Inform and consent: more than just sign here Informed consent, which blends law, medicine, and bioethics, is a multifaceted process to obtain patient permission and enhance patient understanding before health care interventions. Insufficient informed consent may even constitute battery or medical malpractice, for reasons articulated in the landmark 1914 New York case Schloendorff v. Society of New York Hospital. Adoption of the informed consent doctrine was sluggish but reached a groundswell following the Nuremberg Code, the well-known 1972 case Canterbury v.
Introduction This issue's Views and Reviews section aims to offer readers a 360° view of the knowledge accumulated regarding the transfer of mosaic embryos by experts from around the world, as well as an in vitro fertilization worldwide survey on the topic.
Mosaicism between trophectoderm and inner cell mass Defining the actual incidence and prevalence of mosaicism in human blastocysts still remains a difficult task. The small amount of evidence generated by animal and human studies does not support the existence of mechanisms involved in developmental arrest, clonal depletion, or aneuploidy rescue for abnormal cells in euploid/aneuploid embryos during preimplantation development. However, studies in humans are mainly descriptive and lack functional evidence. Understanding the biological mechanisms that beset preimplantation differentiation holds the potential to reveal the role of aneuploidies and gene dosage imbalances in cell fate decision, providing important clues on the origin and evolution of embryonic mosaicism.
Assessing the true incidence of mosaicism in preimplantation embryos Modern technologies applied to the field of preimplantation genetic diagnosis for aneuploidy screening (PGD-A) have improved the ability to identify the presence of mosaicism. Consequently, new questions can now be addressed regarding the potential impact of embryo mosaicism on diagnosis accuracy and the feasibility of considering mosaic embryos for transfer. The frequency of chromosomal mosaicism in products of conception (POCs) of early miscarriages has been reported to be low. Mosaic embryos with an aneuploid inner cell mass are typically lost during the first trimester owing to spontaneous miscarriages.
Chromosomal mosaicism detected during preimplantation genetic screening: results of a worldwide Web-based survey Embryonic mosaicism, the presence of more than one distinct cell line within an embryo, has recently become the focus of growing attention and controversy in the context of preimplantation genetic screening (PGS). To evaluate the extent of mosaic aneuploidy in clinical practice and to gain insight on the practices and views regarding this issue, we conducted a survey using a prospective, 20-item Web-based questionnaire with questions related to practices and views regarding mosaicism in PGS. A total of 102 in vitro fertilization (IVF) units from 32 countries that performed 108,900 IVF cycles annually responded to the survey.
Natural ovarian stimulation (NATOS): effectively natural Given that the so-called “mild” ovarian stimulation procedures, together with their underlying die-hard ideology are, finally, running out of steam under the blows of evidence-based medicine and patient choices, the time has come to take over the concept of “natural” in reproductive care—this time, in the name of efficacy. Indeed, numbers in France indicate the cost of live birth through in vitro fertilization (IVF)-embryo transfer (ET) exceeds US$15,000-, mainly because per-cycle effectiveness of treatments remains low in France and patients often need to undergo repeated cycles to finally conceive.
Detection of mosaicism at blastocyst stage with the use of high-resolution next-generation sequencing A significant proportion of human preimplantation embryos produced during the course of in vitro fertilization (IVF) treatments contain two or more cytogenetically distinct cell lines. This phenomenon, known as chromosomal mosaicism, can involve the presence of cells with different types of aneuploidy in the absence of any normal cells or a mixture of euploid and abnormal cells. Although a high prevalence of mosaicism at the cleavage and blastocyst stages has been appreciated for two decades, the precise frequency of the phenomenon and its consequences for embryo viability have been difficult to quantify.
Advanced maternal age patients benefit from preimplantation genetic diagnosis of aneuploidy Chromosome abnormalities in human embryos may result in implantation failure or miscarriage. These abnormalities are common, and their incidence increases with advancing maternal age, from approximately 40% in fertile egg donors to 80% in patients 41 to 42 years old (1). Preimplantation genetic diagnosis of aneuploidy (PGD-A) is used as a selection tool for euploid embryos with potential to implant and reach term. That chromosome abnormalities are a major cause of embryo loss with advancing maternal age is demonstrated by the observation that once a euploid embryo is transferred to the uterus, it seems to have the same chance of implanting irrespective of maternal age (2).
