Journal of the Turkish-German Gynecological Association, Jun 1, 2019
Objective: We aimed to compare the first trimester screening profiles of spontaneous (n=972) and ... more Objective: We aimed to compare the first trimester screening profiles of spontaneous (n=972) and in in vitro fertilization (IVF) pregnancies (n=339) in a population of patients who had uncomplicated singleton pregnancies comparable for maternal age, gestation, body mass index, and ethnicity. Material and Methods: A non-interventional analysis of retrospective cohort data and review of the literature. Results: All IVF pregnancies were achieved via intracytoplasmic sperm injection using the same ovarian stimulation protocol with recombinant follicle-stimulating hormone and a gonadotropin-releasing hormone antagonist, cetrorelix acetate. The means of the multiple of median (MoM) of pregnancy-associated plasma protein-A (PAPP-A) were slightly lower in the fresh (1.19±0.6 vs 1.33±0.7, respectively; p=0.056) and frozen embryo transfer (1.03±0.5 vs 1.33±0.7, respectively; p=0.036) IVF pregnancies compared with natural conceptions. However, when the medians of the MoMs of PAPP-A and beta-human chorionic gonadotrophin (β-hCG), and their distributions were compared across the mode of conception, there were no differences between IVF pregnancies spontaneous pregnancies. Furthermore, the scatterplot diagram and curve fitting regression analyses revealed no difference in the temporal relations of β-hCG and PAPP-A with each other and gestational age between spontaneous and IVF pregnancies. Conclusion: These results support the notion that uncomplicated singleton IVF pregnancies have similar first trimester screening profiles to spontaneous conceptions.
Molecular Reproduction and Development, Aug 14, 2018
We aimed in this study to explore if sphingosine-1-phosphate (S1P) reduces apoptosis of primordia... more We aimed in this study to explore if sphingosine-1-phosphate (S1P) reduces apoptosis of primordial follicles during cryopreservation of human ovarian cortical samples. Ovarian cortical tissue fragments obtained from young patients who underwent laparoscopic excision of benign ovarian cysts were used for the experiments. The samples were slow-frozen and thawed with and without S1P at 200 and 400µM, cultured for one day, and then were fixed and processed for both histomorphological assessment and detection of apoptosis with immunohistochemistry using apoptosis marker cleaved caspase-3. Follicle counts were expressed as the mean number of follicles per mm 2. The mean number of primordial follicles and in vitro estradiol (E 2) and antimullerian hormone (AMH) production of the slow-frozen and thawed samples were significantly reduced compared to fresh unfrozen samples. S1P treatment at 400 but not 200 µM concentration resulted in a significant increase in the number of surviving primordial follicles and in vitro E 2 and AMH productions of the samples compared to their counterparts slow-frozen without S1P. We found that that there was a significant decrease in the number of primordial follicles with their oocytes stained positive for cleaved caspase-3 in the slow frozen samples S1P 400 µM in comparison to the samples slow-frozen without S1P. These results suggest that S1P may ameliorate follicle atresia occurring in human ovarian cortical samples during cryopreservation.
Die approbierte gedruckte Originalversion dieser Diplomarbeit ist an der TU Wien Bibliothek verfü... more Die approbierte gedruckte Originalversion dieser Diplomarbeit ist an der TU Wien Bibliothek verfügbar. The approved original version of this thesis is available in print at TU Wien Bibliothek. Die approbierte gedruckte Originalversion dieser Diplomarbeit ist an der TU Wien Bibliothek verfügbar. The approved original version of this thesis is available in print at TU Wien Bibliothek.
