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Transarterial embolization (TAE) of renal angiomyolipoma (AML) is effective in treating and preventing hemorrhage. We report our experience using EVOH with a single-center retrospective study of all AML embolized with EVOH between June 2013 and March 2022 at the Montpellier University Hospital. A total of 29 embolizations were carried out in 24 consecutive patients (mean age: 53.86 years; 21 women and 3 men) with 25 AMLs for severe bleeding, symptomatic AML, tumor size > 4 cm, or presence of aneurysm(s) > 5 mm. Data collected included imaging and clinical outcomes, tuberous sclerosis complex status, change in AML volume, rebleeding, renal function, volume and concentration of EVOH used, and complications. Out of 29 embolizations performed for 25 AMLs, four were performed in an emergency. Technical success was achieved for 24/25 AMLs. Mean AML volume reduction was 53.59% after a mean follow-up time of 446 days using MRI or CT scan. Aneurysms on angiogram and the symptomatological nature of AML, as well as secondary TAE and multiple arterial pedicles, were statistically associated ( p < 0.05). Two patients (8%) underwent nephrectomy after TAE. Four patients had a second embolization. Minor and major complication rates were 12% and 8%, respectively. Neither rebleeding nor renal function impairment was noticed. TAE of AML using EVOH is, thus, highly effective and safe.

According to the World Health Organization, half the adult population around the world suffers from headaches. Even though this condition remains in most cases innocuous, it can have a major impact on the patient's quality of life but also on public health expenditure. Moreover, most patients manage their headaches on their own, without consulting a doctor. Therefore, self-medication can eventually lead to drug overuse, and consequently the emergence of a secondary disease called medication-overuse headache (MOH). The detection and follow-up of these unconventional patients represent a major challenge. Some of the latest technology advancements seem to be tailored and fitting for this context. The goal of this study is to investigate medication overuse in French patients suffering from headaches using the chatbot Vik Migraine. Data collection and analysis were assembled from answers to a questionnaire of 28 questions divided into three parts: socio-demographic profile, drug consumption, and medical follow-up. The study showed that medication overuse was often linked to increased headache frequency. Prescription drugs like triptans and opioids, were the most overused drugs among the cohort. This suggests that healthcare professionals could play a critical role in targeting these drugs in prevention of overuse., Competing Interests: AB, VM, RR, AG, and BB are employees of Wefight. BC own shares of Wefight., (Copyright © 2022 Bézie, Morisseau, Rolland, Guillemassé, Brouard and Chaix.)

Aim: To explore nurses' experiences of horizontal violence (HV) in three diverse non-affiliated organisations within a single city in the USA., Background: Horizontal violence, also called workplace bullying or lateral violence, is a long-standing nursing issue., Method: Content analysis was used to analyse open-format textual responses from 126 registered nurses., Results: A powerful collective story emerged from nurses' shared experiences with HV, describing the characters and the setting in which HV and its consequences exist. Nurses' depictions of HV were consistent despite the different organisational structures of their workplaces suggesting that hospital type is not the explanation for HV, rather the culture of acute care nursing. Nurses want change and asked for tactics to resolve HV within their institutions; some provided specific solutions., Conclusion: Nurse managers must continue to address HV by using a variety of known tactics, as well as adopting new evidence-based interventions as they are identified. The anti-bullying message should be disseminated through professional nursing organisations as well as in local health-care establishments., Implications for Nursing Management: Nurse managers need to be the culture champions who hold individuals accountable for HV and foster professionalism through their leadership., (© 2016 John Wiley & Sons Ltd.)

Background Osteoid osteoma of the wrist is rare and treatment is still in debate. Case Description We report on a patient with osteoid osteoma of the head of the ulna, as an unusual cause of pain on the ulnar side of the wrist. The diagnostic delay was 4 years. A previous ulna shortening surgery was performed because of misdiagnosis. The diagnosis was made with bone scan and computed tomography (CT). A surgical resection was performed. The symptoms disappeared, and full range of motion was recovered. Literature Review Osteoid osteoma on the head of the ulna had never been described before. Clinical Relevance This case demonstrates that osteoid osteoma can mimic ulnocarpal impingement syndrome.

