Author Interviews, Fertility, Genetic Research, Science / 17.07.2015

Stephen A. Krawetz, Ph.D. Associate Director C.S. Mott Center for Human Growth and Development, Charlotte B. Failing Professor of Fetal Therapy and Diagnosis, Department of Obstetrics and Gynecology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201MedicalResearch.com Interview with: Stephen A. Krawetz, Ph.D. Associate Director C.S. Mott Center for Human Growth and Development, Charlotte B. Failing Professor of Fetal Therapy and Diagnosis, Department of Obstetrics and Gynecology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201 Medical Research: What is the background for this study? What are the main findings? Dr. Krawetz: The current study developed over approximately the past 20 years of work in my laboratory.  In the mid 1990s, along with David Miller, we independently discovered that sperm contain RNA.  This was followed by our joint publication in The Lancet that began to describe the RNAs in normal fertile males along with our paper in Nature that showed that RNA was delivered to the oocyte at fertilization.  Following these studies we assessed the ability of RNAs to be used as markers of morphologically abnormal sperm (teratozoospermia).  My laboratory then had the opportunity to explore the complexity of the population of sperm RNAs using Next Generation Sequencing.   We recently began the translation of this work from the bench to bedside which takes us to the current paper in Science Translational Medicine that was a multi-institutional collaborative effort.  Members of the team include Dr. Meritxell Jodar, Edward Sendler, Robert Goodrich, from my laboratory, along with Dr. Clifford L. Librach, Dr. Sergey I. Moskovtsev, and Sonja Swanson - CReATe Fertility Center, University of Toronto; Dr. Russ Hauser -Harvard University and Dr. Michael P. Diamond, Georgia Regents University. Here we tackled the issue of idiopathic infertility, that is, unknown infertility, since the couple appears normal in all respects.  We specifically framed our study as the contribution of the male and female as a couple towards the birth of a healthy child focusing on male idiopathic infertility within the setting of a Reproductive Clinic.  Representative publications from my laboratory that outline this part of my research program appear below. 1)            Jodar, M., Sendler, E., Moskovtsev, S. Librach, C., Goodrich, R., Swanson, S., Hauser, R., Diamond, M. and Krawetz, S.A. (2015) Absence of sperm RNA elements correlates with idiopathic male infertility. Science Translational Medicine, 7(295):295re6. 2)            Sendler, E., Johnson, G.D., Mao, S., Goodrich, R.J., Diamond, M.P., Hauser, R., and Krawetz, S.A. (2013) Stability, Delivery and Functions of Human Sperm RNAs at Fertilization.  Nucleic Acids Research 41:4104-4117. PMID: 23471003 3)            Platts, A.E., Dix, D. J., Chemes, H.E., Thompson, K.E., Goodrich, R., Rockett, J. C., Rawe, V.Y., Quintana, S., Diamond, M.P., Strader, L.F. and Krawetz, S.A. (2007)  Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs.  Human Molecular Genetics. 16:763-773.  PMID: 17327269 4)            Ostermeier, G.C., Miller, D., Huntriss, J.D., Diamond, M.P. and Krawetz, S.A. (2004) Delivering spermatozoan RNA to the oocyte.  Nature 429:154.  PMID: 15141202 5)            Ostermeier, G.C., Dix, D.J., Miller, D., Khatri, P. and Krawetz, S.A. (2002) Spermatozoal RNA profiles of normal fertile men. The Lancet. 360:773-777.  PMID: 12241836 (more…)
Author Interviews, CDC, OBGYNE / 07.05.2015

Dmitry Kissin, MD Health scientist CDC Division of Reproductive HealthMedicalResearch.com Interview with: Dmitry Kissin, MD Health scientist CDC Division of Reproductive Health Medical Research: What is the background for this study? Dr. Kissin: Due to the frequent transfer of more than one embryo during assisted reproductive technology (ART) treatments, such as in vitro fertilization (IVF), many ART-conceived children are born as multiples (twins, triplets and higher order). Multiple births, even twins, carry increased risk for both mothers and children. In the U.S., the practice guidelines published by the American Society for Reproductive Medicine (ASRM) and the Society for Assisted Reproductive Technology (SART) provide recommendations on how many embryos to transfer in order to balance safety with the effectiveness of assisted reproductive technology. In an effort to reduce multiple births and associated complications, it is important to evaluate embryo transfer practices that contribute to these outcomes. Medical Research: What are the main findings? Dr. Kissin: Using data from the CDC’s National ART Surveillance System (NASS), we found that the majority of ART-related multiple births in the U.S. resulted from assisted reproductive technology cycles practiced in accordance with ASRM/SART guidelines and involved the transfer of two embryos. Almost half of ART-related multiple births resulted from transferring two fresh blastocysts (embryos cultured for 5/6 days) to favorable- or average-prognosis patients less than 35 years and donor-egg recipients, or two frozen/thawed embryos to patients less than 35 years. (more…)
Author Interviews, Occupational Health, Sexual Health, Stanford / 09.03.2015

