Preparation of nano cellulose fibers and its application in kappa-carrageenan based film.

Bio-based nanocomposite films were successfully developed using nanofibrillated cellulose (NFC) as the reinforcing phase and kappa-carrageenan (KCRG) as the matrix. NFC was successfully synthesis from short stable cotton fibers by chemo-mechanical process. The bionanocomposites were prepared by incorporating 0.1, 0.2, 0.3, 0.4, 0.5, and 1wt% of the NFC into a KCRG matrix using a solution casting method there characterization was done in terms of thermal properties (DSC), morphology (SEM), water vapor transmission rate (WVTR), oxygen transmission rate (OTR), X-ray diffractograms (XRD), and tensile properties. The main conclusion arising from the analysis of the result is that the bionanocomposites containing 0.4wt% of NFC exhibited the highest enhancement in tensile strength it is almost 44% improvement. WVTR and OTR results showed improvement of all nanocomposite film compare to control KCRG film.

Antifungal Activity of Leaves of Mangroves Plant Acanthus licifolius Against Aspergillus fumigatus.

The antifungal activity of chloroform extract of leaves of Acanthus ilicifolius was evaluated in Aspergillus fumigatus infected mice. Swiss albino mice (60) were divided into five groups. All the groups were immunosuppressed with cyclophosphamide and cortisone acetate couple of days prior to intranasal inoculation with Aspergillus fumigatus conidia (10(6)) in all the groups, except the first. Treatment was initiated at 24 h of fungal inoculation and continued up to day 14, and included amphotericin B (1 mg/kg orally) for group III and extract of Acanthus ilicifolius at 250 mg and 500 mg/kg for group IV and V, respectively. Groups I and II received sterile water orally for the same period. From each group, three mice were sacrificed after 1 h and the remaining mice on the 14(th) day of inoculation. One hour post-inoculation lung colony forming unit count confirmed the delivery of conidia into the lungs. Colony forming unit count, intensity of gross necropsy changes and histopathological changes were highest in group II. It improved in group III and also in groups IV and V in dose-dependent manner. Lesions were absent in the noninfected group. Lesions included maximum granulomatous inflammation of lung, multifocal diffused necrotic granulomas on kidney and moderate microgranulomas on liver. From this study, it was concluded that chloroform extract of Acanthus ilicifolius contains active principles that are absorbed after oral administration to produce systemic effects when given at 500 mg/kg dose.

Administration of recombinant human FSH (solution in cartridge) with a pen device in women undergoing ovarian stimulation.

This study evaluated the first multiple-use pen device for the self-administration of recombinant FSH. The pen device is used for the subcutaneous injection of a pre-mixed ready-to-use solution of follitropin beta from a multiple-dose cartridge, and has flexible dosing capabilities. In the ease-of-use questionnaire, 90% of subjects rated the overall experience of self-injecting follitropin beta using the pen device as 'very good' (on day 6). The comprehension questionnaire revealed that prior to the first injection and during the second injection, the follitropin beta cartridge was properly loaded into the pen device by 96.7 and 100% of the subjects respectively. The questionnaire also showed that the correct dose was selected and self-administered by 98.3 and 100% of the subjects respectively. Biochemical and ongoing pregnancy rates per attempt were 56.7 and 45.0% respectively. The pen device is safe, effective, and easy to use for self-administering recombinant FSH during ovarian stimulation.

Reducing the risk of high-order multiple pregnancy after ovarian stimulation with gonadotropins.

