Luca Maria Schonauer

Direct transport of progesterone from vagina to uterus.

Objective To compare progesterone concentrations in serum and endometrial tissue from hysterectomy specimens after vaginal or intramuscular (IM) administration of progesterone gel. Methods This was a randomized open study of 14 post-menopausal women undergoing transabdominal hysterectomies. Participants received either vaginal progesterone gel, 90 mg, or IM progesterone, 50 mg, at 8:00 AM and 8:00 PM on the day before surgery and at 6:00 AM on the day of surgery. Venous blood samples for progesterone measurement were collected at 8:00 AM on the day before surgery (baseline) and during surgery. After removal of the uterus, the endometrium was sampled from the anterior and posterior walls. Results were expressed as ratios of endometrial to serum progesterone concentrations × 100. Results Ratios of endometrial to serum progesterone concentrations were markedly higher in women who received vaginal progesterone (14.1 median, 8.5–59.4 range; 95% confidence interval [CI] 9.89, 38.79) compared with IM injections (1.2 median, 0.5–13.1 range; 95% CI −0.48, 7.39) (P < .005). Conclusion Ratios of endometrial to serum progesterone concentrations were higher after vaginal administration of progesterone than after IM injections. Our findings in endometrial tissue specimens from hysterectomies excluded the possibility of contamination by progesterone that remained in the vagina.

Topical anaesthesia for diagnostic hysteroscopy and endometrial biopsy in postmenopausal women: a randomised placebo‐controlled double‐blind study

OBJECTIVE To evaluate the efficacy and safety of topical anaesthesia in reducing pain and incidence of vasovagal reactions during diagnostic hysteroscopy with endometrial biopsy in postmenopausal women. DESIGN Randomised placebo-controlled double-blind study. SETTING University hospital. PARTICIPANTS Eighty postmenopausal women undergoing diagnostic hysteroscopy and endometrial biopsy. INTERVENTIONS Two millilitres of 2% mepivacaine or saline solution were injected transcervically into the uterine cavity before performing the procedures. MAIN OUTCOME MEASURES Evaluation of pain reduction on a visual analogue scale and continuous monitoring of heart rate and blood pressure. RESULTS The use of the anaesthetic significantly reduced the pain experienced at hysteroscopy and endometrial biopsy. The occurrence of vasovagal reactions was significantly lower in the anaesthetised group. CONCLUSIONS Topical anaesthesia attenuated pain and effectively prevented the occurrence of vasovagal reactions during hysteroscopy and endometrial biopsy in postmenopausal women.1 Flannelly G, Langhan H, Jandial L, Mann E, Campbell M, Kitchcner H. A study of treatment failures following large loop excision of the transformation zone for thc treatment of cervical intraepithelial neoplasia. Br JObstet GynaecolI997; 104: 71 8722. Prendiville W, Cullimore J, Nonnan S. Large Loop excision of the transformation zone (LLETZ): a new method of management for women with cervical intraepithelial neoplasia. Br J Ohstet Gynaecol 2

Acute effects of transdermal estradiol administration on plasma levels of nitric oxide in postmenopausal women

OBJECTIVE To investigate the acute effects of transdermal E2 administration on nitric oxide (NO) plasma levels in postmenopausal women. DESIGN Randomized, placebo-controlled trial. SETTING Normal human volunteers in an academic research environment. PATIENT(S) Twenty healthy postmenopausal women. INTERVENTION(S) Transdermal administration of 100 micrograms/d E2 or placebo. MAIN OUTCOME MEASURE(S) Plasma concentrations of NO stable oxidation products and serum concentrations of E2 were assessed before and 24 hours after the administration. RESULT(S) In the group treated with E2 mean concentration of NO metabolites 24 hours after patch application (37.31 +/- 7.62 mumol/L) resulted significantly higher than baseline (21.04 +/- 5.71 mumol/L) and the control group (23.50 +/- 4.03 mumol/L). The correlation between the mean percent increase in NO metabolites and absolute E2 concentrations 24 hours after the E2 administration was statistically significant. CONCLUSION(S) Transdermal administration of E2 to healthy postmenopausal women increases the plasma levels of NO and this supports the hypothesis that a NO-related mechanisms may contribute to the cardiovascular protective effect of estrogens in postmenopause.

