Vaccination during pregnancy by race/ethnicity: a focus on American Indians/Alaska Natives.

BACKGROUND: Vaccination during pregnancy reduces the incidence of infections and their associated adverse outcomes in both mothers and infants. The American College of Obstetricians and Gynecologists has recommended influenza and Tdap vaccination during pregnancy since 2004 and 2013, respectively. Several studies have examined disparities in vaccination rates during pregnancy by race/ethnicity. However, none have included American Indians/Alaska Natives as a specific racial/ethnic group on a national level. Current literature suggests that American Indian/Alaska Native infants experience increased morbidity and mortality from both influenza and pertussis infections compared with most other groups in the United States. OBJECTIVE: This study aimed to evaluate the uptake of influenza and Tdap vaccinations during pregnancy by race/ethnicity, with a specific focus on American Indian/Alaska Native people. STUDY DESIGN: This cross-sectional study used data from the Pregnancy Risk Assessment Monitoring System. Comparisons of vaccine uptake across racial/ethnic groups (American Indian/Alaska Native, Asian, non-Hispanic Black, non-Hispanic White, Hispanic, and "None of the above") were evaluated using weighted logistic regression analyses to estimate prevalence odds ratios with 95% confidence intervals. Models were adjusted for maternal age, parity, maternal education, marital status, payment method at delivery, prenatal care in first trimester, maternal smoking status, Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) participation, and receipt of influenza vaccine reported by a health care provider. RESULTS: For both vaccines, Asian respondents had the highest uptake (influenza, 70.1%; Tdap, 68.2%), whereas Black respondents reported the lowest uptake (influenza, 44.4%; Tdap, 57.9%). For the influenza vaccine, American Indian/Alaska Native respondents demonstrated a higher uptake compared with White respondents, and the magnitude of difference increased markedly after adjusting for respondent characteristics (adjusted odds ratio, 1.74; 95% confidence interval, 1.58-1.90). In the unadjusted analyses, Black individuals reported influenza vaccination at approximately half the rate of their White counterparts during pregnancy. This effect was attenuated but remained lower after adjustment for respondent characteristics (adjusted odds ratio, 0.73; 95% confidence interval, 0.70-0.76). For the Tdap vaccine, American Indian/Alaska Native respondents reported lower uptake than White respondents; however, this difference disappeared when adjusted for respondent characteristics (adjusted odds ratio, 0.99; 95% confidence interval, 0.83-1.19). Asian and Hispanic respondents displayed a similar uptake compared with their White counterparts for both vaccines. CONCLUSION: Our findings indicate that there are racial/ethnic disparities in influenza and Tdap vaccination rates among pregnant individuals in the United States. Demonstration of increased uptake among American Indian/Alaska Native people in the crude analysis may reflect the success of various public health interventions through Tribal and Indian Health Service hospitals. Nonetheless, vaccination status during pregnancy remains seriously below national guideline recommendations. Greater measures must be taken to support preventative care in marginalized populations, with particular emphasis on community-driven solutions rooted in justice.

Assessment of clinical pregnancies in up to eight ovarian stimulation with intrauterine insemination treatment cycles in those unable to proceed with in vitro fertilization.

OBJECTIVE: To study the primary objective of clinical pregnancy (CP) rate per ovarian stimulation with intrauterine insemination (OS-IUI) treatment cycle in patients with repetitive cycles up to a maximum of 8 cycles. DESIGN: Retrospective cohort. SETTING: Large fertility clinic. PATIENTS: A total of 37,565 consecutive OS-IUI cycles from 18,509 patients were included in this study. INTERVENTIONS: Those with anovulatory diagnoses, tubal factor infertility, male factor infertility, using donor sperm, canceled cycles, and those with missing data for either baseline characteristics or outcome were excluded. The CP rate was analyzed using generalized estimating equations and controlled for age, stimulation protocol, and body mass index. MAIN OUTCOMES MEASURES: Clinical pregnancy was defined as intrauterine gestation with fetal heartbeat visible on ultrasound. RESULTS: A total of 37,565 consecutive OS-IUI cycles from 2002 through 2019 at a private practice facility were evaluated. All cycles met inclusion criteria and were used in generalized estimating equation modeling. Patients aged <35 years comprised 47.6% of the cohort. After adjustment for confounders, the mean predicted probability of CP for cycles one to 8 was 15.7% per cycle. The mean predicted probability of CP in aggregated data from cycles 2 to 4 was only 1.7% lower compared with cycle 1 as the referent (16.7% vs. 15.0%, 95% confidence interval [CI] 2nd: 0.88 {0.82, 0.95}, 3rd: 0.86 {0.79, 0.93}, 4th: 0.88 {0.79, 0.98}). However, the 15.0% mean predicted probability of CP for the second through the fourth cycle was concordant with the mean for all included cycles (15.7%). The mean predicted probability of CP of cycles 5 to 8 was not significantly different compared with the referent (16.7% vs. 16.1%, 95% CI 5th: 0.97 [0.85, 1.11], 6th: 0.93 [0.79, 1.10], 7th: 1.01 [0.81, 1.26], 8th: 1.01 [0.76, 1.34]). The modeling of consecutive cycles suggested that the adjusted cumulative predicted probability of CP from OS-IUI continues to increase with each of the 8 successive cycles. CONCLUSION: Clinical pregnancy rates are satisfactory in up to 8 consecutive OS-IUI treatment cycles. These data are useful for counseling, especially in those patients for whom in vitro fertilization is not financially or ethically feasible.

