effect of coasting on intracytoplasmic sperm injection outcome in antagonist and agonist cycle

Background: Coasting can reduce the ovarian hyperstimulation syndrome [OHSS] risk in ovulation induction cycles before intracytoplasmic sperm injection [ICSI]. This study aimed to investigate the effect of gonadotropin-releasing hormone [GnRH] agonist and GnRH antagonist protocols to controlled ovarian hyperstimulation [COH] cycles with coasting on the parameters of ICSI cycles and the outcome

Materials and Methods: In a retrospective cohort study, 117 ICSI cycles were performed and coasting was applied due to hyperresponse, between 2006 and 2011. The ICSI outcomes after coasting were then compared between the GnRH agonist group [n=91] and the GnRH antagonist group [n=26]

Results: The duration of induction and the total consumption of gonadotropins were found to be similar. Estradiol [E[2]] levels on human chorionic gonadotropin [hCG] day were found higher in the agonist group. Coasting days were similar when the two groups were compared. The number of mature oocytes and the fertilization rates were similar in both groups; however, the number of grade 1 [G1] embryos and the number of transferred embryos were higher in the agonist group. Implantation rates were significantly higher in the antagonist group compared to the agonist group. Pregnancy rates/embryo transfer rates were higher in the antagonist group; however, this difference was not statistically significant [32.8% for agonist group vs. 39.1% for antagonist group, P>0.05]

Conclusion: The present study showed that applying GnRH-agonist and GnRH-antagonist protocols to coasted cycles did not result in any differences in cycle parameters and clinical pregnancy rates

Microdose GnRH agonist flare-up versus ultrashort GnRH agonist combined with fixed GnRH antagonist in poor responders of assisted reproductive techniques cycles

This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasing hormone [GnRH] agonist flare combined with the fixed multidose GnRH antagonist protocol in poor responders undergoing ovarian stimulation. In this randomized clinical trial, 120 women who were candidates for assisted reproductive techniques [ART] and had histories of one or more failed in vitro fertilization [IVF] cycles with three or fewer retrieved oocytes were prospectively randomized into two groups. Group I [60 patients] received the microdose flare-up regimen and group II [60 patients] received the ultrashort GnRH agonist combined with fixed GnRH antagonist. There were no significant differences between the groups in the number of used gonadotropin ampoules [p=0.591], duration of stimulation [p=0.610], number of retrieved oocytes [p=0.802], fertilization rate [p=0.456], and the number of transferred embryos [p=0.954]. The clinical pregnancy rates were statistically similar in group I [10%] compared with group II [13.3%, p=0.389]. According to our results, there is no significant difference between these protocols for improving the ART outcome in poor responders. Additional prospective, randomized studies with more patients is necessary to determine the best protocol [Registration Number: IRCT201105096420N1]

Impacto da radioterapia e da quimioterapia sobre o aparelho genital feminino: procedimentos terapêuticos / Radiotherapy and chemotherapy impact on female genital apparatus: therapeutic procedures

No presente estudo apresentamos os diversos procedimentos terapêuticos existentes com o intuito de obter-se proteção e melhoria dos danos induzidos por radioterapia e quimioterapia no aparelho genital feminino.

The aim of this study is obtain a convenient analysis of different therapeutic methods to improve better conditions before and after radiotherapy and chemotherapy in the female genital apparatus.

Protocolo largo con análogos de GnRH versus protocolo corto con antagonistas: ¿existen diferencias en cuanto a los resultados de los ciclos de FIV-ICSI? / Protocol with GnRH analogues vs antagonists of GnRH: exist differences in the results of the IVF-ICSI cycles?

Objetivo: Valorar si existen diferencias en los resultados de los ciclos de FIV-ICSI en función del protocolo de estimulación empleado. Método: Estudio retrospectivo descriptivo de pacientes infértiles que fueron sometidas a ciclos de FIV-ICSI en el Hospital Universitario La Paz, entre los meses de enero y septiembre de 2010, comparando un protocolo largo de estimulación con análogos de GnRH vs un protocolo corto con antagonistas de GnRH. Las variables analizadas fueron: tasa de gestación, necesidad de cancelación del ciclo, dosis total de gonadotropinas requerida durante la estimulación, niveles de estradiol sérico el día de la administración de la hCG, número de folículos puncionados, complejos obtenidos, número de ovocitos maduros y de embriones conseguidos. Resultados: No hubo diferencias estadísticamente significativas en los resultados de los ciclos en función del protocolo de estimulación empleado, en ninguna de las variables analizadas. Conclusiones: Este estudio no encontró diferencias en los resultados de los ciclos de FIV-ICSI con relación al uso de análogos o antagonistas de GnRH. Es necesarios más estudios con mayores tamaños muestrales para definir qué tipo de pacientes serían subsidiarias de recibir cada tratamiento para conseguir resultados óptimos.

