Human implantation: The complex interplay between endometrial receptivity, inflammation, and the microbiome.

Human embryo implantation is an intricate spatiotemporal process that involves the intimate association between the embryo and the endometrium of the mother. During implantation, the endometrium undergoes a dynamic cascade of gene activation and repression, largely driven by autocrine, paracrine, and endocrine action. Steroid hormones, such as estrogen and progesterone, act on a variety of targets including cellular adhesion molecules (CAMs), cytokines, and growth factors to facilitate the implantation process. Given the synchrony required to achieve implantation, it is unsurprising that embryo implantation represents a substantial problem for infertility patients. This is due to a complex interplay taking place at the level of the endometrium. This review discusses the intricacies of embryo implantation including the window of implantation, the cyclical phases of the endometrium, the implantation process itself, and features of endometrial receptivity. Additionally, we will discuss new research regarding inflammatory reproductive biology, epigenetics and microRNA, and the role of the vaginal and endometrial microbiome in implantation. A better understanding of embryo implantation and the interactions occurring at the level of the blastocyst and the endometrium will improve patient care for infertile patients who experience this frustrating challenge.

A call to action: unified clinical practice guidelines for oncofertility care.

By 2030, WHO estimates that 1.4 million reproductive-aged women will be diagnosed with cancer annually. Fortunately, cancer is no longer considered an incurable disease in many cases. From 2008-2014, 85% of women under the age of 45 years diagnosed with cancer survived. This increase in survival rate has shifted attention from focusing exclusively on preserving life to focusing on preserving quality of life after treatment. One aspect of this is preserving the ability to have a biological family. Oncofertility, the field that bridges oncology and reproductive endocrinology with the goal of preserving fertility, offers these patients hope. Though it is clear that ASCO and ASRM recognize the importance of fertility preservation as an aspect of comprehensive oncology care, there are not yet unified guidelines for oncologists and fertility specialists for treating oncofertility patients. First, we identify the need for reproductive counseling prior to cancer treatment, as many patients report that their fertility preservation concerns are not addressed adequately. We then delineate multi-modal fertility preservation options that are available and appropriate for different patients with corresponding outcomes using different treatments. We discuss the unique challenges and considerations, including ethical dilemmas, for delivering timely and comprehensive care specifically for oncofertility patients. Finally, we address the multidisciplinary team that includes oncologists, reproductive endocrinologists, surgeons as well as their staff, nurses, genetic counselors, mental health professionals, and more. Since oncofertility patient care requires the coordination of both physician teams, one set of unified guidelines will greatly improve quality of care.

N6-methyladenine is an epigenetic marker of mammalian early life stress.

Recent evidence described 6-methyladenine (6 mA) as a novel epigenetic regulator in a variety of multicellular species, including rodents; however, its capacity to influence gene expression in the mammalian brain remains unknown. We examined if 6 mA is present and regulated by early life stress associated with predator odor exposure (POE) within the developing rat amygdala. Our results provide evidence that 6 mA is present in the mammalian brain, is altered within the Htr2a gene promoter by early life stress and biological sex, and increased 6 mA is associated with gene repression. These data suggest that methylation of adenosine within mammalian DNA may be used as an additional epigenetic biomarker for investigating the development of stress-induced neuropathology.