Infertility patients in general and those with celiac disease may be able to breathe a sigh of relief Celiac disease (CD) is a disorder characterized by an autoimmune reaction triggered by sensitivity to gluten, the protein component of wheat, barley, and rye. Celiac disease is present in approximately 1%–2% of the general population, and existing studies have postulated a potential effect on duration of reproductive years, fertility, and pregnancy outcomes. There have been multiple meta-analyses of cohort studies and case–control studies that attempt to elucidate the association between reproductive disorders and incidence of CD (1, 2); these studies found associations between unexplained infertility, recurrent miscarriage, or intrauterine growth restriction and risk of CD.
Introduction For more than a century, the uterine cavity has been considered a sterile site maintained by the cervical plug. Humans are like coral that need symbiosis with microorganisms to be completely functional. In the era of precision medicine, the endometrial factor and specifically the microbiological view have long been neglected in reproduction, because it was considered an old concept with no potential improvement. In the last decade, important discoveries, led by improving technology, namely next generation sequencing, have been made in the study of microbial communities not only in the vagina but also in the endometrial cavity and its implication in reproductive health and disease, particularly chronic endometritis.
Endometritis: new time, new concepts Endometritis is subdivided into two categories. Acute endometritis is symptomatic and characterized by microabscess formation and neutrophil invasion in the endometrial superficial epithelium, gland lumina, and uterine cavity. Chronic endometritis is rather silent and recognized as unusual plasmacyte infiltration in the endometrial stromal areas. Over the last decade, studies have disclosed the potential association between poor reproductive outcomes and endometritis, particularly chronic endometritis.
Antimüllerian hormone: Don't put all the eggs in one basket Antimüllerian hormone (AMH), produced by preantral and early antral follicles of the ovary, serves as a quantitative measure of ovarian reserve and has changed the landscape of IVF practice. A commercial test for AMH has been available for more than 15 years and has become a standard part of female infertility assessment over the past decade. With a single blood test, clinicians can use AMH to roughly predict clinical response to controlled ovarian hyperstimulation and make treatment decisions accordingly (1).
Cervicovaginal microbiota, women's health, and reproductive outcomes The human microbiome project has shown a remarkable diversity of microbial ecology within the human body. The vaginal microbiota is unique in that in many women it is most often dominated by Lactobacillus species. However, in some women it lacks Lactobacillus spp. and is comprised of a wide array of strict and facultative anaerobes, a state that broadly correlates with increased risk for infection, disease, and poor reproductive and obstetric outcomes. Interestingly, the level of protection against infection can also vary by species and strains of Lactobacillus, and some species although dominant are not always optimal.
Optimal management of symptomatic cesarean scar defects Cesarean delivery has a number of known short- and long-term risks and consequences. Clinical guidelines aimed at reducing nonmedically indicated cesarean delivery and induction of labor under 39 completed weeks have been released by the American College of Obstetricians and Gynecologists in an effort to reduce such births. Yet according to the National Vital Statistics Report, the total U.S. cesarean delivery rate reached a high of 32.9% of all births in 2009, up 60% from 20.7% in 1996.
Clinically integrated health care: optimizing our approach to reproductive medicine Couples seeking medical consultation for infertility have typically been evaluated separately when commencing their reproductive health assessment, due largely to well-established, historical health care delivery patterns and norms (1). Reproductive medicine is unique when compared to other aspects of health care as it involves the intersection of two separate patients, each with their own unique medical conditions and reproductive concerns, in order to achieve the same common goal—the live birth of offspring.
Endometriosis and pregnancy outcome In this issue, Nirgianakis et al. (1) present a retrospective analysis of the complications of pregnancy after laparoscopic excision of deep infiltrating endometriosis (DIE). Most important is that excision of DIE does not affect the increased risk of placenta previa, gestational hypertension, and intrauterine growth retardation (IUGR) associated with endometriosis. In addition, the risk of a vaginal delivery was not increased in the entire group or in the 26 women with a vaginal excision of endometriosis.
Are infertile patients at greater risk of cesarean delivery? Over the last 30 years cesarean section delivery (CSD) rates have been steadily rising in the U.S., and around the globe. Current rates approximate 32% in the general population, and about 45% of infertile women who are treated with assisted reproductive technology (ART) are delivered by CSD. Why? Do clinicians have a lower threshold for delivering so-called precious in vitro fertilization (IVF) pregnancies by CSD electively? Are infertile patients inherently at higher risk for cesarean delivery than fertile couples? Could infertility treatments be associated with higher rates of CSD? Are there other factors to consider?
