Advanced Reproductive Age and Fertility Liu, Kimberly, MD; Case, Allison, MD; Cheung, Anthony P., MD ...
Journal of obstetrics and gynaecology Canada,
11/2011, Volume:
33, Issue:
11
Journal Article
Peer reviewed
Abstract Objective To improve awareness of the natural age-related decline in female and male fertility with respect to natural fertility and assisted reproductive technologies (ART) and provide ...recommendations for their management, and to review investigations in the assessment of ovarian aging. Options This guideline reviews options for the assessment of ovarian reserve and fertility treatments using ART with women of advanced reproductive age presenting with infertility. Outcomes The outcomes measured are the predictive value of ovarian reserve testing and pregnancy rates with natural and assisted fertility. Evidence Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in June 2010, using appropriate key words (ovarian aging, ovarian reserve, advanced maternal age, advanced paternal age, ART). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated into the guideline to December 2010. Values The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table). Benefits, harms, and costs Primary and specialist health care providers and women will be better informed about ovarian aging and the age-related decline in natural fertility and about options for assisted reproductive technology. Recommendations 1. Women in their 20s and 30s should be counselled about the agerelated risk of infertility when other reproductive health issues, such as sexual health or contraception, are addressed as part of their primary well-woman care. Reproductive-age women should be aware that natural fertility and assisted reproductive technology success (except with egg donation) is significantly lower for women in their late 30s and 40s. (II-2A) 2. Because of the decline in fertility and the increased time to conception that occurs after the age of 35, women > 35 years of age should be referred for infertility work-up after 6 months of trying to conceive. (III-B) 3. Ovarian reserve testing may be considered for women ≥ 35 years of age or for women < 35 years of age with risk factors for decreased ovarian reserve, such as a single ovary, previous ovarian surgery, poor response to follicle-stimulating hormone, previous exposure to chemotherapy or radiation, or unexplained infertility. (III-B) 4. Ovarian reserve testing prior to assisted reproductive technology treatment may be used for counselling but has a poor predictive value for non-pregnancy and should be used to exclude women from treatment only if levels are significantly abnormal. (II-2A) 5. Pregnancy rates for controlled ovarian hyperstimulation are low for women > 40 years of age. Women > 40 years should consider IVF if they do not conceive within 1 to 2 cycles of controlled ovarian hyperstimulation. (II-2B) 6. The only effective treatment for ovarian aging is oocyte donation. A woman with decreased ovarian reserve should be offered oocyte donation as an option, as pregnancy rates associated with this treatment are significantly higher than those associated with controlled ovarian hyperstimulation or in vitro fertilization with a woman’s own eggs. (II-2B) 7. Women should be informed that the risk of spontaneous pregnancy loss and chromosomal abnormalities increases with age. Women should be counselled about and offered appropriate prenatal screening once pregnancy is established. (II-2A) 8. Pre-conception counselling regarding the risks of pregnancy with advanced maternal age, promotion of optimal health and weight, and screening for concurrent medical conditions such as hypertension and diabetes should be considered for women > age 40. (III-B) 9. Advanced paternal age appears to be associated with an increased risk of spontaneous abortion and increased frequency of some autosomal dominant conditions, autism spectrum disorders, and schizophrenia. Men > age 40 and their partners should be counselled about these potential risks when they are seeking pregnancy, although the risks remain small. (II-2C)
Frequent right ventricular (RV) pacing can lead to a decline in left ventricular ejection fraction (LVEF).
This study aimed to identify incidence and predictors of RV pacing-induced cardiomyopathy ...(PICM).
We retrospectively studied 1750 consecutive patients undergoing pacemaker implantation between 2003 and 2012. Patients were included if baseline LVEF was normal, single-chamber ventricular or dual-chamber pacemaker (but not implantable cardioverter-defibrillator or biventricular pacemaker) was implanted, frequent (≥20%) RV pacing was present, and repeat echocardiogram was available ≥1 year after implantation. PICM was defined as ≥10% decrease in LVEF, resulting in LVEF <50%. Patients with alternative causes of cardiomyopathy were excluded. Predictors of the development of PICM were identified using multivariate Cox proportional hazards modeling.
Of 257 patients meeting study criteria, 50 (19.5%) developed PICM, with a decrease in mean LVEF from 62.1% to 36.2% over a mean follow-up period of 3.3 years. Those who developed PICM were more likely to be men, with lower baseline LVEF and wider native QRS duration (bundle branch blocks excluded; P = .005, P = .03, and P = .001, respectively). In multivariate analysis, male gender (hazard ratio 2.15; 95% confidence interval 1.17-3.94; P = .01) and wider native QRS duration (hazard ratio 1.03 per 1 ms increase; 95% confidence interval 1.01-1.05; P < .001) were independently associated with the development of PICM. Native QRS duration >115 ms was 90% specific for the development of PICM.
PICM may be more common than previously reported, and risk for its occurrence begins below the commonly accepted threshold of 40% pacing burden. Men with wider native QRS duration (particularly >115 ms) are at increased risk. These patients warrant closer follow-up with a lower threshold for biventricular pacing.
