Cecilia T. Valdes

Surgical treatment of symptomatic colorectal endometriosis

The approach to the treatment of bowel endometriosis has varied greatly. In this paper we present 77 consecutive patients with deep colorectal endometriosis treated with a full-thickness resection. Gynecologic procedures included conservative laparotomies for preserving fertility (39 patients); hysterectomy with bilateral salpingo-oophorectomy (29 patients); bilateral salpingo-oophorectomy (2 patients); left salpingo-oophorectomy (1 patient) and resection of pelvic endometriosis in patients with previous ablative surgery (6 patients). A low anterior bowel resection was performed in 68 patients (88.3%); a disc excision of the anterior rectal wall in 5 (6.5%); sigmoid resection in 3 (3.9%), and partial cecal resection in 1 (1.3%). The postoperative febrile morbidity was 10.4%, with no apparent anastomotic leaks. Of 33 patients who attempted to conceive postoperatively, 13 achieved a term pregnancy (39.4%). Complete relief of pelvic symptoms was obtained in 38 patients (49.4%); improvement in 30 (39%); no improvement in 8 (10.4%); and worsening of symptoms in 1 (1.2%). There has been no recurrence of symptomatic bowel endometriosis during 1 to 9 years of follow-up. Full-thickness resection of the colon for the treatment of deep bowel endometriosis is a safe procedure with low morbidity, good postoperative relief of symptoms, and favorable pregnancy rates.

Insulin resistance improves in hyperandrogenic women treated with Lupron

OBJECTIVE To examine if changes in insulin sensitivity and glucose effectiveness in women with polycystic ovarian disease (PCOD) occurred after ovarian androgen suppression with a GnRH agonist, leuprolide acetate (LA, Lupron; TAP Pharmaceuticals, Deerfield, IL) using the minimal model method. DESIGN Twelve patients with PCOD were tested in the untreated state (baseline) and after 6 weeks of LA treatment. Subjects were divided into two groups based on the degree of impairment of their baseline insulin sensitivity index (SI; (min-1) (microU/mL-1): mild insulin resistance (SI > 1) or severe insulin resistance (SI < 1). RESULTS In all patients, serum T was significantly decreased from elevated baseline levels to normal female concentrations after 6 weeks of LA therapy. Insulin sensitivity in PCOD patients with mild insulin resistance significantly improved from baseline after 6 weeks of LA therapy, whereas no change in SI on LA therapy was seen in PCOD women with severe insulin resistance. Glucose utilization independent of increased insulin secretion did not change as a function of LA treatment in either group. CONCLUSION These findings indicate a significant improvement in SI in mildly insulin-resistant women with PCOD after suppression of ovarian function with LA treatment.

Ultrasound evaluation of female genital tract anomalies: a review of 64 cases

Sixty-four patients with an ultrasound diagnosis of an anomaly of the female genital tract were studied retrospectively to determine the accuracy and usefulness of sonographic examination of these anomalies in the pregnant (64%) and the nonpregnant (36%) patient. Ultrasound diagnoses in 46 patients with follow-up included: (1) bicornuate/septate uterus in 21 cases, (2) uterus didelphys in 18 cases, (3) cervical and vaginal atresia in three cases, (4) obstructed lower but normal upper genital tract in two cases, and (5) abnormal-appearing uterus in two cases. Ultrasound diagnosis was compared with hysterosalpingographic and/or surgical findings in 43 patients and with physical examination in three patients. Scan results were classified as diagnostic in 26%, confirmatory in 63%, and incorrect in 11%. Ultrasound is a reliable clinically useful method of studying genital tract anomalies in gynecologic patients.

