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Obesity-Related Causes of Stillbirth Detailed in Pitt Analysis

PITTSBURGH, Aug. 26, 2015 – Obese women are nearly twice as likely as their lean counterparts to have stillborn babies for several specific, potentially preventable medical reasons, a new University of Pittsburgh Graduate School of Public Health analysis reveals.

Placental diseases and hypertension were the most common causes of stillbirth among obese women, according to the study, published online and scheduled for the October issue of the American Journal of Clinical Nutrition. The research was supported by the National Institutes of Health (NIH).

“We’ve known for some time that obese women are more likely to have stillbirths, but this is one of the first and most comprehensive efforts to figure out why,” said lead author Lisa Bodnar, Ph.D., M.P.H., R.D., associate professor in Pitt Public Health’s Department of Epidemiology. “Our hope is that this work can be used to better counsel women on the importance of a healthy pre-pregnancy weight and monitor them for complications during pregnancy that may threaten the survival of their fetuses.”

“This study also could be used to guide prevention efforts at a societal level,” she said. “If we can reduce pre-pregnancy obesity by even a small amount, through environmental or policy changes, we could significantly reduce the burden of stillbirth.”

Annually there are 3.2 million stillbirths worldwide and, of high-income countries, the U.S. is among those with the highest rates. Recent research shows that obesity is likely responsible for more stillbirths in high-income countries than other risk factors, such as smoking or advanced maternal age.

Dr. Bodnar and her colleagues examined records from 658 stillbirths that occurred between 2003 and 2010 at Magee-Womens Hospital of UPMC, which has one of the largest labor and delivery units in the country. Stillbirths were defined as cases where the baby had reached at least 16 weeks gestation and showed no evidence of life after delivery. A panel of obstetricians reviewed each case and assigned a cause of the stillbirth.

The mothers were classified as lean (normal weight or underweight), overweight, obese or severely obese based on their pre-pregnancy body mass index, a measure of weight versus height.

The rate of stillbirth per 1,000 births ranged from 7.7 for lean women to 17.3 for severely obese women.

Maternal hypertension – or high blood pressure in the mother; placental diseases or disorders where the placenta does not properly sustain the unborn baby; fetal abnormalities where the baby would have been unlikely to live if it made it to birth; and umbilical cord abnormalities were all more common in the more obese women.

“Obstetricians should monitor obese patients for these complications and quickly treat conditions like hypertension if they arise in order to reduce risk of stillbirth,” said senior author Hyagriv N. Simhan, M.D., professor and chief of the division of maternal-fetal medicine and medical director of obstetrical services at Magee. “However, we’d like to see these women before they even become pregnant. When a doctor has an obese patient who is considering pregnancy, she should be referred to a maternal-fetal medicine specialist who can counsel her on the benefits of losing weight before pregnancy, as well as safe approaches to weight loss.”

Additional authors on this research are W. Tony Parks, M.D., Kiran Perkins, M.D., Sarah J. Pugh, M.P.H., Maisa Feghali, M.D., Karen Florio, D.O., Omar Young, M.D., and Sarah Bernstein, M.D., all of Pitt; and Robert W. Platt, Ph.D., of McGill University.

This research was funded by NIH grant R21 HD067851.

Magee Surgeon Leads Treatment Guidelines for Identical Twin Pregnancies

PITTSBURGH, August 5, 2015 – A monochorionic twin pregnancy, a pregnancy in which identical twins share one placenta, faces unique complications that can threaten the health and life of both babies, requiring an increased understanding of treatment techniques for the mother. Today, in work led by Stephen Emery, M.D., a maternal-fetal medicine surgeon with Magee-Womens Hospital of UPMC, the North American Fetal Therapy Network published evidence-based and consensus-driven recommendations for the management of such pregnancies in the journal Obstetrics and Gynecology.

“Identical twin pregnancies present some of the most challenging complications a maternal-fetal medicine specialist can face,” said Dr. Emery, who is the paper’s lead author. “With timely diagnosis and intervention, we can improve pregnancy outcomes. We hope these guidelines help general obstetric practitioners understand some of the complexities that can affect the development of identical twins sharing one placenta. These guidelines also should help with patient counseling, including when a woman experiencing a complication should be referred to a regional treatment center and how to co-manage her care when she returns after treatment.”

