Serene S. Srouji

Pregnancy outcomes following robot-assisted myomectomy

STUDY QUESTION What are the characteristics of the pregnancy outcomes in women undergoing robot-assisted laparoscopic myomectomy (RALM) for symptomatic leiomyomata uteri? SUMMARY ANSWER Despite a high prevalence of women with advanced maternal age, obesity and multiple pregnancy in our cohort, the outcomes are comparable with those reported in the literature for laparoscopic myomectomy. WHAT IS KNOWN ALREADY Reproductive outcomes after traditional laparoscopic myomectomy are well documented. However, reproductive outcomes following robotic myomectomy are not well studied. This paper describes the pregnancy outcomes for a large cohort of women after robotic myomectomy. STUDY DESIGN, SIZE, DURATION This is a retrospective cohort of women who became pregnant after robot-assisted myomectomy at three centers. Of the 872 women who underwent robotic myomectomy during the period October 2005-November 2010, 107 subsequently conceived resulting in 127 pregnancies and 92 deliveries through 2011. PARTICIPANTS/MATERIAL, SETTING, METHODS Women of reproductive age with fibroids who wanted a minimally invasive treatment option and desired uterine preservation were recruited. We conducted a multicentre study with three centers, two in a private practice and one in an academic setting. Pregnancy outcomes and their relationship to myoma characteristics were analyzed. MAIN RESULTS AND ROLE OF CHANCE Mean ± SD age at myomectomy was 34.8 ± 4.5 years and 57.4% [95% confidence interval (CI) 48.0, 66.3] of women were overweight or obese. The mean number of myomas removed was 3.9 ± 3.2 with a mean size of 7.5 ± 3.0 cm and mean weight of 191.7 ± 144.8 g. Entry of the myoma into the endometrial cavity occurred in 20.6% (95% CI 15.0, 27.7) of patients. The mean time to conception was 12.9 ± 11.5 months. Assisted reproduction techniques were employed in 39.4% (95% CI 32.6, 46.7) of these women. Seven twin pregnancies and two triplet pregnancies occurred, for a multiple pregnancy birth rate of 9.8% (95% CI 5.0, 17.8). Spontaneous abortions occurred in 18.9% (95% CI 13.0, 26.6). Preterm delivery prior to 35 weeks of gestational age occurred in 17.4% (95% CI 10.9, 26.5). One uterine rupture (1.1%; 95% CI 0.3, 4.7) was documented. Pelvic adhesions were discovered in 11.4% (95% CI 7.0, 18.0) of patients delivered by Cesarean section. Higher preterm delivery rates were significantly associated with a greater number of myomas removed and anterior location of the largest incision (compared with all other sites) in logistic regression analyses (P = 0.01). None of the myoma characteristics were related to spontaneous abortion. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION Given the retrospective nature of the data collection, some pregnancies may not have been captured. In addition, owing to the high prevalence of infertility patients in this cohort, the data cannot be used to counsel women who are undergoing RALM about fertility rates after surgery. GENERALIZABILITY TO OTHER POPULATIONS Prospective studies are needed to determine if the results shown in our cohort are generalizable to all women seeking a minimally invasive option for the conservative treatment of symptomatic fibroids with pregnancy as a desired outcome. STUDY FUNDING/COMPETING INTEREST(S) There was no funding source for this study.

Estrogen Negative Feedback on Gonadotropin Secretion: Evidence for a Direct Pituitary Effect in Women

CONTEXT Studies in humans and animals indicate that estrogen negative feedback occurs at the level of the hypothalamus, but it is unclear whether estrogen also exerts an inhibitory effect directly at the pituitary. OBJECTIVES The aim of the study was to determine whether estrogen has a direct negative feedback effect at the pituitary and whether this varies with aging. DESIGN AND SETTING A GnRH antagonist and graded doses of GnRH were used to isolate pituitary responsiveness before and after estrogen administration in Clinical Research Center studies at an academic medical center. SUBJECTS Subjects were healthy postmenopausal women aged 48-56 yr (n = 8) or 70-75 yr (n= 8). INTERVENTIONS A suppressive dose of the NAL-GLU GnRH antagonist was administered, followed by graded doses of GnRH before and after 1 month of estrogen administration. RESULTS LH and FSH responses to GnRH decreased after estrogen administration (P = 0.01 and P = 0.0001, respectively). The ratio of FSH to LH amplitudes decreased in response to estrogen (P = 0.04) indicating a greater sensitivity of FSH than LH to inhibition by estrogen. The inhibitory effect of estrogen on FSH was attenuated with aging (P = 0.02), but was maintained for LH (P = 0.4). CONCLUSIONS Studies that control for endogenous GnRH and estradiol demonstrate a direct pituitary site of estrogen negative feedback on LH and FSH responsiveness to GnRH in women. The effect of estrogen on FSH responsiveness is greater than on LH and is attenuated with aging. These studies indicate that estrogen negative feedback occurs directly at the pituitary and contributes to the differential regulation of FSH and LH secretion.

