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Biomedical subjects

G Lavy

Publications and source records attributed to G Lavy.

At least 19 recordsLinked to original sources

Luteinizing response to human chorionic gonadotropin does not predict outcome in gonadotropin releasing hormone agonist-suppressed/human menopausal gonadotropin-stimulated in vitro fertilization (IVF) cycles.

OBJECTIVE: The purpose of this study was to determine if early luteinizing potential in gonadotropin releasing hormone agonist (GnRH-a)-suppressed/human menopausal gonadotropin (hMG)-stimulated IVF cycles is predictive of cycle outcome. DESIGN, PATIENTS: The study was a prospective evaluation of 41 women beginning a GnRH-a-suppressed/hMG-stimulated IVF cycle. SETTING: The in vitro fertilization program of a tertiary care institution was the study setting. MAIN OUTCOME MEASURES: The main outcome measures were (1) estradiol (E2) and progesterone (P) levels on the day of human chorionic gonadotropin (hCG) administration and the following day and (2) the ovarian response to ovulation induction and clinical outcome. RESULTS: Ten of the 41 women achieved a clinical pregnancy (24.4%). There was no significant difference in progesterone (P) levels on the day of or the day following hCG administration between the pregnant and the nonpregnant groups. Both groups exhibited a significant rise in P level in response to hCG. There was no significant difference in E2 levels on the day of hCG between the two groups. The serum E2 did not rise significantly in response to hCG in either group. Patients who became pregnant had significantly more oocytes retrieved, fertilized, cleaved, and transferred. CONCLUSIONS: Clinical response and outcome in GnRH-a-suppressed/hMG-stimulated IVF cycles are not predicted by early luteinizing potential as indicated by the response of E2 or P to hCG.

Adult↗

A model-based prediction for transvaginal ultrasonographic identification of early intrauterine pregnancy.

OBJECTIVE: Our objective was to develop a mathematic model for the prediction of transvaginal ultrasonographic identification of intrauterine gestation as a function of human chorionic gonadotropin titer or gestational age. STUDY DESIGN: In this prospective, descriptive study normal intrauterine pregnancies of 31 patients from the Yale in vitro fertilization and embryo transfer program and infertility clinic were studied. Logistic regression analysis was used to develop a probability curve of transvaginal ultrasonographic detection of intrauterine pregnancy as a function of human chorionic gonadotropin titer or gestational age with a 5 MHz vaginal transducer. RESULTS: A model-based prediction was constructed. It revealed that nearly all intrauterine sacs should be identified by a human chorionic gonadotropin titer of 3000 mIU/ml (first international reference preparation) or by a gestational age of 37 days on the basis of the 5 MHz vaginal transducer. CONCLUSIONS: A model-based prediction for transvaginal ultrasonographic identification of early intrauterine pregnancy is presented that can be readily adapted by individual institutions using their own ultrasonographic equipment and human chorionic gonadotropin assay.

Chorionic Gonadotropin↗

Selection bias in in vitro fertilization programs.

Pregnancy rates per cycle reported from different in vitro fertilization-embryo transfer programs vary widely. While several programs have reported constant pregnancy rates per cycle, others report declining pregnancy rates. Selection biases at the point of entry and between cycles are discussed as possible explanations of these discrepancies.

Bias↗

Flow cytometric analysis of deoxyribonucleic acid in human granulosa cells as a function of chronological age and ovulation induction regimen.

