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Wuntakal R.,Havering and Redbridge University Hospitals Trust | Seshadri S.,The Center for Reproductive and Genetic Health | Montes A.,Guys and St Thomas Hospital NHS Foundation Trust | Lane G.,Guys and St Thomas Hospital NHS Foundation Trust
Cochrane Database of Systematic Reviews | Year: 2016

Background: Ovarian cancer is seventh most common cancer in women worldwide. Approximately 1.3% of women will be diagnosed with ovarian cancer at some point during their life time. The majority of tumours arise from surface of the ovary (epithelial). Two thirds of these women will present with advanced disease, requiring aggressive treatment, which includes debulking surgery (removal of as much disease as possible) and chemotherapy. However, most women (75%) with advanced epithelial ovarian cancer (EOC) will relapse following surgery and chemotherapy. Patients who relapse are treated with either platinum or non-platinum drugs and this is dependent on the platinum-sensitivity and platinum-free interval. These drug regimens are generally well-tolerated although there are potential severe side effects. New treatments that can be used to treat recurrence or prevent disease progression after first-line or subsequent chemotherapy are important, especially those with a low toxicity profile. Hormones such as luteinising hormone releasing hormone (LHRH) agonists have been used in the treatment of relapsed EOC. Some studies have shown objective remissions, while other studies have shown little or no benefit. Most small studies report a better side-effect profile for LHRH agonists when compared to standard chemotherapeutic agents used in EOC. Objectives: To compare the effectiveness and safety of luteinising hormone releasing hormone (LHRH) agonists with chemotherapeutic agents or placebo in relapsed epithelial ovarian cancer (EOC). Search methods: We searched the Cochrane Gynaecological Cancer Group trials register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase up to January 2016. We also searched registers of clinical trials and abstracts of scientific meetings. Selection criteria: Randomised controlled trials (RCTs) that compared LHRH agonists with chemotherapeutic agents or placebo in relapsed EOC. Data collection and analysis: Two review authors independently assessed whether relevant studies met the inclusion criteria, retrieved data and assessed risk of bias. Main results: Two studies, including 97 women, met our inclusion criteria: one assessed LHRH agonist (leuprorelin) use in relapsed (platinum-resistant and platinum-refractory) EOC in comparison with a chemotherapeutic agent (treosulfan) (Du Bois 2002); the other examined LHRH agonist (decapeptyl) versus a placebo (Currie 1994). Since both studies had different control groups, a meta-analysis was not possible. There may be little or no difference between treatment with leuprorelin or treosulfan in overall survival (OS) (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.58 to 1.67; very low-quality evidence) or progression-free survival (PFS) at six and 12 months (risk ratio (RR) 0.61, 95% CI 0.22 to 1.68, and RR 0.65, 95% CI 0.12 to 3.66; very low-quality evidence), respectively (Du Bois 2002). The duration of follow-up was 2.5 years and quality of life (QoL) was not reported in this study. Alopecia and fatigue were probably more common with treosulfan than leuprorelin (alopecia RR 0.32, 95% CI 0.12 to 0.91 (very low-quality evidence)). There may be little or no difference in other Grade 3/4 side effects: nausea and vomiting (RR 0.65, 95% CI 0.12 to 3.66 (very low-quality evidence)); neurotoxicity (RR 0.32, 95% CI 0.01 to 7.71 (very low-quality evidence)) and neutropenia (RR 0.97, 95% 0.06 to 14.97 (very low-quality evidence)), The Currie 1994 study, which compared decapeptyl treatment with placebo, reported mean PFS of 16 weeks verus 11.2 weeks, respectively. No relative effects measures or P value at a particular time point were reported. Overall survival (OS) and QoL outcomes were not reported. In addition, adverse events were only mentioned for the decapeptyl group. Adverse events were incompletely reported (no adverse events in decapeptyl group, but not reported for the placebo group). Authors' conclusions: Based on this review of two small RCTs, there is not enough evidence to comment on the safety and effectiveness of LHRH agonists in the treatment of platinum-refractory and platinum-resistant (relapsed) EOC. Overall, the quality of evidence for all outcomes (including OS, PFS, QoL and adverse events) is very low. © 2016 The Cochrane Collaboration.


Nur Semerci C.,Pamukkale University | Eser M.,Pamukkale University | Tufan L.S.,Pamukkale University | Kalkan T.,Pamukkale University | And 3 more authors.
Turkiye Klinikleri Journal of Medical Sciences | Year: 2012

A 30-year-old male patient referred to our clinic for unraveling the underlying etiology of the azoospermia. He had no unusual medical history. At physical examination, obesity, short neck and gynecomastia were noted. All hormone levels were normal except estradiol which was 2-fold higher than the upper limit. Having azoospermia in the spermiogram, scrotal ultrasonography was normal. Cytogenetic analysis and fluorescence in situ hybridization were performed subsequently, 45,X,add(21)(p10) and 45,X,add(21)(p10).ish der(Y;21) (q12;p10) were found, respectively. On C-banding, dicentric staining of translocated chromosome was observed. NOR banding was negative. Molecular genetics studies using multiplex polymerase chain reaction revealed the presence of Y chromosome sequences at SRY, AZFa, AZFb, AZFc regions. © 2012 by Türkiye Klinikleri.


