The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
Johan Smitz - One of the best experts on this subject based on the ideXlab platform.
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cumulus cell gene expression predicts better cleavage stage embryo or blastocyst development and pregnancy for icsi patients
Human Reproduction, 2011Co-Authors: Sandra Wathlet, Ingrid Segers, Tom Adriaenssens, G Verheyen, H Van De Velde, Wim Coucke, P Devroey, Johan SmitzAbstract:background: Cumulus cell (CC) gene expression is suggested as a non-invasive analysis method to predict oocyte competence. There are, however, important between-patient differences in CC gene expression. These can be compensated when expression results are combined with patient and cycle characteristics using a multiple regression analysis model. methods: From ICSI patients stimulated with GnRH antagonist and recombinant FSH (n ¼ 25) or GnRH agonist and highly purified menotrophin (n ¼ 20), CC were collected and oocytes were individually fertilized and cultured. CC were analyzed for the expression of Syndecan 4 (SDC4), Prostaglandin-endoperoxide synthase 2 (PTGS2), Versican (VCAN), Activated leukocyte cell adhesion molecule, Gremlin 1, transient receptor potential cation channel, subfamily M, member 7 (TRPM7), Calmodulin 2 and Inositol 1,4,5-trisphosphate 3-kinase A (ITPKA) using quantitative PCR. Results were analyzed in relation to the stimulation protocol. Within-patient variation in gene expression was related to oocyte maturity and developmental potential. Models predictive for normal embryo or blastocyst development and pregnancy in single embryo transfer cycles were developed. results: Mature oocytes have higher PTGS2 and lower VCAN expression in their cumulus. All genes except VCAN had a positive correlation with good embryo or blastocyst morphology and were used to develop predictive models for embryo or blastocyst development (P , 0.01). Specific models were obtained for the two stimulation protocols. In both groups, better cleavage-stage embryo prediction relied on TRPM7 and ITPKA expression and pregnancy prediction relied on SDC4 and VCAN expression. In the current data set, the use of CC expression for pregnancy prediction resulted in a sensitivity of .70% and a specificity of .90%. conclusions: Multivariable models based on CC gene expression can be used to predict embryo development and pregnancy.
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differences in collagen expression in cumulus cells after exposure to highly purified Menotropin or recombinant follicle stimulating hormone in a mouse follicle culture model
Biology of Reproduction, 2009Co-Authors: Tom Adriaenssens, Claire Mazoyer, Ingrid Segers, Sandra Wathlet, Johan SmitzAbstract:Extracellular matrix (ECM) formation by cumulus cells is an important process that determines fertilization and embryo quality. Several collagen types are present in the ovarian follicular ECM and are related to proliferation, steroidogenesis, and luteinization. In vitro mouse follicles can optimally grow and provide developmentally competent oocytes with 10 IU/L recombinant follicle-stimulating hormone (rFSH). As a model for superovulation, experiments with 100 IU/L rFSH or 100 IU/L highly purified Menotropin (HP-hMG) exposure during antral growth were undertaken. Col4a1, Col4a2, and Col6a2 expression levels were analyzed at three time points during antral growth and at a 4-h interval up to 16 h after ovulation induction using quantitative PCR. The presence and induction of the collagen mRNA and protein were confirmed in cumulus from in vivo- and in vitro-grown follicles, and TGFBs 1 and 2 were assayed as potential regulators. The study revealed that exposure to 100 IU/L FSH, as in both superovulation conditions, significantly influenced the follicle morphology and slowed down nuclear maturation and mucification (P < 0.05). This coincided with an increased expression of the three collagens in the cumulus-oocyte complex at the end of antral growth and in the first hours following the ovulatory dose of human chorionic gonadotropin (P < 0.05). The increased expression might reflect a differentiation but is most likely due to a precocious luteinization of the cumulus. Growth in HP-hMG resulted in higher Tgfb1 mRNA and protein levels, fewer COCs with an increased collagen expression and with a more synchronous nuclear maturation. This suggests that the presence of luteinizing hormone activity tempered the effect of the elevated FSH dose.
