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Biomedical subjects

W S Maxson

Publications and source records attributed to W S Maxson.

At least 19 recordsLinked to original sources

Use of a sensitive urine pregnancy test before endometrial biopsies taken in the late luteal phase.

Endometrial biopsies for evaluation of the luteal phase should be taken within 2 days of the onset of menses. When these guidelines are followed and patients present at least 12 days after the thermogenic shift on BBT, the ICON pregnancy test is extremely rapid, sensitive, specific, and has predictive values close to 100%. If a biopsy is undertaken before this time there may be an increased risk of false negative results (i.e., a decreased sensitivity). The improved technology in urine pregnancy tests has now made it feasible to obtain accurate urine pregnancy tests before endometrial instrumentation with an increased level of confidence. It is recommended that this technology be used in the management of patients undergoing endometrial biopsies in the late luteal phase.

Biopsy

Absorption of oral progesterone is influenced by vehicle and particle size.

The oral route of progesterone administration has long been considered impractical because of poor absorption and short biologic half-life. Recent reports suggest that micronization of progesterone enhances absorption and increases serum and tissue levels of progesterone. This study checks serum progesterone levels before and 0.5, 1, 2, 3, 4, and 6 hours after oral administration of 200 mg of progesterone in seven subjects. Progesterone was plain milled, micronized, plain milled in oil, micronized in oil, or micronized in enteric-coated capsules. All patients exhibited a significant increase in serum progesterone levels after oral progesterone administration. Mean peak progesterone levels (30.3 +/- 7.0 ng/ml) (p less than 0.005) were achieved with micronized progesterone in oil at 2.0 +/- 0.3 (p less than 0.05) hours after administration. Four types of oral progesterone had equivalent mean peak elevations and mean times to peak: plain milled, 9.6 +/- 2.5 ng/ml at 4.0 +/- 0.5 hours; micronized 13.2 +/- 2.4 ng/ml at 3.2 +/- 0.4 hours; plain milled in oil, 11.3 +/- 3.0 ng/ml at 4.0 +/- 0.5 hours; and micronized in enteric-coated capsules, 11.2 +/- 3.0 ng/ml at 4.1 +/- 0.7 hours. Contrary to traditional teaching, these data show that significant serum progesterone levels can be achieved by oral administration. Absorption can be significantly improved by the physical characteristics of the progesterone and the vehicle used with oral administration.

Absorption

Localization of transferrin and its receptor in ovarian follicular cells: morphologic studies in relation to follicular development.

Granulosa cells perform an essential role in ovarian follicle and ovum development. Proliferating cells have an absolute requirement for iron, which is delivered by transferrin with subsequent intracellular transport via the transferrin receptor. Because iron and transferrin concentration increase in follicular fluid with advancing follicular maturation, the authors studied the distribution of transferrin and its receptor in rat and human granulosa cells with light and electron microscopic immunohistochemistry. Intense cytoplasmic staining was found in granulosa cells, with immunostaining enhancement occurring with advanced follicle maturation, including the periovulatory period. Immunoelectron microscopy showed transferrin throughout the cytoplasm, often in proximity to polyribosomes and vesicular structures. When transferrin was absent in the culture medium used to maintain granulosa cells, diminished transferrin immunostaining was seen. Based on these findings, the authors conclude that follicular maturation is closely related to high levels of cellular transferrin and transferrin receptor. Acquisition of transferrin occurs primarily by either ultrafiltration or facilitated diffusion, whereas de novo local synthesis does not have a major role.

Animals

Menopausal hormone replacement therapy with continuous daily oral micronized estradiol and progesterone.

The safety and efficacy of a daily combination of micronized estradiol (E2) (0.7-1.05 mg) and progesterone (200-300 mg) were evaluated in ten menopausal women with moderate to severe vasomotor symptoms and/or vaginal atrophy over a 12-month study interval. For comparison, five similar women were placed on conjugated estrogens, 0.625 mg daily, and medroxyprogesterone acetate, 10 mg daily, for the first 10 days of each calendar month for 12 months. Patients were evaluated at 0, 1, 3, 6, and 12 months. Estrogens rose significantly from baseline in both groups (P less than .01). Progesterone increased significantly above baseline in the E2 and progesterone group (P less than .01), but did not change in the conjugated estrogens and medroxyprogesterone acetate users. All women on E2 and progesterone had a decrease in total cholesterol and an increase in high-density lipoprotein cholesterol from baseline (P less than .01). Those on conjugated estrogens and medroxyprogesterone acetate had no significant change from baseline in total cholesterol; however, they did have an increase in high-density lipoprotein cholesterol values (P less than .01). In the E2 and progesterone group, the endometrial histology became completely quiescent and there was no uterine bleeding after 6 months of observation. Four of five women on conjugated estrogens and medroxyprogesterone acetate continued regular withdrawal bleeding throughout the study period, but no endometrial hyperplasia was encountered. This study demonstrates that the daily administration of a combination of micronized E2 and progesterone results in symptomatic improvement, minimal side effects, an improved lipid profile, and amenorrhea without endometrial proliferation or hyperplasia in menopausal women.

