Publications by authors named "Michele R Hacker"

202 Publications

Spontaneous version after preterm prelabor rupture of membranes.

J Matern Fetal Neonatal Med 2021 Sep 1:1-8. Epub 2021 Sep 1.

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Background: Preterm prelabor rupture of membranes (PPROM), defined as rupture of membranes before the onset of labor at < 37 weeks' gestation, affects approximately 3% of all pregnancies. For PPROM prior to 34 weeks' gestation, in the absence of contraindications to expectant management, antibiotics are administered to increase the latency period and reduce the incidence of maternal and neonatal infection. The latency period additionally provides an opportunity for fetal presentation to change, which impacts the mode of delivery. It is important to better understand the incidence of spontaneous version after PPROM to enhance patient counseling with regard to the mode of delivery.

Objective: To determine the incidence of discordant fetal presentation, resulting from spontaneous version, between admission for PPROM and time of delivery for cephalic and non-cephalic fetuses among patients diagnosed with PPROM prior to 34 weeks' gestation and to compare characteristics of those with and without discordant fetal presentation.

Study Design: We performed a retrospective cohort study of singleton pregnancies diagnosed with PPROM identified using ICD-9/10-CM codes, < 34 weeks' gestation, admitted to a tertiary care center's antepartum service from 2011-2018. Patients were included if the fetal presentation was documented by ultrasound within 48 h of admission and PPROM, and delivery occurred >24 h after PPROM. Data are presented as proportions, median (interquartile range) or risk ratio and 95% confidence interval.

Results: We included 209 patients. Patient age, body mass index, parity, and race/ethnicity were similar among patients with cephalic and non-cephalic fetal presentations at admission. Patients with cephalic presentation at time of PPROM presented at a later gestational age than patients with a non-cephalic presentation. Among patients with a cephalic presentation at admission, the incidence of non-cephalic presentation at delivery was 11.7% (19/162), whereas with non-cephalic presentation at admission, the incidence of cephalic presentation at delivery was 21.3% (10/47). While there was an increased risk of spontaneous version resulting in a discordant presentation at delivery with non-cephalic presentation, this relationship was attenuated and not significant when adjusted for gestational age at time of PPROM.​ Patients with discordant presentation presented with PPROM at an earlier gestational age and had a longer latency period compared to patients with a concordant presentation. Patient age, body mass index, amniotic fluid assessment at admission, and infant birth weight were similar in those with and without a change in fetal presentation.

Conclusion: Discordant fetal presentation resulting from spontaneous version from cephalic to non-cephalic presentation after PPROM occurred in 11.7% (19/162) of patients, while discordant presentation from non-cephalic to cephalic presentation occurred in 21.3% (10/47) of patients. Given the limited published data on spontaneous version after PPROM these results may impact patient counseling.
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http://dx.doi.org/10.1080/14767058.2021.1950137DOI Listing
September 2021

Endocrine disrupting chemical-associated hair product use during pregnancy and gestational age at delivery: a pilot study.

Environ Health 2021 07 28;20(1):86. Epub 2021 Jul 28.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.

Background: Prenatal endocrine disrupting chemical (EDC) exposure has been associated with increased risk of preterm birth. Non-Hispanic Black women have higher incidence of preterm birth compared to other racial/ethnic groups and may be disproportionately exposed to EDCs through EDC-containing hair products. However, research on the use of EDC-associated hair products during pregnancy and risk of preterm birth is lacking. Therefore, the objective of this pilot study was to estimate associations of prenatal hair product use with gestational age at delivery in a Boston, Massachusetts area pregnancy cohort.

Methods: The study population consisted of a subset of participants enrolled in the Environmental Reproductive and Glucose Outcomes (ERGO) Study between 2018 and 2020. We collected self-reported data on demographics and hair product use using a previously validated questionnaire at four prenatal visits (median: 12, 19, 26, 36 weeks' gestation) and abstracted gestational age at delivery from medical records. We compared gestational age and hair product use by race/ethnicity and used linear regression to estimate covariate-adjusted associations of product use and frequency of use at each study visit with gestational age at delivery. Primary models were adjusted for maternal age at enrollment and delivery method.

Results: Of the 154 study participants, 7% delivered preterm. Non-Hispanic Black participants had lower mean gestational age at delivery compared to non-Hispanic White participants (38.2 vs. 39.2 weeks) and were more likely to report ever and more frequent use of hair products. In regression models, participants reporting daily use of hair oils at visit 4 had lower mean gestational age at delivery compared to non-users (β: -8.3 days; 95% confidence interval: -14.9, -1.6). We did not find evidence of associations at earlier visits or with other products.

Conclusions: Frequent use of hair oils during late pregnancy may be associated with shorter gestational duration. As hair oils are more commonly used by non-Hispanic Black women and represent potentially modifiable EDC exposure sources, this may have important implications for the known racial disparity in preterm birth.
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http://dx.doi.org/10.1186/s12940-021-00772-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316883PMC
July 2021

Lenvatinib targets PDGFR-β pericytes and inhibits synergy with thyroid carcinoma cells: novel translational insights.

J Clin Endocrinol Metab 2021 Jul 24. Epub 2021 Jul 24.

Laboratory of Human Thyroid Cancers Preclinical and Translational Research, Division of Experimental Pathology, Cancer Research Institute (CRI), Cancer Center, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Context: Pericyte populations abundantly express tyrosine-kinases (TK, e.g. PDGFR-β) and impact therapeutic response. Lenvatinib is a clinically available TK inhibitor (TKI) that targets PDGFR-β. Duration of therapeutic response was shorter in patients with greater disease burden and metastasis. Patients may develop drug resistance and tumor progression.

Objectives: to develop a gene signature of pericyte abundance to assess with tumor aggressiveness, and determine both the response of thyroid-derived pericytes to lenvatinib and their synergies with thyroid carcinoma-derived cells.

Design: Using a new gene signature, we estimated the relative abundance of pericytes in papillary thyroid carcinoma (PTC) and normal thyroid (NT) TCGA samples. We also co-cultured CD90 +;PAX8 - thyroid-derived pericytes and BRAF WT/V600E-PTC-derived cells to determine effects of co-culture on paracrine communications and lenvatinib response.