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differences in collagen expression in cumulus cells after exposure to highly purified Menotropin or recombinant follicle stimulating hormone in a mouse follicle culture model short title ovarian stimulation effect on cc gene expression summary senten
2009Co-Authors: Claire Mazoyer, Ingrid Segers, Sandra Wathlet, Johan Smitz, Tom AdriaenssensAbstract:Extra cellular matrix formation (ECM) by cumulus cells is an important process that determines fertilization and embryo quality. Several collagen types are present in the ovarian follicular ECM and are related to proliferation, steroidogenesis and luteinization. In vitro mouse follicles can optimally grow and provide developmentally competent oocytes with 10IU/L rFSH. As a model for superovulation, experiments with 100IU/L rFSH or 100IU/L HP-hMG exposure during the antral growth were undertaken. Col4a1, Col4a2 and Col6a2 expression levels were analyzed at 3 time points during antral growth and at a 4 hour interval up to 16 hours after ovulation induction, using QPCR. The presence and induction of the collagen mRNA and protein were confirmed in cumulus from in vivo and in vitro grown follicles and TGFB1 and 2 were assayed as potential regulators. The study revealed that exposure to 100IU/L FSH, as in both superovulation conditions, significantly influenced the follicle morphology and slowed down nuclear maturation and mucification (p<0.05). This coincided with an increased expression of the 3 collagens in the cumulus oocyte complex (COC) at the end of antral growth and in the first hours following the ovulatory dose of hCG (p<0.05). The increased expression might reflect a differentiation but is most likely due to a precocious luteinization of the cumulus. Growth in HP-hMG resulted in higher Tgfb1 mRNA and protein levels, less COC with an increased collagen expression and with a more synchronous nuclear maturation. This suggests that the presence of LH-activity tempered the effect of the elevated FSH dose.
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differences in collagen expression in cumulus cells after exposure to highly purified Menotropin or recombinant follicle stimulating hormone in a mouse follicle culture model short title ovarian stimulation effect on cc gene expression summary senten
2009Co-Authors: Claire Mazoyer, Ingrid Segers, Sandra Wathlet, Johan Smitz, Tom AdriaenssensAbstract:Extra cellular matrix formation (ECM) by cumulus cells is an important process that determines fertilization and embryo quality. Several collagen types are present in the ovarian follicular ECM and are related to proliferation, steroidogenesis and luteinization. In vitro mouse follicles can optimally grow and provide developmentally competent oocytes with 10IU/L rFSH. As a model for superovulation, experiments with 100IU/L rFSH or 100IU/L HP-hMG exposure during the antral growth were undertaken. Col4a1, Col4a2 and Col6a2 expression levels were analyzed at 3 time points during antral growth and at a 4 hour interval up to 16 hours after ovulation induction, using QPCR. The presence and induction of the collagen mRNA and protein were confirmed in cumulus from in vivo and in vitro grown follicles and TGFB1 and 2 were assayed as potential regulators. The study revealed that exposure to 100IU/L FSH, as in both superovulation conditions, significantly influenced the follicle morphology and slowed down nuclear maturation and mucification (p<0.05). This coincided with an increased expression of the 3 collagens in the cumulus oocyte complex (COC) at the end of antral growth and in the first hours following the ovulatory dose of hCG (p<0.05). The increased expression might reflect a differentiation but is most likely due to a precocious luteinization of the cumulus. Growth in HP-hMG resulted in higher Tgfb1 mRNA and protein levels, less COC with an increased collagen expression and with a more synchronous nuclear maturation. This suggests that the presence of LH-activity tempered the effect of the elevated FSH dose.
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endocrine profile in serum and follicular fluid differs after ovarian stimulation with hp hmg or recombinant fsh in ivf patients
Human Reproduction, 2006Co-Authors: Johan Smitz, P Devroey, Anders Nyboe Andersen, Joancarles ArceAbstract:BACKGROUND: Highly purified menotrophin (HP-hMG) has been associated with fewer oocytes retrieved and a higher proportion of top-quality embryos compared with recombinant FSH (rFSH). METHODS: A randomized, assessor-blind, multinational trial in 731 women undergoing IVF after stimulation with HP-hMG (MENOPUR) (n = 363) or rFSH (GONAL-F) (n = 368) following a long GnRH agonist protocol was conducted. Blood was collected before, during and after stimulation. Fluid was collected from follicles ≥17 mm. RESULTS: Serum androstenedione, total testosterone and free androgen index (FAI) were higher (P < 0.001) with HP-hMG than with rFSH after starting stimulation. At the end of stimulation, serum estradiol was higher (P = 0.031) with HP-hMG, whereas progesterone was higher (P < 0.001) with rFSH, even after adjusting for ovarian response. Serum LH was not different between treatments. Mean mid- and end-follicular hCG levels in the HP-hMG group were 2.5 and 2.9 IU/I, respectively. Follicular fluid levels of FSH, LH, hCG, androstenedione, testosterone, FAI and estradiol and ratios of estradiol: androstenedione, estradiol: total testosterone and estradiol: progesterone were higher (P < 0.001) with HP-hMG, whereas progesterone was higher (P < 0.001) with rFSH. CONCLUSION: Major differences in serum and follicular fluid endocrine profile exist after stimulation with HP-hMG or rFSH. Exogenous LH activity induces a differential endocrine environment influencing oocyte quantity and quality, which may be of relevance for clinical outcome.
Tom Adriaenssens - One of the best experts on this subject based on the ideXlab platform.
