Kenan Omurtag

Decreased Spermatogenesis, Fertility, and Altered Slc2A Expression in Akt1−/− and Akt2−/− Testes and Sperm:

Akt is serine/threonine protein kinase associated with various cellular processes and 3 different isoforms exist. This work describes the reproductive phenotype of Akt1−/− and Akt2−/− in male mice. The seminiferous tubule diameter in Akt1−/− testes was less than wild-type or Akt2−/− testes. The expression of phospho-phosphatase and tensin homologue deleted on chromosome 10 (p-PTEN) and phospho-glycogen synthase kinase 3β (GSK-3β) was elevated in Akt1−/− testes. Alterations in expression and localization to the plasma membrane of several facilitative glucose transporters (Slc2a8, 9a and 9b) were detected in these knockout compared to wild-type mice. Apoptotic sperm were more prevalent in both null mice compared to wild-type mice, whereas sperm concentration and motility were significantly lower in the null sperm. Finally, Akt2−/− sperm had a markedly decreased fertilization rate by in vitro fertilization (IVF) and resulting embryos displayed increased fragmentation and poor growth. These results suggest that altered SLC2A expression and increased PTEN and GSK3β activity may be responsible for the decreased spermatogenesis, sperm maturation, and fertilization in the Akt1−/− and Akt2−/− male mice.

Cycle cancellation and pregnancy after luteal estradiol priming in women defined as poor responders: a systematic review and meta-analysis

STUDY QUESTION Does a luteal estradiol (LE) stimulation protocol improve outcomes in poor responders to IVF? SUMMARY ANSWER LE priming is associated with decreased cycle cancellation and increased chance of clinical pregnancy in poor responders WHAT IS KNOWN ALREADY Poor responders to IVF are one of the most challenging patient populations to treat. Many standard protocols currently exist for stimulating these patients but all have failed to improve outcomes. STUDY DESIGN, SIZE, DURATION Systematic review and meta-analysis including eight published studies comparing assisted reproduction technology (ART) outcomes in poor responders exposed to controlled ovarian hyperstimulation with and without LE priming. A search of the databases MEDLINE, EMBASE and PUBMED was carried out for studies in the English language published up to January 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS Studies evaluating women defined as poor responders to ART were evaluated. These studies were identified following a systematic review of the literature and data were analyzed using the DerSimonian-Laird random effects model. The main outcomes of interest were cycle cancellation rate and clinical pregnancy. Although the definition of clinical pregnancy varied between studies, the principal definition included fetal cardiac activity as assessed by transvaginal ultrasonography after 5 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE A total of 2249 publications were identified from the initial search, and the bibliographies, abstracts and other sources yielded 11 more. After excluding duplications, 1227 studies remained and 8 ultimately met the inclusion criteria. Compared with women undergoing non-LE primed protocols (n = 621), women exposed to LE priming (n = 468) had a lower risk of cycle cancellation [relative risk (RR): 0.60, 95% confidence interval (CI): 0.45-0.78] and an improved chance of clinical pregnancy (RR: 1.33, 95% CI: 1.02-1.72). There was no significant improvement in the number of mature oocytes obtained or number of zygotes obtained per cycle. LIMITATIONS, REASONS FOR CAUTION These findings are limited by the body of literature currently available. As the poor responder lacks a concrete definition, there is some heterogeneity to these results, which merits caution when applying our findings to individual patients. Furthermore, the increased clinical pregnancy rate demonstrated when using the LE protocol may be principally related to the decreased cycle cancellation rate. WIDER IMPLICATIONS OF THE FINDINGS The LE protocol may be of some utility in the poor responder to IVF and may increase clinical pregnancy rates in this population by improving stimulation and thereby decreasing cycle cancellation. STUDY FUNDING/COMPETING INTERESTS NIH K12 HD063086 (ESJ, MGT), NIH T32 HD0040135-11 (KAR), F32 HD040135-10 NIH (KRO), 5K12HD000849-25 (PTJ). No competing interests.