Results: Pericyte abundance is significantly higher in BRAF V600E-PTC with hTERT mutations and copy number alterations compared to NT or BRAF WT-PTC samples, even when data are corrected for clinical-pathologic confounders. We have identified upregulated pathways important for tumor survival, immunomodulation, RNA transcription, cell cycle regulation, cholesterol metabolism. Pericyte growth is significantly increased by PDGF-BB, which activates phospho(p)-PDGFR-β, pERK1/2 and pAKT. Lenvatinib strongly inhibits pericyte viability by down-regulating MAPK, pAKT and p-p70S6-kinase downstream PDGFR-β. Critically, lenvatinib significantly induces higher BRAF WT/V600E-PTC cell death when co-cultured with pericytes, as a result of pericyte targeting via PDGFR-β.

Conclusions: This is the first thyroid-specific model of lenvatinib therapeutic efficacy against pericyte viability, which disadvantages BRAF WT/V600E-PTC growth. Assessing pericyte abundance in patients with PTC could be essential to selection rationales for appropriate targeted therapy with lenvatinib.
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http://dx.doi.org/10.1210/clinem/dgab552DOI Listing
July 2021

Ambient PM gross β-activity and glucose levels during pregnancy.

Environ Health 2021 06 14;20(1):70. Epub 2021 Jun 14.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.

Background: Exposure to ionizing radiation has been associated with insulin resistance and type 2 diabetes. In light of recent work showing an association between ambient particulate matter (PM) gross β-activity and gestational diabetes mellitus (GDM) among pregnant women, we examined pregnancy glucose levels in relation to PM gross β-activity to better understand this pathway.

Methods: Our study included 103 participants receiving prenatal care at Beth Israel Deaconess Medical Center in Boston, MA. PM gross β-activity was obtained from US Environmental Protection Agency's RadNet program monitors, and blood glucose levels were obtained from the non-fasting glucose challenge test performed clinically as the first step of the 2-step GDM screening test. For each exposure window we examined (i.e., moving average same-day, one-week, first-trimester, and second-trimester PM gross β-activity), we fitted generalized additive models and adjusted for clinical characteristics, socio-demographic factors, temporal variables, and PM with an aerodynamic diameter ≤ 2.5 μm (PM). Subgroup analyses by maternal age and by body mass index were also conducted.

Results: An interquartile range increase in average PM gross β-activity during the second trimester of pregnancy was associated with an increase of 17.5 (95% CI: 0.8, 34.3) mg/dL in glucose concentration. Associations were stronger among younger and overweight/obese participants. Our findings also suggest that the highest compared to the lowest quartile of one-week exposure was associated with 17.0 (95% CI: - 4.0, 38.0) mg/dL higher glucose levels. No associations of glucose were observed with PM gross β-activity during same-day and first-trimester exposure windows. PM was not associated with glucose levels during any exposure window in our data.

Conclusions: Exposure to higher levels of ambient PM gross β-activity was associated with higher blood glucose levels in pregnant patients, with implications for how this novel environmental factor could impact pregnancy health.
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http://dx.doi.org/10.1186/s12940-021-00744-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204493PMC
June 2021

Strategies to improve postpartum glucose screening rates are needed.

J Obstet Gynaecol Res 2021 Aug 26;47(8):2641-2645. Epub 2021 May 26.

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

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.
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http://dx.doi.org/10.1111/jog.14868DOI Listing
August 2021

Associations between electronic nicotine delivery systems and birth outcomes.

J Matern Fetal Neonatal Med 2021 May 24:1-8. Epub 2021 May 24.

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Objectives: Nicotine crosses the placenta and is a known teratogen. The use of electronic nicotine delivery systems (ENDS) has increased among pregnant women in the US, but there is limited knowledge about their effects on birth outcomes. We examined the associations between ENDS and cigarette use during pregnancy with birth outcomes.

Methods: We conducted a cross-sectional analysis of 57,046 respondents from 32 US states in the 2016-2017 Pregnancy Risk Assessment Monitoring System. Respondents self-reported use of ENDS and cigarettes during the last 3 months of pregnancy; this was linked with birth outcomes documented on the birth certificate, including birth weight, gestational age, small-for-gestational age, and preterm birth.

Results: During the last 3 months of pregnancy, 0.5% of women used ENDS only, 0.8% were dual users of ENDS and cigarettes, and 8.0% used cigarettes only. In adjusted models, infants of women who used ENDS only weighed 57.8 grams less (95% CI -134.2, 18.6;  = .14) and were born 0.21 weeks earlier (95% CI -0.45, 0.03;  = .09) than infants of non-users. Infants born to dual users were 193.9 grams less (95% CI -274.9, -112.8;  < .01) and had a 1.93 higher odds of being born small-for-gestational age (95% CI 1.31, 2.83;  < .01) than infants of non-users.

Conclusions: Our results provide some indication that prenatal ENDS use may adversely affect birth outcomes by reducing birth weight and gestational age. Estimates were imprecise, suggesting that larger samples of ENDS users with more detailed information about patterns of use are needed.
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http://dx.doi.org/10.1080/14767058.2021.1929156DOI Listing
May 2021

Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women.

JAMA 2021 06;325(23):2370-2380

Harvard Medical School, Boston, Massachusetts.

Importance: Pregnant women are at increased risk of morbidity and mortality from COVID-19 but have been excluded from the phase 3 COVID-19 vaccine trials. Data on vaccine safety and immunogenicity in these populations are therefore limited.

Objective: To evaluate the immunogenicity of COVID-19 messenger RNA (mRNA) vaccines in pregnant and lactating women, including against emerging SARS-CoV-2 variants of concern.

Design, Setting, And Participants: An exploratory, descriptive, prospective cohort study enrolled 103 women who received a COVID-19 vaccine from December 2020 through March 2021 and 28 women who had confirmed SARS-CoV-2 infection from April 2020 through March 2021 (the last follow-up date was March 26, 2021). This study enrolled 30 pregnant, 16 lactating, and 57 neither pregnant nor lactating women who received either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines and 22 pregnant and 6 nonpregnant unvaccinated women with SARS-CoV-2 infection.

