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Neal G Mahutte

Publications and source records attributed to Neal G Mahutte.

10 recordsLinked to original sources

Medical management of endometriosis-associated pain.

In the coming years, basic science research into the mechanisms of endometriosis development and persistence almost certainly will open new avenues for treatment. A wide armamentarium of medical therapies already exists, however. The efficacy of most of these methods in reducing endometriosis-associated pain is well established. The choice of which to use depends largely on patient preference after an appropriate discussion of risks, side effects, and cost. Typically, oral contraceptives and NSAIDs are first-line therapy because of their low cost and mild side effects (Box 6). Because of its greater potential for suppressing endometrial development, consideration should be given to prescribing a low-dose monophasic oral contraceptive continuously. If adequate relief is not obtained or if side effects prove intolerable, consideration should be given to the use of progestins (oral, intramuscular, or IUD) or a GnRH agonist with immediate add-back therapy. Progestins are less expensive, but GnRH agonists with add-back may be better tolerated. If none of these medications proves beneficial or if side effects are too pronounced, then repeat surgery is warranted. The surgery may have analgesic value and serves to reconfirm the diagnosis. Finally, if endometriosis is identified at the time of surgery, then consideration should be given to prescribing medical therapy postoperatively.

Anti-Inflammatory Agents, Non-Steroidal↗

Increased pregnancy-associated plasma protein-A (PAPP-A) concentrations in peritoneal fluid of women with endometriosis.

PROBLEM: Pregnancy-associated plasma protein-A (PAPP-A) belongs to a group of glycoproteins isolated from extracts of human placenta. Healthy ovarian and uterine tissues are also known to express PAPP-A. We hypothesized that PAPP-A levels might also be elevated in the peritoneal fluid (PF) of women with endometriosis, and examined variations in PF PAPP-A during the menstrual cycle and with the severity of the disease. METHOD OF STUDY: PF PAPP-A were measured in 60 women with endometriosis and 38 women without endometriosis using a high-sensitivity immunofluorometric assay. RESULTS: We found that the mean level of PAPP-A was higher in PF from patients with endometriosis than controls (p = 0.003). Furthermore, significant correlation was found between the stages of endometriosis and the levels of PAPP-A in these patients (r = 0.39, p = 0.009). The concentrations of PAPP-A in PF were significantly higher in the secretory phase than the proliferative phase of the menstrual cycle in both women with and without endometriosis (p = 0.009 and P = 0.002, respectively). Finally, among the controls, women undergoing tubal ligation had significantly lower mean PF levels of PAPP-A than women with infertility or pelvic pain (p = 0.001). CONCLUSION: We conclude that PF levels of PAPP-A vary during the menstrual cycle, and are highest in the secretory phase. We also find that PF PAPP-A levels are significantly increased in women with endometriosis, and that the degree of elevation corresponds to the extent of disease.

Adult↗

Twenty-year history of endometriosis-associated pelvic pain: too much surgery or not enough?

A 36-year-old woman with a 20-year history of endometriosis-associated pelvic pain was a unique case from a total of 700 patients with endometriosis recently evaluated at Yale University. Her previous treatments included 11 surgical procedures related to pelvic pain or endometriosis. Multiple recurrences of endometriosis were documented. Although clearly an unusual case, our patient highlights the importance of using even the most advanced surgical techniques judiciously.

Adult↗

Increased levels of interleukin-15 in the peritoneal fluid of women with endometriosis: inverse correlation with stage and depth of invasion.

BACKGROUND: Interleukin (IL)-15 is a novel cytokine with immunoregulatory and angiogenic properties. We compared IL-15 levels in the peritoneal fluid (PF) of women with and without endometriosis. METHODS: PF samples were obtained from 55 women with endometriosis (23 with superficial peritoneal implants, 19 with deep endometriotic implants and 13 with ovarian endometriomas). Eighteen women with normal pelvic anatomy undergoing tubal sterilization served as controls. RESULTS: PF IL-15 concentrations were increased in women with endometriosis (2.7 +/- 0.5 pg/ml) versus controls (2.1 +/- 0.3 pg/ml; P < 0.001). However, IL-15 levels were higher in women with superficial peritoneal implants (2.9 +/- 0.5 pg/ml) than women with deep endometriotic implants (2.6 +/- 0.4 pg/ml; P = 0.01) or ovarian endometriomas (2.2 +/- 0.4 pg/ml; P < 0.001). IL-15 was also higher in women with deep implants than in those with endometriomas (P < 0.05). PF IL-15 correlated inversely with both depth of invasion (r = -0.52) and the stage of endometriosis (r = -0.42). PF IL-15 levels demonstrated little variation during the menstrual cycle, and did not discriminate between women with infertility or pelvic pain. CONCLUSION: PF IL-15 levels are increased in women with endometriosis. However, IL-15 levels are inversely correlated with the depth of invasion and disease stage, suggesting a possible role for this cytokine in the early pathogenesis of endometriosis.

Adult↗

Inverse correlation between peritoneal fluid leptin concentrations and the extent of endometriosis.

