Incremental health care resource utilization and costs associated among patients with Parkinson's disease psychosis and incident dementia: An analysis of medicare beneficiaries.

BACKGROUND: Real-world evidence examining the incremental health care resource use (HCRU) and cost burden of incident dementia among patients with Parkinson's disease psychosis (PDP) are needed within the United States (US). OBJECTIVES: To compare HCRU and cost burden between PDP patients with incident dementia (PDP + D) versus without incident dementia (PDP). METHODS: A retrospective analysis of inpatient (Part A), outpatient (Part B), and prescription drug (Part D) claims from the 100% Medicare sample was conducted to compare PDP + D patients versus PDP patients between 01/01/14-12/31/18. Patients with a diagnosis of dementia, psychosis, secondary parkinsonism, or other psychotic disorders, during 12-month pre-index were excluded. Patients in both groups were matched using 1:1 propensity score matching (PSM) methodology using 31 variables (age, sex, race, region and 27 Elixhauser comorbidity characteristics). Differences in 12-month post-index HCRU rates and mean per patient per year (PPPY) costs for all-cause inpatient (IP) hospitalizations, and by type of IP stay (i.e., short-term [ST-stay], skilled nursing facility [SNF-stay] and long-term [LT-stay]) were analyzed via logistic and gamma log-link regression models. RESULTS: Of the 12,484 patients who met our study criteria, 1855 PSM-matched cohorts were identified. Mean age, gender, and comorbidities were similar in PSM groups. Approximately, 50.3% with PDP + D reported ≥1 all-cause IP hospitalizations versus 36.0% with PDP (p < 0.05) during 12-month follow-up. Specifically, all-cause ST-stay, SNF-stay, and LT-stay among PDP + D versus PDP patients were: 45.2% versus 35.7%, 28.3% versus 15.7%, and 8.5% versus 6.0% (p < 0.05), respectively. Psychiatric-related ST-stay, SNF-stay, and LT-stay among PDP + D versus PDP patients were: 12.3% versus 9.0%, 7.5% versus 3.4%, and 2.4% versus 1.2% (p < 0.05), respectively. Mean PPPY all-cause IP hospitalization costs for PDP + D patients versus PDP patients was $17,891 (±29,882) versus $11,599 (±$25,247) (p < 0.05). CONCLUSIONS: Patients with PDP + D experience significantly higher all-cause and psychiatric-related IP hospitalizations, including ST-stays, LT stays, and SNF stays. They also had 54% greater mean PPPY IP hospitalization costs versus PDP patients.

Embryo biopsy and maternal and neonatal outcomes following cryopreserved-thawed single embryo transfer.

BACKGROUND: Contemporary embryo biopsy in the United States involves the removal of several cells from a blastocyst that would become the placenta for preimplantation genetic testing. Embryos are then cryopreserved while patients await biopsy results, with transfers occurring in a subsequent cycle as a single frozen-thawed embryo transfer, if euploid. OBJECTIVE: We sought to determine if removal of these cells for preimplantation genetic testing was associated with adverse obstetrical or neonatal outcomes after frozen-thawed single embryo transfer. STUDY DESIGN: We linked assisted reproductive technology surveillance data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System to birth certificates and maternal and neonatal hospitalization discharge diagnoses in Massachusetts from 2014 to 2017, considering only singleton births after frozen-thawed single embryo transfers. We compared outcomes of cycles having embryo biopsy (n=585) to those having no biopsy (n=2191) using chi-square for categorical and binary variables and logistic regression for adjusted odds ratios and 95% confidence intervals, adjusting for mother's age, race, education, parity, body mass index, birth year, insurance, and all infertility diagnoses. RESULTS: Considering no biopsy as the reference, there was no difference between groups with respect to preeclampsia (adjusted odds ratio, 0.82; 95% confidence interval, 0.42-1.61; P=.5685); pregnancy-induced hypertension (adjusted odds ratio, 0.85; 95% confidence interval, 0.46-1.59; P=.6146); placental disorders, including placental abruption, placenta previa, placenta accreta, placenta increta, and placenta percreta (adjusted odds ratio, 1.16; 95% confidence interval, 0.60-2.24; P=.6675); preterm birth (adjusted odds ratio, 1.22; 95% confidence interval 0.73-2.03; P=.4418); low birthweight (adjusted odds ratio, 1.12; 95% confidence interval, 0.58-2.15; P=.7355); cesarean delivery (adjusted odds ratio, 1.04; 95% confidence interval, 0.79-1.38; P=.7762); or gestational diabetes mellitus (adjusted odds ratio, 0.83; 95% confidence interval, 0.50-1.38; P=.4734). In addition, there was no difference between the groups for prolonged hospital stay for mothers (adjusted odds ratio, 1.23; 95% confidence interval, 0.83-1.80; P=.3014) or for infants (95% confidence interval, 1.29; 95% confidence interval, 0.72-2.29; P=.3923). CONCLUSION: Embryo biopsy for preimplantation genetic testing does not increase the odds for diagnoses related to placentation (preeclampsia, pregnancy-related hypertension, placental disorders, preterm delivery, or low birthweight), maternal conditions (gestational diabetes mellitus), or maternal or infant length of stay after delivery.