Exposure to persistent organic pollutants in newborn dried blood spots and childhood acute myeloid leukemia.

Acute myeloid leukemia (AML) is a rare malignancy representing 15-20% of all leukemia diagnoses among children. Maternal exposure to persistent organic pollutants is suggestive of increased risk for childhood AML based on existing evidence. We aimed to evaluate the relationship between persistent organic pollutants and childhood AML using newborn dried bloodspots (DBS) from the Michigan BioTrust for Health. We obtained data on AML cases diagnosed prior to 15 years of age (n = 130) and controls (n = 130) matched to cases on week of birth from the Michigan Department of Health and Human Services. We quantified levels of dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), and polybrominated diphenyl ether congener 47 (BDE-47) in newborn DBS. We also evaluated other organochlorine pesticides, polychlorinated biphenyls, polybrominated biphenyl congener 153, and polybrominated diphenyl ethers, though these were not further evaluated as >60% of observations were above the limit of detection for these chemicals. To evaluate the association between each chemical and AML, we used multivariable conditional logistic regression. In our multivariable model of HCB adjusted for month of birth, maternal age at delivery, and area poverty, we observed no association with AML (Odds Ratio [OR] per interquartile range increase: 1.17, 95% CI: 0.80, 1.69). For p,p'-DDE, ORs were significantly lower for those exposed to the highest tertile of p,'p-DDE (≥0.29 pg/mL, OR: 0.32, 95% CI: 0.11, 0.95) compared to the first tertile (<0.09 pg/mL). We observed no statistically significant associations between HCB and BDE-47 and AML. We observed a reduced odds of exposure to p,'p-DDE and an increased, though imprecise, odds of exposure to HCB among AML cases compared to controls. Future studies would benefit from a larger sample of AML patients and pooling newborn DBS across multiple states to allow for additional variability in exposures and evaluation of AML subtypes, which may have differing etiology.

Association between obesity and fecundity in patients undergoing intrauterine insemination.

Objective: To determine if an association exists between body mass index (BMI) and fecundity after intrauterine insemination (IUI). Design: Retrospective cohort study. Setting: Academic-based fertility clinic. Patients: Patients undergoing IUI July 2007 to May 2012. Interventions: None. Main Outcome Measures: Primary outcome: live-birth rate (LBR) per IUI cycle; secondary outcomes: positive pregnancy test and clinical pregnancy rates (CPRs). Results: A total of 1959 cycles were performed on 661 women (mean age, 31.9 ± 4.9 years). When examined by obesity class, LBR and CPR were similar for women with class I, II, and III obesity when compared with women with normal BMI. However, class III obese women (adjusted risk ratio [aRR], 1.70; 95% confidence interval [CI], 1.12-2.59) had increased pregnancy rates compared with normal BMI, but no differences in pregnancy rates were observed for women with class I or II obesity. In addition, pregnancy rates (aRR, 1.50; 95% CI, 1.12-2.02) and CPR (aRR, 1.51; 95% CI, 1.07-2.14) were higher in overweight women relative to normal BMI. Notably, among patients with ovulatory dysfunction, CPRs after IUI were reduced by 43% in obese women (aRR, 0.57; 95% CI, 0.37-1.07), whereas women without ovulatory dysfunction were twice as likely to achieve a clinical pregnancy when they were obese (aRR, 1.96; 95% CI, 1.19-3.24). The CIs for the obesity risk ratios in each stratum of ovulatory function exhibited no overlap, suggesting evidence of potential effect modification by ovulatory function. Conclusions: LBRs after IUI were similar across BMI subgroups. This is in contrast to research of in vitro fertilization treatments showing lower LBR with increasing BMI. However, obesity may adversely affect IUI CPR in those with ovulatory dysfunction in particular. The reason for this discrepancy is unclear and warrants further study.

The Relation Between Travel Distance and Overall Survival for HPV-Associated Cancers in a High-Burden State.

