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Kulak D.,Gynecology and Womens Health | Kulak D.,University Reproductive Assoct | Jindal S.K.,MontefioResearch Institute for Reproductive Medicine and Health | Jindal S.K.,Yeshiva University | And 6 more authors.
Fertility and Sterility | Year: 2016

Objective To assess the relationship between live birth rates (LBRs) and the incidence of under-reported cycles by IVF clinics. Design Cohort study. Setting Not applicable. Patient(s) All patients undergoing IVF cycles in the aforementioned clinics. Intervention(s) Not applicable. Main Outcome Measure(s) The reporting percentage (RP), defined as number of cycles with reported pregnancy rates divided by total cycles performed. Results from cryopreservation cycles are only presented by SART if an embryo transfer occurs. Thus, RP decreases as incidence of embryo or oocyte banking cycles increases. The LBRs in women aged <35 years were compared between clinics. Result(s) The median RP of all clinics was 93%-97%. Clinics with RP <80% increased from 2 in 2004 to 30 in 2012. Twenty-one clinics had an RP that fell 2 standard deviations below the mean in any year. Over the 9 years, there was a negative correlation between RP and LBR of -0.17, but for the 21 outlier clinics the correlation increased to -0.26. In 2012 alone, in outlier clinics, for every 10% drop in RP there was an associated rise in LBR of 4.3%; some clinics reported 40% fewer cycles than the median. Conclusion(s) In clinics with very low RP, the cycles that are reported have higher success rates. Regardless of intent, the reduction of reported data to SART makes it increasingly difficult for clinicians and patients to accurately assess a clinic's success rates. © 2016 American Society for Reproductive Medicine.

Greenseid K.,Institute for Reproductive Medicine and Science of St Barnabas | Jindal S.,Yeshiva University | Jindal S.,MontefioResearch Institute for Reproductive Medicine and Health | Hurwitz J.,Reproductive Medicine Associates of Connecticut | And 2 more authors.
Reproductive Sciences | Year: 2011

Objective: To investigate if a diagnosis of diminished ovarian reserve (DOR) is associated with a differential gene profile of ovarian granulosa cells (GCs) in infertile women undergoing in vitro fertilization (IVF). Design: Prospective Cohort Study. Setting: Academic IVF Program. Patients: Infertile women <38 years were prospectively enrolled into 2 groups: normal ovarian reserve (NOR, follicle-stimulating hormone [FSH] < 10 mIU/mL, n = 4) and DOR (FSH ≥ 10.0 mIU/mL, n = 4). Interventions: Cumulus (C) and mural (M) GCs were isolated at egg retrieval; messenger RNA was extracted and transcribed. Main Outcome Measure(s): Differential gene expression in cerebellar granule cells (CGCs) in the 2 groups was assessed by cDNA microarray. Microarray findings were validated by quantitative real-time polymerase chain reaction (qRTPCR) in CGCs and explored in multinucleated giant cells (MGCs). Results: Of the 1256 differentially regulated genes identified in CGCs of women with DOR, the insulin-like growth factor (IGF) family was a biologically relevant gene family of a priori interest. Downregulation of IGF1 and IGF2 ligands (-3.28- and -2.54-fold, respectively), and their receptors, (-3.53- and -1.32-fold downregulation of IGF1R and IGF2R, respectively) was identified in luteinized CGCs in women with DOR compared to those with NOR. Downregulation of both IGF1 and IGF 2 ligands (-4.35- and 3.89-fold, respectively) was furthermore observed in MGCs in women with DOR compared to those with NOR; no differences in the expression of respective receptors were however observed in MGCs in the 2 groups. Conclusions: Components of the IGF gene family are downregulated in GCs of women with DOR. These findings maybe contributory to the reproductive compromise observed in women with DOR, and merit further exploration. © 2011 The Author(s).

