Stephanie N. Morris

Effects of Lifetime Exercise on the Outcome of In Vitro Fertilization

OBJECTIVE: To estimate whether exercise before the first cycle of in vitro fertilization (IVF) affects cycle outcomes. METHODS: A total of 2,232 patients were prospectively enrolled before undergoing their first cycle of IVF for the treatment of infertility from 1994–2003 at three IVF clinics in the greater Boston area. The primary IVF outcomes of interest included successful live birth and four points of cycle failure: cycle cancellation, failed fertilization, implantation failure, and pregnancy loss. Unconditional logistic regression adjusting for observed confounders was used to quantify the relation between self-reported exercise and cycle outcome. RESULTS: In general, women who reported regular exercise were no more likely to have a live birth compared with those women who did not report exercise (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.7–1.0; P=.07). Women who reported exercising 4 hours or more per week for 1–9 years were 40% less likely to have a live birth (OR 0.6, CI 0.4–0.8) and were almost three times more likely to experience cycle cancellation (OR 2.8, CI 1.5–5.3) and twice as likely to have an implantation failure (OR 2.0, CI 1.4–3.1) or pregnancy loss (OR 2.0, CI 1.2–3.4) than women who did not report exercise. In general, women who participated in cardiovascular exercise had a 30% lower chance of successful live birth (OR 0.7, CI 0.6–0.9) than women who reported no exercise. CONCLUSION: Regular exercise before in vitro fertilization may negatively affect outcomes, especially in women who exercised 4 or more hours per week for 1–9 years and those who participated in cardiovascular exercise. LEVEL OF EVIDENCE: II-2

Molecular network analysis of endometriosis reveals a role for c-Jun-regulated macrophage activation.

The molecular correlates of heterogeneous endometriosis symptoms support a role for innate inflammatory responses converging upon c-Jun and NFκB signaling cascades. Endometriosis: Embracing Complexity Despite its widespread contribution to infertility and debilitating pelvic pain, treatments for endometriosis—an invasive displacement of endometrial tissue outside the uterus—primarily address symptoms and fall short on combating the underlying disease. Avenues for targeted intervention have been lacking, in part due to significant patient heterogeneity that hampers reproducible findings across diverse study populations. To overcome this hurdle, Beste et al. have applied a data-driven strategy to uncover the natural variation in pelvic inflammatory status across a broad cohort of endometriosis patients. By naïvely characterizing comprehensive molecular profiles for each patient, the authors were able to identify a coherent signature of macrophage activity that was otherwise obscured by conventional staging criteria. Further experiments on isolated macrophages revealed a refined signature that unexpectedly implicated the c-Jun N-terminal kinase (JNK) signaling pathway. By confirming that small-molecule inhibition of JNK signaling broadly curbed macrophage inflammatory activity, this work provides a possible lead for future experimental and clinical studies into curtailing the deleterious inflammatory response to endometriotic lesions. If this general approach is validated in larger populations, such profiles may also be helpful as a complementary tool to better identify patients at greater risk for recurrence who would benefit from aggressive treatment. Clinical management of endometriosis is limited by the complex relationship between symptom severity, heterogeneous surgical presentation, and variability in clinical outcomes. As a complement to visual classification schemes, molecular profiles of disease activity may improve risk stratification to better inform treatment decisions and identify new approaches to targeted treatment. We use a network analysis of information flow within and between inflammatory cells to discern consensus behaviors characterizing patient subpopulations. Unsupervised multivariate analysis of cytokine profiles quantified by multiplex immunoassays identified a subset of patients with a shared “consensus signature” of 13 elevated cytokines that was associated with common clinical features of endometriosis, but was not observed among patient subpopulations defined by morphologic presentation alone. Enrichment analysis of consensus markers reinforced the primacy of peritoneal macrophage infiltration and activation, which was demonstrably elevated in ex vivo cultures. Although familiar targets of the nuclear factor κB family emerged among overrepresented transcriptional binding sites for consensus markers, our analysis provides evidence for an unexpected contribution from c-Jun, c-Fos, and AP-1 effectors of mitogen-associated kinase signaling. Their crucial involvement in propagation of macrophage-driven inflammatory networks was confirmed via targeted inhibition of upstream kinases. Collectively, these analyses suggest a clinically relevant inflammatory network that may serve as an objective measure for guiding treatment decisions for endometriosis management, and in the future may provide a mechanistic endpoint for assessing efficacy of new agents aimed at curtailing inflammatory mechanisms that drive disease progression.