Purpose: To assess the association between travel distance to an academic health system and overall survival for patients with human papillomavirus (HPV)-associated cancers. Methods: Using hospital-based cancer registry data from 2005-2019, we calculated unidirectional travel distance from each patient's geocoded address to our academic health center through network analysis. We categorized distance as short (<25 miles), intermediate (25-74.9 miles), or long (≥75 miles). The primary outcome was time from the date of initial diagnosis to the date of death or last contact. We used multivariable Cox proportional hazards regression to evaluate the association between travel distance and overall survival. We also estimated the adjusted observed 5-year survival rate. Results: Patients with HPV-associated cancers traveling distances that were intermediate (hazard ratio [HR], 1.23; 95% CI, 1.06-1.43) and long (HR, 1.15; 95% CI, 1.01-1.32) had a higher hazard of death than the short-distance group. The adjusted 5-year observed survival rates for HPV-associated cancers were lowest in the intermediate-distance group (60.4%) compared with the long-(62.6%) and short-distance (66.2%) groups. Conclusions: Our findings indicate that travel distance to an academic health center was associated with overall survival for patients with HPV-associated cancers, reflecting the importance of considering travel burden in improving patient outcomes.

Sperm very long-chain polyunsaturated fatty acids: relation to semen parameters and live birth outcome in a multicenter trial.

OBJECTIVE: To determine whether the levels of sperm very long-chain polyunsaturated fatty acids (VLC-PUFAs) are correlated with sperm parameters and the outcome of live birth after conventional therapy for unexplained infertility. DESIGN: Cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation randomized controlled trial. SETTING: Multicenter randomized controlled trial. PATIENTS: Male partners from 185 couples with unexplained infertility who provided baseline semen samples for analysis. INTERVENTION: We determined the levels of VLC-PUFAs in total lipid isolated from sperm membranes using liquid chromatography-mass spectrometry/mass spectrometry analyses. MAIN OUTCOME MEASURES: Sperm concentration, motility, morphology, total motile count (TMC), and live birth after standard treatment for unexplained infertility. RESULTS: Total VLC-PUFA percentage was positively correlated with sperm concentration (Spearman's rank correlation (rs) 0.56, P<.0001), TMC (rs = 0.40, P<.0001), and morphology (rs = 0.26, P=.0005). After adjustment for male body mass index, age, and race, a one-standard-deviation increase in the percentage of total VLC-PUFA was associated with a 62% increase in the geometric mean (GM) of sperm concentration (GM Ratio: 1.62 [95% confidence intervals {CI}: 1.45, 1.82]) and a 43% increase in the geometric mean of TMC (GM Ratio: 1.43 [95% CI; 1.24, 1.63]). Although no evidence of association was observed for sperm motility, a positive relationship was also observed between the percentage of total VLC-PUFA and sperm morphology [adjusted incidence rate ratio (IRR) for one-standard-deviation increase in total VLC-PUFA: 1.18 (95% CI; 1.02, 1.36)]. After adjustment for female age and treatment group, the probability of a live birth outcome was 72% more likely among those in the third tertile of hydroxylated VLC-PUFA percentage than in the first tertile (RR 1.72 [95% CI; 1.01, 2.94]). CONCLUSIONS: The positive correlation between sperm VLC-PUFAs percentage and sperm parameters, as well as the significant association between hydroxylated VLC-PUFA percentage and the outcome of live birth, strongly suggest that this class of fatty liquid chromatography-mass spectrometry/mass spectrometry acids is essential for normal sperm structure and function.

HPV vaccination coverage and factors among American Indians in Cherokee Nation.

PURPOSE: We estimated human papillomavirus (HPV) vaccine initiation coverage among American Indian adolescents and identified factors associated with HPV vaccination among parents of these adolescents. METHODS: We developed, tested, and disseminated a survey to a random sample of 2,000 parents of American Indian adolescents aged 9-17 years who had accessed Cherokee Nation Health Services from January 2019 to August 2020. We used log-binomial regression to estimate the unadjusted and adjusted weighted prevalence proportion ratios (PPR) and 95% confidence intervals (CI) for adolescent HPV vaccine initiation. RESULTS: HPV vaccine initiation coverage (≥ 1 dose) was 70.7% among adolescents aged 13-17 years. The prevalence of HPV vaccine initiation was higher among American Indian adolescents whose parents were aware of the HPV vaccine (adjusted weighted PPR 3.41; 95% CI 2.80, 4.15) and whose parents received a recommendation from their provider (adjusted weighted PPR 2.70; 95% CI 2.56, 2.84). The most common reasons reported by parents to vaccinate their children were to protect them against HPV-associated cancers (25.7%) and receiving a recommendation from a healthcare provider (25.0%). Parents cited vaccine safety concerns as the main reason for not getting their children vaccinated (33.2%). CONCLUSIONS: HPV vaccine initiation coverage among American Indian adolescents in Cherokee Nation was consistent with the national survey estimates. However, allaying parental concerns about vaccine safety and encouraging providers to recommend the HPV vaccine could improve coverage.

Follicular phase length is not related to live birth outcome in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination cycles in a multicenter trial.

