Polycystic ovary syndrome and risk of adverse pregnancy outcomes: a registry linkage study from Massachusetts.
Do women with polycystic ovary syndrome (PCOS) have a greater risk of adverse pregnancy complications (gestational diabetes, preeclampsia, cesarean section, placental abnormalities) and neonatal outcomes (preterm birth, small for gestational age, prolonged delivery hospitalization) compared to women without a PCOS diagnosis and does this risk vary by BMI, subfertility and fertility treatment utilization?
Deliveries to women with a history of PCOS were at greater risk of complications associated with cardiometabolic function, including gestational diabetes and preeclampsia, as well as preterm birth and prolonged length of delivery hospitalization.
Prior research has suggested that women with PCOS may be at increased risk of adverse pregnancy outcomes. However, findings have been inconsistent possibly due to lack of consistent adjustment for confounding factors, small samples size and other sources of bias.
Massachusetts deliveries among women ≥18 years old during 2013-2017 from state vital records linked to hospital discharges, observational stays and emergency department visits were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) and the Massachusetts All-Payers Claims Database (APCD).
PCOS was identified by ICD9 and ICD10 codes in APCD prior to index delivery. Relative risks (RRs) and 95% CI for pregnancy and delivery complications were modeled using generalized estimating equations with a log link and a Poisson distribution to take multiple cycles into account and were adjusted a priori for maternal age, BMI, race/ethnicity, education, plurality, birth year, chronic hypertension and chronic diabetes. Tests for homogeneity investigated differences between maternal pre-pregnancy BMI categories (<30, ≥30, <25 and ≥25 kg/m2) and between non-infertile deliveries and deliveries that used ART or had a history of subfertility (defined by birth certificates, SART CORS records, APCD or hospital records).
Among 91 825 deliveries, 3.9% had a history of PCOS. Women with a history of PCOS had a 51% greater risk of gestational diabetes (CI: 1.38-1.65) and a 25% greater risk of preeclampsia (CI: 1.15-1.35) compared to women without a diagnosis of PCOS. Neonates born to women with a history of PCOS were more likely to be born preterm (RR: 1.17, CI: 1.06-1.29) and more likely to have a prolonged delivery hospitalization after additionally adjusting for gestational age (RR: 1.23, CI: 1.09-1.40) compared to those of women without a diagnosis of PCOS. The risk for gestational diabetes for women with PCOS was greater among women with a pre-pregnancy BMI <30 kg/m2.
PCOS was defined by ICD documentation prior to delivery so there may be women with undiagnosed PCOS or PCOS diagnosed after delivery included in the unexposed group. The study population is limited to deliveries within Massachusetts among most private insurance payers and inpatient or observational hospitalization in Massachusetts during the follow-up window, therefore there may be diagnoses and or deliveries outside of the state or outside of our sample that were not captured.
In this population-based study, women with a history of PCOS were at greater risk of pregnancy complications associated with cardiometabolic function and preterm birth. Obstetricians should be aware of patients' PCOS status and closely monitor for potential pregnancy complications to improve maternal and infant perinatal health outcomes.
This work was supported by the NIH (R01HD067270). S.A.M. receives grant funding from NIH, AbbVie and the Marriot Family Foundation; payment/honoraria from the University of British Columbia, World Endometriosis Research Foundation and Huilun Shanghai; travel support for attending meetings for ESHRE 2019, IASP 2019, National Endometriosis Network UK meeting 2019; SRI 2022, ESHRE 2022; participates on the data safety monitoring board/advisory board for AbbVie, Roche, Frontiers in Reproductive Health; and has a leadership role in the Society for Women's Health Research, World Endometriosis Research Foundation, World Endometriosis Society, American Society for Reproductive Medicine and ESHRE. The other authors have no conflicts of interest.
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Farland LV
,Stern JE
,Liu CL
,Cabral HJ
,Coddington CC
,Diop H
,Dukhovny D
,Hwang S
,Missmer SA
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Pregnancy outcomes in women with endometriosis and/or ART use: a population-based cohort study.
What is the association between endometriosis and adverse pregnancy outcomes with ART use and non-use?
Endometriosis and ART use are both associated with increased risk of preterm birth, antepartum haemorrhage, placenta praevia and planned birth (caesarean delivery or induction of labour).
There are contradictory findings on the association between endometriosis and adverse pregnancy outcomes, and many large studies have not considered the effect of ART use.
Population-based cohort study of 578 221 eligible pregnancies during 2006-2015, comparing pregnancy outcomes across four groups (No endo/no ART, No endo/ART, Endo/no ART and Endo/ART).
All female residents of New South Wales, Australia aged 15-45 years and their index singleton pregnancy of at least 20 weeks gestation or 400 g birthweight. Linked hospital, pregnancy/birth and mortality data were used. Modified Poisson regression with robust error variances was used to estimate adjusted risk ratios (aRRs) and 99% CIs, adjusting for sociodemographic and pregnancy factors.
