Expanded carrier screening for recessively inherited disorders: economic burden and factors in decision-making when one individual in a couple is identified as a carrier.

PURPOSE: When undergoing expanded carrier screening (ECS), couples are often screened sequentially to reduce need for a second individual's test. It is unknown how often partners of individuals found to be carriers complete the recommended testing with a sequential approach and what factors contribute to decision-making regarding partner testing. Additionally, the economic burden placed on individuals by ECS testing and its effect on partner testing has not been evaluated. METHODS: In part 1, all individuals at a university-affiliated reproductive endocrinology and infertility practice identified to be carriers of a recessively inherited mutation using the Counsyl/Foresight ECS were included. Conditions were categorized by severity according to a previously described classification system. In part 2, all individuals who underwent ECS with a single test provider between September 1, 2013 and February 1, 2020 were contacted via email to complete a confidential and anonymized online survey. RESULTS: In part 1, a total of 2061 patients were screened. 36.9% were carriers of one or more recessively inherited disorders. Twenty-seven percent of positively screened individuals did not have their partner screened. Carriers of a moderate condition had a trend towards a reduced odds for having their partner screened compared to a profound condition (OR 0.36, 95% CI 0.12-1.05, p = 0.06). Number of conditions was not predictive of subsequent partner screening (OR 0.95, 95% CI 0.72-1.25, p = 0.72). In part 2, the cost of ECS was not covered by insurance for 54.5% (103/189) and most paid over $300 out-of-pocket for testing (47.6%). The most common reason for not completing partner testing was that the results would not alter their course when seeking conception (33.3%). 73.5% of patients knew that the largest benefit of ECS comes from knowing a partner's results as well as their own. CONCLUSIONS: Not all carriers of recessively inherited disorders choose to undergo partner screening. Patients found to be carrier of more debilitating genetic disorders may be more likely to screen their reproductive partners. For many, ECS testing is not covered by insurance, and this test may impose a significant economic burden. For some patients, the results of ECS would not change what they would do when seeking conception. Providers should evaluate whether a patient's ECS result would change their treatment course prior to testing.

Procreative Non-Maleficence: A South African Human Rights Perspective on Heritable Human Genome Editing.

If the safety and efficacy issues relating to heritable genome editing can be resolved, how should liberal democratic societies regulate the use of this technology by prospective parents who wish to effect edits to the genomes of their prospective children? We suggest that recent developments in South African law can be useful in this regard. The country's apex court recently recognized as a legal principle that the scope of possible reproductive decisions that parents may make when using new reproductive technologies excludes decisions that will cause harm to the prospective child-the principle of procreative non-maleficence. We suggest that the principle of procreative non-maleficence provides a mechanism for striking an equitable balance between two competing interests that are given legal recognition in most liberal democracies: the reproductive rights of prospective parents and the state's duty to protect child welfare.

[Development of microfluidic technology in reproductive researches].

Reproduction is one of the most basic characteristics of organisms, and the guarantee of the continuation and evolution of a species. As the country with world's largest population, China has been gradually increasing its investment in research on the reproductive system in recent years, particularly in the field of basic research. The rapid development and wide application of the microfluidic technology since its birth are sufficient to explain its application prospect. Currently, infertility and birth defects are major problems in the field of reproduction. Micro-reproductive technologies, including microfluidic and organs-on-chips, are formed through the combination of a wide range of basic science and bioengineering technologies. In reproductive research, microfluidic technology display several advantages:flexible design of the microchannel shape and size to better simulate the physiological environment, the low consumption of microfluidic chip, and highly integrated microfluidic technology. Microfluidic technology has been applied to various processes including sperm vitality evaluation and screening, sperm chemotaxis, cumulus oophorus cell removal, zona pellucida removal, ootid localization and screening, fertilization, early embryo culture and reproductive organ simulation. This paper introduces the recent progress in reproductive research based on microfluidic technology and its application prospects.

