STUDY QUESTION
Does the prewash total motile sperm count (TMSC) have a better predictive value for spontaneous ongoing pregnancy (SOP) than the World Health Organization (WHO) classification system?
...SUMMARY ANSWER
The prewash TMSC shows a better correlation with the spontaneous ongoing pregnancy rate (SOPR) than the WHO 2010 classification system.
WHAT IS KNOWN ALREADY
According to the WHO classification system, an abnormal semen analysis can be diagnosed as oligozoospermia, astenozoospermia, teratozoospermia or combinations of these and azoospermia. This classification is based on the fifth percentile cut-off values of a cohort of 1953 men with proven fertility. Although this classification suggests accuracy, the relevance for the prognosis of an infertile couple and the choice of treatment is questionable. The TMSC is obtained by multiplying the sample volume by the density and the percentage of A and B motility spermatozoa.
STUDY DESIGN, SIZE, DURATION
We analyzed data from a longitudinal cohort study among unselected infertile couples who were referred to three Dutch hospitals between January 2002 and December 2006. Of the total cohort of 2476 infertile couples, only the couples with either male infertility as a single diagnosis or unexplained infertility were included (n = 1177) with a follow-up period of 3 years.
PARTICIPANTS/MATERIALS, SETTING, METHODS
In all couples a semen analysis was performed. Based on the best semen analysis if more tests were performed, couples were grouped according to the WHO classification system and the TMSC range, as described in the Dutch national guidelines for male infertility. The primary outcome measure was the SOPR, which occurred before, during or after treatments, including expectant management, intrauterine insemination, in vitro fertilization or intracytoplasmic sperm injection. After adjustment for the confounding factors (female and male age, duration and type of infertility and result of the postcoital test) the odd ratios (ORs) for risk of SOP for each WHO and TMSC group were calculated. The couples with unexplained infertility were used as reference.
MAIN RESULTS AND THE ROLE OF CHANCE
A total of 514 couples did and 663 couples did not achieve a SOP. All WHO groups have a lower SOPR compared with the unexplained group (ORs varying from 0.136 to 0.397). Comparing the couples within the abnormal WHO groups, there are no significant differences in SOPR, except when oligoasthenoteratozoospermia is compared with asthenozoospermia OR 0.501 (95% CI 0.311–0.809) and teratozoospermia OR 0.499 (95% CI: 0.252–0.988), and oligoasthenozoospermia is compared with asthenozoospermia OR 0.572 (95% CI: 0.373–0.877). All TMSC groups have a significantly lower SOPR compared with the unexplained group (ORs varying from 0.171 to 0.461). Couples with a TMSC of <1 × 106 and 1–5 × 106 have significantly lower SOPR compared with couples with a TMSC of 5–10 × 106 respectively, OR 0.371 (95% CI: 0.215–0.64) and OR 0.505 (95% CI: 0.307–0.832).
LIMITATIONS, REASON FOR CAUTION
To include all SOPs during the follow-up period of 3 years, couples were not censured at the start of treatment.
WIDER IMPLICATIONS OF THE FINDINGS
Roughly, three prognostic groups can be discerned: couples with a TMSC <5, couples with a TMSC between 5 and 20 and couples with a TMSC of more than 20 × 106 spermatozoa. We suggest using TMSC as the method of choice to express severity of male infertility.
STUDY FUNDING/COMPETING INTEREST(S)
None.
Objective
Use of several immunomodulatory agents has been associated with reduced numbers of cardiovascular (CV) events in epidemiologic studies of rheumatoid arthritis (RA). However, it is unknown ...whether time‐averaged disease activity in RA correlates with CV events.
Methods
We studied patients with RA whose cases were followed in a longitudinal US‐based registry. Time‐averaged disease activity was assessed during followup using the area under the curve of the Clinical Disease Activity Index (CDAI), a validated measure of RA disease activity. Age, sex, presence of diabetes mellitus, hypertension, or hyperlipidemia, body mass index, family history of myocardial infarction (MI), use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), presence of CV disease, and baseline use of an immunomodulator were assessed at baseline. Cox proportional hazards regression models were examined to determine the risk of a composite CV end point that included MI, stroke, and death from CV causes.
Results
A total of 24,989 patients who had been followed up for a median of 2.7 years were included in these analyses. During followup, we observed 534 confirmed CV end points, for an incidence rate of 7.8 per 1,000 person‐years (95% confidence interval 95% CI 6.7–8.9). In models adjusted for variables noted above, a 10‐point reduction in the time‐averaged CDAI was associated with a 21% reduction in CV risk (95% CI 13–29). These results were robust in subgroup analyses stratified by the presence of CV disease, use of corticosteroids, use of NSAIDs or selective cyclooxygenase 2 inhibitors, and change in RA treatment, as well as when restricted to events adjudicated as definite or probable.
