Long-acting GnRH Agonist Research Articles

The influence of morphologic grading and COS protocol on the outcomes of Day 5 versus Day 6 single fresh blastocyst transfers: a retrospective analysis of clinical outcomes from one center experience.

The purpose of this study was to evaluate whether the blastocyst morphologic grading and the protocol of controlled ovarian stimulation (COS) would influence pregnancy outcomes, aiming to provide guidance when choosing blastocyst transfer. The clinical data of 612 patients who received single fresh blastocyst transfer for first cycle, as well as the data of 253 patients who had already delivered were analyzed retrospectively. The patients were divided into two groups according to blastocyst formation time (D5 or D6). The following subgroup analyses were performed: (i) the morphologic grading of blastocyst and (ii) the protocol of COS. We observed that D5 single embryo transfer (SET) were associated with higher clinical pregnancy rate (CPR, 59.04% vs. 31.73%, P < 0.001) and live birth rate (LBR, 43.90% vs. 24.04%, P < 0.001) than D6 SET following fresh cycle. Patients in D5 group experienced more good blastocysts transfer (45.47%vs. 13.46%, P < 0.001) and less poor blastocysts transfer (9.64%vs. 45.19%, P < 0.001) than patients in D6 group. As to early stage and good quality blastocysts, the CPR and LBR were similar between D5 and D6 group. GnRH antagonist protocol had a demonstrable inferiority comparing with the early-follicular-phase long-acting GnRH-agonist long protocol (EFLL) or the mid-luteal-phase long-acting GnRH-agonist long protocol (MLLL) with regard to the CPR and LBR in D6-SET group. The analysis found that ovarian reserve of patients in D6-SET group was comparatively worse than that of patients in D5-SET group and D6-SET patients represented a subgroup of infertility patients usually having relatively poor embryo quality. The results should be interpreted with caution as the very low numbers in the respective group limited the use of statistical tests and the real significance values.

Effect of recombinant LH supplementation timing on clinical pregnancy outcome in long-acting GnRHa downregulated cycles

BackgroundTimely and moderate luteinizing hormone (LH) supplementation plays positive roles in in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) cycles with long-acting gonadotropin-releasing hormone agonist (GnRHa) pituitary downregulation. However, the appropriate timing of LH supplementation remains unclear.MethodsWe carried out a retrospective cohort study of 2226 cycles at our reproductive medicine centre from 2018 to 2020. We mainly conducted smooth curve fitting to analyse the relationship between the dominant follicle diameter when recombinant LH (rLH) was added and the clinical pregnancy outcomes (clinical pregnancy rate or early miscarriage rate). In addition, total cycles were divided into groups according to different LH levels after GnRHa and dominant follicle diameters for further analysis.ResultsSmooth curve fitting showed that with the increase in the dominant follicle diameter when rLH was added, the clinical pregnancy rate gradually increased, and the early miscarriage rate gradually decreased.ConclusionsIn long-acting GnRHa downregulated IVF/ICSI-ET cycles, the appropriate timing of rLH supplementation has a beneficial impact on the clinical pregnancy outcome. Delaying rLH addition is conducive to the clinical pregnancy rate and reduces the risk of early miscarriage.

Adverse impact of elevated progesterone levels on human chorionic gonadotropin trigger day on blastocyst transfer outcomes in gonadotropin-releasing hormone agonist cycles

ObjectiveDose an elevated serum progesterone (P) level on the human chorionic gonadotropin (hCG) trigger day have a negative effect on clinical pregnancy outcomes for embryos transferred at different stages of development in long-acting gonadotropin-releasing hormone agonist (GnRHa) in vitro fertilization-embryo transfer (IVF-ET) cycles? Study designThis was a noninterventional, retrospective, observational, single-centre cohort study. A total of 1951 patients received long-acting GnRHa for pituitary downregulation in IVF-ET cycles at Nanjing Drum Tower Hospital from January 2018 to December 2020. The serum P levels on the day of hCG administration were measured, together with other cycle parameters, to explore the relationship between P levels and the clinical pregnancy rate (CPR) of different embryos transferred. ResultsWhen the serum P level on the hCG day was higher than 1.5 ng/mL, the CPR did not decrease significantly. There was no correlation between the CPR of cleavage-stage embryo transfer and the serum P level on the hCG day. In addition, the interaction analysis suggested that the CPR of patients undergoing blastocyst transfer decreased as serum P levels on the hCG day increased. Progesterone levels on the day of hCG administration were closely related to the CPR of blastocyst transfer rather than cleavage-stage embryo transfer. ConclusionAn increased serum P level on the day of hCG administration did not affect the CPR of cleavage-stage embryo transfer, but it reduced the CPR of blastocyst transfer cycles.

