Association between gestational exposure to solar activity and pregnancy loss using live births from a Massachusetts-based medical center.

BACKGROUND: Solar activity has been linked to biological mechanisms important to pregnancy, including folate and melatonin levels and inflammatory markers. Thus, we aimed to investigate the association between gestational solar activity and pregnancy loss. METHODS: Our study included 71,963 singleton births conceived in 2002-2016 and delivered at an academic medical center in Eastern Massachusetts. We studied several solar activity metrics, including sunspot number, Kp index, and ultraviolet radiation, with data from the NASA Goddard Space Flight Center and European Centre for Medium-Range Weather Forecasts. We used a novel time series analytic approach to investigate associations between each metric from conception through 24 weeks of gestation and the number of live birth-identified conceptions (LBICs) -the total number of conceptions in each week that result in a live birth. This approach fits distributed lag models to data on LBICs, adjusted for time trends, and allows us to infer associations between pregnancy exposure and pregnancy loss. RESULTS: Overall, the association between solar activity during pregnancy and pregnancy loss varied by exposure metric. For sunspot number, we found that an interquartile range increase in sunspot number (78·7 sunspots) in all of the first 24 weeks of pregnancy was associated with 14·0 (95% CI: 6·5, 21·3) more pregnancy losses out of the average 92 LBICs in a week, and exposure in weeks ten through thirteen was identified as a critical window. Although not statistically significant, higher exposure to Kp index and to UV radiation across all 24 weeks of pregnancy was associated with more and less pregnancy losses, respectively. CONCLUSION: While exposure to certain metrics of solar activity (i.e., sunspot number) throughout the first 24 weeks of pregnancy may be associated with pregnancy losses, exposure to other metrics were not. Solar activity is a complex phenomenon, and more studies are needed to clarify underlying pathways.

Risk Profiling In Vitro Fertilization Pregnancies that Develop Placenta Accreta Spectrum.

OBJECTIVE: The objective of this study is to assess whether, among a cohort of placenta accreta spectrum (PAS) patients, antenatal suspicion of PAS was less likely in in vitro fertilization (IVF) compared with non-IVF patients. In addition, we aimed to assess whether IVF patients exhibited similar risk factors for PAS compared with non-IVF patients. STUDY DESIGN: This is an international multicenter retrospective study of patients with pathologically confirmed PAS (accreta, increta, percreta) between 1998 and 2021. PAS patients were identified through a central international PAS database. Antenatal and pathological criteria are specific to each institution. Pregnancies that resulted from IVF were compared with non-IVF pregnancies. Comparisons were made using a chi-square or Fisher's exact test for categorical variables and Wilcoxon rank-sum test for continuous variables. RESULTS: Of the 692 pregnancies included, 44 were in the IVF group and 648 were in the non-IVF group. The IVF group was less likely to have had a prior cesarean delivery (70.5 vs. 91%, p < 0.01) but a similar prevalence of placenta previa (63.6 vs. 68.1%, p = 0.12) compared with the non-IVF group. The IVF group was also less likely to have either a prior cesarean delivery or placenta previa than the non-IVF group (79.5 vs. 95.4%, p < 0.01). Antenatal detection of PAS was less common in the IVF group compared with the non-IVF group (40.9 vs. 60.5%, p < 0.01, respectively), even when adjusted for maternal age, prior cesarean delivery, prior uterine surgery, placenta previa and site (risk ratio: 0.70, 95% confidence interval: 0.62-0.81). The IVF group had less severe pathological disease compared with the non-IVF group (p = 0.02). CONCLUSION: Pregnant people with PAS who underwent IVF are less likely to have an antenatal suspicion compared with non-IVF patients. This finding may be explained by the lower incidence of prior cesarean deliveries and/or placenta previa as well as less severe forms of PAS. KEY POINTS: · IVF group is less likely to have antenatal PAS suspicion.. · IVF group is less likely to have had prior cesarean delivery.. · Risk profile for PAS differs in IVF pregnancies..

Cerclage plus Adjuvant Vaginal Progesterone for Preterm Birth Prevention in Patients with a Short or Dilated Cervix without Prior Preterm Birth.

