Dual trigger with gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves oocyte yield in normal responders on GnRH-antagonist cycles.

OBJECTIVE: During in vitro fertilization (IVF) cycles, final oocyte maturation is usually triggered by human Chorionic Gonadotropin (hCG) for its known effect in mimicking Luteinizing Hormone (LH) surge; however, with the widespread use of the 'antagonist protocol', Gonadotropin Releasing Hormone agonist (GnRHa) is being more commonly employed as a trigger in order to minimize or eliminate the risk of ovarian hyper-stimulation syndrome (OHSS). Many studies proved its efficacy in inducing oocyte maturation and its safety in preventing OHSS in high-risk groups. Moreover, some studies showed that GnRHa trigger may improve oocyte yield. This study aimed to further explore any beneficial effect of adding GnRHa to hCG (dual trigger) on oocyte yield and fertilization rate in normal responder women. METHODS: We retrospectively reviewed and analyzed the data from 127 patients on antagonist protocol (67 dual trigger and 60 HCG trigger). RESULTS: The number of total oocytes, the number of MII oocytes and the number of fertilized oocytes were all significantly higher with the dual trigger protocol compared to hCG-only trigger. However, there is no significant difference in clinical pregnancy rate. CONCLUSIONS: Using the dual trigger improved the number and quality of oocytes, and the fertilization rate in normal responders.

HCG trigger versus GnRH agonist trigger in PCOS patients undergoing IVF cycles: frozen embryo transfer outcomes.

OBJECTIVE: The use of Gonadotrophin releasing hormone agonist (GnRHa), with freeze-all strategy followed by frozen embryo transfer (FET) has been found to eliminate the risk of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovarian syndrome (PCOS) undergoing IVF cycles. However, physicians still hesitate to routinely use GnRHa as a trigger, replacing human chorionic gonadotrophin (hCG), for concerns of compromised cycle outcome. We aimed to evaluate outcomes following the transfer of embryos in FET cycles obtained from GnRHa trigger in comparison with hCG trigger in PCOS patients of Asian origin. METHODS: Prospective observational cohort study. 210 PCOS patients undergoing IVF in an antagonist protocol who were randomized in the previous study (to evaluate if GnRHa trigger is a better alternative than hCG in PCOS patients to prevent OHSS; Group A: GnRHa trigger (n=92)] and Group B: hCG trigger (n=101)], were followed up in FET cycles to assess the outcomes. RESULTS: The odds of cumulative live birth rate per stimulation cycle favors GnRHa trigger against the hCG trigger [OR=2.15; (CI 1.2-3.83); p=0.008]. A significantly higher number of mature oocytes (19.1±11.7 versus 14.1±4.3; p<0.001) and blastocysts (4.2±1.63 versus 3.26±1.22; p<0.001) were available in the GnRHa group as compared to the hCG group. CONCLUSION: The cumulative live birth rate was better following transfer of frozen-thawed embryos generated from GnRHa-triggered cycles compared to hCG trigger. Hence, in PCOS undergoing IVF, as a good practice point, hCG trigger should be replaced by a GnRHa trigger with vitrification of all embryos followed by FET.

Thermal manipulation and GnRHa therapy applied to the reproduction of lambari-do-rabo-amarelo, Astyanax altiparanae females (Characiformes: Characidae) during the non-breeding season.

