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Research and Discovery Pathways Programs
Medical Student Research Program Overview

Obstetrics and Gynecology 2020 Projects

Project Title: Ethical Dilemmas and Policy Surrounding In Vitro Fertilization and other Assisted Reproductive Technologies

Faculty Mentor: Melissa Bright 
Email: mbright08@ufl.edu 

Student: Molly Nyren 
Email: mollyquinn@ufl.edu 

Research Project Description:

Infertility is usually defined as an inability to become pregnant after at least 12 months of unprotected intercourse, or 6 months if the woman is 35 or older (1). While humankind has likely struggled with infertility most of its history, modern medicine has only recently developed treatment for infertility. Such treatments are called Assisted Reproductive Technology (ART), one of which is In Vitro Fertilization (IVF). In 1978, Louise Brown, born to Lesley and John Brown, was the first baby born via IVF (2). In 1984, the first IVF quadruplets were born and the first child was born from a frozen embryo (2). This was the beginning of a new era of ART, and many ethical questions arose in its train.

There are many ethical issues that we ought to address when any new treatment is discovered. Some are fundamental and broad, such as what counts as a disease or illness or whether healthcare is a human right. Even if one believes that healthcare is a human right, one must nevertheless determine what falls within the scope of healthcare considered as a right. There are certain procedures and services that are considered elective and are exempt from insurance coverage, e.g. cosmetic plastic surgery. Other services are considered fundamental and should be universally accessible, such as lifesaving emergency care. Such questions arise in the context of fertility generally as well: is infertility a disease, an illness, or neither? Is it the kind of inability of function that calls for medical intervention? If so, is it something everyone ought to have access to? Would mandated coverage be economically feasible? Other subjects are more specific to ART and IVF, such as the problem of multiple births or multiple gestation pregnancies, the consideration of egg freezing, and pre-implantation genetic testing (3). Many of these questions remain heavily debated in the literature.

Despite the ethical debates, some headway has been made in the policy realm for IVF and ART. Since the genesis of IVF in 1978, 16 states have since mandated that insurers cover, or at least offer coverage of, infertility treatments (4). Notably, three of these states, California, Louisiana, and New York, specifically exclude coverage for IVF procedures specifically. Such mandates might be costly for the state since the Affordable Care Act came into play as it requires States to take on the additional costs generated by the mandate (5). Even if the State mandates coverage of IVF or ART, it does not necessarily mean that everyone will be able to afford the procedures. It has been noted that only about 6 of the 16 states which mandate some kind of coverage ensure “meaningful” access to ART services (6). It is important to know not only if a service is “covered” by ones insurance, but what the Out-of-Pocket (OOP) Cost is, what the co-pay or co-insurance is, and whether the service counts towards the OOP maximum. Simply put, it is important to know if the coverage, mandated or otherwise, actually improves access.

The ethical questions surrounding ART, and especially IVF, are complex. The problems often intersect with other moral and political views. For example, the moral overlap between abortion and frozen embryos. It is important for those wishing to enter the debate and advocate for a position to be well informed concerning the ethical arguments posed for and against ART and IVF. Additionally, it is important to understand the economical reasons for and against the coverage of ART and IVF. Finally, the insurance policy surrounding ART and IVF is limited and difficult to understand. In order to advocate for a position, it is important for such advocates to be informed on what is currently available. As mentioned, while 16 states have passed mandates regarding ART coverage, the actual coverage to the insurance recipient varies widely. Some states require the ART coverage merely be offered as a part of some insurance packages, while others mandate ART be covered by all insurance providers, but not IVF. Finally, there are questions on an individual level about what the OOP cost for insurance recipients is for IVF treatment. If the average cost of an IVF cycle is $12,000-17,000 (4), but insurance only covers $5,000 of that, there may still be limited access for low socioeconomic status people, despite mandated “coverage.”

The goal of this project is to review and summarize the current ethical debates surrounding ART and its coverage, with a focus on IVF. All sides of the debate will be featured, with economic and moral considerations included. The purpose of this is to provide the reader with a guided outline of the current ethical landscape so that they can render their own informed, ethical judgments. Additionally, this project will provide an understanding of coverage in states with a mandate. Coverage is not the same as access, so understanding what coverage entails lends to understanding what access to ART looks like in the states with mandates. This information is difficult to find in the literature. Thus, the goal is to bring to light access issues in states with a mandate. While the scientific history has been laid out previously (2), the political proceedings which led to the insurance mandates currently in place are not clearly understood. This work will also uncover the basis on which the decisions to mandate were made where possible.

  1. Centers for Disease Control and Prevention. 2017 Assisted Reproductive Technology Fertility Clinic Success Rates Report. Atlanta (GA): US Dept of Health and Human Services; 2019.
  2. Kamel RM. Assisted Reproductive Technology after the Birth of Louise Brown. J Reprod Infertil 2013; 14(3): 96-109.
  3. Brezina PR, Zhao Y. The Ethical, Legal, and Social Issues Impacted by Modern Assisted Reproductive Technologies. Obstet Gynecol Int 2012; 2012: 686253.
  4. National Conference of State Legislatures. State laws related to insurance coverage for infertility treatment. Available at http://www.ncsl.org/research/health/insurance-coverage-for-infertility-laws.aspx. Accessed March 6, 2020
  5. Andrews M. Health law tempers new state coverage mandates. Kaiser Health News, 2014. Available at: http://khn.org/news/health-law-tempers- new-state-coverage-mandates/. Accessed March 6, 2020.
  6. Adashi E, Dean L. Access to and use of Infertility Services in the United States: Framing the Challenges. Fertil Steril 2016; 105(5):1113-8.

Project Title: First Trimester Screening for Cardiac Remodeling in Fetuses of Mothers with Pre-Gestational Diabetes

Faculty Mentor: Reem Abu-Rustum 
Email: raburustum@ufl.edu

Student: Kayleigh Porritt 
Email: kporritt@ufl.edu

Research Project Description:

Pre-gestational diabetes is a known risk factor for congenital heart defects and glycemic control during pregnancy reduces the instance of congenital heart defects(^1). In addition, it has been shown to lead to fetal cardiac remodeling as early as the second trimester of pregnancy. Cardiac remodeling is defined as “genome expression resulting in molecular, cellular and interstitial changes and manifested clinically as changes in size, shape and function of the heart resulting from cardiac load or injury”(^2). These changes in size and shape include heavier and thicker walls of the fetal heart, as has been shown by studies of stillborn fetuses of diabetic mothers(^3). Altered fetal genes and molecular markers important for organogenesis(^2) lead to distorted geometry. Other factors that negatively impact formation of the fetal heart are elevated maternal HbA1C, hypoglycemia, hypocalcemia, polycythemia, and hyperbilirubinemia, all of which are observed in diabetic mothers(^4).

