Infertility is a symptom, not a disease.
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Female↗
Biomedical subjects
P Y Lu
Publications and source records attributed to P Y Lu.
Selection of summary measures for ART?
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Blastocyst↗
Comparison of the sperm quality necessary for successful intrauterine insemination with World Health Organization threshold values for normal sperm.
OBJECTIVE: To compare World Health Organization threshold values for normal sperm with the initial sperm quality necessary for successful IUI. DESIGN: Retrospective study. SETTING: Private fertility clinic. PATIENT(S): One thousand eight hundred forty-one couples undergoing 4,056 cycles of IUI. INTERVENTION(S): Intrauterine insemination. MAIN OUTCOME MEASURE(S): Relation of initial sperm quality to fecundity. RESULT(S): Progressive motility and total motile sperm count were the initial sperm characteristics most closely related to pregnancy on discriminant analysis. The per-cycle pregnancy rate averaged 11.1% during the first three IUI cycles. Pregnancy rates were > or = 8.2% per cycle when the initial sperm values were a concentration of > or = 5 X 10(6)/mL, a total count of > or = 10 X 10(6), progressive motility of > or = 30%, or a total motile sperm count of > or = 5 x 10(6). Minimal increases in fecundity occurred when initial values were greater than these threshold levels. The lowest initial values that resulted in pregnancy were a concentration of 2 x 10(6)/mL, a total count of 5 x 10(6). motility of 17%, and a total motile sperm count of 1.6 X 10(6). Pregnancy rates were <3.6% when initial values were between the threshold levels and the lowest levels. CONCLUSION(S): The sperm quality that is necessary for successful IUI is lower than World Health Organization threshold values for normal sperm. Intrauterine insemination is effective therapy for male factor infertility when initial sperm motility is > or = 30% and the total motile sperm count is > or = 5 X 10(6). When initial values are lower, IUI has little chance of success.
Adult↗
The effect of presynaptic catecholamine depletion on 6-hydroxymelatonin sulfate: a double blind study of alpha-methyl-para-tyrosine.
Because it is a competitive inhibitor of tyrosine hydroxylase, alpha-methyl-para-tyrosine (AMPT) is used to study psychiatric disorders. Melatonin serves as a biological marker of catecholamine function since its secretion is regulated by noradrenergic neurons via beta-adrenergic receptors in the pineal gland. Ten healthy volunteers were administered AMPT in a double-blind placebo controlled study. When subjects received AMPT, nocturnal 6-hydroxymelatonin sulfate (6-SM) decreased significantly as compared with promethazine (night 1 P=0.002; and night 2 P=0.001). Urinary MHPG also decreased on both study days (DF1,9 F=9.82, GG=0.0121). Nocturnal 6-SM excretion and melatonin secretion correlated highly (r=0.91, P=0.0007). Behavioral ratings did not reveal a difference in symptomatology and did not correlate with changes in 6-SM or MHPG. This study demonstrates in healthy controls that 6-SM reliably reflects presynaptic catecholamine depletion induced by AMPT without the emergence of behavioral symptoms.
Adult↗
Future use of clomiphene in ovarian stimulation. A role for clomiphene in the 21st century?
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Clomiphene↗
Adenovirus-mediated transduction of ribozymes abrogates HER-2/neu and pleiotrophin expression and inhibits tumor cell proliferation.
The combination of specific gene targeting technologies with efficient gene delivery systems could provide the means to evaluate the concept of anticancer strategies designed to block expression of potentially rate-limiting tumor promoting factors. Here, we constructed adenoviruses expressing hammerhead-ribozymes targeted to two of these factors, the tyrosine kinase receptor HER-2/neu or the growth factor pleiotrophin (PTN). Adenovirus-mediated transduction of either HER-2/neu- or PTN-targeted ribozymes depleted the respective RNAs and inhibited protein expression significantly in three different human cancer cell lines. This resulted in almost complete abrogation of HER-2/neu- or PTN-dependent cancer-cell proliferation, thus demonstrating the feasibility of this approach as a future cancer gene therapy.
Adenoviridae↗
Relationship of clomiphene dose and patient weight to successful treatment.
