Teeter-Totter or Tapestry: A Life in Academic Medicine.

Constructing a career in academic medicine involves more than a focus on work-life balance. That image of a teeter-totter suggests that life is what happens when you are not working. The nature of the scope of interests (clinical, research, teaching) and values (service, leadership, curiosity, transparency, and honesty) creates a larger framework through which home life and work life become one interwoven tapestry. The author reflects on these perspectives as she looks back on a career in academic medicine.

An Estimation of the Risk of Pseudotumor Cerebri among Users of the Levonorgestrel Intrauterine Device.

Because of a previous association of pseudotumor cerebri (PTC) with levonorgestrel, we wished to evaluate the use of levonorgestrel-eluting intrauterine devices ("levonorgestrel intrauterine systems", LNG-IUS) in our University of Utah and Rigshospitalet PTC patients. In our retrospective series, PTC prevalence was approximately 0.18% and 0.15% in the LNG-IUS population versus 0.02% and 0.04% in the non-LNG-IUS population (Utah and Rigshospitalet, respectively), with no significant differences in PTC signs and symptoms among the two groups. Our investigation suggests that women with an LNG-IUS may have increased risk of developing PTC but does not suggest an LNG-IUS can cause PTC.

Progestins for contraception: modern delivery systems and novel formulations.

Since the development of combined oral contraceptives over 50 years ago, significant innovations have occurred in the domain of the progestin. Evolving knowledge of progestin mechanism of action and physiology has allowed for development of novel progestins with limited steroid receptor cross-reactivity, decreased side effect profiles, and pharmacokinetics optimized for modern delivery systems. This review summarizes current knowledge of progestin physiology, modern delivery systems, and developments of progestin agonists and antagonists for contraception.

Lactogenesis after early postpartum use of the contraceptive implant: a randomized controlled trial.

OBJECTIVE: To evaluate lactogenesis after early postpartum insertion of the etonogestrel contraceptive implant. METHODS: Healthy peripartum women with healthy, term newborns who desired the etonogestrel implant for contraception were randomly assigned to early (1-3 days) or standard (4-8 weeks) postpartum insertion. The primary outcomes, time to lactogenesis stage II and lactation failure, were documented by a validated measure. The noninferiority margin for the mean difference in time to lactogenesis stage II was defined as 8 additional hours. Secondary data (device continuation and contraceptive use, breast milk analysis, supplementation rates, side effects, and bleeding patterns) were collected at periodic intervals for 6 months. RESULTS: Sixty-nine women were enrolled. Thirty-five were randomly assigned to early insertion and 34 to standard insertion. There were no statistically significant differences between the groups in age, race, parity, mode of delivery, use of anesthesia, or prior breastfeeding experience. Early insertion was demonstrated to be noninferior to standard insertion in time to lactogenesis stage II (early: [mean±standard deviation] 64.3±19.6 hours; standard: 65.2±18.5 hours, mean difference, -1.4 hours, 95% confidence interval [CI] -10.6 to 7.7 hours). Early insertion was also demonstrated to be noninferior to standard insertion in incidence of lactation failure (1/34 [3%] in the early insertion group, 0/35 [0%] in the standard insertion group [risk difference, 0.03, 95% CI -0.02 to 0.08]). Use of formula supplementation was not significantly different between the groups. Milk composition at 6 weeks was not significantly different between the groups. CONCLUSION: Breastfeeding outcomes were similar in women who underwent early compared with standard postpartum insertion of the etonogestrel implant. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00847587.

A superior mesenteric vein thrombosis associated with in vitro fertilization.

