii] significantly lower sex-hormone binding globulin (SHBG). Even if most of the parameters evaluated were statistically similar in the two sets of comparisons, interesting differences were observed. Women with PCOS exhibit higher androgen levels at baseline, after adrenal suppression and at the buserelin test, further to a higher ovarian volume. Of note, the percentage of women with HOMA-IR≥2.5 and serum insulin levels were greater in PCOS group compared to EuHyperA women. Moreover, within women with PCOS, the HR subgroup has higher insulin levels compared to the NR subgroup, when OGTT is performed. The alteration of the glucose-insulin balance and elevation of circulating androgens were more pronounced in PCOS, thus indicating that [i.] metabolic alterations might be crucial in the onset of PCOS itself and, [ii] EuHyperA might represent a milder form of PCOS.

Mental Health Diagnoses and Suicidality Among Transgender Youth in Hospital Settings.

Purpose: The purpose of this analysis is to: 1) describe the most common mental health diagnoses in the emergency department (ED) and inpatient hospital settings among transgender and gender diverse (TGD) youth vs. matched controls and 2) evaluate if a gender-affirming hormone therapy (GAHT) or gonadotropin-releasing hormone agonist (GnRHa) prescription decreased the risk of suicidality within these settings. Methods: Using the PEDSnet dataset (years 2009-2019), TGD youth aged 8-18 (n = 3414, with a median age at last visit of 16.2 [14.4, 17.7] years, were propensity-score matched to controls (n = 13,628, age 16.6 [14.2, 18.3] years). Relative risks of the most common mental health diagnoses within ED and inpatient settings were calculated for TGD youth compared with controls. Recurrent time-to-event analysis was used to examine whether GAHT or GnRHa attenuated the risk of suicidality among subsamples of TGD youth. Results: TGD youth had a higher relative risk (95% confidence interval [CI]) of mental health diagnoses and suicidality in the ED (5.46 [4.71-6.33]) and inpatient settings (6.61 [5.28-8.28]) than matched controls. TGD youth prescribed GAHT had a 43.6% lower risk of suicidality (hazard ratio [HR] = 0.564 [95% CI 0.36-0.89]) compared with those never prescribed GAHT during our study period or before GAHT initiation. TGD youth who were prescribed GnRHa therapy had a nonstatistically significant reduction in ED or inpatient suicidality diagnoses compared with those never prescribed GnRHa (HR = 0.79 [0.47-1.31]). Conclusion: Although risk of mental health diagnoses and suicidality in ED and inpatient settings was high among TGD youth, a GAHT prescription was associated with a significant reduction in suicidality risk.

[Comparative Study of the Embryo Development and Clinical Outcomes of 3 Ovarian Stimulation Protocols in Different Age Groups]. / 不同年龄段人群三种促排卵方案胚胎发育及临床结局比较.

