The aim of this review is to present information related to oocyte cryopreservation, and particularly oocyte vitrification, performed to preserve fertility in oncologic and social indications. The success rates of oocyte cryopreservation have increased with the widespread use of the vitrification technique and are currently similar to those of in vitro fertilization performed with fresh oocytes. Vitrification is the most successful technique for oocyte cryopreservation. The most important factors that influence the success rate are the patient's age at the time of vitrification and the number of mature oocytes frozen. Thus, live birth rates differ for each age depending on the number of oocytes thawed and the freezing method. The American Society of Reproductive Medicine and the American Society of Clinical Oncology recommend presenting the option of oocyte cryopreservation for fertility preservation in cancer patients. Besides cancer patients, use of oocyte vitrification is increasing in women who wish to postpone pregnancy age and to have reproductive freedom with the development of the cryopreservation technique and the achievement of pregnancy rates similar to the use of fresh oocytes. Patients are provided consultancy service in terms of indication, the success rates by age, and the total number of oocytes frozen. It should be emphasized that this procedure is not a type of insurance policy for fertility, especially in elective oocyte cryopreservation.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

To evaluate fertility preservation outcomes in breast cancer women with different hormonal receptor profiles before oncological treatment.

The study population included women with a diagnosis of breast cancer who underwent fertility preservation from 2009 until 2018 at a university-affiliated tertiary hospital. Stimulation parameters and fertility preservation outcomes were compared among the following receptor-specific profile groups: (1) estrogen receptor positive (ER+) versus estrogen receptor negative (ER-), (2) triple-negative breast cancer (TNBC) versus estrogen and progesterone receptor positive (ER+/PR+), and (3) TNBC versus non-TNBC. Primary outcome was the total number of mature oocytes. Secondary outcomes included the number of retrieved oocytes, the peak estradiol level, and the number of follicles > 14 mm on the final oocyte maturation trigger day.

A total of 155 cycles were included in the final analysis. These were divided into the exposure groups of ER+ (n = 97), ER- (n = 58), ER+/PR+ (n = 85), TNBC (n = 57), and non-TNBC (n = 98). Cycle outcomes revealed similar number of retrieved oocytes and follicles > 14 mm on the trigger day. Women with TNBC had significantly lower number of mature oocytes compared with those with ER + PR+ (7 (5-11) versus 9 (7-15); p = 0.02) and non-TNBC (7 (5-11) versus 9 (7-16); p = 0.01) status. Triple-negative breast cancer profile was associated with a significant reduction in the chance of developing over 10 mature oocytes (OR 0.41; 95% CI 0.19-0.92).

Among the different hormonal receptor profiles in breast cancer, the TNBC subtype has a negative effect on fertility preservation outcomes.

Many cancers presenting in children and adolescents are curable with surgery, chemotherapy, and/or radiotherapy. Potential adverse consequences of treatment include sterility, infertility, or subfertility as a result of gonad removal, damage to germ cells as a result of adjuvant therapy, or damage to the pituitary and hypothalamus or uterus as a result of irradiation. In recent years, treatment of solid tumors and hematologic malignancies has been modified in an attempt to reduce damage to the gonadal axis. Simultaneously, advances in assisted reproductive technology have led to new possibilities for the prevention and treatment of infertility. This clinical report reviews the medical aspects and ethical considerations that arise when considering fertility preservation in pediatric and adolescent patients with cancer.

Purpose: To evaluate awareness of female cancer patients about fertility impairment following cancer treatment. Patients and Methods: This cross-sectional study was conducted in Imam Hossein Hospital between March 2014 and July 2015. Women of childbearing age with cancer who were treated in an oncology clinic and referred for follow-up were asked to fill out the questionnaire designed for this purpose. The process of filling out the questionnaire was managed by a resident of clinical oncology during patient interviews. Results: Two hundred forty-seven patients with mean age of 35.5 years were included. The most common cancers were breast cancer (61.9%) and gynecologic cancer (10.9%). Among all patients, 22.7% had received information about infertility risk. The likelihood that women would have received information about fertility varied by cancer type. Among women with gynecologic cancers, only 59.3% had received information about the effects of treatment on fertility despite having cancers of the reproductive system. Moreover, 19.6% of women with breast cancer and 18.5% of those with other cancers had received fertility information (p < 0.001). Significance of Results: Knowledge and awareness of female cancer patients of childbearing age about the impact of cancer treatment on fertility and fertility preservation are limited. A structured program is required to provide complete information regarding the risk of fertility impairment following cancer treatment and increase the knowledge of these patients to enable them to make a proper decision about fertility preservation.