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cumulus cell gene expression predicts better cleavage stage embryo or blastocyst development and pregnancy for icsi patients
Human Reproduction, 2011Co-Authors: Sandra Wathlet, Ingrid Segers, Tom Adriaenssens, G Verheyen, H Van De Velde, Wim Coucke, P Devroey, Johan SmitzAbstract:background: Cumulus cell (CC) gene expression is suggested as a non-invasive analysis method to predict oocyte competence. There are, however, important between-patient differences in CC gene expression. These can be compensated when expression results are combined with patient and cycle characteristics using a multiple regression analysis model. methods: From ICSI patients stimulated with GnRH antagonist and recombinant FSH (n ¼ 25) or GnRH agonist and highly purified menotrophin (n ¼ 20), CC were collected and oocytes were individually fertilized and cultured. CC were analyzed for the expression of Syndecan 4 (SDC4), Prostaglandin-endoperoxide synthase 2 (PTGS2), Versican (VCAN), Activated leukocyte cell adhesion molecule, Gremlin 1, transient receptor potential cation channel, subfamily M, member 7 (TRPM7), Calmodulin 2 and Inositol 1,4,5-trisphosphate 3-kinase A (ITPKA) using quantitative PCR. Results were analyzed in relation to the stimulation protocol. Within-patient variation in gene expression was related to oocyte maturity and developmental potential. Models predictive for normal embryo or blastocyst development and pregnancy in single embryo transfer cycles were developed. results: Mature oocytes have higher PTGS2 and lower VCAN expression in their cumulus. All genes except VCAN had a positive correlation with good embryo or blastocyst morphology and were used to develop predictive models for embryo or blastocyst development (P , 0.01). Specific models were obtained for the two stimulation protocols. In both groups, better cleavage-stage embryo prediction relied on TRPM7 and ITPKA expression and pregnancy prediction relied on SDC4 and VCAN expression. In the current data set, the use of CC expression for pregnancy prediction resulted in a sensitivity of .70% and a specificity of .90%. conclusions: Multivariable models based on CC gene expression can be used to predict embryo development and pregnancy.
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differences in collagen expression in cumulus cells after exposure to highly purified Menotropin or recombinant follicle stimulating hormone in a mouse follicle culture model
Biology of Reproduction, 2009Co-Authors: Tom Adriaenssens, Claire Mazoyer, Ingrid Segers, Sandra Wathlet, Johan SmitzAbstract:Extracellular matrix (ECM) formation by cumulus cells is an important process that determines fertilization and embryo quality. Several collagen types are present in the ovarian follicular ECM and are related to proliferation, steroidogenesis, and luteinization. In vitro mouse follicles can optimally grow and provide developmentally competent oocytes with 10 IU/L recombinant follicle-stimulating hormone (rFSH). As a model for superovulation, experiments with 100 IU/L rFSH or 100 IU/L highly purified Menotropin (HP-hMG) exposure during antral growth were undertaken. Col4a1, Col4a2, and Col6a2 expression levels were analyzed at three time points during antral growth and at a 4-h interval up to 16 h after ovulation induction using quantitative PCR. The presence and induction of the collagen mRNA and protein were confirmed in cumulus from in vivo- and in vitro-grown follicles, and TGFBs 1 and 2 were assayed as potential regulators. The study revealed that exposure to 100 IU/L FSH, as in both superovulation conditions, significantly influenced the follicle morphology and slowed down nuclear maturation and mucification (P < 0.05). This coincided with an increased expression of the three collagens in the cumulus-oocyte complex at the end of antral growth and in the first hours following the ovulatory dose of human chorionic gonadotropin (P < 0.05). The increased expression might reflect a differentiation but is most likely due to a precocious luteinization of the cumulus. Growth in HP-hMG resulted in higher Tgfb1 mRNA and protein levels, fewer COCs with an increased collagen expression and with a more synchronous nuclear maturation. This suggests that the presence of luteinizing hormone activity tempered the effect of the elevated FSH dose.
