RESUMO
As more premenopausal patients undergo fertility preserving cancer treatments, there is an increased need for fertility counseling and ovarian sparing strategies. Many patients receive gonadotoxic chemotherapeutic agents which can put them at risk of primary ovarian insufficiency or profoundly diminished ovarian reserve. Traditionally, estradiol and follicle stimulating hormone (FSH) values have been used to evaluate ovarian function but more recently, reproductive endocrinologists have been proponents of anti-mullerian hormone (AMH) as a validated measure of ovarian potential. While the gold standard for fertility preservation remains oocyte cryopreservation, data suggest there may be additional interventions that can mitigate the gonadotoxic effects of chemotherapeutic agents. The main objectives of this focused review were to quantify the risk of primary ovarian failure associated with the most common chemotherapies used in treatment of gynecologic cancers and to evaluate and recommend potential interventions to mitigate toxic effects on ovarian function. Chemotherapeutic agents can cause direct loss of oocytes and primordial follicles as well as stromal and vascular atrophy and the extent is dependent upon mechanism of action and age of the patient. The risk of ovarian failure is the highest with alkylating agents (42.2 %), anthracyclines (<10-34 % in patients under 40 years versus 98 % in patients aged 40-49), taxanes (57.1 %) and platinum agents (50 %). Multiple trials demonstrate that gonadotropin releasing hormone (GnRH) agonists, when administered concurrently with chemotherapy, may have protective effects, with more patients experiencing resumption of a regular menstruation pattern and recovering ovarian function more quickly post-treatment. Premenopausal patients receiving chemotherapy for the treatment of gynecologic cancers should receive adequate counseling on the potential adverse effects on their fertility. Although oocyte cryopreservation remains the gold standard for fertility preservation, there is some evidence to suggest that GNRH agonists could help maintain and preserve ovarian function and should be considered.
RESUMO
OBJECTIVE: To assess risk factors associated with loss to follow up in patients referred for colposcopy after abnormal cervical cytology during pregnancy in a Southern safety net hospital population. METHODS: An urban colposcopy center was queried for patients referred for follow up of abnormal cervical cytology during pregnancy and the postpartum period. Patients were identified through a standardized referral code in the electronic medical record. Multivariable logistic regression was used to compare patient characteristics between those who followed up for colposcopy and those lost to follow up. Independent risk factors assessed included age, parity, race, insurance, HIV status, history of mental illness, BMI, gestational age and trimester at screening, cytology at colposcopy referral, interval days until colposcopy, and biopsy histology. RESULTS: 1063 patients were identified, with 40.8% of patients who completed referred colposcopy. Patient characteristics predictive for colposcopy follow up included: maternal age at referral cervical cytology >30 years (1.67; 1.27-2.20; < 0.003), gestational age < 18 weeks at abnormal cervical cytology (1.57; 1.23-2.01; <0.0002), maternal race non-African American (2.20; 1.32-3.65; <0.0024) and with high grade cervical cytology (2.42; 1.81-3.24; <0.0001). CONCLUSION: In this population, inadequate follow up for abnormal cervical cytology during pregnancy is prominent, especially among those with younger maternal age, African American (AA) race, cervical cytology completed at later gestational ages of pregnancy, and low-grade initial cytology. Higher no-show rate among AA patients supports well-documented health disparities and need for further investigation and protocols to identify those at risk for loss to follow up.
RESUMO
Ancestral sequence reconstruction (ASR) is a still-burgeoning method that has revealed many key mechanisms of molecular evolution. One criticism of the approach is an inability to validate its algorithms within a biological context as opposed to a computer simulation. Here we build an experimental phylogeny using the gene of a single red fluorescent protein to address this criticism. The evolved phylogeny consists of 19 operational taxonomic units (leaves) and 17 ancestral bifurcations (nodes) that display a wide variety of fluorescent phenotypes. The 19 leaves then serve as 'modern' sequences that we subject to ASR analyses using various algorithms and to benchmark against the known ancestral genotypes and ancestral phenotypes. We confirm computer simulations that show all algorithms infer ancient sequences with high accuracy, yet we also reveal wide variation in the phenotypes encoded by incorrectly inferred sequences. Specifically, Bayesian methods incorporating rate variation significantly outperform the maximum parsimony criterion in phenotypic accuracy. Subsampling of extant sequences had minor effect on the inference of ancestral sequences.