OBJECTIVE: To describe a case of superior mesenteric vein thrombosis associated with IVF. DESIGN: Case report. SETTING: University teaching hospital. PATIENT(S): A 33-year-old female developed progressive abdominal pain several days after ET in her first IVF cycle. A computed tomography scan 12 days after ET showed a superior mesenteric vein thrombosis. INTERVENTION(S): Therapeutic anticoagulation. MAIN OUTCOME MEASURE(S): Resolution of the superior mesenteric vein thrombosis with therapeutic anticoagulation. RESULT(S): Early diagnosis and treatment of a superior mesenteric vein thrombosis associated with IVF led to a favorable outcome. CONCLUSION(S): Endocrine alterations consequent to controlled ovarian hyperstimulation for IVF place patients at risk for thromboembolic events. Thromboembolic events may occur during an IVF cycle in the absence of overt ovarian hyperstimulation, an inherited thrombophilia, or pregnancy. Early diagnosis and treatment of superior mesenteric vein thrombosis can lead to a favorable outcome. Treatment guidelines for superior mesenteric vein thrombosis in setting of IVF are discussed.

Gynecologic care in hematopoietic stem cell transplant patients: a review.

UNLABELLED: Over 4500 hematopoietic stem cell transplants (HSCT) are performed on patients in the United States each year. As HSCT patients shift their survivorship care from large transplant centers to community health care providers, many gynecologists are assuming their pre- and post-HSCT gynecologic care. This article reviews recommendations, current research, and expert opinions on the gynecologic care of HSCT patients. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completing this educational activity, the physician should be better able to implement strategies for the prevention and management of menstrual bleeding during hematopoietic stem cell transplants; educate female patients regarding Fertility Preservation options before hematopoietic stem cell transplantation; and apply posthematopoietic stem cell transplant reproductive care screening and treatment recommendations for bone health, sexual health, and secondary cancer development.

Decreased sperm motility is associated with air pollution in Salt Lake City.

OBJECTIVE: To study the correlation between indices of air pollution and sperm parameters. DESIGN: Ecological study. SETTING: Contained geographic area. PATIENT(S): Resident men presenting for semen analysis or artificial insemination. INTERVENTION(S): Analysis of levels of particulate air pollution (particulate matter [PM] 2.5) over a five-year period in relation to sperm parameters obtained from semen analyses and separately in relation to sequences of sperm parameters at the time of semen preparations for artificial insemination. To account for the duration of spermatogenesis (72 days), "corrected" variables were created by shifting backward 1, 2, 3 and 4 months each of the semen parameters. The final analysis corrected for season of the year and current temperature. MAIN OUTCOME MEASURE(S): Sperm concentration, sperm motility and sperm morphology. RESULT(S): The study included 1,699 semen analyses and 877 inseminations. PM 2.5 levels were highest in the winter months, when the ambient temperature was the lowest. Semen analysis data showed that values of PM 2.5 were negatively correlated to sperm motility two months and three months following the recording of the PM 2.5 values. Artificial insemination data also showed that sperm motility correlated negatively with PM 2.5 values recorded three months previously. CONCLUSION(S): Both semen analysis and sperm parameters data obtained from men presenting for multiple inseminations over time showed that air pollution is associated with reduced sperm motility two to three month after exposure.

Characterization of therapy and costs for patients with uterine fibroids in Utah Medicaid.

OBJECTIVES: To determine in an eligible Utah Medicaid population (1) medical and drug costs associated with treating uterine fibroids (UFs) and (2) the cost and incidence of hysterectomy complications. METHODS: Medical and drug cost analyses were based on data from 897 premenopausal patients with UFs included in the Utah Medicaid database from 1996 to 2004. UF-related medical and pharmacy costs were determined from first diagnosis of UFs until a related procedure or until estimated menopause. Outcomes for patients treated with a procedure (hysterectomy, myomectomy, or embolization), medication, and watchful waiting (no procedure, no UF-related drug) were compared. When determining hysterectomy complication rates for the population of women in the Medicaid database, a total of 1,323 pre- or postmenopausal patients with UFs were included. RESULTS: Overall, 20% of patients were treated with medication, 33% with a procedure, and 47% with watchful waiting. Mean total UF costs were: $11,996 (procedure), $2,703 (medication), and $2,118 (watchful waiting). Mean eligibility months were 8.8, 28.8, and 14.1, respectively. Costs/eligible month were: $1,358 (procedure), $151 (watchful waiting), and $94 (medication). The mean hysterectomy cost was $12,107. CONCLUSION: Treatment for UFs is expensive with a mean cost of $5,504 per study patient. The highest costs are seen in patients receiving procedures, which can lead to complications; 15% in this study. Costs for watchful waiting are similar to costs in patients receiving UF-related drugs. Consideration should be given to using non-surgical therapies for the treatment of UFs before procedures are performed.

