Single-versus multiple-dose human chorionic gonadotropin for ovulation induction: effect on luteal function and pregnancy rate.
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Anovulation↗
Biomedical subjects
B H Yuen
Publications and source records attributed to B H Yuen.
A simple handling technique for mammalian oocytes and embryos during preparation for transmission electron microscopy.
Due to their small size, mammalian oocytes and embryos pose unique problems during preparation for transmission electron microscopy. This paper outlines a method which combines protein embedding with centrifugation to locate the specimens on the face of a Beem capsule mould. This method facilitates both the processing of oocytes with minimal loss and rapid location of the specimens within the block for simultaneous sectioning, staining and examination.
Animals↗
Effects of hydroxyflutamide on rats treated with a superovulatory dose of pregnant mare serum gonadotropin.
Immature female rats treated with superovulatory doses of pregnant mare serum gonadotropin (PMSG) were used to study the effects of the antiandrogen hydroxyflutamide on steroid production, particularly the biologically active androgens, in two experiments. In the first experiment, animals were given either 5 mg hydroxyflutamide or vehicle alone at 30 and 36 h following 40 IU PMSG. Compared with the vehicle group, hydroxyflutamide treatment significantly reduced the percentage of degenerate oocytes recovered from oviducts (p less than 0.05). Serum levels of testosterone and androstenedione, and their aromatized product 17 beta-estradiol, significantly decreased (p less than 0.05) in the hydroxyflutamide-treated group; however, nonaromatizable androgen, 5 alpha-dihydrotestosterone, was not affected. In the second experiment, ovaries obtained 48 h after stimulation with 4 or 40 IU PMSG were incubated with and without hydroxyflutamide (10(-5) M) and (or) testosterone (10(-7) M) to study [4-14C]pregnenolone metabolism to major steroids. In 40 IU stimulated ovaries, hydroxyflutamide significantly decreased the metabolism of pregnenolone to progesterone (p less than 0.01) and androstenedione (p less than 0.01), while the production of 17 beta-estradiol increased significantly (p less than 0.05); however, pregnenolone conversions to testosterone and 5 alpha-dihydrotestosterone were not affected. Testosterone completely reversed the hydroxyflutamide-induced alteration of pregnenolone metabolism. In contrast, there was no difference in the pregnenolone conversion patterns between untreated and hydroxyflutamide or hydroxyflutamide plus testosterone groups in 4 IU stimulated ovaries. Present results confirm our previous finding that hydroxyflutamide decreases the percentage of abnormal oocytes recovered from superovulating rats and indicates that this hydroxyflutamide effect may be partly mediated by altered ovarian steroidogenesis following inhibition of androgen binding in the ovary.
Androgens↗
Suppression of luteinizing hormone secretion by atrial and brain natriuretic peptides in ovariectomized rats.
Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) are present in brain regions regulating LH secretion. Similarities in the molecular structure of these peptides suggest similar physiological function within the brain. This study examined the effects of centrally administered BNP and ANP on LH secretion in mature ovariectomized (OVX) rats. Intracerebroventricular (icv) administration of 2 nmol ANP or BNP decreased mean plasma LH concentration and LH pulse amplitude (P less than 0.05 for ANP; P less than 0.01 for BNP; n = 8/group) and frequency (P less than 0.01 for ANP and BNP). LH secretion was not affected by ANP or BNP at a lower concentration (0.2 nmol, icv; P greater than 0.05; n = 8/group). It was concluded that ANP and BNP may be involved in central regulation of LH secretion. Mechanisms possibly involved in suppression of LH secretion by ANP and BNP were also examined. OVX rats were treated with an opioid antagonist, naloxone (0.5 mg, iv), 45, 75, and 105 min after ANP or BNP (2 nmol, icv). Naloxone eliminated suppression of mean plasma LH concentration and LH pulse amplitude by 2 nmol ANP and BNP (P less than 0.05; n = 7/group). OVX rats were treated with a dopamine antagonist, pimozide (0.6 mg/kg, sc), 90 min before treatment with ANP or BNP (2 nmol, icv). Pimozide pretreatment blocked suppression of LH secretion by ANP or BNP (P less than 0.05; n = 9/group). Naloxone alone did not affect LH secretion (P greater than 0.05; n = 5). It was concluded that components of ANP and BNP suppression of LH secretion may depend upon opioid and dopamine activity.