Cholesterol

Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites.

Progesterone and its metabolites were measured in serum extracts by radioimmunoassay and gas chromatography-mass spectrometry, respectively, after ingestion of micronized progesterone by eight postmenopausal women. One subject received 400 mg of micronized progesterone orally that induced a hypnotic state that lasted for approximately 2 hours. Blood samples were drawn periodically from all subjects for measurement of progesterone and its metabolites in serum. Levels of serum progesterone and its metabolites increased significantly from baseline values and reached a peak between 2 and 6 hours after oral progesterone administration. Significant quantities of five compounds (progesterone, 5 alpha-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha,20 beta-diol, and 5 beta-pregnan-3 alpha-ol-11,20-dione) that have been reported to possess anesthetic qualities were identified. The sedative and hypnotic effects of oral administration of progesterone may be mediated through those compounds.

Administration, Oral

Efficacy of a modified oxidized cellulose fabric in the prevention of adhesion formation.

A new fabric of regenerated oxidized cellulose (TC-7) was evaluated for the prevention of postoperative adhesions. Standardized injuries were performed on the uterine fundal serosa, the unilateral uterine cornu, and the contralateral ovary in 24 New Zealand rabbits. TC-7 was applied to the injured surfaces in 12 rabbits utilizing a randomized study design. At second-look laparotomy 3 weeks later, adhesions were graded without knowledge of the treatment category in the 22 rabbits surviving the study. There were no statistically significant differences in adhesion formation between treated and control animals at any of the injury sites. No gross or histologic residua of the TC-7 were evident 3 weeks after intraperitoneal application. Further studies will be needed to clarify the clinical role of this new fabric.

Animals

Combination clomiphene citrate/human menopausal gonadotropin stimulation protocols for in vitro fertilization-embryo transfer.

Various protocols have been utilized for stimulation of multiple ovarian follicles in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). Previous studies have suggested that the combination of clomiphene citrate (CC) and human menopausal gonadotropins (hMG) is superior to either CC or hMG alone in terms of follicular development, oocyte recovery, and embryo transfer. However, no significant increase in viable pregnancy rates has been reported with any of the protocols. This report examines five different CC/hMG protocols. While differences were seen in terms of serum estradiol response and fertilization rates of mature oocytes among the various protocols, no significant differences were found in terms of follicular development, oocyte recovery, embryo transfer, or pregnancy. The pregnancy rate in IVF-ET appears unaffected by variations in the dose and timing of CC and hMG in a combination protocol.

Adult

Follicular fluid transferrin levels in preovulatory human follicles.

There is transferrin-like protein present in the follicular fluid of stimulated ovarian cycles. The transferrin concentration correlates with the follicular morphologic maturity and steroidogenesis, varies among follicles, and often exceeds serum concentrations. An intermediate range of transferrin concentration is associated with the highest likelihood of oocyte fertilization in vitro. The biological significance of these observations may relate to an optimum degree of follicle maturation.

Body Fluids

Antiestrogenic effect of clomiphene citrate in a multiple follicular stimulation protocol.

End-organ antiestrogenic effects of clomiphene citrate (CC) have been demonstrated in the female reproductive tract at the levels of the ovary, cervix, and endometrium. However, it has not been established whether this effect is manifested during concomitant human menopausal gonadotropin (hMG) administration, as occurs in hMG/CC stimulations of multiple follicular development. To assess this question a review was made of serum estradiol (E2) and cervical mucus in 47 hMG and 56 hMG/CC stimulations on days -2, -1, 0, and +1 relative to the day of hCG administration. E2 levels (pg/ml) were significantly lower in the hMG as compared to the hMG/CC group. However, comparing the hMG and hMG/CC groups, cervical mucus scores were significantly higher in the former. Furthermore, an analysis of covariance demonstrated that the cervical mucus scores on each day were significantly lower in the hMG/CC group (P less than 0.001). Thus, in hMG/CC stimulations for in vitro fertilization (IVF), despite the concomitant administration of pharmacologic doses of hMG, CC exerts an antiestrogenic effect on at least one end organ, cervical mucus production. Potentially, this antiestrogenic effect in IVF stimulations would be exerted at other female reproductive tract sites including the endometrium; however, its clinical significance, if any, is unclear.