Relwani R.,Laureate Medical Group | Relwani R.,MontefioResearch Institute for Reproductive Medicine and Health | Berger D.,MontefioResearch Institute for Reproductive Medicine and Health | Santoro N.,University of Colorado at Denver | And 7 more authors.
Reproductive Sciences | Year: 2011

Background: Male infertility affects approximately 6% of reproductive-aged men. It has been suggested that overweight men or men with obese body mass index (BMI) experience prolonged time to pregnancy, though the influence of male BMI on fertility remains understudied. Aims: We hypothesized that BMI is inversely correlated with fertility, manifested by reduced sperm concentration, motility, and morphology. Methods: Males of age 18 to 50 with semen analyses and self-reported BMI were included (n = 530). Patient parameters analyzed included age, BMI, smoking, urological, and fertility history. Leutinizing hormone (LH), Follicle-stimulating hormone, testosterone, steroid hormone-binding globulin (SHBG) and free androgen index (FAI) levels (n = 55), and selective serotonin reuptake inhibitor (SSRI) use (n = 12) were also measured. Results: The men in this study had a mean BMI of 28.2 ± 4.9 kg/m2 (range = 15-60), which is considered overweight, and a mean semen concentration of 55.4 ± 46.8 million/mL, which is in normal range, according to WHO standard. No consistent relationship was observed between increasing BMI and sperm concentration, motility, or morphology, although the testosterone levels trended downward with increasing BMI; there was a suggestion for decreased sperm concentration in current smokers. Men treated with combination SSRI and other psychotropic agent therapy (n = 12) had significantly reduced sperm motility (P =.009). Not unexpectedly, prior urological surgery (n = 77) was associated with lower sperm concentration (P =.0001) and morphology (P =.0008). When in vitro fertilization-embryo transfer (IVF-ET) was used as a treatment modality (n = 121), male BMI was not a significant predictor of clinical pregnancy (P =.06). Conclusions: In our study, we did not observe a significant association between male BMI and sperm concentration, motility or morphology, or clinical pregnancy following IVF-ET. Significantly, SSRI use may affect sperm parameters negatively. © The Author(s) 2011.

McAvey B.,Yeshiva University | McAvey B.,MontefioResearch Institute for Reproductive Medicine and Health | Zapantis A.,MontefioResearch Institute for Reproductive Medicine and Health | Jindal S.K.,Yeshiva University | And 5 more authors.
Fertility and Sterility | Year: 2011

Objective: To evaluate the association between the number of mature (metaphase II [MII]) oocytes per assisted reproductive technology (ART) cycle and the likelihood of live birth. Design: Retrospective study. Setting: Academic infertility practice. Patient(s): Seven hundred thirty-seven infertile women undergoing their initial fresh embryo, nondonor IVF or intracytoplasmic sperm injection cycle at Montefiore's Institute for Reproductive Medicine and Health between January 2002 and December 2008. Intervention(s): None. Main Outcome Measure(s): Live birth. Result(s): Two hundred twenty-four cycles resulted in a live birth (30.4%). Live birth cycles had significantly more MII oocytes obtained per cycle as compared with their unsuccessful counterparts (11.0 ± 5.9 vs. 9.7 ± 6.2, respectively). Multivariate logistic regression was done to determine the minimum number of MII oocytes per cycle as a predictor of live birth after adjustment for age and historical maximum FSH values. Cycles that included the average number of MII in this cohort were used as a reference group. For cycles with five or fewer MII oocytes obtained, there was a statistically significant decrease in the likelihood of a live birth as compared with the reference group (odds ratio 0.61, 95% confidence interval 0.38-0.99). However, cycles with six or fewer obtained MII oocytes were not less likely to result in a live birth when compared with the reference group (odds ratio 0.69, 95% confidence interval 0.45-1.08). Conclusion(s): In our cohort, there was an advantage to obtaining six or more MII oocytes during the fresh oocyte retrieval compared with five or fewer oocytes. There was not an advantage, however, to obtaining 10 or more or 15 or more oocytes as compared with obtaining 6-9 oocytes. The strategy of aiming for a greater number of oocytes in an ART cycle should be revisited. Copyright © 2011 American Society for Reproductive Medicine, Published by Elsevier Inc.

