Lauren R Alesi, Quynh-Nhu Nguyen, Jessica M Stringer, Amy L Winship, Karla J Hutt
{"title":"The future of fertility preservation for women treated with chemotherapy.","authors":"Lauren R Alesi, Quynh-Nhu Nguyen, Jessica M Stringer, Amy L Winship, Karla J Hutt","doi":"10.1530/RAF-22-0123","DOIUrl":"10.1530/RAF-22-0123","url":null,"abstract":"<p><p>Cytotoxic chemotherapies have been a mainstay of cancer treatment, but are associated with numerous systemic adverse effects, including impacts to fertility and endocrine health. Irreversible ovarian damage and follicle depletion are side-effects of chemotherapy that can lead to infertility and premature menopause, both being major concerns of young cancer patients. Notably, many women will proceed with fertility preservation, but unfortunately existing strategies don't entirely solve the problem. Most significantly, oocyte and embryo freezing do not prevent cancer treatment-induced ovarian damage from occurring, which may result in the impairment of long-term hormone production. Unfortunately, loss of endogenous endocrine function is not fully restored by hormone replacement therapy. Additionally, while GnRH agonists are standard care for patients receiving alkylating chemotherapy to lessen the risk of premature menopause, their efficacy is incomplete. The lack of more broadly effective options stems, in part, from our poor understanding of how different treatments damage the ovary. Here, we summarise the impacts of two commonly utilised chemotherapies - cyclophosphamide and cisplatin - on ovarian function and fertility, and discuss the mechanisms underpinning this damage. Additionally, we critically analyse current research avenues in the development of novel fertility preservation strategies, with a focus on fertoprotective agents.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9624816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charvi Kanodia, Michael P Rimmer, Kathleen Duffin, Rod T Mitchell
{"title":"Impact of taxane-based chemotherapeutics on male reproductive function.","authors":"Charvi Kanodia, Michael P Rimmer, Kathleen Duffin, Rod T Mitchell","doi":"10.1530/RAF-22-0134","DOIUrl":"10.1530/RAF-22-0134","url":null,"abstract":"<p><strong>Lay summary: </strong>Men and boys with cancer treated with chemotherapy are known to have reduced fertility following their treatment. This is because some chemotherapy drugs can damage the cells in the testicles that make sperm. This study found there is limited information available on the effect of one group of chemotherapy drugs, called taxanes, on testicular function and fertility. More studies are needed to aid clinicians in advising patients on how this taxane-based chemotherapy may affect their future fertility.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10083651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9335393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinwe U Nwachukwu, Robert S Robinson, Kathryn J Woad
{"title":"Effect of insulin-like growth factor system on luteinising angiogenesis.","authors":"Chinwe U Nwachukwu, Robert S Robinson, Kathryn J Woad","doi":"10.1530/RAF-22-0057","DOIUrl":"10.1530/RAF-22-0057","url":null,"abstract":"<p><p>Preovulatory follicle growth and the luteal transition requires intense angiogenesis. This enables progesterone production to increase sufficiently to support a pregnancy. Inadequate follicular or luteal vascularisation can lead to reduced ovarian function and thus compromise fertility. Insulin-like growth factor 1 (IGF1) and IGF2 regulate multiple ovarian processes and are key links between an animal's reproductive and metabolic status. This study investigated the role that the IGF system plays in regulating luteinising follicular endothelial cell (EC) networks and progesterone production in vitro. Bovine luteinising follicular angiogenesis cultures were treated with 1) LR3-IGF1 (10 or 100ng/ml) under basal and angiogenic-stimulated conditions or 2) IGF1 receptor inhibitor (picropodophyllin (PPP); 1µM) in the presence or absence of LR3-IGF1, IGF2, or combined LR3-IGF1+IGF2 (10ng/ml). EC networks were quantified by von Willebrand factor immunohistochemistry. Progesterone production was analysed by ELISA and cell proliferation was determined by MTT assay. LR3-IGF1 had limited effects on