The Impact of Fertility Goals on Long-term Quality of Life in Reproductive-aged Women Who Underwent Myomectomy versus Hysterectomy for Uterine Fibroids.

STUDY OBJECTIVE: The objective of this study is to compare quality of life (QOL) for myomectomy with hysterectomy 1 to 5 years after surgical management for fibroids. This study evaluated the difference in QOL in a population of women of reproductive age, including those who desire fertility. DESIGN: A retrospective cohort study. INTERVENTIONS: Not applicable. SETTING: A large academic hospital. PATIENTS: A total of 142 women who underwent hysterectomy or myomectomy in 2015 to 2020. Included patients were women aged 18 years or older who underwent surgical intervention owing to uterine fibroids. MEASUREMENTS AND MAIN RESULTS: The 36-Item Short Form Health Survey (SF-36) provides a total score as a single measure of health-related QOL. The Uterine Fibroid Symptom Quality of Life Questionnaire for Hysterectomy and Myomectomy (UFS-QOL) is a patient-reported outcome measure of fibroid symptoms and health-related QOL after hysterectomy and myomectomy. There was no significant difference in SF-36 QOL scores in women after myomectomy who desired fertility compared with those who did not desire fertility, except in the social functioning domain (p = .025). UFS-QOL scores in women after myomectomy who desired fertility were not significantly different compared with women after myomectomy who did not desire fertility (p = .37). There were no significant differences between women who underwent myomectomy and hysterectomy in overall QOL scores on the SF-36 (p = .13) and UFS-QOL scores (p = .16). CONCLUSION: Myomectomy is not associated with significant differences in measures of general health and QOL compared with hysterectomy, making it a viable fibroid management option for women who desire fertility. Our study highlights the importance of discussing fertility goals and QOL when counseling patients for surgical fibroid treatment.

A multimodal approach to reducing post-caesarean opioid use: a quality improvement initiative.

OBJECTIVE: To evaluate the impact of a QI initiative to reduce post-caesarean opioid use. DESIGN: Retrospective cohort study. SETTING: Academic hospital in the USA. POPULATION: Women over 18 years undergoing caesarean section. METHODS: A quality improvement (QI) initiative titled Reduced Option for Opioid Therapy (ROOT) was implemented in women undergoing caesarean section. The intervention included implementation of a postpartum order set maximising the use of scheduled NSAIDs and acetaminophen. Additionally, nursing education promoted non-opioid therapy as first-line, with opioids reserved for breakthrough pain. Performance feedback was provided to nursing staff on a bimonthly basis. Post-caesarean opioid use was reviewed in the 6 months before and after implementation of ROOT. MAIN OUTCOME MEASURES: The primary outcome was the total morphine milligram equivalents (MME) consumed during the postpartum admission. Secondary outcomes included opioid use per postoperative day, the proportion of opioid-free admissions, the percentage of patients discharged with a prescription for opioids, prescription size, and pain scores. RESULTS: Following implementation of ROOT, median inpatient opioid use decreased by more than 60%, from 75 to 30 MME per admission (P < 0.001). The proportion of opioid-free admissions increased from 12.6% pre-intervention to 30.7% post-intervention (P < 0.001). Additionally, the median opioid dose prescribed at discharge decreased in the post-intervention cohort, and the proportion of patients discharged without an opioid prescription increased. The reduction in opioids was associated with a slight decrease in patient-reported pain scores. CONCLUSIONS: Implementation of ROOT significantly reduced opioid use while achieving comparable pain control. TWEETABLE ABSTRACT: Nursing education, and use of an order set prioritising non-opioid analgesics reduces post-caesarean opioid use.

The impact of endometriosis on embryo morphokinetics: embryos from endometriosis patients exhibit delayed cell cycle milestones and decreased blastulation rates.