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differences in collagen expression in cumulus cells after exposure to highly purified Menotropin or recombinant follicle stimulating hormone in a mouse follicle culture model short title ovarian stimulation effect on cc gene expression summary senten
2009Co-Authors: Claire Mazoyer, Ingrid Segers, Sandra Wathlet, Johan Smitz, Tom AdriaenssensAbstract:Extra cellular matrix formation (ECM) by cumulus cells is an important process that determines fertilization and embryo quality. Several collagen types are present in the ovarian follicular ECM and are related to proliferation, steroidogenesis and luteinization. In vitro mouse follicles can optimally grow and provide developmentally competent oocytes with 10IU/L rFSH. As a model for superovulation, experiments with 100IU/L rFSH or 100IU/L HP-hMG exposure during the antral growth were undertaken. Col4a1, Col4a2 and Col6a2 expression levels were analyzed at 3 time points during antral growth and at a 4 hour interval up to 16 hours after ovulation induction, using QPCR. The presence and induction of the collagen mRNA and protein were confirmed in cumulus from in vivo and in vitro grown follicles and TGFB1 and 2 were assayed as potential regulators. The study revealed that exposure to 100IU/L FSH, as in both superovulation conditions, significantly influenced the follicle morphology and slowed down nuclear maturation and mucification (p<0.05). This coincided with an increased expression of the 3 collagens in the cumulus oocyte complex (COC) at the end of antral growth and in the first hours following the ovulatory dose of hCG (p<0.05). The increased expression might reflect a differentiation but is most likely due to a precocious luteinization of the cumulus. Growth in HP-hMG resulted in higher Tgfb1 mRNA and protein levels, less COC with an increased collagen expression and with a more synchronous nuclear maturation. This suggests that the presence of LH-activity tempered the effect of the elevated FSH dose.
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differences in collagen expression in cumulus cells after exposure to highly purified Menotropin or recombinant follicle stimulating hormone in a mouse follicle culture model short title ovarian stimulation effect on cc gene expression summary senten
2009Co-Authors: Claire Mazoyer, Ingrid Segers, Sandra Wathlet, Johan Smitz, Tom AdriaenssensAbstract:Extra cellular matrix formation (ECM) by cumulus cells is an important process that determines fertilization and embryo quality. Several collagen types are present in the ovarian follicular ECM and are related to proliferation, steroidogenesis and luteinization. In vitro mouse follicles can optimally grow and provide developmentally competent oocytes with 10IU/L rFSH. As a model for superovulation, experiments with 100IU/L rFSH or 100IU/L HP-hMG exposure during the antral growth were undertaken. Col4a1, Col4a2 and Col6a2 expression levels were analyzed at 3 time points during antral growth and at a 4 hour interval up to 16 hours after ovulation induction, using QPCR. The presence and induction of the collagen mRNA and protein were confirmed in cumulus from in vivo and in vitro grown follicles and TGFB1 and 2 were assayed as potential regulators. The study revealed that exposure to 100IU/L FSH, as in both superovulation conditions, significantly influenced the follicle morphology and slowed down nuclear maturation and mucification (p<0.05). This coincided with an increased expression of the 3 collagens in the cumulus oocyte complex (COC) at the end of antral growth and in the first hours following the ovulatory dose of hCG (p<0.05). The increased expression might reflect a differentiation but is most likely due to a precocious luteinization of the cumulus. Growth in HP-hMG resulted in higher Tgfb1 mRNA and protein levels, less COC with an increased collagen expression and with a more synchronous nuclear maturation. This suggests that the presence of LH-activity tempered the effect of the elevated FSH dose.
P Devroey - One of the best experts on this subject based on the ideXlab platform.
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a randomized assessor blind trial comparing highly purified hmg and recombinant fsh in a gnrh antagonist cycle with compulsory single blastocyst transfer
Fertility and Sterility, 2012Co-Authors: P Devroey, Antonio Pellicer, Anders Nyboe AndersenAbstract:Objective To compare the efficacy and safety of highly purified Menotropin (hphMG) and recombinant FSH (rFSH) for controlled ovarian stimulation in a GnRH antagonist cycle with compulsory single-blastocyst transfer. Design Randomized, open-label, assessor-blind, parallel groups, multicenter, noninferiority trial. Setting Twenty-five infertility centers in seven countries. Patient(s) Seven hundred forty-nine women. Intervention(s) Controlled ovarian stimulation with hphMG or rFSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer on day 5 in one fresh or subsequent frozen blastocyst replacement in natural cycles initiated within 1 year of each patient's start of treatment. Main Outcome Measure(s) Ongoing pregnancy (primary end point) and live birth rates, as well as pharmacodynamic parameters. Result(s) The ongoing pregnancy rate after a fresh cycle was 30% with hphMG versus 27% with rFSH for the per-protocol (PP) population and 29% versus 27% for the intention-to-treat (ITT) population. Noninferiority of hphMG compared to rFSH was established. Considering frozen cycles initiated within 1 year, the cumulative live birth rate for a single stimulation cycle was 40% and 38% for women treated with hphMG and rFSH, respectively (both PP and ITT). Significant differences in pharmacodynamic end points were found between the two gonadotropin preparations. Conclusion(s) Highly purified hMG is at least as effective as rFSH in GnRH antagonist cycles with compulsory single-blastocyst transfer. Clinical Trial Registration Number NCT00884221.