The resulting thickened interventricular septum and right ventricular free wall causes poor diastolic function, longer isovolumetric relaxation time, higher left myocardial performance index(^5,6) and altered ventricular rotation(^1,4) that impact fetal and neonatal well-being. Pharmacological treatment to decrease remodeling include ACE inhibitors, beta blockers, and aldosterone antagonists(^5). Therefore, earlier screening and diagnosis may potentially allow for intervention and result in more favorable outcome and less cardiac remodeling.

Due to size limitations, it is now known how early the cardiac remodeling occurs. As such, extrapolating sonographic data from first trimester fetuses will allow for determining how early it occurs and what the main associations are to identify sonographic and non-sonographic markers for early diagnosis. This would allow for targeted prenatal care to improve fetal and neonatal outcomes.

Aims:

  1. Evaluate fetal cardiac structure longitudinally in diabetic pregnancies and controls. Focus especially between 12-36 weeks’ gestation to determine earliest signs of cardiac remodeling.
  2. Evaluate fetal cardiac function longitudinally in diabetic pregnancies and controls to determine earliest signs of functional changes as they relate to cardiac structural changes.
  3. Evaluate placental dimensions, perfusion, epigenetic, genetic, and molecular markers longitudinally in diabetic pregnancies and controls between 12-36 weeks to correlate with fetal cardiac remodeling
  4. Evaluate impact of maternal glucose control (tracked with HbA1C) on the gestational age at which remodeling starts.

References:

  1. Simeone RM, Devine OJ, Marcinkevage JA, Gilboa SM, Razzaghi H, Bardenheier BH, Sharma AJ, Honein MA. Diabetes and congenital heart defects: a systematic review, meta-analysis, and modeling project. Am J Prev Med. 2015 Feb;48(2):195-204. doi:101.1016/j.amapre.2014.09.002 Epub 2014 Oct 14. Review.
  2. Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling – concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000;35(3):569-82.
  3. Russell NE, Holloway P, Quinn S, Foley M, Kelehan P, McAuliffe FM. Cardiomyopathy and cardiomegaly in stillborn infants of diabetic mothers. Pediatr Dev Pathol 2008;11:10-4.
  4. Evers IM, de Valk HW, Visser GH. Risk of complications of pregnancy in women with type I diabetes: nationwide prospective study in the Netherlands. BMJ 2004;328:915.
  5. Azevedo PS, Polegato BF, Minicucci MF, Paiva SAR, Zornoff AM. Cardiac remodeling: concepts, clinical impact, pathophysiological mechanism and pharmacologic treatment. Arq Bras Cardiol 2016; 106(1): 62-69
  6. Russel NE, Foley M, Kinsley BT, Firth RG, Codffey M, McAuliffe FM. Effect of pregestational diabetes mellitus on fetal cardiac function and structure. Am J Obstet Gynecol 2008;199:312e1-312.e7

Project Title: Testing for Sexually Transmitted Infections in an elderly population

Faculty Mentor: Jessica Heft
Email: jmo44@ufl.edu  

Student: Emma Albrecht and Alexandra Hernandez 
Email: ealbrecht@ufl.edu; adhernandez@ufl.edu

Research Project Description:

Beginning in March of 2020, many hospitals across the United States stopped performing any “elective surgeries.” Along with shelter-in-place and stay-at-home legislative orders, the stopping of non-urgent surgeries was implemented to limit viral exposure for patients and hospital staff as well as to preserve personal protective equipment (PPE).1,2 On March 20th, Florida Governor Ron DeSantis issued an Executive Order prohibiting any “non-urgent or non-emergency procedure or surgery.”3 Elective surgeries make up the vast majority of cases performed in the U.S. and range from things like knee replacements to colonoscopies to cataract surgery. The term “elective surgery” can be confused with “cosmetic surgery,” but in this instance also includes any medically necessary surgery that can be delayed without harming a patient’s health or safety.4 In gynecology, this includes most hysterectomies, laparoscopic tubal ligations, and quality-of-life surgeries for vaginal prolapse or urinary incontinence.5

At the University of Florida, our group created and published a protocol to categorize and prioritize surgeries to assist with the de-escalation of scheduled elective cases.6 As we pass the peak of the pandemic and reach a point where it is safe to resume elective surgeries, it is important to have a similar plan in place to return to our normal practices.7 An important factor in this planning is to understand our patients’ perspectives on rescheduling surgery and the impact the COVID-19 delay has had on their care.

The purpose of this research study is to understand the perspective of patients whose gynecologic surgeries were canceled as a result of the COVID-19 pandemic. We are hoping to use this information to improve our approach to surgery rescheduling.

References:

  1. American College of Surgeons. “COVID-19: recommendations for management of elective surgical procedures.” Clinical Issues and Guidance. https://www.facs.org/covid-19/clinical-guidance/elective-surgery. Accessed April 24, 2020.
  2. Soremekun OA, Zane RD, Walls A, et al. “Cancellation of scheduled procedures as a mechanism to generate hospital bed surge capacity-a pilot study.” Prehospital and Disaster Medicine. 2011 Jun;26(3):224–229.
  3. State of Florida Office of the Governor. “Executive order number 20-72: emergency management – COVID-19 – non-essential elective medical procedures.” March 20, 2020.
  4. Adrian Diaz BA, Sarac AR, Schoenbrunner JE, et al. “Elective surgery in the time of COVID-19. The American Journal of Surgery, 2020. doi: 10.1016/j.amjsurg.2020.04.014
  5. American College of Obstetricians & Gynecologists. “Joint statement on elective surgeries.” Clinical Information. https://www.acog.org/news/news-releases/2020/03/joint-statement-on-elective-surgeries. Accessed April 20, 2020.
  6. Weber LeBrun EE, Moawad NS, Rosenberg EI, et al. “COVID-19 pandemic: staged management of surgical services for gynecology and obstetrics.” American Journal of Obstetrics & Gynecology, 2020. doi: 10.1016/j.ajog.2020.03.038
  7. American College of Surgeons. “Joint statement: roadmap for resuming elective surgery after COVID-19 pandemic.” Clinical Issues and Guidance. https://www.facs.org/covid-19/clinical-guidance/roadmap-elective-surgery. Accessed April 24, 202

Project Title: IPV and substance use in pregnancy

Faculty Mentor: Melissa Bright 
Email: mbright08@ufl.edu 

Student: Estherland Duqueney 
Email: eduqueney@ufl.edu 

Research Project Description:

Intimate violence is defined as physical, sexual, and emotional abuse by former or current intimate partners. Each year, roughly 1.5 million women in the United States report being physically or sexually abused by their partner; it is estimated that up to 8% of women experience this violence during pregnancy. Research shows that experiencing IPV during pregnancy is associated with a multitude of pregnancy-specific behaviors. Specifically, IPV in pregnancy can lead to an increase in substance use.