Sperm protamine 1/protamine 2 ratios are related to in vitro fertilization pregnancy rates and predictive of fertilization ability.

OBJECTIVE: To evaluate whether aberrant sperm P1/P2 ratios are predictive of abnormal fertilizing ability and are related to in vitro fertilization (IVF) outcome. DESIGN: Prospective case-control study. SETTING: University-based infertility and IVF clinic. PATIENT(S): Forty-three male infertility patients with an abnormally reduced P1/P2 ratio, 251 patients with a normal P1/P2 ratio, and 121 patients with an abnormally elevated P1/P2 ratio. INTERVENTION(S): Human IVF, the sperm penetration assay (SPA), and sperm protamine quantification via nuclear protein extraction, gel electrophoresis, and densitometry analysis. MAIN OUTCOME MEASURE(S): Sperm P1/P2 ratios; P1 and P2 quantities; SPA scores; and IVF-fertilization, embryo-quality, pregnancy, delivery, and spontaneous-abortion rates. RESULT(S): Standard IVF fertilization rates and SPA scores were significantly reduced in patients with abnormally low and high P1/P2 ratios. In vitro fertilization embryo quality was comparable between these groups, but pregnancy rates were significantly reduced in patients with abnormally reduced P1/P2 ratios. CONCLUSION(S): The P1/P2 ratio has a significant relationship to sperm fertilization ability. The relationship between protamines and fertilization ability is not understood but may be either a reflection of generalized abnormalities during spermiogenesis or an indication of protamine deficiency acting as a regulator or checkpoint of spermatogenesis.

Comparison of four media types during 3-day human IVF embryo culture.

The aim of this study was to compare the effectiveness of human tubal fluid (HTF), G1.2, Sage Cleavage and Life Global media for IVF outcome during 3-day culture of human embryos. A three-phase auto-controlled study was conducted in which IVF outcome was compared between (1) HTF and G1.2, (2) HTF and Cleavage, and (3) Cleavage and Life Global. In phase 1, no differences in embryo quality were observed between HTF and G1.2. However, embryos derived from intracytoplasmic sperm injection (ICSI) displayed significantly improved quality when grown in HTF versus G1.2. No differences in pregnancy and implantation rates were observed in cases where embryos transferred were grown exclusively in HTF or G1.2 media. In phase 2, embryo quality was significantly improved for embryos cultured in Cleavage versus HTF media (P < 0.001). However, pregnancy, implantation and spontaneous abortion rates were similar between the two media. In phase 3, there were no differences in embryo quality, pregnancy, implantation, and spontaneous abortion rates between Cleavage and Life Global media. Overall, the data indicate that Life Global and Cleavage media yield similar results in a 3-day IVF culture programme. Cleavage medium is superior to HTF, as evidenced by significantly improved embryo quality (P < 0.001). Meanwhile, HTF medium is superior to G1.2 for ICSI cases.

Correlation of sperm penetration assay score with polyspermy rate in in-vitro fertilization.

