Differences in ICSI utilization rates among states with insurance mandates for ART coverage

Background Assisted reproductive technology (ART) insurance mandates promote more selective utilization of ART clinic resources including intracytoplasmic sperm injection (ICSI). Our objective was to examine whether ICSI utilization differs by state insurance mandates for ART coverage and assess if such a difference is associated with male factor, preimplantation genetic testing (PGT), and/or live birth rates. Methods In this retrospective analysis of the Centers for Disease Control (CDC) data from 2018, ART clinics in ART-mandated states (n = 8, AR, CT, HI, IL, MD, MA, NJ, RI) were compared individually to one another and with non-mandated states in aggregate (n = 42) for use of ICSI, male factor, PGT, and live birth rates. ANOVA was used to evaluate differences between ART-mandated states and non-mandated states. Individual ART-mandated states were compared using Welch t-tests. Statistical significance was determined by Bonferroni Correction. Results There were significant differences in ICSI rates (%, mean ± SD) between MA (53.3 ± 21.3) and HI (90.7 ± 19.6), p = 0.028; IL (86.5 ± 18.7) and MA, p = 0.002; IL and MD (57.2 ± 30.8), p = 0.039; IL and NJ (62.0 ± 26.8), p = 0.007; between non-mandated states in aggregate (79.9 ± 19.9) and MA, p = 0.006, and NJ (62.0 ± 26.8), p = 0.02. Male factor rates of HI (65.8 ± 16.0) were significantly greater compared to CT (18.8 ± 8.7), IL (26.0 ± 11.9), MA (26.9 ± 6.6), MD (29.3 ± 9.9), NJ (30.6 ± 17.9), and non-mandated states in aggregate (29.7 ± 13.7), all p < 0.0001. No significant differences were reported for use of PGT and/or live birth rates across all age groups regardless of mandate status. Conclusions ICSI use varied significantly among ART-mandated states while demonstrating no differences in live birth rates. These data suggest that the prevalence of male factor and the presence of a state insurance mandate are not the only factors influencing ICSI use. It is suggested that other non-clinical factors may impact the rate of ICSI utilization in a given state

Socially assistive robotics for post-stroke rehabilitation

BACKGROUND: Although there is a great deal of success in rehabilitative robotics applied to patient recovery post stroke, most of the research to date has dealt with providing physical assistance. However, new rehabilitation studies support the theory that not all therapy need be hands-on. We describe a new area, called socially assistive robotics, that focuses on non-contact patient/user assistance. We demonstrate the approach with an implemented and tested post-stroke recovery robot and discuss its potential for effectiveness. RESULTS: We describe a pilot study involving an autonomous assistive mobile robot that aids stroke patient rehabilitation by providing monitoring, encouragement, and reminders. The robot navigates autonomously, monitors the patient's arm activity, and helps the patient remember to follow a rehabilitation program. We also show preliminary results from a follow-up study that focused on the role of robot physical embodiment in a rehabilitation context. CONCLUSION: We outline and discuss future experimental designs and factors toward the development of effective socially assistive post-stroke rehabilitation robots

Psychological experience and coping strategies of patients in the Northeast US delaying care for infertility during the COVID-19 pandemic.

BACKGROUND: On March 17, 2020 an expert ASRM task force recommended the temporary suspension of new, non-urgent fertility treatments during an ongoing world-wide pandemic of Covid-19. We surveyed at the time of resumption of fertility care the psychological experience and coping strategies of patients pausing their care due to Covid-19 and examined which factors were associated and predictive of resilience, anxiety, stress and hopefulness. METHODS: Cross sectional cohort patient survey using an anonymous, self-reported, single time, web-based, HIPPA compliant platform (REDCap). Survey sampled two Northeast academic fertility practices (Yale Medicine Fertility Center in CT and Montefiore\u27s Institute for Reproductive Medicine and Health in NY). Data from multiple choice and open response questions collected demographic, reproductive history, experience and attitudes about Covid-19, prior infertility treatment, sense of hopefulness and stress, coping strategies for mitigating stress and two validated psychological surveys to assess anxiety (six-item short-form State Trait Anxiety Inventory (STAl-6)) and resilience (10-item Connor-Davidson Resilience Scale, (CD-RISC-10). RESULTS: Seven hundred thirty-four patients were sent invitations to participate. Two hundred fourteen of 734 (29.2%) completed the survey. Patients reported their fertility journey had been delayed a mean of 10 weeks while 60% had been actively trying to conceive \u3e 1.5 years. The top 5 ranked coping skills from a choice of 19 were establishing a daily routine, going outside regularly, exercising, maintaining social connection via phone, social media or Zoom and continuing to work. Having a history of anxiety (p \u3c 0.0001) and having received oral medication as prior infertility treatment (p \u3c 0.0001) were associated with lower resilience. Increased hopefulness about having a child at the time of completing the survey (p \u3c 0.0001) and higher resilience scores (p \u3c 0.0001) were associated with decreased anxiety. Higher reported stress scores (p \u3c 0.0001) were associated with increased anxiety. Multiple multivariate regression showed being non-Hispanic black (p = 0.035) to be predictive of more resilience while variables predictive of less resilience were being a full-time homemaker (p = 0.03), having received oral medication as prior infertility treatment (p = 0.003) and having higher scores on the STAI-6 (\u3c 0.0001). CONCLUSIONS: Prior to and in anticipation of further pauses in treatment the clinical staff should consider pretreatment screening for psychological distress and provide referral sources. In addition, utilization of a patient centered approach to care should be employed

