Seminar recap: Unwanted pregnancy — A high-risk perinatal condition?

Obesity, diabetes, high blood pressure, tobacco use — there are a variety of reasons that a pregnancy can be classified as “high risk.”

But one factor that isn’t currently considered by most healthcare providers is whether the pregnancy itself is wanted to begin with, and data collected by the Perinatal Data System suggests that it’s something that healthcare providers may want to start taking into account.

Tim Dye, Ph.D.

Tim Dye, Ph.D.

Tim Dye, Ph.D., Professor in the Department of Obstetrics and Gynecology, and director of biomedical informatics at the CTSI, shared data from an analysis of the Perinatal Data System, which includes several hundred thousand pregnant women from the 22-county region of the Finger Lakes and Central New York. The seminar, which took place on Tuesday, Oct. 14, was part of the CTSI Seminar Series on Women’s Health.


Dye began studying the topic in the 90’s, when New York State began funding the Perinatal Data System. As part of the completion of a birth certificate, women were asked a standardized question “Thinking back to just before you were pregnant, how did you feel about becoming pregnant?” Based on responses from the approximately 300,000 live births that Dye and his team have currently sorted in the upstate New York registry:

  • 65 percent of live births were intended at conception, meaning the woman wanted to become pregnant when she did, or even sooner.
  • 28 percent had mistimed pregnancies, meaning they’d wanted to become pregnant, but not until later in life.
  • 7 percent were unwanted pregnancies, meaning they did not want to become pregnant at the time of conception, or at any point in the future.

The 7 percent of unwanted pregnancies represented approximately 20,000 women, giving a large enough sample size for Dye’s team to make some associations. After parsing the data, Dye found that the strongest statistical relationships to unwanted pregnancies were women who live in poverty, women with lower educational levels, and women at both extremes of the age spectrum (under 17, or over 40).

Women with pre-existing medical conditions, such as hypertension, diabetes, or other chronic illnesses, were also more likely to have an unwanted pregnancy.

“So it’s probably the women who are least likely to be able to financially deal with having an unwanted pregnancy who are the most likely to have one,” said Dye.

Additionally, women with unwanted pregnancies are also more likely to have maternal infections. They were also more likely to have a pre-term birth.


Many people assume that those with unwanted pregnancies are less likely to have or seek prenatal care, said Dye. But this isn’t actually true, as Dye’s statistics showed that 98 percent of women with unwanted pregnancies do have some amount of prenatal care.

This means that most women are encountering healthcare professionals at some point before they give birth. But despite the suggestive data about the various risks, women with unwanted pregnancies were actually no more likely to be referred for high-risk care than were other women.

“We certainly see that pregnancies unwanted at conception that result in a live birth are different from other pregnancies,” said Dye. “So it could well be a marker for pregnancy that might lead to different kinds of complications, exposures, and risks.”

For many factors, we don’t fully understand why this is the case yet, said Dye. But since it’s not a variable that is even assessed at intake all the time, unwanted pregnancies aren’t often dealt with clinically at this point.

Said Dye: “That may be something that providers should start thinking about.”

CTSI Pilot Program: Exploring a new bladder cancer treatment

Approximately 75,000 people each year are diagnosed with bladder cancer, making it one of the most common cancers in the United States.

But for a variety of reasons, therapies have lagged behind.

Elizabeth Guancial, M.D.

Elizabeth Guancial, M.D.

“The outcomes have not improved in 30 years,” said Elizabeth Guancial, M.D., assistant professor of medicine, hematology/oncology. “For the most part, we use the same treatments that we did in the 70’s and 80’s.”

Guancial is hoping that she’s on the verge of a new potential treatment. Working alongside Shu-Yuan Yeh, Ph.D., she is testing therapies that involve targeting the estrogen receptor, which could potentially be administered as adjuvant treatment for those at risk for developing metastatic disease after their bladders have been removed.

Their research, which began over the summer, is supported by a CTSI Pilot Grant.

Guancial and Yeh’s research focuses on the patients who have a dangerous form of muscle-invasive bladder cancer, which can spread to other organs. These patients represent about 30 percent of those with the disease, and they are usually treated through surgical removal of the organ, which helps to keep the cancer from spreading.

Shu-Yuan Yeh, Ph.D.

Shu-Yuan Yeh, Ph.D.

Ideally, these patients would receive chemotherapy in the aftermath to prevent the cancer from returning. But many patients with bladder cancer are older and have other medical problems, said Guancial. If they are too sick for chemotherapy, then their outcomes are far worse — these patients see their cancer returning about 50 percent of the time.

Should Guancial and Yeh’s hypothesis prove correct, hormone therapy could be a potential treatment for these post-op patients.

“I don’t think that estrogen therapy could shrink down a tumor. I wouldn’t expect it to kill any cells,” said Guancial. “But it may be able to modulate the ability for bladder cancer to grow or metastasize to other sites.”