Antiadhesion barrier gels: time for evidence-informed practice in gynecologic surgery? The Prevention of Adhesions Post Abortion (PAPA) study published by Hooker and coworkers (1) reports a decrease in the occurrence of intrauterine adhesions (IUAs) after the intrauterine application of auto-crosslinked hyaluronic acid (ACP) gel after dilation and curettage (D&C) for miscarriage in women with at least one previous D&C. The mean adhesion scores and the amount of moderate to severe IUAs were both statistically significantly lower after the application of the antiadhesion barrier gel compared with D&C alone (1).
Using family members as gamete donors or gestational carriers The use of adult intrafamilial gamete donors and gestational surrogates is generally ethically acceptable when all participants are fully informed and counseled, but consanguineous arrangements or ones that simulate incestuous unions should be prohibited. Adult child-to-parent arrangements require caution in order to avoid coercion, and parent-to-adult child arrangements are acceptable in limited situations. Programs that choose to participate in intrafamilial arrangements should be prepared to spend additional time counseling participants and ensuring that they have made free, informed decisions.
The most well kept secret, embryo culture media: a smart reveal from an expert The introduction of in vitro fertilization (IVF) treatments was only possible when all those investigations that took place in tissue culture were adapted for human embryos. But human embryo culture is very different from other cell culture, because somatic cells are surrounded by the extracellular fluid rich in nutrients whereas embryos are simply bounded by a very low amount of uterine fluid that reflects location and chronologic changes (1). Since the beginning of assisted reproductive technology (ART) in the 1980s, media conception, configuration, and composition may have changed dramatically, and we may consider that a portion of the improved success in IVF programs came along with enhanced formulations and detailed user protocols (2).
Healthy diets and men's contribution to fertility; is semen quality good enough? In this issue of Fertility and Sterility, Oostingh and colleagues (1) report an association between greater adherence to a data-derived “healthy” dietary pattern, characterized by higher intakes of legumes, vegetables, cereals, fruits, and olive oil, and higher semen quality—particularly sperm concentration and progressive motility—among men from couples planning pregnancy. This article adds to the growing literature relating adherence to healthy diet patterns and greater semen quality including previous work from this group among couples undergoing infertility treatment, as well as work from other groups including studies reporting higher semen quality with greater adherence to healthy diets among men in the United States, Europe and Asia (2, 3).
Long-awaited long-term follow-up of reproductive parameters in female offspring conceived with the use of intracytoplasmic sperm injection There have been great advances in many assisted reproduction laboratory techniques and procedures since the first successful live birth as a result of in vitro fertilization (IVF) in 1978. One of the most notable overall, particularly for the treatment of male-factor infertility, was the advent of intracytoplasmic sperm injection (ICSI). Although many clinicians and patients who have benefitted from this technology hail it as a breakthrough, there are questions regarding how the need to use this technique to achieve reproductive success may affect future generations; one particular area of interest in this regard is the potential for reproductive success in the offspring.
ASRM standard embryo transfer protocol template: a committee opinion Standardization improves performance and safety. A template for standardizing the embryo transfer procedure is presented here with 12 basic steps supported by published scientific literature and a survey of common practice of SART programs; it can be used by ART practices to model their own standard protocol.
Guidance on the limits to the number of embryos to transfer: a committee opinion Based on American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology data available through 2014, ASRM's guidelines for the limits on the number of embryos to be transferred in in vitro fertilization (IVF) cycles have been further refined in continuing efforts to promote singleton gestation and reduce the number of multiple pregnancies. This version replaces the document titled Criteria for number of embryos to transfer: a committee opinion that was published most recently in August of 2013 (Fertil Steril 2013;99:44–6).
Obesity pandemic: causes, consequences, and solutions—but do we have the will? Obesity has become pandemic owing to an obesogenic environment (inexpensive calorie dense food, technologies and structure of communities that reduce or replace physical activity, and inexpensive nonphysical entertainment) and excessive emphasis on low fat intake resulting in excessive intake of simple carbohydrates and sugar. Effects are greater for women owing to their smaller size and extra weight gain with each pregnancy, with 38% of American adult women being obese. Women are responsible for more than three-fourths of the more than 400 billion dollars of excess direct health care expenditures due to obesity.
Obesity and female infertility: potential mediators of obesity's impact The worldwide upward trend in obesity has been dramatic, now affecting more than 20% of American women of reproductive age. Obesity is associated with many adverse maternal and fetal effects prenatally, but it also exerts a negative influence on female fertility. Obese women are more likely to have ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. Women with polycystic ovarian syndrome who are also obese demonstrate a more severe metabolic and reproductive phenotype.
