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.

hCG free beta-subunit an early marker of outcome of in vitro fertilization clinical pregnancies.

In the in vitro fertilization (IVF) and embryo transfer (ET) program at Yale, 32% of pregnancies abort by 16 weeks. With the objective of predicting outcome, serum hCG titers were determined in serial samples from 48 women with clinical pregnancy (conception where fetal sac demonstrated by ultrasound). Although the mean hCG levels were lower at 8-14, 15-21, 22-28 and 29-35 days post-ET in the 18 women who eventually aborted, 0.18 (range 0.01-0.49), 1.5 (0.05-4.7), 6.4 (0.68-27), and 15 nmol/L (0.35-59), respectively, than in the 30 women whose pregnancy went to term, 0.48 (0.01-5.5), 2.2 (0.33-20), 10 (0.46-25), and 116 nmol/L (0.76-335) respectively, the ranges overlapped significantly, limiting the use of serum hCG in prediction. In earlier studies, the free beta-subunit of hCG was demonstrated in the serum of women with natural fertilization pregnancy, 2-6 weeks post ovulation. We used the RIA with 1E5 free beta-subunit monoclonal antibody to measure this component in the IVF serial blood samples. Of the 30 women who had pregnancies that went to term, samples from 28 were positive for this marker by 28 days post-ET (0.02-3.0 nmol/L). In 18 women who aborted, however, only 1 had a detectable serum hCG free beta-subunit level by 28 days post-ET. We conclude that a detectable serum hCG free beta-subunit level by 28 days post-ET may indicate normal term pregnancy outcome.

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.

The effect of insulin on oestradiol and progesterone release by normal and diabetic placentae in vitro.

In an attempt to define better the metabolic differences between normal, insulin-dependent and non-insulin-dependent diabetes, we have compared the effect of insulin on the secretion of oestradiol and progesterone in term placental explant culture. Placentae from non-diabetic and from diabetic, non-insulin-dependent diabetic patients demonstrated a similar response to incubation with insulin. This response consisted of a dose-dependent increase in both oestradiol and progesterone in the incubation media after 24 h. In contrast, the placentae of insulin-dependent diabetics showed a decrease in oestradiol and no change in progesterone secretion following exposure to insulin. These differences in response to insulin may underlie other metabolic differences between the placentae in the different groups.

The role of ACTH in placental steroidogenesis.

We have studied the possible function of the placental adrenocorticotrophic hormone-(ACTH-) like substance (PALS) in placental steroidogenesis by measuring oestradiol (E2) and progesterone (P4) in term human placental explants incubated with commercially available porcine ACTH I-39. There was a dose-dependent increase in the E2 and P4 released into the medium at 24 h as compared to controls. At 48 h, no significant effect was noted. Propranolol (10(-5) M) did not block the effect of ACTH on P4 release. The data suggest that ACTH may have a regulatory role on placental steroidogenesis. The possible mechanisms of action of PALS on the placenta and the adrenal are discussed, and the role of PALS in the maintenance of pregnancy and in maternal response to stress is suggested.

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)

Endometrial ablation for intractable uterine bleeding: hysteroscopic resection.

Twenty-one patients with intractable uterine bleeding were treated by resectoscopic ablation of the endometrium. All the patients were worked up thoroughly to rule out hormonal or anatomic reasons for their bleeding. In addition, various hormonal regimens were tried to stop the bleeding. Our technique used the modified urologic resectoscope, which is inserted into the uterine cavity. The entire endometrial cavity was ablated using 30 W of coagulating current. Of the 21 patients treated, 14 had blood dyscrasias, four were poor anesthetic risks, and three refused hysterectomy. There were no complications from the procedure. Three patients died from their primary disease, and all the rest, except for one, remained amenorrheic. We conclude that the use of the resectoscope for endometrial ablation is a successful, efficient, safe, and readily available way to treat intractable uterine bleeding.

A new device to facilitate intrauterine instillation of dextran 70 for hysteroscopy.

Dextran 70, a commonly used distension medium for diagnostic and operative hysteroscopy, is difficult to handle because of its high viscosity, which makes manual instillation cumbersome. We have developed an electric pump that facilitates the instillation of this distension medium at hysteroscopy. This new device is safe and easy to use, and improves the view of the uterine cavity during the procedure. Our initial experience using this pump in 43 hysteroscopic procedures is encouraging.