The North American Fetal Therapy Network is a consortium of 30 medical institutions across the U.S. and Canada with established expertise in fetal therapy and complex fetal disorders. For this publication, the consortium identified nine disorders to highlight, including:

  • Twin-to-twin transfusion syndrome, a disease of the placenta in which blood passes disproportionately from one baby to the other through connecting blood vessels within their shared placenta. One baby receives too much blood, overloading his or her cardiovascular system while the other baby doesn’t receive enough and develops low blood volume. Left untreated, this condition is almost always fatal for both twins.
  • Selective growth restriction, when a disproportionate share of the placenta causes inadequate nutrition and consequently growth restriction in one of the twins. Increasingly, selective growth restriction is being recognized as a major complication for monochorionic twin pregnancies because it is frequently associated with pregnancy loss and poor neurological outcomes.
  • Twin anemia polycythemia sequence, a form of twin-to-twin transfusion syndrome characterized by chronic, slow blood transfusion between the twins, which is believed to develop due to very small caliber artery-to-vein vessels that develop between the twins. One twin becomes severely anemic while the other has too many red blood cells (polycythemia), resulting in serious problems for both.

Menopause Associated with More Fat Around Heart, Raising Risk for Heart Disease

PITTSBURGH, July 22, 2015 – Late- and post-menopausal women have significantly greater volumes of fat around their hearts – a risk factor for heart disease – than their pre-menopausal counterparts, a University of Pittsburgh Graduate School of Public Health study has shown for the first time.

The finding, published online and scheduled for the Sept. 1 issue of The Journal of Clinical Endocrinology & Metabolism, likely can be attributed to changing hormone levels and could guide potentially life-saving interventions. The work was funded by the National Institutes of Health (NIH) and American Heart Association (AHA).

“Cardiovascular disease is the leading cause of death in women, and it increases after age 50 – the average age when a woman is going through menopause,” said lead author Samar R. El Khoudary, Ph.D., M.P.H., assistant professor in Pitt Public Health’s Department of Epidemiology. “By showing that menopause appears to be associated with a shift in fat deposits that leads to more fat around the heart, we’ve uncovered a new potential contributor to increased risk of cardiovascular disease in women.”

Weight gain in women during and after menopause has long been attributed to aging, rather than menopause itself. However, recent research identified changes in body fat composition and distribution due to menopause-related hormonal fluctuations.

No previous study had evaluated whether those changes in fat distribution during menopause affect cardiovascular fat. Increased and excess fat around the heart and vasculature can be more detrimental than abdominal fat, causing local inflammation and leading to heart disease. Doubling certain types of cardiovascular fat can lead to a more than 50 percent increase in coronary events.

Dr. El Khoudary and her team evaluated clinical data, including blood samples and heart CT scans, on 456 women from Pittsburgh and Chicago enrolled in the Study of Women’s Health Across the Nation (SWAN). The women averaged about 51 years of age and were not on hormone replacement therapy.

As concentrations of the sex hormone estradiol – the most potent estrogen – declined during menopause, greater volumes of cardiovascular fat were found. The finding held even after the team took into account the effects of age, race, obesity, physical activity, smoking, alcohol consumption, medication use and chronic diseases.

“Developing prevention strategies to reduce cardiovascular fat in women at midlife may reduce their heart disease risk, especially knowing that the menopausal transition puts women at risk for excess fat around their hearts,” said Dr. El Khoudary. “Previous studies suggest that reducing heart fat is feasible through weight loss or weight management, but these studies only looked at small numbers of people and there have been no clinical trials linking cardiovascular outcomes with heart fat changes due to weight management interventions. Clearly there is a need for larger scale studies to determine the best intervention strategies to help post-menopausal women reduce fat near the heart.”

Dr. El Khoudary and her research team are working on seeking more funds to evaluate whether cardiovascular fat volumes progress over time in midlife women, and, if so, whether this progression will be associated with greater evolution in atherosclerosis and more cardiovascular events in post-menopausal women.

Additional authors on this study are senior author Karen A. Matthews, Ph.D., of Pitt; and co-authors Kelly J. Shields, Ph.D., of Allegheny Health Network; Imke Janssen, Ph.D., and Lynda H. Powell, Ph.D., both of Rush University Medical Center; Carrie Hanely and Emma Barinas-Mitchell, Ph.D., both of Pitt; Matthew Budoff, M.D., of the Los Angeles Biomedical Research Institute; and Susan A. Everson-Rose, Ph.D., of the University of Minnesota Medical School.