OBJECTIVE: The primary objective was to determine if vaginal progesterone following cerclage for cervical length <10 mm or cervical dilation in patients without a history of spontaneous preterm birth (sPTB) decreased the risk of preterm birth at <34 weeks' gestation compared with cerclage alone. Secondary objectives were to determine if vaginal progesterone following cerclage (1) decreased the risk of preterm birth at <24, <28, and <37 weeks' gestation and (2) increased the latency period from cerclage placement to delivery compared with treatment with cerclage alone. STUDY DESIGN: Multicenter retrospective cohort study from 2015 to 2020 of singleton pregnancies, without prior sPTB, who had cerclage placement <24 weeks' gestation for cervical length <10 mm or cervical dilation. Exposure defined as cerclage plus vaginal progesterone postoperatively (dual therapy) and unexposed as cerclage alone (monotherapy), based on surgeon preference. RESULTS: We included 122 patients, 78 (64%) treated with dual therapy and 44 (36%) treated with monotherapy. In the crude analysis, dual therapy was associated with a lower risk of delivery at <28 weeks' gestation (13%) compared with monotherapy (34%; crude risk ratio: 0.38 [95% confidence interval, CI: 0.19-0.75]). When adjusted for preoperative vaginal progesterone, results were attenuated (adjusted risk ratio: 0.45 [95% CI: 0.20-1.01]). In both the crude and adjusted analyses, the risk of sPTB was not statistically different at <24, <34 or <37 weeks' gestation. Dual therapy was associated with a greater pregnancy latency from cerclage to delivery (16.3 vs. 14.4 weeks; p = 0.04), and greater gestational age at delivery (37.3 vs. 35.8 weeks' gestation; p = 0.02) compared with monotherapy. CONCLUSION: While not statistically significant, the risk of sPTB was lower at all gestational ages studied in patients treated with dual therapy compared with monotherapy. Dual therapy was associated with longer pregnancy latency and greater gestational age at delivery compared with monotherapy. KEY POINTS: · Dual therapy did not decrease preterm birth risk compared with monotherapy.. · Dual therapy prolonged pregnancy compared with monotherapy.. · Dual therapy can be considered but further studies are needed..

Bias Amplification and Variance Inflation in Distributed Lag Models Using Low-Spatial-Resolution Data.

Distributed lag models (DLMs) are often used to estimate lagged associations and identify critical exposure windows. In a simulation study of prenatal nitrogen dioxide (NO2) exposure and birth weight, we demonstrate that bias amplification and variance inflation can manifest under certain combinations of DLM estimation approaches and time-trend adjustment methods when using low-spatial-resolution exposures with extended lags. Our simulations showed that when using high-spatial-resolution exposure data, any time-trend adjustment method produced low bias and nominal coverage for the distributed lag estimator. When using either low- or no-spatial-resolution exposures, bias due to time trends was amplified for all adjustment methods. Variance inflation was higher in low- or no-spatial-resolution DLMs when using a long-term spline to adjust for seasonality and long-term trends due to concurvity between a distributed lag function and secular function of time. NO2-birth weight analyses in a Massachusetts-based cohort showed that associations were negative for exposures experienced in gestational weeks 15-30 when using high-spatial-resolution DLMs; however, associations were null and positive for DLMs with low- and no-spatial-resolution exposures, respectively, which is likely due to bias amplification. DLM analyses should jointly consider the spatial resolution of exposure data and the parameterizations of the time trend adjustment and lag constraints.

Traffic-Related Air Pollution and Ultrasound Parameters of Fetal Growth in Eastern Massachusetts.

Previous studies have examined the association between prenatal nitrogen dioxide (NO2)-a traffic emissions tracer-and fetal growth based on ultrasound measures. Yet, most have used exposure assessment methods with low temporal resolution, which limits the identification of critical exposure windows given that pregnancy is relatively short. Here, we used NO2 data from an ensemble model linked to residential addresses at birth to fit distributed lag models that estimated the association between NO2 exposure (resolved weekly) and ultrasound biometric parameters in a Massachusetts-based cohort of 9,446 singleton births from 2011-2016. Ultrasound biometric parameters examined included biparietal diameter (BPD), head circumference, femur length, and abdominal circumference. All models adjusted for sociodemographic characteristics, time trends, and temperature. We found that higher NO2 was negatively associated with all ultrasound parameters. The critical window differed depending on the parameter and when it was assessed. For example, for BPD measured after week 31, the critical exposure window appeared to be weeks 15-25; 10-parts-per-billion higher NO2 sustained from conception to the time of measurement was associated with a lower mean z score of -0.11 (95% CI: -0.17, -0.05). Our findings indicate that reducing traffic emissions is one potential avenue to improving fetal and offspring health.

A novel approach to joint prediction of preeclampsia and delivery timing using semicompeting risks.

