Homogenização da coorte folicular pela administração de estradiol em ciclos de estimulação ovariana controlada com antagonista de GnRH protocolo de doses múltiplas

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Recombinant luteinizing hormone supplementation to recombinant follicle-stimulation hormone during induced ovarian stimulation in the GnRH-agonist protocol: A meta-analysis

Purpose: to compare the efficacy of recombinant LH supplementation for controlled ovarian stimulation in recombinant FSH and GnRH-agonist protocol.Methods: Search strategies included on-line surveys of databases. The fixed effects model was used for odds ratio and effect size (weighted mean difference). Four trials fulfilled the inclusion criteria.Results: a fewer days of stimulation (p < 0.0001), a fewer total amount of r-FSH administered (p < 0.0001) and a higher serum estradiol levels on the day of hCG administration (p < 0.0001) were observed for the r-LH supplementation protocol. However, differences were not observed in number of oocyte retrieved, number of mature oocytes, clinical pregnancy per oocyte retrieval, implantation and miscarriage rates.Conclusions: more randomized controlled trials are necessary before evidence-based recommendations regarding exogenous LH supplementation in ovarian stimulation protocols with FSH and GnRH-agonist for assisted reproduction treatment can be provided.

Adjuvant therapy with GnRH agonists/tamoxifen in breast cancer should be a good council for patients with hormone receptor-positive tumours and wish to preserve fertility

Infertility represents one of the main long-term consequences of the chemotherapy used for the adjuvant treatment of breast cancer. Approximately 60-65% of breast cancers express the nuclear hormone receptor in premenopausal women. Adjuvant endocrine therapy is an integral component of care for patients with hormone receptor-positive (HR+) tumours. The GnRH agonist (GnRHa) alone or in combination with tamoxifen produces results at least similar to those obtained with the different chemotherapy protocols in patients with HR+ breast cancer with respect to recurrence-free survival and overall survival. It is time to indicate adjuvant therapy with GnRHa associated with tamoxifen for patients with breast cancer (HR+ tumours) if they want to preserve their reproductive function. The evaluation of ovarian reserve tests: follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume 6 months, and 1 year after the end of therapy with GnRHa/tamoxifen must be realised. The recurrence-free survival and overall survival should be analysed. The major implication of this hypothesis will be to avoid adjuvant chemotherapy for patients with breast cancer (HR+ tumours) that request fertility preservation. It is expected that ovarian function should not be altered in almost all cases and subsequent pregnancy a real possibility. (C) 2012 Elsevier Ltd. All rights reserved.

GnRH agonist versus GnRH antagonist in IVF/ICSI cycles with recombinant LH supplementation: DNA fragmentation and apoptosis in granulosa cells

Objective: To compare the level of apoptosis and DNA fragmentation in the human granulosa cell (GC) layer exposed to an agonist or antagonist of GnRH in intracytoplasmic sperm injection (ICSI) cycles supplemented with recombinant LH (rLH).Study design: Patients without ovulatory dysfunction, aged <= 37 years and in their first ICSI cycle were prospectively randomised to receive either a long GnRH agonist protocol or a multi-dose antagonist protocol. In both groups, recombinant FSH supplemented with rLH was used for ovarian stimulation, and the GCs were collected during oocyte denudation. The GCs were then analysed for DNA fragmentation by TUNEL assay and for apoptosis using the annexin-V assay. The outcomes were given as the percentage of GCs with DNA fragmentation and apoptosis out of the total number of GCs analysed. Comparison of the agonist versus the antagonist group was performed using the Mann-Whitney test.Results: DNA fragmentation: 32 patients were included in either the GnRH agonist group (n = 16) or the antagonist group (n = 16). The percentage of GCs with positive DNA fragmentation did not differ significantly (P = 0.76) between the agonist group (15.5 +/- 9.4%) and the antagonist group (18.8 +/- 13.3%). Apoptosis: 28 patients were included in either the GnRH agonist group (n = 14) or the antagonist group (n = 14). The percentage of GCs positive for apoptosis did not differ significantly (P = 0.78) between the agonist group (34.6 +/- 14.7%) and the antagonist group (36.5 +/- 22%).Conclusions: The results suggest that therapy with either an agonist or antagonist of GnRH is associated with comparable levels of DNA fragmentation and apoptosis in granulosa cells in ICSI cycles supplemented with rLH. (C) 2012 Elsevier B.V. All rights reserved.

Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis

Background: The effects of gonadotrophin-releasing hormone agonist (GnRH-a) administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes.Methods: The research strategy included the online search of databases. Only randomized studies were included. The outcomes analyzed were implantation rate, clinical pregnancy rate (CPR) per transfer and ongoing pregnancy rate. The fixed effects model was used for odds ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after ICSI procedures.Results: All cycles presented statistically significantly higher rates of implantation (P < 0.0001), CPR per transfer (P = 0.006) and ongoing pregnancy (P = 0.02) in the group that received luteal-phase GnRH-a administration than in the control group (without luteal-phase-GnRH-a administration). When meta-analysis was carried out only in trials that had used long GnRH-a ovarian stimulation protocol, CPR per transfer (P = 0.06) and ongoing pregnancy (P = 0.23) rates were not significantly different between the groups, but implantation rate was significant higher (P = 0.02) in the group that received luteal-phase-GnRH-a administration. on the other hand, the results from trials that had used GnRH antagonist multi-dose ovarian stimulation protocol showed statistically significantly higher implantation (P = 0.0002), CPR per transfer (P = 0.04) and ongoing pregnancy rate (P = 0.04) in the luteal-phaseGnRH- a administration group. The majority of the results presented heterogeneity.Conclusions: These findings demonstrate that the luteal-phase single-dose GnRH-a administration can increase implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by considering the heterogeneity between the trials, it seems premature to recommend the use of GnRH-a in the luteal phase. Additional randomized controlled trials are necessary before evidence-based recommendations can be provided.

Effects of recombinant LH supplementation to recombinant FSH during induced ovarian stimulation in the GnRH-agonist protocol: a matched case-control study

Background: Some studies have suggested that the suppression of endogenous LH secretion does not seem to affect the majority of patients who are undergoing assisted reproduction and stimulation with recombinant FSH (r-FSH). Other studies have indicated that a group of normogonadotrophic women down-regulated and stimulated with pure FSH preparations may experience low LH concentrations that compromise the IVF parameters. The present study aimed to compare the efficacy of recombinant LH (r-LH) supplementation for controlled ovarian stimulation in r-FSH and GnRH-agonist (GnRH-a) protocol in ICSI cycles.Methods: A total of 244 patients without ovulatory dysfunction, aged < 40 years and at the first ICSI cycle were divided into two groups matched by age according to an ovarian stimulation scheme: Group I (n = 122): Down-regulation with GnRH-a + r-FSH and Group II (n = 122): Downregulation with GnRH-a + r-FSH and r-LH (beginning simultaneously).Result(s): The number of oocytes collected, the number of oocytes in metaphase II and fertilization rate were significantly lower in the Group I than in Group II (P = 0.036, P = 0.0014 and P = 0.017, respectively). In addition, the mean number of embryos produced per cycle and the mean number of frozen embryos per cycle were statistically lower (P = 0.0092 and P = 0.0008, respectively) in Group I than in Group II. Finally the cumulative implantation rate (fresh+thaw ed embryos) was significantly lower (P = 0.04) in Group I than in Group II. The other clinical and laboratory results analyzed did not show difference between groups.Conclusion: These data support r-LH supplementation in ovarian stimulation protocols with r-FSH and GnRH-a for assisted reproduction treatment.

