Morcellation for Gynecologic Surgery.

Morcellation is necessary for many women with fibroids who choose to undergo laparoscopic myomectomy or hysterectomy. After open and laparoscopic myomectomy, myometrial cells can be detected in the abdomen and pelvis. After morcellation, careful inspection for and removal of tissue fragments and copious irrigation and suctioning of fluid can remove residual tissue with or without the use of containment bags. Leiomyosarcoma has a poor prognosis because of early hematogenous metastasis and has a high propensity for recurrence despite the performance of total abdominal hysterectomy. Eliminating residual tissue in the pelvis and abdomen should be the goal after morcellation.

The prevalence of occult leiomyosarcoma in women undergoing presumed fibroid surgery and outcomes after morcellation.

PURPOSE OF REVIEW: To review the data-derived prevalence rates for occult leiomyosarcoma (LMS), and outcomes for women who have these tumors inadvertently morcellated. RECENT FINDINGS: In 2014, the Food and Drug Administration presented data showing the prevalence rates of occult LMS at 2.02/1000 surgeries for presumed benign fibroids. They also attributed poorer outcomes for women undergoing power morcellation of these tumors. Two more recent meta-analyses have shown much lower rates, as low as one in 8300 surgeries when including only prospective studies, and one in 1428 surgeries when including both prospective and retrospective studies. When looking at outcomes, both studies show no difference in outcomes when comparing power or any other type of morcellation. The most recent data suggest that even intact removal has no advantage when looking at mortality rates. SUMMARY: Prevalence of occult LMS remains quite rare, but outcomes after intact removal or any type of morcellation appear to be no different.

What is the Future of Open Intraperitoneal Power-Morcellation of Fibroids?

In November 2014, the Food and Drug Administration (FDA) calculated that for every 498 women having surgery for presumed fibroids, one woman would be found to have an occult leiomyosarcoma (LMS). The FDA issued a safety communication warning against the use of laparoscopic morcellators in the majority of women undergoing myomectomy or hysterectomy for treatment of fibroids. This communication was prompted by concern that if a patient had an occult LMS, the morcellator might spread tumor cells within the peritoneal cavity. We submit that the FDA directive was based on a flawed and misleading analysis. More rigorous evidence estimates the prevalence of LMS among women operated upon for presumed uterine fibroids at approximately one in 2000 women, significantly lower than the FDA's estimate. In addition, there is no reliable evidence that morcellation influences survival or that power-morcellation is inferior to vaginal or mini-lap morcellation with a scalpel. Recent publication shows that open surgery carries more risk for women when compared with minimally invasive surgery. Although the possibility of occult LMS should be considered by women and their gynecologists, we suggest that current morcellation techniques be continued for women who wish to benefit from minimally invasive surgery. Investigation into new and, hopefully, better morcellating devices may make the procedure safer for women.

Outcome of occult uterine leiomyosarcoma after surgery for presumed uterine fibroids: a systematic review.

There is concern that morcellation of occult leiomyosarcomas during surgery to treat presumed myomas may substantially worsen patient outcome. We reviewed the existing medical literature to better understand whether such a risk was demonstrable and, if so, what the magnitude of that risk might be. We identified 4864 articles initially, of which 60 were evaluated in full. Seventeen were found to have outcomes information and are included in this review. Six studies addressed the question of whether morcellation of occult leiomyosarcomas resulted in inferior outcomes as compared with en bloc uterine and tumor removal. In these 6 studies, results suggested that en bloc removal may result in improved survival and less recurrence; however, the data are highly biased and of poor quality. There is no reliable evidence that morcellation, power or otherwise, substantially results in tumor upstaging. There is no evidence from these 17 studies that power morcellation differs in any way from other types of morcellation or even simple myomectomy insofar as patient outcome. Whether electromechanical morcellation poses a unique danger to the patient with occult leiomyosarcoma is an unanswered question and one clearly in need of more extensive investigation before conclusions are drawn and policies created.

