J. C. Korevaar

Reproductive outcome after PGD in couples with recurrent miscarriage carrying a structural chromosome abnormality: a systematic review

BACKGROUND Preimplantation genetic diagnosis (PGD) has been stated to improve live birth rates compared with natural conception in couples with recurrent miscarriage (RM) carrying a structural chromosome abnormality. It is unclear to what extent this claim can be substantiated by evidence. A systematic review of the literature was performed on the reproductive outcome of these couples after natural conception or after PGD. METHODS MEDLINE, EMBASE and the Cochrane database were searched until April 2009. Trials, patient series and case reports describing reproductive outcome in couples with RM carrying a structural chromosome abnormality after natural conception and/or after PGD were included. Since no randomized controlled trials or non-randomized comparative studies were found, separate searches for both groups were conducted. Primary outcome measure was live birth rate per couple. Secondary outcome measure was miscarriage rate per couple. RESULTS Four observational studies reporting on the reproductive outcome of 469 couples after natural conception and 21 studies reporting on the reproductive outcome of 126 couples after PGD were found. After natural conception, live birth rate per couple varied between 33 and 60% (median 55.5%) after parental chromosome analysis; miscarriage rate ranged from 21 to 40% (median 34%). After PGD, live birth rate per couple varied between 0 and 100% (median 31%) after parental chromosome analysis; miscarriage rate ranged from 0 to 50% (median 0%). CONCLUSIONS Currently, there are insufficient data indicating that PGD improves the live birth rate in couples with RM carrying a structural chromosome abnormality.

Does adding metformin to clomifene citrate lead to higher pregnancy rates in a subset of women with polycystic ovary syndrome

BACKGROUND An RCT among newly diagnosed, therapy naive women with polycystic ovary syndrome (PCOS) showed no significant differences in ovulation rate, ongoing pregnancy rate or spontaneous abortion rate in favour of clomifene citrate plus metformin compared with clomifene citrate. We wanted to assess whether there are specific subgroups of women with PCOS in whom clomifene citrate plus metformin leads to higher pregnancy rates. METHODS Subgroup analysis based on clinical and biochemical parameters of 111 women randomized to clomifene citrate plus metformin compared with 114 women randomized to clomifene citrate plus placebo. The data for age, BMI, waist–hip ratio (WHR) and plasma testosterone were available in all women, 2 h glucose in 80% of women and homeostatic model assessment for assessing insulin sensitivity (HOMA) in 50% of women. RESULTS Of the women who were allocated to the metformin group, 44 women (40%) reached an ongoing pregnancy. In the placebo group, 52 women (46%) reached an ongoing pregnancy. There was a significantly different chance of an ongoing pregnancy for metformin versus placebo between subgroups based on age and WHR (P = 0.014). There was a positive effect of metformin versus placebo on pregnancy rate in older women (≥28 years) with a high WHR, a negative effect of metformin versus placebo in young women (<28 years) regardless of their WHR and no effect in older, not viscerally obese women. No significant differences in effect of treatment were found for groups based on BMI, 2 h glucose, HOMA or plasma testosterone. CONCLUSIONS Metformin may be an effective addition to clomifene citrate in infertile women with PCOS, especially in older and viscerally obese patients.

Consecutive or non-consecutive recurrent miscarriage: is there any difference in carrier status?

BACKGROUND Carrier status of a structural balanced chromosome abnormality is associated with recurrent miscarriage. There is, at present, no evidence of the impact of the sequence of preceding pregnancies on the probability of carrier status. The aim of our study was therefore to examine whether the history of consecutive versus non-consecutive miscarriages in couples with two or more miscarriages has any impact on the probability of carrying a chromosome abnormality. METHODS A nested case-control study was performed in six centres for clinical genetics in the Netherlands. Couples referred for chromosome analysis after two or more miscarriages were included: 279 couples with a carrier of a structural chromosomal abnormality and 428 non-carrier couples who served as controls. Univariable and multivariable logistic regression analyses, corrected for known risk factors for carrier status, were performed. The main outcome measure was the probability of carrier status. RESULTS Two hundred and fifty-six of 279 (92%) carrier couples and 381 of 428 (89%) non-carrier couples had experienced consecutive miscarriages (P = 0.21). A history of two or three consecutive miscarriages did not alter the probability of carrier status when compared with two [odds ratio (OR) 0.90, 95% confidence interval (CI) 0.48-1.7] or three (OR 0.71, 95% CI 0.39-1.3) non-consecutive miscarriages. CONCLUSIONS The sequence of preceding pregnancies is not a risk factor for carrier status. Therefore, couples with miscarriages interspersed with healthy child(ren) should be managed the same as couples with consecutive miscarriages regarding chromosome diagnosis.