EC growth parameters, whilst PPP (p<0.001) markedly reduced EC growth parameters (by 60-70%). Cell proliferation was slightly increased (by 3-5%) by LR3-IGF1 (p<0.001). LR3-IGF1 had variable effects on progesterone production, whilst PPP reduced progesterone concentration (p<0.001) with or without LR3-IGF1 or IGF2 alone or in combination. IGF1 was detected in cell conditioned media and was increased by LH (50ng/ml) (p<0.001). In conclusion, exogenous IGF1 and IGF2 had minimal effects on luteinising follicular angiogenesis and progesterone production, but the inhibitory effect of the IGFR1 inhibitor (PPP) suggests that IGF1 receptor signalling is critical for the development of EC networks and progesterone production in luteinising follicular cells.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10160534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9420606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah McCredie, Belinda An, Monika McShane, William Leigh Ledger, Christos Venetis
{"title":"Serum anti-müllerian hormone (AMH) concentration during pregnancy: a longitudinal study.","authors":"Sarah McCredie, Belinda An, Monika McShane, William Leigh Ledger, Christos Venetis","doi":"10.1530/RAF-22-0128","DOIUrl":"10.1530/RAF-22-0128","url":null,"abstract":"<p><p>A prospective longitudinal cohort study aimed to longitudinally examine the kinetics of Anti-müllerian hormone (AMH) during the first two trimesters of pregnancy. Pregnant women with stored 1st trimester serum samples were recruited at 24-28 weeks gestation during their gestational diabetes testing, where they provided an additional serum sample. The samples were analysed for AMH, oestradiol and progesterone concentrations. A decrease in serum AMH was observed in 40 out of 45 (88.9%) (95% CI 75.9% to 96.3%) of the participants in this study. The median serum AMH concentration was 10.9 pmol/L in the 1st trimester and 6.5 pmol/L during the 2nd trimester, with a significantly different distribution of the values between the 1st and the 2nd trimester AMH samples (p<0.001). The median percentage of AMH difference of -39.8%. This study demonstrated a significant decrease in serum AMH levels from the 1st to the 2nd trimester of pregnancy. The absolute decrease in AMH levels seems to be positively associated with 1st trimester AMH levels, whereas the percentage of AMH difference is not. Further studies are required to elucidate the potential physiological mechanisms of this finding.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10160537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9420073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily Bailie, Mila Maidarti, Stuart Jack, Robert Hawthorn, Neale Watson, Evelyn Telfer, Richard A Anderson
{"title":"The ovaries of transgender men indicate effects of high dose testosterone on the primordial and early growing follicle pool.","authors":"Emily Bailie, Mila Maidarti, Stuart Jack, Robert Hawthorn, Neale Watson, Evelyn Telfer, Richard A Anderson","doi":"10.1530/RAF-22-0102","DOIUrl":"10.1530/RAF-22-0102","url":null,"abstract":"<p><p>Androgens are essential in normal ovarian function and follicle health but hyperandrogenism, as seen in polycystic ovary syndrome, is associated with disordered follicle development. There are few data on the effect of long-term exposure to high levels of testosterone as found in transgender men receiving gender-affirming endocrine therapy. In this study, we investigate the effect of testosterone on the development, morphological health and DNA damage and repair capacity of human ovarian follicles in vivo and their survival in vitro. Whole ovaries were obtained from transgender men (mean age: 27.6 ± 1.7 years; range 20-34 years, n = 8) at oophorectomy taking pre-operative testosterone therapy. This was compared to cortical biopsies from age-matched healthy women obtained at caesarean section (mean age: 31.8±1.5 years; range= 25-35 years, n=8). Cortical tissues were dissected into fragments and either immediately fixed for histological analysis or cultured for 6 days and subsequently fixed. Follicle classification and morphological health were evaluated from histological sections stained with H&E and expression of γH2AX as a marker of DNA damage by IHC. In uncultured tissue, testosterone exposure was associated with reduced follicle growth activation, poor follicle health and increased DNA damage. After 6 days of culture, there was enhanced follicle activation compared to control with further deterioration in morphological health and increased DNA damage. These data indicate that high circulating concentrations of testosterone have effects on the primordial and small-growing follicles of the ovary. These results may have implications for transgender men receiving gender-affirming therapy prior to considering pregnancy or fertility preservation measures.