Berger D.S.,MontefioResearch Institute for Reproductive Medicine and Health | Zapantis A.,MontefioResearch Institute for Reproductive Medicine and Health | Merhi Z.,University of Vermont | Younger J.,Yeshiva University | And 3 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2014

Purpose: The association between pronuclear (PN) scoring of embryos from assisted reproductive technology (ART) and clinical pregnancy remains controversial. We hypothesized that embryos with PNs scored on the day of fertilization check offer better embryo selection on day 3 and higher CPR compared to non-PN scored embryos. Methods: Patients (19-46 years) undergoing IVF/ICSI cycles at Montefiore's Institute for Reproductive Medicine and Health between January 2006 and December 2009 were included in our study. We analyzed fresh day 3 cycles only with autologous oocytes and partner's fresh sperm (n=344). A total of 1,899 embryos were included. We compared CPR from non-PN scored embryos (Group 1, n=835) with PN scored embryos (Group 2, n=1,064). Composite scores by patient were developed based on embryo disposition. We also assessed traditional embryo grading derived from cell number, fragmentation and cell symmetry. Data analysis included chi square and t test to determine if PN scoring was associated with improved CPR, and to compare the additional variables. Results: CPR between Group 1 and Group 2 were not different (p=0.91). CPR was significantly associated with female age, number of mature oocytes retrieved, number of day 3 embryos and grade of embryos transferred on day 3 (p<0.05). Conclusion: PN scoring was not associated with improved CPR in day 3 embryo transfers. Mean grade of transferred embryos continues to be a well-established, independent predictor of CPR. We conclude that further refinement of embryo grading by PN scoring is not beneficial. © 2014 Springer Science+Business Media.

Merhi Z.O.,University of Vermont | Keltz J.,New York University | Zapantis A.,MontefioResearch Institute for Reproductive Medicine and Health | Younger J.,Yeshiva University | And 6 more authors.
Obesity | Year: 2013

Objective Male adiposity is detrimental for achieving clinical pregnancy rate (CPR) following assisted reproductive technologies (ART). The hypothesis that the association of male adiposity with decreased success following ART is mediated by worse embryo quality was tested. Design and Methods Retrospective study including 344 infertile couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles was performed. Cycle determinants included number of oocytes retrieved, zygote PN-score, total number of embryos available on day 3, number of embryos transferred, composite day 3 grade for transferred embryos, composite day 3 grade per cycle, and CPR. Results Couples with male body mass index (BMI) over 25 kg m-2 (overweight and obese) exhibited significantly lower CPR compared to their normal weight counterparts (46.7% vs. 32.0% respectively, P = 0.02). No significant difference was observed for any embryo quality metrics when analyzed by male BMI: mean zygote PN-scores, mean composite day 3 grades for transferred embryos or composite day 3 grades per cycle. In a multivariable logistic regression analysis adjusting for female age, female BMI, number of embryos transferred and sperm concentration, male BMI over 25 kg m-2 was associated with a lower chance for CPR after IVF (OR = 0.17 [95% CI: 0.04-0.65]; P = 0.01) but not after ICSI cycles (OR = 0.88 [95% CI: 0.41-1.88]; P = 0.75). In this cohort, male adiposity was associated with decreased CPR following IVF but embryo quality was not affected. Conclusions Embryo grading based on conventional morphologic criteria does not explain the poorer clinical pregnancy outcomes seen in couples with overweight or obese male partner. Copyright © 2013 The Obesity Society.

Nejat E.J.,Yeshiva University | Nejat E.J.,MontefioResearch Institute for Reproductive Medicine and Health | Jindal S.,Yeshiva University | Jindal S.,MontefioResearch Institute for Reproductive Medicine and Health | And 5 more authors.
Human Reproduction | Year: 2011

