------------- cut here -----------------          HICNet Medical Newsletter                                              Page 13 Volume  6, Number 10                                           April 20, 1993                         Gonorrhea -- Colorado, 1985-1992                        ================================                    SOURCE: MMWR 42(14)   DATE: Apr 16, 1993       The number of reported cases of gonorrhea in Colorado increased 19.9%  from 1991 to 1992 after declining steadily during the 1980s. In comparison, in  the United States, reported cases of gonorrhea in 1992 continued an overall  decreasing trend (1). This report summarizes an analysis of the increase in  gonorrhea in Colorado in 1992 and characterizes trends in the occurrence of  this disease from 1985 through 1992.       In 1992, 4679 cases of gonorrhea were reported to the Colorado Department  of Health (CDH) compared with 3901 cases reported in 1991. During 1992,  reported cases increased 22.7% and 17.5% among females and males, respectively  (Table 1). Similar increases occurred among blacks, whites, and Hispanics  (15.6%, 15.1%, and 15.9%, respectively); however, the number of reported cases  with race not specified increased 88% from 1991 to 1992 and constituted 9.7%  of all reported cases in 1992. Although the largest proportional increases by  age groups occurred among persons aged 35-44 years (80.4%) and greater than or  equal to 45 years (87.7%), these age groups accounted for only 11.0% of all  reported cases in 1992. Persons in the 15-19-year age group accounted for the  largest number of reported cases of gonorrhea during 1992 and the highest age  group-specific rate (639 per 100,000).       Reported cases of gonorrhea increased 32.9% in the five-county Denver  metropolitan area (1990 population: 1,629,466) but decreased elsewhere in the  state (Table 1). Half the cases of gonorrhea in the Denver metropolitan area  occurred in 8.4% (34) of the census tracts; these represent neighborhoods  considered by sexually transmitted diseases (STDs)/acquired immunodeficiency  syndrome (AIDS) field staff to be the focus of gang and drug activity.       When compared with 1991, the number of gonorrhea cases diagnosed among  men in the Denver Metro Health Clinic (DMHC, the primary public STD clinic in  the Denver metropolitan area) increased 33% in 1992, and the number of visits  by males to the clinic increased 2.4%. Concurrently, the number of cases  diagnosed among women increased by 1%. Among self-identified heterosexual men,  the number of gonorrhea cases diagnosed at DMHC increased 33% and comprised  94% of all cases diagnosed in males, while the number of cases diagnosed among  self-identified homosexual men remained low (71 and 74 in 1991 and 1992,  respectively).       Four selected laboratories in the metropolitan Denver area (i.e., HMO,  university hospital, nonprofit family planning, and commercial) were contacted  to determine whether gonorrhea culture-positivity rates increased. Gonorrhea  culture-positivity rates in three of four laboratories contacted increased  23%-33% from 1991 to 1992, while the rate was virtually unchanged in the  fourth (i.e., nonprofit family planning).       From 1985 through 1991, reported cases of gonorrhea among whites and  Hispanics in Colorado decreased; in comparison, reported cases among blacks   HICNet Medical Newsletter                                              Page 14 Volume  6, Number 10                                           April 20, 1993  increased since 1988 (Figure 1). During 1988-1992, the population in Colorado  increased 9.9% for blacks, 9.8% for Hispanics, and 4.5% for whites. In 1992,  the gonorrhea rate for blacks (1935 per 100,000 persons) was 57 times that for  whites (34 per 100,000) and 12 times that for Hispanics (156 per 100,000)  (Table 1). Among black females, reported cases of gonorrhea increased from  1988 through 1992 in the 15-19-year age group; among black males, cases  increased from 1989 through 1992 in both the 15-19-and 20-24-year age groups.   Reported by: KA Gershman, MD, JM Finn, NE Spencer, MSPH, STD/AIDS Program; RE  Hoffman, MD, State Epidemiologist, Colorado Dept of Health. JM Douglas, MD,  Denver Dept of Health and Hospitals. Surveillance and Information Systems Br,  Div of Sexually Transmitted Diseases and HIV Prevention, National Center for  Prevention Svcs, CDC.   