Intramural Leiomyomas and Fertility: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate fertility outcomes based on size and number of intramural leiomyomas and outcomes after removal. DATA SOURCES: Online searches: MEDLINE, ClinicalTrials.gov , PubMed, Cochrane Library, and PROSPERO Library from 1994 to 2023. METHODS OF STUDY SELECTION: A total of 5,143 studies were identified, with inclusion of 13 study groups. TABULATION, INTEGRATION AND RESULTS: Outcomes for size and number of leiomyomas were reported with clinical pregnancy rates and ongoing pregnancy or live-birth rates. In data sets with maximum leiomyoma diameters of less than 6 cm for study inclusion, women with leiomyomas smaller than 3 cm had lower clinical pregnancy rates than women without leiomyomas, with an odds ratio (OR) of 0.53 (95% CI, 0.38-0.76) and, for ongoing pregnancy or live-birth rates, an OR of 0.59 (95% CI, 0.41-0.86). The ORs for clinical pregnancy rates in women with intermediately-sized leiomyomas (those between 3 cm and 6 cm) were lower than in women without leiomyomas, with an OR at 0.43 (95% CI, 0.29-0.63) and, for ongoing pregnancy or live-birth rates, an OR at 0.38 (95% CI, 0.24-0.59). In data sets without exclusion for women with larger-sized leiomyomas, clinical pregnancy rates were lower for those with leiomyomas smaller than 5 cm compared with those without leiomyomas, with an OR of 0.75 (95% CI, 0.58-0.96). Women with leiomyomas larger than 5 cm showed no differences in clinical pregnancy rate compared with women without leiomyomas, with an OR of 0.71 (95% CI, 0.32-1.58). Although women with a single leiomyoma in any location had no differences in outcomes, those with more than one leiomyoma had lower clinical pregnancy rates and ongoing pregnancy or live-birth rates, with an OR of 0.62 (95% CI, 0.44-0.86) and 0.57 (95% CI, 0.36-0.88), respectively. The clinical pregnancy rate for women undergoing myomectomy for intramural leiomyomas was no different than those with intramural leiomyomas in situ, with an OR of 1.10 (95% CI, 0.77-1.59). CONCLUSION: Even small intramural leiomyomas are associated with lower fertility; removal does not confer benefit. Women with more than one leiomyoma in any location have reduced fertility.

Letrozole for ovulation induction and controlled ovarian hyperstimulation.

PURPOSE OF REVIEW: Letrozole, an aromatase inhibitor, is the newest addition to our armamentarium in the treatment of infertility. It is utilized in much the same way as clomiphene citrate, but with some additional benefits. In this review, the latest studies will be summarized with emphasis on dose, duration of use, safety, number of mature follicles, and pregnancy outcomes. RECENT FINDINGS: Letrozole has fewer side effects, and a shorter half-life than clomiphene citrate, and no demonstrable effect upon the receptivity of the endometrium. It is efficacious in treating women with chronic anovulation, unexplained infertility and diminished ovarian reserve. Its safety is superior to clomiphene citrate. Utilizing bio-equivalent doses, letrozole pregnancy rates are equal or superior to clomiphene citrate. Several studies suggest situations where it is more efficacious than gonadotropin treatment. SUMMARY: With further study, this drug could replace clomiphene citrate as the primary medication for chronic anovulation and/or unexplained infertility. It could augment or even obviate the use of gonadotropins in the treatment of women who have been unsuccessful in achieving pregnancy with clomiphene citrate. It may also be an adjunct for women with diminished ovarian reserve. Further studies are needed to determine optimal dosing and long term safety for women treated with the drug.

MR hysterosalpingography with an angiographic time-resolved 3D pulse sequence: assessment of tubal patency.

OBJECTIVE: The purpose of our study was to determine if tubal patency can be assessed by MR hysterosalpingography (HSG) using a clinically available MR angiographic sequence (3D time-resolved imaging of contrast kinetics [TRICKS]). This capability would enhance the value of MRI in women with infertility. CONCLUSION: MR HSG effectively shows tubal patency and can be considered when both conventional HSG and standard MRI are necessary for the evaluation of women with infertility, such as in women with suspected uterine anomalies or extrauterine disease.

Conservative surgical management of uterine myomas.

Uterine fibroids are a major gynecologic problem in American women, and several alternatives have been developed. Conservative treatment, with the goal of treating the fibroid but retaining the uterus, is a frequent choice among women who require therapy during their early to middle reproductive years. A variety of conservative surgical approaches exist; each has advantages and disadvantages for the clinician and the patient. Some are well-established techniques, whereas others are still in the investigational stage. None has been evaluated adequately for its effects on future fertility. To this end, it is imperative that investigators continue to evaluate these surgical procedures so that the clinician can provide accurate and comprehensive information when faced with a patient who desires one or more of these approaches. Furthermore, it is critical for the practitioner to stay informed about these procedures so that patients can be given a full complement of options.

U.S. Food and Drug Administration's Guidance Regarding Morcellation of Leiomyomas: Well-Intentioned, But Is It Harmful for Women?

The U.S. Food and Drug Administration (FDA) is warning against the use of laparoscopic power morcellators in the majority of women undergoing myomectomy or hysterectomy for the treatment of leiomyomas because of the concern for inadvertent spread of tumor cells if an undiagnosed cancer were present. The authors, representing a 45-member review group, reviewed the current literature to formulate prevalence rates of leiomyosarcoma in women with presumed leiomyomas and to asses reliable data regarding patient survival after morcellation. The authors disagree with the FDA's methodology in reaching their conclusion and provide clinical recommendations for care of women with leiomyomas who are planning surgery.

Angiogenic effects of norplant contraception on endometrial histology and uterine bleeding.