PURPOSE: To compare morphokinetic parameters in embryos obtained from women with and without endometriosis. METHODS: We evaluated a total of 3471 embryos resulting from 434 oocyte retrievals performed at a single academic center. One thousand seventy-eight embryos were obtained from women affected by endometriosis and 2393 came from unaffected controls. All embryos were cultured in a time-lapse incubator chamber for up to 6 days. IVF cycle outcomes and morphokinetic parameters collected prospectively were retrospectively reviewed. RESULTS: Morphokinetic data suggest that embryo development is impaired in embryos obtained from women with endometriosis (EE). EE were slower to achieve the 2-8 cell stages compared to control embryos (CE) (p < 0.001); additionally, time to compaction was delayed compared to CE (p = 0.015). The timing of late developmental events, including morulation and blastulation was also delayed in the endometriosis cohort (p < 0.001). In addition to demonstrating delayed cell cycle milestones, EE were less likely than controls to progress to morula, blastocyst, and expanded blastocyst stages (p < 0.001). Furthermore, a smaller proportion of embryos in the endometriosis group fell into optimal kinetic ranges for cc2 (p = 0.003), t5 (p = 0.019), tSB (p < 0.001), and tEB (p = 0.007). There were no significant differences in clinical pregnancy or live birth rates between groups. CONCLUSION: Embryos from endometriosis patients demonstrate impairments in both early and late developmental events, and progress to the morula, blastocyst, and expanded blastocyst stages at lower rates than control embryos. Despite these differences, IVF outcomes are similar for patients with and without endometriosis.

Characterizing the endometrial fluid cytokine profile in women with endometriosis.

PURPOSE: To compare growth factor and cytokine profiles in the endometrial secretions of patients with and without endometriosis to determine whether a particular protein profile is predictive of the disease. METHODS: Patients undergoing laparoscopic gynecologic surgery for benign indications were recruited for this prospective cohort study. Prior to surgery, endometrial fluid was aspirated and multiplex immunoassay was used to quantify 7 cytokines and growth factors. During surgery, each patient was staged according to the ASRM staging system for endometriosis. Cytokines and growth factors were evaluated using the Mann-Whitney and Kruskal-Wallis tests. Combinations of cytokines were evaluated using logistic regression analysis, and ROC curves were generated to evaluate the predictive capacity of the assay. RESULTS: Endometrial secretions were analyzed from 60 patients. Nineteen had stage 3-4 endometriosis, 19 had stage 1-2 disease, and 22 had no endometriosis. There were no significant differences between controls and stage 1-2 endometriosis; however, levels of IL-1α and IL-6 were significantly increased in women with moderate-to-severe disease. A combination of IL-1α, IL-1ß, and IL-6 in endometrial secretions predicts stage 3-4 endometriosis with an AUC of 0.78. A threshold value of 118 pg/mL yields a sensitivity of 75% and specificity of 70%. CONCLUSION: Aspiration of endometrial fluid is a safe and effective approach for evaluating the endometrial profile of women with endometriosis. Women with moderate-to-severe endometriosis demonstrate a distinct cytokine profile compared to controls. A combination of IL-1α, IL-1ß, and IL-6 in the endometrial secretions is predictive of stage 3-4 endometriosis, but is not predictive of minimal-to-mild disease.

Preservation of gonadal function in women undergoing chemotherapy: a systematic review and meta-analysis of the potential role for gonadotropin-releasing hormone agonists.

