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Mathieu Luyckx,1,2 Raffaella Votino,1 Jean-Luc Squifflet,1,2 Jean-François Baurain2,31Gynecology and Andrology Unit, 2Centre du cancer, Gynecologic Oncology Group, 3Medical Oncology Unit, Cliniques Universitaires Saint-Luc, Brussels, BelgiumObjective: Our aim was to review the profile of vintafolide (EC145) and its rationale for use in platinum-resistant ovarian cancer. First we investigated the folate receptors (FRs), folate's pathway into cells, and its expression in normal and cancerous cells, before detailing the mechanism of action of vintafolide, its clinical applications, and the results of different study phases.Materials and methods: A literature search was conducted through Pubmed/Medline, Google, ClinicalTrials.gov and websites of pharmaceutical companies. Only articles in English were selected. All articles investigating folate receptor expression in ovarian cancer were selected first, than articles reviewing platinum resistance. Papers about vintafolide were collected, while those talking about synthesis and biochemistry concerns were excluded. The different Phase I and II studies were read, and an update on the website of pharmaceuticals companies were added.Results: FR is a bundle-membrane receptor that is expressed normally in some normal tissues on the apical surface of cells, but highly expressed in ovarian cancer cells (>80%). It collects folate through endocytosis. Chemotherapy does not modify its expression in ovarian cancer cells, and its expression appears to be mostly associated with a poor prognosis and platinum resistance. Vintafolide is a folate-desacetylvinblastine monohydrazide conjugate, allowing a liberation of the drug into the cytoplasm of cancerous cells via the FR-α (FR α) and endocytosis, with high specificity. Phase I studies showed a 2.5 mg bolus dose to be nontoxic, with moderately adverse events. Phase II clinical trials for the first time demonstrated a statistically significant improvement in disease-free survival in patients with platinum-resistant ovarian cancer, and in those with a very poor prognosis who had already received three to four lines of systemic chemotherapy. The greater benefits were observed in patients with highly expressed FR α.Conclusion: Vintafolide is a promising targeted agent for recurrent platinum-resistant ovarian cancer, first, thanks to its mechanism of action and the characteristics of FRα in ovarian cancer, and, second, because of the favorable results observed in the first clinical trials on platinum-resistant ovarian cancer. Phase III clinical trials are currently ongoing and are expected to confirm these results.Keyword: folate receptor, platinum-resistant ovarian cancer, chemotherapy

Emergency Contraception (EC) has been gaining attention for its controversial nature, from the ethical, moral and religious perspectives. Objecting health professionals feel that the implementation of certain procedures or the prescription of some drugs would engender a conflict of conscience. That is also true in the context of reproductive medicine and not only limited to EC, but including abortion and some medically-assisted procreation procedures; all such procedures have created a rift between sexuality and procreation that has substantial ethical complexities. Provided that respect for conscience is essential, and codified in many national and international statutes, any refusal to provide services or medication should be limited if it might negatively affect a patient's health, is based on scientific misinformation, or could bring about inequalities of any kind. First and foremost, any imposition of religious or moral beliefs on patients should not be countenanced. In fact, any form of conscientious objection that could harm patient well-being should be allowed only if the fundamental duty towards patients can be effectively discharged. The right to thorough and unbiased information is crucial so as to enable patients to make well-informed decisions. Moreover, as the WHO has remarked, access to safe and legal reproductive services should be fostered particularly in at-risk, resource-poor areas. [ABSTRACT FROM AUTHOR]

Emergency contraception (EC) has been prescribed for decades, in order to lessen the risk of unplanned and unwanted pregnancy following unprotected intercourse, ordinary contraceptive failure, or rape. EC and the linked aspect of unintended pregnancy undoubtedly constitute highly relevant public health issues, in that they involve women's self-determination, reproductive freedom and family planning. Most European countries regulate EC access quite effectively, with solid information campaigns and supply mechanisms, based on various recommendations from international institutions herein examined. However, there is still disagreement on whether EC drugs should be available without a physician's prescription and on the reimbursement policies that should be implemented. In addition, the rights of health care professionals who object to EC on conscience grounds have been subject to considerable legal and ethical scrutiny, in light of their potential to damage patients who need EC drugs in a timely fashion. Ultimately, reproductive health, freedom and conscience-based refusal on the part of operators are elements that have proven extremely hard to reconcile; hence, it is essential to strike a reasonable balance for the sake of everyone's rights and well-being.