Editorial Note: The increase in reported gonorrhea cases in Colorado in 1992  may represent an overall increase in the occurrence of this disease or more  complete reporting stimulated by visitations to laboratories by CDH  surveillance staff during 1991-1992. The increases in confirmed gonorrhea  cases at DMHC and in culture-positivity rates in three of four laboratories  suggest a real increase in gonorrhea rather than a reporting artifact.  However, the stable culture-positivity rate in the nonprofit family planning  laboratory (which serves a network of clinics statewide) indicates that the  gonorrhea increase did not uniformly affect all segments of the population.       One possible explanation for the increased occurrence of gonorrhea in  Colorado may be gang- and drug-related sexual behavior, as implicated in a  recent outbreak of drug-resistant gonorrhea and other STDs in Colorado Springs  (2). Although the high morbidity census tracts in the Denver metropolitan area  coincide with areas of gang and drug activity, this hypothesis requires  further assessment. To examine the possible role of drug use -- implicated  previously as a factor contributing to the national increase in syphilis (3-6)  -- the CDH STD/AIDS program is collecting information from all persons in whom  gonorrhea is diagnosed regarding drug use, exchange of sex for money or drugs,  and gang affiliation.       The gonorrhea rate for blacks in Colorado substantially exceeds the  national health objective for the year 2000 (1300 per 100,000) (objective  19.1a) (7). Race is likely a risk marker rather than a risk factor for  gonorrhea and other STDs. Risk markers may be useful for identifying groups at  greatest risk for STDs and for targeting prevention efforts. Moreover, race- specific variation in STD rates may reflect differences in factors such as  socioeconomic status, access to medical care, and high-risk behaviors.       In response to the increased occurrence of gonorrhea in Colorado,  interventions initiated by the CDH STD/AIDS program include 1) targeting  partner notification in the Denver metropolitan area to persons in groups at  increased risk (e.g., 15-19-year-old black females and 20-24-year-old black  males); 2) implementing a media campaign (e.g., public service radio   HICNet Medical Newsletter                                              Page 15 Volume  6, Number 10                                           April 20, 1993  announcements, signs on city buses, newspaper advertisements, and posters in  schools and clinics) to promote awareness of STD risk and prevention targeted  primarily at high-risk groups, and 3) developing teams of peer educators to  perform educational outreach in high-risk neighborhoods. The educational  interventions are being developed and implemented with the assistance of  members of the target groups and with input from a forum of community leaders  and health-care providers.   References  1. CDC. Table II. Cases of selected notifiable diseases, United States, weeks  ending December 26, 1992, and December 28, 1991 (52nd week). MMWR 1993;41:975.   2. CDC. Gang-related outbreak of penicillinase-producing Neisseria gonorrhoeae  and other sexually transmitted diseases -- Colorado Springs, Colorado, 1989- 1991. MMWR 1993;42:25-8.   3. CDC. Relationship of syphilis to drug use and prostitution -- Connecticut  and Philadelphia, Pennsylvania. MMWR 1988;37:755-8, 764.   4. Rolfs RT, Goldberg M, Sharrar RG. Risk factors for syphilis: cocaine use  and prostitution. Am J Public Health 1990;80:853-7.   5. Andrus JK, Fleming DW, Harger DR, et al. Partner notification: can it  control epidemic syphilis? Ann Intern Med 1990;112:539-43.   6. Gershman KA, Rolfs RT. Diverging gonorrhea and syphilis trends in the  1980s: are they real? Am J Public Health 1991;81:1263-7.   7. Public Health Service. Healthy people 2000: national health promotion and  disease prevention objectives--full report, with commentary. Washington, DC:  US Department of Health and Human Services, Public Health Service, 1991; DHHS  publication no. (PHS)91-50212.              