We examined whether the proliferative index of granulosa cells as determined by flow cytometry varied with a women's age or ovulation induction regimen that included leuprolide acetate (LA). This prospective cohort study included three groups of patients undergoing assisted reproductive technologies. Group I consisted of 9 women age less than or equal to 30 yr, who received LA plus human menopausal gonadotropin (hMG). Group II included 9 women age more than or equal to 40 yr, who received LA plus hMG. Group III consisted of 6 women age less than or equal to 30 yr who received hMG alone. A total of 79 preovulatory follicles containing greater than 10(4) granulosa cells were obtained from these 24 women and examined by flow cytometry. Group I was compared to group II to match for ovulation induction regimen and to examine proliferative index as a function of age. Group I was compared to group III to match for age and to examine proliferative index as a function of ovulation induction regimen. Outcome measures included proliferative index of granulosa cells as a function of age, ovulation induction regimen, ampules of hMG, estradiol on day of hCG, and serum FSH. Group I demonstrated a greater proliferative index than group II: 23.4% +/- 1.4 vs. 18.4% +/- 0.96 (P less than 0.01). Group I had a greater proliferative index than group III: 23.4% +/- 1.4 vs. 11.9 +/- 0.61 (P less than 0.001). Although both age and the presence of LA appeared to affect the PI, multiple linear regression demonstrated that only the addition of LA and not age, per se, had an independent effect upon granulosa cells undergoing proliferation (P less than 0.0005). We conclude that LA followed by hMG leads to an increase in the percentage of granulosa cells undergoing proliferation when compared to ovulation induction regimens that include hMG alone. Chronological age does not appear to have a significant independent influence upon the proliferative index.

Adult↗

Interinstitutional variability of follicle-stimulating hormone and estradiol levels.

OBJECTIVE: To evaluate the variability of follicle stimulating hormone (FSH) and estradiol (E2) results from different laboratories. DESIGN: Prospective analyses of sera separated and frozen, obtained from 15 female patients in the follicular phase. All kits used for radioimmunoassay (RIA) for FSH were from the Second International Reference Preparation (IRP). Four different kits were used for FSH and three for E2. SETTING: Sera obtained from each patient were separated into five test tubes and frozen. Analysis of all samples was done on the same day in each one of five participating hospital-based RIA laboratories (North Shore, Cornell, Yale, Mount Sinai, and Norfolk). PARTICIPANTS: Fifteen consecutive patients from the assisted reproductive technology program at North Shore University Hospital participated in the study. MAIN OUTCOME MEASURES: After FSH and E2 levels were tabulated for each laboratory, mean levels were calculated. RESULTS: Using the Bonferroni adjusted pairwise multiple comparisons analysis, significant differences were found between three groups of laboratories within the FSH results and three different groups within the E2 results. CONCLUSIONS: [1] Different results may be obtained on the same sera for FSH and E2 at different laboratories; [2] for FSH, even though the same IRP is used, different results are reached; [3] for E2, even when the same kits are used, results may be significantly different. These results suggest that specific FSH and E2 levels used to predict chances for achieving a viable pregnancy through in vitro fertilization should be interpreted with caution across institutions.

Estradiol↗

The role of office hysteroscopy in in vitro fertilization.

Twenty-eight patients participated prospectively in a study to evaluate the impact of hysteroscopically detected uterine and cervical anomalies on the success rate of ET in an IVF-ET program. All participants had a normal intrauterine cavity by standard HSG. All the patients had a diagnostic office hysteroscopy under paracervical block before commencing COH. Because our IVF program does not include hysteroscopy as a requirement before undergoing IVF and because the significance of mild intrauterine abnormalities is not yet known, the hysteroscopic findings were not relayed to the personnel involved in the IVF-ET procedure. Sixteen patients (group I) had a normal hysteroscopic evaluation. Twelve patients (group II) had abnormal hysteroscopic findings including small uterine septa, small submucous fibroids, uterine hypoplasia and cervical ridges. Although no difference in patients or cycle characteristics was present, there was a significant difference in the clinical PR between patients in groups I and II. In conclusion, in an IVF-ET program patients with normal hysterography but abnormal hysteroscopic findings had a significantly lower clinical PR, demonstrating the importance of performing hysteroscopy before IVF-ET.

Adult↗

Nafarelin versus leuprolide in ovulation induction for in vitro fertilization: a randomized clinical trial.

