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Biomedical subjects

R V Haning

Publications and source records attributed to R V Haning.

At least 55 records · Page 3Linked to original sources

Artificial donor insemination: fresh versus frozen semen; the patient as her own control.

The efficacies of fresh versus cryopreserved semen in the treatment of male factor infertility by artificial insemination by donor (AID) semen were directly compared by using the patient as her own control. In any one cycle, either fresh or frozen semen was used. The type of semen preparation was randomly assigned for the first cycle and varied thereafter according to donor availability. The same donor was used for a given patient in six consecutive cycles. We treated 381 patients in this way. In 676 cycles fresh semen was used and 128 pregnancies were achieved. Fecundability, the chance of getting pregnant per cycle of exposure, was 18.9% with fresh semen. In 1200 cycles cryopreserved semen was used and 60 pregnancies occurred, for a fecundability of 5.0%. Therefore, in our clinic, fresh semen is more than three times as likely to induce pregnancy as frozen semen. The design that has been used in this therapeutic protocol provides a technique for internal quality control of the cryopreservation process and for the investigation of other variables potentially affecting the success rates with AID.

Female↗

Diagnosis-specific serum 17 beta-estradiol (E2) upper limits for treatment with menotropins using a 125I direct E2 assay.

Statistical evaluation of 133 cycles of induction of ovulation using generalized linear models demonstrated that the occurrence and severity of ovarian hyperstimulation was influenced by the serum 17 beta-estradiol (E2) concentration (P less than 0.001), conception (P less than 0.001), and the endocrinologic diagnosis, polycystic ovary syndrome (PCO) or hypothalamic amenorrhea (HA) (P less than 0.01). When menotropins were administered between 5:00 P.M. and 8:00 P.M. and blood was drawn at 8:00 A.M., an upper limit for serum E2 in patients with HA of 2417 pg/ml or an upper limit for patients with PCO of 3778 pg/ml gave an approximate 5% risk of severe ovarian hyperstimulation in conception cycles and a 1.3% risk of severe hyperstimulation in nonconception cycles. Comparison of our E2 radioimmunoassay involving extraction and chromatography to the Pantex immunodirect Estradiol 125I kit (Pantex, Santa Monica, CA) demonstrated no detectable systematic error, allowing the use of these limits with either assay. The ovulating injection of human chorionic gonadotropin was given at 5:00 P.M. to 8:00 P.M. on the evening of blood drawing as soon as the first follicle reached an average diameter of 14 mm or greater. The ultrasound parameters allow the chance of pregnancy to be optimized and the chance of multiple gestation to be minimized. Serum E2 monitoring indicates when the risk of ovarian hyperstimulation is too great for human chorionic gonadotropin to be given.

Amenorrhea↗

Two direct radioimmunoassays for 17 beta-estradiol evaluated for use in monitoring in vitro fertilization.

Two direct 125I radioimmunoassays for 17 beta-estradiol were evaluated by comparing results with those obtained by a comparison RIA involving extraction and chromatography (x) and with ultrasound parameters of ovarian activity. The correlation coefficients (R2) for the Immuchem Covalent-Coat Solid Phase 125I results (y1) and the Pantex Immuno-direct results (y2) with the comparison method results were 0.56 and 0.96, respectively, after log transformation of data (N = 42). Similar differences were observed in the correlations with the ultrasound parameters. We also evaluated the untransformed data by linear regression and obtained: y1 = 254 + 0. 410x (R2 = 0.65) and y2 = 48.2 + 0. 749x (R2 = 0.96). Between- and within-assay variations for a serum pool containing 17 beta-estradiol at 1278 pg/mL were respectively 9.0% and 9.4% for Immuchem , 3.3% and 6.7% for Pantex , and 7.3% and 9.4% for the comparison method; for the 267 pg/mL pool, these were 21.8% and 16.6% for Immuchem , 4.7% and 4.6% for Pantex , and 21.2% and 13.1% for the comparison method. Differences in the results obtained with the Pantex method and the comparison method were not clinically significant for monitoring superovulation for in vitro fertilization; the performance of the Immuchem method was less satisfactory.

Estradiol↗

Plasma estradiol is superior to ultrasound and urinary estriol glucuronide as a predictor of ovarian hyperstimulation during induction of ovulation with menotropins.

