Biomedical subjects
Publications and source records attributed to A Lewin.
Multiple ovarian follicles were successfully induced in a patient undergoing superovulation for a gamete intrafallopian transfer (GIFT) procedure despite the presence of an undiagnosed ectopic pregnancy. Midluteal gonadotropin releasing hormone agonist (GnRH-a) treatment should be coupled with mechanical contraception in the previous cycle in patients with patent tubes.
Ultra miniature coaxial cable has been used, with microscopic techniques, to fabricate interstitial hyperthermia applicators having diameters of 0.20 mm, 0.33 mm, and 0.58 mm; commercial applicators have a diameter of 1.1 mm. Animal studies with the 0.33 mm diameter applicators have shown that they produce less local tissue trauma than the larger-diameter devices. All of these applicators operate at 915 MHz and have similar heating patterns because they use the conventional monopole design and the catheters have been approximately scaled to the dimensions of each size applicator. We have measured the heating (SAR) patterns of these applicators in tissue-simulating phantoms, both singly and in arrays, using a miniature electric field probe. As an intermediate step to patient trials, we have examined the ability of these applicators to provide effective heating of perfused tissue, using pig thigh and liver as models. Test results suggest that the durability and power handling capabilities of our submillimeter applicators are adequate for use in patients. These new applicators should be useful in the percutaneous treatment of deep-seated tumors and in intraoperative treatments. The applicators also permit intraluminal or intravascular access to tumors.
Nine hundred sixteen hamster oocytes were cryopreserved with the ultrarapid freezing method using five different cryoprotective solutions: 3 mol/L dimethylsulphoxide (DMSO) plus 0.25 mol/L sucrose, 3 mol/L DMSO, 3 mol/L propanediol plus 0.25 mol/L sucrose, 3 mol/L propanediol and 10% glycerol. One hundred eighty fresh oocytes served as controls. The viability of the oocytes was evaluated using morphologic parameters, Trypan blue staining and the sperm penetration assay. The viability rates based on morphologic parameters and Trypan blue staining were 82.3%, 65.0%, 51.4%, 33.0% and 0%, respectively, as compared to 100% in the controls. The sperm penetration rates were 27.0%, 0%, 9.8%, 0% and 0%, respectively, as compared to 94-98% in the controls. Our results indicate that among the various cryoprotective solutions used for ultrarapid freezing, 3 mol/L DMSO plus 0.25 mol/L sucrose gave the best results, with a viability rate of 82.3% and a sperm penetration rate of 27%.
Explore the source record for details and available documents.
Chromosomal mosaicism is one of several unanswered dilemmas in first-trimester prenatal diagnosis. We report the course of a pregnancy in which a normal karyotype was detected on direct CVS preparation and fetal blood, 100 per cent trisomy 21 in one long-term CVS culture, and low-rate trisomy 21 mosaicism in a second long-term CVS culture and amniocentesis. The phenotypically normal infant had a 6 per cent mosaicism of trisomy 21. It appears that a persistent low-rate mosaicism in different tissues may be indicative of the true status of the fetus.
Sixty-seven in vitro fertilization (IVF) patients who underwent ultrasonically guided oocyte pickup (OPU) after induction of superovulation with human menopausal gonadotropins were submitted to two different protocols of embryo transfer. In the first group of 33 patients, four to five embryos were transferred to the uterus 48 hr after OPU. In the second group of 34 patients two to three embryos were transferred at 48 hr after OPU and two other embryos were transferred after freezing and thawing 48 hr later (96 hr after OPU). The pregnancy rate achieved in the double embryo transfer (ET) protocol was significantly higher than in the single-ET protocol (32.4 vs. 18.2%, respectively; P less than 0.05).
The results of two human menopausal gonadotropin (hMG) protocols of ovulation induction for in vitro fertilization (IVF) were compared. With the first protocol, 28 women (group 1) were treated with an hMG dosage which was increased stepwise. With the second, 30 women (group 2) were treated with a high dose of hMG for 2 days, then given a constant daily dose. The two groups were compared with regard to ovarian response, luteal phase and laboratory and clinical outcomes of IVF. They were comparable as regards the total number of hMG doses required, the number of large follicles (mean diameter greater than 15 mm) on day 0 (day of human chorionic gonadotropin (hCG) administration), serum estrogen (E2) and progesterone (P) levels throughout the cycle and IVF laboratory and clinical outcomes. They differed significantly (p less than 0.01) only in the number of secondary smaller follicles (mean diameter less than 15 mm) observed on day 0 (3.7 +/- 0.4 for group 1 and 5.3 +/- 0.4 for group 2). Manipulating the hMG dosage during the early-mid follicular phase does not affect follicular synchrony, the number of oocytes harvested and the number of embryos achieved.