HICNet Medical Newsletter                                              Page 16 Volume  6, Number 10                                           April 20, 1993                  Effectiveness in Disease and Injury Prevention             Impact of Adult Safety-Belt Use on Restraint Use Among             Children less than 11 Years of Age -- Selected States,                                  1988 and 1989             ======================================================                    SOURCE: MMWR 42(14)   DATE: Apr 16, 1993       Motor-vehicle crashes are the leading cause of death among children and  young adults in the United States and account for more than 1 million years of  potential life lost before age 65 annually (1). Child safety seats and safety  belts can substantially reduce this loss (2). From 1977 through 1985, all 50  states passed legislation requiring the use of child safety seats or safety  belts for children. Although these laws reduce injuries to young children by  an estimated 8%-59% (3,4), motor-vehicle crash-related injuries remain a major  cause of disability and death among U.S. children (1), while the use of  occupant restraints among children decreases inversely with age (84% usage for  those aged 0-4 years; 57%, aged 5-11 years; and 29%, aged 12-18 years) (5). In  addition, parents who do not use safety belts themselves are less likely to  use restraints for their children (6). To characterize the association between  adult safety-belt use and adult-reported consistent use of occupant restraints  for the youngest child aged less than 11 years within a household, CDC  analyzed data obtained from the Behavioral Risk Factor Surveillance System  (BRFSS) during 1988 and 1989. This report summarizes the findings from this  study.       Data were available for 20,905 respondents aged greater than or equal to  18 years in 11 states * that participated in BRFSS -- a population-based,  random-digit-dialed telephone survey -- and administered a standard Injury  Control and Child Safety Module developed by CDC. Of these respondents, 5499  (26%) had a child aged less than 11 years in their household. Each respondent  was asked to specify the child's age and the frequency of restraint use for  that child. The two categories of child restraint and adult safety-belt use in  this analysis were 1) consistent use (i.e., always buckle up) and 2) less than  consistent use (i.e., almost always, sometimes, rarely, or never buckle up).  Data were weighted to provide estimates representative of each state. Software  for Survey Data Analysis (SUDAAN) (7) was used to calculate point estimates  and confidence intervals. Statistically significant differences were defined  by p values of less than 0.05.       Each of the 11 states had some type of child restraint law. Of these, six  (Arizona, Kentucky, Maine, Nebraska, Rhode Island, and West Virginia) had no  law requiring adults to use safety belts; four (Idaho, Maryland, Pennsylvania,  and Washington) had a secondary enforcement mandatory safety-belt law (i.e., a  vehicle had to be stopped for a traffic violation before a citation for nonuse  of safety belts could be issued); and one state (New York) had a primary  enforcement mandatory safety-belt law (i.e., vehicles could be stopped for a  safety-belt law violation alone). In nine states, child-passenger protection   HICNet Medical Newsletter                                              Page 17 Volume  6, Number 10                                           April 20, 1993  laws included all children aged less than 5 years, but the other two states  used both age and size of the child as criteria for mandatory restraint use.  The analysis in this report subgrouped states into 1) those having a law  requiring adult safety-belt use (law states), and 2) those without such a law  (no-law states).       Overall, 21% of children aged less than 11 years reportedly were not  consistently restrained during automobile travel. Both child restraint use and  adult restraint use were significantly higher (p less than 0.05, chi-square  test) in law states than in no-law states (81.1% versus 74.3% and 58.7% versus  43.2%, respectively).       High rates of restraint use for children aged less than or equal to 1  year were reported by both adults indicating consistent and less than  consistent safety-belt use (Figure 1). Adults with consistent use reported  high rates of child-occupant restraint use regardless of the child's age  (range: 95.5% for 1-year-olds to 84.7% for 10-year-olds). In comparison, for  adults reporting less than consistent safety-belt use, the rate of child- occupant restraint use declined sharply by the age of the child (range: 93.1%  for 1-year-olds to 28.8% for 10-year-olds). When comparing children of  consistent adult safety-belt users with children of less than consistent adult  safety-belt users, 95% confidence intervals overlap for the two youngest age  groups (i.e., aged less than 1 and 1 year).       