Integrating HPV testing for primary screening?

Cervical cancer, the second most common cancer in young women in France, is still today imperfectly screened even with the advent of primary prevention for this cancer in the form of prophylactic HPV vaccination. Indeed, the cervical Pap smear and its cytologic analysis, both operator and reader dependent, have limited sensitivities requiring repeated samplings and above all, producing a high rate of falsely negative tests. Although most cancers occur in women who are either not or insufficiently screened, the problem with cervical smears is the fact that cancers are also often diagnosed in young women having follow-ups in accordance with professional guidelines. The absence of an organized screening in France results in an inadequate female population coverage. Nowadays, it is unanimously recognized that high-risk papillomaviruses (HR HPV) represent the only independent risk factor for cervical cancer and that there cannot be any disease without this virus. It is therefore this strong association between a viral agent and the cervical cancer which opened the door firstly, to the notion of prophylactic vaccination and secondly, to the integration of HR HPV testing in the screening for precancerous lesions. Molecular biological techniques based on the HR HPV genome detection within the female genital tract have shown a very high sensitivity without any inter and intraobserver variability and an excellent negative predictive value. Their integration in the primary screening for cervical cancer would improve the relevance of the latter and would suit the need for a wider population coverage and even for an organized screening thanks to the possibility for self-sampling. The specificity of these tests is inferior to that of the cervical smear, but the management of the falsely positive HPV tests has proved to be efficient by sorting residual cells obtained from liquid-based cytology. What is urgent in France is the need for an organized screening programme in order to improve population coverage and, this does not go against neither a vaccination promotion nor the integration of new technologies. Moreover, the last three randomized trials published in October 2007 have shown that it was quite safely possible to extend the time interval between two consecutive viral testing and thus improving the cost-effectiveness of cervical cancer screening. The aim of this work was to analyze publications on the subject in order to conclude, according to proof levels obtained by different studies, on its usefulness in the secondary prevention of cervical cancer.     

Do the risks of preimplantation genetic testing for aneuploidy outbalance the benefits?

Die Gynäkologie - Much has been achieved in the field of preimplantation genetic testing for aneuploidy (PGT-A; previously preimplantation genetic screening, PGS) in recent years, particularly...     

Women’s opinions of legal requirements for drug testing in prenatal care

Purpose: To explore women’s attitudes and perceptions regarding legal requirements for prenatal drug testing.

Methods: Web-based survey of 500?US women (age 18–45) recruited from a market research survey panel. A 24-item questionnaire assessed their opinion of laws requiring doctors to routinely verbal screen and urine drug test patients during pregnancy; recommendations for consequences for positive drug tests during pregnancy; and opinion of laws requiring routine drug testing of newborns. Additional questions asked participants about the influence of such laws on their own care-seeking behaviors. Data were analyzed for associations between participant characteristics and survey responses using Pearson’s chi-squared test.

Results: The majority of respondents (86%) stated they would support a law requiring verbal screening of all pregnant patients and 73% would support a law requiring universal urine drug testing in pregnancy. Fewer respondents were willing to support laws that required verbal screening or urine drug testing (68% and 61%, respectively) targeting only Medicaid recipients. Twenty-one percent of respondents indicated they would be offended if their doctors asked them about drug use and 14% indicated that mandatory drug testing would discourage prenatal care attendance.

Conclusion: Women would be more supportive of policies requiring universal rather than targeted screening and testing for prenatal drug use. However, a noteworthy proportion of women would be discouraged from attending prenatal care – a reminder that drug testing policies may have detrimental effects on maternal child health.     

Anti-Müllerian hormone testing is useful for individualization of stimulation protocols in oocyte donors

While the age of a donor is a fundamental factor to the success of donor IVF, no serum markers have been demonstrated to be useful in predicting variability of ovarian response in individual donors. Anti-Müllerian hormone (AMH) has been described as an accurate marker of ovarian response in patients undergoing IVF, but has not been applied to oocyte donors. AMH concentrations from 104 anonymous oocyte donors between the ages of 21-32 years were studied and IVF outcome parameters compared. AMH was correlated with several parameters including the number of oocytes retrieved (r = 0.232, P = 0.024), the peak oestradiol concentrations (r = 0.235, P = 0.024) and the need to decrease gonadotrophin dose in order to avoid ovarian hyperstimulation syndrome (r = 0.274, P = 0.007). Receiver operating curve analysis was able to identify an AMH threshold that rendered about 70% sensitivity and 70% specificity for predicting the need to decrease gonadotrophin dosing. The clinical pregnancy rate was 77% per recipient and was not related to the donors' AMH concentrations. For oocyte donors, measurement of AMH appears most useful for determining gonadotrophin sensitivity in order to mitigate symptoms consistent with ovarian hyperstimulation.     