P-464 Long-acting GnRH agonist ovulation trigger to avoid ovarian hyperstimulation and to combine oocyte cryopreservation with ovarian suppression during chemotherapy

Abstract Study question Is long-acting GnRH agonist (GnRHa) trigger an efficacious and safe option in oocyte cryopreservation cycles before chemotherapy, when ovarian suppression is planned? Summary answer The flare-up effect of long-acting GnRHa is able to induce the final oocytes’ maturation and subsequently suppress ovarian function for chemotherapy What is known already When both oocyte cryopreservation and gonadal suppression during chemotherapy with long-acting GnRHa are accepted by the patient for fertility preservation (FP), the first injection of GnRHa is administered few days after oocyte retrieval in order to start oncological therapies as soon as possible. Some cases of ovarian hyperstimulation (OHSS) have been described in this setting, as a consequence of the initial flare-up effect on recently stimulated ovaries. The subsequent risks (including a possible delay in the start of chemotherapy) may discourage physicians from proposing gonadal suppression in combination with oocyte cryopreservation, denying women a FP opportunity with proven efficacy. Study design, size, duration Prospectively collected data from 75 oncological patients who underwent ovarian stimulation for oocyte cryopreservation from 2016 to 2021 were evaluated. From 2020 all patients for whom ovarian suppression after cryopreservation was planned were offered long-acting GnRHa trigger. All other patients were enrolled as controls, stratified for triggering method used (highly purified Chorionic Gonadotrophin 10000 UI or short acting GnRHa 0.2 mg). Participants/materials, setting, methods All the ovarian stimulation cycles for oocyte cryopreservation in oncological patients before chemotherapy were performed in a single tertiary level public fertility centre. Cycle outcomes were evaluated accordingly to the trigger method. Maturation rate was defined as number of cryopreserved mature oocytes/total number of oocytes retrieved. Results were compared by Mann-Whitney U test or Chi-Square test, as appropriate. When the long-acting GnRHa was used for triggering, luteal phase hormones were assessed. Main results and the role of chance After controlled ovarian stimulation (COS) with standard or random start antagonist protocol, 13 women received the long-acting GnRHa trigger (Triptorelin 3.75 mg. Group A) 36 hours before oocyte retrieval, 37 women received highly purified Chorionic Gonadotrophin 10000 UI (Group B) and 25 women the short-acting GnRHa (Triptorelin 0.2 mg. Group C). The groups were comparable in terms of demographic and clinical parameters. Median number of mature cryopreserved oocytes in group A was 11 (range 7-18) with a maturation rate of 80% (68-100), 9 (0-24) with a maturation rate of 78% (43-100) in group B, and 12 (0-34), 79% (50-100) in group C (no statistically significative difference). There was no case of OHSS in Group A. One patient in group B and one in group C developed OHSS after administration of long-acting GnRH in the luteal phase after COS (five days after oocytes retrieval). Five days after oocyte retrieval (7 days after trigger), serum FSH median level in group A was 1.29 mUI/ml (0.48-2.50) and LH median level was 1.04 mUI/ml (0.26-2.46). Limitations, reasons for caution We are aware that our data should be confirmed by more robust randomized studies and higher numbers. Wider implications of the findings We report for the first time the efficacy of long-acting GnRHa in obtaining mature oocytes and in guaranteeing complete suppression by chemotherapy initiation. The feasibility of this strategy is an important step in reducing the risk of OHSS, giving the opportunity to combine oocyte cryopreservation and ovarian suppression during chemotherapy. Trial registration number not applicable

Effects of a GnRH agonist on sex behavior in females of the southern giant pouched rat.

In general, males should be particularly attentive to cues of sexual availability and females should advertise accordingly. Vaginal patency (i.e., the openness of the vagina) is a reliable indicator of sexual maturity; if the vagina is closed, the female is unable to copulate. The southern giant pouched rat (Cricetomys ansorgei) is unusual because females can have fully fused vaginal openings (i.e., vaginal nonpatency) despite being considered 'adults' by other metrics. Moreover, some females reversibly close their vaginal openings. Thus, vaginal patency in the pouched rat is a 'flexible' reproductive state. We subcutaneously implanted a long-acting GnRH agonist (deslorelin), which over time inhibits sex steroid secretion, to better understand the endocrinology and social behavior relating to vaginal patency in this species. We hypothesized that altering GnRH would impact both patency and behavior through its effects on circulating levels of estradiol. Six months of deslorelin treatment did not alter vaginal patency. Behaviorally, deslorelin-treated females spent less time interacting with, and were more aggressive towards males (compared to controls). Notably, deslorelin did not alter female scent marking. We conclude that behavioral receptivity, but not vaginal patency, is impacted by GnRH hormonal cascades in the pouched rat.