Aims: To assess if there exist any differences in the results of the IVF-ICSI cycles depending on the stimulation protocol employed. Methods: Retrospective descriptive study of infertile patients who underwent IVF-ICSI cycles at La Paz University Hospital, between January and September 2010, comparing sitmulation protocol with GnRH agonists vs antagonists of GnRH. The variables analyzed were pregnancy rate, cancellation rate, total dose of gonadotropin required for stimulation, serum estradiol levels on the day of hCG administration, number of follicles punctured, complexes obtained, number of mature oocytes and of embryos obtained. Results: No statistically significant differences where found in the results of cycles depending on the protocol of stimulation used in any of the variables analyzed. Conclusions: This study didn't find any difference in the outcome of IVF-ICSI cycles in relation to the use of GnRH agonists or antagonists. We need more studies with larger sample sizes to determine which is the best treatment to each patient in order to achieve optimal results.

Hormônios utilizados na estimulação ovariana / Hormones used for ovarian stimulation

A fertilização in vitro (FIV) se tornou uma opção estabelecida e altamente eficiente para tratar a infertilidade conjugal de várias causas etiológicas. Por meio de uma hiperestimulação ovariana controlada, pode-se obter múltiplos oócitos de boa qualidade que potencialmente podem ser fertilizados, desenvolvidos e formar embriões. As gonadotrofinas são drogas fundamentais para essa estimulação. Com o uso de vários protocolos, conseguiu-se melhorar a estimulação folicular e a qualidade dos oócitos recrutados, a prevenção da liberação precoce de hormônio luteinizante, a diminuição das taxas de cancelamento de procedimentos e uma melhora nas taxas de gravidez. Esta revisão busca atualizar os conhecimentos sobre os hormônios atualmente utilizados com essa finalidade

In vitro fertilization (IVF) has become an established, highly efficient therapy for treating infertility of various etiologic causes. One of the major goals of IVF therapy is to obtain multiple fertilizable oocytes of good quality that can lead to diploid fertilization and early embryo development through a controlled ovarian hyperstimulation. Gonadotropins are the fundamental agents used in ovulation stimulation. Significant improvements were observed in the stimulation of follicular development and in the quality of developing oocytes; in the prevention of a premature luteinizing hormone release; in the cancellation rates; and an overall improvement in the total reproductive potential by using several different protocols. This review intends to update the knowledge about the hormones used in this process

Cessation of Gonadotropin-Releasing Hormone Antagonist on Triggering Day: An Alternative Method for Flexible Multiple-Dose Protocol

This study was performed to analyze retrospectively outcomes of stimulated in vitro fertilization (IVF) cycles where the gonadotropin-releasing hormone (GnRH) antagonist was omitted on ovulation triggering day. A total of 92 consecutive IVF cycles were included in 65 women who are undergoing ovarian stimulation with recombinant FSH. A GnRH antagonist, cetrorelix 0.25 mg/day, was started when leading follicle reached 14 mm in diameter until the day of hCG administration (Group A, 66 cycles) or until the day before hCG administration (Group B, 26 cycles). The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and the number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in Group B compared to Group A (2.7+/-0.8 vs. 3.2+/-0.9 ampoules). There was no premature luteinization in the subjects. The proportion of mature oocytes (71.4% vs. 61.7%) and fertilization rate of mature (86.3+/-19.7% vs. 71.8+/-31.7%) was significantly higher in Group B. There were no significant differences in embryo quality and clinical pregnancy rates. Our results suggest that cessation of the GnRH antagonist on the day of hCG administration during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising IVF results.

