ABSTRACT
STUDY QUESTION: Is cervical intraepithelial neoplasia (CIN) associated with reduced fecundability, defined as the probability of conceiving per menstrual cycle? SUMMARY ANSWER: Overall, we observed no meaningful association between CIN and fecundability, regardless of surgical status, although a recent diagnosis of moderate or severe CIN might be associated with slightly reduced fecundability for 2 years after diagnosis. WHAT IS KNOWN ALREADY: About 15% of couples experience infertility. Few studies have examined the influence of CIN on fertility, and the results have been inconsistent. No study has investigated the association between fecundability and pathologist-reported CIN diagnoses, particularly with respect to the recency of the specific CIN diagnoses. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 9586 women trying to conceive. The women were enrolled from 1 June 2007 to 3 February 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women were invited to complete a baseline questionnaire and bimonthly follow-up questionnaires for up to 12 months or until pregnancy occurred. Data on cervical cytologies and biopsies were retrieved from The National Pathology Registry (DNPR), which holds records of all cervical specimens examined in Denmark. Women were categorized based on their most severe diagnosis of CIN: no lesion, other cervical changes, mild CIN (CIN1), or moderate/severe CIN (CIN2+) with or without surgery. To investigate the association between CIN and fecundability, we computed fecundability ratios (FR) and 95% confidence intervals (CI) using a proportional probabilities regression model. We adjusted for age at study entry, partner age, body mass index, smoking status, timing of intercourse, parity, education, number of sexual partners, and household income. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with no lesion, the adjusted FRs (95% CI) for the association between CIN and fecundability were: other cervical lesions, 0.97 (0.91-1.04); CIN1, 1.04 (0.96-1.13); CIN2+ no surgery, 1.00 (0.82-1.22); and CIN2+ with surgery 0.99 (0.89-1.10). The FRs (95% CI) for a recent diagnosis (<2 years) of CIN were 0.98 (0.86-1.11) for other cervical lesions; 1.13 (0.99-1.29) for CIN1; 0.89 (0.62-1.26) for CIN2+ no surgery and 0.91 (0.75-1.10) for CIN2+ with surgery compared with the no lesion group. LIMITATIONS, REASONS FOR CAUTION: In the analyses, we adjusted for several covariates related to the women. However, we had little information on the male partners which could lead to unmeasured confounding as fecundability is a couple-based measure of fertility. Furthermore, a CIN diagnosis may not be constant as it may regress or progress spontaneously; therefore, it is possible that we have misclassified some women, especially women categorized as having normal cells or CIN1. WIDER IMPLICATIONS OF THE FINDINGS: Our results contribute important knowledge to women who are concerned about their future fertility after receiving a CIN diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by The Danish Cancer Society (R167-A11036-17-S2). The overall cohorts were funded by the National Institute of Child Health and Human Development (R01-HD086742 and R03-HD094117). The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.
ABSTRACT
BACKGROUND: Nondepolarising muscle relaxants (NDMRs) provide optimal conditions for tracheal intubation and improve surgical conditions. Several clinical conditions, diseases and pharmacological interactions have been suggested to cause resistance towards NDMRs that may translate into difficult intubation or inadequate operating conditions during surgery. OBJECTIVE: The aim of this study was to evaluate the current evidence of patient groups with resistance towards NDMRs. A prolonged onset time was defined as a difference that exceeded 25% compared with controls. DESIGN: A systematic review of randomised controlled trials and cohort studies. DATA SOURCES: A comprehensive search was performed in 2016 in PubMed and EMBASE. ELIGIBILITY CRITERIA: Patients with conditions or diseases, or patients taking medication, which lead to resistance towards current NDMRs (rocuronium, vecuronium, cisatracurium, atracurium, mivacurium and pancuronium). Included outcomes were onset time defined as the time between administration of NDMR to maximal (90, 95 or 100%) depression of baseline twitch height of the first twitch in a train-of-four. RESULTS: Twenty-five studies were included. Strong evidence supports a prolonged onset time of rocuronium in patients with thermal injury and Duchenne muscular dystrophy. Moderate evidence supports a prolonged onset time of NDMRs during hypothermia and in patients with infection, oculopharyngeal muscular dystrophy, liver cirrhosis treated with ulinastatin, when remifentanil is administered prior to administration of an NDMR, in fasting patients being rehydrated intravenously prior to administration of NDMR, in children with end-stage renal failure and in patients with atrial or ventricular septal defects. CONCLUSION: A prolonged onset time should be suspected in patients with thermal injury and Duchenne's muscular dystrophy. Further, evidence supports a prolonged onset time in patients with infection, oculopharyngeal muscular dystrophy, congenital heart defects, kidney failure, liver cirrhosis treated with ulinastatin along with remifentanil or intravenous fluids administered prior to NDMR.
