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M J Gast

Publications and source records attributed to M J Gast.

At least 19 recordsLinked to original sources

Endometrial thickness is a valid monitoring parameter in cycles of ovulation induction with menotropins alone.

OBJECTIVE: To evaluate the ability of an ultrasound (US)-measured periovulatory endometrial thickness to predict conception in hMG-stimulated cycles. DESIGN: Retrospective. SETTING: A university-based tertiary practice. PATIENTS: One hundred twelve patients undergoing 292 cycles of ovulation induction with hMG alone. MAIN OUTCOME MEASURES: A periovulatory transvaginal US measurement of endometrial thickness was obtained during cycles of ovulation induction with hMG alone. Clinical pregnancy was defined by fetal cardiac activity. Sensitivity and false-positive rates for multiple discriminatory values of endometrial thickness were calculated and a relative operating characteristic (ROC) curve was constructed to evaluate the performance of this test as a predictor of pregnancy. RESULTS: Thirty-eight of 292 cycles resulted in pregnancy. Conception and nonconception cycles showed similar demographics, diagnoses, peak E2, maximum number of follicles, midluteal P, and mean endometrial thickness. Ovulatory dysfunction was a more frequent diagnosis in the conception group. Relative operating characteristic analysis for endometrial thickness as a predictor of pregnancy yielded an area under the curve of 0.623 +/- 0.049 (mean +/- SD). CONCLUSION: Endometrial thickness is a valid screening test for conception outcome in cycles stimulated with hMG. A periovulatory endometrial thickness > or = 10 mm defined 91% of conception cycles. No pregnancy occurred when the endometrium measured < 7 mm.

Adult

The evolution of new agents for ovulation induction.

The field of clinical ovulation-induction therapy has remained relatively static for over 30 years. This field promises to benefit from advances in our understanding of the biology of ovulation, and from exciting new work in the areas of molecular and cellular biology and in the biochemistry of steroids, gonadotropins, and their receptors. New therapies with recombinant gonadotropins and their analogues show promise for the near future. Advances in our ability to stimulate and suppress the reproductive axis through central mechanisms also show some promise. In the long term, our understanding of the mechanisms involved in folliculogenesis and oocyte maturation may be combined with an enhanced ability to dissect these processes that lead to disordered ovulation. Our improved understanding of the implantation process may well lead to an ability to create nearly universal nidation in women who are undergoing ART or who have implantation disorders. This article discusses some of the many new opportunities in the clinical and basic science of ovulation induction. New technologies, such as those available through the Human Genome Project, and the use of genetic manipulation of animal models will stimulate additional new avenues of research.

Female

Evolution of clinical agents for ovulation induction.

Since the first use of human urinary gonadotropins in the 1960s, the number of agents available for ovulation induction has remained fairly static. However, the nature of gonadotropin therapy is expected to change rapidly in the near future, and by the end of the decade these changes may be augmented by nongonadotropin ovulation induction therapies. Newer agents described in the literature include highly purified preparations of follicle-stimulating hormone and recombinant forms of follicle-stimulating hormone, luteinizing hormone, and human chorionic gonadotropin. Protein fragments, cytokines, and growth factors also show great promise as ovulation adjuncts. Other promising approaches being explored are the use of genetically engineered human gonadotropin derivatives, the creation of chimeric proteins, and gene therapy.

Animals

Does intrauterine insemination offer an advantage to cervical cap insemination in a donor insemination program?

OBJECTIVE: To compare pregnancy outcome after IUI versus cervical cap insemination in a donor insemination program. DESIGN: A randomized prospective clinical trial in which patients were alternately inseminated with cryopreserved human semen using either IUI or cervical cap insemination methods. SETTING: The donor insemination program at Washington University School of Medicine. PATIENTS: Forty-two women with either isolated male factor or male factor plus corrected ovulatory dysfunction using clomiphene citrate underwent 141 cycles of donor insemination. MAIN OUTCOME MEASURES: Clinical pregnancy rates (PRs) defined as a viable intrauterine gestation > 12 weeks or delivered were compared between groups using the chi 2 test. RESULTS: Clinical PRs were significantly higher in the IUI group (16.4%) compared with the cervical cap insemination group (5.9%). The spontaneous abortion rates were similar between the IUI (1.4%) and cervical cap insemination groups (4.4%). CONCLUSIONS: These findings suggest an advantage to IUI over cervical cap insemination in a donor insemination program.

