Pinar Tulay

Number of embryos biopsied as a predictive indicator for the outcome of preimplantation genetic diagnosis by fluorescence in situ hybridisation in translocation cases

This study aimed to investigate the optimum number of embryos to be biopsied in order to increase the likelihood of obtaining a balanced/normal embryo following preimplantation genetic diagnosis (PGD) by fluorescence in situ hybridisation (FISH) for translocation carriers. Patients with low number of fertilised oocytes (≤5) or low number of embryos available for PGD (<7) underwent multiple hormonal stimulation cycles and their embryos from each cycle were vitrified and accumulated to obtain at least three embryos for PGD. Fifty-seven PGD cycles were performed for translocation carriers by FISH on day 3 of embryo development. PGD and pregnancy outcomes were examined according to the number of embryos biopsied. The cancellation rates of embryo transfer for the reciprocal translocation carriers were 40% when more than eight embryos were biopsied and it was as high as 78% when low number of embryos (less than nine) were biopsied. For Robertsonian translocation carriers, when more than eight embryos were biopsied, there were no embryo transfer cancellations. This study showed that when there are more than nine embryos biopsied for PGD, the likelihood of obtaining a balanced embryo and positive pregnancy outcome is significantly higher (P < 0.05) in such the overall pregnancy rate was 63% for reciprocal and 86% for Robertsonian carriers. This was reduced to only 7% for reciprocal and 14% for Robertsonian translocation carriers when less than nine embryos were biopsied. One of the limitations of this study was that the analysis was performed by FISH and more studies should investigate the outcomes of embryo accumulation following comprehensive chromosome analysis.

The role of human papillomaviruses in cancer progression

The role of human papillomaviruses in cancer progression Pinar Tulay, Nedime Serakinci Department of Medical Genetics, Faculty of Medicine, Near East University, 999058 Nicosia, Cyprus. Correspondence to: Dr. Nedime Serakinci, Department of Medical Genetics, Faculty of Medicine, Near East University, 999058 Nicosia, Cyprus. E-mail: nedimeserakinci@gmail.com The importance of human papillomavirus (HPV) infection and its role in the progress of cancer have been widely evaluated. The understanding of HPV association with certain cancers, such as cervical cancer, is very well established. A big step forward in the prevention of HPV associated cancers with the use of early detection by screening strategies has also been taken. In the last decade, development of HPV vaccination has reduced the number of cases in HPV infections and infection induced cancers. In this report, we review the HPV pathogenesis and highlight the mechanism of HPV involvement in cancer development.

Is the interchromosomal effect present in embryos derived from Robertsonian and reciprocal translocation carriers particularly focusing on chromosome 10 rearrangements

The aim of this study was to analyse the possible occurrence of the interchromosomal effect (ICE) in human preimplantation embryos obtained from Robertsonian and reciprocal translocation carriers focusing on ones with chromosome 10 rearrangements who were undergoing preimplantation genetic diagnosis (PGD) and to investigate whether offering aneuploidy screening would be beneficial to these patients. Cleavage stage embryos from translocation carriers undergoing PGD were biopsied. Multicolour fluorescence in situ hybridisation for the chromosomes involved in the translocation in addition to nine more chromosomes (13, 15, 16, 17, 18, 21, 22, X and Y) was used in the analysis. The control group involved embryos obtained from age-matched patients undergoing preimplantation genetic screening (PGS). Cumulative aneuploidy rate in embryos derived from both Robertsonian and reciprocal translocation carriers was found to be similar with the control group. Therefore no ICE was observed in cleavage stage embryos obtained from these carriers. More than half of the embryos with chromosome 10 rearrangements had aneuploidy for which an increased aneuploidy rate was more apparent in male carriers. Thus, it is possible that there is a risk of ICE in reciprocal carriers with chromosome 10 rearrangements. This study showed that there is no ICE in embryos derived from Robertsonian and reciprocal translocation carriers. However high rates of aneuploidy in structurally normal chromosomes were detected in embryos derived from these carriers and thus aneuploidy screening in addition to PGD may increase the pregnancy rates of these patients.

Role of Mesenchymal Stem Cells in Cancer Development and Their Use in Cancer Therapy

Stem cells have the ability to perpetuate themselves through self-renewal and generate mature cells of a particular tissue through differentiation. Mesenchymal stem cells (MSCs) play an important role in tissue homeostasis - supporting tissue regeneration. MSCs are rare pluripotent cells supporting hematopoietic and mesenchymal cell lineages. MSCs have a great therapeutic potential in cancer therapy, as well as stem cell exosome and/or microvesicle-mediated tissue regeneration. In this review, the use of hMSCs in stem cell-mediated cancer therapy is discussed.

Double faced role of human mesenchymal stem cells and their role challenges in cancer therapy.