Prenatal testing for adult-onset conditions: cui bono?

There is a widespread consensus in the medical and bioethical communities that minor children should not be tested for untreatable adult-onset genetic diseases. This paper looks at the implications for prenatal genetic testing. What is the purpose of such testing? Who is intended to benefit? Is it the prospective parents, to enable them to make informed reproductive decisions? Or society, by reducing the prevalence of genetic diseases? Or can prenatal testing for adult-onset conditions be done 'for the sake of the child'? While the last justification, if plausible, would provide a better justification than the other two, it is not clear that even reproductive autonomy justifies prenatal genetic testing for untreatable adult-onset diseases. Nor can a rationale be provided by the other possibilities since neither society nor the future child is likely to be benefited by such testing.     

Is BMD testing appropriate for all menopausal women?

The United States Preventive Services Task Force has provided an evidence-based guideline indicating that bone mineral density (BMD) testing is appropriate for all women aged 65 or older. This does not preclude BMD testing in younger postmenopausal women but places the onus on the treating physician to justify the procedure to the patient and often the patient's insurance carrier. There are very few circumstances in which BMD testing is appropriate for healthy premenopausal women, but BMD testing in younger postmenopausal women is often appropriate: when there is a family history of osteoporosis with fracture, a personal history of fracture as an adult, and a medical, surgical or therapeutic history that might be associated with accelerated bone loss or increased risk of fracture. Medical conditions include intestinal diseases associated with malabsorption, such as non-tropical sprue, or primary hyperparathyroidism. Women who have neurologic conditions that increase the risk of falling should also be tested. There are data to suggest that patients with hemoglobinopathy are at increased risk for osteoporosis. Surgical conditions include the increasingly performed surgery for obesity and other surgery resulting in bowel resection (e.g., for inflammatory bowel disease). The major medication-related concern is corticosteroid therapy, but chronic or over-treatment with thyroxine, and chronic heparin therapy, should also be considered risk factors for osteoporosis. When performing a BMD test for the first time, it is essential to remember that 50% of women at menopause will have a negative T-score, but this does not imply that the patient has indeed lost any bone from her peak bone mass.     

Is testing for aspirin response worthwhile in high-risk pregnancy?

Objective

To explore the clinical impact of aspirin dosage adjustment in pregnant women at high risk of hypertensive disorders.

Study design

In this retrospective observational study including women with pre-existing hypertension, pre-gestational diabetes or previous placental-mediated complications, we compared the rates of pre-eclampsia, early-onset and severe pre-eclampsia between women who used 81 mg of aspirin (ASA) throughout pregnancy without platelet function analyser (PFA-100^®) monitoring (“group ASA no PFA”) and those in whom the aspirin dosage was adjusted according to PFA-100^® results (“group ASA and PFA”).

Results

270 women were included in the analyses, 111 in group ASA and PFA and 159 in group ASA no PFA. Aspirin was started before 13 weeks in 71.7% of women in group ASA no PFA and in 79.3% of those in group ASA and PFA. PFA-100^® monitoring was associated with a lower rate of pre-eclampsia (15.3% vs. 30.8%; aOR 0.36, 95%CI 0.19-0.67) and severe pre-eclampsia (3.6% vs. 15.1%; aOR 0.22, 95% CI 0.07-0.66), after adjustment for various risk factors for pre-eclampsia. The rate of early-onset pre-eclampsia was not statistically different between the two groups (7.2% vs. 13.2%; aOR 0.42, 95%CI 0.17-1.04). The rate of pre-eclampsia was higher in women who needed an increase in aspirin dosage (11/43, 25.6%) than in those who did not (6/68, 8.8%, p = 0.03).

Conclusion

Our results suggest that a strategy involving platelet function testing and individualized dosing is effective in preventing pre-eclampsia in high risk women. PFA testing should not be considered as standard practice, however, until prospective controlled randomized trials have confirmed these observations.     

Is human papillomavirus testing of value in clinical practice?