Objectives: augmented and not augmented women without dystocia were compared to investigate associations between oxytocin and adverse birth outcomes. Augmented women with and without dystocia were compared, to investigate associations between dystocia and adverse birth outcomes., Design: a cohort of low-risk nulliparous women originally included in a randomised controlled trial., Setting: the Department of Obstetrics and Gynaecology, Østfold Hospital Trust, Norway., Participants: the study population consists of 747 well defined low-risk women., Measurements: incidence of oxytocin augmentation, and associations between dystocia and augmentation, and mode of delivery, transfer of newborns to the intensive care unit, episiotomy and postpartum haemorrhage., Findings: of all participants 327 (43.8%) were augmented with oxytocin of which 139 (42.5%) did not fulfil the criteria for dystocia. Analyses adjusted for possible confounders found that women without dystocia had an increased risk of instrumental vaginal birth (OR 3.73, CI 1.93-7.21) and episiotomy (OR 2.47, CI 1.38-4.39) if augmented with oxytocin. Augmented women had longer active phase if vaginally delivered and longer labours if delivered by caesarean section if having dystocia. Among women without dystocia, those augmented had higher body mass index, gave birth to heavier babies, had longer labours if vaginally delivered and had epidural analgesia more often compared to women not augmented., Key Conclusion: in low-risk nulliparous without dystocia, we found an association between the use of oxytocin and an increased risk of instrumental vaginal birth and episiotomy., Implications for Practice: careful attention should be paid to criteria for labour progression and guidelines for oxytocin augmentation to avoid unnecessary use., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To test the use of acronyms to increase women's knowledge of female prodromal and myocardial infarction (MI) symptoms using acronyms, and the appropriate response to these symptoms., Design: A quasi-experimental design., Method: An educational program, emphasizing two acronyms, was presented and knowledge of female heart attack, prodromal symptoms, and appropriate response was tested before and after the presentation., Participants: The sample consisted of 51 women., Results: Knowledge scores increased from 81% pre-test to 91% post-test. This difference was statistically significant on a paired sample t-test, with each subject serving as her own control. Scores measuring knowledge of content specific to the acronyms also improved and were statistically significant., Conclusion: Lack of knowledge of female heart attack symptoms may contribute to the delay of women seeking care and appropriate treatment, thus increasing morbidity and mortality. The findings from this study demonstrated that an educational program that focused on the use of acronyms was effective in increasing women's knowledge of female prodromal and MI symptoms.

Objective: Left ventricular (LV) resynchronization with epicardial lead placement after failed coronary sinus cannulation can be achieved with minimally invasive robotic-assisted (RA) or minithoracotomy (MT) incisions. We evaluated early outcomes and costs after RA and MT epicardial LV lead implantation at our academic center., Methods: From 2005 to 2010, 24 patients underwent minimally invasive RA or MT epicardial LV lead placement for resynchronization. Patient characteristics, electrophysiologic features, outcomes, and costs were analyzed., Results: Ten patients underwent RA and 14 underwent MT minimally invasive LV lead placement, with no 30-day mortality in either group. Younger patients underwent RA epicardial lead placement (63.8 ± 15.4 vs 75.6 ± 10.0 years; P = 0.03). In addition, although both groups had comparable body surface areas, RA patients had significantly higher body mass index versus MT patients (44.4 ± 17.5 vs 26.9 ± 7.1 kg/m, respectively; P = 0.003). Premorbid risk and cardiovascular profiles were similar across groups. Importantly, pacing threshold, impedance, and postoperative QRS interval were equivalent between groups. Significantly, both operating room and mechanical ventilation durations were higher with RA epicardial placement (P < 0.001). Despite equivalent outcomes, incision-to-closure interval was 48 minutes shorter with MT (P = 0.002). Absolute differences in direct costs between groups were negligible. Despite these differences, resource utilization and lengths of stay were equivalent., Conclusions: Epicardial LV lead placement is efficacious with either approach. Early outcomes and mortality are equivalent. Greater tactile feedback during operation and equivalent short-term outcomes suggest that MT minimally invasive LV lead placement is the more favorable approach for epicardial resynchronization.