PURPOSE: To evaluate the available randomized controlled trials (RCTs) in the literature investigating the use of gonadotropin-releasing hormone agonist (GnRHa) co-treatment for ovarian preservation in women receiving chemotherapy. METHODS: A systematic review of the literature was performed from 1960 through 2017 to identify relevant RCTs. Included patients had lymphoma, ovarian cancer, or breast cancer. The primary outcome was the proportion of women who retained ovarian function after chemotherapy. Extracted data points included study design, patient characteristics, and proportion of women who developed premature ovarian failure (POF). A risk of bias assessment was performed according to the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. The pooled odds ratio was calculated, and outcomes of individual studies were compared using the random-effects model with the inverse-variance method and the DerSimonian-Laird estimator. RESULTS: Twenty-nine RCTs were identified, and 10 met criteria for inclusion in the meta-analysis. An analysis of patients who did not develop POF after chemotherapy revealed eight studies supporting the use of GnRHa (OR 1.83; 95% CI 1.34-2.49). The duration of benefit of GnRHa is unclear. An analysis of three studies with outcome data at 2 years revealed a non-significant OR of 0.53 (95% CI 0.22-1.30) for the preservation of ovarian function with GnRHa treatment. CONCLUSION: GnRHa may have a protective effect against the development of POF after gonadotoxic chemotherapy; however, the duration of benefit is unclear and requires further study.

Oncofertility program implementation increases access to fertility preservation options and assisted reproductive procedures for breast cancer patients.

BACKGROUND AND OBJECTIVES: Breast cancer treatment can cause premature ovarian failure, yet the majority of young cancer patients do not receive adequate education about treatment effects before initiating chemotherapy. We studied the impact of an oncofertility program on access to fertility preservation. METHODS: An oncofertility program was initiated to foster collaboration between oncologists and reproductive endocrinologists, and to help increase access to fertility preservation. Documented conversations about fertility concerns, specialist referrals, appointments, and fertility preservation procedures were compared between breast cancer patients from 2004 to 2006, before oncofertility program initiation, and 2007-2012, after program initiation. The study included women <45, stages 0-III, diagnosed before (n = 278) and after (n = 515) program initiation. RESULTS: Demographics for the cohorts were similar. Fertility discussions (P < 0.0001), patients interested in maintaining fertility at diagnosis (P = 0.0041), referrals to reproductive endocrinologists (P < 0.0001), appointments (P < 0.0001), and fertility preservation procedures (P < 0.0183) increased significantly after programmatic implementation. CONCLUSIONS: An oncofertility program increased discussions about fertility preservation and access to assisted reproductive procedures. This program positively impacted compliance with national guidelines advising reproductive-age cancer patients to be offered fertility preservation counseling as an initial component of the multidisciplinary care plan. J. Surg. Oncol. 2017;115:116-121. © 2016 Wiley Periodicals, Inc.

Comparison of Radiation Exposure for Pregnant Patients Requiring Intervention for Suspected Obstructing Nephrolithiasis.

OBJECTIVE: To identify the differences in radiation exposure per suspected stone episode between percutaneous nephrostomy tube (PCN), stent, and primary ureteroscopy (URS).The incidence of nephrolithiasis in pregnancy is low; however, repercussions for both mother and fetus can be significant. In cases of suspected obstructing nephrolithiasis, intervention may be required, including ureteral stent, PCN, or URS, with the potential for multiple subsequent procedures that often utilize fluoroscopy. METHODS: Pregnant patients who required an intervention (stent, PCN, or URS) for suspected obstructing nephrolithiasis were retrospectively reviewed. The primary outcome was total fluoroscopy exposure per suspected stone episode. Secondary outcomes included fluoroscopic exposure per procedure and number of procedures required. RESULTS: After excluding patients with renal anomalies and incomplete radiation data, 78 out of 100 patients were included in the analysis. Forty patients (51.3%) underwent initial stent placement, 22 (28.2%) underwent initial PCN placement, and 16 (20.5%) underwent primary URS. Total mean radiation exposure per stone episode was significantly higher in patients who underwent PCN, (286.9 mGy vs 3.7 mGy (stent) and 0.2 mGy (URS), P <.001). In addition, patients who underwent initial PCN placement had significantly more procedures (P <.001) and mean radiation exposure per procedure was higher (P <.001). More than 40% of PCNs experienced dysfunction, and mean duration between PCN exchanges was 16.5 days. CONCLUSION: In pregnant patients with suspected obstructing nephrolithiasis requiring intervention, initial PCN placement was associated with a significantly higher number of procedures, radiation exposure per procedure, and total radiation exposure per suspected stone episode compared to stent and URS.

