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Background: Neonatal jaundice, defined as an excess of bilirubin in blood at birth or shortly thereafter, has a disproportionately high impact in low-resource settings. Three quarters of deaths from jaundice occur in sub-Saharan Africa and south Asia. Jaundice is easily treated with blue light phototherapy; however, accurate, low-cost bilirubin monitoring is essential to guide effective phototherapy treatment in low-resource settings. To address this need, we developed BiliDx, a low-cost, portable reader that quantifies bilirubin concentration in a few drops of blood applied to a lateral flow card. BiliDx measures absorbance at three wavelengths: blue (bilirubin), amber (haemoglobin interference), and red (background) and can perform measurements in less than 5 mins at the point of care, without the need for a costly centrifuge or extensive training. Here, we compare the accuracy of BiliDx against a standard laboratory bilirubinometer and a transcutaneous bilirubinometer. Methods: This study took place in two central hospitals in Malawi. We included samples from neonates being treated in neonatal wards and deemed to be at risk for jaundice or who were undergoing phototherapy. Guardians provided written informed consent. We measured bilirubin using three devices: BiliDx, a bilirubinometer (Reichert UNISTAT), and a transcutaneous bilirubinometer (Drager JM-105), with a total of 475 measurements per device. Training (149 measurements) and validation (326 measurements) sets were created by ordering the first measurement per patient from lowest to highest UNISTAT bilirubin; every third measurement was selected for the training set. The training set was used to fit a model that correlated bilirubin concentration to absorbances at three wavelengths. The validation set was used to make an unbiased evaluation of the accuracy of the model. Findings: We enrolled 456 neonates between August 7 and December 12, 2019; 247 of 326 (75%) of BiliDx measurements in the validation set were within 2 mg/dL of UNISTAT measurements, compared with 44 of 281 (6%) of quantitative transcutaneous measurements. No adverse events occurred. Interpretation: BiliDx can provide accurate bilirubin monitoring. BiliDx is more accurate than transcutaneous bilirubinometry, a technology often endorsed for its non-invasive, portable nature. Limitations include that only ten nurses used BiliDx and only central hospitals were included. Testing of the BiliDx device is ongoing; we aim to collect enough measurements >20 mg/dL to assess the accuracy of BiliDx over the intended bilirubin concentration range of 0–35 mg/dL. Future studies will evaluate usability among a larger group of nurses and hospital settings. Funding: USAID Saving Lives at Birth Award No. 7200AA18FA0016.