The objective of this review was to evaluate the current status of human papillomavirus testing in predicting the presence of high-grade or invasive disease in the cervix in women with Papanicolaou smears reported as atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion. This is a review of many of the studies already published evaluating the utility of human papillomavirus testing as part of the triage for patients whose Papanicolaou smears were reported as ASCUS or low-grade squamous intraepithelial lesion. Two triage approaches for follow-up of such patients are presented, and recommendations are made as to which is most cost-effective and safe. Data related to human papillomavirus testing were obtained with both currently available commercial kits for detection of high-risk human papillomavirus and the polymerase chain reaction. There was variation in results reported, possibly related to populations studied. The approach to management by cytologic screening and colposcopy, when indicated, appeared over the long term to be equal to human papillomavirus testing. In our opinion current human papillomavirus testing is of little clinical use to the practitioner. Its use should be limited to appropriately designed and implemented research studies.     

Assessment of resident surgical skills: is testing feasible?

OBJECTIVE: We have previously shown that in a single residency program objective structured assessment of technical skills (OSATS) is a reliable and valid method of assessing surgical competency. Our goal was to establish feasibility of this evaluation instrument when administered at multiple residency programs throughout the US, and assess the impact of a laboratory-based surgical curriculum on results. STUDY DESIGN: An OSATS exam was administered to 116 residents from 5 residency programs. One of the residency programs had participated in a comprehensive surgical curriculum over a 4-year period of time. The exam consisted of 3 open and 3 laparoscopic tasks. Residents were graded by both a blinded and unblinded examiner with task-specific checklist, global rating scale, pass/fail assessment, and tasks were timed. All tasks were performed on life-like models. RESULTS: Examinations were successfully completed at all sites. Each exam required 90 minutes of resident time. Reliability indices calculated with Cronbach's alpha were .97 for overall global rating and .95 for checklists. Interrater reliability between blinded and unblinded examiners ranged from .71 to .97 for individual tasks and was .95 overall. Assessment of construct validity (the ability to distinguish among residency levels) found significant differences among the residents for both blinded and unblinded examiners for all evaluation outcomes except time. For the test overall, the global rating scale showed significant differences among all 4 residency levels. The checklist showed significant differences at three levels (PGY3-4 >PGY2 >PGY1). Approximate cost for replaceable items was 40 US dollars to 150 per resident depending on which tasks were chosen. Comparison of scores between residents who received a laboratory-based curriculum and those who did not revealed significantly higher scores and shorter time to complete tasks for the group who received additional training. CONCLUSION: Large-scale testing has confirmed that OSATS is an objective, reliable, and valid method to assess surgical skills, and can easily be administered in most residency programs. A laboratory-based surgical curriculum improved test results and reduced time to complete tasks.     

Cesarean section: is pretransfusion testing for red cell alloantibodies necessary?

BACKGROUND: Routine pretransfusion testing for red cell alloantibodies (RBCab) in cesarean patients is standard practice in many obstetric centers. The objective of the present study was to evaluate the usefulness of this test. METHOD: A retrospective study was conducted using computerized registers to extract data on blood transfusions and the occurrence of RBCab in cesarean patients. RESULTS: A total of 4434 admissions for cesarean section were identified. Only 10 patients (0.23%) had clinically significant RBCab, which had not been previously detected. Blood transfusions were required in relation to 147 cesarean sections (3.3%). A number of preoperative conditions, traditionally believed to be risk factors for preoperative and postpartum hemorrhage, occurred more frequently in transfused patients than in nontransfused. The probability of a cesarean patient having a previously undetected clinically significant RBCab and receiving a blood transfusion during admission for delivery was estimated to be 9.0 x 10(-5) (1 in 11 050 cesarean sections). Analyses of the time relationships between cesarean sections and initiation of blood transfusions indicated that most often there would be enough time for postoperative antibody screening and/or cross matching if the routine pretransfusion testing was omitted. CONCLUSION: These findings suggest that routine pretransfusion testing in cesarean patients can be omitted.     

Inconclusive results in preimplantation genetic testing: go for a second biopsy?