Reported child-occupant restraint use in law states generally exceeded  that in no-law states, regardless of age of child (Table 1). In addition,  higher adult educational attainment was significantly associated with  increased restraint use for children, a factor that has also been associated  with increased adult safety-belt use (8).   Reported by: National Center for Injury Prevention and Control; National  Center for Chronic Disease Prevention and Health Promotion, CDC.   Editorial Note: The findings in this report are consistent with others  indicating that adults who do not use safety belts themselves are less likely  to employ occupant restraints for their children (6,9). Because these  nonbelted adults are at increased risk of crashing and more likely to exhibit  other risk-taking behaviors, children traveling with them may be at greater  risk for motor-vehicle injury (10).       Educational attainment of adult respondents was inversely associated with  child restraint use in this report. Accordingly, occupant-protection programs  should be promoted among parents with low educational attainment. Because low  educational attainment is often associated with low socioeconomic status, such  programs should be offered to adults through health-care facilities that serve  low-income communities or through federal programs (i.e., Head Start) that are  directed at parents with young children.       Injury-prevention programs emphasize restraining young children. In  addition, however, efforts must be intensified to protect child occupants as   HICNet Medical Newsletter                                              Page 18 Volume  6, Number 10                                           April 20, 1993  they become older. Parents, especially those with low educational attainment,  those who do not consistently wear safety belts, and those from states that do  not have mandatory safety-belt use laws, should be encouraged to wear safety  belts and to protect their children by using approved child safety seats and  safety belts. Finally, the increased use of restraints among children may  increase their likelihood of using safety belts when they become teenagers --  the age group characterized by the lowest rate of safety-belt use and the  highest rate of fatal crashes (5).   References  1. CDC. Childhood injuries in the United States. Am J Dis Child 1990;144:627- 46.   2. Partyka SC. Papers on child restraints: effectiveness and use. Washington,  DC: US Department of Transportation, National Highway Traffic Safety  Administration, 1988; report no. DOT-HS-807-286.   3. Guerin D, MacKinnon D. An assessment of the California child passenger  restraint requirement. Am J Public Health 1985;75:142-4.   4. Hall W, Orr B, Suttles D, et al. Progress report on increasing child  restraint usage through local education and distribution programs. Chapel  Hill, North Carolina: University of North Carolina at Chapel Hill, Highway  Safety Research Center, 1983.   5. National Highway Traffic Safety Administration. Occupant protection trends  in 19 cities. Washington, DC: US Department of Transportation, National  Highway Traffic Safety Administration, 1991.   6. Wagenaar AC, Molnar LJ, Margolis LH. Characteristics of child safety seat  users. Accid Anal Prev 1988;20:311-22.   7. Shah BV, Barnwell BG, Hunt PN, LaVange LM. Software for Survey Data  Analysis (SUDAAN) version 5.50 Software documentation. Research Triangle  Park, North Carolina: Research Triangle Institute, 1991.   8. Lund AK. Voluntary seat belt use among U.S. drivers: geographic,  socioeconomic and demographic variation. Accid Anal Prev 1986;18:43-50.   9. Margolis LH, Wagenaar AC, Molnar LJ. Use and misuse of automobile child  restraint devices. Am J Dis Child 1992;146:361-6.   10. Hunter WW, Stutts JC, Stewart JR, Rodgman EA. Characteristics of seatbelt  users and non-users in a state with a mandatory use law. Health Education   HICNet Medical Newsletter                                              Page 19 Volume  6, Number 10                                           April 20, 1993  Research 1990;5:161-73.   * Arizona, Idaho, Kentucky, Maine, Maryland, Nebraska, New York, Pennsylvania,  Rhode Island, Washington, and West Virginia.                                           HICNet Medical Newsletter                                              Page 20 Volume  6, Number 10                                           April 20, 1993                     Publication of CDC Surveillance Summaries                    =========================================                    SOURCE: MMWR 42(14)   DATE: Apr 16, 1993       Since 1983, CDC has published the CDC Surveillance Summaries under  separate cover as part of the MMWR series. Each report published in the CDC  Surveillance Summaries focuses on public health surveillance; surveillance  findings are reported for a broad range of risk factors and health conditions.       