This research was supported by NIH grants U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554 and HL065591; and AHA grant 12CRP11900031.

Lower Birth Weight Associated with Proximity of Mother’s Home to Gas Wells

PITTSBURGH, June 3, 2015 – Pregnant women living close to a high density of natural gas wells drilled with hydraulic fracturing were more likely to have babies with lower birth weights than women living farther from such wells, according to a University of Pittsburgh Graduate School of Public Health analysis of southwestern Pennsylvania birth records.

The finding does not prove that the proximity to the wells caused the lower birth weights, but it is a concerning association that warrants further investigation, the researchers concluded. The study was funded by The Heinz Endowments and published in the current issue of PLOS ONE.

“Our work is a first for our region and supports previous research linking unconventional gas development and adverse health outcomes,” said co-author Bruce Pitt, Ph.D., chair of Pitt Public Health’s Department of Environmental and Occupational Health. “These findings cannot be ignored. There is a clear need for studies in larger populations with better estimates of exposure and more in-depth medical records.”

Unconventional gas development includes horizontal drilling and high volume hydraulic fracturing, known as “fracking.” It allows access to large amounts of natural gas trapped in shale deposits. Prior to 2007, only 44 wells were known to be drilled in Pennsylvania’s Marcellus Shale with such technology. From 2007 to 2010, that expanded to 2,864 wells.

The Pitt Public Health research team cross-referenced birth outcomes for 15,451 babies born in Washington, Westmoreland and Butler counties from 2007 through 2010 with the proximity of the mother’s home to wells drilled using unconventional gas development. They divided the data into four groups, depending on the number and proximity of wells within a 10-mile radius of the mothers’ homes.

Mothers whose homes fell in the top group for proximity to a high density of such wells were 34 percent more likely to have babies who were “small for gestational age” than mothers whose homes fell in the bottom 25 percent. Small for gestational age refers to babies whose birth weight ranks them below the smallest 10 percent when compared to their peers.

The researchers took into account many factors that could influence a newborn’s weight – including whether the mother smoked, her prenatal care, race, education, age and whether she’d had previous babies, as well as the gender of the baby – and the finding still held.

“Developing fetuses are particularly sensitive to the effects of environmental pollutants,” said Dr. Pitt. “We know that fine particulate air pollution, exposure to heavy metals and benzene, and maternal stress all are associated with lower birth weight.”

In southwestern Pennsylvania, the waste fluids produced through hydrofracturing, called “flowback,” can contain benzene. Unconventional gas development also creates an opportunity for air pollution through flaring of methane gas at the well heads and controlled burning of natural gas that releases volatile organic compounds, including benzene, toluene, ethylbenzene and xylene. Increased truck traffic and diesel-operated compressors also can contribute to air and noise pollution.

“It is important to stress that our study does not say that these pollutants caused the lower birth weights,” said Dr. Pitt. “Unconventional gas development is dynamic and varies from site to site, changing the potential for human exposure. To draw firm conclusions, we need studies that thoroughly assess the exposure of a very large number of pregnant women to not just the gas wells, but other potential pollutants.”

Shaina L. Stacy, Ph.D., a recent graduate of Pitt Public Health, is lead author on this research, and Evelyn Talbott, Dr.P.H., epidemiology professor at the school, is senior author. Additional authors are LuAnn L. Brink, Ph.D., and Bernard D. Goldstein, M.D., both of Pitt Public Health; and Jacob C. Larkin, M.D., and Yoel Sadovsky, M.D., both of Magee-Womens Research Institute and Pitt School of Medicine.

X-linked Gene Mutations Cause Some Cases of Male Infertility, Pitt Study Says

PITTSBURGH, May 13, 2015 – Some cases of male infertility are due to mutations in the maternal X chromosome that prevent development of viable sperm, according to a study led by researchers at the University of Pittsburgh School of Medicine and the Magee-Womens Research Institute (MWRI). The study was published online today in the New England Journal of Medicine.

Nearly half of cases of male infertility not due to a physical obstruction are estimated to have genetic roots, and about 20 percent of infertile men have azoospermia, meaning they don’t make sperm, explained co-principal investigator Alexander Yatsenko, M.D., Ph.D., assistant professor of obstetrics, gynecology and reproductive medicine, Pitt School of Medicine, and an MWRI investigator. He noted the only causes for infertility that have been identified are defects of sex chromosomes, such as the deletions of the Y (male) chromosome or duplication of the entire X (female) chromosome in Klinefelter syndrome.

