 | Dr. Charles Lockwood, chair of the Department of Obstetrics, Gynecology & Reproductive Sciences, is shown here performing an ultrasound. |
Department integrates pioneering research and clinical care
Being 38 years old without a child or a partner no longer sends waves of panic through successful pharmaceutical company executive Christine Ostrowski.
Thanks to an innovative procedure called oocyte cryopreservation being performed at the Yale Fertility Center by researchers in the Department of Obstetrics, Gynecology & Reproductive Sciences, she has a bit of insurance. Ostrowski will take hormones to increase the natural production of eggs during her cycle; then specialists will harvest those eggs and freeze the mature ones at -196° Celsius for future use when she is ready to conceive.
Although the procedure, which suspends the aging process of the eggs indefinitely, is not guaranteed to succeed, just making the decision to have it done has relieved much of the pressure Ostrowski has felt since turning 35.
"I have a lot more peace of mind," she says. "Mentally, this option has really helped my outlook. I feel much more at ease, with less stress. As soon as you hit 35, all the articles about declining fertility start popping out of magazines and newspapers. This is a way of leaving open the possibility of one day having my own child. If I don't end up getting married, and I decide to be a single mother, I'll be using younger eggs that have a better chance of being fertilized."
According to Dr. Pasquale Patrizio, who is introducing oocyte cryopreservation at Yale Ob/Gyn, the current success rate hovers around two to three babies born per 100 eggs. These figures are likely to improve, as the technique -- still considered experimental by the American Society for Reproductive Medicine -- is refined, he says. The success rate also depends on the age of the patient, he notes: If eggs are frozen when women are younger than age 35, there is a better chance for a successful pregnancy.
"As with in-vitro fertilization in the early days, this procedure is still evolving," says Patrizio, who has teamed with a scientist from Bologna, Italy, to conduct further research to improve clinical application. "Embryo cryopreservation has a higher success rate but, for personal reasons, it is not an option for some women."
The latter group includes Maria Longobardi, a 34-year-old mother of two who is freezing her eggs to aid in conceiving a third child. For personal reasons, embryo freezing was not an option for Longobardi.
"I'm glad there is a procedure available to help me and my husband conceive that will not compromise my personal and religious beliefs," says Longobardi.
Oocyte cryopreservation is also an appealing option to women in other circumstances, explains Patrizio. Cancer patients can freeze their eggs before undergoing chemotherapy and use them when they are cancer-free to conceive a child. Working with oncologists at the Yale Cancer Center, Patrizio and his colleague Dr. Emre Seli can help to preserve the future fertility of young cancer patients. With the establishment of a full clinical range of male infertility services, the Yale Fertility Center also offers hope of fertility preservation to young men diagnosed with cancer.
Patrizio and colleagues are applying microarray technology as a research tool to identify which eggs are the best quality with the most potential for leading to a live birth. They have also recently implemented a pre-implantation genetic diagnosis (PGD) service.
Oocyte cryopreservation is just one of many clinical innovations and basic research initiatives by faculty members in the Department of Obstetrics, Gynecology & Reproductive Sciences at the School of Medicine. The hallways leading to the research labs are buzzing with talk of promising research in progress. Studies spearheaded by Yale Ob/Gyn experts in a variety of disciplines are being published in leading peer-reviewed journals, and funding from private and government sources is flowing in.
Under the leadership of the department's chair, Dr. Charles J. Lockwood, the Anita O'Keefe Young Professor of Women's Health and chief of ob/gyn at Yale-New Haven Hospital, those research dollars are increasing. In fact, funding from the National Institutes of Health (NIH) has tripled over the past five years. According to NIH rankings, Yale Ob/Gyn has moved from 10th to 4th place among ob/gyn departments nationwide, and the department currently has over $7 million in annual NIH grant support.
"The ongoing achievements of our faculty members highlight the growth in the quality and quantity of research as well as clinical expertise at Yale Ob/Gyn in areas such as reproductive endocrinology, fertility, prematurity prevention and ovarian cancer detection and treatment," says Lockwood, whose own research interests include the regulation of uterine bleeding, recurrent pregnancy loss and premature birth.
In addition to his many administrative duties, Lockwood maintains a busy high-risk obstetrical practice. He has been cited on the "Best Doctors" list by American Health Magazine and since 1995 has been annually cited as a "Best Doctor" by New York Magazine and a Castle and Connolly survey.
Well-versed in clinical research himself, Lockwood discovered the first biochemical predictor of prematurity and the first ultrasound biometric screen for fetal Down syndrome. His research team was also the first to elaborate the biochemical mechanisms underlying menstruation and abruption-associated preterm deliveries. Lockwood was recently named president nominee of the Society for Gynecological Investigation, the world's leading research organization in reproductive sciences.