Analysis and prediction of risk factors of ovarian hyperstimulation caused by Long-acting GnRH agonist protocol in follicular phase.

The aim of the study was to explore the risk factors of ovarian hyperstimulation in patients undergoing long-acting gonadotropin-releasing hormone (GnRH) agonist protocol in follicular phase of ovulation induction therapy and to establish a predictive model. A total of 1289 patients who received Long-acting GnRH agonist protocol in follicular phase for ovulation induction in the Fujian Provincial Maternity and Child Health Hospital from July 1, 2018, to July 31, 2019, were selected. Among them, 33 patients developed moderate/severe ovarian hyperstimulation syndrome. The relevant indicators of the two groups were followed up for comparison, and Lasso regression was used to screen independent risk factors and construct a nomogram prediction model. A receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the discrimination and calibration of the prediction model. Univariate analysis suggested that the woman's age, basal antral follicle number (AFC), total gonadotropin (Gn) dose, Gn starting dose, basal estradiol (E2) level, basal anti-Müllerian hormone (AMH) value, number of follicles obtained, Gn start day E2, the difference in follicle-stimulating hormone (FSH) value and Gn starting day were statistically significant. Significant indicators of univariate analysis and clinical significance were included in the Lasso regression model, and AFC, woman's age, polycystic ovary syndrome, Gn starting dose and number of follicles obtained were finally screened as final predictors. The ROC curve indicated that the area under the curve (AUC) was 0.812. Ovarian hyperstimulation caused by long-acting GnRH agonist protocol in follicular phase for ovulation stimulation has a certain predictability. Paying attention to the patient's age, AFC, Gn starting dose, number of follicles obtained, and whether PCOS is evident may lead to early detection of ovarian hyperstimulation syndrome, which has clinical guiding significance.

Abstract P5-18-05: Long-acting GnRH agonist ovulation trigger to avoid ovarian hyperstimulation and to combine oocyte cryopreservation with ovarian suppression during chemotherapy

Abstract Background: Oocyte cryopreservation and gonadal suppression during chemotherapy with long-acting GnRH agonists (GnRHa) are standard fertility preservation (FP) methods in women with breast cancer. When both strategies are accepted by the patient, the first injection of GnRHa is frequently administered few days after oocyte retrieval in order to start oncological therapies as soon as possible. GnRHa suppress gonadal function after an initial stimulation phase due to a gonadotropins surge. Consequently, some cases of ovarian hyperstimulation (OHSS) have been described following GnRHa administration during the luteal phase of an oocyte cryopreservation cycle, as a consequence of the initial flare-up effect on recently stimulated ovaries. OHSS is associated with specific complications, such as an increased thromboembolic risk and a possible delay in the start of chemotherapy. These risks may discourage physicians from proposing gonadal suppression in combination with oocyte cryopreservation, denying women a FP opportunity with proven efficacy. However, since the same flare up effect of short-acting GnRHa (e.g. Triptorelin 0.2 mg) is commonly used to trigger ovulation in high responding infertile patients, we propose the initiation of long-acting GnRHa administration at triggering. Our hypothesis is that by inducing ovulation with long-acting GnRHa we meet the last requirement for oocytes maturation and create suppression by the time patients start chemotherapy, without the need of a further injection in the luteal phase. Methods From 2016 to 2020, 70 consecutive ovarian stimulation cycles for oocyte cryopreservation in oncological patients before chemotherapy were performed in a single university centre. Cycle outcomes were evaluated accordingly to the trigger method. Maturation rate was defined as number of cryopreserved mature oocytes/total number of oocytes retrieved. When the long-acting GnRHa was used for triggering, luteal phase hormones were assessed. Results After controlled ovarian stimulation (COS) with standard or random start antagonist protocol, ten women received the long-acting GnRHa trigger (Decapeptyl 3.75 mg, Ipsen. Group A) 36 hours before oocyte retrieval, 37 received highly purified Chorionic Gonadotrophin (Gonasi HP 10000 UI, IBSA. Group B) and 23 the short-acting GnRHa (Decapeptyl 0.2 mg, Ipsen. Group C). The groups were comparable in terms of demographic and clinical parameters. Median number of mature cryopreserved oocytes in group A was 14 (range 8-22) with a maturation rate of 81% (68-100), versus 9 (0-24) with a maturation rate of 78% (43-100) in group B, and 9 (3-34), 78% (38-100) in group C. There was no case of OHSS in Group A. Two patients developed OHSS after administration of long-acting GnRH in the luteal phase after COS, one in Group B and one in Group C. Five days after oocyte retrieval (7 days after trigger), serum FSH median level in group A was 1.28 mUI/ml (0.48-2.50) and LH median level was 1.04 mUI/ml (0.26-2.46). Conclusion We report for the first time the efficacy of long-acting GnRHa in obtaining mature oocytes and, at the same time, in guaranteeing complete suppression by chemotherapy initiation. We are aware that our data should be confirmed by more robust studies and higher numbers. Nevertheless, the feasibility of this strategy is an important step in reducing the risk of OHSS after ovarian stimulation while giving the opportunity to combine oocyte cryopreservation and ovarian suppression during chemotherapy, with proven efficacy as options to preserve fertility and ovarian function, respectively. Citation Format: Claudia Massarotti, Matteo Lambertini, Sara Stigliani, Fausta Sozzi, Paola Scaruffi, Paola Anserini. Long-acting GnRH agonist ovulation trigger to avoid ovarian hyperstimulation and to combine oocyte cryopreservation with ovarian suppression during chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-18-05.

