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Biomedical subjects

J Jarrell

Publications and source records attributed to J Jarrell.

At least 19 recordsLinked to original sources

Association of semen quality and occupational factors: comparison of case-control analysis and analysis of continuous variables.

OBJECTIVE: To compare two statistical approaches, case-control and analysis of continuous parameters of semen, in examining the relationship between occupational exposures and male reproductive function. DESIGN: Case-control study. SETTING: Males providing semen samples at a university infertility clinic. PATIENT(S): Nonvasectomized males who provided at least one semen sample at an infertility clinic. MAIN OUTCOME MEASURE(S): Standard clinical semen analysis. RESULT(S): Analyses using a dichotomous dependent variable did not uncover significant associations between any occupational factor and infertility case status. However, linear models incorporating continuous variables identified a number of occupational factors that were associated with specific parameters of semen. A reduction in percentage of progressive sperm and an increase in percentage of coiled tail sperm defects in welders, compared with unexposed subjects, were found. Significant dose-response relationships between level of perceived job stress and percentage of progressive sperm, total motile count, morphology, abnormal heads, and coiled tail defects were found. CONCLUSION(S): The findings suggest that subtle changes in semen variables, possibly associated with workplace exposure, may be detected only with parametric analyses of continuous variables of semen.

Adult↗

A randomized, controlled trial of nurse-midwifery care.

BACKGROUND: In 1990 a pilot nurse-midwifery program was implemented in a tertiary care hospital in a major western Canadian city. a randomized, controlled trial was conducted to determine if, when maternal and newborn patient outcomes were compared, the midwifery program was as effective as traditional, low-risk health care available in the city. METHODS: All low-risk women who requested and qualified for nurse-midwifery care were randomly assigned to an experimental or control group. RESULTS: One hundred one women received care from nurse-midwives and 93 received standard care from either an obstetrician or family physician. The rate of cesarean delivery in the nurse-midwife group was 4 percent compared with 15.1 percent in the physician group. The episiotomy rate, excluding cesarean deliveries, for the nurse-midwife group was 15.5 percent compared with 32.9 percent in the physician group. The rates of epidural anesthesia for pain relief in labor were 12.9 percent and 23.7 percent, respectively. Statistically significant differences were found ultrasound examinations, amniotomy, intravenous drug administration during labor, dietary supplements, length of hospital stay, and admission of infants to the neonatal intensive care unit. CONCLUSIONS: The results clearly support the effectiveness of the pilot nurse-midwifery program and suggest that more extensive participation of midwives in the Canadian health care system is an appropriate use of health care dollars.

Adult↗

Factors predicting outcome in 215 consecutive thawed embryo replacements.

This retrospective study was undertaken to determine which factors were associated with outcome in thawed embryo replacement cycles. The number of embryos replaced and the response to exogenous ovarian stimulation in the original IVF cycle were significantly associated with the conception rate.

Cryopreservation↗

A randomized trial of in vitro fertilization versus conventional treatment for infertility.

OBJECTIVE: To evaluate the effectiveness of IVF in couples with infertility. DESIGN: Two hundred forty-five consecutive couples with infertility were randomized to receive one cycle of IVF treatment (experimental group) or to wait for a period of 6 months before receiving IVF treatment, during which time other infertility treatments could have been undertaken (control group). SETTING: Patients were referred to the Fertility Clinic at Chedoke-McMaster Hospitals, a university-associated institution in Hamilton, Ontario, Canada, in which IVF has been offered to couples since 1984. PATIENTS: Couples with infertility (mean duration of 65 months) not corrected by conventional treatment. They came from all socioeconomic classes, and the costs of IVF treatment, except medication, were covered by the Ontario Health Insurance Plan. MAIN OUTCOME MEASURE: Pregnancy was confirmed by ultrasound documentation of a gestational sac or histologic examination of tissue. Outcomes included livebirth, spontaneous abortion, and ectopic pregnancy. The overall pregnancy rate (PR) and the interval-to-pregnancy duration were compared in each group. RESULTS: Univariate analysis demonstrated a significant beneficial effect of IVF treatment in patients with bilateral severe tubal disease. Although in other diagnostic categories the crude and cumulative PRs in the experimental group were higher than in the control group, the differences did not reach statistical significance. Among the early IVF group, those with endometriosis had significantly more pregnancies when compared with other diagnostic categories. Although IVF increases the likelihood of pregnancy by 40% with severe tubal disease, the overall 31% increase associated with IVF was not statistically significant. CONCLUSIONS: There was a significant difference in favor of treatment in patients with severe bilateral tubal disease. For couples with other causes of infertility, the confidence limits around the treatment effect included unity. To reject the null hypothesis of no treatment effect, a larger sample size or a meta-analysis to combine the results of similar trials is required.