BACKGROUND: Preeclampsia is a pregnancy complication that contributes substantially to perinatal morbidity and mortality worldwide. Existing approaches to modeling and prediction of preeclampsia typically focus either on predicting preeclampsia risk alone, or on the timing of delivery following a diagnosis of preeclampsia. As such, they are misaligned with typical healthcare interactions during which the 2 events are generally considered simultaneously. OBJECTIVE: This study aimed to describe the "semicompeting risks" framework as an innovative approach for jointly modeling the risk and timing of preeclampsia and the timing of delivery simultaneously. Through this approach, one can obtain, at any point during the pregnancy, clinically relevant summaries of an individual's predicted outcome trajectories in 4 risk categories: not developing preeclampsia and not having delivered, not developing preeclampsia but having delivered because of other causes, developing preeclampsia but not having delivered, and developing preeclampsia and having delivered. STUDY DESIGN: To illustrate the semicompeting risks methodology, we presented an example analysis of a pregnancy cohort from the electronic health record of an urban, academic medical center in Boston, Massachusetts (n=9161 pregnancies). We fit an illness-death model with proportional-hazards regression specifications describing 3 hazards for timings of preeclampsia, delivery in the absence of preeclampsia, and delivery following preeclampsia diagnosis. RESULTS: The results indicated nuanced relationships between a variety of risk factors and the timings of preeclampsia diagnosis and delivery, including maternal age, race/ethnicity, parity, body mass index, diabetes mellitus, chronic hypertension, cigarette use, and proteinuria at 20 weeks' gestation. Sample predictions for a diverse set of individuals highlighted differences in projected outcome trajectories with regard to preeclampsia risk and timing, and timing of delivery either before or after preeclampsia diagnosis. CONCLUSION: The semicompeting risks framework enables characterization of the joint risk and timing of preeclampsia and delivery, providing enhanced, meaningful information regarding clinical decision-making throughout the pregnancy.

Androgenetic alopecia incidence in transgender and gender diverse populations: A retrospective comparative cohort study.

BACKGROUND: Androgenetic alopecia (AGA) is a significant challenge for many transgender and gender diverse (TGD) patients, but the rate of AGA among TGD patients receiving gender-affirming hormone therapy (GAHT) compared to cisgender patients has not yet been studied on a large scale. OBJECTIVE: We examined the incidence of AGA among TGD patients receiving GAHT compared to cisgender patients. METHODS: Retrospective cohort study using electronic health records from 37,826 patients seen at Fenway Health between August 1, 2014, and August 1, 2020. Crude and adjusted incidence rate ratios (aIRR) for AGA were calculated using Poisson regression. RESULTS: TGD patients receiving masculinizing GAHT had aIRR 2.50, 95% CI 1.71-3.65 and 1.30, 95% CI 0.91-1.86 compared to cisgender women and cisgender men, respectively. The rate of AGA for TGD patients receiving feminizing GAHT was not significantly different compared to cisgender men but was significantly increased compared to cisgender women (aIRR 1.91, 95% CI 1.25-2.92). LIMITATIONS: Inability to determine causation and limited generalizability. CONCLUSION: TGD patients receiving masculinizing GAHT have 2.5 times the rate of AGA compared to cisgender women, whereas TGD patients on feminizing GAHT did not have a significantly increased rate of AGA compared to cisgender men.

The Association between Placenta Accreta Spectrum Severity and Incidence of Small for Gestational Age Neonates.

OBJECTIVE: The aim of the study is to evaluate whether pathologic severity of placenta accreta spectrum (PAS) is correlated with the incidence of small for gestational age (SGA) and neonatal birthweight. STUDY DESIGN: This was a multicenter cohort study of viable, non-anomalous, singleton gestations delivered with histology-proven PAS. Data including maternal history, neonatal birthweight, and placental pathology were collected and deidentified. Pathology was defined as accreta, increta, or percreta. The primary outcome was rate of SGA defined by birth weight less than the 10th percentile. The secondary outcomes included incidence of large for gestational age (LGA) babies as defined by birth weight greater than the 90th percentile as well as incidence of SGA and LGA in preterm and term gestations. Statistical analysis was performed using Chi-square, Kruskal-Wallis, and log-binomial regression. Increta and percreta patients were each compared with accreta patients. RESULTS: Among the cohort of 1,008 women from seven United States centers, 865 subjects were included in the analysis. The relative risk (RR) of SGA for increta and percreta did not differ from accreta after adjusting for confounders (adjusted RR = 0.63, 95% confidence interval [CI]: 0.36-1.10 for increta and aRR = 0.72, 95% CI: 0.45-1.16 for percreta). The results were stratified by placenta previa status, which did not affect results. There was no difference in incidence of LGA (p = 1.0) by PAS pathologic severity. The incidence of SGA for all PAS patients was 9.2% for those delivered preterm and 18.7% for those delivered at term (p = 0.004). The incidence of LGA for all PAS patients was 12.6% for those delivered preterm and 13.2% for those delivered at term (p = 0.8203). CONCLUSION: There was no difference in incidence of SGA or LGA when comparing accreta to increta or percreta patients regardless of previa status. Although we cannot suggest causation, our results suggest that PAS, regardless of pathologic severity, is not associated with pathologic fetal growth in the preterm period. KEY POINTS: · PAS severity is not associated with SGA in the preterm period.. · PAS severity is not associated with LGA.. · Placenta previa does not affect the incidence of SGA in women with PAS..

