- Calorie restriction does not influence oocyte quality in oocytes from POLG mitochondrial mutator mice. [Journal Article]
- PlosPLoS One 2018; 13(9):e0204373
- It has recently been demonstrated that moderate adult onset caloric restriction (e.g. calorie restriction; CR) has a positive impact on female fertility in aged mice, due in large to preventing the a...
It has recently been demonstrated that moderate adult onset caloric restriction (e.g. calorie restriction; CR) has a positive impact on female fertility in aged mice, due in large to preventing the age-associated decline in the quality of oocytes available for fertilization. The impact of CR on oocyte quality has been attributed, at least in part, to mitochondrial functions. In mitochondrial DNA (mtDNA) mutator mice (PolgD257A/D257A), which harbor a mutation in the proofreading mtDNA polymerase-gamma (POLG), mitochondrial mutations rapidly accumulate, resulting in a premature aging phenotype and female infertility. As CR has been shown to extend both lifespan and 'healthspan' as well as improve oocyte quality in aged mice, we investigated whether adult onset CR could improve oocyte quality in the POLG mouse. Female PolgD257A/D257A mice exhibited infertility based on an inability to produce litters through natural mating. Analysis of oocytes from 8-9-month-old PolgD257A/D257A mice on CR following hormone stimulation revealed no improvement in the number of oocytes ovulated. Furthermore, CR did not result in a greater percentage of metaphase II oocytes, with the majority of the oocytes prematurely arrested at the germinal vesicle stage. Finally, CR did not improve the abnormal mitochondrial distribution or pronounced defects in meiotic spindle assembly and chromosomal distribution observed in the ad libitum fed PolgD257A/D257A. Taken together, these data suggest that although CR benefits oocyte quality and fertility outcomes in naturally aged female mice, it does not sufficiently improve oocyte quality in PolgD257A/D257A.
- Patient and physician preferences for first-line treatment of classical Hodgkin lymphoma in Germany, France and the United Kingdom. [Journal Article]
- BJBr J Haematol 2018 Sep 21
- First-line treatments for classical Hodgkin lymphoma (HL) include ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and BEACOPPescalated (escalated dose bleomycin, etoposide, adriamycin, cycloph...
First-line treatments for classical Hodgkin lymphoma (HL) include ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and BEACOPPescalated (escalated dose bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone). To further improve overall outcomes, positron emission tomography-driven strategies and ABVD or BEACOPP variants incorporating the antibody-drug conjugate brentuximab vedotin (BV) or anti-PD1 antibodies are under investigation in advanced-stage patients. The present study aimed to elicit preferences for attributes associated with ABVD, BEACOPPescalated and BV-AVD (BV, adriamycin, vinblastine and dacarbazine) among patients and physicians. Cross-sectional online discrete choice experiments were administered to HL patients (n = 381) and haematologists/oncologists (n = 357) in France, Germany and the United Kingdom. Included attributes were progression-free survival (PFS), overall survival (OS), and the risk of neuropathy, lung damage, infertility and hospitalisation due to adverse events. Whereas 5-year PFS and OS were the most important treatment attributes to patients, the relative importance of each attribute and preference weights for each level varied among physicians according to the description of the hypothetical patient for whom treatment was recommended. PFS and OS most strongly influenced physicians' recommendations when considering young female patients who did not want children or young male patients. Infertility was more important to physicians' treatment decision than PFS when considering young women with unknown fertility preferences, whereas hospitalisations due to adverse events played the largest role in treatment decisions for older patients.
- "Creating a family after battling cancer is exhausting and maddening": Exploring real-world experiences of young adult cancer survivors seeking financial assistance for family-building after treatment. [Journal Article]
- PPsychooncology 2018 Sep 20
- CONCLUSIONS: After cancer, YAs face numerous psychosocial and financial difficulties in their pursuits of family-building when ART/adoption is needed to achieve parenthood. Survivors interested in future children may benefit from follow-up fertility counseling post-treatment including discussion of ART options, surrogacy, and adoption, as appropriate, and potential barriers. Planning for the financial cost and burden in particular may help to avoid or mitigate financial stress later on.
- C-Abl is not actıvated in DNA damage-induced and Tap63-mediated oocyte apoptosıs in human ovary. [Journal Article]
- CDCell Death Dis 2018 Sep 20; 9(10):943
- There is a controversy in literature as to whether c-Abl is crucial for the induction of TAp63-mediated apoptosis and whether that inhibition of c-Abl with imatinib, which was designed to inhibit the...
There is a controversy in literature as to whether c-Abl is crucial for the induction of TAp63-mediated apoptosis and whether that inhibition of c-Abl with imatinib, which was designed to inhibit the oncogenic kinase BCR-ABL and c-kit, protects oocytes from chemotherapy-induced apoptosis in mice. No human data are available on this issue. We therefore aimed to explore whether genomic damage induced by chemotherapy drug cisplatin activates c-Abl along with TAp63 and the inhibition of c-Abl with imatinib prevents cisplatin-induced oocyte death and follicle loss in human ovary. Exposure to cisplatin induced DNA damage, activated TAp63 and SAPK/JNK pathway, and triggered apoptosis in the oocytes and granulosa cells. However, TAp63 activation after cisplatin was not associated with any increase in the expression of c-Abl. Imatinib did not prevent cisplatin-induced apoptosis of the granulosa cells or oocytes. Moreover, treatment with this drug resulted in the formation of bizarre shaped follicles lacking oocytes and increased follicular atresia by inducing apoptosis of granulosa cells and oocytes. Similar toxic effects were observed when ovarian tissue samples were incubated with a c-kit antagonist drug anti-CD117, but not with another c-Abl tyrosine kinase inhibitor GNF-2, which lacks an inhibitory action on c-kit. Intraperitoneal administration of imatinib to the xenografted animals produced similar histomorphological abnormalities in the follicles in human ovarian grafts and did not prevent cisplatin-induced follicle loss when co-administered with cisplatin. Our findings provide, for the first time, a molecular evidence for ovarian toxicity of this drug in human. Furthermore, this study together with two previous case reports of a severely compromised ovarian response to gonadotropin stimulation and premature ovarian failure in patients, while receiving imatinib, further heighten the concerns about its potential gonadotoxicity on human ovary and urge caution in its use in young female patients.