Hormonal Replacement Treatment for Frozen-Thawed Embryo Transfer With or Without GnRH Agonist Pretreatment: A Retrospective Cohort Study Stratified by Times of Embryo Implantation Failures.

ObjectiveTo evaluate the efficacy of the long-acting gonadotropin-releasing hormone agonist (GnRH-a) administration before hormone replacement treatment for frozen-thawed embryo transfer in women with different times of embryo implantation failures.MethodsA retrospective cohort study was performed between January 2015 and December 2019. A total of 9263 women who underwent frozen-thawed embryo transfer were included in the study. The study is divided into three parts based on the times of embryo implantation failures. The sample sizes were 4611 for no implantation failure, 3565 for one failure and 1087 for multiple failures. Two endometrium preparation protocols, HRT and HRT with GnRH-a pretreatment (G-HRT), were compared. Confounding factors were treated by propensity score matching and generalized estimation equation.ResultsFor women with no failure of embryo implantation, the live birth rate was not statistically different when they underwent HRT and G-HRT (HRT: 42.75% [498/1165], G-HRT: 45.24% [527/1165], P=0.2261). Similar outcome also appeared in women with one failure of embryo implantation (HRT: 47.22% [535/1133], G-HRT: 50.31% [570/1131], P=0.1413). For women with multiple failures of embryo implantation, the live birth rate was significantly difference (HRT: 38.74% [117/302], G-HRT: 45.48% [357/785], P=0.0449). When stratified by age, the live birth rate is similar for women older than 37 years. Generalized estimation equation showed that GnRH agonist pretreatment was independently associated with the live birth rate for women with multiple failures (adjust OR: 1.5, 95%CI: [1.12-2.00]).ConclusionFor women with no/one failure of embryo implantation, the live birth rate is similar between HRT and G-HRT protocols. For women with multiple failure of embryo implantation, GnRH agonist pretreatment is beneficial to raise the live birth rate.

Causes and Effects of Oocyte Retrieval Difficulties: A Retrospective Study of 10,624 Cycles.

Oocyte retrieval is a routine procedure during the application of assisted reproduction technology. However, technical difficulties experienced during oocyte retrieval and the subsequent unsatisfactory number of oocytes obtained are rarely reported. The current study included 10,624 oocyte retrieval cycles from April 2015 to June 2018, and patients were followed up until February 2019. Patients were divided into two groups depending on whether the oocyte number obtained reached the >14-mm follicle number on the day of hCG administration. In the oocyte retrieval not satisfactory (ORNS) group, there were 1,294 cycles, and in the oocyte retrieval satisfactory (ORS) group, there were 9,330 cycles. ORNS patients were older, had a longer duration of infertility, had higher follicle-stimulating hormone, and were more likely to have endometriosis. The ORS group had a higher rate of the use of a follicular phase long-acting gonadotropin-releasing hormone (GnRH) agonist long ovarian stimulation protocol and a lower rate of the use of a luteal phase short-acting GnRH agonist long protocol. The ORNS group had fewer total number of days of FSH stimulation. On human chorionic gonadotropin day, the ORNS group had higher luteinizing hormone (LH), lower estradiol, and lower progesterone levels. After oocyte retrieval, the oocyte quality and fresh cycle transplantation rate were higher in the ORNS group. An unsatisfactory oocyte retrieval number did not influence the clinical pregnancy rate, miscarriage rate, or live birth rate during the fresh cycles. The cumulative pregnancy rate and the live birth rate were lower in the ORNS group. In conclusion, with a similar number of matured follicles, ORNS was more likely to occur in ovarian dysfunction patients. The follicular phase long-acting GnRH agonist long protocol had lower oocyte retrieval difficulty during IVF/ICSI. ORNS does not affect embryo quality or the fresh cycle pregnancy rate, but it significantly reduces the cumulative pregnancy rate and the live birth rate.