The most commonly used substance in pregnancy is tobacco, followed by alcohol, cannabis and other illicit substances. However, polysubstance use can be as high as 50% as reported in some studies. There is strong data showing that prenatal substance use can lead to outcomes such as lower birth rates, small for gestational age, admission into the neonatal intensive care unit, and infant mortality. This is the reason why prenatal care providers screen all patients for substance abuse disorders in pregnancy using a validated screening tool. IVP in pregnancy can also be associated with detrimental outcomes for the infant. Violence on pregnant women significantly increased risk for low birth weight infants, pre-term delivery and neonatal death.

Both prenatal substance use and IPV are serious public health issues that can be linked with harmful health outcomes for the mother and infant. Taken together, these studies have assessed the outcomes of IPV and substance use separately. This retrospective study will analyze the associations between IPV and prenatal substance use measured early in pregnancy and a number of outcomes for the infant.

It is hypothesized that infants born to mothers with a history of IPV, and substance use during pregnancy will have a higher risk of developing negative health outcomes.

Aim 1: Identify pregnant women with experiences of IPV or substance use during pregnancy. The investigators will request medical record numbers of all women who attended an initial prenatal care visit at UFHealth Women’s Clinic, medical plaza from Jan 1, 2014 to Jan 1, 2019. The investigators will identify responses to IPV screening tool collected in the OB registration packet and responses to 4Ps (substance use) screening tool collected in the OB registration packet.
Aim 2: Identify infants born to mothers with experiences of IPV or substance use during pregnancy. The investigators will request medical record numbers of the infants born to women who attended an initial prenatal care visit at UFHealth Women’s Clinic, medical plaza from Jan 1, 2014 to Jan 1, 2019.
Aim 3: Define the health outcomes associated with maternal IPV or substance use on infants. The investigators will extract the following information from the infants’ medical record: diagnosis of in utero substance exposure, number of primary care visits attended at 2 months, up-to-date on immunizations at 2 months, number of ED visits by 2 months. Once data has been extracted, the investigators will conduct correlation and chi-square analyses examining associations between self-reported IPV and substance use with infant outcomes.

References:

  1. Alhusen, J. L., Ray, E., Sharps, P., & Bullock, L. (2015). Intimate partner violence during pregnancy: maternal and neonatal outcomes. Journal of women’s health (2002), 24(1), 100–106. https://doi.org/10.1089/jwh.2014.4872
  2. Cha, S., Masho, S.W. (2014). Discussions About Intimate Partner Violence During Prenatal Care in the United States: The Role of Race/Ethnicity and Insurance Status. Matern Child Health J 18, 1413–1422). doi:10.1007/s10995-013-1381-z
  3. Connelly, C. (2013). Is Screening for Depression in the Perinatal Period Enough? The Co-Occurrence of Depression, Substance Abuse, and Intimate Partner Violence in Culturally Diverse Pregnant Women. Journal of Womens Health, 22(10). doi:10.1089/jwh.2012.4121
  4. Forray, A. (2016). Substance use during pregnancy. PubMed, 5. doi: 10.12688/f1000research.7645.1
  5. Sarkar, N. N. (2008). The impact of intimate partner violence on women’s reproductive health and pregnancy outcome. Journal of Obstetrics and Gynecology, 28(3), 266-271. doi:10.1080/01443610802042415

Project Title: Incisional Negative Pressure Wound Therapy for Cesarean Delivery in Morbidly Obese Patients: A Review

Faculty Mentor: William Patrick Duff 
Email: duffp@ufl.edu 

Student: Margaret Ann Kreher 
Email: mkreher@ufl.edu

Research Project Description:

As rates of obesity and severe obesity rise in the United States, we see the marked adverse effects extending to the obstetric population. The obesity rate among women in the US is estimated at 40%, and the rate of class 3 obesity (severe or morbid obesity defined as a BMI greater than 40 kg/m2) was 9.8% in 2014, up from 7.6% in 2005.1 Moreover, over half of women at the start of prenatal care present with obesity.2 In addition to the heightened risks these patients face during prenatal management, a clear dose-response relationship has been found between increasing BMI and rates of wound complication following cesarean delivery. A cohort study in 2014 found post-cesarean wound disruption or infection increasing from 6.6% in non-obese patients, to 9.2% in patients with BMI 30.0-39.9, 16.8% for BMI 40.0-49.9, and 22.9% for BMI greater than 50. Higher BMI also correlated with higher rates of midline vertical incision, longer surgery duration, greater blood loss, and less frequent subcuticular skin closure.3 Overall, surgical site infections are the number one cause of hospital-acquired infections, accounting for expenditures of approximately $10 billion annually in the US.4

Recently, in an attempt to reduce the frequency of surgical site infection, negative pressure wound therapy has been adapted for the treatment of closed surgical incisions (incisional NPWT). In 2010 and 2011, two iNPWT devices became available. They act via an adhesive dressing connected to a battery-powered vacuum that exerts negative pressure to remove fluid from the wound site, either into a portable canister or via evaporation through a semipermeable dressing. Theories for the mechanisms of NPWT include removal of interstitial fluid and optimization of blood flow, as well as mechanical deformation which stimulates growth factors and granulation tissue formation.5 Biomechanical studies further demonstrate that, when applied to closed surgical incisions, these devices increase perfusion,6 reduce lateral stresses at the suture, and redirect the stresses to mimic intact tissue.7 They also improve lymphatic drainage, thus decreasing seroma and hematoma formation.8 In a recent meta-analysis including results from arthroplasty, lower extremity and abdominal wounds, sternotomy, lower extremity and spinal fractures, and breast reduction surgeries, there was a significantly lower rate of postoperative wound infection, seroma formation, and wound exudate with iNPWT compared with standard dressings.9

Incisional NPWT presents a potential opportunity to improve outcomes for obstetric patients undergoing cesarean delivery, particularly those at high risk for postoperative infection due to obesity. A review synthesizing the available evidence on iNPWT as it relates to cesarean delivery and severe obesity would guide the UF Department of Obstetrics & Gynecology in its decisions to implement the technique for our patients.

