Silk-elastinlike copolymers enhance bioaccumulation of semisynthetic glycosaminoglycan ethers for prevention of radiation induced proctitis.

Radiation-induced proctitis (RIP) is a debilitating adverse event that occurs commonly during lower abdominal radiotherapy. The lack of prophylactic treatment strategies leads to diminished patient quality of life, disruption of radiotherapy schedules, and limitation of radiotherapy efficacy due to dose-limiting toxicities. Semisynthetic glycosaminoglycan ethers (SAGE) demonstrate protective effects from RIP. However, low residence time in the rectal tissue limits their utility. We investigated controlled delivery of GM-0111, a SAGE analogue with demonstrated efficacy against RIP, using a series of temperature-responsive polymers to compare how distinct phase change behaviors, mechanical properties and release kinetics influence rectal bioaccumulation. Poly(lactic acid)-co-(glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid)-co-(glycolic acid) copolymers underwent macroscopic phase separation, expelling >50% of drug during gelation. Poloxamer compositions released GM-0111 cargo within 1 h, while silk-elastinlike copolymers (SELPs) enabled controlled release over a period of 12 h. Bioaccumulation was evaluated using fluorescence imaging and confocal microscopy. SELP-415K, a SELP analogue with 4 silk units, 15 elastin units, and one elastin unit with lysine residues in the monomer repeats, resulted in the highest rectal bioaccumulation. SELP-415K GM-0111 compositions were then used to provide localized protection from radiation induced tissue damage in a murine model of RIP. Rectal delivery of SAGE using SELP-415K significantly reduced behavioral pain responses, and reduced animal mass loss compared to irradiated controls or treatment with traditional delivery approaches. Histological scoring showed RIP injury was ameliorated for animals treated with GM-0111 delivered by SELP-415K. The enhanced bioaccumulation provided by thermoresponsive SELPs via a liquid to semisolid transition improved rectal delivery of GM-0111 to mice and radioprotection in a RIP model.

Idiopathic premature ovarian failure: what is the most suitable ovarian stimulation protocol?

OBJECTIVE: To evaluate the ovarian response to ovarian stimulation in women with idiopathic premature ovarian failure (POF) in a prospective, controlled, and sequential crossover pilot study. MATERIALS AND METHODS: Ten women with idiopathic premature ovarian failure and normal karyotype were included in the study. Phase I was comprised of three consecutive control cycles consisting each of estrogen progestin sequential therapy. Phase II was comprised of three consecutive treatment cycles combining the use of gonadotropin-releasing hormone agonist (GnRHa) in the background of estrogen priming, followed by gonadotropin ovarian stimulation and corticosteroid immunosuppression. RESULTS: Ovulation rates in the treatment cycles (0/10; 0%) did not differ from control cycles (0/10; 0%). CONCLUSIONS: The findings of this pilot study showed that the combination of estrogen priming, corticosteroid immune-suppression, GnRHa pituitary desensitization, and followed by gonadotropin ovarian stimulation is ineffective in restoring ovarian function in women with idiopathic POF.

Temporal trends in human semen parameters in New England in the United States, 1989-2000.

The current study explores trends in semen parameters in New England in the United States. A retrospective review was performed of 551 semen analysis records from 1989 to 2000 at Vincent Memorial Andrology Laboratory of Massachusetts General Hospital. After age adjustment, semen pH and motility significantly increased 0.05 units/year and 2.33%/year, respectively, while sperm with normal morphology decreased 0.33%/year. Sperm concentration showed a small upward trend. The year of birth in the present study ranged from 1932 to 1981; 2% were born between 1932 and 1941, 13% between 1942 and 1951, 48% between 1952 and 1961, 36% between 1962 and 1971, and 1% were born between 1972 and 1981. There were significant positive relationships between year of birth and semen volume (0.04 mL/1-year interval increase in year of birth) and motility (0.61 percent/1-year interval increase in year of birth), as well as with sperm concentration and morphology. Overall, there were temporal and year of birth trends in several human semen parameters.

Outcome and resource use associated with myomectomy.

OBJECTIVE: To evaluate the outcomes and cost of myomectomy through retrospective claims data analysis. METHODS: The study was performed using a retrospective database of private insurance claims from 1995 to 1997. Records were selected for analysis based on the presence of ICD-9-CM procedure and/or CPT-4 codes associated with myomectomy. In addition, diagnosis of uterine leiomyoma and related symptoms for these patients were confirmed through ICD-9-CM diagnosis codes. Inpatient, outpatient, and physician costs were estimated. All cost data were converted into 1997 dollars. RESULTS: A total of 4394 women, between the ages of 14 and 70, were available for analysis. Of these, 3305 were classified by type of myomectomy procedure, and complete data were available on 820 at 1 year and 236 at 2 years. Abdominal myomectomies were the most common procedures, followed by hysteroscopic and laparoscopic myomectomies. Conversion to a more invasive procedure occurred in 5.4% of the patients. The rate of additional surgeries was 8.3% in 6 months, 10.6% in 1 year, and 16.5% in 2 years. Overall cost increased from an initial 6,737 dollars per patient to 7,575 dollars in 1 year and to 8,001 dollars in 2 years. CONCLUSION: The repeat procedures required after the initial myomectomy add significantly to total cost and highlight the importance of assessing post-procedure health care use. This comprehensive analysis facilitates the systematic evaluation of myomectomy with current and emerging alternative treatments for uterine leiomyomas.