Uncommon Surgical Emergencies in the Adult Gynecologic Patient: Two Cases of Missed Diagnosis of Outflow Tract Obstruction from Congenital Uterine Anomalies.

Gynecologic emergencies may result from congenital uterine anomalies (CUAs) with outflow tract obstruction. Not limited to the "classic" presentation of an adolescent amenorrheic pain patient, such anomalies should be part of the differential diagnosis for adult female patients presenting with severe pelvic pain. Obstructed rudimentary noncommunicating cavitary horns may result in severe chronic or acute pain and necessitate urgent surgical management. While two-dimensional (2D) ultrasound is often the initial diagnostic tool, three-dimensional (3D) ultrasound and MRI can accurately delineate CUAs for definitive diagnosis. When excision of a rudimentary horn is required, a laparoscopic approach is preferable. This case series focuses on two adult patients with severe pelvic pain due to unicornuate uteruses with obstructed noncommunicating cavitated rudimentary horns. Both cases involve a delayed diagnosis, the inability to make the diagnosis at standard surgical observation, and the resultant need for urgent surgical management.

Reproductive Longevity and Aging: Geroscience Approaches to Maintain Long-Term Ovarian Fitness.

Increases in delayed childbearing worldwide have elicited the need for a better understanding of the biological underpinnings and implications of age-related infertility. In women 35 years and older the incidences of infertility, aneuploidy, and birth defects dramatically increase. These outcomes are a result of age-related declines in both ovarian reserve and oocyte quality. In addition to waning reproductive function, the decline in estrogen secretion at menopause contributes to multisystem aging and the initiation of frailty. Both reproductive and hormonal ovarian function are limited by the primordial follicle pool, which is established in utero and declines irreversibly until menopause. Because ovarian function is dependent on the primordial follicle pool, an understanding of the mechanisms that regulate follicular growth and maintenance of the primordial follicle pool is critical for the development of interventions to prolong the reproductive life span. Multiple pathways related to aging and nutrient-sensing converge in the mammalian ovary to regulate quiescence or activation of primordial follicles. The PI3K/PTEN/AKT/FOXO3 and associated TSC/mTOR pathways are central to the regulation of the primordial follicle pool; however, aging-associated systems such as the insulin-like growth factor-1/growth hormone pathway, and transsulfuration/hydrogen sulfide pathways may also play a role. Additionally, sirtuins aid in maintaining developmental metabolic competence and chromosomal integrity of the oocyte. Here we review the pathways that regulate ovarian reserve and oocyte quality, and discuss geroscience interventions that leverage our understanding of these pathways to promote reproductive longevity.

Late-life intermittent fasting decreases aging-related frailty and increases renal hydrogen sulfide production in a sexually dimorphic manner.

Global average life expectancy continues to rise. As aging increases the likelihood of frailty, which encompasses metabolic, musculoskeletal, and cognitive deficits, there is a need for effective anti-aging treatments. It is well established in model organisms that dietary restriction (DR), such as caloric restriction or protein restriction, enhances health and lifespan. However, DR is not widely implemented in the clinic due to patient compliance and its lack of mechanistic underpinnings. Thus, the present study tested the effects of a somewhat more clinically applicable and adoptable DR regimen, every-other-day (EOD) intermittent fasting, on frailty in 20-month-old male and female C57BL/6 mice. Frailty was determined by a series of metabolic, musculoskeletal, and cognitive tasks performed prior to and toward the end of the 2.5-month dietary intervention. Late-life EOD fasting attenuated overall energy intake, hypothalamic inflammatory gene expression, and frailty in males. However, it failed to reduce overall caloric intake and had a little positive effect in females. Given that the selected benefits of DR are dependent on augmented production of the gasotransmitter hydrogen sulfide (H2S) and that renal H2S production declines with age, we tested the effects of EOD fasting on renal H2S production capacity and its connection to frailty in males. EOD fasting boosted renal H2S production, which positively correlated with improvements in multiple components of frailty tasks. Therefore, late-life initiated EOD fasting is sufficient to reduce aging-related frailty, at least in males, and suggests that renal H2S production capacity may modulate the effects of late-life EOD fasting on frailty.