Objective: To evaluate the effect of follicular phase length (FPL) on pregnancy outcomes and endometrial thickness (ET) among women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination (OS-IUI) with clomiphene citrate, letrozole, or gonadotropins. Design: Cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation randomized controlled trial. Setting: Multicenter randomized controlled trial. Patients: A total of 869 couples with unexplained infertility who underwent OS-IUI treatment cycles as part of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation study. Interventions: FPL was evaluated as a categorical variable defined by quintiles (q1: ≤11 days, q2: 12 days, q3: 13 days, q4: 14-15 days, and q5: ≥16 days). Main outcome measures: Clinical pregnancy, live birth rates, and ET. Results: Decreasing FPL quintiles did not reduce clinical pregnancy or live birth rates in unadjusted or adjusted models with all treatment groups combined or when stratified by the ovarian stimulation medication. All FPL categories had significantly thinner ET compared with the 5th quintile (≥16 days) among women treated with clomiphene citrate or letrozole. Similar but diminished associations were observed among women who underwent ovarian stimulation with gonadotropins, but the observed differences were limited to those with FPL of 12 days or shorter when compared with FPL ≥16 days. Conclusions: Although shorter FPL was associated with reduced ET, it was not associated with the outcomes of clinical pregnancy or live birth in women with unexplained infertility undergoing OS-IUI in all treatment groups combined. Similar patterns existed when analyses of clinical pregnancy and live birth rates were stratified by treatment. Clinical trial registration: NCT01044862.

Assessing urinary phenol and paraben mixtures in pregnant women with and without gestational diabetes mellitus: A case-control study.

Prior studies have identified the associations between environmental phenol and paraben exposures and increased risk of gestational diabetes mellitus (GDM), but no study addressed these exposures as mixtures. As methods have emerged to better assess exposures to multiple chemicals, our study aimed to apply Bayesian kernel machine regression (BKMR) to evaluate the association between phenol and paraben mixtures and GDM. This study included 64 GDM cases and 237 obstetric patient controls from the University of Oklahoma Medical Center. Mid-pregnancy spot urine samples were collected to quantify concentrations of bisphenol A (BPA), benzophenone-3, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, butylparaben, methylparaben, and propylparaben. Multivariable logistic regression was used to evaluate the associations between individual chemical biomarkers and GDM while controlling for confounding. We used probit implementation of BKMR with hierarchical variable selection to estimate the mean difference in GDM probability for each component of the phenol and paraben mixtures while controlling for the correlation among the chemical biomarkers. When analyzing individual chemicals using logistic regression, benzophenone-3 was positively associated with GDM [adjusted odds ratio (aOR) per interquartile range (IQR) = 1.54, 95% confidence interval (CI) 1.15, 2.08], while BPA was negatively associated with GDM (aOR 0.61, 95% CI 0.37, 0.99). In probit-BKMR analysis, an increase in z-score transformed log urinary concentrations of benzophenone-3 from the 10th to 90th percentile was associated with an increase in the estimated difference in the probability of GDM (0.67, 95% Credible Interval 0.04, 1.30), holding other chemicals fixed at their medians. No associations were identified between other chemical biomarkers and GDM in the BKMR analyses. We observed that the association of BPA and GDM was attenuated when accounting for correlated phenols and parabens, suggesting the importance of addressing chemical mixtures in perinatal environmental exposure studies. Additional prospective investigations will increase the understanding of the relationship between benzophenone-3 exposure and GDM development.

Antibiotic Prophylaxis to Prevent Obesity-Related Induction Complications in Nulliparae at Term: a pilot randomized controlled trial.

BACKGROUND: Women with obesity are at increased risk of complications during and after labor and delivery, including puerperal infection and cesarean delivery. As labor induction has become increasingly common, it is crucial to find ways to decrease complication rates in this high-risk population. OBJECTIVE: This study aimed to explore the effect of prophylactic antibiotics during labor induction of nulliparous women with obesity on the rates of cesarean delivery and puerperal infection and to estimate the parameters needed to calculate the sample size for a larger, multicenter trial. STUDY DESIGN: In this randomized, placebo-controlled pilot trial, nulliparous patients with a body mass index of ≥30 kg/m2 were randomized to either prophylactic antibiotics (500 mg azithromycin for 1 dose and 2 g cefazolin every 8 hours for up to 3 doses) or placebo, administered starting at the beginning of labor induction. The exclusion criteria were known fetal anomaly, fetal demise, multifetal gestation, ruptured membranes >12 hours, infection requiring antibiotics at the start of labor induction, and/or allergy to azithromycin or beta-lactam antibiotics. The co-primary outcomes were rates of puerperal infection (composite of chorioamnionitis, endometritis, and/or cesarean delivery wound infection) and cesarean delivery. Participants were followed up for 30 days after delivery, and maternal and neonatal demographic and outcome data were collected. Proportions and 95% confidence limits were calculated for each of these outcomes. RESULTS: From January 2019 to May 2021, 101 patients were randomized in the class III stratum (1 patient who was randomized ultimately did not undergo labor induction). From February 2020 to May 2021, 38 and 47 patients were randomized to class I and II strata, respectively (to assess the effect of obesity class on the outcomes expected to be influenced by antibiotic prophylaxis). In the antibiotics and placebo groups, the rates of cesarean delivery were 29.0% (95% confidence interval, 19.8-38.3) and 39.8% (95% confidence interval, 29.8-49.7), respectively, and puerperal infection occurred in 8.6% (95% confidence interval, 2.9-14.3) and 9.7% (95% confidence interval, 3.7-15.7), respectively. In the subgroup with class III obesity, in the antibiotics and placebo groups, the rates of cesarean delivery were 33.3% (95% confidence interval, 20.4-47.9) and 46.0% (95% confidence interval, 32.2-59.8), respectively, and puerperal infection occurred in 7.8% (95% confidence interval, 0.5-15.2) and 10.0% (95% confidence interval, 1.7-18.3), respectively. Note that this pilot study was not powered to detect differences of this magnitude but rather to estimate parameters. CONCLUSION: The administration of prophylactic antibiotics during labor induction of nulliparous patients with obesity resulted in a 27% lower cesarean delivery rate overall and a 28% lower rate in patients with class III obesity. A larger trial is warranted to evaluate these differences.

