A Warning Call for Fertility Preservation Methods for Women Undergoing Gonadotoxic Cancer Treatment

Malignant hematological conditions have recognized an increased incidence and require aggressive treatments. Targeted chemotherapy, accompanied or not by radiotherapy, raises the chance of defeating the disease, yet cancer protocols often associate long-term gonadal consequences, for instance, diminished or damaged ovarian reserve. The negative effect is directly proportional to the types, doses, time of administration of chemotherapy, and irradiation. Additionally, follicle damage depends on characteristics of the disease and patient, such as age, concomitant diseases, previous gynecological conditions, and ovarian reserve. Patients should be adequately informed when proceeding to gonadotoxic therapies; hence, fertility preservation should be eventually regarded as a first-intention procedure. This procedure is most beneficial when performed before the onset of cancer treatment, with the recommendation for embryos or oocytes’ cryopreservation. If not feasible or acceptable, several options can be available during or after the cancer treatment. Although not approved by medical practice, promising results after in vitro studies increase the chances of future patients to protect their fertility. This review aims to emphasize the mechanism of action and impact of chemotherapy, especially the one proven to be gonadotoxic, upon ovarian reserve and future fertility. Reduced fertility or infertility, as long-term consequences of chemotherapy and, particularly, following bone marrow transplantation, is often associated with a negative impact of recovery, social and personal life, as well as highly decreased quality of life.

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Cyber Physical direction of irrigated agriculture development

10.5194/egusphere-egu21-7265 ◽

2021 ◽

Author(s):

Anatoly Zeyliger ◽

Olga Ermolaeva

Keyword(s):

Natural Resources ◽

Agricultural Production ◽

Negative Impact ◽

External Environment ◽

Irrigated Agriculture ◽

Agricultural Crops ◽

The One ◽

The Impact

<p>Until recently, new technologies introduced into irrigated agriculture were mainly aimed at developing one or several related control actions. However, the needs of society to increase the volume and improve the quality of agricultural products have led to significant qualitative changes in irrigated agriculture. The various robotic systems used for this have proven their effectiveness in the mechanization and automation of the irrigation process, as well as in the application of chemical fertilizers and chemical protection of agricultural crops from diseases and pests. This resulted in higher yields while lowering production costs.Nowadays, biotechnologies currently being developed and being introduced into irrigated agriculture, as well as systems for controlling and monitoring environmental impacts, are aimed at solving problems related to further increasing the efficiency of the use of natural resources, while minimizing the risks of negative impact on components and services of the environment.This is largely due to the impact of the rapid development of IC and sensor technologies aimed at creating production management systems based on the cyber-physical systems (CPS) paradigm. For this, there are using a holistic vision of the structure and cybernetic methods of management, artificial intelligence technologies, as well as digital platforms for integrating information flows between sub-subsystems of management, control, monitoring and decision support.In this context, the main difference between developed agricultural CPSs from the existing industrial agricultural systems focused on current economic efficiency lies in the plane of making agricultural production sustainable in the long term based on a balance between economic efficiency and the quality of natural resources used and services of the environment. From this point of view, irrigated agriculture focuses on the efficient use of natural resources, which are water, soil and air, as well as renewable and non-renewable (fossil) energy. At the same time, weather are considered as the impact of the external environment providing an irreplaceable source of water, heat and energy resources but with stochastic characteristics that are difficult to formalize. In connection with this diversity, a CPSs are built taking into account a complex compromise that takes into account many aspects of the negative impact of intensive agricultural production technologies on the qualitative and quantitative characteristics of these resources, not only in the place of their use, but also on the external environment beyond these limits. In this regard, water resources are one of the most important factors necessary, on the one hand, to impart long-term sustainability to irrigated agriculture, and on the one hand, as a factor that can lead in the near future to a significant decrease in fertility, as well as to a negative impact on the environmental services of the surrounding area. This contribution discusses some points of the development of an agricultural irrigation CPS&#8217; subsystem aimed to monitor the soil moisture content at the root zone of the soil cover at the scale of irrigated agricultural crops and their relationship with industrial sprinkling technologies.Acknowledgments: The reported study was funded by RFBR, project number 19-29-05261 mk</p>

