Fertility Preservation Outcomes in Adolescent and Young Adult Feminizing Transgender Patients.

BACKGROUND: Fertility preservation enables patients undergoing gonadotoxic therapies to retain the potential for biological children and now has broader implications in the care of transgender individuals. Multiple medical societies recommend counseling on fertility preservation before initiating therapy for gender dysphoria; however, outcome data pre- and posttreatment are limited in feminizing transgender adolescents and young adults. METHODS: The University of Pittsburgh Institutional Research Board approved this study. Data were collected retrospectively on transgender patients seeking fertility preservation between 2015 and 2018, including age at initial consultation and semen analysis parameters. RESULTS: Eleven feminizing transgender patients accepted a referral for fertility preservation during this time; consultation occurred at median age 19 (range 16-24 years). Ten patients attempted and completed at least 1 semen collection. Eight patients cryopreserved semen before initiating treatment. Of those patients, all exhibited low morphology with otherwise normal median semen analysis parameters. In 1 patient who discontinued leuprolide acetate to attempt fertility preservation, transient azoospermia of 5 months' duration was demonstrated with subsequent recovery of spermatogenesis. In a patient who had previously been treated with spironolactone and estradiol, semen analysis revealed persistent azoospermia for the 4 months leading up to orchiectomy after discontinuation of both medications. CONCLUSIONS: Semen cryopreservation is a viable method of fertility preservation in adolescent and young adult transgender individuals and can be considered in patients who have already initiated therapy for gender dysphoria. Further research is needed to determine the optimal length of time these therapies should be discontinued to facilitate successful semen cryopreservation.

Conception rates and contraceptive use after bariatric surgery among women with infertility: Evidence from a prospective multicenter cohort study.

BACKGROUND: Lack of prospective trials have resulted in a dearth of information regarding postbariatric surgery conception rates in women with a preoperative history of infertility. OBJECTIVE: To examine associations between preoperative history of infertility and postbariatric surgery conception. SETTING: A multicenter cohort study at 10 United States hospitals (2006-2009). METHODS: Participants completed a preoperative reproductive health questionnaire, with annual postoperative assessments for up to 7 years until January 2015. This report was restricted to women 18- to 44-years old with no history of menopause, hysterectomy, or hormone replacement therapy. The primary outcomes were postoperative (0 to <90 mo) conception rate, early conception rate (0 < 18 mo), and postoperative unprotected intercourse with a male partner while not trying to conceive. RESULTS: Of 740 eligible women, 650 (87.8%) provided required responses. Median interquartile range (IQR) preoperative age was 34 (30-39) years and follow-up was 6.5 (5.9-7.0) years. Nulliparous women with a preoperative history of infertility represented 8.0% (52/650) of the total cohort, 63.5% (33/52) of whom had never conceived. Compared with women without this history, these women had a higher postoperative conception rate (121.2 [95% confidence interval (CI), 102.3-143.5]/1000 versus 47.0 [95%CI, 34.2-62.9]/1000 woman-yr; P < .001), early conception rate (115.4 [95%CI, 96.1-138.5]/1000 versus 33.9 [95%CI, 23.6-47.1]/1,000 woman-yr; P < .01), and a higher risk of unprotected intercourse (ARR 1.48 [95% CI, 1.14-1.90], P = 0.003). CONCLUSION: After bariatric surgery, preoperative history of infertility and nulliparity was associated higher conception rates and unprotected intercourse.

Biologic therapeutics and molecular profiling to optimize wound healing.

Non-healing wounds represent a significant cause of morbidity and mortality for a large portion of the adult population. Wounds that fail to heal are entrapped in a self-sustaining cycle of chronic inflammation leading to the destruction of the extracellular matrix. Among cancer patients, malnutrition, radiation, physical dehabilitation, chemotherapy, and the malignancy itself increase the likelihood of chronic wound formation, and these co-morbidity factors inhibit the normal wound healing process. Current wound treatments are aimed at some, but not all, of the underlying causes responsible for delayed healing of wounds. These impediments block the normal processes that allow normal progression through the specific stages of wound healing. This review summarizes the current information regarding the management and treatment of complex wounds that fail to heal normally and offers some insights into novel future therapies [Menke N, Ward KR, Diegelmann R. Non-healing wounds. Emerg Med Rep 2007; 28(4).,Menke NB, Ward KR, Witten TM, Bonchev DG, Diegelmann RF. Impaired wound healing. Clin Dermatol 2007;25:19-25].

Geographic access to assisted reproductive technology health care in the United States: a population-based cross-sectional study.