Introduction: Existing randomised controlled trials (RCTs) comparing a freeze-all embryo transfer strategy and a fresh embryo transfer strategy have shown conflicting results. A freeze-all or a fresh transfer policy may be preferable for some couples undergoing in-vitro fertilisation (IVF), but it is unclear which couples would benefit most from each policy, how and under which protocols. Therefore, we plan a systematic review and individual participant data meta-analysis of RCTs comparing a freeze-all and a fresh transfer policy., Methods and Analysis: We will search electronic databases (Medline, Embase, PsycINFO and CENTRAL) and trial registries (ClinicalTrials.gov and the International Clinical Trials Registry Platform) from their inception to present to identify eligible RCTs. We will also check reference lists of relevant papers. The search was performed on 23 September 2020 and will be updated. We will include RCTs comparing a freeze-all embryo transfer strategy and a fresh embryo transfer strategy in couples undergoing IVF. The primary outcome will be live birth resulting from the first embryo transfer. All outcomes listed in the core outcome set for infertility research will be reported. We will invite the lead investigators of eligible trials to join the In dividual participant data meta-analysis of trials comparing f r o zen versus f r esh e m bryo transfer strategy (INFORM) collaboration and share the deidentified individual participant data (IPD) of their trials. We will harmonise the IPD and perform a two-stage meta-analysis and examine treatment-covariate interactions for important baseline characteristics., Ethics and Dissemination: The study ethics have been granted by the Monash University Human Research Ethics Committee (Project ID: 30391). The findings will be disseminated via presentations at international conferences and publication in peer-reviewed journals., Prospero Registration Number: CRD42021296566., Competing Interests: Competing interests: RW reports grants from the NHMRC and NHMRC Centre for Research Excellence in Women's Health in Reproductive Life (CRE WHiRL). LNV reports personal fees from Merck, Merck Sharpe and Dohme, Ferring, outside the submitted work. AP reports grants and personal fees from Gedeon Richter, Ferring Pharmaceuticals and Merck A/S and personal fees from IBSA, outside the submitted work. CB reports grants and personal fees from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S and Organon, and personal fees from IBSA and Abbott outside the submitted work. CS is a co-inventor of Igenomix SL and Head of Scientific Advisory Board at Igenomix SL. BWM is supported by a NHMRC Investigator grant (GNT1176437). BWM reports personal fees from ObsEva and Merck, and travel support from Merck, outside the submitted work. SB is the Editor in Chief of Human Reproduction Open. AM reports grants from HTA/NIHR, travel/meeting support from Ferring and Pharmasure and participation in a Ferring advisory board. All other authors do not have competing interests to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To identify relationships between the size of punctured ovarian follicles and subsequent embryology outcomes., Design: Prospective observational cohort study., Setting: Private fertility center., Patients: One hundred fifty-seven oocyte retrievals performed during the study period., Interventions: The diameter of punctured follicles was ultrasonically measured during routine oocyte collection. The resulting embryos were group-cultured to the blastocyst stage and classified into 8 groups according to follicle size (≤9.5, 10-12.5, 13-15.5, 16-18.5, 19-21.5, 22-24.5, 25-27.5, and ≥28 mm)., Main Outcome Measure: Rate of good-quality blastocysts per follicle puncture., Results: This study included 4,539 follicle punctures, 2,348 oocytes, 1,772 mature oocytes, 1,258 bipronuclear (2pn) oocytes, and 571 good-quality blastocysts derived from 157 oocyte retrievals. The per-puncture yields of oocytes, mature oocytes, 2pn oocytes, and good-quality blastocysts were associated with the size of the punctured follicle. The rates of good-quality blastocysts per punctured follicle were 2.2% (≤9.5 mm), 6.2% (10-12.5 mm), 11.9% (13-15.5 mm), 14.5% (16-18.5 mm), 18.9% (19-21.5 mm), 17.5% (22-24.5 mm), 15.9% (25-27.5 mm), and 16.0% (≥28 mm). When compared with the overall average, punctures of follicles in groups ≤12.5 mm in diameter had significantly inferior yields of good-quality blastocysts, whereas punctures of follicles in groups 19-24.5 mm in diameter were associated with significantly greater than average yields of good-quality blastocysts. Other groups did not differ significantly from average. No correlation was observed between follicle diameter and ploidy of biopsied blastocysts., Conclusions: Punctures of follicles ≤12.5 mm in diameter rarely result in good-quality blastocysts. The yield of good-quality blastocysts progressively increases with follicle size up to approximately 19 mm in diameter, with no substantial decline above that size. The ploidy of the blastocysts that form appears to be unaffected by follicle size., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine if the change in endometrial thickness following exogenous progesterone (P) initiation correlates with outcome following autologous transfer of a single thawed blastocyst., Methods: The study is a retrospective observational cohort study conducted at a private fertility center. Patients scheduled for thawed blastocyst transfer received artificial endometrial preparation (artificial cycle FET) and underwent serial ultrasonography. The main outcomes were the rate of ongoing pregnancy (fetal heart motion at 12 weeks of gestation) and early pregnancy loss. Logistic regression was used to test for correlations between these outcomes and the change in endometrial thickness while adjusting for potential confounders (patient age, embryo quality, and the use of genetic testing)., Results: There were 232 qualifying autologous single-blastocyst transfers in the 20-month study period ending 31 December 2019. Mean endometrial thicknesses were 3.8 mm, 10.0 mm, and 11.2 mm at baseline, P initiation, and at transfer, respectively. The change in endometrial thickness after exogenous P exposure ranged from - 5 to + 9 mm and negatively correlated with ongoing pregnancy in logistic regression analyses. Specifically, ongoing pregnancy rates per transfer were 63.2% in 19 cases where endometria compacted by 10% or more, 64.2% in 95 cases where there was unchanged endometrial thickness, and 52.5% in 118 cases where endometria expanded., Conclusions: The change in endometrial thickness after P initiation was associated with the probability of ongoing pregnancy but not with early pregnancy loss. Ongoing pregnancy rates were greater in endometria with negative growth (compaction) when compared to endometria that grew (expanded) after P exposure., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Research focusing on improving hydration status and knowledge in female indoor-sport athletes is limited. Investigators have demonstrated that hydration education is an optimal tool for improving the hydration status of athletes., Objective: To assess the hydration status and fluid intake of collegiate female indoor-sport athletes before and after a 1-time educational intervention., Design: Controlled laboratory study., Setting: Collegiate women's volleyball and basketball practices., Patients or Other Participants: A total of 25 female collegiate volleyball and basketball athletes (age = 21 ± 1 years, height = 173.5 ± 8.7 cm, weight = 72.1 ± 10.0 kg) were assessed during 6 days of practices., Intervention(s): Participants' hydration status and habits were monitored for 3 practice days before they underwent a hydration educational intervention. Postintervention, participants were observed for 3 more practice days., Main Outcome Measure(s): Change in body mass, fluid consumed, urine specific gravity (Usg), urine color (Ucol), and sweat rate were recorded for 6 practice days. Participants completed a hydration-knowledge questionnaire before and after the intervention., Results: Three-day mean Usg and Ucol were considered euhydrated prepractice (Usg = 1.015 ± 0.006, Ucol = 4 ± 1) and remained euhydrated postpractice (Usg = 1.019 ± 0.005, Ucol = 5 ± 2) during the preintervention period. Decreased prepractice Ucol (P < .01) and increased hydration knowledge (P < .01) were present postintervention. Basketball athletes had greater body mass losses from prepractice to postpractice than did volleyball athletes (P < .001). Overall increases were evident when we compared prepractice and postpractice measures of Usg and Ucol in the preintervention (P < .001 and P = .001, respectively) and postintervention (P = .001 and P < .001) period, respectively. No correlation was found between hydration knowledge and physiological indices of hydration and fluid intake., Conclusions: Overall, female collegiate indoor-sport athletes were hydrated and knowledgeable on hydration. However, our variable findings indicated that further research on these athletes is needed; clinically, attention should be given to the individual needs of each athlete. More examination will demonstrate whether a 1-time educational intervention may be an effective tool for improving hydration status in this population., (© by the National Athletic Trainers' Association, Inc.)

