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Hanevik H.I.,Fertilitetsklinikken Sor | Tanbo T.,University of Oslo | Kahn J.A.,Fertilitetsklinikken Sor
Reproductive BioMedicine Online | Year: 2010

There is substantial variability in ovarian response to exogenous gonadotrophins in women undergoing ovarian stimulation for IVF. Genetic variation in signalling pathways of the ovary could influence ovarian stimulation outcome. Studies have shown a correlation between the serum concentration of anti-Müllerian hormone (AMH) and ovarian stimulation outcome. This paper present a retrospective case-controlled genetic association study designed to test the association between single nucleotide polymorphisms (SNP) in the AMH signalling pathway and two clinically important outcomes of ovarian stimulation: low and high response. Blood samples from 53 high responders, 38 low responders and 100 controls were analysed for eight SNP of interest. Odds ratios and 95% confidence intervals were estimated by a binary logistic regression model adjusting for age and body mass index. As far as is known, this is the first report on the influence of these SNP, present in approximately 19% of women, on ovarian stimulation outcome. No statistically significant association was found between any of the SNP studied and high or low response to ovarian stimulation. It seems unnecessary to detect these SNP when applying the serum concentration of AMH as a predictor of ovarian response to stimulation. Many infertile couples are treated by IVF. Part of this treatment is to pharmacologically stimulate the ovaries to develop many oocytes simultaneously. This process is called ovarian stimulation. Some women respond either too little (low responders) or too much (high responders) to ovarian stimulation. Both these situations are unfavourable to the woman. This study evaluates whether these chances of having one of these two outcomes of ovarian stimulationare influenced by variation in the gene for anti-Müllerian hormone (AMH) or its receptor. This is done by taking blood samples from three groups of patients: low responders, high responders and controls with a normal response. These blood samples were analysed to see if the variation in the genes for AMH or its receptor were different in the three groups. They were not, and so we conclude that the genetic variation that exists in the AMH and receptor signalling pathway is not a major determinant of ovarian stimulation outcome. © 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. Source


Hanevik H.I.,Fertilitetsklinikken Sor | Tanbo T.,University of Oslo | Kahn J.A.,Fertilitetsklinikken Sor
Gynecological Endocrinology | Year: 2012

Ovarian hyperstimulation syndrome (OHSS) is a serious complication following controlled ovarian hyperstimulation (COH) for in vitro fertilization. OHSS has a range of clinical features from mild abdominal distention to severe thromboembolic events. Several clinical manifestations of OHSS such as ascites and hemoconcentration can be attributed to increased vascular permeability. Vascular endothelial growth factor (VEGF) and its receptor VEGFR2 have been identified as an important signaling system in mediating this increase. There is considerable genetic variation in the VEGF/R2 signaling system. We present the first study to examine if single nucleotide polymorphisms (SNPs) in the genes encoding the VEGF/R2 signaling system are associated with OHSS following COH. Blood samples from 53 OHSS patients and 100 controls were analyzed for six SNPs of interest. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by a multivariate logistic regression model. We found an association between the VEGF +405cc genotype and OHSS (OR 3.4, 95% CI 1.0111.7). This finding requires confirmation from other patient populations. © 2012 Informa UK, Ltd. Source


Hanevik H.I.,Fertilitetsklinikken Sor | Tanbo T.,University of Oslo | Kahn J.A.,Fertilitetsklinikken Sor
Reproductive BioMedicine Online | Year: 2011

There is substantial variability in ovarian response to exogenous gonadotrophins in women undergoing ovarian stimulation for IVF. Genetic variation in signalling pathways of the ovary may influence ovarian stimulation outcome. One previous study showed an association between single nucleotide polymorphisms (SNP) in the gene for bone morphogenetic protein 15 (BMP15) and ovarian hyperstimulation syndrome (OHSS). This article presents a retrospective case-controlled genetic-association study designed to test the association between SNP in the BMP15 gene and two clinically important outcomes of ovarian stimulation: low and high response. Blood samples from 53 high responders, 38 low responders and 100 controls were analysed for five SNP of interest. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by a multivariate logistic regression model. We found an association between the BMP15 -9G allele and high response to ovarian stimulation (OR = 2.7, 95% CI = 1.3-5.7). This association confirms previous findings in a different population and strengthens the case for an association between this SNP and ovarian stimulation outcome. Many infertile couples are treated by IVF. Part of this treatment is to pharmacologically stimulate the ovaries to develop many oocytes simultaneously. This process is called ovarian stimulation. Some women respond either too little (low responders) or too much (high responders) to ovarian stimulation. Both these situations are unfavourable to the woman. This study evaluates whether the chance of having low or high response to ovarian stimulation is influenced by variations in the gene for bone morphogenetic protein 15 (BMP15). This was done by taking blood samples from three groups of patients: low responders, high responders and controls with a normal response. The blood samples were analysed to see if variations in the genes for BMP15 were unevenly distributed between the three groups. We found that patients having a variation in the BMP15 gene called -9G were more likely to have a high response to ovarian stimulation than controls. This confirms findings from a previous study in another population, and we conclude that the -9G variant in the BMP15 gene is likely to be associated with high response to ovarian stimulation. © 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. Source


Hanevik H.I.,Fertilitetsklinikken Sor | Tanbo T.,University of Oslo | Kahn J.A.,Fertilitetsklinikken Sor
Reproductive Biology and Endocrinology | Year: 2014

Background: The most common genetic variant of luteinizing hormone (LH), variant-betaLH, has a different bioactivity than the wildtype. Carrying the variant allele was associated with an increased consumption of exogenous gonadotropin to achieve optimal ovarian response for in vitro fertilization procedures (IVF). The aim of this study was to examine if variant-betaLH was also more common in patients with a poor ovarian response to exogenous gonadotropin which negatively influenced treatment outcome.Findings: 36 patients with poor ovarian response to ovarian stimulation for IVF and 98 controls with a normal response were genotyped for variant-betaLH using DNA sequencing. The carrier frequency in the control group was 17%. No association was found between poor ovarian response and variant-betaLH.Conclusions: Testing patients for variant-betaLH prior to IVF is unlikely to predict poor ovarian response. © 2014 Hanevik et al.; licensee BioMed Central Ltd. Source


Hanevik H.I.,Fertilitetsklinikken Sor | Isfoss B.L.,Telemark Hospital | Bergh A.,Fertilitetsklinikken Sor | Friberg M.,Fertilitetsklinikken Sor | Kahn J.A.,Fertilitetsklinikken Sor
Analytical and Quantitative Cytology and Histology | Year: 2010

OBJECTIVE: To examine whether simplified histopathologic criteria and a dedicated pathologist could influence the diagnostic accuracy of testicular biopsy. STUDY DESIGN: Original reports from general pathologists on 99 consecutive testicular biopsies were retrospectively classified according to reported presence or absence of mature spermatids. A dedicated pathologist rediagnosed the material blindly according to the same criterion. The resulting data were compared with testicular sperm extraction (TESE) results from the in vitro fertilization laboratory. RESULTS: General pathologists' diagnoses predicted TESE results with a positive predictive value (PPV) of 0.97 and a negative predictive value (NPV) of 0.78. The dedicated pathologist's diagnoses yielded a PPV of 1.0 and a significantly improved NPV of 0.96. CONCLUSION: Visualization of mature spermatids in a testicular biopsy is an excellent predictor of TESE results, especially in the hands of a dedicated pathologist. We therefore recommend simplified pathology reporting on testicular biopsies from azoospermic men and examination by a dedicated pathologist. © Science Printers and Publishers, Inc. Source

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