High-sensitivity C-reactive protein levels and pregnancy outcomes in women with unexplained infertility after ovarian stimulation with intrauterine insemination in a multicenter trial.

Objective: To determine if chronic inflammation, assessed by basal high-sensitivity C-reactive protein (hs-CRP) levels, is associated with pregnancy outcomes in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination. Design: Prospective cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial. Setting: Multicenter university-based randomized controlled trial. Patients: A total of 781 couples with unexplained infertility. Interventions: Secondary analysis. Main Outcome Measures: Adjusted risk ratios of live birth, clinical pregnancy, and pregnancy loss rates by hs-CRP levels. Results: Associations between hs-CRP levels and clinical pregnancy rates were not observed after adjustment for baseline body mass index. There were fewer live births among women with higher hs-CRP levels, although confidence intervals crossed 1.0. The risk of pregnancy loss was greater in women with increased hs-CRP levels (1-3 mg/L: risk ratio [RR], 1.67; 95% confidence interval [CI], 1.00-2.79; >3-10 mg/L: RR, 1.84; 95% CI, 1.06-3.20; and >10 mg/L: RR, 2.14; 95% CI, 1.05-4.36 compared to women with hs-CRP <1 mg/L). Conclusions: This investigation suggests that chronic inflammation may increase the risk of pregnancy loss but not impact the clinical pregnancy rate in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination. Associations between inflammation and pregnancy outcomes in women with infertility merit further investigation. Clinical Trial Registration Number: clinicaltrials.gov NCT01044862.

Barriers and Factors Associated with HPV Vaccination Among American Indians and Alaska Natives: A Systematic Review.

American Indian and Alaska Native (AI/AN) persons bear a disproportionate burden of human papillomavirus (HPV)-associated cancers and face unique challenges to HPV vaccination. We undertook a systematic review to synthesize the available evidence on HPV vaccination barriers and factors among AI/AN persons in the United States. We searched fourteen bibliographic databases, four citation indexes, and six gray literature sources from July 2006 to January 2021. We did not restrict our search by study design, setting, or publication type. Two reviewers independently screened the titles and abstracts (stage 1) and full-text (stage 2) of studies for selection. Both reviewers then independently extracted data using a data extraction form and undertook quality appraisal and bias assessment using the modified Mixed Methods Appraisal Tool. We conducted thematic synthesis to generate descriptive themes. We included a total of 15 records after identifying 3017, screening 1415, retrieving 203, and assessing 41 records. A total of 21 unique barriers to HPV vaccination were reported across 15 themes at the individual (n = 12) and clinic or provider (n = 3) levels. At the individual level, the most common barriers to vaccination-safety and lack of knowledge about the HPV vaccine-were each reported in the highest number of studies (n = 9; 60%). The findings from this review signal the need to develop interventions that target AI/AN populations to increase the adoption and coverage of HPV vaccination. Failure to do so may widen disparities.

Does the ultrasound appearance of the endometrium during treatment with assisted reproductive technologies influence pregnancy outcomes?

We evaluated endometrial pattern, defined as the relative echogenicity of the endometrium on a longitudinal uterine ultrasonic section, as a surrogate for endometrial receptivity in an attempt to evaluate the association between endometrial pattern and pregnancy outcome in women who underwent ART treatment. The primary outcome was live birth and secondary outcomes were clinical intrauterine pregnancy and miscarriage. Potential associations were evaluated using cluster-weighted generalized estimating equations to account for within-couple correlation among repeated ART cycles while adjusting for potentially confounding variables. There were 1034 ART cycles with embryo transfer (778 fresh, 256 frozen) among 695 women (median age: 31.0 (6.0) years). The average number of embryos transferred per cycle was 2.1. The clinical intrauterine pregnancy rate per transfer was 56.0% for fresh and 54.3% for frozen cycles. The overall live birth rate per embryo transfer was 48.4%. Live birth rates were unchanged when the endometrium was semi-trilinear (RR:0.91 CI:0.74,1.12) or unilinear (RR:1.15 CI:0.89,1.49) in comparison to trilinear endometrium after controlling for potentially confounding variables. Results were similar when analysed separately for fresh and frozen cycles and when evaluating associations with clinical intrauterine pregnancy and miscarriage rates. It appears that endometrial pattern does not significantly affect live birth in ART and our data do not support cancelling an ART cycle if the endometrium is less than trilinear.

