Infertility and Center

Ankara, Turkey

Infertility and Center

Ankara, Turkey
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Coughlan C.,Royal Hallamshire Hospital | Ledger W.,Royal Hospital for Women | Wang Q.,Sun Yat Sen University | Liu F.,Women and Children Hospital of Guangdong Province | And 6 more authors.
Reproductive BioMedicine Online | Year: 2014

Recurrent implantation failure refers to failure to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles in a woman under the age of 40 years. The failure to implant may be a consequence of embryo or uterine factors. Thorough investigations should be carried out to ascertain whether there is any underlying cause of the condition. Ovarian function should be assessed by measurement of antral follicle count, FSH and anti-Müllerian hormone. Increased sperm DNA fragmentation may be a contributory cause. Various uterine pathology including fibroids, endometrial polyps, congenital anomalies and intrauterine adhesions should be excluded by ultrasonography and hysteroscopy. Hydrosalpinges are a recognized cause of implantation failure and should be excluded by hysterosalpingogram; if necessary, laparoscopy should be performed to confirm or refute the diagnosis. Treatment offered should be evidence based, aimed at improving embryo quality or endometrial receptivity. Gamete donation or surrogacy may be necessary if there is no realistic chance of success with further IVF attempts. Recurrent implantation failure is an important cause of repeated IVF failure. It is estimated that approximately 10% of women seeking IVF treatment will experience this particular problem. It is a distressing condition for patients and frustrating for clinicians and scientists. In this review, we have discussed the definition and management of the possible underlying causes of recurrent implantation failure.


Elinati E.,University of Strasbourg | Kuentz P.,University of Strasbourg | Kuentz P.,Center Hospitalier University Of Besancon | Redin C.,University of Strasbourg | And 29 more authors.
Human Molecular Genetics | Year: 2012

To date, mutations in two genes, SPATA16 and DPY19L2, have been identified as responsible for a severe teratozoospermia, namely globozoospermia. The two initial descriptions of the DPY19L2 deletion lead to a very different rate of occurrence of this mutation among globospermic patients. In order to better estimate the contribution of DPY19L2 in globozoospermia, we screened a larger cohort including 64 globozoospermic patients. Twenty of the new patients were homozygous for the DPY19L2 deletion, and 7 were compound heterozygous for both this deletion and a point mutation. We also identified four additional mutated patients. The final mutation load in our cohort is 66.7% (36 out of 54). Out of 36 mutated patients, 69.4% are homozygous deleted, 19.4% heterozygous composite and 11.1% showed a homozygous point mutation. The mechanism underlying the deletion is a non-allelic homologous recombination (NAHR) between the flanking low-copy repeats. Here, we characterized a total of nine breakpoints for the DPY19L2 NAHR-driven deletion that clustered in two recombination hotspots, both containing direct repeat elements (AluSq2 in hotspot 1, THE1B in hotspot 2). Globozoospermia can be considered as a new genomic disorder. This study confirms that DPY19L2 is the major gene responsible for globozoospermia and enlarges the spectrum of possible mutations in the gene. This is a major finding and should contribute to the development of an efficient molecular diagnosis strategy for globozoospermia. © The Author 2012. Published by Oxford University Press. All rights reserved.


Kuentz P.,University of Strasbourg | Kuentz P.,Center Hospitalier University | Vanden Meerschaut F.,Ghent University | Elinati E.,University of Strasbourg | And 10 more authors.
Human Reproduction | Year: 2013