“Eight times out of 10, conventional genetic testing doesn’t reveal a chromosomal problem, so the cause is considered idiopathic or unknown,” Dr. Yatsenko said. “This study is among the first to describe specific gene mutations on the X chromosome that contribute to azoospermia and male infertility.”

First, the research team scanned the genomes of 15 men with azoospermia and found a deletion in part of the DNA coding of the testis-expressed gene 11 (TEX11) on the X-chromosome, which men inherit from their mothers. The alteration caused meiotic arrest, meaning the precursor cells could not properly undergo meiosis, the cell division process that produces daughter cells with half the parental chromosomes for reproduction.

Then, they found similar TEX11 gene mutations and meiotic arrest in two out of 49 men diagnosed with idiopathic azoospermia from the Center for Fertility and Reproductive Endocrinology at Magee-Womens Hospital of UPMC, and the Institute of Human Genetics of the Polish Academy of Sciences in Poznan, Poland. Also, TEX11 gene errors were found in five out of 240 infertile men from the Center of Reproductive Medicine and Andrology in Münster, Germany.

Dr. Yatsenko noted that it might be possible for an older father, whose precursor sperm cells have a greater likelihood of acquiring a mutation, to pass along the genetic error to his daughter, which could make it impossible for her son to make viable sperm. Also, men without seminal sperm who undergo a procedure to have a few rare, viable sperm extracted from the testes to attempt conception with in vitro fertilization could unknowingly pass a TEX11 gene mutation to a daughter, making her a carrier.

“This research suggests screening for TEX11 gene mutations might be useful in cases of otherwise unexplained azoospermia,” Dr. Yatsenko said. “It might be possible to one day correct these problems with gene therapy and other interventions. More work must be done to identify other genetic causes of male infertility.”

The team included co-senior author Frank Tüttelmann, M.D., and others from of the University of Münster, Germany; the University of Pittsburgh; and the Polish Academy of Sciences.

The project was funded by grant HD058073 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the Pennsylvania Department of Health; MWRI; the University of Pittsburgh; the Polish National Science Centre; and the German Research Foundation.

Magee, UPCI Researchers Seek New Targets for Ovarian Cancer Treatment

PHILADEPHIA, April 19, 2015 – Identifying molecular changes that occur in tissue after chemotherapy could be crucial in advancing treatments for ovarian cancer, according to research from Magee-Womens Research Institute and Foundation (MWRIF) and the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter, presented today at the American Association for Cancer Research (AACR) Annual Meeting 2015.

For years now, intraperitoneal chemotherapy, a treatment which involves filling the abdominal cavity with chemotherapy drugs after surgery, has been considered the standard of care for ovarian cancer. According to Shannon Grabosch, M.D., a gynecologic oncology fellow at Magee-Womens Hospital of UPMC and the study’s lead investigator, treatment advances for this disease haven’t moved forward as quickly as they have for other cancers.

“The addition of intraperitoneal chemotherapy for women with ovarian cancer was one of the biggest achievements in improving survival outcomes, but unfortunately, we still don’t understand the biological mechanisms by which this works,” said Dr. Grabosch. “We wanted to understand what changes occurred to the local tumor environment after chemotherapy was administered, with the idea that these changes could eventually be targets for new, personalized ovarian cancer treatments.”

Dr. Grabosch and her team examined peritoneal cavity fluid and peripheral blood samples of 13 patients. The samples were obtained prior to intraperitoneal treatment and after the first and second rounds of chemotherapy. Using multiple sequencing techniques, Dr. Grabosch and her team identified chemotherapy-induced molecular changes.

“We were able to identify changes in both miRNA and genes which appear to be related to chemotherapy. Furthermore, we identified different, significant changes between the peritoneal cavity and blood samples, proving that the local tumor environment is an underutilized wealth of information,” said Dr. Grabosch. “Now we need larger studies to determine whether the changes that occur in the tumor microenvironment after chemotherapy could be potential targets for new, more personalized drugs and to further understand the mechanisms of intraperitoneal chemotherapy.”

Additional authors on this research, which was funded by the Magee-Womens Research Institute and Foundation and the Gynecologic Oncology Group, are Anda M. Vlad, M.D., Ph.D., Tianzhou Ma, M.S., Jyothi Mony, Ph.D., Mary Strange, M.S., Joan Brozick, M.H.A., Julia Thaller, M.B.A., George Tseng, Ph.D., Xin Huan, Ph.D., Katie Moore, M.D., Kunle Odunsi, M.D., Ph.D., and Robert P. Edwards, M.D., all with MWRIF and UPCI.