Objective: The influence of body mass index (BMI) as a risk factor for isolated off-pump coronary artery bypass (OPCAB) surgery is unknown. We postulated that BMI ≥ 30 kg/m(2) would adversely affect outcomes following OPCAB at our institution., Methods: From 2002 to 2009, we selected 742 patients (primary, N = 709 [95.6%], re-operative, N = 33 [4.45%]) who underwent isolated OPCAB for analysis. Patients were stratified into groups by BMI: non-obese (BMI < 30 kg/m(2) ) and obese (BMI ≥ 30 kg/m(2)). Preoperative risk, operative characteristics, and postoperative outcomes were analyzed. Risk-adjusted models evaluated the occurrence of any complication and mortality., Results: Overall crude mortality was 1.5% (11/742). When compared to non-obese (26.12 ± 2.72 kg/m(2)) recipients, the obese (35.81 ± 5.69 kg/m(2)) comprised younger patients (62.46 ± 9.96 years, p < 0.001). Number of diseased vessels, Left ventricular ejection fraction, and baseline renal function was equivalent across groups. Diabetes (53.24%) and hypertension (90.59%) were more prevalent among obese patients (p < 0.001, respectively). Internal mammary artery utilization (p = 0.47), endoscopic vein harvest (p = 0.74), and intra-aortic balloon pump use (p = 0.58) were similar between groups. Interestingly, postoperative blood product requirement was lower in obese versus non-obese recipients (47.35% vs. 56.72%, p < 0.01). Furthermore, intensive care unit stay (p = 0.93), mortality (p = 0.56), and discharge to home (p = 0.09) remained equivalent between groups. Importantly, multivariable logistic regression did not identify BMI ≥ 30 kg/m(2) as an independent predictor of any complication (p = 0.21) or mortality (p = 0.74)., Conclusions: Obesity does not influence operative characteristics or effect outcomes after OPCAB. BMI ≥ 30 kg/m(2) should not be considered a prohibitive risk factor in isolated off-pump coronary revascularization., (© 2011 Wiley Periodicals, Inc.)

Objective: To investigate possible differences in operative delivery rate among low-risk women, randomised to an alongside midwifery-led unit or to standard obstetric units within the same hospital., Design: Randomised controlled trial., Setting: Department of Obstetrics and Gynaecology, Østfold Hospital Trust, Tromsø, Norway., Population: A total of 1111 women assessed to be at low risk at onset of spontaneous labour., Methods: Randomisation into one of three birth units: the special unit; the normal unit; or the midwife-led unit., Main Outcome Measures: Total operative delivery rate, augmentation, pain relief, postpartum haemorrhage, sphincter injuries and intrapartum transfer, Apgar score <7 at 5 minutes, metabolic acidosis and transfer to neonatal intensive care unit., Results: There were no significant differences in total operative deliveries between the three units: 16.3% in the midwife-led unit; 18.0% in the normal unit; and 18.8% in the special unit. There were no significant differences in postpartum haemorrhage, sphincter injuries or in neonatal outcomes. There were statistically significant differences in augmentation (midwife-led unit versus normal unit RR 0.73, 95% CI 0.59-0.89; midwife-led unit versus special unit RR 0.69, 95% CI 0.56-0.86), in epidural analgesia (midwife-led unit versus normal unit RR 0.68, 95% CI 0.52-0.90; midwife-led unit versus special unit RR 0.64, 95% CI 0.47-0.86) and in acupuncture (midwife-led unit versus normal unit RR 1.45, 95% CI 1.25-1.69; midwife-led unit versus special unit RR 1.45, 95% CI 1.22-1.73)., Conclusions: The level of birth care does not significantly affect the rate of operative deliveries in low-risk women without any expressed preference for level of birth care., (© 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.)

Objective: To estimate if an interventional program causes a decrease in the frequency of anal sphincter ruptures., Methods: A total of 12,369 vaginal deliveries between 2002 and March 2007 were enrolled in the interventional cohort study. Slowing the delivery of the infant's head and instructing the mother not to push while the head is delivered was the intervention. Data were analyzed in relation to occurrence of anal sphincter tears., Results: The proportion of parturients with anal sphincter tears decreased significantly during the study period from 4.03% (285 of 7,069) to 1.17% (42 of 3,577) (P<.001). A similar decrease was observed for instrumental deliveries (from 16.26% to 4.90%; P<.001) and noninstrumental deliveries (from 2.70% to 0.72%; P<.001). Although the number of patients with fourth-degree anal sphincter ruptures from 2002 through 2004 was 10, 13, and 11 per year, respectively, there was just one fourth-degree anal sphincter rupture during the whole study period of 18 months (P<.001). The number of episiotomies increased from 13.9% (980 of 7,069) in the years 2002-2004, to 23.1% during the first 9 months of the intervention (416 of 1,776; P<.001), but decreased to 21.1% (381 of 1,801) during the last 9 months of the intervention., Conclusion: As a result of this intervention the number of anal sphincter ruptures was reduced from 4.03% to 1.17%., Level of Evidence: II.

