Therapeutic assessment of N-formyl-methionyl-leucyl-phenylalanine (fMLP) in reducing periprosthetic joint infection.

Despite many preventive measures, including prophylactic antibiotics, periprosthetic joint infection (PJI) remains a devastating complication following arthroplasty, leading to pain, suffering, morbidity and substantial economic burden. Humans have a powerful innate immune system that can effectively control infections, if alerted quickly. Unfortunately, pathogens use many mechanisms to dampen innate immune responses. The study hypothesis was that immunomodulators that can jumpstart and direct innate immune responses (particularly neutrophils) at the surgical site of implant placement would boost immune responses and reduce PJI, even in the absence of antibiotics. To test this hypothesis, N-formyl-methionyl-leucyl-phenylalanine (fMLP) (a potent chemoattractant for phagocytic leukocytes including neutrophils) was used in a mouse model of PJI with Staphylococcus aureus (S. aureus). Mice receiving intramedullary femoral implants were divided into three groups: i) implant alone; ii) implant + S. aureus; iii) implant + fMLP + S. aureus. fMLP treatment reduced S. aureus infection levels by ~ 2-Log orders at day 3. Moreover, fMLP therapy reduced infection-induced peri-implant periosteal reaction, focal cortical loss and areas of inflammatory infiltrate in mice distal femora at day 10. Finally, fMLP treatment reduced pain behaviour and increased weight-bearing at the implant leg in infected mice at day 10. Data indicated that fMLP therapy is a promising novel approach for reducing PJI, if administered locally at surgical sites. Future work will be toward further enhancement and optimisation of an fMLP-based therapeutic approach through combination with antibiotics and/or implant coating with fMLP.

Hypothalamic-pituitary suppression with oral contraceptive pills does not improve outcome in poor responder patients undergoing in vitro fertilization-embryo transfer cycles.

PURPOSE: To evaluate and compare the use of OCP with GnRHa for hypothalamic-pituitary suppression in poor responder IVF patients. METHODS: Retrospective analysis of IVF-ET cycles of poor responders. Hypothalamic-pituitary suppression with OCP (Group I, n = 29) or GnRHa (Group II, n = 52), followed by stimulation with gonadotropin, oocyte retrieval, and embryo transfer. Baseline characteristics and cycle outcomes were compared. RESULTS: 73 women underwent 81 cycles from 1/1/1999 to 1/1/2000. Baseline characteristics were similar. 31/81 (38%) cycles were cancelled (Group I, 14/29 (48%) vs. Group II, 17/52 (33%), NS). Cycle outcomes including amount of gonadotropin, number of eggs retrieved, number of embryos transferred, and embryo quality were similar. Patients in Group I required fewer days of stimulation to reach oocyte retrieval. Pregnancy outcomes were similar in the two groups. CONCLUSION: Our retrospective analysis revealed no improvement in IVF cycle outcomes in poor responders who received OCPs to achieve hypothalamic-pituitary suppression instead of GnRHa.

Treatment of hematotrachelos after dilatation and curettage. A case report.

BACKGROUND: Hematotrachelos, accumulation of menstrual blood in a dilated cervix, is a rare disorder accompanying cervical stenosis. In this report, hematotrachelos was diagnosed by vaginal sonography and treated in a novel way. CASE: A 39-year-old woman with progressive hypomenorrhea following dilation and curettage for dysfunctional uterine bleeding was diagnosed with hematotrachelos using vaginal sonography. Cervical dilatation and evacuation of the hematotrachelos were performed. A latex nasopharyngeal airway was utilized as a temporary stent and allowed drainage and maintained cervical patency. Normal menstrual flow was resumed, and the hematotrachelos did not recur. CONCLUSION: Hematotrachelos may be a rare complication of routine dilatation and curettage. The diagnosis is confirmed by transvaginal sonography. Treatment is successful with cervical dilatation and placement of a temporary latex nasopharyngeal airway.

Colony stimulating factor-1 in human follicular fluid.