Pervasive Chemical Potentially Alters Levels of a Pregnancy Hormone that Influences Sex Development

PITTSBURGH, March 5, 2015 – Exposure to hormone-altering chemicals called phthalates – which are found in many plastics, foods  and personal care products – early in pregnancy is associated with a disruption in an essential pregnancy hormone and adversely affects the masculinization of male genitals in the baby, according to research led by the University of Pittsburgh Graduate School of Public Health.

The findings, presented today at the Endocrine Society’s 97th annual meeting in San Diego and funded by the National Institute of Environmental Health Sciences, focus on the role of the placenta in responding to these chemicals and altering levels of a key pregnancy hormone. These results suggest that there may be reason to push routine clinical testing earlier in pregnancy to check for the effects of chemicals and help guide potential interventions to protect the health of the baby.

“Phthalates are pervasive,” said Jennifer Adibi, M.P.H., Sc.D., assistant professor of epidemiology at Pitt Public Health. “Reducing exposure to phthalates and other hormone-disrupting chemicals is something that needs to be addressed at a societal level through consumer advocacy and regulation, and education of health care providers.”

The research builds on a study led by Shanna S. Swan, Ph.D., of the Icahn School of Medicine at Mount Sinai that was published in February in the journal Human Reproduction. Dr. Swan is senior investigator on this presentation, which provides new information about how phthalates target a key pregnancy hormone called human chorionic gonadotropin (hCG), which is made by the placenta and can be measured in the mother’s blood and urine.

“The placenta, which is an extension of the fetus and a target of the chemicals in our bodies, broadcasts information early in pregnancy, through hCG, about what might be occurring to the fetus from chemical exposure,” said Dr. Adibi. “A long-term benefit of this research might be the development of new knowledge and methods for earlier screening in pregnancy, with the potential to act on this information to improve the long-term health of the future child.”

Dr. Adibi and her colleagues analyzed data collected from approximately 350 women and their babies who participated in a multicenter investigation called The Infant Development and the Environment Study (TIDES). Between 2010 and 2012, the women gave blood and urine samples in their first trimester of pregnancy and allowed researchers to take measurements of the babies at birth.

Higher levels of two molecules that are produced when phthalates are digested – mono-n-butyl and monobenzyl phthalate – in the mothers’ urine early in pregnancy were significantly associated with lower levels of hCG in women carrying male babies and with higher hCG in those carrying female babies.

The new research also looked at hCG in relation to a biological marker called anogenital distance, which is the distance between the anus and genitals. In men, a short anogenital distance is associated with decreased sperm count and infertility.

Higher levels of hCG in the mother’s blood were associated with a shorter anogenital distance in male babies. The researchers estimate that about 20 to 30 percent of the phthalate effect on the babies’ genitals could be attributed to the influence of phthalates on hCG, specifically mono-n-butyl and mono-ethylhexyl phthalate.

“Our study is the first to look at hCG as a target of phthalate exposure in pregnancy,” said Dr. Adibi. “There is growing societal concern over pediatric disorders that have a basis in the fetal period and which may be more common in one sex or another, such as autism, attention deficit disorder, obesity, asthma and infertility. It is important to find out if chemicals in our food or environment might influence these conditions.”

The participants in this study were enrolled at prenatal clinics in California, Washington, Minnesota and New York. Dr. Adibi is looking ahead to future studies where she will enroll women in the earliest stages of pregnancy at clinics in Pittsburgh to assess exposures to endocrine disruptors and measure effects on the placenta and the baby.

Additional researchers on this study are Myoung Keun Lee, M.S., of Pitt; Ashley I. Naimi, Ph.D., of McGill University; Emily Barrett, Ph.D., of the University of Rochester; Ruby Nguyen, Ph.D., and Bruce Redmon, M.D., both of the University of Minnesota; Sheela Sathyanarayana, M.D., M.P.H., of the University of Washington; and Kara Saperston, M.D., Mari-Paule Thiet, M.D., Sarah Janssen, M.D., Ph.D., M.P.H., and Lawrence Baskin, M.D., all of the University of California.

This research was funded by National Institutes of Environmental Health Sciences grants 1 K99 ES017780-01 and 5 R00 ES017780-06. TIDES was funded by National Institute of Environmental Health Sciences grants R01 ES016863-04 and R01 ES016863-02S4.