Occult primary ovarian insufficiency (also known as incipient ovarian failure or diminished ovari... more Occult primary ovarian insufficiency (also known as incipient ovarian failure or diminished ovarian reserve) is defined as serum AMH level 1.1ng/mL in women under age 30. Limited data is available regarding the prevalence of occult POI, the preceding menstrual characteristics and its natural course in otherwise healthy young females. We aimed in this prospective observational study to determine the prevalence of occult POI in young females (< age 30) screened with serum AMH measurement; and analyze the patterns of change in their menstruation at initial assessment and one-year follow-up in relation to the changes in ovarian reserve quantitatively assessed with AMH and AFC. 963 young female college students under age 30 voluntarily participated in this study. 43 of them (4.4%) were diagnosed with occult POI as their AMH levels were 1.1ng/mL. Thirty-eight (83.4%) of them have regular cycles and denied any menstrual irregularity in the last 12 months. This rate was not statistically different from 7.3% of those with AMH>1.1ng/mL who reported at least one abnormal menstrual cycle in the last year (p = 0.36). Cycle length was significantly shorter in females with AMH 1.1ng/mL compared to those with AMH>1.1ng/mL (25.1±3.2 vs. 31.2±2.8 respectively, p<0.001). Karyotype, FMR-1 mutation analyses and auto-antibody screening returned normal in all. At one-year follow-up AMH, AFC and mean cycle length were further reduced compared to their values at initial assessment. Now, a greater proportion of the participants with occult POI were menstruating regularly at every 21 days compared to the initial evaluation one year ago (39.5% vs. 13.9% respectively, p = 0.013). Twenty-five underwent oocyte cryopreservation. These findings underscore the importance of screening young females with AMH for possible occult POI. It also emphasizes that young females with critically diminished ovarian reserve may continue to menstruate regularly without any characteristic menstrual abnormality other than shortening of cycle length.
Molecular Reproduction and Development, Jun 5, 2017
Obtaining and fertilizing mature oocytes from immature follicles that were grown outside the body... more Obtaining and fertilizing mature oocytes from immature follicles that were grown outside the body has conceptually attracted scientists for centuries, with initial attempts first documented in the 19th century. Significant progress has been made since then, due in part to a better understanding of folliculogenesis and improved techniques of in vitro follicle growth. Indeed, in vitro growth is now considered a reasonable approach to preserve or restore fertility when immature follicles and their oocytes need to be grown and matured outside the body. Certain patients would benefit from in vitro follicle growth, particularly those who carry a risk of cancer re-seeding after grafting of frozen-thawed ovarian tissue or who are at the risk of premature ovarian failure due to several intrinsic ovarian defects and genetic mutations that lead to accelerated follicle atresia and early exhaustion of the ovarian reserve. This review provides an update on the current status of in vitro growth of preantral human follicles, from initial efforts to the most recent achievements. K E Y W O R D S follicle culture, human, in vitro follicle growth, oocyte, ovary, tissue culture Current cell culture techniques do not support complete follicle development in vitro, so in vitro follicle culture is not considered an established method for application to human assisted reproduction.
European Journal of Obstetrics & Gynecology and Reproductive Biology, Mar 1, 2018
Objective(s): We aimed to analyze if anti-apoptotic agent sphingosine-1-phosphate offers protecti... more Objective(s): We aimed to analyze if anti-apoptotic agent sphingosine-1-phosphate offers protection against in vitro follicle atresia during culture of human ovarian cortical samples. Study design: A translational research study of ex-vivo and in-vitro models of human ovarian tissue. Material and Methods: Ovarian cortical tissue fragments (1x0.5cm) were obtained from young patients (n=15 mean ageSD: 29.42.5) undergoing laparoscopic excision of benign ovarian cysts. The samples were cultured for 4 days in 24-well format culture plate using conventional culture techniques. S1P was added to culture media at 200 and 400M with S1P produced significantly higher amounts of E2 (2339321 vs. 1156125 pg/mL respectively, p<0.01) compared to control samples. Conclusions: These results suggest that S1P promotes follicle survival in human ovarian cortical samples in vitro.
Journal of the Turkish-German Gynecological Association, Oct 22, 2018
We aimed to compare the first trimester screening profiles of spontaneous (n=972) and IVF pregnan... more We aimed to compare the first trimester screening profiles of spontaneous (n=972) and IVF pregnancies (n=339) in a population of patients who had uncomplicated singleton pregnancies comparable for maternal age, gestation, BMI, and ethnicity. Material and Methods: A non-interventional analysis of retrospective cohort data and review of the literature. Results: All IVF pregnancies were achieved via ICSI using the same ovarian stimulation protocol with recombinant FSH and a GnRH antagonist, cetrorelix acetate. The means of the multiple of median (MoM) of PAPP-A were slightly lower in the fresh (1.19±0.6 vs. 1.33±0.7, respectively; p=0.056) and frozen ET (1.03±0.5 vs. 1.33±0. 7, respectively; p=0.036) IVF pregnancies compared with natural conceptions. However, when the medians of the MoMs of PAPP-A and b-hCG, and their distributions were compared across the mode of conception, there were no differences between IVF pregnancies spontaneous pregnancies. Furthermore, the scatterplot diagram and curve fitting regression analyses revealed no difference in the temporal relations of b-hCG and PAPP-A with each other and gestational age between spontaneous and IVF pregnancies. Conclusion: These results support the notion that uncomplicated singleton IVF pregnancies have similar first trimester screening profiles to spontaneous conceptions.
