Sachdev, D., Yamada, R., Lee, R., Sauer, M. V., & Ananth, C. V. (2023). Risk of Stroke Hospitalization After Infertility Treatment. JAMA network open, 6(8), e2331470. https://doi.org/10.1001/jamanetworkopen.2023.31470
Sachdev D, Yamada R, Lee R, Sauer MV, Ananth CV. Risk of Stroke Hospitalization After Infertility Treatment. JAMA network open. 2023;6(8):e2331470. doi:10.1001/jamanetworkopen.2023.31470
Sachdev, D., et al. "Risk of Stroke Hospitalization After Infertility Treatment." JAMA network open, vol. 6, no. 8, 2023, pp. e2331470.
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Stroke accounts for 7% of pregnancy-related deaths in the US. As the use of infertility treatment is increasing, many studies have sought to characterize the association of infertility treatment with the risk of stroke with mixed results.
Objective
To evaluate the risk of hospitalization from hemorrhagic and ischemic strokes in patients who underwent infertility treatment.
Design, Setting, and Participants
This population-based, retrospective cohort study used data abstracted from the Nationwide Readmissions Database, which stores data from all-payer hospital inpatient stays from 28 states across the US, from 2010 and 2018. Eligible participants included individuals aged 15 to 54 who had a hospital delivery from January to November in a given calendar year, and any subsequent hospitalizations from January to December in the same calendar year of delivery during the study period. Statistical analysis was performed between November 2022 and April 2023.
Exposure
Hospital delivery after infertility treatment (ie, intrauterine insemination, assisted reproductive technology, fertility preservation procedures, or use of a gestational carrier) or after spontaneous conception.
Main Outcomes and Measures
The primary outcome was hospitalization for nonfatal stroke (either ischemic or hemorrhagic stroke) within the first calendar year after delivery. Secondary outcomes included risk of stroke hospitalization at less than 30 days, less than 60 days, less than 90 days, and less than 180 days post partum. Cox proportional hazards regression models were used to estimate associations, which were expressed as hazard ratios (HRs), adjusted for confounders. Effect size estimates were corrected for biases due to exposure misclassification, selection, and unmeasured confounding through a probabilistic bias analysis.
Results
Of 31 339 991 patients, 287 813 (0.9%; median [IQR] age, 32.1 [28.5-35.8] years) underwent infertility treatment and 31 052 178 (99.1%; median [IQR] age, 27.7 [23.1-32.0] years) delivered after spontaneous conception. The rate of stroke hospitalization within 12 months of delivery was 37 hospitalizations per 100 000 people (105 patients) among those who received infertility treatment and 29 hospitalizations per 100 000 people (9027 patients) among those who delivered after spontaneous conception (rate difference, 8 hospitalizations per 100 000 people; 95% CI, -6 to 21 hospitalizations per 100 000 people; HR, 1.66; 95% CI, 1.17 to 2.35). The risk of hospitalization for hemorrhagic stroke (adjusted HR, 2.02; 95% CI, 1.13 to 3.61) was greater than that for ischemic stroke (adjusted HR, 1.55; 95% CI, 1.01 to 2.39). The risk of stroke hospitalization increased as the time between delivery and hospitalization for stroke increased, particularly for hemorrhagic strokes. In general, these associations became larger for hemorrhagic stroke and smaller for ischemic stroke following correction for biases.
Conclusions and Relevance
In this cohort study, infertility treatment was associated with an increased risk of stroke-related hospitalization within 12 months of delivery; this risk was evident as early as 30 days after delivery. Timely follow-up in the immediate days post partum and continued long-term follow-up should be considered to mitigate stroke risk.
Yamada R et al., 2024·Journal of internal medicine·Free to read
Cardiovascular disease is a major cause of maternal mortality, but the extent to which infertility treatment is implicated in heart disease remains unclear. To evaluate the association between infertility treatment and postpartum heart disease. We designed a retrospective cohort study of patients who delivered in the United States between 2010 and 2018. The primary outcome was hospitalization within 12-month post-delivery due to heart disease (including ischemic heart disease, atherosclerotic heart disease, cardiomyopathy, hypertensive disease, heart failure, and cardiac dysrhythmias). We estimated the rate difference (RD) of hospitalizations among patients who conceived with infertility treatment and those who conceived spontaneously. Associations were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs), derived from Cox proportional hazards regression after adjustment for potential confounders. Infertility treatment was recorded in 0.9% (n = 287,813) of 31,339,991 deliveries. Rates of heart disease hospitalizations with infertility treatment and with spontaneous conception were 550 and 355 per 100,000, respectively (RD 195, 95% CI: 143-247; adjusted HR 1.99, 95% CI: 1.80-2.20). The most important increase in risk was observed for hypertensive disease (adjusted HR 2.16, 95% CI: 1.92-2.42). This increased risk was apparent as early as 30-day post-delivery (HR 1.61, 95% CI: 1.39-1.86), with progressively increasing risk up to a year. Although the absolute risk of postpartum heart disease hospitalization is low, infertility treatment is associated with an increased risk, especially for hypertensive disease. These findings highlight the importance of timely postpartum follow-ups in patients who received infertility treatment.