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cumulus cell gene expression predicts better cleavage stage embryo or blastocyst development and pregnancy for icsi patients
Human Reproduction, 2011Co-Authors: Sandra Wathlet, Ingrid Segers, Tom Adriaenssens, G Verheyen, H Van De Velde, Wim Coucke, P Devroey, Johan SmitzAbstract:background: Cumulus cell (CC) gene expression is suggested as a non-invasive analysis method to predict oocyte competence. There are, however, important between-patient differences in CC gene expression. These can be compensated when expression results are combined with patient and cycle characteristics using a multiple regression analysis model. methods: From ICSI patients stimulated with GnRH antagonist and recombinant FSH (n ¼ 25) or GnRH agonist and highly purified menotrophin (n ¼ 20), CC were collected and oocytes were individually fertilized and cultured. CC were analyzed for the expression of Syndecan 4 (SDC4), Prostaglandin-endoperoxide synthase 2 (PTGS2), Versican (VCAN), Activated leukocyte cell adhesion molecule, Gremlin 1, transient receptor potential cation channel, subfamily M, member 7 (TRPM7), Calmodulin 2 and Inositol 1,4,5-trisphosphate 3-kinase A (ITPKA) using quantitative PCR. Results were analyzed in relation to the stimulation protocol. Within-patient variation in gene expression was related to oocyte maturity and developmental potential. Models predictive for normal embryo or blastocyst development and pregnancy in single embryo transfer cycles were developed. results: Mature oocytes have higher PTGS2 and lower VCAN expression in their cumulus. All genes except VCAN had a positive correlation with good embryo or blastocyst morphology and were used to develop predictive models for embryo or blastocyst development (P , 0.01). Specific models were obtained for the two stimulation protocols. In both groups, better cleavage-stage embryo prediction relied on TRPM7 and ITPKA expression and pregnancy prediction relied on SDC4 and VCAN expression. In the current data set, the use of CC expression for pregnancy prediction resulted in a sensitivity of .70% and a specificity of .90%. conclusions: Multivariable models based on CC gene expression can be used to predict embryo development and pregnancy.
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endocrine profile in serum and follicular fluid differs after ovarian stimulation with hp hmg or recombinant fsh in ivf patients
Human Reproduction, 2006Co-Authors: Johan Smitz, P Devroey, Anders Nyboe Andersen, Joancarles ArceAbstract:BACKGROUND: Highly purified menotrophin (HP-hMG) has been associated with fewer oocytes retrieved and a higher proportion of top-quality embryos compared with recombinant FSH (rFSH). METHODS: A randomized, assessor-blind, multinational trial in 731 women undergoing IVF after stimulation with HP-hMG (MENOPUR) (n = 363) or rFSH (GONAL-F) (n = 368) following a long GnRH agonist protocol was conducted. Blood was collected before, during and after stimulation. Fluid was collected from follicles ≥17 mm. RESULTS: Serum androstenedione, total testosterone and free androgen index (FAI) were higher (P < 0.001) with HP-hMG than with rFSH after starting stimulation. At the end of stimulation, serum estradiol was higher (P = 0.031) with HP-hMG, whereas progesterone was higher (P < 0.001) with rFSH, even after adjusting for ovarian response. Serum LH was not different between treatments. Mean mid- and end-follicular hCG levels in the HP-hMG group were 2.5 and 2.9 IU/I, respectively. Follicular fluid levels of FSH, LH, hCG, androstenedione, testosterone, FAI and estradiol and ratios of estradiol: androstenedione, estradiol: total testosterone and estradiol: progesterone were higher (P < 0.001) with HP-hMG, whereas progesterone was higher (P < 0.001) with rFSH. CONCLUSION: Major differences in serum and follicular fluid endocrine profile exist after stimulation with HP-hMG or rFSH. Exogenous LH activity induces a differential endocrine environment influencing oocyte quantity and quality, which may be of relevance for clinical outcome.
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similar ovulation rates but different follicular development with highly purified menotrophin compared with recombinant fsh in who group ii anovulatory infertility a randomized controlled study
Human Reproduction, 2006Co-Authors: Peter Platteau, P Devroey, Anders Nyboe Andersen, Adam H Balen, P Sorensen, L Helmgaard, Joancarles ArceAbstract:BACKGROUND: The contribution of the LH activity in menotrophin preparations for ovulation induction has been investigated in small trials conducted versus FSH preparations. The objective of this study was to demonstrate non-inferiority of highly purified urinary menotrophin (HP-HMG) versus recombinant FSH (rFSH) with respect to the primary outcome measure, ovulation rate. METHODS: This was a randomized, open-label, assessor-blind, multinational study. Women with anovulatory infertility WHO Group II and resistant to clomiphene citrate were randomized (computer-generated list) to stimulation with HP-HMG (n = 91) or rFSH (n = 93) using a low-dose step-up protocol. RESULTS: The ovulation rate was 85.7% with HP-HMG and 85.5% with rFSH (per-protocol population), and non-inferiority was demonstrated. Significantly fewer intermediate-sized follicles were observed in the HP-HMG group (P < 0.05). The singleton live birth rate was comparable between the two groups. The frequency of ovarian hyperstimulation syndrome and/or cancellation due to excessive response was 2.2% with HP-HMG and 9.8% with rFSH (P = 0.058). CONCLUSIONS: Stimulation with HP-HMG is associated with ovulation rates at least as good as a rFSH in anovulatory WHO Group II women. LH activity modifies follicular development so that fewer intermediate-sized follicles develop. This could have a positive impact on the safety of ovulation induction protocols.