Summaries for each of the reports published in the most recent (March 19,  1993) issue of the CDC Surveillance Summaries (1) are provided below. All  subscribers to MMWR receive the CDC Surveillance Summaries, as well as the  MMWR Recommendations and Reports, as part of their subscriptions.   SURVEILLANCE FOR AND COMPARISON OF BIRTH DEFECT PREVALENCES                                IN TWO GEOGRAPHIC                          AREAS -- UNITED STATES, 1983-88        Problem/Condition: CDC and some states have developed surveillance  systems to monitor the birth prevalence of major defects.       Reporting Period Covered: This report covers birth defects surveillance  in metropolitan Atlanta, Georgia, and selected jurisdictions in California for  the years 1983-1988.       Description of System: The California Birth Defects Monitoring Program  and the Metropolitan Atlanta Congenital Defects Program are two population- based surveillance systems that employ similar data collection methods. The  prevalence estimates for 44 diagnostic categories were based on data for 1983- 1988 for 639,837 births in California and 152,970 births in metropolitan  Atlanta. The prevalences in the two areas were compared, adjusting for race,  sex, and maternal age by using Poisson regression.       Results: Regional differences in the prevalence of aortic stenosis, fetal  alcohol syndrome, hip dislocation/dysplasia, microcephalus, obstruction of the  kidney/ureter, and scoliosis/lordosis may be attributable to general  diagnostic variability. However, differences in the prevalences of arm/hand  limb reduction, encephalocele, spina bifida, or trisomy 21 (Down syndrome) are  probably not attributable to differences in ascertainment, because these  defects are relatively easy to diagnose.       Interpretation: Regional differences in prenatal diagnosis and pregnancy  termination may affect prevalences of trisomy 21 and spina bifida. However,  the reason for differences in arm/hand reduction is unknown, but may be  related to variability in environmental exposure, heterogeneity in the gene  pool, or random variation.       Actions Taken: Because of the similarities of these data bases, several  collaborative studies are being implemented. In particular, the differences in  the birth prevalence of spina bifida and Down syndrome will focus attention on  the impact of prenatal diagnosis. Authors: Jane Schulman, Ph.D., Nancy   HICNet Medical Newsletter                                              Page 21 Volume  6, Number 10                                           April 20, 1993  Jensvold, M.P.H, Gary M. Shaw, Dr.P.H., California Birth Defects Monitoring  Program, March of Dimes Birth Defects Foundation. Larry D. Edmonds, M.S.P.H.,  Anne B. McClearn, Division of Birth Defects and Developmental Disabilities,  National Center for Environmental Health, CDC.                         INFLUENZA -- UNITED STATES, 1988-89       Problem/Condition: CDC monitors the emergence and spread of new influenza  virus variants and the impact of influenza on morbidity and mortality annually  from October through May.       Reporting Period Covered: This report covers U.S. influenza surveillance  conducted from October 1988 through May 1989.       Description of System: Weekly reports from the vital statistics offices  of 121 cities provided an index of influenza's impact on mortality; 58 WHO  collaborating laboratories reported weekly identification of influenza  viruses; weekly morbidity reports were received both from the state and  territorial epidemiologists and from 153 sentinel family practice physicians.  Nonsystematic reports of outbreaks and unusual illnesses were received  throughout the year.       Results: During the 1988-89 influenza season, influenza A(H1N1) and B  viruses were identified in the United States with essentially equal frequency  overall, although both regional and temporal patterns of predominance shifted  over the course of the season. Throughout the season increases in the indices  of influenza morbidity in regions where influenza A(H1N1) predominated were  similar to increases in regions where influenza B predominated. Only 7% of  identified viruses were influenza A(H3N2), but isolations of this subtype  increased as the season waned, and it subsequently predominated during the  1989-90 season. During the 1988-89 season outbreaks in nursing homes were  reported in association with influenza B and A(H3N2) but not influenza  A(H1N1).       