Contained tissue extraction using power morcellation: prospective evaluation of leakage parameters

BACKGROUND Safe tissue removal is a challenge for minimally invasive procedures such as myomectomy, supracervical hysterectomy, or total hysterectomy of a large uterine specimen. There is concern regarding disruption or dissemination of tissue during this process, which may be of particular significance in cases of undetected malignancy. Contained tissue extraction techniques have been developed in an effort to mitigate morcellation-related risks. OBJECTIVE The objective of the study was to quantify perioperative outcomes of contained tissue extraction using power morcellation, specifically evaluating parameters of tissue or fluid leakage from within the containment system. STUDY DESIGN This was a study including a multicenter prospective cohort of adult women who underwent minimally invasive hysterectomy or myomectomy using a contained power morcellation technique. Blue dye was applied to the tissue specimen prior to removal to help identify cases of fluid or tissue leakage from within the containment system. RESULTS A total of 76 patients successfully underwent the contained power morcellation protocol. Mean time for the contained morcellation procedure was 30.2 minutes (±22.4). The mean hysterectomy specimen weight was 480.1 g (±359.1), and mean myomectomy specimen weight was 239.1 g (±229.7). The vast majority of patients (73.7%) were discharged home the same day of surgery. Final pathological diagnosis was benign in all cases. Spillage of dye or tissue was noted in 7 cases (9.2%), although containment bags were intact in each of these instances. CONCLUSION Findings are consistent with prior work demonstrating the feasibility of contained tissue extraction; however, further refinement of this technique is warranted.

Women’s Preferences for Minimally Invasive Incisions

STUDY OBJECTIVE To determine whether traditional, robotic, or single-site laparoscopic incisions are more appealing to women. DESIGN Descriptive study using a survey (Canadian Task Force classification III). SETTING Single-specialty referral-based gynecology practice. PATIENTS All patients older than 18 years who came for care to the Newton-Wellesley Hospital Minimally Invasive Gynecological Surgery Center from April 2, 2010, to June 30, 2010. INTERVENTIONS Three identical photos of an unscarred female abdomen were each marked with a black pen to indicate typical incision lengths and locations for robotic, single-site, and traditional laparoscopic surgery. Subjects were then asked to rank these incisions in order of preference. Additional demographic and surgical history questions were included in the survey. MEASUREMENTS AND MAIN RESULTS Two-hundred fifty of 427 patients (58.5%) returned surveys, and of these, 241 completed critical survey elements. Preference for traditional laparoscopic incisions was 56.4% (95% confidence interval [CI], 50.1%-62.7%), for a single incision was 41.1% (95% CI, 34.8%-47.3%), and for robotic surgery was 2.5% (95% CI, 0.5%-4.5%). Two-sample test of proportion (Z test) showed the difference in preference for traditional over the other methods to be significant: p = .007 for a single incision and p <.001 for robotic surgery. Multivariatble analysis for factors influencing choice of single-site incision demonstrated that Latina/Hispanic ethnicity was the only significant factor (p = .02). CONCLUSION Women prefer both single-site and traditional laparoscopic incisions over robotic procedures. Inasmuch as aesthetics are an important consideration for many women and clinical outcomes are similar, during the informed-consent procedure, location and length of incisions should be included in the discussion of risks, benefits, and alternatives.

Minimally invasive specialists and rates of laparoscopic hysterectomy.

Background and Objective: Despite the prevalence of hysterectomy for treatment of benign gynecologic conditions, providers nationwide have been slow to adopt minimally-invasive surgical techniques. Our objective is to investigate the impact of a department for minimally invasive gynecologic surgery (MIGS) on the rate of laparoscopic hysterectomy at an academic community hospital without robotic technology. Methods: This retrospective observational study included all patients who underwent hysterectomy for benign indications from January 1, 2004, through December 31, 2012. The primary outcome was route of hysterectomy: open, laparoscopic, or vaginal. Secondary outcomes of interest included length of stay and factors associated with an open procedure. Results: In 2004, only 24 (8%) of the 292 hysterectomies performed for benign conditions at Newton-Wellesley Hospital (NWH) were laparoscopic. The rate increased to more than 50% (189/365) by 2008, and, in 2012, 72% (316/439) of hysterectomies were performed via a traditional laparoscopic approach. By 2012, more than 93% (411/439) of all hysterectomies were performed in a minimally invasive manner (including total laparoscopic hysterectomy [TLH], laparoscopic supracervical hysterectomy [LSH], total vaginal hysterectomy [TVH], and laparoscopy-assisted vaginal hysterectomy [LAVH]). More than 85% of the hysterectomies at NWH in 2012 were outpatient procedures. By this time, the surgeons preference or lack of expertise was rarely cited as a factor leading to open hysterectomy. Conclusions: A large diverse gynecologic surgery department transformed surgical practice from primarily open hysterectomy to a majority (>72%) performed via the traditional laparoscopic route and a large majority (>93%) performed in a minimally invasive manner in less than 8 years, without the use of robotic technology. This paradigm shift was fueled by patient demand and by MIGS department surgical mentorship for generalist obstetrician/gynecologists.

