SUMMER 2005

2106 South 17th StreetWilmington, North Carolina 28401 p) 910.362.9511 f) 910.362.9512 www.wilmingtonpathology.com

COVER STORY: HISTOLOGIC DATING OF THE ENDOMETRIUM FOR INFERTILITY SCREENING...A THING OF THE PAST

OTHER STORIES: NEW BEGINNINGS MEET OUR COURIERS

IN THE NEWS: NEW HOME ON THE HORIZON UNCW LEARNING ALLIANCE NEXTWAVE DIAGNOSTIC LABORATORIES CELEBRATES ITS FIRST ANNIVERSARY

CHRISTOPHER D. MCKINNEY, M.D., F.C.A.P., F.A.S.C.P.Board Certified, Anatomic and Clinical Pathology

Areas of Expertise: Immunohistochemistry, Flow Cytometry, Image Analysis, and Molecular Testing in Neoplastic Diseases

CAROLINA M. MONTES, M.D.Board Certified, Anatomic and Clinical Pathology, Dermatopathology

Areas of Expertise: Dermatopathology General Surgical Pathology

DEBRA BUDWIT NOVOTNY, M.D., F.C.A.PBoard Certified, Anatomic and Clinical Pathology, Cytopathology

Areas of Expertise: Gynecologic Pathology, Cytopathology, and Breast Pathology

The Doctors of Wilmington PathologyBABATUNDE A. OLATIDOYE, M.D., F.C.A.P.Board Certified, Anatomic and Clinical Pathology, Cytopathology

Areas of Expertise: Cytopathology, Breast Pathology, Head / Neck Pathology, and Oral Pathology

BRIAN C. SHIRO, M.D., F.C.A.P., F.A.S.C.PBoard Certified, Anatomic and Clinical Pathology

Areas of Expertise: Gastrointestinal Pathology, Oral Pathology, and Immunohistochemistry

GREGORY E. STEINKRAUS, Ph.D., A.B.M.M.Diplomate, American Board of Medical Microbiology

Areas of Expertise: Antimicrobial Therapy and Susceptibility Testing; Immunology, Allergy, and Autoimmune Diseases; Respiratory Tract Infections; Noscomial Infections; and Molecular Diagnostic Testing

JOHN F. (JEFF) TURNER, JR., M.D., F.C.A.P.Board Certified, Anatomic and Clinical Pathology Hematology Special Qualification

Areas of Expertise: Neoplastic Hematopathology, General Surgical Pathology, and Non-neoplastic Hematopathology

Over fifty years ago, Noyes, Hertig and Rock (1) published their landmark article on criteria for histologic dating of the endometrial biopsy in the inaugural issue of Fertility and Sterility, which has continued to be one of the most often cited articles from that journal. Their dating criteria to date have endured as the gold standard among methods in clinical practice for the evaluation of luteal function and for the diagnosis of luteal phase deficiency.

The study design of Noyes et al had a number of flaws. First and most importantly, the tissue samples were largely obtained from infertile women. Second, the postovulatory day of tissue specimens was estimated in retrospect based on a presumed uniform secretory phase of 14 days, with the postovulatory day assigned between biopsy day and the onset of next menses. Several subsequent studies have demonstrated that the normal secretory (luteal) phase does vary in duration. Third, histologic criteria have inherent interpretive subjectivity, such that dating differences within a 2-day interval were subsequently generally considered to be normal and acceptable.

In the past year, investigators from the divisions/departments of Reproductive Endocrinology and Infertility, Obstetics and Gynecology and Pathology at UNC-Chapel Hill published a critical re-analysis of these histologic dating criteria (2). Dr. Debra Novotny was the principle designer of the histologic arm of this study, and reviewed the histologic slides in a blinded fashion in conjunction with two other internationally recognized gynecological pathologists. Tissue samples were obtained from 130 healthy fertile volunteers, obtained prospectively, randomized from 1 to 14 days from the midcycle urinary luteinizing hormone (LH) surge. The three pathologists independently scored 32 distinct histologic features in each of the biopsies, and dated the endometrium using traditional histologic criteria.

The results showed that traditional endometrial histologic dating criteria are much less temporally distinct and discriminating than originally decribed, due to considerable intersubject, intrasubject, and interobserver variability. Neither traditional dating criteria nor any combination of the best performing histologic features could reliably distinguish any specific cycle day or narrow

Histologic Dating Of The Endometrium For Infertility Screening...a Thing Of The PastBy Debra B. Novotny, M.D.