In this study, we aimed to investigate if the gonadotropin-releasing hormone (GnRH) agonist and a... more In this study, we aimed to investigate if the gonadotropin-releasing hormone (GnRH) agonist and antagonist have any effect on the follicle-stimulating hormone (FSH)-induced-growth of early antral follicles of mice, cultured in vitro, and expressing cognate receptors for FSH and GnRH. For this purpose, small antral follicles were isolated from mouse ovaries and randomly assigned to the groups as control, FSH only, FSH + GnRH agonist, and FSH + GnRH antagonist, and they were cultured for five days. Methods: The ovaries of C57BL/6 mice (n=24), which were 21 days old, were removed after euthanasia. Small antral follicles measuring ~200μ in diameter were mechanically isolated after the enzymatic digestion of the ovaries with collagenase and DNase-I. The expression of FSH and GnRH receptors in these follicles was validated by quantitative real time-polymerase chain reaction. Isolated follicles were randomly assigned into four different groups, each consisting of 20-30 follicles: control, FSH only, FSH + GnRH agonist, and FSH + GnRH antagonist. Results: The FSH treatment significantly enhanced the in vitro growth of the follicles compared to those cultured without FSH after five days of the culture period. The antrum formation was markedly enhanced, and cumulus-oophorus complexes were more easily visible in the FSH-treated follicles compared to control follicles. The mean diameters of follicles treated with the FSH + GnRH agonist or the FSH + GnRH antagonist were not significantly different from those treated with FSH only, but they were significantly greater than control follicles. Conclusion: These results may suggest that the GnRH agonist and antagonist do not appear to adversely affect the FSH-induced proliferation of mitotic non-luteinizing granulosa cells and the growth of early antral follicles of mice in vitro.
International Journal of Human Sciences./ Uluslararası İnsan Bilimleri Dergisi, 2016
Approximately 46 million women experience abortion all around the world every year and about 22 m... more Approximately 46 million women experience abortion all around the world every year and about 22 million of those being done in precarious conditions. 13 % of the maternal mortality is associated with unsafe abortion practices. Every year near 5 million women are hospitalized because of unsafe abortion. The cost for treatment of the complications related to unsafe abortion is estimated to be 680 million dollars annually. Two third of the maternal mortality occurs in African countries and when these rates are thoroughly analysed it can be seen that African and Asian countries' law limit abortion practices. In the developed countries where discretionary abortion is not legally limited, maternal mortality rates stay under 1 %, on the other hand, abortion limited/banned countries show the highest rates.
d Calculated as the number of 2 pronuclei oocytes divided by the total number of oocytes retrieve... more d Calculated as the number of 2 pronuclei oocytes divided by the total number of oocytes retrieved. e Visit 8 corresponds to Day 14 +/-2 days after embryo transfer. f Live birth data were collected by each study site after the end-of-study visit. g Calculated using the total number of neonates for the denominator.
Development of in vitro technologies that will allow the culture of early stage follicles before ... more Development of in vitro technologies that will allow the culture of early stage follicles before antral stage is an essential part of research in reproductive biology in order to understand the ovarian folliculogenesis better. Current evidence suggests that oocyte and somatic cells-derived growth factors interacting with each other and extracellular matrix proteins at paracrine level are involved in this early, gonadotrophin-independent phase of follicle growth. Basement membrane matrix protein (Matrigel™) is a soluble gel rich in extracellular matrix proteins and growth factors. Activin A promotes preantral follicle growth in vivo by inducing the proliferation of granulosa cells and by upregulating the expression of FSH receptor and aromatase enzyme. We hypothesized that activin A and matrigel may provide a better in vitro environment for early stage preantral follicles. Preantral follicles isolated from 14-21 day old BALB/c mice were cultured in matrigel ± activin A for four days. The growth (119.4% versus 45.4%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05; respectively) and survival rates (76.3% versus 43.7%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05; respectively) of the follicles treated with activin A were significantly higher compared to those without activin A. These results suggest that Activin A and matrigel provide a better in vitro milieu for the growth of isolated ovarian follicles.