Objective: To evaluate a new fully automated antimüllerian hormone (AMH) assay for prediction of poor ovarian response (POR) to ovarian stimulation defined as four or fewer oocytes retrieved., Design: Prospective cohort study., Setting: Thirteen private and academic fertility centers in the United States., Patients(s): A total of 178 women undergoing their first in vitro fertilization (IVF) cycle eligible for the study were consented and enrolled, with data available from 160 women for prediction of POR and 164 women for AMH correlation with antral follicle count (AFC)., Intervention(s): None., Main Outcome Measure(s): Cutoff point for AMH that predicts POR. Correlation of AMH with AFC, and cutoff point for AMH that correlates with antral follicle count >15., Result(s): The mean AMH among the poor responders was 0.74 ng/mL, compared with 3.20 ng/mL for normal to high responders. The AMH cutoff at 90% specificity for predicting POR with the use of the receiver operating characteristic (ROC) curve was 0.93 ng/mL, with an associated sensitivity of 74.1%. For prediction of POR, ROC analysis showed that AMH (area under the ROC curve [AUC] = 0.929) was significantly better than FSH (AUC = 0.615; P<.0001). AMH was positively correlated with AFC (Spearman rho = 0.756). The AMH at 90% sensitivity for AFC >15 was 1.75, with specificity of 59.1%., Conclusion(s): A fully automated AMH assay can be a useful biomarker for predicting POR in IVF cycles. Because AMH cutoff points vary depending on the assay used, future studies should continue to calibrate test results to clinically important outcomes., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate birth weight differences between patients randomized to fresh or thawed ET., Design: Post hoc analysis of results from two similar randomized trials., Setting: Private fertility center., Patient(s): One hundred thirty-four first-time IVF patients, ages 18-40 years at oocyte retrieval, who had live birth., Intervention(s): Patients were randomly assigned to have either fresh blastocyst transfer or all bipronuclear oocytes frozen followed by thaw, extended culture, and blastocyst transfer in a subsequent cycle. Preimplantation genetic screening was not allowed., Main Outcome Measure(s): Mean birth weight., Result(s): After allowing for the contributions of multiple significant variables (gestational age at birth, the presence of a vanished twin, number of infants delivered) in multiple linear regression, the adjusted mean birth weight was 166 g (95% confidence interval, 43-290 g) lower after fresh blastocyst transfer when compared with transfer of blastocysts derived from thawed bipronuclear oocytes., Conclusion(s): Birth weights are lower in cycles with fresh blastocyst transfer after controlled ovarian stimulation than in transfers of frozen-thawed embryos in the absence of ovarian stimulation. This finding confirms similar results reported in many retrospective studies., Clinical Trial Registration Numbers: NCT00963625 and NCT00963079., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This retrospective cohort analysis examined the effects of maternal age on the incidence of factors associated with embryo-endometrium asynchrony in fresh autologous blastocyst transfer. The study included 1169 routine fresh autologous blastocyst transfers. The main outcome measure was asynchronous transfer defined by delayed (day 6) blastocyst transfer or elevated pre-ovulatory serum progesterone level. Compared with patients younger than 35 years, patients 35 years or older had increased risk of having at least one risk factor for asynchronous transfer, including premature progesterone elevation or delayed blastocyst transfer (RR 1.36; 95% CI 1.24 to 1.50). The older group had increased risk of simultaneously having both risk factors (RR 1.61, 95% CI 1.17 to 2.21) compared with the younger group. In patients younger than 35 years, live birth rate per transfer was 62.9% with day 5 transfer and low progesterone, declining to 27.9% for day 6 transfer combined with elevated progesterone. In patients 35 years or older, live birth rate per transfer was 38.0% with day 5 transfer and low progesterone, declining to 18.1% for day 6 transfer combined with elevated progesterone. Indicators of embryo-endometrium asynchrony increase in prevalence as women age and asynchrony disproportionately decreases birth rates in older patients., (Copyright © 2016. Published by Elsevier Ltd.)

Objective: To compare outcomes for patients randomized to have all embryos cryopreserved at the blastocyst stage or at the bipronuclear stage with subsequent post-thaw culture to the blastocyst stage., Design: Randomized controlled trial., Setting: Private fertility center., Patient(s): This study included 140 women, age 18-40 years, with at least eight antral follicles, and day 3 FSH <10 IU/L undergoing IVF., Intervention(s): After oocyte retrieval, subjects were randomized to have entire embryo cohorts cryopreserved at either the bipronuclear stage (2PN Cryo group) or at the blastocyst stage (Blast Cryo group)., Main Outcome Measure(s): Ongoing pregnancy (viable fetal heart motion at 10 weeks' gestation) per oocyte retrieval through the first transfer attempt., Result(s): No significant differences were observed between the two study groups in age at retrieval, body mass index, antral follicle count, day 3 FSH level, or IVF cycle parameters. No significant differences were observed in ongoing pregnancy rate per retrieval (62.0%; 95% confidence interval [CI], 50.3%-72.4%) in the 2PN Cryo group; and 55.1%; 95% CI, 42.6%-67.1% in the Blast Cryo group), implantation rate (60.0% vs. 62.7%), ongoing pregnancy rate per thaw (62.0% vs. 59.4%), ongoing pregnancy rate per transfer (67.7% vs. 69.1%), and the cumulative ongoing pregnancy rate per retrieval from all thaws to date of embryos derived from the study retrieval cycle (64.8% vs. 60.9%)., Conclusion(s): Freeze-all at the blastocyst stage or at the bipronuclear stage has similar efficacy and IVF outcomes. The choice between them may depend primarily on logistical factors., Clinical Trial Registration Number: NCT01247987., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The GnRH agonist trigger alters traditional IVF paradigms when compared with hCG-only triggers. The agonist trigger induces rapid luteolysis and therefore separates the oocyte maturation aspect of LH from the luteal support previously afforded by lingering hCG. This might allow customized and more optimal luteal support. The agonist trigger option also allows continued stimulation and subsequent trigger of high responders with reasonable safety, potentially leading to retrievals of larger cohorts of mature oocytes. It may also reduce the number of retrievals needed to achieve a large family. The agonist trigger might alter other paradigms as well, such as making oocyte donation more efficient per stimulation by virtually eliminating follicular-phase cycle cancellation, coasting, and premature triggering. There are both corresponding potential benefits and drawbacks of using the agonist trigger and the shifting paradigms it allows., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Implantation failure has various causes, including impaired uterine receptivity following ovarian stimulation. This retrospective cohort study compared outcomes in patients with prior implantation failure who elected to undergo another fresh cycle versus those who opted for embryo cohort cryopreservation (freeze-all) and subsequent thaw. There were 269 patients with implantation failure following fresh autologous blastocyst transfer opting to undergo a subsequent cycle, with 163 choosing another fresh cycle and 106 electing freeze-all and subsequent thaw. Multiple logistic regression analysis indicated that cohort cryopreservation was associated with greater chance of live birth when compared with another fresh cycle (P < 0.0001). The odds ratio for live birth with freeze-all relative to a fresh cycle was 3.8 (95% CI 2.1-7.2). A second analysis was then performed using cumulative live birth rate as the outcome measure. Multiple logistic regression indicated freeze-all was associated with greater cumulative live birth rate than was a fresh cycle (OR 1.9, 95% CI 1.1-3.3, P = 0.0287). These findings suggest that, following implantation failure with fresh blastocysts, patients have a significantly greater chance of live birth with freeze-all and subsequent thaw than with another fresh cycle., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Recent dramatic increases in success rates with frozen-thawed embryo transfer (FET) are encouraging, as are numerous findings of several reduced risks with FET when compared with fresh transfer. These reduced risks include low birth weight and prematurity, among others. However, FET is also associated with increased risks of macrosomia and large for gestational age. There have been reports of greater implantation and pregnancy rates with FET than with fresh autologous embryo transfer, suggesting superior endometrial receptivity in the absence of ovarian stimulation. As cryo-technology evolves, there is potential for further increase in FET success rates, but for now it may be best to follow an individualized approach, balancing fresh transfer and embryo cohort cryopreservation options while considering patient characteristics, cycle parameters, and clinic success rates., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to test sex differences in sagittal plane thoracic (T), lumbar (L), and pelvic (P) angles measured during the sit-and-reach (SR) test and hip joint angle during a passive straight leg raise (SLR) test in men and women matched for SR scores. Thirty-five men and 35 women performed a standard SR and SLR test. Among the 70 subjects, 25 male and female pairs were identified using <5% difference in the SR score as the pairing criterion. Both SR and SLR tests were videotaped and subsequently analyzed using a computer software angle tool to measure T, L, and P angles during the SR test and hip joint angle during the SLR test. In paired men (M) and women (W), P angle (M: 96.6 ± 9.4° vs. W: 104.7 ± 12.4°) and hip joint angle (M: 87.1 ± 10.5° vs. W: 100.4 ± 12.1°) were lower and L angle (M: 26.3 ± 10.8° vs. W: 21.1 ± 7.6°) was greater in men. There was no difference in the T angle (53.3 ± 11.6° vs. 51.2 ± 11.4°) between men and women. Correlation coefficient indicated that the SR score was moderately associated with the P angle in both men (r = 0.82) and women (r = 0.83), whereas the traditional criterion measure for hip flexibility, SLR hip joint angle, demonstrated a relatively low correlation to SR scores in both men (r = 0.60) and women (r = 0.56). These data indicate that the SR score does not distinguish spine and pelvic flexibility differences in men and women and does not adequately assess hip flexibility.