BACKGROUND: The role of leptin in reproductive processes has received increasing attention. Because leptin has intrinsic angiogenic properties, may be induced by inflammatory cytokines and induces matrix metalloproteinases, we examined peritoneal fluid (PF) leptin concentrations in women with endometriosis. METHODS: PF samples were collected from 60 women undergoing laparoscopy for endometriosis, and 18 controls undergoing tubal sterilization. Fifty of the women with endometriosis had received no prior hormonal treatment, while 10 with moderate- severe endometriosis were using GnRH agonists. RESULTS: Women with untreated endometriosis had significantly higher (mean +/- SD) PF leptin levels (34.9 +/- 7.9 ng/ml) than controls (17.9 +/- 4.1 ng/ml; P < 0.001). However, PF leptin levels were inversely correlated with the stage of disease (r = -0.62; P < 0.001). Nevertheless, women with stage III-IV endometriosis maintained significantly higher PF leptin levels (26.3 +/- 4.8 ng/ml; P < 0.001) than controls. Although PF leptin levels were significantly higher in the secretory versus proliferative phase of the menstrual cycle, they remained higher in both phases in women with untreated endometriosis. PF leptin levels in women on GnRH agonists were similar to controls. CONCLUSIONS: PF leptin levels are elevated in women with endometriosis, but inversely correlated with extent of disease. These findings suggest a potential role for leptin in the pathogenesis of peritoneal endometriosis.

Adult↗

Failed fertilization: is it predictable?

PURPOSE OF REVIEW: The purpose of this review is to critically examine the ability of screening tests to predict fertilization failure. RECENT FINDINGS: Failed fertilization occurs in 5-10% of in-vitro fertilization cycles and 2-3% of intracytoplasmic sperm injection cycles. Failed fertilization may result from impaired spermatozoa, oocyte deficiencies or defects in the in-vitro sperm/oocyte medium. In the in-vitro fertilization setting most cases are caused by male factor deficiencies, whereas failure of oocyte activation is the most common cause of failed fertilization after intracytoplasmic sperm injection. Although the standard semen analysis has limited ability to predict fertilization failure, strict sperm morphology criteria, sperm-zona binding ratios and zona pellucida induced acrosome reaction tests provide increased capacity to avoid this outcome. The quality of the semen sample on the day of oocyte retrieval and fertilization performance in previous in-vitro fertilization cycles may also guide the appropriate use of intracytoplasmic sperm injection. However, the routine use of the latter technique in cases of non-male factor infertility is contraindicated. SUMMARY: The ever improving techniques highlighted in this analysis offer improved ability to predict failed fertilization.

Female↗

Uterine chemokines in reproductive physiology and pathology.

PROBLEM: Chemokines are increasingly recognized as important regulators of uterine function. METHODS OF STUDY: The following is a review of uterine chemokines, especially monocyte chemotactic protein (MCP)-1, interleukin (IL)-8, and regulated-upon-activation normal-T-cell-expressed and -secreted (RANTES) protein, in reproductive physiology and pathology. RESULTS: It is increasingly clear that IL-8, MCP-1, RANTES and their receptors are produced by endometrial, myometrial, and trophoblast cell types in a timed and co-ordinated manner. In addition to the regulation of leukocyte migration and function, uterine chemokines also display specific roles in endometrial angiogenesis, apoptosis, proliferation, and differentiation. IL-8, MCP-1 and RANTES are regulated by local growth factors and cytokines such as tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, and IL-1. IL-8 takes part in cervical ripening and parturition. IL-8, MCP-1 and RANTES are also found at high levels in the peritoneal fluid of women with endometriosis. CONCLUSION: Co-ordination of chemokine-chemokine receptor interactions plays an important role in the menstrual cycle and successful pregnancy. Moreover, unbalanced chemokine expression contributes to pathologic conditions typified by uncontrolled cellular proliferation, migration and invasion.

Cervical Ripening↗

Poor responders: does the protocol make a difference?

An inadequate response to gonadotropins during in-vitro fertilization treatment may result in cycle cancellation, fewer embryos available for transfer and decreased pregnancy rates. For these reasons, numerous strategies to improve ovarian stimulation in poor responders have been proposed. These include variations in the type, dose and timing of gonadotropins, gonadotropin-releasing hormone agonists and gonadotropin-releasing hormone antagonists. Unfortunately, despite optimism generated by studies using retrospective controls, epidemiologically sound trials have been scarce. Indeed, of the three prospective randomized trials performed in poor responders to date no compelling advantage for one stimulation protocol over another has been established. Although this lack of improvement may reflect inadequate sample sizes, an alternative explanation is simply that the protocol, after a certain point, does not make a difference. Aside from oocyte donation, greater hope for poor responders may rest in aneuploidy screening, in-vitro oocyte maturation and cytoplasm/nuclear transfer.

Clinical Protocols↗

New advances in the understanding of endometriosis related infertility.

The association between endometriosis and infertility is complex. Nevertheless, in the absence of tubal distortion considerable evidence suggests four principle factors likely to contribute to subfertility. These include impaired folliculogenesis, decreased fertilization, inflammatory factors in follicular, peritoneal and reproductive tract fluid, and implantation defects. The potential impact of each of these is critically examined. The role of endometriomas, prior surgeries and donor oocytes is also discussed.

Embryo Implantation↗