Análisis de la eficacia de las técnicas de reproducción asistida: una revisión sistemática / Analysis of the effectiveness of assisted reproduction techniques: a systematic review

Existe un alto número de personas afectadas por infertilidad que requieren de técnicas de reproducción asistida. Por ello, el objetivo de esta revisión ha sido analizar la efectividad de las intervenciones llevadas a cabo en dichas técnicas. Se realizó una revisión sistemática, por pares, en doce bases de datos. Los criterios de inclusión fueron: ensayos clínicos aleatorizados, publicados entre 2011 y 2016, y con una puntuación mayor que dos en la escala Jadad. Las intervenciones farmacológicas efectivas encontradas fueron la administración de hormonas: gonadotropina coriónica humana intrauterina, gonadotrofina y dehidroepiandrosterona, y de metformina. Se localizó una intervención quirúrgica efectiva, raspado endometrial. No se halló ninguna intervención no farmacológica efectiva. Existe una heterogeneidad tanto de intervenciones incluidas en las técnicas de reproducción asistida, como de criterios para medir efectividad (tasa de embarazo, tasa de nacidos vivos o tasa de implantación), siendo necesaria una unificación de criterios

There are a high number of people affected by infertility who require assisted reproduction techniques. For this reason the aim of this review was to analyze the effectiveness of the interventions carried out using these techniques. A systematic peer review was performed on twelve databases. Inclusion criteria were: randomized clinical trials, published between 2011 and 2016, and with a score greater than two on the Jadad scale. The pharmacological interventions that proved effective were the administration of hormones, intrauterine human chorionic gonadotropin, gonadotrophin and dehydroepiandrosterone, and metformin. An effective surgical intervention, endometrial scratching, was identified. No effective non-pharmacological interventions were found. Assisted reproduction techniques show heterogeneity in both the interventions included and effectiveness criteria (pregnancy rate, live birth rate or implantation rate), which makes a unification of criteria necessary

¿Debemos incorporar la preservación de la fertilidad en el protocolo diagnóstico-terapéutico del cáncer? / Should we incorporate fertility preservation into the diagnostic-therapeutic protocol for cancer?

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Sperm Encapsulation from 1985 to Date: Technology Evolution and New Challenges in Swine Reproduction.

In the last 30 years, encapsulation technology has been applied to different species to minimize the loss of spermatozoa after artificial insemination. In particular, the vehiculation of boar sperm cells in barium alginate membrane has proved a valid strategy to reduce the risk of polyspermy and optimize in vivo fertilizing yields. Controlled release of male gametes into the female genital tract has reduced the minimum fertilizing dose of spermatozoa. Notwithstanding these results, encapsulation has not yet reached commercial application, largely due to the additional costs of production. However, encapsulation could be useful in advanced reproductive technology, such as sex sorting, to store sorted boar semen. The controlled release of flow cytometrically sorted spermatozoa could be a promising strategy to reduce the number of cells necessary for each insemination and hence allow the widescale use of sex sorting in this species.

Reflexiones legales y éticas en torno a la maternidad subrogada / Legal and ethical reflections concerning the surrogate motherhood

En el presente artículo pretendemos abordar la problemática de la maternidad subrogada como método de reproducción asistida, prohibido en España. El objeto de estudio de este trabajo es analizado desde la perspectiva legal y ética, llegando a la conclusión de que ante una hipotética regulación legal, entendemos que el médico no está obligado éticamente a colaborar en el proyecto de maternidades subrogadas, lo que sin duda abre un amplio campo sobre la ética deliberativa de la responsabilidad (AU)

In the present article, we try to approach the issue of surrogacy as a prohibited assisted reproduction treatment in Spain. The subject of study of this work will be analyzed from the legal and ethical perspective. We understand that, arriving at the conclusion that before a hypothetical legal regulation, the doctor is not ethically forced to collaborate legally in the project of surrogacy, thus widening the scope for the deliberative responsibility ethics (AU)

The two classes of primordial follicles in the mouse ovary: their development, physiological functions and implications for future research.

Ovarian follicles are the basic functional units in the mammalian ovary. This review summarizes early pioneering studies and focuses on recent progress that has shown that there are two distinct classes of primordial follicles in the ovary: the first wave of primordial follicles that are activated immediately after they are formed and the adult primordial follicles that are activated gradually in later life. These two separate classes have been proposed for two decades, but sufficient experimental evidence to support this hypothesis has only been obtained recently using newly developed follicular tracing techniques in genetically modified mouse models. These two follicle populations differ from each other primarily in terms of their developmental dynamics and their contributions to ovarian physiology. It is apparent now that these two follicle populations should be treated separately, and such knowledge will hopefully lead to a more in-depth understanding of how distinct types of primordial follicles contribute to physiologic and pathologic alterations of the mammalian ovary.

