Reproducción asistida en Chile: una mirada global para el desafío de ofrecer un acceso oportuno / Assisted Reproduction in Chile: a global overview of the challenge of providing an opportune access

En el año 2018 se conmemoraron 40 años desde el primer resultado exitoso producto de una fertilización in vitro (FIV), el nacimiento de Louise Brown en Inglaterra. Se estima que a la fecha han nacido más de 8 millones de seres humanos gracias a las tecnologías de reproducción asistida (TRA), técnicas que están en constante avance y desarrollo. Sin embargo, a pesar de ser cada vez más relevantes como tratamiento de la infertilidad, su acceso todavía es muy limitado y poco equitativo, alcanzando menos del 15% de la población a nivel global. En esta revisión analizamos los aspectos epidemiológicos de la infertilidad y exponemos el contraste entre la necesidad teórica de TRA y los ciclos realizados a nivel mundial, reflejando el bajo acceso a los tratamientos. Se enfatiza la realidad latinoamericana y con especial detalle la chilena, explorando tanto su dimensión histórica como actual, perfilando los desafíos que como país deberemos enfrentar en los próximos años.

The 40-year anniversary of the first in vitro fertilization (IVF) newborn, Louise Brown in England, was celebrated in 2018. To date, over 8 million children have been born with assisted reproductive technologies (ART), a group of techniques in continuous development. Despite the increasing relevance of such technologies as treatments for infertility, the access to ART has been limited to less than 15% of the world population.In this review, we analyze the epidemiological aspects of infertility and present the contrast between the theoretical demand and the actual number of ART cycles performed worldwide, reflecting the low access to infertility treatments. We put emphasis on the Latin American historic and current context, then provide more details on the Chilean reality, and finally outline the challenges Chile will face in the future regarding access to ART.

Implementación de técnicas de reproducción asistida en el Centro de Reproducción Humana de la Universidad de Valparaíso: resultados del primer trienio (2015 - 2017) / Implementation of assisted reproduction techniques at the Center of Human Reproduction of the Universidad de Valparaíso: results of the first triennium (2015 - 2017)

INTRODUCCIÓN Y OBJETIVOS: La infertilidad es una enfermedad altamente prevalente que afecta aproximadamente a un 8-10% de las parejas en edad reproductiva. Las Técnicas de Reproducción Asistida (TRA) han experimentado un importante incremento en el número de tratamientos realizados, no obstante, el acceso en Chile sigue siendo limitado y centralizado. El presente estudio resume la experiencia y los resultados de TRA del primer trienio del Centro de Reproducción Humana de la Universidad de Valparaíso (CRHUV). MÉTODOS: Estudio de cohorte retrospectiva de las pacientes sometidas a TRA en el CRHUV desde 1 de enero de 2015 a 31 diciembre 2017. Se realizó un análisis descriptivo e inferencial. La distribución de variables fue analizada con la prueba de Shapiro-Wilk. Para variables cualitativas se usó la prueba exacta de Fisher. RESULTADOS: Se iniciaron un total de 581 ciclos. Para un total de 340 ciclos en fresco con ovocitos propios, la tasa de embarazo (TE) y de parto (TP) por ciclo aspirado fue de 43,5% y 36,7% respectivamente. En el mismo grupo, la TE y TP por transferencia embrionaria fue de un 48,4% y un 40,9% respectivamente, siendo superior al comparar transferencia doble con un embrión (p < 0,05). También se observó un aumento de TE en menores de 35 años (p < 0,05). La TE y TP por transferencia embrionaria fue semejante en transferencia de embriones frescos y congelados. Al transferir embriones producto de ovocitos donados se observó un incremento significativo de la TE y TP con tasas de 73,1% y 61,5% respectivamente. Las tasa globales y estratificadas de embarazo y parto fueron comparables en el trienio estudiado con los resultados de la REDLARA. CONCLUSIÓN: La exitosa implementación del CRHUV se respalda en los resultados comparables a lo reportado por literatura internacional.