Basal Plate Myofibers and the Risk of Placenta Accreta Spectrum in the Subsequent Pregnancy: A Large Single-Center Cohort.

OBJECTIVE: We aimed to evaluate whether there is a significant association between a placental pathology diagnosis basal plate myofibers (BPMF) in an index pregnancy with placenta accreta spectrum (PAS) in the subsequent pregnancy. STUDY DESIGN: We conducted a retrospective nested cohort study of all cases with a histopathological finding of BPMF between August 2012 and March 2020 at a single tertiary referral center. Data were collected for all subjects (cases and controls) with at least two consecutive pregnancies (the initial index pregnancy and at least one subsequent pregnancy) accompanied by a concomitant record of histopathological study of the placenta at our center. The primary outcome was pathologically confirmed PAS in the subsequent pregnancy. Data are presented as percentage or median, interquartile range accordingly. RESULTS: A total of n = 1,344 participants were included, of which n = 119 (index cases) carried a contemporaneous histopathological diagnosis of BPMF during the index pregnancy and n = 1,225 did not (index controls). Among the index cases, patients with BPMF were older (31.0 [20, 42] vs. 29.0 [15, 43], p < 0.001), more likely to have undergone in vitro fertilization (IVF) for conception (10.9 vs. 3.8%, p = 0.001) and were of a more advanced gestational age at delivery (39.0 [25, 41] vs. 38.0 [20, 42], p = 0.006). In the subsequent pregnancy, the rate of PAS was significantly higher among the BPMF index cases (6.7 vs. 1.1%, p < 0.001). After adjusting for maternal age and IVF, a histopathological diagnosis of BPMF in an index pregnancy was shown to be a significant risk factor for PAS in the subsequent gestation (hazard ratio: 5.67 [95% confidence interval: 2.28, 14.06], p < 0.001). CONCLUSION: Our findings support that a histopathological diagnosis of BPMF is an independent risk factor for PAS in the subsequent pregnancy. KEY POINTS: · BPMF may indicate morbid adherence of placenta.. · Patients with BPMF were older and more likely to have undergone IVF for conception.. · The BPMF in the current pregnancy is an independent risk factor for PAS in the subsequent pregnancy..

PCOS and the risk of pre-eclampsia.

RESEARCH QUESTION: What is the association between polycystic ovary syndrome (PCOS) and pre-eclampsia? Data suggest that patients with PCOS are at increased risk of developing pre-eclampsia; however, several studies have not found an independent association between the two. DESIGN: A retrospective case-control study of singleton deliveries at a tertiary care hospital from 2011 to 2015. Patients with pre-eclampsia (cases) were matched to the next delivery without pre-eclampsia (controls) on gestational age week. Medical history data, a diagnosis or clinical features of PCOS and obstetric data, including pre-eclampsia, were abstracted from the medical record. Groups were compared with the chi-squared test, and conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). OR were adjusted for maternal age at delivery and race/ethnicity. RESULTS: This study included 435 cases and 435 controls. Cases were more likely to be Black compared with controls. Age, comorbidities, features of PCOS and use of IVF were similar between groups. Patients with pre-eclampsia were not more likely to have PCOS (8.3%) than those without pre-eclampsia (6.2%, adjusted OR 1.40, 95% CI 0.81-2.30). Sensitivity analyses for body mass index and parity suggested an increased pre-eclampsia risk for patients with PCOS and these additional factors, however no group showed a statistically significant association between PCOS and pre-eclampsia. CONCLUSIONS: In this study, a history of PCOS was not associated with the risk of pre-eclampsia. Further investigation is necessary to determine whether there are subgroups of PCOS patients who are at increased risk of pre-eclampsia.

