Pathways to fatherhood: evaluating the priorities of self-identified gay and bisexual men pursuing family building options.

Objective: To assess the priorities and decisions of gay and bisexual men pursuing fatherhood. Design: Cross-sectional study. Setting: Internet-based survey. Patients: Gay and bisexual men who were interested in pursuing or had previously pursued family building options. Interventions: None. Main Outcome Measures: This study aimed to assess the attitudes of respondents regarding the following: mode of achieving parenthood and the relative importance of a genetic link to offspring; the relative importance of factors considered when selecting an oocyte donor (OD); and the relative importance of factors associated with selecting a gestational carrier (GC). Access to care and financial considerations were also analyzed. Results: Of the 110 respondents, most (68.2%) desired parenthood via an OD and GC. This was consistent with 53.2% of respondents reporting that a genetic link to a child was "extremely important" or "important." Most couples (86.6%) desired to use sperm from both partners. In addition, 40.5% of respondents reported that a twin gestation would be the most ideal pregnancy outcome. Medical history was considered the most important factor when selecting an OD (83.5%), whereas pregnancy history was considered the most important selection criterion for a GC (86.2%). Furthermore, 89.1% of respondents reported that the fertility services they desired were available to them, although 33.0% reported they would have to travel to another state for care. Conclusions: Understanding the circumstances of gay and bisexual men pursuing fatherhood allows for individualized care. Since several respondents desired twin pregnancies, it is important to counsel patients regarding the risks of multiple gestation and determine the motivations for this preference.

The efficacy of add-ons: selected IVF "add-on" procedures and future directions.

Since the advent of ART, technology has continuously evolved to improve embryology and pregnancy outcomes. However, not all technologies that are integrated into practice have convincing evidence of clinical effectiveness, and they often increase the financial burden of fertility care. We discuss here a selection of commonly utilized IVF "add-ons" and discuss the existing evidence for their utility. The procedures included in this review are time-lapse imaging of embryos, assisted hatching, EmbryoGlue, sperm DNA testing, egg activation with calcium ionophore, endometrial receptivity array, and physiological intracytoplasmic sperm injection (PICSI). While there is rather limited supporting evidence for nearly all IVF add-ons that we reviewed, there is strong demand from patients, physicians, and the biotechnology industry to continue further research and development in this arena. We propose that all add-on procedures should provide true efficacy for the patient, and reproductive endocrinologists should inform patients of the costs and benefits of utilizing various technologies before they undergo treatment. In the future, add-ons that show clear evidence of efficacy and justifiable cost should be incorporated into routine practice, while others that do not meet these criteria should be phased out entirely.

Infertility treatment and the risk of small for gestational age births: a population-based study in the United States.

OBJECTIVE: To evaluate the association between infertility treatments and small for gestational age (SGA) births. DESIGN: Cross-sectional study. SETTING: United States, 2015-2019. PATIENTS: Women (n = 16,836,228) who delivered nonmalformed, singleton live births (24-44 weeks' gestation). INTERVENTIONS: Any infertility treatment, including assisted reproductive technology (ART) and prescribed fertility-enhancing medications. MAIN OUTCOME MEASURES: Small for gestational age birth, defined as sex-specific birth weight <10% for gestational age. Associations between SGA and infertility treatment were derived from Poisson regression with robust variance. Risk ratios (RR) and 95% confidence intervals (CI) were derived after adjusting for confounders. In a sensitivity analysis, we corrected for nondifferential exposure misclassification and unmeasured confounding biases. RESULTS: Subsequently, 1.4% (n = 231,177) of pregnancies resulted from infertility treatments (0.8% ART and 0.6% fertility-enhancing medications). Of these, SGA births occurred in 9.4% (n = 21,771) and 11.9% (n = 1,755,925) of pregnancies conceived with infertility treatment and naturally conceived pregnancies, respectively (adjusted RR, 1.07; 95% CI, 1.06, 1.08). However, after correction for misclassification bias and unmeasured confounding, infertility treatment was associated with a 27% reduced risk of SGA (bias-corrected RR, 0.73; 95% CI, 0.53, 0.85). Similar trends were seen for analyses stratified by exposure to ART and fertility-enhancing medications, as well as for SGA <5th and <3rd percentiles. CONCLUSIONS: Exposure to infertility treatment is associated with a reduced risk of SGA births. These findings, which are contrary to some published reports, may reflect changes in the modern practice of infertility care, maternal lifestyle, and compliance with prenatal care within the infertile population. Until these findings are corroborated, the associations must be cautiously interpreted.

