Desire for biological parenthood and patient counseling on the risk of infertility among adolescents and adults with hemoglobinopathies.

BACKGROUND: Both diagnosis and treatment of hemoglobinopathies have been associated with an increased risk of fertility impairment. German guidelines recommend annual monitoring of fertility parameters to enable early detection of fertility impairment and/or to offer fertility preservation (FP) when indicated. We explored the general desire for parenthood, the frequency of recalling fertility counseling and testing, and the utilization of FP in adolescents and adults with hemoglobinopathies. PROCEDURE: In a cross-sectional study, patients aged 12-50 years, treated in Germany, Austria, or Switzerland, were surveyed on fertility-related aspects. Medical data, including fertility testing results, were collected from patient records. RESULTS: Overall, 116/121 eligible patients, diagnosed with sickle cell disease (70.7%), thalassemia (27.6%), or other hemoglobinopathy (1.7%), participated in our study (57.8% female, median age 17.0 years, range 12-50 years). All participants required treatment of the underlying hemoglobinopathy: 68.1% received hydroxyurea, 25.9% required regular blood transfusions, and 6.0% underwent hematopoietic stem cell transplantation (HSCT). Most patients (82/108, 75.9%) stated a considerable to strong desire for (future) parenthood, independent of sex, education, diagnosis, or subjective health status. Fertility counseling was only recalled by 32/111 patients (28.8%) and least frequently by younger patients (12-16 years) or those treated with regular blood transfusions or hydroxyurea. While fertility testing was documented for 59.5% (69/116) in medical records, only 11.6% (13/112) recalled previous assessments. FP was only used by 5.4% (6/111) of patients. CONCLUSION: Most patients with hemoglobinopathies wish to have biological children, yet only few recalled fertility counseling and testing. Adequate patient counseling should be offered to all patients at risk for infertility.

Investigation of the Effects of Metallic Nanoparticles on Fertility Outcomes and Endocrine Modification of the Hypothalamic-Pituitary-Gonadal Axis.

Nanotechnology is a very disruptive twenty-first-century revolution that will allow social and economic welfare to increase although it also involves a significant human exposure to nanoparticles. The aim of the present study was to contribute to the elucidation on whether metallic nanoparticles have a potential to induce fertility impairments. Regulatory studies that observed official OECD guidelines 415, 416 and 422 have failed to detect any fertility alterations caused by nanoparticle exposure. However, the scientific literature provides evidence that some nanoparticles may cause gonad impairments although the actual impact on fertility remains uncertain. This aim of the present study is to revisit the previously published RNAseq studies by analyzing the effects of several nanoparticles on the transcriptome of T98G human glioblastoma cells given that glial cells are known to play a pivotal role in the regulation of gonadotropin releasing hormone neurons. We found evidence that nanoparticles impair the gonadotropin releasing hormone receptor pathway and several related biological process like, among others, the cellular response to follicular stimulating hormone, cellular response to gonadotropin stimulus, cellular response to hormone stimulus, response to steroid hormone, ovulation cycle and response to estradiol. We propose that nanoparticles interfere with the ability of glial cells to regulate gonadotropin-releasing hormone neurons and, subsequently, the hypothalamic-pituitary-gonadal axis, potentially leading to fertility impairments. To our knowledge, this is the first proposal of a mode of action based on endocrine disruption for explaining the possible effects of nanoparticles on fertility. Whether these finding can be extended to other types of nanoparticles requires further investigation.

Oxidative Stress-Induced Male Infertility: Role of Antioxidants in Cellular Defense Mechanisms.

Male infertility is linked to several environmental and mutagenic factors. Most of these factors, i.e., lifestyle, radiations, and chemical contaminations, work on the fundamental principles of physics, chemistry, and biology. Principally, it may induce oxidative stress (OS) and produce free radicals within the cells. The negative effect of OS may enhance the reactive oxygen species (ROS) levels in male reproductive organs and impair basic functions in a couple's fertility. Evidence suggests that infertile men have significantly increased ROS levels and a reduced antioxidant capacity compared with fertile men. Although, basic spermatic function and fertilizing capacity depend on a delicate balance between physiological activity of ROS and antioxidants to protect from cellular oxidative injury in sperm, that is essential to achieve pregnancy. The ideal oxidation-reduction (REDOX) equilibrium requires a maintenance of a range of ROS concentrations and modulation of antioxidants. For this reason, the chapter focuses on the effects of ROS in sperm functions and the current concepts regarding the benefits of medical management in men with diminished fertility and amelioration of the effect to improve sperm function. Also, this evidence-based study suggests an increasing rate of infertility that poses a global challenge for human health, urging the need of health care professionals to offer a correct diagnosis, comprehension of the process, and an individualized management of the patients.