Vitamin D3 Regulates Follicular Development and Intrafollicular Vitamin D Biosynthesis and Signaling in the Primate Ovary

There is an increasing recognition that vitamin D plays important roles in female reproduction. Recent studies demonstrated that 1α,25-dihydroxyvitamin D3 (VD3), the biologically active form of vitamin D, improved ovarian follicle survival and growth in vitro. Therefore, we investigated the direct effects of VD3 at the specific preantral and antral stages of follicular development, and tested the hypothesis that vitamin D receptor (VDR) and enzymes critical for vitamin D biosynthesis are expressed in the primate ovary. Fourteen adult rhesus macaques provided ovarian tissue. Secondary and antral follicles were isolated for PCR analysis on VDR, vitamin D3 25-hydroxylase, and 25-hydroxyvitamin D3-1α-hydroxylase. VDR protein localization was determined by immunohistochemistry on ovarian sections. Isolated secondary follicles were cultured under conditions of control and VD3 supplementation during the preantral or antral stage. Follicle survival, growth, steroid and anti-Müllerian hormone (AMH) production, as well as oocyte maturation were evaluated. In vivo- and in vitro-developed follicles were also assessed for genes that are critical for vitamin D biosynthesis and signaling, gonadotropin signaling, steroid and paracrine factor production, and oocyte quality. The mRNA encoding VDR, 25-hydroxylase, and 1α-hydroxylase was detectable in in vivo- and in vitro-developed preantral and antral follicles. The 25-hydroxylase was elevated in cultured follicles relative to in vivo-developed follicles, which further increased following VD3 exposure. VD3 treatment increased 1α-hydroxylase in in vitro-developed antral follicles. The absence of VD3 during culture decreased VDR expression in in vitro-developed antral follicles, which was restored to levels comparable to those of in vivo-developed antral follicles by VD3 supplementation. Positive immunostaining for VDR was detected in the nucleus and cytoplasm of granulosa cells and oocytes. While only survival was improved in preantral follicles treated with VD3, VD3 supplementation promoted both survival and growth of antral follicles with increased estradiol and AMH production, as well as oocyte maturation. Thus, Vitamin D biosynthesis and signaling systems are expressed in primate ovarian follicles. Our findings support a role for VD3 in regulating follicular development in a stage-dependent manner, as well as the intrafollicular vitamin D biosynthesis and signaling, directly in the ovary

What factors in rural and remote extended clinical placements may contribute to preparedness for practice, from the perspective of students and clinicians?

What factors in rural and remote extended clinical placements may contribute to preparedness for practice, from the perspective of students and clinicians? Michele Daly, David Perkins, Koshila Kumar, Chris Roberts and Malcolm Moore Background: Community based rural education opportunities have expanded in Australia, attracting more medical students to placements in rural and remote settings. Aim: To identify the factors in an integrated, community engaged rural placement that may contribute to preparedness for practice (P4P), from the perspective of students and clinicians Methods: Forty two semi-structured interviews with medical students, supervisors and clinicians analysed thematically. Results: Opportunities for clinical learning, personal and professional development and cultural awareness were reported by students and clinicians as key factors that contribute to preparedness for practice. Potential barriers in rural and remote settings included geographical and academic isolation, perceived educational risk and differing degrees of program engagement. Conclusions: A longitudinal clinical placement in a rural setting may enable development of enhanced competencies leading to P4P. A rural setting can help provide a unique experience through hands-on learning, enhanced personal and professional development opportunities and observation of the cultural and contextual impact on health

Potential Mechanisms for Racial and Ethnic Differences in Antimüllerian Hormone and Ovarian Reserve

Accumulating evidence suggests that reproductive potential and function may be different across racial and ethnic groups. Racial differences have been demonstrated in pubertal timing, infertility, outcomes after assisted reproductive technology (ART) treatment, and reproductive aging. Recently, racial differences have also been described in serum antimüllerian hormone (AMH), a sensitive biomarker of ovarian reserve, supporting the notion that ovarian reserve differs between racial/ethnic groups. The existence of such racial/ethnic differences in ovarian reserve, as reflected by AMH, may have important clinical implications for reproductive endocrinologists. However, the mechanisms which may underlie such racial differences in ovarian reserve are unclear. Various genetic factors and environmental factors such as obesity, smoking, and vitamin D deficiency which have been shown to correlate with serum AMH levels and also display significant racial/ethnic variations are discussed in this review. Improving our understanding of racial differences in ovarian reserve and their underlying causes may be essential for infertility treatment in minority women and lead to better reproductive planning, improved treatment outcomes, and timely interventions which may prolong reproductive lifespan in these women

