Methodology of human embryo transfer following assisted reproduction.
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Publications and source records attributed to A Lewin.
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OBJECTIVE: To evaluate whether a previously successful in vitro fertilization and embryo transfer (IVF-ET) cycle is a favorable prognostic factor for a subsequent cycle. DESIGN: A retrospective comparison between current IVF patients who have previously conceived in an IVF versus natural cycle. SETTING: The IVF unit of a university hospital. PATIENTS: Group A consisted of 51 patients (70 cycles of IVF-ET) who previously conceived in an IVF-ET cycle, and group B included 141 patients (201 cycles of IVF-ET) who previously conceived in a natural cycle. All couples with male factor infertility were excluded. Ovulation induction protocol was identical for both groups and consisted of gonadotropin-releasing hormone agonist pretreatment followed by gonadotropin stimulation. MAIN OUTCOME MEASURES: Pregnancy rate per ET, cumulative pregnancy rate, and livebirth rate in both groups. RESULTS: The following parameters were comparable for both groups: age, menotropin dosage required for an adequate stimulation, ovarian response, mean number of oocytes retrieved per cycle, fertilization and cleavage rates, and the mean number of embryo transferred. Group A attained a significantly higher pregnancy rate (PR) than group B (31.4% versus 19.4%). Group A also achieved a significantly higher livebirth rate (22.9% versus 11.4%) than group B. Similarly, the cumulative PR curves and the cumulative livebirth rate curves for three consecutive IVF-ET cycles differed significantly between the two groups. CONCLUSION: A previous successful IVF cycle is a positive prognostic factor for a repeated IVF attempt. This effect could be because of either an improved endometrial response or a better embryo quality. It may be that this patient population is relatively immune to the known untoward effects of ovulation induction on endometrial development and, therefore, may represent a potential clinical model that can be used to further identify the factors influencing uterine receptivity after ovulation induction.
OBJECTIVE: To examine the effect of GnRH analogue (GnRH-a) on the quality of frozen-thawed embryos and the pregnancy rate (PR) resulting from transfer. DESIGN: A retrospective study of two groups of women undergoing transfers of frozen-thawed embryos. In group 1 ovulation induction with hMG was begun after hypophyseal desensitization with GnRH-a for 2 weeks. In group 2 ovulation was induced with hMG only. The freezing and thawing techniques were identical for both groups. SETTING: In vitro fertilization unit at a university hospital. PATIENTS: The study group (group 1) included 108 women who underwent 137 transfer cycles of frozen-thawed embryos, and the control group (group 2) included 44 women in 51 cycles of thawed ETs. INTERVENTIONS: Ovum pick-up and ET techniques were the same for both groups. Methods of embryo freezing and thawing were identical, as were the morphological criteria for grading the embryos. RESULTS: The morphology of embryos was similar in both groups, as was the number of embryos that had at least 50% intact blastomeres (83% +/- 23% and 78% +/- 30% for group 1 and group 2, respectively). The PR (16 of 137 [11.7%] and 6 of 51 [11.8%], respectively) as well as the abortion rate (30%) were similar for both groups. CONCLUSIONS: The use of GnRH-a does not affect the quality of embryos nor the pregnancy outcome. Because the yield of frozen embryos per ovum pick-up is higher in cycles stimulated by GnRH-a/hMG, the PR per pick-up cycle is thus anticipated to be higher.
The diagnosis of inappropriate intrauterine fetal growth in triplet pregnancies requires normal standard sonographically determined growth curves. The aim of the present study was to establish such nomograms. The biparietal diameter (BPD), femur length, head and abdominal circumferences (HC, AC) were once in 3 weeks sonographically evaluated in 108 normal triplet fetuses. The resulting growth curves were compared with those of normal singleton fetuses. The data showed that, compared with singletons, the mean triplet fetal BPD progressively lags to a maximum of 2 1/2 weeks as pregnancy continuous from the 25th to the 36th gestational week. Similarly, mean femur length of triplet fetuses gradually shortfalls to the greatest of 2 weeks as gestation advances from the 25th to the 36th week. HC to AC ratio of the triplet fetuses does not differ from the singletons curve. It may be concluded that a normal fetal growth curve in triplet pregnancies demonstrates a 1- to 3-week delay compared with singleton gestations.
Sonographic growth curves of 47 normal triplet pregnancies were compared with those of 71 uncomplicated twin gestations. Starting from the 25th week, the biparietal diameter in triplets was found to lag progressively compared with that of twins, reaching a mean difference of 2 weeks at 36 weeks gestation. Similarly, a significant difference was found between the femur length and head to abdomen circumference ratio growth curves of triplets and twins. It is concluded that as pregnancy continues from the 25th to the 36th gestational week, there is a significant delay in the growth patterns of normal triplet pregnancies compared with twin gestations.