Sex differences in infant health following ART-treated, subfertile, and fertile deliveries.

PURPOSE: Among infants following ART-treated, subfertile, and fertile deliveries to determine (1) the presence and magnitude of sex differences in health outcomes and (2) whether the presence of sex differences varied among maternal fertility groups. METHODS: Retrospective cohort analysis of infants born in Massachusetts (MA) in 2004-2013 who were conceived by ART. The Society for Assisted Reproductive Technology Clinic Outcome Reporting System was linked to the Pregnancy to Early Life Longitudinal data system, which links birth certificates to hospital discharge records for MA mothers and infants. Included were singletons born via ART-treated, subfertile, and fertile deliveries. Multivariable logistic regression was used to model the association between infant sex and health outcomes, controlling for maternal demographic and health characteristics. RESULTS: A total of 16,034 ART-treated, 13,277 subfertile, and 620,375 fertile singleton live births were included. For all three groups, males had greater odds of being preterm (AOR range 1.15-1.2), having birth defects (AOR range 1.31-1.71), experiencing respiratory (AOR range 1.33-1.35) and neurologic (AOR range 1.24-1.3) conditions, and prolonged hospital stay (AOR range 1.19-1.25) compared to females. The interaction between maternal fertility group and infant sex for all infant outcomes was nonsignificant, denoting that the presence of sex differences among fertile, subfertile, and ART groups did not vary. CONCLUSION: Sex differences in birth outcomes of infants following ART-treated, subfertile, and fertile deliveries exist but the magnitude of these differences does not vary among these maternal fertility groups.

Optimizing the control group for evaluating ART outcomes: can outpatient claims data yield a better control group?

PURPOSE: We previously developed a subfertile comparison group with which to compare outcomes of assisted reproductive technology (ART) treatment. In this study, we evaluated whether insurance claims data in the Massachusetts All Payers Claims Database (APCD) defined a more appropriate comparison group. METHODS: We used Massachusetts vital records of women who delivered between 2013 and 2017 on whom APCD data were available. ART deliveries were those linked to a national ART database. Deliveries were subfertile if fertility treatment was marked on the birth certificate, had prior hospitalization with ICD code for infertility, or prior fertility treatment. An infertile group included women with an APCD outpatient or inpatient ICD 9/10 infertility code prior to delivery. Fertile deliveries were none of the above. Demographics, health risks, and obstetric outcomes were compared among groups. Multivariable generalized estimating equations were used to calculate adjusted relative risk (aRR) and 95% confidence intervals (CI). RESULTS: There were 70,726 fertile, 4,763 subfertile, 11,970 infertile, and 7,689 ART-treated deliveries. Only 3,297 deliveries were identified as both subfertile and infertile. Both subfertile and infertile were older, and had more education, chronic hypertension, and diabetes than the fertile group and less than the ART-treated group. Prematurity (aRR = 1.15-1.17) and birthweight (aRR = 1.10-1.21) were increased in all groups compared with the fertile group. CONCLUSION: Although the APCD allowed identification of more women than the previously defined subfertile categorization and allowed us to remove previously unidentified infertile women from the fertile group, it is not clear that it offered a clinically significantly improved comparison group.

Early Autism Spectrum Disorders in Children Born to Fertile, Subfertile, and ART-Treated Women.

INTRODUCTION: We examined the prevalence of autism spectrum disorders (ASDs) in Massachusetts (MA) comparing children born via assisted reproductive technology (ART) and children born to women with indicators of subfertility but no ART (Subfertile), to children born to women with neither ART nor indicators of subfertility (Fertile). We assessed the direct, indirect, and total effects of ART and subfertility on ASD among singletons. METHODS: This study included 10,147 ART, 8072 Subfertile and 441,898 Fertile MA resident births from the MA Outcome Study of ART (MOSART) database linked with Early Intervention program participation data. ART included fresh in vitro fertilization (IVF), fresh intracytoplasmic sperm injection (ICSI), and frozen embryo transfer. We estimated the prevalence of ASD by fertility group. We used logistic regression to assess the natural direct effect (NDE), natural indirect effect (NIE) through preterm birth, and total effects of each fertility group on ASD. RESULTS: The NDE indicated that, compared to the Fertile group, the odds of ASD were not statistically higher in the ART (ORNDE 1.07; 95% CI 0.88-1.30), Subfertile (ORNDE 1.11; 95% CI 0.89-1.38), IVF (ORNDE 0.91; 95% CI 0.68-1.22), or ICSI (ORNDE 1.13; 95% CI 0.84-1.51) groups, even if the rate of preterm birth was the same across all groups. The total effect (product of NDE and NIE) was not significant for ART (ORTotal Effect 1.08; 95% CI 0.89-1.30), Subfertile (ORTotal Effect 1.11; 95% CI 0.89-1.38), IVF (ORTotal Effect 0.92; 95% CI 0.69-1.23), or ICSI (ORTotal Effect 1.13; 95% CI 0.84-1.52). CONCLUSION: Compared to children born to Fertile women, children born to ART, ICSI, or IVF, or Subfertile women are not at increased risk of receiving an ASD diagnosis.