OBJECTIVE: To evaluate colony stimulating factor-1 (CSF-1) concentrations in serum and follicular fluid (FF) at the time of oocyte retrieval and to test for presence of messenger RNA (mRNA) for CSF-1 and its receptor, c-fms, in FF cells. DESIGN: Collection of serum and FF at the time of oocyte retrieval. SETTING: A university IVF program. PATIENT(S): Forty-five women undergoing oocyte retrieval for IVF. INTERVENTION(S): Serum and FF were obtained from 24 women, and FF only was obtained from 21 women. MAIN OUTCOME MEASURE(S): Colony-stimulating factor-1 concentrations were determined by RIA, and the presence of mRNA for CSF-1 and c-fms was determined by reverse transcriptase-polymerase chain reaction. RESULT(S): Mean FF concentrations of CSF-1 were significantly higher than mean serum levels (10.0 +/- 1.3 and 3.6 +/- 0.3 (+/-SE) ng/mL, respectively). Colony-stimulating factor-1 and c-fms message were detected in FF cells, and alternatively spliced forms of CSF-1 message were present. CONCLUSION(S): The presence of CSF-1, a primary regulator of tissue macrophages, in FF, and the presence of mRNA for CSF-1 and its receptor c-fms in FF-derived cells, suggest a role for this growth factor in ovarian function.

Levels of interferon-gamma and tumor necrosis factor-alpha in sera and cervical mucus of fertile and infertile women: implication in infertility.

Concentrations of two immune cytokines, namely interferon-gamma (INF-gamma) and tumor necrosis factor-alpha (TNF-alpha), were determined in the sera and cervical mucus samples of fertile (n = 16), idiopathic infertile (n = 44), and immunoinfertile women (n = 45) to investigate their role, if any, in female infertility. Sera of idiopathic infertile women demonstrated significantly (P < 0.0001) higher levels of INF-gamma compared to those in fertile controls, whether expressed as pg/ml or pg/mg serum protein. Similarly, sera of immunoinfertile women demonstrated significantly (P = 0.0008) higher levels of INF-gamma compared to fertile controls and idiopathic infertile women. Cervical mucus of idiopathic infertile women also demonstrated significantly (P < 0.0001) higher concentrations of INF-gamma compared to those in fertile controls. Cervical mucus of immunoinfertile women demonstrated significantly (P < 0.0001) higher concentrations of INF-gamma compared to those in fertile controls and idiopathic infertile women. INF-gamma levels in serum did not significantly (P > 0.05) correlate (r = 0.12-0.43) with the concentrations in cervical mucus, when all the three groups were compared together. However, when the serum levels were compared with the cervical mucus concentrations by condition, only the idiopathic infertile group showed a significant (P = 0.005) correlation (r = 0.70). Serum levels of TNF-alpha did not differ significantly (P > 0.05) among three groups of women. Cervical mucus concentrations of TNF-alpha, however, varied among groups with levels being significantly (P = 0.04) higher-in idiopathic infertile women compared with fertile controls and in immunoinfertile women significantly (P = 0.0007) higher than in fertile controls as well as idiopathic infertile women. TNF-alpha levels in serum correlated (r = 0.65) significantly (P < 0.001) with the concentrations in cervical mucus when all the three groups were compared together or individually by infertility condition. These findings suggest the involvement of cytokines in infertility, and thus may have potential applications in diagnosis and treatment of female infertility.

Basal serum follicle stimulating hormone (FSH) and estradiol levels as predictors of pregnancy in unstimulated donor insemination cycles.