Conclusion
Our findings showed that reduced time‐averaged disease activity in RA is associated with fewer CV events.
Long-term trends in neuroblastoma incidence and survival in unscreened populations are unknown. We explored trends in incidence, stage at diagnosis, treatment and survival of neuroblastoma in the ...Netherlands from 1990 to 2014.
The Netherlands Cancer Registry provided data on all patients aged <18 years diagnosed with a neuroblastoma. Trends in incidence and stage were evaluated by calculating the average annual percentage change (AAPC). Univariate and multivariable survival analyses were performed for stage 4 disease to test whether changes in treatment are associated with survival.
Of the 593 newly diagnosed neuroblastoma cases, 45% was <18 months of age at diagnosis and 52% had stage 4 disease. The age-standardized incidence rate for stage 4 disease increased at all ages from 3.2 to 5.3 per million children per year (AAPC + 2.9%, p < .01). This increase was solely for patients ≥18 months old (3.0–5.4; AAPC +3.3%, p = .01). Five-year OS of all patients increased from 44 ± 5% to 61 ± 4% from 1990 to 2014 (p < .01) and from 19 ± 6% to 44 ± 6% (p < .01) for patients with stage 4 disease. Multivariable analysis revealed that high-dose chemotherapy followed by autologous stem cell rescue and anti-GD2-based immunotherapy were associated with this survival increase (HR 0.46, p < .01 and HR 0.37, p < .01, respectively).
Incidence of stage 4 neuroblastoma increased exclusively in patients aged ≥18 months since 1990, whereas the incidence of other stages remained stable. The 5-year OS of stage 4 patients improved, mostly due to the introduction of high-dose chemotherapy followed by stem cell rescue and immunotherapy.
•The incidence of stage 4 neuroblastoma increased 2.9% per year between 1990 and 2014.•Five-year overall survival of stage 4 patients improved from 19 ± 6% to 44 ± 6%.•High-dose chemotherapy and immunotherapy contributed most to the improved survival.
BACKGROUND A substantial number of subfertile couples discontinues fertility care before achieving pregnancy. Most studies on dropouts are related to IVF. The aim here is to examine dropout rates at ...all stages of fertility care. METHODS We analysed a consecutive cohort of 1391 couples, referred to our secondary care hospital between January 2002 and December 2006. Discontinuation rates were studied at six stages. Stage I: immediately after first visit, Stage II: during diagnostic workup, Stage III: after finishing diagnostic workup but before treatment, Stage IV: during or after non-IVF treatment, Stage V: during IVF, Stage VI: after at least 3 cycles of IVF. Reasons to discontinue and spontaneous pregnancy rates after discontinuation were secondary outcomes. RESULTS In our cohort 319 couples dropped out of fertility care, 76.8%, 95% confidence interval (CI): 72.2–81.4 on their own initiative and 23.2% (95% CI: 18.6–27.8) on doctor's advice. Percentage (95% CI) of couples discontinuing per stage were: Stage I 6.0% (3.4–8.6), Stage II 3.4% (1.5–5.5), Stage III 35.7% (30.5–41.0), Stage IV 23.5% (18.9–28.2), Stage V 17.9% (13.7–22.1) and Stage VI 13.5% (9.7–17.2). Main reasons for dropout (%, 95% CI) were ‘emotional distress’ (22.3%, 17.7–26.8), ‘poor prognosis’ (18.8%, 14.5–23.1) and ‘reject treatment’ (17.2%, 13.1–21.4). The spontaneous ongoing pregnancy rate after discontinuation was 10% (6.7–13.3). CONCLUSION About half of the couples stopped before any fertility treatment was started and one-third stopped after at least one IVF cycle. The main reasons for withdrawal were emotional distress and poor prognosis. This insight may help to improve quality of patient care by making care more responsive to the needs and expectations of subfertile couples.
BACKGROUND
This study examined the relationship between emotional distress as measured by the Hospital Anxiety and Depression Scale (HADS) and the Fertility Quality of Life (FertiQoL) questionnaire.
...METHODS
The FertiQoL and HADS were distributed to a random sample of 785 patients attending 29 Dutch clinics for medically assisted reproduction. FertiQoL was psychometrically tested for reliability. Pearson's correlations were calculated between subscales of FertiQoL and HADS. Using an independent t-test, differences between patient subgroups were computed for both instruments. The threshold for clinically meaningful depression/anxiety on the HADS subscales was used to ascertain the critical threshold for high distress on the FertiQoL scales.