This four-center, 20-week, open-label study evaluated transdermal clonidine as an adjunct to enalapril 10 mg daily and demonstrated patterns of compliance. Seventy-four mildly to moderately hypertensive patients (mean seated blood pressure, 150/101 mm Hg) received enalapril 10 mg once daily as initial monotherapy. In 66 patients, the seated diastolic blood pressure remained greater than or equal to 90 mm Hg at the trough blood levels of enalapril. Transdermal clonidine (3.5 cm2, 7.0 cm2, or 10.5 cm2, equivalent to 0.1 mg, 0.2 mg, and 0.3 mg clonidine/day, respectively) then was added as needed to achieve blood pressure control. Forty-eight patients achieved diastolic blood pressures less than 90 mm Hg on concomitant therapy; 44 patients completed 8 weeks of maintenance dosing with a mean blood pressure of 134/85 mm Hg. Oral compliance, as measured by an electronic device that was actuated each time the medication vial was opened, varied from 48 to 140%. Compliance with the transdermal clonidine regimen was excellent; the patch was worn as directed during 96% of the patient-weeks of therapy. The authors conclude that blood pressure can be controlled by a combination of transdermal clonidine and enalapril in patients that do not adequately respond to enalapril monotherapy. Patients poorly complying with oral regimens may be candidates for a trial of transdermal clonidine monotherapy.
Morphologic studies of the endometrium have demonstrated that varying the duration of an artificial follicular phase (AFP) in women with ovarian failure did not adversely affect its developmental capacity. The aim of this study was to evaluate whether such manipulations of endometrial stimulation could influence the pregnancy rate in women undergoing oocyte donation (OD). Twenty-nine women were investigated in 51 cycles of OD. Endometrial preparation was performed with a fixed dose of micronized estradiol, 4 mg/day, administered for 5-35 days in accordance with oocyte availability. On the day of donation progesterone in oil, 50 mg/day, was added to the regimen. Oocytes were donated anonymously by patients undergoing routine in vitro fertilization. Fifteen clinical pregnancies were achieved, for a success rate of 29.4%. Using logistic regression analysis the success rate was found to be closely associated with the duration of estrogen stimulation. The pregnancy rate was 7.7, 52, and 7.7% after an AFP of 4-11, 12-19, and 20-29 days, respectively. It seems that for optimal results in an OD program, estrogen stimulation should be kept at between 12 and 19 days. These results also imply that, contrary to endometrial morphology, which seems to be tolerant to extreme AFP durations, functional receptivity is less permissive and is adversely affected by such manipulations.
Preference for a particular chewing side may be influenced by several factors, one of which could be the functional contact area on each side of the dentition. In this study, interocclusal wax records were made for each of the 30 subjects. A digital image of the transilluminated wax record was analysed to group 'grey' values into categories of wax thickness. The total area for tight and intermediate tooth contacts was calculated for both the left- and right-hand sides of each subject. The chewing-side preference was recorded. No correlation was found between the area of occlusal contact on one side and the preference for chewing on that side. Occlusal contact area does not appear to be a determinant of chewing-side preference.
Rhizobium species strain NGR234 is the most promiscuous known rhizobium. In addition to the non-legume Parasponia andersonii, it nodulates at least 70 genera of legumes. Here we show that the nodulation genes of this bacterium determine the production of a large family of Nod-factors which are N-acylated chitin pentamers carrying a variety of substituents. The terminal non-reducing glucosamine is N-acylated with vaccenic or palmitic acids, is N-methylated, and carries varying numbers of carbamoyl groups. The reducing N-acetyl-glucosamine residue is substituted on position 6 with 2-O-methyl-L-fucose which may be acetylated or sulphated or non-substituted. All three internal residues are N-acetylated. At pico- to nanomolar concentrations, these signal molecules exhibit biological activities on the tropical legumes Macroptilium and Vigna (Phaseoleae), as well as on both the temperate genera Medicago (Trifoliae) and Vicia (Viciae). These data strongly suggest that the uniquely broad host range of NGR234 is mediated by the synthesis of a family of varied sulphated and non-sulphated lipo-oligosaccharide signals.