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clinical outcome following stimulation with highly purified hmg or recombinant fsh in patients undergoing ivf a randomized assessor blind controlled trial
Human Reproduction Update, 2006Co-Authors: Anders Nyboe Andersen, P Devroey, J C ArceAbstract:BACKGROUND: LH activity may influence treatment response and outcome in IVF cycles. METHODS: A randomized, assessor-blind, multinational trial compared ongoing pregnancy rates (primary end-point) in 731 women undergoing IVF after stimulation with highly purified menotrophin (HP-hMG) (n = 363) or recombinant FSH (rFSH) (n = 368) following a long GnRH agonist protocol. Patients received identical pre- and post-randomization interventions. One or two embryos were transferred on day 3. RESULTS: More oocytes were retrieved (P < 0.001) after rFSH treatment (11.8) compared with HP-hMG treatment (10.0), but a higher proportion developed into top-quality embryos (P = 0.044) with HP-hMG (11.3%) than with rFSH (9.0%). At the end of stimulation, lower estradiol (E 2 ) (P = 0.031) and higher progesterone (P < 0.001) levels were found with rFSH, even after adjusting for follicular response. The distribution of hypo-, iso- and hyper-echogenic endometrium showed a significant (P = 0.023) shift towards the hyperechogenic pattern after rFSH treatment. The ongoing pregnancy rate per cycle was 27% with HP-hMG and 22% with rFSH [odds ratio (95% confidence interval): 1.25 (0.89-1.75)]. CONCLUSION: Superiority of HP-hMG over rFSH in ongoing pregnancy rate could not be concluded from this study, but non-inferiority was established. Pharmacodynamic differences in follicular development, oocyte/embryo quality, endocrine response and endometrial echogenicity exist between HP-hMG and rFSH preparations, which may be relevant for treatment outcome.
Sandra Wathlet - One of the best experts on this subject based on the ideXlab platform.
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cumulus cell gene expression predicts better cleavage stage embryo or blastocyst development and pregnancy for icsi patients
Human Reproduction, 2011Co-Authors: Sandra Wathlet, Ingrid Segers, Tom Adriaenssens, G Verheyen, H Van De Velde, Wim Coucke, P Devroey, Johan SmitzAbstract:background: Cumulus cell (CC) gene expression is suggested as a non-invasive analysis method to predict oocyte competence. There are, however, important between-patient differences in CC gene expression. These can be compensated when expression results are combined with patient and cycle characteristics using a multiple regression analysis model. methods: From ICSI patients stimulated with GnRH antagonist and recombinant FSH (n ¼ 25) or GnRH agonist and highly purified menotrophin (n ¼ 20), CC were collected and oocytes were individually fertilized and cultured. CC were analyzed for the expression of Syndecan 4 (SDC4), Prostaglandin-endoperoxide synthase 2 (PTGS2), Versican (VCAN), Activated leukocyte cell adhesion molecule, Gremlin 1, transient receptor potential cation channel, subfamily M, member 7 (TRPM7), Calmodulin 2 and Inositol 1,4,5-trisphosphate 3-kinase A (ITPKA) using quantitative PCR. Results were analyzed in relation to the stimulation protocol. Within-patient variation in gene expression was related to oocyte maturity and developmental potential. Models predictive for normal embryo or blastocyst development and pregnancy in single embryo transfer cycles were developed. results: Mature oocytes have higher PTGS2 and lower VCAN expression in their cumulus. All genes except VCAN had a positive correlation with good embryo or blastocyst morphology and were used to develop predictive models for embryo or blastocyst development (P , 0.01). Specific models were obtained for the two stimulation protocols. In both groups, better cleavage-stage embryo prediction relied on TRPM7 and ITPKA expression and pregnancy prediction relied on SDC4 and VCAN expression. In the current data set, the use of CC expression for pregnancy prediction resulted in a sensitivity of .70% and a specificity of .90%. conclusions: Multivariable models based on CC gene expression can be used to predict embryo development and pregnancy.
