Carole L. Kowalczyk

Thrombosis and hormone replacement therapy in postmenopausal women.

OBJECTIVE The effects of postmenopausal hormone replacement therapy on thrombosis remain controversial. We tested the hypothesis that estrogen or progesterone has no significant effect on thrombosis by means of newly developed markers of blood clotting, specifically prothrombin fragment 1 + 2, a marker of factor Xa generation, and thrombin-antithrombin III complex, a marker of thrombin generation. STUDY DESIGN A prospective study that included 106 women, 68 postmenopausal women on hormone replacement therapy and 38 postmenopausal controls, was performed. Plasma levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex were measured by enzyme-linked immunosorbent assay. Multivariate analysis of the covariance was used for statistical analysis, controlling for patients age because the hormone replacement therapy group was older. RESULTS There were no statistically significant differences between the hormone replacement therapy and control groups in either of the clotting parameters measured. A comparison of the levels of prothrombin fragment 1 + 2 and thrombin-antithrombin III complex in patients receiving estrogen alone or estrogen plus progestin also revealed no differences. CONCLUSIONS Current doses of postmenopausal hormone replacement therapy do not appear to enhance in vivo clotting. Thromboembolic complications among postmenopausal women receiving hormone replacement therapy may therefore be secondary to congenital or other acquired coagulation defects.

Selective embryo reduction in a heterotopic pregnancy using potassium chloride injection resulting in a hematosalpinx

OBJECTIVE To incorporate conservative management of a heterotopic pregnancy using injection of KCl into the ectopic pregnancy (EP). DESIGN A retrospective case report. SETTING A patient referred to an academic institution in the division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, incorporating the ultrasound (US) and operating room facilities. INTERVENTION(S) Using US as a guide, KCl was injected into the chorionic cavity of an EP. MAIN OUTCOME MEASURE(S) Resolution of ectopic gestational tissue with resultant hematosalpinx requiring exploratory laparotomy. Uncomplicated prenatal course of intrauterine pregnancy. RESULT(S) Injection of KCl into the chorionic cavity of EP resulting in resolution of gestational tissue but complicated by hematosalpinx in the fallopian tube. CONCLUSION(S) Selective embryo reduction of a tubal heterotopic pregnancy remains a viable therapeutic option.

Pediatric and adolescent gynecology experience in academic and community OB/GYN residency programs in Michigan

OBJECTIVES The purpose of this study is to assess training in Pediatric and Adolescent Gynecology (PAG) at the Obstetrics and Gynecology (OB/GYN) resident level. SETTING Two large Michigan programs were studied: a university-based, inner-city program, and a suburban, community-based program. Seventy-one questionnaires were distributed to the residents, and descriptive and inferential analysis of answers to demographic, training, attitude, and knowledge-based questions regarding PAG was performed. RESULTS Sixty-one questionnaires were returned, a response rate of 86%. The majority of respondents reported no PAG rotations or clinics and recalled limited didactic sessions with only 0-2 lectures. Ninety-eight percent of university residents and 94% of community residents requested more PAG training. Comfort levels about PAG issues were assessed on a 5 point scale (1 = low, 5 = high comfort); university residents scored 3.7 with pediatric patients and 4.4 with adolescents, and community residents scored 4.0 with the pediatric age group and 4.3 with adolescents. However, both groups responded with familiarity to knowledge based questions only 61% of the time. CONCLUSIONS OB/GYN residents in both academic and community programs report little experience and scant training in PAG but express interest in obtaining the skills and information needed. It is concerning that residents lack the basic knowledge that is required for the routine daily care of this patient population. More emphasis needs to be placed on these issues in OB/GYN residency training programs.

Midcycle increase of prolactin seen in normal women is absent in subjects with unexplained infertility

OBJECTIVE To compare the bioactive and immunoactive PRL in normal and unexplained infertility subjects. DESIGN Prospective study. SETTING Department of Obstetrics and Gynecology, Wayne State University and The University of Michigan. PATIENT(S) Twelve normal, fertile women compared with 12 patients with unexplained infertility. INTERVENTION(S) Serum samples were obtained across the menstrual cycle and for each subject, 5 pools were prepared by combining serum aliquots from the early follicular, late follicular, midcycle, and midluteal and late luteal phases of the cycle. MAIN OUTCOME MEASURE(S) Niobium lymphoma cell bioassay and an immunoradiometric assay were used to quantitate PRL. RESULT(S) A midcycle increase in PRL was seen in controls by both assays and these levels were greater compared with other cycle stages. Comparison of midcycle PRL between groups showed differences only between bioactive PRL (34.2 +/- 8.3 versus 19.2 +/- 3.4 ng/mL [conversion factor to SI unit, 1.00]). The ratios between bioactive and immunoactive PRL were comparable. Significant correlation between bioactive and immunoactive PRL was seen for both control (r = 0.616) and unexplained infertility (r = 0.660) groups. CONCLUSION(S) The midcycle elevations of bioactive and immunoactive PRL seen in normal women were absent in women with unexplained infertility. This alteration in PRL dynamics may be a part of subtle differences in the reproductive hormone profile of women with unexplained infertility compared with their fertile counterparts.