Main Outcomes And Measures: SARS-CoV-2 receptor binding domain binding, neutralizing, and functional nonneutralizing antibody responses from pregnant, lactating, and nonpregnant women were assessed following vaccination. Spike-specific T-cell responses were evaluated using IFN-γ enzyme-linked immunospot and multiparameter intracellular cytokine-staining assays. Humoral and cellular immune responses were determined against the original SARS-CoV-2 USA-WA1/2020 strain as well as against the B.1.1.7 and B.1.351 variants.

Results: This study enrolled 103 women aged 18 to 45 years (66% non-Hispanic White) who received a COVID-19 mRNA vaccine. After the second vaccine dose, fever was reported in 4 pregnant women (14%; SD, 6%), 7 lactating women (44%; SD, 12%), and 27 nonpregnant women (52%; SD, 7%). Binding, neutralizing, and functional nonneutralizing antibody responses as well as CD4 and CD8 T-cell responses were present in pregnant, lactating, and nonpregnant women following vaccination. Binding and neutralizing antibodies were also observed in infant cord blood and breast milk. Binding and neutralizing antibody titers against the SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern were reduced, but T-cell responses were preserved against viral variants.

Conclusion And Relevance: In this exploratory analysis of a convenience sample, receipt of a COVID-19 mRNA vaccine was immunogenic in pregnant women, and vaccine-elicited antibodies were transported to infant cord blood and breast milk. Pregnant and nonpregnant women who were vaccinated developed cross-reactive antibody responses and T-cell responses against SARS-CoV-2 variants of concern.
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http://dx.doi.org/10.1001/jama.2021.7563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120446PMC
June 2021

Vertical transmission of SARS-CoV-2: consider the denominator.

Am J Obstet Gynecol MFM 2021 07 29;3(4):100386. Epub 2021 Apr 29.

Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA; Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA.

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http://dx.doi.org/10.1016/j.ajogmf.2021.100386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081748PMC
July 2021

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

Matern Child Health J 2021 Jul 27;25(7):1110-1117. Epub 2021 Apr 27.

Harvard Medical School, Boston, MA, USA.

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.
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http://dx.doi.org/10.1007/s10995-021-03129-zDOI Listing
July 2021

Evaluating meaningful levels of financial toxicity in gynecologic cancers.

Int J Gynecol Cancer 2021 06 15;31(6):801-806. Epub 2021 Apr 15.

Department of Obstetrics and Gynecology, The University of Alabama, Birmingham, Alabama, USA.

Objective: The Comprehensive Score for Financial Toxicity (COST) is a validated instrument measuring the economic burden experienced by patients with cancer. We evaluated the frequency of financial toxicity at different COST levels and stratified risk factors and associations with cost-coping strategies by financial toxicity severity.

Methods: We analyzed previously collected survey data of gynecologic oncology patients from two tertiary care institutions. Both surveys included the COST tool and questions assessing economic and behavioral cost-coping strategies. We adapted a proposed grading scale to define three groups: no/mild, moderate, and severe financial toxicity and used χ, Fisher's exact test, and Wilcoxon rank sum test to compare groups. We used Poisson regression to calculate crude and adjusted risk ratios for cost-coping strategies, comparing patients with moderate or severe to no/mild financial toxicity.

Results: Among 308 patients, 14.9% had severe, 32.1% had moderate, and 52.9% had no/mild financial toxicity. Younger age, non-white race, lower education, unemployment, lower income, use of systemic therapy, and shorter time since diagnosis were associated with worse financial toxicity (all p<0.05). Respondents with moderate or severe financial toxicity were significantly more likely to use economic cost-coping strategies such as changing spending habits (adjusted risk ratio (aRR) 2.7, 95% CI 1.8 to 4.0 moderate; aRR 3.6, 95% CI 2.4 to 5.4 severe) and borrowing money (aRR 5.5, 95% CI 1.8 to 16.5 moderate; aRR 12.7, 95% CI 4.3 to 37.1 severe). Those with severe financial toxicity also had a significantly higher risk of behavioral cost-coping through medication non-compliance (aRR 4.6, 95% CI 1.2 to 18.1).

Conclusions: Among a geographically diverse cohort of gynecologic oncology patients, nearly half reported financial toxicity (COST <26), which was associated with economic cost-coping strategies. In those 14.9% of patients reporting severe financial toxicity (COST <14) there was also an increased risk of medication non-compliance, which may lead to worse health outcomes in this group.
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http://dx.doi.org/10.1136/ijgc-2021-002475DOI Listing
June 2021

Comparison of Trendelenburg Angles in Vaginal, Laparoscopic, and Robotic Uterovaginal Apical Prolapse Repairs.

J Minim Invasive Gynecol 2021 Apr 20. Epub 2021 Apr 20.

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center (Drs. Jaresova, Hacker, and Li, and Ms. Macharia), Boston, Massachusetts; Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School (Dr. Jaresova), Boston, Massachusetts; Department of Obstetrics and Gynecology, Mount Auburn Hospital (Dr. Warda), Cambridge, Massachusetts. Electronic address:

Study Objective: To compare the Trendelenburg angle used in laparoscopic uterovaginal apical prolapse repairs with the angles used in vaginal and robotic uterovaginal apical prolapse repairs.

Design: Prospective, multicenter cohort study from May 2015 to December 2016.

Setting: Two academic teaching hospitals.

Patients: Sixty patients who underwent vaginal high uterosacral ligament suspension, laparoscopic sacrocolpopexy, or robotic sacrocolpopexy performed by 6 surgeons board-certified in female pelvic medicine and reconstructive surgery.

Interventions: Measurement of Trendelenburg angle and time spent in Trendelenburg during surgery.

