Kenneth A. Burry

Vascular endothelial growth factor levels in serum and follicular fluid of patients undergoing in vitro fertilization

OBJECTIVE To define the relationship between serum and follicular fluid (FF) levels of vascular endothelial growth factor (VEGF), E2, and P in patients undergoing IVF; to quantify the effects of hCG on serum levels of VEGF during early pregnancy, and to report serial measurements of serum and ascites fluid levels of VEGF in a patient with severe ovarian hyperstimulation syndrome (OHSS). DESIGN Prospective observational study. SETTING University IVF program. PATIENTS(S) Women undergoing conventional IVF, receiving donated oocytes or spontaneously conceiving. One patient hospitalized with severe OHSS. MAIN OUTCOME MEASURE(S) Concentrations of VEGF, E2, and P in serum, FF, or peritoneal fluid. RESULT(S) At the time of egg retrieval, FF VEGF concentrations were positively correlated with serum and FF P concentrations and with patient age. At 11 to 14 days after ET, pregnant recipients of autologous fresh embryos had higher serum VEGF levels than both nonpregnant recipients of autologous fresh embryos and pregnant recipients of donor eggs. Elevated serum VEGF levels in a patient with severe OHSS coincided with the clinical onset and recurrence of symptoms. CONCLUSION(S) In patients undergoing IVF, FF VEGF levels at the time of egg retrieval correlated with the degree of follicular luteinization. There is a significant ovarian contribution to circulating VEGF levels during early gestation. Elevated serum VEGF levels may be a factor in the etiology of OHSS symptoms.

Efficacy and safety of low, standard, and high dosages of an estradiol transdermal system (Esclim) compared with placebo on vasomotor symptoms in highly symptomatic menopausal patients

Abstract Objective: Our purpose was to evaluate the efficacy and safety of 3 dosages of Esclim, delivering 0.025 mg, 0.050 mg, or 0.100 mg 17β-estradiol per 24 hours, in the treatment of moderate to severe vasomotor symptoms. Study Design: In this double-blind, placebo-controlled, parallel-group, multicenter trial, 196 highly symptomatic menopausal women received 12 weeks of continuous unopposed treatment with 1 of the 3 dosages of Esclim or a matching placebo patch. Results: The reduction in frequency of moderate to severe vasomotor symptoms was statistically significant compared with placebo ( P Conclusion: All 3 dosages of Esclim were effective in the treatment of vasomotor symptoms. The efficacy and safety of Esclim 25 indicate a good risk-benefit ratio. (Am J Obstet Gynecol 1999;181:71-9.)

Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain

OBJECTIVES To determine the effectiveness of a 3-month course of nafarelin and, furthermore, to determine the long-term efficacy in patients treated for 3 and 6 months with nafarelin for symptoms associated with endometriosis. DESIGN Double-blind, prospective, multicenter, clinical trial. SETTING Fifteen reproductive endocrine clinics throughout the United States. PATIENTS One hundred seventy-nine women with pelvic pain and endometriosis. INTERVENTIONS Patients were assigned randomly to 3 months nafarelin followed by 3 months of placebo (n = 91) or to 6 months nafarelin (n = 88) in a prospective, randomized, double-blind multicenter trial. Patients were followed for 12 months after cessation of therapy. MAIN OUTCOME MEASURES Patient-reported pain scores and physician-reported physical exam findings. RESULTS Pain scores dropped significantly by the end of treatment in both groups. Symptoms recurred in both groups, and pain scores gradually increased during the follow-up period but always remained below baseline in both groups. No significant difference in efficacy was noted between the groups. A total of 26% of patients in each group underwent retreatment for recurrent symptoms. CONCLUSIONS A 3-month course of nafarelin provided effective symptom relief for endometriosis. One year follow-up demonstrated continued pain relief but with gradual return of symptoms.