Two randomized controlled trials assessing use of iNPWT in cesarean delivery for obese patients report conflicting results. A trial conducted in Denmark found that iNPWT reduced the relative risk of surgical site infection by 50% compared to a standard dressing.10 On the other hand, a trial at the University of Texas found no difference in wound morbidity (including wound disruption and infection) and saw no patient subgroups trending toward a benefit with iNPWT.11 Preliminary analysis comparing the studies reveals notable differences in overall BMI (47 in the negative trial versus 35 in the positive trial), blood loss, surgery duration, emergent nature of the cesarean, type of incision (vertical midline versus transverse), the type of device used, and the duration that the device was left in. Because the evidence for iNPWT in obese patients having cesarean delivery collectively is not definitive, we hypothesize that additional factors including those listed may be key in formulating the indications for optimal use of the device.

In this literature review, the goal is to (1) synthesize the evidence for the mechanisms supporting incisional negative pressure wound therapy, including application to cases of extreme obesity; and (2) assess the effectiveness of incisional negative pressure wound therapy compared to conventional wound dressings in women having cesarean delivery.

References:

  1. Flegal, K. M., Kruszon-Moran, D., Carroll, M. D., Fryar, C. D., & Ogden, C. L. (2016). Trends in obesity among adults in the United States, 2005 to 2014. Jama, 315(21), 2284-2291.
  2. Cunningham, F., Leveno, K., Bloom, S., Spong, C. Y., & Dashe, J. (2014). Williams obstetrics, 24e. Mcgraw-hill.
  3. Conner, S. N., Verticchio, J. C., Tuuli, M. G., Odibo, A. O., Macones, G. A., & Cahill, A. G. (2014). Maternal obesity and risk of postcesarean wound complications. American journal of perinatology, 31(04), 299-304.
  4. Anderson, D. J., Podgorny, K., Berrios-Torres, S. I., Bratzler, D. W., Dellinger, E. P., Greene, L., … & Kaye, K. S. (2014). Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infection Control & Hospital Epidemiology, 35(S2), S66-S88.
  5. Morykwas, M. J., Simpson, J., Punger, K., Argenta, A., Kremers, L., & Argenta, J. (2006). Vacuum-assisted closure: state of basic research and physiologic foundation. Plastic and reconstructive surgery, 117(7S), 121S-126S.
  6. Atkins, B. Z., Wooten, M. K., Kistler, J., Hurley, K., Hughes, G. C., & Wolfe, W. G. (2009). Does negative pressure wound therapy have a role in preventing poststernotomy wound complications?. Surgical innovation, 16(2), 140-146.
  7. Wilkes, R. P., Kilpad, D. V., Zhao, Y., Kazala, R., & McNulty, A. (2012). Closed incision management with negative pressure wound therapy (CIM) biomechanics. Surgical innovation, 19(1), 67-75.
  8. Kilpadi, D. V., & Cunningham, M. R. (2011). Evaluation of closed incision management with negative pressure wound therapy (CIM): hematoma/seroma and involvement of the lymphatic system. Wound Repair and Regeneration, 19(5), 588-596.
  9. Hyldig, N., Birke‐Sorensen, H., Kruse, M., Vinter, C., Joergensen, J. S., Sorensen, J. A., … & Bille, C. (2016). Meta‐analysis of negative‐pressure wound therapy for closed surgical incisions. British Journal of Surgery, 103(5), 477-486.
  10. Hyldig, N., Vinter, C. A., Kruse, M., Mogensen, O., Bille, C., Sorensen, J. A., … & Laursen, J. B. (2019). Prophylactic incisional negative pressure wound therapy reduces the risk of surgical site infection after caesarean section in obese women: a pragmatic randomised clinical trial. BJOG: An International Journal of Obstetrics & Gynaecology, 126(5), 628-635.
  11. Hussamy, D. J., Wortman, A. C., McIntire, D. D., Leveno, K. J., Casey, B. M., & Roberts, S. W. (2019). Closed Incision Negative Pressure Therapy in Morbidly Obese Women Undergoing Cesarean Delivery: A Randomized Controlled Trial. Obstetrics & Gynecology, 134(4), 781-789.

Project Title: The Relative Efficacy and Applicability of Ovarian Tissue Transplantation as an Alternative to Oocyte Harvesting for Fertility Preservation in Female Cancer Patients

Faculty Mentor: Alice Rhoton-Vlasak 
Email: rhotona@ufl.edu 

Student: Marisa Kometas 
Email: mkom95@ufl.edu 

Research Project Description:

Although innovations in oncological treatment strategies have increased the survival rates of female cancer patients by more than 1.6% within the last five years (Shi), the gonadotoxicity associated with many of these therapeutic approaches still often leads to ovarian damage, infertility and ovarian insufficiency. The loss of the steroidogenic and gametogenic capacity of ovarian tissue is a source of significant morbidity among cancer survivors, and the American Society of Clinical Oncology (ASCO) guidelines recommend that oncologists educate their patients about the potential for treatment-related infertility and include a reproductive specialist on the treatment team (Lee). However, surveys indicate that only 61% of oncologists discuss the impact of gonadotoxic treatments on future fertility, and that 45% never and only 15% routinely refer their female patients to reproductive specialists (Forman). In another survey, only 53.3% of pediatric oncologists reported that they felt sufficiently knowledgeable about and confident in the utility of innovative fertility treatments to discuss them with their patients (Goodwin). These educational and referral barriers primarily arise from lack of awareness of the field of Oncofertility and recent technological developments in ovarian tissue preservation and controversy surrounding the efficacy of innovative treatments relative to clinically-validated fertility treatments. Oncologists and reproductive specialists continue to debate the efficacy and applicability of various fertility preservation strategies. Embryo and oocyte cryopreservation, by vitrification, are widely considered to be the best-established techniques (Kim). More than half a million pregnancies involving frozen-thawed embryos have resulted in live births, and similar success has been achieved using oocyte cryopreservation (Gosden). Unfortunately, pre-pubescent female cancer patients in need of immediate gonadotoxic therapies are not eligible for either of these fertility-preservation treatments. This patient population could strongly benefit from ovarian tissue cryopreservation since tissue can be taken from females of any age without the need to delay cancer treatment to perform ovarian stimulation (Kim). Since ovarian function generally resumes between 2-8 months post-transplant, and continues for approximately 7 years (American Society for Reproductive Medicine), this population could also benefit from some degree of prophylaxis against the loss of steroidogenic capacity that induces amenorrhea and premature menopause. Moreover, ovarian tissue cryopreservation can be used to preserve hundreds of primordial follicles simultaneously (Seli)- a yield significantly greater than that obtained by either oocyte and embryo preservation protocols (which focus on the preservation individual oocytes or embryos).

