Ronald relman and Claudia Cohen Center for Reproductive Medicine

Cornell, New York, United States

Ronald relman and Claudia Cohen Center for Reproductive Medicine

Cornell, New York, United States

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Ginsberg M.,Howard Hughes Medical Institute | James D.,Howard Hughes Medical Institute | James D.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Ding B.-S.,Howard Hughes Medical Institute | And 14 more authors.
Cell | Year: 2012

ETS transcription factors ETV2, FLI1, and ERG1 specify pluripotent stem cells into induced vascular endothelial cells (iVECs). However, iVECs are unstable and drift toward nonvascular cells. We show that human midgestation c-Kit- lineage-committed amniotic cells (ACs) can be reprogrammed into vascular endothelial cells (rAC-VECs) without transitioning through a pluripotent state. Transient ETV2 expression in ACs generates immature rAC-VECs, whereas coexpression with FLI1/ERG1 endows rAC-VECs with a vascular repertoire and morphology matching mature endothelial cells (ECs). Brief TGFβ-inhibition functionalizes VEGFR2 signaling, augmenting specification of ACs into rAC-VECs. Genome-wide transcriptional analyses showed that rAC-VECs are similar to adult ECs in which vascular-specific genes are expressed and nonvascular genes are silenced. Functionally, rAC-VECs form stable vasculature in Matrigel plugs and regenerating livers. Therefore, short-term ETV2 expression and TGFβ inhibition with constitutive ERG1/FLI1 coexpression reprogram mature ACs into durable rAC-VECs with clinical-scale expansion potential. Banking of HLA-typed rAC-VECs establishes a vascular inventory for treatment of diverse disorders. © 2012 Elsevier Inc.


Butler J.M.,New York Medical College | Gars E.J.,New York Medical College | James D.J.,New York Medical College | James D.J.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | And 4 more authors.
Blood | Year: 2012

Transplantation of ex vivo expanded human umbilical cord blood cells (hCB) only partially enhances the hematopoietic recovery after myelosuppressive therapy. Incubation of hCB with optimal combinations of cytokines and niche cells, such as endothelial cells (ECs), could augment the efficiency of hCB expansion. We have devised an approach to cultivate primary human ECs (hECs) in serum-free culture conditions. We demonstrate that co-culture of CD34+ hCB in direct cellular contact with hECs and minimal concentrations of thrombopoietin/Kit-ligand/Flt3-ligand resulted in a 400-fold expansion of total hematopoietic cells, 150-fold expansion of CD45+CD34+ progenitor cells, and 23-fold expansion of CD45+ Lin-CD34hi+CD45RA-CD49f+ stem and progenitor cells over a 12-day period. Compared with cytokines alone, co-culture of hCB with hECs permitted greater expansion of cells capable of multilineage engraftment and serial transplantation, hallmarks of long-term repopulating hematopoietic stem cells. Therefore, hECs establish a cellular platform for expansion of hematopoietic stem and progenitor cells and treatment of hematologic disorders. © 2012 by The American Society of Hematology.


Reichman D.E.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Chung P.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Meyer L.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Greenwood E.,Cornell University | And 2 more authors.
Fertility and Sterility | Year: 2013

Objective: To determine whether patients who failed an in vitro fertilization (IVF) cycle can proceed with a subsequent IVF cycle after waiting only one menstrual cycle, or whether there is a benefit to allowing two or more menstrual cycles to elapse before proceeding. Design: Retrospective cohort study. Setting: Academic medical center. Patient(s): All patients undergoing IVF cycles at The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, from January 1, 2002 to November 1, 2011, in whom two consecutive gonadotropin-releasing hormone (GnRH)-antagonist IVF cycles with identical stimulation protocols took place 35-140 days apart, excluding patients in whom the first cycle resulted in a clinical pregnancy. Intervention(s): None. Main Outcome Measure(s): IVF outcomes were compared for 164 patients who initiated a cycle after waiting only one menstrual cycle (35-55 days from previous oocyte retrieval) versus 557 patients waiting two or more menstrual cycles (56-140 days) from their last retrieval before proceeding with their successive cycle start, stratifying for age. Result(s): No differences were detected regarding E2 response, oocyte yield, fertilization, or embryo development when comparing patients waiting only one cycle with those waiting two or more cycles, nor were those parameters different when comparing patients' index cycles with their immediate preceding failed cycles. Moreover, clinical outcomes regarding clinical pregnancy, live birth, and cycle cancellation were similar between both study groups. Conclusion(s): Delaying successive IVF cycle start for two or more menstrual cycles likely offers no advantage over pursuing repeated IVF after one menstrual cycle.