Adult↗

Alteration of primate ovary surface epithelium by exposure to hexachlorobenzene: a quantitative study.

Hexachlorobenzene (HCB) is a fungicide and a pollutant of increasing concern in industrialized regions of the world. Reproductive failure is one of the effects of HCB upon mammals. Alteration of cell shape in the ovary surface epithelium (OSE) of Cynomolgus monkeys following oral administration of HCB was observed in this study. At the lowest dose used, 0.1 mg/kg body weight, a dosage that is associated with follicular degeneration, HCB caused quantifiable changes in length-to-width ratios of OSE. Measurement of cell shape by light microscopy offers a reliable indication of OSE changes induced by HCB.

Animals↗

The effect of medroxyprogesterone acetate (Provera) on ovarian radiosensitivity.

Medroxyprogesterone acetate (Provera) is a drug that is commonly given to young women with cancer during chemotherapy and radiation to control heavy bleeding associated with anovulation. Because hypothalamic-pituitary-ovarian suppression has been associated with ovarian protection from the effects of chemotherapy and medroxyprogesterone acetate has been identified as a radiosensitizing agent, we explored the effects of medroxyprogesterone acetate on a rat model with known radiation injury characteristics. Sprague-Dawley rats were treated with medroxyprogesterone acetate or vehicle from day 22 to day 37 of life and were either irradiated or sham-irradiated on day 30 of life and then killed on day 44. Radiation with medroxyprogesterone acetate administration produced a greater loss in preantral and healthy control follicles than in control follicles. No suppression of luteinizing hormone or follicle-stimulating hormone had occurred by day 30 but ovarian glutathione content was reduced. These findings indicate that the administration of medroxyprogesterone acetate with radiotherapy may enhance ovarian injury.

Animals↗

An evaluation of the serum FSH as a biomarker for ovarian toxicity in the rat.

There is a need for a biomarker to evaluate numbers of oocytes in an ovary exposed to various exogenous toxicants. Experiments that had been previously reported were reviewed to assess the serum FSH as such a biomarker. Rats that had been exposed to direct ovarian radiation and direct ovarian radiation with cyclophosphamide were reviewed to ascertain the relationship of follicle numbers to the serum FSH. Under the conditions of reduced serum estrogen, linear regression analysis indicated that the serum FSH correlated best with the calculated volume of antral follicles. Receiver operating characteristic curves were calculated to determine that an elevation of the serum FSH two standard deviations above the mean had the greatest diagnostic power in predicting a significant loss in both the number of healthy follicles and the calculated volume of healthy antral follicles. The serum FSH as a biomarker appears to have utility as a measure of the ovarian content of healthy antral follicles rather than as a measure of the total number of oocytes alone.

Animals↗

Effects of ionizing radiation and pretreatment with [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide on developing rat ovarian follicles.

To assess the effects of a gonadotropin-releasing hormone agonist, [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance.

Animals↗

Ovarian toxicity of cyclophosphamide alone and in combination with ovarian irradiation in the rat.

The effects of radiation and chemotherapy on gonadal function are relevant to the morbidity induced by such treatments. Cyclophosphamide given i.p. to rats on Day 30 of age delayed vaginal opening, prevented vaginal cyclicity, and caused a reduction in serum estradiol and progesterone. Antral follicular atresia increased in a dose-dependent fashion in response to cyclophosphamide (0 mg/kg, 53.5%; 1 mg/kg, 67.3%; 50 mg/kg, 65.7%; 100 mg/kg, 73.9%; 150 mg/kg, 92.2%). Despite such alterations in ovarian function, serum gonadotrophins did not rise. The concurrent administration of 0, 20, 30, 40, 50, and 60 Gy of radiation to the exteriorized ovaries in rats receiving 50 mg/kg cyclophosphamide induced widespread loss of primordial, preantral, and healthy antral follicles associated with reduction in serum progesterone and estradiol. Such irradiation induced dose-related increases in serum follicle-stimulating hormone and luteinizing hormone. Parenteral cyclophosphamide and local irradiation appear to induce ovarian toxicity by different mechanisms.

