Imaging the Uterus in Placenta Accreta Spectrum Disorder.

Antenatal diagnosis of placenta accreta spectrum (PAS) improves maternal and neonatal outcomes by allowing for multidisciplinary planning and preparedness. Ultrasound is the primary imaging tool. Simplification and standardization of placental evaluation and reporting terminology allows improved communication and understanding between teams. Prior to 10 weeks of gestation, gestational sac position and least myometrial thickness surrounding the gestational sac help PAS diagnosis very early in pregnancy. Late first-, second-, and third-trimester evaluation includes comprehensive evaluation of the placenta, transabdominal and transvaginal with partially full maternal urinary bladder, and by color Doppler. Subsequently, the sonologist should indicate whether the evaluation was optimal or suboptimal; the level of suspicion as low, moderate, or high; and the extent as focal, global, or extending beyond the uterus. Other complementary imaging modalities such as 3D-power Doppler ultrasound, magnetic resonance imaging (MRI), and vascular topography mapping strive to improve antenatal placental evaluation but remain investigational at present. KEY POINTS: · Antenatal imaging, primarily using ultrasound with partially full maternal urinary bladder, is an essential means of evaluation of those at risk for PAS.. · Simplification and standardization of placental evaluation and reporting will allow improved communication between the multidisciplinary teams.. · Gestational sac location prior to 10 weeks of gestation and four markers after that (placental lacunae and echostructure, myometrial thinning, hypoechoic zone with or without bulging between placenta and myometrium, and increased flow on color Doppler)..

Genetic Screening and Teratogenic Exposures: Considerations in Caring for the Uterus Transplant Patient.

Counseling the uterus transplant patient requires an enhanced knowledge of unique genetic challenges that include an understanding of the spectrum of Mayer-Rokitansky-Küster-Hauser syndrome. Patients should understand their options for genetic screening and testing including preimplantation genetic testing for aneuploidy, genetic screening, and diagnostic testing. This patient population is potentially at risk for fetal anomalies due to the increased susceptibility to infections, such as cytomegalovirus. There are management strategies to minimize this risk. The risk of teratogenicity from mycophenolate is eliminated by a washout period before embryo transfer.

Antepartum Care of the Uterus Transplant Patient: The Experience of 3 Successful US Centers.

We offer consensus recommendations for the antepartum management of the uterus transplant pregnancy based on our experience at 3 US centers. Patient access to accurate information is important to manage expectations and make informed decisions. Unique aspects of medical management include monitoring tacrolimus levels and performing cervical biopsies for rejection. Low-dose aspirin for preeclampsia is routinely used. Vigilant screening for gestational diabetes and preeclampsia allows for the prompt diagnosis and treatment of these common complications. We aim to deliver patients at 37 to 38 weeks by cesarean section. Shared decision making dominates whether to consider future pregnancies and timing of hysterectomy.

The impact of the emergence of COVID-19 on women's prenatal genetic testing decisions.

OBJECTIVE: We conducted a study to examine the impact of COVID on patients' access and utilization of prenatal genetic screens and diagnostic tests at the onset of the COVID-19 pandemic in the United States. METHODS: We conducted telephone interviews with 40 patients to examine how the pandemic affected prenatal genetic screening and diagnostic testing decisions during the initial months of the pandemic in the United States. An interview guide queried experiences with the ability to access information about prenatal genetic testing options and to utilize the tests when desired. Audio recordings were transcribed and coded using NVivo 12. Analysis was conducted using Grounded Theory. RESULTS: The pandemic did not alter most participants' decisions to undergo prenatal genetic testing. Yet, it did impact how participants viewed the risks and benefits of testing and timing of testing. There was heightened anxiety among those who underwent testing, stemming from the risk of viral exposure and the fear of being alone if pregnancy loss or fetal abnormality was identified at the time of an ultrasound-based procedure. CONCLUSION: The pandemic may impact patients' access and utilization of prenatal genetic tests. More research is needed to determine how best to meet pregnant patients' decision-making needs during this time.

Decision-making for prenatal genetic screening: how will pregnant women navigate a growing number of aneuploidy and carrier screening options?

