Women's experiences of diagnosis and management of polycystic ovary syndrome: a mixed-methods study in general practice.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common lifelong metabolic condition with serious associated comorbidities. Evidence points to a delay in diagnosis and inconsistency in the information provided to women with PCOS. AIM: To capture women's experiences of how PCOS is diagnosed and managed in UK general practice. DESIGN AND SETTING: This was a mixed-methods study with an online questionnaire survey and semi-structured telephone interviews with a subset of responders. METHOD: An online survey to elicit women's experiences of general practice PCOS care was promoted by charities and BBC Radio Leicester. The survey was accessible online between January 2018 and November 2018. A subset of responders undertook a semi-structured telephone interview to provide more in-depth data. RESULTS: A total of 323 women completed the survey (average age 35.4 years) and semi-structured interviews were conducted with 11 women. There were five key themes identified through the survey responses. Participants described a variable lag time from presentation to PCOS diagnosis, with a median of 6-12 months. Many had experienced mental health problems associated with their PCOS symptoms, but had not discussed these with the GP. Many were unable to recall any discussion about associated comorbidities with the GP. Some differences were identified between the experiences of women from white British backgrounds and those from other ethnic backgrounds. CONCLUSION: From the experiences of the women in this study, it appears that PCOS in general practice is not viewed as a long-term condition with an increased risk of comorbidities including mental health problems. Further research should explore GPs' awareness of comorbidities and the differences in PCOS care experienced by women from different ethnic backgrounds.

Parental experiences of prenatal whole exome sequencing (WES) in cases of ultrasound diagnosed fetal structural anomaly.

OBJECTIVE: To explore parental experiences of whole exome sequencing (WES) for prenatal diagnosis and ascertain what influenced their decision-making to undergo testing. METHOD: Twelve women comprised a purposeful sample in a series of semistructured interviews. All had received a fetal anomaly diagnosis on ultrasound. A topic guide was used, and transcripts were thematically analyzed to elicit key themes. RESULTS: Five main themes (parental experiences of prenatal WES, need for information, consent/reasons for prenatal WES, sources of support for prenatal WES, and return of WES findings to families) emerged, some with multiple subthemes. CONCLUSIONS: Parents desired as much information as possible and appreciated information being repeated and provided in various formats. Many struggled with clinical uncertainty relating to the cause and prognosis following a fetal anomaly diagnosis and found it difficult to balance the risks of invasive testing against their need for more definitive information. Parents trusted their clinicians and valued their support with decisions in pregnancy. Testing was sometimes pursued to reassure parents that their baby was "normal" rather than to confirm an underlying genetic problem. Parents were motivated to undergo WES for personal and altruistic reasons but disliked waiting times for results and were uncertain about what findings might be returned.

Prenatal whole exome sequencing: the views of clinicians, scientists, genetic counsellors and patient representatives.

OBJECTIVE: Focus groups were conducted with individuals involved in prenatal diagnosis to determine their opinions relating to whole exome sequencing in fetuses with structural anomalies. METHOD: Five representatives of patient groups/charities (PRGs) and eight clinical professionals (CPs) participated. Three focus groups occurred (the two groups separately and then combined). Framework analysis was performed to elicit themes. A thematic coding frame was identified based on emerging themes. RESULTS: Seven main themes (consent, analysis, interpretation/reinterpretation of results, prenatal issues, uncertainty, incidental findings and information access) with subthemes emerged. The main themes were raised by both groups, apart from 'analysis', which was raised by CPs only. Some subthemes were raised by PRGs and CPs (with different perspectives). Others were raised either by PRGs or CPs, showing differences in patient/clinician agendas. CONCLUSIONS: Prenatal consent for whole exome sequencing is not a 'perfect' process, but consent takers should be fully educated regarding the test. PRGs highlighted issues involving access to results, feeling that women want to know all information. PRGs also felt that patients want reinterpretation of results over time, whilst CPs felt that interpretation should be performed at the point of testing only. © 2016 John Wiley & Sons, Ltd.

BAC chromosomal microarray for prenatal detection of chromosome anomalies in fetal ultrasound anomalies: an economic evaluation.