Unleashing the potential of stem cells to help poor responders There have been multiple advances in assisted reproductive technology (ART) since the first baby from in vitro fertilization (IVF) baby was born 40 years ago, including intracytoplasmic sperm injection and preimplantation genetic testing. However, one patient group remains the most challenging – the poor responder (PR). After attempting multiple IVF cycles that are often cancelled due to little or no ovarian response, devastated PR patients feel they have little or no hope to conceive with their own eggs.
The pros and cons of preimplantation genetic testing for aneuploidy: clinical and laboratory perspectives To contribute to a balanced debate, we invited leading proponents and opponents of preimplantation genetic testing for aneuploidy (PGT-A) to briefly summarize their arguments. Four contributors debate the pros and cons from a clinical perspective, two consider technical aspects related to the validation and accuracy of current methodologies, and finally two consider the implications of chromosomal mosaicism, which has recently been identified using next-generation sequencing–based chromosome copy number analysis.
Is preimplantation genetic testing for aneuploidy an essential tool for embryo selection or a costly ‘add-on’ of no clinical benefit? Chromosome aneuploidy is common in human gametes and preimplantation embryos and is a major cause of in vitro fertilization (IVF) failure, miscarriage, and still births, with an incidence at birth of less than 0.3%. Most aneuploidies originate in the oocyte through errors in maternal meiosis and these increase exponentially in women in their late 30s and early 40s. This is associated with a sharp increase in the incidence of miscarriage and a corresponding decline in live birth rates in these women following IVF.
Speak up! Equipping women with polycystic ovary syndrome to have high quality encounters with their providers Polycystic ovary syndrome (PCOS) is a complex, multisystem disorder affecting reproductive, metabolic, and psychological well-being across the life span. Healthcare providers from a variety of disciplines are involved in caring for women with PCOS. As our understanding of the complicated pathophysiology of this endocrine disorder evolves, providers face the daunting challenge of supplying evidence-based and up-to-date care to this population of women.
Can any meta-analysis help us manage polycystic ovary syndrome? Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in reproductive age women. The clinical features are well known and include oligo-ovulation, hyperandrogenism presenting as acne, and hirsutism, and many have multicystic ovaries. In the last three decades, global research efforts have produced an astonishing array of publications focused on this syndrome. Unquestionably, the most important advance has been the recognition that hyperinsulinemia, stemming from insulin resistance (IR), leads to excess androgen production.
The role of immunotherapy in in vitro fertilization: a guideline Adjuvant immunotherapy treatments in in vitro fertilization (IVF) aim to improve the outcome of assisted reproductive technology (ART) in both the general ART population as well as subgroups such as patients with recurrent miscarriage or implantation failure. The purpose of this guideline is to evaluate the role of immunomodulating therapy in ART. Unfortunately, many of the evaluated therapies lack robust evidence from well-designed adequately powered randomized controlled trials to support their use.
Increasing evidence of the role of the sperm epigenome in embryogenesis: oligoasthenoteratozoospermia, altered embryo DNA methylation, and miscarriage The evidence supporting a role for sperm in facilitating normal embryogenesis has been accumulating since early human in vitro fertilization (IVF) studies first hinted at associations between altered semen analysis parameters and increased levels of embryo fragmentation. Within the last decade, studies have demonstrated that human sperm contain a unique epigenome with histone modifications and DNA methylation patterns at key genes involved in embryonic development. Further, mounting evidence suggests a poising of these genes for transcriptional activation, that this “epigenetic poising” of embryonic genes is conserved in nature, and that alterations in the epigenetic marks at specific loci are associated with altered embryogenesis and poor outcomes during IVF (1).
Relevance of assessing the uterine microbiota in infertility Technical advances in massive parallel sequencing have allowed the characterization of the whole reproductive tract microbiome in all the compartments beyond the vagina. The microbiota in the uterine cavity seem to be a continuum from the microbiota in the vagina, but several works have reported significant differences between vaginal and endometrial microbiota, highlighting the relevance of assessing the upper genital tract microbiota to better understand the potential roles of bacteria in the physiological and pathological processes taking place in the uterine cavity, including embryo implantation, pregnancy maintenance, and other gynecological diseases.
Current status and future prospects of noninvasive preimplantation genetic testing for aneuploidy Preimplantation genetic testing for aneuploidy (PGT-A) aims to assist in the identification of euploid embryos generated using assisted reproductive technology, allowing them to be prioritized for transfer. The selection of euploid embryos should, theoretically, lead to a reduction in the risks of miscarriage, aneuploid conception, and implantation failure. Any strategy improving the likelihood that the embryo selected for transfer is viable should reduce the time required to achieve a pregnancy using assisted reproductive technology.
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