Journal of the Turkish-German Gynecological Association, Jun 1, 2019
Objective: We aimed to compare the first trimester screening profiles of spontaneous (n=972) and ... more Objective: We aimed to compare the first trimester screening profiles of spontaneous (n=972) and in in vitro fertilization (IVF) pregnancies (n=339) in a population of patients who had uncomplicated singleton pregnancies comparable for maternal age, gestation, body mass index, and ethnicity. Material and Methods: A non-interventional analysis of retrospective cohort data and review of the literature. Results: All IVF pregnancies were achieved via intracytoplasmic sperm injection using the same ovarian stimulation protocol with recombinant follicle-stimulating hormone and a gonadotropin-releasing hormone antagonist, cetrorelix acetate. The means of the multiple of median (MoM) of pregnancy-associated plasma protein-A (PAPP-A) were slightly lower in the fresh (1.19±0.6 vs 1.33±0.7, respectively; p=0.056) and frozen embryo transfer (1.03±0.5 vs 1.33±0.7, respectively; p=0.036) IVF pregnancies compared with natural conceptions. However, when the medians of the MoMs of PAPP-A and beta-human chorionic gonadotrophin (β-hCG), and their distributions were compared across the mode of conception, there were no differences between IVF pregnancies spontaneous pregnancies. Furthermore, the scatterplot diagram and curve fitting regression analyses revealed no difference in the temporal relations of β-hCG and PAPP-A with each other and gestational age between spontaneous and IVF pregnancies. Conclusion: These results support the notion that uncomplicated singleton IVF pregnancies have similar first trimester screening profiles to spontaneous conceptions.
Molecular Reproduction and Development, Aug 14, 2018
We aimed in this study to explore if sphingosine-1-phosphate (S1P) reduces apoptosis of primordia... more We aimed in this study to explore if sphingosine-1-phosphate (S1P) reduces apoptosis of primordial follicles during cryopreservation of human ovarian cortical samples. Ovarian cortical tissue fragments obtained from young patients who underwent laparoscopic excision of benign ovarian cysts were used for the experiments. The samples were slow-frozen and thawed with and without S1P at 200 and 400µM, cultured for one day, and then were fixed and processed for both histomorphological assessment and detection of apoptosis with immunohistochemistry using apoptosis marker cleaved caspase-3. Follicle counts were expressed as the mean number of follicles per mm 2. The mean number of primordial follicles and in vitro estradiol (E 2) and antimullerian hormone (AMH) production of the slow-frozen and thawed samples were significantly reduced compared to fresh unfrozen samples. S1P treatment at 400 but not 200 µM concentration resulted in a significant increase in the number of surviving primordial follicles and in vitro E 2 and AMH productions of the samples compared to their counterparts slow-frozen without S1P. We found that that there was a significant decrease in the number of primordial follicles with their oocytes stained positive for cleaved caspase-3 in the slow frozen samples S1P 400 µM in comparison to the samples slow-frozen without S1P. These results suggest that S1P may ameliorate follicle atresia occurring in human ovarian cortical samples during cryopreservation.
Die approbierte gedruckte Originalversion dieser Diplomarbeit ist an der TU Wien Bibliothek verfü... more Die approbierte gedruckte Originalversion dieser Diplomarbeit ist an der TU Wien Bibliothek verfügbar. The approved original version of this thesis is available in print at TU Wien Bibliothek. Die approbierte gedruckte Originalversion dieser Diplomarbeit ist an der TU Wien Bibliothek verfügbar. The approved original version of this thesis is available in print at TU Wien Bibliothek.