The angiotensin II (ANGII) receptor AT1 plays an important role in the control of hydromineral balance, mediating the dipsogenic and natriorexigenic effects and neuroendocrine responses of ANGII. While estradiol (E2) is known to modulate several actions of ANGII in the brain, the molecular and cellular mechanisms of the interaction between E2 and ANGII and its physiological role in the control of body fluids remain unclear. We investigated the influence of E2 (40 μg/kg) pretreatment and extracellular-signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) cell signaling on the dipsogenic and natriorexigenic effects, as well as the neuroendocrine responses to angiotensinergic central stimulation in ovariectomized rats (OVX). We showed that the inhibitory effect of E2 on ANGII-induced water and sodium intake requires the ERK1/2 and JNK signaling pathways. On the other hand, E2 pretreatment prevents the ANGII-induced phosphorylation of ERK and JNK in the lamina terminalis. E2 therapy decreased oxytocin (OT) and vasopressin (AVP) secretion and decreased ERK1/2 phosphorylation in the supraoptic and paraventricular nuclei (SON and PVN, respectively). We found that the AVP secretion induced by ANGII required ERK1/2 signaling, but OT secretion did not involve ERK1/2 signaling. Taken together, these results demonstrate that E2 modulates ANGII-induced water and sodium intake and AVP secretion by affecting the ERK1/2 and JNK pathways in the lamina terminalis and ERK1/2 signaling in the hypothalamic nuclei (PVN and SON) in OVX rats.

Fertility preservation strategies warrant non-invasive viability assessment of preantral follicles (PAF) such as staining with Neutral Red (NR) that is incorporated by viable follicles. To optimize the procedure, we firstly determined the lowest concentration and shortest exposure time needed for optimal viability screening of isolated bovine PAF. Secondly, we combined this protocol to a vitrification procedure to assess cryotolerance of the stained follicles.

Isolated PAF (900, divided over 6 replicates) were cultured in DMEM/Ham's F12 (Culture Medium - Cm) for 4 days (38.5 °C, 5% CO2). On D0, D2 and D4, follicles were stained, by adding NR medium (NRm = Cm with different concentrations NR) after which viability was assessed by counting stained/non-stained PAF every 30 min for a period of 2 h.

Following a binary logistic regression analysis with staining as a result (yes/no) versus log-concentration, a probability model could be fitted, indicating that the proportion of stained follicles remained stable after 30 min when 15 μg/ml NR was used, without compromising follicular health and viability. Consequently, using this protocol, no significant effect of staining prior to vitrification, was found on PAF viability immediately after warming or following 4 days of culture.

In conclusion, we propose NR staining as a non-invasive, non-detrimental viability assessment tool for PAF, when applied at 15 μg/ml for 30 min, being perfectly compatible with PAF vitrification.