Adverse pregnancy, birth, and infant outcomes in twins: effects of maternal fertility status and infant gender combinations; the Massachusetts Outcomes Study of Assisted Reproductive Technology.

BACKGROUND: It is unknown whether the risk of adverse outcomes in twin pregnancies among subfertile women, conceived with and without in vitro fertilization, differs from those conceived spontaneously. OBJECTIVE: We sought to evaluate the effects of fertility status on adverse perinatal outcomes in twin pregnancies on a population basis. STUDY DESIGN: All twin live births of ≥22 weeks' gestation and ≥350 g birthweight to Massachusetts resident women in 2004 through 2010 were linked to hospital discharge records, vital records, and in vitro fertilization cycles. Women were categorized by their fertility status as in vitro fertilization, subfertile, or fertile, and by twin pair genders (all, like, unlike). Women whose births linked to in vitro fertilization cycles were classified as in vitro fertilization; those with indicators of subfertility but without in vitro fertilization treatment were classified as subfertile; all others were classified as fertile. Risks of 6 adverse pregnancy outcomes (gestational diabetes, pregnancy hypertension, uterine bleeding, placental complications [placenta abruptio, placenta previa, and vasa previa], prenatal hospitalizations, and primary cesarean) and 9 adverse infant outcomes (very low birthweight, low birthweight, small-for-gestation birthweight, large-for-gestation birthweight, very preterm [<32 weeks], preterm, birth defects, neonatal death, and infant death) were modeled by fertility status with the fertile group as reference, using multivariate log binomial regression and reported as adjusted relative risk ratios and 95% confidence intervals. RESULTS: The study population included 10,352 women with twin pregnancies (6090 fertile, 724 subfertile, and 3538 in vitro fertilization). Among all twins, the risks for all 6 adverse pregnancy outcomes were significantly increased for the subfertile and in vitro fertilization groups, with highest risks for uterine bleeding (adjusted relative risk ratios, 1.92 and 2.58, respectively) and placental complications (adjusted relative risk ratios, 2.07 and 1.83, respectively). Among all twins, the risks for those born to subfertile women were significantly increased for very preterm birth and neonatal and infant death (adjusted relative risk ratios, 1.36, 1.89, and 1.87, respectively). Risks were significantly increased among in vitro fertilization twins for very preterm birth, preterm birth, and birth defects (adjusted relative risk ratios, 1.28, 1.07, and 1.26, respectively). CONCLUSION: Risks of all maternal and most infant adverse outcomes were increased for subfertile and in vitro fertilization twins. Among all twins, the highest risks were for uterine bleeding and placental complications for the subfertile and in vitro fertilization groups, and neonatal and infant death in the subfertile group. These findings provide further evidence supporting single embryo transfer and more cautious use of ovulation induction.

Pregnancy, birth, and infant outcomes by maternal fertility status: the Massachusetts Outcomes Study of Assisted Reproductive Technology.