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Onkofertilitás és kezelési lehetőségei. Irodalmi áttekintés

Orvosi Hetilap ◽

10.1556/650.2017.30730 ◽

2017 ◽

Vol 158 (18) ◽

pp. 683-691

Author(s):

Tamás Sápy ◽

Róbert Póka

Keyword(s):

Fertility Preservation ◽

Biological Therapy ◽

Young Patients ◽

The United States ◽

Reproductive Organs ◽

Interdisciplinary Field ◽

Future Fertility ◽

Harmful Effects

Abstract: Surgical and radiological treatment as well as chemotherapy and biological therapy may have harmful effects on young patients’ future fertility. Increasingly greater emphasis has been put on ensuring these patients’ long-term quality of life, therefore, in addition to survival, preserving their prospective fertility is also among our aims. The term ’oncofertility’ has been compounded from two expressions, ’oncology’ and attempts to ’fertility preservation’. In gynecology, fertility preservation involves not only special surgical procedures but also interventions intended to preserve gametes, reproductive organs and embryos. Although the term ‘oncofertility’ was created in the United States of America, it has become an interdisciplinary field of science worldwide. By gaining grounds steadily, it has attracted special attention among experts. In addition to the subdivisions of classical oncology and gynecology, knowledge of oncofertility is broadening so rapidly that one cannot expect experts to be 100% up-to-date in one or another modality. It is special guidance by consultants in oncofertility that can make occasional co-operation among oncologists, radiotherapists, surgeons and infertility specialists really effective. Orv Hetil. 2017; 158(18): 683–691.

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Fertility Preservation and Long-Term Monitoring of Gonadotoxicity in Girls, Adolescents and Young Adults Undergoing Cancer Treatment

Cancers ◽

10.3390/cancers13020202 ◽

2021 ◽

Vol 13 (2) ◽

pp. 202

Author(s):

Kaja Michalczyk ◽

Aneta Cymbaluk-Płoska

Keyword(s):

Quality Of Life ◽

Young Adults ◽

Reproductive Health ◽

Cancer Treatment ◽

Fertility Preservation ◽

Adolescents And Young Adults ◽

Young Females ◽

Adolescent Cancer

Chemo- and radio-therapy can often affect reproductive organs impairing hormonal regulation, fertility, and sexual function. As cancer treatments become more effective and many patients have long term survival, concerns related to patient’s quality of life and reproductive health become relevant. It is especially important for girls and young females facing cancer therapy who have not yet started family planning. Chemotherapy protocols using alkylating agents and abdominal radiotherapy, which are frequently used in the treatment of childhood and adolescent cancer, can cause gonadal injury. The most common clinical manifests are ovarian hormone insufficiency, premature ovarian insufficiency, early menopause and infertility. In this review we assess current literature and summarize current recommendations on the reproductive function of girls and young females undergoing cancer treatment and their follow-up. Fertility preservation methods are discussed, including psychological and ethical considerations and barriers. Improvement of reproductive health and quality of life of adolescents and young adults (AYA) undergoing cancer treatment is an important issue. Further research should be continued to develop efficient and accessible methods for fertility preservation in young patients. An expert panel including oncologists, radiation oncologists, endocrinologists and gynecologists should always consider fertility preservation in pediatric, adolescent and AYA cancer patients, minding patients’ medical condition, cancer staging and potential risk of treatment-related gonadotoxicity.