Tolerability of the mini-pan-endoscopic approach (transvaginal hydrolaparoscopy and minihysteroscopy) versus hysterosalpingography in an outpatient infertility investigation

OBJECTIVE To compare the acceptance and tolerability of the mini-pan-endoscopic approach (transvaginal hydrolaparoscopy [THL] combined with minihysteroscopy) versus hysterosalpingography (HSG) for evaluating tubal patency and the uterine cavity in an outpatient infertility investigation. DESIGN Randomized controlled study. SETTING University hospital. PATIENT(S) Twenty-three infertile patients without obvious pelvic pathology. INTERVENTION(S) Women were randomly divided into two groups. One group underwent minihysteroscopy and THL with tube chromoperturbation as first investigation and HSG within the following 7 days, while in the other group the investigation sequence was inverted. Women reported pain experienced before and at the end of procedures. MAIN OUTCOME MEASURE(S) Mean duration of procedures, level of pain experienced, diagnostic agreement about tubal patency and uterine cavity normality. RESULT(S) THL and minihysteroscopy took significantly more time but was significantly less painful than HSG. Regarding tubal patency, in 95.5% of cases THL agreed with HSG. In one case, HSG diagnosed a bilateral obstruction of tubes, whereas at THL a bilateral spreading of methylene blue was seen. Agreement on intrauterine pathologies between minihysteroscopy and HSG was poor (43%); the number of intrauterine abnormalities found at hysteroscopy was significantly greater than at HSG. CONCLUSION(S) THL in association with minihysteroscopy provided more information and was better tolerated than HSG in an outpatient infertility investigation.

Coordination of early antral follicles by luteal estradiol administration provides a basis for alternative controlled ovarian hyperstimulation regimens.

OBJECTIVE To investigate whether luteal E(2) administration reduces size discrepancies of early antral follicles. DESIGN Prospective, crossover study. SETTING ART unit, Clamart, France. PATIENT(S) Sixty women and 120 cycles. INTERVENTION(S) On cycle day 3 (baseline day 3), all women underwent measurements of early antral follicles by ultrasound and serum FSH and ovarian hormones. From day 20 until the next cycle day 2, 30 of them received oral 17beta-E(2), whereas the remaining women served as controls. The day after E(2) discontinuation (E(2) day 3) or on subsequent cycle day 3 (control day 3), participants were reevaluated as on baseline day 3. MAIN OUTCOME MEASURE(S) Magnitude of follicular size discrepancies. RESULT(S) Follicular size discrepancies and follicular diameters were significantly attenuated on E(2) day 3 (3.7 +/- 0.5 mm) as compared with baseline day 3 (4.9 +/- 1.0 mm), but not in controls (5.0 +/- 0.8 vs. 4.9 +/- 0.8 mm). FSH (4.3 +/- 1.9 vs. 7.3 +/- 3.3 mIU/mL) and inhibin B (34 +/- 28 vs. 71 +/- 32 pg/mL) levels were consistently lower on E(2) day 3 than on baseline day 3 but remained unchanged in controls. CONCLUSION(S) Luteal E(2) administration reduces the size and improves the homogeneity of early antral follicles on day 3. This approach may be instrumental in synchronizing follicular development during controlled ovarian hyperstimulation.