BACKGROUND: The incidence of multiple gestation after therapy for infertility is especially high among women in whom ovulation is induced with gonadotropins. Whether the number of high-order multiple pregnancies (those with three or more fetuses) can be reduced is not known. METHODS: We analyzed data on 3347 consecutive treatment cycles in 1494 infertile women, 441 of which resulted in pregnancy. The data collected included the peak serum estradiol concentration, the number of follicles 16 mm or larger in diameter, and the total number of follicles on the day of induction of ovulation with human chorionic gonadotropin. Receiver-operating-characteristic curves and ordinal logistic-regression analyses were used to identify values that predicted multiple conceptions. RESULTS: Among the 441 pregnancies, 314 resulted from the conception of singletons, 88 of twins, 22 of triplets, 10 of quadruplets, 5 of quintuplets, and 2 of sextuplets. Neither the number of follicles 16 mm or larger nor peak serum estradiol concentrations greater than 2000 or 2500 pg per milliliter (7342 or 9178 pmol per liter) (the cutoff values currently in wide use) were significantly associated with the incidence of high-order multiple pregnancy. However, increasing total numbers of follicles and increasing peak serum estradiol concentrations correlated significantly with an increasing risk of high-order multiple pregnancy (P<0.001), as did younger age (P=0.008). The risk of high-order multiple pregnancy was significantly increased in women with a peak serum estradiol concentration of 1385 pg per milliliter (5084 pmol per liter) or higher (multivariate odds ratio, 1.9; 95 percent confidence interval, 1.3 to 2.8) or with seven or more follicles (multivariate odds ratio, 2.1; 95 percent confidence interval, 1.2 to 3.9) on the day of induction of ovulation. CONCLUSIONS: Gonadotropin stimulation that is less intensive than is currently customary may reduce the incidence of high-order multiple pregnancy in infertile women, though only to a limited extent and at the expense of overall pregnancy rates.

Estradiol/progesterone substitution in the luteal phase improves pregnancy rates in stimulated cycles--but only in younger women.

Innumerable studies have attempted to demonstrate that hormonal support of the luteal phase during ovulation induction cycles improves pregnancy rates. None has, however, so far been able to confirm the validity of such treatment conclusively, possibly because most studies only utilized progesterone substitution. Since luteal phase endometrium also requires estradiol support, this study attempted to investigate whether hormone substitution with progesterone and estradiol would be more successful in improving pregnancy rates. Amongst approximately 7500 consecutive ovulation induction cycles were identified prospectively which were characterized by a precipitous drop of luteal phase serum estradiol levels by more than 50% over a 48 hour period within 10 days from hCG administration. Those cycles were prospectively randomized to oral micronized estradiol substitution (Group I) or not (Group II), while both groups received routine progesterone substitution of the luteal phase. Cycles were then evaluated in regards to the occurrence of chemical, ectopic and clinical pregnancies. One hundred sixty-three Group I cycles resulted in 34 pregnancies (20.9%), which compared favorably to 21 pregnancies in 167 Group II patients (12.6%) (x2[1] = 4.06; p < 0.04). The advantage for Group I cycles (29/95 pregnancies, 31%) vs. Group II cycles (16/105, 15%) became even more pronounced when only women up to age 35 years were evaluated. Estradiol substitution maintained a significant advantage until age 38 (x2 [1] = 6.87; p < 0.009). While gravidity did not affect pregnancy success, estradiol substitution in Group I benefited nulliparous (23% pregnancy rate) over multiparous women (12% pregnancy rate) (x2 [2] = 6.86; p< 0.03). This association was, however, age-dependent. A combined estradiol and progesterone substitution of the luteal phase of ovulation induction cycles increases the overall pregnancy rate. Since estradiol substitution was initiated in this study only once a precipitous drop in serum estradiol levels had already taken place, an even larger improvement in pregnancy rates could conceivably be possible if earlier estradiol substitution of the luteal phase is initiated. A further expansion of investigations of similar protocols for routine ovulation induction and in vitro fertilization (IVF) cycles may be indicated, especially in women below age 38 years and in nulliparous females.

Generic human menopausal gonadotropin (hMG) in place of more costly follicle-stimulating hormone (FSH) for routine ovulation induction.