INTRODUCTION AND OBJECTIVES: Infertility is a highly prevalent disease that affects approximately 8-10% of couples in reproductive age. Assisted reproduction techniques (ART) have experienced a significant increase in the number of treatments performed, however, access in Chile remains limited and centralized. This study summarizes the experience and results of the first triennium of the Center for Human Reproduction of the Universidad de Valparaíso (CRHUV). METHODS: Retrospective cohort study of patients undergoing ART at the CRHUV from January 1, 2015 to December 31, 2017. A descriptive and inferential analysis was performed. The distribution of the variables was analyzed with the Shapiro-Wilk test. For qualitative variables, Fisher's exact test was used. RESULTS: A total of 581 cycles were started. For a total of 340 fresh cycles with own oocytes, the pregnancy (RP) and delivery (DR) rate per oocyte retrival was 43.5% and 36.7%. In the same group, PR and DR per embryo transfer was 48.4% and 40.9%, being higher when comparing double with a single embryo transfer (p <0.05). A higher PR was also observed in < 35 years patients (p <0.05). The PR and DR per embryo transfer was similar using fresh and frozen embryo. In oocytes donation, a significant increase in PR and RD per embryo transfer was observed with rates of 73.1% and 61.5%, respectively. The global and stratified rates of pregnancy and delivery were comparable in the studied triennium compared to the results of REDLARA. CONCLUSION: The successful implementation of the CRHUV is supported by results comparable to those reported by international literature.

Assisted reproductive technology: prevalence and associated factors in Southern Brazil

ABSTRACT OBJECTIVE: To assess the prevalence of successful assisted reproductive technology and to identify the associated factors. METHODS: This population-based birth cohort study was carried out with 4,333 pregnant women expected to deliver in 2015 in the urban area of Pelotas, Southern Brazil. Use of an assisted reproductive technology procedure, type of assisted reproductive technology [in vitro fertilization or intracytoplasmic sperm injection or artificial insemination], number of embryos transferred, success of embryo transfer, number of attempts, and reported reasons for seeking assisted reproductive technology were the main outcomes measured. Use of an assisted reproductive technology procedure was analyzed according to sociodemographic, nutritional, reproductive history, and behavioral characteristics. Unadjusted and adjusted analyses were performed by logistic regression. RESULTS: Among the 4,275 newborns enrolled in the Pelotas 2015 Birth Cohort Study, 18 births (0.4%) were conceived by assisted reproductive technology. Most cases of assisted reproductive technology were by in vitro fertilization (70.6%). All cycles were performed in private clinics under direct out-of-pocket payment. Even after controlling for confounders, maternal age > 35 years, nulliparity and high family monthly income were strongly associated with assisted reproductive technology. CONCLUSIONS: The use of assisted reproductive technology services was reported by only a few women in the Pelotas 2015 Birth Cohort Study. Our study highlights sociodemographic factors associated to assisted reproductive technology procedures. To better understand the patterns and barriers in overall use of assisted reproductive technology services over time, national-level trend studies in assisted reproductive technology treatments and outcomes, as well as studies exploring the characteristics of women who have sought this kind of treatment are needed in low-middle income countries.

Práticas reprodutivas lésbicas: reflexões sobre genética e saúde / Lesbian reproductive practices: reflections on genetics and health

Resumo A relação entre ciência, tecnologia e capital, intrínseca às Tecnologias Reprodutivas (TR), torna estas uma possibilidade de escolha reprodutiva e uma alternativa para lésbicas que querem ter filhos. O artigo se propõe a refletir sobre os projetos formulados a partir dos depoimentos de casais de lésbicas que utilizaram ou que tinham planos de utilizar as TR. Foram entrevistados oito casais de mulheres com idade entre 26 e 45 anos, todas autodeclaradas brancas e com nível superior completo, residentes na Grande São Paulo/SP, entre 2010-2011. Os resultados revelam a preferência das entrevistadas pelo doador proveniente de banco de esperma e também a valorização da informação sobre o histórico familiar de saúde do doador. Destaca-se o interesse pela importação de sêmen de banco americano, em razão de uma alegada pouca disponibilidade de amostras no Brasil e por ele conter mais informações sobre os doadores. Assim, ao mesmo tempo que as TR possibilitam uma parentalidade não biológica, a genética é valorizada concorrendo para uma medicalização do parentesco.

Abstract The relationship between science, technology and capital, which are intrinsic to Reproductive Technologies (RT), makes them a possibility of reproductive choice and an alternative for lesbians who wish to have children. The article seeks to reflect on the projects formulated based on the statements of lesbian couples who had used or had plans to use RT. Interviews were conducted with eight couples of women with ages between 26 and 45, all self-declared Caucasians, who had completed higher education and were living in the Greater São Paulo region between 2010 and 2011. The results reveal the preference of the respondents for donor sperm originating from a sperm bank and also the importance placed on information on the family history of health of the donor. A noteworthy finding is the interest in importing from an American sperm bank, because of an alleged limited availability of samples in Brazil and the fact that they provide more information about the donors. Thus, while RT enable non-biological parenting, genetics is considered important thereby contributing to the medicalization of parenthood.