RESULTS
FertiQoL and HADS were completed by 583 patients (response 74%). Reliability of FertiQoL scales was high (reliability coefficient between 0.72 and 0.91). Significant negative correlations were found between FertiQoL subscales and HADS scores for anxiety and depression, ranging from −0.29 to −0.71. Means on FertiQoL scales and HADS scales of couples undergoing an assisted reproductive technology (ART) treatment and a non-ART treatment did not differ significantly. Patients scoring above the HADS threshold for pathology on anxiety had an average FertiQoL score of 58.8, whereas patients exceeding the HADS depression threshold had a FertiQoL total score of 51.9 (range 0–100).
CONCLUSIONS
Our study confirms the expected negative relation between quality of life as measured by FertiQoL and anxiety and depression. The data support that FertiQoL reliably measures QoL in women facing infertility. FertiQoL enables clinicians to tailor care more specifically to the patient in a comprehensive way.
This review provides an overview of how women adjust emotionally to the various phases of IVF treatment in terms of anxiety, depression or general distress before, during and after different ...treatment cycles. A systematic scrutiny of the literature yielded 706 articles that paid attention to emotional aspects of IVF treatment of which 27 investigated the women’s emotional adjustment with standardized measures in relation to norm or control groups. Most studies involved concurrent comparisons between women in different treatment phases and different types of control groups. The findings indicated that women starting IVF were only slightly different emotionally from the norm groups. Unsuccessful treatment raised the women’s levels of negative emotions, which continued after consecutive unsuccessful cycles. In general, most women proved to adjust well to unsuccessful IVF, although a considerable group showed subclinical emotional problems. When IVF resulted in pregnancy, the negative emotions disappeared, indicating that treatment-induced stress is considerably related to threats of failure. The concurrent research reviewed, should now be underpinned by longitudinal studies to provide more information about women’s long-term emotional adjustment to unsuccessful IVF and about indicators of risk factors for problematic emotional adjustment after unsuccessful treatment, to foster focused psychological support for women at risk.
The aim of this study was to gain more insight into long-term psychological adjustment to IVF in women. METHODS: In a prospective cohort study, 298 women entering their first IVF treatment cycle ...(including ICSI) completed standardized psychological questionnaires before the start of the treatment, just after the last treatment cycle, and 6 months and 3–5 years after the last treatment cycle. The main outcome measures were state anxiety, depression and mode of adaptation to unsuccessful IVF. RESULTS: Anxiety and depression were found at follow-up to return to baseline levels following treatment not resulting in a live birth, after an initial increase during treatment. On the contrary, treatment resulting in a live birth was found to lead to a more positive long-term emotional status. Women who focused on new life goals as a mode of adaptation 3–5 years after IVF without a live birth showed lower levels of anxiety and depression compared with those who persisted in their attempts to get pregnant. CONCLUSIONS: Treatment that resulted in a live birth led to more positive emotional adjustment. In addition, most women who did not give birth to a child after treatment adjusted well psychologically. Positive adjustment was related to developing new life goals rather than persisting in attempts to get pregnant. Helping women to change life goals after abandoning treatment might have beneficial effects on the adaptation process.
STUDY QUESTION
Do the quality of life (QoL) and the risk factors for emotional problems during and after treatment of infertile women differ from their partners?
SUMMARY ANSWER
Women have lower ...levels of fertility-related QoL, and more and differing risk factors for emotional problems during and after treatment than their partners.
WHAT IS KNOWN ALREADY?
The psychological impact of infertility in patients negatively affects their QoL and is also related to increased discontinuation of treatment. Moreover, psychological factors might positively affect pregnancy rates. However, it is still unclear if differences in QoL and emotional status exist between infertile women and their partners. So far, research mainly focused on generic instruments to measure patients' QoL in the area of fertility care.
STUDY DESIGN, SIZE, DURATION
A cross-sectional study of infertile couples within 32 Dutch fertility clinics.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We included infertile women and their partners (both heterosexual and lesbian couples) under any treatment and at any stage of treatment in one of the 32 participating clinics. Per clinic, 25–75 patients were randomly selected depending on clinic size. In total, 1620 women and their partners were invited separately to complete the FertiQoL and SCREENIVF questionnaires to measure their level of QoL and risk factors for emotional problems during and after treatment, respectively.