Incidence of small-for-gestational-age infant birthweight following early intertwin fetal growth discordance in dichorionic and monochorionic twin pregnancies.

BACKGROUND: Serial growth scans are routinely recommended for twin pregnancies to identify fetal growth restriction (defined as an estimated fetal weight of <10th percentile), which can result in increased perinatal morbidity and mortality. However, the clinical significance of early intertwin growth discordance in the absence of fetal growth restriction remains unclear. OBJECTIVE: This study aimed to compare the rates of small-for-gestational-age infants among twin pregnancies with intertwin growth discordance in the absence of fetal growth restriction with that among twin pregnancies with concordant, normal growth identified by ultrasound between 24 0/7 and 31 6/7 weeks' gestation. STUDY DESIGN: This was a retrospective cohort study of twin deliveries at a single hospital from 2010 to 2019. Pregnancies without fetal growth restriction were categorized as discordant or concordant using the earliest prenatal growth ultrasound between 24 0/7 and 31 6/7 weeks' gestation. Discordance was defined as an estimated fetal weight difference of ≥18% between twins. Pregnancies with major fetal anomalies, no growth ultrasound between 24 0/7 and 31 6/7 weeks' gestation, or twin-twin transfusion syndrome were excluded. The cohort was stratified by chorionicity. Our primary outcome was small-for-gestational-age defined as <10th percentile per the Fenton growth curve at delivery. Secondary outcomes included gestational age at delivery, mode of delivery, neonatal intensive care unit admission, length of stay, and neonatal complications and placental pathology. RESULTS: Of the 707 twin pregnancies that met the inclusion criteria, 558 (79%) were dichorionic and 149 (21%) were monochorionic. Most pregnancies were concordant on ultrasound between 24 0/7 and 31 6/7 weeks' gestation (dichorionic, 93%; monochorionic, 87%). Regardless of chorionicity, twin pregnancies with discordance at ultrasound, were more likely to have a small-for-gestational-age infant than concordant twin pregnancies (dichorionic: 51% vs 29%; P=.002; monochorionic: 65% vs 24%; P<.001). Furthermore, women with twin pregnancies with discordance were delivered at an earlier gestational age (dichorionic: 36 weeks [interquartile range, 33-36] vs 34 weeks [interquartile range, 34-38]; P<.001; monochorionic: 34 weeks [interquartile range, 32-34] vs 36 weeks [interquartile range, 34-37]; P=.003). Pregnancies with growth discordance were more likely to be delivered by cesarean delivery (dichorionic: 90% vs 72%; P=.01; monochorionic: 65% vs 60%; P=.70), although this was only statistically significant for dichorionic twin pregnancies. Neonates of pregnancies with growth discordance had a higher incidence of respiratory distress syndrome (dichorionic: 54% vs 37%; P=.04; monochorionic: 70% vs 45%; P=.04) and neonatal intensive care unit admission (dichorionic: 71% vs 50%; P=.01; monochorionic: 90% vs 65%; P=.03). Furthermore, dichorionic infants had longer neonatal intensive care unit stays (30 [interquartile range, 18-61] vs 18 [interquartile range, 10-35] days; P=.02). CONCLUSION: Regardless of chorionicity, twin pregnancies with discordance without fetal growth restriction identified on growth ultrasound between 24 0/7 and 31 6/7 weeks' gestation were nearly twice as likely to develop small-for-gestational-age neonates, deliver earlier in gestation, and experience greater neonatal morbidity than twin pregnancies without discordance. Patients with pregnancies complicated by isolated intertwin discordance between 24 0/7 and 31 6/7 weeks' gestation will need counseling regarding adverse perinatal outcomes.

The Society for Pediatric Pathology Task Force grading system for placenta accreta spectrum and its correlation with clinical outcomes.