In order to compare the effectiveness of 8:00 A.M. plasma 17 beta-estradiol (E2), 24-hour urinary estriol glucuronide (E3G), and ultrasound as predictors of ovarian hyperstimulation, 70 cycles of induction of ovulation with 5:00 P.M. to 8:00 P.M. injection of menotropins from 28 subjects were evaluated. Hyperstimulation was four times more frequent in pregnancy than in nonpregnancy cycles (P less than 0.005). The hyperstimulation score (range, 0 to 6) was correlated with plasma E2 (0.63, P less than 0.01), the number of follicles (0.31, P less than 0.05), the duration of treatment (0.31, P less than 0.05), and urinary E3G (0.25, P less than 0.05). Plasma E2 was the best predictor of the hyperstimulation score, and plasma E2 was far superior to both urinary E3G and the number of follicles. Management with ultrasound alone is insufficient to prevent severe ovarian hyperstimulation. With this protocol, human chorionic gonadotropin may be given as soon as the first follicle reaches 1.4 cm in diameter as long as plasma E2 is less than 4000 pg/ml. The values of plasma E2 are dependent on the interval between blood sampling and injection of menotropins.

Estradiol↗

Hysterosalpingography with oil contrast medium enhances fertility in patients with infertility of unknown etiology.

Previous studies have suggested increased fertility rates following hysterosalpingography (HSG) using oil as compared with aqueous contrast medium. To compare the possible fertility-enhancing effects of two agents used for HSG, this prospective randomized study evaluated the subsequent fertility rates in 121 patients who underwent HSG, in which either oil or aqueous contrast medium was used. After random assignment to either agent, patients were observed for four menstrual cycles after HSG without resorting to any therapy other than clomiphene citrate where indicated. The pregnancy rates for the four cycles after HSG were compared with chi-square analysis in the total study and in the diagnostic subgroups. The subgroup with infertility of unknown cause had a significantly higher pregnancy rate after HSG with oil than after HSG with aqueous contrast medium. No significant difference was seen for any other subgroup or for the overall cohort.

Contrast Media↗

Interrelationships among human chorionic gonadotropin (hCG), 17 beta-estradiol, progesterone, and estriol in maternal serum: evidence for an inhibitory effect of the fetal adrenal on secretion of hCG.

In normal pregnancy, maternal serum hCG reaches a maximum concentration about 8-10 weeks after the last menstrual period and then decreases. To investigate the possibility that this decrease in hCG is produced by an inhibitory effect of steroids originating in the feto-placental unit, hCG, progesterone, 17 beta-estradiol, and estriol were determined by specific RIAs in 341 serum specimens obtained from 229 different pregnancies. Expressions for predicted hCG as a function of estimated trophoblastic mass and percent predicted hCG were determined to correct for the increase in hCG with increasing trophoblastic mass. The relationships between hCG and progesterone, 17 beta-estradiol, estriol, or estimated trophoblastic mass were not linear. Expression of the hCG data as percent predicted hCG produced linear relationships between hCG and each of the above steroids. Both hCG itself and percent predicted hCG were shown to have a negative regression on estriol (P less than 0.001) and a positive regression on progesterone (P less than 0.001), but not on 17 beta-estradiol (P greater than 0.05), in a multiple linear regression on all three steroids. These data suggest that hCG production is inhibited by a steroid originating in the fetal adrenal. This inhibitory effect plateaus in late pregnancy, allowing a minor late increase in hCG due to increasing trophoblastic mass.

Adrenal Glands↗

Effects of prostaglandins, dibutyryl cAMP, LHRH, estrogens, progesterone, and potassium on output of prostaglandin F2 alpha, 13, 14-dihydro-15-keto-prostaglandin F2 alpha, hCG, estradiol, and progesterone by placental minces.

In order to compare the endocrine response of placental minces to luteinizing hormone releasing hormone (LHRH) and dibutyryl cAMP (dbcAMP) and to screen for effects of potential stimulatory and inhibitory substances, the simultaneous outputs of PGF2 alpha, 13, 14-dihydro-15-keto-prostaglandin F2 alpha (PGFM), progesterone, 17 beta-estradiol, and hCG were evaluated during a 4 hour incubation in 5 placentas. The output of hCG was highest for 12-week placentas, intermediate for a 16 week placenta, and lowest for term placentas. The output of 17 beta-estradiol by 12 and 16 week placentas in the presence of 30 microM dehydroepian-drosterone sulfate (DHEAS) was greater than that by term placentas. Progesterone output was apparently independent of gestational age although some variation between 12-week placentas was demonstrated. Output of PGF2 alpha was lower in 12 and 16-week placentas than in term placentas and that of PGFM was lower in 12-week placentas than in term placentas. LHRH (100 nM) produced stimulation of PGF2 alpha output (P less than .005) and a trend toward inhibition of progesterone output (which failed to achieve statistical significance) but no stimulation of hCG under these conditions. Stimulation of the outputs of hCG (P less than .005) and PGF2 alpha (P less than .001) and inhibition of that of progesterone (P less than .005) was produced by 20 mM dbcAMP. DHEAS inhibited output of progesterone (P less than .01) and PGF2 alpha (P less than .01). There were no effects of potassium, estrogens, progesterone, or prostaglandins on output of any measured substance.

