The context matters: The use of communicative intentions by mothers to their children during playtime and mealtime.

This study examined the use of various communicative intentions (CIs) of mothers directed to their children in two contexts: playtime and mealtime at two linguistic stages: preverbal and single-word. The study revealed that statements were most prevalent during mealtime, while both statements and directives were prevalent during playtime. Particularly, directives were more frequent during playtime than during mealtime. Moreover, the number of CIs directed to children in the preverbal stage was higher than children in the single-word stage. These findings emphasize the role of context and culture on the mother-child language use in general and CIs in particular.

Content words in Hebrew child-directed speech.

The goal of the study was to examine whether the 'noun-bias' phenomenon, which exists in the lexicon of Hebrew-speaking children, also exists in Hebrew child-directed speech (CDS) as well as in Hebrew adult-directed speech (ADS). In addition, we aimed to describe the use of the different classes of content words in the speech of Hebrew-speaking parents to their children at different ages compared to the speech of parents to adults (ADS). Thirty infants (age range 8:5-33 months) were divided into three stages according to age: pre-lexical, single-word, and early grammar. The ADS corpus included 18 Hebrew-speaking parents of children at the same three stages of language development as in the CDS corpus. The CDS corpus was collected from parent-child dyads during naturalistic activities at home: mealtime, bathing, and play. The ADS corpus was collected from parent-experimenter interactions including the parent watching a video and then being interviewed by the experimenter. 200 utterances of each sample were transcribed, coded for types and tokens and analyzed quantitatively and qualitatively. Results show that in CDS, when speaking to infants of all ages, parents' use of types and tokens of verbs and nouns was similar and significantly higher than their use of adjectives or adverbs. In ADS, however, verbs were the main lexical category used by Hebrew-speaking parents in both types and tokens. It seems that both the properties of the input language (e.g. the pro-drop parameter) and the interactional styles of the caregivers are important factors that may influence the high presence of verbs in Hebrew-speaking parents' ADS and CDS. The negative correlation between the widespread use of verbs in the speech of parents to their infants and the 'noun-bias' phenomenon in the Hebrew-child lexicon will be discussed in detail.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Laparoscopic adnexectomy in a prepubertal Turner mosaic female with isodicentric Y.

Laparoscopic adnexectomy was performed in a prepubertal girl with mosaic Turner's syndrome containing an isodicentric Y chromosome. Cytogenetic analysis of lymphocytes and streak gonads are discussed.

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.

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.

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.

The predictive value and the management of cycles with low initial estradiol levels.

This study was undertaken to examine the predictive value of low estradiol (E2) after 5 days of human menopausal gonadotropin (hMG) stimulation response to therapy in that cycle. We further examined whether the outcome of such cycles can be improved by increasing the hMG dose. When 18 cycles in which day 8 E2 was less than or equal to 50 pg/mL were compared with 48 cycles with corresponding E2 levels of 51 to 150 pg/mL, the former showed a significantly worse response to subsequent hMG therapy. To determine the effect of an increase in hMG dose we studied 48 cycles with day 8 E2 of 51 to 150 pg/mL. In 32 cycles hMG dose was increased from three to a mean of five ampules a day, after 5 days of therapy. In 16 cycles it was kept constant at three ampules per day. Although a tendency towards lower fertilization rate was observed in the higher hMG groups, no significant differences were observed in the results between the two groups. We thus conclude that very low E2 levels after 5 days of gonadotropin therapy are predictive of low response in that cycle, and that in cycles with day 8 E2 of 51 to 150 pg/mL, increasing the dosage of hMG on day 8 and beyond does not alter the course of the cycle.

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.

Femoral neuropathy after laparoscopy. A case report.

Femoral neuropathy has been reported to occur after abdominal hysterectomies and has been related to nerve compression by abdominal wound retractors. We report a case of a 35-year-old woman with infertility who developed unilateral femoral nerve palsy after laparoscopy and hysteroscopy. This rare complication, secondary to extreme flexion, abduction and lateral rotation of the hip joint, can be prevented by careful preoperative patient positioning.

Evidence of gonadal and gonadotropin antibodies in women with a suboptimal ovarian response to exogenous gonadotropin.

Failure to respond to human menopausal gonadotropin (hMG) with adequate ovarian stimulation is associated with a poor prognosis in subsequent cycles in women participating in an in vitro fertilization/embryo transfer program. Sera from 26 menstruating women (mean age 38 +/- 4.3 years) identified as "low responders" with either tubal or male factor infertility, mean baseline FSH values of 11 mIU/mL, and peak serum estradiol levels lower than 300 pg/mL were assessed for specific antibodies to human ovary and gonadotropins. Twenty-five infertile women with tubal or male factor infertility with a good response to hMG served as controls. Ninety-two percent of low responders had antibodies to FSH and 65% had antibodies to LH when assessed by enzyme-linked immunosorbent assay. Similarly, 77% of low responders had ovarian antibodies. No hepatic antibodies were found in the sera of low responders, indicating that the positivity was not a general interaction with cell components. None of the "good responders" had antibodies to gonadotropins or to ovarian or liver tissue. The significant differences in antibodies between the groups supports a possible immunologic cause for low ovarian stimulation response to gonadotropin.