Health-Related Quality of Life and Posttraumatic Stress Disorder among Survivors of Left-Sided Native Valve Endocarditis

BACKGROUND The long-term prognosis of endocarditis is described primarily in relation to clinical outcome measures-for example, such complications as cerebrovascular accident, cardiac failure, need for cardiac surgery, relapse rate, and mortality. To our knowledge, to date, no studies have examined the health-related quality of life and the prevalence of long-term persistence of physical symptoms for survivors of left-sided native valve endocarditis. METHODS We conducted a prospective follow-up study of patients treated for left-sided native valve endocarditis from 1 November 2000 through 31 October 2003 in 23 hospitals in the Netherlands. Of 86 patients eligible to participate, 55 completed questionnaires administered 3 m and 12 m after discharge; an additional 12 patients completed questionnaires 12 m after discharge only, making a total of 67 patients in our study. Persistence of symptoms and employment status were recorded. The health-related quality of life was measured by using the Dutch version of the Medical Outcomes Study Short Form 36-item health survey and the Posttraumatic Stress Disorder questionnaire. RESULTS Three months after the end of antimicrobial treatment, 41 (75%) of 55 patients still had physical symptoms. Twelve months after the end of antimicrobial treatment, 36 (54%) of 67 patients still had physical symptoms. Before the episode of endocarditis, 30 (81%) of 37 patients aged < or =60 years were employed and working. At 3 m follow-up, 16 (52%) of 31 patients returned to work, and at 12 m follow-up, 24 (65%) of 37 patients were working. One year after discharge, the health-related quality of life was impaired in 5 of 8 dimensions, compared with age-adjusted standard values, and 7 (11%) of 64 patients suffered from posttraumatic stress disorder. CONCLUSIONS A year after discharge, most survivors of left-sided native valve endocarditis still had persisting symptoms and a seriously diminished quality of life, and 11% of patients suffered from posttraumatic stress disorder.

Prognostic Value of Serial C-Reactive Protein Measurements in Left-Sided Native Valve Endocarditis

BACKGROUND The clinical course of left-sided native valve infective endocarditis varies from uncomplicated disease to fulminant infection. Although several factors are known to affect clinical outcome, it is difficult to predict morbidity and mortality in individual patients. The objective of this study was to determine the value of serial C-reactive protein (CRP) measurements as a predictor of clinical outcome. METHODS One hundred twenty-three consecutive patients who fulfilled the Duke criteria for definite left-sided native valve infective endocarditis were prospectively enrolled. Poor outcome was defined as serious infectious complications or death. Patients were followed up for 12 weeks after the end of antimicrobial therapy. Multivariate analysis was used to examine the relative importance of the CRP level as a predictor of poor outcome after adjusting for age, abscess, multivalvular involvement, and Staphylococcus aureus infection. RESULTS After 1 week of therapy, the adjusted odds ratio for poor outcome was 10.3 (95% confidence interval, 2.2-49.4) for patients with CRP levels in the highest tertile (>122 mg/L [to convert to nanomoles per liter, multiply by 9.524]) vs the lowest tertile (1-69 mg/L). A low percentage decline during the first week of treatment was statistically significantly associated with a higher risk of poor outcome (logistic regression coefficient, 1.1; P = .009). At no point in time did CRP level predict the need for cardiac surgery. CONCLUSION High CRP level after 1 week of treatment and a slow percentage decline in CRP level during the first week of treatment are indicators of poor clinical outcome.

Extension of antimicrobial treatment in patients with left-sided native valve endocarditis based on elevated C-reactive protein values

The aim of this non-randomized study was to investigate whether there is any benefit in the extension of antimicrobial treatment in patients with left-sided native valve endocarditis in whom C-reactive protein levels are still elevated after a standard course of therapy. There was no statistically significant difference in outcome between the group of patients in which treatment was extended in comparison to the group in which treatment was ended at the recommended time. It is unlikely that there is much to gain from extending treatment based on elevated C-reactive protein levels alone.