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10160535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9562287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dareen Mattar, Warakorn Cheewasopit, Moafaq Samir, Philip G Knight
{"title":"Does kisspeptin exert a local modulatory effect on bovine ovarian steroidogenesis?","authors":"Dareen Mattar, Warakorn Cheewasopit, Moafaq Samir, Philip G Knight","doi":"10.1530/RAF-22-0088","DOIUrl":"10.1530/RAF-22-0088","url":null,"abstract":"<p><p>Kisspeptin, a hypothalamic neuropeptide encoded by the KISS1 gene, has a pivotal role in promoting GnRH secretion in mammals. Kisspeptin and its receptor (KISS1R) are also expressed in certain peripheral tissues including gonads, suggesting intra-gonadal roles. Such actions at the level of the bovine ovary have not been explored previously. The current aims were to determine whether KISS1 and its receptor (KISS1R) are expressed in the bovine ovary and whether kisspeptin or a kisspeptin antagonist can modulate ovarian steroid production by cultured ovarian cells. Granulosa (GC) and theca interna (TC) were collected from antral follicles (3-18 mm) categorized into five class sizes. Early, mid and regressing corpora lutea (CL) were also collected for RT-qPCR analysis of KISS1 and KISS1R expression. Bovine TC and GC cultured under both non-luteinizing (serum-free) and luteinizing (serum-supplemented) conditions were treated for 4 days with kisspeptin-10 (10-10-10-6M) or kisspeptin antagonist (p234; 10-10-10-6M), alone and in combination with either FSH (GC), LH (TC) or forskolin (luteinized GC/TC). Steroid secretion (GC: oestradiol, progesterone; TC: androstenedione, progesterone; luteinized GC/TC: progesterone) was measured by ELISA and viable cell number determined by neutral red uptake assay. KISS1 and KISS1R transcripts were detected in TC, GC and CL with significant differences between follicle categories and CL stages. However, neither kisspeptin-10 nor kisspeptin antagonist affected steroid secretion or viable cell number in any of the four ovarian cell culture models. As such, the hypothesis that kisspeptin has a direct intra-ovarian role to modulate follicular or luteal steroidogenesis, or cell proliferation/survival, is not supported.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10855649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tsafrir S Kolatt, Yoel Shufaro, Shlomo Mashiach, Bernard Czernobilsky, Sarit Aviel-Ronen, Liat Apel-Sarid, Mazal Dahan, Yuval Or
{"title":"Revealing the uterine blood vessel network via virtual pathology.","authors":"Tsafrir S Kolatt, Yoel Shufaro, Shlomo Mashiach, Bernard Czernobilsky, Sarit Aviel-Ronen, Liat Apel-Sarid, Mazal Dahan, Yuval Or","doi":"10.1530/RAF-22-0135","DOIUrl":"10.1530/RAF-22-0135","url":null,"abstract":"<p><strong>Background: </strong>The distribution of the blood vessel network at any point in time in any body tissue, may provide valuable information with regards to the tissue condition and its angiogenesis functionality. The blood vessel three-dimensional network of the endometrium goes through a process of change over a relatively short period of 4 weeks on average. It is well accepted that this angiogenesis is closely related to the success or failure of the implantation of the embryo Objective and rationale: Our study aims to present a method to follow the three-dimensional evolution of the superficial blood vessel distribution in the endometrium throughout the uterine cycle.</p><p><strong>Method: </strong>This method utilizes differences in the observed broadband colors of the blood vessels in order to assess their depth coordinate below the endometrial tissue surface. We implemented the method using microscopic images of fresh, ex-vivo, endometrial samples of different cycle days to obtain the statistical evolution track of the superficial blood vessel population in both human and animal (swine) samples.