PURPOSE: The purpose of this study was to evaluate the utility of basal serum follicle stimulating hormone and estradiol levels in predicting pregnancy in women undergoing artificial insemination with donor sperm for severe male factor infertility. METHOD: A retrospective chart review of 48 women who had at least 2 cycles of artificial insemination with donor sperm and who had undergone testing for basal serum follicle stimulating hormone and estradiol levels prior to or during therapy. RESULTS: There was no difference in age or mean basal serum follicle stimulating hormone between women who conceived (clinical pregnancy) and those who did not. Women who conceived had significantly lower mean serum basal estradiol levels (P = 0.02) and significantly fewer numbers of treatment cycles (P = 0.041). The highest pregnancy rate was among those women with normal basal serum follicle stimulating hormone and estradiol levels. Receiver operating characteristic curve analysis revealed basal serum estradiol to be a more reliable predictor of pregnancy than follicle stimulating hormone. CONCLUSIONS: Basal serum follicle stimulating hormone and estradiol levels may be useful in predicting success with artificial insemination with donor sperm. It may be useful to obtain basal serum follicle stimulating hormone and estradiol prior to initiating artificial insemination with donor sperm.

Potential limiting factors in resident training for laparoscopic management of ectopic pregnancies.

STUDY OBJECTIVE: To evaluate resident exposure and training in operative laparoscopic management of ectopic pregnancy (EP). DESIGN: A review and comparison of the profile and management of consecutive series of patients with EP in two different clinical settings. SETTING: A university-affiliated obstetrics and gynecology residency program caring for indigent women, and a private, office-based infertility practice. PATIENTS: Fifty-three consecutive patients with EP treated surgically in an infertility practice (group 1) were compared with 68 such women managed in a residency program (group 2). RESULTS: Evaluation at the time of hospital admission confirmed significantly lower systolic and diastolic blood pressures (mean +/- SD 106.2 +/- 12.2 mm Hg vs 114.8 +/- 9.1 and 61.1 +/- 14.4 mm Hg vs 71.7 +/- 11.8 mm Hg, p <0.05) and hemoglobin (10.9 +/- 2.7 g/dl vs 12.2 +/- 2.2 g/dl, p <0.05), and higher pulse rates (96.1 +/- 12.1 bpm vs 84.0 +/- 7.7 bpm, p <0.01) for groups 2 and 1, respectively. The mean gestational age at diagnosis was greater in group 2 (52.1 +/- 14.8 days) than in group 1 (46.7 +/- 11.1 days, p <0.05). That the overall clinical picture in group 2 was more serious was confirmed by a larger mean gestational mass (4.4 +/- 3.1 cm vs 2.8 +/- 2.6 cm, p <0.01), more frequent rupture (69% vs 21%, p <0.01), and a larger hemoperitoneum (547 +/- 488 ml vs 215 +/- 202 ml, p <0. 05). Similarly, 49% of group 2 patients required postoperative or intraoperative blood transfusion, compared with 13% of group 1 (p <0. 01). Forty-four of 53 women in group 1 were managed laparoscopically (83%), whereas only 16 (24%) in group 2 were so treated (p <0.05). CONCLUSION: Patients in group 2 were more hemodynamically compromised, had more advanced gestations, and had more ruptured EPs, leading to decreased opportunities for laparoscopic management. Active resident participation in operative management of nonindigent women with EP may be necessary to ensure appropriate training.

Management of endometriosis in women older than 40 years of age.

Endometriosis in women older than 40 years of age presents unique therapeutic challenges to the practicing physician. Management requires the evaluation of reproductive goals and a determination of the objectives of therapy, including symptomatic relief and avoidance or delay of recurrence of disease. Important considerations in this age group include diminished fertility and impending menopause. The diagnosis and treatment for endometriosis-associated infertility must be undertaken in an expedient manner. Assisted reproductive technologies may be effective therapies for these patients. Conservative surgery may be necessary to preserve reproductive potential, but definitive surgery may be indicated in women with long-standing pelvic pain. Estrogen replacement therapy may be used in menopausal women with a history of endometriosis.

Endocrine function of granulosa cell tumors in vivo.