Yale Ob/Gyn also boasts six busy clinical practices, including the Yale Fertility Center, Yale Maternal-Fetal Medicine, Yale Gynecologic Oncology, Yale Urogynecology and Reconstructive Pelvic Surgery, Yale Family Planning and Yale Reproductive Endocrinology.
In addition to oocyte cryopreservation, the physicians at Yale Fertility Center offer state-of-the-art care in both female and male infertility. Yale Ob/Gyn physician scientists developed the first in-vitro fertilization (IVF) program in the northeast and the first egg donor and gestational surrogacy program in New England.
Led by section chiefs Dr. Edmund F. Funai and Dr. Errol R. Norwitz, the Yale Maternal-Fetal Medicine practice offers the latest care for women with high-risk pregnancies. The team of 11 perinatologists, fellows, nurses, sonographers and genetic counselors offer cutting-edge prenatal testing and diagnosis as well as fetal therapy. The practice now offers immediate results through the First-Trimester Risk Assessment Program, which provides expectant parents with results at the time of the ultrasound, as opposed to waiting two weeks to estimate the risk of having a baby with chromosomal abnormalities like Down syndrome or trisomy 18. They deliver over 500 very-high-risk private patients who come from as far away as New Jersey and Pennsylvania for their care.
Yale Maternal-Fetal Medicine physician scientists pioneered obstetrical ultrasound; invented fetal heart rate monitoring and fetal echocardiography; and developed fetal blood sampling and fetal transfusion. The section's director of obstetrical ultrasound and the department's vice chair for obstetrics, Dr. Joshua A. Copel, recently helped to establish U.S. standards for first-trimester Down Syndrome risk assessment through participation in the national BUN and FASTER trials.
Recent research from scientists in the Section of Maternal-Fetal Medicine include a study by Dr. Catalin Buhimschi showing that specific substances in the urine of pregnant women could serve as a screening/diagnostic tool for preeclampsia (hypertension during pregnancy). Buhimschi and his team received a March of Dimes Award for best research in prematurity at the 2006 Society for Maternal Fetal Medicine meeting. He found that preterm birth risk can be quickly and accurately detected using proteomic profiling.
Other research by Dr. Mert Ozan Bahtiyar shows that women with a history of caesarean deliveries do not have a higher risk of a subsequent stillbirth. A study by Dr. Michael Paidas shows that pregnancy complications are related to low levels of an anti-clotting protein, and another by Dr. Edmund F. Funai revealed that preeclampsia in pregnancy increases risk of future cardiovascular disease and death.
Within Yale Reproductive Endocrinology, which is led by Dr. Aydin Arici, Yale Ob/Gyn clinicians offer treatment for menopause and women's reproductive disorders such as pelvic pain, abnormal uterine bleeding and endometriosis. Minimally invasive surgical procedures are also offered.
Recent research from faculty in this section include groundbreaking work by Dr. Hugh S. Taylor showing that Methoxychlor, a common insect pesticide used on food crops, may interfere with proper development and function of the reproductive tract, leading to reduced fertility in women. Taylor and his co-investigators are also participating in the Kronos Early Estrogen Prevention Study trial with seven other national institutions to study the possible beneficial effects of early estrogen use on heart disease. Additionally, Taylor and his research team have linked early and long-term estrogen therapy with fewer wrinkles and less skin rigidity in postmenopausal women.
Dr. Thomas R. Rutherford is the section chief of Yale Gynecologic Oncology. His current clinical trial will assess the effects of combining anti-cancer drug phenoxodiol with docetaxel to treat women with recurrent ovarian cancer.
Dr. Peter E. Schwartz, the John Slade Ely Professor of Obstetrics, Gynecology and Reproductive Sciences and vice chair for gynecology, established the Yale Early Detection Program for Ovarian Cancer in 1990. His research led to the first clinical trial using anti-estrogens for management of women with advanced or recurrent ovarian cancer. His recent research features a state-of-the-art treatment program for aggressive uterine cancer, which he developed with Yale Ob/Gyn fellow Dr. Michael G. Kelly. The treatment increases survival from the aggressive uterine papillary serous carcinoma and spares some patients the need for additional therapy. Schwartz is also currently conducting a cervical cancer treatment trial.
Gynecologic Oncology features a program titled "Discovery to Cure: Advancing the Prevention, Early Detection and Treatment of Women's Reproductive Cancers." It is one of the leading initiatives in the country in gynecologic oncology medicine, specializing in ovarian, breast, cervical and uterine cancer. "Discovery to Cure's" premise is that any reproductive cancer can be cured if detected early. The program uses genomics, proteomics and radiological imaging -- MRI and ultrasound -- to aid in the early detection of these cancers, which are often asymptomatic in their early stages.
"'Discovery to Cure' brings innovation directly from the laboratory at Yale into practice -- where it can do the most good for the women who need it," says Schwartz.
The program's basic science director, Dr. Gil Mor, recently developed a blood test to detect ovarian cancer before major symptoms develop. It allows identification of the disease at a stage when it can be effectively treated.