O impacto da infertilidade: narrativas de mulheres com sucessivas negativas pelo tratamento de reprodução assistida / The impact of infertility: women's narratives with negative successive by assisted reproduction treatment

Objetivos: Descrever os impactos psicossociais da infertilidade em mulheres que tentam engravidar sem sucesso por meio da reprodução assistida. Métodos: Estudo observacional descritivo com abordagem qualitativa e exploratória. Os prontuários foram obtidos por meio de uma clínica de reprodução assistida em Goiânia-GO. Foram feitas quatro entrevistas com mulheres que se enquadraram nos critérios de inclusão e exclusão, por meio da técnica de entrevista semiestruturada. Resultados: Foram analisadas quatro categorias consideradas chave: diagnóstico e início do tratamento; falta de um apoio social; sentimento de fracasso; e perspectivas. A infertilidade gera uma série de sentimentos, como angústia, depressão, culpa, medo, exclusão social. Além disso, diminui a qualidade de vida e afeta diretamente na relação das mulheres com seus parceiros, parentes e ambiente de trabalho. Porém, apesar das frustrac¸ões o sentimento que prevaleceu é o de seguir tentando. Conclusões: O sofrimento psicossocial das mulheres frente aos sucessivos resultados negativos necessita ser mais bem abordado no âmbito das clínicas especializadas, para oferecer apoio psicossocial precoce para o enfrentamento das possíveis frustrações com os resultados negativos.(AU)

Objectives: Describe the psychosocial impact of infertility in women trying to conceive without success through assisted reproduction. Methods: This is a descriptive observational study with qualitative and exploratory approach. The records were obtained through assisted reproduction clinic in Goiânia-GO. Four interviews with women were conducted to meet the criteria for inclusion and exclusion, through semi-structured interview technique. Results: Four categories were analyzed considered key: diagnosis and initiation oftreatment; lack of social support, feelings of failure and future prospects. Infertility generates a series of feelings such as anxiety, depression, guilt, fear, social exclusion; decrease quality of life and directly affect the women's relationship with their partners, family and work environment. However, despite the frustrations the feeling that prevailed is trying to follow. Conclusions: The psychosocial suffering of women facing the successive negative results need to be better addressed in the context of specialized clinics providing early psychosocial support to cope with possible frustrations with negative results.(AU)

Infertilidade masculina decorrente de microdeleções no cromossomo Y / Male infertility caused by microdeletions on Y chromosome

Objetivo: Abordar a infertilidade masculina causada pela microdeleção no cromossomo Y e apresentar possíveis tratamentos por meio das técnicas de reprodução humana assistida. Métodos: Levantamento de dados da literatura científica na área da medicina reprodutiva. Resultados: Quando comparadas com outras causas de infertilidade, as microdeleções do cromossomo Y são relativamente frequentes. O cromossomo Y é essencial para a determinação sexual masculina e no seu braço longo há regiões responsáveis pela espermatogênese. São elas AZFa, AZFb e AZFc. Essas regiões podem ser deletadas e por conter múltiplos genes essenciais para a espermatogênese podem causar infertilidade masculina. Graças aos avanços da medicina, hoje vários casos de infertilidade são tratáveis por meio das técnicas de reprodução assistida. Dentre as técnicas, a MSOME se destaca por ser uma metodologia que seleciona apenas espermatozoides morfologicamente normais para serem usados na inseminação e aumentar as chances de gestação. Conclusões: A infertilidade masculina tem aumentado consideravelmente nos últimos anos e as causas genéticas são uma das grandes consequências disso. As microdeleções do cromossomo Y podem causar desde uma oligozoospermia leve a uma azoospermia, a depender da região AZF afetada. Para as causas mais leves, o casal pode recorrer a algumas técnicas de reprodução assistida e para as causas mais graves a solução para o casal pode ser usar gametas doados.(AU)