Transfer of a cosmid containing nodSU from Rhizobium sp. NGR234 to Rhizobium fredii USDA257 expands the host range for nodulation to include the perennial tropical legumes, Leucaena leucocephala and Leucaena diversifolia. Complementation experiments with a series of subclones established that nodS and its associated nod-box promoter from NGR234 are sufficient to confer this extended host-range phenotype to L. leucocephala. Strain USDA257 contains its own copy of nodSU, including upstream nod-box sequences. Although both nucleotide and deduced amino acid sequences of the reading frames are homologous between the two strains, there are gaps within the promoter region and the 5'-end of nodS of USDA257. Consequently, the deduced NodS protein of USDA257 is shorter than its counterpart from NGR234, and the distance between the nod-box and the initiation codon is greater. A 36 bp deletion encompasses the extreme right border of the USDA257 nod-box and extends into the upstream leader sequence. Transcriptional fusions with both nod-boxes confirmed that the promoter from NGR234 is flavonoid-inducible, and that the nod-box from USDA257 is not. These observations were corroborated by Northern analysis with a nodS-containing Xhol fragment as hybridization probe. Flavonoid-induced cells of NGR234 gave an intense signal, but those of USDA257 yielded only a weak trace of hybridization. EcoRI fragments with homology to nodSU of USDA257 are present in 17 of 35 tested strains, including several representatives of Bradyrhizobium japonicum, Rhizobium sp., R. loti, and R. fredii. Two wild-type, leucaena-nodulating strains of Rhizobium sp. lack this homology. We conclude that a genetic defect in expression of nodS accounts for the inability of USDA257 to nodulate leucaena and that diverse rhizobia may have evolved alternative mechanisms to nodulate this legume species.
The Bioself 110 electronic basal body temperature (BBT) measurement device was employed in 18 women undergoing in vitro fertilization (IVF). This microcomputer-operated device records, charts and accurately analyzes the mean temperature measurements. These temperature recordings were used in addition to transvaginal ovarian sonography and serum estradiol and progesterone levels. The BBT rise correlated significantly (p < 0.0002) with progesterone elevation following human chorionic gonadotropin (hCG) administration. It is suggested that this electronic device may be used as an additional tool in the detection of premature progesterone secretion in IVF cycles.
Intrauterine bone marrow transplantation (BMT) may represent a new approach for correction of a large variety of genetic disorders in utero. The procedure may become feasible for more genetic disorders in the future, since a large majority of potentially correctible diseases can be diagnosed at an early stage of gestation in utero using molecular probes that permit analysis of small biologic samples and even few cells that may be obtained by chorionic villi biopsy and/or amniocentesis. Haploidentical paternal marrow (2 cases) and sibling bone marrow cells from a disease-free family members, were infused into the fetus. GVHD was avoided following in vitro T-lymphocyte depletion using monoclonal antilymphocyte (CDW52) antibodies (Campath-1) without affecting stem cell viability, similarly to the procedures in routine use in clinical BMT programs in man. Three women underwent intrauterine BMT at 34, 23 and 25 weeks of gestation for metachromatic leucodystrophy (Arylsulfatase A deficiency, 2 cases) and beta thalassemia major (1 case), respectively. A total of 33 x 10(8), 30 x 10(8) and 30 x 10(8) bone marrow cells were infused intraperitoneally (1 case), intraportally plus intraperitoneally (2 cases) with no fetal distress. Although the procedure was uneventful and no clinical evidence of GVHD was observed following delivery, correction of the basic disorders was not accomplished because of anticipated rejection of marrow allografts.(ABSTRACT TRUNCATED AT 250 WORDS)
Stretching the duration of an artificial follicular phase in an oocyte donation program facilitates greatly the synchronization between the donor and the recipient. In order to investigate the limits of such a prolonged endometrial preparation, 18 patients with ovarian failure were studied during 20 treatment cycles. These patients were prospectively and randomly divided into three groups (A, B, and C in eight, six, and six cycles respectively). All groups were treated with oral estradiol and estriol (at a 2:1 ratio), 4 mg/day for 21, 28, and 35 days, respectively. At this stage 50 mg/day of intramuscular progesterone was added for additional 7 days. Endometrial adequacy was evaluated by late follicular and midluteal endometrial biopsies. During treatment no patient suffered from breakthrough bleeding. The mean estradiol and progesterone levels during the follicular and luteal phases did not differ significantly between groups. All late follicular biopsies showed a normal proliferative endometrium with no signs of glandular cystic hyperplasia. The midluteal biopsy showed a secretory endometrium adequate for 18.6 +/- 1.8, 21.8 +/- 1.8, and 18.6 +/- 1.5 days in groups A, B, and C, respectively, with no significant glandular-stromal disparity. We conclude that an artificial prolonged follicular phase does not seem to affect adversely the endometrial preparation in an oocyte donation program.
A method of analysing jaw movements was developed by converting jaw displacements into a matrix of frequency distributions. Low frequencies were first filtered out; then quartiles and modes were used to describe the remaining core. Eight different types of measures (variables) were developed to describe the proportions and density of a core of movement. These variables were repeatable at successive recording sessions, yet accurate enough to reveal differences in chewing patterns between right- and left-sided chewing. All eight variables of jaw displacement were required to discriminate between the chewing sides of 15 subjects. A statistical model was developed to express the principal components of jaw movement. The first component consisted of variables that expressed the shape of the chewing cycle; the second, its distribution about the midline; the third, the prevalence of a bimodal pathway in the sagittal plane. There was a wide variation in patterns of chewing movements, which appear to be consistent with normal masticatory function. A multivariate model appears to be required to describe chewing movements.