Objective: The main purpose of this study is to compare the embryo development and clinical outcomes of women in different age groups undergoing in vitro fertilization (IVF) processes using gonadotrophin-releasing hormone (GnRH) antagonist protocol, GnRH agonist long protocol, and early follicular phase protocol. We aim to provide reliable reference for future clinical treatments. Methods: We conducted a detailed analysis of patients who underwent treatment between January 2021 and February 2023. 1) In the overall patient population, we comprehensively compared the basic characteristics, the embryo development, and the clinical outcomes of patients treated with three different ovarian stimulation protocols, including the GnRH antagonist protocol group (n=4173), the agonist long protocol group (n=2410), and the early follicular phase long protocol group (n=341). 2) We divided the overall population into three age groups, one group for patients under 30 years old (n=2576), one for patients aged 30-35 (n=3249), and one for patients older than 35 years old (n=1099). Then, we compared the three stimulation protocols based on the group division. We separately compared the embryo development and clinical outcomes of patients using the three stimulation protocols in the under 30 years old, the 30-35 years old, and the over 35 years old age groups. With this analysis, we aimed to explore the response of different age groups to different stimulation protocols and their impact on the success rate of IVF. Results: 1) In the overall population, we found that the average number of oocytes retrieved in the GnRH agonist long protocol group was significantly higher than that in the GnRH antagonist protocol group ([13.85±7.162] vs. [13.36±7.862], P=0.0224), as well as the early follicular phase long protocol group ([13.85±7.162] vs. [11.86±6.802], P<0.0001). Patients in the GnRH antagonist protocol group not only had a significantly lower starting dose of gonadotrophin (Gn) compared to the other two groups (P<0.05) but also had a significantly lower number of days of Gn use (P<0.05). The blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups, significantly higher compared to the GnRH agonist long protocol group (64.91% vs. 62.35%, P<0.0001) and the early follicular phase long protocol group (64.91% vs. 61.18%, P=0.0001). However, there were no significant differences in the clinical pregnancy rates or the live birth rates among the three groups treated with different ovarian stimulation protocols (P>0.05). 2) In the <30 age group, the blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups, significantly higher compared to the GnRH agonist long protocol group (66.12% vs. 63.33%, P<0.0001) and the early follicular phase long protocol group (66.12% vs. 62.13%, P=0.0094). In the 30-35 age group, the blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups, significantly higher compared to the GnRH agonist long protocol group (64.88% vs. 62.93%, P=0.000 9) and the early follicular phase long protocol group (64.88% vs. 60.39%, P=0.0011). In the >35 age group, the blastocyst formation rate in the GnRH antagonist protocol group was significantly higher than that in the GnRH agonist long protocol group (59.83% vs. 56.51%, P=0.0093), while there was no significant difference compared to that of the early follicular phase long protocol group (P>0.05). In the three age groups, we found that there were no significant differences in clinical pregnancy rate, live birth rate, and neonatal outcome indicators (fetal weight and Apgar score) among the three stimulation protocols (antagonist protocol, GnRH agonist long protocol, and early follicular phase long protocol) (P>0.05). The findings showed no significant differences between clinical and neonatal outcomes in patients of all ages, regardless of the ovarian stimulation protocol, suggesting that the three ovarian stimulation protocols have similar therapeutic effects in patients of different ages. The results of this study have important implications for the selection of an appropriate ovarian stimulation protocol and the prediction of treatment outcomes. Conclusion: In the younger than 30 and 30-35 age groups, the GnRH antagonist protocol showed a more significant advantage over the GnRH agonist long protocol and the early follicular phase long protocol. This suggests that for younger and middle-aged patients, the antagonist protocol may lead to better outcomes during ovarian stimulation. In the older than 35 age group, while the antagonist protocol still outperformed the GnRH agonist long protocol, there was no significant difference compared to the early follicular phase long protocol. This may imply that with increasing age, the early follicular phase long protocol may have effects similar to the antagonist protocol to some extent. The advantages of the antagonist protocol lie in its ability to reduce stimulation duration and the dosage of GnRH, while enhancing patient compliance with treatment. This means that patients may find it easier to accept and adhere to this treatment protocol, thereby improving treatment success rates. Particularly for older patients, the use of the antagonist protocol may significantly increase the blastocyst formation rate, which is crucial for improving the success rates. Although there were no significant differences in the clinical outcomes of patients treated with the three protocols in each age group, further research is still needed to validate these findings. Future multicenter studies and increased sample sizes may help comprehensively assess the efficacy of different stimulation protocols. Additionally, prospective studies are needed to further validate these findings and determine the optimal treatment strategies.

Insulin sensitivity, body composition and bone mineral density after testosterone treatment in transgender youth with and without prior GnRH agonist therapy.

Background: 1.8% of youth identify as transgender; a growing proportion are transgender male (female sex, male gender identity). Many receive gonadotropin releasing hormone agonist (GnRHa) therapy to suppress endogenous puberty and/or will start testosterone to induce secondary sex characteristics that align with gender identity. Objectives: To determine the effects of 12 months of testosterone on cardiometabolic health among transgender youth, including insulin sensitivity, body composition, and bone mineral density and whether changes in outcomes differ based on prior GnRHa treatment. Methods: Participants (n = 19, baseline age 15.0 ± 1.0 years) were examined prior to and 12 months after testosterone therapy in a longitudinal observational study. Fasted morning blood draw, a 2-hour 75-gram oral glucose tolerance test, body composition and bone mineral density (dual-energy X-ray absorptiometry) were assessed at baseline and 12 months. Insulin sensitivity was estimated by HOMA-IR and Matsuda index. Changes were compared with mixed linear regression models evaluating time (baseline, 12 months), group (GnRHa treatment yes/no), and their interaction. Results: In the entire cohort, fasted insulin decreased (median [25,75 %ile]: -3 [-5, 0] mIU/L, p = 0.044) and 2-hour glucose increased (mean ± standard deviation): +18.5 ± 28.9 mg/dL, p = 0.013 from baseline after 12 months of testosterone therapy. There were no significant changes in HOMA-IR (p = 0.062) or Matsuda index (p = 0.096), nor by GnRHa status. Absolute (+6.2 [4.7, 7.5] kg, p = 0.016) and percent fat-free mass increased (+7.3 [5.4, 9.1] %, p = 0.003) and percent fat mass declined (-7.4 [-9.3, 5.3]%, p = 0.005) for the entire cohort. There were time*group interactions for absolute (p = 0.0007) and percent fat-free mass (p = 0.033). There were time*group interactions for bone mineral content (p = 0.006). Conclusions: Twelve months of testosterone in transgender adolescents resulted in changes in body composition and bone mineral density, with baseline differences between the +/-GnRHa group and convergence after 12 months. There were no changes in insulin sensitivity over time or between groups.