- Neonate female to male ratio after assisted reproduction following antagonist and agonist protocols. [Journal Article]
- MMedicine (Baltimore) 2018; 97(38):e12310
- We retrospectively compared neonatal sex after antagonist- versus long-stimulation protocols followed by fresh in vitro fertilization (IVF) or fresh intracytoplasmic sperm injection (ICSI) with eithe...
We retrospectively compared neonatal sex after antagonist- versus long-stimulation protocols followed by fresh in vitro fertilization (IVF) or fresh intracytoplasmic sperm injection (ICSI) with either protocol. We reviewed data for 762 IVF/ICSI cycles in 2015, including 23 IVF procedures. We summarized sex outcomes in the entire cohort, and for the additional subgroups: embryo transfer day and number of embryos transferred, and number of oocytes recovered and maternal age. Among 169 live births for all protocols combined, 50.9% of babies were male, and we saw no difference between the antagonist versus long-stimulation groups (52.3% vs 48.3% male babies, respectively; P = .740). Our results also showed no significant difference in sex proportion when comparing IVF versus ICSI, although a higher proportion of babies were male with the antagonist-ICSI protocol. Differences between the additional subgroups were also neither clinically nor statistically significant.
- Factors affecting the live-birth rate in women with diminished ovarian reserve undergoing IVF-ET. [Journal Article]
- AGArch Gynecol Obstet 2018 Sep 19
- CONCLUSIONS: Maternal age, the stage and number of embryos transferred were independent impact factors affecting the live-birth rate in women with DOR seeking for assisted conception.
- Fertility in classical galactosaemia, a study of N-glycan, hormonal and inflammatory gene interactions. [Journal Article]
- OJOrphanet J Rare Dis 2018 Sep 19; 13(1):164
- CONCLUSIONS: These results validate our previous findings and provide novel experimental evidence for dysregulation of genes LEP, LEPR, ANXA1, ICAM1 and SEPT4 for CG patients and combined with our findings of abnormalities of IgG glycosylation, hormonal and leptin analyses elaborate on the systemic glycosylation and cell signalling abnormalities evident in CG which likely influence the pathophysiology of POI.
- Effect of Physical Exercise on Endometriosis Experimentally Induced in Rats. [Journal Article]
- RSReprod Sci 2018 Sep 19; :1933719118799205
- Endometriosis is characterized by the growth of endometrial tissue outside the uterine cavity. The prevalence of endometriosis among women experiencing pain, infertility, or both is as high as 35% to...
Endometriosis is characterized by the growth of endometrial tissue outside the uterine cavity. The prevalence of endometriosis among women experiencing pain, infertility, or both is as high as 35% to 50%. The most common symptoms of endometriosis are dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. Evidence has suggested that endometriosis symptoms result from a local inflammatory peritoneal reaction caused by ectopic endometrial implants that undergo cyclic bleeding. On the other hand, regular physical exercise seems to have protective effects against diseases that involve inflammatory processes such as type 2 diabetes and colon and breast cancer. On this basis, it is possible that the practice of physical exercise may have beneficial effects on endometriosis. Therefore, the objective of this study was to evaluate the possible anti-inflammatory effect of physical exercise on endometriosis experimentally induced in rats.
- Advances in Fertility Preservation for Young Women With Cancer. [Journal Article]
- ASAm Soc Clin Oncol Educ Book 2018 May 23; (38):27-37
- Female patients of reproductive age with cancer often require treatment that can compromise their future fertility. Treatment-related infertility is an important cancer survivorship issue and is asso...
Female patients of reproductive age with cancer often require treatment that can compromise their future fertility. Treatment-related infertility is an important cancer survivorship issue and is associated with depression and diminished quality of life. Recent advances in reproductive health care provide the opportunity to preserve fertility prior to the initiation of cancer therapy. Clinical guidelines recommend that oncology providers counsel patients about the risk of treatment-related infertility and fertility preservation options, and that they refer those who are interested in fertility preservation to fertility specialists. Guidelines endorse the use of assisted reproductive techniques (ART) provided by reproductive endocrinologists to preserve fertility in young female patients with cancer. In addition, ovarian suppression with gonadotropin-releasing hormone (GnRH) agonists may be considered for ovarian protection during chemotherapy. This article reviews currently available and emerging ART for fertility preservation in female patients of reproductive age with cancer and current data supporting the use of ovarian suppression for ovarian protection during chemotherapy in this population. We also review the uptake of fertility services and discuss barriers to fertility preservation in female patients of reproductive age with cancer.
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- Paraoxonase 1 (PON1) attenuates sperm hyperactivity and spontaneous acrosome reaction. [Journal Article]
- AAndrology 2018 Sep 17
- CONCLUSIONS: PON1 may have a positive effect on fertility via its ability to prevent early spontaneous sperm capacitation and AR before reaching the female genital tract.