Cytologic parameters of the vaginal epithelium in 59 women undergoing in vitro fertilization-embryo transfer (ET) were correlated with plasma levels of 17-beta estradiol and progesterone on the oocyte pickup (OPU) and ET days. On the OPU day a late proliferative/late proliferative-early secretory pattern was observed in 84.6% of the 13 women who conceived (group 1) but in only 52% of the 46 who failed to conceive (group 2) (P less than .04). On the ET day a secretory phase appeared in 100% and 61% of group 1 and 2 patients, respectively (P less than .01). Between the OPU and ET days the mean karyopyknotic index dropped by 60% and 13% in group 1 and 2 patients, respectively (P less than .001). It seems that a high estrogenic effect followed by an advanced progestational environment, on the OPU and ET days, respectively, can provide a favorable milieu for implantation.
Fifty-eight follicular fluids (FF) were obtained from 18 women undergoing in vitro fertilization (IVF). Follicular development was induced by human menopausal gonadotropin (hMG) and follicular aspiration was performed 36 hr after an ovulatory dose of human chorionic gonadotropin (hCG). Two stages of oocyte-corona-cumulus complexes (OCCCs) morphological maturation was identified in this population: intermediate and mature. FF from which intermediate and mature OCCCs were obtained did not differ in 17 beta-estradiol (E2), progesterone (P), and cholesterol levels. Fifty OCCCs were fertilized and eight were not fertilized. No difference was found in E2, P, and cholesterol levels in those two populations of OCCCs. Forty hours after insemination 50% of the oocytes were at the two-cell stage and 50% were at the three-cell stage. Steroids and cholesterol levels did not differ in FF from which those two groups of embryos originated. A direct correlation was found among the levels of cholesterol, E2, and P in the FF. An inverted ratio of high-density lipoprotein (HDL) to low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) was found in FF compared to serum in 10 women. It is concluded that FF cholesterol levels have no value in predicting follicular maturation.
The direct action of insulin on human granulosa lutein cells (GLCs) in long-term cultures obtained from in vitro fertilization (IVF) cycles was investigated. Progesterone (P) secretion by GLC increased progressively in both basal and human chorionic gonadotropin (hCG; 100 mIU/ml) stimulated conditions up to 4 days in culture, and plateaued thereafter. Insulin (0.0025 mU/ml to 2500 mU/ml) had no effect on either basal or hCG stimulation during the culture period. GLC in culture formed a monolayer and multiplied at a rate of approximately once every 3 days. Neither morphology nor cell division was affected by insulin in supraphysiologic levels (25 mU/ml). These results suggest that GLC obtained from preovulatory follicles in an IVF program are already stimulated maximally by in vivo exposure to high doses of human menopausal gonadotropin (hMG)/hCG administered to the women. Contrary to its stimulatory effect on early preovulatory granulosa cells, insulin dose not affect P production, cellular morphology, or growth rate of luteinized granulosa cells.
In order to establish criteria for selection of the best ova in in-vitro fertilization-embryo transfer (IVF-ET) programes we have examined the follicular fluid (FF) levels of plasminogen activator (PA), collagenolytic activity, progesterone (P) and alpha 2 macroglobulin (alpha 2M) and related them to the success of pregnancy. PA activity was similar in FF of pregnant and nonpregnant cycles, 13.8 +/- 3.9 mU/ml versus 14.6 +/- 2.9 (mean +/- SEM) respectively. By contrast, FF from pregnant cycles exhibited lower collagenolytic activity (49.6 +/- 3.9% versus 67.9 +/- 3.0; P less than 0.001). Likewise, in a semi-quantitative assay of alpha 2M, only 18.4% of the aspirates from pregnant cycles showed a precipitation line, whereas 76.8% of those from non-pregnant cycles were positive. Levels of P in aspirates from pregnant cycles were in the intermediate range, as compared with those from non-pregnant cycles (0.06-5.5 micrograms/ml versus 0.02-12.0 micrograms/ml). All these assays can be completed before ET and performed in IVF-ET programmes. In conclusion, it seems that a combination of follicular alpha 2M levels and collagenolytic activity, and to a lesser extent addition of P assay, may serve as good criteria for selecting the best embryos for establishment of pregnancy.
Explore the source record for details and available documents.
RNase treatment of a cell-free translation system prevents transport of mitochondrial precursor proteins from that system into isolated yeast mitochondria. This inhibition depends on the presence of ribosomes in the reticulocyte lysate; if they are cleared by centrifugation, RNase treatment does not specifically inhibit protein uptake by mitochondria. Since protein import can occur in the absence of polyribosomes, RNase treatment does not degrade a structure essential for this process. Rather, the inhibition may be an effect of degraded ribosomes.