Two patients with granulosa cell tumors of the ovary, endometrial hyperplasia, elevated serum estradiol (E2) concentrations and depressed FSH levels were studied preoperatively using intravenous administration of FSH, LH and gonadotropin-releasing hormone. In patient 1, serum E2 increased from a baseline of 72.7 to 116.8 pg/ml 60 min after hCG stimulation, with a peak level of 571.4 pg/ml 96 h after hCG administration; there was a rapid postoperative decline to 16 pg/ml. Ovarian venous E2 on the tumor side was 6,979 pg/ml. In patient 2, E2 increased from a baseline of 91 to 449 pg/ml at 20 h after FSH administration. Intraoperative ovarian venous E2 was 9,788 pg/ml. Inhibin, which was elevated in patient 1 prior to stimulation (736 fmol/ml), peaked 96 h after hCG administration. Ovarian venous inhibin concentration in patient 1 was 2,911 fmol/ml. The baseline inhibin concentration in patient 2 was not elevated (249 fmol/ml), but there was an elevation of inhibin in response to FSH administration (757 fmol/ml), but no response to hCG. Ovarian inhibin concentration was not different between the tumor and contralateral sides in patient 2. Both granulosa cell tumors were responsive to exogenous gonadotropin stimulation. Although only one tumor made significant baseline levels of inhibin, the production of inhibin by both tumors was apparently stimulated by FSH.

Outpatient laparoscopic management of ectopic pregnancy with a local methotrexate injection.

Nine patients with unruptured tubal ectopic gestations were treated as outpatients utilizing a laparoscopically directed injection of methotrexate into the tubal mass. The initial quantitative serum human chorionic gonadotropin values ranged from 34 to 17,100 mIU/mL. Eight of nine subjects had complete resolution of the pregnancy over the ensuing 10-33 days; the remaining patient, with plateauing human chorionic gonadotropin levels, required a laparotomy.

CA 125 levels in abruptio placentae.

The diagnosis of abruptio placentae is frequently difficult despite ultrasonography; additional diagnostic parameters would be useful. Maternal serum CA 125, which is believed to derive from the decidua, is elevated in the first trimester and immediately after delivery when placental separation occurs, possibly because of decidual disruption. Serum CA 125 was measured in 27 patients beyond 20 weeks' gestation who were first seen with vaginal bleeding and in 17 control patients of similar gestational age and labor status. Mean (+/- SD) CA 125 levels were higher (p less than 0.01) among patients with abruptio placentae (105.9 +/- 115 U/ml) than among those with alternate sources of bleeding (13.7 +/- 10 U/ml) or control patients (18.2 +/- 11.7 U/ml). Mean (+/- SD) serum CA 125 levels in seven control patients within 6 hours post partum (194 +/- 80.5 U/ml) were higher than those among patients first seen with abruptio placentae (p less than 0.01). Sensitivity and specificity of CA 125 for abruptio placentae were 70% and 94%, respectively. Our data support a decidual source for CA 125 and may indicate utility of CA 125 as a marker for abruptio placentae.

Relaxin, CA-125, progesterone, estradiol, Schwangerschaft protein, and human chorionic gonadotropin as predictors of outcome in threatened and nonthreatened pregnancies.

Progesterone (P), estradiol (E2), relaxin, CA-125, Schwangerschaft protein, and human chorionic gonadotropin (hCG) were measured in 221 pregnancies (less than or equal to 77 days gestation). The cohort was divided into asymptomatic subjects (group I, n = 117) and those with threatening symptoms (group II, n = 104). Outcome was ascertained as viable (normal at 14 weeks, n = 131), spontaneous abortion (n = 58), or ectopic gestation (n = 32). Statistical analysis revealed no differences in the mean maternal or gestational ages among the viable pregnancies, abortions, and ectopics in group I and group II. In group I, significant differences in the means were noted for P, hCG, relaxin, and CA-125 among those destined to abort, compared with those who were not. In group II, differences were noted in P, hCG, relaxin, and E2 when viable and nonviable pregnancies were compared. Within group II, there were significant differences between the means of E2 and CA-125 when the aborters were contrasted with ectopics. Receiver operating characteristic curve analysis revealed that P was the single most reliable predictor and was most effective in threatened pregnancies. Stepwise logistic regression of the six markers in group II provided an equation of possible clinical utility in differentiating abortion versus ectopic pregnancy in threatened gestations based on CA-125 and E2 levels.