Drorit Hochner-Celnikier

The effect of ethinyl estradiol on endometrial thickness and uterine volume during ovulation induction by clomiphene citrate

OBJECTIVE To assess the deleterious effect of clomiphene citrate (CC) on the development of the endometrium and its improvement by the addition of ethinyl estradiol (E2). PARTICIPATING PATIENTS: Infertility-treated patients, monitored for induction of ovulation or timing of insemination (control group). DESIGN We studied four groups of women during an ovulatory cycle with various treatment schedules. Group 1: untreated patients; group 2: patients treated by CC; group 3: patients treated by CC + ethinyl E2; group 4: patients treated by human menopausal gonadotropin. Follow-up of the patients was done by vaginal ultrasonography and measurements of blood E2. RESULTS In the group treated by CC, both endometrial thickness and uterine volume growth during the follicular phase were lower as compared with untreated controls and menotropin-treated patients. The addition of ethinyl E2 to these patients reversed this deleterious effect of CC without interfering with ovulation. CONCLUSION Ethinyl E2 may reverse the deleterious effect of CC on endometrial development during the follicular phase.

Expression of gelatinase B by trophoblast cells: down-regulation by progesterone.

OBJECTIVE It is now accepted that gelatinase B (92 kd type IV collagenase) is involved in blastocyst implantation and trophoblast invasion. However, little is known about the regulation of this enzyme at the fetomaternal interface. Progesterone has been demonstrated to inhibit gelatinase B secretion from endometrial cells, myometrium, and cervical fibroblasts. Interestingly, the promotor of gelatinase B contains a progesterone-responsive element that may explain transcriptional activation of this metalloproteinase by progesterone. It may be hypothesized that progesterone secreted from trophoblast cells, representing the fetal part of the fetomaternal interface, may have a role in the regulation of gelatinase secretion and blastocyst implantation. STUDY DESIGN To this end, use was made of first-trimester trophoblast cells obtained from first-trimester pregnancy terminations. The trophoblast cells were separated by trypsin degradation and fractionation on Percoll gradients. Metalloproteinase activity was measured by zymography, and the expression of the gelatinase B messenger ribonucleic acid was determined by the solution hybridization/ribonuclease protection assay. RESULTS Primary cell cultures of trophoblasts from first trimesters of pregnancy constitutively elaborated two species of type IV collagenases (gelatinase A and B) as assessed on a gelatin matrix. Treatment with progesterone decreased the accumulation of a gelatinase B species in a dose-dependent fashion. Administration of a progesterone receptor antagonist onapristone (ZK-98.299) neutralized the progesterone inhibitory effect on the gelatinase B in a dose-dependent fashion, thus supporting the presumption that the progesterone effect is receptor mediated. Progesterone significantly attenuated the expression of gelatinase B by trophoblast cells, an effect that was neutralized by ZK-98.299. CONCLUSION These observations provide strong indirect support for the participation of progesterone in the regulation of gelatinase B in trophoblast cells. It may be an important regulator of gelatinase production at the fetomaternal interface.

The role of midtrimester targeted fetal organ screening combined with the “triple test” and maternal age in the diagnosis of trisomy 21: A retrospective study☆☆☆★

OBJECTIVE Our purpose was to evaluate the role of fetal ultrasonography in prenatal detection of trisomy 21. STUDY DESIGN A retrospective study was performed on all cases of trisomy 21 diagnosed prenatally or postnatally between January 1990 and December 1993 in the Jerusalem metropolitan area. Our program of prenatal detection of trisomy 21 is a three-tiered, chronologically progressive screening that includes maternal age, biochemical serum markers, and targeted fetal organ survey. Sixty-seven thousand ninety-two babies were born during the study period; 17,084 maternal biochemistry analyses (triple test) were performed; and 6315 fetuses were karyotyped. RESULTS One hundred eight cases of trisomy 21 were diagnosed prenatally and postnatally. The overall rate of detection of trisomy 21 was 92.2% when our recommendations were followed. Among those cases diagnosed prenatally, 66.6% of trisomy 21 cases had been referred for fetal karyotyping because of maternal age > or = 35 years, 18.5% because of abnormal triple test results, and 11.1% because of fetal ultrasonographic findings associated with trisomy 21. Among women < 35 years old, 80% of trisomy 21 cases were detected prenatally. Of these, 50% had been referred for karyotyping because of triple test results and 30% because of abnormal ultrasonographic findings. CONCLUSION Midtrimester ultrasonographic targeted fetal organ screening plays a critical role in prenatal diagnosis of trisomy 21 among women under the age of 35 years.

Sexual function and quality of life for women with mild-to-moderate stress urinary incontinence.

INTRODUCTION Sexual function is affected by stress urinary incontinence with or without pelvic organ prolapse. The aim of the study was to describe the sexual function of women with mild-to-moderate stress urinary incontinence, with or without pelvic organ prolapse (up to stage 2) and examine correlations with symptoms and quality of life. This investigation was part of a large, randomized, clinical trial of women with stress urinary incontinence who participated in an exercise intervention. METHODS Women included in the study suffered from stress urinary incontinence as measured by a pad test and were interested in an exercise intervention. All participants underwent assessment for prolapse staging. Instruments included: the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), Incontinence Quality of Life Questionnaire (I-QOL), and a health and urinary leakage questionnaire. RESULTS One hundred and eighty-seven ambulatory women, aged 20 to 65 years, had a mean sexual function score of 36.9 (standard deviation [SD] 5.9). No significant correlation was found between the sexual function scores and quantity of urinary leakage. A significant correlation existed between the sexual function and I-QOL scores (P < .001). An additional finding was that women with urgency symptoms were older (P= .04) and had significantly lower sexual function scores (mean 35.7; SD 6.4) than those who did not report urgency (mean 38.7; SD 4.6; P < .001). DISCUSSION Women with mild-to-moderate stress urinary incontinence, without or with lower stages of pelvic organ prolapse, demonstrated good sexual function, which correlated with physical and psychosocial factors. Health professionals need to perform multifaceted intake assessments on women with urinary leakage to customize their health promotion regimen.

Sonographic evaluation of the uterus in postmenopausal women receiving tamoxifen: characterization of mid-uterine abnormalities

BACKGROUND Tamoxifen is known to exert agonist estrogenic effects on the uterus. Its use in postmenopausal women has also been associated with various endometrial and uterine abnormalities that can be detected by endovaginal sonography. OBJECTIVE To study postmenopausal patients receiving tamoxifen who were referred for evaluation following the detection of abnormal uterine findings by endovaginal sonography. METHODS Fifty-two women treated with tamoxifen for breast cancer who were found to have an abnormal uterine sonogram constituted the study population. Uterine sonograms were reviewed and clinical and sonographic data were correlated with the results of the histologic examinations. RESULTS Forty-five women demonstrated a thickened mid-uterine structure. Of these, in thirty-nine patients (87%) either no tissue of scant fragments of normal endometrium were obtained on curettage, and six women (13%) had endometrial hyperplasia. Seven women had fluid loculation lined by thin endometrium. Their subsequent histologic examination was normal. The sonograms of the women who demonstrated an appearance of a thickened endometrium but no neoplasia, characteristically demonstrated hyperechogenic cystic area with no midline echo. CONCLUSIONS Among 52 postmenopausal patients receiving tamoxifen presented with an abnormal uterine sonogram, 39 (75%) women were found to have a thick mid-uterine structure resembling a thickened endometrium without histologic evidence of neoplasia. This phenomenon can be characterized by typical sonographic features, and may be differentiated from other uterine abnormalities.