Training the Next Generation in Oncofertility: Part 2

This is the 2nd in a 3-part blog series featuring Oncofertility Consortium superstar, Laxmi Kondapalli, MD, MSCE.  In this post, we focus on her time at the University of Pennsylvania. To read the 1st blog, click here.

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Knowing that she wanted to continue to work in fertility preservation and receive superior training, Laxmi only applied to a limited number of reproductive endocrinology (REI) fellowships, one being at the University of Pennsylvania (Penn). What better place to graduate onto than Penn where she could remain in the hub of the Consortium while building her skills as a top clinician?  According to Laxmi, “Penn was a perfect fit for me because it’s excellent for REI training and the reason why I wanted to go to Penn was because they also have a specialized training program in clinical epidemiology.”

Another significant component of Laxmi’s career path and something pertinent to her decision to go to Penn, was her ability to do research and collaborate with bench scientists.  Laxmi says, “I think with my skill set, I’m really a clinician at heart – I would be much better at doing clinical research and patient facing research, and that’s why I chose Penn.” At Penn, she was able to really focus on the clinical aspects of fertility preservation, laying the framework for the well-rounded doctor she was to become.

Laxmi spent 3 years at Penn (2008-2011) getting clinical experience in REI and earning a Masters of Science in Clinical Epidemiology, working with some of the top clinicians in the field. “I worked with [Consortium member] Clarisa Gracia and saw fertility preservation patients with her both in-patient and out patient.  I was able to navigate patients and care for them in terms of doing the egg and embryo banking, doing the ovarian transpositions and we also did a fair number of cases of ovarian tissue freezing as well.”

For Laxmi, one of the most significant aspects of her tenure at Penn was the opportunity to do a variety of different things in her field.  It was important to her to be trained in ovarian transplantation, as very few clinicians actually know how to do this. During her 2nd yr of fellowship, Laxmi trained with Sherman Silber in St. Louis spending two days in the operating room with him learning his technique for vitrification of ovarian tissue and for transplantation. Laxmi says, “That was a very cool opportunity and why I think that I’m very unique in terms of my background because a lot of people say that they do fertility preservation and they kind of know how to bank eggs and embryos, but I have a much more global perspective about this field, and I’ve had great opportunities to get specialized training and some very high tech, cool things like ovarian transplantation.”

As her time at Penn came to a close mid-2011, Laxmi was on to her next big adventure…

 

Training the Next Generation in Oncofertility: Part I

Laxmi Kondapalli being interviewed by Dayle Cedars from Channel 7 news in Denver

One of the many, if not one of the most, important aims of the Oncofertility Consortium and its emphasis on fertility preservation research and clinical care, is “training the next generation.” Not only is the mission of the Consortium to improve fertility outcomes for patients undergoing cancer treatment, but it is also to ensure that future basic scientists and clinicians continue to expand current knowledge, research, clinical practice, and training in fertility preservation outcomes.  Laxmi Kondapalli, MD, MSCE, Assistant Professor of Obstetrics and Gynecology at the University of Colorado and Women’s Reproductive Health Research Scholar in the Division of Reproductive Endocrinology and Infertility is a realization of this goal. Let’s start at the beginning…

In March 2006, Laxmi was finishing up her residency training at Northwestern University in Obstetrics and Gynecology when she met Teresa K Woodruff, PhD, Director of the Oncofertility Consortium. Laxmi shared her interest in Reproductive Endocrinology (REI) with Dr. Woodruff, but expressed her desire to do basic science/bench research first, before embarking on clinical training and practice. According to Laxmi, “Meeting Dr. Woodruff changed the trajectory of my career.  She has incredible vision, particularly for someone who is not a clinician, on how to bridge science with individual care.”