Abortion, Spontaneous

Long-term follow-up of couples after hamster egg penetration testing.

OBJECTIVE: To determine the clinical usefulness of the zona-free hamster egg penetration test as a long-term prognostic indicator for future pregnancy. SETTING: Division of Reproductive Endocrinology and Infertility at the Washington University Medical Center. PARTICIPANTS: All couples (n = 148) who had a hamster egg penetration assay performed between March 1, 1985 and December 31, 1986 were identified and followed with direct or telephone contact up to 68 months after the initial assay. MAIN OUTCOME MEASURE: The monthly fecundity rates using life table analysis and the 5-year incidence of pregnancy were categorized by the percentage of hamster eggs penetrated and by history of previous urologic surgery. RESULTS: There were no significant differences in the rate nor incidence of pregnancy in couples with hamster egg penetration scores of 0%, > 0% and < or = 10%, > 10% and < or = 20%, or > 20%. Although men with previous urologic surgery tended to have lower scores, there was no significant difference in the 5-year incidence of pregnancy. CONCLUSION: The hamster egg penetration score is not predictive of incidence of pregnancy nor time to conception.

Adult

Pregnancy in a woman with a uterine septum. A case report.

A term pregnancy occurred in the presence of a significant uterine septum. The changes in the anatomic appearance of the septum were documented sonographically throughout the gestation. A complete workup for other causes of pregnancy loss and attention to obstetric detail are central to the management of such patients.

Abortion, Spontaneous

Rh isoimmunization complicating a triplet gestation. A case report.

A case occurred of Rh isoimmunization complicating a triplet gestation. Management of that extremely rare situation required careful attention to the problems inherent in both multiple pregnancy and isoimmunization. Amniocentesis and frequent antepartum fetal monitoring were the cornerstones of therapy.

Adult

Therapeutic donor insemination: a prospective randomized study of scheduling methods.

OBJECTIVE: To compare basal body temperature (BBT) graphs and urinary luteinizing hormone (LH) monitoring in scheduling therapeutic donor insemination. DESIGN: Participants were prospectively randomized to the BBT or LH groups. SETTING: Participants were private patients of the Reproductive Endocrine Division at Washington University School of Medicine. PATIENTS: Inclusion criteria were designed to assure an isolated male factor. Seventy-four of 113 patients completed the study; 18 had ongoing treatment at the end of the study. INTERVENTIONS: Basal body temperature graphs were physician interpreted and appointments prospectively chosen. Luteinizing hormone patients monitored daily urine samples and scheduled an appointment the day after the detected surge. MAIN OUTCOME MEASURES: Fecundity rates, cumulative pregnancy rates, and cost per pregnancy were all prospectively evaluated. RESULTS: Life table analysis yielded a 6-month cumulative probability of pregnancy of 36.3% in the LH group and 65.1% in the BBT group (P less than 0.025). The total cost per pregnancy was lower in the BBT group (+6,212 versus +3,997; P less than 0.001). CONCLUSIONS: This randomized prospective study demonstrates significant therapeutic and economic advantages when therapeutic donor insemination is prospectively scheduled by BBT graphs.

Body Temperature

Isolation and characterization of the gene from a human genome encoding 17 beta-estradiol dehydrogenase: a comparison of Jar and BeWo choriocarcinoma cell lines.