Evolución del método de fecundación in vitro en España: 1993-2010 / Evolution of in vitro fertilization in Spain: 1993-2010

Introducción: El objetivo del presente estudio fue comparar los cambios en el uso de la intracytoplasmatic sperm injection (ICSI) en España, así como discutir las posibles causas. Métodos: Se analizaron los datos del Registro de la Sociedad Española de Fertilidad (SEF) en el uso de fecundación in vitro (FIV)/ICSI entre los años 1993-2010 con ovocitos propios y donados. Además se analizaron las causas que indicaron la FIV/ICSI y el porcentaje de ciclos realizados con ovocitos propios a mujeres mayores de 40 años. Resultados: El uso de ICSI aumentó del 4% en 1993 al 89% en 2010 en ciclos de técnicas en reproducción asistida con ovocitos propios y del 59% en 1999 al 93% en 2008 en ciclos con ovocitos donados. En el periodo 1993-2001 se observa una disminución de indicaciones de FIV/ICSI por factor femenino y un aumento por factor masculino y esterilidad de origen desconocido (EOD), pero a partir de 2001 estos porcentajes permanecen estables. Una evolución similar se observa en el porcentaje de ciclos con ovocitos propios realizados a mujeres mayores de 40 años. Conclusiones: El uso de la ICSI va en aumento, pero es difícil determinar factores clínicos específicos que expliquen estas diferencias. Dado que la ICSI no proporciona mayores tasas de embarazo que la FIV convencional en parejas cuya causa de esterilidad no sea el factor masculino y además supone un incremento en los costes, algunas parejas estériles podrían beneficiarse de un uso menos frecuente de ICSI (AU)

Introduction: The aim of this study was to compare the changes in the use of intracytoplasmatic sperm injection (ICSI) in Spain and to discuss the possible causes for these changes. Methods: We analysed the data of the Spanish Fertility Society registry on the use of in vitro fertilization (IVF)/ICSI between 1993-2010 with own and donated oocytes. We also studied the reasons for indicating IVF or ICSI and the percentage of cycles performed with own oocytes in the case of women over 40 years. Results: The use of ICSI increased from 4% in 1993 to 89% in 2010 in assisted reproductive technology cycles with own oocytes, and from 59% in 1999 to 93% in 2008 for cycles with donated oocytes. In the 1993-2001 period, a decrease was observed in the indications for IVF/ICSI due to the female factor, together with an increase in these indications due to the male factor or to infertility of unknown origin. However, these percentages have remained stable since 2001. A similar trend has been observed in the percentage of cycles with own oocytes performed with women aged over 40 years. Conclusions: The use of ICSI is increasing, although it is difficult to determine the specific clinical factors that may explain these differences. Since ICSI does not produce higher pregnancy rates than conventional IVF in couples whose cause of infertility is not the male factor and it is also more costly, some infertile couples could benefit from less frequent use of ICSI (AU)

On the cutting edge: ethical responsiveness to cesarean rates.

Cesarean delivery rates have been steadily increasing worldwide. In response, many countries have introduced target goals to reduce rates. But a focus on target goals fails to address practices embedded in standards of care that encourage, rather than discourage, cesarean sections. Obstetrical standards of care normalize use of technology, creating an imperative to use technology during labor and birth. A technological imperative is implicated in rising cesarean rates if physicians or patients fear refusing use of technology. Reproductive autonomy is at stake since a technological imperative undermines patients' ability to choose cesareans or refuse use of technology increasing the likelihood of cesareans. To address practices driven by a technological imperative I outline three physician obligations that are attached to respecting patient autonomy. These moral obligations show that a focus on respect for autonomy may prove not only an ideal ethical response but also an achievable practical response to lowering cesarean rates.

Reproduction in chinchilla (Chinchilla lanigera): current status of environmental control of gonadal activity and advances in reproductive techniques.