Occult primary ovarian insufficiency (also known as incipient ovarian failure or diminished ovari... more Occult primary ovarian insufficiency (also known as incipient ovarian failure or diminished ovarian reserve) is defined as serum AMH level 1.1ng/mL in women under age 30. Limited data is available regarding the prevalence of occult POI, the preceding menstrual characteristics and its natural course in otherwise healthy young females. We aimed in this prospective observational study to determine the prevalence of occult POI in young females (< age 30) screened with serum AMH measurement; and analyze the patterns of change in their menstruation at initial assessment and one-year follow-up in relation to the changes in ovarian reserve quantitatively assessed with AMH and AFC. 963 young female college students under age 30 voluntarily participated in this study. 43 of them (4.4%) were diagnosed with occult POI as their AMH levels were 1.1ng/mL. Thirty-eight (83.4%) of them have regular cycles and denied any menstrual irregularity in the last 12 months. This rate was not statistically different from 7.3% of those with AMH>1.1ng/mL who reported at least one abnormal menstrual cycle in the last year (p = 0.36). Cycle length was significantly shorter in females with AMH 1.1ng/mL compared to those with AMH>1.1ng/mL (25.1±3.2 vs. 31.2±2.8 respectively, p<0.001). Karyotype, FMR-1 mutation analyses and auto-antibody screening returned normal in all. At one-year follow-up AMH, AFC and mean cycle length were further reduced compared to their values at initial assessment. Now, a greater proportion of the participants with occult POI were menstruating regularly at every 21 days compared to the initial evaluation one year ago (39.5% vs. 13.9% respectively, p = 0.013). Twenty-five underwent oocyte cryopreservation. These findings underscore the importance of screening young females with AMH for possible occult POI. It also emphasizes that young females with critically diminished ovarian reserve may continue to menstruate regularly without any characteristic menstrual abnormality other than shortening of cycle length.
Molecular Reproduction and Development, Jun 5, 2017
Obtaining and fertilizing mature oocytes from immature follicles that were grown outside the body... more Obtaining and fertilizing mature oocytes from immature follicles that were grown outside the body has conceptually attracted scientists for centuries, with initial attempts first documented in the 19th century. Significant progress has been made since then, due in part to a better understanding of folliculogenesis and improved techniques of in vitro follicle growth. Indeed, in vitro growth is now considered a reasonable approach to preserve or restore fertility when immature follicles and their oocytes need to be grown and matured outside the body. Certain patients would benefit from in vitro follicle growth, particularly those who carry a risk of cancer re-seeding after grafting of frozen-thawed ovarian tissue or who are at the risk of premature ovarian failure due to several intrinsic ovarian defects and genetic mutations that lead to accelerated follicle atresia and early exhaustion of the ovarian reserve. This review provides an update on the current status of in vitro growth of preantral human follicles, from initial efforts to the most recent achievements. K E Y W O R D S follicle culture, human, in vitro follicle growth, oocyte, ovary, tissue culture Current cell culture techniques do not support complete follicle development in vitro, so in vitro follicle culture is not considered an established method for application to human assisted reproduction.
European Journal of Obstetrics & Gynecology and Reproductive Biology, Mar 1, 2018
Objective(s): We aimed to analyze if anti-apoptotic agent sphingosine-1-phosphate offers protecti... more Objective(s): We aimed to analyze if anti-apoptotic agent sphingosine-1-phosphate offers protection against in vitro follicle atresia during culture of human ovarian cortical samples. Study design: A translational research study of ex-vivo and in-vitro models of human ovarian tissue. Material and Methods: Ovarian cortical tissue fragments (1x0.5cm) were obtained from young patients (n=15 mean ageSD: 29.42.5) undergoing laparoscopic excision of benign ovarian cysts. The samples were cultured for 4 days in 24-well format culture plate using conventional culture techniques. S1P was added to culture media at 200 and 400M with S1P produced significantly higher amounts of E2 (2339321 vs. 1156125 pg/mL respectively, p<0.01) compared to control samples. Conclusions: These results suggest that S1P promotes follicle survival in human ovarian cortical samples in vitro.
Journal of the Turkish-German Gynecological Association, Oct 22, 2018
We aimed to compare the first trimester screening profiles of spontaneous (n=972) and IVF pregnan... more We aimed to compare the first trimester screening profiles of spontaneous (n=972) and IVF pregnancies (n=339) in a population of patients who had uncomplicated singleton pregnancies comparable for maternal age, gestation, BMI, and ethnicity. Material and Methods: A non-interventional analysis of retrospective cohort data and review of the literature. Results: All IVF pregnancies were achieved via ICSI using the same ovarian stimulation protocol with recombinant FSH and a GnRH antagonist, cetrorelix acetate. The means of the multiple of median (MoM) of PAPP-A were slightly lower in the fresh (1.19±0.6 vs. 1.33±0.7, respectively; p=0.056) and frozen ET (1.03±0.5 vs. 1.33±0. 7, respectively; p=0.036) IVF pregnancies compared with natural conceptions. However, when the medians of the MoMs of PAPP-A and b-hCG, and their distributions were compared across the mode of conception, there were no differences between IVF pregnancies spontaneous pregnancies. Furthermore, the scatterplot diagram and curve fitting regression analyses revealed no difference in the temporal relations of b-hCG and PAPP-A with each other and gestational age between spontaneous and IVF pregnancies. Conclusion: These results support the notion that uncomplicated singleton IVF pregnancies have similar first trimester screening profiles to spontaneous conceptions.