Measurements And Main Results: Twenty patients were enrolled in each procedure group. The median maximum angle of Trendelenburg was significantly greater in the laparoscopic group (22° [20-25]) than in the vaginal group (15° [6-19]; p <.001) and the robotic group (19° [16-21]; p = .02). The participants in the laparoscopic group spent significantly more time overall in Trendelenburg (176 minutes [143-221]) than those in the robotic group (150 minutes [127-161]; p = .01) and those in the vaginal group (120 minutes [86-128]; p <.001). The participants in the laparoscopic and robotic groups spent similar amounts of time in maximum Trendelenburg (116 minutes [52-164] and 117 minutes [61-134], respectively; p = .56), whereas the participants in the vaginal group spent significantly less time in maximum Trendelenburg (10 minutes [7-38]) than those in the laparoscopic group (p <.001). The total median operative time was highest for the laparoscopic approach (211 minutes [173-270]), followed by the robotic approach (181 minutes [165-201]) and the vaginal approach (162 minutes [128-186]; p = .008).

Conclusion: The median maximum angle of Trendelenburg was highest in laparoscopic sacrocolpopexy-followed by robotic sacrocolpopexy-and lowest in vaginal high uterosacral ligament suspension. Patients who underwent robotic sacrocolpopexy spent less time in Trendelenburg than those who underwent the laparoscopic approach. Prolonged, steep Trendelenburg is often not required for any of the 3 surgical procedures, but a vaginal approach should be considered for those at high risk of complications from Trendelenburg position.
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http://dx.doi.org/10.1016/j.jmig.2021.04.001DOI Listing
April 2021

Adverse psychosocial factors in pregnancy and preterm delivery.

Paediatr Perinat Epidemiol 2021 Sep 5;35(5):519-529. Epub 2021 Mar 5.

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Background: Mental health symptoms, stress, and low psychosocial resources are associated with preterm delivery. It is unknown if there are groups of women who experience similar patterns of these adverse psychosocial factors during pregnancy and if the risk of preterm delivery differs among these groups.

Objective: To identify groups of women with similar patterns of adverse psychosocial factors during pregnancy and determine whether the risk of preterm delivery differs among these groups.

Methods: Spontaneous Prematurity and Epigenetics of the Cervix (SPEC) is a prospective cohort study of pregnant women, aged 18 and older. In this analysis, we included women who enrolled after 24 August 2014 and delivered by 20 January 2019. As women could enrol more than once, our cohort included 774 women with 787 pregnancies. We conducted a latent class analysis to identify groups of women with similar patterns of adverse psychosocial factors during pregnancy based on their responses to measures assessing depression, perceived stress, anxiety (pregnancy-related and generalised), stressful life events, resilience, and social support (partner and friend/family). After identifying the latent classes, we used log-binomial regression to compare the incidence of preterm delivery among the classes.

Results: The median age among participants was 33.2 years (interquartile range 30.3-36.3), and the majority were non-Hispanic white (56.9%). We identified three classes of adverse psychosocial factors (few, some, and many factors). In total, 63 (8.0%) pregnancies resulted in a preterm delivery. Compared to participants with few factors, the risk of preterm delivery was no different among participants with some (RR 1.23, 95% CI 0.68, 2.25) and many adverse factors (RR 1.62, 95% CI 0.73, 3.62).

Conclusions: We identified three groups of pregnant women with similar patterns of adverse psychosocial factors. We did not observe a difference in the risk of preterm delivery among the classes.
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http://dx.doi.org/10.1111/ppe.12756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380636PMC
September 2021

Elevated serum progesterone during in vitro fertilization treatment and the risk of ischemic placental disease.

Pregnancy Hypertens 2021 Jun 13;24:7-12. Epub 2021 Feb 13.

Boston IVF, Waltham, MA, USA.

Background: Elevated progesterone on the day of human chorionic gonadotropin (hCG) administration is associated with decreased live birth rates in IVF cycles. The association with adverse pregnancy outcomes is unknown.

Objectives: Assess the association between serum progesterone on the day of hCG administration and the risk of ischemic placental disease [IPD; preeclampsia, placental abruption, and/or small for gestational age (SGA)].

Methods: We conducted a retrospective cohort study of autologous fresh IVF cycles resulting in delivery between 2005 and 2018. All IVF procedures were conducted at a large, university-affiliated infertility center. Patients were divided into tertiles based on their serum progesterone level on the day of hCG administration; the lowest tertile served as the reference group. We identified pregnancies complicated by preeclampsia and placental abruption using ICD-9/10 codes and medical record review. We defined SGA as < 10th percentile using U.S. growth curves.

Results: The cohort included 166 deliveries in the lowest tertile of progesterone (0.2-0.73 ng/ml), 166 deliveries in the middle (0.64-1.05 ng/ml) and 167 deliveries in the highest tertile (1.05-5.6 ng/ml). Compared with the lowest tertile, the risk of IPD was greater in the middle (RR 1.6; 95% CI 1.1-2.5) tertile after adjustment for age, parity, number of oocytes retrieved, and estradiol. The highest tertile was also not associated with an increased risk of IPD.

Conclusion: In an IVF population, elevated serum progesterone in the range of 0.64-1.05 ng/mL on the day of hCG administration was associated with a small increased risk of IPD.
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http://dx.doi.org/10.1016/j.preghy.2021.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159861PMC
June 2021

Crowdsourcing to measure financial toxicity in gynecologic oncology.

Gynecol Oncol 2021 05 5;161(2):595-600. Epub 2021 Feb 5.

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USA.

Objective: To utilize a novel crowdsourcing method to measure financial toxicity and its effects among a national cohort of gynecologic cancer patients.

Methods: Crowdsourcing methods were used to administer an online survey to women in the United States with gynecologic cancers. We used the Comprehensive Score for Financial Toxicity (COST) tool to measure financial toxicity and the EQ-5D-3L to measure quality of life (QOL). Based on prior work, we defined high financial toxicity as a COST score ≤ 23. We assessed correlation of COST scores with QOL. We used log-binomial regression to examine associations between high financial toxicity and cost-coping strategies.

Results: Among the final study sample of 334 respondents, 87% were white, median age at diagnosis was 55 (interquartile range 47-63), 52% had stage III or IV disease and 90% had private insurance or Medicare. Median COST score was 24 (interquartile range 15-32) and 49% of respondents reported high financial toxicity. Greater financial toxicity was correlated with worse QOL (p < 0.001). Participants reporting high financial toxicity were more likely to use cost-coping strategies, including spending less on basic goods (RR: 3.3; 95% CI: 2.1-5.1), borrowing money or applying for financial assistance (RR: 4.0; 95% CI: 2.4-6.9), and delaying or avoiding care (RR: 5.6; 95% CI: 2.6-12.1).