Lambari-do-rabo-amarelo Astyanax altiparanae in the wild reproduce during spring and summer, but females undergo vitellogenesis throughout the year, including the non-spawning winter period when water temperatures are low. The present study investigated the physiological role of temperature modulation on the hypothalamus-pituitary-gonads axis of lambari during winter, as well as the effects of gonadotropin releasing hormone agonist (GnRHa) therapy. Captive females were exposed to two different temperatures (20 °C and 27 °C) and were injected weekly with GnRHa for 21 days during winter (Control, CTR; Low dose; LD and high dose of GnRHa, HD). At the end of the 21-days period gonadosomatic index (GSI), oocyte stage of development and theoretical fecundity were evaluated, together with plasma levels of 17ß-estradiol (E2). Gene expression of the two pituitary gonadotropins follicle-stimulating hormone (fshß) and luteinizing hormone (lhß), as well as hepatic vitellogenin-A (vtgA) expression were also analyzed. At the end of the experimental period, females from the six different experimental conditions were induced to spawn using human chorionic gonadotropin (hCG). Spawning performance parameters and plasma levels of the maturation inducing steroid (MIS) were analyzed. Gene expression of fshß did not change with temperature manipulation, but females exposed to 27 °C and supplemented with a HD of GnRHa exhibited an increased fshß gene expression, associated with higher E2 levels. The higher water temperature alone was able to increase E2 levels. At both water temperatures GnRHa injections induced a decrease in E2 levels. GnRHa injected females had a lower vtgA gene expression levels at 20 °C. Even with differences in the gene expression of gonadotropins among the various temperature/GnRHa treatments, GSI and oocyte diameter did not change, but GnRHa enhanced the number of vitellogenic oocytes at 20 °C. The reproductive performance of lambari induced to spawn with hCG was better after the combined treatment with GnRHa and summer temperature.

Desencadenantes de la maduración ovocitaria en ciclos de fecundación in vitro / Triggers of oocyte maturation in cycles of in vitro fertilization

Tradicionalmente, desde que se iniciaron las técnicas de reproducción asistida, se solía usar un bolo de 5 000-10 000 UI de gonadotropina coriónica humana para la maduración final de los ovocitos como método estándar. Recientemente, se ha introducido un nuevo concepto, en el que los agonistas de la hormona liberadora de gonadotropina juegan un papel esencial en este campo. Ofrece importantes ventajas, entre las que se incluyen: una virtual prevención completa del síndrome de hiperestimulación ovárica. No obstante, algunos estudios defienden que el uso de hormona liberadora de gonadotropina puede ocasionar un defecto en la fase lútea que puede finalizar en una disminución en las tasas de implantación, en las tasas de gestación clínica o en un aumento de las tasas de aborto precoz. Así pues, en esta revisión analizamos las diferentes opciones terapéuticas para desencadenar la maduración final de los ovocitos en las técnicas de reproducción asistida, y discutimos los riesgos, beneficios y posibles complicaciones del uso de los agonistas de la GnRH como inductor de ovulación en ciclos de fecundación in vitro/inyección intracitoplasmática de espermatozoides(AU)

Traditionally, a bolus of 5000-10000 IU human chorionic gonadotropin (hCG) was used for final follicular maturation and ovulation as a standard method since assisted reproduction techniques started (ART). Recently, a new concept in which the releasing gonadotropin hormone agonists (GnRH-a) play an essential role has been introduced. This offers important advantages, including virtually prevention of ovarian hyperstimulation syndrome (OHSS). However, some studies described that using GnRH-a, could lead to defects in the luteal-phase that may result in a reduction of the implantation and clinical pregnancy rates; and also in an increase of early abortion rates. Therefore, the aim of this review is the analysis of different pharmaceutical options to trigger final oocyte maturation in ART, and the discussion of the risks, benefits and likely complications associated with the use of GnRH-a as an inductor of the ovulation during in vitro fecundation/intracitoplasmatic sperm injection cycles (IVF/ICSI)(AU)

Strategies for the management of OHSS: Results from freezing-all cycles.

OBJECTIVE: To compare the use of GnRH agonist (GnRHa) or hCG trigger in potential OHSS patients undergoing freeze-all programs. We also compared the clinical outcomes when fresh versus freeze-thawed embryo transfers were performed in cycles with a high number of retrieved oocytes. METHODS: The study included potential OHSS patients who received GnRHa (n=74) or hCG (n=49) trigger. The protocols were compared with respect to the clinical outcomes. We also compared the clinical outcomes of cycles in which hCG trigger was used and more than 20 MII oocytes were retrieved when: fresh embryo transfer protocol (n=153) or freeze-all protocol (n=123) were performed. RESULTS: A decreased serum estradiol level, a decreased number of retrieved oocytes, an increased MII retrieved rate, and decreased fertilization rate was observed in the hCG when compared with the GnRHa group. No significant differences were noted concerning clinical outcomes. When fresh cycles were compared with frozen-thawed cycles, the estradiol serum level and the number of cryopreserved embryos were higher in the frozen-thawed cycles. The clinical pregnancy rate was higher among freeze-all cycles, as well as the implantation and cumulative pregnancy rates, when compared with fresh embryo transfer cycles. CONCLUSION: The use of GnRHa trigger may be a good alternative to prevent the OHSS in patients presenting an extreme ovarian response to COS, leading to similar clinical outcomes, when compared with the traditional hCG trigger. Moreover, our findings demonstrated that the strategy of freezing-all embryos not only decreases the risk of OHSS but also leads to a better pregnancy rate.