Contraceptive Counseling at Dermatologist’s Office Improves Knowledge of Effectiveness For Women Taking Acne Drug, Pitt Study Finds

PITTSBURGH, Feb. 4, 2014 – Providing women who take a powerful acne drug with a fact sheet about contraception while visiting the dermatologist can significantly improve their awareness of the most effective birth control options and may prevent unintended pregnancies and birth defects that can be caused by the drug, according to a University of Pittsburgh School of Medicine study published Feb. 4 in the journal JAMA Dermatology.

Isotretinoin, formerly marketed as Accutane, is an effective drug for the treatment of acne, but is also considered a teratogen, or a drug that can cause birth defects. Because of this, the Food and Drug Administration (FDA) strictly regulates the distribution of the drug to women of childbearing age. Through the FDA’s iPLEDGE program, woman who are prescribed the drug must pledge to use two forms of contraception, in addition to taking regular pregnancy tests while on the drug and online tests to make sure they understand the dangers of getting pregnant while taking the drug.

Despite the regulations, 122 pregnancies affected by isotretinoin were reported in the U.S. during the first year of the iPLEDGE program. Pitt researchers have been studying this and found gaps in patients’ knowledge about the most effective forms of contraception.

“While contraceptive counseling isn’t something a dermatologist has to do on a daily basis – like an obstetrician or gynecologist would – it does matter for young women using these drugs. Our goal was to show that a simple intervention like our handout could be added to dermatology office visits to enhance contraceptive counseling and decrease the number of exposed fetuses through more effective means of contraception,” said Carly A. Werner, M.D., a UPMC resident in the Department of Obstetrics, Gynecology and Reproductive Sciences and lead author on the study.

In the study, researchers surveyed 100 women from a single dermatology clinic between April and May 2014. Prior to viewing the contraceptive fact sheet, 75 percent overestimated the effectiveness of condoms, while 51 percent did the same for oral contraceptives. Thirty-four percent of women said they had never heard of contraceptive implants, and 16 percent had never heard of IUDs, or intrauterine contraceptive devices, despite their effectiveness being much higher than that of condoms and oral options.

Researchers surveyed those women again after they had reviewed the fact sheet and found significant improvement in knowing about contraceptives.

“This shows us that dermatologists can make a difference by providing women who take this drug more education regarding effective forms of contraception,” said Laura Ferris, M.D., Ph.D., director of clinical trials for UPMC’s Department of Dermatology, who was a co-author on the study.

The researchers recommended that future study is needed to determine how much the information provided on the fact sheet was retained and if it does reduce the risk of medication-induced birth defects.

Other collaborators were Melissa J. Papic, B.S., and Eleanor Bimla Schwarz, M.D., both with the University of Pittsburgh.

The study was funded in part by FDA grant U01FD004253-01.

Robert P. Edwards, MD, Named Chair of the Department of Obstetrics, Gynecology, and Reproductive Sciences

PITTSBURGH, Jan. 21, 2015 – The University of Pittsburgh School of Medicine and UPMC are proud to announce the appointment of Robert P. Edwards, MD, as chair of the Department of Obstetrics, Gynecology, and Reproductive Sciences, effective Jan. 1, 2015. Dr. Edwards is succeeding W. Allen Hogge, MD, who retired at the end of December 2014 after 22 years of distinguished service.

Dr. Edwards received his medical degree from the University of Pittsburgh School of Medicine and completed an internship in surgery at the University of California, San Francisco. He also completed a residency in obstetrics and gynecology at Magee-Womens Hospital of UPMC, and two postdoctoral fellowships at the University of Alabama; one in immunology and microbiology, and another in gynecologic oncology.

His first independent appointment was in 1993 as an assistant professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of Pittsburgh with a secondary appointment in the UPMC Department of Surgery. In 2000, Dr. Edwards was promoted to associate professor. From 1993 through 2001, he was director of the Division of Gynecologic Oncology at Magee, and he was a clinical investigator in the Magee-Womens Research Institute (MWRI). Starting in 2002, Dr. Edwards spent three years at the University of Louisville School of Medicine in the Departments of Microbiology and Immunology, and Obstetrics, Gynecology, and Women’s Health. In 2005, Dr. Edwards returned to Pitt as vice chair for Clinical Affairs in the Department of Obstetrics, Gynecology, and Reproductive Sciences, a senior investigator in MWRI, and director of Gynecologic Oncology Research and Outreach at Magee. In 2008, tenure was conferred, and he was appointed full professor. In 2010, Dr. Edwards was appointed executive vice chair of Gynecologic Services and co-director of the Ovarian Cancer Center of Excellence at Magee.