Urinary β-Core Fragment as a Predictor of Abnormal Pregnancy at 4–6 Weeks’ Gestation

Currently, transvaginal ultrasound and serial serum beta-hCG measurements are used to differentiate normal versus abnormal gestations in the first trimester of pregnancy. These techniques have been found to be ineffective when the gestations are earlier than 6 weeks. This study was conducted to determine if urinary beta-core fragment, the urine degradation product of beta-hCG, could be used to distinguish normal from abnormal gestations between 4 and 6 weeks. Urine samples were obtained from 27 patients on initial presentation to the emergency room or outpatient settings with gestations at 4-6 weeks by sure last menstrual period. The urine was then frozen at -40 degrees C and sent for beta-core assay analysis. Eighteen women with normal intrauterine pregnancies and nine abnormal pregnancies, including ectopics and spontaneous abortions, were studied. Pearson correlations were performed with a p < 0.05 considered significant. In the normal gestations, there was a positive correlation between beta-core fragment and gestational age at 4-6 weeks (r = 0.461, p < 0.05). This correlation was not evident in abnormal gestations (r = 0.360, p = 0.34). In early pregnancy, beta-core fragment correlates positively with gestational age which is not apparent in abnormal counterparts. This finding suggests that urinary beta-core fragment may be a promising marker to differentiate normal early pregnancies from abnormal gestations.

An Association Between Precocious Puberty and Fragile X Syndrome

STUDY OBJECTIVE To determine the FMR1 gene status in a 10-year, 10-month-old girl with a history of precocious puberty and a family history of fragile X syndrome. DESIGN Case report. SETTING The outpatient facility of the Division of Adolescent Medicine and the Division of Genetic and Metabolic Disorders at Childrens Hospital of Michigan and the Medical Genetics and Birth Defects Center of Henry Ford Hospital, Detroit, Michigan. PARTICIPANT A 10-year, 10-month-old girl with a history of precocious puberty. INTERVENTION Evaluation for menorraghia, DNA extraction, and fragile X gene analysis of blood samples from the patient and her mother. MAIN OUTCOME MEASURES Identification of a full mutation in the FMR1 gene. RESULTS Southern blot analysis of the FMR1 gene identified a full mutation in the daughter with approximately 750 repeats of the CGG sequence. Methylation studies showed that the full mutation was completely methylated. FMR1 DNA studies on her mother identified a premutation of approximately 100 repeats. CONCLUSIONS This report identifies a young girl with a history of precocious puberty and fragile X syndrome. It is also the first report of molecular genetic FMR1 studies in a female with precocious puberty. A possible association between the two conditions is suggested and warrants further investigation.

Gonococcal Infection in Cerebrospinal Fluid and the Presence of a Ventriculoperitoneal Shunt

BACKGROUND Neisseria gonorrhoeae is one of the most common organisms associated with pelvic disease in a woman of reproductive age. CASE We present an unusual case of cerebrospinal fluid infection with N. gonorrhoeae in a woman with a ventriculoperitoneal shunt who complained of abdominal pain. Her shunt was removed and after adequate antibiotic therapy, it was re-inserted. CONCLUSION Sexually active women, especially those with ventriculoperitoneal shunts, should be encouraged to use a barrier method of contraception, and should have a pelvic examination as part of their evaluation when they present with complaints of abdominal pain.

The Relationship Between Sexual Experiences, Sexual Abuse and Teenage Pregnancy in A Large Inner City Population.