A review of the pathophysiology of recurrent implantation failure.

Implantation is a critical step in human reproduction. The success of this step is dependent on a competent blastocyst, receptive endometrium, and successful cross talk between the embryonic and maternal interfaces. Recurrent implantation failure is the lack of implantation after the transfer of several embryo transfers. As the success of in vitro fertilization has increased and failures have become more unacceptable for patients and providers, the literature on recurrent implantation failure has increased. While this clinical phenomenon is often encountered, there is not a universally agreed-on definition-something addressed in an earlier portion of this Views and Reviews. Implantation failure can result from several different factors. In this review, we discuss factors including the maternal immune system, genetics of the embryo and parents, anatomic factors, hematologic factors, reproductive tract microbiome, and endocrine milieu, which factors into embryo and endometrial synchrony. These potential causes are at various stages of research and not all have clear implications or immediately apparent treatment.

The role of pharmacotherapy in the treatment of endometriosis across the lifespan.

INTRODUCTION: Endometriosis is estimated to affect 10% of reproductive-aged women. The gold standard for treatment is surgery; however, surgery carries a significant morbidity and cost burden. There is an ongoing need for safe, effective medical therapies for endometriosis patients, both in conjunction with and independent of surgical interventions. Most conventional therapies for endometriosis work by a similar mechanism, and efficacy is variable. In recent years, there has been increased interest in the development and testing of novel pharmacotherapies for endometriosis. AREAS COVERED: This review discusses both conventional and emerging treatments for endometriosis. The authors present the application of these drugs in different presentations of endometriosis across the lifespan and discuss how emerging therapies might fit into future medical management of endometriosis. Conventional therapies include nonsteroidal anti-inflammatory drugs, combined oral contraceptives, progestins, GnRH agonists/antagonists, and aromatase inhibitors. Emerging therapies are focused on disease-specific targets such as endothelial growth factor receptors. EXPERT OPINION: The field of endometriosis therapy is moving toward modifying the immune and inflammatory milieu surrounding endometrial implants. If these drugs show efficacy in clinical trials, combining them with current medical treatment is expected to result in a profound impact on symptom and disease burden for patients who suffer from endometriosis worldwide.

Fertility Preservation in Women With Endometriosis.

Infertility affects 30% to 50% of women with endometriosis. Women with endometriosis are at risk of decreased ovarian reserve, both because of the pathophysiology of the disease and iatrogenic injury resulting from surgical intervention. Fertility preservation must occur at multiple levels, including careful selection of surgical candidates, avoidance of repeat procedures, and meticulous surgical technique. Fertility preservation with oocyte or ovarian tissue cryopreservation may be considered on an individual basis for women with endometriosis, particularly those at risk of bilateral ovarian injury, such as women with bilateral endometriomas.

Role of robotic surgery in treating fibroids and benign uterine mass.

Fibroid uterus can be managed medically, surgically, or through non-extirpative procedures, depending on the clinical situation. Myomectomy may be beneficial, especially to those desiring to preserve the uterus and/or fertility, with outcomes comparable to those of hysterectomy, with a laparoscopic approach being favored when feasible. For definitive therapy, hysterectomy can be pursued where the surgical approach should be individualized. Comparison of robotic-assisted laparoscopic approach shows that the robotic approach may be favored for cases with higher complexity and multiple fibroids in myomectomy; however, no clear advantage is seen with hysterectomy at this time, necessitating further research in the area of robotics for hysterectomy in benign uterine mass treatment to justify the cost.

Bowel injury in gynecologic laparoscopy: a systematic review.