Our objective was to examine the relationship between patient weight and the dose of clomiphene required for pregnancy so as to assess the validity of recommendations that the dose of clomiphene be limited to 100 mg. We retrospectively analysed the weight-dose relationship in 1681 clomiphene pregnancies and the relationship between dose and pregnancy, births, multiple births, number of pre-ovulatory follicles and endometrial thickness in 2841 cycles of clomiphene treatment, 25-250 mg, for 5 days before intrauterine insemination (IUI). Doses of clomiphene >100 mg/day were used before pregnancies in 27.4% of patients who weighed >90 kg and in 14.7% of all pregnancies. In IUI cycles, pregnancies and births, but not multiple births or abortions, were related to dose. An increase in dose from 25 to 100 mg resulted in higher pregnancy and birth rates, and in an increase in the average number of pre-ovulatory follicles > or =12 mm in diameter, from 2.0 to 2.8, with no additional increase at higher doses. Endometrial thickness and cycle day of insemination were not related to dose. We conclude that doses of clomiphene may safely be increased beyond 100 mg, and that doses > or =100 mg are required in significant numbers of patients.
Body Weight↗
Ovulation induction and IUI in older women.
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Adult↗
Elective versus emergency cesarean hysterectomy on a teaching service--1981 to 1991.
We compared the differences in morbidity of elective and emergency cesarean hysterectomy (CH) in a training program. Records of patients who had elective or emergency CH were reviewed for information reflecting perioperative morbidity and fetal outcome. Eighty-eight CHs were elective and 18 were emergencies. Compared to emergency CHs, operative time for elective CHs was 30 minutes less, intraoperative blood loss was 700 mL lower, less postoperative blood replacement was needed, and hospital stay was 3.5 days shorter. Emergency CH had nearly twice the frequency of postoperative febrile morbidity and a three-times-higher rate of morbidity due to other causes. CHs were done at a gestational age of 36 or more weeks in 81.6% of elective cases, compared to only 50% of emergency cases. Mean birth weight of newborns delivered electively was 900 g higher, and Apgar scores were better. These data show that CHs done by house staff in training have a significantly lower complication rate when the operations are elective rather than emergent.
Adult↗
Efficacy of calcium ionophore A23187 oocyte activation for generating parthenotes for human embryo research.
PURPOSE: Our purpose was to examine the efficacy of Ca-A23187 to activate human oocytes and produce parthenotes for research purposes. We examined the feasibility of using fluorescence in situ hybridization (FISH) to study the sex chromosome constitution of activated oocytes. METHODS: One hundred eight nonfertilized oocytes from our IVF program were exposed to Ca-A23187. Oocyte activation was determined by the presence of pronuclear (PN) development. FISH was done on chromosome preparations using X and Y dual-colored probes. Polyploidic and parthenogenetically activated oocytes from our IVF program served as controls. RESULTS: Of the 108 oocytes, 59 (55%) had no PN, 38 (35%) one PN, 10 (9%) two PN, and 1 (0.9%) three PN. Fiftyseven oocytes (53%) were not recovered following spreading and no chromatin was observed on 14 slides (13%) after FISH. This contrasted with 50 of 227 (22%) and 3 of 227 (1.7%) loss rates, respectively, for controls (P < 0.0001). Eight of 49 activated oocytes underwent cleavage. FISH was performed on 37 oocytes. Of 21 zero-PN oocytes, I had no FISH signals, 15 had a single X, 4 had two X's, and I had four X's. For one-PN oocytes, two had no FISH signals, seven had one X, and three had two X's. For two-PN oocytes, two had no FISH signals and two had two X's. FISH results were consistent with a maternal origin of genetic material. CONCLUSIONS: Ca-A23187 resulted in a 45% activation rate, with 16% of oocytes progressing to cleavage before degeneration. Oocyte activation with Ca-A23187 allowed the generation of parthenotes for human embryo research. FISH was useful for evaluation of oocytes and parthenotes.
Blastomeres↗
The impact of gender on alpha-methyl-para-tyrosine mediated changes in prolactin secretion and 6-hydroxymelatonin sulfate excretion.
