[In vitro fertilization outcome in patients with polycystic ovary syndrome treated with GnRH analogue]

Polycystic ovarian syndrome [PCOS] is the most common endocrinological disorders that affect approximately 5-7% of women in reproductive age. There is not any consensus about the efficient in vitro fertilization [IVF] protocol for patients with PCOS. The aim of the present study was to compare the half and one-third dose depot gonadotropin-releasing hormone [GnRH] agonist protocols versus the GnRH antagonist protocol in PCOS patients. In the present study, we retrospectively evaluated 119 infertile women with PCOS. The patients entered in the study in accordance with Rotterdam criteria. According to GnRH analogue used for pituitary suppression, patients were divided into three groups: half and one-third dose depot GnRH agonist protocols and GnRH antagonist protocol. In GnRH agonist protocol, half or one-third dose depot Decapeptyl [1.875 mg, 1.25 mg] was injected on 21[st] day of previous cycle. In GnRH antagonist cycles, cetrotide 0.25 mg were administered daily when the leading follicles reached 14 mm. All basal and controlled ovarian hyperstimulation [COH] characteristics were analyzed. Basal characteristics including: age, FBS, prolactin, hirsutism, length of menstrual cycle were similar between 3 groups. Statically significant decreases in days of stimulation, number of gonadotrophin ampoules and metaphase two [MII] oocytes were found in GnRH antagonist protocol [P<0.001, P<0.001 and P=0.045], while the decrease in biochemical pregnancy [P=0.083] and live birth rate [P=0.169] wasn't significant. Number of embryos transferred were similar in the half and one-third dose depot GnRH agonist and GnRH antagonist cycles [P=0.881]. The incidence of OHSS weren't significantly different between 3 groups [5%, 4.9% and 12.8%, P=0.308]. Our study suggest that one-third dose depot GnRH agonist protocol could be a suitable choice for treatment of PCOS because of lower incidence of ovarian hyperstimulation syndrome [OHSS] as compared with half dose depot GnRH agonist and higher pregnancy rate as compared with GnRH antagonist.

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.

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.

Proposta de metodologia para tratamento individualizado com iodo-131 em pacientes portadores de hipertireoidismo da doença de Graves / Proposal of a methodology for individualized iodine-131 therapy for Graves' disease in patients with hyperthyroidism

OBJETIVO: Diferentes métodos são usados para determinar atividade do radioiodo para tratamento de hipertireoidismo (doença de Graves). Alguns não consideram a dose absorvida pela tireóide ou os parâmetros necessários para este cálculo. A relação entre dose absorvida e atividade administrada depende da meia-vida efetiva, da captação do iodo e da massa da tireóide de cada paciente. O objetivo deste trabalho é propor uma metodologia para tratamento individualizado com 131I em pacientes portadores de hipertireoidismo da doença de Graves. MATERIAIS E MÉTODOS: Usou-se um simulador de tireóide-pescoço desenvolvido no Instituto de Radioproteção e Dosimetria contendo solução de 131I, para calibração da gama-câmara e sonda cintilométrica do Serviço de Medicina Nuclear do Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro. RESULTADOS: O campo de visão colimador-detector apresentou valores compatíveis com o tamanho da glândula para as distâncias de 25 cm (sonda de captação) e 45,8 cm (gama-câmara). Os fatores de calibração (cpm/kBq) foram 39,3 ± 0,78 e 4,3 ± 0,17, respectivamente. O intervalo entre 14 e 30 horas da curva de retenção permite o cálculo de atividade entre dois pontos, para determinação da meia-vida efetiva do iodo na tireóide. CONCLUSÃO: A utilização de equipamentos usualmente disponíveis em serviços de medicina nuclear é viável, tornando esta metodologia simples, eficaz e de baixo custo.

OBJECTIVE: Several methods are utilized for determining the radioiodine activity in the treatment of Graves' disease (hyperthyroidism). Some of this methods do not take into consideration the thyroid absorbed dose or the necessary parameters for this estimation. The association between absorbed dose and administered activity depends on effective half-life, iodine uptake and thyroid mass of each patient. The present study was aimed at developing a methodology for individualized 131I therapy for Graves' disease in patients with hyperthyroidism of the Graves' disease. MATERIALS AND METHODS: A neck-thyroid phantom developed at Instituto de Radioproteção e Dosimetria, containing a standard solution of 131I, was utilized for calibrating the scintillation gamma camera and uptake probe installed in the Department of Nuclear Medicine of the Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro. RESULTS: The view angle of the collimator/detector assembly presented values compatible with the thyroid gland size for distances of 25 cm (uptake probe) and 45.8 cm (scintillation gamma camera). Calibration factors were 39.3 ± 0.78 and 4.3 ± 0.17 cpm/kBq, respectively. The 14-30-hour interval in the retention curve allows the estimation of activity between two points for determining the effective iodine half-life in the thyroid. CONCLUSION: The utilization of equipment usually available in nuclear medicine clinics is feasible, so this is a simple, effective and low cost methodology.