GnRH agonist versus GnRH antagonist in assisted reproduction cycles: oocyte morphology

Background: The selection of developmentally competent human gametes may increase the efficiency of assisted reproduction. Spermatozoa and oocytes are usually assessed according to morphological criteria. Oocyte morphology can be affected by the age, genetic characteristics, and factors related to controlled ovarian stimulation. However, there is a lack of evidence in the literature concerning the effect of gonadotropin-releasing hormone (GnRH) analogues, either agonists or antagonists, on oocyte morphology. The aim of this randomized study was to investigate whether the prevalence of oocyte dysmorphism is influenced by the type of pituitary suppression used in ovarian stimulation.Methods: A total of 64 patients in the first intracytoplasmic sperm injection (ICSI) cycle were prospectively randomized to receive treatment with either a GnRH agonist with a long-term protocol (n: 32) or a GnRH antagonist with a multi-dose protocol (n: 32). Before being subjected to ICSI, the oocytes at metaphase II from both groups were morphologically analyzed under an inverted light microscope at 400x magnification. The oocytes were classified as follows: normal or with cytoplasmic dysmorphism, extracytoplasmic dysmorphism, or both. The number of dysmorphic oocytes per total number of oocytes was analyzed.Results: Out of a total of 681 oocytes, 189 (27.8 %) were morphologically normal, 220 (32.3 %) showed cytoplasmic dysmorphism, 124 (18.2%) showed extracytoplasmic alterations, and 148 (21.7%) exhibited both types of dysmorphism. No significant difference in oocyte dysmorphism was observed between the agonist- and antagonist- treated groups (P > 0.05). Analysis for each dysmorphism revealed that the most common conditions were alterations in polar body shape (31.3%) and the presence of diffuse cytoplasmic granulations (22.8%), refractile bodies (18.5%) and central cytoplasmic granulations (13.6%). There was no significant difference among individual oocyte dysmorphisms in the agonist- and antagonist-treated groups (P > 0.05).Conclusions: Our randomized data indicate that in terms of the quality of oocyte morphology, there is no difference between the antagonist multi-dose protocol and the long-term agonist protocol. If a GnRH analogue used for pituitary suppression in IVF cycles influences the prevalence of oocyte dysmorphisms, there does not appear to be a difference between the use of an agonist as opposed to an antagonist.

Remoção temporária de bezerros em dois momentos do protocolo de sincronização da ovulação GnRH-PGF2α-BE em vacas Nelore pós-parto

Os efeitos da remoção temporária de bezerros (RB) sobre características foliculares e taxas de ovulação e de prenhez de vacas Nelore foram avaliados em dois experimentos quando da inseminação artificial em tempo fixo (IATF), utilizando-se um protocolo à base de GnRH-PGF2α-BE. No experimento 1, 139 vacas Nelore, lactantes, cíclicas ou acíclicas, receberam um protocolo hormonal envolvendo a aplicação de 100±g de análogo GnRH no dia zero (D0-GnRH), 25mg de PGF2α no dia 7 (D7-PGF2α) e 1,0mg de benzoato de estradiol no dia 8 (D8-BE). Os animais foram aleatoriamente distribuídos para serem submetidas ou não à RB (48 horas) antes da aplicação de GnRH (RB1) ou após a aplicação de PGF2α (RB2). Avaliaram-se o diâmetro folicular (DF) nos dias 0 (D0) e 9 (D9) do protocolo e as taxas de ovulação (T0), advindas dos tratamentos. As vacas acíclicas que receberam RB1 apresentaram maiores DF no D0 (P<0,05) e taxa de ovulação (P<0,05) quando da aplicação de GnRH, em relação às que não receberam RB1. Nas vacas cíclicas, não houve efeito da RB1 sobre as variáveis analisadas. As vacas que receberam RB2 apresentaram maiores DF no D9 (P<0,05) e taxa de ovulação (P<0,01) quando da aplicação de BE, em relação às que não receberam a RB2. No experimento 2, 376 vacas da raça Nelore, lactantes, foram submetidas ao mesmo protocolo hormonal e aos mesmos tratamentos do experimento 1, mas foram inseminadas 24 a 30 horas após a aplicação de BE no D8, visando avaliar a taxa de prenhez após a IATF. A taxa de prenhez foi maior nos animais que receberam as duas RB em relação às que não receberam RB (29,8% vs 10,6%; P<0,05). A remoção de bezerros associada ao protocolo hormonal aplicado pode ter aumentado as taxas de prenhez devido às maiores taxas de ovulação, em resposta ao GnRH ou ao benzoato de estradiol.