BACKGROUND: Prenatal genetic screens, including carrier screening (CS) and aneuploidy screening (AS), comprise an important component of reproductive healthcare delivery. Clinical practice guidelines emphasize the importance of informed decision-making and patient's preferences regarding the use of these screens. Yet, it is unclear how to achieve this ideal as prenatal genetic screening options rapidly become more complex and increasingly available to patients. With increased complexity and availability of reproductive testing options, decision-support strategies are critical to prepare patients to consider AS and/or CS. METHODS: A self-administered survey evaluated knowledge and decision-making preferences for expanded carrier (CS) and aneuploidy (AS) prenatal screening. The survey was administered to participants before their first prenatal visit to assess baseline decision-making needs and preference at the initiation of prenatal care. Analysis was approached as a descriptive process. RESULTS: Participants had similar familiarity with the concepts associated with AS compared to CS; mean knowledge scores for CS was 0.59 [possible range 0.00 to 1.00] and 0.55 for AS. Participants reported preferences to learn about a range of conditions, including those with severe or mild impact, childhood-onset, and adult-onset. Decision-making preference with respect to learning about the associated disease phenotypes for the contained on AS and CS panel shifted with the complexity of the panel, with a greater preference to learn about conditions post-test compared pre-test education as panels increased from 5 to 100 conditions. CONCLUSION: Patients' baseline knowledge of prenatal genetic screens coupled with evolving decision-making preferences presents challenges for the delivery of prenatal genetic screens. This calls for the development and implementation of innovative approaches to support pregnant patients' decision-making commensurate with advances in prenatal genomics.

Uterus transplantation: state of the art in 2021.

PURPOSE: To provide a comprehensive review of uterus transplantation in 2021, including a discussion of pregnancy outcomes of all reported births to date, the donor and recipient selection process, the organ procurement and transplant surgeries, reported complications, postoperative monitoring, preimplantation preparation, and ethical considerations. METHODS: Literature review and expert commentary. RESULTS: Reports of thirty-one live births following uterus transplantation have been published from both living and deceased donors. The proper selection of donors and recipients is a labor-intensive process that requires advanced planning. A multidisciplinary team is critical. Reported complications in the recipient include thrombosis, infection, vaginal stricture, antenatal complications, and graft failure. Graft rejection is a common occurrence but rarely leads to graft removal. While most embryo transfers are successful, recurrent implantation failures in uterus transplant patients have been reported. Rates of preterm delivery are high but appear to be declining; more data, including long-term outcome data, is needed. CONCLUSIONS: Uterus transplantation is an emerging therapy for absolute uterine factor infertility, a condition previously without direct treatment options. It is paramount that reproductive health care providers are familiar with the uterus transplantation process as more patients seek and receive this treatment.

First birth from a deceased donor uterus in the United States: from severe graft rejection to successful cesarean delivery.

Uterus transplantation is the only known potential treatment for absolute uterine factor infertility. It offers a unique setting for the investigation of immunologic adaptations of pregnancy in the context of the pharmacologic-induced tolerance of solid organ transplants, thus providing valuable insights into the early maternal-fetal interface. Until recently, all live births resulting from uterus transplantation involved living donors, with only 1 prior birth from a deceased donor. The Cleveland Clinic clinical trial of uterus transplantation opened in 2015. In 2017, a 35 year old woman with congenital absence of the uterus was matched to a 24 year old parous deceased brain-dead donor. Transplantation of the uterus was performed with vaginal anastomosis and vascular anastomoses bilaterally from internal iliac vessels of the donor to the external iliac vessels of the recipient. Induction and maintenance immunosuppression were achieved and subsequently modified in anticipation of pregnancy 6 months after transplant. Prior to planned embryo transfer, ectocervical biopsy revealed ulceration and a significant diffuse, plasma cell-rich mixed inflammatory cell infiltrate, with histology interpreted as grade 3 rejection suspicious for an antibody-mediated component. Aggressive immunosuppressive regimen targeting both cellular and humoral rejection was initiated. After 3 months of treatment, there was no histologic evidence of rejection, and after 3 months from complete clearance of rejection, an uneventful embryo transfer was performed and a pregnancy was established. At 21 weeks, central placenta previa with accreta was diagnosed. A healthy neonate was delivered by cesarean hysterectomy at 34 weeks' gestation. In summary, this paper highlights the first live birth in North America resulting from a deceased donor uterus transplant. This achievement underscores the capacity of the transplanted uterus to recover from a severe, prolonged rejection and yet produce a viable neonate. This is the first delivery from our ongoing clinical trial in uterus transplantation, including the first reported incidence of severe mixed cellular/humoral rejection as well as the first reported placenta accreta.

New Frontier: Role of the Radiologist in Uterine Transplantation.

