RESUMEN
BACKGROUND: Our objective was to conduct a pilot study to determine if transcervical administration of polidocanol foam (PF) with or without doxycycline or benzalkonium chloride (BZK) would prevent pregnancy in baboons. METHODS: In study phase 1, adult cycling baboons underwent a hysterosalpingogram to evaluate tubal patency prior to transcervical infusion of 20 mL of 5% PF followed by 1 mL of saline containing 100 mg doxycycline (5%/doxy; n=5), 3% PF plus doxycycline (3%/doxy; n=4), 3% PF with 0.01% BZK (3%/BZK; n=4) or no additional treatment (control; n=9). Immediately following treatment, animals received intramuscular depot medroxyprogesterone acetate (DMPA, 2 mg/kg) to suppress cyclicity during healing and were then socially housed with males of proven fertility. The primary outcome was pregnancy within six cycles of resumption of menses (efficacy phase 1). During study phase 2, PF-treated females from study phase 1 contributed additional cycles (6-8) of exposure (efficacy phase 2), and 5 control females who had recovered from medical abortion (after study phase 1 pregnancy) were subsequently treated with 5% PF (with DMPA) and exposed to breeding (efficacy phase 1; n=3 six cycles, n=2 five cycles). RESULTS: All females resumed normal menstrual cycles and mating activity after DMPA. During efficacy phase 1, 7/9 (78%) control females became pregnant. In contrast, fewer pregnancies occurred in PF-treated females: 5% PF 0/5 (0%), 5%/doxy 1/5 (20%), 3%/doxy 1/4 (25%) and 3%/BZK 1/4 (25%). During efficacy phase 2, only one additional pregnancy occurred (3%/BZK). CONCLUSIONS: A single transcervical treatment with 5% PF prevented pregnancy in most baboons. Cotreatment with doxycycline or BZK did not improve results. IMPLICATIONS: Transcervical intrauterine administration of PF resulted in a high rate of tubal occlusion with prevention of pregnancy; refinements are needed to increase the contraceptive rate following a single treatment to near 100%.
Asunto(s)
Papio/fisiología , Polietilenglicoles/administración & dosificación , Preñez , Soluciones Esclerosantes/administración & dosificación , Esterilización Tubaria/métodos , Animales , Compuestos de Benzalconio/administración & dosificación , Anticoncepción/métodos , Anticonceptivos Femeninos/administración & dosificación , Doxiciclina/administración & dosificación , Femenino , Histerosalpingografía/efectos de los fármacos , Masculino , Acetato de Medroxiprogesterona/administración & dosificación , Ciclo Menstrual/efectos de los fármacos , Proyectos Piloto , Polidocanol , Embarazo , Índice de EmbarazoRESUMEN
OBJECTIVE: Our long-term goal is to develop a nonsurgical method of fallopian tubal occlusion for the purpose of permanent contraception. We have previously demonstrated that transcervical administration of 5% polidocanol foam (PF) can create tubal occlusion in macaques but that multiple treatments are required. In this study, we assessed the efficacy of various regimens of PF with and without depomedroxyprogesterone acetate (DMPA) (to control ovarian cycle phase) in the baboon. STUDY DESIGN: Adult cycling female baboons were evaluated for tubal patency by hysterosalpingography and then received a transcervical infusion of PF with (+) or without (-) an intramuscular injection of DMPA (3.5 mg/kg). Two concentrations of PF were compared: 1% [(+) DMPA, n=5; (-) DMPA, n=3] and 5% [(+) DMPA, n=4; (-) DMPA, n=3]. Controls received (+) DMPA (n=2) or (-) DMPA, (n=3) only. The reproductive tracts were removed 1-3 months after treatment for examination. RESULTS: No fallopian tubal occlusion was observed in negative controls (±DMPA). Histologic complete tubal occlusion was observed in 3/8 of females treated with 1% PF and in 6/7 treated with 5% PF. Histologic evaluation suggested that 1% PF is associated with prolonged chronic inflammation (more than 2-3 months), while 5% treatment eliminates the epithelial lining, at least focally, and resolves into complete occlusion within 1-2 months. This pattern of complete occlusion was seen in all 4 females that received 5% PF (+DMPA) and in 2/3 that received 5% PF (-DMPA). CONCLUSION: In a baboon model of transcervical permanent contraception, a single treatment with 5% PF resulted in complete tubal occlusion more reliably (85%) than 1% PF (38%). Cotreatment with DMPA may improve treatment results with 5% PF but requires additional study. IMPLICATIONS: A finding that a single transcervical treatment with 5% PF can occlude the fallopian tubes of baboon supports further study of this approach as a novel strategy for permanent contraception for women.
