Tag Archives: Michael Diamond

Frontline treatments show best results for unexplained infertility

A breast cancer drug with promise for improving the chance that couples with unexplained infertility can have a baby without increasing their risk of multiple births apparently does not deliver, according to a comparative study.

“The question was could we reduce the risk of twins and triplets without negatively impacting the total number of women who can conceive?” said Dr. Michael P. Diamond, reproductive endocrinologist and Chairman of the Department of Obstetrics and Gynecology at the Medical College of Georgia at Georgia Regents University.

In a study published in the New England Journal of Medicine, researchers showed pregnancy rates and live birth rates were significantly lower in women treated with letrozole, an aromatase inhibitor that enables ovulation, than those receiving the frontline drugs gonadotropin or clomiphene. As an example, live birth rates were 32.3 percent in women taking gonadotropin and 18.7 percent with letrozole.

The cancer drug has been used off-label for infertility for several years because of anecdotal reports that it could help women conceive with less risk of multiple births. Diamond participated in another study published last summer, also in NEJM, that showed letrozole was better than clomiphene at improving rates of ovulation, conception, pregnancy and live birth in women with polycystic ovary syndrome. PCOS affects 5-10 percent of reproductive-age women whose major infertility problem is that they don’t ovulate.

But letrozole’s success in women with PCOS does not hold up when the cause of infertility is unclear. While patients with unexplained infertility taking letrozole did have a significantly lower number of multiple births than those taking gonadotropins, those rates were comparable to clomiphene, said Diamond, the new study’s corresponding author. Letrozole therapy did result in a significantly reduced number of multiple births compared with gonadotropin, but its rates were two-and-a-half times higher than clomiphene’s.

“The conclusion for couples with unexplained infertility is that clomiphene probably still remains the first-line therapy,” Diamond said of the widely used drug that enables production of more eggs and the hormones that support them.

Women taking gonadotropin, which is given by shot rather than by tablet like the other two drugs, had the highest rate of pregnancy and live births, but it also had the highest multiple birth rate, Diamond noted. Gonadotropin therapy resulted in 24 sets of twins and 10 sets of triples. Letrozole and clomiphene therapy produced only twins, which generally result in fewer complications during pregnancy and after birth than triplets. There were no significant differences among the three treatment arms in resulting birth defects or newborn complications.

The study looked at 900 women age 18 to 40 with unexplained infertility at 12 centers across the nation through the Cooperative Reproductive Medicine Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

A third of patients were randomly assigned to receive up to four cycles of ovarian stimulation with gonadotropin, clomiphene or letrozole; there was no placebo group. Researchers obtained an investigational new drug application with the Food and Drug Administration for the study since letrozole is currently only approved for breast cancer treatment.

Like clomiphene, letrozole actually tricks the body into making more estrogen. Clomiphene, which is a selective estrogen receptor modulator, binds to estrogen receptors when estrogen levels are high so the brain gets the message to make even more, Diamond said. The pituitary gland gets stimulated by the hypothalamus, and patients make follicle stimulation hormone, which enables the eggs to mature, and more luteinizing hormone, which stimulates ovulation, enabling the mature egg to be released for fertilization. Letrozole produces similar results by blocking estrogen production, Diamond said.

“In a typical monthly cycle, there is usually one follicle and one egg that develop to the point of ovulation,” Diamond said. “What happens with the fertility drugs, you are overriding the mechanisms which usually only lead to development of one dominant follicle and release of one egg.”

Women are diagnosed with unexplained infertility if they have been trying for a year to get pregnant and there are no obvious problems such as lack of ovulation, an abnormal uterus or evidence of inflammation, such as endometriosis. Some of the women may have already had a previous child.

Yale University provided data coordination for the study. Diamond is also GRU’s senior vice president for research.

GRU among 15 centers awarded federal funding to train physician-scientists in ob-gyn

Georgia Regents University is among 15 institutions in the nation to receive federal funding to help train the next generation of physician-scientists in obstetrics and gynecology.

GRU will receive $1.7 million over the next five years from the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development to train obstetrician-gynecologists to also become independent investigators in diverse women’s health fields such as infertility and high-risk pregnancy.