BACKGROUND: Births to subfertile women, with and without infertility treatment, have been reported to have lower birthweights and shorter gestations, even when limited to singletons. It is unknown whether these decrements are due to parental characteristics or aspects of infertility treatment. OBJECTIVE: The objective of the study was to evaluate the effect of maternal fertility status on the risk of pregnancy, birth, and infant complications. STUDY DESIGN: All singleton live births of ≥22 weeks' gestation and ≥350 g birthweight to Massachusetts resident women in 2004-2010 were linked to hospital discharge and vital records. Women were categorized by their fertility status as in vitro fertilization, subfertile, or fertile. Women whose births linked to in vitro fertilization cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System were classified as in vitro fertilization. Women with indicators of subfertility but not treated with in vitro fertilization were classified as subfertile. Women without indicators of subfertility or in vitro fertilization treatment were classified as fertile. Risks of 15 adverse outcomes (gestational diabetes, pregnancy hypertension, antenatal bleeding, placental complications [placenta abruptio and placenta previa], prenatal hospitalizations, primary cesarean delivery, very low birthweight [<1500 g], low birthweight [<2500 g], small-for-gestation birthweight [z-score ≤-1.28], large-for-gestation birthweight [z-score ≥1.28], very preterm [<32 weeks], preterm [<37 weeks], birth defects, neonatal death [0-27 days], and infant death [0-364 days of life]) were modeled by fertility status with the fertile group as reference and the subfertile group as reference, using multivariate log binomial regression and reported as adjusted risk ratios and 95% confidence intervals. RESULTS: The study population included 459,623 women (441,420 fertile, 8054 subfertile, and 10,149 in vitro fertilization). Women in the subfertile and in vitro fertilization groups were older than their fertile counterparts. Risks for 6 of 6 pregnancy outcomes and 6 of 9 infant outcomes were increased for the subfertile group, and 5 of 6 pregnancy outcomes and 7 of 9 infant outcomes were increased for the in vitro fertilization group. For 4 of the 6 pregnancy outcomes (uterine bleeding, placental complications, prenatal hospitalizations, and primary cesarean) and 2 of the infant outcomes (low birthweight and preterm) the risk was greater in the in vitro fertilization group, with nonoverlapping confidence intervals to the subfertile group, indicating a substantially higher risk among in vitro fertilization-treated women. The highest risks for the in vitro fertilization women were uterine bleeding (adjusted risk ratio, 3.80; 95% confidence interval, 3.31-4.36) and placental complications (adjusted risk ratio, 2.81; 95% confidence interval, 2.57-3.08), and for in vitro fertilization infants, very preterm birth (adjusted risk ratio, 2.13; 95% confidence interval, 1.80-2.52), and very low birthweight (adjusted risk ratio, 2.15; 95% confidence interval, 1.80-2.56). With subfertile women as reference, risks for the in vitro fertilization group were significantly increased for uterine bleeding, placental complications, prenatal hospitalizations, primary cesarean delivery, low and very low birthweight, and preterm and very preterm birth. CONCLUSION: These analyses indicate that, compared with fertile women, subfertile and in vitro fertilization-treated women tend to be older, have more preexisting chronic conditions, and are at higher risk for adverse pregnancy outcomes, particularly uterine bleeding and placental complications. The greater risk in in vitro fertilization-treated women may reflect more severe infertility, more extensive underlying pathology, or other unfavorable factors not measured in this study.

Inpatient hospitalizations in women with and without assisted reproductive technology live birth.

PURPOSE: The aim of this study is to evaluate frequency of hospitalization before, during, and after assisted reproductive technology (ART) treatment by cycle outcome. METHODS: Six thousand and one hundred thirty women residing in Massachusetts undergoing 17,135 cycles of ART reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SARTCORS) from 2004 to 2011 were linked to hospital discharges and vital records. Women were grouped according to ART treatment cycle outcome as: no pregnancy (n = 1840), one or more pregnancies but no live birth (n = 968), or one or more singleton live births (n = 3322). Hospital delivery discharges during 1998-2011 were categorized as occurring before, during, or after the ART treatment. The most prevalent ICD-9 codes for non-delivery hospital discharges were compared. Groups were compared using chi square test using SAS 9.3 software. RESULTS: The proportion of any hospitalization was 57.0, 58.3, and 91.3% for women with no pregnancy, no live birth, and ART singleton live birth, respectively; the proportion of non-delivery hospitalizations was 30.4, 31.0, and 28.3%, respectively. The non-ART delivery proportion after ART treatment did not differ by group (33.4, 36.2, and 36.9%, respectively, p = 0.17). Most frequent non-delivery diagnoses (including fibroids, obesity, ectopic pregnancy, depression, and endometriosis) also did not differ by group. A secondary analysis limited to only women with no delivery discharges before the first ART cycle showed similar results. CONCLUSIONS: All groups had live birth deliveries during the study period, suggesting an important contribution of non-ART treatment or treatment-independent conception to overall delivery and live births. Hospitalizations not associated with delivery suggested similarity in morbidity for all ART patients regardless of success with ART treatment.

Perinatal outcomes of singleton siblings: the effects of changing maternal fertility status.

