Contribution of immunology to implantation failure of euploid embryos Outcomes in assisted reproduction have seen marked improvement. With increased ability in the embryology laboratory to use extended embryo culture which in turn enables other selective techniques, such as trophectoderm biopsy and comprehensive chromosome screening, the chance of success per embryo transfer is increased. However, even the selection of a euploid blastocyst, which selects out many embryonic factors, does not yield successful implantation and ultimately delivery in all cases. Among the factors that affect implantation failure of apparently reproductively competent embryos, the immune system has been perhaps both the most plausible and the most debated.
Endometriosis on the uterosacral ligament: a marker of ureteral involvement To evaluate the association between ultrasound measurements of endometriosis nodules on the uterosacral ligament (USL) and the risk of ureteral involvement, as well as to assess whether associations with other ultrasound variables increase the sensitivity and specificity of the diagnosis of ureteral endometriosis.
Sex and gender: you should know the difference Embryos do not have a “gender”; rather, they have a “sex.” Gender refers to social and cultural distinctions between sexes, not biological ones. An embryo's “maleness” or “femaleness” should therefore be defined by its biological sex (i.e., sex chromosome pair).
Mode of conception does not appear to affect placental volume in the first trimester To study whether infertility treatments, including IVF and non-IVF fertility treatments, are associated with diseases of placental insufficiency in early gestation. First trimester placental volumes by ultrasound and chorionic villi weight during sampling (CVS) were performed to detect differences between pregnancies conceived spontaneously versus with fertility treatments.
Immune modulation treatments—where is the evidence? While advances in assisted reproductive techniques have been substantial, failure of the apparently viable embryo to implant remains a source of distress and frustration to patients and specialists alike. The unique maternal immunological response to the embryo and the notion that defects in early placentation underlie the great complications of pregnancy have focused attention on the therapeutic potential of peri-implantation immunomodulation. On the face of it, the rationale for this approach is very attractive.
Gamete donation: current practices, public opinion, and unanswered questions The landscape of family building, pregnancy and conception has changed dramatically in this century. Over the past 20 years, the number of births from gamete donation has increased exponentially from 30,000 to 60,000 in the United States (1). However, such numbers are merely estimates and are likely to be poor estimates because there are few tracking systems. Additionally, in the 1980s and 1990s the majority of U.S. recipients of donor sperm were straight, married couples experiencing infertility.
Preconception assisted reproductive technology counseling in the age of Zika The recent Zika virus (ZIKV) epidemic that has affected the South and Central Americas, the Caribbean, and the United States has forced couples considering pregnancy in endemic areas to make extremely tough decisions based on a paucity of information. Physicians are tasked with the difficult task of providing meaningful counseling regarding the magnitude of the risk following exposure, transmission, and the likelihood of fetal malformations based on extremely limited data. Arguably, reproductive endocrinologists providing advanced care face an even more difficult challenge.
Introduction In the past few years we have witnessed reproductive immunology taking a leading role after repeated implantation failure. We still face the problem of even euploid embryos that either fail to implant or are miscarried. These focused articles present the attending clinician with the most recent evidence to understand how immunology contributes to human reproduction, what can be done at the clinical level, and what is still an area for research and should not be offered to patients outside of a clinical research scenario.
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.
Current experience concerning mosaic embryos diagnosed during preimplantation genetic screening The concept of embryos containing multiple cell lines (mosaicism) is not new, but much attention has been paid to this concept recently owing to recent advances in molecular techniques to analyze human embryos. Mosaicism in embryos has been known and reported for some time, originally in early cleavage-stage embryos diagnosed with the use of fluorescence in situ hybridization (FISH). However, the early data have come under attack owing to the limited ability of FISH to reliably detect the actual copy number count of chromosomes as well as potential ascertainment bias of those early studies, which were all performed on already analyzed embryos found to be aneuploid.
Transferring embryos with genetic anomalies detected in preimplantation testing: an Ethics Committee Opinion Patient requests for transfer of embryos with genetic anomalies linked to serious health-affecting disorders detected in preimplantation testing are rare but do exist. This Opinion sets out the possible rationales for a provider's decision to assist or decline to assist in such transfers. The Committee concludes in most clinical cases it is ethically permissible to assist or decline to assist in transferring such embryos. In circumstances in which a child is highly likely to be born with a life-threatening condition that causes severe and early debility with no possibility of reasonable function, provider transfer of such embryos is ethically problematic and highly discouraged.
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