P–644 Effect of a reduced dose of long-acting gonadotropin releasing hormone (GnRH) agonist versus short-acting GnRH agonist on pregnancy outcome in patients undergoing ICSI/ET cycles

Abstract Study question Are pregnancy outcome different between reduced dose of long-acting GnRH agonist and short-acting GnRH agonist in patients undergoing ICSI/ET cycles? Summary answer Clinical outcomes were not significantly different between the two group. What is known already There is no consensus on which of two GnRH agonist protocol is the most effective form and it has been challenging which one improves the clinical pregnancy rate. Study design, size, duration This is randomized clinical trial that 394 patients, who were candidates for ICSI/ET, were included in this study between April 2019 and January 2020. Participants/materials, setting, methods Patients were randomly divided into two groups using blocks of 8; hereby every 8 subjects were randomized, four were allocated to the long-acting GnRH agonist, and four were allocated to the short-acting GnRH agonist randomly. Main results and the role of chance No significant difference was noted between the two groups in progesterone and estradiol levels at hCG administration day. Despite no significant difference between the two groups in ART outcomes, interestingly rate of ovarian hyperstimulation syndrome (OHSS) occurrence was significantly higher in the short-acting group (P = 0.005). Limitations, reasons for caution We couldn’t evaluate the long-term consequence of pregnancy including live birth rate and effect of GnRH analogue on fetus. Wider implications of the findings: A lower rate of OHSS occurrence in the long-acting group, and similar ART outcomes in both groups. Trial registration number IRCT20190609043845N1

Influence of female age on the fresh cycle live birth rate of different controlled ovarian hyperstimulation protocols in poor ovarian response patients

Objective: To investigate the influence of age on the fresh cycle live birth rate in patients with poor ovarian response in different controlled ovarian hyperstimulation groups. Methods: The clinical data of 3 342 patients in The First Affiliated Hospital of Zhengzhou University from February 2014 to November 2018 were retrospectively collected, including early-follicular phase long-acting gonadotropin-releasing hormone (GnRH) agonist long protocol group (1 375 cases), mid-luteal phase short-acting GnRH agonist long protocol group (1 161 cases) and GnRH antagonist protocol group (806 cases); each group was divided into 4 subgroups according to age: ≤30 years, 31－35 years, 36－40 years and >40 years, the pregnancy outcomes in each age subgroup were analyzed under different controlled ovarian hyperstimulation protocols. Results: In early-follicular phase long-acting GnRH agonist long protocol group, the final live birth rates of each age subgroup were 39.4% (228/579), 36.1% (135/374), 16.6% (48/290) and 3.0% (4/132); in mid-luteal phase short-acting GnRH agonist long protocol group, live birth rates of each age subgroup were 32.1% (99/308), 20.8% (55/264), 13.0% (45/346) and 7.0% (17/243); in GnRH antagonist protocol group, live birth rates of each age subgroup were 22.8% (26/114), 16.3% (25/153), 11.2% (31/278), and 3.8% (10/261); the live birth rate of each group decreased significantly with the increase of age (all P<0.01). When the age≤35 years old, the fresh cycle live birth rate of the early-follicular phase long-acting GnRH agonist long protocol group was significantly better than those of the other two groups (all P<0.01). The multivariate logistic regression analysis of age and live birth rate of the three controlled ovarian hyperstimulation groups showed age was the independent influence factor (OR=0.898, 95%CI: 0.873-0.916, P<0.01; OR=0.926, 95%CI: 0.890-0.996, P<0.01; OR=0.901, 95%CI: 0.863-0.960, P<0.01). Conclusions: Age is an independent influencing factor for the prediction of fresh cycle live birth rate in low ovarian response patients. No matter which controlled ovarian hyperstimulation protocol is adopted, the final live birth rate decreases significantly with the increase of women's age. In addition, the early-follicular phase long-acting GnRH agonist long protocol has the highest fresh cycle live birth rate among all controlled ovarian hyperstimulation groups.