Fertility preservation: nonsurgical and surgical options.

Improved surveillance and treatment regimens have resulted in decreased mortality rates among cancer patients, allowing these women to focus on survival and quality of life, including the ability to preserve their fertility. The treatments that have improved survival among both adults and children diagnosed with cancer are often gonadotoxic, especially those that employ high doses of alkylating agents and radiation therapy directed near or toward the pelvis. The impact on the ovarian reserve is related to the accelerated depletion of the primordial germ cell pool resulting from these therapies. Nonsurgical approaches to fertility preservation, including embryo cryopreservation from in vitro fertilization, oocyte cryopreservation from controlled ovarian hyperstimulation, and in vitro maturation of oocytes, are discussed. Surgical approaches such as conservative gynecologic surgery, ovarian transposition, and ovarian tissue cryopreservation are reviewed. Guidelines from the American Society for Reproductive Medicine and the American Society of Clinical Oncology classify these treatments into established and experimental procedures, and they provide the practitioner with an optimal approach to preserve the fertility of these patients before the initiation of their cancer therapies.

A comprehensive review of Ashermanʼs syndrome: causes, symptoms and treatment options

Purpose of review Intrauterine adhesions, also known as Ashermans syndrome, can have an impact on both reproductive outcomes and gynaecologic symptoms. Understanding the cause of intrauterine adhesions and the common clinical presentation will increase awareness of the condition and guide the patient to appropriate therapy. Surgical management offers favourable fertility outcomes and is often successful in restoring menstruation. Recent findings Surgical management with hysteroscopic lysis of adhesions is the gold standard for treatment and adopting an office-based approach offers several advantages. Prevention of reformation of adhesions remains challenging and no single method for preventing recurrence has shown superiority. Cell-based therapies using endometrial stem/progenitor cells hold promise for future use in regenerating inadequate endometrium. Summary Increased awareness of the symptoms suggestive of intrauterine adhesive disease, as well as recognition of common causes and preceding events, is crucial for early diagnosis, patient counselling and treatment. Video abstract http://links.lww.com/COOG/A36.

Benign vaginal villi noted at time of defibulation of female genital cutting.

BACKGROUND: Female genital cutting is a cultural practice in Africa and the Middle East. As more patients who have undergone this procedure are seen in the United States and undergo surgical revision of the scarred labia, new clinical findings will arise. CASE: At the time of surgical revision of female genital cutting, small clusters of villi were noted on the vaginal and labial mucosa of 3 patients. Pathological examination revealed benign-appearing papillary structures. These villi completely resolved by the 6-week postoperative visit. CONCLUSION: Female genital cutting may lead to a vaginal environment that predisposes women to benign changes in the vaginal mucosa that resolve after the closed (infibulated) labia are surgically revised.

Managing Postoperative Pain After Minimally Invasive Gynecologic Surgery in the Era of the Opioid Epidemic

In this review, we examine the evidence behind nonopioid medication alternatives, peripheral nerve blocks, surgical techniques, and postoperative recovery protocols that can help minimize and effectively treat postoperative pain after minimally invasive gynecologic surgery (MIGS). Because of the depth and heterogeneity of the data, a narrative review was performed of reported interventions. A comprehensive review was performed of PubMed, Embase, and the Cochrane Database with a focus on randomized controlled trials. In the absence of literature specific to benign gynecology, similar specialty or procedural data were reviewed. A variety of nonopioid medications, surgical techniques, and postoperative recovery protocols have shown significant improvements in postoperative pain after gynecologic surgery. Nonopioid medication options that are beneficial include acetaminophen, nonsteroidal anti-inflammatories, and antiepileptics. Incision infiltration with local anesthesia also significantly reduces pain. Surgically, minimally invasive approaches, reducing the laparoscopic trocar size to <10 mm, and evacuating the pneumoperitoneum at the end of the case all have significant benefits. Lastly, enhanced recovery pathways show promise in reducing pain after MIGS. By using a multimodal approach, minimally invasive gynecologic surgeons can help to minimize and manage postoperative pain with less reliance on opioid pain medications.

Opioid Use After Laparoscopic Hysterectomy: Prescribing Practices and Preoperative Predictors [5Q]

INTRODUCTION:Gynecologists can address the prescription opioid epidemic by prescribing appropriate quantities of postoperative opioids. Our goals were to measure opioid use after laparoscopic hysterectomy (LH) and to survey patients to identify factors that are predictive of higher opioid use.METHOD