Asunto(s)
Anticonceptivos Femeninos/administración & dosificación , Trompas Uterinas/efectos de los fármacos , Polietilenglicoles/administración & dosificación , Esterilización Tubaria/métodos , Adhesivos Tisulares/administración & dosificación , Administración Intravaginal , Animales , Anticonceptivos Femeninos/efectos adversos , Anticonceptivos Femeninos/farmacología , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Células Epiteliales/patología , Trompas Uterinas/citología , Trompas Uterinas/inmunología , Trompas Uterinas/patología , Femenino , Histerosalpingografía/efectos de los fármacos , Inyecciones Intramusculares , Acetato de Medroxiprogesterona/administración & dosificación , Acetato de Medroxiprogesterona/efectos adversos , Acetato de Medroxiprogesterona/farmacología , Ciclo Menstrual/efectos de los fármacos , Papio anubis , Papio hamadryas , Proyectos Piloto , Polidocanol , Polietilenglicoles/efectos adversos , Polietilenglicoles/farmacología , Salpingitis/inducido químicamente , Salpingitis/diagnóstico por imagen , Salpingitis/inmunología , Salpingitis/patología , Soluciones Esclerosantes/administración & dosificación , Soluciones Esclerosantes/efectos adversos , Soluciones Esclerosantes/farmacología , Esterilización Tubaria/efectos adversos , Adhesivos Tisulares/efectos adversos , Adhesivos Tisulares/farmacología , Cremas, Espumas y Geles Vaginales/administración & dosificación , Cremas, Espumas y Geles Vaginales/efectos adversos , Cremas, Espumas y Geles Vaginales/farmacologíaRESUMEN
OBJECTIVE: The goal of this study was to quantify changes in uterine volume during and after chemotherapy for breast cancer. MATERIALS AND METHODS: Fifty-eight patients (mean age 42 years) with advanced breast cancer undergoing treatment with FLAC (5-fluorouracil, leucovorin, Adriamycin, and cyclophosphamide) were studied with serial pelvic CT. The transverse, anteroposterior, and sagittal measurements of the uterus were taken in each of the CT scans. The uterine volumes were calculated, normalized to baseline volumes, and graphically displayed for each patient. The temporal changes in uterine volume were correlated to the dates of chemotherapy administration and menstrual status. RESULTS: There was a striking and consistent loss of uterine volume with chemotherapy. This phenomenon was observed in 55 (95%) of the 58 patients. The mean minimum uterine volume was 58.3 +/- 20.2% compared with the baseline. This loss of uterine volume began after the administration of the first cycle of chemotherapy and progressed during subsequent cycles. It coincided with loss of normal menses in all patients. After completion of chemotherapy, there was a recovery of the uterine volume in 12 of the 16 patients who had follow-up CT. The mean recovery uterine volume was 108.4 +/- 49.8% of baseline. Menses recovered in four of these. CONCLUSION: Chemotherapy causes loss of uterine volume, which usually recovers after the withdrawal of chemotherapy in premenopausal women. This change should not be mistaken for a therapeutic response of primary or secondary malignancy within the uterus or be confused with subsequent uterine changes due to tamoxifen.