A review of the biology of reproduction of chinchilla, focusing on environmental control of the gonadal activity, is presented. Chinchilla is a South American hystricomorph rodent genus currently considered almost extinct in the wild. However, a domestic form is still widespread in breeding farms around the world. Information regarding their reproductive biology has been obtained from studies on captive animals. In the case of Chinchilla lanigera, a seasonal reproductive pattern has been frequently reported in breeding facilities, but factors that might trigger gonadal activity have not been identified. The available information on reproductive productivity in farms worldwide shows a range of 1.2 to 2.4 deliveries per female per yr (with up to 2.1 weaned young per female per yr). Indeed, as found in all rodents, chinchillas can multiply at high fecundity and fertility rates (4 to 6 follicles mature during estrous cycles). Some new research avenues are postulated to improve the control of gonadal activity by means of environmental and/or pharmacologic factors. Furthermore, reproductive techniques that have been validated in chinchilla are reviewed (noninvasive hormone monitoring, semen collection, sperm cryopreservation, estrus induction), and several technical steps are proposed to be able to achieve AI. Because domesticated chinchilla still share some genomic characteristics with their counterparts in the wild, validated reproductive techniques in chinchilla males and females might contribute to the success of breeding programs.

Protocolo de sincronización de celo en vacas de lidia con monta natural / Effective estrus synchronization protocol for fight cows undergo natural mount

La reproducción en la ganadería de lidia se encuentra condicionada por una serie de factores que pueden afectar tanto al semental como a las vacas de vientre, entre los que se pueden destacar el estrés derivado del manejo, la sanidad, el hábitat y la alimentación, así como la selección a la que han sido sometidos los progenitores. Es por esto que diferentes técnicas reproductivas que se aplican en otros bovinos no dan buenos resultados y provocan que el ganadero de bravo descarte su utilización. El objetivo de este estudio es obtener un protocolo de sincronización del celo válido para una ganadería de lidia con monta natural, para planificar la paridera. El estudio que llevamos a cabo se realizó en 20 vacas de la raza de lidia de diferentes edades y 1 semental de 8 años ya utilizado con anterioridad, que formaban un lote de reproductores de una explotación de lidia de la zona centro. Se empleó con las vacas un protocolo de sincronización de celo en dos manejos. Inicialmente se utiliza una esponja intravaginal de progestágeno y a los 8 días se inyecta por vía intramuscular gonadotropina coriónica equina y prostaglandina F2alfa, introduciendo entonces al animal sincronizado al cercado con el semental para monta natural. La sincronización y posterior introducción al cercado de monta se realizó de modo gradual con 4 vacas en cada grupo de sincronización. Los resultados obtenidos fueron positivos, con un incremento de la fertilidad en el conjunto de animales sincronizados hasta un 85%(AU)

Reproduction in fightingbull farm is conditioned by some factors that affect the stud and the cattle, where it emphasizes the stress derived of the using, the health, the environment and the food, just as the selection that have been subjected breeding. It means that different breeding techniques put into practice in other bovines don’t give good results and cause that bullfight farmer discard the use. The objective of this study is to obtain a estrus synchronization protocol valid for a bullfight farm with natural mount, to plan the births. This study was made in 20 bullfight cows with different ages and 1 eight years old stud used before, that formed one breeding lot in a bullfight farm of de centre zone. A estrus synchronization protocol in two steps was used. Firstly it was put progestin sponge in the vagina for 8 days and it was inyected intramuscular equine chorionic gonadotropine and F2alpha prostaglandine with cow, introducing then the synchronized animal in the enclosure with the stud, to the natural mount. The synchronization and the introduction to the enclosure were made gradual, with 4 cattle in each synchronization group. The results obtained were positive, with an increase of the fertility in the group of synchronized animals up to the 85%(AU)

Embarazo heterotópico diagnosticado en una cesárea a término / Gestational sack over a previous cesarean section scar: case report and review of the literature

El embarazo heterotópico está aumentando su incidencia como consecuencia del avance de las técnicas de reproducción asistida. Es importante realizar un diagnóstico precoz pues la rotura de la gestación ectópica puede llegar a ser una urgencia potencialmente mortal. Presentamos un atípico caso clínico en el que el diagnóstico de la gestación extrauterina se realizó en el transcurso de una cesárea electiva a término (AU)