Utilização da contagem de folículos antrais para predição do padrão de resposta em ciclos de hiperestimulação controlada com antagonista de GnRH / Use of antral follicle count to predict the response pattern in controlled ovarian hyperstimulation cycles with GnRH antagonist

OBJETIVO: verificar se existe relação preditiva entre a contagem de folículos antrais (CFA) no segundo dia do ciclo com o padrão de resposta em ciclos de hiperestimulação ovariana controlada para injeção intracitoplasmática de espermatozóide (ICSI). MÉTODOS: estudo prospectivo, desenvolvido de maio de 2004 a maio de 2005, no qual 51 pacientes com idade <37 anos foram submetidas a reprodução assistida/ICSI, em protocolo de hiperestimulação ovariana com gonadotrofina recombinante e antagonista de hormônio liberador de gonadotrofinas (GnRH). Foi realizada ultra-sonografia transvaginal (USTV) no segundo dia do ciclo, para contagem do número de folículos de 2 a 10 mm, quando do início do estímulo, dados comparados com o número de folículos >15 mm no dia do desencadeamento da ovulação, número total e em metáfase II de oócitos captados, número de embriões de boa qualidade transferidos e taxa de gestação. A análise estatística foi realizada pelos testes t de Student e de Mann-Whitney, com significância estatística de 5 por cento (p<0,05). RESULTADOS: o grupo de estudo teve média de idade de 32,4 anos. A CFA média foi de 7,1, com mínimo de 1 e máximo de 16. Considerando a CFA como variável principal, foi observada correlação direta significativa com o número de folículos acima de 15 mm no dia do desencadeamento da ovulação (p=0,0001), o número total (p=0,0001) e em metáfase II (p=0,0001) de oócitos captados. Tal correlação entre a CFA e gravidez não foi observada (p=0,43). Não foi demonstrada uma correlação significativa entre a CFA e o número de embriões de boa qualidade transferidos (p=0,081). CONCLUSÕES: a CFA no segundo dia do ciclo estimulado pode ser utilizada na predição da qualidade da estimulação ovariana, do número de oócitos captados e do número de oócitos maduros em ciclos de fertilização in vitro utilizando antagonista de GnRH.

PURPOSE: to establish whether there is a predictive relationship between the antral follicle count (AFC) on the second day of the cycle and the response pattern in controlled ovarian hyperstimulation cycles for intracytoplasmic sperm injection (ICSI). METHODS: a prospective study developed from May 2004 to May 2005, in which 51 patients aged <37 years old were submitted to assisted reproduction/ICSI in ovarian hyperstimulation protocol with gonadotropin recombinant and gonadotropin-releasing hormone (GnRH) antagonist. A transvaginal ultrasonography was performed on the second day of the cycle, to count the number of follicles measuring 2 to 10 mm, at the beginning of stimulus, data compared with the number of follicles with >15 mm on the day of ovulation triggering, the total number of oocytes retrieved and in metaphases II, the number of good quality embryos transferred and pregnancy rate. The statistical analysis was performed by the t-Student test and the Mann-Whitney test, with statistical significance of 5 percent (p<0.05). RESULTS: the mean age in the study group was 32.4 years. The AFC average was 7.1, minimum of 1 and maximum of 16. Considering AFC as a main variable, a significant direct correlation was observed with the number of follicles >15 mm on the day of ovulation triggering (p=0.0001), the total number of oocytes retrieved (p=0.0001) and those in metaphases II (p=0.0001). Such correlation between AFC and pregnancy was not observed (p=0.43). There was no significant correlation between AFC and the number of good quality embryos transferred (p=0.081). CONCLUSIONS: AFC on the second day of the stimulated cycle can be used to predict the quality of ovarian stimulation, the number of oocytes retrieved and the number of mature oocytes in in vitro fertilization cycles using GnRH antagonist.

[Use of GNRH antagonist [cetrorelix] in controlled ovarian hyperstimulation in women with polycystic ovary disease]