Uso de antagonista de GnRH (cetrorelix) em dose única para evitar ovulações prematuras em ciclos de fertilização assistida / Single dose of GnRH antagonist (cetrorelix) to avoid premature ovulation in assisted fertilization cycles

OBJETIVO: verificar a eficácia de uma dose única subcutânea de acetato de cetrorelix em evitar a ovulaçäo prematura em ciclos de fertilizaçäo assistida. MÉTODOS: estudo prospectivo, randomizado e controlado, pelo qual foram avaliados 20 ciclos de estimulaçäo ovariana em mulheres submetidas a fertilizaçäo assistida, 10 das quais utilizaram o esquema tradicional de bloqueio hipofisário com análogos de GnRH em doses diárias (grupo controle) e 10 utilizaram antagonista de GnRH em dose única de 3 mg no 7º dia de estimulaçäo ovariana (grupo cetrorelix). Foram dosados FSH, LH, estradiol e progesterona no soro no primeiro e sétimo dia da estimulaçäo, no dia da injeçäo de HCG e no dia da captaçäo de oócitos. Os grupos foram comparados entre si quanto a eficácia do bloqueio hipofisário (nível de progesterona no dia da aplicaçäo do HCG) e desempenho nos ciclos de fertilizaçäo assistida (ampolas de gonadotrofinas utilizadas, folículos maiores que 18 mm, oócitos captados, taxas de fertilizaçäo, implantaçäo e gravidez) utilizando os testes de Mann-Whitney e exato de Fisher. RESULTADOS: näo houve diferença significativa entre os grupos controle e cetrorelix, respectivamente, para a mediana da idade (31,5 e 34 anos), índice de massa corpórea (24 e 22), ampolas de gonadotrofinas utilizadas (34 e 32), folículos recrutados (3,5 e 3,0), oócitos captados (11 e 5), embriöes obtidos (4 e 3), taxas de fertilizaçäo (93,7 e 60 por cento, p = 0,07) e gravidez (50 e 60 por cento, p = 0,7). Em ambos os grupos observou-se bloqueio hipofisário eficaz durante o período de estimulaçäo ovariana. CONCLUSÖES: estes resultados confirmam a eficácia da dose única de 3 mg de acetato de cetrorelix em prevenir ovulaçöes prematuras em pacientes submetidas a fertilizaçäo assistida, mostrando tendência a obtençäo de menor número de embriöes e menores taxas de fertilizaçäo no grupo cetrorelix em relaçäo ao grupo controle. As taxas de implantaçäo e gravidez foram semelhantes entre os dois grupos. Estudos prospectivos com maior número de pacientes säo necessários para confirmar estes achados

Uso de antagonistas de GnRH (Cetrorelix) en reproducción asistida: primer informe en la literatura mexicana / Use of GnRH antagonists (cetrorelix) in assisted reproduction: first report in Mexican literature

The use of GnRH antagonists in assisted reproduction techniques (ARTs) has been shown to be effective in blocking the luteinizing hormone (LH), without a repercussion on ovaric response. The present study reports the use of a GnRH antagonist (cetrorelix) 0.25 mg/d s.c. in patients stimulated with recombinant FSH (rFSH) for IVF/ICSI. 44 patients with mean age of 33.3 years were included in this study, four patients were receptors for oocyte donation program and another patients was receptor for frozen embryos. Controlled ovarian stimulation was carried out with rFSH, starting on day 3 of menstrual cycle. The total mean dose used was 3.570 +/- 1.102 UI for each patient. The LH serum concentrations were monitored during ovaric stimulation, in two patients a premature LH surge (> 10 UI/L) was detected. The oocytes were collected 36 hours after hCG administration, the mean preovulatory oestradiol was 4.006 +/- 2.418 pg/mL. The mean total oocytes retrieved was 10.8 +/- 7.4 per patient, the fertilization rate was 58.3, in only three patients fertilization was failed. No difference was observed in oocyte retrieval, fertilization rate, implantation rate between both groups (GnRH antagonists versus GnRH agonists). The embryo transfer was realized on day 3, and only two patients was on blastocyst stage. In 17 of 41 patients with successful transfer, pregnancy was achieved in the group with antagonists, and 8 of 20 patients in the group with agonists. In conclusion Cetrorelix prevents adequately premature LH surges and allows an effective ovaric response in controlled stimulation in IVF cycles, except in patients in oocyte donation programs who require higher cetrorelix doses.

Current status of fertility control methods in India.