Shortly after her meeting with Dr. Woodruff, Laxmi started working in the Woodruff Lab in August 2006. It was at the start of her tenure in the lab when she found out that Dr. Woodruff was one of the finalists for the prestigious National Institutes of Health (NIH) Roadmap Grant (aka, the grant that brought the “idea” of the Oncofertility Consortium to fruition). Together, they put the 1,000 page grant together over a 10 week period with help from members of the Woodruff Lab and other academics from within Northwestern and around the country. Laxmi explains, “It was being at the right place at the right time and the Oncofertility Consortium was a perfect fit for me because of my interest in REI and because it was a way for me to really see how you can translate work that we do in the laboratory to really impact clinical and patient care.”

In 2007, the Oncofertility Consortium was funded by the NIH, and Laxmi was A) not only a first-time grant writer, but a grant writer for one of the biggest grants given out (“for me, it was a valuable experience on so many levels”), B) processing and freezing A LOT of ovarian tissue in her lab work and C) navigating patients with the Fertility Preservation Patient Navigator who was receiving referrals from all over the country to do tissue freezing. By 2008, after two years in the Woodruff Lab working hands on with tissue, Laxmi was ready to embark on an REI fellowship and she had her sights set on an institution that would allow her to expand her work in fertility preservation while ideally being involved with the Oncofertility Consortium.

Stay tuned for Part 2 of the amazing, fabulous Laxmi Kondapalli success story!

New Evidence that IVF Hormones are Not Linked to Breast Cancer

Today we are continuing our coverage of the scientific correlation, or lack thereof, between infertility treatments and cancer. We’ve recently put out two blogs discussing new scientific examinations of hormonal stimulation and breast and ovarian cancer. A third study has just been published on the roles of three important hormones, follicle stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotropin (hCG), on breast cancer cell growth.

In the paper, “Impact of infertility regimens on breast cancer cells: follicle-stimulating hormone and leuteinizing hormone lack a direct effect on breast cell proliferation in vitro,” researchers examined how FSH, LH, and hCG affect the growth and proliferation of multiple breast cancer cell lines in the laboratory. These three hormones are used during in vitro fertilization (IVF) to stimulate the development of a woman’s follicles, which are then removed and fertilized with sperm.

The authors, Boukaidi, Cooley, Hardy, Matthews, Zelivianski, and Jeruss, examined how breast cancer cell lines in a 3D culture system responded to the three hormones.  The found that, when treated with individual hormones, neither the growth nor division of breast cancer cells were altered. In addition, one of the cell lines did respond to a combination of FSH and hCG, which caused decreased cell division and size. This result provides evidence that FSH, LH, and hCG may not directly increase breast cancer risk during infertility treatments.

Future studies will be needed to further explore the effects of additional factors, such as estrogen, on breast cancer growth and proliferation. Read the full article in Fertility and Sterility.

Assisted Reproductive Technology (ART) in Ireland: Ethics, Legislation, and Responsibility

An interesting journal article that came across my desk analyzes the ambiguous guidelines issued for assisted reproductive technologies (ART) in Ireland.  As it stands, there is no controlling legislation for ART in Ireland, so the guidelines issued by the Medical Council (the group responsible for setting professional and ethical medical guidelines in Ireland) are what reproductive scientists and clinicians must follow in their work. “The Evolution of Health Policy Guidelines for Assisted Reproduction in the Republic of Ireland, 2004-2009,” by David J. Walsh, Mary L. Ma, and Eric Scott Sills in Health Research Policy and Systems compares the policy guidelines set forth in 2004 to the most current guidelines issued in 2009 by the Medical Council, arguing that copious guidelines need to be established.

A positive change that can be seen in the revised guidelines issues in 2009, is the Council’s support for more accreditation for ART practitioners and better record keeping and auditing practices. However, the overwhelming ambiguity placed on surplus embryos,  donor compensation  and embryo disposition may restrict access to IVF services. While the Medical Council states that the ultimate responsibility for the regulation of ART falls to the Oireachtas (national parliament or legislature of Ireland), the Oireachtas have remained silent on these issues  leaving the burden up to the Medical Council.