Individual culture leads to decreased blastocyst formation but does not affect pregnancy outcomes in the setting of a single, vitrified-warmed euploid blastocyst transfer.

PURPOSE: To evaluate embryology and pregnancy outcomes following individual and group embryo culture in the setting of contemporary laboratory practices and freeze-all cycles. METHODS: Patients underwent ovarian stimulation followed by intracytoplasmic sperm injection (ICSI). Embryos proceeded through individual culture and then underwent preimplantation genetic testing for aneuploidy (PGT-A) via trophectoderm biopsy. In a subsequent cycle, participants underwent single embryo transfer of a vitrified-warmed, euploid embryo. Outcomes were compared to controls undergoing group culture during the same time frame. The Mann-Whitney U test and logistic regression models were utilized. RESULTS: Outcomes were assessed for 144 patients whose embryos underwent individual culture and 449 controls whose embryos underwent group culture. There were no significant differences in fertilization rates between groups (81.7% for individual culture vs. 84.1% for group culture, p = 0.22). However, individual culture was associated with a decreased rate of blastocyst formation compared to group culture (43.5% vs. 48.5%, p < 0.01). Following single, vitrified-warmed euploid blastocyst transfer, there were no significant differences between individual culture and group culture, respectively, in rates of positive ßhCG (81.9% vs. 81.5%, p = 0.91), sustained implantation (63.9% vs. 65.0%, p = 0.80), biochemical miscarriage (16.7% vs. 12.3%, p = 0.18), or clinical miscarriage (1.4% vs. 4.2%, p = 0.13). CONCLUSION: While individual culture appears to negatively impact the rate of usable blastocyst formation compared to group culture, there were no significant differences in pregnancy outcomes following transfer of a single, vitrified-warmed euploid blastocyst.

Anti-Cancer Tumor Cell Necrosis of Epithelial Ovarian Cancer Cell Lines Depends on High Expression of HDM-2 Protein in Their Membranes.

OBJECTIVE: Patients with epithelial ovarian cancers experience the highest fatality rates among all gynecological malignancies which require development of novel treatment strategies. Tumor cell necrosis was previously reported in a number of cancer cell lines following treatment with a p53-derived anti-cancer peptide called PNC-27. This peptide induces necrosis by transmembrane pore formation with HDM-2 protein that is expressed in the cancer cell membrane. We aimed to extend these studies further by investigating expression of membrane HDM-2 protein in ovarian cancer as it relates to susceptibility to PNC-27. PROCEDURES: Herein, we measured HDM-2 membrane expression in two ovarian cancer cell lines (SKOV-3 and OVCAR-3) and a non-transformed control cell line (HUVEC) by flow cytometric and western blot analysis. Immunofluorescence was used to visualize colocalization of PNC-27 with membrane HDM-2. Treatment effects with PNC-27 and control peptide were assessed using a MTT cell proliferation assay while direct cytotoxicity was measured by lactate dehydrogenase (LDH) release and induction of apoptotic markers; annexin V and caspase-3. RESULTS: HDM-2 protein was highly expressed and frequently detected in the membranes of SKOV-3 and OVCAR-3 cells; a prominent 47.6 kDa HDM-2 plasma membrane isoform was present in both cell lines whereas 25, 29, and 30 kDa isoforms were preferentially expressed in OVCAR-3. Notably, PNC-27 colocalized with HDM-2 in the membranes of both cancer cell lines that resulted in rapid cellular necrosis. In contrast, no PNC-27 colocalization and cytotoxicity was observed with non-transformed HUVEC demonstrating minimal expression of membrane HDM-2. CONCLUSIONS: Our results suggest that HDM-2 is highly expressed in the membranes of these ovarian cancer cell lines and colocalizes with PNC-27. We therefore conclude that the association of PNC-27 with preferentially expressed membrane HDM-2 isoforms results in the proposed model for the formation of transmembrane pores and epithelial ovarian cancer tumor cell necrosis, as previously described in a number of solid tissue and hematologic malignancies.