Background We explored the relevance of blood type to ovarian reserve, as reflected by early follicular phase FSH levels. Methods For this cross-sectional observational study, early follicular phase serum levels of FSH (mIU/ml) and estradiol (E2, pg/ml), and information on blood type (A, B, AB and O) and patient age were procured for female patients, ≤45 years age (n = 544), who were undergoing fertility evaluation at one of two tertiary care facilities. Serum FSH > 10 mIU/ml was taken to reflect diminished ovarian reserve (DOR). Data distribution for FSH and age was analyzed and non-parametric tests used for comparisons across blood groups. Multivariable logistic regression analyses determined the relationship between elevated FSH and respective blood types after adjusting for age and study site. Results Prevalence of blood types according to order of frequency was: O (45), A (35), B (16) and AB (5). After adjusting for age and study site, patients with blood type O were twice as likely to exhibit FSH > 10 mIU/ml compared with those with A or AB blood types [odds ratio (OR) 2.36; 95 confidence interval (CI) 1.274.41; P = 0.007], and three times as likely to manifest FSH > 12m IU/ml (OR 3.48, 95 CI 1.467.32, P = 0.004). The B blood group antigen failed to exhibit any relationship with ovarian reserve as reflected by baseline FSH (P> 0.05). Conclusions The A blood group antigen appears to be protective for ovarian reserve, whereas blood type O appears to be associated with DOR, in a relationship that is independent of advancing age. Further studies are needed to establish causality and identify the underlying mechanisms for the association. © 2011 The Author.

Merhi Z.,University of Vermont | Zapantis A.,MontefioResearch Institute for Reproductive Medicine and Health | Berger D.S.,MontefioResearch Institute for Reproductive Medicine and Health | Jindal S.K.,MontefioResearch Institute for Reproductive Medicine and Health | Jindal S.K.,Yeshiva University
Journal of Assisted Reproduction and Genetics | Year: 2013

Purpose: Serum anti-Mullerian hormone (AMH) levels estimate ovarian reserve. The purpose of this study was to identify a minimum serum AMH level that correlates with acceptable clinical pregnancy rate (CPR) in women with severe diminished ovarian reserve (DOR) undergoing in vitro fertilization (IVF). Methods(s): A historical cohort of severe DOR participants (age ≥35) with day 3 FSH of >10 ng/mL were included (n = 120). Participants were categorized into 3 groups: AMH <0.2 (Group 1, n = 38), AMH = 0.2-0.79 (Group 2, n = 57) and AMH ≥ 0.8 (Group 3, n = 25) ng/mL. The main outcome was CPR. The number of retrieved and mature oocytes, transferred embryos, spontaneous abortion (SAB) and live birth (LB) rates were also evaluated. Result(s): Among the three groups, there was no difference in day 3 FSH and estradiol, total gonadotropins dose used per cycle, or LB. Participants in Group 1 were two years older than those in Group 2 and had significantly higher BMI than those in Groups 2 and 3. The three groups significantly differed in AFC (Group 1< Group 2< Group 3; p = 0.001) and cycle cancellation rate (Group 1> Group 2> Group 3; p = 0.006), and had a trend toward significance in SAB rate (Group 1> Group 2> Group 3; p = 0.06). Group 3 had significantly more retrieved and mature oocytes than Groups 1 or 2. Group 2 and 3 had significantly higher CPR per cycle start compared to Group 1. Although Group 2 had significantly fewer oocytes retrieved and mature oocytes than Group 3, CPR per cycle start for both groups was not different. ROC curve indicated that the point of maximal inflection between lower and higher CPR represents an AMH value of 0.2 ng/mL. Conclusion(s): AMH of 0.2 ng/mL appears to be a meaningful threshold for predicting CPR in women with severe DOR at our practice. This information can be crucial during the pre-cycle counseling of these women. © 2013 Springer Science+Business Media New York.

Merhi Z.,University of Vermont | Buyuk E.,Yeshiva University | Berger D.S.,MontefioResearch Institute for Reproductive Medicine and Health | Zapantis A.,MontefioResearch Institute for Reproductive Medicine and Health | And 4 more authors.
Human Reproduction | Year: 2013

