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Follicle Stimulating Hormone and Anti-Müllerian Hormone per Oocyte in Predicting in vitro Fertilization Pregnancy in High Responders: A Cohort Study  [PDF]
Andrea Weghofer, Ann Kim, David H. Barad, Norbert Gleicher
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034290
Abstract: Background Follicle stimulating hormone (FSH) and Anti-Müllerian hormone (AMH) are utilized to differentiate between good and poor response to controlled ovarian hyperstimulation. Their respective roles in defining functional ovarian reserve remain, however, to be elucidated. To better understand those we investigated AMH and FSH per oocyte retrieved (AMHo and FSHo). Methodology/Principal Findings Three-hundred and ninety-six women, undergoing first in vitro fertilization cycles, were retrospectively evaluated. Women with oocyte yields >75th percentile for their age group were identified as high responders. In a series of logistic regression analyses, AMHo and FSHo levels were then evaluated as predictive factors for pregnancy potential in high responders. Patients presented with a mean age of 38.0±5.0 years, mean baseline FSH of 11.8±8.7 mIU/mL and mean AMH of 1.6±2.1 ng/mL. Those 88 women, who qualified as high responders, showed mean FSH of 9.7±6.5 mIU/mL, AMH of 3.1±3.1 ng/mL and oocyte yields of 15.8±7.1. Baseline FSH and AMH did not predict pregnancy in high responders. However, a statistically significant association between FSHo and pregnancy was observed in high responders, both after univariate regression (p = 0.02) and when adjusted for age, percentage of usable embryos, and number of embryos transferred (p = 0.03). Rate of useable embryos also significantly affected pregnancy outcome independently of FSHo (p = 0.01). AMHo was also associated with clinical pregnancy chances in high responders (p = 0.03) and remained significant when adjusted for usable embryos and number of embryos transferred (p = 0.04). Conclusions AMHo and FSHo are predictive of pregnancy potential in high responders, but likely reflect different responsibilities in recruitment and maturation of growing follicle cohorts.
Ovarian volume and antral follicle count for the prediction of low and hyper responders with in vitro fertilization
Janet Kwee, Mariet E Elting, Roel Schats, Joseph McDonnell, Cornelis B Lambalk
Reproductive Biology and Endocrinology , 2007, DOI: 10.1186/1477-7827-5-9
Abstract: One hundred and ten regularly menstruating patients, aged 18–39 years, participated in this prospective study, randomized, by a computer designed 4-blocks system study into two groups. Fifty six patients underwent a CCCT, and 54 patients underwent an EFORT. All patients underwent a transvaginal sonography to measure the basal ovarian volume and count of basal antral follicle. In all patients, the test was followed by a standard IVF treatment. The result of ovarian hyperstimulation during IVF treatment, expressed by the total number of follicles, was used as gold standard.The best prediction of ovarian reserve (Y) was seen in a multiple regression prediction model that included, AFC, Inhibin B-increment in the EFORT and BOV simultaneously (Y = -3.161 + 0.805 × AFC (0.258-1.352) + 0.034 × Inh. B-incr. (0.007-0.601) + 0.511 BOV (0.480-0.974) (r = 0.848, p < 0.001). Univariate logistic regression showed that the best predictors for poor response were the CCCT (ROC-AUC = 0.87), the bFSH (ROC-AUC = 0.83) and the AFC (ROC-AUC = 0.83). Multiple logistic regression analysis did not produce a better model in terms of improving the prediction of poor response. For hyper response, univariate logistic regression showed that the best predictors were AFC (ROC-AUC = 0.92) and the inhibin B-increment in the EFORT (ROC-AUC = 0.92), but AFC had better test characteristics, namely a sensitivity of 82% and a specificity 89%. Multiple logistic regression analysis did not produce a better model in terms of predicting hyper response.In conclusion AFC performs well as a test for ovarian response being superior or at least similar to complex expensive and time consuming endocrine tests. It is therefore likely to be the test for general practise.Real time two-dimensional (2D) pelvic ultrasonography is a relatively accurate and reliable method of determining ovarian volume and morphology [1]. Interobserver and intraobserver measurements have been shown to be very low when using transvaginal so
Involvement of Bone Morphogenetic Proteins (BMPs) in Ovarian Function and Infertility
A.A. Vireque, R.M. Reis, A.A.M. Rosa e Silva, L.O.T. Resende, E.M. Ferreira, A.C.J.S. Rosa e SilvaR.A. Ferriani
The Open Reproductive Science Journal , 2008, DOI: 10.2174/1874255600801010011]
Abstract: Advances in assisted reproduction techniques and the treatment of diseases known to be correlated with infertility such as polycystic ovary syndrome and premature ovarian failure require a better understanding of ovarian physiology. Despite the enormous quantity of information produced over the last two decades, the mechanisms controlling follicular development are not fully understood. Ovarian function is regulated by interactions between gonadotropins, follicle stimulating hormone, luteinizing hormone and local ovarian factors such as inhibins, activins, bone morphogenetic protein- 15 (BMP-15) and growth differentiation factor-9 (GDF-9), all members of the transformation and growth factor-β (TGF-β) superfamily. There is evidence of a functional ovarian BMP system with countless genes involved in normal follicular development and in fertility. The present review summarizes the ligands of the TGF-β superfamily, their receptors and signaling pathways and discusses the ovarian functions of the BMPs secreted by the oocytes as critical regulators of fertility.
