Marfan syndrome is associated with increased risk for gynecologic disorders and maternal complications.

PURPOSE: To determine whether patients with Marfan syndrome are at an increased risk for reproductive disorders. METHODS: This retrospective cohort study was conducted using the US collaborative network on the TriNetX research network of health care organizations. We included female patients aged 18-44 and identified a cohort of 4347 patients with Marfan syndrome (ICD-10 Q87.4). Our control cohort consisted of 16,424,990 patients without a diagnosis of Marfan syndrome or Ehlers-Danlos syndrome (ICD-10 Q79.6). The primary outcomes included gynecologic diagnoses such as dysmenorrhea and endometriosis, and our secondary outcomes included urogynecologic, fertility, and obstetric outcomes, all identified by ICD-10 codes. We conducted a relative risk analysis with a p-value of <0.05 considered significant. RESULTS: Patients with Marfan syndrome were at an increased risk for pelvic and perineal pain, dysmenorrhea, abnormal uterine bleeding, endometriosis (all p <0.0001), dyspareunia (p =0.0009), leiomyoma (p =0.0076), polyp of female genital tract (p =0.016), urinary incontinence (p <0.0001), female genital prolapse (p =0.0006), fertility testing (p =0.0075), cesarean delivery (p =0.0003), gestational hypertension (p =0.0012), and pre-eclampsia (p =0.0024) compared to the control group following an adjusted, matched comparison. CONCLUSIONS: Patients with Marfan syndrome have an increased risk of numerous reproductive disorders and obstetric complications compared to patients without this diagnosis.

Pelvic Floor Dysfunction Among Persons With Marfan and Loeys-Dietz Syndrome.

IMPORTANCE: Connective tissue disorders are proposed in the literature to be predisposing risk factors for pelvic floor disorders. Prior data characterizing the prevalence of and symptom burden related to pelvic floor disorders are limited for individuals with Marfan syndrome and are nonexistent for those with Loeys-Dietz syndrome. OBJECTIVE: The objective of this study was to determine the prevalence and severity of symptoms related to pelvic floor disorders among individuals with Marfan syndrome and Loeys-Dietz syndrome using the Pelvic Floor Distress Inventory-20 (PFDI-20). STUDY DESIGN: In this cross-sectional study, a survey including the PFDI-20 was administered to biologically female individuals older than 18 years with a confirmed diagnosis of Marfan syndrome or Loeys-Dietz Syndrome. Respondents were solicited through the websites, email lists, and social media forums of The Marfan Foundation and The Loeys-Dietz syndrome Foundation. RESULTS: A total of 286 respondents were included in the final analysis, 213 with Marfan syndrome and 73 with Loeys-Dietz syndrome. The median PFDI-20 score of the cohort was 43.8. Individuals with Loeys-Dietz syndrome had higher PFDI-20 scores and were more likely to have established risk factors for pelvic floor disorders that correlated with their PFDI-20 scores compared with those with Marfan syndrome. CONCLUSIONS: Respondents with Marfan syndrome and Loeys-Dietz syndrome experience a high burden of symptoms related to pelvic floor disorders. Despite the similar pathophysiology and clinical manifestations of these disorders, there were differences in PFDI-20 responses that may suggest that these diseases differ in the ways they affect the pelvic floor.

An exploratory study comparing the quality of contraceptive counseling provided via telemedicine versus in-person visits.

OBJECTIVE: Telemedicine for contraceptive services is purported to improve contraceptive access, yet few studies assess the quality of contraceptive counseling provided remotely. We assessed the quality of contraceptive counseling during telemedicine and office visits. STUDY DESIGN: We conducted a cross-sectional study at Cleveland Clinic Women's Health Institute to compare contraceptive counseling quality between telemedicine (synchronous video) and office visits. We identified eligible patients through ambulatory encounters with primary contraceptive management or counseling ICD-10 codes. Respondents completed a survey assessing demographics, quality of contraceptive counseling, contraceptive method choice, an affinity for technology, and attitudes toward telemedicine. We used the validated Interpersonal Quality of Family Planning (IQFP) scale to assess counseling quality. We used the Wilcoxon rank-sum test, Pearson's chi-square test and Fisher's exact test to compare baseline characteristics. RESULTS: Of all eligible patients, 110 of 380 (29%) completed the survey. Of those who were successfully contacted by phone or mail, 110 of 201 (55%) completed the survey. The IQFP scores were 'high quality' for 28 of 52 (54%) of telemedicine-visit respondents vs 37 of 58 (64%) of office-visit respondents (p = 0.29). The birth control pill was the most popular method, chosen by 27 of 52 (52%) of telemedicine-visit respondents and 24 of 58 (41%) of office-visit respondents (p = 0.27). Telemedicine respondents identified ease of communication and less scheduling difficulty as factors that promote telemedicine use. Office-visit respondents identified privacy and communication concerns as factors that deter telemedicine use. CONCLUSION: When patients self-select the encounter type, their assessment of the quality of contraceptive counseling among telemedicine and office visits is similar, with no statistically significant differences in the contraceptive method chosen. Results from this single-center study support the integration of telemedicine in contraceptive service provision. IMPLICATIONS: The quality of contraceptive counseling is similar among telemedicine and office visits. Telemedicine visits for contraceptive counseling should be routinely offered, and existing services should be expanded.

Suppression of premature transcription termination leads to reduced mRNA isoform diversity and neurodegeneration.

Tight regulation of mRNA isoform expression is essential for neuronal development, maintenance, and function; however, the repertoire of proteins that govern isoform composition and abundance remains incomplete. Here, we show that the RNA kinase CLP1 regulates mRNA isoform expression through suppression of proximal cleavage and polyadenylation. We found that human stem-cell-derived motor neurons without CLP1 or with the disease-associated CLP1 p.R140H variant had distinct patterns of RNA-polymerase-II-associated cleavage and polyadenylation complex proteins that correlated with polyadenylation site usage. These changes resulted in imbalanced mRNA isoform expression of long genes important for neuronal function that were recapitulated in vivo. Strikingly, we observed the same pattern of reduced mRNA isoform diversity in 3' end sequencing data from brain tissues of patients with neurodegenerative disease. Together, our results identify a previously uncharacterized role for CLP1 in mRNA 3' end formation and reveal an mRNA misprocessing signature in neurodegeneration that may suggest a common mechanism of disease.

Efficient GFP-labeling and analysis of spermatogenic cells using the IRG transgene and flow cytometry.

Spermatogenesis is a highly ordered developmental program that produces haploid male germ cells. The study of male germ cell development in the mouse has provided unique perspectives into the molecular mechanisms that control cell development and differentiation in mammals, including tissue-specific gene regulatory programs. An intrinsic challenge in spermatogenesis research is the heterogeneity of germ and somatic cell types present in the testis. Techniques to separate and isolate distinct mouse spermatogenic cell types have great potential to shed light on molecular mechanisms controlling mammalian cell development, while also providing new insights into cellular events important for human reproductive health. Here, we detail a versatile strategy that combines Cre-lox technology to fluorescently label germ cells, with flow cytometry to discriminate and isolate germ cells in different stages of development for cellular and molecular analyses.