MAIN RESULTS AND THE ROLE OF CHANCE
A total of 946 women (response rate 58%) and 670 partners (response rate 41%) completed the questionnaire set. As 250 women and 150 partners were already pregnant, questionnaires from 696 women and 520 partners could be analysed. Women scored significantly lower on the FertiQoL total scores B = −6.31; 95% confidence interval (CI) = −7.63 to 4.98 and three of the FertiQoL subscales (Emotional, Mind–Body and Social) than their partners, indicating lower QoL. Scores on the SCREENIVF questionnaire were significantly higher for women (B = 0.22; 95% CI = 0.06–0.38), indicating that women are more at risk for developing emotional problems (and these factors differed from those of their partners) during and after fertility treatment than their partners.
LIMITATIONS, REASONS FOR CAUTION
Although the number of participants is high (n = 1216), the relatively low response rate, especially for partners (41%), may have influenced the results through selection bias. An analysis of non-responders could not be performed. The FertiQoL and SCREENIVF questionnaires, which have been validated only in women starting a first IVF cycle, should also be validated for studying partners. In addition, the SCREENIVF questionnaire has been validated in Dutch women only and further research in an international setting is also required.
WIDER IMPLICATIONS OF THE FINDINGS
Our study results represent the Dutch infertile population as more than one-third of all Dutch clinics participated in the study. As the FertiQoL questionnaire is an internationally validated questionnaire already, these results can be put in a more broader and international perspective.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by Merck Sharp & Dohme (MSD), The Netherlands. There are no competing interests.
BACKGROUND: A longitudinal study into the course of the emotional response to IVF from pre-treatment to 6 months post-treatment and factors that contributed to that course. METHODS: A total of 148 ...IVF patients and 71 partners completed self-report questionnaires on anxiety, depression, personality characteristics, meaning of fertility problems, coping, marital relationship and social support at pre-treatment. Assessments of anxiety and depression were repeated immediately following the final treatment cycle and again 6 months later (follow-up). RESULTS: Women showed an increase of both anxiety and depression after unsuccessful treatment and a decrease after successful treatment. Men showed no change in anxiety and depression either after successful or after unsuccessful treatment. In the 6 months after unsuccessful treatment, women showed no recovery. At follow-up, >20% of the women showed subclinical forms of anxiety and/or depression. Personality characteristics, meaning of the fertility problems, and social support determined the course of the emotional response. CONCLUSIONS: Most women adjusted well to unsuccessful treatment, but at follow-up, a considerable proportion still showed substantial emotional problems. Personality characteristics, pre-treatment meaning of the fertility problems and social support have demonstrated the adjustment to unsuccessful IVF in women. This allows early identification of women at risk as well as tailored interventions.
CONTEXT Improved survival of children with cancer has been accompanied by multiple treatment-related complications. However, most studies in survivors of childhood cancer focused on only 1 late ...effect. OBJECTIVE To assess the total burden of adverse health outcomes (clinical or subclinical disorders “adverse events”) following childhood cancer in a large cohort of childhood cancer survivors with long-term and complete medical follow-up. DESIGN, SETTING, AND POPULATION Retrospective cohort study of 1362 five-year survivors of childhood cancer treated in a single institution in the Netherlands between 1966 and 1996. All survivors were invited to a late-effects clinic for medical assessment of adverse events. Adverse events occurring before January 2004 were graded for severity in a standardized manner. MAIN OUTCOME MEASURES Treatment-specific prevalence of adverse events (according to severity) at end of follow-up and relative risk of high or severe burden of disease (≥2 severe or ≥1 life-threatening or disabling adverse events) associated with various treatments. RESULTS Medical follow-up was complete for 94.3% of survivors (median follow-up, 17.0 years). The median attained age at end of follow-up was 24.4 years. Almost 75% of survivors had 1 or more adverse events, and 24.6% had 5 or more adverse events. Furthermore, 40% of survivors had at least 1 severe or life-threatening or disabling adverse event. A high or severe burden of adverse events was observed in 55% of survivors who received radiotherapy only and 15% of survivors treated with chemotherapy only, compared with 25% of survivors who had surgery only (adjusted relative risks, 2.18 95% confidence interval, 1.62–2.95 and 0.65 95% confidence interval, 0.46–0.90, respectively). A high or severe burden of adverse events was most often observed in survivors of bone tumors (64%) and least often in survivors of leukemia or Wilms tumor (12% each). CONCLUSIONS In young adulthood, a substantial proportion of childhood cancer survivors already has a high or severe burden of disease, particularly after radiotherapy. This underscores the need for lifelong risk-stratified medical surveillance of childhood cancer survivors.
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