National Health ObservancesJULYUV Safety Month

AUGUSTNational Immunization Awareness Month

SEPTEMBERGynecologic Cancer Awareness MonthOvarian Cancer Awareness MonthLeukemia and Lymphoma Awareness MonthProstate Cancer Awareness Month

Phone DirectoryMain office ................................................................910.362.9511

Fax ..............................................................................910.362.9512

Patient Billing ............................................................800.851.5194

Physician Office Billing ..................... Cheryl Tolley 910.202.1727

Cytology .............................................. Jeff Celeste 910.202.1730

Andrology ............................................ Jeff Celeste 910.202.1730

Patient Reports .................................Peg Wagner 910.202.1722

Client Service .................................... Melissa Davis 910.202.1719

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Our couriers crisscross New Hanover, Brunswick, Pender and Onslow Counties on a daily basis logging over 450 miles a day transporting specimens and supplies between clients and our laboratory. We have four couriers working simultaneously to ensure quick and efficient service. You may see any of them in your office, as each one is trained to cover routes for one another. This team of dedicated and highly dependable individuals realizes their cargo is irreplaceable and takes meticulous care to guarantee every specimen reaches our laboratory in a timely fashion. As the most visible associates of WPA, our couriers are required to be conscientious drivers, courteous, professional and helpful.

Marsh Watkins celebrated her five-year anniversary with WPA this spring. As a board certified phlebotomist and certified medical assistant, she originally began working for our cytology department. Because Marsh is a people person, she soon welcomed the opportunity to become a courier and have daily

contact with our clients. On her regular route, Marsh takes care of our clients whose practices are located near New Hanover Regional Medical Center. As our senior courier, she also handles other aspects of our courier department including the accurate distribution of supplies, patient reports and monitoring the specimen “call-in” phone line. Marsh takes great pride in her duties and always carries a smile.

Vickie Nowell is our courier who truly goes the distance. She joined WPA in July 2002 and her daily route takes her from Southport and Supply in Brunswick County all the way to Burgaw in Pender County—covering over 150 miles in a single day. With her bubbly personality and infectious laugh, Vickie is

a wonderful ambassador to our clients whose practices are located so far from our facility. She strives to make them feel connected to WPA giving them the same care and attention they would receive if they were our lab’s next-door neighbor.

Even though Anthony Murphy has been with us only since November 2004, he has been a tremendous asset. Prior to joining our group, he spent eight years working as a courier and service representative for a national laboratory. In addition, he has training as a phlebotomist. Anthony takes care of our Jacksonville

and Onslow County clients and has been very successful in widening our service area in that region. His experience and dedication are evident in everything he does, as he is knowledgeable, professional and efficient.

The latest addition to our courier staff is Kerry Gray. She joined WPA in February 2005 and runs all of our routes as needed. Her background includes working for a company that managed transportation for senior citizens so being on the road is nothing new to her. Her energy level and hard work are a wonderful

benefit to our laboratory.

One of our couriers is far from home right now. Dave Pattison is serving with the 81st RRC (Regional Readiness Command) in Iraq. He left in January and could be deployed for as long as eighteen months. This is the second time Dave as been called for duty to serve in the Middle East since joining WPA in 2003.

Dave’s route mainly consisted of our clients in the Hampstead, Ogden and Jacksonville areas. We appreciate Dave’s willingness to serve his country and our thoughts are with him for a quick and safe return.

interval of days. For example, according to the criteria of Noyes et al, subnuclear cytoplasmic vacuoles should be absent by luteal day 4, yet Murray et al demonstrated that these frequently persist in fertile women well beyond this time frame. Additionally, 49 women underwent a repeat second endometrial biopsy in a subsequent menstrual cycle on the same luteal day. The data for this subset of women also suggested that between-cycle variation among normal women is quite common and may be observed in up to one-third of between-cycle comparisons.

Subsequent to the above publication by Murray et al, a multi-institutional study supported by the National Institutes of Health/National Institute of Child Health and Human Development, National Cooperative Reproductive Medicine Network also published their findings with regard to the reliability of histologic dating of the endometrium (3). This multicenter study evaluated 619 endometial biopsies in both fertile and infertile couples. Biopsies were also evaluated using Noyes et al histologic criteria. An out-of-phase biopsy was defined as a greater than 2-day delay in the histologic maturation of the endometrium relative to the detection of the urinary LH surge. There were 301 mid and 318 late luteal phase biopsies. Out-of-phase biopsy results poorly discriminated between women from fertile and infertile couples in either the midluteal (fertile: 49.4%, infertile: 43.2%) or late luteal phase (fertile: 35.3%, infertile: 23.0%). These authors also concluded that the timed endometial biopsy followed by histologic dating of the endometrium provides no clinically useful information as a screening test in the initial evaluation of couples with infertility.