Cervix Mucus

Comparison of two brands of clomiphene citrate for stimulation of follicular development in a program for in vitro fertilization.

Although clomiphene citrate (CC) is used frequently to stimulate multiple follicular development in in vitro fertilization programs, comparison of the two commercially available types has been limited. Therefore, a comparison was made of Serophene (Serono Laboratories, Inc., Randolph, MA) and Clomid (Merrell Dow Pharmaceuticals, Inc., Cincinnati, OH), using the same dosage regimen of CC (150 mg/day for days 3 to 7 of the cycle). Weights and ages of the two groups were not different. Serum estradiol (E2) levels were significantly elevated in Clomid cycles, but the number of developing follicles was not different between the two brands. The percentages of patients in each group who underwent laparoscopy, oocyte recovery, oocyte fertilization, and embryo transfer were also equivalent. Among patients undergoing laparoscopy, no differences in oocyte recovery, oocyte fertilization, and embryo development were noted. Thus, despite greater elevation of serum E2 levels with Clomid, no difference in stimulation regimen outcome was observed.

Adult

Cycle of conception endometrial biopsy.

Although controversial, the diagnosis of luteal phase inadequacy and its therapy may improve reproductive outcome, but an endometrial biopsy in the cycle of conception (COC) might theoretically interrupt an intrauterine pregnancy. Fifty-four biopsies obtained in the COC were identified, and patient outcome was documented. Eleven (20%) of the 54 women who underwent COC biopsy did not deliver viable infants. Two patients had ectopic pregnancies, and nine had early abortions, including one whose biopsy specimen contained an early implantation site and another with a trisomy 16 fetus. Although COC endometrial biopsy did not appear to increase the incidence of fetal wastage, biopsy information provided no predictive information suggestive of ultimate pregnancy outcome. Because no useful information is gained from a COC biopsy, we recommend either that pregnancy be avoided or a sensitive pregnancy test be employed for detection in a cycle in which a biopsy is to be performed.

Abortion, Spontaneous

Comparison of human menopausal gonadotropin, clomiphene citrate, and combined human menopausal gonadotropin-clomiphene citrate stimulation protocols for in vitro fertilization.

Human menopausal gonadotropins (hMG) and clomiphene citrate (CC), either alone or in combination, are frequently used for in vitro fertilization (IVF) in an attempt to maximize the number of oocytes recovered and the number of embryos transferred. However, direct comparison of the relative efficacy of these protocols in the same institution has been limited. To evaluate this question, the authors examined the outcome of 304 consecutive women attempting IVF. One hundred eighty-one women received hMG, 42 received CC, and 81 received combination hMG/CC. The percentages of women undergoing laparoscopy were not different among the groups (69%, 71%, and 74%, respectively), nor were the rates of oocyte recovery (94%, 100%, and 100%). However, the percentage of women achieving oocyte fertilization (77%, 83%, and 93%) and embryo transfer (73%, 83%, and 90%) were significantly greater among those who had received hMG/CC stimulation. A comparison of hMG/CC with hMG and CC cycles revealed a statistically significant increase in the total number of developing follicles (4.5 +/- 0.3, 3.3 +/- 0.2, and 3.1 +/- 0.3, respectively; P = 0.0137), total oocytes recovered (4.1 +/- 0.3, 3.2 +/- 0.2, and 2.5 +/- 0.2; P = 0.0011), and embryos transferred (2.2 +/- 0.2, 1.4 +/- 0.2, and 1.4 +/- 0.2; P = 0.0013). However, there was no significant difference in the occurrence of ongoing pregnancies. Thus, in terms of the per-patient number of follicles, oocytes, and embryo transfers, combined hMG/CC stimulation appears to be superior to either hMG or CC alone. However, to date the combined regimen has not improved pregnancy rates.

Clomiphene

Ureteral abnormalities in women with endometriosis.

High-volume intravenous urography was performed in 63 women with surgically proven endometriosis. Subtle abnormalities were found in 15.9% of these women. No patient had urologic symptoms, and there was no evidence of hydroureter or ureteral obstruction on the IVP. Long-term follow-up study will be required to determine whether or not these lesions will progress and cause ureteral obstruction.

Adult

Estrogen replacement therapy.

The popularity of estrogen therapy for the menopausal woman seems to be on the rise again, with new evidence on the risks and treatment of osteoporosis and the protective effect of progestin on the endometrium becoming clearer. The risks of estrogen treatment must remain a prime concern of the practitioner, and hazards may be minimized through careful patient selection, education, examination, treatment, and follow-up. The resurgence of interest in the plight of the menopausal woman has stimulated an increasing number of competent investigators to attempt to solve the mysteries that until recently have been evaluated and treated by anecdote and homeopathic ministrations.

Adult