Conclusions: Crowdsourcing is an effective tool to measure financial toxicity. Nearly half of respondents reported high financial toxicity, which was significantly associated with worse QOL, utilization of cost-coping strategies and delays or avoidance of care.
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http://dx.doi.org/10.1016/j.ygyno.2021.01.040DOI Listing
May 2021

Understanding Rising Electronic Cigarette Use.

Obstet Gynecol 2021 03;137(3):521-527

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, the Departments of Environmental Health and Epidemiology, Harvard T.H. Chan School of Public Health, the Region 1 New England Pediatric Environmental Health Specialty Unit, and the Division of General Pediatrics, Department of Pediatrics, Boston Children's Hospital, Boston, and the School of Social Work, Boston College, Chestnut Hill, Massachusetts.

Vaping is the act of inhaling an aerosol generated by an electronic cigarette (e-cigarette), a battery-powered device that heats a reservoir of liquid, typically nicotine-containing, to deliver contents to the user. E-cigarettes were initially introduced as a means of smoking cessation, although evidence of their effectiveness is limited. There is a widespread perception that these products are a safer alternative to conventional cigarettes, driven in large part by marketing efforts by e-cigarette manufacturers. Yet to achieve vaporization, temperatures are so high that components of the device hardware, such as metals, plastics, rubber and foam, are aerosolized and inhaled along with the vaporized e-liquid containing nicotine, flavoring and solvents. We do not fully understand the health consequences of such aerosol exposure, particularly long-term effects, but short-term negative cardiovascular and respiratory effects have been demonstrated. Very few studies have evaluated the reproductive effect of e-cigarette use. We do not know whether vaping during pregnancy affects birth outcomes or the lifelong health of the fetus. There has been an exponential rise in the use of e-cigarettes in the United States since their introduction, particularly among youths, while concurrently there has been a laudable reduction in conventional cigarette use. It is imperative that obstetrician-gynecologists have a basic understanding of e-cigarettes, screen all patients as is consistently done for conventional smoking, and provide resources to patients about potential negative consequences of use.
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http://dx.doi.org/10.1097/AOG.0000000000004282DOI Listing
March 2021

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

Reprod Biomed Online 2021 Mar 29;42(3):572-578. Epub 2020 Nov 29.

Boston IVF, Waltham MA, USA.

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.
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http://dx.doi.org/10.1016/j.rbmo.2020.11.019DOI Listing
March 2021

Racial and ethnic representation in epigenomic studies of preterm birth: a systematic review.

Epigenomics 2020 Dec 2. Epub 2020 Dec 2.

Division of Neonatology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

We conducted a systematic review evaluating race/ethnicity representation in DNA methylomic studies of preterm birth. PubMed, EMBASE, CINHAL, Scopus and relevant citations from 1 January 2000 to 30 June 2019. Two authors independently identified abstracts comparing DNA methylomic differences between term and preterm births that included race/ethnicity data. 16 studies were included. Black and non-Hispanic Black deliveries were well represented (28%). However, large studies originating from more than 95% White populations were excluded due to unreported race/ethnicity data. Most studies were cross-sectional, allowing for reverse causation. Most studies were also racially/ethnically homogeneous, preventing direct comparison of DNA methylomic differences across race/ethnicities. In DNA methylomic studies, Black women and infants were well represented. However, the literature has limitations and precludes drawing definitive conclusions.
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http://dx.doi.org/10.2217/epi-2020-0007DOI Listing
December 2020

Maternal anxiety and depression in pregnancy and DNA methylation of the glucocorticoid receptor gene.

Epigenomics 2020 Nov 20. Epub 2020 Nov 20.

Division of Neonatology, Children's Hospital of Pennsylvania, Philadelphia, PA 19104, USA.

To quantify associations of anxiety and depression during pregnancy with differential cord blood DNA methylation of the glucorticoid receptor (). Pregnancy anxiety, trait anxiety and depressive symptoms were collected using the Pregnancy Related Anxiety Scale, State-Trait Anxiety Index and Edinburgh Postnatal Depression Scale, respectively. methylation was determined at four methylation sites. DNA methylation of CpG 1 in the CpG island shore was higher in infants born to women with high pregnancy anxiety (β 2.54, 95% CI: 0.49-4.58) and trait anxiety (β 1.68, 95% CI: 0.14-3.22). No significant association was found between depressive symptoms and methylation. We found that maternal anxiety was associated with increased CpG island shore methylation.
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http://dx.doi.org/10.2217/epi-2020-0022DOI Listing
November 2020

Associations of Maternal Trait Anger Expression and Lifetime Traumatic and Non-traumatic Experiences with Preterm Birth.

Matern Child Health J 2021 Apr 18;25(4):635-644. Epub 2020 Nov 18.

Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Objectives: Most studies examining psychosocial factors contributing to preterm birth (PTB) have focused on negative life events. Studies examining the influence of negative emotion, in particular maternal anger, remain sparse. We examined associations of maternal trait anger expression and lifetime traumatic and non-traumatic experiences with the risk of PTB.

Methods: Mother-newborn pairs were enrolled in the PRogramming of Intergenerational Stress Mechanisms pregnancy cohort based in Boston and New York City. Women completed the State-Trait Anger Expression Inventory-2 (STAXI-2), Life Stressor Checklist-Revised (LSC-R), and Childhood Trauma Questionnaire (CTQ) in pregnancy. We used modified Poisson regression to estimate the relative risk (RR) of PTB (1) in relation to continuous STAXI-2 Anger Expression-In (AX-I) and Anger Expression-Out (AX-O) subscales, (2) in relation to continuous LSC-R scores, and (3) between women who did versus did not experience childhood sexual, emotional, and/or physical abuse in six separate models. We also examined interactions between maternal anger expression and lifetime stress/childhood trauma.