“We want individuals with fire in their belly to be able to get involved in research,” said Dr. Michael P. Diamond, chairman of the Department of Obstetrics and Gynecology at the Medical College of Georgia at GRU, the university’s senior vice president for research and principal investigator for the new program in Augusta. “It’s a great opportunity to train clinicians to be clinical investigators.”

Diamond had been a research director on the Women’s Reproductive Health Research Career Development Program since its inception in 1998. When he came to MCG and GRU in 2013 from Wayne State University, Diamond’s goals included starting a program here.

The program is available for junior faculty as well as residents or fellows who have just completed training at locations across the nation or at MCG. National recruitment efforts start in September. The program funds two positions at a time for a maximum of five years in Augusta. Federal dollars will help support the salaries and the research of the program scholars.

Having committed time for research is difficult for physicians, particularly more junior physicians trying to juggle building a practice and a solid research program, Diamond said. The federal grant enables the physicians to focus on research at least 30 hours weekly.

The program will not only be important to individuals, but also to the medical school and university as it strives to reach the next level of academic achievement nationally, Diamond said. More minds focused on finding new knowledge will also help drive treatment forward for a variety of conditions affecting women, he said.

Dr. Nita J. Maihle, a breast cancer researcher who is associate director of education for the GRU Cancer Center and professor in the MCG Department of Biochemistry and Molecular Biology, is the program director. Dr. Ayman Al-Hendy, an obstetrician-gynecologist who directs his department’s Division of Translational Research, is recruitment director; and Dr. Lara M. Stepleman, psychologist and co-director of the GRU Educational Innovation Institute, is assisting the evaluation of the scholars.

Scholars can select mentors from a sizeable group of faculty who want to help more junior colleagues with their research career development, Diamond said. Examples include Dr. Larry B. Layman, chief of the Section of Reproductive Endocrinology, Infertility and Genetics, and an NIH-funded investigator pursuing better understanding of clinical problems such as delayed puberty.

Other institutions receiving federal funding this year for the program are the University of Alabama at Birmingham; Northwestern University at Chicago; Oregon Health & Science University; University of Pennsylvania; Magee-Women’s Research Institute and Foundation; University of Washington; University of California, San Francisco; University of Michigan; University of California, San Diego; University of Utah; Women and Infants Hospital-Rhode Island; Wayne State University; University of Colorado, Denver; and Yale University.

According to the 2014 Physician-Scientist Workforce Working Group Report from the NIH, issues such as years of reductions in federal funding to support research, increasing clinical demands and the increased cost of medical education translate to a shortage of both physician-scientists and mentors across many specialties. The career development grant strives to reverse this national trend and train the next generation of physician-scientists in obstetrics and gynecology, Diamond said.

For more information, contact Diamond at michael.diamond@gru.edu or 706-721-3591, Maihle at nmaihle@gru.edu or 706-421-5991 and Al-Hendy at aalhendy@gru.edu or 706-721-3591.

Dr. Michael Diamond named Senior Vice President for Research

In an email released Wednesday, Provost Gretchen Caughman announced that Dr. Michael Diamond had been named Senior Vice President for Research, effective immediately.

“Dr. Diamond brings broad leadership and research experience to the position, in which he will oversee all aspects of the university’s research enterprise,” Caughman said.

Diamond had been serving as Interim SVP for Research since September.

After 19 years at Wayne State University, he joined GRU in early 2013 as the inaugural Vice President for Clinical and Translational Sciences. He is a reproductive endocrinologist and expert in designing and implementing clinical trials whose study focus includes infertility and procedure-related adhesions.

While at GRU Diamond has created the Division of Clinical and Translational Sciences, formed research committees focused on improving research processes, led a comprehensive review of research policies and procedures, and oversaw the identification and implementation of new research software.

 

Dr. Mark Hamrick to resume academic duties in research

Dr. Mark W. Hamrick has resigned his role as Senior Vice President for Research effective Sept. 1 and will return to the Department of Cellular Biology & Anatomy to focus on research into bone biology.

“While it is a loss for us to lose Mark in this administrative role, we are grateful that his contributions to GRU’s research enterprise will continue,” said Dr. Gretchen B. Caughman, Executive Vice President for Academic Affairs and Provost. “He has worked tirelessly to advance research at GRU, and his accomplishments have included overhauling the intramural grants program, launching the Institute for Regenerative & Reparative Medicine, and organizing the first Augusta Research Symposium on Advances in Warrior Care. Mark is an outstanding colleague, and I look forward to his continued scientific contributions.”