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The depressing (negative) effect of oestradiol benzoate on the in vitro secretion of LH and FSH by the pituitary gland of the LRH-pretreated long-term ovariectomized rat changes into the augmentative (positive) effect after discontinuation of the LRH-pretreatment

Acta Endocrinologica ◽

10.1530/acta.0.1100329 ◽

1985 ◽

Vol 110 (3) ◽

pp. 329-337 ◽

Cited By ~ 2

Author(s):

G. A. Schuiling ◽

H. Moes ◽

T. R. Koiter

Keyword(s):

Depressing Effect ◽

Ovx Rats ◽

Gonadotrophin Secretion ◽

Oestradiol Benzoate ◽

Negative Effect ◽

Positive Effect ◽

Perifusion System

Abstract. The effect of pretreatment in vivo with oestradiol benzoate on in vitro secretion of LH and FSH was studied in long-term ovariectomized (OVX) rats both at the end of a 5-day continuous in vivo pretreatment with LRH and 4-days after cessation of such LRH pretreatment. Rats were on day 0 sc implanted with osmotic minipumps which released LRH at the rate of 250 ng/h. Control rats were implanted with a piece of silicone elastomer with the dimensions of a minipump. On days 2 and 4 the rats were injected with either 3 μg EB or with oil. On day 5 part of the rats were decapitated and the in vitro autonomous (i.e. non-LRH-stimulated) and 'supra-maximally' LRHstimulated release of LH and FSH was studied using a perifusion system. From other rats the minipumps were removed on day 5 and perifusion was performed on day 9. On the 5th day of the in vivo LRH pretreatment the pituitary LH/FSH stores were partially depleted; the pituitaries of the EB-treated rats more so than those of the oil-injected rats. EB alone had no significant effect on the content of the pituitary LH- and FSH stores. On day 9, i.e. 4 days after removal of the minipumps, the pituitary LH and FSH contents had increased in both the oil- and the EB injected rats, but had not yet recovered to control values. In rats not subjected to the 5-days pretreatment with LRH EB had a positive effect on the supra-maximally LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. EB had no effect on the non-stimulated secretion of FSH. After 5 days of in vivo pretreatment with LRH only, the in vitro non-stimulated and supra-maximally LRH-stimulated secretion of both LH and FSH were strongly impaired, the effect correlating well with the LRH-induced depletion of the pituitary LH/FSH stores. In such LRH-pretreated rats EB had on day 5 a negative effect on the (already depressed) LRH-stimulated secretion of LH (not on that of FSH). EB had no effect on the non-stimulated LH/FSH secretion. It could be demonstrated that the negative effect of the combined LRH/EB pretreatment was mainly due to the depressing effect of this treatment on the pituitary LH and FSH stores: the effect of oestradiol on the pituitary LRH-responsiveness (release as related to pituitary gonadotrophin content) remained positive. In LRH-pretreated rats, however, this positive effect of EB was smaller than in rats not pretreated with LRH. Four days after removal of the minipumps there was again a positive effect of EB on the LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. The positive effect of EB on the pituitary LRH-responsiveness was as strong as in rats which had not been exposed to exogenous LRH. The non-stimulated secretion of FSH was again not affected by EB. The results demonstrate that the effect of EB on the oestrogen-sensitive components of gonadotrophin secretion consists of two components: an effect on the pituitary LRH-responsiveness proper, and an effect on the pituitary LH/FSH stores. The magnitude of the effect of EB on the LRH-responsiveness is LRH dependent: it is very weak (almost zero) in LRH-pretreated rats, but strong in rats not exposed to LRH as well as in rats of which the LRH-pretreatment was stopped 4 days previously. Similarly, the effect of EB on the pituitary LH and FSH stores is LRH-dependent: in the absence of LRH, EB has no influence on the contents of these stores, but EB can potentiate the depleting effect of LRH on the LH/FSH-stores. Also this effect disappear after cessation of the LRH-pretreatment.

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Long-term effects of childhood cancer treatment on hormonal and ultrasound markers of ovarian reserve

Yearbook of Paediatric Endocrinology ◽

10.1530/ey.16.9.8 ◽

2019 ◽

Author(s):

van den Berg MH ◽

Overbeek A ◽

Lambalk CB ◽

Kaspers GJL ◽

Bresters D ◽

...