We present the case of a pregnant woman with an 8-week history of amenorrhea and insertion of a gestational sac over a previous cesarean section scar. Methotrexate treatment was unsuccessful and laparotomy was performed. We provide a literature review and update on the incidence, diagnostic methods and current treatment options of this entity (AU)

Perfiles de expresión génica en hombres infértiles que se someten a reproducción asistida / Gene expression profiles of infertile men who undergo assisted reproduction

Introducción. El espermiograma tiene una capacidad diagnóstica limitada a la hora de predecir una gestación en las técnicas de reproducción asistida. Parámetros moleculares como los ARN mensajeros presentes en el esperma no se evalúan. Nuestro grupo ha realizado listados de genes diferencialmente expresados (GDE) de muestras de semen que lograban un embarazo (E) frente aquellas que no (NE), en pacientes que se sometían a ciclos de IAH o de ICSI. El objetivo era caracterizar los perfiles de expresión, usando la tecnología del microarray, de muestras de semen que logran o no embarazo en ciclos de IAH o ICSI. Material y métodos. 30 muestras de semen (10 lograron embarazo [E=10] y 10 no [NE=10]) se obtenían de pacientes que se sometían a un ciclo de IAH y 10 muestras de semen (E=5, NE=5) que se sometían a uno de ICSI con ovocitos de donantes. Finalmente se realizaron 4 microarrays con las muestras de semen que lograban embarazo frente aquellas que no para ambas técnicas evaluándose los GDE que había entre los grupos E y NE tanto en IAH como en ICSI. Resultados. El número total de genes (NTG) detectados en el microarray de IAH fue de 19.938 y 19.229 en ICSI. El número total de GDE fue de 950 en IAH y 49 en ICSI. Conclusiones. Los datos revelan que los factores moleculares requeridos para lograr embarazo son diferentes según la técnica utilizada. Conclusiones. Estas diferencias pueden ser potencialmente empleadas como marcadores de éxito en ambas técnicas y como futura herramienta terapéutica (AU)

Introduction. Basic sperm analysis has insufficient predictive power on pregnancy achievement in assisted reproductive techniques (ARTs). Molecular parameters such as as mRNA present within spermatozoa are not assessed. Our group listed differentially expressed genes (DEG) from sperm samples (SS) from that achieve pregnancy (group P) vs. those that do not (group NP) using microarray technology in couples undergoing homologous IUI and ICSI. The aim is to use microarray technology to characterise the different gene expression profiles (EP) between SS that achieve pregnancy or not in ICSI and IUI cycles. Material and methods. Ten SS (5 that achieved and 5 that did not achieve pregnancy) were obtained from IP undergoing ICSI and 20 (10 that achieved and 10 did not achieve pregnancy) IAH cycles with oocytes from young donors and their healthy female partners respectively. After freezing aliquots of the SS employed for both treatments and their respective mRNA expression profiles were compared. Finally 4 microarrays were performed in duplicate with sperm samples from group P vs. NP from both techniques and those DEG were evaluated at least twice, with statistically significant differences between P and NP SS for each group. Results. Total number of genes (TNG) in IUI microarray was 19938 and 19229 in ICSI. The total number of DEG (950) in the IAH group was much greater than in the ICSI group (49). Conclusions. These data reveal that molecular features required for pregnancy are different in IUI and ICSI procedures. Conclusions. These differences could be potentially employed to detect ICSI and IUI success markers or to improve pregnancy rates in these procedures (AU)

[New strategies for fertility preservation in young women with cancer]. / Neue Strategien zur Fertilitätserhaltung bei jungen Frauen mit malignen Erkrankungen.

Especially young women with cancer face rising survival rates due to remarkable progress in oncologic therapies. Preserving fertility is a major concern for both patients and their next of kin. Well established reproductive technologies such as cryopreservation of fertilized oocytes after in vitro fertilization already make fertility preservation possible for some patients. This review is dedicated to the emerging techniques that are becoming widely accepted for fertility preservation in young women and girls with cancer, such as auto transplantation of ovarian tissue cryopreservation and in vitro maturation (IVM) of either oocytes or follicles. First results are encouraging. But some challenges still have to be tackled in order for these novel technologies to be routinely employed with the aim of successful fertility preservation.