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Fellows in Reproductive Endocrinology and Infertility training are expected to complete 18 months of clinical, basic, or epidemiological research. The goal of this research is not only to provide the basis for the thesis section of the oral board exam but also to spark interest in reproductive medicine research and to provide the next generation of physician-scientists with a foundational experience in research design and implementation. Incoming fellows often have varying degrees of training in research methodology and, likewise, different career goals. Ideally, selection of a thesis topic and mentor should be geared toward defining an “answerable” question and building a practical skill set for future investigation. This contribution to the JARG Young Investigator’s Forum revisits the steps of the scientific method through the lens of one recently graduated fellow and his project aimed to test the hypothesis that “sequential oxygen exposure (5% from days 1 to 3, then 2% from days 3 to 5) improves blastocyst yield and quality compared to continuous exposure to 5% oxygen among human preimplantation embryos.”

Purpose The purposes of this study were to evaluate public opinion regarding fertility treatment and gamete cryopreservation for transgender individuals and identify how support varies by demographic characteristics. Methods This is a cross-sectional web-based survey study completed by a representative sample of 1111 US residents aged 18–75 years. Logistic regression was used to calculate odd ratios (ORs) and 95% confidence intervals (CIs) of support for/opposition to fertility treatments for transgender people by demographic characteristics, adjusting a priori for age, gender, race, and having a biological child. Results Of 1336 people recruited, 1111 (83.2%) agreed to participate, and 986 (88.7%) completed the survey. Most respondents (76.2%) agreed that “Doctors should be able to help transgender people have biological children.” Atheists/agnostics were more likely to be in support (88.5%) than Christian–Protestants (72.4%; OR = 3.10, CI = 1.37–7.02), as were younger respondents, sexual minorities, those divorced/widowed, Democrats, and non-parents. Respondents who did not know a gay person (10.0%; OR = 0.20, CI = 0.09–0.42) or only knew a gay person without children (41.4%; OR = 0.29, CI = 0.17–0.50) were more often opposed than those who knew a gay parent (48.7%). No differences in gender, geography, education, or income were observed. A smaller majority of respondents supported doctors helping transgender minors preserve gametes before transitioning (60.6%) or helping transgender men carry pregnancies (60.1%). Conclusions Most respondents who support assisted and third-party reproduction also support such interventions to help transgender people have children.

Purpose To evaluate the association between serum progesterone (P) levels on the day of embryo transfer (ET) and pregnancy rates in fresh donor IVF/ICSI cycles. Methods Fresh donor cycles with day 3 ET from 10/2007 to 8/2012 were included ( n  = 229). Most cycles (93 %) were programmed with a gonadotropin releasing hormone (GnRH) agonist; oral, vaginal or transdermal estradiol was used for endometrial priming, and intramuscular P was used for luteal support (50–100 mg/day). Recipient P levels were measured at ET, and P dose was increased by 50–100 % if <20 ng/mL per clinic practice. The main outcome measure was rate of live birth (> = 24 weeks gestational age). Generalized estimating equations were used to account for multiple cycles from the same recipient, adjusted a priori for recipient and donor age. Results Mean recipient serum P at ET was 25.5 ± 10.1 ng/mL. Recipients with P  < 20 ng/mL at ET, despite P dose increases after ET, were less likely to achieve clinical pregnancy (RR = 0.75, 95 % CI = 0.60–0.94, p  = 0.01) and live birth (RR = 0.77, 95 % CI = 0.60–0.98, p  = 0.04), as compared to those with P  ≥ 20 ng/mL. P dose increases were more often required in overweight and obese recipients. Conclusions Serum P levels on the day of ET in fresh donor IVF/ICSI cycles were positively correlated with clinical pregnancy and live birth rates. An increase in P dose after ET was insufficient to rescue pregnancy rates. Overweight and obese recipients may require higher initial doses of P supplementation. Future research is needed to define optimal serum P at ET and the interventions to achieve this target.

PurposeTo explore clinical benefit of performing two intrauterine inseminations (IUI) 24 h apart—a double IUI vs. a single IUI among lesbian and single women.MethodsRetrospective cohort study using electronic medical record review during a 17-year period (11/1999–3/2017). A total of 11,396 patients at a single academic-affiliated private practice were included in this study. All cycles with a single or double IUI were included. A sub-analysis of first cycles only (n = 10,413) was also performed. Canceled IVF cycles converted to IUI were excluded. T tests and Wilcoxon rank-sum tests were used for continuous data, and chi-square for categorical data. Multivariable logistic regression controlled for patient age, day 3 follicle-stimulating hormone (D3 FSH), body mass index (BMI), peak estradiol (E2), and post-wash total motile sperm counts to model the association between IUI number and ongoing pregnancy rate (OPR) according to sperm source (autologous vs. donor). Generalized estimating equations and mixed effect models accounted for multiple cycles from the same woman. Adjusted odds ratio (AOR) with 95% CI was determined. Sub-analyses of sexual orientation and partner status were performed to compare heterosexual couples with proven infertility to women with lesbian and single women.ResultsDuring the study period, 22,452 cycles met inclusion criteria (single IUI 1283 vs. double IUI 21,169). Mean patient age and BMI were similar between groups. For couples using autologous sperm, OPR was significantly higher with double IUI (12.0% vs. 14.1%; p = 0.0380). A similar increase was observed for donor sperm OPR among heterosexual couples (14.4% vs. 16.2%), though this did not reach statistical significance (p = 0.395). A sub-analysis restricted to donor sperm demonstrates a clinical benefit of second IUI in heterosexual couples, 8.5% vs. 17.6% OPR (AOR 2.94; CI 1.00–10.99; p = 0.0496). When lesbian and single patients were evaluated, there was no difference (17.2% vs. 15.2%; AOR 0.99; CI 0.59–1.70; p = 0.0958).ConclusionsDouble IUI is associated with a significantly higher OPR for heterosexual couples using an autologous or donor sperm source. The benefit of a second IUI is less clear in patients with undocumented fertility status using donor sperm, such as single and lesbian women.