Interpretation: The alternating temporal and geographic predominance of  influenza strains A(H1N1) and B during the 1988-89 season emphasizes the  importance of continual attention to regional viral strain surveillance, since  amantadine is effective only for treatment and prophylaxis of influenza A.       Actions Taken: Weekly interim analyses of surveillance data produced  throughout the season allow physicians and public health officials to make  informed choices regarding appropriate use of amantadine. CDC's annual  surveillance allows the observed viral variants to be assessed as candidates  for inclusion as components in vaccines used in subsequent influenza seasons.  Authors: Louisa E. Chapman, M.D., M.S.P.H., Epidemiology Activity, Office of  the Director, Division of Viral and Rickettsial Diseases, National Center for  Infectious Diseases; Margaret A. Tipple, M.D., Division of Quarantine,  National Center for Prevention Services, CDC. Suzanne Gaventa Folger, M.P.H.,  Health Investigations Branch, Division of Health Studies, Agency for Toxic  Substances and Disease Registry. Maurice Harmon, Ph.D., Connaught   HICNet Medical Newsletter                                              Page 22 Volume  6, Number 10                                           April 20, 1993  Laboratories, Pasteur-Mirieux Company, Swiftwater, Pennsylvania. Alan P.  Kendal, Ph.D., European Regional Office, World Health Organization,  Copenhagen, Denmark. Nancy J. Cox, Ph.D., Influenza Branch, Division of Viral  and Rickettsial Diseases, National Center for Infectious Diseases; Lawrence B.  Schonberger, M.D., M.P.H., Epidemiology Activity, Office of the Director,  Division of Viral and Rickettsial Diseases, National Center for Infectious  Diseases, CDC.   Reference  1. CDC. CDC surveillance summaries (March 19). MMWR 1993;42(no. SS-1).                                   HICNet Medical Newsletter                                              Page 23 Volume  6, Number 10                                           April 20, 1993    ::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::                             Clinical Research News ::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::                            Clinical Research News for                               Arizona Physicians                   Vol. 4, No. 4, April 1993     Tucson, Arizona  Published monthly by the Office of Public Affairs at The University of Arizona                             Health Sciences Center.                       Copyright 1993, The University of Arizona                   High Tech Assisted Reproductive Technologies  Following the birth of the first in vitro fertilization-embryo transfer (IVF- ET) baby in 1978, a host of assisted reproductive technologies have been  developed that include IVF-ET, gamete intrafallopian tube transfer (GIFT),  embryo cryopreservation (freezing) and gamete micromanipulation. Together,  these technologies are referred to as the high-tech assisted reproductive  technology (ART) procedures.   Ovulation induction, sperm insemination and surgery for tubal disease and/or  pathology still are the mainstays of the therapies available for infertility  management. However, when these fail, it almost always is appropriate to  proceed with one of the ART procedures.   Therefore, in addition to a comprehensive basic and general infertility  service at The University of Arizona Center for Reproductive Endocrinology and  Infertility, there is a program of Assisted Reproduction that specializes in  ART procedures. This program serves as a tertiary provider for those patients  in the state of Arizona whose infertility problems cannot be resolved by the  traditional therapies.   The following article (on back) describes the ART procedures available in our  Center, clarifies appropriate applications for each, and considers the  realistic expectations for their success. Procedures included are:   o in vitro  o fertilization - embryo transfer (IVF-ET),  gamete intrafallopian tube    transfer  o (GIFT),  cryopreservation of human embryos and  gamete micromanipulation.  This article also considers ongoing research in our program that is directed  towards improved success of these technologies.    