Since 2017, over 130 live births have been reported following successful ovarian tissue cryopreservation worldwide, and pregnancy rates of 29% and live birth rates of 23% have been reported at five major European centers (American Society of Reproductive Medicine). In light of growing evidence of its safety and efficacy, the American Society for Reproductive Medicine accepted ovarian tissue cryopreservation as a clinically-established treatment in December 2019. However, although ovarian tissue cryopreservation is used routinely in Europe, and has been implemented at fertility preservation centers in China, Korea, and Japan, data remains limited regarding the most effective method of freezing the tissue, the risk for cryopreserving tumor cells with the tissue, and the potential for preserving long-term endocrine function using this procedure. Despite these lingering questions, as promising data continues to emerge, ovarian tissue cryopreservation will likely become more widespread in the United States. This systematic review seeks to present and analyze the most recent advances in ovarian tissue cryopreservation to determine which methods of ovarian tissue harvesting, cryopreservation, and transplantation most successfully restore fertility and hormone function- with emphasis on slow-freezing and vitrification. By also comparing the efficacy of ovarian tissue cryopreservation protocols to the clinically-established embryo and oocyte cryopreservation techniques, this paper also examines the potential role that ovarian tissue cryopreservation could play in the treatment of non-pediatric oncologic patients. After assessing the distribution of ovarian tissue cryopreservation centers, and the procedures used worldwide, this study also proposes beginning a registry to track transplant outcomes in the United States.

By providing a more immediate and efficient method of preserving fertility (Kim), and by simultaneously combatting against early-onset menopause in young women, ovarian tissue cryopreservation and transplantation may prove more effective than both embryo and oocyte cryopreservation- the current standard treatments for fertility preservation. The following paper will review current oncological and reproductive medicine literature to ascertain the evidence supporting these assertions- and to determine the extent to which ovarian tissue cryopreservation can be implemented in pediatric cancer patients in need of gonadotoxic treatments.

This systematic review seeks to survey the current scientific literature for information information regarding ovarian tissue harvesting, preservation, and transplantation methods, efficacy relative to more well-established fertility-preservation (such as oocyte harvesting), and potential applications. After objectively assessing each source’s quality of methodology and relevance to the research question, the data will be analyzed to determine which methods of ovarian tissue harvesting, preservation, and transplantation most successfully restore fertility and hormone function (in terms of both number of pregnancies culminating in live births and hormonal levels). Emphasis will be placed on comparing the slow-freezing and vitrification methods of ovarian tissue harvesting. The efficacy of the most optimal techniques will then be compared to that of well-established, mainstream fertility-preserving techniques such as oocyte preservation. Subsequent to this analysis, the data will be reviewed to determine how ovarian tissue transplantation has been and can potentially be applied to patient populations- with emphasis on fertility-preservation in oncological pediatric patients.

References:

  1. American Society for Reproductive Medicine. “Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion.” Fertility and Sterility, no 112 (2019): pp 1022-1033. accessed April 3, 2020. Doi.org/10.1016/j.fertnstert.2019.09.013
  2. Dalman, Azam, Mehdi Totonchi, et al. “Slow freezing versus vitrification technique for human ovarian tissue cryopreservation: an evaluation of histological changes, WNT signaling pathway and apoptotic genes expression.” Cryobiology, no 79 (2017): pp 29-36. accessed March 4, 2019. doi: 10.1016/j.cryobiol.2017.09.007.
  3. Donnez, Jacques, Marie-Madeleine Dolmans, et al. “Natural hormone replacement therapy with a functioning ovary after the menopause: dream or reality?” Reproductive Biomedicine Online 37. no. 3 (2018): pp. 359-366. Accessed March 4, 2019. doi: 10.1016/j.rbmo.2018.05.018.
  4. Donnez, Jaques, Marie-Madeleine Dolmans. “Ovarian tissue freezing: current status.” Current Opinion in Obstetrics and Gynecology, no. 27 (2015): pp. 2222-230. Accessed March 4, 2019. doi: 10.1097/GCO.0000000000000171.
  5. Donnez, Jacques, Diego Manavella, and Marie-Madeleine Dolmans. “Techniques for ovarian tissue transplantation and results.” Minerva Ginecologica 70. no. 4 (2018): pp. 424-431. Accessed March 4, 2019. doi: 10.23736/S0026-4784.18.04228-4.
  6. Forman, EJ, CK Anders, et al. “Pilot survey of oncologists regarding treatment-related infertility and fertility preservation in female cancer patients.” Journal of Reproductive Medicine, no. 54 (2009): pp. 203-207. Accessed March 4, 2019. doi.
  7. Fortin, Anne, Henri Azais, et al. “Laparoscopic ovarian tissue harvesting and orthotopic ovarian cortex grafting for fertility preservation: less is more.” Fertility and Sterility 111, no 2 (2019): pp 408-410. Accessed March 4, 2019. doi: 10.1016/j.fertnstert.2018.11.022.
  8. Gastal, GDA, FLN Aquiar, et al. “Effect of cryopreservation techniques on proliferation and apoptosis of cultured equine ovarian tissue.” Theriogenology, no. 126 (2019): pp. 88-94. Accessed March 4, 2019. doi: 10.1016/j.theriogenology.2018.11.034.
  9. Goodwin, T, Elizabeth Oosterhuis, et al. “Attitudes and practices of pediatric oncology providers regarding fertility issues.” Pediatric Blood Cancer, no. 48 (2007): pp. 80-85. Accessed March 4, 2019. doi:
  10. Gosden R. “Cryopreservation: a cold look at technology for fertility preservation.” Fertility and Sterility, no. 96 (2011): pp. 264-268. Accessed March 4, 2019. doi:
  11. Kim, Sooyoung, Youngi Lee, et al. “Ovarian tissue cryopreservation and transplantation in patients with cancer.” Obstetrics and Gynecology Science 61, no. 4 (2018):pp. 431-442. Accessed March 4, 2019. doi: 10.5468/ogs.2018.61.4.431.
  12. Kokotsaki, Maria, Mario Mairhofer, et al. “Impact of vitrification on granulosa cell survival and gene expression.” Cryobiology, no. 85 (2018): pp. 73-78. Accessed March 4, 2019. doi: 10.1016/j.cryobiol.2018.09.006.
  13. Kristensen, S.G., Q Liu, et al. “A simple method to quantify follicle survival in cryopreserved human ovarian tissue.” Human Reproduction 33, no. 12 (2018): pp. 2276-2284. Accessed March 4, 2019. doi: 10.1093/humrep/dey318.
  14. Kristensen, S.G., Susanne Poors, et al. “Time from referral to ovarian tissue cytopreservation in a cohort of Danish women.” Acta Obstetricia et Gynecologica Scandinavica, no. 1 (2019): pp. Accessed March 4, 2019. doi: 10.1111/aogs.13575.
  15. Ladanyi, Camille, Amir Mor, et al. “Recent advances in the field of ovarian tissue cryopreservation and opportunities for research.” Journal of Assisted Reproduction and Genetics 34, no. 6 (2017): 709-722. Accessed March 4, 2019. doi: 10.1007/s10815-017-0899-1.
  16. Lee, SJ, AH Partridge, et al. “American Society of Clinical Oncology recommendations on fertility preservation in cancer patients.” Journal of Clinical Oncology, no. 24 (2006): pp. 2917-2031. Accessed March 4, 2019. doi:
  17. Li, Y., J. Liebenthron, et al. “Ovarian tissue cryopreservation for patients with premature ovary insufficiency caused by cancer treatment: optimal protocol.” Climacteric. no. 24 (2019): pp. 1-7. Accessed March 4, 2019. doi: 10.1080/13697137.2018.1554644.
  18. Seli, E, J Tangir. “Fertility preservation options for female patients with malignancies.” Current Opinion in Obstetrics and Gynecology, no. 17 (2005): pp. 299-308. Accessed March 4, 2019 doi:
  19. Shi, Quingquan, Yidong Xie, Yan Wang, and Shangwei Li. “Vitrification versus slow freezing for human ovarian tissue cryopreservation: a systematic review and meta-analysis.” Scientific Reports 7, no. 8538 (2017): pp. Accessed March 4, 2019. doi: 10.1038/s41598-017-09005-7.
  20. Silber, S. “Ovarian tissue cryopreservation and transplantation: scientific implications.” Journal of Assisted Reproduction and Genetics, no. 33 (2016): pp. 1595- 1603. Accessed March 4, 2019. doi:
  21. Takai, Yasushi. “Recent advances in oncofertility care worldwide and in Japan.” Reproductive Medicine and Biology 17, no.4 (2018): pp. 356-368. Accessed March 4, 2019. doi: 10.1002/rmb2.12214