Nanoparticle incorporation of melittin reduces sperm and vaginal epithelium cytotoxicity

Melittin is a cytolytic peptide component of bee venom which rapidly integrates into lipid bilayers and forms pores resulting in osmotic lysis. While the therapeutic utility of free melittin is limited by its cytotoxicity, incorporation of melittin into the lipid shell of a perfluorocarbon nanoparticle has been shown to reduce its toxicity in vivo. Our group has previously demonstrated that perfluorocarbon nanoparticles containing melittin at concentrations <10 µM inhibit HIV infectivity in vitro. In the current study, we assessed the impact of blank and melittin-containing perfluorocarbon nanoparticles on sperm motility and the viability of both sperm and vaginal epithelial cells. We found that free melittin was toxic to sperm and vaginal epithelium at concentrations greater than 2 µM (p<0.001). However, melittin nanoparticles were not cytotoxic to sperm (p = 0.42) or vaginal epithelium (p = 0.48) at an equivalent melittin concentration of 10 µM. Thus, nanoparticle formulation of melittin reduced melittin cytotoxicity fivefold and prevented melittin toxicity at concentrations previously shown to inhibit HIV infectivity. Melittin nanoparticles were toxic to vaginal epithelium at equivalent melittin concentrations ≥20 µM (p<0.001) and were toxic to sperm at equivalent melittin concentrations ≥40 µM (p<0.001). Sperm cytotoxicity was enhanced by targeting of the nanoparticles to the sperm surface antigen sperm adhesion molecule 1. While further testing is needed to determine the extent of cytotoxicity in a more physiologically relevant model system, these results suggest that melittin-containing nanoparticles could form the basis of a virucide that is not toxic to sperm and vaginal epithelium. This virucide would be beneficial for HIV serodiscordant couples seeking to achieve natural pregnancy.

The affordable care act's impact on fertility care.

The Supreme Courts decision upholding the constitutionality of the Affordable Care Act (ACA) provides an opportunity to review its impact on fertility care in the United States. After examining the legislation, we identified several core areas that might affect patients struggling with infertility. Although changes to the tax code, elimination of denying insurance to those with pre-existing conditions, and an overriding theme of maternity care within the ACA are easy to qualify and quantify, due to the incremental nature of the ACA, it remains to be seen whether the ACA will alter the current status quo of access to fertility care.

Sperm Recovery and IVF after Testicular Sperm Extraction (TESE): Effect of Male Diagnosis and Use of Off-Site Surgical Centers on Sperm Recovery and IVF

Objective Determine whether testicular sperm extractions and pregnancy outcomes are influenced by male and female infertility diagnoses, location of surgical center and time to cryopreservation. Patients One hundred and thirty men undergoing testicular sperm extraction and 76 couples undergoing 123 in vitro fertilization cycles with testicular sperm. Outcome Measures Successful sperm recovery defined as 1–2 sperm/0.5 mL by diagnosis including obstructive azoospermia (n = 60), non-obstructive azoospermia (n = 39), cancer (n = 14), paralysis (n = 7) and other (n = 10). Obstructive azoospermia was analyzed as congenital absence of the vas deferens (n = 22), vasectomy or failed vasectomy reversal (n = 37) and “other”(n = 1). Sperm recovery was also evaluated by surgical site including infertility clinic (n = 54), hospital operating room (n = 67) and physician’s office (n = 11). Treatment cycles were evaluated for number of oocytes, fertilization, embryo quality, implantation rate and clinical/ongoing pregnancies as related to male diagnosis, female diagnosis, and use of fresh or cryopreserved testicular sperm. Results Testicular sperm recovery from azoospermic males with all diagnoses was high (70 to 100%) except non-obstructive azoospermia (31%) and was not influenced by distance from surgical center to laboratory. Following in vitro fertilization, rate of fertilization was significantly lower with non-obstructive azoospermia (43%, p = <0.0001) compared to other male diagnoses (66%, p = <0.0001, 59% p = 0.015). No differences were noted in clinical pregnancy rate by male diagnosis; however, the delivery rate per cycle was significantly higher with obstructive azoospermia (38% p = 0.0371) compared to diagnoses of cancer, paralysis or other (16.7%). Women diagnosed with diminished ovarian reserve had a reduced clinical pregnancy rate (7.4% p = 0.007) compared to those with other diagnoses (44%). Conclusion Testicular sperm extraction is a safe and effective option regardless of the etiology of the azoospermia. The type of surgical center and/or its distance from the laboratory was not related to success. Men with non-obstructive azoospermia have a lower chance of successful sperm retrieval and fertilization.