In many countries of the developed world, there is an increasing trend toward delay in childbearing from 30 to 40 years of age for various reasons. This is unfortunately concordant with an increasing incidence of breast cancer in women who have not yet completed their family. The current choice for premenopausal women with breast cancer is adjuvant therapy which includes cytotoxic chemotherapy, ovarian ablation (by surgery, irradiation, or chemical ovarian suppression), anti-estrogen therapy, or any combination of these. Although the use of adjuvant therapies with cytotoxic drugs can significantly reduce mortality, it raises issues of the long-term toxicity, such as induction of an early menopause and fertility impairment. The risk of infertility is a potential hardship to be faced by the patients following treatment of breast cancer. The offspring of patients who became pregnant after completion of chemotherapy have shown no adverse effects and congenital anomalies from the treatment, but sometimes high rates of abortion (29%) and premature deliveries with low birth weight (40%) have been demonstrated. Therefore, the issue of recent cytotoxic treatment remains controversial and further research is required to define a "safety period" between cessation of treatment and pregnancy. Preservation of fertility in breast cancer survivors of reproductive age has become an important issue regarding the quality of life. Currently, there are several potential options, including all available assisted technologies, such as in vitro fertilization and embryo transfer, in vitro maturation, oocyte and embryo cryopreservation, and cryopreservation of ovarian tissue. Because increased estrogen levels are thought to be potentially risky in breast cancer patients, recently developed ovarian stimulation protocols with the aromatase inhibitor letrozole and tamoxifen appear to provide safe stimulation with endogenous estrogen. Embryo cryopreservation seems to be the most established fertility preservation strategy, providing a 25-35% chance of pregnancy. In addition, oocyte freezing can be considered as an alternative in patients who are single and in those who do not wish a sperm donor. Although ovarian tissue harvesting appears to be safe, experience regarding ovarian transplantation is still limited due to low utilization, so the true value of this procedure remains to be determined. Nevertheless, in clinical situations in which chemotherapy needs to be started in young patients facing premature ovarian failure, ovarian tissue preservation seems to be a promising option for restoring fertility, especially in conjunction with other options like immature oocyte retrieval, in vitro maturation of oocytes, oocyte vitrification, or embryo cryopreservation. It seems that in vitro maturation is a useful strategy because it improves oocyte or cryopreservation outcome in breast cancer patients undergoing ovarian stimulation for fertility preservation.

The issue of taking into consideration future fertility in young women with breast cancer and Hodgkin's lymphoma [HL] will become more and more common and represent a growing clinical challenge for gynecologists and oncologists. The present paper will review literature data on the attempts of preventing chemotherapy-induced ovarian damage in these women and on their fertility outcome. Gonadotropin-releasing hormone [Gn-RH] agonists have been widely investigated as agents able to prevent ovarian failure in animal models and in humans. The majority of the studies on women with breast cancer and HL have shown a protective effect of Gn-RH agonists. A recent meta-analysis of five randomized trials, including 528 premenopausal breast cancer patients, revealed that relative risk [RR] of developing premature ovarian failure within one year was 0.40 (95% confidence interval [CI] = 0.21-0.75) for the women who received Gn-RH agonists with chemotherapy compared to those who received chemotherapy alone. However, the concurrent administration of Gn-RH agonists during chemotherapy appeared to have no effect on spontaneous pregnancy rates. Limited information are available about pregnancies in breast cancer and HL survivors, but the current literature appears to show no apparent increase in pregnancy complications, spontaneous abortions, or congenital abnormalities compared to general obstetric population.

The objective of this study is to investigate young breast cancer patients' preferred and actual involvement in decision-making about surgery, chemotherapy, and adjuvant endocrine therapy (AET).

A total of 442 women aged 18-40 years at the time of the diagnosis participated in the region-wide ELIPPSE40 cohort study (southeastern France). Logistic regression analyses were performed on various factors possibly affecting patients' preferred and perceived involvement in the decisions about their cancer treatment.

The women's mean age was 36.8 years at enrollment. Preference for a fully passive role in decision-making was stated by 20.7% of them. It was favored by regular breast surveillance (p = 0.04) and positive experience of being informed about cancer diagnosis (p = 0.02). Patients' preferences were independently associated with their reported involvement in decision-making about surgery (p = 0.01). A fully passive role in decision-making about chemotherapy and AET was more likely to be reported by patients who perceived their involvement in decision-making about surgery as having been fully passive (adjusted odds ratio = 4.8, CI95% [2.7-8.7], and adjusted odds ratio = 9.8, CI95% [3.3-29.2], respectively). This study shows a significant relationship between the use of antidepressants and involvement in decision-making about surgery, and confirms the relationship between impaired quality of life (in the psychological domain) and a fully passive role in decisions about cancer treatment.

Patients' involvement in decision-making about chemotherapy and AET was strongly influenced by their experience of decision-making about surgery, regardless of their tumor stage and history of breast or ovarian cancer. When decisions are being made about surgery, special attention should be paid to facilitating breast cancer patients' involvement in the decision-making.