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differences in collagen expression in cumulus cells after exposure to highly purified Menotropin or recombinant follicle stimulating hormone in a mouse follicle culture model
Biology of Reproduction, 2009Co-Authors: Tom Adriaenssens, Claire Mazoyer, Ingrid Segers, Sandra Wathlet, Johan SmitzAbstract:Extracellular matrix (ECM) formation by cumulus cells is an important process that determines fertilization and embryo quality. Several collagen types are present in the ovarian follicular ECM and are related to proliferation, steroidogenesis, and luteinization. In vitro mouse follicles can optimally grow and provide developmentally competent oocytes with 10 IU/L recombinant follicle-stimulating hormone (rFSH). As a model for superovulation, experiments with 100 IU/L rFSH or 100 IU/L highly purified Menotropin (HP-hMG) exposure during antral growth were undertaken. Col4a1, Col4a2, and Col6a2 expression levels were analyzed at three time points during antral growth and at a 4-h interval up to 16 h after ovulation induction using quantitative PCR. The presence and induction of the collagen mRNA and protein were confirmed in cumulus from in vivo- and in vitro-grown follicles, and TGFBs 1 and 2 were assayed as potential regulators. The study revealed that exposure to 100 IU/L FSH, as in both superovulation conditions, significantly influenced the follicle morphology and slowed down nuclear maturation and mucification (P < 0.05). This coincided with an increased expression of the three collagens in the cumulus-oocyte complex at the end of antral growth and in the first hours following the ovulatory dose of human chorionic gonadotropin (P < 0.05). The increased expression might reflect a differentiation but is most likely due to a precocious luteinization of the cumulus. Growth in HP-hMG resulted in higher Tgfb1 mRNA and protein levels, fewer COCs with an increased collagen expression and with a more synchronous nuclear maturation. This suggests that the presence of luteinizing hormone activity tempered the effect of the elevated FSH dose.
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differences in collagen expression in cumulus cells after exposure to highly purified Menotropin or recombinant follicle stimulating hormone in a mouse follicle culture model short title ovarian stimulation effect on cc gene expression summary senten
2009Co-Authors: Claire Mazoyer, Ingrid Segers, Sandra Wathlet, Johan Smitz, Tom AdriaenssensAbstract:Extra cellular matrix formation (ECM) by cumulus cells is an important process that determines fertilization and embryo quality. Several collagen types are present in the ovarian follicular ECM and are related to proliferation, steroidogenesis and luteinization. In vitro mouse follicles can optimally grow and provide developmentally competent oocytes with 10IU/L rFSH. As a model for superovulation, experiments with 100IU/L rFSH or 100IU/L HP-hMG exposure during the antral growth were undertaken. Col4a1, Col4a2 and Col6a2 expression levels were analyzed at 3 time points during antral growth and at a 4 hour interval up to 16 hours after ovulation induction, using QPCR. The presence and induction of the collagen mRNA and protein were confirmed in cumulus from in vivo and in vitro grown follicles and TGFB1 and 2 were assayed as potential regulators. The study revealed that exposure to 100IU/L FSH, as in both superovulation conditions, significantly influenced the follicle morphology and slowed down nuclear maturation and mucification (p<0.05). This coincided with an increased expression of the 3 collagens in the cumulus oocyte complex (COC) at the end of antral growth and in the first hours following the ovulatory dose of hCG (p<0.05). The increased expression might reflect a differentiation but is most likely due to a precocious luteinization of the cumulus. Growth in HP-hMG resulted in higher Tgfb1 mRNA and protein levels, less COC with an increased collagen expression and with a more synchronous nuclear maturation. This suggests that the presence of LH-activity tempered the effect of the elevated FSH dose.
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differences in collagen expression in cumulus cells after exposure to highly purified Menotropin or recombinant follicle stimulating hormone in a mouse follicle culture model short title ovarian stimulation effect on cc gene expression summary senten
2009Co-Authors: Claire Mazoyer, Ingrid Segers, Sandra Wathlet, Johan Smitz, Tom AdriaenssensAbstract:Extra cellular matrix formation (ECM) by cumulus cells is an important process that determines fertilization and embryo quality. Several collagen types are present in the ovarian follicular ECM and are related to proliferation, steroidogenesis and luteinization. In vitro mouse follicles can optimally grow and provide developmentally competent oocytes with 10IU/L rFSH. As a model for superovulation, experiments with 100IU/L rFSH or 100IU/L HP-hMG exposure during the antral growth were undertaken. Col4a1, Col4a2 and Col6a2 expression levels were analyzed at 3 time points during antral growth and at a 4 hour interval up to 16 hours after ovulation induction, using QPCR. The presence and induction of the collagen mRNA and protein were confirmed in cumulus from in vivo and in vitro grown follicles and TGFB1 and 2 were assayed as potential regulators. The study revealed that exposure to 100IU/L FSH, as in both superovulation conditions, significantly influenced the follicle morphology and slowed down nuclear maturation and mucification (p<0.05). This coincided with an increased expression of the 3 collagens in the cumulus oocyte complex (COC) at the end of antral growth and in the first hours following the ovulatory dose of hCG (p<0.05). The increased expression might reflect a differentiation but is most likely due to a precocious luteinization of the cumulus. Growth in HP-hMG resulted in higher Tgfb1 mRNA and protein levels, less COC with an increased collagen expression and with a more synchronous nuclear maturation. This suggests that the presence of LH-activity tempered the effect of the elevated FSH dose.