Objective: To discern the potential effect of ovarian stimulation on implantation potential by comparing ongoing pregnancy rates from matched blastocysts in fresh and frozen-thawed single-embryo-transfer cycles., Design: Matched cohort study., Setting: Private fertility center., Patient(s): Ninety-three matched pairs of single-blastocyst transfer., Intervention(s): Fresh and frozen-thawed embryo transfers were matched on embryo parameters and patient age., Main Outcome Measure(s): Ongoing pregnancy at 10 weeks' gestation., Result(s): The fresh and frozen-thawed groups did not differ significantly in blastocyst diameter, inner cell mass size, trophectoderm cell count, patient age, use of genetic screening, or presence of supernumerary embryos. The ongoing pregnancy rate was significantly greater in the frozen-thawed group than in the fresh group for transfers of day 6 blastocysts (54.3% vs. 17.1%, respectively), but not for day 5 blastocysts (60.9% vs. 56.5%, respectively). This resulted in the overall ongoing pregnancy rate to be significantly greater in the frozen-thawed group than in the fresh group (55.9% vs. 26.9%, respectively)., Conclusion(s): Autologous day 6 blastocysts transferred in frozen-thawed cycles have significantly greater chance of viable implantation than morphologically equivalent embryos transferred in fresh cycles. This advantage appears to result from impaired implantation of day 6 blastocysts in fresh transfers after ovarian stimulation, suggesting that embryo-endometrium asynchrony is a major cause of impaired endometrial receptivity after ovarian stimulation., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to determine the reliability of a computer software angle tool that measures thoracic (T), lumbar (L), and pelvic (P) angles as a means of evaluating spine and pelvic flexibility during the sit-and-reach (SR) test. Thirty adults performed the SR twice on separate days. The SR test was captured on video and later analyzed for T, L, and P angles using the computer software angle tool. During the test, 3 markers were placed over T1, T12, and L5 vertebrae to identify T, L, and P angles. Intraclass correlation coefficient (ICC) indicated a very high internal consistency (between trials) for T, L, and P angles (0.95-0.99); thus, the average of trials was used for test-retest (between days) reliability. Mean (±SD) values did not differ between days for T (51.0 ± 14.3 vs. 52.3 ± 16.2°), L (23.9 ± 7.1 vs. 23.0 ± 6.9°), or P (98.4 ± 15.6 vs. 98.3 ± 14.7°) angles. Test-retest reliability (ICC) was high for T (0.96) and P (0.97) angles and moderate for L angle (0.84). Both intrarater and interrater reliabilities were high for T (0.95, 0.94) and P (0.97, 0.97) angles and moderate for L angle (0.87, 0.82). Thus, the computer software angle tool is a highly objective method for assessing spine and pelvic flexibility during a video-captured SR test.

