Joel S. Krasnow

Elevated serum levels of vascular endothelial growth factor in patients with preeclampsia

Objective To determine whether altered levels of vascular endothelial growth factor (VEGF) may be implicated in the pathogenesis of preeclampsia, and whether VEGF mediates the endothelial cell activation that is involved in the pathogenesis of the clinical syndrome. Methods In a cross-sectional study, maternal serum samples in late pregnancy (at the time of clinical disease) were collected from 78 nulliparous women. These subjects were subdivided into those with preeclampsia (n = 27), nonproteinuric pregnancy-induced hypertension (n = 15), and normal pregnant women (n = 36). In a nested case-control study, in addition to samples taken before delivery, samples were obtained in early pregnancy (before clinical disease) and 24–48 hours postpartum from 12 of the patients with preeclampsia, 12 of those with nonproteinuric pregnancyinduced hypertension, and 12 of the normal pregnant subjects. Umbilical cord blood was sampled from 14 of the preeclamptic and 16 of the normal pregnant subjects. We measured VEGF levels in all samples using an immunofluorometric assay. Results In most samples collected before delivery, VEGF levels were below the lower limit of detection. However, the proportion of detectable levels was higher in the preeclampsia group (seven of 27) than in the normotensive group (one of 36, P < .05). The proportion in the nonproteinuric pregnancy-induced hypertension group (two of 15) did not differ significantly from the other groups. Levels in the patients with preeclampsia were not elevated before clinical disease. Levels of VEGF in umbilical blood samples were higher than in maternal venous blood, although there were no significant differences between groups. Conclusion Serum VEGF levels were elevated in patients with preeclampsia, which suggests that the growth factor has a role in the endothelial cell activation that occurs in the disease.

Vascular permeability factor and vascular endothelial growth factor in ovarian hyperstimulation syndrome: a preliminary report *

Objective To determine whether serum levels of vascular permeability factor (VPF) are elevated in patients with ovarian hyperstimulation syndrome (OHSS) and to determine if luteinizing granulosa cells may be a source of VPF. Design Prospective observational study. Setting University IVF and GIFT program. Patients Eight consecutive IVF and GIFT patients at high risk for OHSS. Main Outcome Measures Vascular permeability factor concentration in serum and follicular fluid. Results Serum VPF was significantly higher (15.2 ± 4.0 pM; mean ± SEM) on day +14 in the group who developed severe OHSS compared with those who did not. Follicular fluid VPF (171.5 ± 18.5 pM) was approximately 100-fold greater than serum (1.7 ± 1.3 pM) or peritoneal fluid (2.5 ± 1.3 pM) 36 hours after hCG administration. Conclusion Vascular permeability factor is elevated in patients with severe OHSS and the ovary may be a source of VPF secretion.

Adhesion formation from release of dermoid contents in the peritoneal cavity and effect of copious lavage: a prospective, randomized, blinded, controlled study in a rabbit model*†

OBJECTIVES To determine, in a rabbit model, whether peritoneal exposure to dermoid cyst material produces inflammation and adhesions above control levels and whether saline lavage reduces the degree of peritoneal reaction. DESIGN A prospective, randomized, blinded, controlled study of adhesion formation. Thirty New Zealand white female rabbits were assigned randomly to five experimental groups: [1] laparoscopy with intraperitoneal injection of human dermoid material, [2] laparoscopy with intraperitoneal injection of human dermoid material and subsequent lavage to clear all visible dermoid material, [3] laparoscopy with saline lavage, [4] laparoscopy with intraperitoneal injection of human follicular fluid (antigenic control), and [5] laparoscopy alone. MAIN OUTCOME MEASURES Six weeks after initial laparoscopy, inflammation and adhesions were scored in several categories via visual assessment (range 0 to 15) and histologic microscopic evaluation (range 0 to 24). Data were evaluated using Kruskal-Wallis and Mann-Whitney U nonparametric tests. RESULTS For groups 1, 2, 3, 4, and 5, respectively, mean +/- SEM total inflammation-adhesion scores were 13.85 +/- 0.55, 2.90 +/- 1.15, 0 +/- 0, 1.50 +/- 1.00, and 0 +/- 0 for clinical evaluation and 16.83 +/- 1.22, 7.33 +/- 1.76, 0 +/- 0,0 +/- 0, and 0 +/- 0 for histologic evaluation. Using nonparametric tests, significant differences were found between groups in clinical and histologic scores. CONCLUSIONS Dermoid material produces a significant peritonitis. Results of the clinical evaluation demonstrate that saline lavage brings inflammation and adhesion formation close to control levels. However, results of the histologic evaluation suggest that the decrement in inflammation as a result of lavage may be less dramatic than that found by clinical evaluation.