BACKGROUND: The sperm penetration assay (SPA) is used to predict the fertilizing capacity of sperm. Thus, some programs rely on SPA scores to formulate insemination plans in conjunction with in-vitro fertilization (IVF) cycles. The purpose of this study was to evaluate if a relationship exists between SPA scores and polyspermy rates during conventional IVF cycles. METHODS: A total of 1350 consecutive IVF patients using conventional IVF insemination were evaluated in the study. Oocytes were inseminated three hours post-retrieval by the addition of 150,000 to 300,000 progressively motile sperm. Approximately 18 hours after insemination, the oocytes were evaluated for fertilization by the visualization of pronuclei. The presence of three or more pronuclei was indicative of polyspermy. Polyspermy rates, fertilization success, embryo quality, and pregnancy rates were analyzed retrospectively to evaluate their relationship with SPA score, count, motility, number of progressively motile sperm inseminated, oocyte pre-insemination incubation time, patient age, and diagnosis. RESULTS: A significant positive relationship was observed between SPA score and polyspermy rate (rs = 0.10, p < 0.05). Patients with a normal SPA score had significantly higher polyspermy rates than those with abnormal SPA scores (6.3% +/- 1.5% vs. 2.0% +/- 0.7%, p < 0.05). Fertilization percentage was significantly lower in the group with severely abnormal SPA scores versus all other SPA groups (57.5% +/- 2.1% vs. 70.2% +/- 1.3%, p < 0.005). Although embryo quality was not affected, both clinical pregnancy and implantation rates improved slightly as SPA score increased. In addition, there was a decrease in the rate of spontaneous abortion as SPA score increased. CONCLUSIONS: These data indicate SPA score is positively correlated with polyspermy rates and IVF fertilization percentage. Additionally, there is a slight increase in clinical pregnancy rates, and embryo implantation rates with increased SPA. Furthermore, there is a slight decrease in spontaneous abortions rates related to increased SPA.

Use of outcomes-based data in reducing high-order multiple pregnancies: the role of age, diagnosis, and embryo score.

OBJECTIVE: To identify high-risk categories for high-order multiple pregnancy (HMP) in in vitro fertilization (IVF), establish clinic-specific HMP risk data for counseling use, and verify their utility in reducing HMP. DESIGN: Before and after intervention study. SETTING: Two IVF programs using the same embryology laboratory and IVF protocols. PATIENT(S): All IVF patients undergoing fresh embryo transfers. INTERVENTION(S): Use of clinic-specific age, diagnosis, and embryo score (ES) risk data in assessing individual HMP risk during informed consent. MAIN OUTCOME MEASURE(S): HMP and pregnancy outcomes. RESULT(S): In determining clinic-specific high risk categories and developing outcomes-based HMP risk data for counseling, the good outcome rate (GR) was defined as the percentage of singleton or twin deliveries per cycle and the bad outcome rate included no pregnancy or nondelivered pregnancies (miscarriages, multifetal reduction) and HMP per cycle. During 1995 to 1999, age <35 years, calculated morphologic ES, and donor egg (DE) cycles were factors shown by logistic regression to statistically significantly affect the GR. The optimal GRs for DE <35 and >or=35 years (donor age), and non-DE cycles <35 years were achieved with two (57.7%), three (43.2%), and three (43.2%) embryos transferred, respectively. A DE <35 years with >or=3 embryos transferred had the highest risk for HMP. The GR correlated (0.91) with the ES according to the formula: GR = 3.3 + 2.0 ES, when ES range was between 4 and 26. Clinic-specific risks for HMP based on age, diagnosis, and ES were developed and considered while counseling for ET during 2004. The clinic-specific HMP risk data made for a reduction in the HMP rate of 90.9% for DE-IVF (11.8% to 1%) and 53.8% for all IVF (9.1% to 4.2%), without decreases in clinical pregnancy or delivery rates. Physicians showing the greatest decline (64%) in HMP had no reduction in pregnancy or delivery rates. CONCLUSION(S): The use of clinic-specific HMP risk data in counseling based on age, diagnosis, and ES provided a 53% to 64% reduction in HMP without affecting rates of pregnancy or delivery. The clinic-specific ES system correlated closely with good outcomes. A standardized ES system may provide useful information for counseling during ET informed consent.

Elevated sperm chromosome aneuploidy and apoptosis in patients with unexplained recurrent pregnancy loss.