Hypoparathyroidism and T cell immune defect in a patient with 10p deletion syndrome

At least a dozen cases of partial deletion of the short arm of chromosome 10 have been described since the first report in 1975) Pertinent physical findings in these children include down-slanting palpebrai fissures, ear anomalies, frontal bossing, micrognathia, and developmental delay. We report an additional child with 10p deletion who initially presented with hypocalcemia and was later discovered to have a T cell defect. Whether or not this immune defect is categorized as partial DiGeorge syndrome, this patient does have an immune defect primarily involving the T cell system, associated with a chromosomal deletion.

Short-term Lupron or danazol therapy for pelvic endometriosis * † ‡

OBJECTIVE To compare the efficacy of a 3-month trial of leuprolide acetate (LA; Lupron; TAP Pharmaceuticals, Deerfield, IL) versus danazol (Danocrine; Scenofi Winthrup Pharmaceuticals, New York, NY) therapy on laparoscopically proven endometriosis. DESIGN Endometriosis severity was assessed at the time of laparoscopy and patients were randomized to receive 0.1 mg SC LA (n = 22) or 800 mg danazol orally (n = 18) daily for 3 months. A second laparoscopy and/or laparotomy was performed to assess the change in the extent of endometriosis and for surgical therapy. SETTING Private practice at a university-affiliated hospital. PATIENTS Forty patients with mild, moderate, or severe endometriosis. Ten patients were excluded. INTERVENTION Three-month treatment randomly assigned to either LA or danazol. MAIN OUTCOME MEASURES Prospective measurement of American Fertility Society endometriosis scores and size of ovarian endometriomata before and after therapy via laparoscopy. RESULTS The mean endometriosis score including adhesions decreased significantly from 36 +/- 4.9 to 29 +/- 5.0 (mean +/- SEM) with LA and from 34 +/- 6.4 to 29 +/- 6.5 with danazol. The mean laparoscopic endometriosis score not including adhesions decreased from 27 +/- 3.5 to 22 +/- 3.4 with LA and 22 +/- 3.5 to 19 +/- 3.1 with danazol. Seven of 18 (39%) endometriomata responded to LA and 6 of 15 (40%) endometriomata responded to danazol. CONCLUSION We conclude that both danazol and LA will reduce endometriosis scores after a 3-month course of therapy. Larger clinical trials are needed to compare short courses of therapy with the more established 6-month trials. A 3-month versus a 6-month course of therapy offers obvious benefits including decreased cost and decreased side effects.

ANDROGEN RESPONSES TO ACUTELY INCREASED ENDOGENOUS INSULIN LEVELS IN HYPERANDROGENIC AND NORMAL CYCLING WOMEN

We examined androgen responses in hyperandrogenic (polycystic ovarian disease [PCOD]) and normal women after an acute endogenous insulin elevation. Standard intravenous glucose tolerance tests (IVGTTs), modified to include a tolbutamide injection 20 minutes after IVGTTs, were performed. Polycystic ovarian disease patients were studied in the untreated state, after 6 weeks of ovarian androgen suppression with leuprolide acetate, after a 6-week rest period, and after 6 weeks of antiandrogen therapy with spironolactone. Normal menstruating women were studied during the early follicular, midcycle, and luteal phases of a single cycle. An acute rise in insulin did not alter serum testosterone or androstenedione levels in PCOD or normal women. A significant rise in dehydroepiandrosterone sulfate after modified IVGTTs was found in both hyperandrogenic and normal cycling women. Although these results are not supportive of the theory that insulin acts on the ovary to stimulate androgen production, they may be because of the short time course of insulin elevation that occurs during an IVGTT.