Kang H.-J.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Imperato-Mcginley J.,Weill Cornell Medical Center | Zhu Y.-S.,Weill Cornell Medical Center | Rosenwaks Z.,Ronald relman And Claudia Cohen Center For Reproductive Medicine
Fertility and Sterility | Year: 2014

A most interesting and intriguing male disorder of sexual differentiation is due to 5α-reductase-2 isoenzyme deficiency. These male infants are born with ambiguous external genitalia due to a deficiency in their ability to catalyze the conversion of T to dihydrotestosterone. Dihydrotestosterone is a potent androgen responsible for differentiation of the urogenital sinus and genital tubercle into the external genitalia, urethra, and prostate. Affected males are born with a clitoral-like phallus, bifid scrotum, hypospadias, blind shallow vaginal pouch from incomplete closure of the urogenital sinus, and a rudimentary prostate. At puberty, the surge in mainly T production prompts virilization, causing most boys to choose gender reassignment to male. Fertility is a challenge for affected men for several reasons. Uncorrected cryptorchidism is associated with low sperm production, and there is evidence of defective transformation of spermatogonia into spermatocytes. The underdeveloped prostate and consequent low semen volumes affect sperm transport. In addition, semen may not liquefy due to a lack of prostate-specific antigen. In the present review, we discuss the 5α-reductase-2 deficiency syndrome and its impact on human fertility. © 2014 American Society for Reproductive Medicine, Published by Elsevier Inc.


Reichman D.E.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Greenwood E.,Cornell University | Meyer L.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Kligman I.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Rosenwaks Z.,Ronald relman And Claudia Cohen Center For Reproductive Medicine
Fertility and Sterility | Year: 2012

Objective: To investigate the incidence of negative serum hCG level after initial IM trigger injection and whether such cycles can be salvaged through repeat administration of IM hCG. Design: Retrospective cohort study. Setting: Academic medical center. Patient(s): All patients undergoing IVF at the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, from January 1, 2005 to November 1, 2011. Intervention(s): Repeat hCG administration in cases of failed initial trigger. Main Outcome Measure(s): Fertilization, implantation, clinical pregnancy, and live birth rates were analyzed in the index population compared with a control population matched for age, year of cycle start, diagnosis, stimulation protocol, number of prior IVF attempts, oocyte yield, and number of embryos transferred. Result(s): The incidence of failed initial IM hCG injection was low, occurring in only 0.25% of the 17,298 fresh IVF cycles at our center during the study period. Of the 41 patients undergoing retrieval who received a second IM injection of hCG approximately 24 hours after the first, the live birth rate was 39.02%. Compared with matched controls, there were no statistical differences in oocyte maturity, fertilization, implantation, clinical pregnancy, or live birth rates. Conclusion(s): Although the incidence of failed hCG injection is rare, this study reveals that cycles characterized by incorrect initial administration or failed absorption of hCG can be salvaged by early detection and repeat injection. Assisted reproductive technology (ART) programs may benefit their patients through the assessment of either urine pregnancy tests or measurement of quantitative serum β-hCG levels before retrieval, thereby preventing empty follicle syndrome. © 2012 by American Society for Reproductive Medicine.


Reichman D.E.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | White P.C.,University of Texas Southwestern Medical Center | New M.I.,Mount Sinai Hospital | Rosenwaks Z.,Ronald relman And Claudia Cohen Center For Reproductive Medicine
Fertility and Sterility | Year: 2014

Congenital adrenal hyperplasia (CAH) is the most frequently encountered genetic steroid disorder affecting fertility. Steroid hormones play a crucial role in sexual development and reproductive function; patients with either 21- hydroxylase or 11β-hydroxylase deficiency thus face immense challenges to their fertility. Given the relevance of CAH in reproductive medicine as well as the diagnostic challenges posed by the phenotypic overlap with polycystic ovary syndrome, we review the reproductive pahophysiology of both classic and nonclassic CAH and present contemporary treatment options. © 2014 American Society for Reproductive Medicine, Published by Elsevier Inc.


Reichman D.E.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Goldschlag D.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Rosenwaks Z.,Ronald relman And Claudia Cohen Center For Reproductive Medicine
Fertility and Sterility | Year: 2014