The transition in biopsy timing from blastomere to trophectoderm biopsy has led to a remarkable decrease in the percentage of undiagnosed blastocysts. However, patients with few or no euploid blastocysts can be affected by this residual percentage of diagnosis failure. The aim of this study is to assess whether blastocyst rebiopsy and revitrification is an efficient and safe procedure to be applied in cases of no results after analysis. Fifty-three patients agreed to the warming of 61 blastocysts to perform a second biopsy and PGT-A by aCGH. Only 75.4% of the blastocysts survived, reexpanded, and could be rebiopsied. After the second biopsy and analysis, 95.6% of the blastocysts were successfully diagnosed with an euploidy rate of 65.9%. Eighteen euploid blastocysts were warmed and transferred to 18 patients with a 100% survival and reexpansion rate. Seven clinical pregnancies have been achieved with 4 live births, 1 ongoing pregnancy, and 2 miscarriages. Thus, although few transfers of rebiopsied and revitrified blastocysts have been performed till date, our preliminary results show that this approach is efficient and safe to be applied for undiagnosed blastocysts, as it ultimately allows the transfer of euploid blastocysts and good clinical outcomes.     

How do women of diverse backgrounds value prenatal testing outcomes?

OBJECTIVES: To describe women's preferences for prenatal testing outcomes and to explore their association with sociodemographic characteristics and attitudes. METHODS: We conducted a cross-sectional study of 584 racially/ethnically and socioeconomically diverse pregnant women aged 16 to 47 years recruited from 23 San Francisco Bay Area practices. We assessed preferences for 12 potential prenatal testing outcomes using the time trade-off metric for all outcomes and the standard gamble metric for two outcomes. Preferences were calculated on a scale of 0 (death) to 1 (perfect health). Participants also completed a sociodemographic and attitude survey. RESULTS: Highest preference scores were assigned to outcomes resulting in the birth of a chromosomally normal infant (mean = 0.91-0.93; median = 0.99-1.00). Lower scores were obtained for outcomes involving pregnancy loss (mean = 0.69-0.87; median = 0.76-0.92), which were correlated with attitudes regarding miscarriage, pregnancy termination, and Down syndrome. The lowest scores were assigned to Down syndrome-affected births (mean = 0.67-0.69; median = 0.73-0.75), which also were correlated with attitudes toward Down syndrome. We did not find a statistically significant relationship between participants' preference scores and age. CONCLUSION: Preferences for prenatal testing outcomes vary according to the pregnant women's underlying attitudes about pregnancy loss and Down syndrome, and not according to her age. Current age/risk-based guidelines should account for individual variation in patient preferences.     

Non-invasive prenatal testing for fetal sex determination: is ultrasound still relevant?

Early prenatal diagnosis of fetal sex is necessary to optimize pregnancy management in families known to be at risk of some heritable disorders. The demonstration of cell-free fetal DNA (cffDNA) in the mother's blood has made it possible to identify Y chromosome sequences in maternal blood and to determine fetal sex noninvasively, during the first trimester. This procedure can significantly reduce the number of invasive procedures for women with fetuses at risk of sex-linked diseases and optimize the management of these pregnancies. Fetal sex can be diagnosed by ultrasound with the same sensitivity and specificity, but later in pregnancy.     

Anxiety and prenatal testing: do women with soft ultrasound findings have increased anxiety compared to women with other indications for testing?

OBJECTIVE: To determine whether there is a difference in anxiety levels in women referred for soft ultrasound findings, AMA, and abnormal serum marker screens, all of whom have a similar risk for chromosome abnormalities, in order to provide an understanding of patients' anxiety, which may enhance the genetic counseling process. METHODS: Two self-administered questionnaires were completed after the genetic counseling session. Participants were recruited from multiple prenatal clinics throughout Houston, Texas. The State-Trait Anxiety Inventory Form Y was used to measure anxiety in study participants. Both state and trait anxiety were assessed. Differences between groups were examined using one-way analysis of variance, crosstabulation, chi-square, and Tukey multiple comparisons analysis. A p-value of < 0.05 was considered significant. RESULTS: Two hundred fifteen women participated in the study: 124 AMA, 55 abnormal maternal serum screens, and 36 soft ultrasound findings. Our findings revealed that women with soft ultrasound findings and abnormal maternal serum screens had significantly higher state anxiety than women who are AMA. State anxiety in women with soft ultrasound findings was not significantly different from women with abnormal maternal serum screens. No significant difference was found between the three groups for trait anxiety. Perceived risk, decision to undergo amniocentesis, education level, and income were factors that significantly affected the women's anxiety scores. However, none of these factors proved to be successful indicators of state or trait anxiety. CONCLUSION: A woman's referral indication is associated with different levels of anxiety as compared to the actual numerical risk for chromosome abnormalities presented during a genetic counseling session.     