PURPOSE: A large part of infertility treatment involves the use of exogenous gonadotropins. The last decade has seen a progressive switch from human menopausal gonadotropin (hMG), the original gonadotropin product, to progressively more costly products, primarily or exclusively containing follicle-stimulating hormone (FSH). Though obviously at least in part driven by marketing efforts of pharmaceutical companies, this switch has received relatively little scrutiny despite its obvious cost implications. We therefore investigated whether a switch back to a generic or less costly hMG-driven ovulation induction protocol would affect patient outcome after ovulation induction and, by implications, with other assisted reproductive technologies. METHODS: We prospectively studied clinical pregnancy rates in a large number of consecutive ovulation induction cycles in a well-defined patient population (group 1) which, after October of 1997, had been switched from a predominantly FSH to an hMG-driven protocol, based on an institutional formulary change. Until a transition period (between July and September 1997), this patient population had been on a primarily FSH-driven protocol (between July 1996 and June 1997). In parallel, we evaluated a second patient population (group 2), which was managed by the same physicians outside of formulary requirements and remained almost exclusively on principally FSH-driven ovulation induction cycles. RESULTS: FSH- and hMG-driven ovulation induction protocols did not differ in pregnancy outcome during the prospective study period. Group 1 patients, however, demonstrated a significant increase in pregnancy rates after the switch from FSH to hMG stimulation had taken place (P = 0.02), while group 2 patients demonstrated no change in pregnancy rate during the same time period. CONCLUSIONS: Generic hMG products do not adversely affect pregnancy rates in comparison to more costly FSH products in routine ovulation induction cycles and should be considered an appropriate alternative to more expensive FSH products.

Impact of the "physician factor" on pregnancy rates in a large assisted reproductive technology program: do too many cooks spoil the broth?

OBJECTIVE: To determine whether in one program with unified treatment protocols, patients can expect varying treatment outcomes with different physicians. DESIGN: Retrospective data analysis. SETTING: University-affiliated infertility center with 14 physicians. PATIENT(S): One thousand eight hundred fifty IVF cycles performed consecutively between August 1995 and June 1997. INTERVENTION(S): The pregnancy rate and implantation rate per ET were evaluated for individual physicians between August 1995 and June 1996 (phase I). Physicians with lower success rates underwent strict supervision from July 1996 to June 1997 (phase II). MAIN OUTCOME MEASURE(S): Variations in success rates between physicians. RESULT(S): The pregnancy rate varied among the physicians from 13.2%-37.4%, and the implantation rate varied from 4.4%-14%. Some physicians' outcomes improved between phase I and phase II of the study, whereas others' did not. The pregnancy and implantation rates varied significantly for some physicians, depending on whether they were responsible for the choice of stimulation protocol, supervision of cycle monitoring, or ET in their own or other physicians' patients. CONCLUSION(S): Outcomes of IVF vary depending on the treating physician. Lower than expected pregnancy and implantation rates usually are not caused by poor ET techniques alone, but appear to be disproportionately the consequences of poor cycle stimulation.

Resection of uterine septum using gynaecoradiological techniques.

This paper presents further refinements in our technique for the resection of uterine septum. Fourteen patients [infertility (n = 9) and recurrent miscarriages (n = 5)] underwent in-office resection of a uterine septum under fluoroscopic control. The main outcome measure was complete resection of uterine septum. Resections were carried out using either hysteroscopic scissors in combination with a specially designed uterine balloon catheter, or microlaparoscopy scissors in conjunction with a cervical cannula. In all patients the septum was successfully resected without any intra-operative complications. We conclude that ambulatory gynaecoradiological resection of uterine septa is a safe and simple procedure. It avoids utilization of expensive operating room time, general anaesthesia, and some complications associated with hysteroscopic resection, such as fluid retention and electrolyte imbalance.

Octreotide is not useful for clomiphene citrate resistance in patients with polycystic ovary syndrome but may reduce the likelihood of ovarian hyperstimulation syndrome.