BACKGROUND: The terminology and diagnostic criteria presently used by pathologists to report placenta accreta spectrum is inconsistent and does not reflect current knowledge of the pathogenesis of this disease. OBJECTIVE: In 2020, the perinatal subcommittee of the Society for Pediatric Pathology Placenta Accreta Task Force proposed a new pathologic grading system for placenta accreta spectrum. We sought to correlate the clinical outcomes with the classification into each group in the new placenta accreta spectrum grading system. STUDY DESIGN: The pathology reports of patients with histopathologic confirmation of placenta accreta spectrum were reviewed in 2 academic referral centers by placental pathologists. Pathologic grading was assigned based on the new grading system according to which placenta accreta spectrum is categorized into 5 groups depending on the depth of invasion, from grade p1 with no invasion into the uterine wall to grade p3E with invasion beyond the uterine wall to the adjacent organs. Patient characteristics and clinical outcomes were compared among these groups. A univariate analysis was performed, and a multivariate linear or binomial regression was employed when needed. RESULTS: A total of 683 patients with placenta accreta spectrum were identified. Of those, 407 were included for histology review. There were 92 patients (23%) categorized into the grade p1 group, 74 (18%) in the grade p2 group, 84 (20%) in the grade p3A group, 121 (30%) in the grade p3D group, and 36 (9%) in the grade p3E group. There was a significant association between the pathology grading and the number of red blood cells transfused (ß=1.14; 95% confidence interval, 0.48-1.79) and the postoperative complications including the rate of readmission (risk ratio, 1.93; 95% confidence interval, 1.26-2.94) and bladder injury (risk ratio, 1.81; 95% confidence interval, 1.23-2.68) after adjustment for antenatal diagnosis and other variables. The pathology grading was not associated with the estimated blood loss (P=.072). CONCLUSION: The new pathology grading system accurately reflects maternal outcomes and complications of placenta accreta spectrum. We encourage the utilization of this new pathologic grading system because it is designed to omit discrepancies in placenta accreta spectrum reporting and to standardize communication.

Multifoetal gestations mediate the effect of in vitro fertilisation (IVF) on ischaemic placental disease in autologous oocyte IVF more than donor oocyte IVF.

BACKGROUND: Ischaemic placental disease (IPD) affects 16%-23% of pregnancies in the United States. In vitro fertilisation (IVF) is a risk factor for IPD, and the magnitude of increase in risk differs for individuals using donor oocytes (donor IVF) versus their own oocytes (autologous IVF). In addition, multifoetal gestations, which are more common in IVF than non-IVF pregnancies, also are a risk factor for IPD. OBJECTIVE: To quantify the contribution of multifoetal gestations to the association between IVF and IPD. METHODS: We conducted a retrospective cohort study at a tertiary hospital from 1 January, 2000 to 1 August 2018 using electronic medical records and state vital statistics data. IPD was defined as preeclampsia, placental abruption, small for gestational age (SGA) birth or an intrauterine foetal demise due to placental insufficiency. We used mediation analysis to decompose the total effect of IVF on IPD into a natural direct effect and an indirect effect through multifoetal gestations. We repeated the analyses separately for donor and autologous IVF. All models were adjusted for maternal age, race, parity, insurance, year of delivery and account for multiple pregnancies per person. RESULTS: We identified 86,514 deliveries, of which 281 resulted from donor IVF and 4173 resulted from autologous IVF. IVF pregnancies had 1.99 (95% CI 1.88, 2.10) times the risk of IPD compared to non-IVF pregnancies, and 75.5% of this increased risk was mediated by multifoetal gestations. Autologous IVF pregnancies had 1.95 (95% CI 1.84, 2.07) times the risk of IPD compared to non-IVF pregnancies, and the per cent mediated was 78.8%. Donor IVF pregnancies had 2.50 (95% CI 2.09, 2.92) times the risk of IPD, but the per cent mediated was 37.5%. CONCLUSION: The majority of the association between autologous IVF and IPD was mediated through multifoetal gestations; however, this was not the case for donor IVF pregnancies.

Multiple cryopreservation-warming cycles, coupled with blastocyst biopsy, negatively affect IVF outcomes.

RESEARCH QUESTION: Do multiple cryopreservation-warming cycles, coupled with blastocyst biopsy, negatively affect IVF outcomes? DESIGN: Patients undergoing IVF with homologous single embryo transfer, and who underwent trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A) between 2013 and 2017, were divided into three groups based on degree of embryonic micromanipulation: once-biopsied, once-cryopreserved (group BC, n = 2603), once-biopsied, twice-cryopreserved (group CBC, n = 95) and twice-biopsied, twice-cryopreserved (group BCBC, n = 15). The primary outcome was live birth; secondary outcomes included positive serum pregnancy test, clinical pregnancy and miscarriage. RESULTS: Group CBC had a significantly lower chance of live birth (adjusted RR 0.57, 95% CI 0.41 to 0.79) and clinical pregnancy (adjusted RR 0.67, 95% CI 0.53 to 0.85) compared with group BC. Miscarriage rates were similar between groups BC and CBC (adjusted RR 1.3, 95% CI 0.64 to 2.7). CONCLUSIONS: Multiple cryopreservation-warming cycles, coupled with blastocyst biopsy, negatively affect IVF outcomes. Although PGT-A is thought to improve reproductive outcomes on a per transfer basis, caution must be exercised in counselling patients on the possibility of diminishing returns owing to further embryonic micromanipulation after an embryo has been cryopreserved.