Antral follicle assessment as a tool for predicting outcome in IVF--is it a better predictor than age and FSH?

PURPOSE: The purpose of this study is to determine if baseline antral follicle assessment may serve as additional information in predicting in vitro fertilization outcome. METHODS: Prospective, descriptive preliminary study of in vitro fertilization outcome. From July 1998 to July 1999, 224 patients underwent antral follicle assessment (follicle 2-6 mm in diameter) on baseline of the planned, stimulated in vitro fertilization cycle. The outcomes were analyzed with respect to antral follicle assessment (< or = 6 or > 6), basal cycle day 3 follicle stimulated hormone (< or = 10 or > 10 IU/L) and maternal age (< or = 35 or > 35 years). RESULTS: The clinical pregnancy rate was significantly higher in the group with baseline antral follicle > 6 compared to that in the group with antral follicle < or = 6 (51% vs. 19%, respectively). Controlling for patient age, and basal follicle stimulated hormone, the pregnancy rate was significantly higher in the group with antral follicle > 6 compared to that in the group with antral follicle < or = 6. The cancellation rate was significantly increased with advancing maternal age, elevated basal follicle stimulated hormone levels, and baseline antral follicle < or = 6. The cancellation rate was significantly higher in the group with antral follicle < or = 6 compared to that in the group with antral follicle > or = 6 (33% vs. 1%, respectively). CONCLUSIONS: In vitro fertilization outcome is strongly correlated with both maternal ages, basal cycle, day 3 follicle, stimulated hormone, and antral follicle assessment. Antral follicle assessment was a better predictor of in vitro fertilization outcome than were age or follicle stimulated hormone. Antral follicle assessment may provide a marker for ovarian age that is distinct from chronological age or hormonal markers.

Analysis of follicular fluid hormone concentrations and granulosa cell mRNA levels for the inhibin-activin-follistatin system: relation to oocyte and embryo characteristics.

OBJECTIVE: To explore the potential roles of inhibin, activin, and follistatin in human oocyte development by quantifying their intrafollicular biosynthesis. DESIGN: Prospective, nonrandomized study. SETTING: An IVF unit and academic research laboratory. PATIENT(S): Thirty one patients undergoing IVF. INTERVENTION(S): Human menopausal gonadotropins or human FSH (or both) were administered. Single-follicle aspirates (n = 110) were collected for analysis. MAIN OUTCOME MEASURE(S): Concentrations of dimeric, total and pro-alphaC inhibin forms; activin A; follistatin; estradiol; and progesterone were measured in follicular fluids. Granulosa-cell mRNA was analyzed for alpha, beta A, and beta B inhibin and activin subunits; follistatin; activin receptors; and beta-actin. Hormone concentrations and mRNA levels were correlated with oocytes or embryos from the same follicles. RESULT(S): Levels of progesterone and follistatin were significantly greater in follicles containing MI or MII oocytes than in those containing GV oocytes. Inhibin alpha-subunit mRNA levels were significantly higher in follicles containing maturing oocytes, the highest-quality oocytes, and oocytes that were subsequently fertilized. In contrast, inhibin alpha-subunit mRNA levels were significantly lower in follicles from which higher-quality embryos were obtained. CONCLUSION(S): Inhibin alpha-subunit biosynthesis is associated with normal oocyte and follicle maturation, but excessive alpha-inhibin is associated with poor embryo quality. None of the hormones analyzed were associated with oocyte or embryo quality.

New developments in operative hysteroscopy.

Although there is a plethora of new devices currently being investigated that can ablate the endometrial cavity successfully, it is most certain that a strong place remains for operative hysteroscopy for the therapy of benign uterine conditions. New instruments that continue to make operative hysteroscopy a safer and easier procedure to perform should continue in their development.

The SCID mouse: an experimental model for endometriosis.

The purpose of this study was to validate the suitability of the severe combined immunodeficient (SCID) mouse as an experimental model for endometriosis, by defining the morphological and histological features of induced endometrial implants, and characterizing specific biochemical properties of these implants. Human secretory endometrial tissues were injected into the peritoneal cavity of SCID/SCID CB17 mature female mice. Successful peritoneal implantation was observed in 55 of 57 (96.5%) SCID mice and consisted of circumscribed elevated nodules. Haematoxylin-eosin staining of implanting lesions demonstrated the presence of endometrial glandular tissue in a mixed background of stromal and inflammatory cells. When progesterone was administered to mice, epithelial glands underwent well-defined secretory changes. Immunohistochemical analysis using polyclonal human pan-cytokeratin antibodies demonstrated selective positive staining in the glandular epithelium of the human implants with none in the surrounding stroma. In-situ hybridization analysis using complement component 3 cDNA radiolabelled riboprobes yielded significantly more intense signals in glands compared to stroma. As human endometrial implants in SCID mice were shown to retain specific histological, functional and biochemical properties, we conclude that the SCID mouse is an attractive animal model for the study of endometriosis.

Complications of hysteroscopy.

Most of the complications of hysteroscopy are avoidable and, fortunately, rare. With improved training, experience, and technology, most of these complications should become extinct. There will always be some unavoidable complications as well as difficulties resulting from inexperience. A goal for the future is to teach operating room personnel how to recognize and treat these complications to ensure the best patient outcome possible. Once gynecologic surgeons recognize the safety and efficacy of diagnostic and operative hysteroscopy as a minimally invasive option to treat benign uterine pathology, these procedures will proliferate and result in better patient care and improved quality of life.