In summary, traditional histologic dating of the endometrium is not a valid clinical diagnostic tool. It does not have the accuracy or the precision necessary to provide a valid method for the diagnosis of luteal phase deficiency, if such exists. Nonetheless, if clinically suspected, endometrial biopsy remains

useful to exclude other potential causes of infertility, such as chronic endometritis, hyperplasia or neoplasia.

Clinicians who wish to receive a reprint of the published article by Murray et al (2) may direct their requests to Dr. Novotny at debra.novotny@wilmpath.com.

References:

Noyes RW, Hertig AW, Rock J. Dating the endometrial biopsy. Fertil Steril 1950;1:3-25.

Murray MJ, Meyer WR, Zaino RJ, Lessey BA, Novotny DB, Ireland K, Zeng D, Fritz MA. A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women. Fertil Steril 2004;81:1333-1343.

Coutifaris C, Myers ER, Guzick DS, Diamond MP, Carson SA, Legro RS, McGovern PG, Schlaff WD, Carr BR, Steinkampf MP, Silva S, Vogel DL, Leppert PC, for the NICHD National Cooperative Reproductive Medicine Network. Histologic dating of timed endometrial biopsy tissue is not related to fertility status. Fertil Steril 2004;82:1264-1272.

Biosketch:

Dr. Debra Budwit Novotny received the degree of Doctor of Medicine with Honors from the University of North Carolina at Chapel Hill. She is fellowship trained in both surgical pathology and cytopathology, and is board certified in Anatomic and Clinical Pathology with subspecialty board certification in Cytopathology. Prior to joining Wilmington Pathology Associates in 2000, Dr. Novotny was a tenured Associate Professor of Pathology and Laboratory Medicine at UNC-Chapel Hill, where she served as a member of the faculty for ten years. She is the author or co-author of over 100 peer-reviewed publications. Dr. Novotny is a member of several professional organizations, including an elected member of the International Society of Gynecological Pathologists.

UNCW Learning AllianceWilmington Pathology is pleased to have been

selected to serve as an Alliance Partner for a

team of UNCW MBA students. The students

work all day at local companies and attend

class in the evening. Wilmington Pathology

and other Alliance Partners provide the real

life business experience to apply what they

learn in the classroom.

Wilmington Pathology benefits from fresh ideas

from bright local MBA students and the students

benefit from real life business interactions

through an analysis of the healthcare industry

and by making strategic recommendations for

growth and process improvement.

New Home on the Horizon

Early this Fall Wilmington Pathology will

be moving to a new location on 17th

Street. The 15,000 square foot building will

also be the home for NextWave Diagnostic

Laboratories. The new facilities will provide

patients with improved access and allow the

group to implement new technologies and

medical advances.

NextWave Diagnostic Laboratories Celebrates its First Anniversary Early in 2004 NextWave Diagnostic Laboratories

was created by several principals from

Wilmington Pathology in response to a desire by

healthcare providers for a higher level of service

and accessibility within our community. With

the addition of NextWave, we are now able

to offer an additional level of care, providing

expertise in clinical laboratory medicine that the

people of our communities deserve. NextWave

provides services including STAT testing and

same-day results to physician offices, surgery

centers, hospitals and nursing homes.

Fertility

On July 15th, Wilmington Pathology Associates will bid a fond farewell to one of its senior partners, Gregory S. Henderson, M.D., Ph.D. Dr. Henderson joined the practice in 1998 and was instrumental in the development and opening of our independent cytology laboratory in June 2000. He constantly strives for excellence in

everything he does and his philosophy has taught us all that what we do—and doing it well—makes a difference to our clients and to their patients.

Dr. Henderson has accepted the position of Associate Chairman of the Department of Pathology, Director of Anatomic Pathology, and Director of Laboratory Outreach at Ochsner Clinic Foundation (OCF) in New Orleans effective September 1, 2005. Widely

recognized as centers for excellence in research, patient care and education, OCF is a not-for-profit, comprehensive health care system that includes a clinic, hospital, and health plan providing services in over 24 locations throughout Southeast Louisiana with more than 600 physicians in nearly 70 medical specialties.

While embarking upon this new venture with his wife, Isabelle, and daughters, Margaux and Ava, he will be also be continuing his work with the HPV Foundation he created from the proceeds of his first book, “WOMEN AT RISK: The HPV Epidemic and Your Cervical Health.” This book explains one of the most dangerous, yet relatively unknown, sexually transmitted diseases: human papillomavirus (HPV), the primary cause of cervical cancer. The foundation promotes awareness locally, nationally and internationally on this epidemic. He will be greatly missed but we wish him well in his new and exciting endeavor.

In The News

New Beginnings

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Meet Our Couriers