Keyword(s):

Cancer Treatment ◽

Childhood Cancer ◽

Ovarian Reserve ◽

Long Term Effects

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The impact of lymphedema on health-related quality of life up to 10 years after breast cancer treatment

npj Breast Cancer ◽

10.1038/s41523-021-00276-y ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Mads G. Jørgensen ◽

Navid M. Toyserkani ◽

Frederik G. Hansen ◽

Anette Bygum ◽

Jens A. Sørensen

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Cancer Treatment ◽

Breast Cancer Treatment ◽

Health Related Quality ◽

Related Quality ◽

Health Related ◽

The Impact

AbstractThe impact of breast cancer-related lymphedema (BCRL) on long-term quality of life is unknown. The aim of this study was to investigate the impact of BCRL on health-related quality of life (HRQoL) up to 10 years after breast cancer treatment. This regional population-based study enrolled patients treated for breast cancer with axillary lymph node dissection between January 1st 2007 and December 31th 2017. Follow up and assessments of the included patients were conducted between January 2019 and May 2020. The study outcome was HRQoL, evaluated with the Lymphedema Functioning, Disability and Health Questionnaire, the Disabilities of the Arm, Shoulder and Hand Questionnaire and the Short Form (36) Health Survey Questionnaire. Multivariate linear logistic regression models adjusted for confounders provided mean score differences (MDs) with 95% confidence intervals in each HRQoL scale and item. This study enrolled 244 patients with BCRL and 823 patients without BCRL. Patients with BCRL had significantly poorer HRQoL than patients without BCRL in 16 out of 18 HRQoL subscales, for example, in physical function (MDs 27, 95%CI: 24; 30), mental health (MDs 24, 95%CI: 21; 27) and social role functioning (MDs 20, 95%CI: 17; 23). Age, BMI, BCRL severity, hand and dominant arm affection had only minor impact on HRQoL (MDs < 5), suggesting a high degree of inter-individual variation in coping with lymphedema. This study showed that BCRL is associated with long-term impairments in HRQoL, especially affecting the physical and psychosocial domains. Surprisingly, BCRL diagnosis rather than clinical severity drove the largest impairments in HRQoL.

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Long-Term Cryopreservation Does Not Affect Quality of Peripheral Blood Stem Cell Grafts: A Comparative Study of Native, Short-Term and Long-Term Cryopreserved Haematopoietic Stem Cells

Cell Transplantation ◽

10.1177/09636897211036004 ◽

2021 ◽

Vol 30 ◽

pp. 096368972110360

Author(s):

Daniel Lysak ◽

Michaela Brychtová ◽

Martin Leba ◽

Miroslava Čedíková ◽

Daniel Georgiev ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Statistical Significance ◽

Extended Period ◽

High Dose ◽

Atp Production ◽

Cd34 Cells ◽

Negative Effect

Cryopreserved haematopoietic progenitor cells are used to restore autologous haematopoiesis after high dose chemotherapy. Although the cells are routinely stored for a long period, concerns remain about the maximum storage time and the possible negative effect of storage on their potency. We evaluated the effect of cryopreservation on the quality of peripheral stem cell grafts stored for a short (3 months) and a long (10 years) period and we compared it to native products.The viability of CD34+ cells remained unaffected during storage, the apoptotic cells were represented up to 10% and did not differ between groups. The clonogenic activity measured by ATP production has decreased with the length of storage (ATP/cell 1.28 nM in native vs. 0.63 in long term stored products, P < 0.05). Only borderline changes without statistical significance were detected when examining mitochondrial and aldehyde dehydrogenase metabolic activity and intracellular pH, showing their good preservation during cell storage. Our experience demonstrates that cryostorage has no major negative effect on stem cell quality and potency, and therefore autologous stem cells can be stored safely for an extended period of at least 10 years. On the other hand, long term storage for 10 years and longer may lead to mild reduction of clonogenic capacity. When a sufficient dose of stem cells is infused, these changes will not have a clinical impact. However, in products stored beyond 10 years, especially when a low number of CD34+ cells is available, the quality of stem cell graft should be verified before infusion using the appropriate potency assays.