Insulin-like growth factor I promotes leiomyoma cell growth in vitro☆

OBJECTIVE Our purpose was to determine whether insulin-like growth factors I and II preferentially stimulate uterine leiomyoma cells versus myometrial cells in monolayer culture. STUDY DESIGN Leiomyomas and normal myometrium were obtained at hysterectomy from five premenopausal women. Specimens were enzymatically digested for use in primary monolayer cell cultures. By use of serum-free media, insulin-like growth factor I or II was added in 1, 10, and 100 ng/ml concentrations to both cell types with the patient serving as her own control. Cell number, prolactin production, and proliferative index values were measured on day 15 of cell culture. RESULTS Significant increases in cell number were found in the leiomyoma cultures (p < 0.05) treated with 10 and 100 ng/ml insulin-like growth factors I but not with insulin-like growth factors II. Neither factor exerted a stimulatory effect on myometrial cells. CONCLUSION Insulin-like growth factors I preferentially stimulates leiomyoma cells in monolayer culture. These results suggest an autocrine-paracrine role in vivo for this factor in conjunction with gonadal steroids in promoting leiomyoma growth.

Intrauterine insemination outperforms intracervical insemination in a randomized, controlled study with frozen, donor semen

OBJECTIVE To assess the efficacy of intrauterine insemination (IUI) in a donor insemination program. DESIGN Prospective randomized clinical trial. SETTING Donor insemination program. PATIENTS, PARTICIPANTS Women undergoing insemination were randomly assigned to receive either IUI or intracervical insemination for a maximum of six cycles. INTERVENTIONS None. MAIN OUTCOME MEASURE(S) Cycle fecundity rates between the two routes were compared. RESULTS The monthly fecundity rate for intracervical insemination was 5.1% compared with 23% by IUI. By life table analysis, pregnancy rates for IUI were significantly higher than intracervical insemination (P = 0.02). CONCLUSIONS Intrauterine insemination with quarantined donor sperm is superior to intracervical insemination.

Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen.

OBJECTIVE The objective of this study was to evaluate the serum levels of progesterone resulting from the application of a progesterone cream to the skin. STUDY DESIGN Six postmenopausal women were evaluated at a university clinic over a 4-week period. RESULTS Transdermal estradiol 0.05 mg was applied 2 days before the first application of progesterone (30 mg/d) and was continued throughout the study. Patches were changed twice a week. Progesterone cream was applied once a day for 2 weeks. On day 15 and for the next 2 weeks, the progesterone cream was applied twice daily (60 mg/d). Serum 17beta-estradiol and progesterone were measured at 9 different times over a 24-hour period on day 1 and at weekly intervals for the 4-week duration of the study. Serum 17beta-estradiol concentrations varied among women, with mean concentrations of 40 to 64 pg/mL observed. Consistency in 17beta-estradiol concentrations was found within individual persons throughout the study. Serum progesterone concentrations also varied among women, with mean concentrations ranging from 1.6 to 3.3 ng/mL. After 2 weeks of percutaneous dosing, progesterone concentrations were sustained for at least 8 hours and were consistent within a given person. An appropriate increase in progesterone concentration occurred after 4 weeks compared with 2 weeks of application. Individually, a 0.53 correlation, significant at P <.0001, was seen between the absorption of 17beta-estradiol and progesterone. CONCLUSION Significant increases in serum concentrations of progesterone were observed in all of the women studied. The percutaneous absorption of progesterone correlates strongly with the absorption of transdermal 17beta-estradiol. There is variance in absorption of progesterone just as with 17beta-estradiol, and the 2 measures are closely correlated. The percutaneous application of progesterone cream appears to be a safe and effective route of administration.

Effects of estrogen and progestin on aortic size and compliance in postmenopausal women

OBJECTIVE Our purpose was to determine whether sex steroids alter aortic size and compliance in postmenopausal women. STUDY DESIGN Twenty-six postmenopausal women were randomized to receive either conjugated estrogens 0.625 mg per day (group 1) or conjugated estrogens 0.625 mg per day and medroxyprogesterone 2.5 mg per day (group 2). Aortic cross-sectional area was measured by magnetic resonance imaging before and after 3 months of hormone therapy. RESULTS Estradiol levels increased in both group 1 and group 2 (p < 0.0001). Ascending aortic cross-sectional area increased from 439 +/- 7 mm2 to 466 +/- 7 mm2 in group 1 (p < 0.008) but was unchanged in group 2. Within the range of aortic pressures studied, no change in aortic compliance could be detected. CONCLUSION Estrogen therapy in postmenopausal women was associated with an increase in aortic size; but this effect was not detectable with the addition of progestin. The potential antagonistic effect of progestin on estrogen-induced aortic enlargement suggests that the favorable cardiovascular effects of postmenopausal estrogen therapy cannot be automatically extended to the combination estrogen-progestin.

