Lecture Summaries

1 Introduction
  • Getting to know each other
  • Course overview
  • Literature and database searches
  • Introduction to the field of assisted reproduction and infertility led by the instructors
2 The effect of age on reproduction in men and women While it is widely accepted in popular culture that the quality of a woman's eggs worsens with age, the basis of the maternal age effect on aneuploidy (an abnormal number of chromosomes) is not entirely clear. Using the first paper, we will explore the association of maternal age with meiotic errors resulting in an extra copy of Chromosome 21 leading to Down Syndrome, providing a modern understanding of a phenomenon that has been recognized for nearly 100 years. Paternal age is also becoming increasingly recognized as a significant factor in reproductive success. Our second paper presents findings on the adverse impact of advanced paternal age on assisted reproductive technology outcome.
3 Gonadal stem cells It has been a long held belief that female germ cells in mammals—unlike in most other species—never establish a stem cell population and have only a limited lifespan ending in menopause. We will first discuss a paper presenting evidence of germline stem cells (GSCs) in female mice and thus directly contesting this highly accepted belief. We will then move on to a second high profile paper that presents a direct challenge to the existence of the circulating GSCs. We will discuss how to think about these two opposing findings, the nature of scientific controversy across disciplines and the impact of these findings on the field of assisted reproduction.
4 Cryopreservation of human embryos and oocytes While cryopreservation of embryos was achieved in mammals (mouse) in the early 1970s and the first human was born from a cryopreserved embryo in 1984, methods for the cryopreservation of early stage human embryos and oocytes have been evolving for the last 30 years. In some countries, up to 40% of children born through assisted reproductive technology (ART) are derived from cryopreserved oocytes or early embryos. Companies like Apple and Facebook recently started to offer a novel benefit—oocyte freezing for female employees. We will discuss the most common cryopreservation procedures, their advantages and potential risks and the dilemmas associated with long-term storage and disposal of oocytes and embryos.
5 Characterization of infertility Clinical evaluation of a couple struggling with infertility is a complicated and multifaceted process. In about 10% of clinical evaluations, the precise cause of infertility will never be identified or even narrowed to one partner. Here, we will learn about two methods for assessing fertility in couples and evaluate their merits as well as their downsides. From the first paper, we will discuss antral follicle counts—a popular diagnostic tool used to estimate the remaining reproductive years in women by counting these fluid filled sacs that each contain one oocyte. From the second paper, we will discuss a screenings tool for microdeletions on the Y chromosome that have been linked to diminished sperm production in men.
6 Sex chromosome constitution and fertility Klinefelter syndrome (XXY male) is the most common sex chromosome aneuploidy (affecting 1:500 to 1:1000 live births) and the second most common condition caused by the presence of extra chromosomes after Down Syndrome. Principal effects include hypogonadism and sterility. From the first paper, we will discuss germ cell loss in a mouse model of Klinefelter syndrome. From the second paper, we will discuss a human case of Klinefelter complicated by another genetic alteration and speculate about causes of the curious phenotype of this person.
7 Embryo culture, assessment, selection and transfer Up to 60% of human embryos created by IVF techniques are aneuploid, and this number worsens with maternal age. Consequently, much effort has been expended to identify the best embryos for transfer to optimize the chance for a single, successful implantation and pregnancy. State-of-the-art embryo testing involves removal of a single cell from a blastomere and subjecting it to genetic testing. However, because single-cell testing is time consuming and expensive, many clinics have simply relied on visual observation of embryo development. The first paper presents the caveats of morphokinetic assessment of embryo quality. The second paper we will discuss involves a technique of screening by whole-genome sequencing to identify embryos that are not suitable for transfer. This technology promises to be faster and cheaper than previous methods, and is therefore likely to be widely adopted.
8 Visit to Boston area IVF clinic  No Lecture Summary
9 Mouse models with abnormal reproductive phenotypes Over 200 mouse models present abnormal reproductive phenotypes. Some are directly relevant to common problems in human reproduction, while others reveal the molecular complexity of the many biological processes involved. Reduced fertility in men has a well-documented association with testicular germ cell tumors. In this class, we will discuss two different mouse models that exhibit both of these conditions and speculate about the molecular basis for this association observed in humans.
10 Seminal fluid–more than just a carrier of sperm Seminal fluid not only promotes the survival and competence of spermatozoa but also contains potent signaling agents that influence female reproductive physiology to improve the chances of conception and reproductive success. Male-to-female seminal fluid signalling occurs in many animals, including all mammals examined to date. We will begin with a discussion of a paper presenting data from mice describing the impact of seminal plasma on implantation, progression of pregnancy, and postnatal outcomes in offspring mediated through effects on female reproductive tissues. We will move on to a discussion of a paper that conducts a meta-analysis (a study combining the results of several studies in order to achieve a higher statistical power for the measure of interest), of the effect of seminal plasma on IVF treatment success in humans.
11 Promise and challenges in reprogramming adult cells to gametes Recent advances with induced pluripotent stem cells (iPS cells) suggest an intriguing new avenue for infertile couples. From the first paper, we will read about researchers at Kyoto University who generated mouse pups from oocytes derived from skin cells. Following up, as reported in the second paper, researchers in the U.K. and Israel used human skin cells to generate germ cells, the precursors to egg and sperm. We will discuss these papers while focusing on important differences between mouse and human stem cells and the similarities and differences between stem cells and germ cells.
12 Student paper presentations and discussions
  • Each student will give a 15 min oral presentation about her / his chosen paper. This paper should be selected by Week 11 and approved by the instructor.
  • The presentation should use approximately 12–15 slides.
  • The first slide should present the paper title, authors and their affiliations, journal, journal volume, pages and year of publication.
  • The next 2–3 slides should contain background information. Students should describe the most important knowledge in the field before the research was conducted and explain any key terms crucial for understanding the presentation.
  • The following 1–2 slides should address the main techniques.
  • The next 5–7 slides should present the most important results—the key figures and tables, the key control experiments, and their implications. Critical judgment should be expressed.
  • The final slide should describe conclusions offered by the authors and students' evaluation of the validity of these conclusions.
  • During each presentation and afterwards, there will be a class discussion.
  • Course summary.
  • Student evaluations.