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Efficient Cryopreservation of Populus tremula by In Vitro-Grown Axillary Buds and Genetic Stability of Recovered Plants

Plants ◽

10.3390/plants10010077 ◽

2021 ◽

Vol 10 (1) ◽

pp. 77

Author(s):

Elena O. Vidyagina ◽

Nikolay N. Kharchenko ◽

Konstantin A. Shestibratov

Keyword(s):

Survival Rate ◽

Axillary Buds ◽

Long Term Storage ◽

Average Survival ◽

Transgenic Lines ◽

Ssr Loci ◽

One Step ◽

The One

Axillary buds of in vitro microshoots were successfully frozen at –196 °C by the one-step freezing method using the protective vitrification solution 2 (PVS2). Microshoots were taken from 11 transgenic lines and three wild type lines. Influence of different explant pretreatments were analyzed from the point of their influence towards recovery after cryopreservation. It was found out that the use of axillary buds as explants after removal of the apical one increases recovery on average by 8%. The cultivation on growth medium of higher density insignificantly raises the regenerants survival rate. Pretreatment of the osmotic fluid (OF) shows the greatest influence on the survival rate. It leads to the increase in survival rate by 20%. The cryopreservation technology providing regenerants average survival rate of 83% was developed. It was based on the experimental results obtained with explant pretreatment. Incubation time in liquid nitrogen did not affect the explants survival rate after thawing. After six months cryostorage of samples their genetic variability was analyzed. Six variable simple sequence repeat (SSR) loci were used to analyze genotype variability after the freezing-thawing procedure. The microsatellite analysis showed the genetic status identity of plants after cryopreservation and of the original genotypes. The presence of the recombinant gene in the transgenic lines after cryostorage were confirmed so as the interclonal variation in the growth rate under greenhouse conditions. The developed technique is recommended for long-term storage of various breeding and genetically modified lines of aspen plants, as it provides a high percentage of explants survival with no changes in genotype.

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Novel REST Truncation Mutations Causing Hereditary Gingival Fibromatosis

Journal of Dental Research ◽

10.1177/0022034521996620 ◽

2021 ◽

pp. 002203452199662

Author(s):

J.T. Chen ◽

C.H. Lin ◽

H.W. Huang ◽

Y.P. Wang ◽

P.C. Kao ◽

...

Keyword(s):

Nuclear Localization ◽

Genetic Disorder ◽

Dominant Negative ◽

Dominant Negative Effect ◽

Wild Type ◽

Negative Effect ◽

Localization Signal ◽

Gingival Fibromatosis

Hereditary gingival fibromatosis (HGF) is a rare genetic disorder featured by nonsyndromic pathological overgrowth of gingiva. The excessive gingival tissues can cause dental, masticatory, and phonetic problems, which impose severe functional and esthetic burdens on affected individuals. Due to its high recurrent rate, patients with HGF have to undergo repeated surgical procedures of gingival resection, from childhood to adulthood, which significantly compromises their quality of life. Unraveling the genetic etiology and molecular pathogenesis of HGF not only gains insight into gingival physiology and homeostasis but also opens avenues for developing potential therapeutic strategies for this disorder. Recently, mutations in REST (OMIM *600571), encoding a transcription repressor, were reported to cause HGF (GINGF5; OMIM #617626) in 3 Turkish families. However, the functions of REST in gingival homeostasis and pathogenesis of REST-associated HGF remain largely unknown. In this study, we characterized 2 HGF families and identified 2 novel REST mutations, c.2449C>T (p.Arg817*) and c.2771_2793dup (p.Glu932Lysfs*3). All 5 mutations reported to date are nonsenses or frameshifts in the last exon of REST and would presumably truncate the protein. In vitro reporter gene assays demonstrated a partial or complete loss of repressor activity for these truncated RESTs. When coexpressed with the full-length protein, the truncated RESTs impaired the repressive ability of wild-type REST, suggesting a dominant negative effect. Immunofluorescent studies showed nuclear localization of overexpressed wild-type and truncated RESTs in vitro, indicating preservation of the nuclear localization signal in shortened proteins. Immunohistochemistry demonstrated a comparable pattern of ubiquitous REST expression in both epithelium and lamina propria of normal and HGF gingival tissues despite a reduced reactivity in HGF gingiva. Results of this study confirm the pathogenicity of REST truncation mutations occurring in the last exon causing HGF and suggest the pathosis is caused by an antimorphic (dominant negative) disease mechanism.