STUDY QUESTION: Does DPY19L2 status influence intracytoplasmic sperm injection (ICSI) outcomes with or without assisted oocyte activation (AOA)?SUMMARY ANSWERDPY19L2 mutations have no major impact on ICSI outcomes in globozoospermic patients.WHAT IS KNOWN ALREADYGlobozoospermia is a rare and severe teratozoospermia characterized by round-headed spermatozoa lacking an acrosome. Recently, it has been shown that DPY19L2 mutations can be found in a vast majority of, but not all, globozoospermic patients (66.7%). These patients suffer from primary infertility due to a sperm-related oocyte activation deficiency secondary to the absence of an acrosome that can be overcome by the application of AOA.STUDY DESIGN, SIZE, DURATIONCohort study, retrospective, 34 patients, 83 cycles.MATERIALS, SETTING, METHODSClinical and biologic data were collected from 29 patients mutated for DPY19L2 and 5 non-mutated patients. In total, 35 ICSI cycles using AOA and 48 conventional ICSI cycles were included in the analysis. Patients were divided into groups according to whether or not they were mutated for DPY19L2 and whether or not they received AOA. MAIN RESULTS AND THE ROLE OF CHANCE: Regardless of the presence of a DPY19L2 mutation, the fertilization rates with AOA are restored to normal when compared with conventional ICSI in our cohort of globozoospermic patients. Also, when performing ICSI plus AOA, both mutated and non-mutated cases have similar positive hCG rates, ongoing pregnancy rates and live birth rates per transfer. On the contrary, the fertilization rate in globozoospermic patients using conventional ICSI is correlated with the presence of a DPY19L2 mutation, with slightly better, although still very low, fertilization rates in patients carrying a DPY19L2 mutation. Nevertheless, when performing conventional ICSI, both mutated and non-mutated cases have similar very low positive hCG rates, ongoing pregnancy rates and live birth rates per transfer.LIMITATIONSA limitation of this study is the low number of included non-mutated cases. WIDER IMPLICATIONS OF THE FINDINGS: We propose a pathway for the clinical management of globozoospermic patients depending on the phenotype that includes several diagnostic and therapeutic steps. STUDY FUNDING/COMPETING INTEREST(S): None. © 2013 The Author.


Coughlan C.,Jessop Wing Assisted Conception Unit | Coughlan C.,Sun Yat Sen University | Coughlan C.,Infertility and Center | Coughlan C.,University of New South Wales | And 16 more authors.
Journal of Reproductive Medicine | Year: 2014

Objective: To examine factors affecting the outcome of the endometrial scratch in women with recurrent implantation failure. Study design: A total of 57 eligible patients with a history of recurrent implantation failure underwent an endometrial biopsy in the luteal phase of the menstrual cycle in the month immediately preceding the embryo transfer cycle. The comparative group consisted of a retrospective cohort of 66 women with recurrent implantation failure but without endometrial biopsy. There were no significant differences between the intervention and control groups in terms of age, follicle-stimulating hormone (FSH), free androgen index, anti-Müllerian hormone, body mass index, the number of embryos transferred, and the number of embryo transfer cycles. Results: The clinical pregnancy rate in the intervention group (53%) was significantly (p<0.001) higher than that of the control group (15%). The only predictive factor was FSH. Women with FSH ≤ 10 IU/L had a pregnancy rate of 57.8%, significantly (p<0.05) higher than that (20%) of women with FSH > 10 IU/L. Conclusion: Women with a normal FSH are more likely to derive benefit from endometrial scratch. © Journal of Reproductive Medicine®, Inc.


Molinari E.,University of Turin | Molinari E.,Infertility and Center | Evangelista F.,University of Turin | Racca C.,University of Turin | And 2 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2012

Purpose: To clarify if birefringent structures of human oocytes and embryos, measurable by polarized light microscopy, have any value in predicting the chance of pregnancy in human in vitro fertilization and may halp to identify the most competent oocytes and embryos. Methods: The inner layer of the zona pellucida (IL-ZP) and the meiotic spindle (MS) were analyzed by polarized light microscopy in 258 oocytes and in the 209 embryos deriving from them. Data obtained from 102 ICSI cycles with conception were compared with those obtained in 156 cycles without conception. The retardance and area of the IL-ZP, as well as the retardance, length of the major axis, and area of the MS were measured. Furthermore, polarized light microscopy parameters were related to the embryo morphological score by multiple regression analysis. Result(s): The mean area of the IL-ZP of both oocytes and embryos was significantly lower in conception than in nonconception cycles (p=0.0001 for oocytes and p=0.002 for embryos). The area of the IL-ZP in embryos was significantly, inversely related to the embryo morphological score (p=0.011). The area, the major axis length and the retarcance of theMS, as well as the retardance of the IL-ZP in oocytes and embryos were comparable in conception and non-conception cycles. Conclusion: The area of the IL-ZP of the human oocytes may represent a marker of oocyte competence, as oocytes with a low IL-ZP area are more frequently obtained in conception cycles. When measured in embryos, a low IL-ZP area identifies embryos with a high chance of implantation. © Springer Science+Business Media, LLC 2012.