Endometrial Leukocytes Are Altered Numerically and Functionally in Women with Implantation Defects

PROBLEM: A significant cohort of women with autoimmune thyroid disease (ATD) also suffer from reduced fertility. The finding that neither exogenous hormones nor donor eggs correct the infertility suggests that the problem involves an inherent endometrial defect.

Sperm recovery and survival: two tests that predict in vitro fertilization outcome

OBJECTIVES To determine if human sperm recovery during swim-up and sperm survival after 24 hours, as obtained from a screening semen specimen, are predictive of subsequent IVF and clinical pregnancy rates (PRs) and to determine if these techniques can identify men with normal semen analysis parameters and poor IVF success. DESIGN Historical prospective study. SETTING All semen evaluations and IVF cycles were performed at the University of Pittsburgh, Magee-Womens Hospital, Pittsburgh, Pennsylvania. PATIENTS, PARTICIPANTS Couples undergoing IVF at Magee-Womens Hospital from August 1988 through June 1993. INTERVENTIONS A screening semen analysis and swim-up procedure were performed on all couples undergoing IVF. The number of spermatozoa recovered after swim-up and the percentage of motile spermatozoa present after a 24-hour incubation were recorded. MAIN OUTCOME MEASURES Fertilization and PRs were compared according to the parameters obtained from routine semen analysis, the number of spermatozoa obtained with swim-up, and the percentage of motile spermatozoa at 24 hours. RESULTS Using chi2 or Fishers exact test, fertilization rates were significantly different according to the number of spermatozoa recovered after swim-up (< or = 2.0 and > 2.0 x 10(6) spermatozoa recovered, 48.3% versus 71.4%) as were PRs (16.9% versus 29.8%). Similarly, the percentage of motile spermatozoa present at 24 hours (< or = 20% and > 20%) discriminated between fertilization rates (45.9% versus 65.8%) and PRs (16.4% versus 36.5%). Among a subset of men with normal semen analyses and total motile sperm counts > or = 40 x 10(6), the results from swim-up and survival discriminated between men with high and low fertilization and PRs. Receiver operating characteristic analysis revealed that swim-up results better discriminated between pregnant and nonpregnant IVF patients than sperm motility, but that the percentage of motile spermatozoa present at 24 hours was no better in this regard than sperm motility. CONCLUSIONS The number of spermatozoa recovered after swim-up and the percentage of spermatozoa that maintain their motility after 24 hours were both helpful in assessing IVF and PRs and may be helpful in altering physicians to a subset of men having normal semen analysis parameters yet poor IVF success.

Endometriosis impairs the efficacy of gamete intrafallopian transfer: results of a case-control study*

OBJECTIVE To determine whether pelvic endometriosis impairs the efficacy of GIFT. DESIGN Matched follow-up study. SETTING University-based assisted reproduction program. PARTICIPANTS Patients undergoing GIFT between 1987 and 1991. Cases had a primary diagnosis of endometriosis. Controls had no endometriosis and were matched with cases according to age, number of mature eggs transferred, and sperm grade. INTERVENTION Gamete intrafallopian transfer was performed in all patients in an identical manner independent of their underlying diagnosis. MAIN OUTCOME MEASURES Pregnancy and delivery rates. RESULTS Of 114 laparoscopic egg retrievals performed in the endometriosis group, there were 37 pregnancies (32.5%) and 27 deliveries (23.7%). Of the 214 retrievals in the control group, there were 101 pregnancies (47.2%) and 76 deliveries (35.5%). Mantel-Haenszel estimates of relative risk indicated that endometriosis significantly impaired pregnancy and delivery rates. There was no statistically significant difference in pregnancy rates according to severity of disease among endometriosis cases. There was no statistically significant difference in pregnancy rates according to severity of disease among endometriosis cases. CONCLUSIONS Our finding that GIFT pregnancy rates were lower in women with a primary diagnosis of endometriosis than in matched controls suggests that endometriosis is associated with reduced efficacy of GIFT.