Results: Younger, single, minority women had higher outward anger expression and inward anger suppression. AX-I and AX-O scores were higher among women who experienced abuse in childhood and who had higher lifetime stress. Maternal lifetime stress, outward anger expression, and inward anger suppression were associated with an increased risk of PTB in separate models; however, stress, trauma and anger did not interact to further increase the risk of PTB. CONCLUSIONS FOR PRACTICE: Higher anger expression and higher lifetime stress experiences were associated with an increased risk of PTB among a racially and ethnically diverse sample of pregnant women.
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http://dx.doi.org/10.1007/s10995-020-03026-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035151PMC
April 2021

Maternal psychosocial functioning, obstetric health history, and newborn telomere length.

Psychoneuroendocrinology 2021 01 4;123:105043. Epub 2020 Nov 4.

Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA, USA; Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, Philadelphia, PA, USA.

There is growing interest in elucidating the determinants of newborn telomere length, given its potential as a biomarker of lifetime disease risk affected by prenatal exposures. There is limited evidence that increased maternal stress during pregnancy predicts shorter newborn telomere length. However, the few studies published to date have been conducted primarily with small samples utilizing inconsistent definitions of maternal stress. Moreover, the potential influence of fetal sex as a moderator of maternal stress effects on newborn telomere length has been largely ignored despite compelling evidence of likely impact. In a prospective cohort study of pregnant women seeking routine prenatal care, we tested whether a range of maternal measures of stressor exposures, subjective feelings of stress, and mental health (depression, anxiety) were associated with newborn telomere length assessed from cord blood among 146 pregnant women and their newborn infants. We further examined whether the pattern of associations differed by infant sex. Sociodemographic and maternal and newborn health indicators were considered as potential covariates. When examined within the whole sample, none of the maternal psychosocial measures were associated with newborn telomere length. Among potential covariates, maternal history of smoking and preeclampsia in a previous pregnancy were negatively associated with newborn telomere length. In adjusted linear regression analyses that considered potential sex-specific effects, maternal depression, general anxiety, and pregnancy-specific anxiety symptoms were positively associated with newborn telomere length among males. Overall, the findings provide some evidence for an association between maternal psychosocial wellbeing in pregnancy and newborn telomere length in males, although in the opposite direction than previously reported. Maternal smoking and obstetric history prior to conception may be associated with shorter offspring telomere length.
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http://dx.doi.org/10.1016/j.psyneuen.2020.105043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732207PMC
January 2021

Blasts from the past: is morphology useful in PGT-A tested and untested frozen embryo transfers?

Reprod Biomed Online 2020 Dec 22;41(6):981-989. Epub 2020 Jul 22.

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston MA, USA; Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston MA, USA; Boston IVF, 103 2nd Avenue, Waltham MA, USA. Electronic address:

Research Question: Day of cryopreservation, inner cell mass (ICM) grade, trophectoderm grade and blastocyst expansion grade have been associated with differences in live birth rate in frozen embryo transfer (FET) cycles. This study sought to examine the likelihood of live birth and whether the morphological grade of the blastocyst is more or equally useful in FET cycles among preimplantation genetic testing for aneuploidies (PGT-A) tested and untested blastocysts.

Design: This was a retrospective cohort study of 6271 vitrified-warmed, autologous, single-embryo transfer cycles among patients undergoing IVF from July 2013 to December 2017 at a single, university-affiliated infertility practice. The primary outcome was live birth, calculated by generalized estimating equations.

Results: Among PGT-A tested embryos, inferior ICM grade was associated with a lower chance of live birth (ICM grade B versus A: adjusted risk ratio [aRR] 0.91, 95% confidence interval [CI] 0.84-0.99). Among untested blastocysts there was a lower live birth rate in blastocysts cryopreserved on day 6 versus day 5 (aRR 0.87, 95% CI 0.78-0.96), and those with inferior pre-vitrification trophectoderm grade (trophectoderm grade B versus A: aRR 0.86, 95% CI 0.79-0.94). Blastocysts with a higher pre-vitrification expansion grade (pre-vitrification expansion grade 5 versus 4: aRR 1.1, 95% CI 1.01-1.2) were associated, but ICM grade was not associated (ICM grade B versus A: aRR 0.93, 95% CI 0.86-1.02), with chance of live birth.

Conclusions: Among PGT-A untested blastocysts, assessing embryo quality by day of cryopreservation, trophectoderm grade and expansion grade may help to identify embryos with the highest likelihood of live birth. Identifying euploid embryos by PGT-A appears to homogenize the cohort, making blastocyst morphological grade and day of cryopreservation less important.
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http://dx.doi.org/10.1016/j.rbmo.2020.07.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872471PMC
December 2020

Cost-effectiveness of Surgical Treatment Pathways for Prolapse.

Female Pelvic Med Reconstr Surg 2021 02;27(2):e408-e413

Objective: To evaluate the cost-effectiveness of surgical treatment pathways for apical prolapse.

Study Design: We constructed a stochastic Markov model to assess the cost-effectiveness of vaginal apical suspension, laparoscopic sacrocolpopexy, and robotic sacrocolpopexy. We modeled over 5 and 10 years, with 9 pathways accounting for up to 2 separate surgical repairs, recurrence of symptomatic apical prolapse, reoperation, and complications, including mesh excision. We calculated costs from the health care system's perspective.

Results: Over 5 years, compared with expectant management, all surgical treatment pathways cost less than the willingness-to-pay threshold of US $50,000 per quality adjusted life-years. However, among surgical treatments, all but 2 pathways were dominated. Of the remaining 2, laparoscopic sacrocolpopexy followed by vaginal repair for apical recurrence was not cost-effective compared with the vaginal-only approach (incremental cost-effectiveness ratio [ICER], >$500,000). Over 10 years, all but the same 2 pathways were dominated. However, starting with the laparoscopic approach in this case was more cost-effective with an ICER of US $6,176. If the laparoscopic approach was not available, starting with the robotic approach similarly became more cost-effective at 10 years (ICER, US $35,479).