INTRODUCTION: To determine the cost-effectiveness of prenatal chromosomal microarray (CMA) when performed for structural anomalies on fetal ultrasound scan over conventional techniques. METHOD: A decision tree was populated using data from a prospective cohort of women undergoing testing when a fetal ultrasound scan showed a structural abnormality. Nine strategies of testing were modeled including combinations of the tests: QFPCR, G-band karyotyping, CMA and FISH for DiGeorge (22q) microdeletion. RESULTS: When CMA costs GBP 405 and using a 1-Mb BAC array it would cost GBP 24,600 for every additional case detected by CMA over a combination of QFPCR, followed by G-band karyotype, followed lastly by FISH (for DiGeorge syndrome). If CMA is performed instead of conventional karyotyping alone it costs GBP 33,000 for every additional case detected. However, if the cost of CMA is reduced to GBP 360 than when CMA is performed instead of conventional karyotyping alone it would cost GBP 9,768 for every additional case detected. DISCUSSION: The use of a prenatal BAC CMA is not currently cost-effective when compared to other testing strategies. However, as CMA costs decrease and resolution (and detection rates) increase it is likely to become the cost-effective option of the future.

Placenta chorioangioma: a rare case and systematic review of literature.

OBJECTIVES: Placental chorioangioma is a relatively rare condition that often results in serious prenatal complications and adverse pregnancy outcome. We report a case of a large chorioangioma that was prenatally diagnosed at 23 weeks with polyhydramnios and fetal anemia. With prenatal monitoring, transplacental therapy with a COX-2 inhibitor and intrauterine transfusion, the pregnancy resulted in the live birth at 30 weeks. Due to the paucity of evidence relating to the management protocols in cases of placental chorioangiomas, we have conducted a systematic review of the literature. METHODS: All reported cases in the English language were captured using the electronic databases. Bibliographies of relevant articles were manually searched. RESULTS: Sixty-four articles were included reporting 112 cases of placental chorioangioma. In 79, there was no prenatal treatment and in 33 there was in-utero treatment. A systematic comparison of antenatal complications and pregnancy outcomes was performed. No strong conclusion could be made due to the low number and quality of the reported cases. CONCLUSION: Placenta chorioangioma represents a challenge with its potentially serious complications adversely affecting pregnancy outcome. An international registry of pregnancies with this rare complication and documentation of pregnancy outcomes will improve the evidence base for prospective management.

Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound.

The genetic etiology of non-aneuploid fetal structural abnormalities is typically investigated by karyotyping and array-based detection of microscopically detectable rearrangements, and submicroscopic copy-number variants (CNVs), which collectively yield a pathogenic finding in up to 10% of cases. We propose that exome sequencing may substantially increase the identification of underlying etiologies. We performed exome sequencing on a cohort of 30 non-aneuploid fetuses and neonates (along with their parents) with diverse structural abnormalities first identified by prenatal ultrasound. We identified candidate pathogenic variants with a range of inheritance models, and evaluated these in the context of detailed phenotypic information. We identified 35 de novo single-nucleotide variants (SNVs), small indels, deletions or duplications, of which three (accounting for 10% of the cohort) are highly likely to be causative. These are de novo missense variants in FGFR3 and COL2A1, and a de novo 16.8 kb deletion that includes most of OFD1. In five further cases (17%) we identified de novo or inherited recessive or X-linked variants in plausible candidate genes, which require additional validation to determine pathogenicity. Our diagnostic yield of 10% is comparable to, and supplementary to, the diagnostic yield of existing microarray testing for large chromosomal rearrangements and targeted CNV detection. The de novo nature of these events could enable couples to be counseled as to their low recurrence risk. This study outlines the way for a substantial improvement in the diagnostic yield of prenatal genetic abnormalities through the application of next-generation sequencing.

Exome Sequencing in Fetuses with Structural Malformations.

Prenatal diagnostic testing is a rapidly advancing field. An accurate diagnosis of structural anomalies and additional abnormalities in fetuses with structural anomalies is important to allow "triage" and designation of prognosis. This will allow parents to make an informed decision relating to the pregnancy. This review outlines the current tests used in prenatal diagnosis, focusing particularly on "new technologies" such as exome sequencing. We demonstrate the utility of exome sequencing above that of conventional karyotyping and Chromosomal Microarray (CMA) alone by outlining a recent proof of concept study investigating 30 parent-fetus trios where the fetus is known to have a structural anomaly. This may allow the identification of pathological gene anomalies and consequently improved prognostic profiling, as well as excluding anomalies and distinguishing between de novo and inherited mutations, in order to estimate the recurrence risk in future pregnancies. The potential ethical dilemmas surrounding exome sequencing are also considered, and the future of prenatal genetic diagnosis is discussed.