Language Preference and Risk of Primary Cesarean Delivery: A Retrospective Cohort Study.

OBJECTIVES: While some medical indications for cesarean delivery are clear, subjective provider and patient factors contribute to the rising cesarean delivery rates and marked disparities between racial/ethnic groups. We aimed to determine the association between language preference and risk of primary cesarean delivery. METHODS: We conducted a retrospective cohort study of nulliparous, term, singleton, vertex (NTSV) deliveries of patients over 18 years old from 2011-2016 at an academic medical center, supplemented with data from the Massachusetts Department of Public Health. We used modified Poisson regression with robust error variance to calculate risk ratios for cesarean delivery between patients with English language preference and other language preference, with secondary outcomes of Apgar score, maternal readmission, blood transfusion, and NICU admission. RESULTS: Of the 11,298 patients included, 10.3% reported a preferred language other than English, including Mandarin and Cantonese (61.7%), Portuguese (9.7%), and Spanish (7.5%). The adjusted risk ratio for cesarean delivery among patients with a language preference other than English was 0.85 (95% CI 0.72-0.997; p = 0.046) compared to patients with English language preference. No significant differences in risk of secondary outcomes between English and other language preference were found. DISCUSSION: After adjusting for confounders, this analysis demonstrates a decreased risk of cesarean delivery among women who do not have an English language preference at one institution. This disparity in cesarean delivery rates in an NTSV population warrants future research, raising the question of what clinical and social factors may be contributing to these lower cesarean delivery rates.

Strategies to improve postpartum glucose screening rates are needed.

AIMS: Women with gestational diabetes mellitus (GDM) require postpartum glucose screening, as they have a 70% lifetime risk of developing Type 2 diabetes mellitus. However, less than half complete postpartum screening. METHODS: We conducted a retrospective chart review of patients who delivered at our institution from 2001 to 2019. Inclusion criteria were patients with gestational diabetes who were at least 18 years old and had delivered an infant at >24 weeks of gestation. Our primary outcome was completion of postpartum gestational diabetes screening. RESULTS: The majority of patients (62%) did not complete screening. After adjusted risk ratio analyses, the only variables that remained significantly associated with an increased likelihood of completing screening were Asian race and having prenatal care at one particular community health center, which served a predominantly Asian population. CONCLUSIONS: This community health center protocol for scheduling patients with GDM that complied with recommendations for postpartum care, indicating that evidence-based methods can improve maternal health.

Placenta Accreta Spectrum: In Vitro Fertilization and Non-In Vitro Fertilization and Placenta Accreta Spectrum in a Massachusetts Cohort.

OBJECTIVE: The incidence of placenta accreta spectrum (PAS) has been increasing in the United States. In addition, there has also been an increase in the utilization of in vitro fertilization (IVF). The IVF pregnancies confer an increased risk of adverse obstetric and neonatal outcomes, but there is limited data on whether IVF is associated with PAS. The aim of this study is to assess the association between IVF and the risk of PAS. STUDY DESIGN: This was a retrospective cohort study of deliveries from January 1, 2013 to August 1, 2018 at a tertiary hospital in the Massachusetts. IVF pregnancies were compared with non-IVF pregnancies, and PAS diagnosis was confirmed by histopathology reports. Hospital administrative data and medical record review were used, and supplemented with data from birth certificates from the Massachusetts Department of Public Health. RESULTS: We identified 28,344 pregnancies that met inclusion criteria, of which 1,418 (5.0%) were IVF pregnancies. The overall incidence of PAS was 0.4% (2.2% in the IVF group and 0.3% in the non-IVF group). Women who underwent IVF had 5.5 times the risk of PAS (95% confidence interval [CI]: 3.4-8.7) compared with women in the non-IVF group, adjusted for maternal age, nulliparity, and year of delivery (Table 5). Compared with women in the non-IVF group, the IVF group had fewer prior cesarean deliveries (22.6 vs. 64.2%) and a lower prevalence of placenta previa (19.4 vs. 44.4%). CONCLUSION: Women with an IVF pregnancy carry an increased risk of PAS compared with non-IVF. Among women who underwent IVF, there was a lower prevalence of prior cesarean deliveries and placenta previa. Future work is needed to identify the mechanism of association for this increased risk as well as a reliable tool for antenatal detection in this cohort of women. KEY POINTS: · IVF pregnancies have higher risk of PAS than non-IVF pregnancies.. · IVF pregnancies with PAS do not exhibit common risk factors.. · IVF may be an independent risk factor for PAS..