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P–749 Knowledge of women undergoing surgery for endometrioma regarding the impact of the disease and its treatment on ovarian reserve and fertility

Human Reproduction ◽

10.1093/humrep/deab130.748 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

M Horan ◽

L Glover ◽

P Downey ◽

M Wingfield

Keyword(s):

Ovarian Reserve ◽

Negative Impact ◽

Histological Diagnosis ◽

Ovarian Cysts ◽

Medical Setting ◽

Future Fertility ◽

Group 2 ◽

Ovarian Endometriomas ◽

The Impact ◽

Group 1

Abstract Study question Do women undergoing surgery for endometrioma due to pain, a cyst and/or subfertility understand the impact of the disease and its treatment on ovarian reserve and fertility. Summary answer The majority of women treated in a fertility setting are well informed compared to those in a general medical setting. What is known already: Infertility affects 30% to 50% of women with endometriosis. Ovarian endometriomas are reported in 17–44% of infertile women with endometriosis and are typically associated with more severe disease. Endometriomas are associated with diminished ovarian reserve, due to the endometrioma per se or due to surgical interventions required to treat and excise the disease. ESHRE guidelines recommend that women should be informed pre-operatively of the potential reduction in ovarian reserve associated with surgery and that ovarian reserve tests should be performed when future fertility is a concern. Study design, size, duration In conjunction with our histopathology colleagues we identified a cohort of women with a histological diagnosis of one or more ovarian endometriomas who underwent surgery in our unit between 2010 and 2019. We developed a scoping questionnaire, targeted at women currently over the age of 40, who had previously undergone surgery for endometrioma under the age of 35. Patients were contacted by telephone and consent obtained to send an email with a survey link. Participants/materials, setting, methods We identified 47 women who had a histological diagnosis of endometrioma. Of these, 30 were contactable by telephone, of whom 29 consented to being sent information regarding the study and a link to the questionnaire. 21 women completed the survey. Respondents were divided into 2 groups for analysis. Group 1 cited ‘fertility’ or ‘both pain and fertility’ as an indication for their surgery while group 2 had ‘pain’ or ‘ovarian cysts’ but no fertility concerns. Main results and the role of chance: The majority (62%) of patients were diagnosed with endometriosis while aged 25–34. The indication for surgery was evenly divided between pain (32%), fertility (37%) and ovarian cysts (37%). 60% of women reported having endometriomas diagnosed preoperatively. Striking differences were noted between groups 1 and 2. Of the women who cited ‘fertility’ or ‘both pain and fertility’ (n = 9) as an indication for their surgery, 78% (n = 7) reported being aware of any possible negative impact of endometriosis on their fertility, with 78% also being aware of the possible negative impact of surgery for endometriosis on their fertility. This compared to only 36% (n = 4) and 27% (n = 3) respectively in Group 2. In group 1, 56% (n = 5) remembered having an AMH level checked pre operatively while 78% (n = 7) also had an ultrasound pre-operatively. In contrast, only 33% (n = 3) of Group 2 remember having an AMH level checked pre operatively though 64% (n = 7) had an ultrasound pre-operatively. Of those whose surgery was performed by a fertility specialist, 75% (n = 6) reported being aware of the impact of endometriosis and also the impact of surgery on ovarian reserve, compared to 44% (n = 4) of those who surgery was performed by a non-fertility specialist. Limitations, reasons for caution This is a retrospective study and the numbers are small. We were only able to identify women with an endometrioma via pathology records, so those with no excision of disease (eg those who had ablation of an endometrioma) were excluded from this analysis. Wider implications of the findings: This suggests the majority of patients treated in a fertility setting are counselled regarding the benefit of surgery but also the risk to ovarian reserve. This is not the case in other settings. It is time to disseminate guidelines such as those produced by ESHRE to our general gynaecology colleagues. Trial registration number Not applicable

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