PURPOSE: The objective of this study was to evaluate the effect of changing fertility status on perinatal outcomes of singleton siblings, conceived with and without assisted reproductive technology (ART). METHOD: A longitudinal cohort study of Massachusetts resident women having two consecutive singleton births during 2004-2010 was performed. Women were classified as ART (A), subfertile (S), or fertile (F) and categorized by their fertility status in each birth as A-A, A-S, S-A, S-S, F-A, F-S, and F-F. Within categories, adjusted mean birthweights, gestations, and birthweight Z scores were estimated with linear generalized estimating equations. Risks of low birthweight (LBW, <2500 g), preterm birth (PTB, <37 weeks), and placental complications were modeled using logistic regression by fertility status as adjusted odds ratios (AORs) and 95 % confidence intervals (CIs). RESULTS: Birthweights in second pregnancies averaged 74-155 g higher, except for births to F-A women, who averaged -16 g lower. Most women had a reduction in length of gestation in their second pregnancies, with F-A women having the largest decline (-0.5 weeks). In first birth models, the risks for LBW and placental complications were increased for subfertile (AOR 1.39 [1.07-1.81] and 1.97 [1.33-2.93], respectively) and ART women (AOR 1.58 [1.29-1.93] and 3.40 [2.64-4.37], respectively). Second birth models showed increased risks for ART births of LBW (AOR 3.13 [2.19-4.48]) and placental complications (AOR 2.45 [1.56-3.86]) and greater risks of PTB for both ART (AOR 2.37 [1.74-3.23]) and subfertile women (AOR 1.47 [1.02-2.13]). CONCLUSIONS: Declining fertility status, with and without assisted reproductive technology treatment, is associated with increasing risks for adverse outcomes, greatest for women whose fertility status declined the most.

The effect of father's age in fertile, subfertile, and assisted reproductive technology pregnancies: a population based cohort study.

PURPOSE: To compare ages of mothers and of fathers at delivery in couples who are fertile, subfertile, and subfertile treated with assisted reproductive technology (ART) and to characterize birth outcomes in the ART population according to paternal age. METHODS: Live birth deliveries in Massachusetts between July, 2004 and December, 2008 were identified from vital records and categorized by maternal fertility status and treatment as ART, subfertile or fertile. The ART births were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database to obtain cycle-specific treatment data. Parental ages were obtained from birth certificates. Age of mothers and fathers were compared using ANOVA for continuous measures and χ (2) for categories. Risks of prematurity (<37 weeks), low birthweight (<2,500 g), and low birthweight z-score (small for gestatational age, SGA) were modeled using logistic regression by categories of paternal age as adjusted odds ratios and 95 % CI. RESULTS: The study population included 9,092 ART, 6,238 subfertile, and 318,816 fertile deliveries. Paternal ages in the ART and subfertile groups were similar and differed significantly from those of the fertile group. Maternal age in the ART and subfertile groups averaged 5-6 years older than their fertile counterparts and fathers averaged 4-5 years older with twice as many being older than 37. The risks for prematurity, low birthweight and SGA did not increase with increasing paternal age. CONCLUSIONS: Fathers in ART- treated and subfertile couples are older than in their fertile counterparts. Older paternal age was not assoicated with increased risk for prematurity, low birthweight, or SGA.

Healthcare resource utilization among nursing home residents with Parkinson's disease psychosis: an analysis of Medicare beneficiaries treated with pimavanserin or other-atypical antipsychotics.

Aim: Real-world healthcare resource use (HCRU) burden among patients with Parkinson's disease psychosis (PDP) treated with pimavanserin (PIM) versus other atypical antipsychotics (other-AAPs) including quetiapine (QUE) in long term care (LTC) and nursing home (NH) settings are lacking. This analysis examines HCRU differences among residents in LTC/NH settings who initiate PIM versus QUE or other-AAPs. Methods: A retrospective analysis of LTC/NH residents with PDP from the 100% Medicare claims between 1 April 2015 and 31 December 2021 was conducted. Treatment-naive residents who initiated ≥6 months continuous monotherapy with PIM or QUE or other-AAPs between 04/01/16 and 06/30/2021 were propensity score matched (PSM) 1:1 using 31 variables (age, sex, race, region and 27 Elixhauser comorbidity characteristics). Post-index (i.e., 6 months) HCRU outcomes included: proportion of residents with ≥1 all-cause inpatient (IP) hospitalizations and emergency room (ER) visits. HCRU differences were assessed via log binomial regression and reported as relative risk ratios (RR) and 95% confidence intervals after controlling for dementia, insomnia and index year. Results: From a total of PIM (n = 1827), QUE (n = 7770) or other-AAPs (n = 9557), 1:1 matched sample (n = 1827) in each cohort were selected. All-cause IP hospitalizations (PIM [29.8%]) versus QUE [36.7%]) and ER visits (PIM [47.3%] versus QUE [55.8%]), respectively, were significantly lower for PIM. PIM versus QUE cohort also had significantly lower RR for all-cause IP hospitalizations and ER visits, respectively, (IP hospitalizations RR: 0.82 [0.75. 0.9]; ER visits RR: 0.85 [0.8. 0.9]). PIM versus other-AAPs also had lower likelihood of HCRU outcomes. Conclusion: In this analysis, LTC/NH residents on PIM monotherapy (versus QUE) had a lower likelihood of all-cause hospitalizations (18%) and ER (15%) visits. In this setting, PIM also had lower likelihood of all-cause HCRU versus other-AAPs.

Falls and Fractures among Nursing Home Residents Treated with Pimavanserin versus Other Atypical Antipsychotics: Analysis of Medicare Beneficiaries with Parkinson's Disease Psychosis.

