| 11. |
- Mörse, Helena, et al.
(författare)
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Acute onset of ovarian dysfunction in young females after start of cancer treatment.
- 2013
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 60:4, s. 676-681
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Female childhood cancer survivors are at risk of ovarian failure and premature ovarian insufficiency. We hereby present an interim analysis of a prospective observational study of ovarian function during cancer treatment of young females in relation to clinical factors. PROCEDURE: Thirty-four consecutive female cancer patients aged 0-18 year were included after informed consent. Serum/Plasma levels of anti-Müllerian hormone (AMH), inhibin B, FSH, LH, and oestradiol (E2) were measured at diagnosis and every 3-4 months during and after treatment. RESULTS: All patients had detectable AMH levels at diagnosis. Eleven patients had reached menarche (mean age 14½ years) and the remaining patients had a mean age of 6½ years. They all showed a rapid decline in AMH after 3 months of treatment, regardless of AMH at diagnosis, age, menarche, or treatment given. Those given radiotherapy below the diaphragm and/or stem cell transplantation (SCT) (n = 9) had no ovarian recovery during or 1½-year after treatment. However, recovery was observed in those given standard treatment for acute lymphatic leukemia (n = 7) already during maintenance chemotherapy. For the remaining patients, longer follow-up is required for analysis of ovarian recovery after treatment. CONCLUSIONS: Rapid ovarian dysfunction is observed in all females after initiation of cancer treatment as measured by AMH and inhibin B. Our data regarding those who require abdominal radiotherapy and/or SCT confirms the recommendations in the Nordic countries where these patients are eligible for cryopreservation of ovarian cortical tissue before start of cancer treatment. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.
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| 12. |
- Mörse, Helena, et al.
(författare)
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Reliability of AMH in Serum after Long-term Storage at -80°C and an Extended Thawing Episode
- 2016
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Ingår i: Annals of Clinical and Laboratory Research. - 2386-5180. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Measurement of anti-Müllerian hormone (AMH) is a valuable clinical tool for evaluating ovarian function. The present study aims to evaluate the reliability of AMH measurements obtained from samples kept for long-term storage with or without intermittent thawing.Methods and findings: Serum samples from 35 young female cancer patients were prospectively collected and stored at -80°C from 2007 until 2010. In 2011, AMH was analyzed with the DSL assay. During storage, the samples were exposed to a freezer error in 2013 that resulted in their being thawed up to 11°C for a maximum of 21 days and then refrozen. In 2014, the same samples (new aliquots) were analyzed with the Ansh-AMH assay. To test the reliability of the results from 2014, we conducted a thawing experiment on serum samples from 10 randomly selected females and compared the Ansh-AMH results for samples stored in a freezer with aliquots from the same samples that were stored at 11°C for 1, 3, 7, 14, and 21 days, respectively. Average AMH levels were 1.6 times higher when assayed with the Ansh-AMH compared with the DSL-AMH, which is in line with reported agreement between these types of assays. The same difference between the assays was found in samples that differed two years in storage time. The Ansh-AMH levels from ten serum samples without long-term storage were not influenced by exposure to 11°C for up to 21 days.Conclusions: The results indicate that long-term storage at -80°C and episodes of thawing have little impact on AMH levels analyzed with current methods. These data are reassuring and enable longitudinal studies to be planned that will analyze all collected serum samples simultaneously.
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| 13. |
- Mörse, Helena, et al.