Relationship between semen regurgitation and pregnancy rates with intrauterine insemination.

OBJECTIVE: To evaluate the relationship between semen regurgitation and intrauterine insemination (IUI) outcomes. We hypothesized that clinical pregnancy rates and live birth rates would be reduced when regurgitation occurred. DESIGN: Retrospective cohort study. SETTING: A university-based reproductive endocrinology and infertility clinic. PATIENT(S): Retrospective review of 1,957 IUI cycles performed on 660 patients between July 2007 and May 2012. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was live birth. Secondary outcomes were positive serum pregnancy result and clinical pregnancy. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a cluster-weighted generalized estimating equations method to estimate modified Poisson regression models with robust standard errors to account for multiple IUI cycles in the same patient. RESULT(S): Live birth rates were similar in IUI cycles with and without regurgitation (6.3% vs. 6.8%, respectively, RR = 0.82, 95% CI [0.53-1.26]). Clinical pregnancy rates in the presence or absence of regurgitation were 10.5% vs. 10.0% (RR = 0.99, 95% CI [0.73-1.35]). Positive serum pregnancy tests after IUI did not differ by regurgitation status (15.0% vs. 15.4%, RR = 0.97, 95% CI [0.75-1.24]). Results were unchanged when adjusted for covariates (age, race and ethnicity, body mass index, duration of infertility, medication, infertility diagnosis, total motile count, and method of sperm preparation). CONCLUSION(S): The presence of regurgitation during the IUI procedure is not related to pregnancy outcome.

Clinical effectiveness of adding azithromycin to antimicrobial prophylaxis for cesarean delivery.

BACKGROUND: A recent large clinical trial demonstrated an approximately 50% decrease in the rate of postoperative infection in women who were laboring and/or had rupture of membranes for >4 hours and who received azithromycin in addition to standard preoperative antibiotic prophylaxis at the time of cesarean delivery. Given these results, our institution made a policy change in May 2017 to add azithromycin to standard preoperative prophylaxis for all cesarean deliveries. OBJECTIVE: This study aimed to evaluate the clinical effectiveness of adding azithromycin to preoperative antibiotic prophylaxis for cesarean delivery. STUDY DESIGN: We conducted a before-and-after cohort study of women delivered via cesarean delivery at our institution. The preimplementation group included women who delivered from March 1, 2016, to February 28, 2017, (before an institutional practice change of adding azithromycin to standard preoperative prophylaxis), and the postimplementation group included women who delivered from September 1, 2017, to August 31, 2018 (allowing a 6-month period for uptake of the practice change). The primary outcome was a composite of postoperative infections (endometritis, wound infection, other maternal infections). Unadjusted and adjusted risk ratios and 95% confidence intervals were estimated using a modified Poisson regression model. RESULTS: In the preimplementation (n=1171) and postimplementation (n=1168) groups, the incidence rates of the composite outcomes were 4.7% and 5.3%, respectively (P=.49). Both unadjusted (relative risk, 1.13; 95% confidence interval, 0.78-1.62) and adjusted (adjusted relative risk, 1.06; 95% confidence interval, 0.74-1.52) comparisons were not significantly different. In addition, results were statistically nonsignificant, but in the direction of lower rates of infection, in the after cohort for women in labor and/or with rupture of membranes for ≥4 hours (relative risk, 0.88 [95% confidence interval, 0.56-1.39]; adjusted relative risk, 0.82 [95% confidence interval, 0.52-1.30]) and for women with clinical chorioamnionitis (relative risk, 0.37 [95% confidence interval, 0.08-1.67]; data too sparse for adjusted analysis). In the subgroup of women who were not in labor, the after cohort had a statistically nonsignificant increased risk of the composite outcome in both unadjusted (relative risk, 1.53; 95% confidence interval, 0.86-2.72) and adjusted (adjusted relative risk, 1.48; 95% confidence interval, 0.83-2.65]) comparisons. CONCLUSION: In clinical practice, the addition of azithromycin to standard preoperative antibiotic prophylaxis for cesarean delivery may have an effect size smaller than seen in the large clinical trial prompting this practice change. Extrapolation of this regimen to women not in labor may be ineffective.

Metabolic syndrome in obesity: treatment success and adverse pregnancy outcomes with ovulation induction in polycystic ovary syndrome.

