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Cancer is a major public health problem around the world. Currently, about 5% of women diagnosed with cancer are of reproductive age. These young survivors may face compromised fertility. The effects of chemotherapeutic agents on ovarian reserve and its clinical consequences are generally inferred from a variety of surrogate markers of ovarian reserve, all aiming to provide prognostic information on fertility or the likelihood of success of infertility treatment. Until recently, the mechanisms that are responsible for chemotherapy-induced ovarian damage were not fully elucidated. The understanding of these mechanisms may lead to targeted treatments to preserve fertility. In this manuscript, we will review the current knowledge on the mechanism of ovarian damage and clinical impact of chemotherapy agents on fertility. Cancer is a major public health problem around the world and is the second leading cause of death in the USA [1]. In 2016, approximately 844,000 new cases of cancer will be diagnosed in women in the USA [1]. In recent years, the remarkable screening, diagnostic and therapeutic advances in oncology practice improved the prognosis for many cancer patients, adding years to their anticipated survival. In fact, all these measures have resulted in a 23% drop in the cancer death rates from 1991 to 2012 [1].Currently, about 5% of cancers affects women younger than 50 years [1]. As young patients with these once-fatal malignancies become long-term survivors, many must face the potentially devastating complications of the treatment. Young survivors will likely face compromised fertility that is now recognized as among the most prevalent long-term side effects of cancer therapy. The prospect of partial or total infertility can significantly add to anxiety and emotional strain during disease management, and may also compromise quality of life [2]. To offset these risks, women can be offered several options for fertility preservation, including conservative cancer management, and cryopreservation of oocyte, embryo or ovarian tissue. Embryo and oocyte cryopreservation are considered established fertility preservation techniques and have been widely applied across the world [3,4]. On the other hand, ovarian tissue cryopreservation is still considered an experimental technique, despite advances in recent years [5].Studies exploring the mechanisms behind the actions of the different chemotherapy agents are providing greater information as to the specific effects of each agent on the different cell types of the ovary. The effects of antineoplastic agents on the ovaries are clinically inferred from a variety This article will review all the mechanism and clinical impact of chemotherapy on ovarian reserve. Ovarian agingThe ovary has a finite endowment of primordial follicles that is established during the second half of intrauterine life, followed by a steady decline until menopause. Each primordial follicle consists of an immature oocyte surrounded by a single layer of granulosa cells. The primordial follicles constit...

The environmental contaminant arsenic causes cancer, developmental retardation, and other degenerative diseases and, thus, is a serious health concern worldwide. Paradoxically, arsenic also may serve as an antitumor therapy, although the mechanisms of its antineoplastic effects remain unclear. Arsenic exerts its toxicity in part by generating reactive oxygen species. We show that arsenic-induced oxidative stress promotes telomere attrition, chromosome end-to-end fusions, and apoptotic cell death. An antioxidant, N-acetylcysteine, effectively prevents arsenic-induced oxidative stress, telomere erosion, chromosome instability, and apoptosis, suggesting that increasing the intracellular antioxidant level may have preventive or therapeutic effects in arsenic-induced chromosome instability and genotoxicity. Embryos with shortened telomeres from late generation telomerase-deficient mice exhibit increased sensitivity to arsenic-induced oxidative damage, suggesting that telomere attrition mediates arsenic-induced apoptosis. Unexpectedly, arsenite did not cause chromosome endto-end fusions in telomerase RNA knockout mouse embryos despite progressively damaged telomeres and disrupting embryo viability. Together, these findings may explain why arsenic can initiate oxidative stress and telomere erosion, leading to apoptosis and anti-tumor therapy on the one hand and chromosome instability and carcinogenesis on the other.Arsenic is a significant environmental concern worldwide because millions of people are at risk of drinking water contaminated by arsenic (1, 2). Epidemiological data show that chronic exposure of humans to inorganic arsenic is associated with hepatic injury, peripheral neuropathy, and increased rates of a wide variety of cancers, particularly of the skin, lung, bladder, and liver (3-5). Arsenic also produces toxic effects on the female reproductive system, including ovarian dysfunction (6), aberrant embryo development and lethality (7,8), and postnatal growth retardation (9). Interestingly, it also has proven useful for anti-cancer therapy (10 -12), although the mechanisms underlying its paradoxical (antineoplastic) effects remain unclear.Many possible modes of arsenic action have been proposed, including chromosomal abnormalities, oxidative stress, altered DNA repair and DNA methylation patterns, altered cell proliferation, abnormal gene amplification, and inhibition of p53 and telomerase (5, 13-18). In particular, arsenic exerts its toxicity by generating reactive oxygen species (ROS) 1 (19 -22). Mitochondria, the main source of ROS production, which also play a crucial role in the control of apoptosis (23, 24), have been implicated in arsenite-induced apoptosis (21, 25). Thus, mitochondrial dysfunction may explain the cytotoxicity and degenerative effects induced by arsenic. How ROS links arsenic exposure to carcinogenesis is still not well understood.Vertebrate telomeres consist of tandem repeats of G-rich sequence that cap the ends of chromosomes, protecting them from fusion and chromosomal instability...

An equilibrium needs to be established by the cellular and acellular components of the ovarian follicle if developmental competence is to be acquired by the oocyte. Both cumulus cells (CCs) and follicular fluid (FF) are critical determinants for oocyte quality. Understanding how CCs and FF influence oocyte quality in the presence of deleterious systemic or pelvic conditions may impact clinical decisions in the course of managing infertility. Given that the functional integrities of FF and CCs are susceptible to concurrent pathological conditions, it is important to understand how pathophysiological factors influence natural fertility and the outcomes of pregnancy arising from the use of assisted reproduction technologies (ARTs). Accordingly, this review discusses the roles of CCs and FF in ensuring oocyte competence and present new insights on pathological conditions that may interfere with oocyte quality by altering the intrafollicular environment.

Polycystic ovary syndrome represents 80% of anovulatory infertility cases. Treatment initially includes preconception guidelines, such as lifestyle changes (weight loss), folic acid therapy to prevent the risk of fetal neural tube defects and halting the consumption of tobacco and alcohol. The first-line pharmacological treatment for inducing ovulation consists of a clomiphene citrate treatment for timed intercourse. The second-line pharmacological treatment includes the administration of exogenous gonadotropins or laparoscopic ovarian surgery (ovarian drilling). Ovulation induction using clomiphene citrate or gonadotropins is effective with cumulative live birth rates of approximately 70%. Ovarian drilling should be performed when laparoscopy is indicated; this procedure is typically effective in approximately 50% of cases. Finally, a high-complexity reproduction treatment (in vitro fertilization or intracytoplasmic sperm injection) is the third-line treatment and is recommended when the previous interventions fail. This option is also the first choice in cases of bilateral tubal occlusion or semen alterations that impair the occurrence of natural pregnancy. Evidence for the routine use of metformin in infertility treatment of anovulatory women with polycystic ovary syndrome is not available. Aromatase inhibitors are promising and longer term studies are necessary to prove their safety.

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This study was supported by the National Council for Scientific and Technological Development (CNPq), Brazil. The authors declare no conflicts of interest.

Objective To evaluate whether the presence or severity of endometriosis affects the outcome of assisted reproductive techniques (ART). Methods RR = 0.94 (95% CI, clinical pregnancy, RR = 0.90 (95% CI,