Determinants of utilization of cryopreservation of germ cells in adolescent cancer patients in four European countries.

Infertility is a relevant late-effect following cancer treatment; yet, a large proportion of survivors cannot recall having been informed of this risk. In an intervention study, we examined if and how supportive patient information material on fertility/fertility-preserving measures influences utilization of cryopreservation in adolescent cancer patients. The control group, recruited 03/2014-01/2016, received the usual patient education at initial diagnosis. The intervention group, recruited 04/2016-10/2017, received patient education supported by a fertility flyer and brochure. Patients and parents were each asked questions on utilization of cryopreservation in a questionnaire 3 and 6 months after initial diagnosis. Patient core and therapy data were obtained from medical records. Overall, cryopreservation rates showed no significant difference between the control (32.7%, n = 37/113) and intervention group (36.6%, n = 37/101). In the control group, cryopreservation was associated with gender (OR 0.100, CI 0.023-0.427), age (OR 1.559, CI 1.077-2.258) and recalling information on fertility protection (OR 33.663, CI 2.100-539.574); in the intervention group, cryopreservation was related to gender (OR 0.093, CI 0.026-0.330) and the estimated infertility risk (OR 43.665, CI 2.157-883.974).Conclusion: Cryopreservation rates did not overall increase following the intervention; however, the individual risk seemed to be brought into attention more: Those at risk, including younger patients, cryopreserved at higher rates.What is Known:•Infertility is a relevant late-effect following adolescent cancer.•Guidelines recommend to offer fertility protection before cancer treatment.•A relevant proportion of adolescents with cancer are not aware of this risk.•Fertility protection seems under-used in cancer patients at risk for infertility.What is New:•Information material on fertility and protection in adolescents did not increase overall rates of cryopreservation.•Cryopreservation rates were improved according to individual risk for infertility.•Our flyers and brochures on fertility in cancer patients are available in various languages.

Fertility education for adolescent cancer patients: Gaps in current clinical practice in Europe.

OBJECTIVE: As adolescent cancer patients may suffer from infertility following treatment, fertility counselling is essential. Our aim was to explore the current situation in four European countries in terms of (I) education about the risk for infertility, (II) counselling on fertility preservation, (III) patients' knowledge on fertility, (IV) sufficiency of information and (V) uptake of cryopreservation. METHODS: In total, 113 patients (13-20 years) at 11 study centres completed a self-report questionnaire three and six months after cancer diagnosis. Multivariate logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: As many as 80.2% of participants reported having received education about the risk for infertility prior to treatment, 73.2% recalled counselling on fertility preservation. Only 52.3% stated they felt sufficiently informed to make a decision. Inability to recall counselling on fertility preservation (OR = 0.03, CI: 0.00-0.47) and female gender (OR = 0.11, CI: 0.03-0.48) was associated with lower use of cryopreservation, whereas older age was associated with higher use. CONCLUSION: Fertility counselling was available to a relatively high proportion of patients, and it did influence the utilisation of cryopreservation. However, many patients did not feel sufficiently informed. Further improvement is needed to enable adolescent cancer patients to make an informed decision on fertility preservation.

Fertility knowledge and associated empowerment following an educational intervention for adolescent cancer patients.

INTRODUCTION/OBJECTIVES: Fertility preservation is a major concern for adolescent cancer patients; yet, educational gaps remain. Our intervention study examined whether specially designed educational materials regarding fertility preservation increase knowledge and empowerment of patients and parents. METHODS: Eleven paediatric-oncological centres in four European countries agreed to enrol all eligible patients and parents in a questionnaire survey at 3 and 6 months after diagnosis. Treating physicians were surveyed on their medical consultation regarding fertility. RESULTS: Educational intervention increased knowledge in both patients (n = 113 and n = 101 in the control and intervention groups, respectively) and parents (n = 111 and n = 99 in the control and intervention groups, respectively), but the difference did not achieve statistical significance (knowledge difference patients: 5.6% (t0)/13.1% (t1); parents: 6.4% (t0)/3.8% (t1)). Parents of older patients (OR = 1.3, 95%CI = 1.1-1.7) and higher educational groups (OR = 6.2, 95%CI = 2.1-18.3) in the intervention group (OR = 1.9, 95%CI = 1.03-3.7) achieved higher knowledge levels. Empowerment was significantly improved in both patients (p = 0.046, d = 0.27) and parents (p = 0.046, d = 0.48) in the intervention group. DISCUSSION/CONCLUSIONS: In our study, the use of specifically prepared flyers and brochures successfully raised the level of fertility preservation knowledge in parents of older patients as well as parents with higher educational levels. Overall, the intervention improved patient and parent empowerment. Subsequent projects will include simpler information and digital material to particularly reach out to younger and less educated individuals.