Wright JD et al., 2013·Obstetrics and gynecology·Free full text on PubMed Central
To examine the use of inpatient hysterectomy and explore changes in the use of various routes of hysterectomy and patterns of referral. The Nationwide Inpatient Sample was used to identify all women aged 18 years or older who underwent inpatient hysterectomy between 1998 and 2010. Weighted estimates of national trends were calculated and the number of procedures performed estimated. Trends in hospital volume and across hospital characteristics were examined. After weighting, we identified a total 7,438,452 women who underwent inpatient hysterectomy between 1998 and 2010. The number of hysterectomies performed annually rose from 543,812 in 1998 to a peak of 681,234 in 2002; it then declined consistently annually and reached 433,621 cases in 2010. Overall, 247,973 (36.4%) fewer hysterectomies were performed in 2010 compared with 2002. From 2002 to 2010 the number of hysterectomies performed for each of the following indications declined: leiomyoma (-47.6%), abnormal bleeding (-28.9%), benign ovarian mass (-63.1%), endometriosis (-65.3%), and pelvic organ prolapse (-39.4%). The median hospital case volume decreased from 83 procedures per year in 2002 to 50 cases per year in 2010 (P<.001). The number of inpatient hysterectomies performed in the United States has declined substantially over the past decade. The median number of hysterectomies per hospital has declined likewise by more than 40%. III.
Business and Reimbursement · Quality and Outcome Tracking
Although robotically assisted hysterectomy for benign gynecologic conditions has been reported, little is known about the incorporation of the procedure into practice, its complication profile, or its costs compared with other routes of hysterectomy. To analyze the uptake of robotically assisted hysterectomy, to determine the association between use of robotic surgery and rates of abdominal and laparoscopic hysterectomy, and to compare the in-house complications of robotically assisted hysterectomy vs abdominal and laparoscopic procedures. DESIGN, SETTING, Cohort study of 264,758 women who underwent hysterectomy for benign gynecologic disorders at 441 hospitals across the United States from 2007 to 2010. Uptake of and factors associated with utilization of robotically assisted hysterectomy. Complications, transfusion, reoperation, length of stay, death, and cost for women who underwent robotic hysterectomy compared with both abdominal and laparoscopic procedures were analyzed. Use of robotically assisted hysterectomy increased from 0.5% in 2007 to 9.5% of all hysterectomies in 2010. During the same time period, laparoscopic hysterectomy rates increased from 24.3% to 30.5%. Three years after the first robotic procedure at hospitals where robotically assisted hysterectomy was performed, robotically assisted hysterectomy accounted for 22.4% of all hysterectomies. The rates of abdominal hysterectomy decreased both in hospitals where robotic-assisted hysterectomy was performed as well as in those where it was not performed. In a propensity score-matched analysis, the overall complication rates were similar for robotic-assisted and laparoscopic hysterectomy (5.5% vs 5.3%; relative risk [RR], 1.03; 95% CI, 0.86-1.24). Although patients who underwent a robotic-assisted hysterectomy were less likely to have a length of stay longer than 2 days (19.6% vs 24.9%; RR, 0.78, 95% CI, 0.67-0.92), transfusion requirements (1.4% vs 1.8%; RR, 0.80; 95% CI, 0.55-1.16) and the rate of discharge to a nursing facility (0.2% vs 0.3%; RR, 0.79; 95% CI, 0.35-1.76) were similar. Total costs associated with robotically assisted hysterectomy were $2189 (95% CI, $2030-$2349) more per case than for laparoscopic hysterectomy. Between 2007 and 2010, the use of robotically assisted hysterectomy for benign gynecologic disorders increased substantially. Robotically assisted and laparoscopic hysterectomy had similar morbidity profiles, but the use of robotic technology resulted in substantially more costs.
Progesterone, supplied in a variety of formulations, is commonly used in assisted reproduction. However, even the commonly accepted uses of progesterone in fertility care are believed to be largely empirical, as are the current available treatment options. While a critical balance of estrogen and progesterone is necessary for successful embryo implantation, achieving that balance is subject to differences in prescribing practice. In evaluating recommendations for the use of progesterone, discussion of its role in assisted-reproduction procedures must distinguish between known therapeutic benefits and empirical benefits.