BACKGROUND: Obesity is common in women with polycystic ovary syndrome. polycystic ovary syndrome and obesity are associated with reduced fertility. The effect of metabolic syndrome on the success of infertility treatment and pregnancy outcomes in women with polycystic ovary syndrome undergoing ovulation induction has not been investigated. OBJECTIVE: The objectives of this study were to determine the associations of metabolic syndrome on the rate of live birth after ovulation induction and pregnancy complications in obese women with polycystic ovary syndrome and determine whether there is a difference in outcomes concerning specific medications used for ovulation induction. STUDY DESIGN: This prospective cohort analysis used data collected from participants in the Pregnancy in Polycystic Ovary Syndrome II clinical trial conducted by the Reproductive Medicine Network. In the Pregnancy in Polycystic Ovary Syndrome II trial, 750 women with polycystic ovary syndrome and infertility were randomized to either clomiphene citrate or letrozole for ovulation induction for 1 to 5 cycles or until pregnancy occurred. Cox regression and modified Poisson regression, chi-square test, and Student t test or Wilcoxon test were used in this study. Outcomes of interest were rates of live birth and clinical pregnancy and pregnancy complications. Having metabolic syndrome was defined by the presence of at least 3 of 5 cardiometabolic risk factors (waist circumference of >88 cm, low high-density lipoprotein cholesterol of <50 mg/dL, triglycerides of ≥150 mg/dL, systolic blood pressure of ≥130 or diastolic blood pressure of ≥85 mm Hg, and fasting glucose of >100 mg/dL). In addition, we used a continuous metabolic syndrome z score. Body mass index categories were defined as normal (body mass index of <25 kg/m2), high (25 to 35 kg/m2), and very high (>35 kg/m2). RESULTS: As illustrated in the Table, early pregnancy losses showed no difference by metabolic syndrome. Fewer women achieved a clinical pregnancy (20.5% vs 29.7%; P=.007) or had a live birth (16.5% vs 27%; P=.001) in the presence of metabolic syndrome. Early pregnancy losses showed no difference by metabolic syndrome status. However, at least 1 pregnancy complication occurred more often with metabolic syndrome: 61.9% (26 of 42 cases) with metabolic syndrome vs 44.4% (59 of 133 cases) (P=.05) without metabolic syndrome. Gestational diabetes mellitus (35.7% vs 18.2%; P=.02) and macrosomia (21.4% vs 8.3%; P=.02) were more common in the presence of metabolic syndrome. After adjustment for other potential confounders, the rate ratio for live births for a 1-unit change in the metabolic syndrome z score was 0.89 (95% confidence interval, 0.79-1.00; P=.04) for those whose body mass index was 25 to 35 kg/m2. For the very high body mass index subgroup (>35 kg/m2), the independent effects of metabolic syndrome from obesity were harder to discern. The rate of live birth was higher with the use of letrozole, although metabolic syndrome had a different detrimental effect concerning the medication given. The overall incidence of pregnancy complications was high (approximately 49%) in the Pregnancy in Polycystic Ovary Syndrome II trial and the 2 medications. Letrozole was associated with more obstetrical complications in the presence of metabolic syndrome, and clomiphene was associated with a lower rate of live birth rate when metabolic syndrome was present. CONCLUSION: Metabolic syndrome is a risk factor that lowers the rate of live birth after ovulation for women with polycystic ovary syndrome, independent of obesity, and it is particularly associated with a lower rate of live birth for women using clomiphene compared with women using letrozole. In addition, metabolic syndrome is a risk factor for pregnancy complications for women with obesity using letrozole. Furthermore, having metabolic syndrome is a risk factor for gestational diabetes mellitus and macrosomia.

Urinary total arsenic and arsenic methylation capacity in pregnancy and gestational diabetes mellitus: A case-control study.

Previous studies suggest arsenic exposure may increase the risk of gestational diabetes mellitus (GDM). However, prior assessments of total arsenic concentrations have not distinguished between toxic and nontoxic species. Our study aimed to investigate the relationships between inorganic arsenic exposure, arsenic methylation capacity, and GDM. Sixty-four cases of GDM and 237 controls were analyzed for urinary concentrations of inorganic arsenic species and their metabolites (arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)), and organic forms of arsenic. Inorganic arsenic exposure was defined as the sum of inorganic and methylated arsenic species (iSumAs). Methylation capacity indices were calculated as the percentage of inorganic arsenic species [iAs% = (As3 + As5)/iSumAs, MMA% = MMA/iSumAs, and DMA% = DMA/iSumAs]. Multivariable logistic regression was performed to evaluate the association between inorganic arsenic exposure, methylation capacity indices, and GDM. We did not observe evidence of a positive association between iSumAs and GDM. However, women with GDM had an increased odds of inefficient methylation capacity when comparing the highest and lowest tertiles of iAs% (adjusted odds ratio (aOR) = 1.48, 95% CI 0.58-3.77) and MMA% (aOR = 1.95 (95% CI 0.81-4.70) and a reduced odds of efficient methylation capacity as indicated by DMA% (aOR = 0.62 (95% CI 0.25-1.52), though the confidence intervals included the null value. While the observed associations with arsenic methylation indices were imprecise and warrant cautious interpretation, the direction and magnitude of the relative measures reflected a pattern of lower detoxification of inorganic arsenic exposures among women with GDM.