Bladder cancer can be tough to study in the mouse model since the organ is so tiny, making the implantation of cancer cells challenging. But Yeh has previously studied bladder cancer in mice, and has developed a method of study that does not include the risk of perforating the organ through surgery.

The CTSI Pilot Grant is allowing Guancial and Yeh to research the effects in mice in the hopes of generating data that would support an R01 application.

“There are important strengths in this Pilot Study,” said Richard Moxley, M.D., associate director for funding programs at the CTSI. “The investigative team is multidisciplinary and experienced in the methodology, the investigator has a strong mentor, and they are pursuing a very interesting hypothesis that suggests different roles for the estrogen receptor subtypes in the pathomechanism that underlies bladder cancer.

“If the mouse model and cell model data in these experiments prove promising, these findings are very likely to stimulate new therapeutic strategies in humans with bladder cancer.”

Guancial believes that human trials could proceed relatively quickly, if the treatment is proven effective in mice. The drugs that would target the estrogen receptor are already commonly used in patients with breast cancer, meaning they wouldn’t need to go through their own FDA approval.

“That kind of paves the way,” she said. “If this works within mice, we can think about moving on to people.”

Seminar recap: Reproductive Issues in People with Epilepsy

For those with epilepsy, the impact of the condition stretches far into other parts of their lives, affecting, among other things, their reproductive health.

Men with epilepsy have decreased sperm counts, and their sperm have abnormal morphology and impaired motility, making it harder for them to father children. Women, meanwhile, have higher rates of menstrual disorders due to their endocrine dysfunction, the type of epilepsy that they have, and they tend to have higher rates of polycystic ovary syndrome, due in part to the effect of epilepsy medications.

Lynn Liu, M.D.

Lynn Liu, M.D.

On Oct. 7, Lynn Liu, M.D., associate professor of neurology, pediatrics, and anesthesia at URMC, spoke at the CTSI Seminar Series on Women’s Health, sharing her experience treating patients with epilepsy who are attempting to have children, and offering directions for future studies.

Variety of issues

Before discussing hormonal issues, Liu mentioned the myriad obstacles that patients with epilepsy face.

Due to their condition, people with epilepsy are often barred from driving. This makes it tougher to get a job, putting many of them in lower economic brackets. Often, they live with family members, who are able to take care of them if and when they have a seizure.

“But if they’re not working, they feel overprotected by their family who feel obliged to take care of them, and they become more and more isolated,” said Liu.

These factors combine to raise the likelihood of mental health issues, which are borne out both in practice, and in the statistics — at least 30 percent of people with epilepsy have a mood disorder or some sort. They are also 10 times as likely to take their own lives.

They’re also less likely to marry, and more likely to divorce, said Liu, though she cautioned that this can depend on their age of epilepsy onset.

Physiological differences also exist, due to the release of hormones that occurs during seizure. Estrogen and progesterone levels are altered, which can affect fertility. Prolactin, a necessary hormone for sexual gratification, is also released during seizure, causing many patients with epilepsy to not have enough when they are intimate.

Treatment and other areas of need

Even if women are able to become pregnant, they must deal with the worry that they could have a seizure and fall, injuring the developing child. Seizure during delivery is also a concern; Liu recommends that her pregnant patients be reassured that a Caesarean section could be possible.

In the meantime, there are a variety of medications available to pregnant women with epilepsy. The challenge for both physicians and their patients is to find the right balance of medication that controls the seizures and doesn’t harm the fetus. Seizures themselves can cause birth defects, so they need to be controlled as much as possible, but medications can have side effects.

For example, said Liu. “All women of childbearing age should be on folic acid anyway, but “many of our seizure medicines have anti-folic properties,” so women with epilepsy especially should take folic acid.”

Various studies are currently being done on how much folic acid is appropriate, Liu said that data isn’t yet available on the ideal amount.

And while there are a few treatments available for men with epilepsy who are experiencing sexual dysfunction, there hasn’t been much research done on what can be done for women.

Said Liu: “It’s a lot harder of a question and an area worthy of a lot of exploration, because we don’t have a tremendous amount of options for women who have sexual dysfunction and decreased gratification.”

Director’s Update – October 2014

Every month, the CTSI Stories Blog will post excerpts from ongoing conversations with the institute’s co-directors.

Below, Harriet Kitzman discusses team science in the academic medical center, and how the Collaborations & Services pillar of the CTSI is supporting research collaboration.

Tell me a little bit more about team science in an academic medical center.HarrietKitzman2

There has been a transformation in the scientific community about the importance of teams in the development of solutions to our most complex problems. However, in many ways, the culture of academic medical (and health science) centers are yet to be aligned structurally with the ever increasing functions of teams.  We still are preparing through education and research training, for the self-sufficient independent scientist role. Similarly, academic reward systems have historically centered on the independent contributions of the scientist, many of which are difficult to identify in fully functioning collaborative science teams where novel ideas and approaches come not from individuals but from the synergy that emerges when dynamic ideas are integrated.