Objective To determine the predictive attributes of antimüllerian hormone (AMH) in terms of oocyte yield, cycle cancellation, and pregnancy outcomes. Design Retrospective cohort. Setting Academic center. Patient(s) All patients initiating IVF at the Weill-Cornell Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine from April 2010 through January 2013. Intervention(s) In vitro fertilization without preimplantation genetic testing. Main Outcome Measure(s) Number of oocytes retrieved, cycle cancellation, clinical and ongoing pregnancy, implantation, and miscarriage rates. Result(s) Antimüllerian hormone was positively correlated with number of eggs retrieved. Number of oocytes retrieved increased with increasing AMH within each age group and diminished slightly within AMH groupings as age increased. Overall, AMH was significantly correlated with risk of cycle cancellation, with an area under the curve (AUC) of 0.74. Patients with undetectable AMH had a 13.3-fold increased risk of cancellation as compared with patients with an AMH >2.0 ng/mL. Antimüllerian hormone had an AUC of 0.83 for prediction of three or fewer oocytes; undetectable AMH exhibited sensitivity and specificity of 21.1% and 98.2%, respectively, for three or fewer oocytes retrieved. Antimüllerian hormone was less predictive of pregnancy, with AUCs ranging from 0.55 to 0.65. Even with undetectable AMH, 23.5% of patients <40 years old achieved live birth after transfer. Conclusion(s) Antimüllerian hormone is a fairly robust metric for the prediction of cancellation and how many oocytes may be retrieved after stimulation but is a relatively poor test for prediction of pregnancy after any given treatment cycle. Patients with extremely low levels of AMH still can achieve reasonable treatment outcomes and should not be precluded from attempting IVF solely on the basis of an AMH value. © 2014 American Society for Reproductive Medicine, Published by Elsevier Inc. All rights reserved.


Kofinas J.D.,New York Presbyterian Hospital | Elias R.T.,Ronald relman and Claudia Cohen Center for Reproductive Medicine
Women's Health | Year: 2014

Aim: To determine whether a follicle-stimulating hormone (FSH)/luteinizing hormone (LH) ratio over 3 in the setting of a normal FSH (<12 IU/l) is associated with a higher rate of failed controlled ovarian stimulation cycles. Design: Retrospective cohort. Materials & methods: A total of 676 patients were identified; 198 patients had a FSH/LH ratio >3 and 477 patients had a FSH/LH ratio <3. Exclusion criteria included: age >40 years; estradiol (E2) prime protocols; E2 at start >70 pg/ml; and FSH at start >12 IU/l. The main outcome measure was cycle cancellation. Results: An elevated FSH/LH ratio >3 was more likely to result in the individual's cycle cancelled (15 vs 5.24%; p = 0.0001). The total gonadotropin dosage was greater in the higher ratio versus lower ratio group (2636 vs 2242 IU; significant). Peak E2 was significantly lower in the FSH/LH >3 group (peak E2: 1635 vs 1942 pg/ml). Conclusion: The value of the FSH/LH ratio in patients with normal FSH levels, may have a role in determining the appropriate stimulation protocol and predict cycle cancellations. © 2014 Future Medicine Ltd.


Reichman D.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Rosenwaks Z.,Ronald relman And Claudia Cohen Center For Reproductive Medicine
Seminars in Reproductive Medicine | Year: 2015

In general, standardized in vitro fertilization (IVF) protocols and practice regimens can be applied with success for most patients. Such approaches, however, may not be effective for some women who do not fit the mold and for whom highly individualized treatments are more suitable. In this article, we outline our personal experience and treatment approaches for these challenging patients. © 2015 by Thieme Medical Publishers, Inc.


Reichman D.E.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Davis O.K.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Zaninovic N.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Rosenwaks Z.,Ronald relman And Claudia Cohen Center For Reproductive Medicine | Goldschlag D.E.,Ronald relman And Claudia Cohen Center For Reproductive Medicine
Fertility and Sterility | Year: 2012

Objective: To report the first case of fertility preservation in a premenarcheal female by use of controlled ovarian hyperstimulation and oocyte cryopreservation. Design: Case report. Setting: Reproductive endocrinology and infertility unit of a tertiary care university-based medical center. Patient(s): A 13-year-old premenarcheal female with Tanner stage 3 breast development and Tanner stage 1 pubic hair diagnosed with myelodysplastic syndrome, referred by her medical oncologist for fertility preservation before undergoing a potentially sterilizing antineoplastic therapy. Intervention(s): Evaluation of ovarian reserve, ovarian stimulation, transvaginal oocyte aspiration, in vitro maturation of immature oocytes, and oocyte cryopreservation. Main Outcome Measure(s): Cryopreservation of mature oocytes. Result(s): Successful controlled ovarian hyperstimulation allowed for the cryopreservation of 18 mature oocytes before the patient's gonadotoxic treatment. The oocyte retrieval and cryopreservation did not delay the patient's planned chemotherapy. Conclusion(s): Ovarian stimulation and oocyte cryopreservation can be successfully performed in premenarcheal/peripubertal patients, thus providing a viable alternative to ovarian tissue freezing for fertility preservation in the pediatric population. Copyright © 2012 American Society for Reproductive Medicine, Published by Elsevier Inc.

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