Background: The aim of the study was to investigate the obstetric outcome for low-risk pregnant women delivering in a larger community hospital with 1800 deliveries annually. The investigation was carried out before the implementation of a differentiated plan for maternity care., Material and Methods: From January through June 2002, 920 women delivered. 520 were retrospectively considered low risk with spontaneous start of labour (56.5% of all labours). They were selected according to defined criteria. The results of this group with 197 nulliparous (37.7%) and 323 multiparous (62.1%) women are presented., Results: There were 520 live newborns. 466 infants (89.6%) had an Apgar score > or = 8 after 1 minute; 509 a score > or = 8 after 5 minutes. In this low-risk group, 10.4% instrumental deliveries were performed, 2.7% caesareans and 7.7% vacuum extractions. In nulliparous women, the instrumental delivery rate was 19.7%, among the multiparous 4.6%. A surprisingly high number of low-risk women (38.7 %) were stimulated during labour with oxytocin, 62% of the primiparous and 24% of the multiparous. The indications for this were often obscure. Among oxytocin-stimulated primiparous women, 31.2% had an instrumental delivery, against 1.3% in non-stimulated women. Epidural analgesia was given to 22.3% of all low-risk women; of these, 91.4% received oxytocin. 3.1% had a perineal tear grade > or = 3., Interpretation: The assistance given to women in a larger community hospital is more geared towards progress of labour than that given in smaller hospitals and midwife-controlled maternity homes. Frequent use of oxytocin to enhance contractions and epidural analgesia probably increases the rate of instrumental deliveries. This investigation points to the necessity of developing differentiated plans for maternity care given to low-risk women delivering in larger community hospitals, in line with a policy adopted by the Norwegian parliament.

In an effort to assess potential ecological hazards to amphibian species in selected regions within New Hampshire, the traditional Frog Embryo Teratogenesis Assay-Xenopus (FETAX), a 14-/21 day tail resorption thyroid disruption assay and >30 day limb development tests were conducted with representative surface water and sediment samples. Two separate sets of samples collected from five sites were evaluated. The primary objectives of the study were to determine if samples were capable of inducing early embryo-larval maldevelopment, to determine if maldevelopment included limb defects, to determine if thyroxine co-administration altered the rates of limb malformation and to evaluate the impact of the samples on growth rates, developmental progress and metamorphic climax. Results from these studies suggested that pond water and sediment extract samples, but not whole sediment samples, from B2, FW, LP and W ponds were capable of inducing abnormal early embryo-larval development. In addition, water samples from B2 and W ponds induced significant abnormal hindlimb development. Some abnormal forelimb development was noted in the tail resorption studies, but not to the same extent as the hindlimbs. Each of the water samples induced appreciable developmental delay, including the paired reference site B1, which could be reversed by the addition of exogenous thyroxine., (Copyright 2001 John Wiley & Sons, Ltd.)

Objective: Our purpose was to test the hypothesis that omitting the first three pills of the contraceptive cycle leads to ovulation., Study Design: Ninety-nine women, randomly assigned to 1 of 3 treatments of combined oral contraceptives, completed the study. Treatments contained ethinyl estradiol and either monophasic gestodene, triphasic gestodene, or monophasic desogestrel. Pituitary-ovarian activity was monitored by ultrasonography of the ovaries and assay of serum concentrations of estradiol, progesterone, and follicle-stimulating hormone over 1 normal cycle (study period 1) and 1 cycle after an extended pill-free interval of 10 days (study period 2)., Results: None of the women experienced normal ovulation as evaluated by ultrasonography and serum progesterone concentrations. However, follicle-stimulating hormone reached a maximal serum concentration in most women during the first 7 pill-free days, indicating complete pituitary recovery, and increases in serum estradiol concentrations were seen in each woman although with marked interindividual variation. During study period 2 we found follicles of >18 mm in 24%, 24%, and 40% of the monophasic gestodene, triphasic gestodene, and monophasic desogestrel groups, respectively., Conclusions: Follicular growth up to preovulatory size is common in women missing the first one to three pills of their contraceptive cycle. Although this creates the prerequisite for ovulation, normal ovulation did not occur when pill omissions were limited to only 3 days.

Large quantities of a number of man-made chemicals with the potential to disrupt the developing endocrine and nervous systems in wildlife and humans have been released into the environment. These chemicals are particularly damaging during the embryonic, fetal, and early postnatal periods because they resemble or interfere with the hormones, neurotransmitters, growth factors, and other signaling substances that normally control development. The effects are in many cases irreversible and often are expressed as changes in function rather than as obvious birth defects or clinical diseases. Functional changes pose challenges in documenting the extent of the lesion, especially in the case of neuroendocrinological damage. In the past decade, researchers have added new dimensions to their research strategies in order to compensate for these difficulties. The new approaches reveal more about the extent of the distribution of and exposure to chemicals that interfere with the endocrine and nervous systems and strengthen the links between exposure and damage in developing wildlife and humans. Based on this new knowledge, opportunities abound for extensive multi-disciplinary research involving developmental neurotoxicity.