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.

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.

Pregnancy following tubocornual anastomosis.

We have reviewed the pregnancy rate and outcome of 25 patients who underwent tubocornual anastomosis for correction of proximal tubal occlusion at Yale-New Haven Hospital between 1977 and 1981. Tubal occlusion was the result of previous tubal sterilization in 17 patients (11 laparoscopic electrocautery and 6 tubal ligation) and previous tubal infection in 8. Fourteen of the patients conceived (56%). Viable pregnancy was achieved in nine patients (36%) and tubal pregnancy in three (12%). No significant difference in pregnancy rates was found between patients with diseased cornua and those previously sterilized by either electrocautery or tubal ligation. Tubal length of greater than or equal to 4 cm following corrective surgery as compared with less than or equal to 4 cm did not influence pregnancy rates. The patients with the shorter oviducts had a higher rate of early pregnancy wastage. All three tubal pregnancies occurred in patients with reoccluded fallopian tubes as demonstrated by a hysterosalpingogram. We conclude that tubocornual anastomosis still remains the treatment of choice for patients with proximal tubal obstruction.

Ectopic pregnancy: its relationship to tubal reconstructive surgery.

Ectopic pregnancy is the shady companion of tubal surgery. Among patients with ectopic pregnancy, relatively few have a history of tubal surgery as their underlying etiologic factor when compared with other etiologies such as PID. Nevertheless, a history of tubal surgery should place the patient at a higher-risk group for ectopic pregnancy; 3% to 20% of these patients will encounter an ectopic pregnancy after the corrective surgery. The incidence of ectopic pregnancy after tubal surgery is extremely variable and is closely linked to the degree of restoration of normal functional and anatomic integrity after the surgical procedure. This depends, to a large extent, on the amount of previous damage to the tube and its potential reversibility. Major improvements in surgical technique can, therefore, have reduced, but not eliminated, the occurrence of tubal pregnancy. The incidence of ectopic pregnancy associated with any given tubal surgical procedure should be taken into consideration when surgery is contemplated. When the risk of ectopic pregnancy is unacceptably high, or when the patient is reluctant to be exposed to a high risk of ectopic pregnancy, IVF-ET could be offered as an alternative. Table 11 represents the incidence of ectopic pregnancy associated with the various surgical procedures. The figures demonstrate the wide variation in outcome for the same procedure.

Ovarian stimulation for in vitro fertilization and embryo transfer, human menopausal gonadotropin versus pure human follicle stimulating hormone: a randomized prospective study.

A randomized, prospective study was conducted to compare ovarian stimulation with human menopausal gonadotropin (hMG) and human follicle-stimulating hormone (hFSH) in an in vitro fertilization and embryo transfer (IVF-ET) program. Minimal inclusion criteria included age less than or equal to 37, tubal infertility, regular menstrual cycles before IVF, and a normal semen analysis. Equivalent doses (225 IU/day) of either hMG (N = 20) or hFSH (N = 20) were administered, and the patients followed by serum estradiol (E2) levels and pelvic ultrasound. Parameters related to the ovarian response to therapy, the number and quality of ova recovered, and the cycle outcome were compared in the two groups using the Student's t-test and chi-square analysis. No difference was detected between the groups in peak E2 levels (828 +/- 78 versus 819 +/- 79 in the hMG and hFSH groups, respectively), day of human chorionic gonadotropin (hCG) administration (9.3 +/- 0.3 versus 9.7 +/- 1.01), occurrence of spontaneous luteinizing hormone (LH) surge (44% versus 27%, P greater than 0.05, chi square analysis), average number of ova recovered (5.0 +/- 0.7 versus 5.6 +/- 1), ova maturation (7.5% versus 12.7% rate of immature ova), rate of normal and abnormal fertilization (9.2% versus 8.1% polyspermic fertilization), cleavage stage at transfer (3.6 +/- 0.4 versus 3.4 +/- 0.7 cells per embryos), the number of embryos transferred (2.5 +/- 0.3 versus 2.6 +/- 0.3), or the occurrence of pregnancy (1 in the hMG group and 2 in the hFSH group).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

A paired analysis of in vitro fertilization and cleavage rates of first- versus last-recovered preovulatory human oocytes exposed to varying intervals of 100% CO2 pneumoperitoneum and general anesthesia.