PubMed | Royal Hospital for Women, Sun Yat Sen University, Monash IVF, Royal Hallamshire Hospital and 3 more.
Type: Journal Article | Journal: Reproductive biomedicine online | Year: 2014

Recurrent implantation failure refers to failure to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles in a woman under the age of 40 years. The failure to implant may be a consequence of embryo or uterine factors. Thorough investigations should be carried out to ascertain whether there is any underlying cause of the condition. Ovarian function should be assessed by measurement of antral follicle count, FSH and anti-Mullerian hormone. Increased sperm DNA fragmentation may be a contributory cause. Various uterine pathology including fibroids, endometrial polyps, congenital anomalies and intrauterine adhesions should be excluded by ultrasonography and hysteroscopy. Hydrosalpinges are a recognized cause of implantation failure and should be excluded by hysterosalpingogram; if necessary, laparoscopy should be performed to confirm or refute the diagnosis. Treatment offered should be evidence based, aimed at improving embryo quality or endometrial receptivity. Gamete donation or surrogacy may be necessary if there is no realistic chance of success with further IVF attempts.


Dondorp W.,Maastricht University | De Wert G.,Maastricht University | Pennings G.,Ghent University | Shenfield F.,University College London | And 4 more authors.
Human Reproduction | Year: 2013

This Task Force document revisits the debate about the ethics of sex selection for non-medical reasons in the light of relevant new technological developments. First, as a result of improvement of the Microsort® flow cytometry method, there is now a proven technique for preconception sex selection that can be combined both with IVF and IUI. Secondly, the scenario where new approaches that are currently being developed for preimplantation genetic screening (PGS) may lead to such screening becoming a routine part of all IVF treatment. In that scenario professionals will more often be confronted with parental requests for transfer of an embryo of a specific sex. Thirdly, the recent development of non-invasive prenatal testing based on cell-free fetal DNA in maternal plasma allows for easy and safe sex determination in the early stages of pregnancy. While stressing the new urgency that these developments give to the debate, the Task Force did not come to a unanimous position with regard to the acceptability of sex selection for non-medical reasons in the context of assisted reproduction. Whereas some think maintaining the current ban is the best approach, others are in favour of allowing sex selection for non-medical reasons under conditions that take account of societal concerns about the possible impact of the practice. By presenting these positions, the document reflects the different views about this issue that also exist in the field. Specific recommendations include the need for a wider delineation of accepted 'medical reasons' than in terms of avoiding a serious sex-linked disorder, and for a clarification of the legal position with regard to answering parental requests for 'additional sex selection' in the context of medically indicated preimplantation genetic diagnosis, or routine PGS. © 2013 The Author. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Dondorp W.,Maastricht University | De Wert G.,Maastricht University | Pennings G.,Ghent University | Shenfield F.,University College London | And 4 more authors.
Human Reproduction | Year: 2012

The recent introduction of oocyte vitrification has significantly advanced the outcome of oocyte cryopreservation, leading to clinical results comparable to those achieved in IVF using fresh oocytes, as reported by experienced centres. This has lead to new debate, both in the professional community and in society at large, about the acceptability of offering this technology to reproductively healthy women who want to cryopreserve their oocytes against the threat of time. Given the many demands calling for simultaneous realization in a relatively short period of their lives, many women who want to have children feel to be under considerable pressure. The option of oocyte cryopreservation may in fact give them more breathing space. In this document, it is concluded that the arguments against allowing this application of the technology are not convincing. The recommendations include the need for adequate information of women interested in oocyte cryopreservation, also in order to avoid raising false hopes. The message must remain that womens best chances of having a healthy child are through natural reproduction at a relative early age. Centres offering this service must have the necessary expertise to employ oocyte cryopreservation efficiently with the so far non-standardized protocols. As data about long-term safety is still lacking, centres also have a responsibility to contribute to the collection of these data. © 2012 The Autho.