Vaginal Versus Oral E2 Administration: Effects on Endometrial Thickness, Uterine Perfusion, and Contractility

OBJECTIVE To compare the effects of vaginal or oral E(2) administration on endometrial thickness, uterine perfusion, and contractility. DESIGN Prospective, randomized, crossover study. SETTING Assisted Reproduction Unit, Clamart, France. PATIENT(S) Thirty-nine infertile women undergoing 78 E(2)/P cycles. INTERVENTION(S) Women received micronized 17beta-E(2), 2 mg/day orally (cycle days 1 to 28) and P, 300 mg/day vaginally (cycle days 15 to 28). After a menstrual cycle washout interval, women received a similar treatment except that 17beta-E(2) was administered vaginally. MAIN OUTCOME MEASURE(S) Endometrial thickness, mean uterine artery pulsatility index, endometrial blood flow, and uterine contraction frequency assessed in ultrasound scans on cycle days 14 and 18. RESULT(S) On day 14, the endometrium was thicker (8.7 +/- 0.6 vs. 7.1 +/- 0.3 mm, P< .0001), pulsatility index values were lower (2.4 +/- 0.1 vs. 3.0 +/- 0.2, P< .0002), and endometrial blood flow tended to be increased in the vaginal E(2) cycles as compared to the oral E(2) cycles. On day 18, similar differences remained. However, P-induced decrease in contraction frequency was slighter in vaginal E(2) cycles (33% vs. 18%, P< .0003). CONCLUSION(S) Vaginal E(2) administration improves endometrial proliferation and uterine perfusion, presumably because of combined local and systemic effects, but may interfere with P-induced uterine relaxation.

Resectoscopic treatment of uterus didelphys with unilateral imperforate vagina complicated by hematocolpos and hematometra: case report

OBJECTIVE To describe a technique for treating hematocolpos and hematometra in patients with uterus didelphys and unilateral imperforate vagina involving the use of resectoscopy under ultrasonographic control. DESIGN Case report. SETTING University hospital. PATIENT(S) A 13-year-old girl with uterus didelphys with unilateral hematometra, hematocolpos, and ipsilateral renal agenesis. The girl complained of severe abdominal pain, which appeared with each of her menses. INTERVENTION(S) The intervention was performed by a vaginoscopic approach to preserve the integrity of the hymen. The first incision on the vaginal wall was performed in correspondence with the hematocolpos under continuous ultrasonographic guidance with the use of a straight resectoscopic loop. Resection of the vaginal septum was continued with the use of an angled resectoscopic loop until almost complete excision of the septum was achieved. MAIN OUTCOME MEASURE(S) Clinical, echographic, and vaginoscopic findings before the operation and 2 and 6 months after the operation. RESULT(S) The surgical procedure was easy to perform. Almost complete excision of the septum was achieved with just a few passages of the resectoscope. Complete drainage of both the hematocolpos and the hematometra was confirmed by ultrasonography. The postoperative period was completely uneventful. Clinical and vaginoscopic evaluations 6 months after the operation confirmed the integrity of the hymen, the complete resolution of clinical symptoms, and the persistence of a large communication between the two vaginas. CONCLUSION(S) Resectoscopic excision under ultrasonographic guidance of the vaginal septum in a girl with uterus didelphys with unilateral hematometra and hematocolpos was effective and easy to perform, and it fully respected the integrity of the reproductive system.

Tolerability and Cardiovascular Complications of Outpatient Diagnostic Minihysteroscopy Compared with Conventional Hysteroscopy