Treatment of Uterine Fibroid Symptoms With Relugolix Combination Therapy

(Abstracted from N Engl J Med 2021;384:630–642) Approximately 25% of women with uterine fibroids experience symptoms, most commonly heavy menstrual bleeding (HMB) or fibroid-associated pain. Long-acting gonadotropin-releasing hormone (GnRH) agonists are effective for the medical management of uterine fibroids, but their duration of use is limited by hypoestrogenic sequelae.

Predictive Factors forLive Birth in Fresh In Vitro Fertilization/Intracytoplasmic Sperm Injection Treatment in Poor Ovarian Reserve Patients Classified by the POSEIDON Criteria.

The mechanisms underlying poor ovarian response (POR) in assisted reproductive technology remain unclear, there is no consensus on the management of poor responders, the POSEIDON stratification classifies infertility patients into “expected” or “unexpected” groups to provide a more nuanced picture of POR, but few researchers have discussed the independent predictive factors (smoothed plots and the threshold effect) for live birth in POR patients classified by the new criteria. We conducted a retrospective cohort study using clinical data from 6,580 POR patients classified by the POSEIDON criteria in the First Affiliated Hospital of Zhengzhou University, and explored the live birth based on the results before and after the threshold inflection point of each independent influencing factor. Among 6,580 poor ovarian reserve patients classified by the POSEIDON criteria, 1,549 (23.54%) had live births, and 5,031 (76.46%) did not have live births. Multivariate logistic regression analysis showed that female age (OR 0.901; 95% CI 0.887~0.916; P < 0.001), body mass index (OR 0.963; 95% CI 0.951~0.982; P < 0.001), antral follicle counting (OR 1.049; 95% CI 1.009~1.042; P < 0.001) and controlled ovarian hyperstimulation protocol were independent factors predicting live birth in patients with POR. The threshold effect analysis found that the inflection point of female age was 34 years old, and when age was > 34 years old, the probability of live birth in POR patients dropped sharply (OR 0.7; 95% CI 0.7~0.8; P < 0.001). The inflection point of BMI was 23.4 kg/m2, and BMI had a negative correlation with live birth (OR 0.963; 95% CI 0.951~0.982; P < 0.001). The threshold inflection point of AFC was 8n. Female age, BMI, AFC and COH protocol were independent predictive factors associated with live birth in POR patients classified by the POSEIDON criteria. The smooth curve fit and threshold effect analyses provide clinical management strategies for these patients. In addition, the early-follicular-phase long-acting GnRH-agonist long protocol seems to have a higher live birth rates than other protocols. It is worth highlighting that BMI should be considered as well in the POSEIDON criteria.

Diagnosis and management of precocious sexual maturation: an updated review.

The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. It is classified as central precocious puberty when premature maturation of the hypothalamic-pituitary-gonadal axis occurs, and as peripheral precocious puberty when there is excessive secretion of sex hormones, independent of gonadotropin secretion. Precocious sexual maturation is more common in girls, generally central precocious puberty of idiopathic origin. In boys, it tends to be linked to central nervous system abnormalities. Clinical evaluation should include a detailed history and physical examination, including anthropometric measurements, calculation of growth velocity, and evaluation of secondary sexual characteristics. The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. Hormonal assessment and imaging are required for diagnosis and identification of the etiology. Genetic testing should be considered if there is a family history of precocious puberty or other clinical features suggestive of a genetic syndrome. Long-acting gonadotropin-releasing hormone analogs are the standard of care for central precocious puberty management, while peripheral precocious puberty management depends on the etiology.Conclusion: The aim of this review is to address the epidemiology, etiology, clinical assessment, and management of precocious sexual maturation. What is Known: • The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. • Long-acting gonadotropin-releasing hormone agonist (GnRHa) is the standard of care for CPP management, and adequate hormone suppression results in the stabilization of pubertal progression, a decline in growth velocity, and a decrease in bone age advancement. What is New: • Most cases of precocious sexual maturation are gonadotropin-dependent and currently assumed to be idiopathic, but mutations in genes involved in pubertal development have been identified, such as MKRN3 and DLK1. • A different preparation of long-acting GnRHa is now available: 6-month subcutaneous injection.

Comparison of the Long-Acting GnRH Agonist Follicular Protocol with the GnRH Antagonist Protocol in Women Undergoing In Vitro Fertilization: A Systematic Review and Meta-analysis.