OBJECTIVE: To determine whether octreotide is effective for ovulation induction in patients with polycystic ovary syndrome (PCOS) and clomiphene citrate resistance or for reduction of the risk of ovarian hyperstimulation syndrome (OHSS) with gonadotropin therapy. DESIGN: Prospective, double-blind, placebo-controlled, crossover trial. SETTING: Private infertility practice. PATIENT(S): Twelve patients with PCOS undergoing therapy for infertility. INTERVENTION(S): The patients were assigned randomly to receive either octreotide or placebo. Those with clomiphene citrate-resistant PCOS received clomiphene citrate, 150 mg. Patients at risk for the development of OHSS received urinary FSH for ovulation induction. MAIN OUTCOME MEASURE(S): Ovulation, pregnancy, the development of OHSS, and levels of fasting insulin, insulin-like growth factor 1, insulin-like growth factor binding proteins 1 and 3, testosterone, androstenedione, DHEAS, E2, LH, and FSH. RESULT(S): Octreotide significantly reduced levels of fasting insulin, insulin-like growth factor 1, and LH in both clomiphene citrate- and urinary FSH-stimulated cycles. Levels of insulin-like growth factor binding protein 3 were increased. Two of six clomiphene citrate-stimulated cycles reached ovulation with the use of either octreotide or placebo. In urinary FSH-stimulated cycles, patients who received octreotide had significantly lower E2 levels at the time of hCG administration and fewer mature follicles. No cases of OHSS occurred in either group. One pregnancy occurred in each group. CONCLUSION(S): Octreotide was no more effective than placebo for clomiphene citrate resistance in patients with PCOS, but it did reduce E2 levels and follicle numbers when combined with urinary FSH. Thus, octreotide may reduce the incidence of OHSS in patients with PCOS.

Prospective randomized trial comparing the outcome and cost of in vitro fertilization with that of a traditional treatment algorithm as first-line therapy for couples with infertility.

OBJECTIVE: To determine whether IVF or a standard infertility treatment algorithm results in better outcome and/or lower cost when used as first-line therapy for couples with infertility. DESIGN: Prospective, randomized clinical study. SETTING: University-affiliated infertility clinic. PATIENT(S): Couples with newly diagnosed infertility and no prior treatment. INTERVENTION(S): Couples were randomized to undergo either IVF (group 1, n = 46) or a standard infertility treatment algorithm (group 2, n = 50) as initial therapy for infertility. MAIN OUTCOME MEASURE(S): Pregnancy rates and costs per couple, per month of treatment, and per pregnancy. RESULT(S): Pregnancy rates were higher in group 2 than in group 1. Costs per couple were not statistically different, although a trend toward higher costs was apparent in group 1, reflected by a higher median cost per clinical pregnancy established and a higher cost per month of treatment. Whereas cost differences between the groups diminished over time, pregnancy rates remained the same. CONCLUSION(S): In vitro fertilization currently does not represent an appropriate first-line treatment option for couples with infertility. The use of a standard infertility treatment algorithm results in a higher pregnancy rate and lower cost and therefore should be the preferred treatment approach.

Cost considerations with infertility therapy: outcome and cost comparison between health maintenance organization and preferred provider organization care based on physician and facility cost.

Of 98 retrospectively selected patient couples insured under one scheme (group I) who, based on performance of a hysterosalpingogram (HSG), were assumed to be under active infertility care, 96 were confirmed as infertile. These were matched by date, patient age and time of HSG to 96 patients under infertility care (group II). Both patient populations were then prospectively evaluated for outcome and cost of treatment. Total physician charges for groups I and II were similar. However, charges per achieved clinical pregnancy were higher in group I than group II since group I patients demonstrated a lower pregnancy rate (28/96, 29%) than group II patients (41/96, 43%) (P=0.05). Within group I, pregnancy rates were identical, whether treatment was provided by generalists or subspecialists. In group II, all care was provided by specialists. The number of days of treatment did not vary between groups I and H, though generalists in group I provided significantly fewer treatment days than specialists in either group I (P=0.003) or in group II (P=0.021). This was primarily due to a significantly higher patient drop-out rate in group I patients, and especially amongst those who received care from generalists (P < 0.0019). Group I patients also encountered significantly more surgical procedures than group H patients (P=0.0016). If physician charges are discounted and customary surgical facility costs are added, the actual cost structure for fertility care in group I patients was dramatically higher than in group II patients. The most cost-effective format to provide infertility care of high quality appears to be a managed care setting in which subspecialists provide a majority of care and in which patient choice is restricted to those subspecialists.