STUDY OBJECTIVE To assess acceptability and cardiovascular complications of hysteroscopy performed with minihysteroscopes compared with those performed with conventional hysteroscopes. DESIGN Prospective, randomized clinical trial (Canadian Task Force classification I). SETTING Academic research center. PATIENTS One hundred women with abnormal uterine bleeding. INTERVENTIONS Hysteroscopy with a 3.5-mm minihysteroscope or conventional 5-mm endoscope with no anesthesia. MEASUREMENTS AND MAIN RESULTS Duration of examinations, pain, and occurrence of vasovagal reactions were recorded. Pain was assessed by visual analog scale ranging from zero to 20 before (pain expectancy) and at the end of the procedure. Occurrence of vasovagal reactions was assessed by monitoring blood pressure and pulse rate at 1-minute intervals during the procedure. A heart rate of less than 60/minute or a reduction greater than 20% compared with baseline was considered a vasovagal reaction; similarly, a reduction in blood pressure exceeding baseline value by 20% was considered a result of vagal stimulation. Mean duration was shorter for minihysteroscopy than for conventional hysteroscopy. The mean (SD) level of pain experienced during minihysteroscopy also was significantly lower (0.76 +/- 0.65 vs 1.46 +/- 0.86, 95% CI-1.0-0.4, p <0.0001). The number of instrumentally recorded (1 vs 11 cases) and clinical vasovagal reactions (0 vs 6 cases) was also significantly lower in the minihysteroscopy group than in the conventional hysteroscopy group (p <0.002 and <0.02, respectively). CONCLUSION New-generation minihysteroscopes make hysteroscopy easier and less painful, and carry a lower risk of vasovagal reactions than hysteroscopy performed with conventional instruments. In our experience, minihysteroscopy with vaginoscopic approach and saline distention is well tolerated, effective, and a true outpatient procedure.

Effects of short-term transdermal estradiol administration on plasma levels of nitric oxide in postmenopausal women

OBJECTIVE To assess the effects of short-term transdermal E2 administration on nitric oxide (NO) plasma levels in postmenopausal women. DESIGN Randomized, placebo-controlled trial. SETTING Healthy volunteers in an academic research environment. PATIENT(S) Twenty-eight healthy postmenopausal women. INTERVENTION(S) Transdermal administration of E2 (100 microg/d) or placebo on days 1 and 4 of a 1-week treatment regimen. MAIN OUTCOME MEASURE(S) Serum concentrations of E2 and plasma concentrations of NO stable oxidation products were assessed on day 1, before placement of the patch, and subsequently on days 2, 3, and 6. RESULT(S) The mean concentration of NO metabolites on days 2, 3, and 6 was significantly greater in the E2 group (40.08+/-15.42 micromol/L, 38.05+/-18.82 micromol/L, and 42.03+/-16.81 micromol/L on days 2, 3, and 6, respectively) compared with both baseline levels (23.07+/-5.79 micromol/L) and the placebo group (23.51+/-4.06 micromol/L, 21.64+/-4.72 micromol/L, and 21.81+/-4.46 micromol/L on days 2, 3, and 6, respectively). CONCLUSION(S) During a 1-week treatment regimen with transdermal E2, plasma levels of NO in postmenopausal women were significantly higher than baseline levels on days 2, 3, and 6. This suggests that the effect of estrogens on NO synthesis is rapid and that it is maintained with repeated administration.

Luteal estradiol administration strengthens the relationship between day 3 follicle-stimulating hormone and inhibin B levels and ovarian follicular status.

OBJECTIVE To investigate whether the prevention of early follicular growth by luteal E(2) administration improves the relationship between day 3 hormone measurements and the ovarian follicular status. DESIGN Prospective, cohort study. SETTING Assisted reproductive technology unit in Clamart, France. PATIENT(S) One hundred sixty-two infertile women. INTERVENTION(S) Participants received oral 17beta-E(2), 4 mg/day, from day 20 to the next cycle day 1 (n = 81) or served as controls (n = 81). Serum E(2), inhibin B, and FSH were measured during the 3 days after E(2) discontinuation (FD1, FD2, and FD3) in E(2)-treated women and on cycle day 3 (CD3) in controls. Early antral follicles were counted at ultrasound scans on FD3 and CD3. MAIN OUTCOME MEASURE(S) Hormonal-follicular correlations on FD3 and CD3. RESULT(S) As expected, after E(2) withdrawal, inhibin B and FSH increased from FD1 to FD3 whereas E(2) decreased. Correlations between FSH and inhibin B and follicular counts were stronger on FD3 than on CD3. CONCLUSION(S) Luteal E(2) administration notably strengthens the relationship between serum FSH and inhibin B levels and the number of antral follicles on day 3. This approach may represent an alternative test of ovarian follicular status.