What is of interest is that teams in science are growing, often with little regard for the science of the process of doing team science. The science of team science (which is concerned with understanding and managing environmental conditions that support or hinders team science initiatives), is in many ways in its infancy. Although there is a long history of the study of small groups in the social sciences, and developing teams in business and health services, there is limited utilization of what has been learned in those fields to team science in academic health centers. More importantly, despite our understanding of the frequency with which fledgling teams fail, there are few projects that are focused on trying to understand why some fail and others are productive and sustained – the science of team science. The emerging complexity of teams will require us to focus on the functional aspects as well as the outcomes.  If we are to succeed, we will need to uncover the dynamic organizational patterns, socio-political climate, individual and groups functions that drive successful collaboration in team science. Our studies in the science of team science will need to be multi-level and utilize novel as well as accepted methods.

So understanding team science is the first step. What DO we know about it? 

Well, there was one study recently — Steve Dewhurst wrote about it in the Democrat & Chronicle — that talked about how the best team science combines novelty and conventionality. So a successful scientific team often is one that uses conventionally-accepted methods, but does so across disciplines to solve a new problem.

We already have a few programs in place that promote team science — the funding for the Incubator Program, for example, has always had a requirement for team science. Now, we’re studying some of the other things that go on here. For example, the SRB Data Blitz! — Tom Fogg has been the one developing that — we’re trying to measure outcomes of those events so we can do things systematically and determine what works.

How about the “Services” part of the “Collaborations & Services” pillar?

We are retaining services such as the Research Navigator and other programs that already exist within the CTSI under this pillar, and we’re working to enhance those services through other channels. Because regardless of how many navigators we have here, there needs to be something that directs researchers to the program, and the researchers themselves need to know that it can provide them with some assistance.

Going back to that study that Steve Dewhurst wrote about, an interaction with the CTSI is often a more formal or conventional type of relationship. It’s a contrast to the informal structures and interactions — the conversations that researchers have with others in different fields that they don’t always interact with — that really drives the novelty portion of team science. So while the Research Navigator Program gets the questions answered, it’s the more informal connections that actually create those new questions.

Previous director’s updates:

September 2014 – Karl Kieburtz talks about why the CTSI is beefing up its informatics team.
August 2014 – Nana Bennett discusses the new Population Health pillar.
July 2014 – Harriet Kitzman offers her takeaways from the Mini Summer Research Institute.
June 2014 – Karl Kieburtz gives an overview of the CTSI’s six pillars.

Seminar Recap: Studies in Uterine Fibroids

Most tumors, when discovered, are dealt with quickly — through removal, chemotherapy, or otherwise.

But uterine fibroids, benign in all but the rarest of circumstances, present an opportunity for researchers.

Donna Baird, Ph.D.

Donna Baird, Ph.D.

“Usually, when you find a tumor, you want to take it out,” said Donna Baird, Ph.D., principal investigator, epidemiology, for the National Institute of Environmental Health Sciences. “Fibroids are one of the rare times when you can look at tumor growth and describe it.”

Baird, a guest lecturer at the CTSI Seminar Series on Women’s Health on Sept. 30, shared her research on uterine fibroids, outlining her current work and offering new directions for future studies.

What we know

Uterine fibroids are smooth muscle tissue tumors which grow in the uterus of a majority of women in the middle to late reproductive years. They are extraordinarily common — in the United States, 70 percent of white women and 80 percent of African American women develop uterine fibroids at some point — and most of them are asymptomatic, with many women never realizing that they have them.

But some fibroids do grow to the point where treatment is necessary. Historically, uterine fibroids have been the leading cause of hysterectomies in the United States.

“So it’s a major health problem,” said Baird.

There are a handful of established risk factors — women in their middle-to-late reproductive years are most likely to develop fibroids, African Americans are at higher risk than white Americans, and early age of menarche and nulliparity also increase risk. But since uterine fibroid development is so common, simply measuring incidence may not provide much information about preventing development of disabling symptoms that are treated with major medical procedures, said Baird.

So, in a recent study, Baird’s group instead decided to focus on fibroid growth, enrolling 116 pre-menopausal women with clinically-relevant fibroids and measuring fibroid growth via MRIs over the course of a year.

While there was a wide variety of fibroid growth and shrinkage during the study period, the fibroids in the majority of women grew only a small amount — an average of 9 percent every six months.

Baird also found in a later study that about a third of fibroids seen at the beginning of pregnancy actually disappeared by 4 months after birth, consistent with their hypothesis that parity is protective because tumor tissue will be cleared during the process of postpartum uterine remodeling.