Higher prevalence of obesity and overweight without an adverse metabolic profile in girls with central precocious puberty compared to girls with early puberty, regardless of GnRH analogue treatment.

OBJECTIVES: 1. To determine BMI, obesity/overweight rates, glucose and lipids at baseline, during GnRHa treatment and shortly after therapy discontinuation in female children with CPP and EP. 2. To compare this response to that seen in a similar group of untreated patients. METHODS: A retrospective analysis of 71 children with either CPP (n = 37) or EP (n = 34) was undertaken. Forty three were treated with a GnRHa for at least 2 years, while 28 were followed without treatment. RESULTS: At the time of diagnosis, a higher BMI (z-score of 1.1 ± 0.8 vs. 0.6 ± 0.7, p = 0.004) and a higher prevalence of obesity/overweight (72.9 vs. 35.3%, p = 0.001) was observed in subjects with CPP when compared to those with EP. Children with EP had higher fasting glucose and total cholesterol than those with CPP. BMI z-score, obesity/overweight rates, fasting glucose and lipids did not change significantly in girls with CPP or EP during 3 yrs of follow up, regardless of treatment. Weight z-scores were higher at 3 years in treated than in untreated girls with CPP (p = 0.02), while it was higher in untreated than in GnRHa-treated patients with EP at baseline, 1, 2 and 3 years (p = 0.007, p = 0.002, p = 0.02 and p = 0.04, respectively) and remained so shortly after stopping therapy (p = 0.03). CONCLUSIONS: There is a high prevalence of obesity/overweight in girls with CPP and EP at diagnosis. However, this risk is greater in CPP than in EP girls. BMI, Obesity/overweight rates, fasting glucose and lipids remained stable in CPP and EP girls regardless of therapy. Weight z-scores were found to be higher in treated CPP girls and in untreated girls with EP.

A single histrelin implant is effective for 2 years for treatment of central precocious puberty.

We investigated whether a "yearly" histrelin implant would provide pubertal suppression when left in place for 2 years. Equivalent suppression was observed when comparing 12 and 24 months in 33 children with central precocious puberty. A single implant for 2 years reduces cost and number of implant procedures.

Time to menarche and final height after histrelin implant treatment for central precocious puberty.

OBJECTIVE: To compare final height, change in body mass index (BMI), and time from end of treatment until menarche in girls with central precocious puberty treated with the histrelin implant versus depot gonadotropin releasing hormone agonist injections. STUDY DESIGN: Chart review, interview, and final height measurements of 2 groups of girls with central precocious puberty; triptorelin depot (TD) group: 23 girls were treated from age 8.4 ± 0.3 with monthly injections of TD, for 26.7 ± 2.5 months; histrelin implant group: 11 girls were treated from age 8.7 ± 0.3 years for 28.4 ± 3.7 months, of whom 9 initially received monthly TD injections for 1.5-39 months. Final height, BMI (pretreatment vs recent), and time between either implant removal or last injection to menarche were compared. RESULTS: Time between removal of implant or last injection and menarche was 9.3 ± 1.5 (histrelin implant group) versus 16.1 ± 1.7 (TD group) months (P = .02). Predicted height at implant insertion was 156.8 ± 2.6 cm, and final height was 161.1 ± 2.0 cm (not significant [NS]). Predicted height for TD was 155.2 ± 1.9 cm and final height was 157.9 ± 1.7 cm (NS). Change from onset of treatment to final BMI-SDS for histrelin implant was -0.41 ± 0.3, and for TD was -0.03 ± 0.2 (NS). CONCLUSIONS: Menarche occurred sooner after implant removal. There was no difference in final height or BMI outcomes between the 2 treatment modalities.