The purpose of this study was to investigate the extent of the effects of hormonal replacement therapy (HRT) on the mammographic breast pattern in postmenopausal women. In a hospital-based study mammographic examinations of 81 postmenopausal women were evaluated retrospectively, before and after 1-2 years of treatment with oestrogens or a combination of oestrogens and progestagens. Each individual mammographic film was examined separately, and the glandular tissue was classified according to a modified Wolfe classification. In a screening-centre-based study two consecutive mammograms, with a 2-year interval, of 645 women, of whom 70 were using some kind of hormone therapy, were evaluated retrospectively. In the hospital-based study 31 % of patients treated with combination HRT showed an increase in fibroglandular tissue compared with only 8.7 % in the group treated with oestrogens alone. The difference was statistically significant (p = 0.046). In the screening-based study 14.3 % of the women using hormonal therapy showed an increase, whereas in the non-users no increase was found (p = 1.24 x 10(-10)). After beginning HRT many women (between 14 and 25 % in our experience) can be expected to undergo a mammographically detectable increase in fibroglandular tissue. Radiologists should be aware of the aetiology of such changes, and can obtain information on HRT most conveniently by having the technologist routinely question each patient.

This study was designed to compare the efficacy and safety of two sizes of Lyrelle, a new matrix design transdermal oestrogen patch, with Estraderm TTS 50, a reservoir system. Three hundred and ninety-four (394) hysterectomised postmenopausal women between 30 and 65 years of age participated in this open-label, randomised, multicentre clinical trial. The main efficacy criterion was the reduction in the mean number of hot flushes per day at six months. Secondary efficacy end points included other climacteric symptoms as well as various psychofunctional and genitourinary disorders. A significant decrease from baseline in the mean number of hot flushes/day was observed in all three groups from the end of cycle 1, reaching 90% at the end of cycle 7. there was no statistically significant difference between Lyrelle 50 and Estraderm at any time point for any parameter; however, between-group differences between Lyrelle 80 and Estraderm for various parameters were seen in the first three cycles in favour of Lyrelle 80. A similar impact on blood lipid levels was observed in all three groups, without significant between-group differences. We conclude that the new Lyrelle patch is a highly effective system for transdermal oestrogen replacement therapy that may enhance long-term patient compliance.

Objective: To investigate the changes in plasma lipids and lipoproteins, low-density lipoprotein (LDL) oxidizability, and plasma homocysteine during postmenopausal sequential 3-monthly hormone replacement therapy., Design: Open longitudinal prospective study., Setting: Gynecological outpatient department of a university hospital., Patient(s): Thirty-nine healthy nonhysterectomized postmenopausal women., Intervention(s): Oral conjugated estrogen, 0.625 mg/d, combined with oral medrogestone 10 mg/d during the last 14 days of each 84-day treatment cycle. The treatment was given for four treatment cycles of 84 days (1 year)., Main Outcome Measure(s): Plasma lipids and lipoproteins, LDL oxidizability, and plasma homocysteine., Result(s): After 1 year of treatment plasma concentrations of total cholesterol and LDL cholesterol were 3.5% and 8.7% lower, respectively. High density lipoprotein cholesterol, apolipoprotein A-I, and triglycerides were 6.5%, 9.0% and 16% higher, respectively. Apolipoprotein B concentration remained unchanged. The results on LDL oxidizability were inconsistent. Plasma homocysteine decreased with 12.3% during the first 6 months of treatment in women with higher homocysteine concentrations at baseline. These values returned to baseline levels during the second half year of treatment., Conclusion(s): This sequential hormone regimen induced beneficial changes in the conventional lipid and lipoprotein risk estimators, whereas the observed changes in the other markers remained inconclusive and/or of minor importance.

Objective: In women who use oral contraceptives with low estrogen doses, a quiescent endometrium is frequently produced. Further reduction of the estrogen dose would not be expected to alter this effect. In this open-label study, the effects on the endometrium of a monophasic oral contraceptive containing 75 micrograms gestodene and 20 micrograms ethinylestradiol were assessed., Method: Biopsies were performed on 25 women on therapy. The biopsies were performed during the late luteal phase (last 7 days) in the pretreatment cycle and during days 15-21 in cycle 6 for 13 subjects (Group A) and during days 15-21 in cycle 3 and during the late luteal phase (last 7 days) in the post-treatment cycle for 12 subjects (Group B)., Results: All subjects completed six cycles of treatment. Nine of 13 subjects pretreatment and nine of 12 subjects at cycle 3 were characterized by the pathologist as having a secretory endometrium. Four of 13 subjects at cycle 6 and ten of 11 subjects post-treatment also demonstrated a secretory endometrium. Pre-decidual changes were seen in one, two, two and zero subjects at pretreatment, after three cycles, six cycles, and post-treatment, respectively. Six subjects had an atrophic endometrium at cycle 6., Conclusions: With monophasic gestodene/ethinylestradiol 75 micrograms/20 micrograms, a secretory or inactive endometrium was present in most subjects. Thus, the effects on the endometrium of this oral contraceptive containing a reduced estrogen dose are consistent with those produced by other low-estrogen-dose combination oral contraceptives.