Bay B et al., 2019·BJOG : an international journal of obstetrics and gynaecology
To assess the risk of stillbirth in low-risk in vitro fertilisation (IVF) pregnancies. Register-based national cohort study. Denmark 2003-2013. Cohort of 425 732 singleton pregnancies including 10 235 conceived following IVF/intracytoplasmic sperm injection (ICSI), 4521 conceived following intrauterine insemination (IUI), and 410 976 spontaneously conceived. Information on pregnancy, obstetrical risk factors, stillbirth, and fertility treatment was obtained from the Danish national health registers for all pregnancies after gestational week 21+6 . We estimated the overall and gestational age-specific risk of stillbirth in low-risk term pregnancies following IVF, ICSI, and IUI. Further, we estimated the association between stillbirth and IVF and ICSI respectively as well as fresh or frozen-thawed embryo transfer. Risk of stillbirth. The number of stillbirths in spontaneously conceived and IVF/ICSI low-risk term pregnancies was 525 (0.1%) and 35 (0.3%), respectively. In multivariate analysis, the risk of stillbirth in pregnancies following IVF/ICSI was increased (odds ratio 2.1, 95% CI 1.4-3.1). The risk of stillbirth was correspondingly increased in time-to-event analyses taking risk time for each fetus into account from gestational week 37 and onwards (hazard ratio 2.4, 95% CI 1.6-3.6). In sub-analyses, the risk of stillbirth was increased for pregnancies following ICSI (odds ratio 2.2, 95% CI 1.2-3.1), but not IVF (odds ratio 1.7, 95% CI 0.9-3.1). We found a systematically increased risk of stillbirth in low-risk term pregnancies following IVF/ICSI. Whether the risk was related to the treatment or to underlying subfertility is uncertain. The results may indicate a need for obstetrical surveillance for these pregnancies when reaching term. Increased risk of stillbirth in low-risk term pregnancies following fresh cycle IVF/ICSI.
Chih HJ et al., 2021·BMC Pregnancy and Childbirth·Free full text on PubMed Central
Hypertensive disorders of pregnancy (HDP) is one of the most common pregnancy complications and causes of maternal morbidity and mortality. Assisted reproductive technology (ART) has been associated with adverse pregnancy outcomes, including HDP. However, the impact of multiple pregnancies, oocyte donation, as well as fresh and frozen embryo transfer needs to be further studied. We conducted a systematic review and meta-analyses to evaluate the association between ART and HDP or preeclampsia relative to spontaneous conception (SC).
We identified studies from EMBASE, MEDLINE, and Cochrane Library (up to April 8, 2020) and manually using structured search strategies. Cohort studies that included pregnancies after in vitro fertilization (IVF) with or without intracytoplasmic sperm fertilization (ICSI) relative to SC with HDP or preeclampsia as the outcome of interest were included. The control group was women who conceived spontaneously without ART or fertility medications. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. Numbers needed to harm (NNH) were calculated based on absolute risk differences between exposure and control groups.
Eighty-five studies were included after a screening of 1879 abstracts and 283 full text articles. Compared to SC, IVF/ICSI singleton pregnancies (OR 1.70; 95% CI 1.60-1.80; I2 = 80%) and multiple pregnancies (OR 1.34; 95% CI 1.20-1.50; I2 = 76%) were both associated with higher odds of HDP. Singleton pregnancies with oocyte donation had the highest odds of HDP out of all groups analyzed (OR 4.42; 95% CI 3.00-6.51; I2 = 83%). Frozen embryo transfer resulted in higher odds of HDP (OR 1.74; 95% CI 1.58-1.92; I2 = 55%) than fresh embryo transfer (OR 1.43; 95% CI 1.33-1.53; I2 = 72%). The associations between IVF/ICSI pregnancies and SC were similar for preeclampsia. Most interventions had an NNH of 40 to 100, while singleton and multiple oocyte donation pregnancies had particularly low NNH for HDP (16 and 10, respectively).
Our meta-analysis confirmed that IVF/ICSI pregnancies are at higher odds of HDP and preeclampsia than SC, irrespective of the plurality. The odds were especially high in frozen embryo transfer and oocyte donation pregnancies.