Lysis of intrauterine adhesions using gynecoradiologic techniques.

OBJECTIVE: To present further experience with in-office lysis of intrauterine adhesions under fluoroscopic control using a specially designed catheter. DESIGN: Prospective study. SETTING: Medical school-affiliated infertility center. PATIENT(S): Seventeen infertile patients undergoing routine gynecoradiologic investigation as part of an initial infertility workup. INTERVENTION(S): The initial hysterosalpinography was performed with a commercially available uterine catheter that seals off the uterine cavity before injection of contrast. If intrauterine adhesions were diagnosed, an immediate attempt at lysis was made using the catheter's balloon tip or hysteroscopic scissors, which were inserted through the main port of the catheter. The procedures were carried out using a paracervical block or IV analgesia. MAIN OUTCOME MEASURE(S): Normal uterine cavity after lysis of intrauterine adhesions. RESULT(S): Seventeen patients underwent lysis of intrauterine adhesions. In 13 patients (9 mild, 3 moderate, and 1 severe), the adhesions were lysed successfully (81.2%). Among those, nine procedures were performed with the balloon and four with scissors. In 4 cases (2 moderate and 2 severe), lysis of adhesions was only partially successful. These procedures had to be abandoned prematurely because of patient discomfort before attempting the use of scissors (n = 1), extravasation of dye into the myometrium making visualization difficult (n = 1), and thick, fibrotic adhesions that were resistant to scissors (n = 2). CONCLUSION(S): In-office lysis of intrauterine adhesions under gynecoradiologic control can be carried out safely in the majority of patients, using minimally invasive techniques. The potential cost savings in comparison with endoscopic procedures, which require utilization of expensive operating room time, are especially relevant in today's cost-conscious managed care environment. Only failures of in-office procedures would reach the operating room under the algorithm proposed here.

Limited success using the "flare" protocol in poor responders in cycles with low basal follicle-stimulating hormone levels during in vitro fertilization.

OBJECTIVE: To assess an alternate protocol for stimulating poor responders. DESIGN: Prospective clinical study. SETTING: University-affiliated infertility clinic. PATIENT(S): Eighty poor responders. INTERVENTION(S): Stimulation was withheld until patients fulfilled the following criteria: basal FSH < or = 12 mIU/mL (conversion factor to SI unit, 1.00) with concurrent E2 level < or = 100 pg/mL (conversion factor to SI unit, 3.671), and P level < or = 1.0 ng/mL (conversion factor to SI unit, 3.467). They then started leuprolide acetate on cycle day 2 and a high dose of gonadotropins on cycle day 3. MAIN OUTCOME MEASURE(S): Stimulation response and pregnancy rates (PRs). RESULT(S): Nineteen cycles (23.8%) were canceled because of poor ovarian response. The mean E2 level on day of hCG was 2,578 +/- 1,339 pg/mL (9,464 +/- 4,915 pmol/L) (range, 789 to 5934 pg/mL [2,896 to 21,784 pmol/L]). The number of oocytes retrieved was 10 +/- 6.6 (range, 1 to 37). Nine patients did not have ET (failed fertilization [n = 5], no cleavage of preembryos [n = 3], freeze all [n = 1]). The number of pre-embryos transferred was 3.9 +/- 1.6 (range, 1 to 8). The clinical pregnancy rate was 7 of 61 (11.5%) per retrieval, and 7 of 52 (13.4%) per transfer with an implantation rate of 7 of 201 (3.5%). Three patients miscarried with an ongoing PR of 4 of 61 (6.5%) per retrieval and 4 of 52 (7.6%) per transfer. CONCLUSION(S): Poor responders undergoing controlled ovarian hyperstimulation with the "flare" protocol in cycles with low basal FSH will often show adequate ovarian response and reach oocyte retrieval and ET. The PRs, however, remain low.