Robot-assisted laparoscopic myomectomy compared with standard laparoscopic myomectomy.

OBJECTIVE: To compare surgical outcomes of laparoscopic myomectomy and robot-assisted laparoscopic myomectomy. METHODS: Retrospective cohort study of 115 consecutive laparoscopic myomectomy and 174 consecutive robot-assisted laparoscopic myomectomy performed at Brigham and Womens Hospital over a period of 31 months. Uterine incisions were closed in multiple layers (running barbed suture was used for most cases in the laparoscopic myomectomy group). Surgical outcomes measured included operative time, estimated intraoperative blood loss, length of hospital stay, and perioperative complications. Odds ratios and 95% confidence intervals were calculated from multivariable logistic regression models; adjusted geometric means were estimated from linear regression models on logged outcomes because of skewed distributions. RESULTS: Surgical groups were similar in age, body mass index, and leiomyoma characteristics. Robot-assisted laparoscopic myomectomy had significantly longer operative time than laparoscopic myomectomy (adjusted geometric mean of 195.1 compared with 118.3 minutes, P<.001) and higher estimated blood loss (adjusted geometric mean of 110.0 compared with 85.9 mL, P=.04), but postoperative complications were similar. CONCLUSION: Robot-assisted laparoscopic myomectomy and laparoscopic myomectomy have similar operative outcomes in a high-volume surgical practice. Operative time and intraoperative estimated blood loss were significantly greater in the robot-assisted laparoscopic myomectomy group, but the level of statistical significance for intraoperative estimated blood loss was marginal and the clinical significance was undetermined. Use of barbed suture in the laparoscopic myomectomy group may account for these differences. LEVEL OF EVIDENCE: II

Risk of Leakage and Tissue Dissemination With Various Contained Tissue Extraction (CTE) Techniques: An in Vitro Pilot Study

STUDY OBJECTIVE To evaluate risk of leakage and tissue dissemination associated with various contained tissue extraction (CTE) techniques. DESIGN In vitro study (Canadian Task Force classification: II-1). SETTING Academic hospital simulation laboratory. INTERVENTION Beef tongue specimens weighing 400 to 500 g were stained using 5 mL indigo carmine dye and morcellated under laparoscopic guidance within a plastic box trainer. CTE was performed via 3 different techniques: a stitch-sealed rip-stop nylon bag and multi-port approach; a one-piece clear plastic 50 × 50-cm isolation bag and multi-port approach; or a 1-piece clear plastic 50 × 50-cm isolation bag and single-site approach. Four trials of each CTE method were performed and compared with an open morcellation control. All bags were insufflated to within 10 to 25 mmHg pressure with a standard CO2 insufflator. Visual evidence of spilled tissue or dye was recorded, and fluid washings of the box trainer were sent for cytologic analysis. MEASUREMENTS AND MAIN RESULTS Blue dye spill was noted in only 1 of 12 CTE trials. Spillage was visualized from a seam in 1 of the 4 stitch-sealed rip-stop nylon bags before morcellation of the specimen. The only trial in which gross tissue chips were visualized in the box trainer after morcellation was the open morcellation control. However, cytologic examination revealed muscle cells in the open morcellation washings and in the washings from the trial with dye spill. Muscle cells were not observed at cytologly in any of the other samples. CONCLUSION CTE did not result in any leakage or tissue dissemination with use of the single-site or multi-port approach when using a 1-piece clear plastic 50 × 50-cm isolation bag. Further studies are needed to corroborate these findings in an in vivo context and to evaluate use of alternate bag options for specimen containment.

Increased frequency of occult fragile X-associated primary ovarian insufficiency in infertile women with evidence of impaired ovarian function

BACKGROUND The FMR1 premutation is associated with overt primary ovarian insufficiency (POI). However, its prevalence in women with occult POI (i.e. menstrual cycles, but impaired ovarian response) has not been examined. We hypothesized that both the FMR1 premutation and intermediate allele is more frequent in infertile women with occult POI than in controls, and that a repeat length cutoff might predict occult POI. METHODS All subjects were menstruating women <42 years old and with no family history of unexplained mental retardation, autism or fragile X syndrome. Cases had occult POI defined by elevated FSH or poor response to gonadotrophin therapy (n = 535). Control subjects (n = 521) had infertility from other causes or were oocyte donors. Prevalence of the FMR1 premutation and intermediate alleles was examined and allele length was compared between controls and women with occult POI. RESULTS The frequency of the premutation (7/535 versus 1/521; P< 0.05) and intermediate alleles (17/535 versus 7/521; P< 0.05) was higher in women with occult POI than in controls. The allele with the greatest number of CGG repeats was longer in women with occult POI compared with controls (32.7 ± 7.1 versus 31.6 ± 4.3; P < 0.01). A receiver operating characteristic curve examining repeat length as a test for occult POI had an area of 0.56 ± 0.02 (P < 0.01). A repeat cutoff of 45 had a specificity of 98%, but a sensitivity of only 5% to identify occult POI. The positive predictive value was only 21% for a fertility population that has ∼ 22% of its patients with occult POI. CONCLUSIONS The data suggest that FMR1 premutations and intermediate alleles are increased in women with occult POI. Thus, FMR1 testing should be performed in these women as some will have fragileX-associated POI. Although the FMR1 repeat lengths were longer in women with occult POI, the data do not support the use of a repeat length cutoff to predict occult POI.

