Alternative facts and morcellation.

PURPOSE OF REVIEW: Since the recent black-box warning regarding the use of electromechanical morcellation, there has been a hesitancy to utilize the product and even to perform other types of morcellation by gynecologists. Unfortunately, this Food and Drug Administration action and the continued public criticisms of this procedure are grounded in poor data and faulty reasoning. To truly perform informed consent to patients considering procedures involving morcellation, a thorough review of the facts, not alternative facts, must be communicated. RECENT FINDINGS: Misrepresentation of the ethics surrounding this procedure, the role of informed consent and the risks and benefits as determined by evidence-based medicine have led to confusion and poor public policy. Today's evidence suggests that the procedure is indeed ethical when full disclosure of the risks and benefits is presented via informed consent. Risks of the procedure have been exaggerated significantly, and little attention has been paid to the risks of denying morcellation procedures to patients. Attempts to condemn gynecologists as acting contrary to established surgical principles do not coincide with facts. SUMMARY: Morcellation is a controversial technique which undoubtedly has a role as well as limitations. To appropriately determine if the procedure is indicated and acceptable to the patient, full disclosure of the best available evidence is necessary.

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.

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.

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.

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.

The use of high dose letrozole in ovulation induction and controlled ovarian hyperstimulation.

Letrozole, an aromatase inhibitor, has been demonstrated to be effective as an ovulation induction and controlled ovarian hyperstimulation agent. However, dose administration has generally been limited to 5 days at 2.5 to 7.5 mg daily. We undertook a retrospective review of over 900 treatment cycles using letrozole in doses as high as 12.5 mg per day. Results indicate that such doses do indeed offer benefit to patients; in that there is increased follicular growth and a higher number of predicted ovulations with higher doses of the drug. However, increasing doses does not produce a detrimental effect upon endometrial thickness. High-dose letrozole may be of value in women who fail to respond adequately to lower doses. Furthermore, randomized trials are needed to determine whether high-dose letrozole might actually be optimal as a starting dose for certain treatment groups.

The surgical treatment of fibroids for infertility.

Uterine fibroids are a major gynecologic disorder among women and commonly found in the infertile couple. Although numerous surgical techniques exist to destroy or remove these tumors, the role of such surgical procedures in the infertile woman has been heavily debated. The primary reason for this is a lack of evidence of a cause-and-effect relationship between fibroids and subfertility. However, review of the evidence suggests that submucous myomas and possibly intramural myomas both serve to decrease female fertility. A second reason for caution is concern over the impact of surgical treatment on fertility enhancement. For submucous myomas, hysteroscopic myomectomy has proven capable of increasing fertility rates, although this statement may not apply to type 2 submucous myomas. No evidence currently exists for a beneficial effect on fertility of surgical intervention for intramural or subserous fibroids. More randomized treatment trials are clearly needed to clarify the role of myomectomy and other procedures in the infertile woman with type 2 submucous and intramural myomas.

Fibroids and reproduction.

Uterine fibroids are commonly seen in women with reproductive disorders such as infertility, spontaneous abortion (SAB), and obstetric complications. Although it is certain that these tumors can occasionally cause such pathophysiology, it is critical to understand the rate of such occurrences, the degree of causality of the fibroids, and our ability to ameliorate the problems via surgical treatment. Evaluation of the available data is hampered by poor quality studies, heterogeneity of the disease, and confounding factors affecting outcomes. Nevertheless, the best available evidence suggests the following: (1) Submucous myomas decrease fertility and increase SAB rates; myomectomy is likely to be of value; (2) intramural myomas may decrease fertility, but the issue is less clear; they do seem to increase rates of miscarriage; there is no solid evidence that myomectomy restores the patient to normal; (3) subserosal myomas do not impair fertility but may enhance the rate of SAB; and (4) fibroids increase the risk of several obstetric complications, including cesarean delivery, malpresentation, postpartum hemorrhage, retained placenta, intrauterine growth retardation, preterm labor, placenta previa, and abruption. Higher quality studies are desperately needed to add confidence to these tenuous conclusions.

A call for more transparency of registered clinical trials on endometriosis.

In response to the pressing need for more efficacious and safer therapeutics for endometriosis, there have been numerous reports in the last decade of positive results from animal and in vitro studies of various compounds as potential therapeutics for endometriosis. A handful of these have undergone phase II/III clinical trials. Since the announcement of the International Committee of Medical Journal Editors that mandated registration as a prerequisite for publication, 57 endometriosis-related clinical trials have been registered at ClinicalTrials.gov, an Internet-based public depository for information on drug studies. Among them, 25 are listed as completed, and 2 as suspended. There are 15 completed phase II/III trials, which evaluated the efficacy of various promising compounds. Yet only three of the 15 trials (20%) have published their results. The remaining 12 (80%) studies so far have not published their findings. We argue that this apparent lack of transparency will actually not benefit the trial sponsors or the public, and will ultimately prove detrimental to research efforts attempting to develop more efficacious and safer therapeutics for endometriosis. Thus we call for more transparency of clinical trials on endometriosis.

Fibroids and infertility: an updated systematic review of the evidence.

OBJECTIVE: To investigate the effect of fibroids on fertility and of myomectomy in improving outcomes. DESIGN: Systematic literature review and meta-analysis of existing controlled studies. SETTING: Private center for Reproductive endocrinology and infertility. PATIENT(S): Women with fibroids and infertility. INTERVENTION(S): A systematic literature review, raw data extraction and data analysis. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, spontaneous abortion rate, ongoing pregnancy/live birth rate, implantation rate, and preterm delivery rate in women with and without fibroids, and in women who underwent myomectomy. RESULT(S): Women with subserosal fibroids had no differences in their fertility outcomes compared with infertile controls with no myomas, and myomectomy did not change these outcomes compared with women with fibroids in situ. Women with intramural fibroids appear to have decreased fertility and increased pregnancy loss compared with women without such tumors, but study quality is poor. Myomectomy does not significantly increase the clinical pregnancy and live birth rates, but the data are scarce. Fibroids with a submucosal component led to decreased clinical pregnancy and implantation rates compared with infertile control subjects. Removal of submucous myomas appears likely to improve fertility. CONCLUSION(S): Fertility outcomes are decreased in women with submucosal fibroids, and removal seems to confer benefit. Subserosal fibroids do not affect fertility outcomes, and removal does not confer benefit. Intramural fibroids appear to decrease fertility, but the results of therapy are unclear. More high-quality studies need to be directed toward the value of myomectomy for intramural fibroids, focusing on issues such as size, number, and proximity to the endometrium.