(författare)
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Severe gonadotoxic insult manifests early in young girls treated for Ewing sarcoma
- 2016
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Ingår i: Medicine. - 0025-7974. ; 95:33
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Tidskriftsartikel (refereegranskat)abstract
- We prospectively investigated anti-Müllerian hormone (AMH) as a measure of ovarian insult in young females during and after treatment for Wilms tumor (WT), osteosarcoma (OS), and Ewing sarcoma (ES). Twenty-one female childhood cancer patients, with a mean age of 7.9 years (range 0.6-17), entered the study. Levels of AMH, follicle-stimulating hormone (FSH), and luteinizing hormone were monitored at diagnosis and every 3 to 4 months during, and regularly for a mean of 2.6 years after treatment. A profound decline in AMH was seen in the majority of the 21 study patients 3 to 4 months after the beginning of treatment, the exception being patients with WT, of whom 60% showed no such decline. During the remaining treatment, all patients except those with WT not treated with whole abdominal radiotherapy or stem cell transplantation (SCT) had AMH below detection limit. After completion of treatment, patients with OS and WT (without whole abdominal radiotherapy and SCT) recovered in AMH and had FSH in the normal range. In contrast, ES patients showed no AMH recovery and highly fluctuating FSH in the first years of follow-up, except for the 2 youngest patients, who had a late, slow AMH recovery. In conclusion, young female ES patients already showed signs of severe ovarian dysfunction during the first years after cancer treatment similar to patients treated with SCT and abdominal radiotherapy, in contrast to females with WT and OS. Fertility counseling and information concerning fertility preservation procedures should be considered before starting to treat young females with ES.
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| 14. |
- Pla, Indira, et al.
(författare)
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Proteome of fluid from human ovarian small antral follicles reveals insights in folliculogenesis and oocyte maturation
- 2021
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 36:3, s. 756-770
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Is it possible to identify by mass spectrometry a wider range of proteins and key proteins involved in folliculogenesis and oocyte growth and development by studying follicular fluid (FF) from human small antral follicles (hSAF)?SUMMARY ANSWER: The largest number of proteins currently reported in human FF was identified in this study analysing hSAF where several proteins showed a strong relationship with follicular developmental processes.WHAT IS KNOWN ALREADY: Protein composition of human ovarian FF constitutes the microenvironment for oocyte development. Previous proteomics studies have analysed fluids from pre-ovulatory follicles, where large numbers of plasma constituents are transferred through the follicular basal membrane. This attenuates the detection of low abundant proteins, however, the basal membrane of small antral follicles is less permeable, making it possible to detect a large number of proteins, and thereby offering further insights in folliculogenesis.STUDY DESIGN, SIZE, DURATION: Proteins in FF from unstimulated hSAF (size 6.1 ± 0.4 mm) were characterised by mass spectrometry, supported by high-throughput and targeted proteomics and bioinformatics. The FF protein profiles from hSAF containing oocytes, capable or not of maturing to metaphase II of the second meiotic division during an IVM (n = 13, from 6 women), were also analysed.PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected FF from hSAF of ovaries that had been surgically removed from 31 women (∼28.5 years old) undergoing unilateral ovariectomy for fertility preservation.MAIN RESULTS AND THE ROLE OF CHANCE: In total, 2461 proteins were identified, of which 1108 identified for the first time in FF. Of the identified proteins, 24 were related to follicular regulatory processes. A total of 35 and 65 proteins were down- and up-regulated, respectively, in fluid from hSAF surrounding oocytes capable of maturing (to MII). We found that changes at the protein level occur already in FF from small antral follicles related to subsequent oocyte maturation.LIMITATIONS, REASONS FOR CAUTION: A possible limitation of our study is the uncertainty of the proportion of the sampled follicles that are undergoing atresia. Although the FF samples were carefully aspirated and processed to remove possible contaminants, we cannot ensure the absence of some proteins derived from cellular lysis provoked by technical reasons.WIDER IMPLICATIONS OF THE FINDINGS: This study is, to our knowledge, the first proteomics characterisation of FF from hSAF obtained from women in their natural menstrual cycle. We demonstrated that the analysis by mass spectrometry of FF from hSAF allows the identification of a greater number of proteins compared to the results obtained from previous analyses of larger follicles. Significant differences found at the protein level in hSAF fluid could predict the ability of the enclosed oocyte to sustain meiotic resumption. If this can be confirmed in further studies, it demonstrates that the viability of the oocyte is determined early on in follicular development and this may open up new pathways for augmenting or attenuating subsequent oocyte viability in the pre-ovulatory follicle ready to undergo ovulation.STUDY FUNDING/COMPETING INTEREST(S): The authors thank the financial support from ReproUnion, which is funded by the Interreg V EU programme. No conflict of interest was reported by the authors.TRIAL REGISTRATION NUMBER: N/A.