Gonadotropin-releasing hormone agonists vary in structure and route of administration. We performed this study to compare patient response to intranasal nafarelin acetate versus subcutaneous leuprolide acetate as adjuncts to ovulation induction for in vitro fertilization (IVF). Forty-two patients entering their first cycle of IVF were randomized to receive either nafarelin acetate or leuprolide acetate. Patient characteristics in the two groups did not differ significantly, nor did cycle cancellation rates or outcome. There was no significant difference in patient response as indicated by follicular phase serum levels of estradiol (E2), FSH, or LH, luteal phase E2, and progesterone. Luteal phase progesterone-dependent endometrial protein was significantly lower in those taking nafarelin acetate, though it remained in the normal range. However, those receiving nafarelin acetate required significantly less human menopausal gonadotropin (hMG) and had significantly more embryos frozen for later transfer than those receiving leuprolide acetate. Intranasal nafarelin acetate can be used successfully in ovulation induction regimens that include GnRH agonists. The use of nafarelin acetate may decrease a patient's hMG requirement and increase the number of frozen embryos available for later transfer as compared with leuprolide acetate. Further studies are needed to optimize the dosing regimen.

Administration, Intranasal↗

Corpus luteum function in successful in vitro fertilization cycles.

The function of the corpus luteum in early pregnancy has been subject to some controversy. The purpose of our study was to determine the life span of the corpus luteum in early pregnancy after successful GnRH-a/hMG stimulation in IVF-ET. The study consisted of a retrospective analysis of patients after 12 successful singleton intrauterine IVF-ET cycles. Serum samples were obtained during early pregnancy beginning 14 days after hCG administration. The levels of 17 alpha-OHP, hCG, P, and E2 were measured in each sample. A significant negative correlation was noted between 17 alpha-OHP and date from hCG. The x-intercept of the regression line allowed estimation of the life span of the corpus luteum to be 72 +/- 25 days. In conclusion, in GnRH-a/hMG-stimulated IVF-ET cycles that result in a singleton pregnancy, the functional life span of the corpus luteum averages 72 days.

17-alpha-Hydroxyprogesterone↗

Multinuclear spermatozoa associated with polyploidy.

We are reporting on a possible association between multinucleated spermatozoa and polyploidy after in vitro fertilization. The semen from the male partner of a couple with 40% polyploidy on three in vitro fertilization attempts was examined by light and transmission electron microscopy. In that sample 10% to 12% of spermatozoa demonstrated conjoined or double heads. The significance of these findings is discussed.

Adult↗

Early pituitary desensitization and ovarian suppression with leuprolide acetate is associated with in vitro fertilization-embryo transfer success.

OBJECTIVE: To determine if the timing of the onset of pituitary desensitization and ovarian suppression using follicular phase leuprolide acetate (LA) is associated with in vitro fertilization-embryo transfer (IVF-ET) success for pregnancy. DESIGN: Retrospective series of IVF patients undergoing pituitary desensitization and ovarian suppression before beginning controlled ovarian hyperstimulation for IVF-ET. SETTING: Tertiary infertility practice. PATIENTS: Seventy-eight women for 80 cycles began LA on day 1 of their menstrual cycle. After 11 days of LA, 47 (59%) cycles in group I had suppressed serum estradiol (E2) levels less than 40 pg/mL, in contrast to 33 (41%) cycles in group II not adequately suppressed, thereby requiring additional days to achieve suppression. INTERVENTIONS: Controlled ovarian hyperstimulation was started when patients were satisfactorily suppressed, i.e., E2 less than 40 pg/mL. MAIN OUTCOME MEASURE(S): Mean E2 response, ampules of human menopausal gonadotropin, cancellation rates, number of oocytes retrieved, fertilization rates, and pregnancy rates (PRs) per cycle were examined between groups I and II. RESULTS: Group I demonstrated a greater mean E2 response on the day of human chorionic gonadotropin 1,735 pg/mL versus 1,470 pg/mL (P = 0.008), a greater fertilization rate 64% versus 55% (P = 0.02), and a higher PR per cycle 34% versus 12% (P = 0.036) compared with group II. CONCLUSIONS: Women who achieved desensitization-suppression within 11 days of initiating LA demonstrated a more favorable outcome for IVF-ET than those who did not.

Chorionic Gonadotropin↗

Heterogeneity in patient populations explains differences in in vitro fertilization programs.