Dr. Michael Diamond, Vice President of Clinical and Translational Sciences and Chair of the Department of Obstetrics and Gynecology at the Medical College of Georgia, will serve as Interim Senior Vice President for Research.

Hamrick became Interim Vice President for Research in 2010 and was named to the position permanently in 2011. His research in improving bone strength is funded by the National Institutes of Health and the U.S. Department of the Army.

As Senior Vice President for Research, he oversees all aspects of the university’s research enterprise, including developing a strategic plan to advance GRU’s goals related to sponsored research programs.

Hamrick received GRU’s 2009 Innovation in Teaching Award, 2009 and 2010 Exemplary Teaching Awards, and 2005 Outstanding Young Faculty Award in Basic Sciences. In his role at GRU, he has also provided administrative oversight to implement the new electronic platforms for research administration and recruited new leadership in the Office of Innovation Commercialization, clinical research, and Laboratory Animal Services.  He developed new research communications, Research Impact and GResearch, with the Office of Communications and Marketing, and established new, collaborative research partnerships with the Savannah River National Lab and Georgia Tech.

“I am grateful for the opportunity to have led one of this university’s most critical missions,” Hamrick said. “It has been an honor to serve the hundreds of scientists here, who I truly believe are making a significant impact and lessening the burden of illness on our society with their important work.”

Distinctive brain blood flow patterns associated with sexual dysfunction

diamondwebfront[1]Premenopausal women who aren’t interested in sex and are unhappy about this reality have distinctive blood flow patterns in their brains in response to explicit videos compared to women with normal sexual function, researchers report.

A study of 16 women – six with normal sexual function and 10 with clear symptoms of dysfunction – showed distinct differences in activation of brain regions involved in making and retrieving memories, and determining how attentive they are to their response to sexual stimuli, researchers report in the journal Fertility and Sterility.

Up to 20 percent of women may have this form of sexual dysfunction, called hypoactive sexual desire disorder, for which there are no proven therapies, said Dr. Michael P. Diamond, Chairman of the Department of Obstetrics and Gynecology at the Medical College of Georgia at Georgia Regents University.

Researchers hope that a clearer understanding of physiological differences in these women will provide novel therapy targets as well as a method to objectively assess therapies, said Diamond, the study’s senior author.

“There are site-specific alterations in blood flow in the brains of individuals with hypoactive sexual disorders versus those with normal sexual function,” Diamond said. “This tells me there is a physiologic means of assessing hypoactive sexual desire and that as we move forward with therapeutics, whether it’s counseling or medications, we can look to see whether changes occur in those regions.”

Viagra, developed in the 1990s as way to increase the heart rate of sick babies, was approved by the Food and Drug Administration in 1998 to also treat male impotence, a major cause of sexual dysfunction. While several more options for men have been developed since, no FDA-approved options are available for women experiencing hypoactive sexual desire, Diamond said.  He notes that a possible critical flaw in developing and evaluating therapies for women may be the inability to objectively measure results, other than with a woman’s self-reporting of its impact on sexual activity.

Years ago, Diamond, a reproductive endocrinologist, became frustrated by the inability to help these women. In fact, many women did not bother discussing the issue with their physicians, possibly because it’s an awkward problem with no clear solutions, he said.

While still at Wayne State University, he and his colleagues began looking for objective measures of a woman’s sexual response, identifying sexually explicit film clips, then using functional magnetic resonance imaging, which measures real-time brain activation in response to a stimulus, to look at responses.

Their latest study links acquired hypoactive sexual desire disorder to a distinct pattern of blood flow in the brain, with significant activation of cortical structures involved in attention and reflection about emotion and mental state. Researchers noted that paying more attention to response to sexual stimuli already is implicated in sexual dysfunction.  They also note activation of the anterior cingulate gyrus, an area involved in a broad range of emotions including homeostasis, pain, depression, and apathy.  Another key area was the amygdala, which has a central role in processing emotion, learning, and memory.

Women with normal sexual function showed significantly greater activation of areas such as the right thalamus – a sort of relay station for handling sensory and motor input – that also plays a role in sexual arousal.  They also experienced activation of the parahippocampal gyrus, involved in making and recalling memories.  Interestingly, this area has been found to be more significantly activated in women with surgical menopause receiving hormone therapy.