To investigate perinatal outcomes associated with fertility treatments, including assisted reproductive technology (ART), intrauterine insemination with ovulation stimulation (IUI), and ovulation stimulation alone (OS). Population-representative cross-sectional survey of women with live births, 2004-2008. Florida, Maryland, and Utah, USA. 21 803 women, weighted to represent 1 022 597 women. Survey and birth certificate data were analysed with logistic regression models adjusted for age, education, race, income, and parity, using separate models for singletons and all births. We used two referent groups: (1) women who never used fertility treatment and (2) subfertile women conceiving without treatment. Preterm birth (<37 weeks), very preterm birth (<34 weeks), low birthweight (<2500 g), and very low birthweight (<1500 g). Referent group 1: In singletons, ART was associated with preterm birth (OR 3.28; 95% CI 1.74, 6.20) and low birthweight (OR 2.91; 95% CI 1.99, 4.26). OS was also associated with low birthweight (OR 1.62; 95% CI 1.19, 2.19). Including all births, treatment was associated with preterm birth and low birthweight: ART (OR 6.21; 95% CI 4.21, 9.16 and OR 6.51; 95% CI 4.85, 8.73); IUI (OR 2.10; 95% CI 1.24, 3.56 and OR 2.41; 95% CI 1.54, 3.76); OS (OR 1.40; 95% CI 1.01, 1.94 and OR 2.10; 95% CI 1.60, 2.75), respectively. Referent group 2: ART was associated with both outcomes in all births, but not singletons. Preterm birth and low birthweight associated with fertility treatments are largely attributable to multiple gestation, but are also related to underlying subfertility. Preterm birth is associated with subfertility, and with fertility treatments through multiple gestation.
To determine whether there are any increases in pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies after assisted reproductive technology (ART) compared with those conceived naturally. Meta-analysis. University-affiliated teaching hospital. PATIENT(S): Singleton pregnancies conceived with ART and naturally. INTERVENTION(S): PubMed, Google Scholar, Cochrane Libraries and Chinese database were searched through March 2015 to identify studies that met pre-stated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators. MAIN OUTCOME MEASURE(S): Pregnancy-related complications and adverse pregnancy outcomes. RESULT(S): Fifty cohort studies comprising 161,370 ART and 2,280,241 spontaneously conceived singleton pregnancies were identified. The ART singleton pregnancies had a significantly increased risk of pregnancy-induced hypertension (relative risk [RR] 1.30, 95% confidence interval [CI] 1.04-1.62; I(2) = 79%), gestational diabetes mellitus (RR 1.31, 95% CI 1.13-1.53; I(2) = 6%), placenta previa (RR 3.71, 95% CI 2.67-5.16; I(2) = 72%), placental abruption (RR 1.83, 95% CI 1.49-2.24; I(2) = 22%), antepartum hemorrhage (RR 2.11, 95% CI 1.86-2.38; I(2) = 47%), postpartum hemorrhage (RR 1.29, 95% CI 1.06-1.57; I(2) = 65%), polyhydramnios (RR 1.74, 95% CI 1.24-2.45; I(2) = 0%), oligohydramnios (RR 2.14, 95% CI 1.53-3.01; I(2) = 0%), cesarean sections (RR 1.58, 95% CI 1.48-1.70; I(2) = 92%), preterm birth (RR 1.71, 95% CI 1.59-1.83; I(2)=80%), very preterm birth (RR 2.12, 95% CI 1.73-2.59; I(2) = 90%), low birth weight (RR 1.61, 95% CI 1.49-1.75; I(2) = 80%), very low birth weight (RR 2.12, 95% CI 1.84-2.43; I(2) = 67%), small for gestational age (RR 1.35, 95% CI 1.20-1.52; I(2) = 82%), perinatal mortality (RR 1.64, 95% CI 1.41-1.90; I(2)=45%), and congenital malformation (RR 1.37, 95% CI 1.29-1.45; I(2)=41%). Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. No evidence of publication bias was observed. CONCLUSION(S): The ART singleton pregnancies are associated with higher risks of adverse obstetric outcomes. Obstetricians should manage these pregnancies as high risk.
Assisted Reproduction › Safety and Risks › Maternal Complications
PMID 37647063 37647063 DOI 10.1001/jamanetworkopen.2023.31470 10.1001/jamanetworkopen.2023.31470 Sachdev et al. 2023, Sachdev 2023
Cite this article
Sachdev, D., Yamada, R., Lee, R., Sauer, M. V., & Ananth, C. V. (2023). Risk of Stroke Hospitalization After Infertility Treatment. JAMA network open, 6(8), e2331470. https://doi.org/10.1001/jamanetworkopen.2023.31470
Sachdev D, Yamada R, Lee R, Sauer MV, Ananth CV. Risk of Stroke Hospitalization After Infertility Treatment. JAMA network open. 2023;6(8):e2331470. doi:10.1001/jamanetworkopen.2023.31470
Sachdev, D., et al. "Risk of Stroke Hospitalization After Infertility Treatment." JAMA network open, vol. 6, no. 8, 2023, pp. e2331470.
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