OBJECTIVE: To evaluate the efficacy of in vitro fertilization and embryo transfer (IVF-ET). DESIGN: Two different models for pregnancy rates in IVF-ET have been developed: a beta-geometric model and a split population model. SETTINGS: All IVF cycles were performed at the Yale University School of Medicine in New Haven, Connecticut. PATIENTS, PARTICIPANTS: All patients undergoing 1,257 IVF-ET cycles performed between the years 1983 through 1987. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The probability of achieving a viable pregnancy per cycle. RESULTS: Because both models provide excellent explanations for our data distribution, the decline in the conditional probability of achieving pregnancy after a given number of unsuccessful cycles may be inferred. CONCLUSIONS: These findings question the justification of continuing IVF-ET treatment beyond some threshold number of cycles.

Embryo Transfer↗

Measurement of CA125, carcinoembryonic antigen, and alpha-fetoprotein in ovarian cyst fluid: diagnostic adjunct to cytology.

This study used CA125, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) to classify ovarian cysts by measuring the levels of the three antigens; this information was useful when fluid obtained through laparoscopic puncture of ovarian cysts was submitted for cytologic examination from patients for whom tissue was unavailable for classification. We studied 136 consecutive cyst fluids (108 benign, 28 malignant) and correlated the findings with the tissue diagnosis. All three antigens were very low (CEA, less than 0.5 ng/ml; CA125, 55-2,143 mu/ml; and AFP, less than 4.8 ng/ml) in follicular and lutein cysts. Markedly elevated CA125 (296-1,950,000 mu/ml) and low CEA (0.5-220 ng/ml) and AFP (less than 4.8 ng/ml) levels were seen in patients with serous neoplasms, both benign and malignant. Elevated CEA (greater than 600 ng/ml) and CA125 (56-65,330 mu/ml) levels were seen in primary mucinous cystadenoma and cystadenocarcinoma. Two patients with colonic carcinoma metastatic to the ovary had an elevated CEA (greater than 600 ng/ml) and a normal CA125. Only one patient, with a malignant teratoma, had an elevated AFP. The adjunctive use of CEA and CA125 is recommended for the classification of ovarian cysts.

Antigens, Tumor-Associated, Carbohydrate↗

Comparison of singleton and multiple pregnancies in in vitro fertilization (IVF) and embryo transfer (ET).

The purpose of this study was to analyze factors associated with multiple gestations in IVF-ET. Twenty-seven multiple gestations conceived following IVF-ET resulted in the delivery of 20 sets of twins and three sets of triplets. One quadruplet pregnancy was terminated due to heavy bleeding. There were four "vanishing sacs," two of which resulted in a twin pregnancy and two in singletons. These were compared to 88 singleton IVF-ET gestations. The only significant difference found was the higher numbers of embryos transferred in the multiple gestation group. No difference was found between the two groups in diagnosis, stimulation protocol, estradiol, response, number of eggs, fertilization, and cleavage rate. Maternal age was younger in the multiple-gestation group, though not statistically significant. It is thus suggested that limitation of the number of embryos transferred is the only means to reduce the incidence of multiple gestations in IVF-ET.

Adult↗

Preembryo biopsy and analysis of blastomeres by in situ hybridization.

We developed a method for the biopsy of preimplantation mouse embryos (preembryos) at the four- to eight-cell stage, which uses partial zona pellucida dissection. The preembryos were collected in calcium- and magnesium-free phosphate-buffered saline solution with 0.01% ethylenediaminetetraacetic acid, 0.1 mol/L sucrose, and 4 mg/ml of bovine serum albumin to facilitate removal of blastomeres. This allows entry of a fine micropipette into the perivitelline cavity with subsequent removal of a single blastomere by gentle suction. The majority of embryos (75%) from which biopsy specimens were obtained in this fashion developed to the blastocyst stage. The blastomeres obtained were mainly intact and they were fixed to glass slides. After permeabilization, in situ hybridization was performed with chromosome X- and chromosome 3-specific probes. Human unfertilized eggs and blastomeres from human polyspermic embryos also have been analyzed by in situ hybridization with chromosome specific probes. The combination of nondestructive embryo biopsy and in situ hybridization is a possible approach for preimplantation genetic diagnosis.