Conclusions: All minimally invasive surgical approaches for apical prolapse repair are cost-effective when compared with expectant management. Among surgical treatments, the vaginal-only approach is the only cost-effective option over 5 years. However, over a longer period, starting with a laparoscopic (or robotic) approach becomes cost-effective. These results help inform discussions regarding the surgical approach for prolapse.
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http://dx.doi.org/10.1097/SPV.0000000000000948DOI Listing
February 2021

Composite Outcomes After Posterior Colporrhaphy With and Without Biologic Graft Augmentation.

Female Pelvic Med Reconstr Surg 2021 02;27(2):e414-e417

Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA.

Objectives: To compare subjective and objective failure after posterior colporrhaphy with and without biologic graft augmentation.

Methods: We conducted a retrospective chart review and telephone survey of patients who underwent a posterior colporrhaphy with and without biologic graft augmentation from 2005 to 2019. Patients who underwent a sacrocolpopexy, uterosacral ligament suspensions, or anterior sacrospinous ligament fixation were excluded. We determined objective, subjective, and composite failure rates.

Results: Although 137 patients met eligibility criteria, 56 did not have valid contact information and, therefore, were excluded from the study. Of the 81 with valid contact information, 67 (83%) agreed to participate. There were 24 (36%) who had a native tissue repair and 43 (64%) who had biologic graft augmentation. Median telephone follow-up was 73 months (interquartile range [IQR], 36-117). Objective failure was similar for the biologic graft (37%) and the native tissue (42%) groups (P = 0.72). Subjective failure was twice as likely among the biologic graft group (60%) compared with the native tissue group (33%, P = 0.03). Patients with a biologic graft reported a median Pelvic Floor Distress Inventory-Short Form 20 improvement of 31 (IQR, 8-33), while those with a native tissue repair reported a median improvement of 45 (IQR, 4-46). Overall, 78% were satisfied, 85% would recommend the procedure, and 84% reported symptomatic improvement. Reoperation occurred for 15% of patients.

Conclusions: Although biologic graft-augmented posterior colporrhaphy may be a safe and effective treatment option, the use of biologic grafts in the posterior compartment does not appear to confer a significant long-term benefit to traditional posterior colporrhaphy.
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http://dx.doi.org/10.1097/SPV.0000000000000949DOI Listing
February 2021

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

Hum Reprod 2020 10;35(10):2356-2364

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

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.
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http://dx.doi.org/10.1093/humrep/deaa161DOI Listing
October 2020

Psychotropic medication use during pregnancy and gestational age at delivery.

Ann Epidemiol 2021 01 22;53:34-41.e2. Epub 2020 Aug 22.

Department of Epidemiology, Boston University School of Public Health, Boston, MA.

Purpose: The purpose of this study was to evaluate the association between psychotropic medication use during pregnancy and gestational age at delivery, after adjusting for depressive symptom and perceived stress severity.

Methods: We analyzed data on singleton live births from 2914 female Pregnancy Study Online participants, aged 21 to 45, with a reported conception from 6/2013 to 6/2018. Women reported psychotropic medication use at 8 to 12 weeks' and ~32 weeks' gestation. We measured depressive symptoms using the Major Depressive Inventory and perceived stress using the 10-item Perceived Stress Scale. Data on gestational age at delivery were based on self-reports and/or birth certificates. We used restricted mean survival time models, stratifying by severity of depressive symptoms (Major Depression Inventory <25 vs. ≥25) and perceived stress (Perceived Stress Scale <20 vs. ≥20).

Results: Two hundred and ten (7.2%) participants reported using psychotropic medications during pregnancy. Mean gestational age at delivery among women who never used psychotropic medications was 38.2 weeks (95% confidence interval: 37.7, 38.7), whereas it was 37.3 weeks (95% confidence interval: 36.7, 37.9) among women who used psychotropic medications during pregnancy. Results were similar across strata of depressive symptoms and perceived stress.

Conclusions: Our data indicate that the association between psychotropic medication use and gestational age at delivery is not confounded by indication.
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http://dx.doi.org/10.1016/j.annepidem.2020.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736493PMC
January 2021

Pregnancy-associated changes in cervical noncoding RNA.

Epigenomics 2020 06 18;12(12):1013-1025. Epub 2020 Aug 18.

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

To identify pregnancy-associated changes in cervical noncoding RNA (ncRNA), including miRNA and long noncoding RNA (lncRNA), and their potential effects on biologic processes. We enrolled 21 pregnant women with term deliveries (≥37 weeks' gestation) in a prospective cohort and collected cervical swabs before 28 weeks' gestation. We enrolled 21 nonpregnant controls. We analyzed miRNA, lncRNA and mRNA expression, applying a Bonferroni correction. Five miRNA and three lncRNA were significantly differentially (>twofold change) expressed. Putative miRNA targets are enriched in genes mediating organogenesis, glucocorticoid signaling, cell adhesion and ncRNA machinery. Differential cervical ncRNA expression occurs in the setting of pregnancy. Gene ontology classification reveals biological pathways through which miRNA may play a biologic role in normal pregnancy physiology.
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http://dx.doi.org/10.2217/epi-2019-0231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546170PMC
June 2020

Resilience During Pregnancy by Race, Ethnicity and Nativity: Evidence of a Hispanic Immigrant Advantage.

J Racial Ethn Health Disparities 2021 Aug 17;8(4):892-900. Epub 2020 Aug 17.

Division of Neonatology, Children's Hospital of Philadelphia, Roberts Pediatric Research Building, 2716 South Street, 19th Floor, Suite 19361, Philadelphia, PA, 19146, USA.