Ghevaria H.,University College London | SenGupta S.,University College London | Shmitova N.,University College London | Serhal P.,The Center for Reproductive and Genetic Health | Delhanty J.,University College London
Reproductive BioMedicine Online | Year: 2015

Diagnostic application of array comparative genomic hybridization (aCGH) in preimplantation genetic diagnosis for reciprocal and Robertsonian translocations has revealed 55-65% embryos with additional aneuploidies with or without translocation-related imbalances. The occurrence of these extra abnormalities with the balanced form of the translocation reduces the number of embryos suitable for transfer. Eighty-three embryos were followed up on days 5-7 of development from 23 infertile or sub-fertile carriers for whole chromosome and segmental aneuploidies present in addition to the balanced or unbalanced translocations detected on aCGH diagnosis. Embryos were analysed by fluorescence in-situ hybridization (n = 63) and aCGH (n = 20). Meiotic aneuploidy affected 35% of embryos and 47% had mitotic events; 15% had both types. Meiotic and mitotic events were almost equal (60 versus 64), 97 affected whole chromosomes (58 meiotic, 39 mitotic) and 27 were segmental (two meiotic, 25 mitotic). In 85.5% of embryos with whole chromosome additional aneuploidies, the aneuploidy was present throughout or in more than 50% of cells. All embryos diagnosed as abnormal (translocation balanced or unbalanced) after aCGH diagnosis at cleavage stage would have remained unsuitable for transfer if tested at later stages of development. Additional aneuploidies merit full consideration when considering the choice of embryos to transfer. © 2015 Reproductive Healthcare Ltd.


Naja R.P.,University College London | Dhanjal S.,University College London | Doshi A.,The Center for Reproductive and Genetic Health | Serhal P.,The Center for Reproductive and Genetic Health | And 2 more authors.
Prenatal Diagnosis | Year: 2016

Objectives: Mosaicism in certain dominant disorders may result in a ‘non-Mendelian’ transmission for the causative mutation. Preimplantation genetic diagnosis (PGD) is available for patients with inherited disorders to achieve an unaffected pregnancy. We present our experience for two female patients with different dominantly inherited autosomal disorders; neurofibromatosis type 1 (NF1) and tuberous sclerosis complex type 2 (TSC2). Methods: PGD protocol development was carried out using single cells from the patients. PGD was carried out on polar bodies and different embryonic cells. Results: Protocol development for NF1 using lymphocytes from the patient suggested mosaicism for the mutation. This was supported further by quantitative fluorescent-PCR performed on genomic DNA. During PGD, polar bodies and blastomeres lacked the mutation that probably was absent or present at very low levels in the patient's germline. Single lymphocyte analysis during protocol development for TSC2 did not indicate mosaicism; however, analysis of single buccal cells and multiple embryo biopsies across two consecutive IVF/PGD cycles confirmed gonosomal mosaicism. Conclusions: The trend in PGD is for blastocyst biopsy followed by whole genome amplification, eliminating single cell analysis. In the case of certain dominantly inherited disorders, pre-PGD single cell analysis is beneficial to identify potential mosaicism that ensures robust protocols. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.


PubMed | The Center for Reproductive and Genetic Health and University College London
Type: Journal Article | Journal: Reproductive biomedicine online | Year: 2016

Diagnostic application of array comparative genomic hybridization (aCGH) in preimplantation genetic diagnosis for reciprocal and Robertsonian translocations has revealed 55-65% embryos with additional aneuploidies with or without translocation-related imbalances. The occurrence of these extra abnormalities with the balanced form of the translocation reduces the number of embryos suitable for transfer. Eighty-three embryos were followed up on days 5-7 of development from 23 infertile or sub-fertile carriers for whole chromosome and segmental aneuploidies present in addition to the balanced or unbalanced translocations detected on aCGH diagnosis. Embryos were analysed by fluorescence in-situ hybridization (n = 63) and aCGH (n = 20). Meiotic aneuploidy affected 35% of embryos and 47% had mitotic events; 15% had both types. Meiotic and mitotic events were almost equal (60 versus 64), 97 affected whole chromosomes (58 meiotic, 39 mitotic) and 27 were segmental (two meiotic, 25 mitotic). In 85.5% of embryos with whole chromosome additional aneuploidies, the aneuploidy was present throughout or in more than 50% of cells. All embryos diagnosed as abnormal (translocation balanced or unbalanced) after aCGH diagnosis at cleavage stage would have remained unsuitable for transfer if tested at later stages of development. Additional aneuploidies merit full consideration when considering the choice of embryos to transfer.

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