Animals↗

Manifestation of diabetes mellitus on mouse follicular and pre-embryo development: effect of hyperglycemia per se.

Animal models of diabetes mellitus during pregnancy have repeatedly suggested that maternal hyperglycemia was teratogenic during organogenesis, and thus may contribute to diabetic teratogenesis. However, little attention has been focused on the effects of hyperglycemia on pre-organogenic development. In this report, we examine the effect of hyperglycemia (950 mg glucose/dL) on the development of mouse pre-embryos in vitro. B6C3F1 mice were superovulated with 5 U pregnant mare serum gonadotropin (PMSG) followed by 5 U human chorionic gonadotropin (hCG) 48 hours later. Two cell pre-embryos were recovered 48 hours later, pooled together, and randomly assigned to different treatment groups. Cultures were performed in HAM's F-10 media (Gibco, Long Island, NY) with 0.1% bovine serum albumin (BSA; Sigma, St. Louis, MO) BSA at 37 degrees C in an atmosphere of 5% CO2, 5% O2, and 90% N2 with 15 to 30 embryos per milliliter of culture fluid. Cultures were viewed daily at 24, 48, and 72 hours after culturing, with recording of the development. Compared with control pre-embryos (n = 216), embryos cultured in elevated glucose levels (950 mg/dL) (n = 226) demonstrated marked growth retardation as assessed both by (1) distribution of developmental stages at each observation point (24 hours, P less than .001; 48 hours, P less than .006; 72 hours, P less than .001); and (2) a difference in the average rank sums indicating a delay in maturation (P less than .005). In a second protocol group, pre-embryos were cultured in an equivalent amount of L-glucose; no impairment in development compared with controls was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Purine levels and metabolism in human follicular fluid.

Adenosine (ADO) in low micromolar levels and hypoxanthine (HYP) in millimolar levels have been shown to inhibit maturation of cumulus-enclosed oocytes. To determine the effect of ovarian stimulation with gonadotrophins on follicular purine metabolism, we measured ADO, HYP, inosine (INO), adenine (ADE) and cyclic AMP (cAMP) levels in follicular fluid (FF) from natural (n = 7) or human menopausal gonadotrophin/human chorionic gonadotrophin (HMG/HCG)-stimulated (n = 35) cycles. Purines were extracted immediately (natural cycles) or within 30 min of recovery (HMG/HCG cycles) and analysed by high pressure liquid chromatography (HPLC). The concentration of all ADE purines in FF was in the low micromolar range (1-20 microM); cAMP levels were markedly increased (greater than 100 microM) in FF of HMG/HCG-treated patients. While ADO levels were within the range effective for inhibition of oocyte maturation, those of HYP were not. No correlation was found between purine levels in FF and ovum maturation. Purine levels in FF of natural cycles were uniformly lower than those of stimulated cycles. Significant conversion of 5'-AMP into ADO, ADO into INO and INO into HYP occurred within 1 h when FF was incubated at 25 but not at 4 degrees C. These purine levels in human FF confirm our previous findings with bovine FF and suggest a possible role of ADO, but not of HYP, in the inhibition of oocyte maturation in the human.

Adenine↗

Monitoring therapy with a gonadotropin-releasing hormone analog: utility of MR imaging.

The utility of magnetic resonance (MR) imaging in assessing response to therapy with a gonadotropin-releasing hormone (GnRH) analog was assessed in 19 women with uterine leiomyomas and 19 women with endometriosis. There was a significant reduction in individual fibroid volumes at 3 months (P less than .05) and at 6 months (P less than .005) in the drug group, whereas there was no significant change in the placebo group. Vessel conspicuity significantly decreased at 3 months (P less than .02) and at 6 months (P less than .01) in the drug group but not in the placebo group. In the patients with endometriosis, there was a significant decrease (P less than .0006) in the number of endometriomas visualized. Significant changes were also noted in the pelvis in women who were receiving the GnRH analog. After 6 months of therapy, the identifiability of the ovaries was significantly poorer (P less than .05). The authors conclude that the utility of conservative therapy with a GnRH analog can be quantitatively assessed with MR imaging.

Abdominal Neoplasms↗