BACKGROUND: Reducing falls and fractures remains an important clinical goal in managing older residents with Parkinson's disease psychosis (PDP) in long-term care/nursing home (LTC/NH) settings. OBJECTIVES: This analysis examined risk of all-cause falls or fractures among PDP residents on continuous monotherapy with pimavanserin (PIM) versus (i) other atypical antipsychotics (AAPs) [quetiapine (QUE), risperidone (RIS), olanzapine (OLA), aripiprazole (ARI)] and (ii) QUE. METHODS: A retrospective analysis of parts A, B, and D claims from a 100% Medicare sample (2013-2019) in LTC/NH settings was conducted. LTC/NH residents in the USA initiating continuous monotherapy (PIM versus other AAPs; PIM versus QUE) for ≥ 6 months between 01 January 2014 and 31 December 2018 were 1:1 propensity score matched (PSM) on 31 variables (age, sex, race, region, and 27 Elixhauser comorbidities). Outcomes included three measures: risks of falls only, fractures only, and falls/fractures during 6-months follow-up. Demographic characteristics were described using chi-square and t-tests. Generalized linear models were used to assess difference in risks of falls/fractures. RESULTS: Of 7187 residents, 47.59% (n = 3420) were female and mean age was 78.8 (± 7.75) years. In total, 14% (n = 1005) were on PIM and 86% (n = 6182) were on other AAPs. After PSM, falls only among PIM residents (n = 1005) was 4.58% (n = 46) versus 7.66% (n = 77) for other AAPs (n = 1005) [relative risk (RR) = 0.63 (0.46, 0.86), p < 0.05] and 8.26% (n = 83) for QUE (n = 1005) residents (p < 0.05). Fractures only among PIM residents was 1.39% (n = 14) compared with 2.09% (n = 21) for other AAPs (p = 0.31) and 1.89% (n = 19) for QUE (p = 0.49), respectively. Taken together, falls/fractures among PIM residents were 5.67% (n = 57) versus 9.05% (n = 91) for other AAPs [RR = 0.63 (0.46, 0.86), p < 0.05] and 9.55% (n = 96) for QUE (p < 0.05), respectively. CONCLUSIONS: In this analysis of LTC/NH residents with PDP, PIM had a 37% and 41% lower risk of all-cause falls/fractures versus other AAPs and versus QUE, respectively.

A risk factor profile for placenta accreta spectrum in pregnancies conceived with assisted reproductive technology.

Objective: To identify independent risk factors for placenta accreta spectrum among pregnancies conceived with assisted reproductive technology. Design: Retrospective cohort study. Setting: Tertiary hospital. Patients: Individuals who conceived with assisted reproductive technology and reached 20 weeks' gestation or later from 2011 to 2017. Interventions: Patient and cycle data was abstracted from hospital records and supplemented with state-level data. Poisson regression was used for multivariate analyses and reported as adjusted relative risks (aRR). Main Outcome Measures: Clinical or histologic placenta accreta spectrum. Results: Of 1,975 qualifying pregnancies, 44 (2.3%) met criteria for accreta spectrum at delivery. In the multivariate model, significant risk factors included low-lying placenta at delivery (aRR, 15.44; 95% CI 7.76-30.72), uterine factor infertility or prior uterine surgery (aRR, 4.68; 95% CI, 2.72-8.05), initial low-lying placentation that resolved (aRR, 3.83; 95% CI, 1.90-7.73), and use of frozen embryos (aRR, 3.02; 95% CI, 1.66-5.48). When the fresh vs frozen variable was replaced with controlled ovarian hyperstimulation, the final model did not change (aRR, 2.40 for unstimulated cycles, 95% CI, 1.32-4.38). With frozen transfers, the accreta rate was 16% when the endometrial thickness was < 6mm vs 3.8% with thicker endometrium (P=.02). Conclusions: Among pregnancies conceived with assisted reproductive technology, accreta spectrum is associated with low placental implantation (even when resolved), uterine factor infertility and prior uterine surgery, and the use of frozen embryo transfer or unstimulated cycles.

A unique placenta previa risk factor profile for pregnancies conceived with assisted reproductive technology.