Modeling the Effect of Cigarette Smoke on Hexose Utilization in Spermatocytes

We set out to determine whether the addition of an aryl hydrocarbon receptor (AHR) antagonist has an effect on glucose/fructose utilization in the spermatocyte when exposed to cigarette smoke condensate (CSC). We exposed male germ cells to 5 and 40 μg/mL of CSC ± 10 μmol/L of AHR antagonist at various time points. Immunoblot expression of specific glucose/fructose transporters was compared to control. Radiolabeled uptake of 2-deoxyglucose (2-DG) and fructose was also performed. Spermatocytes utilized fructose nearly 50-fold more than 2-DG. Uptake of 2-DG decreased after CSC + AHR antagonist exposure. Glucose transporters (GLUTs) 9a and 12 declined after CSC + AHR antagonist exposure. Synergy between CSC and the AHR antagonist in spermatocytes may disrupt the metabolic profile in vitro. Toxic exposures alter energy homeostasis in early stages of male germ cell development, which could contribute to later effects explaining decreases in sperm motility in smokers.

Spanish language content on reproductive endocrinology and infertility practice websites

OBJECTIVE To analyze the use of Spanish language translation on the websites of reproductive endocrinology and infertility (REI) practices in the context of evidence of underuse of infertility services by minority populations. DESIGN Cross-sectional survey of websites from REI practices. SETTING Not applicable. PATIENT(S) None. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Assessment of the relationship between having a Spanish-translated website and REI practice characteristics. Variables included concurrent use of social media, size of the practice, Spanish-speaking practitioner in the practice, being a private or a university-based practice, being in a mandated insurance state, and being in an area with different levels of percentage of Hispanic population, adjusted for annual income levels of the population. RESULT(S) Of the 376 REI practice websites analyzed, 101 (27%) offered at least some information in Spanish. We identified 97 Spanish-speaking practitioners at 71 REI practices. Having a Spanish-translated website was significantly associated with the practices use of social media, having an international/out-of-town web page, and having a Spanish-speaking physician in the practice. The size of the practice, as measured in number of cycles reported per year, was not associated with having a translated website. In practices located in the top 60 metropolitan areas by Hispanic population, the odds of having a Spanish-translated website were only related to the percentage of Hispanic population after adjusting for state-mandated insurance and average annual income level of the Hispanic population. Sixty-six of the websites with Spanish-translated content had been automatically translated. An additional eight websites were partially translated automatically. CONCLUSION(S) REI practices in metropolitan areas with a higher percentage of Hispanics were more likely to reach out to this minority population by translating their website content into Spanish. These practices were also more likely to use social media. Future studies are needed to determine whether the availability of Spanish language content on REI websites is associated with increased use of reproductive services by this minority population.

Curbside consultations in the era of social media connectivity and the creation of the Society for Reproductive Endocrinology and Infertility Forum