The current study assessed the relationship between serum concentrations of human chorionic gonadotrophin (HCG) measured in the peri-implantation period and various outcome measures following blastocyst transfer in IVF cycles. The study group included 767 autologous IVF cycles, each with the transfer of two fresh blastocysts in a 6-year study period, ending 31 December 2009. Outcome measures were ectopic pregnancy, biochemical pregnancy loss, ongoing pregnancy, spontaneous abortion and multiple pregnancy. Peri-implantation serum HCG concentration measured 5 days after blastocyst transfer was highly predictive of these outcome measures. These findings suggest embryonic implantation and developmental fate are largely determined by 5 days after blastocyst transfer and that very early serum HCG measurements may be useful markers of IVF outcome., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Clinical pregnancy rates of 80% and 65% were observed in cycles using thawed and fresh embryos, respectively, although embryo quality indicators revealed morphologically and numerically inferior embryo cohorts after cryopreservation. Subsequent logistic regression analysis controlled for differences in embryo quality and revealed significantly greater probability of clinical pregnancy with thawed embryos when compared with fresh, suggesting a negative effect of ovarian stimulation on endometrial receptivity., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare success rates between fresh ETs after ovarian stimulation and frozen-thawed ETs (FET) after artificial endometrial preparation, to compare endometrial receptivity., Design: Randomized, controlled trial., Setting: Private fertility center., Patient(s): There were 53 patients completing fresh blastocyst transfer (fresh group) and 50 patients completing FET (cryopreservation group). All were first-time IVF patients aged <41 years, with cycle day 3 FSH <10 mIU/mL and 8-15 antral follicles., Intervention(s): Randomized to fresh or thawed ET., Main Outcome Measure(s): Clinical pregnancy rate per transfer., Result(s): The clinical pregnancy rate per transfer was 84.0% in the cryopreservation group and 54.7% in the fresh group. The implantation rates were 70.8% and 38.9%, respectively. The ongoing pregnancy rates per transfer (at 10 weeks' gestation) were 78.0% and 50.9%, respectively. The attributable risk percentage of implantation failure due to reduced endometrial receptivity in the fresh group was 64.7%., Conclusion(s): The clinical pregnancy rate per transfer was significantly greater in the cryopreservation group than in the fresh group. These results strongly suggest impaired endometrial receptivity in fresh ET cycles after ovarian stimulation, when compared with FET cycles with artificial endometrial preparation. Impaired endometrial receptivity apparently accounted for most implantation failures in the fresh group. ClinicalTrials.gov Identifier: NCT00963625., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This retrospective study of fresh autologous blastocyst transfers in high responders compared ongoing pregnancy rates in cycles that followed trigger with GnRH agonist (GnRHa) alone with standard luteal support, GnRHa alone with enhanced luteal support, or GnRHa with concomitant low-dose hCG (dual trigger). Ongoing pregnancy rates were significantly increased with the dual trigger or with enhanced luteal support, whereas the incidence of clinically significant ovarian hyperstimulation syndrome was 0.0% in the groups receiving only GnRHa and 0.5% (1 of 182) in patients receiving GnRHa with concomitant low-dose hCG., (Copyright © 2011. Published by Elsevier Inc.)

The magnitude of the LH surge after GnRH agonist "trigger" was correlated with oocyte yield and maturity and was suboptimal in approximately half of the cycles. A modest reduction in oocyte yield and maturity was observed when the serum level of LH 12 hours after GnRH agonist trigger was less than the median value (52 IU/L), and a dramatic reduction in yield and maturity was observed when that level was less than 12 IU/L., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether embryo cryopreservation in cycles with elevated preovulatory P followed by thaw, extended culture, and transfer results in greater ongoing pregnancy rates than fresh blastocyst transfer., Design: Retrospective matched cohort study., Setting: Private fertility center., Patient(s): The study group consisted of 118 consecutive thaws of bipronucleate (2PN) oocytes derived from autologous cycles with elevated preovulatory P, resulting in 95 blastocyst transfers. The control group was selected by matching on the number of 2PN oocytes and patient age and consisted of 118 fresh cycles with elevated preovulatory P, including 108 fresh autologous blastocyst transfers. All patients were <41 years old at the time of stimulation., Intervention(s): None., Main Outcome Measure(s): Implantation and ongoing pregnancy rates., Result(s): The study group had significantly fewer blastocysts per 2PN oocyte than the control group (19.7% vs. 36.8%, respectively) and a significantly greater cancellation rate (19.5% vs. 8.5%, respectively). However, the ongoing pregnancy rate per cycle was significantly higher in the study group than in the control group (56.8% vs. 32.2%, respectively), resulting from greater rates of implantation (56.8% vs. 26.9%, respectively) and of ongoing pregnancy per transfer (70.5% vs. 35.2%, respectively)., Conclusion(s): In cycles with elevated preovulatory P, the probabilities of implantation and ongoing pregnancy are increased if all 2PN oocytes are cryopreserved and subsequently thawed and cultured to the blastocyst stage before transfer., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This retrospective cohort study compared blastocyst transfers in 136 fresh oocyte donor cycles and 69 autologous cycles using blastocysts derived from culture of thawed bipronuclear oocytes, all with oocytes derived from patients or donors less than 35 years old. The autologous cycles and oocyte donor cycles had similar rates of implantation (65.9% vs. 62.1%, respectively) and ongoing pregnancy (79.7% vs. 75.0%, respectively), suggesting that autologous blastocysts transferred after post-thaw extended culture have viability and implantation potential that are comparable with those of blastocysts transferred in fresh oocyte donor cycles., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To describe success rates with bipronuclear (2PN) oocyte cryopreservation, followed by thaw, extended culture, and blastocyst transfer., Design: Retrospective study., Setting: Private fertility center., Patient(s): There were 48 blastocyst transfers after post-thaw extended culture in patients less than 35 years old and 43 transfers in patients 35-40 years old., Intervention(s): Patients opted for cryopreservation of their entire cohorts at the 2PN stage. Thawed 2PN oocytes were cultured to the blastocyst stage before transfer., Main Outcome Measure(s): Implantation, ongoing pregnancy., Result(s): Among patients less than 35 years old at oocyte retrieval, there were 59 thaws of 2PN oocytes, 48 blastocyst transfers, and 40 ongoing pregnancies (79.2% per transfer), the implantation rate was 64.2%, and the ongoing pregnancy rate (PR) per thaw was 64.4%. Among patients 35-40 years of age at retrieval, there were 58 thaws, 43 blastocyst transfers, and 22 ongoing pregnancies (51.2% per transfer), the implantation rate was 44.0%, and the ongoing PR per thaw was 39.3%. Patients less than 35 years old had significantly greater rates of implantation and ongoing pregnancy than did patients 35-40 years of age. Patients with 12 or more 2PN oocytes had significantly greater rate of ongoing pregnancy than those with fewer than 12 2PN oocytes., Conclusion(s): Post-thaw extended culture and blastocyst transfer yield high rates of implantation and ongoing pregnancy. Ongoing PRs decline with increasing age.