Human mesenchymal stem cells (hMSCs) are multipotent non-hematopoietic precursor cells with the ability to differentiate into several tissue types. The use of hMSCs has gained significant importance in cancer therapies as well as a large number of degenerative disease therapies due to their homing abilities. However, these cells may undergo spontaneous transformation leading to them bypassing naturally built-in cell controls that could lead to senescence and carcinogenesis. Therefore, although MSCs have great potential for cancer therapy, they also risk the development of cancer, which provides them with double-faced characteristics for both cancer development and therapy. The potential use of hMSCs in therapeutics from the aspect of in vitro expansion of hMSCs and telomere dynamic is discussed.

Oocyte Donors’ Awareness on Donation Procedure and Risks: A Call for Developing Guidelines for Health Tourism in Oocyte Donation Programmes

Objective In the recent years, oocyte donation programmes have widely spread worldwide becoming the drive of health tourism. In some countries the donation programmes are tightly regulated; whereas in some, the guidelines or regulations are not well defined. The aim of this study was to evaluate the donors’ awareness of the donation programmes and the ethical consequences in enrolling these programmes. Material and Methods A detailed questionnaire-based survey was conducted to evaluate the donors’ main drive to get involved in the donation programme and the donor’s knowledge and awareness of risk factors. Results Majority of the donors (70%) were undergoing donation programmes for financial gains through compensation. The donors were especially not aware of the long-term medical risks and the possibility of identity exposure through genetic screening. Conclusion The health professionals have the main duty to counsel the donors about the basic procedures and any possible problems they may face during the donation programmes. Reimbursement of oocyte donors is a slippery slope path in oocyte donation programmes. High compensation may make women to think that donation is a profession without considering possible risks. Furthermore, with the wider use of direct-toconsumer genetic testing, genetic anonymity may be at risk, thus the donors have to be counselled properly. Therefore, in this era of health tourism, it is crucial to set up well-defined counselling bodies in all oocyte donation centres and enable the donors to make an informed choice in becoming oocyte donors.

PGD management scheme for older females with balanced translocations: Do older females have less chance of balanced embryo transfer?

OBJECTIVE Carriers of reciprocal and Robertsonian translocations have a higher risk of experiencing infertility and repeated miscarriages. It is well established that with advancing maternal age, the risk of aneuploidies in embryos increases. In this study, the chance of developing balanced embryos in translocation carriers with advanced maternal age was analyzed to establish a management scheme for couples seeking fertility treatment and preimplantation genetic diagnosis (PGD). MATERIAL AND METHODS Biopsy was performed on cleavage-stage embryos. Multicolor fluorescence in situ hybridization was used for PGD. The translocation carriers underwent a total of 55 cycles of PGD. Genetics diagnosis and cycle outcomes of PGD cases were examined. RESULTS This study showed that the chance of obtaining a balanced embryo from the Robertsonian translocation carriers was significantly less when the maternal age is advanced. Similar rates for balanced embryos were obtained from the reciprocal translocation carriers. CONCLUSION The results of this study show that maternal age plays an important role and that genetic counselling and planning for a PGD cycle in translocation carriers, particularly for Robertsonian carriers, must be accordingly adapted.

The Route to HPV-Associated Neoplastic Transformation: A Review of the Literature.

Human papillomaviruses (HPVs)-small, nonenveloped viruses with double-stranded circular DNA-are believed to have a role in the progression of cancer. However, the exact mechanisms are not well established. The interference of HPV proteins, especially E6 and E7, in the cell cycle is considered to be the main pathway. It is still questioned whether the expression of these proteins or the viral load is more important in neoplastic transformation. Furthermore, HPV is believed to adapt mechanisms to evade the host cell immune system; persistent HPV infection may also play a role in oncogenic transformation by causing genomic instability and local immune suppression. These factors may cause accumulation of genomic alterations within the host cell and integration of the viral genome into the host genome. In recent years, epigenetic modifications, such as methylation, have also been considered to take part in neoplastic transformation. All of these alterations to the genome may be favorable to the development of cancer. This article highlights the association of HPV in neoplastic transformation and cancer progression.

Poor embryo development and preimplantation genetic diagnosis outcomes of translocations involving chromosome 10: Do we blame genetics?

Balanced reciprocal translocation carriers are usually phenotypically normal. Although the reproductive risk of these carriers varies, they generally have a lower chance to produce normal or balanced gametes. Preimplantation genetic diagnosis (PGD) is offered to these patients to increase their chances of becoming pregnant by selecting a balanced embryo for transfer. This study aimed to analyse the development and the PGD outcome of the embryos obtained from reciprocal translocation carriers focusing on ones with chromosome 10 rearrangements. In total, 27 reciprocal translocation carriers underwent 31 cycles of PGD. PGD was performed using multicolour fluorescence in situ hybridisation for 298 embryos and of these 136 were obtained from couples carrying translocations involving chromosome 10 rearrangements. Carriers of translocations involving chromosome 10 rearrangements have a lower chance of producing normal or balanced embryos compared with the carriers with other rearrangements. The development of embryos obtained from the patients with chromosome 10 rearrangements was impaired and only a limited number of embryos developed to the blastocyst stage.