Tag Archives: Obstetrics and Gynecology

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.

Al-Hendy receives top honors from the Society for Reproductive Investigation

AUGUSTA, Ga. – Dr. Ayman Al-Hendy, an obstetrician-gynecologist and molecular biologist at the Medical College of Georgia at Georgia Regents University and GRHealth, has received two top honors from the Society for Reproductive Investigation.

The President’s Achievement Award honors a junior society member with an outstanding record of scientific investigation and a promising research career. The Rogerio A. Lobo Award, which honors the former society President and Editor-in-Chief of the journal Reproductive Sciences, recognizes outstanding contributions to reproductive sciences by a society member.

Al-Hendy was honored during the society’s 62nd Annual Meeting in San Francisco this week. He has been a member of the society, formerly known as the Society for Gynecologic Investigation, since 2001.

Al-Hendy, who came to MCG last year from Meharry Medical College and Vanderbilt University Medical Center in Nashville, is Director of the MCG Department of Obstetrics and Gynecology Division of Translational Research and GRU’s Director of Interdisciplinary Translational Research.

His clinical and research interests include improving women’s health care and eliminating disparities, gynecologic endoscopy, and research in reproductive genetics, stem cell biology, and gene therapy. A major focus is fibroids, uterine growths affecting up to 75 percent of women, which can complicate pregnancy and cause excessive bleeding. Al-Hendy is pursuing non-surgical treatment of these typically non-cancerous tumors, which thrive on estrogen and progesterone. He has found that fibroids also tend to thrive in a low vitamin D environment and is pursuing use of the widely available vitamin supplement as a treatment/prevention strategy. Parallel basic science studies are looking at the genetics of why the tumors thrive without vitamin D. Al-Hendy is also a principal investigator in clinical trials looking at drugs that block the progesterone receptor, which, like estrogen receptors, are common in fibroids.

He is a member of the American Society of Reproductive Medicine Research Committee, Chairman of the society’s Health Disparity Special Interest Group and a former Chairman of its Fibroid Special Interest Group programs. He has served on numerous National Institutes of Health Special Emphasis Panels and Study Sections, which most recently includes serving for five years as a Full Member and currently as Chairman of the Integrative & Clinical Endocrinology and Reproduction Study Section.

Breast cancer drug is also effective infertility treatment for polycystic ovary syndrome

Dr. Michael Diamond
Dr. Michael Diamond

AUGUSTA, Ga. – A drug already used to treat breast cancer may be an effective fertility treatment as well for women with polycystic ovary syndrome, physicians say.

A national study of 750 women with PCOS, a condition affecting 5-10 percent of reproductive-age women, showed rates of ovulation, conception, pregnancy, and live birth were all higher in women taking letrozole than in those taking the usual front-line medication clomiphene, according to a study in the New England Journal of Medicine.

“There was a lot of anecdotal evidence and small studies suggesting that letrozole could help these patients conceive,” said Dr. Michael Diamond, reproductive endocrinologist and Chairman of the Department of Obstetrics and Gynecology at the Medical College of Georgia at Georgia Regents University. “This large, randomized trial in women comparing it to conventional therapy supports those earlier reports.”

Diamond, a study co-author, participated in the trials while at Wayne State University. Dr. Richard S. Legro, reproductive endocrinologist at Penn State College of Medicine, is the study’s corresponding author.

In fact, women taking letrozole had a 44 percent better chance of having a baby than women taking clomiphene, the authors wrote, surmising that letrozole may assume clomiphene’s front- line fertility treatment status for these women. The safety profile on both drugs, including the common infertility treatment risk of multiple pregnancies, was similar.

Study participants, age 18-39, were followed for up to five treatment cycles at a dozen centers across the nation. The primary outcome researchers were looking for was a baby.

Constantly elevated estrogen levels mean women with PCOS essentially don’t ovulate, Diamond said. Higher-than-usual testosterone levels produce other disease hallmarks such as excessive body hair, acne, and a tendency to be overweight.

Letrozole, an aromatase inhibitor, blocks the usual conversion of testosterone to estradiol, the most potent form of estrogen, so the woman has low estrogen levels and the brain thinks it’s time to tell the ovaries to ovulate. Clomiphene, a selective estrogen receptor modulator, blocks estrogen receptors in the brain so it thinks estrogen levels are low and prompts ovulation.

Diamond chairs FDA-convened panel on dissecting fibroids to ease removal

AUGUSTA, Ga. – Dr. Michael Diamond, reproductive endocrinologist and Chairman of the Department of Obstetrics and Gynecology at the Medical College of Georgia at Georgia Regents University, this week is chairing a U.S. Food and Drug Administration Panel regarding the practice of morcellation of uterine fibroids to enable easy removal through small incisions.

In April, the FDA discouraged the practice because of the potential for cancer spread from morcellation of undiagnosed uterine malignancies. The follow-up public meeting of the FDA’s Obstetrics and Gynecological Medical Devices Panel is set for Thursday and Friday in Washington.

An estimated 1 in 350 women who have a hysterectomy to remove the uterus because of fibroids or who have surgical removal of just the fibroids, called a myomectomy, have a previously undiagnosed uterine cancer, according to the FDA. Use of the technique, laparoscopic power morcellation, can result in spread of cancer to the abdomen and pelvis and worsen long-term survival, the April 17 FDA recommendation states. Health care providers and patients should consider alternative treatment options for symptomatic uterine fibroids, according to the FDA.

Diamond is also GRU’s Vice President for Clinical and Translational Sciences and MCG’s Associate Dean for Research. He is serving his fourth term as a consultant to the Obstetrics and Gynecological Medical Devices Panel of the FDA’s Center for Devices and Radiological 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.

 

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.