HICNet Medical Newsletter                                              Page 24 Volume  6, Number 10                                           April 20, 1993                             Future Areas of Research  In addition to ongoing research that is directed exclusively toward the  management of infertile couples, we are developing the technology to assist  couples who are at risk for producing embryos with a serious hereditary  disease.   This technology involves biopsying the preimplantation human embryo and then  subjecting the biopsied cells to genetic analysis using either DNA  amplification or fluorescent in situ hybridization.   There are recent reports of the successful application of DNA amplification by  other centers, for example, for diagnosis of the genes for cystic fibrosis and  hemophilia. We hope to apply and further focus fluorescent in situ  hybridization technology for probing the X chromosome, the identification of  which will provide a scientific basis for counselling patients who exhibit  sex-linked disorders.   The considerable clinical application of such technology lies in the fact that  it circumvents the need for prenatal diagnosis, in addition to the possibility  of a subsequent termination of affected fetuses, in order to avoid the birth  of affected children.    Catherine Racowsky, Ph.D. Associate Professor and Director of Research Department of Obstetrics and Gynecology College of Medicine  University of Arizona Tucson, Arizona                 Applications, Success Rates and Advances for the                            Management of Infertility  The following are the ART procedures available at The University of Arizona  Center for Reproductive Endocrinology and Infertility.        In Vitro Fertilization - Embryo Transfer is the core ART procedure of our  Assisted Reproduction Program.  This procedure involves retrieval of  unfertilized eggs from the ovary, their insemination in vitro in a dish, and  the culture of resultant embryos for 1 or 2 days, before they are transferred  to the patient's uterus. All cultures are maintained in an incubator under  strictly controlled atmospheric and temperature conditions. Before being  processed for use in insemination, semen samples are evaluated in our  andrology laboratory using both subjective light microscopy and computer-  HICNet Medical Newsletter                                              Page 25 Volume  6, Number 10                                           April 20, 1993  assisted semen analyses. To ensure an adequate number of eggs with which to  perform IVF-ET, or indeed, GIFT, follicular development is typically  stimulated, with gonadotropins (perganol, metrodin), gonadotropin releasing  hormone (GnRH, Factrel, lutrepulse) and/or GnRH analogues (lupron, Depo  lupron, synarel). Occasionally, however, IVF-ET is accomplished with eggs  obtained in non-stimulated cycles. While some programs utilize laparoscopic  egg retrieval in the operating room with the patient under general anesthesia,  we undertake the less costly approach of ultrasound-guided retrieval in our  Infertility Unit, with the patient sedated.        Couples who resort to IVF-ET exhibit such pathologies as tubal  deficiencies, ovulatory dysfunction, endometriosis, and/or mild forms of male  factor infertility.  According to the United States IVF Registry, the overall  success rate for IVF-ET nationwide has stabilized at about 14 percent per  cycle. Results from our program, involving 86 patients who have undergone 173  IVF-ET cycles, reflect a comparable success rate.       Nevertheless, the overall incidence of success with this procedure is  disconcertingly low and emphasizes the need to address those physiological  factors that limit achievement of a higher percentage of pregnancies.  Well  recognized predictors of outcome include patient age, response to exogenous  ovarian stimulation, quality of sperm and number of repeated IVF-ET cycle  attempts. However, among these, age is the single most significant determinant  of conception. Therefore, it is critical that such patients are referred to an  Assisted Reproduction Program at the earliest opportunity following failure of  traditional therapies.       The underlying basis for the negative effect of age on fertility has not  been clearly delineated beyond recognition that: 1) the number of eggs  available for retrieval declines markedly with age; 2) fertilization rates  significantly decrease in eggs retrieved from patients who are over 40 years;  and 3) provided the appropriate hormonal background is present, age is  unrelated to uterine competency to sustain pregnancy. Ongoing research in our  Center, therefore, is investigating physiological changes in the egg that may  be impacted by age. We have determined that more than 50 percent of eggs that  fail to fertilize in vitro are chromosomally abnormal, and that a significant  proportion of these abnormalities are accountable to patient age. Currently,  the only recourse for such patients is to use eggs obtained from a donor. Our  program has initiated recruitment of volunteer egg donors to satisfy the needs  of a list of recipients interested in this form of therapy.        