This study compares the in vitro fertilization and cleavage rates of paired first- and last-recovered preovulatory human oocytes that were exposed to a 100% CO2 pneumoperitoneum and general anesthesia. In 305 consecutive cycles of laparoscopy, 1741 oocytes (5.7/cycle) were recovered. The exact time of aspiration (T) was recorded for each oocyte. The time interval (T1 to T2) between recovery of first and last oocytes ranged from 0 to 38 minutes and represented differences in the exposure time of first and last oocytes to the CO2 pneumoperitoneum and to general anesthesia. For all cycles (n = 305) without regard for T1 to T2, last-recovered oocytes fertilized less often than first-recovered eggs (P = 0.06; McNemar's test). When T1 to T2 was short (less than or equal to 5 minutes), first- and last-recovered oocytes fertilized at comparable rates (70.8% and 74.0%). When only cycles with T1 to T2 greater than 5 minutes were considered (n = 209), the difference in fertilization rates between first and last oocytes (68.5% versus 56.4%) was highly significant (P less than 0.01; McNemar's test). Pairing negated differences due to patient, cycle, or semen variables and first- and last-recovered oocytes had comparable maturity scores (4.0 +/- 0.5 versus 4.3 +/- 0.8). There were no significant differences in cleavage rates for first- and last-recovered oocytes that fertilized, regardless of the exposure interval (T1 to T2). We conclude that exposure to a 100% CO2 pneumoperitoneum and/or general anesthesia may adversely affect oocyte quality.

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.

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.

Laparoscopic and transvaginal ova recovery: the effect on ova quality.

Transvaginal follicle aspiration guided by transvaginal ultrasound for ova recovery is rapidly gaining popularity in many centers practicing in vitro fertilization and embryo transfer (IVF-ET). Cycle outcome following this new method has not been directly compared to the traditional, laparoscopic recovery technique. To this end, the authors evaluated multiple parameters in 66 laparoscopic (group A), and 44 transvaginal ova recovery procedures (group B) in patients undergoing IVF-ET. No statistically significant differences could be demonstrated between the groups in all but the rate of ova fertilization. The rate of fertilization was higher in the ova recovered by transvaginal follicle aspiration (59.6 versus 69.2%; P less than 0.01). No difference could be demonstrated between the groups in the other parameters examined, which included the number of ova recovered (5.7 +/- 0.4 versus 6.0 +/- 0.7), ova maturity (87 versus 84% intermediate ova), rate of polyspermic fertilization (3.9 versus 5%), rate of cleavage (88 versus 91%), cleavage stage at transfer (3.7 +/- 0.8 versus 3.5 +/- 0.4 cells per embryo), number of embryos transferred per patient (2.7 +/- 0.1 versus 3.3 +/- 0.2), and pregnancy rates. The potential detrimental effects of general anesthesia and CO2 pneumoperitoneum present during laparoscopy but not ultrasound guided recovery on ova quality may underlie the observed difference in fertilization between the groups.

Luteal rescue in in vitro fertilization-embryo transfer.

The luteal phase hormone profiles of two groups participating in the Yale in vitro fertilization (IVF) program were compared. A control group (group I) consisted of 28 women (28 cycles) who received our standard ovulation induction regimen (no luteal phase support). The treatment group (group II) consisted of 40 women (42 cycles) who were prospectively studied after receiving luteal phase support with 10,000 IU human chorionic gonadotropin (hCG) 5 days after the initial hCG dose. The groups were matched for age and cause of infertility. Estradiol (E2) and progesterone (P) were measured on the day of embryo transfer and every 3 to 4 days thereafter. Luteal phase hCG support significantly augmented (1) E2 and P levels in the conception cycles of group II compared with group I and (2) P levels in the nonconception cycles of group II compared with group I. The midluteal decline in E2 and P that was observed in group I was minimized or prevented in group II. An ongoing pregnancy rate of 19% was achieved in group II. This was not statistically different from the 13% ongoing pregnancy rate noted in a separate group of 163 tubal factor couples undergoing IVF after our standard ovulation induction regimen during the period of the study. In summary, the luteal phase hormone profiles of IVF cycles were improved by supplementation with hCG. It is concluded that this type of intervention may serve to rescue potentially failing corpora lutea and thereby optimize the peri-implantation hormonal milieu.