Gurgan T.,Infertility and Center | Gurgan T.,Hacettepe University | Demirol A.,Infertility and Center | Guven S.,Karadeniz Technical University | And 3 more authors.
Fertility and Sterility | Year: 2011

Objective: To evaluate the effectiveness of IV calcium infusion on prevention of ovarian hyperstimulation syndrome (OHSS) in patients with polycystic ovary syndrome undergoing assisted reproductive techniques cycles. Design: A retrospective comparative study. Setting: Assisted reproduction techniques centre in Turkey. Patient(s): Four hundred fifty-five women with high risk for OHSS. Intervention(s): The patients in group I (n = 84) were administered IV calcium gluconate for prevention of OHSS, and the patients in group II (n = 371) comprised the control group, with no manipulation for prevention of OHSS and were age- and body mass index-matched with the study group. Main Outcome Measure(s): Ovarian hyperstimulation syndrome rate, clinical pregnancy rate. Result(s): Mean (±SD) ages of the women in the calcium infusion group (group I) and the control group (group II) were comparable (30.5 ± 4.3 vs. 31.4 ± 3.9, respectively). Ovarian hyperstimulation syndrome was found in 16.2% (60 patients) in group II, whereas in group I, only 3 patients (3.6%) developed OHSS. Interestingly, all the hyperstimulation cases in group I were mild, and there was no severe effect. Implantation rates were similar in both groups. Furthermore, we obtained clinical pregnancy in nearly 40.5% in group I and 28.8% in group II. The live-birth rate was 38.1% in the calcium infusion group and 24.8% in the control group. Conclusion(s): Intravenous calcium infusion resulted in a significantly lower rate of development of OHSS for patients with polycystic ovary syndrome and high risk of OHSS. This novel therapy may be used for prevention of OHSS effectively. © 2011 by American Society for Reproductive Medicine.


Demirol A.,Infertility and Center | Guven S.,Karadeniz Technical University | Benkhalifa M.,Infertility and Center | Benkhalifa M.,Atl R And D Reproductive Biology And Genetics Laboratory | And 3 more authors.
Reproductive BioMedicine Online | Year: 2010

It is well established that ovarian hyperstimulation syndrome (OHSS) is more frequent in patients with polycystic ovarian syndrome. In-vitro maturation (IVM) of immature oocytes presents a potential alternative for the fertility treatment and prevention of OHSS for these patients. This report describes the case of a 26-year old woman with a successful pregnancy and delivery following the transfer of frozen-thawed embryos derived from in-vitro matured oocytes. She had three failed cycles of ovarian stimulation (using low-dose step-up gonadotrophin protocol) with or without intrauterine insemination cycles, an ovulation-induction cycle with luteal long protocol, two fresh IVM cycle and one frozen-thawed IVM cycle. During the IVF cycle, she developed moderate OHSS and required hospitalization for 3 weeks. Following four unsuccessful IVF or IVM cycles, 15 months after the last cryopreservation, six fertilized oocytes were thawed for a scheduled embryo transfer. Following thawing, four fertilized oocytes survived and cleaved. Four frozen-thawed embryos were transferred. Six weeks after embryo transfer an ongoing intrauterine single pregnancy with fetal heartbeat was confirmed by transvaginal ultrasound. An uneventful pregnancy and delivery via Caesarean section at 39 weeks resulted in the birth of a normal healthy infant. © 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

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