Animals↗

An in vitro fertilization and embryo transfer pilot study: treatment-dependent and treatment-independent pregnancies.

A pilot program of in vitro fertilization and embryo transfer at McMaster University is described. Fourteen couples with a clinical diagnosis of infertility due to apparent tubal dysfunction, with evidence of ovulation, and with normal semen analysis underwent induction of superovulation with human menopausal gonadotropin. At laparoscopy, 82 follicles were aspirated and 19 oocytes were recovered. Eleven oocytes demonstrated cleavage and all inseminated oocytes were transferred 49 to 65 1/2 hours after insemination. In vitro fertilization therapy resulted in two pregnancies, one leading to a spontaneous abortion and the other to the birth of a healthy female infant. At 10 to 12 months after in vitro fertilization therapy in the remaining 12 patients, there were three additional pregnancies (treatment-independent), one ectopic and two intrauterine. One patient was delivered of a healthy female infant. In vitro fertilization therapy should be evaluated by a randomized controlled clinical trial.

Adult↗

An analysis of the effects of increasing doses of ionizing radiation to the exteriorized rat ovary on follicular development, atresia, and serum gonadotropin levels.

There is increasing interest in the effects of environmental and therapeutic agents on the reproductive system, in particular, the ovary. To study the effects of controlled doses of ionizing radiation to the ovary, Sprague-Dawley rats had their ovaries exteriorized and subjected to increasing doses of radiation. There was a significant increase in ovarian follicular atresia, a significant increase in serum follicle-stimulating hormone levels, but no change in serum luteinizing hormone levels. This experimental protocol may facilitate the testing putative radioprotectants.

Animals↗

Suppressor cells in human decidua.

Decidual suppressor cells have been found in the murine system. These cells are absent at the implantation sites of interspecies mouse embryos which become infiltrated by maternal cytotoxic cells. Suppression is also deficient at the sites of the spontaneous resorption of fetuses in allomated intraspecies pregnancies. This study was carried out to determine whether similar suppressor cells were present in the decidua during successful human allopregnancies. Decidua was obtained from gestations of 13 to 15 weeks and from term gestations, and the lymphocytes were tested for their ability to suppress the response of their peripheral blood lymphocytes to concanavalin A. Eight of eight 13- to 15-week decidual lymphocytes proved to be suppressive. At term seven of twelve lymphocyte preparations at a lower concentration of cells and six of seven at a higher concentration showed suppression. Suppressor cells appear to be present in human decidua and may play a role in preventing maternal immunologic attack on the allogenic embryo, thereby preventing spontaneous abortion.

Cells, Cultured↗

Preliminary characterization of two types of suppressor cells in the human uterus.

Survival of the mammalian fetus in an immunologically hostile host has been shown to be determined by the properties of the tissue at the maternal-fetal interface. Suppressor cells have been found in the decidua in both murine and human systems. This study was carried out to further characterize these cells and to determine whether they were present in abnormal early pregnancies and in the endometrium at the time of implantation. Suppressor cells appear in the endometrium after ovulation, and their activity is present in the decidua of successful pregnancies but is absent in missed abortions. Two types of cells have been identified. An early phase large cell appears to be hormone dependent, and later phase small cell appears to be trophoblast dependent. This would suggest that suppressor cells may play a role in protecting the fetal allograft, from the time of implantation, against maternal immunity, thereby allowing a pregnancy to succeed.

Abortion, Missed↗

Evidence for a granulosa cell site of dihydrostestosterone metabolism in the adult rat ovary.

The ovarian enzyme 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) converts dihydrotestosterone (DHT) to 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol), a reduced androgen that does not bind to the granulosa cell androgen receptor. To determine the relative contribution of the granulosa cells to total ovarian 3 alpha-HSD activity, adult rats treated with either medroxyprogesterone acetate (MPA) or vehicle underwent ovarian microdissection. 3 alpha-Hydroxysteroid dehydrogenase is primarily located in excised follicles and corpora lutea, and is inhibited in the follicles but not corpora lutea by MPA (P less than 0.05). Elimination of healthy granulosa cells while maintaining healthy theca cells by irradiation of the exteriorized ovaries with 6000 rads resulted in a marked reduction in 3 alpha-HSD to 19% of control levels on a per-organ basis (P less than 0.01). The granulosa cell is the major ovarian site for 3 alpha-hydroxylation of ring A-reduced C19 steroids in the adult rat.

