First custom next-generation sequencing infertility panel in Latin America: design and first results.

OBJECTIVE: To present the development of the first custom gene panel for the diagnosis of male and female infertility in Latin America. METHODS: We developed a next-generation sequencing (NGS) panel that assesses genes associated with infertility. The panel targeted exons and their flanking regions. Selected introns in the CFTR gene were also included. The FMR1 gene and Y chromosome microdeletions were analyzed with other recommended methodologies. An in-house developed bioinformatic pipeline was applied for the interpretation of the results. Clear infertility phenotypes, idiopathic infertility, and samples with known pathogenic variants were evaluated. RESULTS: A total of 75 genes were selected based on female (primary ovarian insufficiency, risk of ovarian hyperstimulation syndrome, recurrent pregnancy loss, oocyte maturation defects, and embryo development arrest) and male conditions (azoospermia, severe oligospermia, asthenozoospermia, and teratozoospermia). The panel designed was used to assess 25 DNA samples. Two of the variants found were classified as pathogenic and enable the diagnosis of a woman with secondary amenorrhea and a man with oligoasthenoteratozoospermia. Targeted NGS assay metrics resulted in a mean of 180X coverage, with more than 98% of the bases covered ≥20X. CONCLUSION: Our custom gene sequencing panel designed for the diagnosis of male and female infertility caused by genetic defects revealed the underlying genetic cause of some cases of infertility. The panel will allow us to develop more precise approaches in assisted reproduction.

Preliminary experience with a low-cost stimulation protocol that includes letrozole and human menopausal gonadotropins in normal responders for assisted reproductive technologies.

A low-cost stimulation protocol that includes letrozole and hMG in normal responders for assisted reproductive technologies resulted in a satisfactory ongoing pregnancy rate.

Definición y causas de la infertilidad / Infertility: causes and definitions

La infertilidad es un problema común que afecta a una de cada seis parejas. Puede ser definida como la incapacidad de completar un embarazo luego de un tiempo razonable de relaciones sexuales sin tomar medidas anticonceptivas. Las causas del incremento en la prevalencia de la infertilidad son difíciles de establecer. Este aumento podría deberse por lo menos a cuatro factores: postergación del momento en que se deben tener hijos, alteraciones en la calidad del semen debido a hábitos como el tabaquismo y el alcohol, cambios en la conducta sexual y eliminación de la mayoría de los tabúes. El estudio de la pareja infértil siempre se ha enfocado considerando diferentes factores: el ovulatorio (presente en alrededor de 20 por ciento de las parejas), el útero-tubárico-peritoneal (se observa en el 30 por ciento de las parejas), el de migración del semen (10 por ciento de los casos) y el masculino (30 por ciento de las parejas). Cerca de 40 por ciento de todas las parejas infértiles presentan una combinación de factores y aproximadamente el 15 por ciento no evidencia ninguna alteración objetiva que lleve a un diagnóstico definido. Durante las últimas dos décadas se registraron tres cambios importantes en el enfoque de la infertilidad. En primer lugar, la introducción de las tecnologías de reproducción asistida ha brindado una oportunidad de estudiar los procesos reproductivos básicos. En segundo lugar, han ocurrido cambios en las sociedad tales como un aumento en la proporción de mujeres mayores de 35 años que buscan el embarazo; este hecho obedece a que la gente se casa a edades más tardías y posterga el embarazo. En tercer lugar, el desarrollo de la biología molecular y de la genética se han hecho muy importantes para el estudio, diagnóstico y evaluación de las parejas, muchas de ellas consideradas hasta ahora como "parejas infértiles sin explicación".

Definition and causes of infertility.

Infertility is a common problem affecting one couple in six. It can be defined as the incapacity to fulfill pregnancy after reasonable time of sexual intercourse with no contraceptive measures taken. The evidence for changes in the prevalence of infertility is difficult to establish. This increase could be due to at least four factors: delayed childbearing, alterations in semen quality due to habits such as cigarette smoking and alcohol, changes in sexual behaviour and eliminations of most taboos. The study of infertile couple has always been focussed on different factors: ovulatory factor (present in about 20% of couples), utero-tubal peritoneal factor (present in ~30% of couples), semen migration factor (10% of cases) and male factor (30% of couples). Around 40% of all infertile couples exhibit a combination of factors and about 15% of couples may not display any objective alteration leading to a definite diagnosis. During the past two decades there have been three important changes in infertility practice. First, the introduction of assisted reproduction technologies has provided an opportunity to study basic reproductive processes. Second, societal changes have occurred such as the increase in the proportion of women over 35 years old seeking pregnancy. This fact is due to a later age for marriage and postponement of pregnancy. Third, the development of molecular biology and genetics has become very important for the study, diagnosis and assessment of couples, many of them considered until now as "unexplained infertile couples".