Prolactin (PRL) and melatonin (ML) secretion are mediated by dopamine (DA) and norepinephrine (NE), respectively. Alpha-methyl-para-tyrosine (AMPT) inhibits the production of CNS catecholamines (CA). The purpose of the study is to determine: (1) if AMPT inhibition of ML has the same gender-dependent effect as on PRL secretion; (2) if there is a post AMPT-induced NE depletion mood change in men and/or women. In a randomized, double-blind cross-over fashion, five healthy young males and five females were either given five doses of AMPT 1 g (active) or promethazine 50 mg (placebo) over a 28 h period, separated by 4-6 weeks. The PRL and ML concentrations were collected at regular intervals via an indwelling venous catheter and concurrently, two 12 h urinary 6-hydroxymelatonin sulfate (6-MS) measurements were made. Mood and anxiety states of subjects at baseline and post drug were assessed with appropriate rating scales at regular intervals. Light exposure beginning at dusk and lasting until dawn was controlled to no more than 200 lux during all phases of the study. The PRL secretion showed a significant interaction of drug x time (p = .0001) in women and a non-significant trend (p = .056) in men. No difference in PRL secretion was found between the two genders in the placebo condition, whereas the PRL secretion was significantly higher in the AMPT condition in women when compared to men (df 17,119, F = 1.9, p = .021). Total 24 h urinary 6-MS secretion highly correlated with ML secretion expressed as area under the curve (AUC) during both active and placebo experiments (r = 0.8, p < .01) and (r = 0.86, p < or = .01), respectively. The ANOVA reveals a significant interaction of drug x time for 6-SM excretion. There was no gender difference in AMPT suppression of 6-MS excretion. No mood changes were detected in men or women. We conclude that urinary 6-MS is a reliable indirect measure of the degree of AMPT-induced decrease in CNS NE activity as part of overall AMPT-induced reduction of central catecholamine activities. The pre and post AMPT-induced changes in 6-MS are not gender dependent, dissimilar to the AMPT-induced changes in PRL secretion. Therefore, 6-MS, in addition to PRL, should be measured when applying the AMPT paradigm in future research.
Adult↗
Examining serotonin function: a modified technique for rapid tryptophan depletion.
Tryptophan (TRP) depletion was used to study serotonin because the ratio of TRP to large neutral amino acids (TRP/LNAA) determines the quantity of TRP that enters the brain. Because TRP is not universally available, a modified technique of TRP depletion was developed where a 1/4 strength preparation of an amino acid mixture (AAM) replaces TRP as the placebo. Seven healthy subjects could not differentiate between the preparations in this double-blind, placebo-controlled study. Urinary 6-hydroxymelatonin sulfate (6-MS) was monitored as a biochemical marker of serotonin. The TRP/LNAA ratio (GG = 0.001) and 6-MS secretion (GG = 0.024) were decreased, but placebo TRP levels (GG = 0.062) were not altered significantly. This modified technique facilitates the use of TRP depletion in clinical research.
Adult↗
Minimal stimulation achieves pregnancy rates comparable to human menopausal gonadotropins in the treatment of infertility.
OBJECTIVE: To examine the effectiveness of a novel clomiphene citrate (CC) and hMG combination protocol ("minimal stimulation") for controlled ovarian hyperstimulation. Minimal stimulation consists of administering 100 mg/d CC for 5 days followed by a single dose of 150 IU hMG. The results of this analysis are compared with those of an hMG-alone protocol. In vitro fertilization-embryo transfer and donor insemination patients are excluded from this analysis. DESIGN: Retrospective review of minimal stimulation and hMG cycles from January 1, 1989 to December 31, 1992. SETTING: Tertiary care center reproductive endocrinology and infertility clinic. PATIENTS: Two hundred thirty-two women who underwent 549 treatment cycles. MAIN OUTCOME MEASURES: Clinical and multiple pregnancy rates (PRs) and medication costs. RESULTS: Sixty-one women received 106 cycles of minimal stimulation and 183 received 443 cycles of hMG. Although subject groups were not assigned randomly, multivariate analysis detected no significant differences between the treatment groups. The total ampules of hMG required differed significantly (2.0 for minimal stimulation versus 16.8 +/- 8.5 [mean +/- SD] for hMG). Pregnancy rates and multiple gestation rates were similar. Medication expense of minimal stimulation is 21% that of the hMG protocol. CONCLUSIONS: Minimal stimulation is as effective as hMG in the population examined. The comparable PRs and decreased medication costs of minimal stimulation justifies further evaluation of its role in the treatment of infertility.
Adult↗
The king, his knights, and type I errors.
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Clomiphene↗
Endometriosis: current management.