Adipose Gene Expression Prior to Weight Loss Can Differentiate and Weakly Predict Dietary Responders  [PDF]
David M. Mutch, M. Ramzi Temanni, Corneliu Henegar, Florence Combes, Véronique Pelloux, Claus Holst, Thorkild I. A. S?rensen, Arne Astrup, J. Alfredo Martinez, Wim H. M. Saris, Nathalie Viguerie, Dominique Langin, Jean-Daniel Zucker, Karine Clément
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0001344
Abstract: Background The ability to identify obese individuals who will successfully lose weight in response to dietary intervention will revolutionize disease management. Therefore, we asked whether it is possible to identify subjects who will lose weight during dietary intervention using only a single gene expression snapshot. Methodology/Principal Findings The present study involved 54 female subjects from the Nutrient-Gene Interactions in Human Obesity-Implications for Dietary Guidelines (NUGENOB) trial to determine whether subcutaneous adipose tissue gene expression could be used to predict weight loss prior to the 10-week consumption of a low-fat hypocaloric diet. Using several statistical tests revealed that the gene expression profiles of responders (8–12 kgs weight loss) could always be differentiated from non-responders (<4 kgs weight loss). We also assessed whether this differentiation was sufficient for prediction. Using a bottom-up (i.e. black-box) approach, standard class prediction algorithms were able to predict dietary responders with up to 61.1%±8.1% accuracy. Using a top-down approach (i.e. using differentially expressed genes to build a classifier) improved prediction accuracy to 80.9%±2.2%. Conclusion Adipose gene expression profiling prior to the consumption of a low-fat diet is able to differentiate responders from non-responders as well as serve as a weak predictor of subjects destined to lose weight. While the degree of prediction accuracy currently achieved with a gene expression snapshot is perhaps insufficient for clinical use, this work reveals that the comprehensive molecular signature of adipose tissue paves the way for the future of personalized nutrition.
Bone Morphogenetic Protein-9 Induces Osteogenic Differentiation of Rat Dental Follicle Stem Cells in P38 and ERK1/2 MAPK Dependent Manner  [cached]
Conghua Li, Xia Yang, Yujuan He, Guo Ye, Xiaodong Li, Xiaonan Zhang, Lan Zhou, Feng Deng
International Journal of Medical Sciences , 2012,
Abstract: Dental follicle stem cells are a group of cells possessing osteogenic, adipogenetic and neurogenic differentiations, but the specific mechanism underlying the multilineage differentiation remains still unclear. Great attention has been paid to bone morphogenetic protein-9 (BMP-9) due to its potent osteogenic activity. In the present study, rat dental follicle stem cells were isolated and purified, and cells of passage 3 underwent adenovirus mediated BMP-9 gene transfection to prepare dental follicle stem cells with stable BMP-9 expression. Detection of alkaline phosphatase (ALP) and calcium deposition showed dental follicle stem cells transfected with BMP-9 gene could significantly promote the osteogenesis. In addition, SB203580 and PD98059 were employed to block the p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated kinase (ERK1/2), respectively. Detection of ALP and calcium deposition revealed the BMP-9 induced osteogenic differentiation of dental follicle stem cells depended on MAPK signaling pathway.