Bucladesine↗

Effects of dibutyryl cAMP, LHRH, and aromatase inhibitor on simultaneous outputs of prostaglandin F2 alpha, and 13,14-dihydro-15-keto-prostaglandin F2 alpha by term placental explants.

Explants from term human placentas were maintained in culture with daily changes of medium. Daily output of PGF2 alpha and PGFM1 decreased during the course of the incubation. Addition of 4 micrograms/ml DHEAS or 67 micrograms/ml LDL cholesterol had no effect on output of PGF2 alpha or PGFM. Addition of 1.6, 3.2, or 6.4 micrograms/ml of LHRH to the culture plates had no effect on output of PGFM or PGF2 alpha, but LHRH increased hCG output. Dibutyryl cAMP (1mM, 2mM, and 4 mM) increased output of PGF2 alpha, PGFM, and hCG. Aromatase inhibitor decreased hCG output, but it was without effect on output of PGF2 alpha, or PGFM, Significant correlations were demonstrated between progesterone, PGFM, PGF2 alpha, and hCG, suggesting that PGF2 alpha originates in the syncytiotrophoblast cell. The ability of LHRH to stimulate output of hCG but not PGF2 alpha while dbcAMP stimulated both suggests that either PGF2 alpha and hCG arise in different cells or that LHRH does not act through cAMP.

Androstenedione↗

Ultrasound evaluation of estrogen monitoring for induction of ovulation with menotropins.

Twenty-five cycles of induced ovulation with menotropins were investigated blindly with ultrasound to evaluate estrogen monitoring. Plasma 17 beta-estradiol (E2) and urinary estriol glucuronide (E3G) correlated with total ovarian volume (0.58, 0.58), total follicular volume (0.56, 0.52), volume of the largest follicle (0.53, 0.54), and days of administration of menotropins (0.49, 0.44), respectively. The mutual correlations of days of menotropin administration, volume of the largest follicle, E2, and E3G with total follicular volume explained the correlations of E2 and E3G with days of administration of menotropins and with volume of the largest follicle. Thus, multiple small follicles can reproduce the E2 or E3G levels associated with a single mature follicle if they result in the same total follicular volume. As menotropins were administered for progressively longer periods, the number of maturing follicles increased. We conclude that ultrasound appears to be useful for monitoring induction of ovulation with menotropins since it provides more accurate information on follicular number and size than can be obtained by estrogen determinations alone.

Chorionic Gonadotropin↗

Effects of dibutyryl adenosine 3',5'-monophosphate, luteinizing hormone-releasing hormone, and aromatase inhibitor on simultaneous outputs of progesterone, 17 beta-estradiol, and human chorionic gonadotropin by term placental explants.

To contrast the effects of dibutyryl cAMP (dbcAMP) with those of LRH and to evaluate the effects of low density lipoprotein (LDL), dehydroepiandrosterone sulfate (DHEAS), and aromatase inhibitor (4-hydroxy-androst-4-ene-3,17-dione) on the output of hCG, 17 beta-estradiol, and progesterone, term human placental explants were maintained in culture for 6 days with daily changes of medium. The daily outputs of progesterone and hCG were observed to decrease while that of 17 beta-estradiol remained constant during the course of the incubation. The addition of 67 micrograms/ml LDL cholesterol had no effect on the basal output of 17 beta-estradiol, progesterone, or hCG. The addition of 4 micrograms/ml DHEAS increased 17 beta-estradiol output 20-fold, but did not affect the outputs of hCG or progesterone. The addition of 1.6, 3.2, or 6.4 micrograms/ml LRH had no effect on the output of progesterone or 17 beta-estradiol. LRH increased hCG output in Dulbecco's Modified Eagle's Medium with penicillin, streptomycin, insulin, and glucose alone, but not in the presence of added LDL or DHEAS, while dbcAMP (1, 2, and 4 mM) increased the output of hCG in all three media and decreased 17 beta-estradiol output in medium supplemented with DHEAS. Aromatase inhibitor decreased both 17 beta-estradiol and hCG outputs in a dose-dependent fashion, but it was without effect on the output of progesterone. Basal progesterone, basal hCG, and dbcAMP-stimulated hCG outputs were unaffected by the addition of LDL or DHEAS. Both LDL and DHEAS inhibited the stimulatory effect of LRH on the output of hCG. Aromatase inhibitor decreased the output of both hCG and 17 beta-estradiol, but the effect on hCG was direct and not due to the decrease in 17 beta-estradiol.

Androstenedione↗

Danazol and its principal metabolites interfere with binding of testosterone, cortisol, and thyroxin by plasma proteins.