Another dynamic to add to the mix is the reconfiguration of the Medical Council. The Council has 25 members historically comprised of physicians; however, new legislation passed in 2007 requires that 9 of those members cannot be medical practitioners in Ireland or elsewhere. Thus the guidelines set in  2004 and those set in 2009 were established by 2 completely different groups, the first being made up of  mainly “pro-life” members.  This informed many of the original guidelines such as limiting IVF treatment to unexplained infertility and the stipulation that embryos must be donated before deliberately being destroyed. In 2009, the guidelines state that IVF is available to individuals when “no other treatment is likely to be effective,” and the option to donate embryos was retracted making destruction more favorable to donation.

Although the authors agree that ART legislation is the ultimately responsibility of the Oireachtas, they argue that enacting such legislation could take years.  Thus, the authors conclude that the Medical Council should be the deciding body setting comprehensive guidelines for ART in an attempt to address the complex ethical issues that are either being overlooked or underscored. To read, “The Evolution of Health Policy Guidelines for Assisted Reproduction in the Republic of Ireland, 2004-2009,” please click here.

Oncofertility 101: A New Course in Emerging Fertility Preservation Techniques

By Francesca Duncan

Most cancer therapies, while life-preserving, can threaten the future fertility of both males and females.  Fortunately, the menu of fertility preservation options is broad, and due to ongoing research efforts through the Oncofertility Consortium and around the globe, these options are ever-expanding.  Hydrogel-based in vitro follicle growth is one such investigational technology developed by Oncofertility Consortium researchers in which immature follicles are isolated directly from ovarian tissue and grown in alginate, a natural biomaterial derived from algae.  This system supports follicular architecture through terminal stages of follicle development and has been shown in the mouse to produce eggs that give rise to healthy offspring.  Research is now focused on optimizing this system to produce live offspring in primate species.

As interest in learning and applying such technologies to the field of fertility preservation has increased, the Oncofertility Consortium launched a new course entitled: Oncofertility 101: a training course in in vitro follicle growth using alginate hydrogels.”  This is an intense one-day course in which participants experience  hands-on laboratory exercises aimed at learning the fundamentals of follicle micromanipulation, encapsulation, culture, and quality analysis.  This course “ensures that the transmission of technical skills needed to successfully grow healthy follicles in three dimensions are acquired quickly in order to advance the pace of reproductive research” emphasizes Teresa Woodruff, PhD, Director of the Oncofertility Consortium.  In addition to the laboratory exercises, Lonnie Shea, PhD and Min Xu, MD, PhD, both pioneers of this technology, present crucial insight into the evolution of follicle culture biomaterials and the ins and outs of setting up a follicle culture laboratory, respectively.  The course is led by Francesca Duncan, PhD, a Research Associate in the Woodruff Laboratory.

The first Oncofertility 101 course, held in September 2011, was very successful.  Participants came from diverse scientific backgrounds, including basic science, embryology, endocrinology, and biotech.  Participants found the course to be “excellent” and “a great opportunity.”  One person commented: “To really understand a technology I think you need to know how it is done so while I had read considerably about the technique, until yesterday, I did not have that important insight that goes with actually doing the technology… thank you for your time and effort and especially for your patience. It’s been twenty years since I actually sat at the bench and manipulated gametes!”

Oncofertility 101 is held twice a year, and the next course is right around the corner on Monday, March 12th.  This course is free of charge but registration is limited to five participants.  If you are interested in registering or would like more information, please click here.  The second 2012 Oncofertility 101 course will take place on Wednesday, September 26th, to coincide with the 2012 Oncofertility Consortium Conference.

 

 

Infertility Treatments and Ovarian Cancer: Results of a New Study

Last month, we wrote a series of blogs on Giuliana Rancic and the relationship between infertility treatments and breast cancer. A recent study has also raised awareness on such medical advances and the relationship with ovarian cancer. Ovarian cancer occurs in almost 4% of female cancer cases and is the leading cause of death from gynecological cancers.