Animals↗
Effect of prostaglandin F2 alpha on cytosolic free calcium ion concentrations in rat luteal cells.
Changes in cytosolic free calcium concentrations [( Ca2+]i) in response to prostaglandin F2 alpha (PGF2 alpha) were measured in single rat luteal cells, using the calcium-sensitive fluorescent dye fura-2. A total of 112 cells were studied in 20 experiments. The average resting [Ca2+]i was 113 +/- 6.4 nM. In 59 cells (53%), there was a 4.6 +/- 0.2-fold increase in [Ca2+]i within 29.3 +/- 1.0 sec of PGF2 alpha administration, and the cells recovered by 78.0 +/- 4.5 sec. The magnitude of the increase in [Ca2+]i in response to PGF2 alpha was not changed by an increase in the concentration of PGF2 alpha. Perifusion with low calcium buffer reduced, then eliminated, the [Ca2+]i response to PGF2 alpha. Perifusion of cells with PGF2 alpha resulted in a single transient [Ca2+]i response, similar to that after short term exposure to PGF2 alpha. Many (67%) of the cells that responded to PGF2 alpha also responded to GnRH. No additive increase in [Ca2+]i was seen when PGF2 alpha and GnRH were administered together. The source of the calcium appears to be intracellular stores that are shared by GnRH and PGF2 alpha.
Animals↗
Elevated serum testosterone, hirsutism, and virilism associated with combined androgen-estrogen hormone replacement therapy.
Nine postmenopausal women with symptoms and signs of androgen excess due to long-term use of an injectable androgen-estrogen combination were studied retrospectively. Cosmetically disturbing hirsutism was the major complaint in eight subjects. Other symptoms included hot flushes, decreased libido, mood changes, depression, and postmenopausal bleeding in the one patient with an intact uterus. Seven women had clitorimegaly; the clitoral index ranged from 45-120 mm2 (normal up to 35). Serum total testosterone levels were elevated in eight women, ranging from 5.7-14.9 nmol/L (normal up to 2.43). The androgen-estrogen combination was discontinued and oral or transdermal estrogen replacement was instituted. In five women followed serially for 16-24 months, elevated testosterone levels required 12-20 months to return to the normal premenopausal range.
Adult↗
The chromosomal complements of cleaved human embryos resulting from in vitro fertilization.
Chromosome preparations were made from 25 cleaved abnormal human embryos at the two- to eight-cell stage after in vitro fertilization. Morphologically, these embryos showed either variable degrees of degeneration or an abnormal number of pronuclei before first cleavage. Among 14 successfully karyotyped embryos, only 3 had a normal chromosomal complement. Eleven showed chromosomal abnormalities, including triploidy, haploidy, and mosaicism. This finding documents a high incidence of chromosomal errors in morphologically abnormal early preimplantation embryos.
Chromosome Aberrations↗
Hormonal contraception in the postmolar interval.
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Adult↗
Inhibition of aromatase activity by 8-bromo-cyclic adenosine monophosphate in cultured first-trimester human trophoblast.
We have previously shown that 8-bromo-adenosine-3':5'-cyclic monophosphate inhibits production of estradiol from androgen precursors in trophoblast isolated from term placentas. In these experiments we sought to evaluate the effect of 8-bromo-adenosine-3':5'-cyclic monophosphate on aromatase activity in first-trimester trophoblast culture. Trophoblast cells were enzyme dispersed from first-trimester placentas and purified on a Percoll gradient. On the third and fourth day after dispersion cultures were treated with androstenedione or testosterone with and without 2 mmol/L 8-bromo-adenosine-3':5'-cyclic monophosphate. The quantity of estradiol, estrone, progesterone, human placental lactogen, and human chorionic gonadotropin was determined by radioimmunoassay. We concluded that in first-trimester trophoblast, as previously reported in term trophoblast, 8-bromo-adenosine-3':5'-cyclic monophosphate inhibited the production of estradiol from the supplied androgen precursors. Human chorionic gonadotropin and human placental lactogen production was stimulated by 8-bromo-adenosine-3':5'-cyclic monophosphate. Progesterone production was either stimulated or was unchanged by the presence of 8-bromo-adenosine-3':5'-cyclic monophosphate.
8-Bromo Cyclic Adenosine Monophosphate↗
Failure of ovulation induction with pulsatile gonadotropin-releasing hormone and human menopausal gonadotropins in isolated gonadotropin deficiency.