Danazol and its three principal metabolites (2-hydroxy-methylethisterone, 2-hydroxymethyl-1,2-dehydroethisterone, and ethisterone) competitively displace cortisol and testosterone from plasma proteins. This effect is in addition to the reported inhibition of the production of testosterone-binding globulin and thyroxin-binding globulin. We saw no competitive inhibition of thyroxin binding. Concentrations of total testosterone, total cortisol, and total thyroxin were low, whereas percentages of free testosterone, free cortisol, and free thyroxin were abnormally high in women being treated with danazol. Values for testosterone, cortisol, and thyroxin in danazol-treated patients should therefore be appropriately corrected before interpretation. Protein-binding assays for testosterone or cortisol that involve testosterone- or cortisol-binding globulin may be invalid in danazol-treated subjects because of the competitive binding of danazol and its metabolites to these proteins.

Adult↗

Prostaglandins, clonidine and sexual receptivity in the guinea pig.

Prostaglandins E1 and F2 alpha suppressed lordosis in ovariectomized guinea pigs brought into estrus with estradiol benzoate and progesterone. Pretreatment with clonidine prevented this action of the prostaglandins, but if the animals were first given prostaglandin and allowed to go out of estrus, then clonidine did not restore lordosis. In a previous study it was found that the abbreviation of estrus induced by copulation was also blocked by clonidine, again only if it were given before the inhibitory treatment. These results suggest tht prostaglandin, perhaps released from the female reproductive tract, could mediate the inhibitory effect of copulation, and radioimmunoassays of prostaglandin F2 alpha and its principal metabolite PGFM revealed substantial elevations in the concentrations of these materials in trunk blood after copulation. We discuss the possibility that prostaglandins may suppress sexual receptivity by interfering with an alpha-adrenergic mechanism.

Animals↗

Testosterone free index correlates best with dehydroepiandrosterone sulfate.

Correlation coefficients for dehydroepiandrosterone sulfate (DHEAS) were determined in women on menotropin. DHEAS was significantly correlated with testosterone free index (TFI), 0.78**; percentage free testosterone (%FT), 0.66**; androstenedione (delta 4A), 0.66*; luteinizing hormone (LH), 0.55**; LH/follicle-stimulating hormone (FSH) ratio, 0.55**; 17-OH-progesterone (17-P), 0.55**; testosterone (T), 0.53**; weight (WT), 0.40**, urinary estriol glucuronide (E3G), 0.33*; and free cortisol index (FFI), 0.32*, with 43 df but not with prolactin (PRL), 0.25. Normal male DHEAS (3.5 +/- 1.2, 25) (microgram/ml; mean +/- standard deviation, n) was higher than normal female DHEAS (2.4 +/- 1.1, 27), P less than 0.01 and DHEAS in women on oral contraceptives (1.9 +/- 1.1, 17) was slightly lower than in normal females, P greater than 0.2. In the combined population (male, female, and females on oral contraceptives) DHEAS was correlated with TFI (0.56**), T (0.54**), %FT (0.52**), delta 4A (0.40**), and age (-0.40**) with 66 df and 17-P (0.30*) with 54 df. TFI appears to be one determinant of plasma DHEAS, **P less than 0.01. *P less than 0.05.

Amenorrhea↗

Virilism as a late manifestation in the Bardet-Biedl syndrome.

The second case of virilism as a late manifestation of Bardet-Biedl syndrome (BBS) is described, with endocrine and histological evaluation. Both cases manifested ovulatory cycles and developed virilism in adulthood. Elevated plasma testosterone and 17-OH-progesterone were not suppressed by dexamethasone but were suppressed by medroxyprogesterone acetate. Peripheral and ovarian venous blood obtained at the time of surgery demonstrated a marked gradient for testosterone in both ovaries and for progesterone in the ovary bearing the corpus luteum. Histological evaluation of the ovaries demonstrated bilateral ovarian stromal hyperplasia with focal hyperthecosis. Bilateral ovariectomy resulted in complete correction of the endocrine abnormality, although the established hirsutism remains a mark of previous androgen excess.

Adult↗

Laparoscopic findings in twenty-five failures of artificial insemination.

The laparoscopic findings, treatment, and follow-up of 25 patients who failed artificial insemination donor (AID) were retrospectively evaluated. A high incidence (72%) of abnormal pelvic findings was encountered. Endometriosis was found in 60% and pelvic adhesions in 12% of the patients. The incidence of these two entities was not significantly different from their incidence in patients with unexplained infertility in the same institution (44% for endometriosis and 36% for adhesions). After surgical or medical treatment, a pregnancy rate of 22.2% (16.6% for endometriosis and 66.6% for pelvic adhesions) was achieved in patients with positive pelvic findings; in the group with negative pelvic findings, a pregnancy rate of 20% was achieved. The value of diagnostic laparoscopy in AID failures is discussed in the light of the findings presented and the relatively low rate of post-treatment pregnancy.

Adult↗