Norplant, a sc contraceptive device, releases levonorgestrel in a sustained fashion. Its effectiveness is offset by irregular bleeding patterns. Because vascular endothelial growth factor (VEGF) is stimulated by synthetic progestogens in vitro and in vivo, we postulated that correlations between this angiogenic factor and uterine bleeding patterns might exist. Twenty-eight women who were exposed to Norplant and 13 control women were prospectively followed for 6-8 months. Bleeding diaries were collected, hysteroscopies were performed, endometrial biopsies were obtained for standardized histological evaluation, and VEGF histochemical immunostaining (H)-scores were assigned. Cluster determination-34 (CD34) staining was also performed to quantify the number of endometrial blood vessels per high-power field. Irregular uterine bleeding was common among women using Norplant devices. Endometrial VEGF H-scores were greater in women using Norplant than in control women. New findings of this study show that vessel density did not correlate with epithelial VEGF H-scores but was highly associated with the intensity of stromal and perivascular VEGF. VEGF expression in the latter regions correlated significantly with hysteroscopic abnormalities and irregular bleeding. The expression of this angiogenic protein, particularly in the stromal and perivascular compartments, correlated with microvascular density, hysteroscopically documented hypervascularity, and uterine bleeding profiles. Irregular bleeding with Norplant use appears to reflect paracrine-mediated effects on vascular function by angiogenic factors, such as VEGF.

Management of postmenopausal hot flushes with venlafaxine hydrochloride: a randomized, controlled trial.

OBJECTIVE: To examine the efficacy of extended-release venlafaxine for the treatment of postmenopausal hot flushes. METHODS: Eighty postmenopausal women with more than 14 hot flushes per week were randomized to receive treatment with extended-release venlafaxine or placebo. Participants received 37.5 mg daily for 1 week, followed by 75 mg daily for 11 weeks. Daily hot flush severity scores and adverse effects were recorded by subjects. Baseline and monthly follow-up questionnaires assessed patient-perceived hot flush score, quality of life, and sexual function. Participants were treated for 12 weeks. RESULTS: Of the 80 subjects who enrolled in the study, 40 were in the treatment group and 40 in the control group. Of these, 61 completed the study (treatment, n = 29; control, n = 32). Subjective assessment at monthly visits of the effects of hot flush symptoms on daily living were significantly improved in the treatment group (P < .001). Hot flush severity scores based on daily diaries were somewhat lower in the treatment group, but the between-group difference did not reach statistical significance (P = .25). Three side effects, dry mouth, sleeplessness, and decreased appetite, were significantly more frequent in the venlafaxine group, but others, including dizziness, tremors, anxiety, diarrhea, and rash, were significantly less frequent. Ninety-three percent of participants in the venlafaxine group chose to continue treatment at the conclusion of the study. CONCLUSION: Extended-release venlafaxine, 75 mg per day, is an effective treatment for postmenopausal hot flushes in otherwise healthy women, based on a significant decrease in patient-perceived hot flush score.

Therapy for polycystic ovarian syndrome.

Polycystic ovarian syndrome is the most common endocrine disorder in women of reproductive age. Women with this disorder exhibit an array of disorders, including oligo-ovulation, hyperandrogenism, obesity, hyperlipidemia, infertility and insulin resistance. Of the sequelae that women experience, insulin resistance is associated with the most profound long-term morbidity. Initially, treatment regimens targeted specific symptomatology in these women, such as oligomenorrhea or hirsutism. With the discovery of the common association between insulin resistance and polycystic ovarian syndrome, however, we are able to utilize a new class of systemically targeted drugs that work on many of the symptoms found in these women.

The prevalence of occult leiomyosarcoma at surgery for presumed uterine fibroids: a meta-analysis.

There is a concern regarding the risk of occult leiomyosarcomas found at surgery for presumed benign fibroids. We sought to produce a comprehensive review of published data addressing this issue and provide high-quality prevalence estimates for clinical practice and future research. A comprehensive literature search using the PubMed/MEDLINE database and the Cochrane Library was performed. Inclusion criteria were human studies, peer-reviewed, with original data, involving cases for surgery in which fibroid-related indications were the primary reason for surgery, and histopathology was provided. Candidate studies (4864) were found; 3844 were excluded after review of the abstract. The remaining 1020 manuscripts were reviewed in their entirety, and 133 were included in the Bayesian binomial random effect meta-analysis. The estimated rate of leiomyosarcoma was 0.51 per 1000 procedures (95 % credible interval (CrI) 0.16-0.98) or approximately 1 in 2000. Restricting the meta-analysis to the 64 prospective studies resulted in a substantially lower estimate of 0.12 leiomyosarcomas per 1000 procedures (95 % CrI <0.01-0.75) or approximately 1 leiomyosarcoma per 8300 surgeries. Results suggest that the prevalence of occult leiomyosarcomas at surgery for presumed uterine fibroids is much less frequent than previously estimated. This rate should be incorporated into both clinical practice and future research.