Detection of Arytenoid Dislocation Using Pixel-valued Cuneiform Movement.

OBJECTIVES: This study aims to assess utility of pixel-valued movement software in detecting arytenoid dislocation preoperatively. STUDY DESIGN: This is a retrospective analysis. METHODS: Twenty-seven patients diagnosed with unilateral arytenoid dislocation were included. Diagnosis of arytenoid dislocation was confirmed by lack of vocal fold paralysis on preoperative laryngeal electromyography and by intraoperative findings of cricoarytenoid dislocation. A region-tracking software algorithm developed by Zhuang et al was used to analyze 27 preoperative endoscopic videos of patients diagnosed with arytenoid dislocation. Vector analysis measuring cuneiform movement during inspiration was used as an indirect measure of arytenoid movement. Values were normalized using vocal fold length. Two raters blinded to diagnosis of arytenoid dislocation measured vocal fold length and cuneiform movement on both the dislocated and the nondislocated sides. RESULTS: A Wilcoxon signed-rank test indicated that the mean pixel-valued cuneiform movement and standard deviation (SD) were greater for nondislocated (159.24, SD = 73.35) than for dislocated (92.49, SD = 72.11) arytenoids (Z = 3.29, P = 0.001). The interrater correlation coefficient was 0.87 for the dislocated side and 0.75 for the nondislocated side. The intrarater correlation coefficient was 0.87 for the dislocated side and 0.91 for the nondislocated side. The receiver operating characteristic curve revealed an area under the curve between 0.76 and 0.83 (95% confidence interval 0.63-0.90). Analysis by the first and second raters revealed misdiagnosis of laterality of arytenoid dislocation in four and six patients, respectively. CONCLUSIONS: The software program developed by Zhuang et al provides a high-degree of precision, with good interrater and intrarater correlation coefficients. However, high rates of misdiagnosis of arytenoid dislocation and the laborious analysis process using this software program make it of limited utility as a clinical diagnostic tool in its present state.

Mast cells are required for full expression of allergen/SEB-induced skin inflammation.

Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease. We recently described an animal model in which repeated epicutaneous applications of a house dust mite extract and Staphylococcal enterotoxin B induced eczematous skin lesions. In this study we showed that global gene expression patterns are very similar between human AD skin and allergen/staphylococcal enterotoxin B-induced mouse skin lesions, particularly in the expression of genes related to epidermal growth/differentiation, skin barrier, lipid/energy metabolism, immune response, or extracellular matrix. In this model, mast cells and T cells, but not B cells or eosinophils, were shown to be required for the full expression of dermatitis, as revealed by reduced skin inflammation and reduced serum IgE levels in mice lacking mast cells or T cells (TCRß(-/-) or Rag1(-/-)). The clinical severity of dermatitis correlated with the numbers of mast cells, but not eosinophils. Consistent with the idea that T helper type 2 (Th2) cells play a predominant role in allergic diseases, the receptor for the Th2-promoting cytokine thymic stromal lymphopoietin and the high-affinity IgE receptor, FcɛRI, were required to attain maximal clinical scores. Therefore, this clinically relevant model provides mechanistic insights into the pathogenic mechanism of human AD.