Techniques for contained morcellation in gynecologic surgery

OBJECTIVE To demonstrate 2 step-by-step techniques for contained morcellation of uterine tissue. DESIGN Instructional video showing laparoscopic electromechanical morcellation within an endoscopic pouch, and alternatively, tissue extraction via ultra-minilaparotomy. SETTING Academic medical center. PATIENT(S) Women undergoing laparoscopic myomectomy or hysterectomy. INTERVENTION(S) For contained electromechanical morcellation, the specimen is placed within an endoscopic pouch, the edges of which are exteriorized through a 15-mm cannula. The cannula is repositioned inside the pouch for insufflation. A bladed fixation trocar enters the pouch through an assistant port and is secured by its retention disk and balloon tip. Gas inflow is changed to this assistant port, through which the laparoscope is inserted. A power morcellator is introduced via the 15-mm port site, and morcellation thus proceeds within the containment system. Residual fragments of tissue are collectively retrieved by withdrawing the endoscopic pouch. For tissue extraction via ultra-minilaparotomy, the specimen is placed within a pouch that is drawn up through a flexible, self-retaining retractor seated in a 2 to 3-cm incision. The specimen is cored out sharply with a scalpel. MAIN OUTCOME MEASURE(S) None. RESULT(S) Contained morcellation is technically feasible, efficient (mean additional operative time is approximately 30 minutes), and prevents intraperitoneal dispersion of tissue fragments. Our group has safely performed >100 such procedures and removed specimens weighing nearly 1,500 grams. Potential complications include viscous injury upon insertion of the bladed trocar, and pouch failure. CONCLUSION(S) These techniques allow surgeons to adopt the new standard of contained morcellation and permit removal of extensive pathology with a minimally invasive approach.

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.

Aging Attenuates the Pituitary Response to Gonadotropin-Releasing Hormone

CONTEXT Complex changes in GnRH secretion occur with aging in women, but little is known about the effect of aging on the pituitary per se. OBJECTIVE The aim of the study was to determine whether pituitary responsiveness to GnRH is attenuated with aging. DESIGN AND SETTING A GnRH antagonist and graded doses of GnRH were used to isolate pituitary responsiveness in Clinical Research Center studies at an academic medical center. SUBJECTS Subjects were healthy postmenopausal women (PMW) aged 48-57 yr (n = 10) or 70-77 yr (n= 9). INTERVENTIONS A suppressive dose of the NAL-GLU GnRH antagonist (150 microg/kg sc) was administered and was followed by GnRH doses of 25, 75, 250, or 750 ng/kg iv every 4 h. RESULTS The LH response to GnRH was attenuated with aging (P = 0.05) with an interaction between age and dose (P = 0.01) such that the LH amplitude was less in older PMW at the higher doses (250 ng/kg, 50 +/- 9 vs. 29 +/- 4.9 IU/liter, for young and old PMW, respectively, P = 0.02; and 750 ng/kg, 97.7 +/- 11 vs. 70.2 +/- 9.3 IU/liter, P = 0.002), but not the lower doses of GnRH. The FSH response to GnRH was also attenuated with aging in PMW (P = 0.005). CONCLUSIONS In studies that isolated the pituitary from endogenous GnRH stimulation, aging attenuated the LH and FSH responses to exogenous GnRH in PMW. These studies indicate that the pituitary plays a role in the decline in gonadotropin levels with aging, further supporting the potential contribution of age-associated changes in both hypothalamic and pituitary function to reproductive senescence.

MRI-Guided Focused Ultrasound Surgery for Uterine Fibroid Treatment: A Cost-Effectiveness Analysis

OBJECTIVE. The purpose of this article is to evaluate the cost effectiveness of a treatment strategy for symptomatic uterine fibroids that uses MRI-guided focused ultrasound as a first-line therapy relative to uterine artery embolization (UAE) or hysterectomy. MATERIALS AND METHODS. We developed a decision-analytic model to compare the cost effectiveness of three first-line treatment strategies: MRI-guided focused ultrasound, UAE, and hysterectomy. Treatment-specific short- and long-term utilities, lifetime costs, and quality-adjusted life years (QALYs) were incorporated, allowing us to conduct an incremental cost-effectiveness analysis, using a societal willingness-to-pay (WTP) threshold of

Evidence That Increased Ovarian Aromatase Activity and Expression Account for Higher Estradiol Levels in African American Compared With Caucasian Women

50,000/QALY to designate a strategy as cost effective. Sensitivity analyses were subsequently performed on all key parameters. RESULTS. In the base-case analysis, UAE as a first-line treatment of symptomatic fibroids was the most effective and expensive strategy (22.75 QALYs;