Objective: To identify dominant predictors of clinical pregnancy in IVF cycles., Design: Retrospective study., Setting: Private fertility center., Patient(s): The study included 580 fresh autologous IVF cycles with blastocyst transfer., Intervention(s): None., Main Outcome Measure(s): Clinical pregnancy rate., Result(s): A set of 25 suspected predictors was used to develop predictive models of clinical pregnancy in a set of 361 blastocyst transfer cycles. Initial bivariate analysis identified 14 of these variables that were significant enough to be candidate variables for multiple logistic regression. Similar sets of significant variables were identified by using alternative approaches for model construction. The final model included blastocyst diameter, day of blastulation, and preovulatory serum P level as significant predictors of clinical pregnancy. Specifically, clinical pregnancy was predicted by preovulatory serum P of <1.0 ng/mL, blastulation on day 5, and large blastocyst diameter. Of these variables, blastocyst diameter was the most significant predictor of clinical pregnancy in the multivariate models. The final model was validated against a separate set of 219 subsequent blastocyst transfer cycles., Conclusion(s): Pre-ovulatory serum P level, blastulation day, and embryo diameter are simultaneously predictive of clinical pregnancy, and their relationships with clinical pregnancy are consistent with an effect of embryo-endometrium synchrony.

Acceptable rates of fertilization, implantation, clinical pregnancy, ongoing pregnancy, and early pregnancy loss were achieved in high responders after triggering final oocyte maturation with a combination of leuprolide acetate and hCG (1,000 to 2,500 IU). These findings, along with the absence of ovarian hyperstimulation syndrome, suggest that this dual trigger is safe and effective for oocyte maturation in patients with significant risk factors for ovarian hyperstimulation syndrome.

Objective: To compare the effect of day 5 and day 6 blastocyst transfers on patterns of implantation rates and pregnancy rates (PRs) among fresh autologous, oocyte donor, and frozen ET (FET) cycles., Design: Retrospective study., Setting: Private fertility center., Patient(s): The study included 377 fresh autologous cycles, 106 autologous FET cycles, and 56 fresh oocyte donor cycles., Intervention(s): None., Main Outcome Measure(s): Implantation rates and clinical PRs., Result(s): The clinical PR for day 5 blastocyst transfers was higher than for day 6 blastocyst transfers in fresh autologous cycles (PRs, 51.0% and 33.3%, respectively). However, there was no significant difference between transfers of blastocysts cryopreserved on day 5 and day 6 in FET cycles (PRs, 63.6% and 58.9%, respectively). Furthermore, day 6 blastocyst transfers significantly outperformed day 5 transfers in donor cycles (PRs, 63.0% and 86.2%, respectively), a reversal of the pattern seen in the fresh autologous cycles. Day 6 blastocysts were associated with a significantly greater PR in FET cycles than in fresh autologous cycles (58.9% and 33.3%, respectively)., Conclusion(s): The superior PRs with day 5 blastocyst transfers in fresh autologous cycles and with day 6 blastocysts in donor cycles may have resulted from better synchrony with endometrial development. This was further supported by the superior performance of day 6 blastocysts in FET cycles relative to their fresh counterparts. Similar PRs with cryopreserved day 5 and day 6 blastocysts in FET cycles may reflect that, in these cycles, day 5 and day 6 blastocysts had equivalent quality and similar synchrony with the endometrium.

In this retrospective study of 74 oocyte-donor IVF cycles, the rates of fertilization, implantation, clinical pregnancy, ongoing pregnancy, and early pregnancy loss were similar after an agonist or hCG trigger. These findings suggest that the agonist trigger is a viable alternative for oocyte donors with significant risk factors for ovarian hyperstimulation syndrome.

Objective: To determine whether the serum concentration of hCG on the day after hCG administration (abbreviated throughout this article as [hCG]) is related to the incidence of ovarian hyperstimulation syndrome (OHSS), oocyte recovery per follicle, fertilization, blastulation, embryo transfer, implantation, and clinical pregnancy., Design: Retrospective study., Setting: Private infertility clinic., Patient(s): The OHSS study group included 849 non-donor IVF cycles performed between January 1998 and August 2003. The study group for hCG efficacy included 248 nondonor IVF cycles performed between January 2001 and May 2003 with patients younger than 35 years of age., Intervention(s): None., Main Outcome Measure(s): Occurrence of OHSS, severity of OHSS, [hCG], proportion of follicles yielding oocytes, fertilization rate, blastulation rate, transfer rate, implantation rate, and clinical pregnancy rate., Result(s): No significant relationships were observed between [hCG] and the proportion of follicles yielding oocytes, fertilization rate, blastulation rate, or the probabilities of embryo transfer, implantation, or clinical pregnancy. The incidence of OHSS (all types) and OHSS requiring transvaginal paracentesis were predicted by [hCG] (P=.02 and P=.05, respectively) and with follicle count (P<.0001 in both cases)., Conclusion(s): These results suggest that moderated hCG dosage is useful in preventing OHSS without reducing efficacy.