Comparison of the Predictive Value of Antral Follicle Count, Anti-Müllerian Hormone and Follicle-Stimulating Hormone in Women Following GnRH-Antagonist Protocol for Intracytoplasmic Sperm Injection  [PDF]
Shahinaz H. El-Shorbagy
Open Journal of Obstetrics and Gynecology (OJOG) , 2017, DOI: 10.4236/ojog.2017.74045
Abstract: Background: Prediction of ovarian response is one of the prerequisites for women undergoing intracytoplasmic sperm injection (ICSI) treatment prior to the first controlled ovarian stimulation (COS) cycle. Predictive factors may be variable in patients pre-treated with oral contraceptives (OC) for scheduling purposes. Objective: To evaluate antral follicle count (AFC), anti-müllerian hormone (AMH) and basal follicle stimulating hormone (FSH) for predicting ovarian responses in patients under controlled ovarian hyperstimulation randomized to receive either oral contraceptives (OC) or no treatment (non-OC) prior to their first controlled ovarian stimulation (COS) cycle. Study Design: One hundred infertile women randomized to receive OC treatment or no treatment, prior to their first COS cycle; were stimulated with Gonadotropin Releasing Hormone (GnRH) antagonist protocol. During the early follicular phase (day 2) of the two subsequent cycles (cycle A & cycle B) sonographic (AFC, ovarian volume) and endocrine data (AMH, basal FSH) were recorded. Transvaginal ultrasound was performed for all patients to monitor the ovarian response. Total number of oocytes retrieved and number of generated embryos were recorded and patients were categorized according to retrieved oocytes as poor (oocytes < 5), normal (oocytes 5 - 12) or high responders (oocytes > 12). Result(s): AFC, AMH and basal FSH were lower in users than in non-users of hormonal contraception. Poor responders showed less number of oocytes retrieved and had lower AFC and AMH but a higher basal FSH level was recorded in both groups (OC and non-OC). Conclusion: The better predictive value of AMH or AFC, as a single test or in combination will prevent cycle cancellations due to too low or too high ovarian response. AMH in OC group is not affected by OC pretreatment and is superior to other parameters, while AFC is superior to AMH and basal FSH in non-OC group.
Effects of prolonging administration gonadotropin on unexpectedly poor ovarian responders undergoing in vitro fertilization
Zhaolian Wei, Xianxia Cheng, Huirong Li, Yunxia Cao, Lin Cong, Ping Zhou, Jun Li
Reproductive Biology and Endocrinology , 2010, DOI: 10.1186/1477-7827-8-26
Abstract: 922 patients subjected to IVF were divided into two groups according to the predicted criterion of ovarian poor response. 116 patients predicted poor response received the short protocol (group C). The others received the long protocol, among the latter, there were 149 patients undergoing unexpectedly ovarian poor response (group B) and 657 patients exhibited normal ovarian response (group A). The doses of gonadotropin, duration of administration, implantation rate, clinical pregnancy rate and live birth rate were recorded among three groups.The implantation rate of embryo, clinic pregnancy rate and delivery rate are similar between the group A and group B, while there are significant differences between the doses of gonadotropins (35.1 +/- 8.9 ampules vs.53.0 +/- 15.9 ampules) and the duration of administration (15.3 +/- 3.6D vs. 9.8 +/- 2.6D) of these two groups. There are no significant differences about clinical pregnancy rate and live birth rate between group B and group C.Prolonging administration gonadotropin on the unexpectedly poor ovarian responders does not lower live birth rate in vitro fertilization.The success of in vitro fertilization (IVF) depends on careful patient selection and adequate controlled ovarian hyperstimulation. It is estimated that 5%-18% of all IVF cycle are complicated by poor response to ovarian hyperstimulation. Poor response to goandotropin may result in reduction in the pool of embryos available for transfer or cryoperservation, and decrease pregnancy rates. There is still no consensus definition of poor responder [1]. The following criterions had been used to define "poor responders" in practice [2]: No. of mature follicles <2-5; No. of mature oocytes retrieved ≤3; Single dominant follicle; Mean daily gonadoropin dose ≥300 IU; Total gonadotropin dose >40 ampules [3].It is necessary to identify low responders prior to hormonal treatment for in vitro fertilization-embryo transfer, so that the patients can be counseled regarding the