Dr. Edwards is a member of several professional and scientific societies, including the American Association for Cancer Research, the American Association for the Advancement of Science, the American Society for Clinical Oncology, the International Gynecologic Cancer Society, and the Society of Gynecologic Oncologists. He also is a fellow of the American College of Obstetricians and Gynecologists and the American College of Surgeons.

He has received various awards and honors throughout his career including two National Faculty Awards from the Council on Resident Education in Obstetrics and Gynecology (CREOG) of the American Congress of Obstetricians and Gynecologists. Dr. Edwards also has authored or co-authored 177 peer-reviewed research reports published in obstetrics and oncology literature, as well as PLOS ONE, Human Genetics, Nature Genetics, and The New England Journal of Medicine, and he is a member of the editorial board of Gynecology. His prominence is reflected in frequent invitations to lecture in such venues as the Roswell Park Cancer Institute, as well as annual meetings of the Society of Surgical Oncology and the Society of Gynecologic Oncologists.

Dr. Edwards’ research is very well supported and has been since the inception of his independent academic career. Currently, he is co-principal investigator of an ovarian cancer NIH SPORE grant, and he is co-investigator on grants from the United States Army and the Ovarian Cancer Research Foundation.

Dr. Edwards’ research focuses on the diagnosis, pathogenesis, and management of gynecologic cancers. He investigates therapies for cervical and ovarian cancer, combining biologic and immunologic strategies. Clinical trials that he designed and implemented include studies on intraperitoneal interleukin-2 therapy for ovarian cancer, and he was involved in early trials of the human papillomavirus (HPV) vaccine. In his current work, Dr. Edwards is investigating vaccines to treat ovarian cancer, and he is studying the impact of cytoxin on T regulatory cell populations, which are associated with the induction of vaccine responses in ovarian cancer patients. In collaboration with the radiation oncology group, he has also worked to advance radiotherapeutic treatments for vulvar and cervical cancers. In addition to his own research, Dr. Edwards will be a member of the MWRI Board, while Yoel Sadovsky, MD, continues to serve as vice chair of the Department for Research, MWRI’s executive director, and associate dean for Women’s Health and Reproductive Sciences Research.

In addition to his clinical and research activities, Dr. Edwards is a committed teacher and mentor for University of Pittsburgh medical students, residents, and fellows. He is a member of many internal committees at UPMC and Magee. He also has been an ad hoc member of the Ovarian Cancer Research Program Integrated Panel NIH study section and a member of various advisory boards, as well as industry working groups.

Newly-Identified Genetic Mutations Could Help Explain Early Menopause, Infertility

Pittsburgh, Dec. 31, 2014 –Two newly-identified genetic mutations could increase our understanding of the causes behind premature ovarian failure, which is one cause of infertility, and potentially guide options for treating women with the condition, according to research from Magee-Womens Research Institute (MWRI) recently published online in the Journal of Clinical Investigation and the American Journal of Human Genetics.

The mutations, which occurred in women with premature ovarian failure, a condition that causes a woman’s ovaries to stop working prior to 40 years of age, were found in genes that repair damaged DNA in the cells of the ovary that eventually become egg cells. In the U.S., premature ovarian failure affects about one percent of women during their reproductive years, some as early as their teenage years. Apart from compromising fertility, the condition also puts women at high risk for osteoporosis and heart disease.

Researchers from MWRI, in collaboration with international colleagues, performed genome sequencing on blood and skin samples from three families. Each family had at least one woman with premature ovarian failure.

“Most women with premature ovarian failure don’t know why they can’t reproduce, and it can be devastating for them,” said the senior author of the studies, Aleksandar Rajkovic, M.D., Ph.D., a researcher with MWRI and the Marcus Allen Hogge chair in reproductive sciences at the University of Pittsburgh. “Our findings indicate that genetics may play a strong role in this condition and raise the prospect of one day developing therapies to delay the early onset of menopause.”

According to Dr. Rajkovic, this research shows the power of whole genome sequencing. “Now that we understand some of the contributors to premature ovarian failure, we can work toward correcting the condition,” he said.

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