OBJECTIVE: To evaluate the geographic distribution of assisted reproductive technology (ART) clinics and the number of ART clinics within U.S. Census metropolitan areas and to estimate the number of reproductive-age women who have geographic access to ART services in the United States. DESIGN: A population-based cross-sectional study. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of U.S. reproductive-age women living in areas with no ART clinic, a single ART clinic, or more than one ART clinic. RESULT(S): There were 510 ART clinics in the United States in 2009-2013. Multiple ART clinics were present in 76 metropolitan areas (median population of 1.45 million people), where a total of 442 clinics were located. A single ART clinic was present in 68 metropolitan areas (median population of 454,000 people). Among U.S. reproductive-age women in 2010, 38.1 million (60.4% of the U.S. population) lived in an area with multiple ART clinics, 6.8 million (10.8% of the U.S. population) lived in an area with a single clinic, and 18.2 million (28.8% of the U.S. population) lived in an area (metropolitan and nonmetropolitan) with no ART clinics. CONCLUSION(S): Nearby geographic access to ART services is limited or absent for more than 25 million reproductive-age women (39.6% of the U.S. population) in the United States. This population estimate should spur continued policy and technological progress to increase access to ART services.

Contraception and Conception After Bariatric Surgery.

OBJECTIVE: To examine contraceptive practices and conception rates after bariatric surgery. METHODS: The Longitudinal Assessment of Bariatric Surgery-2 is a multicenter, prospective cohort study of adults undergoing first-time bariatric surgery as part of routine clinical care at 10 U.S. hospitals. Recruitment occurred between 2005 and 2009. Participants completed preoperative and annual postsurgical assessments for up to 7 years until January 2015. This report was restricted to women 18-44 years old with no history of menopause, hysterectomy, or estrogen and progesterone therapy. Primary outcomes were self-reported contraceptive practices, overall conception rate, and early (less than 18 months) postsurgical conception. Contraceptive practice (no intercourse, protected intercourse, unprotected intercourse, or tried to conceive) was classified based on the preceding year. Conception rates were determined from self-reported pregnancies. RESULTS: Of 740 eligible women, 710 (95.9%) completed follow-up assessment(s). Median (interquartile range) preoperative age was 34 (30-39) years. In the first postsurgical year, 12.7% (95% CI 9.4-16.0) of women had no intercourse, 40.5% (95% CI 35.6-45.4) had protected intercourse only, 41.5% (95% CI 36.4-46.6) had unprotected intercourse while not trying to conceive, and 4.3% (95% CI 2.4-6.3) tried to conceive. The prevalence of the first three groups did not significantly differ across the 7 years of follow-up (P for all >.05); however, more women tried to conceive in the second year (13.1%, 95% CI 9.3-17.0; P<.001). The conception rate was 53.8 (95% CI 40.0-71.1) per 1,000 woman-years across follow-up (median [interquartile range] 6.5 [5.9-7.0] years); 42.3 (95% CI 30.2-57.6) per 1,000 woman-years in the 18 months after surgery. Age (adjusted relative risk 0.41 [95% CI 0.19-0.89] per 10 years, P=.03), being married or living as married (adjusted relative risk 4.76 [95% CI 2.02-11.21], P<.001), and rating future pregnancy as important preoperatively (adjusted relative risk 8.50 [95% CI 2.92-24.75], P<.001) were associated with early conception. CONCLUSIONS: Postsurgical contraceptive use and conception rates do not reflect recommendations for an 18-month delay in conception after bariatric surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00465829.

Impact of Reduced ATGL-Mediated Adipocyte Lipolysis on Obesity-Associated Insulin Resistance and Inflammation in Male Mice.

Emerging evidence suggests that impaired regulation of adipocyte lipolysis contributes to the proinflammatory immune cell infiltration of metabolic tissues in obesity, a process that is proposed to contribute to the development and exacerbation of insulin resistance. To test this hypothesis in vivo, we generated mice with adipocyte-specific deletion of adipose triglyceride lipase (ATGL), the rate-limiting enzyme catalyzing triacylglycerol hydrolysis. In contrast to previous models, adiponectin-driven Cre expression was used for targeted ATGL deletion. The resulting adipocyte-specific ATGL knockout (AAKO) mice were then characterized for metabolic and immune phenotypes. Lean and diet-induced obese AAKO mice had reduced adipocyte lipolysis, serum lipids, systemic lipid oxidation, and expression of peroxisome proliferator-activated receptor alpha target genes in adipose tissue (AT) and liver. These changes did not increase overall body weight or fat mass in AAKO mice by 24 weeks of age, in part due to reduced expression of genes involved in lipid uptake, synthesis, and adipogenesis. Systemic glucose and insulin tolerance were improved in AAKO mice, primarily due to enhanced hepatic insulin signaling, which was accompanied by marked reduction in diet-induced hepatic steatosis as well as hepatic immune cell infiltration and activation. In contrast, although adipocyte ATGL deletion reduced AT immune cell infiltration in response to an acute lipolytic stimulus, it was not sufficient to ameliorate, and may even exacerbate, chronic inflammatory changes that occur in AT in response to diet-induced obesity.