In an article in the journal Human Reproduction, researchers compared the medical histories of approximately nineteen thousand women who had undergone in vitro fertilization (IVF) to treat infertility and compared them with another six thousand who had experienced infertility and did not undergo IVF. In order for a woman to go through IVF, she first stimulates her ovaries with high levels of hormones to produce multiple eggs from the ovaries, which are then removed and fertilized in a laboratory. In the study, the women who underwent IVF were found to have twice the rates of boarderline ovarian tumors that may or may not require surgery to treat. There were no differences in the overall rates of more advanced, invasive cancer between the two groups of women.

Interestingly, in the study, “Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort,” the dose of hormonal stimulation or number of egg retrieval cycles did not seem to impact ovarian tumor risk. However, a significantly increased risk for ovarian tumor diagnosis occurred in the first year following stimulation, suggesting that hormonal stimulation may promote the growth of pre-existing ovarian tumors.

The authors note that while a difference was seen in the rate of boarderline ovarian tumors between women who underwent hormonal stimulation over those who didn’t, larger studies are required to determine what kinds of changes occur in the ovaries in response to hormonal stimulation and to examine the risk of invasive ovarian cancer compared to borderline ovarian tumors after IVF treatment. Additional factors also increase a woman’s risk of getting ovarian cancer, including genetics, personal history, increased age, hormone replacement therapy, and infertility itself. This information will aid patients and their clinicians in the decision-making process when deciding to participate in some fertility treatments.

The Role of OB/GYN in Comprehensive Cancer Care

What is the role of an obstetrician/gynecologist in cancer care for young women? When you think about cancer and cancer treatment, most likely you’re thinking of oncology and what line of defense will be taken against the cancer. A new article in Clinical Obstetrics and Gynecology from Oncofertility Consortium members, Betty Kong, BA, Robin Skory, BS, and Teresa K Woodruff, PhD, entitled “Creating a Continuum of Care: Integrating Obstetricians and Gynecologists in the Care of Young Cancer Patients,” argues that in some cases, the OB/GYN is the key component in this game.

Kong and Skory are both Woodruff Lab members pursuing dual MD/PhDs at Northwestern University, meaning they want to be involved in both the clinical and research aspects of oncofertility. Clearly they are invested in the scientific pathways oncofertility has to offer, but from a clinical perspective, they assert that obstetrician gynecologists are the best advocates for their patients to help them make informed decisions about their future fertility. According to the authors, “obstetricians and gynecologists [are] the primary physicians to many women during their reproductive years [thus] are in a unique position to be at the forefront of the oncofertility initiative by ensuring [they receive] the proper counseling, referrals, and continuity of care for their patients before, during, and after cancer treatment.”

For many young women, once they’ve reached the pinnacle of pediatric care (18yrs old), they are no longer regularly immersed in follow-up medical care as parents, schools, etc, require. Often the physician they see the most is their OB/GYN, whether it be for birth control options, pre natal care or their yearly exams. Many young women build long-standing patient/physician relationships with their OB/GYN as they did with their pediatricians. It is with this understanding that the authors claim the responsibility for the continuum of care falls upon the OB/GYN in many cases. Thus, the more informed they are in the field of oncofertility, the less patients will encounter a gap in their comprehensive cancer care, specifically in fertility preservation.

An OB/GYN is also in a key role should a cancer diagnosis present itself during a woman’s pregnancy. More studies need to be done on the long term affects of chemotherapy regimes on fetus development and future fertility, but there are treatments that women can undergo in their second and third trimester of pregnancy to try and eradicate the disease. According to the authors, “although it is an uncommon diagnosis, cancer during pregnancy presents a critical scenario that must be carefully treated by a multidisciplinary team of obstetrician gynecologists, medical oncologists, radiation oncologists, surgeons, pediatricians, genetic counselors, and patient navigators.” Again, as the multidisciplinary field of oncofertility develops, it is imperative that clinicians and scientists from diverse fields collaborate to provide patients with the best care possible and the most options for their future fertility.