Buserelin acetate-induced spermiation in Leptodactylus ocellatus and evaluation of semen characteristics / Espermiação com acetato de buserelina em Leptodactylus ocellatus e avaliação de características seminais

By understanding the hormonal action behind the induction of spermiation in Leptodactylus ocellatus can help in the collection of semen for artificial insemination and cryopreservation. The experiments were conducted at the Experimental Frog Farm of the Federal University of Viçosa. Seven L. ocellatus males with the following secondary sexual characteristics were selected: black thorns, developed forelimbs, and amplexus reflex. Spermiation was induced in these animals by applying daily 0.4 g buserelin acetate hormone (GnRHa) for 7 days, being the semen collected 90 min after the application. The volume, color, vigor, motility, sperm concentration, and spermatozoa morphology were subsequently evaluated. Three animals responded to GnRHa induction, enabling the collection of seven samples of semen, and the first sample was collected 97.5h after the first application. The semen of the creole frog presented the following characteristics: an average volume of 0.38 mL, murky color, sperm vigor of 3.71, sperm motility of 77.14%, sperm concentration of 6.60 x 106 SPTZ mL-1, and 69% of normal sperm. GnRHa can induce spermiation in the creole frog. Although the volume of collected semen was low, the color, vigor, motility, concentration, and spermatozoa content showed to be adequate.(AU)

O conhecimento da ação de hormônios na indução à espermiação de Leptodactylus ocellatus pode permitir a coleta de sêmen para estudos de fertilização artificial e criopreservação. O experimento foi realizado no Ranário Experimental da Universidade Federal de Viçosa, onde sete machos de L. ocellatus com as características sexuais secundárias: acúleos negros, membros anteriores desenvolvidos e reflexos ao amplexo foram induzidos à espermiação com aplicação do hormônio acetato de buserelina (GnRHa) na dosagem de 0,4 g, durante sete dias a cada 24h e o sêmen coletado após 90 min. O volume, cor do sêmen, vigor espermático, motilidade espermática, concentração espermática e morfologia dos espermatozoides foram avaliados. Três animais responderam à indução pelo acetato de buserelina permitindo a coleta de sete amostras de sêmen, a primeira após 97,5h da primeira aplicação. O sêmen da rã-manteiga apresentou volume médio de 0,38 mL, coloração turva, vigor espermático de 3,71; motilidade espermática de 77,14%, concentração de 6,60 x 106 SPTZ mL-1 e 69% de espermatozoides normais. O acetato de buserelina pode induzir à espermiação da rã-manteiga. O volume seminal coletado foi baixo, mas a coloração, vigor, motilidade, concentração e número de espermatozoides de L. ocellatus foram adequados.(AU)

Buserelin acetate-induced spermiation in Leptodactylus ocellatus and evaluation of semen characteristics / Espermiação com acetato de buserelina em Leptodactylus ocellatus e avaliação de características seminais

By understanding the hormonal action behind the induction of spermiation in Leptodactylus ocellatus can help in the collection of semen for artificial insemination and cryopreservation. The experiments were conducted at the Experimental Frog Farm of the Federal University of Viçosa. Seven L. ocellatus males with the following secondary sexual characteristics were selected: black thorns, developed forelimbs, and amplexus reflex. Spermiation was induced in these animals by applying daily 0.4 µg buserelin acetate hormone (GnRHa) for 7 days, being the semen collected 90 min after the application. The volume, color, vigor, motility, sperm concentration, and spermatozoa morphology were subsequently evaluated. Three animals responded to GnRHa induction, enabling the collection of seven samples of semen, and the first sample was collected 97.5h after the first application. The semen of the creole frog presented the following characteristics: an average volume of 0.38 mL, murky color, sperm vigor of 3.71, sperm motility of 77.14%, sperm concentration of 6.60 x 106 SPTZ mL-1, and 69% of normal sperm. GnRHa can induce spermiation in the creole frog. Although the volume of collected semen was low, the color, vigor, motility, concentration, and spermatozoa content showed to be adequate.