Introduction and hypothesis The optimal surgery for combined apical and posterior vaginal prolapse is not well defined. Our objective was to examine the anatomic and functional outcomes following sacrocolpopexy (SCP) with or without posterior colporrhaphy (PC). Methods We retrospectively evaluated 258 women who underwent abdominal ( n  = 62) or laparoscopic ( n  = 196) SCP with or without PC. Preoperative anatomic support and standardized bowel symptoms were compared to 6-week and 1-year postoperative values, using Student’s t test and Wilcoxon rank sum test, respectively. Results Six-week follow-up data were available for 235 of 258 (91.1 %) women, while 125 of 258 (48.4 %) women had 1-year anatomic and functional outcomes recorded. While the SCP + PC group had worse posterior descent and bowel function preoperatively, there were no significant differences in postoperative anatomic support or symptoms. Long-term pelvic floor function was similar, as measured by three validated instruments. Reduction in the proportion of women with splinting was greater in the SCP + PC group. Conclusions SCP with or without PC is associated with improved posterior support and decreased obstructive and irritative bowel symptoms at 1 year in women with apical and posterior prolapse.

Purpose To determine embryo and cycle-specific parameters associated with twin live birth in day 3 cryopreserved double embryo transfer (DET) cycles, and to propose a new prediction model for external validation. Methods All cycles with autologous or donor cryopreserved DET of day 3 embryos from 2002 to 2011 at a single academic institution with a singleton or twin live birth were included ( n  = 207). Patient characteristics, post-thaw embryo morphology and freeze-thaw parameters were compared between patients with a single and twin live birth. Results Demographic characteristics were similar, except that patients delivering twins were younger at age of cryopreserved embryo transfer (CET), fewer were parous and more were anovulatory. Duration of embryo storage, time in culture post-thaw, endometrial thickness and use of assisted hatching were comparable. Six predictors of twin delivery were identified: patient age <35 year at CET, intact survival of the lead embryo, resumption of mitosis, 7–8 viable cells in the non-lead embryo, transfer of a lead embryo with ≥7 cells and a sum of ≥14 viable cells in the two transferred embryos. Regression modeling predicted a step-wise increase in the probability of twins with addition of each predictor; with all six present, the risk of twins was predicted to be 53 % and with none present, the risk decreased to 6 %. Conclusions The six identified variables associated with twin live birth following day 3 cryopreserved DET have been applied to derive a prediction model for estimating the risk of twin delivery. External validation of the model is required prior to clinical application.

The idea that noncrop habitat enhances pest control and represents a win–win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win–win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies.

Immune mediated inflammatory diseases (IMIDs) are a heterogeneous group of debilitating, multifactorial and unrelated conditions featured by a dysregulated immune response leading to destructive chronic inflammation. The immune dysregulation can affect various organ systems: gut (e.g., inflammatory bowel disease), joints (e.g., rheumatoid arthritis), skin (e.g., psoriasis, atopic dermatitis), resulting in significant morbidity, reduced quality of life, increased risk for comorbidities, and premature death. As there are no reliable disease progression and therapy response biomarkers currently available, it is very hard to predict how the disease will develop and which treatments will be effective in a given patient. In addition, a considerable proportion of patients do not respond sufficiently to the treatment. ImmUniverse is a large collaborative consortium of 27 partners funded by the Innovative Medicine Initiative (IMI), which is sponsored by the European Union (Horizon 2020) and in-kind contributions of participating pharmaceutical companies within the European Federation of Pharmaceutical Industries and Associations (EFPIA). ImmUniverse aims to advance our understanding of the molecular mechanisms underlying two immune-mediated diseases, ulcerative colitis (UC) and atopic dermatitis (AD), by pursuing an integrative multi-omics approach. As a consequence of the heterogeneity among IMIDs patients, a comprehensive, evidence-based identification of novel biomarkers is necessary to enable appropriate patient stratification that would account for the inter-individual differences in disease severity, drug efficacy, side effects or prognosis. This would guide clinicians in the management of patients and represent a major step towards personalized medicine. ImmUniverse will combine the existing and novel advanced technologies, including multi-omics, to characterize both the tissue microenvironment and blood. This comprehensive, systems biology-oriented approach will allow for identification and validation of tissue and circulating biomarker signatures as well as mechanistic principles, which will provide information about disease severity and future disease progression. This truly makes the ImmUniverse Consortium an unparalleled approach.

We describe a point-of-use (POU) ultraviolet (UV) disinfection technology, the UV Tube, which can be made with locally available resources around the world for under $50 US. Laboratory and field studies were conducted to characterize the UV Tube's performance when treating a flowrate of 5 L/min. Based on biological assays with MS2 coliphage, the UV Tube delivered an average fluence of 900±80 J/m2 (95% CI) in water with an absorption coefficient of 0.01 cm−1. The residence time distribution in the UV Tube was characterized as plug flow with dispersion (Peclet Number = 19.7) and a mean hydraulic residence time of 36 s. Undesirable compounds were leached or produced from UV Tubes constructed with unlined ABS, PVC, or a galvanized steel liner. Lining the PVC pipe with stainless steel, however, prevented production of regulated halogenated organics. A small field study in two rural communities in Baja California Sur demonstrated that the UV Tube reduced E. coli concentrations to less than 1/100 ml in 65 out of 70 samples. Based on these results, we conclude that the UV Tube is a promising technology for treating household drinking water at the point of use.