Fertility impairment associated with uterine fibroids - a review of literature.

Uterine fibroids (also known as leiomyomas or myomas) are the most common benign tumors affecting reproductive organs in women. They are monoclonal tumors of the uterine smooth muscle, which spring from myometrium. It is estimated that they occur in 50-60% of the female population and rise to 70% by the age of 50. While mostly asymptomatic, myomas can be connected with several conditions, including abnormal bleeding with subsequent anemia, pelvic masses, pelvic pain, bulk symptoms, unfavorable impact on fertility and obstetric complications. Factors, which predispose the emergence of fibroids are: hormones, Afro-American ethnicity, age, obesity, adverse pregnancy outcome history, early menarche, genetic factors, alcohol, caffeine or eating too much red meat. On the other hand, there are factors, which can decrease this risk: pregnancy, early menopause and tobacco smoking. There are several mechanisms of fertility impairment in females with fibroids: alternations in uterus function (flawed blood supply, increased contractility), changes in the normal uterus anatomy, local hormonal changes induced by fibroids. In this review the connection between fibroids and infertility is analyzed.

"If I use family planning, I may have trouble getting pregnant next time I want to": A multicountry survey-based exploration of perceived contraceptive-induced fertility impairment and its relationship to contraceptive behaviors.

Objectives: We aim to assess women's perceptions regarding contraceptive effects on fertility across a diversity of settings in sub-Saharan Africa and how they vary by women's characteristics. We also aim to examine how such beliefs relate to women's contraceptive practices and intentions. Study design: This study uses cross-sectional survey data among women aged 15 to 49 in nine sub-Saharan African geographies from the Performance Monitoring for Action project. Our main measure of interest assessed women's perceptions of contraceptive-induced fertility impairment. We examined factors related to this belief and explored the association between perceptions of contraceptive-induced fertility impairment and use of medicalized contraception (intrauterine device, implant, injectable, pills, emergency contraception) and intention to use contraception (among nonusers). Results: Between 20% and 40% of women across study sites agreed or strongly agreed that contraception would lead to later difficulties becoming pregnant. Women at risk of an unintended pregnancy who believed contraception could cause fertility impairment had reduced odds of using medicalized contraception in five sites; aORs ranged from 0.07 to 0.62. Likewise, contraceptive nonusers who wanted a/another child and perceived contraception could cause fertility impairment were less likely to intend to use contraception in seven sites, with aORs between 0.34 and 0.66. Conclusions: Our multicountry study findings indicate women's perception of contraceptive-induced fertility impairment is common across diverse sub-Saharan African settings, likely acting as a deterrent to using medicalized contraceptive methods. Implications: Findings from this study can help improve reproductive health programs by addressing concerns about contraception to help women achieve their reproductive goals.

Self-reported fertility impairments and help-seeking strategies among young women in Malawi.

This paper analyses wave 4 the Tsogolo la Thanzi survey of n = 1349 Malawian women aged 16-26 to explore the prevalence and predictors of self-reported fertility impairments (difficulties conceiving and/or difficulties carrying a pregnancy to term) and help-seeking strategies. Using descriptive statistics, logistic regression models, and graphic displays, the correlates of self-reporting an impairment and patterns of help-seeking strategies are examined. Nearly 13% (n = 117) of those who had ever tried to conceive reported experiencing a fertility impairment. Age was positively associated with reporting an impairment, while there was a negative association with education and with parity. Of women who reported an impairment, 85.5% sought help. Visiting a hospital or clinic was the most common response, followed closely by going to a traditional healer. Around one-quarter employed multiple help-seeking strategies, highlighting the need for various help-seeking behaviours to be viewed in tandem rather than in isolation.

Fertility-Related Concerns and Uncertainties in Adolescent and Young Adult Childhood Cancer Survivors.

Purpose: This study aimed to uncover the fertility-related concerns and uncertainties in adolescent and young adult (AYA) childhood cancer survivors. Methods: In this qualitative study, participants were recruited from an oncohematology outpatient clinic at a university hospital in Brazil. Twenty-four AYA cancer survivors, aged 18- 24 years (13 men and 11 women), participated in individual semistructured interviews focusing on two parts-sociodemographic and clinical variables and guiding questions that enabled understanding of the concerns and uncertainties regarding the risks of infertility and their impact on relationships and the need for guidance. Data were analyzed using inductive thematic analysis. Results: Four themes were identified from the data-(1) knowledge about fertility, (2) emotional impact and fertility-related uncertainty, (3) sharing the possible risk of infertility with partners, and (4) need for information on possible loss of fertility. Conclusion: The meanings attributed to the loss of fertility after cancer treatment uncovered the need for health professionals to organize survivor services in line with the survivors' needs, and include reproductive concerns and uncertainties in this planning. The study results provide insights for the development of health care services that meet the real needs of this particular population that has long-term follow-up demands.