Infant sex differences in human milk intake and composition from 1- to 3-month post-delivery in a healthy United States cohort.

BACKGROUND: Macronutrient composition of human milk differs by infant sex, but few studies have examined sex differences in other milk components, or their potential modification by maternal body mass index (BMI). AIM: We compared milk intake and human milk hormone and cytokine concentrations at 1- and 3-month post-delivery and tested infant sex by maternal BMI (OW/OB vs. NW) interactions. SUBJECTS AND METHOD: Data were analysed for 346 mother-infant dyads in the Mothers and Infants Linked for Healthy Growth (MILk) Study at 1- and 3-month post-delivery. Infant milk intake was estimated by the change in infant weight after test feedings. Concentrations of glucose, insulin, leptin, adiponectin, interleukin-6 (IL-6), and C-reactive protein (CRP) were measured using ELISA. Multivariable linear regression and linear mixed models were used to estimate sex main effects and their interaction with maternal BMI. RESULTS: Mean glucose concentration at 1 month was 2.62 mg/dl higher for male infants, but no difference at 3 months was observed. Milk intake and concentrations for the other milk components were similar for males and females at both time points. Associations with infant sex did not differ significantly by maternal BMI. CONCLUSIONS: Among healthy United States mother-infant dyads, appetite, and growth-regulating factors in human milk did not differ significantly by infant sex.

Controlled Release Dinoprostone Insert and Foley Compared to Foley Alone: A Randomized Pilot Trial.

OBJECTIVE: The aim of study is to compare, in a pilot study, combined dinoprostone vaginal insert and Foley catheter (DVI + Foley) with Foley alone (Foley) for cervical ripening and labor induction at term. STUDY DESIGN: In this open-label pilot randomized controlled trial, women not in labor, with intact membranes, no prior uterine incision, an unfavorable cervix, gestational age ≥37 weeks, and a live, nonanomalous singleton fetus in cephalic presentation were randomly assigned, stratified by parity, to DVI + Foley or Foley. Oxytocin was used in both groups after cervical ripening. Primary outcome was time to vaginal delivery. RESULTS: From April 2017 to January 2018, 100 women were randomized. Median (25-75th percentile) time to vaginal delivery for nulliparous women was 21.2 (16.6-38.0) hours with DVI + Foley (n = 26) compared with 31.3 (23.3-46.9) hours with Foley (n = 24) (Wilcoxon p = 0.05). Median time to vaginal delivery for parous women was 17.1 (13.6-21.9) hours with DVI + Foley (n = 25) compared with 14.8 (12.7-19.5) hours with Foley (n = 25) (Wilcoxon p = 0.21). Results were also analyzed to consider the competing risk of cesarean using cumulative incidence functions. CONCLUSION: Compared with Foley alone, combined use of the dinoprostone vaginal insert and Foley for cervical ripening may shorten time to vaginal delivery for nulliparous but not parous women.

Endometrial thickness after ovarian stimulation with gonadotropin, clomiphene, or letrozole for unexplained infertility, and association with treatment outcomes.

OBJECTIVE: To study the association of endometrial thickness (EMT) with live birth rates (LBR) in ovarian stimulation with intrauterine insemination (OS-IUI) treatments for unexplained infertility. DESIGN: Prospective cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial. SETTING: Multicenter randomized controlled trial. PATIENTS: A total of 868 couples with unexplained infertility (n=2,459 cycles). INTERVENTIONS: OS-IUI treatment cycles (n = 2,459) as part of the AMIGOS clinical trial. MAIN OUTCOME MEASURES: Live birth rates; unadjusted and adjusted risk ratios (RR) for live birth by EMT category, calculated using generalized estimating equations. RESULTS: The overall mean EMT on day of human chorionic gonadotropin administration in cycles with a live birth was significantly greater than in those without. Compared to the referent EMT group of 9 to 12 mm, the unadjusted RR for live birth for the EMT groups of ≤5 and 6-8 were 0.48 and 0.92, respectively. The test for trend indicated evidence of decreasing LBR with decreasing EMT. After adjustment for ovarian stimulation medication, a linear trend was no longer supported. Stratified analyses revealed no differences in associations by treatment group. CONCLUSIONS: In OS-IUI for unexplained infertility, higher LBR are observed with increasing EMT; however, EMT is not significantly associated with LBR when adjusted for OS treatment type. Appreciable LBR are seen at all EMT, even those of ≤5 mm, suggesting that OS-IUI cycles should not be canceled for thin endometrium. CLINICAL TRIAL REGISTRATION NUMBER: NCT01044862.