Uterine transplantation (UT) is a novel treatment for absolute uterine factor infertility (AUFI) that is currently being performed under experimental protocols in multiple medical centers worldwide. At the time of this publication, there have been at least 10 live births by women with a transplanted uterus. As successful outcomes from this innovative procedure increase, it is likely that more centers will perform UT. Imaging is performed in multiple steps of the UT process, including preoperative imaging of potential donors and recipients, posttransplant surveillance, and monitoring of pregnancy. Fetal imaging is performed by maternal-fetal medicine professionals, but most imaging examinations in UT are performed by radiologists. Given the significant role of imaging in this groundbreaking surgery, radiologists must be familiar with the causes of AUFI and the role of imaging in establishing this diagnosis. Radiologists working in medical centers where UT is performed should understand the role of imaging in preoperative planning and postoperative surveillance. While data regarding complications of UT are preliminary at best, radiologists must be aware of the risk of vascular compromise and graft failure and their imaging features. The authors provide a brief history of UT and define the radiologist's role in pre- and postoperative imaging assessments.©RSNA, 2019.

Making the most of the first prenatal visit: The challenge of expanding prenatal genetic testing options and limited clinical encounter time.

OBJECTIVE: Advances in prenatal genetics place additional challenges as patients must receive information about a growing array of screening and testing options. This raises concerns about how to achieve a shared decision-making process that prepares patients to make an informed decision about their choices about prenatal genetic screening and testing options, calling for a reconsideration of how healthcare providers approach the first prenatal visit. METHODS: We conducted interviews with 40 pregnant women to identify components of decision-making regarding prenatal genetic screens and tests at this visit. Analysis was approached using grounded theory. RESULTS: Participants brought distinct notions of risk to the visit, including skewed perceptions of baseline risk for a fetal genetic condition and the implications of screening and testing. Participants were very concerned about financial considerations associated with these options, ranking out-of-pocket costs on par with medical considerations. Participants noted diverging priorities at the first visit from those of their healthcare provider, leading to barriers to shared decision-making regarding screening and testing during this visit. CONCLUSION: Research is needed to determine how to restructure the initiation of prenatal care in a way that best positions patients to make informed decisions about prenatal genetic screens and tests.

The Impact of Outpatient Prenatal Care Visitor Restrictions on Pregnant Patients and Partners During the COVID-19 Pandemic.

Introduction: During the early months of the COVID-19 pandemic, several health care facilities enacted visitor restrictions to help reduce the spread of SARS-CoV-2 among patients, front-line workers in health care systems, and communities. The impact and burden of policy updates on visitor restrictions put forth by the COVID-19 pandemic can be seen on patients and families, most often in the acute care setting and skilled nursing facilities. Yet, the effects of visitor restrictions in the prenatal care setting were unknown. We conducted a study to investigate the impact of these policies on pregnant patients who received outpatient prenatal care. Methods: We conducted a qualitative study to explore pregnant patients' experiences with prenatal health care delivery between May and July 2020. In-depth interviews were conducted with pregnant patients in the first and second trimester of pregnancy, who received their prenatal care at the onset of the pandemic in the United States. Results: Participants noted increased maternal concern, anxiety, and mental health concerns stemming from the lack of in-person partner support. They noted disappointment and lost experiences for the patient during pregnancy, seeking support from her partner during pregnancy, experiences felt to be critical for postpartum health and wellbeing. There was also concern about the negative impact of restrictions on prenatal care quality and experience. Conclusions: This study demonstrates the impact of visitor restrictions on patients' prenatal care experience and perception of health care quality during the COVID-19 pandemic. Future public health strategies should be individualized to different patient populations addressing knowledge, health literacy, and socioeconomic status, and developed in conjunction with pregnant patients as key stakeholders in the delivery of prenatal health care.

The Successes and Challenges of Implementing Telehealth for Diverse Patient Populations Requiring Prenatal Care During COVID-19: Qualitative Study.

BACKGROUND: Although telehealth appears to have been accepted among some obstetric populations before the COVID-19 pandemic, patients' receptivity and experience with the rapid conversion of this mode of health care delivery are unknown. OBJECTIVE: In this study, we examine patients' prenatal care needs, preferences, and experiences during the COVID-19 pandemic, with the aim of supporting the development of successful models to serve the needs of pregnant patients, obstetric providers, and health care systems during this time. METHODS: This study involved qualitative methods to explore pregnant patients' experiences with prenatal health care delivery at the onset of the COVID-19 pandemic. We conducted in-depth interviews with pregnant patients in the first and second trimester of pregnancy who received prenatal care in Cleveland, Ohio, from May to July 2020. An interview guide was used to probe experiences with health care delivery as it rapidly evolved at the onset of the pandemic. RESULTS: Although advantages of telehealth were noted, there were several concerns noted with the broad implementation of telehealth for prenatal care during the pandemic. This included concerns about monitoring the pregnancy at home; the need for additional reassurance for the pregnancy, given the uncertainties presented by the pandemic; and the ability to have effective patient-provider discussions via a telehealth visit. The need to tailor telehealth to prenatal health care delivery was noted. CONCLUSIONS: Although previous studies have demonstrated that telehealth is a flexible and convenient alternative for some prenatal appointments, our study suggests that there may be specific needs and concerns among the diverse patient groups using this modality during the pandemic. More research is needed to understand patients' experiences with telehealth during the pandemic and develop approaches that are responsive to the needs and preferences of patients.