Objective: To examine the effects of patient age on the growth and transfer of blastocyst-stage embryos., Design: Retrospective clinical study., Setting: Private assisted reproductive technologies center., Patient(s): Three hundred patients between the ages of 18 and 45 undergoing in vitro fertilization., Intervention(s): Bipronucleate oocytes were grown for up to 144 hours and subsequently transferred when at least one embryo attained the expanded blastocyst stage., Main Outcome Measure(s): Oocytes retrieved and fertilized, blastocyst formation rates, implantation rates, and pregnancy rates per retrieval and transfer., Result(s): The rate of cycle cancellation before oocyte retrieval increased significantly with age, and the average number of oocytes per retrieval declined significantly with age. Fertilization rates were unrelated to patient age. The proportion of cycles with expanded blastocysts declined significantly with age. Pregnancy rates per stimulation declined with age, but pregnancy rates per transfer were approximately 50% across the entire age range studied., Conclusion(s): The decline in female fertility with age appears to be the result of reduced numbers of oocytes and the inability of fertilized oocytes to develop to the blastocyst stage. Implantation and pregnancy rates appear to be unaffected by age when blastocysts do form.

Objective: To investigate the predictive value of quantitative measurements of blastocyst morphology on subsequent implantation rates after transfer., Design: Prospective observational study., Setting: Private assisted reproductive technology center., Patient(s): One hundred seventy-four IVF patients receiving transfers of expanded blastocyst-stage embryos on day 5 (n = 112) or day 6 (n = 62) after oocyte retrieval., Intervention(s): None., Main Outcome Measure(s): Blastocyst diameter, number of trophectoderm cells, inner cell mass (ICM) size, ICM shape, and implantation and pregnancy rates., Result(s): Blastocyst diameter and trophectoderm cell numbers were unrelated to implantation rates. Day 5 expanded blastocysts with ICMs of >4,500 microm(2) implanted at a higher rate than did those with smaller ICMs (55% vs. 31%). Day 5 expanded blastocysts with slightly oval ICMs implanted at a higher rate (58%) compared with those with either rounder ICMs (7%) or more elongated ICMs (33%). Implantation rates were highest (71%) for embryos with both optimal ICM size and shape. Pregnancy rates were higher for day 5 transfers of optimally shaped ICMs compared with day 5 transfers of optimally sized ICMs., Conclusion(s): Quantitative measurements of the inner cell mass are highly indicative of blastocyst implantation potential. Blastocysts with relatively large and/or slightly oval ICMs are more likely to implant than other blastocysts.

Objective: To compare the outcome of second and third cycles of in vitro fertilization with blastocyst transfer to the outcome of first attempts at IVF with blastocyst transfer., Design: Retrospective study., Setting: Private ART center., Patient(s): Three hundred and four patients undergoing treatment with in vitro fertilization with blastocyst transfer, 87 of which underwent at least one cycle of re-treatment after failing to achieve pregnancy in their first cycle., Intervention(s): Bipronucleate oocytes were grown for up to 144 hours and subsequently transferred when at least one embryo attained the expanded blastocyst stage., Main Outcome Measure(s): Pregnancy and implantation rates., Result(s): Pregnancy rates per retrieval were significantly higher for patients undergoing their first cycle of in vitro fertilization with blastocyst transfer (36%) compared to those undergoing their second (19%) or their third (9%) cycles of treatment. Implantation rates per embryo were also higher for first cycles of in vitro fertilization with blastocyst transfer (30%) compared to second (18%) or third cycles (8%)., Conclusion(s): Pregnancy and implantation rates decline dramatically in repeated cycles of in vitro fertilization with blastocyst transfer following one or more unsuccessful cycles of in vitro fertilization with blastocyst transfer.

Objective: To compare implantation and pregnancy rates according to the day of embryo transfer (day 5 or 6 after oocyte retrieval) when transfer was postponed until expanded blastocysts developed., Design: Retrospective clinical study., Setting: Private ART center., Patient(s): One-hundred and eighty-three women undergoing blastocyst-stage embryo transfer following in vitro fertilization., Intervention(s): Bipronucleate oocytes were grown for up to 144 hours and subsequently transferred only when at least one embryo attained the expanded blastocyst stage., Main Outcome Measure(s): Implantation and pregnancy rates., Result(s): Blastocysts transferred on day 5 implanted at nearly twice the rate of blastocysts transferred on day 6 (36.3% vs. 19.0%). Pregnancy rates were also almost twice as high among the day 5 transfer patients (59.3% vs. 32.3%). In addition, more blastocysts developed (3.6 vs. 2.4), and more were transferred (2.7 vs. 2.3) to the day 5 transfer patients, although the proportion of expanded blastocysts among the blastocysts that were transferred was the same for the two groups (91.7% vs. 93.6%)., Conclusion(s): Embryos that develop to the expanded blastocyst stage and are transferred on day 5 after retrieval are approximately twice as likely to implant compared to those for which expansion and transfer are delayed until day 6.

Objective: To determine the predictive value of 72-hour blastomere cell number on blastocyst development and to compare success rates of subsequent transfer based on the degree of blastocyst development., Design: Retrospective clinical study., Setting: Private assisted reproductive technology center., Patient(s): Ninety-three women aged 32.0 +/- 5.1 years undergoing oocyte retrieval for IVF., Intervention(s): Bipronucleate oocytes obtained from IVF were grown for up to 168 hours after fertilization and subsequently transferred at the blastocyst stage., Main Outcome Measure(s): Percentages of embryos developing to blastocyst from 72-hour embryos by blastomere cell number and subsequent implantation and pregnancy rates of transferred blastocysts., Result(s): Rates of blastocyst formation and expansion increased as cell numbers at 72 hours increased. Implantation rates were 43% for embryos transferred to women receiving only expanded blastocysts and 17% for embryos transferred to women receiving one or more less developed blastocysts. Pregnancy rates were higher for women receiving only expanded blastocysts than for women receiving one or more less developed blastocysts, although the difference was not significant., Conclusion(s): More developed 72-hour embryos are more likely to become blastocysts and expand. Implantation rates are greater for the transfer of expanded rather than unexpanded blastocysts.