To read the article, “Creating a Continuum of Care: Integrating Obstetricians and Gynecologists in the Care of Young Cancer Patients,” please click here.

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Giuliana Rancic, Infertility Treatments, and Breast Cancer

A few days ago, we posted a blog about Giuliana Rancic’s personal experiences this year, first with infertility treatments, and then with a breast cancer diagnosis. Her story caused people to ask if her infertility treatments were related to her breast cancer diagnosis. Simultaneously, this fall, a scientific article was published that asked a similar question about any potential link between infertility treatments, such as in vitro fertilization (IVF), and breast cancer.

IVF is the process by which a woman’s eggs are combined with sperm in a laboratory setting to produce an embryo. For this procedure, a woman undergoes hormonal stimulation to cause the release of multiple eggs from her ovaries, which are then surgically retrieved. While some studies have previously found that there may be an increased risk for breast cancer in some patients who participate in infertility treatment, no cause-and-effect relationship has been identified. Dr. Jacqueline Jeruss and colleagues recently examined whether exposure to hormones during infertility treatment may cause the development of cancerous breast cells or affect the proliferation of cancer cells. They investigated this question with the use of breast cancer cell lines in a laboratory setting.

In the journal, Human Reproduction, the researchers communicated the effects of estrogen, progesterone and human chorionic gonadotropin (hCG), which are all hormones that are elevated during infertility treatment or early pregnancy, on breast cancer cell lines. In addition, they examined how these cells may be affected by clomiphen citrate, also known as Clomid, a drug frequently used to increase egg production in women prior to egg retrieval. The authors found that Clomid, progesterone, and hCG were all found to either have no effect on breast cancer cells or reduce their division and growth. As hCG is elevated in early pregnancy, this study raises the possibility that pregnancy may actually have protective effects on reducing breast cancer risk.

In the same article, “Effect of infertility treatment and pregnancy-related hormones on breast cell proliferation in vitro,” one type of breast cancer cell line, derived from breast cancer cells that contain estrogen receptors (ER positive), responded to the estrogen treatment with increased cell division and growth. About 70% of breast cancers are ER positive, so women with a predisposition to these cancers, such as those with a BRCA2 mutation, may want to discuss breast cancer risks of infertility treatment with their doctors. However, women with mutations in the BRCA1 gene are more likely to have ER negative tumors, especially those who are diagnosed under age 40. In the study by Cooley et al., BRCA1 breast cancer cells responded to Clomid and progesterone with a decrease in cell division, indicating that BRCA1 women may not be at increased risk for breast cancer after infertility treatments. This information may help women who are at high risk for breast cancer to better understand their risk of breast cancer after infertility or oncofertility treatments.

 

Giuliana Rancic and Oncofertility

Our undergraduate oncofertility reporter, Meredith Wise, brings us the first of two blogs on Giuliana Rancic and her current experiences with infertility and breast cancer. Mrs. Rancic is using her celebrity to educate the world on these important issues, which gives us all something to reflect upon during this holiday season.

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By Meredith Wise—Every day across the country, women diagnosed with cancer must face decisions regarding their treatment and its potential effect on their fertility. But when a celebrity faces the same decisions, suddenly the idea of oncofertility becomes a hot button issue.

On October 17, Giuliana Rancic, a television host for E! News, announced that she had been diagnosed with breast cancer. Rancic, who had been receiving IVF treatment in an attempt to have a baby, had a mammogram at her doctor’s suggestion. Rancic’s mammogram showed a tumor in her breast, and within a week she underwent a double lumpectomy.

Rancic had recently had a miscarriage following a round of IVF, and she credits the baby she lost with saving her life. Without the miscarriage, she would not have thought to schedule a mammogram.