Improving women’s knowledge about prenatal screening in the era of non-invasive prenatal testing for Down syndrome – development and acceptability of a low literacy decision aid

Background

Access to information about prenatal screening is important particularly in light of new techniques such as non-invasive prenatal testing (NIPT). This study aimed to develop and examine the acceptability of a low literacy decision aid (DA) about Down syndrome screening among pregnant women with varying education levels and GPs.

Methods

We developed a DA booklet providing information about first-trimester combined testing, maternal serum screening, and NIPT. GPs and women participated in a telephone interview to examine the acceptability of the DA and measure screening knowledge before and after reading the DA. The knowledge measure was designed to assess whether women had understood the gist of the information presented in the decision aid. It comprised conceptual questions (e.g. screening tells you the chance of having a baby with Down syndrome) and numeric questions (e.g. the accuracy of different screening tests).

Results

Twenty-nine women and 18 GPs participated. Regardless of education level, most women found the booklet ‘very’ clearly presented (n?=?22, 76%), and ‘very’ informative (n?=?23, 80%). Overall, women’s conceptual and numeric knowledge improved after exposure to the DA, from 4% having adequate knowledge to 69%. Women’s knowledge of NIPT also improved after receiving the decision aid, irrespective of education. Most GPs found it ‘very’ clearly presented (n?=?13, 72%), and that it would ‘very much’ facilitate decision-making (n?=?16, 89%).

Conclusions

The DA was found to be acceptable to women as well as GPs. A comprehensive evaluation of the efficacy of the decision aid compared to standard information is an important next step. Strategies are needed on how to implement the tool in practice.

     

Is testing for cytomegalovirus and cystic fibrosis indicated in members of a nonwhite pregnant population in whom the fetus has an echogenic bowel?

The purpose of this study was to determine whether testing for cystic fibrosis (CF) and cytomegalovirus (CMV) infection is necessary in African-American and Hispanic gravidas in whom the fetus had an echogenic bowel. This retrospective study consisted of only African American and Hispanic patients in whom the fetus had an echogenic bowel, referred to the Maternal and Fetal Medicine unit at New Jersey Medical School for a specialized ultrasound, between June 30, 2004, and March 31, 2005. Sixty-five patients met the inclusion criteria for our study. Maternal serum testing for CF was done in 32 patients and all newborns were screened for the disease. There were no positive results for CF. CMV serology was tested in 38 patients and there were no cases of acute congenital CMV infection. In our population of 65 patients, there was one intrauterine growth restricted (IUGR) fetus and five intrauterine fetal demise (IUFD). Although all patients who were tested for CMV infection tested negative, the true incidence in our selected population may be underestimated because some of our patients were not tested. There were no cases of congenital CMV infection and all newborn screening tests for CF were negative. Prenatal diagnosis of fetal echogenic bowel was associated with a 7.6% incidence of IUFD and 1.6% incidence of IUGR.     

Prenatal diagnostic testing among women referred for advanced maternal age in Beijing, 2001–2012

Objective

To determine the proportion of women with advanced maternal age (AMA) undergoing amniocentesis and assess the recommended indication of 35 years or older in China.

Methods

Data were retrospectively evaluated from 9641 patients who underwent diagnostic prenatal amniocentesis in Beijing, China, between January 2001 and December 2012. Maternal age, indication for testing, and karyotype data were collected. Patients referred for AMA were stratified in 2 ways: 35–37 years, 38–40 years, and 41 years or older; and indication of AMA alone or combined with other screening. Outcomes and safety performance were compared among the groups.

Results

From 2001 to 2012, the annual rate of amniocentesis and the proportion of AMA-related indications increased (P < 0.01). Overall, 82 abnormalities were detected. In the AMA group, the spontaneous abortion rate was 0.5% (22/4748). The positive predictive value (PPV) of AMA alone was 0.5% for women aged 35–37 years. Only among women aged 41 years or older was the PPV of AMA alone better than that of AMA plus other indications (2.3% vs 1.5%, respectively).

Conclusion

The PPV of 35 years or older did not offset the risk of spontaneous abortion. AMA alone should not be used as an indication for amniocentesis especially among women aged 35–40 years.