The similar socioeconomic position of black and Hispanic women coupled with better birth outcomes among Hispanic women is termed the "Hispanic Paradox." However, birth outcome disparities among Hispanic women exist by maternal nativity. Persistent unequal exposure over time to stressors contributes to these disparities. We hypothesized that variation in maternal resilience to stressors also exists by race, ethnicity, and nativity. We utilized data from the Spontaneous Prematurity and Epigenetics of the Cervix study in Boston, MA (n = 771) where resilience was measured mid-pregnancy using the Connor Davidson Resilience Scale 25. We assessed resilience differences by race/ethnicity, by nativity then by race, ethnicity, and nativity together. We also assessed the risk of low resilience among foreign-born women by region of origin. We used Poisson regression to calculate risk ratios for low resilience, adjusting for maternal age, education, and insurance. Resilience did not differ significantly across race/ethnicity or by foreign-born status in the overall cohort. US-born Hispanic women were more likely to be in the low resilience tertile compared with their foreign-born Hispanic counterparts (adjusted RR 3.52, 95% CI 1.18-10.49). Foreign-born Hispanic women also had the lowest risk of being in the low resilience tertile compared with US-born non-Hispanic white women (aRR 0.33, 95% CI 0.11-0.98). Resilience did not differ significantly among immigrant women by continent of birth. Overall, foreign-born Hispanic women appear to possess a resilience advantage. Given that this group often exhibits the lowest rates of adverse birth outcomes, our findings suggest a deeper exploration of resilience among immigrant Hispanic women.
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http://dx.doi.org/10.1007/s40615-020-00847-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887131PMC
August 2021

Lead exposure and association with angiogenic factors and hypertensive disorders of pregnancy.

Pregnancy Hypertens 2020 Oct 31;22:93-98. Epub 2020 Jul 31.

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA; Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.

Objectives: Lead exposure has been associated with hypertensive disorders of pregnancy. Angiogenic factors, including soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF), are aberrant in preeclampsia, but have not been correlated with lead levels. We evaluated the association of lead exposure with angiogenic factors.

Study Design: This cross sectional study utilized a convenience sample of singleton pregnancies ≥34 weeks' gestation. Blood lead and angiogenic factors were measured before delivery; bone lead was measured postpartum. We dichotomized bone and blood lead into the top tertile versus the bottom tertiles and used log-binomial regression to assess the association between lead and a high angiogenic ratio.

Main Outcome Measures: The outcomes were high sFlt1 to PlGF ratio and development of a hypertensive disorder of pregnancy.

Results: We enrolled 102 participants, of whom 98 had at least one lead measurement and an angiogenic factor result. Median bone lead was 3.8 ug/g (2.0 - 6.6) and median blood lead was 0.2 ug/dL (0.2 - 0.4). Incidence of hypertensive disorders of pregnancy was 31%. When comparing the highest tertile of bone lead to the bottom two tertiles, there was no association with a high sFlt1/PlGF ratio or hypertensive disorders of pregnancy. Similar results were observed for the exposure of blood lead.

Conclusions: Lead exposure was not an important contributor to an elevated angiogenic factor ratio or hypertensive disorders of pregnancy in our U.S.

Population: However, lead exposure was modest in our population and we cannot exclude a relationship with hypertensive disorders of pregnancy.
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http://dx.doi.org/10.1016/j.preghy.2020.07.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875573PMC
October 2020

Long-term effects of teamwork training on communication and teamwork climate in ambulatory reproductive health care.

J Healthc Risk Manag 2021 Apr 5;40(4):8-15. Epub 2020 Aug 5.

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, 02215.

Background: We previously reported an association between team training in the ambulatory setting and improvements in team climate at 6 and 12 months, but it is unknown whether improvements persist at 2 years.

Study Design: From 2014 to 2015, we enrolled 20 organizations, each operating a varying number of health centers, into a teamwork training initiative. We evaluated teamwork outcomes at baseline and 2 years using a communication behaviors assessment, the TeamSTEPPS Teamwork Perceptions Questionnaire (T-TPQ), and the Patients' Insights and Views of Teamwork (PIVOT) survey.

Results: At 2 years, use of TeamSTEPPS tools and strategies remained increased compared to baseline at many health centers; results ranged from 32% of centers reporting increased use of pauses to identify the patient to 91% reporting increased use of standardized language. Staff T-TPQ responses indicated that TeamSTEPPS implementation was associated with improved perceptions of teamwork in approximately half (49%) of statements at 2 years. Significant improvements occurred in over half of PIVOT survey statements, and patient satisfaction was significantly greater at 2 years compared to baseline.

Conclusions: Patient and staff views of teamwork were significantly improved 2 years after TeamSTEPPS implementation in ambulatory reproductive health care centers, demonstrating positive long-term effects of teamwork training.
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http://dx.doi.org/10.1002/jhrm.21440DOI Listing
April 2021

Association between in vitro fertilization and ischemic placental disease by gestational age.

Fertil Steril 2020 09 22;114(3):579-586. Epub 2020 Jul 22.

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, Massachusetts. Electronic address:

Objective: To evaluate the association between in vitro fertilization (IVF) and ischemic placental disease (IPD), stratified by gestational age.

Design: We performed a secondary analysis of a retrospective cohort study of deliveries.

Setting: Deliveries were performed over 15 years at a single tertiary hospital.

Patient(s): We included all parturients who had a live born infant or an intrauterine fetal demise (IUFD).

Intervention(s): We compared pregnancies resulting from IVF cycles to non-IVF pregnancies.

Main Outcome Measure(s): The primary outcomes were preterm and term IPD (preeclampsia, placental abruption, small-for-gestational age infant [SGA], or an intrauterine fetal demise [IUFD] due to placental insufficiency).

Result(s): Of the 69,084 deliveries during the study period, 3,763 (5.4%) were conceived with IVF. The incidence of preterm delivery was 32.6% in IVF pregnancies and 10.8% in non-IVF pregnancies. Multiple gestations were more common in IVF pregnancies. Compared to non-IVF pregnancies, IVF pregnancies were more likely to develop both preterm and term IPD, even after adjustment for maternal age and parity. The risk of preterm IPD was 4 times higher (95% confidence interval, 3.7-4.4) in patients who underwent IVF compared with those who did not undergo IVF. Among parturients who delivered at ≥37 weeks of gestation, IVF pregnancies had 1.7 times the risk of term IPD (95% confidence interval, 1.6-1.9) compared with non-IVF pregnancies.

Conclusion(s): IVF was strongly associated with preterm IPD. We found a similar, but attenuated, association between IVF and term IPD. The stronger association with preterm IPD suggests an association between IVF and placental insufficiency.
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http://dx.doi.org/10.1016/j.fertnstert.2020.04.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487041PMC
September 2020
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