To evaluate the results of the use of GnRH antagonist [GnRH ant] cetrorelix and GnRH analog [GnRH a] in two matched groups of OPK ICSI patients in a restrospective matched pair analysis. Patients [n = 201] were stimulated with recombinant FSH [rFSH]. In group A [n=98], a dose of 3 mg of Cetrorelix was administred when follicles reached a diameter of> 14 mm. Patients in group B [n=103] were first desensitized with GnRHa triptorelin long protocol. The mean length of stimulation, and the dose of FSH required per patient were significantly higher in group B: [11,2 +/- l,9j vs9,7 +/- 0,7jp<0,00l] and [2209,0 +/- 548,3vs 1411,1 +/- 2179: p<0,001] respectively. The mean E2 level on day of hCG administration was significantly higher in the patients of group B [3347,85 +/- 99 vs 2354,45 +/- 839: p<0,001], however, a progressive increase in serum E2 concentration during the cycle were noted in both groups. A median of 15,9 +/- 5,9 and 17,3 +/- 8,3 [p =0,159 retrived oocytes per patients was obtained respectively in group A and B. The median of mature oocytes per patient were similar in both groups [11,43 +/- 4,2 in group A vs 11,9 +/- 6,4 in group B: p=0,526]. Pregnancy rate were better in group B [31,1 vs 28,6% p = 0,69]. No severe ovarian hyperstimulation [OHSS] occured in group A vs 3 cases in group B. GnRHant and GnRHa provide comparable results in OPK patient, while GnRHant allows a higher flexibility in treatment, a lower dose of FSH required and a shorter period of stimulation

GnRH antagonists in controlled ovarian hyperstimulation protocols in assisted reproductive technique programmes--current concepts.

Gonadotrophin (Gn) preparations eg, human menopausal gonadotrophins, follicle stimulating hormone both urinary and recombinant have been highly successful in achieving controlled ovarian hyperstimulation which has become the standard practice in assisted reproductive technique cycles. The fine programming of cycles requires blocking of endogenous luteinising hormone surge, the final ovulation trigger. GnRH analogues, both agonists and antagonists which were developed by substituting amino acids are highly effective in preventing LH surge. Both agonists and antagonists have been developed generating a fierce debate regarding the superiority of one above another. This article is a brief review of literature and attempts to clarify following issues: (a) Major differences between agonists and antagonists. (b) Brief outline of antagonist protocol. (c) Comparative advantages and disadvantages. (d) Use of antagonists in various categories of patients. (e) Future! Can antagonists replace agonists?

Bone mineral density and body composition in Thai Precocious Puberty girls treated with GnRH agonist.

Treatment of true Precocious Puberty (PP) with GnRH agonist can improve final adult height by suppressing gonadotropin and sex hormone levels that delays the fusion of long bone epiphyseal growth plates. However, deprivation of estrogen may affect the acquisition of peak bone mass, especially in individuals with low calcium intake. Ten Thai girls with idiopathic true PP were evaluated for Bone Mineral Density (BMD) and body composition by DXA scanner (Hologic, Inc) before and after GnRH agonist therapy for 1 year. During treatment, all children were allowed to consume a normal diet without extra calcium supplementation. In addition, serum calcium, phosphate, alkaline phosphatase and osteocalcin were also measured. The results showed that GnRH agonist could improve predicted adult height from 149.4 +/- 5.4 to 153.6 +/- 6.8 cm (p < 0.001). Serum osteocalcin, representing the bone marker formation, decreased from 184.2 +/- 66.7 to 108.6 +/- 35.3 ng/mL (p = 0.012) However, the treatment had no negative effects on BMD lumbar spine and total BMD but increased percentage of fat mass from 25.7 +/- 5.2 to 31.6 +/- 5.5%. (p =0.007). In conclusion, treatment with GnRH agonist in Thai girls with true PP for 1 year can improve PAH without negative effects on BMD but a longer period of treatment needs to be studied.

Análogos do GnRH: bases moleculares e aplicações em reprodução assistida / GnRH analogues: molecular basis and applications in assisted reproduction

O decapeptídeo GnRH é o iniciador central da cascata hormonal reprodutiva. É gerado em neurônios hipotalâmicos a partir de um polipeptídeo precursor por processamento enzimático e liberado de maneira pulsátil na circulação portal para estimular a biossíntese e secreção dos hormônios luteinizante (LH) e folículo-estimulante (FSH) pela hipófise. Baixas doses de GnRH aplicadas de maneira pulsátil equivalem à liberação fisiológica portal e restauram a fertilidade em diferentes condições de anovulação. Por outro lado, altas doses de GnRH causam desensibilização do gonadotrofo e inibem a liberação hipofisária com conseqüente inibição da função ovariana. Pequenas modificações na molécula original do GnRH originam substâncias conhecidas como análogos do GnRH, que podem ser agonistas e antagonistas. Os agonistas provocam uma liberação inicial de gonadotrofinas (flare-up) seguida de desensibilização do gonadotrofo (down regulation). Já os antagonistas agem diretamente sobre o gonadotrofo, através de inibição competitiva dos receptores do GnRH. Esse fenômeno de quiescência hipofisária provocada pelos análogos do GnRH tem extensivas aplicações clínicas e o conhecimento sobre a fisiologia do GnRH é importante para aplicação mais racional destes análogos. Este artigo visa a descrever os mecanismos de ação destes análogos do GnRH, bem como revisar as diferentes indicações clínicas de seu uso em reprodução assistida

Mouse model of male germ cell apoptosis in response to a lack of hormonal stimulation.