Methods of induction of labour: a systematic review.

BACKGROUND: Rates of labour induction are increasing. We conducted this systematic review to assess the evidence supporting use of each method of labour induction. METHODS: We listed methods of labour induction then reviewed the evidence supporting each. We searched MEDLINE and the Cochrane Library between 1980 and November 2010 using multiple terms and combinations, including labor, induced/or induction of labor, prostaglandin or prostaglandins, misoprostol, Cytotec, 16,16,-dimethylprostaglandin E2 or E2, dinoprostone; Prepidil, Cervidil, Dinoprost, Carboprost or hemabate; prostin, oxytocin, misoprostol, membrane sweeping or membrane stripping, amniotomy, balloon catheter or Foley catheter, hygroscopic dilators, laminaria, dilapan, saline injection, nipple stimulation, intercourse, acupuncture, castor oil, herbs. We performed a best evidence review of the literature supporting each method. We identified 2048 abstracts and reviewed 283 full text articles. We preferentially included high quality systematic reviews or large randomised trials. Where no such studies existed, we included the best evidence available from smaller randomised or quasi-randomised trials. RESULTS: We included 46 full text articles. We assigned a quality rating to each included article and a strength of evidence rating to each body of literature. Prostaglandin E2 (PGE2) and vaginal misoprostol were more effective than oxytocin in bringing about vaginal delivery within 24 hours but were associated with more uterine hyperstimulation. Mechanical methods reduced uterine hyperstimulation compared with PGE2 and misoprostol, but increased maternal and neonatal infectious morbidity compared with other methods. Membrane sweeping reduced post-term gestations. Most included studies were too small to evaluate risk for rare adverse outcomes. CONCLUSIONS: Research is needed to determine benefits and harms of many induction methods.

Gelsolin down-regulates lipopolysaccharide-induced intraamniotic tumor necrosis factor-alpha production in the midtrimester of pregnancy.

OBJECTIVE: The purpose of this study was to identify gelsolin in midtrimester amniotic fluid and evaluate its interaction with lipopolysaccharide (LPS). STUDY DESIGN: Supernatants from 40 midtrimester amniotic fluid samples were incubated with Escherichia coli LPS, and gelsolin binding was measured by enzyme-linked immunosorbent assay. Unfractionated aliquots of 25 of the fluids were cultured ex vivo for 24 hours in the presence of LPS and supernatants tested for tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 production, and the influence of antigelsolin antibody was evaluated. RESULTS: Each amniotic fluid was positive for gelsolin that bound to LPS. LPS-induced TNF-alpha production was inversely proportional to the amniotic fluid concentrations of LPS-bound gelsolin (r = -0.5047; P = .006). Preincubation with monoclonal antibody to gelsolin led to an increase in LPS-induced TNF-alpha production (P = .01). There was no relationship between gelsolin and IL-10 production. CONCLUSION: Gelsolin is present in midtrimester amniotic fluid, binds to LPS, and inhibits the induction of TNF-alpha.

Pregnancy-Associated Cardiac Hypertrophy in Corin-Deficient Mice: Observations in a Transgenic Model of Preeclampsia.