The hypothesis has been put forward that humans and wildlife species adverse suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity-as well as along the risk assessment paradigm-hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research.

The aim of the present study was to compare changes in the endogenous androgen environment in healthy women while on low-dose oral contraceptives (OCs). One-hundred healthy women were randomized to receive one of four OCs during six months: 21 tablets of Cilest, Femodeen, Marvelon, or Mercilon. During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded and the following parameters were measured: sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), testosterone (T), free testosterone (FT), 5 alpha-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone-sulphate (DHEA-S) and 17 alpha-hydroxyprogesterone (170HP) while also the free androgen index (FAI) was calculated. Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month. There were no differences on body mass and blood pressure with the use of the four OCs. The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon group when compared to Cilest and Marvelon (approximately 20% vs 45%). Mean serum SHBG and CBG increased significantly in all four groups approximately 250% and 100%, respectively. In each group CBG also increased significantly but less in women taking Mercilon (-75%) as compared to the others (-100%). Current low-dose OCs were found to have similar impact on the endogenous androgen metabolism with significant decreases of serum testosterone, DHT, A, and DHEA-S. They may be equally beneficial in women with androgen related syndromes such as acne and hirsutism.

The effects of gonadotropin stimulation on mouse embryo uptake and incorporation of 35S-methionine were studied. We found that the uptake of 35S-methionine was reduced in embryos of stimulated females in both the two-cell and the blastocyst developmental stage. The incorporation of 35S-methionine into protein was not statistically significantly different between the embryos of stimulated and those of unstimulated females. Qualitatively, protein synthesis was equal in both groups as determined with one-dimensional SDS-PAGE. The results are discussed and we conclude that mouse embryo viability in vivo is decreased by ovarian stimulation.

Objectives: The influence of occupational physical activity on pregnancy duration and birthweight was examined., Methods: In this prospective study information on levels of occupational physical activity was collected during a personal interview before pregnancy, and possible changes were registered during follow-up, which lasted until after birth. Data on pregnancy duration and birthweight were obtained from midwives, physicians, and obstetricians. The occupational energy expenditure was operationalized in intensity and fatigue scores, which were studied as such and in combination with workhours and work speed. The occupational biomechanical load was operationalized in a peak and a chronic pressure score., Results: The participants were part of a group of 260 cleaners, kitchen staff, and clerical workers enrolled from 39 Dutch hospitals between August 1987 and January 1989 before they became pregnant. One hundred and twenty-eight of these women were eligible for study because they became pregnant, they worked at least six weeks during pregnancy, and information on work aspects during pregnancy and pregnancy outcome was complete. Work with a high intensity score, and to a less extent work with a high fatigue score, had the most outstanding effect (up to 18 d shorter) on pregnancy duration when the work speed was high. None of the studied aspects of occupational physical activity showed a relevant influence on birthweight when adjusted for pregnancy duration., Conclusions: This study indicates that the levels of occupational physical load found in the work of nonmedical hospital staff, especially when combined with high work speed, can lead to a shorter pregnancy period.

Objective: To study the contribution of smoking and alcohol consumption to semen quality., Design: Retrospective analysis., Setting: University-based fertility clinic., Patients and Methods: Smoking and alcohol consumption were investigated in a control group (68) and in a group of 47 subjects with defined poor semen quality (PSQ). The control group was composed of subjects whose semen showed a greater than 60% morphological normality, a greater than 60% motility with a linear progression, and a density of greater than 20 million spermatozoa/mL. The group with PSQ was composed of subjects whose semen showed a less than 30% morphological normality, less than 60% motility, characterized by slow, weak motility, and a density of less than 20 million spermatozoa/mL. Medical dossiers were studied regarding the life style of the subjects., Results: The distribution of heavy smokers and light smokers did not differ statistically between the groups. There appeared to be a higher, but statistically insignificant, proportion of heavy smokers in the PSQ group (50%) compared to the control group (32.3%; P < .1); nor were significant differences found between cases and controls with respect to alcohol consumption pattern. In the PSQ group, a comparison of the semen characteristics of the daily drinkers with those of all the other subfertile patients showed no statistical difference concerning semen volume (4.1 +/- 1.9 vs. 3.3 +/- 1.3 mL; P > .1), sperm density (10.6 +/- 7.8 vs. 8.9 +/- 5.8 million spermatozoa/mL; P > or = .1), and percentage of motile spermatozoa (27.0 +/- 15.1 vs. 25.5 +/- 16.1%; P > .1). However, a lower percentage of normal sperm morphology was observed in the daily-drinker group (17.6 +/- 7.2% vs. 23.0 +/- 6.5% for the other subfertile patients; P < .05)., Conclusion: Factors such as smoking and alcohol consumption do not seem to play a pivotal role in the etiology of poor semen quality, but a pattern of excessive alcohol consumption may decrease further an already low percentage of sperm with normal morphology.