Background It is known that many adolescents experience unwanted or coercive sexual acts. One in 5 to 6 females1 2 experience sexual abuse as a child or adolescent with many short and long term consequences, one of which is pregnancy. The objective of this study is to identify how often teenage pregnancies are perceived by the mother to be a result of an abusive sexual experience, and to evaluate the relationship between sexual experience, sexual abuse and teenage pregnancy in a large inner city population. Methods We identified pregnant females aged 19 years or younger presenting for prenatal care at the University Health Center Obstetrics Clinic during a 6 month recruiting period. Consent was obtained, and the identity of the participants shielded by coding the questionnaires numerically. A multiple choice/fill in the blank questionnaire surveyed the mothers regarding their past sexual experiences. A registered nurse was available after completion of the questionnaire to answer questions, to distribute information regarding sexual abuse. community resources and shelters, and to identity ongoing abuse and refer these panicipants to the Social Services Department. Descriptive and inferential analysis, including Fischers Exact Test was performed. Results One hundred and sixty adolescents completed questionnaires. Demographic data revealed the panicipants to be 92% African American and 99% unwed with an age range of 14–20 years and an average age of 18.4 years. Ninety four percent reside in the inner city. Ninety four percent have completed less then a high school education and 72.5% were unemployed. Seventy-nine and one half percent reported no birth control usage. Pregnancy as a result of consensual sex was reported by 96% of the respondents. Current pregnancies were a result of unwelcomed or abusive sexual experiences in 6 (4%) of the participants. Thirteen (8.1%) reported previous unwelcomed sexual experiences (sex due to partner/peer pressure, sexually explicit photographs, and sex while intoxicated), and 47 (29.4%) reported previous abusive sexual experiences (rape, incest, fondling, sex with a person in a position of power: priest, teacher, babysitter). Forty percent of the panicipants who answered questions suggesting previous abusive sexual experiences did not recognize these experiences as abusive. Conclusions Unwelcomed or abusive sexual experiences resulted in pregnancy in only 4% of the study population. However. over one third (37.5%) reported a history of unwelcomed or abusive sexual experiences. and forty percent of these teenagers did not recognize the abuse. Having identified a significant history of unwelcomed and abusive sexual experiences in this study group we must uncover more clearly the risk factors leading to abuse, educate teens to identity abusive situations, and equip them with the resources to seek treatment and prevent recurrences.

Pediatric and Adolescent Gynecology Experience in Two Michigan OB/GYN Residency Programs

Background Pediatric and Adolescent Gynecology (PAG) is an important but long neglected field. While interest has grown tremendously over the past few years, training is still limited, with only two fellowship programs in the United States in 1997–98. The purpose of this study is to assess training and experience in PAG at the OB/GYN resident level. Methods Two programs were studied: in Detroit, MI, Hutzel Hospital (HH), one of the largest academic inner city programs in the country, and William Beaumont Hospital (WB), a community based program in Royal Oak, MI. 71 questionnaires were distributed to OB/GYN residents. Descriptive analysis of answers to demographic, training, attitude, and knowledge based questions in PAG was perlbrmed. Results 57 questionnaires were returned. The majority of respondents reported no experience in PAG with no rotations or clinics and only limited teaching with 0–2 lectures. 97% of HH and 92.3% of WB residents requested more PAG training. Comfort levels regarding sexual history, sex, sexual abuse, physical abuse, substance abuse, and birth control in PAG patients were assessed on a 5 paint scale (1=low, 5=high); HH scored 3.21/5 in pediatric and 4.22/5 in adolescent issues, and WB scored 4.22/5 in pediatric and 4.55/5 in adolescent issues. The most commonly recognized differences in the care of PAG patients were attention to stage of mental development (38.6% in pediatrics/36.4% in adolescents at HH; 38.5%/46.2% at WB), cooperation strategies (38.6%/36.4% at HH; 0%/0% at WB), and parental involvement(15.9%/0.% at HH; 30.8%/7.7% at WB). Residents failed to note the important physical and anatomical differences in the PAG patient(0%/0% at HH; 0%/0% at WB). HH residents responded with familiarity 60.5% and WB residents 59.7% of the time to knowledge based questions (see table). % residents showing familiarity HH WB HH WB Treating imperforate hymen 89 77 Indications for 1st speculum exam 81 83 Treating labial adhesions 89 77 Normallabnonnal hymens 11/41 7/15 Etiology of vulvovaginitis 20 0 Initiation of OCPs 64 31 Etiology of vaginal discharge 63 85 Exam positions 86 69 Conclusions Residents of both academic and community programs report litt1e experience and scant training in PAG. The same residents expressed interest in formal PAG training. Moderate to high levels of confidence in discussing PAG issues reported by both WB and HH residents were not supported by complete answers to knowledge based questions. Many residents demonstrated some familiarity with PAG issues, but Done demonstrated proficiency. It is concerning that residents in OB/GYN lack the basic knowledge that is required in routine daily care of the PAG population. More emphasis to be placed on these issues in residency training programs.