Project Title: Social and Developmental Outcomes of Infants with In-utero Drug Exposure and/or Neonatal Abstinence Syndrome

Faculty Mentor: Melissa Bright 
Email: mbright08@ufl.edu 

Student: Cathleen Mestre 
Email: cathleentmestre@ufl.edu 

Research Project Description:

Neonatal Abstinence Syndrome (NAS) is defined as postnatal drug withdrawal that occurs following substance exposure in-utero. NAS is most commonly associated with opioid use [1]. Over the past 10 years, the U.S. has experienced a 300% increase in the diagnoses of NAS as the opioid epidemic has become a U.S. Public Health Crisis [2]. It is also known that the number of infants exposed to illicit drugs in-utero is much greater than the number receiving NAS diagnoses at birth. Thus, the impact of opioid use on infants is likely even more vast than NAS data indicates. NAS most commonly manifests postnatally as central nervous system irritability, autonomic over-reactivity, and gastrointestinal tract dysfunction [3]. NAS has been linked to a multitude of negative long-term outcomes. NAS infants have an increased risk for preterm birth, birth defects, seizures, smaller overall brain volume and neurodevelopment impairments than those without opioid exposure in utero [4,7]. Additionally, newborns diagnosed with NAS have more behavioral and emotional disorders at 24 months of age [5] and increased rates of depression, anxiety and aggression throughout childhood [6] than those not exposed to substances in-utero.

While an expanding body of research focuses on the physiologic underpinnings of NAS and NICU treatment methods, a paucity of data exists to look at the social and developmental outcomes of these children after they leave the hospital. Understanding the long‐term effects of prenatal substance exposure and NAS on social and developmental outcomes are timely and crucial. A multi-source dataset of medical record data, as well as data from the Departments of Health (DOH) and the Department of Children and Families (DCF), is needed to be able to better understand and identify trends and drive policy interventions aimed to address this critical public health crisis.

Unborn babies whose mothers use illicit substances or opioids are at risk of developing Neonatal Abstinence Syndrome (NAS). NAS is a withdrawal syndrome consisting of behavioral and physical symptoms in a newborn. Physical neonatal outcomes associated with NAS and known in-utero drug exposure is an area of growing research. What is less known, however, is the social and developmental outcomes for these infants after leaving the hospital. Thus, this project hypothesizes that: There will be a significant positive correlation between infants diagnosed with in-utero substance exposure and children through age 5 experiencing worse social and developmental outcomes.

To investigate the social and developmental outcomes of infants diagnosed with Neonatal Abstinence Syndrome and/or in-utero substance exposure after leaving the hospital through 5 years old. Social and Developmental outcomes will be measured via growth statistics, developmental progress (scored by ASQ), well-child care visits, and DCF cases from birth through age 5. Additionally, we aim to investigate maternal predictive determinants of having a child with in-utero substance exposure through variables asked on the Florida Healthy Start questionnaire. Lastly, differences in outcomes based on type of substance exposure and diagnosis of NAS will be examined.

References:

  1. Miller, J. S., Anderson, J. G., & Lindley, L. C. (2020). Behavioral development in children with prenatal substance exposure and neonatal abstinence syndrome: Associated factors and implications. Journal of Child and Adolescent Psychiatric Nursing. doi: 10.1111/jcap.12273
  2. Ko, J. Y., Patrick, S. W., Tong, V. T., Patel, R., Lind, J. N., & Barfield, W. D. (2016). Incidence of neonatal abstinence syndrome‐28 states, 1999–2013. Morbidity and Mortality Weekly Report, 65, 799–802.
  3. Patrick SW, Davis MM, Lehman CU, Cooper WO. Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to 2012. J Perinatol 2015; 35:667.
  4. Sirnes, E., Oltedal, L., Bartsch, H., Eide, G. E., Elgen, I. B., & Aukland, S. M. (2017). Brain morphology in school‐aged children with prenatal opioid exposure: A structural MRI study. Early Human Development, 106‐107, 33–39. https://doi.org/10.1016/j.earlhumdev.2017.01.009
  5. Hall, E. S., McAllister, J., & Wexelblatt, S. (2018). Developmental disorders and medical complications among infants with subclinical intrauterine opioid exposures. Population Health Management, 22(1), 19–24. https://doi.org/10.1089/pop.2018.0016
  6. Nygaard, E., Slinning, K., Moe, V., & Walhovd, K. B. (2016). Behavior and attention problems in eight‐year‐old children with prenatal opiate and poly‐substance exposure: A longitudinal study. PLoS One, 11(6):e0158054. https://doi.org/10.1371/journal.pone.0158054
  7. Stanford Children’s Health- Neonatal Abstinence Syndrome. (n.d.). Retrieved from https://www.stanfordchildrens.org/en/topic/default?id=neonatal-abstinence-syndrome-90-P02387