17-beta-Estradiol dehydrogenase is required for the enzymatic interconversion of estradiol and its weaker related sex steroid, estrone. We isolated and sequenced a complementary deoxyribonucleic acid clone for 17 beta-estradiol dehydrogenase from the BeWo choriocarcinoma cell line. Comparison of the BeWo complementary deoxyribonucleic acid sequence to a previously derived placental complementary deoxyribonucleic acid sequence yields greater than 98% homology. We also isolated the gene for 17 beta-estradiol dehydrogenase from the Jar human choriocarcinoma cell line and elucidated its primary nucleic acid structure. Significant differences in the Jar-deduced complementary deoxyribonucleic acid sequence clearly differentiate it from both the human placental and BeWo forms of 17 beta-estradiol dehydrogenase, indicating the existence of two genes for 17 beta-estradiol dehydrogenase in the human genome. Evaluation of 17 beta-estradiol dehydrogenase gene expression in BeWo and Jar cells was compared with expression in luteinized granulosa cells. Messenger ribonucleic acid for human placental 17 beta-estradiol dehydrogenase was identified in all three cell types as a 1.3 kilobase band on Northern blot analysis. A second messenger ribonucleic acid species measuring 2.1 kilobase was abundantly present in the granulosa cells. Whether these two species of messenger ribonucleic acid are involved in the regulation of the estradiol dehydrogenase genes is yet to be determined.

Base Sequence

Menorrhagia.

Excessive vaginal bleeding, or menorrhagia, is one of the most common presenting symptoms for gynecologic patients. Although this disorder has many possible etiologies, it is generally possible to approach its diagnosis and management in an orderly fashion. When evaluating the menorrhagic patient, it important to gear the work-up toward a differential diagnosis that includes pregnancy-related causes, hormonal problems, iatrogenic etiologies, mechanical intrauterine disorders, infections of the lower genital tract, and gynecologic cancers (PHIMIC). This differential approach can guide the types of historical data obtained from the patient, focus the physical examination, and alert the practitioner to the most appropriate laboratory and radiologic evaluation. Therapy can differ widely, depending on the cause of the bleeding. Most types of menorrhagia respond to medical therapy with oral contraceptives, oral synthetic estrogens or progestins, and long-acting intramuscular progestins or GnRH agonists. Surgical approaches, such as dilatation and curettage or hysterectomy, are less and less a first-line therapy; but innovative surgical techniques such as hysteroscopy and laparoscopic surgery are becoming increasingly important. With rapid, goal-directed diagnosis and specific therapy, the medical complications, anxiety, and discomfort suffered by the woman with menorrhagia can be alleviated quickly.

Female

Isolation and sequencing of a complementary deoxyribonucleic acid clone encoding human placental 17 beta-estradiol dehydrogenase: identification of the putative cofactor binding site.

17 beta-Estradiol dehydrogenase (EC 1.1.1.62) catalyzes the interconversion of estradiol and estrone in human term placenta. We have raised a specific polyclonal antibody to this abundant placental enzyme to study its role in late pregnancy events and its molecular biologic characteristics. In this work the 17 beta-estradiol dehydrogenase antibody was used to isolate and sequence a complementary deoxyribonucleic acid clone encoding about 98% of the amino acid sequence of the 17 beta-estradiol dehydrogenase molecule. This sequence verifies previous sequence data on the molecule's steroid binding site and also localizes a putative nicotinamide adenine dinucleotide binding region similar to that of many other pyridine nucleotide-dependent dehydrogenases. Isolation of the complementary deoxyribonucleic acid for 17 beta-estradiol dehydrogenase expands our knowledge of the structure-function relationships of the enzyme and is a major step in our understanding of its biologic function in pregnancy.

17-Hydroxysteroid Dehydrogenases

Mullerian adenosarcoma of the cervix with heterologous elements: diagnostic and therapeutic approach.

Mullerian adenosarcoma of the cervix with heterologous elements is an extremely rare tumor first described by Roth and colleagues (L. M. Roth, G. L. Pride, and H. M. Sharma, Cancer 37, 1725-1736) in 1976. Since that time there have been only three subsequent reports of these cervical Mullerian adenosarcomas, which seem to occur most often in the postmenarchal age group. Due to the paucity of cases and the unknown biological potential of the tumor, therapy has ranged from simple excision to radical pelvic surgery and vaginectomy combined with both radiotherapy and chemotherapy. We report another case of Mullerian adenosarcoma of the cervix occurring in a teenage woman and make recommendations about diagnostic and therapeutic measures available to the physician.