Y RNA are a class of small non-coding RNA that are largely conserved. Although their discovery was almost 40 years ago, their function is still under investigation. This is evident in cancer biology, where their role was first studied just a dozen years ago. Since then, only a few contributions were published, mostly scattered across different tumor types and, in some cases, also suffering from methodological limitations. Nonetheless, these sparse data may be used to make some estimations and suggest routes to better understand the role of Y RNA in cancer formation and characterization. Here we summarize the current knowledge about Y RNA in multiple types of cancer, also including a paragraph about tumors that might be included in this list in the future, if more evidence becomes available. The picture arising indicates that Y RNA might be useful in tumor characterization, also relying on non-invasive methods, such as the analysis of the content of extracellular vesicles (EV) that are retrieved from blood plasma and other bodily fluids. Due to the established role of Y RNA in DNA replication, it is possible to hypothesize their therapeutic targeting to inhibit cell proliferation in oncological patients.

Emergency Contraception (EC) has been gaining attention for its controversial nature, from the ethical, moral and religious perspectives. Objecting health professionals feel that the implementation of certain procedures or the prescription of some drugs would engender a conflict of conscience. That is also true in the context of reproductive medicine and not only limited to EC, but including abortion and some medically-assisted procreation procedures; all such procedures have created a rift between sexuality and procreation that has substantial ethical complexities. Provided that respect for conscience is essential, and codified in many national and international statutes, any refusal to provide services or medication should be limited if it might negatively affect a patient's health, is based on scientific misinformation, or could bring about inequalities of any kind. First and foremost, any imposition of religious or moral beliefs on patients should not be countenanced. In fact, any form of conscientious objection that could harm patient well-being should be allowed only if the fundamental duty towards patients can be effectively discharged. The right to thorough and unbiased information is crucial so as to enable patients to make well-informed decisions. Moreover, as the WHO has remarked, access to safe and legal reproductive services should be fostered particularly in at-risk, resource-poor areas.

The World Health Organization (WHO) defines infertility as the inability of a sexually active, non-contracepting couple to achieve spontaneous pregnancy within one year. Statistics show that the two sexes are equally at risk. Several causes may be responsible for male infertility; however, in 30-40% of cases a diagnosis of idiopathic male infertility is made in men with normal urogenital anatomy, no history of familial fertility-related diseases and a normal panel of values as for endocrine, genetic and biochemical markers. Idiopathic male infertility may be the result of gene/environment interactions, genetic and epigenetic abnormalities. Numerical and structural anomalies of the Y chromosome represent a minor yet significant proportion and are the topic discussed in this review. We searched the PubMed database and major search engines for reports about Y-linked male infertility. We present cases of Y-linked male infertility in terms of (i) anomalies of the Y chromosome structure/number; (ii) Y chromosome misbehavior in a normal genetic background; (iii) Y chromosome copy number variations (CNVs). We discuss possible explanations of male infertility caused by mutations, lower or higher number of copies of otherwise wild type, Y-linked sequences. Despite Y chromosome structural anomalies are not a major cause of male infertility, in case of negative results and of normal DNA sequencing of the ascertained genes causing infertility and mapping on this chromosome, we recommend an analysis of the karyotype integrity in all cases of idiopathic fertility impairment, with an emphasis on the structure and number of this chromosome.

Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive disorders characterized by defects of adrenal steroidogenesis due to mutations in one of the following enzymes: 21-hydroxylase (21OH), 11β-hydroxylase (11βOH), 17α-hydroxylase (17OH; also known as 17, 20-lyase), 3β hydroxysteroid dehydrogenase type 2 (3βHSD2), steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage (P450scc), and P450 oxidoreductase (POR). More than 95% of congenital adrenal hyperplasia cases are due to mutations in CYP21A2, the gene encoding the adrenal steroid 21-hydroxylase enzyme (P450c21). This work focuses on this type of CAH given that it is the most frequent one. This disease is characterized by impaired cortisol and aldosterone production as well as androgen excess. A variant of the CAH is the non-classic type of CAH (NCCAH), usually asymptomatic before the 5th year of age, diagnosed during puberty especially in patients visiting a fertility clinic. NCCAH is characterized mainly by anovulatory cycles and/or high androgen concentrations. Both types of CAH are associated with infertility. Given that the incidence of NCCAH is greater than that of CAH, patients suffering from NCCAH are more often diagnosed for the first time in a fertility clinic. Thus, screening for NCCAH should always be considered. The causes of infertility in CAH patients are multi-factorial including virilization of external genitalia, altered psychosocial development, and hormonal disorders. The main challenges encountered in assisted reproduction are the androgen excess-associated anovulatory cycles as well as the increased circulating progesterone concentrations during the follicular phase which impact endometrial receptivity, tubal motility, and cervical thickness. Administration of sufficient substitution dose of glucocorticoids usually resolves these problems and leads not only to successful assisted reproduction treatment but also to spontaneous pregnancy. Patients with CAH should be followed by a multidisciplinary team including gynecologist, endocrinologist, and pediatrician., (Copyright © 2019 Chatziaggelou, Sakkas, Votino, Papagianni and Mastorakos.)

Non-coding RNAs (ncRNAs) are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs) has also been included in cancer studies. Studies on the relation between endometrial cancer (EC) and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), antisense RNAs (asRNAs), small nuclear RNAs (snRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), competing endogenous RNAs (ceRNAs), lncRNAs, and long intergenic ncRNAs (lincRNAs) have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular., Competing Interests: The authors declare no conflict of interest.

Objective: To study the pregnancy rate after ulipristal acetate (UPA) therapy for fibroids., Design: Retrospective analysis of a series of 52 patients prospectively included in the PGL4001 (ulipristal acetate) Efficacy Assessment in Reduction of Symptoms Due to Uterine Leiomyomata (PEARL) II and III trials., Setting: Academic hospital., Patient(s): Among the 52 patients, 21 wished to conceive upon treatment completion., Intervention(s): None., Main Outcome Measure(s): Pregnancy rate and live birth rate., Result(s): Twenty-one patients attempted to get pregnant, among whom 15 (71%) succeeded, totaling 18 pregnancies. Among these 18 pregnancies, 12 resulted in the birth of 13 healthy babies and 6 ended in early miscarriage. No regrowth of fibroids was observed during pregnancy., Conclusion(s): We report the first series of pregnancies achieved after UPA treatment. Our data confirm a sustained long-term effect after UPA therapy., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The purpose of this survey was to explore how adults communicate their end-of-life preferences. Face-to-face interviews were conducted with 119 community-dwelling adults who had previously engaged in conversations about their end-of-life preferences. Factors that made it easier to initiate the discussion included having personal experience with illness or death (24.4%), being straightforward (24.4%), or having someone else facilitate the discussion (11.8%). Most described vague end-of-life preferences such as not wanting any machines (41.2%) or heroics (34.5%). Although 22.7% reported using a living will to make their preferences clear, only 5.9% mentioned repeating or reinforcing their preferences. In all, 21% had discussed their end-of-life preferences with their physicians. These findings show discussions about end-of-life preferences frequently lack the clarity and detail needed by significant others and health care providers to honor the preferences. Routine dialogue with health care providers and significant others about end-of-life preferences might provide greater clarity and comfort.