A 30-year-old woman with primary amenorrhea, hypothalamic hypogonadism, decreased sense of smell, and primary infertility failed to respond to pulsatile exogenous gonadotropin-releasing hormone. In addition, failure to respond to stimulation with human menopausal gonadotropins was consistent with concomitant ovarian failure. Perturbation of normal cellular migration during embryogenesis in the regions of the olfactory placode, yolk sac, hindgut, and gonadal ridge may explain both the hypothalamic defect and ovarian failure experienced by this woman. She demonstrates that gonadal failure need not be accompanied by elevated gonadotropin levels; nor do low gonadotropin levels necessarily indicate potentially responsive ovaries. These findings are consistent with the coexistence of isolated gonadotropin deficiency and ovarian failure in the same individual.
Adult↗
Stimulation of progesterone and prostaglandin E2 production by lipoxygenase metabolites of arachidonic acid.
The role of several lipoxygenase metabolites of arachidonic acid in the action of luteinizing hormone-releasing hormone (LHRH) on ovarian hormone production was investigated. Like LHRH, treatment of rat granulosa cells with 5-HETE, 5-HPETE, 12-HETE, 15-HETE or 15-HPETE stimulated progesterone (P) and prostaglandin E2 (PGE2) production. 12-HEPE was most potent and stimulated P and PGE2 equally well. By contrast, 5-HETE stimulated P better than PGE2, while 15-HETE was a potent stimulator of PGE2 but not of P. Stimulation of P and PGE2 by LHRH or 12-O-tetradecanoylphorbol 13-acetate (TPA) was further augmented by several HETEs and HPETEs. Like protein kinase C, arachidonic acid metabolites appear to mediate the multiple actions of LHRH in the ovary.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Effects of a superovulatory dose of pregnant mare serum gonadotropin on follicular steroid contents and oocyte maturation in rats.
Our previous study has shown that superovulatory treatment with pregnant mare serum gonadotropin (PMSG) in rats caused marked alterations in ovarian and serum steroid responses and coincidental increase in degenerate oocytes (Yun et al., 1987). This study examined the effects of superovulatory treatment (20 IU PMSG) on follicular steroid contents and oocyte maturation. Immature female rats aged 28-30 days were injected with 4 or 20 IU PMSG and sacrificed at 24, 48, 60, and 72 hr. Compared to control regimen, follicular content of progesterone (P) in superovulated rats significantly (P less than .05) increased at 48 hr. Androgen (A) content significantly (P less than .01) decreased below control level at 24 hr but significantly (P less than .05) increased above control level at 48 hr and 60 hr. There was no significant change in 17 beta-estradiol (E) content between the two groups. In control regimen, the ratio of A/E sharply decreased and the ratios of P/E and P/A increased steadily from 24 hr. However, superovulatory regimen showed a consistently steady state in the overall ratios of follicular steroids after 24 hr. Nuclear maturation of the majority of control oocytes recovered from oviducts at 72 hr was synchronized at metaphase II, whereas superovulated oocytes displayed different stages varying from prophase I to metaphase II at 24, 48, and 72 hr. The results provide direct evidence of atypical ovulations in superovulated oocytes with premature or asynchronous nuclear maturation and demonstrate a close relationship between meiotically aberrant oocytes and abnormal follicular steroidogenesis following superovulation with PMSG in rats.
Animals↗
Clinical and endocrine response to pulsatile intravenous gonadotropins in refractory anovulation.
We investigated the endocrine response to an experimental protocol in which human menopausal gonadotropin was delivered in pulses every 90-120 minutes by an automated pump. Thirty clomiphene citrate- and gonadotropin-releasing hormone-unresponsive anovulatory women were studied over 107 treatment cycles. In response to episodic intravenous (IV) delivery, pulses of FSH and LH were demonstrable in the circulation. In four World Health Organization (WHO) group I anovulatory women, ovulation occurred in all cycles (N = 8); the pregnancy rate per cycle was 63% and the cumulative pregnancy rate 100%. In 26 WHO group II patients, 42.4% of treatment cycles were in 12 women previously refractory to the intramuscular route of administration; the rate for ovulation was 86% (total of 99 cycles), the pregnancy rate per ovulatory cycle was 14%, and the cumulative pregnancy rate 56%. A mild phlebitis occurred at the site of the IV catheter in 24% of treatment cycles. Intravenous delivery of gonadotropins in small pulses had a dose-sparing effect and was an effective method of treating anovulatory infertile patients refractory to other conventional methods of ovulation induction.