OBJECTIVE: To evaluate sperm chromosome aneuploidy and semen quality in 24 partners of women with unexplained recurrent pregnancy loss and to analyze the data in relation to sperm apoptosis data. METHODS: Semen quality parameters and sperm chromosome aneuploidy for chromosomes X, Y, 13, 18, and 21 were evaluated in the recurrent pregnancy loss patients, fertile controls, and a control group of men from the general population. RESULTS: The mean aneuploidy rate in the recurrent pregnancy loss group was 2.77 +/- 0.22, significantly higher (P <.005) than in either the general population (1.48 +/- 0.12) or in fertile (1.19 +/- 0.11) control groups. In the recurrent pregnancy loss patients, the percentage of aneuploid sperm was correlated to the percentage of apoptotic sperm (r =.62, P <.001). Normal morphology was diminished in the patient group, compared with the general population group (P <.01) and the donor group (P <.001). CONCLUSIONS: These data indicate that some recurrent pregnancy loss patients have a significant increase of sperm chromosome aneuploidy, apoptosis, and abnormal sperm morphology. This study demonstrates a new possible cause of recurrent pregnancy loss.

Prospective, randomized, blinded evaluation of donor semen quality provided by seven commercial sperm banks.

OBJECTIVE: To evaluate variability in donor semen quality between seven commercial donor sperm banks, within sperm banks, and between intracervical insemination and intrauterine insemination. DESIGN: Prospective, randomized, blind evaluation of commercially available donor semen samples. SETTING: An academic andrology laboratory. PATIENT(S): Seventy-five cryopreserved donor semen samples were evaluated. INTERVENTION(S): Samples were coded, then blindly evaluated for semen quality. MAIN OUTCOME MEASURE(S): Standard semen quality parameters, including concentration, motility parameters, World Health Organization criteria morphology, and strict criteria morphology. RESULT(S): Significant differences were observed between donor semen banks for most semen quality parameters analyzed in intracervical insemination samples. In general, the greatest variability observed between banks was in percentage progressive sperm motility (range, 8.8 +/- 5.8 to 42.4 +/- 5.5) and normal sperm morphology (strict criteria; range, 10.1 +/- 3.3 to 26.6 +/- 4.7). Coefficients of variation within sperm banks were generally high. CONCLUSION(S): These data demonstrate the variability of donor semen quality provided by commercial sperm banks, both between banks and within a given bank. No relationship was observed between the size or type of sperm bank and the degree of variability. The data demonstrate the lack of uniformity in the criteria used to screen potential semen donors and emphasize the need for more stringent screening criteria and strict quality control in processing samples.

Body mass index is inversely related to intrafollicular HCG concentrations, embryo quality and IVF outcome.

Decreased periovulatory human chorionic gonadotrophin (HCG) concentrations have been shown to be associated with diminished fertilization rates. This study evaluated if intra-follicular HCG concentration may be related to body mass in 247 IVF patients using their own oocytes and 58 patients receiving donor oocytes, and evaluated if such a relationship might affect IVF outcome. A significant inverse correlation (r = -0.353, P < 0.001) was observed between the body mass index (BMI) and intra-follicular HCG concentration. The mean HCG concentrations were significantly decreased (P < 0.001) in patients with a BMI >30 kg/m(2) compared with patients with a BMI of 20-30 kg/m(2) or BMI <20 kg/m(2) (17.6 versus 45.1 and 52.5%, respectively). The clinical pregnancy rates (P < 0.001) and embryo quality (P < 0.05) were significantly different for the three groups. In donor oocyte recipients, the pregnancy rate was significantly decreased (P < 0.0001) for recipients with a BMI >25 kg/m(2) compared with those with a BMI from 21-25 kg/m(2) and BMI <21 kg/m(2) (43.8 versus 72 and 76.5%, respectively). These data indicate that intra-follicular HCG concentration is inversely related to BMI, and may be related to a concurrent decrease in embryo quality and pregnancy rates.