STUDY QUESTION Do the adipocytokines, leptin and adiponectin affect the granulosa cell expression of anti-Mullerian hormone (AMH) and its receptor (AMHR-II)? SUMMARY ANSWER Leptin suppresses AMH mRNA levels in human luteinized granulosa cells through the JAK2/STAT3 pathway, while adiponectin has no such effect. WHAT IS KNOWN ALREADY AMH is one of the most reliable markers of ovarian reserve. Serum AMH levels decline with obesity. Obesity is associated with elevated leptin and reduced adiponectin levels.STUDY DESIGN, SIZE AND DURATIONThis prospective study included 60 infertile women undergoing fresh IVF and ICSI cycles utilizing autologous oocytes at Montefiore's Institute for Reproductive Medicine and Health between July 2010 and April 2012.PARTICIPANTS/ MATERIALS, SETTING, METHODS Follicular fluid was collected from small (SFs; <14 mm) and large follicles (LFs; ≥14 mm) from 38 participants. Total RNA was extracted separately from mural and cumulus granulosa cells and mRNA levels were measured by RT-PCR. In an additional group of participants (N = 22), primary cumulus and mural granulosa cells (pooled SFs and LFs) were cultured in media alone or with addition of either leptin (N = 7), adiponectin (N = 8) or JAK2/STAT3 inhibitor + leptin (N = 7), and AMH and AMHR-II mRNA levels measured. Levels of AMH, leptin and adiponectin protein were measured in follicular fluid. MAIN RESULTS AND THE ROLE OF CHANCE AMH and AMHR-II mRNA and follicular fluid AMH protein levels were inversely correlated with age. AMH mRNA expression was six times higher in cumulus compared with mural granulosa cells in SFs (P< 0.05) and eight times higher in cumulus compared with mural granulosa cells in LFs (P < 0.001). In follicular fluid, leptin protein level positively correlated (r = 0.7, P = 0.03), while adiponectin protein level inversely correlated (r = -0.46, P = 0.02) with BMI. Leptin treatment suppressed AMH and AMHR-II mRNA in both cumulus and mural granulosa cells (all P < 0.05). In the presence of JAK2/STAT3 inhibitor, leptin treatment did not alter AMH but continued to suppress AMHR-II mRNA in cumulus cells (P = 0.02). Adiponectin treatment did not alter AMH or AMHR-II mRNA levels. LIMITATIONS, REASONS FOR CAUTION This study included a luteinized granulosa cell model as these cells were collected from women who were hyperstimulated with gonadotrophins. The results obtained may not fully extrapolate to non-luteinized granulosa cells. WIDER IMPLICATIONS OF THE FINDINGS Leptin may program abnormal AMH signaling, thereby resulting in ovarian dysfunction. This study opens a new perspective for understanding the low ovarian reserve seen in obese women and provides new insights into potential mechanisms that explain the lower AMH seen in obese women. Whether our findings explain the worse response to ovulation induction observed in obese women needs to be further elucidated.STUDY FUNDING/COMPETING INTERESTSThe study was funded by New England Fertility Society Fellowship Award and Ferring Pharmaceuticals Inc. The authors of the study have no competing interests to report. © 2013 The Author. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Altun T.,Ankara State Research and Training Hospital | Jindal S.,Yeshiva University | Jindal S.,MontefioResearch Institute for Reproductive Medicine and Health | Greenseid K.,Yeshiva University | And 4 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2011

Purpose: Relationships between follicular fluid levels of IL-6 with ovarian response and clinical pregnancy were evaluated in IVF-ET cycles. Methods: Follicular fluid was collected from ovarian follicles ≥∈14 mm, pooled for each patient, and IL-6 levels were assessed using ELISA (n∈=∈68). Relationships between IL-6 levels and IVF cycle parameters were assessed using nonparametric tests, and between IL-6 levels and clinical pregnancy using multivariable logistic regression analyses. Results: Significant positive correlations were observed between IL-6 with age (p∈=∈0.035), and IL-6 with estradiol on the day of hCG (p∈=∈0.011). On adjusted analyses, IVF cycles in patients with IL-6 levels <4.0 pg/ml (median value for the group) demonstrated an almost 4-fold increase in likelihood for clinical pregnancy (p∈=∈0.045). Conclusions: Lower follicular fluid IL-6 levels in IVF patients are associated with increased likelihood of clinical pregnancy. We hypothesize that endometrial receptivity is a likely target for any deleterious influences of elevated IL-6 levels. © 2010 Springer Science+Business Media, LLC.

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