Adult↗
Chromosome analysis of human oocytes failing to fertilize in vitro.
To assess the contribution of chromosome anomalies to the high failure of in vitro fertilization (IVF), 94 unfertilized eggs from 43 women participating in the IVF program were cytogenetically investigated. The mean age of the oocyte donors was 33.6 years. Chromosome karyotypes were obtained in 65 of 94 oocytes: 34 oocytes (52.3%) had a normal haploid chromosome complement; 10 (15.4%) were hypohaploid; 7 (10.8%) were hyperhaploid; 8 were diploid; and 6 were hypodiploid or hyperdiploid (from 36 to 53). Eleven eggs showed prematurely condensed chromosomes of the G1-phase from sperm, as well as a set of maternal metaphase II chromosomes. These results are compared to similar reports in the literature.
Adult↗
Maternal mortality in British Columbia in 1971-86.
We reviewed the 56 maternal deaths in British Columbia in 1971-78 and 1979-86 identified through the provincial Ministry of Health and compared the findings with data for the two preceding 8-year periods. The maternal death rate, defined as the number of deaths directly or indirectly related to pregnancy or delivery per 100,000 live births, decreased from 42 in 1955-62 to 5 in 1979-86. In the same interval the number of direct obstetric deaths decreased from 100 to 10 and the number of indirect deaths from 29 to 8. The number of deaths due to abortion decreased from 32 to 1. There was no change in the number of deaths among North American Indians. There was also no change in the number of deaths due to hypertension, most of which were avoidable; these findings have stimulated intensive teaching efforts to increase recognition and improve management of the problem. Review of maternal deaths can help identify deficiencies in the quality of care and can direct measures aimed at further reducing the maternal death rate.
British Columbia↗
Effects of cyclic adenosine monophosphate on human chorionic gonadotropin and estradiol output by cultured human placental cells.
We have previously shown that adenosine-3',5'-cyclic monophosphate (cAMP) inhibits basal estradiol output in human trophoblast cells. The objective of this study was to investigate further the effect of 8-bromo-cAMP on the conversion of C19 androgens to estradiol by placental cells. Trophoblast cells were prepared from human term placenta and maintained in monolayer culture. On days 3 and 4 of culture, these cells were treated with dehydroepiandrosterone sulfate, androstenedione, or testosterone with or without the concomitant presence of 8-Br-cAMP. 8-Br-cAMP markedly enhanced human chorionic gonadotropin secretion into the culture medium. On the other hand, the concomitant addition of 8-Br-cAMP with the androgen precursors led to an inhibition of estradiol output. The concentrations of androstenedione and dehydroepiandrosterone in the culture medium after treatment with dehydroepiandrosterone sulfate were elevated by the concomitant presence of 8-Br-cAMP. From these results we conclude that 8-Br-cAMP enhances human chorionic gonadotropin output in human term placental cells, whereas the presence of 8-Br-cAMP in cells given androgen precursors inhibits estradiol output, probably at the level of aromatization.
8-Bromo Cyclic Adenosine Monophosphate↗
Endocrine response to selective embryocide in a gonadotropin-induced quintuplet pregnancy.
With the increase of medical induction of ovulation, the incidence of grand multiple pregnancy is becoming more frequent. We report the endocrine response of a quintuplet pregnancy that was reduced at 9 weeks' gestation to a twin pregnancy by selective embryocide and compared with quadruplet, triplet, and twin pregnancies. The human chorionic gonadotropin titer declined fourfold, but there were no clinically significant changes in the progesterone or estradiol levels. We conclude that, despite the drop in human chorionic gonadotropin, the placenta had attained adequate secretory maturation to prevent any significant decline in progesterone and estradiol levels, which demonstrates the efficacy of this procedure at this gestational age.
Abortion, Induced↗
Management of quintuplet pregnancy by selective embryocide.
Selective embryocide was performed as a two-stage procedure in a patient with a quintuplet pregnancy in the first trimester. No complications occurred, and the patient was delivered of healthy twins at term. This procedure may be offered to selected patients with pregnancies with greater than five embryos.
Abortion, Induced↗