Objective: Address male infertility caused by microdeletions on Y chromosome and present possible treatment through assisted human reproduction techniques. Methods: Survey data from the scientific literature in the field of reproductive medicine. Results: When compared with other causes of infertility, the microdeletions on Y chromosome are the relatively frequent. The Y chromosome is essential for male sex determination and there are in his long arm regions responsible for spermatogenesi, it's they AZFa, AZFb and AZFc. Such regions may be deleted causing male infertility by contain multiple genes essential for spermatogenesis. Thanks to advances in medicine, now several cases of infertility are treatable through assisted reproduction techniques. Among the techniques, the MSOME stands out as a methodology that selects only morphologically normal sperm to be used in insemination increasing the chances of pregnancy. Conclusions: Male infertility has increased considerably in recent years and the genetic causes are one ofthe major consequences ofthis. Y chromosome microdeletions can cause mild oligozoospermia or azoospermia depending on the AZF region affected. For lighter causes, the couple may use some assisted reproductive techniques and to the most serious causes the solution to the couple is using donated gametes.(AU)

Evaluation of a father and son with atypical chronic myeloid leukemia with SETBP1 mutations and a review of the literature

We report the case of a father and son diagnosed with atypical chronic myeloid leukemia (aCML). Both patients harbored SETBP1 mutations, which are present in 24.3% of aCML patients. Moreover, both shared the variant encoding p.Pro737His, but the aCML severity was greater in the son because of the presence of two other missense mutations causing p.Asp868Asn and p.Ser885Arg alterations. SETBP1 mutations may be associated with an adverse prognosis, so their detection would help in the diagnosis of aCML and the determination of a patient's prognosis.

Registro chileno de técnicas de reproducción asistida, 2011 / Chilean record of assisted reproduction techniques, 2011

Presentamos el Registro Chileno de Técnicas de Reproducción Asistida realizadas en el año 2011. Siete centros reportaron un total de 1.918 ciclos de reproducción asistida: 161 ciclos de fecundación in vitro (FIV), 1.266 ciclos de inyección intracitoplasmática de espermatozoides (ICSI), 325 ciclos de transferencia de embriones criopreservados, y 166 ciclos de transferencia de embriones producto de ovodonación. La tasa de parto por aspiración en ciclos de FIV fue 18,6 por ciento y en ciclos de ICSI fue 22,0 por ciento. La tasa de parto por transferencia embrionaria en ciclos de transferencia de embriones criopreservados fue 21,5 por ciento; en ciclos de transferencia de embriones producto de ovodonación fue 41,9 por ciento. La edad promedio de las mujeres sometidas a ciclos de IVF/ICSI fue 35,7 años (rango: 22-48 años). El 38 por ciento de los ciclos iniciados fue en mujeres <34 años. A diferencia de años anteriores, la media de embriones transferidos no presentó una disminución, estabilizándose en 2,1. La frecuencia global de parto múltiple en IVF/ICSI fue 24 por ciento; 23 por ciento gemelar y 1 por ciento parto triple y mayor. Concluimos que la tasa de parto de los ciclos de IVF/ICSI se mantiene relativamente estable en relación a años anteriores. Gracias a la criopreservación y la transferencia secuencial de toda la cohorte de embriones producidos, la frecuencia de partos triple descendió considerablemente. Sin embargo, la alta frecuencia de parto doble no ha experimentado ninguna disminución y debe ser el próximo desafío.

We present the Chilean Registry of Assisted Reproductive Technologies performed in 2011. For the first time this registry is performed on a case-by-case basis. Seven centres reported 1,918 cycles: 161 in vitro fertilisation cases (IVF), 1,366 intracytoplasmatic sperm injection cases (ICSI), 325 cryiopreserved embryo transfers, and 158 oocyte donation cycles. The delivery rate per oocyte pick up for IVF and ICSI cycles was 18.6 percent and 22.0 percent, respectively. The delivery rate per embryo transfers for cryopreserved embryo transfer and oocyte donation were 21.5 percent and 41.9 percent, respectively. The mean age of woman undergoing IVF/ICSI was 35.7 years (min 22 max 48 years); 38 percent of initiated cycles were performed in women aged <34 years. As in previous years, the mean number of embryos transferred declined slightly, reaching 2.1. The multiple delivery rate was 24 percent: 23 percent twin and 1 percent triplet and higher. In conclusion the delivery rate in IVF/ICSI cycles remains stable. Thanks to cryopreservation and posterior embryo transfer, the rate of triplet-delivery continues to diminish. However, the rate of twin delivery has not diminished, and remains a challenge.