Changes in endogenous androgen metabolism were compared in healthy women taking one of four low-dose modern oral contraceptives (OCs). One hundred women were randomized to (1) 35 micrograms ethinyl estradiol (EE) + 250 micrograms norgestimate (Cilest); (2) 20 micrograms EE + 150 micrograms desogestrel (Mercilon); (3) 30 micrograms EE + 150 micrograms desogestrel (Marvelon); or (4) 30 micrograms EE + 75 micrograms gestodene (Femodene). During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded, and plasma levels of the following variables were recorded: sex-hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), testosterone, free testosterone, dihydrotestosterone, androstenedione, dihydroepiandrosterone sulfate (DHEAS), and hydroxyprogesterone. The free androgen index was also calculated. These variables were remeasured during the third week of OC intake and during the fourth and sixth cycles. There were no statistically significant differences in androgenic variables among the four OCs. The DHEAS concentration decreased less with the 20 micrograms EE + desogestrel formulation compared with either 30 micrograms EE + desogesterel or norgestimate-containing formulations (20% vs. 45%). Concentrations of SHBG and CBG increased significantly in all four groups (average 263 +/- 119% and 94 +/- 26%, respectively); CBG increased less in women taking 20 micrograms EE + desogestrel (about 75%) than in the other formulations (about 100%). The four modern, low-dose OCs tested had similar impacts on endogenous androgen metabolism, yielding significant decreases in testosterone, dihydrotestosterone, androstenedione, and DHEAS. All of these formulations may be beneficial in women with androgen-related syndromes such as acne and hirsutism. Large studies are under way to establish which of the third-generation OCs is the least androgenic. In vitro studies suggest that norgestimate has the least androgenic profile.

Objective: To investigate the role of inhibin in the human puerperium, by measuring serum levels of immunoreactive inhibin in both lactating and nonlactating women., Design: Prospective, comparative, open study., Setting: Department of obstetrics and gynecology of a university hospital., Patients: Fourteen healthy women who delivered at term: seven lactating women and seven nonlactating women treated with the dopamine-agonist CV 205-502., Main Outcome Measures: Serum immunoreactive inhibin, PRL, FSH, LH, E2, and P., Results: All women showed a rapid decline of immunoreactive inhibin levels during the first postpartum days. Thereafter the pattern depended on the way of feeding. Nonlactating women, with their rapid return of pituitary and ovarian function, showed increasing immunoreactive inhibin levels to a maximum on day 24 (950 +/- 180 U/L). Lactating women did not show ovarian activity despite high FSH levels, and immunoreactive inhibin stayed on a low level (230 +/- 40 U/L on day 24). There was a significant correlation between immunoreactive inhibin and E2., Conclusions: The rapid decline of immunoreactive inhibin (elimination of placental hormone) is followed by an increase in nonlactating women (production by the maturing follicle) and by persistently low levels in lactating women. The lack of adequate levels of immunoreactive inhibin in lactating women may be an explanation of the relatively high FSH levels during lactation.

Objective: To describe changes in the withdrawal bleeding pattern and endometrial histology during a sequential 17 beta-estradiol-dydrogesterone regimen in postmenopausal women., Design: Open-label, non-comparative, prospective study., Setting: Gynecological outpatient department of a university hospital., Patients: Twenty-seven healthy non-hysterectomized postmenopausal women., Interventions: Continuous micronized 17 beta-estradiol supplementation, 2 mg daily, and cyclic administration of dydrogesterone, 10 mg daily for the first half of each 28 day treatment cycle., Main Outcome Measures: Changes in the characteristics of the withdrawal bleeding pattern and the endometrial biopsy histology during 2 years of treatment., Results: The initial withdrawal bleeding was comparable to normal menstruation with respect to amount and duration. During the 2 years of treatment the bleeding showed a significant tendency to become shorter with less blood loss. This was mainly the result of the decrease (P < 0.001) in the number of days per cycle with bleeding grade II (normal menstruation). None of the women developed endometrial hyperplasia, and in almost all women the given hormone replacement therapy regimen induced secretory or atrophic changes of the endometrium., Conclusions: This sequential 17 beta-estradiol-dydrogesterone regimen can be regarded as safe with respect to the prevention of endometrial disease and appeared to foster patient compliance.