A cohort of patients with sickle cell disease, consisting of children, adolescents, and adults, who reported experiencing three or more episodes of vaso-occlusive pain the preceding year, were enrolled in a prospective two-period treatment protocol. Following a 4-month conventional treatment baseline phase, a supplemental cognitive-behavioral pain management program that centered on self-hypnosis was implemented over the next 18 months. Frequency of self-hypnosis group straining sessions began at once per week for the first 6 months, became biweekly for the next 6 months, and finally occurred once every third week for the remaining 6 months. Results indicate that the self-hypnosis intervention was associated with a significant reduction in pain days. Both the proportion of "bad sleep" nights and the use of pain medications also decreased significantly during the self-hypnosis treatment phase. However, participants continued to report disturbed sleep and to require medications on those days during which they did experience pain. Findings further suggest that the overall reduction in pain frequency was due to the elimination of less severe episodes of pain. Non-specific factors may have contributed to the efficacy of treatment. Nevertheless, the program clearly demonstrates that an adjunctive behavioral treatment for sickle cell pain, involving patient self-management and regular contact with a medical self-hypnosis team, can be beneficial in reducing recurrent, unpredictable episodes of pain in a patient population for whom few safe, cost-effective medical alternatives exist.

Pain is the most common problem encountered by patients with sickle cell disease (SCD). We report the results of a survey sent to hematologists and emergency department (ED) physicians regarding their perceptions and practices concerning pain and its management. Hematologists and ED physicians differed considerably in their perceptions about the natural history of the pain, and about the percentage of patients who are addicted to analgesics. Fifty-three percent of the ED physicians and 23% of the hematologists thought that more than 20% of patients are addicted. These beliefs and perceptions about SCD-related pain and the prevalence of addiction must be addressed if clinical care is to be changed substantively.

Some children and adolescents with sickle cell disease experience frequent painful episodes. To gain information about the natural history of the pain and its impact on sleep and school attendance, we developed a home-based diary system. Eighteen children and adolescents completed 4756 diary days, with an average compliance of 75%. Pain was reported on 30% of days and was managed at home nine-tenths of the time. Girls reported more days with pain than did boys, and age was positively correlated with the length of the painful episodes. The pain affected school attendance and sleep. Patients were absent from school on 21% of 3186 school days, with half of the absenteeisms on days with reported pain. Of the pain-associated absenteeisms, two-thirds occurred when pain was managed at home, and one-third when patients were hospitalized. The average consecutive number of school days missed was 2.7. These findings have implications for developmentally critical activities.

To delineate dose ranges, utilization patterns, and the frequency and types of problems encountered, we retrospectively reviewed the medical records of 46 patients with sickle hemoglobinopathies who used patient-controlled analgesia (PCA) a total of 92 times for the management of vasooclusive pain. Patients varied widely in the drug administered, use of basal infusion, individual dose, and total amount of drug received. On the day of heaviest use, the average maximum hourly dose was equivalent to 0.09 mg/kg of morphine. In this study, 11 patients and two families disliked PCA, one patient had respiratory compromise, and one patient tampered with the machine. Patient satisfaction with PCA probably reflects interactions among the psychosocial impact of chronic illness and chronic pain, individual psychological and temperamental factors, environmental contingencies, and the expectations and beliefs of the family and the health-care professionals. Based on this experience, recommendations can be proposed for the use of PCA in this condition.

Objective: Our objective was to develop a mathematic model for the prediction of transvaginal ultrasonographic identification of intrauterine gestation as a function of human chorionic gonadotropin titer or gestational age., Study Design: In this prospective, descriptive study normal intrauterine pregnancies of 31 patients from the Yale in vitro fertilization and embryo transfer program and infertility clinic were studied. Logistic regression analysis was used to develop a probability curve of transvaginal ultrasonographic detection of intrauterine pregnancy as a function of human chorionic gonadotropin titer or gestational age with a 5 MHz vaginal transducer., Results: A model-based prediction was constructed. It revealed that nearly all intrauterine sacs should be identified by a human chorionic gonadotropin titer of 3000 mIU/ml (first international reference preparation) or by a gestational age of 37 days on the basis of the 5 MHz vaginal transducer., Conclusions: A model-based prediction for transvaginal ultrasonographic identification of early intrauterine pregnancy is presented that can be readily adapted by individual institutions using their own ultrasonographic equipment and human chorionic gonadotropin assay.

Adolescence is a time when concerns about independence and self-control are of paramount importance. These developmental issues must be considered when planning treatment for adolescents with acute or chronic pain. Patient-controlled analgesia (PCA) is a method of administering opioids that reinforces patient autonomy. Traditionally, opioids given by PCA are administered via the intravenous or subcutaneous route. Issues of autonomy and control, however, are no less important for patients receiving oral opioids. To augment patient autonomy, we have provided oral medication kept at the bedside (oral bedside PCA) for adolescents with diverse pain problems. We describe our selection criteria and methods for using oral bedside PCA with adolescents and present 4 patients who used this method.

This article is a report of our experience with an interdisciplinary pain service in a large tertiary care pediatric hospital. During the first 2 years of operation, we received 869 consultations and referrals from more than 19 hospital divisions. Postoperative pain was the most frequent reason for consultation (56% of patients). Patients with pain related to cancer and sickle cell disease comprised 25% of the consultations. The remaining patients had a wide variety of primary diagnoses and causes of pain. We calculated the time spent by pain service physicians in direct patient care. The majority (63%) of physician time was spent with a small number of patients (17%). Most of these patients had pain that was unrelated to surgery, cancer, or sickle cell disease, and many posed dilemmas in diagnosis and treatment. Physician time was correlated directly to the use of psychologic and physical therapies for the pain, involving multiple team members. This experience supports the demand for an interdisciplinary pain service in a tertiary care children's hospital. A significant amount of physician time is necessary to provide patient care and to maintain a team approach, however, and pediatricians and other health care professionals who aim to implement such services should be cognizant of the time required.