GIFT - This high-tech ART procedure is performed in the operating room,  usually with the use of a laparoscope and, in contrast to IVF-ET, involves  introducing sperm and freshly retrieved eggs into the lumen of the Fallopian  tube (an average of 3 eggs/tube). Under these circumstances, fertilization  occurs in vivo and, if excess eggs are retrieved, the remainder undergo IVF,  with subsequent options for embryo transfer in that cycle, or freezing for  transfer in a subsequent cycle. This ART procedure is applied to cases in   HICNet Medical Newsletter                                              Page 26 Volume  6, Number 10                                           April 20, 1993  which there is at least one patent Fallopian tube but the couple has such  pathologies as ovulatory dysfunction, endometriosis, male factor infertility  and/or idiopathic infertility.          The data reported in the United States IVF Registry for 1985 through 1990  indicate that the overall success rate with GIFT is higher than that obtained  with the IVF-ET technique (range of clinical pregnancies for GIFT is 24 to 36  percent and for IVF-ET 14 to 18 percent). In view of this fact, one might  expect more patients to be treated with GIFT than IVF-ET. However, in our  program we have taken into account three basic concerns which, while  substantially reducing the number of GIFT cycles performed, benefit the  patient. These concerns are: 1) the increased costs associated with performing  a procedure in the operating room; 2) the risks, albeit minimal, of undergoing  general anesthesia; and 3) the considerable benefits to be accrued from  obtaining direct information on the quality and fertilizability of the eggs,  and the developmental competency of resultant embryos.       The increased success with GIFT undoubtedly reflects the artificial  environment provided by the laboratory in the IVF-ET procedure. Between  January 1, 1991, and December 31, 1992, we have performed a total of 12 GIFT  cycles, with an overall success rate of 20 percent.       Embryo cryopreservation, or freezing, is applied in our program when  embryos result from residual GIFT eggs or from non-transferred IVF embryos.  This procedure not only provides patients with a subsequent opportunity for  success at much reduced costs, but also circumvents the legal and ethical  issues relating to disposal of supernumerary embryos. Therefore, as stipulated  by the American Fertility Society ethical guidelines for ART programs, from  both a practical and an ethical standpoint, all Assisted Reproduction programs  should have the capability of cryopreserving human embrys.       Gamete Micromanipulation - This ART procedure, which is still very new,  is applied to couples who are unaccepting of insemination with donor semen but  who have severe male factor infertility (less than 10 million sperm/ml in  combination with fewer than 20 perccent motile sperm, and/or less than 10  percent sperm with normal morphology). We are currently developing the  procedure of sub-zonal insertion (SZI), which entails injecting sperm under  the coating around the egg, the barrier normally penetrated by the sperm  through enzymatic digestion.       Available data from SZI programs world-wide indicate that only 5 to 10  percent of SZI cycles result in a pregnancy. This statistic undoubtedly  relates to limitations imposed by abnormalities inherent in the sperm.  Therefore, we are currently focusing on the development of improved techniques  for the recognition and selection of sperm chosen for manipulation. Such  efforts are unquestionably worthwhile in view of the fact that this technology  offers the only realistic opportunity for severe male factor patients to  establish conception.   Catherine Racowsky, Ph.D.  HICNet Medical Newsletter                                              Page 27 Volume  6, Number 10                                           April 20, 1993  Associate Professor and Director of Research Department of Obstetrics and Gynecology College of Medicine  --------- end of part 2 ------------