OBJECTIVE: To review the clinical features, theories of pathogenesis, and current treatment of endometriosis-associated pain and infertility. DESIGN: We review the manifestation of endometriosis and the possible mechanisms that lead to its symptoms, examine the efficacy of current therapeutic options for pelvic pain and infertility, and provide specific recommendations for treatment based on the current literature. MATERIAL AND METHODS: Endometriosis is the presence of hormonally responsive endometrial tissue occurring outside the uterine cavity. This condition may be asymptomatic but is often found in association with pelvic pain or infertility (or both). The precise pathogenesis has not been clearly established but likely involves retrograde menstruation with subsequent seeding of endometrial glands at extrauterine sites. The definitive diagnosis and staging of endometriosis are performed by laparoscopy. Various strategies have been used to treat endometriosis including expectant, medical, surgical, and combination management. RESULTS: The efficacy of treatment varies for pelvic pain and infertility. Endometriosis-associated pain may respond to both medical and surgical management. The use of medical therapy for endometriosis-associated infertility is not supported by current studies. Surgical management of infertility may be efficacious when pelvic anatomy is distorted because of endometriosis. The use of superovulation strategies and in vitro fertilization has been shown to be effective in overcoming endometriosis-associated infertility. CONCLUSION: Pelvic pain and infertility in the presence of endometriosis necessitate individualization of therapy to achieve treatment goals. Neither medical nor surgical management is efficacious in all circumstances. As a better understanding of the pathogenesis of endometriosis evolves, treatment of this perplexing condition will probably continue to improve.
Adult↗
Dual color fluorescence in situ hybridization to investigate aneuploidy in sperm from 33 normal males and a man with a t(2;4;8)(q23;q27;p21)
OBJECTIVE: To establish the relative frequency of aneuploidy in sperm from normal and abnormal subjects using dual color fluorescence in situ hybridization and probes for six different chromosomes. DESIGN: Semen from 33 normal males and a patient with a translocation was studied using dual color fluorescence in situ hybridization with probes for chromosomes 4, 7, 8, 12, 18, X and Y. The frequency of aneuploidy for each chromosome is compared with one another and with the patient who had a t(2;4;8)(q23;q27;p21). SETTING: Specimens were obtained from patients at the Mayo Clinic, Rochester, Minnesota. RESULTS: The percentage of sperm with disomy or nullisomy in normal subjects ranged from 0.2% to 0.6% for each of the chromosomes studied. No statistically significant differences were observed between these chromosomes. The frequency of aneuploidy in sperm from a patient with a t(2;4;8) was 3.3% and 4.8% for chromosomes 4 and 8, respectively. CONCLUSION: Fluorescence in situ hybridization was useful to establish the normal range of nullisomic and disomic sperm for six different chromosomes and to study a patient with a clinically significant chromosome abnormality. In normal males, no difference in the frequency of meiotic nondisjunction was observed among the chromosomes studied.
Adult↗
Comparison of morbidity in cesarean section hysterectomy versus cesarean section tubal ligation.
This study was undertaken to compare the morbidity of cesarean section hysterectomy (C-HYST) and cesarean section bilateral tubal ligation (C-BTL) in a nonemergency or elective environment. Charts were reviewed for patients who underwent elective C-HYST or elective C-BTL before the onset of labor, without the use of antibiotics. Demographics, maternal morbidity, operative difficulties and postoperative complications were compared. Statistically significant differences in patient demographics include a higher maternal age in the C-HYST group than for those in the C-BTL group (31.0 +/- 5.8 versus 27.7 +/- 5.4 years; p = 0.002). C-BTL patients had higher gestational ages (39.4 +/- 1.6 versus 38.7 +/- 1.3 years; p = 0.0017). The C-HYST group had a higher estimated blood loss (1,201 +/- 472 versus 718 +/- 364 milliliters; p = 0.001), change in hematocrit level (6.0 +/- 4.4 percent versus 4.5 +/- 3.4 percent; p = 0.013) and operating time (115 +/- 37 versus 74 +/- 26 minutes; p = 0.0001). Blood transfusion was similar in both groups. Febrile morbidity was higher in the C-BTL group (68.0 percent versus 50.0 percent; p = 0.01). Endometritis was the significant determinant of febrile morbidity for the C-BTL group (41.7%) and cuff cellulitis in the C-HYST group (25.6 percent). Intraoperative and postoperative complications between the two groups were rare and not statistically different. Clinical morbidity for C-HYST is not significantly different than C-BTL. Elective C-HYST may be used in place of C-BTL when indications for hysterectomy are present.
Adult↗
Fluorescence relaxation kinetics from rhodopsin and isorhodopsin.
The fluorescence kinetics of bovine rhodopsin and isorhodopsin excited with a single picosecond laser pulse have been measured with a streak camera. The rise and the decay time of the intrinsic fluorescence emission from rhodopsin and isorhodopsin are found to be <12 ps.
Animals↗