OBJECTIVE: To evaluate the incidence of bowel injury in gynecologic laparoscopy and determine the presentation, mortality, cause, and location of injury within the gastrointestinal tract. DATA SOURCES: The PubMed, EMBASE, ClinicalTrials.gov, and Cochrane Library databases were searched. Additional studies were obtained from references of retrieved papers. METHODS OF STUDY SELECTION: Included retrospective studies and randomized controlled trials reported the incidence of bowel injury in gynecologic laparoscopy. Studies were excluded if they were not in English or duplicated data. TABULATION, INTEGRATION, AND RESULTS: Two reviewers extracted data in duplicate from each study regarding incidence, cause, and location of bowel injury. Ninety studies published between 1972 and 2014 met eligibility criteria, representing 474,063 gynecologic laparoscopies. Six hundred four bowel injuries were reported for an incidence of 1 in 769 (0.13%, 95% confidence interval [CI] 0.12-0.14%). The rate of bowel injury varied by procedure, ranging from 1 in 3,333 (0.03%, 95% CI 0.01-0.03%) for sterilization to 1 in 256 (0.39%, 95% CI 0.34-0.45%) for hysterectomy. The small intestine was the most frequently damaged region of the gastrointestinal tract, representing 166 of 354 (47%) injuries. The majority of bowel injuries occurred during abdominal access and insufflation obtained using a Veress needle or trocar placement (201/366, 55% of injuries). Although most bowel injuries were recognized intraoperatively, diagnosis was delayed by more than 1 day in 154 of 375 cases (41%, 95% CI 36-46%). Bowel injuries were managed primarily by laparotomy (80%). Mortality occurred after bowel injury in 5 of 604, or 1 of 125 (0.8%, 95% CI 0.36-1.9%) cases. All deaths occurred as a result of delayed recognition of bowel injury (n=154), making the mortality rate for unrecognized bowel injury 5 in 154 or 1 in 31 (3.2%, 95% CI 1-7%). There were no deaths associated with intraoperatively diagnosed bowel injury. CONCLUSION: The overall incidence of bowel injury in gynecologic laparoscopy is 1 in 769 but increases with surgical complexity. Delayed diagnosis is associated with a mortality rate of 1 in 31.

Impact of Fertility Concerns on Tamoxifen Initiation and Persistence.

BACKGROUND: Adjuvant tamoxifen reduces breast cancer recurrence risk and mortality; however, initiation and treatment persistence are poor for younger patients. We hypothesized that a unique set of factors, including fertility concerns, would contribute to the poor tamoxifen use among premenopausal patients. METHODS: From 2007 to 2012, 515 premenopausal patients younger than age 45 years, with stage 0 to III hormone receptor-positive breast cancer, for whom tamoxifen was recommended, were identified. Clinical and pathologic tumor characteristics, treatment regimens, and fertility concerns were recorded. Clinical factors associated with tamoxifen noninitiation and discontinuation were identified using univariate and multivariable analysis. After the recommendation for tamoxifen, patient reasons for tamoxifen noninitiation or discontinuation were also documented. All statistical tests were two-sided. RESULTS: Based on multivariable analysis, fertility concerns were statistically associated with both noninitiation (odds ratio = 5.04, 95% confidence interval (CI) = 2.29 to 11.07) and early discontinuation (hazard ratio = 1.78, 95% CI = 1.09 to 3.38) of tamoxifen. Other independent predictors of noninitiation included a diagnosis of ductal carcinoma in situ, declining radiation, and not receiving chemotherapy (stage I-III). Additionally, smoking and not receiving radiation therapy were statistically significant predictors of early withdrawal from therapy. Primary patient reasons for noninitiation and early discontinuation included concerns about side effects and fertility. CONCLUSION: This study provided insight into factors associated with tamoxifen use for reproductive-aged breast cancer survivors, with a new focus on fertility. Fertility concerns negatively impacted tamoxifen initiation and continuation among premenopausal patients. Interventions to optimize treatment initiation and persistence for young cancer patients should include access to fertility preservation options.