Review Article Potential Mechanisms for Racial and Ethnic Differences in Antimüllerian Hormone and Ovarian Reserve

Accumulating evidence suggests that reproductive potential and function may be different across racial and ethnic groups. Racial differences have been demonstrated in pubertal timing, infertility, outcomes after assisted reproductive technology (ART) treatment, and reproductive aging. Recently, racial differences have also been described in serum antimüllerian hormone (AMH), a sensitive biomarker of ovarian reserve, supporting the notion that ovarian reserve differs between racial/ethnic groups. The existence of such racial/ethnic differences in ovarian reserve, as reflected by AMH, may have important clinical implications for reproductive endocrinologists. However, the mechanisms which may underlie such racial differences in ovarian reserve are unclear. Various genetic factors and environmental factors such as obesity, smoking, and vitamin D deficiency which have been shown to correlate with serum AMH levels and also display significant racial/ethnic variations are discussed in this review. Improving our understanding of racial differences in ovarian reserve and their underlying causes may be essential for infertility treatment in minority women and lead to better reproductive planning, improved treatment outcomes, and timely interventions which may prolong reproductive lifespan in these women

Biosimilar FSH Preparations- Are They Identical Twins or Just Siblings?

As patents expire on innovator products, there is increasing interest in developing biosimilar products globally. Biosimilars are not exact copies and are not considered generic versions of the reference product. They may differ in strength, purity and contain different composition of isoforms and/or various glycosylation profiles, with the consequent alterations in clinical efficacy or safety. Recently 2 new recombinant FSH preparations were introduced to clinical practice following randomized controlled, phase 3 clinical trials. Both, Bemfola and Ovaleap (R) were referred to the FSH innovator product Gonal-f (TM) (Follitropin alpha), and were found to yield an equivalent number of oocytes (primary end-point), following a long GnRH agonist suppressive protocol in ideal patients, i.e., young, normal responders. However, a closer look at these RCTs reveals a non-significant 4 % difference in clinical and ongoing pregnancy rates, in favor of Gonal f over the biosimilar products, accompanied by half the incidence of OHSS (2.9 vs 5. 2 %, respectively). These studies were underpowered with reference to pregnancy rates, Thus, we believe that further comparative studies are needed in additional patient populations, e.g., older,, poor responders, patients with repeated IVF failures and/or polycystic ovary syndrome, before the universal implementation of biosimilar products for clinical use. Biosimilars are actually a regulatory synonym, facilitating a fast track introduction of a FSH preparation to the COH armamentarium. We therefore recommend against interchanging or substituting innovator and biosimilar agents in clinical practice, and believe that the decision whether to use an innovator or a biosimilar product, should be reserved to the discretion of the treating physician. Furthermore, we believe the time has come that the measurement of the biological activity of FSH in humans should require other methods rather than the Steelman-Pohley assay, such as the determination of dose-response curves in defined populations of women with well-defined outcomes during COH in preparation for ART

Antimüllerian hormone as predictor of implantation and clinical pregnancy after assisted conception: a systematic review and meta-analysis.

OBJECTIVE: To assess whether antimüllerian hormone (AMH) is a predictor of implantation and/or clinical pregnancy in women undergoing assisted reproductive technology. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women undergoing IVF/intracytoplasmic sperm injection in nondonor cycles. INTERVENTION(S): Measurement of serum AMH level. MAIN OUTCOME MEASURE(S): Diagnostic odds ratio (OR) and summary receiver operating characteristic curve (AUC) for AMH as a predictor of implantation and/or clinical pregnancy. RESULT(S): A total of 525 observational studies were identified, of which 19 were selected (comprising 5,373 women). Studies reporting clinical pregnancy rates in women with unspecified ovarian reserve (n = 11), diminished ovarian reserve (DOR) (n = 4), and polycystic ovary syndrome (n = 4) were included, together with studies reporting implantation rates (n = 4). The OR for AMH as a predictor of implantation in women with unspecified ovarian reserve (n = 1,591) was 1.83 (95% confidence interval [CI] 1.49-2.25), whereas the AUC was 0.591 (95% CI 0.563-0.618). The OR for AMH as a predictor of clinical pregnancy in these women (n = 4,324) was 2.10 (95% CI 1.82-2.41), whereas the AUC was 0.634 (95% CI 0.618-0.650). The predictive ability of AMH for pregnancy was greatest in women with DOR (n = 615), with OR and AUC of 3.96 (95% CI 2.57-6.10) and 0.696 (95% CI 0.641-0.751), respectively. In contrast, AMH had no significant predictive ability in women with PCOS (n = 414), with OR and AUC of 1.18 (95% CI 0.53-2.62) and 0.600 (95% CI 0.547-0.653), respectively. CONCLUSION(S): Antimüllerian hormone has weak association with implantation and clinical pregnancy rates in assisted reproductive technology but may still have some clinical utility in counseling women undergoing fertility treatment regarding pregnancy rates, particularly those with DOR