Inhibition of Fatty Acid Binding Protein 4 in Obese Male Mice Adversely Affects Reproductive Parameters.

BACKGROUND: As obesity is increasing worldwide, obese people use various methods to get rid of excess weight. BMS309403 (A drug) is a specific inhibitor of fatty acid binding protein 4. In this study, the effects of the BMS309403 on serum biochemical markers, testis tissue spermatogenesis and apoptotic markers were investigated in male mice. METHODS: Balb/c mice (total=56, each group n=14) were divided into control, obese control, obese solvent and obese drug groups. The obese control, obese solvent and obese drug groups were fed on the high sucrose diet to lead to obesity. After the development of obesity, BMS309403 was orally administered to the obese drug group for six weeks. It was performed in testicular tissues (Johnson Score and apoptosis markers) and biochemical tests (total testosterone, sex hormone binding globulin, inhibin-B tests and free androgen index) were used to evaluate reproductive parameters. The p<0.05 was considered to indicate a statistical significance. RESULTS: Serum fatty acid binding protein 4 levels were higher in obese control group and obese solvent group, compared to control (p<0.05) and obese drug groups (p<0.001). Serum total testosterone, free androgen index, inhibin-B, sex hormone binding globulin levels, testicular tissue B-cell lymphoma-2 expression level and Johnson Score parameters were lower in all obese groups compared with the control group. Inhibin-B levels and Johnson Score results were lower in obese drug group compared to other two obese groups (p<0.05). CONCLUSION: Contrary to expectations, the use of BMS309403 negatively affected male reproductive parameters. Negative changes in reproductive parameters may be a result of the increased lee index of obesity.

Fertility-Related Wishes and Concerns of Adolescent Cancer Patients and Their Parents.

Purpose: Within a multicenter European study, we explored fertility-related wishes, concerns, and decision-making of adolescent cancer patients and their parents. Patients and Methods: Patients and parents were each asked to complete a fertility-related questionnaire 3 months after initial diagnosis. In total, 113 of 142 (79.6%) eligible patients participated; 53.1% were male and the median age was 16 years (range 13-20 years). The questionnaire was completed by 111 parents. Univariate analyses were conducted using nonparametric methods with alpha = 5%. For multivariate analyses, binary logistic regression was conducted. Results: Both patients (86.1%) and parents (96.3%) indicated a strong desire for biological parenthood for themselves/their children. Female patients (odds ratio [OR] = 3.70; confidence interval [CI]: 1.43-9.50) and parents (OR = 2.70; CI: 1.21-6.00) were more likely to report a high fear of cancer recurrence. Patients who estimated their risk for fertility impairment being high were more likely to be concerned about their fertility (OR = 5.69; CI: 1.41-22.98). Parents who received fertility preservation information were more likely to recommend its use to their children (OR = 5.50; CI: 1.07-28.40), whereas parents of female patients were less likely to do so (OR = 0.13; CI: 0.03-0.61). Conclusions: The prospect of fertility following cancer treatment is important for adolescent cancer patients and their parents, yet it is associated with many concerns. Counseling regarding fertility preservation can be more effective when the individual needs of patients and their parents are taken into consideration.

Systemic profiling of ectopic fat deposits in the reproductive tract of dairy cows.

During the transition period, high-yielding dairy cows suffer from negative energy balance, intense lipomobilization and impaired lipid metabolism; this metabolic condition can lead to overburdened triglycerides accumulation in the liver, known as liver lipidosis, which has been associated to impaired fertility in dairy cows. The mechanisms of this impairment can be in principle correlated with the presence and the extent of ectopic fat depots. However, current methods for evaluating fat accumulation in liver and in the reproductive tract suffer from low resolution, sensitivity, and specificity. Confocal microscopes are equipped with Gallium arsenide phosphide detectors, thus enabling the acquisition of intense signals from tissue biopsies. This method could differentiate whether fat deposition occurred without requiring sample sectioning. Here, we examined with this technique liver, uterine and ovarian samples of heifers and regularly slaughtered repeat breeder and overconditioned dairy cows, to quantify lipid droplets and depots at a submicrometer scale with high specificity. With the aid of this technique, we found lipid depots in uterine and ovarian specimens. Moreover, we found that the size and number of depots increased with the degree of liver lipidosis. Further studies are needed to elucidate the relationship between the severity and extent of these deposits and the fertility of lactating dairy cows. Since tissues other than liver display different characteristic lipid droplet distributions, this technique can be potentially employed to shed new light on the pathogenesis of lipidosis and to assess new risk factors for infertility.