Single-twin demise: pregnancy outcome.

Single-twin demise can pose substantial risks for the surviving co-twin, including increased risk of fetal loss, preterm delivery, neurovascular injury, and end-organ damage. In this chapter, we summarise recently published research on the causes of single twin demise, the pathophysiology of injury to the surviving co-twin, and the evidence for current management strategies. The gestation at which single intrauterine fetal demise occurs, and the chorionicity of the multiple pregnancies, are the two most important factors when considering the risks to the surviving twin. Management should include fortnightly ultrasound scans for growth, umbilical artery Doppler studies, and liquor volume. In monochorionic twins, more complex Doppler assessment with middle cerebral artery Doppler velocimetry and a magnetic resonance imaging of the survivor's brain at least 3 weeks after single intrauterine fetal demise occurs should be carried out to look for evidence of neurological morbidity. With no other obstetric complications, dichorionic pregnancies can be delivered at term. Monochorionic pregnancies are more difficult to manage, and are often delivered between 34 and 36 weeks.

"If it helps..." the use of microarray technology in prenatal testing: patient and partners reflections.

The objective was to gain insight into the experiences of women and their partners diagnosed with a fetal abnormality on prenatal ultrasound examination and receiving genetic testing including microarray. Twenty-five semi-structured interviews were performed with women +/- their partners after receiving the results of prenatal genetic testing. Framework analysis was performed to elicit themes and subthemes. Five main themes were recognized; diagnosis, genetic testing, family and support, reflections of the treatment received and emotions. Our results showed that women recall being told about QFPCR for trisomy 13, 18, and 21 but often no further testing. Women expected the conventional karyotype and microarray result would be normal following a normal QFPCR result. There were frequent misconceptions by couples regarding aspects of counseling/testing. Communication of variants of unknown (clinical) significance (VOUS) presents a particularly difficult challenge. Good clear communication by health care professionals is paramount. When counseling women and their partners for fetal chromosomal testing it should be reinforced that although the most common, trisomy 13, 18, and 21 only account for some of the chromosomal changes resulting in abnormal scan findings. Couples should have literature to take home summarizing scan anomalies and reinforcing information about genetic testing.

Co-twin prognosis after single fetal death: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of the effects on the surviving twin of single fetal death comparing monochorionic to dichorionic twins to report the rates of co-twin death, preterm delivery, and neurologic morbidity in the surviving fetus. DATA SOURCES: MEDLINE (inception-December 2010), EMBASE (inception-December 2010), The Cochrane library (inception-December 2010), Web of Science (inception-December 2010), and British Nursing Index (inception-December 2010) were searched electronically. METHODS OF STUDY SELECTION: Selected studies had more than five cases of single fetal death with reports of co-twin death, neurologic morbidity, or both co-twin death and neurologic morbidity. They also must have defined the gestational age of single fetal death and chorionicity. TABULATION, INTEGRATION, AND RESULTS: The search yielded 1,386 citations. Full manuscripts were retrieved for 204 and 22 were included in the review and meta-analysis. Twenty manuscripts were used to calculate overall summary statistics for monochorionic and dichorionic twins showing rates of co-twin death after single fetal death (15% compared with 3%), rates of preterm delivery after single fetal death (68% compared with 54%), the rate of abnormal postnatal cranial imaging after single fetal death (34% compared with 16%), and the rate of neurodevelopmental impairment after single fetal death (26% compared with 2%). Odds ratios (ORs) were calculated from 16 manuscripts. There was no significant difference reported between preterm delivery of monochorionic or dichorionic twins (OR 1.1, 95% confidence interval [CI] 0.34-3.51, P=.9). After single fetal death, monochorionic twins had higher odds of an abnormal cranial imaging after delivery, this was not significant (OR 3.25, 95% CI 0.66-16.1, P=.12). After single fetal death, monochorionic twins were 4.81-times more likely to have neurodevelopmental morbidity (95% CI 1.39-16.6, P<.05). CONCLUSION: Monochorionic twins are at significantly increased odds of co-twin demise and neurodevelopmental morbidity after single fetal death.