In this study, we aimed to investigate if the gonadotropin-releasing hormone (GnRH) agonist and a... more In this study, we aimed to investigate if the gonadotropin-releasing hormone (GnRH) agonist and antagonist have any effect on the follicle-stimulating hormone (FSH)-induced-growth of early antral follicles of mice, cultured in vitro, and expressing cognate receptors for FSH and GnRH. For this purpose, small antral follicles were isolated from mouse ovaries and randomly assigned to the groups as control, FSH only, FSH + GnRH agonist, and FSH + GnRH antagonist, and they were cultured for five days. Methods: The ovaries of C57BL/6 mice (n=24), which were 21 days old, were removed after euthanasia. Small antral follicles measuring ~200μ in diameter were mechanically isolated after the enzymatic digestion of the ovaries with collagenase and DNase-I. The expression of FSH and GnRH receptors in these follicles was validated by quantitative real time-polymerase chain reaction. Isolated follicles were randomly assigned into four different groups, each consisting of 20-30 follicles: control, FSH only, FSH + GnRH agonist, and FSH + GnRH antagonist. Results: The FSH treatment significantly enhanced the in vitro growth of the follicles compared to those cultured without FSH after five days of the culture period. The antrum formation was markedly enhanced, and cumulus-oophorus complexes were more easily visible in the FSH-treated follicles compared to control follicles. The mean diameters of follicles treated with the FSH + GnRH agonist or the FSH + GnRH antagonist were not significantly different from those treated with FSH only, but they were significantly greater than control follicles. Conclusion: These results may suggest that the GnRH agonist and antagonist do not appear to adversely affect the FSH-induced proliferation of mitotic non-luteinizing granulosa cells and the growth of early antral follicles of mice in vitro.
International Journal of Human Sciences./ Uluslararası İnsan Bilimleri Dergisi, 2016
Approximately 46 million women experience abortion all around the world every year and about 22 m... more Approximately 46 million women experience abortion all around the world every year and about 22 million of those being done in precarious conditions. 13 % of the maternal mortality is associated with unsafe abortion practices. Every year near 5 million women are hospitalized because of unsafe abortion. The cost for treatment of the complications related to unsafe abortion is estimated to be 680 million dollars annually. Two third of the maternal mortality occurs in African countries and when these rates are thoroughly analysed it can be seen that African and Asian countries' law limit abortion practices. In the developed countries where discretionary abortion is not legally limited, maternal mortality rates stay under 1 %, on the other hand, abortion limited/banned countries show the highest rates.
d Calculated as the number of 2 pronuclei oocytes divided by the total number of oocytes retrieve... more d Calculated as the number of 2 pronuclei oocytes divided by the total number of oocytes retrieved. e Visit 8 corresponds to Day 14 +/-2 days after embryo transfer. f Live birth data were collected by each study site after the end-of-study visit. g Calculated using the total number of neonates for the denominator.
Development of in vitro technologies that will allow the culture of early stage follicles before ... more Development of in vitro technologies that will allow the culture of early stage follicles before antral stage is an essential part of research in reproductive biology in order to understand the ovarian folliculogenesis better. Current evidence suggests that oocyte and somatic cells-derived growth factors interacting with each other and extracellular matrix proteins at paracrine level are involved in this early, gonadotrophin-independent phase of follicle growth. Basement membrane matrix protein (Matrigel™) is a soluble gel rich in extracellular matrix proteins and growth factors. Activin A promotes preantral follicle growth in vivo by inducing the proliferation of granulosa cells and by upregulating the expression of FSH receptor and aromatase enzyme. We hypothesized that activin A and matrigel may provide a better in vitro environment for early stage preantral follicles. Preantral follicles isolated from 14-21 day old BALB/c mice were cultured in matrigel ± activin A for four days. The growth (119.4% versus 45.4%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05; respectively) and survival rates (76.3% versus 43.7%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05; respectively) of the follicles treated with activin A were significantly higher compared to those without activin A. These results suggest that Activin A and matrigel provide a better in vitro milieu for the growth of isolated ovarian follicles.
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