What is the radiation exposure to patients during a gynecoradiologic procedure?

OBJECTIVE: To evaluate the risk of radiation exposure to infertility patients during a gynecoradiologic procedure. DESIGN: Retrospective clinical study. SETTING: Medical school-affiliated infertility center. PATIENT(S): Three hundred thirty-two consecutive infertility patients undergoing a gynecoradiologic procedure. INTERVENTION(S): Patients underwent a gynecoradiologic procedure as part of their infertility workup and the fluoroscopic exposure time was analyzed. MAIN OUTCOME MEASURE(S): The fluoroscopic exposure (rad time) during gynecoradiologic procedures, including hysterosalpingogram (HSG), selective salpingography, tubal catheterization, and others. RESULT(S): The rad time (mean +/- SD) was 63 +/- 54 seconds for normal HSG (n = 94, range 17 to 404 seconds), 100 +/- 61 seconds for abnormal HSG (n = 53, range 28 to 272 seconds), 111 +/- 57 seconds for unilateral selective salpingography (n = 36, range 31 to 324 seconds), 142 +/- 74 seconds for bilateral selective salpingography (n = 87, range 40 to 430 seconds), 176 +/- 77 seconds for unilateral tubal catheterization (n = 27, range 70 to 342 seconds), and 239 +/- 82 seconds for bilateral tubal catheterization (n = 30, range 110 to 381 seconds). Five patients had other procedures, such as lysis of intrauterine adhesions (n = 2) and resection of an uterine septum (n = 3), for which the rad time was in a range of 180 to 300 seconds. CONCLUSION(S): The radiation exposure of patients during a gynecoradiologic procedure, using previously described standard techniques, is well within established margins of safety.

Infertility treatment dropout and insurance coverage.

OBJECTIVE: To assess early patient dropout rates during infertility treatment as a potential measure of wasted resources. METHODS: The study involved multifaceted population cohorts, including a prospectively observed captive health maintenance organization (HMO) population and retrospectively selected preferred provider organization (PPO) patients. One hundred twenty-eight HMO couples were followed prospectively for 6 months. The insurance carrier retroactively selected 96 couples from their PPO population who were believed to be infertility patients. They were matched by date, age, and time of hysterosalpingography to infertility patients in the carrier's HMO population. Patients were considered treatment dropouts if they either requested their provider to abandon further work-up or treatment, or if they failed to return for an appointment for 3 months. RESULTS: Forty-six of 128 (36%) HMO patients followed prospectively discontinued care within 180 days, with only eight (6.3%) providing defined reasons. Preferred provider organization patients uniformly demonstrated significantly higher dropout rates than HMO patients, a finding already apparent at 60 days (P < .002; odds ratio [OR] 3.67, 95% confidence interval [CI] 1.47-9.97) and 120 days of treatment (P = .002; OR 2.87, 95% CI 1.39-6.06). Among PPO patients, dropout rates were especially pronounced if infertility care was provided by generalists. At billing levels of at least $2000, HMO patients also demonstrated less dropout than PPO patients (P < .001; OR 6.14, 95% CI 2.72-14.79), with generalists again demonstrating a significantly larger patient loss than infertility specialists (P < .001; OR 0.18, 95% CI 0.66-0.49). CONCLUSION: Infertility patients demonstrate a surprisingly large early dropout rate, which is significantly larger if patients receive infertility care from generalists rather than specialists. Newly presenting infertility patients should be carefully evaluated, especially in indemnity situations, before expensive diagnostic and therapeutic interventions are ordered.