Project Title: Effects of State/Local Legislation on Childhood Sexual Abuse Rates

Faculty Mentor: Melissa Bright 
Email: mbright08@ufl.edu 

Student: Sarah Masten and Ashton Naumann
Email: sarahmasten@ufl.edu; ashton.naumann@ufl.edu 

Research Project Description:

Child maltreatment and abuse has largely been studied at an interpersonal level, focusing on relationships within a home and child-level prevention programs. More recent studies have demonstrated the importance of studying the role of policy in reduction of child maltreatment rates, suggesting that risk factors such as poverty, lack of child support, and housing mobility may play important roles in improving child outcomes (Klemens, 2015). With the sparse amount of policy research that has gone into child abuse related topics, the field recognizes that the risk factors involving childhood sexual abuse (CSA) as opposed to other maltreatment are distinct entities (Finkelhor, 1994). For example, CSA appears to be perpetrated by a few repeat offenders (Graham, 1986), females are disproportionately affected compared to males (Finkelhor, 2014), and the median age for abuse in children is older for sexual abuse than it is for overall maltreatment (Elliot, 1995). The scant evidence base for prevention approaches at the community and societal levels remains a critical research gap (Fortson, 2016). These risk and protective factors can be studied at federal, state, or local levels through policies and programs implemented for population health.

While child maltreatment can arise from stressors related to economic policies, we hypothesize that due to the differences in motivation for abuse perpetration, there will be differences in the effective policies for reducing the rate of CSA.

With this project, we aim to identify existing policies (e.g., age of consent, mandatory minimum sentences, pornography laws, mandated K-12 preventive curricula) that correlate as risk or protective factors related to CSA rates. We will develop the first dataset that focuses on state and local policies. Based on our findings, we hope to derive concrete policy recommendations to reduce CSA victimization and/or perpetration.

The project will begin with a systematic review of existing literature discussing associations of established policies, primarily local and state laws, on CSA rates. CSA rates will be operationalized using both victimization and perpetration. Concurrently, counties and/or states who are outliers with regard to CSA rates as reported by state agencies such as “Department of Children & Family Services“ (DCFS) or “Child Protective Services” (CPS) will be examined for unique laws or predisposing characteristics.

From the literature search, a list of policies of interest will be compiled and then evaluated for feasibility of data collection; feasibility will be assessed based on our chosen outcome measures for CSA at a population level (e.g, criminal convictions, victim self-report). Optimal policies will have publically available public data at the county-by-county level. Outcome variables will be assessed pre- and post- implementation of legislation when possible. A REDCap database will be designed to house the resulting data.

References:

  1. Elliott, M., Browne, K., & Kilcoyne, J. (1995). Child sexual abuse prevention: What offenders tell us. Child abuse & neglect, 19(5), 579-594.
  2. Finkelhor, D., Shattuck, A., Turner, H. A., & Hamby, S. L. (2014). The lifetime prevalence of child sexual abuse and sexual assault assessed in late adolescence. Journal of Adolescent Health, 55(3), 329-333.
  3. Finkelhor, D. (1994). The international epidemiology of child sexual abuse. Child abuse & neglect, 18(5), 409-417.
  4. Fortson, B. L., Klevens, J., Merrick, M. T., Gilbert, L. K., & Alexander, S. P. (2016). Preventing child abuse and neglect: A technical package for policy, norm, and programmatic activities.
  5. Graham, K. R. (1996). The childhood victimization of sex offenders: An underestimated issue. International Journal of Offender Therapy and Comparative Criminology, 40(3), 192-203.
  6. Klevens, J., Barnett, S. B., Florence, C., & Moore, D. (2015). Exploring policies to reduce child physical abuse and neglect. Child Abuse & Neglect, 40, 1-11.

Project Title: Psychiatric sequelae of unexpected and emergent perinatal and postpartum outcomes

Faculty Mentor: Dikea Roussos-Ross 
Email: Kroussos@ufl.edu 

Student: Tiagpaul Bhamber 
Email: tbhamber@ufl.edu

Research Project Description:

Perinatal and postpartum mood disorders affect up to 20% of pregnant women. Specific emergent stressors at the time of delivery may significantly increase a woman’s risk of developing anxiety disorders and depressive disorders. The purpose of this study is to determine whether there is an increased incidence of anxiety and/or mood disorders in women whose pregnancies have been affected by the above scenarios. The proposed study will be a retrospective chart analysis. We will utilize electronic medical records from patients who delivered at UF Health Shand’s Hospital in Gainesville.

We hypothesize that there will be an increased incidence of postpartum psychiatric disorders in mothers who experienced complications during pregnancy and delivery. Prior research has suggested some links between perinatal unspecific life-stressors and postpartum mood disorders.

This study aims to determine specific risk factors for postpartum anxiety and mood disorders. The results of this study will be useful to those involved in the care of patients at higher risk for these psychiatric disorders.

References:

  1. Aris-Meijer J, Bockting C, Stolk R, et al. What If Pregnancy Is Not Seventh Heaven? The Influence of Specific Life Events during Pregnancy and Delivery on the Transition of Antenatal into Postpartum Anxiety and Depression. Int J Environ Res Public Health. 2019;16(16):2851. Published 2019 Aug 9.
  2. Bell AF, Carter CS, Davis JM, et al. Childbirth and symptoms of postpartum depression and anxiety: a prospective birth cohort study. Arch Womens Ment Health. 2016;19(2):219‐227.
  3. Biaggi A, Conroy S, Pawlby S, Pariante CM. Identifying the women at risk of antenatal anxiety and depression: A systematic review. J Affect Disord. 2016;191:62‐77.
  4. Brummelte S, Galea LA. Postpartum depression: Etiology, treatment and consequences for maternal care. Horm Behav. 2016;77:153‐166.
  5. Carter FA, Frampton CM, Mulder RT. Cesarean section and postpartum depression: a review of the evidence examining the link. Psychosom Med. 2006;68(2):321‐330.
  6. Field T. Postnatal anxiety prevalence, predictors and effects on development: A narrative review. Infant Behav Dev. 2018;51:24‐32.
  7. Meltzer-Brody S, Howard LM, Bergink V, et al. Postpartum psychiatric disorders. Nat Rev Dis Primers. 2018;4:18022. Published 2018 Apr 26.
  8. Pearlstein T, Howard M, Salisbury A, Zlotnick C. Postpartum depression. Am J Obstet Gynecol. 2009;200(4):357‐364.
  9. Prado DS, Mendes RB, Gurgel RQ, Barreto IDC, Cipolotti R, Gurgel RQ. The influence of mode of delivery on neonatal and maternal short and long-term outcomes. Rev Saude Publica. 2018;52:95. Published 2018 Nov 29.
  10. Shlomi Polachek I, Huller Harari L, Baum M, Strous RD. Postpartum anxiety in a cohort of women from the general population: risk factors and association with depression during last week of pregnancy, postpartum depression and postpartum PTSD. Isr J Psychiatry Relat Sci. 2014;51(2):128‐134.
  11. Silverman ME, Reichenberg A, Savitz DA, et al. The risk factors for postpartum depression: A population-based study. Depress Anxiety. 2017;34(2):178‐187.
  12. Unsal Atan Ş, Ozturk R, Gulec Satir D, et al. Relation between mothers’ types of labor, birth interventions, birth experiences and postpartum depression: A multicentre follow-up study. Sex Reprod Healthc. 2018;18:13‐18.