</p><p><strong>Outcomes: </strong>In human samples we observed a systematic and consistent trend in the BV diameter distribution at different tissue depths. We demonstrate that the magnitude of this trend evolves throughout the course of the female cycle.</p><p><strong>Wider implications: </strong>This method has the potential to further our understanding of the mechanisms of angiogenesis in tissues other than the endometrium. We propose that this method may also contribute to more precise endometrial dating and may assist in more accurate determination of embryo transfer timing within IVF treatments.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fa/90/RAF-22-0135.PMC10083648.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9634293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L C Morley, M Debant, H J Gaunt, N A B Simpson, D J Beech
{"title":"Nitric oxide synthase phosphorylation in fetoplacental endothelium is enhanced by agonism of Piezo1 mechanosensor in small for gestational age babies.","authors":"L C Morley, M Debant, H J Gaunt, N A B Simpson, D J Beech","doi":"10.1530/RAF-22-0100","DOIUrl":"10.1530/RAF-22-0100","url":null,"abstract":"<p><strong>Lay summary: </strong>Friction caused by blood flowing across cells that line blood vessels (endothelial cells) activates sensors of mechanical force. This produces nitric oxide (NO) which widens placental blood vessels, enabling more blood flow to the baby. This study sought to determine whether the mechanical sensor, Piezo1, is important for NO production in fetoplacental endothelial cells (FpECs) and whether the steps in this pathway are different in small for gestational age (SGA) babies, where placental blood flow is often altered. We showed that in healthy FpECs, blood flow increased NO signalling. We suggest that in SGA babies, FpECs have an increase in baseline levels of NO signalling, suggestive of a compensatory drive. Treating healthy and SGA cells with a Piezo1 chemical activator, Yoda1, upregulated NO signalling. This shows that Piezo1 is linked to NO and that in SGA, FpECs have the capacity to further increase NO. Further research will establish whether Piezo1 enhancement leads to increased blood flow in the placenta. If so, Piezo1 could be a new target for developing treatments to prevent poor growth of babies in the womb.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9874955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9159851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bethany Chung, Charlotte Greene, Alice Pearson, Lisa M Starrs, W Colin Duncan
{"title":"The impact of COVID-19 on the assessment and management of ectopic pregnancies.","authors":"Bethany Chung, Charlotte Greene, Alice Pearson, Lisa M Starrs, W Colin Duncan","doi":"10.1530/RAF-22-0073","DOIUrl":"https://doi.org/10.1530/RAF-22-0073","url":null,"abstract":"<p><strong>Lay summary: </strong>During the COVID-19 pandemic, the public delayed seeking medical help, which may have affected the impact of having an ectopic pregnancy. An ectopic pregnancy is when pregnancy tissue grows outside its normal position in the womb, and it can be life-threatening. It can be treated by non-surgical or surgical options, and any delay in seeking help can reduce the options for treatment and increase the need for more urgent management. We wanted to assess whether there were differences in the presentation and management of ectopic pregnancies in a major teaching hospital between 2019 (pre-COVID-19) and 2021 (COVID-19 period). We found that the pandemic did not cause a delay in seeking medical help or cause worse outcomes. In fact, immediate surgical treatment and time in the hospital were less during COVID-19, perhaps because of a desire to avoid admission to hospital. One outcome of COVID-19 is reassurance that we can safely use more non-surgical treatments for ectopic pregnancies.</p>","PeriodicalId":21128,"journal":{"name":"Reproduction & Fertility","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/5f/RAF-22-0073.PMC10083650.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9697200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}