Current study

Since the publication of the growth study, Baird has begun a new study which involves a cohort of 1,696 African American women aged 23-34 in the Detroit area. Her group is following the women for five years and screening with ultrasound every 20 months to identify new fibroids and follow growth of already existing fibroids. They are testing whether Vitamin D could be a preventative in terms of fibroid development.

“If it were found to be effective, it would be wonderful — it’s cheap and it’s easy,” said Baird. “Of course, we have lots of other questions. For example, there’s an interesting hypothesis that heavy bleeding actually causes fibroids.”

They’re also hoping to identify other potential factors that put certain women at higher risk for growing fibroids. Through prevention, Baird and others are hoping to make a dent in the more than $6 billion spent on this understudied women’s health condition each year.

Said Baird: “I think down the road, this is what can happen, and there can be much less surgical treatment and many fewer hysterectomies.”

Seminar Recap: Cognition in the Menopausal Transition

Labeled “The Seven Dwarves of Menopause,” they grinned out at the audience from the projector screen in Helen Wood Hall Auditorium: Itchy, Bitchy, Sweaty, Sleepy, Bloated, Forgetful, and Psycho.

“So, I’m interested in numbers 2, 6, 7, and a little bit of 4,” quipped Miriam Weber, Ph.D., assistant professor of neurology and obstetrics and gynecology, at URMC.

Miriam Weber, Ph.D.

Miriam Weber, Ph.D.

For the past decade, Weber has been studying cognition in women in the menopausal transition. While the symptoms embodied by the Seven Dwarves have long been accepted as common experiences for women in the menopausal transition, there hasn’t been a particularly robust array of science to support the cognitive symptoms until recently.

On Sept. 23 at the CTSI Seminar Series, Weber shared her past work in the field and discussed how her current study is expanding on her previous findings.

What we know

In creating her original study, Weber had a little background from two prior studies. The first, published in 2000 (SWMHS-Mitchell), found that 62 percent of middle-aged women reported an undesirable change in memory. Meanwhile, the longitudinal SWAN study had also found that 40 percent of peri- and post-menopausal women listed “forgetfulness” among a self-reported inventory of their symptoms.

With this data as a backdrop, Weber launched her Rochester Investigation of Cognition Across Menopause (RICAM) study, hoping to expand on the findings. The first study took place in 2005-2006, and a second took place from 2007-2009. Weber is now in the midst of her most comprehensive study yet, which began in 2010 and runs through 2015.

“Memory complaints really do reflect objective performance, maybe not in retentive memory, but in working memory,” said Weber.

Since publishing her initial results, other groups have reported similar findings — other researchers found that memory complaints were associated with loss of verbal memory and attention, that subjectively recorded memory problems were associated with objective measures, and that the brains of post-menopausal women with cognitive complaints were working harder in order to perform to previous levels.

“These are high-functioning women, and they’re not impaired, but they’re noticing subtle differences,” said Weber.

Weber’s study also looked which women were struggling the most with memory symptoms, and found that women in early post-menopause — the first year after the post-menstrual period — were performing worse with verbal learning, verbal memory, and fine motor and dexterity, than women in the late-reproductive stage.

Future directions

In confirming that women are indeed good at self-reporting their memory symptoms during the menopausal transition, Weber offered a few directions for future studies.

Among other suggestions, Weber said that researchers need better measures of symptoms known to impact cognition.

“With that in mind, we just received funding to add to RICAM objective measures of hot flashes and sleep monitors,” said Weber. “That way, we can get subjectively reported symptoms as well as objective measures.”

She’s also hoping to expand the study to multiple sites and make it more representative, which may allow for more parsing of the data.

“Ideally, we need to identify who is at risk for cognitive declines. Clearly, some women are doing better and some who are taking a more significant hit,” said Weber. “So I’m interested in describing in general what the experience is during this time period for all women, but also whether there are certain factors that put some women at increased risk.”

First SRB Data Blitz! Is a Success

The new SRB Data Blitz! Series aims to give a broad and entertaining overview of research programs in the Saunders Research Building. The inaugural session was held on September 24th, 2014 in the Saunders Research Building and featurPictureed both poster and live presentations from members of the Heart Research Follow-up Program. Dr. Wojciech Zareba, Director of the Heart Research Follow-up program, welcomed approximately 40 attendees and offered opening remarks for the event.

Eight posters were setup for attendees to peruse as their own leisure and a slide presentation ran throughout the event, highlighting recent research projects and findings. PDFs of the posters and the presentations are available on the CTSI Website. Additionally, there was a Long QT measurement station where attendees could have their levels assessed in 30 seconds. This technology aids Doctors in identifying patients at risk for heart disease and prescription side Pictureeffects.

Make sure to join us for the next session of the SRB Data Blitz! Series which will be held on October 29th and will feature research from the Developmental Disabilities group. See you then!