Jaw movements during voluntary chewing were recorded from 15 normal subjects with a sirognathograph. A computer program was used to provide a graphic display of the closing strokes in the frontal plane. A record was made of the side from which the jaw approached a central occlusal position. An average of 90 closing strokes was recorded for each subject. In 10 of the subjects, statistical differences were found between the use of the right- and left-hand sides. In these subjects this preference was confirmed by analysis of results from a second set of observations. A model was derived, using multiple regression analysis, which identified a relationship between four jaw-movement variables and an index of preference. A broad chewing pathway, with a bilateral distribution, together with a wide sagittal pathway were characteristics associated with preference. An indication of optimal jaw-movement patterns may be derived from identifying movement variables associated with preferred chewing.
This work was undertaken in order to evaluate retrospectively the relative efficacy of ovulation induction by menotrophins and that of in-vitro fertilization and embryo transfer (IVF-ET) in the treatment of unexplained infertility. These two treatments were compared between two groups of patients: 87 couples undergoing 446 cycles of ovulation induction by menotrophins (group A) and 72 couples undergoing 108 cycles of IVF-ET (group B). A total of 30 and 20 pregnancies were achieved in groups A and B for a rate of 34 and 28% per patient, respectively. A similar cumulative pregnancy rate (CPR) was achieved for three cycles of ovulation induction (23%) and one cycle of IVF-ET (22%). The cumulative live birth rate (CLBR) in group A was 22% after three cycles and exceeded that of one IVF-ET cycle (17%). It is concluded that menotrophin treatment in unexplained infertility is highly beneficial and should precede an IVF attempt.
OBJECTIVE: This work was undertaken to evaluate the correlation between sperm cell morphology and fertilization after zona pellucida slitting in subfertile males. DESIGN: Twenty-two couples who failed at least one in vitro fertilization attempt because of lack of oocytes fertilization underwent a zona-slitting micromanipulative procedure. A total of 245 oocytes were retrieved and inseminated by three different modes: 151 oocytes underwent micromanipulation, 2 were damaged, and the remaining 149 inseminated by the husband's sperm (group A). Fifty-five oocytes were not manipulated and inseminated by the husband's sperm (group B), and 39 oocytes were not manipulated and inseminated by a donor sperm (group C). RESULTS: Fertilization rates were 26.8%, 5.5%, and 53.8% in groups A, B, and C, respectively, and differed significantly between group A and group B. The cleavage rates were lower for oocytes fertilized by the husband's sperm (48.6%) than that obtained by donor (90%), suggesting a sperm factor contributing to this phenomenon. The procedure was most efficient in patients with a total motile sperm count after preparation of greater than or equal to 5 million and with either normal sperm morphology or defects localized to the acrosome or tail region only. Sperm with nuclear morphological abnormalities demonstrated a marked reduction in fertilization potential. CONCLUSION: It is concluded that the zona-slitting technique enhances fertilization of severely subfertile sperm, and its efficacy is affected by sperm morphology and a threshold concentration of motile cells.
Guanfacine, an alpha 2 adrenoceptor agonist, was compared with prazosin hydrochloride for the treatment of patients with mild to moderate essential hypertension in an 8-week, double-blind, randomized, parallel evaluation to determine efficacy and safety. The study consisted of a 2-week screening/weaning period (phase I), a 3-week treatment period with chlorthalidone 25 mg every morning (phase II), and an 8-week double-blind treatment period with diuretic plus prazosin or guanfacine (phase III). Those who had an average seated diastolic blood pressure (BP) of 95 to 114 mm Hg at the end of the phase II period were eligible to enter the phase III period and were randomly assigned to chlorthalidone plus either guanfacine, 1 mg every night, or prazosin, 1 mg three times a day. Of the 102 patients who were randomly assigned to guanfacine or prazosin, 80% completed the entire study. Guanfacine and prazosin appeared to be equally effective and reduced seated as well as standing diastolic and systolic BP. The mean seated systolic and diastolic BP were reduced 11/9 mm Hg by guanfacine and 11/10 mm Hg by prazosin. The mean reduction in seated pulse was 3 beats/minute for guanfacine and no change with prazosin. Similar changes occurred in the standing position. Very few adverse effects were reported during the study. Adverse effects with an incidence of 5% or greater for either drug group were dizziness (6% guanfacine, 8% prazosin), xerostomia (6% guanfacine, 2% prazosin), and somnolence (0% guanfacine, 6% prazosin). Three patients (6%) in the prazosin group experienced symptoms of orthostasis requiring premature discontinuation of the drug and termination from the study.