Nafarelin therapy in endometriosis: Long-term effects on bone mineral density

OBJECTIVE The study intent was to examine long-term effects on bone mass of 3 or 6 months of nafarelin therapy for endometriosis. STUDY DESIGN Women with established endometriosis (N = 173) were randomized to receive nafarelin (200 micrograms intranasally twice a day) for either 3 or 6 months in a double-blind fashion. Bone mineral density was measured by dual energy x-ray absorptiometry at lumbar spine and proximal femoral sites for 18 months. RESULTS Bone mineral density declined at spinal and femoral sites similarly in both 3- and 6-month treatment groups. There was a partial, but incomplete, return to baseline levels after 12 to 15 months of follow-up. The recovery of bone mass was more complete in subjects with higher dietary calcium intakes. CONCLUSION Nafarelin therapy for endometriosis results in a sustained loss of spinal and femoral bone density, particularly in women with lower calcium intakes.

Metabolic changes during medical treatment of endometriosis: Nafarelin acetate versus danazol

In this double-blind study of changes in plasma lipid and lipoprotein concentrations during 6-month medical treatment of endometriosis, 53 patients were randomly assigned to one of four treatment schedules: danazol, 800 mg/day (n = 10); danazol, 600 mg/day (n = 8); intranasal nafarelin acetate, 800 micrograms/day (n = 10); or intranasal nafarelin acetate, 400 micrograms/day (n = 25). Plasma levels of triglycerides, cholesterol, and low-density lipoprotein, very low-density lipoprotein, and high-density lipoprotein cholesterol fractions were obtained before, during, and 1 month after treatment. High-density lipoprotein2 and high-density lipoprotein3 cholesterol concentrations were measured in selected patients. Body weight was also followed. The drugs were equally effective in achieving symptomatic relief and laparoscopically demonstrated resolution of endometriosis but differed significantly in their effects on lipid concentrations. Nafarelin acetate had no adverse effects on serum lipoprotein concentrations, whereas danazol significantly decreased high-density lipoprotein cholesterol (p less than 0.01), as well as the high-density lipoprotein2 subfraction (p less than 0.05), and increased low-density lipoprotein cholesterol (p less than 0.01). Danazol significantly increased body weight (p less than 0.01), whereas nafarelin did not.

An intrauterine insemination-ready cryopreservation method compared with sperm recovery after conventional freezing and post-thaw processing

OBJECTIVE To test a sucrose-glycerol cryoprotectant for IUI-ready sperm preparation. DESIGN Semen aliquots from normozoospermic donors either were subjected to conventional semen freezing (TES and Tris yolk buffer in 7.4% final glycerol) with post-thaw processing or were preprocessed and frozen in HEPES-buffered human tubal fluid with 1% human serum albumin, 4% sucrose, and 6% glycerol. All aliquots were cooled to 4 degrees C, exposed to liquid nitrogen vapors, and stored in liquid nitrogen. Aliquots from each were processed by centrifugation resuspension or by centrifugation in Percoll (Pharmacia, Alameda, CA) before sperm parameters were analyzed. SETTING University-based andrology laboratory. MAIN OUTCOME MEASURE(S) Recovery of motile sperm. RESULT(S) Percoll processing produced preparations with higher percentages of motile cells; however, cryopreserved sperm had a lower recovery of motile sperm compared with Percoll-processed fresh semen or centrifugation/resuspension-processed fresh or frozen samples. The percentages of sperm with normal morphologies were significantly increased in the IUI-ready samples compared with samples frozen conventionally. The IUI-ready Percoll-processed sample produced the best results, with a final mean motility of 36% and an overall yield of motile sperm of 17.4%. CONCLUSION(S) The sucrose-glycerol-based cryoprotectant produced an IUI-ready preparation with motile sperm recovery comparable to that of conventional semen cryopreservation but with improved percent morphology.