Social media, as defined by Wikipedia, the social encyclopedia, is a computer-mediated tool that allows people to create, share, or exchange information, career interests, ideas, and pictures/videos in virtual communities and networks. A Google search for the term yields 1.2 billion hits and you are hard pressed to get through your morning coffee without being asked to give or receive information through one of the many outlets that fall under this umbrella. Given its meteoric rise, it was only a matter of time before electronic connectivitys impact on the medical field was felt. A Pubmed search for ‘‘social media’’ as the keyword in 2007 would have yielded zero search results, although ‘‘social networks’’ were noted to have ‘‘considerable opportunity to advance the public health’’ (1). The first four results for ‘‘social media’’ were listed the ensuing year in 2008 followed by an exponential rise culminating in nearly 4,000 results in the medical literature as of January 2016. Not only is it being studied in terms of patient and physician interaction, it has also become a ‘‘hallway forum’’ for the old curbside consultation. There is little doubt that the way the world electronically communicates is changing, and the medical field is no exception. This evolution in medical communication brings along with it some significant concerns. Many question the validity or trustworthiness of information dispersed on social media given the lack of requirements or disclosure of user qualifications. Most platforms require only an internet connection, circumventing the traditional gatekeepers previously in place in the media. A second concern is the existence of disparities in social media, less having to do with access in modern society, and more having to do with the desire to learn the new skills required to function in this quickly evolving environment— the so called ‘‘digital divide.’’ These issues take a backseat to privacy which is of paramount concern when discussing social media in the medical community. In the era of big datamining, electronicfingerprints are constantly being captured, processed, and analyzed. Indeed, electronic tracking via third party applications allow data miningwithout user consent or knowledge. Socialmedia integration in the work environment can lead to conflicts with employees and employers as popular platforms, such as Facebook, Twitter, Instagram, and others, are used to fulfill professional roles when they are better suited for social communication. These concerns over both patient and personal confidentiality, reputation, and risk management need to be acknowledged and squarely addressed. In a study of 57 general surgery residency programs in 2014, 32% of residents had publically identifiable Facebook profiles that contained unprofessional content ranging from binge drinking and sexually suggestive photographs to clear violations of the Health Insurance Portability and Accountability Act (HIPAA) in 26% of cases (2). In response to this growth and in an attempt to establish guidelines for its membership, the American Congress of Obstetricians and Gynecologists issued Committee Opinion 622 in February 2015, which addressed the use of

Social media in the REI clinic: what do patients want?

PurposeTo elicit patient preferences for social media utilization and content in the infertility clinic.MethodsThis was a cross-sectional survey study conducted in three US fertility practices. Women presenting to the infertility clinic for an initial or return visit were offered an anonymous voluntary social media survey. The survey elicited patient perception of whether social media use in the infertility clinic is beneficial, and preferences regarding topics of interest.ResultsA total of 244 surveys were collected during the study period, of which 54.5% were complete. Instagram is a more popular platform than Twitter across all age groups. Use of both platforms varies by age, with patients ≥ 40 less likely to be active users. The majority of respondents felt that social media provided benefit to the patient experience in the infertility clinic (79.9%). “Education regarding infertility testing and treatment” and “Myths and Facts about infertility” were the most popular topics for potential posts, with 93.4 and 92.0% of patients endorsing interest respectively. The least popular topic was “Newborn photos and birth announcements,” with only 47.4% endorsing interest. A little over half of respondents (56.3%) would feel comfortable with the clinic posting a picture of their infant. The vast majority of patients (96.2%) feel comfortable communicating electronically with their infertility clinic.ConclusionPatients are interested in the use of social media as a forum for patient education and support in the infertility clinic. Patient preferences regarding post topics should be carefully considered.

Care of the transgender or gender-nonconforming patient undergoing in vitro fertilization

ABSTRACT  Background: Assisted reproductive technologies, including in vitro fertilization (IVF), can be utilized for fertility preservation and family building in the transgender and gender-nonconforming population. Methods: This is a retrospective case series from an academic tertiary care center. Results: We present three couples with a transgender or gender-nonconforming member who pursued IVF to build their families. The first case involves a transgender man who suspends hormone therapy to undergo IVF. The second involves a transgender woman who uses her previously banked sperm to undergo IVF with her wife. The third involves a gender nonbinary patient and their cisgender wife who create and transfer embryos from both partners. Conclusion: IVF can provide unique family-building opportunities to transgender and gender-nonconforming patients, and providers should seek to broaden their clinical experience with this population.