Cancer is among the leading causes of death, and malignant diseases of the female genital tract are among the most common sites. Reproductive factors that are also associated with infertility have been identified as risk factors. Hormones are thought to play a role in the induction and promotion of some type of cancers. Hormonal preparations affect the endocrine milieu and, by acting on the reproductive organs themselves, could even have a direct effect on carcinogenesis. Numerous case-control and cohort studies have tried to determine whether fertility medication use increases cancer risk. Overall, the current data is reassuring but most research groups drew conclusions based on a small number of cases and after a relatively short follow-up. Proper counseling prior to fertility medication use is important and further studies on even larger patient groups with more cancer cases are needed to support widespread use of fertility medications.

Fertility preservation (FP) is an effort to retain the fertility of cancer patients, and as an emerging discipline, it plays a central role in cancer care. Because of improvement in diagnostic and therapeutic strategies, an increasingly large number of patients are surviving with cancer. FP specialists should make an effort to spread the significance of FP among reproductive women with cancer and provide appropriate education both for associated physicians and for cancer patients who wish to preserve their fertility. Physicians who take part in the initial diagnosis and management of cancer should consider the importance of early referral of young cancer patients to FP specialists and take care of those patients by providing timely information and appropriate counseling. Individualized treatment strategies should be delivered depending on the patient's situation with appropriate team approach.

Doxorubicin (DXR) is a frontline chemotherapy agent implicated in unintended ovarian failure in female cancer survivors. The fertility preservation techniques currently available for cancer patients are often time and cost prohibitive and do not necessarily preserve endocrine function. There are no drug-based ovary protection therapies clinically available. This study provides the first investigation using dexrazoxane (Dexra) to limit DXR insult in ovarian tissue. In KK-15 granulosa cells, a 3-h DXR treatment increased double-strand (ds) DNA breaks 40%-50%, as quantified by the neutral comet assay, and dose-dependent cytotoxicity. Dexra exhibited low toxicity in KK-15 cells, inducing no DNA damage and less than 20% cell loss. Cotreating KK-15 cells with Dexra prevented acute DXR-induced dsDNA damage. Similarly, Dexra attenuated the DXR-induced 40%-65% increase in dsDNA breaks in primary murine granulosa cells and cells from in vitro cultured murine ovaries. DXR can cause DNA damage either through a topoisomerase II-mediated pathway, based on DXR intercalation into DNA, or through oxidative stress. Cotreating KK-15 cells with 2 μM Dexra was sufficient to prevent DXR-induced, but not H(2)O(2)-induced, DNA damage. These data indicated the protective effects are likely due to Dexra's inhibition of topoisomerase II catalytic activity. This putative protective agent attenuated downstream cellular responses to DXR, preventing H2AFX activation in KK-15 cells and increasing viability as demonstrated by increasing the DXR lethal dose in KK-15 cells 5- to 8-fold (LD(20)) and primary murine granulosa cells 1.5- to 2-fold (LD(50)). These data demonstrate Dexra protects ovarian cells from DXR insult and suggest that it is a promising tool to limit DXR ovarian toxicity in vivo.

In the last decade, fertility preservation has risen as a major field of interest, creating new interactions between oncologists and gynecologists. Various options, such as cryopreservation of ovarian tissue, have been developed and are currently routinely proposed in many centers. However, many of the options remain experimental and should be offered to patients only after adequate counseling. This paper addresses the efficiency and the potential of the different fertility preservation approaches.

Soy-derived isoflavones potentially protect against obesity and depression. In five different studies we examined the influence of soy-containing diets or equol injections on depression, serotonin levels, body weight gain (BW) and white adipose tissue (WAT) deposition in female Long-Evans rats at various stages of life [rats were intact, ovariectomized or experienced natural ovarian failure (NOF)].