Vasectomy reversal semen analysis: new reference ranges predict pregnancy To study the semen analysis values required to cause a pregnancy after vasectomy reversal (VR). Vasectomy reversal is increasingly performed on men who wish to regain fertility after elective sterilization. Despite a thorough understanding of predictors of vasal patency after surgery, little is known about the patients’ semen parameters and pregnancy potential.
Microsurgical excision of testicular mass The video article by Sávio et al. (1). nicely demonstrates a potentially testis-preserving procedure used for either impalpable testicular tumors picked up on ultrasound or palpable tumors in men with a solitary functioning testis. I described a technique for ultrasound-guided needle localization and microsurgical excision of nonpalpable testicular tumors in 2002 (2). This video is a good demonstration of the technique.
Toward standardizing the embryo transfer procedure: from “how to” to “how many” Assisted reproductive technology (ART) has reduced the suffering associated with reproductive impairment for many individuals and couples. The importance and beneficence of in vitro fertiilization (IVF) in the 21st century cannot be overstated. An estimated 7–8 million children have been born through this technology worldwide. ART treatments are, however, not uniformly successful. The majority of in vitro- (and in vivo-) derived embryos are not ultimately viable and will not produce babies. For couples not experiencing infertility, this is not a big problem as most fertile couples will conceive within a few months.
How good is good enough? Defining normal semen parameters after vasectomy reversal Semen analysis remains the foundation of the male infertility evaluation, yet we face constant reminders than in and of itself it is an imperfect proxy for fertility. In this issue of Fertility and Sterility, Majzoub et al. (1) help narrow a void in our understanding; what should a semen analysis look like following vasectomy reversal? Normal semen parameters have been systematically established in fertile men by the World Health Organization (WHO) and abnormal semen parameters are widely studied among men with primary infertility, yet there is no standard for expected semen parameters in the vasectomy reversal population.
Obesity, male infertility, and the sperm epigenome Obesity is a growing epidemic and a common problem among reproductive-age men that can both cause and exacerbate male-factor infertility by means of endocrine abnormalities, associated comorbidities, and direct effects on the fidelity and throughput of spermatogenesis. Robust epidemiologic, clinical, genetic, epigenetic, and nonhuman animal data support these findings. Recent works in the burgeoning field of epigenetics has demonstrated that paternal obesity can affect offspring metabolic and reproductive phenotypes by means of epigenetic reprogramming of spermatogonial stem cells.
Adverse effects of female obesity and interaction with race on reproductive potential Across the reproductive spectrum, obesity is associated with greater risks for adverse health outcomes, including higher rates of infertility, subfertility, early pregnancy loss, fetal deaths and stillbirths, congenital anomalies, and pregnancy complications. The excess reproductive morbidity associated with obesity may increase with longer duration, making the current trends among children and young adults particularly critical in terms of their future reproductive potential. Obese women have a lower chance of pregnancy following in vitro fertilization (IVF), require higher dosages of gonadotropins, and have reduced rates of implantation, clinical intrauterine gestation, and live birth rates and increased rates of pregnancy loss, as well as greater risks for prematurity and preeclampsia even when stratified by plurality.
Introduction Women bear the predominant burden of our obesogenic environment, with a higher incidence of obesity than men, more impact on their fertility and success with treatment, and significant maternal and perinatal morbidity and mortality. In this series, the causes, consequences, and solutions regarding the obesity pandemic, the mechanisms of the effect of obesity on the female and male, the epigenetic consequences of male obesity, the marked effects on perinatal outcomes, and the effects of weight loss before conception and during pregnancy are explored.
Effects of obesity treatment on female reproduction: results do not match expectations The adverse effects of obesity of female reproduction have been extensively documented. However, there are few prospective studies that have examined preconception weight loss interventions. There is a need to develop successful interventions with significant weight loss and compliance and most importantly document the effects of preconception interventions on important perinatal outcomes such as live birth and the health of the infant and mother. The existing data from randomized trials that come closest to meeting these criteria have failed to document improved live-birth rates after the intervention compared with control groups.
Performing the embryo transfer: a guideline A systematic review of the literature was conducted which examined each of the major steps of embryo transfer. Recommendations made for improving pregnancy rates are based on interventions demonstrated to be either beneficial or not beneficial.
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