Can We Harvest More Mature Oocytes by Repeating Gonadotropin-Releasing Hormone Agonist Doses in Polycystic Ovarian Syndrome Patients at Risk of OHSS in Antagonist Cycles? A Randomised Clinical Trial.

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).

Effect of GnRH agonist down-regulation combined with hormone replacement treatment on reproductive outcomes of frozen blastocyst transfer cycles in women of different ages.

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.

Outcomes of Vaginal Repair and Vaginal Repair Combined With GnRHa Administration in the Treatment of Cesarean Section Scar Defects: A Randomized Clinical Trial.

STUDY OBJECTIVE: To prospectively investigate whether the application of vaginal repair (VR) of cesarean section scar defect (CSD) combined with a gonadotropin-releasing hormone agonist (GnRHa) achieve better clinical outcomes than VR alone. DESIGN: A randomized clinical trial. SETTING: University Hospital. PATIENTS: A total of 124 women with CSD were undergoing expectant management from December 2016 to September 2021. 61 were randomized to VR+ GnRHa and 63 to VR alone. INTERVENTION: Vaginal repair combined with GnRHa and vaginal repair alone. MEASURES AND MAIN RESULTS: The primary outcome was the duration of menstruation and thickness of the remaining muscular layer (TRM) at 6 months after surgery. Secondary outcomes included the length, width, and depth of the CSD; operation time; estimated blood loss; hospitalization time; and operative complications. Women were treated with either VR (n = 63) or VR + GnRHa (n = 61). Menstruation and TRM in patients pre vs post comparisons either with VR or VR + GnRHa are significantly improved (p <.05). Significant differences in menstruation duration and TRM occurred in patients treated with VR + GnRHa compared with those treated with VR (p <.05). Moreover, the rate of CSD after surgery in the VR group was significantly higher than that in the VR + GnRHa group (p = .033), and CSD patients in the VR + GnRHa group achieved better therapeutic effects than those in the VR group (p = .017). Patients who received VR + GnRHa had a shorter menstruation duration and a greater increment of TRM postoperatively than patients treated with VR alone (p = .021; p = .002, respectively). CONCLUSION: VR + GnRHa therapy has a greater potential to improve scar healing and reduce the number of menstruation days than VR alone for symptomatic women with CSD.

Pituitary Suppression with Gonadotropin-Releasing Hormone Agonist Prior to Artificial Endometrial Preparation in Frozen-Thawed Embryo Transfer Cycles: A Systematic Review and Meta-Analysis of Different Protocols and Infertile Populations.

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.

Bone Density in Transgender Youth on Gender-Affirming Hormone Therapy.

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.

Transcriptome profiling reveals superovulation with the gonadotropin-releasing hormone agonist trigger impaired embryo implantation in mice.

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 µg of GnRHa (Leuprorelin) 48 h later, while mice 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.

Pretreatment with long-acting gonadotropin-releasing hormone agonists improved pregnancy outcomes after hysteroscopic multiple polypectomies: A retrospective study of 660 frozen-thawed embryo transfer cycles.

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.

[Androgen deprivation therapy and cardiovascular morbidity in prostate cancer: a narrative review]. / Androgendeprivationstherapie und kardiovaskuläre Morbidität beim Prostatakarzinom: ein narratives Review.