Guanfacine, an alpha 2-adrenoceptor agonist, was compared with clonidine as step-2 therapy of mild to moderate essential hypertension in a 24-week, double-blind, randomized, parallel evaluation to determine efficacy, safety and occurrence of withdrawal syndrome. During a 5-week period, patients were weaned from current antihypertensives, if any, and stabilized on step-1 therapy with 25 mg of chlorthalidone once a day. Those with a diastolic blood pressure (BP) from 95 to 114 mm Hg while taking chlorthalidone were randomized to treatment. The 2 agents had equal efficacy; 149 of 270 patients treated with guanfacine (55%) and 164 of 276 treated with clonidine (59%) achieved goal diastolic BP of less than or equal to 90 mm Hg. Terminations because of adverse effects were relatively low. Dry mouth (30% of guanfacine and 37% of clonidine groups) and somnolence (21% of guanfacine and 35% of clonidine groups, p less than 0.05) were reported most frequently. Nonsyncopal dizziness was reported in 11% of guanfacine-treated and 8% of clonidine-treated patients. This difference was not statistically significant. To evaluate the occurrence of a withdrawal syndrome in 316 outpatients and 156 inpatients, vital signs were monitored at least twice a day for up to 7 days after the end of therapy. Segmented 24-hour urine studies were performed on inpatients. Abrupt withdrawal of clonidine produced a rapid increase in diastolic and, especially, systolic BP, whereas guanfacine withdrawal produced more gradual increases. The differences were significant over the first 3 withdrawal days. It is concluded that guanfacine is a safe, effective, second-generation alpha 2-adrenoceptor agonist.(ABSTRACT TRUNCATED AT 250 WORDS)
In eight women with ovarian failure, we induced histologically normal endometrial function during a preparatory cycle consisting of sequential administration of estrogen and progesterone. During a subsequent cycle, endometrial stimulation was synchronized with surrogate-embryo transfer performed on days 16 to 21. Among the eight women, two pregnancies were established by embryo transfer on days 18 and 19. In both women, ovarian tissue was absent, and these patients therefore serve as an in vivo model for the isolated effects of estrogen and progesterone on implantation and maintenance of pregnancy. Treatment with exogenous estrogen was mandatory up to the 11th week of gestation, and treatment with progesterone until the 18th to 22nd weeks. We conclude that it is biologically feasible to simulate the essential hormonal and endometrial milieu of a fertile menstrual cycle and early gestation solely by the administration of estrogen and progesterone. Days 18 to 19 of the cycle are recommended for successful embryo implantation with this treatment program.
Ultrasonically guided follicular aspiration is now routinely used for in vitro fertilization (IVF) in many centers. We present an improved method for oocyte recovery. One hundred nine consecutive patients with mechanical infertility submitted for IVF were included in the study. Superovulation was induced with human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG). Oocyte recovery was ultrasonically guided, the bladder filled with phosphate-buffered saline (PBS), and a cannula with trocar used for single percutaneous puncture. The aspiration needle was of 1.6 mm in internal diameter. When compared to published data using smaller-bore needles, it seems that this improved needle increased the number of oocytes recovered to a mean of 6.5 and the number of embryos replaced to a mean of 3.9 per patient, with a pregnancy rate of 20% per transfer.
The association between in vitro fertilization (IVF) and the zona-free hamster egg sperm penetration assay (SPA) was studied in 134 couples. The indications for IVF were tubal disease in 82 couples, unexplained infertility in 23, male infertility in 10, and combined mechanical and male factors in 19. In general, a positive SPA was a good predictor of subsequent IVF (91 of 107 couples). Specificity (number of couples with fertilization in vitro divided by the number of couples with a positive SPA times 100) was 94% for tubal infertility, 76% for unexplained infertility, and 46% for male infertility. A negative SPA predicted an overall fertilization failure of 78% (21 of 27 couples). Sensitivity of the test (number of couples with IVF failure divided by the number of couples with a negative SPA times 100) was 100% for tubal and unexplained infertility but only 63% for male infertility. The high predictive value of the SPA for subsequent IVF outcome in tubal infertility and unexplained infertility warrants its routine use for prescreening in IVF programs. Because of the lack of association between SPA and IVF in oligoasthenospermia, the bioassay should not be relied upon for predicting IVF outcome in male subfertility. The overall high association between the animal model and human IVF reinforces the use of the SPA for both basic research and clinical decision-making.
This work was undertaken for evaluation of the value of endometrial thickness as an early predictor for the success of in vitro fertilization (IVF). Endometrial changes were evaluated ultrasonographically in 47 women undergoing IVF. A high-dose gonadotropin protocol was used for induction of multiple follicular development. Thirty-seven women did not conceive following the procedure (group I), and 10 conceived (group II). Ultrasonographic endometrial measurements were performed repeatedly throughout the cycle. Serum 17 beta-estradiol and progesterone levels were evaluated concomitantly. Three consecutive growth patterns of the endometrium were observed. The first was a rapid one with a daily growth rate of about 0.5 mm from approximately 9 mm on day -3 to 12 mm on day +2 (day 0 being the day of human chorionic gonadotropin administration). The second phase, following follicular aspiration, showed a decrease in growth rate to about 0.1 mm per day until day +11, when a thickness of about 13 mm was measured. In group I growth was arrested from day +11 until menstruation, whereas in group II an accelerated growth rate of about 0.4 mm per day could be demonstrated from day +14 onward. Endometrial growth did not correlate with serum estradiol or progesterone levels. No conception occurred with an endometrial thickness below 13 mm on day +11. It is concluded that endometrial thickness follows a distinct pattern of growth in human menopausal gonadotropin-induced cycles and does not correlate with serum sex hormones.(ABSTRACT TRUNCATED AT 250 WORDS)