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| 15. |
- Pla, Indira, et al.
(författare)
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Proteomic Alterations in Follicular Fluid of Human Small Antral Follicles Collected from Polycystic Ovaries—A Pilot Study
- 2022
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Ingår i: Life. - : MDPI AG. - 0024-3019 .- 2075-1729. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovaries (PCO) contain antral follicles that arrest growing around 3–11 mm in diameter, perturbing the dominant follicle’s selection and the subsequent ovulatory process. Proteomic alterations of PCO follicular fluid (FF) (i.e., microenvironment in which the oocyte develops until ovulation) have been studied from large follicles in connection with oocyte pickup during ovarian stimulation. The present study aimed to detect proteomic alterations in FF from unstimulated human small antral follicles (hSAF) obtained from PCO. After performing deep-sequencing label-free proteomics on 10 PCO and 10 non-PCO FF samples from unstimulated hSAF (4.6–9.8 mm), 1436 proteins were identified, of which 115 were dysregulated in PCO FF samples. Pathways and processes related to the immune system, inflammation, and oxidative stress appeared to be upregulated in PCO, while extracellular matrix receptors interactions, the collagens-containing extracellular matrix, and the regulation of signaling were downregulated. The secreted proteins SFRP1, THBS4, and C1QC significantly decreased their expression in PCO FF, and this downregulation was suggested to affect future oocyte competence. In conclusion, our study revealed, for the first time, evidence of proteomic alterations occurring in the FF of PCO hSAF that may be related to the dysfunction of follicular growth and subsequent oocyte competence.
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| 16. |
- Rodriguez-Wallberg, Kenny A., et al.
(författare)
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Ovarian tissue cryopreservation and transplantation among alternatives for fertility preservation in the Nordic countries - compilation of 20 years of multicenter experience
- 2016
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : WILEY-BLACKWELL. - 0001-6349 .- 1600-0412. ; 95:9, s. 1015-1026
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. The aim of this study is to report the current status of ovarian tissue cryopreservation among alternatives for fertility preservation in the Nordic countries. Material and methods. A questionnaire was sent to 14 Nordic academic reproductive centers with established fertility preservation programs. It covered fertility preservation cases performed up to December 2014, standard procedures for ovarian tissue cryopreservation and oocyte cryopreservation and reproductive outcomes following ovarian tissue transplantation. Results. Among the Nordic countries, Denmark and Norway practice ovarian tissue cryopreservation as a clinical treatment (822 and 164 cases, respectively) and their programs are centralized. In Sweden (457 cases), ovarian tissue cryopreservation is practiced at five of six centers and in Finland at all five centers (145 cases). Nearly all considered ovarian tissue cryopreservation to be experimental. In Iceland, embryo cryopreservation is the only option for fertility preservation. Most centers use slow-freezing methods for ovarian tissue cryopreservation. Most patients selected for ovarian tissue cryopreservation were newly diagnosed with cancer and the tissue was predominantly retrieved laparoscopically by unilateral oophorectomy. Only minor complications were reported. In total, 46 women have undergone ovarian tissue transplantation aiming at recovering fertility, 17 healthy children have been born and several additional pregnancies are currently ongoing. Whenever patients' clinical condition is permissive, oocyte cryopreservation after hormonal stimulation is preferred for fertility preservation. Between 2012 and 2014, a smaller proportion of females have undergone fertility preservation in the Nordic centers, in comparison to males (1: 3). Conclusions. Overall, ovarian tissue cryopreservation was reported to be safe. Slow freezing methods are still preferred. Promising results of recovery of fertility have been reported in Nordic countries that have initiated ovarian tissue transplantation procedures.
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