Comparison of transdermal versus oral estradiol on endometrial receptivity

OBJECTIVE To compare the effects of oral micronized E2 with transdermal E2 on endometrial receptivity in women undergoing oocyte donation. DESIGN Prospective, randomized, crossover trial. Serum E2 and P concentrations were measured on cycle days 14 and 22 (luteal day +8). Endometrial biopsies were obtained on day 22 and read in a blinded fashion for histology and beta-3-integrin expression. SETTING University-based donor oocyte program. PATIENTS Twenty-seven patients presenting for donor oocytes. MAIN OUTCOME MEASURES Endometrial histology and beta-3-integrin expression. RESULTS The endometrial glandular histology in women given oral micronized E2 was delayed by a mean of 1.6 days in comparison to that of women given transdermal E2. Seventy percent of women given oral E2 displayed a lag > or = 4 days whereas 29.6% given transdermal E2 displayed a similar lag. Serum E2 levels were 1,194 +/- 108.8 pg/mL (mean +/- SEM; conversion factor to SI unit, 3.671) in women on oral micronized E2 and 117.4 +/- 14.0 pg/mL in those on transdermal E2. CONCLUSION The supraphysiologic serum E2 levels associated with oral micronized E2 may have a deleterious impact on endometrial receptivity. The development of more physiologic hormone replacement protocols may enhance endometrial receptivity and lead to improved clinical pregnancy rates.

Decidual leukocyte populations in ectopic pregnancies.

OBJECTIVE To determine whether the recruitment of decidual leukocytes during pregnancy is the same in intrauterine pregnancies (IUPs) versus ectopic pregnancies (EPs). DESIGN Intrauterine decidual samples from both EPs and IUPs were obtained for the evaluation of leukocyte populations. SETTING In vitro experiment. PATIENT(S) Women with EPs and women with IUPs. MAIN OUTCOME MEASURE(S) Immunohistochemical identification of decidual leukocyte populations. RESULT(S) We have analyzed the decidual leukocyte populations from three women with EPs by immunohistochemical analysis. The data demonstrate a leukocyte infiltration similar to that found in decidua from normal pregnancies. CONCLUSIONS(S) These data support the hypothesis that decidual leukocyte recruitment and/or increases during pregnancy is primarily hormonally regulated.

VASCULAR PERMEABILITY FACTOR AND VASCULAR ENDOTHELIAL GROWTH FACTOR IN OVARIAN HYPERSTIMULATION SYNDROME : A PRELIMINARY REPORT

OBJECTIVE To determine whether serum levels of vascular permeability factor (VPF) are elevated in patients with ovarian hyperstimulation syndrome (OHSS) and to determine if luteinizing granulosa cells may be a source of VPF. DESIGN Prospective observational study. SETTING University IVF and GIFT program. PATIENTS Eight consecutive IVF and GIFT patients at high risk for OHSS. MAIN OUTCOME MEASURES Vascular permeability factor concentration in serum and follicular fluid. RESULTS Serum VPF was significantly higher (15.2 +/- 4.0 pM; mean +/- SEM) on day +14 in the group who developed severe OHSS compared with those who did not. Follicular fluid VPF (171.5 +/- 18.5 pM) was approximately 100-fold greater than serum (1.7 +/- 1.3 pM) or peritoneal fluid (2.5 +/- 1.3 pM) 36 hours after hCG administration. CONCLUSION Vascular permeability factor is elevated in patients with severe OHSS and the ovary may be a source of VPF secretion.

Hypothalamic germinoma presenting as delayed pubertal development

Abstract A 16.5 year-old-female was referred for evaluation of primary amenorrhea. Evidence of both anterior and posterior pituitary dysfunction led to the radiologic detection of a tumor in the neurohypophyseal region. A germinoma, which was suspected due to small elevations in serum human chorionic gonadotropin, was confirmed by biopsy. Intracranial tumors are a rare cause of menstrual dysfunction. The endocrine and radiologic evaluation of this patient are discussed. In addition, the treatment and the prognosis for these tumors is presented.