Adolescent

Hormonal evaluation of female infertility and reproductive disorders.

Performance of the male and female reproductive systems reflects the orderly operation of the hypothalamic-pituitary-gonadal axis. Aberrant operation of this axis can result in many different reproductive disorders, including various forms of infertility. Proper evaluation of these disorders involves a multifaceted diagnostic approach, which includes a critical contribution from the clinical laboratory. This adjunctive testing, involving the measurements of peptide and sex-steroid hormone concentrations, allows the clinician to biochemically "dissect" the hypothalamic-pituitary-gonadal axis and ascertain the presence as well as location of the specific defect. In practice, the specific tests utilized during the evaluation of a patient depend upon the underlying disorder. Typically, in evaluating the reproductive disorders discussed in this review, a primary battery of tests is obtained that reflects the initial clinical presentation and physical examination. The results of these initial studies then dictate any secondary testing required to complete the evaluation. Such an approach, in use at our institution, is provided in Table 5. Although this discussion has concentrated on the laboratory assessment of the female reproductive system, it is important to remember the special case of infertility, where couples, in general, are evaluated together by the clinician. The cause of infertility can reside with the female, the male, or, in the cases of immunological "incompatibilities," a combination of the male and the female. As such, rigorous schemes for evaluating male reproductive disorders (1, 3, 89-94) and immunological incompatibilities (95-98) have been developed, and the information derived from such testing represents a critical contribution to establishing the etiology of a couple's infertility. Although the laboratory assessment of peptide and sex-steroid hormone concentrations clearly plays a pivotal role in the evaluation of reproductive disorders, these diagnostic tools probably will continue to change and improve in the years to come. Such changes will probably occur as the finer details of the operation of the hypothalamic-pituitary-gonadal axis become known. With this improved knowledge, we should have the capacity to design assays that will allow more clinically refined and biochemically precise means of diagnosing and treating specific reproductive disorders.

Adult

Mesenteric cysts in pregnancy. A case report.

Mesenteric cysts are rare. These large, often asymptomatic growths may be misinterpreted easily by the clinician as representing either benign or malignant ovarian tumors, renal masses, or hepatic tumors or cysts. We treated a women for a mesenteric cyst complicating her second pregnancy. Because of the increasing use of ultrasound in a wide variety of pregnancy complications, and because of the mesenteric cysts's unique sonographic appearance (resembling that of a benign ovarian tumor), such a cyst must be included in the differential diagnosis of large, cystic abdominal masses in pregnancy.

Adult

Purification and characterization of human myometrial smooth muscle collagenase.

Collagenase has been purified from the culture medium of a human myometrial smooth muscle cell line, and the properties of the pure enzyme compared to those of collagenase from another human mesenchymal cell, the fibroblast. The smooth muscle collagenase was purified using a new, rapid, and convenient three-step purification procedure consisting of chromatography on iminodiacetate-agarose chelated with zinc and on Cibacron Blue-agarose followed by gel filtration on Ultrogel AcA-44. The resultant pure collagenase is secreted as a zymogen indistinguishable from that of the fibroblast enzyme in molecular weight, amino acid composition, and in the nature of its conversion to active enzyme by trypsin. The amino acid sequence of the two enzymes at the trypsin cleavage site is the same. The two collagenases are also indistinguishable immunologically and display essentially identical kinetic behavior on a variety of collagen substrates. Although the two collagenases appear to be identical proteins, the mechanisms which regulate their production appear to be very different. Glucocorticosteroids, which inhibit collagenase production in human skin fibroblasts are without effect in the uterine smooth muscle cell. In contrast, the smooth muscle cell appears to require a component present in fetal bovine serum in order to produce the enzyme.

Amino Acids