OBJECTIVE: To define specific risk factors for placenta previa in pregnancies conceived with assisted reproductive technology (ART). DESIGN: Retrospective cohort. SETTING: Fertility centers and inpatient obstetric units in Massachusetts. PATIENT(S): Patients conceiving with ART and delivering at 20 weeks gestation or later between 2011 and 2017 in Massachusetts. INTERVENTION(S): Patient demographic and medical factors and specific components of their cycles. Data were obtained by linking vital records of the State of Massachusetts to reproductive clinic data obtained from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, and then supplementing this information with laboratory and obstetric data from 2 large academic hospitals. MAIN OUTCOME MEASURE: Associations were tested between multiple cycle- and patient-related factors and placenta previa or low-lying placenta at delivery. After testing for confounders, multivariate models were adjusted for maternal age, history of prior cesarean delivery and birth plurality, and are reported as adjusted relative risks (aRR). RESULT(S): We included 18,939 pregnancies, with 553 (2.9%) having placenta previa at delivery. Advanced maternal age (aRR, 1.25; 95% confidence interval [CI], 1.06-1.48), endometriosis, (aRR, 2.22; 95% CI, 1.71-2.86), and controlled ovarian hyperstimulation (aRR, 1.33; 95% CI, 1.12-1.59) were associated with placenta previa, whereas multiple births (aRR, 0.63; 95% CI, 0.48-0.81) and a history of polycystic ovary syndrome or ovulation disorders (aRR, 0.59; 95% CI, 0.46-0.75) had negative associations. The endometriosis association was strong in nulliparas and the controlled ovarian hyperstimulation association was strong in parous patients in a stratified analysis. No association was seen with prior history of cesarean delivery. CONCLUSION(S): Patients conceiving with ART do not have the typical previa risk factors of prior cesarean delivery and multiple gestations, whereas endometriosis and fresh embryo transfers contributed moderate risk. The embryo transfer process itself may affect previa development in this population.

The impact of single-step and sequential embryo culture systems on obstetric and perinatal outcomes in singleton pregnancies: the Massachusetts Outcomes Study of Assisted Reproductive Technology.

OBJECTIVE: To compare the obstetric and perinatal outcomes of deliveries conceived with embryos from single-step vs. sequential culture media systems. DESIGN: Historical cohort of Massachusetts vital records linked to assisted reproductive technology clinic data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System and laboratory embryology data from two large academic hospital fertility centers. SETTING: Not applicable. PATIENTS: Patients with singleton live birth deliveries between 2004 and 2017 conceived with autologous assisted reproductive technology cycles with fresh blastocyst transfer using either single-step (n = 1,058) or sequential (n = 474) culture media systems. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Associations of single-step vs. sequential culture with obstetric outcomes (mode of delivery, placental abnormalities, pregnancy-induced hypertension, and gestational diabetes) and perinatal outcomes (preterm birth, low birthweight, small-for-gestational-age, and large-for-gestational-age [LGA]) were assessed with multivariate logistic modeling, adjusted for maternal age, race/ethnicity, education, parity, insurance type, protein supplementation, oxygen concentration, fertilization method, and number of transferred embryos. RESULTS: Compared with sequential culture, single-step culture was associated with increased odds of LGA (adjusted odds ratio 2.1, 95% confidence interval 1.04-4.22). There were no statistically significant differences between single-step and sequential culture media systems in the odds of placental abnormalities, pregnancy-induced hypertension, gestational diabetes, prematurity, small-for-gestational-age, or low birthweight. CONCLUSIONS: Single-step culture is associated with increased odds of LGA, indicating that embryo culture media systems may affect perinatal outcomes.

Association of maternal fertility status and receipt of fertility treatment with healthcare utilization in infants up to age four.

OBJECTIVE: This study evaluates differences in child healthcare utilization by maternal fertility status in the first four years of life. STUDY DESIGN: The retrospective cohort evaluated Massachusetts (MA) live born infants using data linked from clinical assisted reproductive technology (ART) data, birth certificates, and hospital discharge records. Hospital records of infants born 2004-2017 to mothers of fertile (no infertility treatments or indicators of infertility), unassisted subfertile (UF, indicators of infertility but no fertility treatment), medically assisted reproduction (MAR, non-ART assistance with reproduction) and ART treatment were studied. Adjusted relative risk (aRR) was calculated using multivariable log binomial regression models. RESULTS: We included 339,426 singleton live-born infants discharged from birth hospitalization. Compared to children born to fertile mothers, those born to UF, MAR and ART-treated mothers were more likely to have hospital-based care (aRR 1.06-1.21) in their first 4 years. CONCLUSIONS: Maternal subfertility with and without treatment was associated with small increases in child healthcare utilization.

Influence of subfertility and assisted reproductive technology treatment on mortality of women after delivery.