Comparison of pregnancy outcomes following preimplantation genetic testing for aneuploidy using a matched propensity score design.

STUDY QUESTION: Does preimplantation genetic testing for aneuploidy (PGT-A) increase the likelihood of live birth among women undergoing autologous IVF who have fertilized embryos? SUMMARY ANSWER: PGT-A is associated with a greater probability of live birth among women 35 years old and older who are undergoing IVF. WHAT IS KNOWN ALREADY: Previous studies evaluating the association between PGT-A and the incidence of live birth may be prone to confounding by indication, as women whose embryos undergo PGT-A may have a lower probability of live birth due to other factors associated with their increased risk of aneuploidy (e.g. advancing age, history of miscarriage). Propensity score matching can reduce bias where strong confounding by indication is expected. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study utilizing data from women who underwent autologous IVF treatment, had their first oocyte retrieval at our institution from 1 January 2011 through 31 October 2017 and had fertilized embryos from this retrieval. If a woman elected to use PGT-A, all good quality embryos (defined as an embryo between Stages 3 and 6 with Grade A or B inner or outer cell mass) were tested. We only evaluated cycles associated with the first oocyte retrieval in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our analytic cohort included 8227 women. We used multivariable logistic regression to calculate a propensity score for PGT-A based on relevant demographic and clinical factors available to the IVF provider at the time of PGT-A or embryo transfer. We used the propensity score to match women who did and did not utilize PGT-A in a 1:1 ratio. We then used log-binomial regression to compare the cumulative incidence of embryo transfer, clinical pregnancy, miscarriage and live birth between women who did and did not utilize PGT-A. Because the risk of aneuploidy increases with age, we repeated these analyses among women <35, 35-37 and ≥38 years old based on the Society for Assisted Reproductive Technology's standards. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, women with fertilized embryos who used PGT-A were significantly less likely to have an embryo transfer (risk ratios (RR): 0.78; 95% CI: 0.73, 0.82) but were more likely to have a cycle that resulted in a clinical pregnancy (RR: 1.15; 95% CI: 1.04, 1.28) and live birth (RR: 1.21; 95% CI: 1.08, 1.35) than women who did not use PGT-A. Among women aged ≥38 years, those who used PGT-A were 67% (RR: 1.67; 95% CI: 1.31, 2.13) more likely to have a live birth than women who did not use PGT-A. Among women aged 35-37 years, those who used PGT-A were also more likely to have a live birth (RR: 1.27; 95% CI: 1.05, 1.54) than women who did not use PGT-A. In contrast, women <35 years old who used PGT-A were as likely to have a live birth (RR: 0.91; 95% CI: 0.78, 1.06) as women <35 years old who did not use PGT-A. LIMITATIONS, REASONS FOR CAUTION: We were unable to abstract several potential confounding variables from patients' records (e.g. anti-Mullerian hormone levels and prior IVF treatment), which may have resulted in residual confounding. Additionally, by restricting our analyses to cycles associated with the first oocyte retrieval, we were unable to estimate the cumulative incidence of live birth over multiple oocyte retrieval cycles. WIDER IMPLICATIONS OF THE FINDINGS: Women aged 35 years or older are likely to benefit from PGT-A. Larger studies might identify additional subgroups of women who might benefit from PGT-A. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. D.S. reports that he is a member of the Cooper Surgical Advisory Board. The other authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Choice of statistical model in observational studies of ART.

Analyzing data on ART presents unique and sometimes complicated challenges related to choosing the unit(s) of analysis and the statistical model. In this commentary, we provide examples of how these challenges arise and guidance for overcoming them. We discuss the implications of different ways to count treatment cycles, considering the perspectives of research questions, data management and analysis and patient counseling. We present the advantages and disadvantages of different statistical models, and finally, we discuss the definition and calculation of the cumulative incidence of live birth, which is a key outcome of research on ART.

The importance of mediation in reproductive health studies.

A mediator is a factor that occurs after the exposure of interest, precedes the outcome of interest (i.e. between the exposure and the outcome) and is associated with both the exposure and the outcome of interest (i.e. is on the pathway between exposure and outcome). Mediation analyses can be valuable in many reproductive health contexts, as mediation analysis can help researchers to better identify, quantify and understand the underlying pathways of the association they are studying. The purpose of this commentary is to introduce the concept of mediation and provide examples that solidify understanding of mediation for valid discovery and interpretation in the field of reproductive medicine.