In general, animals fed a soy-rich diet (Phyto-600) and/or administered equol (@ 5 mg/kg/day) displayed significant decreases in BW and WAT compared to a low-soy diet. When equol was injected alone (5 mg/kg/day), experiments 1, 4, and 5 demonstrated that body weight was significantly decreased. Equol has body weight control effects in females that are dependent on ovarian status and/or age of diet initiation. Experiments 1-4 all displayed no significant differences in depressive-related behavior as measured by the Prosolt forced swim test (PFST) when soy-rich (Phyto-600) or low-soy diets (Phyto-low) or equol treatments (5 mg/kg/day) were tested in female rats at various ages or hormonal status. Results of all the experiments are not presented here due to space limitations, but data from experiment 5 are presented. From conception female rats were exposed to either: a) a soy-rich (Phyto-600) or b) low-soy diet (Phyto-low). After 290 days all rats experienced NOF. At 330 days-old the animals were examined in the Porsolt forced swim test (PFST). One month later a second PFST was performed [after Phyto-low fed animals were injected with equol (5 mg/kg/day) for one week prior to the second PFST]. At the first PFST, serotonin and mobility levels were significantly decreased in the Phyto-low fed animals compared to animals that consumed the Phyto-600 diet. After equol injections at the second PFST, mobility and serotonin levels significantly increased in aged NOF rats fed the Phyto-low diet (to levels comparable to Phyto-600 fed animals).

Consumption of dietary isoflavones or equol exposure in rats has body weight controlling effects and equol specifically may have antidepressant potential dependent upon diet initiation and/or dosage of treatments. The current study demonstrates that equol is able to decrease body weight, abdominal WAT, and depressive-related behavior. While other factors and mechanisms may play a role, in part, the present results provide a greater understanding of how isoflavonoid molecules modulate the brain's influence on behavior.

To evaluate socioeconomic, demographic, and medical factors that influence the referral pattern-either before cancer treatment for fertility preservation (FP, early referral) or post-chemotherapy for assisted reproductive technology (PCART, delayed referral)-in women with breast cancer.

Secondary analysis.

Academic medical centers.

Three hundred fourteen patients with breast cancer who were counseled for FP (n=218) or PCART (n=96) from June 1999 to July 2009.

None.

Factors favoring early referrals.

Mean age at diagnosis was higher in FP vs. PCART (35.3±4.5 years vs. 33.9±4.7 years). Ninety percent presented with cancer stage 1 or 2. From 2000 to 2009 the proportion of referrals for FP increased continually. In 2009, nearly all (95.5%) were for FP. The majority (63.8%) was referred from an academic center. Patients with a family history of breast cancer were more likely to consult for FP (75.2% vs. 64.3% without). There was no association with occupation, income, race, ethnicity, obstetric history, and prior infertility treatment. Only 22.9% of those counseled in PCART, compared with 45.0% in the FP group, proceeded with a procedure.

There has been an increasing trend within the last 10 years for early referral of breast cancer patients to FP. Factors favoring early referrals are older age, early-stage cancer, family history of breast cancer, and academic center involvement. Those seen before cancer treatment are more likely to receive an intervention.

Breast cancer is the most frequent malignant disease among women world wide. Survival has been improving leading to an increasing number of breast cancer survivors, in the US estimated to about 2.6 million.

The literature was reviewed with focus on data from the Nordic countries.

Local therapies such as breast cancer surgery and radiotherapy may cause persistent pain in the breast area, arm, and shoulder reported by 30-50% of patients after three to five years, lymphedema in 15-25% of patients, and restrictions of arm and shoulder movement in 35%. Physiotherapy is the standard treatment for the latter while no pain intervention trials have been published. Chemotherapy may cause infertility and premature menopause, resulting in vasomotor symptoms, sexual dysfunction, and osteoporosis, which are similar to the side effects of endocrine treatment in postmenopausal women. Awareness of cardiotoxicity is needed since anthracyclines, trastuzumab, and radiotherapy can damage the heart. Breast cancer survivors have an increased risk of a major depression and far from all receive adequate anti-depressive treatment. Other psychological symptoms include fear of recurrence, sleep disturbances, cognitive problems, fatigue, and sexual problems.

To improve rehabilitation, specific goals have to be formulated into national guidelines and high priority directed towards research into developing and testing new interventions for alleviating symptoms and side effects experienced by breast cancer survivors.