BACKGROUND: Preeclampsia increases the risk of heart disease. Defects in the protease corin, including the variant T555I/Q568P found in approximately 12% of blacks, have been associated with preeclampsia and cardiac hypertrophy. The objective of this study was to investigate the role of corin and the T555I/Q568P variant in preeclampsia-associated cardiac alterations using genetically modified mouse models. METHODS: Virgin wild-type (WT) and corin knockout mice with or without a cardiac WT corin or T555I/Q568P variant transgene were mated at 3 or 6 months of age. Age- and genotype-matched virgin mice were used as controls. Cardiac morphology and function were assessed at gestational day 18.5 or 28 days postpartum by histologic and echocardiographic analyses. RESULTS: Pregnant corin knockout mice at gestational day 18.5 developed cardiac hypertrophy. Such a pregnancy-associated phenotype was not found in WT or corin knockout mice with a cardiac WT corin transgene. Pregnant corin knockout mice with a cardiac T555I/Q568P variant transgene developed cardiac hypertrophy similar to that in pregnant corin knockout mice. The cardiac hypertrophy persisted postpartum in corin knockout mice and was worse if the mice were mated at 6 instead of 3 months of age. There was no hypertrophy-associated decrease in cardiac function in pregnant corin knockout mice. CONCLUSIONS: In mice, corin deficiency causes cardiac hypertrophy during pregnancy. Replacement of cardiac WT corin, but not the T555I/Q568P variant found in blacks, rescues this phenotype, indicating a local antihypertrophic function of corin in the heart. Corin deficiency may represent an underlying mechanism in preeclampsia-associated cardiomyopathies.

Deceased Donor Uterine Transplantation: Innovation and Adaptation.

This commentary endeavors to share our practical experience in developing and implementing the first uterine transplant clinical trial in the United States. Uterine transplant is a promising novel treatment for uterine factor infertility. After reported successful live births after uterine transplant in Sweden, research teams around the world are either embarking on or are considering the development of uterine transplant protocols. Our observations on the applied rather than theoretical aspects of uterine transplantation research in human subjects are detailed in this article. Important among these considerations are composing a broad and experienced multidisciplinary team as well as performing adequate preclinical preparations, including ideally animal studies and practice organ procurements. Ethical preparation is tantamount to clinical preparation for the complexities inherent in uterine transplant, and our suggestions for updating the current ethical criteria for uterine transplant are outlined here. We also describe our perspectives on the strengths and weaknesses of living compared with deceased donor models. Finally, we describe how a strong program can recover and adapt in the face of setbacks to continue a path toward innovation.

Interpregnancy change in smoking habits and risk of preeclampsia: a population-based study.

BACKGROUND: Maternal smoking has been associated with decreased risk of preeclampsia; however, it is uncertain whether this association is causal. An argument for causality would be strengthened if changes in smoking status across consecutive pregnancies were related to the risk of preeclampsia. METHODS: We used data from the National Swedish Birth Register to ascertain the associations between changes in smoking status during the first two successive pregnancies and risk of preeclampsia in the second pregnancy in 371,627 women between 1992 and 2006. Multivariable logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Compared to women who did not smoke in either pregnancy, the risk of preeclampsia was reduced in women who smoked in both pregnancies (adjusted OR = 0.54; 95% CI = 0.47, 0.63), in those who only smoked in second pregnancy (OR = 0.76; 95% CI = 0.58, 0.99) and, to a lesser extent, in women who smoked only in the first pregnancy (OR = 0.81; 95% CI = 0.70, 0.94). History of preeclampsia in the first pregnancy did not substantially modify these associations. CONCLUSION: These data add support to a causal interpretation of the observed inverse association between smoking during pregnancy and risk of preeclampsia.

Angiogenic factors in superimposed preeclampsia: a longitudinal study of women with chronic hypertension during pregnancy.

Imbalances in circulating angiogenic factors contribute to the pathogenesis of preeclampsia. To characterize levels of angiogenic factors in pregnant women with chronic hypertension, we prospectively followed 109 women and measured soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin, and placental growth factor at 12, 20, 28, and 36 weeks' gestation and postpartum. Superimposed preeclampsia developed in 37 (34%) and was early onset (<34 weeks) in 9 and later onset (≥34 weeks) in 28. Circulating levels of sFlt1 and the ratio of sFlt1 to placental growth factor were higher before clinical diagnosis at 20 weeks' gestation in women who subsequently developed early onset preeclampsia between 28 and 34 weeks compared with levels in women who never developed preeclampsia (P=0.001) or who developed late-onset preeclampsia (P=0.001). Circulating levels of sFlt1, soluble endoglin, and the ratio of sFlt1:placental growth factor were also significantly higher, and placental growth factor levels were significantly lower at the time of clinical diagnosis of superimposed preeclampsia in women with either early or late-onset superimposed preeclampsia compared with levels at similar gestational ages in those with uncomplicated chronic hypertension. We conclude that alterations in angiogenic factors are detectable before and at the time of clinical diagnosis of early onset superimposed preeclampsia, whereas alterations were observed only at the time of diagnosis in women with late-onset superimposed preeclampsia. Longitudinal measurements of angiogenic factors may help anticipate early onset superimposed preeclampsia and facilitate diagnosis of superimposed preeclampsia in women with chronic hypertension.