Project Title: Early prenatal intimate partner violence and substance abuse and perinatal outcomes

Faculty Mentor: Dikea Roussos-Ross 
Email: Kroussos@ufl.edu 

Student: Tiffany Lowtan 
Email: tiffanyamandaa@gmail.com  

Research Project Description:

Intimate partner violence is a problem that disproportionately affects the female population, such that nearly 16% of women will experience some form of IPV during their lifetime, 5% experience IPV annually, and more than half of those impacted by IPV are pregnant women (1,2). It is associated with multiple adverse health outcomes in both non-pregnant and pregnant populations of women, including injury, death, depression, post-traumatic stress, unintended pregnancy, substance use, and chronic pain, among others (3). Due to additional use of physicians, drugs, and hospitalizations, victims of IPV are three times as likely to incur healthcare costs of greater than five thousand dollars (9). Additionally, of women subjected to IPV in early pregnancy, nearly 10% are expected not to follow up for antenatal care (4). Beginning only as recently as 2010, the USPSTF recommends screening for intimate partner violence in women of reproductive age (3). However, there is currently a gap in understanding the clinical diagnostic accuracy of screening tools, and further research is needed to demonstrate which screening tools are most effective. Additionally, despite these recommendations, a 2014 study showed that 6.4% of women reported preconception or prenatal IPV, while only 49.4% of this population reported discussion of IPV during prenatal care, resulting in inadequate prenatal care (8).

Furthermore, current literature demonstrates an association linking IPV and substance use. Victims who have experienced physical IPV have been shown to have increased likelihood of illicit substance use disorder, while victims of psychological IPV are increasingly likely to have comorbid alcohol use disorder (5). Substance use may increase the risk of obstetric complications by up to six times greater than mothers without a current history of substance use disorders during pregnancies. These complications include, but are not limited to spontaneous abortion, preterm birth, placental abruption, growth restriction, and congenital anomalies (6). Among Hispanic women alone, data have shown 23% report substance use and 3.5% report current or recent IPV during pregnancy (7). Such data would suggest a need to pay special attention for possible IPV when substance use is present, and the converse in order to better anticipate potential complications during pregnancy and at delivery.

This project is significant because identifying the prevalence of intimate partner violence and substance use among pregnant mothers, as well as obstetric and neonatal complications, can help to develop a better understanding and anticipation of potential adverse outcomes. This anticipation could affect likelihood for screening and counseling for women in this population, so that such perinatal outcomes can be minimized.

We hypothesize that screening tools, including the 4 P’s, healthy start, and IPV screen, will positively identify substance use and IPV in the maternal population and demonstrate a significant correlation with multiple perinatal outcomes for mother and baby.

The purpose of this study is to determine the correlation between prenatal screenings for intimate partner violence or substance abuse in early pregnancy, incidence of injury and ED visits during pregnancy, and various perinatal outcomes for mother and baby. These results may be important for determining potential complications associated with these risk factors, in order to take early action in managing and minimizing these adverse outcomes.

References:

  1. Breiding MJ, Smith SG, Basile KC, Walters ML, Chen J, Merrick MT. Prevalence and characteristics of sexual violence, stalking, and intimate partner violence victimization–national intimate partner and sexual violence survey, United States, 2011. MMWR Surveill Summ. 2014;63(8):1‐18.
  2. Holden KB, McKenzie R, Pruitt V, Aaron K, Hall S. Depressive symptoms, substance abuse, and intimate partner violence among pregnant women of diverse ethnicities. J Health Care Poor Underserved. 2012;23(1):226‐241. doi:10.1353/hpu.2012.0022
  3. US Preventive Services Task Force, Curry SJ, Krist AH, et al. Screening for Intimate Partner Violence, Elder Abuse, and Abuse of Vulnerable Adults: US Preventive Services Task Force Final Recommendation Statement. JAMA. 2018;320(16):1678‐1687. doi:10.1001/jama.2018.14741
  4. Martin-de-Las-Heras S, Velasco C, Caño A, Luna-Del-Castillo JD, Khan KS. Poor antenatal care attendance is associated with intimate partner violence: Multivariate analysis of a pregnancy cohort. Eur J Obstet Gynecol Reprod Biol. 2019;237:204‐208. doi:10.1016/j.ejogrb.2019.05.001
  5. Salom CL, Williams GM, Najman JM, Alati R. Substance use and mental health disorders are linked to different forms of intimate partner violence victimisation. Drug Alcohol Depend. 2015;151:121‐127. doi:10.1016/j.drugalcdep.2015.03.01
  6. Keegan J, Parva M, Finnegan M, Gerson A, Belden M. Addiction in pregnancy. J Addict Dis. 2010;29(2):175‐191. doi:10.1080/10550881003684723
  7. Connelly CD, Hazen AL, Baker-Ericzén MJ, Landsverk J, Horwitz SM. Is screening for depression in the perinatal period enough? The co-occurrence of depression, substance abuse, and intimate partner violence in culturally diverse pregnant women. J Womens Health (Larchmt). 2013;22(10):844‐852.
  8. Cha S, Masho SW. Discussions about intimate partner violence during prenatal care in the United States: the role of race/ethnicity and insurance status. Matern Child Health J. 2014;18(6):1413‐1422. doi:10.1007/s10995-013-1381-z
  9. Coker AL, Reeder CE, Fadden MK, Smith PH. Physical partner violence and medicaid utilization and expenditures. Public Health Rep. 2004;119(6):557‐567. doi:10.1016/j.phr.2004.09.005