To report outcomes of ophthalmic evaluations in clinical studies of patients receiving fingolimod (Gilenya; Novartis Pharma AG, Basel, Switzerland) for multiple sclerosis (MS).
Analysis done on ...pooled safety data (N = 2615, all studies group) from 3 double-masked, randomized, parallel-group clinical trials (phase 2 core and extension >5 years, and phase 3 FREEDOMS and TRANSFORMS core and extension studies).
Patients aged 18 to 55 years (18-60 years in phase 2 study) diagnosed with relapsing-remitting MS were included. Patients with diabetes mellitus or macular edema (ME) at screening were excluded.
Participants received fingolimod (0.5/1.25 mg), placebo, or interferon beta for the respective study durations. Ophthalmic examination included detailed eye history (at screening), visual acuity (VA) assessment, dilated ophthalmoscopy, optical coherence tomography (OCT), and fluorescein angiography (FA).
Extensive ophthalmic monitoring was performed for all patients. While being studied, patients with abnormal findings on dilated ophthalmoscopy and OCT compatible with ME were further studied by FA. All locally diagnosed ME cases were centrally reviewed by the retina specialist (M.A.Z.) on the Data and Safety Monitoring Board.
Among 2615 patients assessed, 19 confirmed ME cases were observed in fingolimod-treated groups (0.5 mg: n = 4, 0.3%; 1.25 mg: n = 15, 1.2%). Most patients (n = 13, 68%) presented with blurred vision, decreased VA, or eye pain. Macular edema was diagnosed within 3 to 4 months of treatment initiation in most cases (n = 13, 68%); 2 patients had late onset (>12 months) ME. Of the 19 patients with ME, 5 (26%), all treated with fingolimod 1.25 mg, had a history of uveitis compared with 26 (1%) in the all studies group. In most cases (n = 16, 84%), ME resolved after discontinuing the study drug. Eleven patients required topical anti-inflammatory medications. No patient had further vision deterioration.
Fingolimod 0.5 mg is associated with a low incidence of ME in MS studies. Patients with a history of uveitis may be at an increased risk of developing ME. An ophthalmic examination before initiating fingolimod therapy and regular follow-up eye examinations during fingolimod therapy are recommended.
Abstract Objective To review the effect of elective single embryo transfer (eSET) compared with double embryo transfer (DET) following in vitro fertilization (IVF), and to provide guidelines on the ...use of eSET in order to optimize live birth rates and minimize twin pregnancies. Options Rates of live birth, clinical pregnancy, and multiple pregnancy following eSET and DET are compared. Outcomes Live birth, clinical pregnancy, and multiple pregnancy rates, and cost-effectiveness. Evidence Published literature was retrieved through searches of PubMed, Medline, and The Cochrane Library in 2009, using appropriate controlled vocabulary (e.g., elective single embryo transfer) and key words (e.g., embryo transfer, in vitro fertilization, intracytoplasmic sperm injection, assisted reproductive technologies, blastocyst, and multiple pregnancy). Results were restricted to English language systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date restrictions. Searches were updated on a regular basis and incorporated in the guideline to November 2009. Additional references were identified through searches of bibliographies of identified articles and international medical specialty societies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values Available evidence was reviewed by the Joint Society of Obstetricians and Gynaecologist of Canada–Canadian Fertility and Andrology Society Clinical Practice Guidelines Committee and the Reproductive Endocrinology and Infertility Committee of the Society of Obstetricians and Gynaecologists of Canada, and was qualified using the evaluation of evidence criteria outlined in the report of the Canadian Task Force on Preventive Health Care. Benefits, Harms, and Costs This guideline is intended to minimize the occurrence of twin gestations while maintaining acceptable overall live birth rates following IVF-ET. Summary Statements 1. Indiscriminate application of eSET in populations with less than optimal prognosis for live birth will result in a significant reduction in effectiveness compared with DET. (I) 2. In women aged 38 years and over, eSET may result in a significant reduction in live birth rate compared with DET. (II-2) 3. Selective application of eSET in a small group of good-prognosis patients may be effective in reducing the overall multiple rate of an entire IVF population. (II-3) 4. Given the high costs of treatment, uptake of eSET would be enhanced by public funding of IVF treatment. (II-2) Recommendations 1. Patients should be informed of the reductions in both multiple pregnancy rate and overall live birth rate after a single fresh eSET when compared with DET in good-prognosis patients. (I-A) 2. Because the cumulative live birth rate after fresh eSET followed by transfer of a single frozen-thawed embryo is similar but not equivalent to the rate after fresh DET in good-prognosis patients, the eSET strategy should be used in order to avoid multiple pregnancy. (I-A) 3. Women aged 35 years or less, in their first or second IVF attempt, with at least 2 good quality embryos available for transfer should be considered good-prognosis patients. (I-A) 4. In order to maximize cumulative live birth rates following eSET, effective cryopreservation programs should be in place. (I-A) 5. In order to maintain the reduction in the rate of multiples achieved by fresh eSET, eSET should be performed in subsequent frozen-thawed embryo transfer cycles. (II-2A) 6. Because blastocyst stage embryo transfer generally increases the chance of implantation and live birth compared with cleavage stage embryo transfer, eSET should be performed in good-prognosis patients who have good quality blastocysts available. (I-A) 7. In women aged 36 to 37 years, eSET should be considered in good-prognosis patients with good quality embryos, particularly when blastocysts are available for transfer. (II-2A) 8. In oocyte donor–recipient cycles when the donor has good prognosis and when good quality embryos are available, eSET should be performed. (II-2B) 9. In women with medical or obstetrical contraindications to twin pregnancy, eSET should be performed. (III-B) 10. In order to achieve successful uptake of eSET, it is essential to provide patient and physician education regarding the risks of twin pregnancy and regarding the similar cumulative live birth rate following an eSET strategy and DET. (III-C) 11. When considering both direct health care and societal costs, it should be noted that live birth following eSET is significantly less expensive than DET in good-prognosis patients. (I-A) Therefore, from a cost-effectiveness perspective, eSET is indicated in good-prognosis patients. (III-A)
Modern left ventricular assist devices (LVAD) require anti-coagulation (AC) with warfarin and anti-platelet therapy to prevent thromboembolic complications in patients. Gastrointestinal bleeding (GI) ...is a significant adverse event in these patients and treatment typically requires reduction or elimination of AC or anti-platelet therapy. It is not known whether alterations in AC to treat GI bleeding influence subsequent risk of thromboembolic (TE) events during LVAD support.