As a prerequisite for studies using mutant mice, we established a mouse model for induction of male germ cell apoptosis after deprivation of gonadotropins and intratesticular testosterone (T). We employed a potent long acting gonadotropin-releasing hormone antagonist (GnRH-A), acyline, alone or in combination with an antiandrogen, flutamide for effective induction of germ cell apoptosis in mice. Combined treatment with continuous release of acyline (3 mg/kg BW/day) with flutamide (in the form of sc pellets of 25 mg) resulted in almost the same level of suppression of spermatogenesis, as judged by testis weight and by germ cell apoptotic index, in 2 weeks as that reported for rats after treatment with 1.25 mg/kg BW Nal-Glu GnRH-A for the same time period. Within the study paradigm, the maximum suppression of spermatogenesis occurred after a single sc injection of high (20 mg/kg BW) dose of acyline with flutamide. The combined treatment resulted in complete absence of elongated spermatids. Germ cell counts at stages VII-VIII showed a significant (P < 0.05) reduction in the number of preleptotene (27.1%) and pachytene spermatocytes (81.9%), and round spermatids (96.6%) in acyline + flutamide group in comparison with controls. In fact, treatment with a single high (20 mg/kg BW) dose of acyline combined with flutamide in mice achieved same or greater level of suppression, measured by germ cell counts at stages VII-VIII, in two weeks when compared with those reported after daily treatment with Nal-Glu GnRH-A for 4 weeks in rats. Both plasma and testicular T levels were markedly suppressed after administration of acyline alone either by miniosmotic pump or by a single sc injection. Addition of flutamide to acyline had no discernible effect on plasma or intratesticular T levels when compared with acyline alone. These results demonstrate that optimum suppression of spermatogenesis through increased germ cell death is only possible in mice if total abolition of androgen action is achieved and further emphasize the usefulness of acyline + flutamide treated mice as a suitable model system to study hormonal regulation of testicular germ cell apoptosis.

Final adult height in "early normal pubertal girls" treated with gonadotropin releasing hormone agonists.

Gonadotropin releasing hormone (GnRH) agonist has been used worldwide for the treatment of central precocious puberty. However, the results on final adult height (FAH) are discrepant in various studies especially in girls with normal early puberty. Fourteen girls with normal early puberty who were treated with depot GnRH agonists 3.75 mg intramuscular (i.m.) monthly for a mean period of 1.5 +/- 0.4 yr were retrospectively studied. The chronological age and bone age at the beginning of treatment were 9.9 +/- 0.7 yr and 12.6 +/- 0.9 yr, respectively. When the treatment was stopped, all the girls were followed-up until they reached their final adult heights. The results showed that the mean FAH was 154.0 +/- 6.9 cm, which was not significantly different from the predicted adult height (PAH) at start of treatment, 153.1 +/- 6.2 m. All the girls were divided into 2 groups. Group A was girls who had FAH-PAH at the start of treatment > or = 1.5 cm and group B, FAH-PAH at the start of treatment < 1.5 cm. The authors found that only the duration of treatment was different between these 2 groups, 1.7 +/- 0.3 yr in group A and 1.3 +/- 0.3 yr in group B (p = 0.015). In conclusion, GnRH agonist cannot improve the final height outcome in girls with normal early puberty. However, a longer period of treatment may improve the height prognosis.

Effect of casein diet on gonadotropin releasing hormone antagonist induced changes in adrenal gonadal functions in male rats.