Prostate cancer is the most common malignancy in men, mostly affecting older men who harbor an increased prevalence of cardiovascular disease and metabolic syndrome. Androgen deprivation therapy (ADT), the standard therapy for various stages of prostate cancer, further increases the risk for cardiovascular disease and for metabolic syndrome. Therefore, screening for cardiovascular risk factors should be performed prior to the initiation of ADT, and, if necessary, cardiological evaluation and interdisciplinary management should be provided during and after completion of ADT. Moreover, the use of a gonadotropin-releasing hormone (GnRH) antagonist may help reduce cardiovascular risk in patients with cardiovascular disease.

Risk factors for empty follicle syndrome in assisted reproductive technology with gonadotropin-releasing hormone agonist trigger.

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.

Live birth rate of gonadotropin-releasing hormone antagonist versus luteal phase gonadotropin-releasing hormone agonist protocol in IVF/ICSI: a systematic review and meta-analysis.

In vitro fertilization (IVF) and embryo transfer and intracytoplasmic sperm injection (ICSI) have allowed millions of infertile couples to achieve pregnancy. As an essential part of IVF/ICSI enabling the retrieval of a high number of oocytes in one cycle, controlled ovarian stimulation (COS) treatment mainly composes of the standard long gonadotrophin-releasing hormone agonist (GnRH-a) protocol and the gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol. However, the effectiveness of GnRH-ant protocol is still debated because of inconsistent conclusions and insufficient subgroup analyses. This systematic review and meta-analysis included a total of 52 studies, encompassing 5193 participants in the GnRH-ant group and 4757 in the GnRH-a group. The findings of this study revealed that the GnRH-ant protocol is comparable with the long GnRH-a protocol when considering live birth as the primary outcome, and it is a favourable protocol with evidence reducing the incidence of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI, especially in women with polycystic ovary syndrome. Further research is needed to compare the subsequent cumulative live birth rate between the two protocols among the general and poor ovarian response patients since those patients have a lower clinical pregnancy rate, fewer oocytes retrieved or fewer high-grade embryos in the GnRH-ant protocol.

Efficacy and safety of diphereline 11.25 mg, microrelin 11.25 mg, and microrelin 3.75 mg in premenopausal patients with breast cancer: a non-inferiority randomized clinical trial.

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.

Comparison between the modified long gonadotropin-releasing hormone agonist protocol and the non-downregulation protocol in POSEIDON groups: a propensity score matching retrospective cohort study.

Background: In vitro fertilization (IVF) is the main technique to address the infertility issue in the patient-oriented strategy encompassing individualized oocyte number (POSEIDON) population. Adopting appropriate protocols for assisted reproduction technologies (ART) cycles in the POSEIDON group may attain more favorable pregnancy outcomes. Objectives: This study aimed to compare the effectiveness of modified long gonadotropin-releasing hormone agonist protocol and non-downregulation protocol in POSEIDON patients undergoing ART, and to identify the factors affecting the pregnancy outcomes in this group. Design: This study was designed as a propensity score-matched (PSM) retrospective analysis. Participants: The study cohort consisted of 910 patients diagnosed with ovarian hyporesponsiveness and treated by IVF from January 2020 to June 2022. They were followed up until the transfer of the last embryo of the IVF cycle and/or pregnancy at 12 weeks. The study was conducted at the Center of Reproductive Medicine, Tongji Medical College, Wuhan Union Hospital, Huazhong University of Science and Technology. Methods: The patients were divided into Group I and Group II. Group I was treated with modified long gonadotropin-releasing hormone agonist protocol while Group II was put on a non-downregulation protocol. Propensity score matching (PSM) was used to select patients for each group. The subjects were compared in terms of the baseline level, process of controlled ovarian hyperstimulation, and pregnancy outcomes. Binary logistic regression analysis was performed to assess the difference in the cumulative pregnancy rate between the two groups. Results: Of the 910 POSEIDON patients who underwent IVF, 213 received the modified long gonadotropin-releasing hormone agonist protocol and 697 were subjected to the non-downregulation protocol. From the original cohort, PSM matched 174 pairs of patients. No statistically significant difference was found in total gonadotropin (Gn) dose between the two PSM groups, but the average daily Gn dose was lower in Group I and the duration of Gn lasted longer. The number of retrieved oocytes, the number of metaphase II (MII) ooctyes retrieved, normal fertilization, and normal cleavage embryos was significantly higher in Group I than in Group II, but there existed no significant difference in the number of high-quality embryos between the two groups. The single-cycle CPR (cumulative pregnancy rate) was higher in Group I than in Group II (for Group I: before PSM, CPR = 52.6%; after PSM, CPR = 51.7%; for Group II: before PSM, CPR = 34.0%; after PSM, CPR = 34.5%), and the difference was statistically significant. A binary logistic regression analysis in the unmatched patients showed that the CPR of Group II was 0.486 times that of Group I (95% CI: 0.303 to 0.779). Conclusions: The modified long gonadotropin-releasing hormone agonist protocol can be used as an optimal protocol for IVF or ICSI (Intracytoplasmic sperm injection) in POSEIDON patients. Level of evidence: Level III.