Between July 2003 and September 2011, 389 patients (308 male) underwent implantation of a continuous-flow LVAD at the University of Michigan Health System and the Mayo Clinic. Median age at implant was 60 years (range 18 to 79 years). Outcomes were analyzed for the association of GI bleeding events and subsequent TE events, defined as stroke, transient ischemic attack, hemolysis or suspected or confirmed pump thrombosis.
Median survival was 10 months (maximum 7.2 years, total 439 patient-years). TE events occurring within the first 30 days were not counted. Overall survival and freedom from an outcome event were assessed using the Kaplan-Meier method. Associations between GI bleeding and subsequent TE events and survival impact were analyzed as time-dependent covariates. One hundred ninety-nine GI bleeding episodes occurred in 116 of 389 patients (30%) for an event rate of 0.45 GI bleed/patient-year of support. One hundred thirty-eight TE events occurred in 97 of 389 patients (25%) for an event rate of 0.31 TE event/patient-year of support. Median time from LVAD implant to first GI bleed was 5 months (range 1 to 116 months) and to first TE event was 6 months (range 1 to 29 months). For patients who had a TE event after GI bleed, the median interval was 5 months (range 0.5 to 25 months). TE events were 7.4-fold more likely in patients who had a prior GI bleed (range 4.9- to 11.1-fold) (p < 0.001); however, neither the presence of GI bleeding (0.7 to 1.2) nor a TE event (0.8 to 2.0) portended a lower overall survival.
Patients who had GI bleeding were at significantly higher risk for a subsequent TE event. Although the exact cause of this relationship is unknown, it suggests that a reduction in anti-coagulation and anti-platelet management to treat GI bleeds may contribute to this risk.
Ventricular tachyarrhythmias are an important cause of morbidity and mortality in cardiac sarcoidosis. To date, the prevalence and incidence of ventricular tachycardia/ventricular fibrillation ...(VT/VF) in this population remain unknown.
To determine the prevalence and incidence of ventricular tachyarrhythmias in patients with cardiac sarcoidosis and to identify the clinical attributes associated with appropriate implantable cardioverter-defibrillator (ICD) therapies.
We studied 45 patients with ICDs, biopsy-proven systemic sarcoidosis, and cardiac involvement, as evidenced by histopathology, cardiac magnetic resonance imaging, and/or (18)F-fluoro-2-deoxyglucose-positron emission tomography imaging. Device logs and medical records were retrospectively reviewed.
Appropriate ICD therapies for VT/VF were observed in 37.8% of the patients with an incidence of 15% per year. Inappropriate ICD therapies occurred in 13.3% of the patients. Longer ICD follow-up (4.5 ± 3.1 years vs 1.5 ± 1.5 years; P = .001), depressed left ventricular ejection fraction (35.5% ± 15.5% vs 50.9% ± 15.5%; P = .002), and complete heart block (47.1% vs 17.9%; P = .048) were associated with appropriate ICD therapy. While there was no significant difference in the total number of shocks/antitachycardia pacing-terminated events between primary (n = 29) and secondary (n = 16) prevention groups, there was a trend toward more events in the secondary prevention arm after 2 years.
Ventricular tachyarrhythmias requiring ICD therapy were common in patients with cardiac sarcoidosis, with an estimated incidence rate of 15% per year. Longer follow-up, left ventricular systolic dysfunction, and complete heart block were associated with VT/VF. Patients with primary prevention ICDs had high rates of appropriate ICD therapy but not as high as did secondary prevention patients. In the absence of reliable risk stratification techniques, consideration should be given to prophylactic ICD implantation in patients with cardiac sarcoidosis.
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