Registro chileno de técnicas de reproducción asistida, 2010: registro chileno de fecundación in vitro, Sociedad Chilena de Medicina Reproductiva / Chilean registry of assisted reproductive technologies 2010

Objetivo: presentar el registro chileno de técnicas de reproducción asistida realizadas en el año 2010. Por primera vez el registro de los procedimientos fue hecho caso a caso. Resultados: siete centros reportaron un total de 1.238 ciclos de reproducción asistida: 143 ciclos de fecundación in vitro (FIV), 1.087 ciclos de inyección intracitoplasmática de espermatozoides (ICSI), 255 ciclos de transferencia de embriones criopreservados y 158 ciclos de transferencia de embriones producto de ovodonación. La tasa de parto por aspiración en ciclos de FIV fue 21,4 por ciento y en ciclos de ICSI de 26,2 por ciento. La tasa de parto por transferencia embrionaria en ciclos de transferencia de embriones criopreservados fue 19,2 por ciento; en ciclos de transferencia de embriones producto de ovodonación fue 35,3 por ciento. La edad promedio de las mujeres sometidas a ciclos de IVF/ICSI fue 35,5 años (rango: 21 - 53 años); el 40 por ciento de los ciclos iniciados fue en mujeres <34 años. Al igual que en años anteriores, la media de embriones transferidos continuó presentando una leve disminución llegando a 2,1 embriones. La frecuencia global de parto múltiple fue 22,0 por ciento: 21,3 por ciento gemelar y 0,4 por ciento parto triple y mayor. Conclusión: la tasa de parto de los ciclos de IVF/ICSI se mantiene relativamente estable en relación a años anteriores. Gracias a la criopreservación y la transferencia secuencial de toda la cohorte de embriones producidos, la frecuencia de partos triple descendió considerablemente. Sin embargo, la alta frecuencia de parto doble no ha experimentado ninguna disminución y debe ser el próximo desafío.

Aims: to present the chilean registry of assisted reproductive technologies performed in 2010. For the first time this registry is performed on a case-by-case basis. Results: seven centres reported 1,238 cycles: 143 in vitro fertilization cases (IVF); 1,087 intracytoplasmatic sperm injection cases (ICSI); 255 cryiopreserved embryo transfers; and 158 oocyte donation cycles. The delivery rate per oocyte pick up for IVF and ICSI cycles was 21.4 percent and 26.2 percent, respectively. The delivery rate per embryo transfer for cryopreserved embryo transfer and oocyte donation were 19.2 percent and 35.3 percent, respectively. The mean age of woman undergoing IVF/ICSI was 35.5 years (range: 21 - 53 years); 40 percent of cycles were performed in women aged <34 years. As in previous years, the mean number of embryos transferred declined slightly, reaching 2.1 embryos. The multiple delivery rate was 22.0 percent: 21.3 percent twin and 0.4 percent triplet and higher. Conclusion: the delivery rate in IVF/ICSI cycles remains stable. Thanks to cryopreservation and posterior embryo transfer, the rate of triplet-delivery continues to diminish. However, the rate of twin delivery has not diminished, and remains a challenge.

Reproducción asistida en Latinoamérica y Chile / Assisted reproductive techniques in Latin America and Chile

La principal fuente de información acerca de técnicas de reproducción asistida (TRA) en Latinoamérica es el Registro Latinoamericano de Reproducción Asistida (RLA). El RLA se estableció en 1990, y corresponde al primer registro multinacional del mundo. A pesar de su carácter voluntario, reporta más del 90 por ciento de las técnicas de reproducción asistida realizadas anualmente. En los últimos años se han consolidado en la región en general -y en Chile en particularlas tendencias de: mejoría de los resultados; aumento de la edad de las pacientes; fertilización de ovocitos por ICSI; y disminución de la media de embriones transferidos y, consecuentemente, de la frecuencia de partos múltiples. En Chile, siete centros reportan sus casos anualmente al RLA. La mayoría de los ciclos realizados en nuestro país son financiados por las propias parejas, con escasa cobertura por los seguros de salud. Esto se ha traducido en un aumento insuficiente en el acceso a TRA.

The RLA is the main source of information regarding assisted reproductive technologies (ART) procedures performed in the region. Established in 1990, the RLA is the oldest multinational and voluntary registry in the world, and accounts for more than 90 percent of regional ART procedures. Recently, the region (and Chile) has shown a tendency to improved outcomes; oocyte fertilization by means of ICSI; decrease in the number of transferred embryos and, consequently, of the frequency of multiple deliveries. Seven centres report in Chile. The majority of ART cycles performed are covered by the same couples, with minor support of health insurances. This lack of support is probably the main cause of the current insufficient access to ART.