3-Hydroxysteroid Dehydrogenases↗

Studies on the developmental pattern of rat ovarian 3 alpha-hydroxysteroid dehydrogenase: inhibition of the postpubertal activity with medroxyprogesterone acetate in vivo.

The developmental pattern of rat ovarian 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) activity was determined with respect to age, vaginal opening, ovarian histology and serum 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol). The enzyme was assayed by the incubation of [3H]dihydrotestosterone with a portion of whole ovarian cytosol in the presence of 5 X 10(-4) M NADPH. Serum levels of 3 alpha-diol declined from 11.1 +/- 1.2 ng/ml on day 22-3.4 +/- 0.3 ng/ml on day 30 (P less than 0.01). There was no significant change in 3 alpha-HSD during that period which fluctuated from 6.0 +/- 4.0 nmol/h/organ on day 22-8.4 +/- 1.9 nmol/h/organ on day 39. A significant increase on day 42 of 21.1 +/- 6.1 nmol/h/organ occurred well after vaginal opening, corpus luteum formation and the presence of ovarian progesterone; the activity plateaued on day 49 at 31.2 +/- 3.7 nmol/h/organ. In an attempt to inhibit the developmental increase in 3 alpha-HSD activity, medroxyprogesterone acetate (MPA), known inhibitor in vitro was administered to three groups of developing rats in vivo. The administration of MPA at doses of 0.1, 1.0 and 10.0 mg/kg to 30 and 36 day did not inhibit activity when assayed on day 44. In 44-day old rats, the administration of MPA failed to inhibit 3 alpha-HSD activity at 24 h (C-21.1 +/- 2.6; 0.1 mg/kg-19.4 +/- 5.5; 1.0 mg/kg-20.7 +/- 3.7; 10.0 mg/kg-21.1 +/- 3.0 nmol/h/organ) yet there was a significant reduction of 3 alpha-HSD activity when assayed at 48 h (C-21.1 +/- 1.5; 01 mg/kg-9.6 +/- 1.3; 1.0 mg/kg-8.5 +/- 1.9; and 10 mg/kg 5.2 +/- 2.0 nmol/h/organ).

3-Hydroxysteroid Dehydrogenases↗

On the presence and regulation of 3 alpha-hydroxysteroid dehydrogenase in the adult rat ovary.

The presence of 3 alpha-hydroxysteroid dehydrogenase activity in adult rat ovaries was assessed by direct measurement of the conversion of dihydrotestosterone to 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol). This enzyme was indeed found in this tissue with a high specific activity (414--560 nmol of 3 alpha-diol formed/h/mg protein) when compared to other hormone-dependent tissues. During the 4-day rat estrous cycle, the enzymatic activity was found to fluctuate by approximately 30% with the peak of activity at proestrus and the nadir at estrus. Further evidence for the hormonal regulation of this enzymatic activity was obtained with hypophysectomy and hormone replacement studies. Hypophysectomy resulted in a nearly 50% decrease when activity is expressed per ovary but this treatment had no significant effect on the specific activity (per mg ovary or per mg protein) of the enzyme. Hormone replacement, via polydimethylsiloxane capsules, with estradiol-17 beta resulted in a doubling of ovarian 3 alpha-HSD activity per mg protein but no significant change on a per ovary basis while replacement with testosterone caused a major decrease in activity to 15--30% (depending on the mode by which enzyme activity is expressed) of control hypophysectomized animals. These data thus indicate that this enzyme activity is present in the ovary and that it is regulated by gonadotrophins or gonadotrophin-induced steroids. The potential significance of these observations on follicular development and atresia is discussed.

3-Hydroxysteroid Dehydrogenases↗

Observations on the combination of clomiphene citrate-human menopausal gonadotropin-human chorionic gonadotropin in the management of anovulation.

To study the effects of the addition of clomiphene citrate to human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG), 23 cycles of clomiphene citrate-hMG-hCG (CHH) were administered to 10 anovulatory women. Of these 10 women, 5 also received 15 cycles of hMG-hCG (HH). Although there was a significant increase in the ovulation rate in the CHH group (p less than 0.01), there was no difference in the pregnancy rate (p less than 0.05). Patients in the CHH group required significantly less hMG for ovulation induction than the HH group (p less than 0.01). Patients receiving CHH who had low serum levels of follicle-stimulating hormone required significantly more hMG than those with normal values. The luteinizing hormone releasing hormone test may predict those patients who will require less hMG during CHH therapy. The relative safety of the CHH treatment is discussed.

Anovulation↗