A reappraisal of ovarian stimulation strategies used in assisted reproductive technology.

Ovarian stimulation is a fundamental step in assisted reproductive technology (ART) with the intention of inducing ovarian follicle development prior to timed intercourse or intra-uterine insemination and facilitating the retrieval of multiple oocytes during a single in vitro fertilization (IVF) cycle. The basis of ovarian stimulation includes the administration of exogenous gonadotropins, with or without pre-treatment with oral hormonal therapy. Gonadotropin-releasing hormone agonist or antagonist is given in addition to the gonadotropins to prevent a premature rise of endogenous luteinizing hormone that would in turn lead to premature ovulation. With the advancement in technology, various stimulation protocols have been devised to cater for different patient needs. However, ovarian hyperstimulation syndrome and its serious complications may occur following ovarian stimulation. It is also evident that suboptimal ovarian stimulation strategies may have a negative impact on oogenesis, embryo quality, endometrial receptivity, and reproductive outcomes over recent years. This review describes the various forms of pre-treatment for ovarian stimulation and stimulation protocols, and aims to provide clinicians with the latest available evidence.

Comparison of Dydrogesterone and GnRH-a Effects After Laparoscopic Surgery in Patients with Stage III and IV Endometriosis.

Objective: 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.

Fertility and Obstetric Outcomes of Assisted Reproductive Technology (ART) in Women With Adenomyosis Following Gonadotropin-Releasing Hormone Agonist Therapy: A Single-Center Experience.

INTRODUCTION: Adenomyosis is an ambiguous disorder causing a wide variety of implications from dysmenorrhea, heavy menstrual bleeding, and infertility to pregnancy complications. Adenomyosis is associated with altered endocrine and inflammatory milieu, resulting in impaired implantation and reduced fertility potential. It is also associated with increased incidence of obstetric complications such as miscarriage, antepartum hemorrhage, placental mal-position, hypertensive disorders, small for gestational age-intrauterine growth restriction (SGA-IUGR), cesarean section, preterm labor, preterm premature rupture of membranes (PPROM), and neonatal intensive care unit (NICU) admissions. OBJECTIVE: The aim of our study was to investigate the fertility and obstetric outcomes in women with adenomyosis treated with GnRH agonists compared to controls with normal uteri undergoing in-vitro fertilization (IVF) at our center, thereby establishing the role of gonadotropin-releasing hormone (GnRH) agonists in managing sub-fertile women with adenomyosis. MATERIALS AND METHODS: We carried out a retrospective cohort study at our hospital to analyze the effects of adenomyosis on IVF and pregnancy outcomes. This study (n=83) involves women with adenomyosis between the ages of 21 and 37 years who were followed up at our center between 2013 and 2022. The controls (n=83) were selected from women who underwent IVF-intracytoplasmic sperm injection (IVF-ICSI) for tubal or mild male factor infertility with normal appearing uterus within the same time frame. Women with adenomyosis were given GnRH agonist as long/ultralong agonist protocol before controlled ovarian stimulation or as down-regulated frozen embryo transfer (FET). The length of suppression was between one and six months based on the size of the uterus and response to treatment. Fertility and obstetric outcomes were analyzed. RESULTS: The implantation rates were found to be equivocal: 54.2% and 53% in the adenomyosis and control groups, respectively (p=0.208). The cumulative live birth rate was 50.6% and 48.2% in the study and control groups, respectively (p=0.341). The biochemical pregnancy rate and the first- and second-trimester miscarriage rates were not significantly different between the group with adenomyosis and the group with normal uterus. The incidence of preterm deliveries and antepartum hemorrhage was found to be significantly increased in the study group. CONCLUSION: Medical management in women with adenomyosis optimizes the live birth rates giving results at par with the control population.