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follitropin alfa in cycles of intracytoplasmic sperm injection
2016Co-Authors: Ssbiomed Centendocrinology, Sandro C Esteves, Joan C Schertz, Sidney Verza, Danielle T Schneider, Ro C Esteves, Silval Fc ZabagliaAbstract:A comparison of Menotropin, highly-purified Menotropin an
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A comparison of Menotropin, highly-purified Menotropin and follitropin alfa in cycles of intracytoplasmic sperm injection
Reproductive Biology and Endocrinology, 2009Co-Authors: Sandro C Esteves, Joan C Schertz, Sidney Verza, Danielle T Schneider, Silval Fc ZabagliaAbstract:Background Over the last several decades, as a result of an evolution in manufacturing processes, a marked development has been made in the field of gonadotropins for ovarian stimulation. Initially, therapeutic gonadotropins were produced from a simple process of urine extraction and purification; now they are produced via a complex system involving recombinant technology, which yields gonadotropins with high levels of purity, quality, and consistency. Methods A retrospective analysis of 865 consecutive intracytoplasmic sperm injection (ICSI) cycles of controlled ovarian hyperstimulation (COH) compared the clinical efficacy of three gonadotropins (Menotropin [hMG; n = 299], highly-purified hMG [HP-hMG; n = 330] and follitropin alfa [r-hFSH; n = 236]) for ovarian stimulation after pituitary down-regulation. The endpoints were live birth rates and total doses of gonadotropin per cycle and per pregnancy. Results Laboratory and clinical protocols remained unchanged over time, except for the type of gonadotropin used, which was introduced sequentially (hMG, then HP-hMG, and finally r-hFSH). Live birth rates were not significantly different for hMG (24.4%), HP-hMG (32.4%) and r-hFSH (30.1%; p = 0.09) groups. Total dose of gonadotropin per cycle was significantly higher in the hMG (2685 +/- 720 IU) and HP-hMG (2903 +/- 867 IU) groups compared with the r-hFSH-group (2268 +/- 747 IU; p < 0.001). Total dose of gonadotropin required to achieve clinical pregnancy was 15.7% and 11.0% higher for the hMG and HP-hMG groups, respectively, compared with the r-hFSH group, and for live births, the differences observed were 45.3% and 19.8%, respectively. Conclusion Although similar live birth rates were achieved, markedly lower doses of r-hFSH were required compared with hMG or HP-hMG.
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a comparison of Menotropin highly purified Menotropin and follitropin alfa in cycles of intracytoplasmic sperm injection
Reproductive Biology and Endocrinology, 2009Co-Authors: Sandro C Esteves, Joan C Schertz, Sidney Verza, Danielle T Schneider, Silval Fc ZabagliaAbstract:Over the last several decades, as a result of an evolution in manufacturing processes, a marked development has been made in the field of gonadotropins for ovarian stimulation. Initially, therapeutic gonadotropins were produced from a simple process of urine extraction and purification; now they are produced via a complex system involving recombinant technology, which yields gonadotropins with high levels of purity, quality, and consistency. A retrospective analysis of 865 consecutive intracytoplasmic sperm injection (ICSI) cycles of controlled ovarian hyperstimulation (COH) compared the clinical efficacy of three gonadotropins (Menotropin [hMG; n = 299], highly-purified hMG [HP-hMG; n = 330] and follitropin alfa [r-hFSH; n = 236]) for ovarian stimulation after pituitary down-regulation. The endpoints were live birth rates and total doses of gonadotropin per cycle and per pregnancy. Laboratory and clinical protocols remained unchanged over time, except for the type of gonadotropin used, which was introduced sequentially (hMG, then HP-hMG, and finally r-hFSH). Live birth rates were not significantly different for hMG (24.4%), HP-hMG (32.4%) and r-hFSH (30.1%; p = 0.09) groups. Total dose of gonadotropin per cycle was significantly higher in the hMG (2685 +/- 720 IU) and HP-hMG (2903 +/- 867 IU) groups compared with the r-hFSH-group (2268 +/- 747 IU; p < 0.001). Total dose of gonadotropin required to achieve clinical pregnancy was 15.7% and 11.0% higher for the hMG and HP-hMG groups, respectively, compared with the r-hFSH group, and for live births, the differences observed were 45.3% and 19.8%, respectively. Although similar live birth rates were achieved, markedly lower doses of r-hFSH were required compared with hMG or HP-hMG.