OBJECTIVE: To compare incidence, risk factors, and etiology of women's deaths in fertile, subfertile, and undergoing assisted reproductive technology (ART) in the years after delivery. DESIGN: Retrospective cohort. SETTING: University hospital. PATIENT(S): Women who had delivered in Massachusetts. INTERVENTION(S): This study used data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System linked to vital records, hospital stays, and the Massachusetts death file. Mortality of patients delivered from 2004-2013 was evaluated through 2015. The exposure groups, determined on the basis of the last delivery, were ART-treated (linked to Society for Assisted Reproductive Technology Clinic Outcome Reporting System), subfertile (no ART but with indicators of subfertility including birth certificate checkbox for fertility treatment, prior hospitalization for infertility [International Classification of Disease codes 9 628 or V23], and/or prior delivery with checkbox or ART), or fertile (neither ART nor subfertile). Numbers (per 100,000 women-years) and causes of death were obtained from the Massachusetts death file. MAIN OUTCOME MEASURE(S): Mortality of women after delivery in each of the three fertility groups and the most common etiology of death in each. RESULT(S): We included 483,547 women: 16,429 ART, 11,696 subfertile, and 455,422 fertile among whom there were 1,280 deaths with 21.1, 25.5, and 44.7 deaths, respectively, per 100,000 women-years. External causes (violence, accidents, and poisonings) were the most common reasons for death in the fertile group. Deaths occurred on average 46 months after delivery. When external causes of death were removed, there were 19.1, 17.0, and 25.6 deaths per 100,000 women-years and leading causes of death in all groups were cancer and circulatory problems. CONCLUSION(S): The study presents reassuring data that death rates within 5 years of delivery in ART-treated and subfertile women do not differ from those in fertile women.

Health outcomes for Massachusetts infants after fresh versus frozen embryo transfer.

OBJECTIVE: To compare neonatal health outcomes after fresh versus frozen ET (FET). DESIGN: Retrospective analysis of a population-based database of linked clinically assisted reproductive technology (ART) data with state vital records. Multivariable logistic regression was used to model the association between deliveries from fresh versus FET and adverse health outcomes, controlling for maternal characteristics. SETTING: Not applicable. PATIENT(S): Live-born singleton infants born to Massachusetts women who conceived by fresh or FET after ART using autologous oocytes between July 1, 2004, and December 31, 2013. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preterm birth, low birth weight, neonatal mortality, birth defects, organ system conditions. RESULT(S): Compared with infants conceived from fresh embryos, those born to mothers who underwent FET were less likely to be small for gestational age (adjusted odds ratio [AOR] = 0.56; 95% confidence interval [CI], 0.44-0.70) and low birth weight (AOR = 0.72; 95% CI, 0.59-0.88) but more likely to be large for gestational age (AOR = 1.47; 95% CI, 1.26-1.70) and to experience greater odds of infectious disease (AOR = 1.46; 95% CI, 1.03-2.06), respiratory (AOR = 1.23; 95% CI, 1.07-1.41), and neurologic (AOR = 1.32; 95% CI, 1.04-1.68) conditions. There were no statistically significant differences in preterm birth, neonatal mortality, birth defects, cardiovascular, hematologic, and gastrointestinal/feeding conditions, and for infants ≥ 35 weeks, no statistically significant differences in prolonged hospital stay (>3 days for vaginal delivery, >5 days for cesarean). CONCLUSION(S): Compared with infants conceived from fresh ET, those born by FET have higher birth weight but increased odds of infectious disease, hematologic, respiratory, and neurologic abnormalities. These risks should be considered when making decisions on fresh versus FET.

Health of Infants After ART-Treated, Subfertile, and Fertile Deliveries.

OBJECTIVES: To assess the risk of adverse health outcomes for infants after assisted reproductive technology (ART)-treated and subfertile as compared with fertile deliveries. METHODS: Live-born singleton infants ≥23 weeks' gestational age (GA) born in Massachusetts between July 1, 2004, and December 31, 2010, were analyzed by linking a clinical ART database with state vital records. χ2 tests were used to compare the outcomes of fertile (those without ART treatment or other indicators of infertility), subfertile (indicators of infertility, no ART), and ART-treated (linked to ART deliveries) mothers, stratified by GA. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated by using multivariate logistic regression within each GA stratum, controlling for maternal sociodemographic and health characteristics. RESULTS: Compared with infants of fertile mothers (n = 336 705), infants born to subfertile (n = 5043) or ART-treated (n = 8375) mothers were more likely to be preterm (aOR 1.39 [95% CI 1.26-1.54] and aOR 1.72 [95% CI 1.60-1.85], respectively) and have respiratory and gastrointestinal and/or nutritional conditions (aOR range: 1.12-1.18). When stratified by GA, infants of subfertile or ART-treated mothers were at greater risk for congenital malformations and infectious diseases as well as cardiovascular and respiratory conditions (aOR range: 1.30-2.61; 95% CI range: 1.02-4.59). Compared with infants born to subfertile mothers, infants born to ART-treated mothers were at lower risk for being small for GA and having congenital malformations and cardiovascular conditions and at higher risk for infectious disease conditions. CONCLUSIONS: Compared with infants born to fertile mothers, infants of subfertile and ART-treated mothers are at greater risk for adverse health outcomes at birth beyond prematurity. The occurrence and magnitude of these risks vary by GA and organ systems.