IntroductionTo evaluate the effectiveness and safety of long-acting GnRH agonist follicular and GnRH antagonist protocols among women undergoing in vitro fertilization (IVF) using data published in both English-language and Chinese studies.MethodsWe systematically searched the PubMed, Embase, Cochrane, CNKI, and Wanfang databases up to March 2019 for studies comparing long-acting GnRH agonist follicular and GnRH antagonist protocols in women undergoing IVF. The primary outcome was live birth rate; secondary outcomes were clinical pregnancy rate and implantation rate; safety outcomes were ovarian hyperstimulation syndrome (OHSS) and miscarriage rate in fresh cycle. Statistical analysis was done using R software. The study protocol was registered with PROSPERO (CRD42019139396).ResultsIn 11 studies that met the inclusion criteria, 1994 women belonged to the long-acting GnRH agonist follicular protocol group and 1678 to the GnRH antagonist protocol group. Live birth rate (relative risk (RR) 1.61; 95% confidence interval (CI) 1.27, 2.05; P < 0.001), clinical pregnancy rate (RR 1.44; 95% CI 1.32, 1.58; P < 0.001), and implantation rate (RR 1.58; 95% CI 1.44, 1.73; P = 0.001) were higher in the long-acting GnRH agonist follicular protocol compared with the antagonist protocol group. There was no difference in miscarriage rate (RR 0.98; 95% CI 0.58, 1.64; P = 0.98) between the long-acting GnRH agonist follicular and antagonist protocols. However, OHSS rate (RR 1.63; 95% CI 1.15, 2.32; P = 0.0058) was lower in the GnRH antagonist protocol compared to the long-acting GnRH agonist protocol group.ConclusionThe long-acting GnRH agonist follicular protocol was beneficial in improving live birth rate, clinical pregnancy rate, and implantation rate whereas the incidence of OHSS was significantly lower in women undergoing the GnRH antagonist protocol.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-020-01612-7.

Determination of Efficacy of Single and Double 4.7 mg Deslorelin Acetate Implant on the Reproductive Activity of Female Pond Sliders (Trachemys scripta)

Simple SummaryNorth American pond sliders (Trachemys scripta) are invasive alien species that, following the release of pet specimens in the wild over the decades, have established breeding populations outside their native habitat, with detrimental effects on local biodiversity. Their commerce and breeding have been recently banned in the European Union, and national programs are being introduced by Union Members to eradicate and control their presence. Among other means of population control, the use of long-acting drugs for chemically induced infertility could be a promising tool to prevent the reproduction of these animals. Efficacy of single and double intramuscular deslorelin acetate implants was investigated during a one-season follow-up: plasmatic sexual hormones concentration and morphometric evaluation of ovarian activity by computed tomography were performed about every 30 days to detect the differences between the control group (no implant), single-implant group, and double-implant group. Results show no inhibition of reproductive activity for the ongoing reproductive season, but suggest possible infertility starting from the following season.The use of long-acting gonadotropin-releasing hormone (GnRH) agonists to suppress fertility has been poorly investigated in reptiles, and the few available studies show inconsistent results. The efficacy of single and double intramuscular 4.7 mg deslorelin acetate implants in captive pond sliders (Trachemys scripta) was investigated, with 20 animals divided into three groups: a single-implant group (6 animals), a double-implant group (6 animals), and a control group (no implant). During one reproductive season (March to October), plasmatic concentration of sexual hormones (estradiol, progesterone, and testosterone) and ovarian morphometric activity via computed tomography were monitored about every 30 days. A significative decrease in the number of phase II ovarian follicles was detected in the double-implant group compared with the control group, but no significant difference was noted in the number of phase III and phase IV follicles, egg production, and plasmatic concentration of sexual hormones. Results show that neither a single nor a double deslorelin acetate implant can successfully inhibit reproduction in female pond sliders during the ongoing season, but the lower number of phase II follicles in the double-implant group can possibly be associated with reduced fertility in the following seasons.

Considerations for Providing Pediatric Gender-Affirmative Care During the COVID-19 Pandemic

Considerations for Providing Pediatric Gender-Affirmative Care During the COVID-19 Pandemic

Analysis of the Number of Euploid Embryos in Preimplantation Genetic Testing Cycles With Early-Follicular Phase Long-Acting Gonadotropin-Releasing Hormone Agonist Long Protocol