Approximately 48.2% of couples of 15 to 49 years of age practice family planning methods in India. Female sterilization accounts for 34.2%, with male sterilization declining from 3.4% in 1992-93 to 1.9% in 1998-99. Use of the condom increased to 3.1% from 2.4%. There is an urgent need for research to develop new contraceptive modalities especially for men and also for women and to make existing methods more safe, affordable and acceptable. Current efforts in India to develop a male contraceptive are mainly directed towards (i) development of antispermatogenic agents to suppress sperm production, (ii) prevention of sperm maturation, (iii) prevention of sperm transport through vas deferens or rendering these sperm infertile and (iv) prevention of sperm deposition. Research work in the field of prevention of sperm transport through vas deferens has made significant advances. Styrene maleic anhydride (SMA) disturbed the electrical charge of spermatozoa leading to acrosome rupture and consequent loss in fertilizing ability of sperm. A multicentre phase-III clinical trial using SMA is continuing and it is hoped that the SMA approach would be available in the near future as an indigenously developed injectable intra-vasal male contraceptive. The safety and efficacy of available oral contraceptives were evaluated. An indigenously developed oral contraceptive 'Centchorman', which is a nonsteroidal, weakly estrogenic but potently antiestrogenic, was found to be safe and effective and is now being marketed in India since 1991 as a 'once a week' pill. Cyclofem and Mesigyna have been recommended as injectable contraceptives with proper counselling and service delivery by Indian studies. It has been recommended that these injectable contraceptives be added to the existing range of contraceptive methods available in the National Family Planning Programme. Based on the Indian studies CuT 200 was also recommended. Studies have indicated the advantage of intrauterine devices (IUD); they are long acting, relatively easily removed and fertility returns rapidly after their removal. Recent studies have recommended CuT 200 for use up to 5 years. The combination of some plant products i.e. Embelia ribes, Borax and Piper longum has been found to be safe and effective as a female contraceptive and the results of phase-I clinical trials are encouraging. Research work is going on in the country in various areas with special reference to hormonal contraceptive - a three monthly injectable contraceptive, immuno-contraceptives, antiprogestins, etc.

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

Emprego dos Antagonistas do GnRH em Reproduçäo Assistida / GnRH antagonists in assisted reproduction

O desenvolvimento dos antagonistas do hormônio liberador das gonadotrofinas (GnRH) e os princípios de seu uso clínico foram revisados. Os antagonistas do hormônio liberador das gonadotrofinas (GnRH) ligam-se de forma competitiva aos receptores de GnRH e, dessa forma, impedem a açäo estimulatória do GnRH endógeno sobre as células hipofisárias. A vantagem dos antagonistas do GnRH está ligada ao fato de que eles inibem a secreçäo de gonadotrofinas e esteróides sexuais imediatamente após a administraçäo. Os antagonistas do GnRH poderiam ser utilizados no tratamento de leiomiomas uterinos, endometriose, hipertrofia benigna da próstata e nos protocolos de estimulaçäo ovariana controlada, onde já está bem estabelecido o benefício dos agonistas.

Hormonal requirement for blastocyst implantation and a new approach for anti-implantation strategy.

There is a growing awareness of a need for developing novel methods of contraceptive technology which should not only be effective in providing protection against conception but also take into consideration the reproductive health issues confronting men and women. This paper considers the process of embryo implantation as one such potential target. The hormonal basis of embryo implantation in primates has been discussed to indicate that progesterone, and not estrogen, from ovarian source is the primary determinant of embryo-endometrial maturation and their synchronization for implantation. Thus, low dose administration of the anti-progesterone, mifepristone, during early luteal phase has been shown to be an effective anti-implantation approach to for fertility control. Furthermore, the dissociation of endometrial-hormonal synchrony at the time of blastocyst implantation following the post-ovulatory mifepristone administration has been shown to be the physiological basis of its anti-implantation effect with undisturbed circulatory hormone profiles and ovarian functions. Further studies are required to appreciate the full potential and to mollify the limitations of this approach.

Etiología y tratamiento médico de la endometriosis / Endometiosis: etiology and treatment

Se analiza la etiología de la endometriosis, la más viable es ña Sampson quien postula que es la consecuencia del asentamiento de células endometriales que pasan retrogradamente durante la menstruación. Por otra parte parece ser que existe una falla inmunológica local que permite la adherencia y proliferación de estas células endometriales. Se discuten los estudios que hay en liquido peritoneal que demuestran que la respuesta celular inmune es un componente importante de esta enfermedad. En relación al tratamiento médico, el análisis de los resultados permite afirmar que éstos son semejantes cuando se administra Danazol que cuando se administran análogos de GnRH. Finalmente, dadas las tasas de embarazo y de recurrencia en los grupos en tratamiento comparados con grupos control, así como los hallazgos histoógicos después de tratamiento, y el comportamiento de los receptores hormonales en las células endometriales ectópicas, en comparación con los receptores hormonales de las eutópicas, se concluye que el tratamiento hormonal solo produce una supresión incompleta de células endometriósicas y el mayor beneficio está en la inducción de la amenorrea. Por lo tanto, se hacen necesarias mayores investigaciones en la endometriosis que permitan obtener tratamiento con mejores resultados, y probablemente estas investigaciones deben darse en el campo de inmunología.