Bone Morphogenetic Protein-6 (BMP-6) induces atresia in goat primordial follicles cultured in vitro
Araújo, Valdevane Rocha;Lima-Verde, Isabel Bezerra;Name, Khessler Patrícia Olazia;Báo, S?nia Nair;Campello, Cláudio Cabral;Silva, José Roberto Viana;Rodrigues, Ana Paula Ribeiro;Figueiredo, José Ricardo de;
Pesquisa Veterinária Brasileira , 2010, DOI: 10.1590/S0100-736X2010000900010
Abstract: this study investigated the effects of bone morphogenetic protein 6 (bmp-6) on in vitro primordial follicle development in goats. samples of goat ovarian cortex were cultured in vitro for 1 or 7 days in minimum essential medium (control medium) supplemented with different concentrations of bmp-6. follicle survival, activation and growth were evaluated through histology and transmission electron microscopy (tem). after 7 days of culture, histological analysis demonstrated that bmp-6 enhanced the percentages of atretic primordial follicles when compared to fresh control (day 0). nevertheless, bmp-6 increased follicular and oocyte diameter during both culture periods. as the culture period progressed from day 1 to day 7, a significant increase in follicle diameter was observed with 1 or 50ng/ml bmp-6. however, on the contrary to that observed with the control medium tem revealed that follicles cultured for up to 7 days with 1 or 50ng/ml bmp-6 had evident signs of atresia. in conclusion, this study demonstrated that bmp-6 negatively affects the survival and ultrastructure of goat primordial follicles.
Are pregnancy complications increased in poor responders?  [cached]
Huriye Ay?e Parlakgümü?,Bülent Haydardedeo?lu,Erhan ?im?ek,Tayfun ?ok
Journal of the Turkish-German Gynecological Association , 2011,
Abstract: Objective: To investigate whether pregnancy complications are increased in poor responders to ovarian stimulation in IVF treatment.Material and Methods: We reviewed the antenatal follow up and birth records of 26 poor responders to ovarian stimulation and 125 normoresponder patients in an IVF program. Results: Eighty nine (71.2%) of the normoresponders and 22 (84.6%) of the poor responders had no pregnancy complications. Gestational diabetes was present in 18 (14.4%) of the normoresponders and 3 (11.5%) of the poor responders. Seven of the normoresponders had placenta previa (5.6%). Two of the normoresponders (1.6%) had pregnancy induced hypertension. Two (1.6%) of the normoresponders had preeclampsia. One patient from each group had fetal anomaly (3.8% for poor responders vs. 0.8% for normoresponders). Cholestasis of pregnancy was present in two of the normoresponders (1.6%) and the 2 patients (7.7%) who delivered prematurely also belonged to this group.Conclusion: Our results revealed that pregnancy complications were not increased in patients with a reduced ovarian reserve when compared to their age matched counterparts.
Evaluation of Ovarian Reserve by Measurement of the Serum Levels of Anti-Mullerian Hormone and Follicle-Stimulating Hormone in Intracytoplasmic Sperm Injection Cycles  [PDF]
Roshan Nikbakht,Mehrdad Borhani,Gita Yazdani Sarvestani
International Journal of Fertility & Sterility , 2010,
Abstract: Background: It is important to evaluate ovarian reserves prior to intracytoplasmic sperm injection(ICSI) treatment. The aim of this study is to determine the accuracy of anti-mullerian hormone(AMH) as a marker for ovarian reserve and to compare it with day-3 serum follicle-stimulatinghormone (FSH) levels.Materials and Methods: In this analytic, corss-sectional study, sequential sampling was done on70 infertile women who underwent ICSI treatment at Imam Khomeini Hospital, Ahvaz, Iran.Initially, 5cc of venous blood was drawn from each patient to measure serum AMH and FSH levelson the day-3 cycle.Patients were divided into two subgroups according to the numbers of oocytes retrieved. Patientswere classified as good responders if there were four or more oocytes retrieved, whereas patientswith less than four oocytes were poor responders.Results: The basal AMH level correlated with the number of oocytes retrieved (linear Pearsoncorrelation coefficient=0.599), however the basal FSH level had a weakly reverse correlation(correlation coefficient = -0.11).AMH levels had a sensitivity of 85% and specificity of 61.5%, with a cutoff value equal to 2.3 ng/mlwhich was higher than FSH.Conclusion: AMH serum levels are good predictors of ovarian reserve in comparison with FSH.
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