Rancic and husband Bill have made no attempt to conceal her health issues from the public since the beginning of her IVF treatments, and her latest announcement is no different. On Monday, December 5, Rancic announced that her next step in treatment was to have a bilateral mastectomy, which she underwent on December 13.

According to an interview in People magazine, Rancic’s desire to have children, put on hold by her cancer diagnosis, is one reason that she has decided to proceed with the surgery. Rancic hopes that the surgery will allow her to beat her breast cancer once and for all, and that it will prevent her from having to undergo chemotherapy or radiation that could induce early menopause or interfere with future fertility treatments.

Rather than hide from the press, Rancic has used her celebrity status to put her health problems to good work for the public. She and her husband have appeared on numerous talk shows, answered questions for magazines, and have even Tweeted their appreciation of their fans’ support and prayers.

Rancic’s public battles with infertility and breast cancer serve to increase awareness and mobilize the public in the fight to find methods of fertility preservation. Rancic has chosen to undergo a dramatic surgery because she does not want other cancer treatments to further damage her chances of being a parent.

Rancic initially resisted getting a mammogram, believing that at 37, she was too young to have breast cancer. Now she hopes that by sharing her experience, she can remind others of the importance of early detection.

Hopefully, Rancic’s willingness to include her fans in her battles will not only raise awareness for breast cancer, but will also encourage the public to support finding methods of fertility preservation despite having to undergo cancer treatment. Rancic’s experience can raise awareness of oncofertility so that in the future, other women’s best hope against infertility will not be a surgery as radical as a double mastectomy.

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Egg Donation: To Pay or Not to Pay?

A recent blog post in the academic journal, Nature, explores a new report by the Nuffield Council on Bioethics (an organization in England that examines and reports on ethical issues in biology and medicine), suggesting that women who donate their unfertilized eggs to research deserve to be compensated. Currently in the United Kingdom, direct compensation for egg donation to research or for infertility treatments is prohibited by law. In the US, while direct compensation for egg donation to infertile couples/individuals varies by state, the only state that is allowed to use public funding to purchase unfertilized eggs for research purposes is New York.

The report argues that since egg donors are not compensated, researchers must rely on altruistic egg donors, which are few and far between. In a letter written to the academic journal Cell Stem Cell, scientists Kevin Eggan and Douglas Melton from Massachusetts discuss the issues they ran into when trying to recruit egg donors for a study they did in 2006-2007. They spent $100,000 on advertising over a 2-year period and although they initially received over 200 respondents, once they found out they would not be compensated, all but one dropped out of the study. Eggan and Melton’s findings suggest that if direct compensation for unfertilized eggs were legalized, more women would participate in egg donation for research purposes.

Ethical concerns and objections have been raised regarding egg donation, one in particular – the exploitation of the poor and disenfranchised. Some scholars and ethicists argue that if egg donation were monetized, it would lead to the comodification of the vulnerable, particularly poor and college-aged women. If a price tag were put on eggs, might a woman discount the burdens of submitting to egg stimulation and retrieval in exchange for the chance to earn $5,000 to $10,000, the going rate for eggs used in infertility treatments?

The flip side to this argument is that labeling this practice exploitative is overprotective and paternalistic. Why should egg donors for research be required to be more altruistic than those giving their eggs for reproductive purposes? Why compensate one for their time, burden, expenses and risks, but not the other?  Also, it is argued that there is a greater social value in donating eggs for research than there is in donating eggs for infertility treatments. Although at the Oncofertility Consortium, our scientists do not do research on donated eggs, they do study donated human ovarian tissue which is essential for advancing clinical practice in fertility preservation.

There are a number of arguments that can be made (and have been) for or against compensatory egg donation, but the fact remains that researchers residing in areas that compensate egg donors have higher participatory rates for their studies. This suggests that with the proper protocols in the place (i.e., a national registry which tracks egg donors limiting the amount of times they can donate, proportional and modest payments to egg donors, etc…), compensating egg donors for research studies may yield higher participation rates.

 

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