Conception rate in Holstein cows treated with GnRH or hCG on the fifth day post artificial insemination during summer

Vacas da raça Holandesas em lactação (n=158) aos 213±112 dias de lactação e produção de 26±9kg leite/dia, foram aleatoriamente distribuídas em três grupos: controle (GC, n=52, salina); GnRH (GG, n=55, 100mcg de gonadorelina); e hCG (GH, n=51, 2500UI de hCG) aplicado no dia 5 após a inseminação artificial (IA). A temperatura retal foi verificada no momento da IA, e as amostras de sangue coletadas nos dias 5, 7 e 12 após a IA. A concepção foi determinada entre os dias 42 e 49 após IA. As concentrações séricas de progesterona (P4 - ng/ml, média±EPM) para GC, GG, e GH foram, respectivamente: no dia 5: 2,7±0,4, 2,5±0,4 e 3,2±0,4; no dia 7: 4,8±0,4, 4,2±0,4 e 5,7±0,5; e no dia 12 após a IA: 5,2±0,4, 6,9±0,4 e 8,5±0,5. O aumento proporcional na concentração sérica de P4 entre os dias 5 e 7 após IA (GC: 178%, GG: 168%, e GH: 178%) sugere que os tratamentos não induziram efeito luteotrópico no corpo lúteo (CL) existente. O aumento na P4 sérica entre os dias 7 e 12 nos animais tratados com GnRH ou hCG (GG: 164% e GH: 149%, P<0,01) em relação aos animais controle (GC: 18%, P=0,31), sugere a indução de novo CL. Os tratamentos com GnRH ou hCG aumentaram as taxas de concepção nas vacas com temperatura retal abaixo de 39,7°C (GC: 10,1%, n=26; GG: 36,8%, n=27 e GH: 32,8%, n=21), mas não em vacas com temperatura retal acima de 39,7°C (15,2% n=26; 17,8%, n=28 e 24,4%, n=30). Os resultados sugerem que a alta temperatura corporal pode mascarar os efeitos positivos do tratamento com GnRH ou hCG no dia 5 após a IA, na concepção.

Cisto ovariano em vacas de leite: incidência, resposta à aplicação de GnRH e desempenho reprodutivo

A incidência de cistos ovarianos, a resposta ao tratamento com GnRH e os efeitos da ocorrência de cisto no desempenho reprodutivo e na taxa de descarte foram determinados em vacas lactantes da raça Holandesa. Vacas lactantes (n=333) foram avaliadas semanalmente por ultrassonografia a partir da quarta semana pós-parto, visando à detecção de corpos lúteos (CL) e de folículos ovarianos maiores que 10mm. Na sétima semana pós-parto, as vacas foram classificadas: em ciclando (n=248; presença de CL em um dos exames ultrassonográficos); em anestro (n=54; ausência de CL e de folículos >25mm) e com cisto (n=31; ausência de CL e presença de estruturas >25mm), quando foram distribuídas em: grupo-controle (n=16; sem tratamento) e grupo-tratamento (n=15; vacas que receberam uma aplicação de GnRH). A taxa de cura foi de 60,0% no grupo das vacas tratadas e de 87,5% no grupo-controle. As vacas com cistos apresentaram maior intervalo parto-primeira inseminação artificial (P<0,05; 91,4±8,3 vs. 77,8±2,5), maior número de serviços por concepção (P<0,05; 4,4±1,2 vs. 3,6±1,5), maior intervalo parto-concepção (P<0,05; 214,8±25,9 vs. 174,9±7,7) e maior taxa de descarte (P<0,05; 41,2 vs. 21,8%) do que as vacas ciclando. Vacas diagnosticadas com cisto na sétima semana pós-parto apresentaram recuperação espontânea, embora o intervalo parto-concepção e a taxa de descarte tenham sido maiores para essas vacas.