Adult male rats received daily injections (sc) of gonadotropin releasing hormone antagonist (0.2 mg/kg(-1) x day(-1)) for 21 days when they were sacrificed on day 22, adrenal weight, adrenal A5-3beta (delta 5-3beta) hydroxysteroid dehydrogenase (Delta5-3beta-HSD) activity and serum level of corticosterone were increased significantly while testicular 17beta (17beta) hydroxysteroid dehydrogenase (17beta-HSD) activity and serum level of testosterone and spermatogenesis were decreased in the rats fed on 5% casein diet. GnRH antagonist treated rats fed on 20% casein diet, resulted significant decrease in adrenal weight, serum corticosterone and adrenal A5-3beta-HSD activity while testicular 17beta-HSD activity serum testosterone levels and the weights of sex organs were increased with respect to anti GnRH treated rats fed on 5% casein diet. But the GnRH antagonist treated rats fed on 20% casein diet showed decreased spermatogenesis quantitatively and sperm count appeared similar to anti GnRH treated rats fed on 5% casein diet. These results indicate that high casein diet protects adrenocortical activity and stimulates testosterone synthesis without effecting spermatogenic arrest in GnRH antagonist treated rats. It may be concluded that GnRH antagonist in presence of high milk protein diet may be considered to be a suitable antihormone in the development of an ideal male contraceptive.

Gestaçäo após administraçäo do antagonista do GnRH (Cetrorelix) em ciclo de fertilizaçäo in vitro de acordo com o protocolo de múltiplas doses: relato de caso / Pregnancy after administration of midcycle GnRH antagonist Cetrorelix according to the mutiple dose protocol for in vitro fertilization: case report

Os autores relatam um caso de gestaçäo gemelar obtida após um ciclo de fertilizaçäo in vitro com injeçäo intracitoplasmática de espermatozóide (FIV-ICSI), em cujo protocolo de estimulaçäo ovariana foi utilizado o FSH recombinante em associaçäo com o antagonista do GnRH (Cetrorelix), segundo o protocolo de múltiplas doses (0,25 mg/dia a partir do 7§ dia de estímulo). Os resultados obtidos nos recentes estudos de ensaio clínico que analisaram a utilizaçäo do Cetrorelix em ciclos de FIV foram amplamente revisados e comparados aos resultados obtidos com o emprego dos análogos do GnRH

Human granulosa cells in vitro: influence of GnRH/GnRH-agonist on steroidogenesis and on IVF outcome.

Steroidogenic activities of the granulosa cells (GCs) from 84 IVF trials were evaluated with respect to a set of ovarian stimulation regimens. Oestradiol (E2) synthesis of the GCs in vitro (obtained at oocyte retrieval) was compared to the maximal serum E2 levels of the same patients at induction of ovulation. Three stimulation regimens were employed: human post-menopausal gonadotrophin (hMG) alone; hMG accompanied by daily doses of a gonadotrophin releasing hormone agonist (GnRH-a); hMG preceded by a single depot application of the GnRH-a. Plots of E2 synthesis in vitro against serum E2 levels indicated that the GnRH-a directly inhibited E2 synthesis in the granulosa cells. This was confirmed in vitro by adding the agonist to the culture medium: both progesterone (P) and E2 syntheses were reduced in the presence of GnRH-a. Despite this drawback, the success of in vitro fertilization (IVF), as gauged by pregnancies achieved, was best for the group which received the GnRH-a as a single depot dose during the previous menstrual cycle, prior to the commence of stimulation. This success is attributed to the lower incidence of cancellations because of premature leuteinizing hormone (LH) surges which happen sometimes during ovarian stimulation. The implications of a direct influence of GnRH-a on E2 synthesis need to be further investigated.

Hormonal ablation therapy for metastatic prostatic carcinoma: a review.

Hormonal therapy is the standard treatment for metastatic prostatic carcinoma. The conventional surgical or medical androgen ablation therapy seems to have a similar response. Despite a higher response of CAB compared to conventional castration in metastatic disease, the controversy of survival benefit remains unsolved. Immediate treatment should be given in metastatic disease particularly in patients who have minimal metastases. In patients who have progression after CAB, antiandrogens should be withdrawn. The choices of optimal therapies for prostate cancer depend not only on the survival but also the quality of life and cost effect. Thus, the critical factors for approaching prostate cancer are appropriate patient selection and stratification. Implicit with this approach should maximize benefit from maximal androgen ablation therapy for patients who are likely to profit from it. Finally, the development of experiments, clinical trials, and novel therapeutic strategies may provide better management for prostate cancer in the future.