Diabetes-Induced Alterations of Reproductive and Adrenal Function in the Female Rat

Diabetes interferes with reproductive function in laboratory animals. Previous studies in female diabetic rats have not resolved if the reproductive abnormalities observed are at the hypothalamic, pituitary and/or ovarian level. The interaction of the gonadal and adrenal axes has not been studied in the diabetic female rat. The purpose of this study is twofold: first, to determine the level of dysfunction in the hypothalamic-pituitary axis caused by diabetes in the adult female rat controlling for stage of the estrous cycle, and, second, to evaluate basal corticosterone secretion in female diabetic rats. Sixty cycling 40-day-old female rats were randomly assigned to 3 groups; control (n = 32), diabetic (n = 14), and diabetic insulin-replaced animals (n = 14). The level of hyperglycemia in each group was documented by glycosylated hemoglobin levels and biweekly blood glucoses. Three weeks after induction of diabetes, pituitary luteinizing hormone (LH) responsiveness following an i.v. injection of gonadotropin-releasing hormone (GnRH) was assessed in representative diestrous rats from each group. All animals were sacrificed in either diestrus or proestrus for determination of GnRH concentration in the hypothalamus, LH and follicle-stimulating hormone (FSH) content in pituitary and LH, FSH, estradiol and corticosterone in serum. Uterine weight to body weight ratios (a bioassay for estrogen) were also calculated. Hypothalamic GnRH concentration was significantly lower in diabetic versus control diestrous rats. Basal pituitary and serum gonadotropin levels were not different between any groups. GnRH-stimulated serum LH levels were higher in diabetic vs. control and diabetic insulin-treated animals. LH surges occurred in the control and diabetic insulin-replaced but not the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced Inflammatory Transcriptome in the Granulosa Cells of Women With Polycystic Ovarian Syndrome

CONTEXT Polycystic ovarian syndrome (PCOS), the most common endocrine disorder of reproductive-aged women, is associated with systemic low-grade inflammation. OBJECTIVE We propose that increased or altered intrafollicular inflammatory reactions also occur in periovulatory follicles of PCOS patients. DESIGN Gene profiling and quantitative PCR (qPCR) analyses in granulosa-lutein cells (GCs) collected from PCOS and non-PCOS women undergoing in vitro fertilization were compared with serum and follicular fluid (FF) levels of cytokines and chemokines. SETTING This was a university-based study. PATIENTS Twenty-one PCOS and 45 control patients were recruited: demographic, hormone, body mass index, and pregnancy outcomes were abstracted from patient data files. INTERVENTIONS GC cytokine/chemokine mRNAs were identified and analyzed by gene-chip microarrays/qPCR before and after culture with human chorionic gonadotropin, DHT, IL-6, or IL-8; serum/FF cytokine levels were also analyzed. MAIN OUTCOME MEASURES Relative serum/FF cytokine levels and GC cytokine expression before and after culture were compared and related to body mass index. RESULTS The following results were found: 1) PCOS GCs express elevated transcripts encoding cytokines, chemokines, and immune cell markers, 2) based on gene profiling and qPCR analyses, obese PCOS patients define a distinct PCOS disease subtype with the most dramatic increases in proinflammatory and immune-related factors, and 3) human chorionic gonadotropin and DHT increased cytokine production in cultured GCs, whereas cytokines augmented cytokine and vascular genes, indicating that hyperandrogenism/elevated LH and obesity in PCOS women augment intrafollicular cytokine production. CONCLUSIONS Intrafollicular androgens and cytokines likely comprise a local regulatory loop that impacts GC expression of cytokines and chemokines and the presence of immune cells; this loop is further enhanced in the obese PCOS subtype.

Implantation failure of endometrial origin: it is not pathology, but our failure to synchronize the developing embryo with a receptive endometrium

Repeated implantation failure (RIF) is an intriguing, massive failure of reproductive treatment in otherwise healthy women leading to the introduction of empirical adjuvant interventions that are costly, inefficient, and frustrating for our patients. In this article, we will try to convince the readers that RIF is neither a stigma nor a mysterious pathology but rather our failure to diagnose and properly synchronize the euploid blastocyst with the patients personalized window of implantation.

Supernumerary ovary in association with endometriosis

The supernumerary ovary is a rare gynecological entity. There have been 15 reported cases in the literature since the first description by Winckel in 1890. We report the finding of endometriosis in a supernumerary ovary