Diamond notes that the official diagnosis of the sexual disorder requires distress regarding persistent disinterest in sex. Study participants were heterosexual, in stable relationships and had previously viewed sexually explicit images. Those with sexual dysfunction had a mean age of 37 versus 29 in the control group. Part of assessing blood flow patterns included also measuring baseline responses to neutral videos.

Next steps include taking these measurements in a larger number of women and beginning to use brain blood flow patterns to assess therapies, Diamond said.

Researchers at The University of Texas, MD Anderson Cancer Center, the University of Wisconsin at Milwaukee and Wayne State University contributed to the study which was funded in part by the National Institutes of Health.

 

Distinctive brain blood flow patterns associated with sexual dysfunction

diamondwebfront[1]Premenopausal women who aren’t interested in sex and are unhappy about this reality have distinctive blood flow patterns in their brains in response to explicit videos compared to women with normal sexual function, researchers report.

A study of 16 women – six with normal sexual function and 10 with clear symptoms of dysfunction – showed distinct differences in activation of brain regions involved in making and retrieving memories, and determining how attentive they are to their response to sexual stimuli, researchers report in the journal Fertility and Sterility.

Up to 20 percent of women may have this form of sexual dysfunction, called hypoactive sexual desire disorder, for which there are no proven therapies, said Dr. Michael P. Diamond, Chairman of the Department of Obstetrics and Gynecology at the Medical College of Georgia at Georgia Regents University.

Researchers hope that a clearer understanding of physiological differences in these women will provide novel therapy targets as well as a method to objectively assess therapies, said Diamond, the study’s senior author.

“There are site-specific alterations in blood flow in the brains of individuals with hypoactive sexual disorders versus those with normal sexual function,” Diamond said. “This tells me there is a physiologic means of assessing hypoactive sexual desire and that as we move forward with therapeutics, whether it’s counseling or medications, we can look to see whether changes occur in those regions.”

Viagra, developed in the 1990s as way to increase the heart rate of sick babies, was approved by the Food and Drug Administration in 1998 to also treat male impotence, a major cause of sexual dysfunction. While several more options for men have been developed since, no FDA-approved options are available for women experiencing hypoactive sexual desire, Diamond said.  He notes that a possible critical flaw in developing and evaluating therapies for women may be the inability to objectively measure results, other than with a woman’s self-reporting of its impact on sexual activity.

Years ago, Diamond, a reproductive endocrinologist, became frustrated by the inability to help these women. In fact, many women did not bother discussing the issue with their physicians, possibly because it’s an awkward problem with no clear solutions, he said.

While still at Wayne State University, he and his colleagues began looking for objective measures of a woman’s sexual response, identifying sexually explicit film clips, then using functional magnetic resonance imaging, which measures real-time brain activation in response to a stimulus, to look at responses.

Their latest study links acquired hypoactive sexual desire disorder to a distinct pattern of blood flow in the brain, with significant activation of cortical structures involved in attention and reflection about emotion and mental state. Researchers noted that paying more attention to response to sexual stimuli already is implicated in sexual dysfunction.  They also note activation of the anterior cingulate gyrus, an area involved in a broad range of emotions including homeostasis, pain, depression, and apathy.  Another key area was the amygdala, which has a central role in processing emotion, learning, and memory.

Women with normal sexual function showed significantly greater activation of areas such as the right thalamus – a sort of relay station for handling sensory and motor input – that also plays a role in sexual arousal.  They also experienced activation of the parahippocampal gyrus, involved in making and recalling memories.  Interestingly, this area has been found to be more significantly activated in women with surgical menopause receiving hormone therapy.

Diamond notes that the official diagnosis of the sexual disorder requires distress regarding persistent disinterest in sex. Study participants were heterosexual, in stable relationships and had previously viewed sexually explicit images. Those with sexual dysfunction had a mean age of 37 versus 29 in the control group. Part of assessing blood flow patterns included also measuring baseline responses to neutral videos.

Next steps include taking these measurements in a larger number of women and beginning to use brain blood flow patterns to assess therapies, Diamond said.

Researchers at The University of Texas, MD Anderson Cancer Center, the University of Wisconsin at Milwaukee and Wayne State University contributed to the study which was funded in part by the National Institutes of Health.