Compared to women without endometriosis who had pregnancies without ART use, there was increased risk of preterm birth (<37 weeks) in all groups [No endo/ART (aRR 1.85, 99% CI 1.46-2.34), Endo/no ART (aRR 1.24, 99% CI 1.06-1.44), Endo/ART (aRR 1.93, 99% CI 1.11-3.35)] and antepartum haemorrhage [No endo/ART (aRR 1.99, 99% CI 1.39-2.85), Endo/no ART (aRR 1.31, 99% CI 1.03-1.67), Endo/ART (aRR 2.69, 99% CI 1.30-5.56)] among pregnancies affected by endometriosis or ART use, separately and together. There was increased risk of placenta praevia [No endo/ART (aRR 2.26, 99% CI 1.42-3.60), Endo/no ART (aRR 1.66, 99% CI 1.18-2.33)] and planned birth [No endo/ART (aRR 1.08, 99% CI 1.03-1.14), Endo/no ART (aRR 1.11, 99% CI 1.07-1.14)] among pregnancies with endometriosis or ART use, separately. There was increased risk of placental abruption [No endo/ART (aRR 2.36, 99% CI 1.12-4.98)], maternal morbidity [No endo/ART (aRR 1.67, 99% CI 1.07-2.62)] and low birthweight (<2500 g) [No endo/ART (aRR 1.45, 99% CI 1.09-1.93)] among pregnancies with ART use without endometriosis. There was decreased risk of having a large-for-gestational age infant [Endo/no ART (aRR 0.83, 99% CI 0.73-0.94)] among pregnancies with endometriosis without ART use.
Endometriosis is often under-diagnosed and women with a history of hospital diagnosis of endometriosis may represent those with more symptomatic or severe disease. If the effects of endometriosis on pregnancy are greater for those with more severe disease, our results may over-estimate the effect of endometriosis on adverse pregnancy outcomes at a population level. We were unable to assess the effect of endometriosis stage or typology on the study outcomes.
These results suggest that women with endometriosis including those who used ART to achieve pregnancy are a higher-risk obstetric group requiring appropriate surveillance and management during their pregnancy.
This study was supported by the Prevention Research Support Program, funded by the New South Wales Ministry of Health. The funder had no role in the design, data collection and analysis, interpretation of results, manuscript preparation or the decision to submit the manuscript for publication. The authors have no conflicts of interest.
N/A.
Ibiebele I
,Nippita T
,Baber R
,Torvaldsen S
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Relationships between birth weight discordance and maternal and perinatal risks among twin pregnancies conceived following frozen embryo transfer.
Is intertwin birth weight discordance associated with adverse maternal and perinatal outcomes following frozen embryo transfer (FET)?
For twins conceived following FET, intertwin birth weight discordance is related to elevated risks of neonatal mortality irrespective of chorionicity, and the risk of hypertensive disorders of pregnancy (HDP) is elevated for the mothers of dichorionic twins affected by such birth weight discordance.
While the relationships between intertwin birth weight discordance and adverse maternal or fetal outcomes have been studied for naturally conceived twins, similarly comprehensive analyses for twins conceived using ART remain to be performed.
This was a retrospective cohort study of all twin births from 2007 to 2021 at Shanghai Ninth People's Hospital in Shanghai, China that were conceived following FET (N = 6265).
Intertwin birth weight discordance was defined as a 20% difference in neonatal birth weights. The primary study outcome was the incidence of HDP and neonatal death while secondary outcomes included gestational diabetes, placenta previa, placental abruption, intrahepatic cholestasis of pregnancy, preterm premature rupture of the membranes, Cesarean delivery, gestational age, birth weight, stillbirth, birth defect, neonatal jaundice, necrotizing enterocolitis, and pneumonia incidence. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% CIs for maternal and neonatal outcomes. Subgroup analyses were conducted, and Kaplan-Meier survival analysis was used to estimate the survival probability. The sensitivity analysis was performed with a propensity score-based patient-matching model, an inverse probability weighting model, a restricted cubic spline analysis, and logistic regression models using other percentage cutoffs for discordance.
Of 6101 females that gave birth to dichorionic twins during the study interval, birth weight discordance was observed in 797 twin pairs (13.1%). In this cohort, intertwin birth weight discordance was related to an elevated risk of HDP (aOR 1.56; 95% CI 1.21-2.00), and this relationship was confirmed through sensitivity analyses. Hypertensive disease risk rose as the severity of this birth weight discordance increased. Discordant birth weight was also linked to increased odds of neonatal mortality (aOR 2.13; 95% CI 1.03-4.09) and this risk also increased with the severity of discordance. Of the 164 women with monochorionic twins, the discordant group exhibited an elevated risk of neonatal death compared to the concordant group (crude OR 9.00; 95% CI 1.02-79.3).
The limitations of this study are its retrospective nature and the fact that the available data could not specify which twins were affected by adverse outcomes. There is a lack of an established reference birth weight for Chinese twins born at a gestational age of 24-41 weeks.
These findings suggest that twins exhibiting a birth weight discordance are related to an elevated risk of adverse maternal and perinatal outcomes, emphasizing a potential need for higher levels of antenatal surveillance in these at-risk pregnancies.
Authors declare no conflict of interest. This study was funded by the Clinical Research Program of Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JYLJ202118) and the National Natural Science Foundation of China (Grant Nos 82271693 and 82273634).
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Lin J
,Zhu Y
,Wang B
,Du T
,Zhang K
,Zhu Q
,Lin J
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