O conhecimento da ação de hormônios na indução à espermiação de Leptodactylus ocellatus pode permitir a coleta de sêmen para estudos de fertilização artificial e criopreservação. O experimento foi realizado no Ranário Experimental da Universidade Federal de Viçosa, onde sete machos de L. ocellatus com as características sexuais secundárias: acúleos negros, membros anteriores desenvolvidos e reflexos ao amplexo foram induzidos à espermiação com aplicação do hormônio acetato de buserelina (GnRHa) na dosagem de 0,4 µg, durante sete dias a cada 24h e o sêmen coletado após 90 min. O volume, cor do sêmen, vigor espermático, motilidade espermática, concentração espermática e morfologia dos espermatozoides foram avaliados. Três animais responderam à indução pelo acetato de buserelina permitindo a coleta de sete amostras de sêmen, a primeira após 97,5h da primeira aplicação. O sêmen da rã-manteiga apresentou volume médio de 0,38 mL, coloração turva, vigor espermático de 3,71; motilidade espermática de 77,14%, concentração de 6,60 x 106 SPTZ mL-1 e 69% de espermatozoides normais. O acetato de buserelina pode induzir à espermiação da rã-manteiga. O volume seminal coletado foi baixo, mas a coloração, vigor, motilidade, concentração e número de espermatozoides de L. ocellatus foram adequados.

Near-final height in patients with congenital adrenal hyperplasia treated with combined therapy using GH and GnRHa / Altura quase normal em pacientes com hiperplasia adrenal congênita tratados com a combinação de GH e GnRHa

INTRODUCTION: Intrinsic limitations of glucocorticoid therapy in patients with congenital adrenal hyperplasia (CAH) determine frequent loss in final height. The association of secondary central precocious puberty and early epiphyseal fusion is also frequent. In these conditions, GnRHa treatment alone or in combination with GH has been indicated. OBJECTIVES: This is a retrospective study, describing the estatural findings of CAH patients with significant decrease in height prediction, who were submitted to combined GH plus GnRHa therapy up to near-final height. SUBJECTS AND METHODS: We studied 13 patients, eight females and five males, eight with the classical and five with the nonclassical form of the disorder. Treatment with hydrocortisone (10-20 mg/m²/day) or prednisolone (3-6 mg/kg/day) was associated with GnRHa (3.75 mg/months) for 4.0 (1.5) years, and GH (0.05 mg/kg/day) for 3.6 (1.4) years. RESULTS: Stature standard deviation score for bone age improved significantly after GH treatment, becoming similar to target height at the end of the second year of GH treatment. CONCLUSION: We conclude that combined GH plus GnRHa therapy can be useful in a subset of CAH patients with significant reduction of predicted final height associated with poor hormonal control and central precocious puberty.

INTRODUÇÃO: As limitações intrínsecas da terapia com glicocorticoides em pacientes com hiperplasia adrenal congênita (HAC) frequentemente determinam menor altura final. Também é frequente a associação de puberdade precoce central secundária e fusão epifisária precoce. Nessas condições, tem sido indicado o tratamento com GnRHa sozinho ou em combinação com o GH. OBJETIVOS: Este é um estudo retrospectivo que descreve os achados de altura em pacientes com HAC que apresentavam diminuição significativa na altura predita e que foram submetidos ao tratamento combinado de GH com GnRHa até a altura quase normal. SUJEITOS E MÉTODOS: Estudamos 13 pacientes, oito do sexo feminino e cinco do sexo masculino, oito com a forma clássica e cinco com a forma não clássica da doença. O tratamento com hidrocortisona (10-20 mg/m²/dia) ou prednisolona (3-6 mg/kg/day) foi associado com GnRHa (3,75 mg/meses) por 4,0 (1,5) anos, e GH (0,05 mg/kg/dia) por 3,6 (1,4) anos. RESULTADOS: O escore de desvio-padrão da estatura para a idade óssea melhorou significativamente após o tratamento com GH, tornando-se similar à altura normal ao final do segundo ano desse tratamento. CONCLUSÃO: Concluímos que o tratamento de combinação com GH e GnRHa pode ser útil em um subgrupo de pacientes com HAC que apresentem redução significativa da altura final predita, associado com controle hormonal inadequado e puberdade central precoce.