Faculty and staff in the Yale Urogynecology and Reproductive Pelvic Surgery Section, led by Dr. Richard Bercik, treat and study the conditions that leave many women suffering in silence. These include urinary incontinence and urinary tract disorders, prolapse, vulvar pain and sexual dysfunction.
Recent advances in treatment by researchers in this division include Bercik's study of a new clinical procedure that improves treatment for urinary incontinence and prolapse. He is the only physician in the Greater New Haven area using Pro-lift, a minimally invasive procedure that provides increased support for the uterus using a more advanced mesh augmented vaginal repair. In addition, Dr. Kathleen Connell at Yale and her co-authors at the Albert Einstein College of Medicine published research showing that female sexual dysfunction affects a high percentage of women. The Yale Postpartum Pelvic Rejuvenation Program, led by women's health nurse practitioner Cherrilyn Richmond, treats patients with pelvic floor muscle disorders.
Dr. Tamas Horvath, who directs the Reproductive Neuroendocrine Group, led a study showing that eating and body weight is regulated by specific neurons in the brain. He also published work showing a possible link between insomnia and obesity. Research by Dr. Csaba Leranth, a professor in Yale Ob/Gyn's Neuroendocrine Group, revealed that low doses of the environmental contaminant bisphenol-A, widely used to make many plastics found in food-storage containers, can impair brain function, leading to learning disabilities and age-related neurodegenerative diseases.
"These and other advances in clinical and basic science research at Yale Obstetrics, Gynecology & Reproductive Sciences have added hundreds of important pages to the medical literature and made a difference in the lives of countless patients and their families," notes Lockwood. Their research efforts are keeping with Yale's global reach with active ongoing research collaborations with United Kingdom, Italian, Serbian, Hungarian, Turkish, Spanish, Chinese and Australian investigators.
Clinicians and researchers in Yale Ob/Gyn have also lent their skills to further local educational causes and to offer care for people in developing countries around
the world.
For the past three years, the Discovery to Cure High School Internship has fostered the love of science and research in area high school students who show academic promise in science. Created by Mor, the program pairs the students with Yale Ob/Gyn researchers for the summer to work on various research areas. For two years in a row, students who participated in the internship program were selected as semifinalists for the Siemens Westinghouse national competition.
Yale Ob/Gyn international humanitarian efforts include providing annual clinical care for patients in Jamaica, West Indies. Lockwood and Rutherford visit the island yearly as part of a medical relief mission to volunteer their expertise in providing ob/gyn surgical care to the needy. Lockwood was invited to participate by Dr. Steve Rosenman and nurse Denise Walsh of Bridgeport Hospital, who founded the program.
While the nurses, pediatricians and internists see between 250 and 300 patients per session for a wide range of medical conditions, Rutherford and Lockwood perform surgeries up to 18 hours a day for disorders including fibroids and ovarian tumors.
"We brought thousands of pounds of medications and set up clinics for those who can't afford medical care," says Lockwood. "One patient had been waiting seven years for treatment of severe anemia due to fibroids. This past year we performed 25 surgeries in five days." Additional sites of outreach and care by Yale's Ob/Gyn physicians have included Haiti and several Central and South American countries.
Lockwood's vision for future ob/gyn initiatives includes integrating outstanding reproductive science research with cutting-edge, high-quality, compassionate clinical care to advance women's reproductive health.
To maintain Yale Ob/Gyn's clinical and research leadership position, Lockwood is planning to establish a Women's Health Center, which will provide the full range of women's health care at one site. He also plans to create a Center for the Study of Reproduction to produce an ideal environment to bring together a wide range of researchers to foster basic, translational and clinical research in reproductive health.
Lockwood also will expand current research programs focusing on ovarian cancer and early detection, discovering the cause of preeclampsia and prematurity, restoring fertility to women in their late 30s and early 40s and on improving the efficacy of PGD to prevent birth defects.
"The thousands of women now benefiting from Yale Ob/Gyn's wealth of groundbreaking research and clinical care are experiencing just the tip of the iceberg of what's in the pipeline of obstetrical and gynecological care for women," says Lockwood, noting that these advances will likely create a brighter future filled with more options for the offspring of women like Christine Ostrowski and Maria Longobardi.
-- By Karen Peart
T H I S
In Focus: Obstetrics, Gynecology
& Reproductive Sciences
Dr. Pasquale Patrizio (left) has introduced the experimental reproductive technique of oocyte cryopreservation (the harvesting and freezing of eggs) at Yale. He has teamed with Veronica Bianchi (right), a scientist from Bologna, Italy, to improve the clinical application of this still-evolving procedure.
Yale Ob/Gyn's research laboratories include the Center for Research in Reproductive Biology, which includes a Gamete Biology Group, Maternal and Fetal Sciences Group, Neuroendocrine Group, Endometrial Biology Group, Cancer Biology Group and Steroid Hormone Group.
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