Michael L. Eisenberg, M.D. Director, Male Reproductive Medicine and Surgery Assistant Professor Department of Urology Stanford University School of MedicineMedicalResearch.com Interview with: Michael L. Eisenberg, M.D. Director, Male Reproductive Medicine and Surgery Assistant Professor Department of Urology Stanford University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Eisenberg: There has been growing data that a man's overall health may impact his fertility. As such, we wanted to explore this link using the NICHD LIFE Study which has the unique ability to account for both health and work exposure in men with both normal and abnormal fertility. We found that certain aspects of a man's work and health can impact his semen parameters. (more…)
Author Interviews, Stem Cells / 26.02.2015

Jacob (Yaqub) Hanna  M.D. Ph.D. Kimmel Investigator | NYSCF Robertson Investigator The Department of Molecular Genetics Weizmann Institute of Science, IsraelMedicalResearch.com Interview with: Jacob (Yaqub) Hanna  M.D. Ph.D. Kimmel Investigator | NYSCF Robertson Investigator The Department of Molecular Genetics Weizmann Institute of Science, Israel MedicalResearch: Could this be helpful for any individual with infertility problems?  Dr Hanna: Our research is focused on taking skin cell samples and converting them into embryonic-like stem cells (iPS cells) via direct reprogramming and without using embryo derived stem cell lines. Then we are focusing in differentiating these male or female iPS lines into sperm cells or oocytes, respectively. We have succeeded in the first and most important step of the process, where we succeed in reaching the progenitor cell state for sperm and egg (we have not achieved mature sperm and eggs ….Very important to emphasize!). So we are now focusing on completing the second half of this process. Once that is achieved this may become useful for any individual with fertility problems. MedicalResearch: Could this be a viable option ALSO for same-sex couples?  What are the prospects for letting gay or lesbian couples produce progenitor cell state cells from their skin cells? For example, is it conceivable that the "second half" of the protocol could some day also be done in vitro (making fully mature sperm and eggs), so that men could produce egg cells and women sperm cells? (more…)
Author Interviews, OBGYNE / 21.01.2015

Anna Geraghty Department of Integrative Biology University of California, Berkeley, Berkeley,MedicalResearch.com Interview with: Anna Geraghty Department of Integrative Biology University of California, Berkeley, Berkeley, Medical Research: What is the background for this study? What are the main findings? Response: RFRP3 in mammals has been well characterized as a negative regulator of the hormonal reproductive axis. It shuts down release of gonadotropins necessary for successful reproduction, similar to how stress inhibits reproduction. Our lab has previously shown that stress can directly regulate RFRP3 levels in males-both acute and chronic stress lead to an upregulation of RFRP3 levels in the male rat. As a followup to that study, we were interested in looking at whether this response was similar in females, and how that may affect long term fertility. We found that chronic (18 days) of stress led to an increase in RFRP3 levels all all stages of the estrous cycle. This increase was also sustained for at least 4 days, or one whole estrous cycle, after the stress ended- the equivalent to a month menstrual cycle in humans. In rats that were stressed and then allowed to recover for 4 days, animals that were stressed were significantly less successful at reproducing- 76% success rate in controls compared to 21% in the stressed animals. This was a result of a combination of deficits in the mating process- less stressed animals successfully copulated, those that did successfully mate had fewer pregnancies, and gave birth to smaller litters. However, utilizing an inducible virus to knockdown RFRP levels in the hypothalamus specifically during the stress period prevented all of these problems- stressed animals without stress-induced RFRP3 increases looked indistinguishable to controls. (more…)
Author Interviews, Fertility, Stanford / 17.05.2014

Michael Eisenberg, MD, PhD Director, Male Reproductive Medicine and Surgery Assistant Professor, Department of Urology Assistant Professor, Department of Obstetrics and GynecologyMedicalResearch. com Interview with: Michael Eisenberg, MD, PhD Director, Male Reproductive Medicine and Surgery Assistant Professor, Department of Urology Assistant Professor, Department of Obstetrics and Gynecology Stanford School of Medicine
MedicalResearch:   What are the main findings of the study? Dr. Eisenberg: There is an inverse relationship between semen quality and mortality so that as semen quality declines the likliehood of death increases. (more…)
JAMA, OBGYNE / 22.10.2013

Dr. Jennifer Fay Kawwaas MD Department of Gynecology and Obstetrics Emory University School of Medicine, Atlanta, GA, USAMedicalResearch.com Interview with: Dr. Jennifer Fay Kawwaas MD Department of Gynecology and Obstetrics Emory University School of Medicine, Atlanta, GA, USA MedicalResearch.com: What are the main findings of the study? Dr. Kawwaas: Using CDC National ART Surveillance System (NASS) data, we found an increasing trend from 2000 to 2010 in the number of donor egg cycles performed annually and in the percentage of donor cycles that resulted in a good outcome, defined as delivery of a full term infant weighing more than 5.5lbs. Donor and recipient ages remained relatively stable at 28 and 41, respectively, over the 11-year period. Elective single embryo transfer is recommended when the donor is under 35 years old, regardless of recipient’s age; transfer of a single day 5 embryo was associated with an increased chance of good perinatal outcome. Tubal or uterine factor infertility and non-Hispanic Black race were associated with a lower chance of good perinatal outcome. (more…)