Studies have shown that early-follicular phase long-acting gonadotropin-releasing hormone (GnRH) agonist long protocol (EFLL), a popular controlled ovarian hyperstimulation protocol widely used in China, leads to higher rates of implantation and clinical pregnancy, as well as lower rates of spontaneous abortion and ectopic pregnancy in patients undergoing in vitro fertilization treatment. However, the impact of EFLL on euploid embryos and its underlying mechanisms remain unclear. To address these gaps of knowledge, we conducted a retrospective comparative study of 310 preimplantation genetic testing (PGT) cycles with a total of 1,541 embryos using the EFLL protocol or midluteal short-acting GnRH agonist long protocol (MLSL). Patients were matched by PGT subtype [aneuploidies (PGT-A) vs. PGT for chromosomal structural rearrangements (PGT-SR)], age (±2 years), and body mass index (±1 kg/m2). For PGT-A, there was no significant difference in the number of euploid embryos (1.80 ± 1.47 for EFLL vs. 1.84 ± 2.03 for MLSL, p > 0.05) or the rate of euploidy (44.6 vs. 36.9%, p > 0.05). For PGT-SR, the number of euploid embryos in the EFLL group was significantly higher than that in the MLSL group (1.76 ± 1.54 vs. 1.21 ± 1.24, p < 0.05). A higher euploidy rate was also observed with the EFLL protocol compared with that obtained in MLSL (31.9 vs. 25.7%), although the difference was not statistically significant (p > 0.05). Compared with the MLSL protocol, more euploid embryos were achieved when using the EFLL protocol in PGT-SR, demonstrating the value in PGT-SR. To the best of our knowledge, this study is the first one to compare embryonic outcomes between EFLL and MLSL, providing key insights into the clinical application of EFLL in PGT cycles. In the light of the limited sample size of our study, we recommend that these questions be explored using a larger prospective study.

Differential effects of testosterone on circulating neutrophils, monocytes, and platelets in men: Findings from two trials.

Testosterone treatment increases erythrocytes in men, but its effects on leukocyte and platelet counts are unknown and could affect its safety. To determine whether testosterone affects circulating leukocytes and platelets in men. Secondary analyses of two randomized testosterone trials were performed: the 5α-reductase (5aR) and OPTIMEN trials. In 5aR trial,102 healthy men, 21-50years (mean age 38), received a long-acting GnRH agonist, and 50, 125, 300, or 600mg/week testosterone enanthate (TE) plus placebo or 2.5mg/ day dutasteride for 20weeks. In OPTIMEN, 78 functionally limited men, ≥65years (mean age 72) with protein intake≤0.83gkg-1 day-1 , were randomized to controlled diets with 0.8gkg-1 day-1 protein or 1.3gkg-1 day-1 protein plus placebo or TE (100mg/week) for 6months.Changes from baseline in total and differential leukocyte count, and platelet count were evaluated. In 5aR, testosterone administration was associated with increases in total leukocyte (estimated change from baseline 40, 490, 1230, and 1280 cells/µL, P<.001), neutrophil (65.1, 436.1, 1177.2, and 1192.2 cells/µL, P<.001), monocyte (-20.2, 24.5, 90.6, and 143.9 cells/µL, P<.001), platelet (-7.3, 8.4, 8.7, and 8.9×103 cells/µL, P=.033), and erythrocyte counts. Testosterone did not affect absolute lymphocyte count. Similar increase in total leukocyte count was observed with testosterone treatment in OPTIMEN (change 0.77×103 cells/µL, P vs placebo=0.004). Testosterone administration in men differentially increases neutrophil and monocyte counts. These findings, together with its erythropoietic effects, suggest that testosterone promotes the differentiation of hematopoietic progenitors into the myeloid lineage. These findings have potential mechanistic, therapeutic, and safety implications.

Adult height after gonadotropin-releasing hormone agonist treatment in girls with early puberty: A meta-analysis.

This analysis of previously published reports was performed to examine the effects of gonadotropin-releasing hormone (GnRH) agonist treatment on adult height and the factors associated with adult height outcomes. GnRH agonists are first-line agents in the treatment of precocious puberty. However, studies regarding the treatment effect on subjects with early puberty have reported inconsistent results. A total of 14 studies identified from a search of electronic databases (AMED, EMBASE, MEDLINE and RISS) were included. Controlled studies with girls who developed puberty before 10years of age and measurements of the adult heights of the subjects were selected. Studies using only long-acting GnRH agonists to suppress puberty were included. Adult height, duration of the treatment, age at the start of treatment and bone age advancement were analysed. The mean age of the subjects ranged from 6.3 to 9.0years. The meta-analysis showed a pooled mean difference in adult height of 3.2cm and a 95% confidence interval of 1.3-5.1cm. The height difference between the treated subjects and controls was significantly associated with the duration of treatment (P=.005) rather than the age at the start of treatment (P=.084) or the difference between bone age and chronological age (P=.427). Administration of GnRH agonists in girls who develop early puberty and demonstrate advanced bone age may be effective for increasing adult height, especially if a sufficiently long treatment duration can be achieved.