Osteoporosis is a common disorder in postmenopausal women, which is probably due to decreased ovarian function. Currently, hormone replacement therapy (HRT), involving administration of estrogen and progestogen, is successfully applied to reduce bone resorption. We studied the effect of HRT on 23 postmenopausal women. This consisted of a combination of 17 beta-estradiol and dydrogesterone, on the serum level of 1,25-dihydroxyvitamin D (1,25(OH)2D) after 0, 6, 12, and 24 months. We found mean serum concentrations (+/- SD) of 1,25(OH)2D of 130.5 pmol/liter (46.1), 152.7 pmol/liter (45.1), 170.8 pmol/liter (64.0), and 155.2 pmol/liter (59.7), respectively. The baseline values in these women were found to be significantly lower than those during therapy (P < or = 0.005). No statistically significant differences were observed when comparing the estrogen-only phase with the combined estrogen-progestogen phase. It is concluded that HRT results in an increase in the serum 1,25(OH)2D concentration which lasts for at least 2 years. This increase may partly explain the preventive effect of HRT on osteoporosis. Furthermore, these results suggest that dydrogesterone does not influence the estrogen-induced changes in serum 1,25(OH)2D concentration.

In a prospective study we investigated the possible changes in fasting serum total homocysteine concentrations during continuous micronized 17 beta-oestradiol, 2 mg daily, in combination with cyclic dydrogesterone, 10 mg daily during the first 14 days of each 28 day cycle, in 21 healthy non-hysterectomized postmenopausal women. During the first six cycles mean serum homocysteine decreased by 10.9% (P = 0.013), after which no further significant changes were found during the 2 years of treatment. A 16.9% decrease (P = 0.017; n = 8) was found in women with high homocysteine concentrations, while in women with low homocysteine concentrations (n = 13) no significant changes were observed. The observed decrease in high homocysteine concentrations in postmenopausal women may in part contribute to the decreased risk of developing cardiovascular disease during hormone replacement therapy.

A multidisciplinary study was conducted on a total of 100 women with congenital absence of vagina and uterus, the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. It was possible to analyse whether the MRKH syndrome can be considered as a single clinical entity or whether two or more syndromes lie behind the title 'the MRKH syndrome'. Complete gynaecological and laparoscopic data were available on all of the patients. The patients were divided into two groups on the basis of the laparoscopic data: a typical and an atypical form of the MRKH syndrome. We performed various diagnostic investigations to establish whether there were any associated congenital anomalies. These tests included general physical examination, radiographs of the vertebral column, the upper extremities and intravenous urography (IVU), and general otorhinolaryngological and ossicular chain examinations. Associated anomalies were most common in the group with the atypical form of the MRKH syndrome. These findings suggest that there might be two different syndromes in this patient group, namely an isolated form of congenital agenesis of the vagina and uterus and a more generalized condition, in which agenesis of the vagina and uterus is a major and perhaps even obligatory characteristic. The term MRKH syndrome should no longer be used for the atypical group. A suggestion has been made to call this type the GRES [genital (G), renal (R), ear (E), skeletal (S)] syndrome.

Changes in the low-density lipoprotein (LDL) subfractions, determined with gradient gel electrophoresis (GGE), were prospectively studied during hormone replacement therapy (HRT) in 23 healthy nonhysterectomized postmenopausal women. LDL subfractions were analyzed by densitometric scanning of the gels. We observed significant changes in the LDL subfraction profile toward a smaller particle size (P < .001). These changes could almost completely be attributed to the hormonal treatment regimen (P < .01), and may indicate an effect partially opposite to the other reported changes in the lipid profile.

Objective: To study the possible changes in serum lipids and lipoproteins during hormone replacement therapy with special emphasis on the possible effects brought about by the progestogen., Design: Open-label randomized prospective comparative study., Setting: Gynecological outpatient department of an university hospital., Patients: Thirty-three healthy hysterectomized postmenopausal women., Interventions: Continuous oral supplementation with conjugated estrogens, 0.625 mg daily, was administered either alone (group I; N = 18) or in combination with cyclic medrogestone, 5 mg daily during the last 12 days of each 28 days treatment cycle (group II; N = 15)., Main Outcome Measure: Changes in serum lipids, lipoproteins and apolipoproteins after three, six and 13 treatment cycles., Results: After 1 year of treatment significant increases were observed in mean high-density lipoprotein (HDL) cholesterol, its subfractions, and apolipoprotein A-I in group I and II: HDL cholesterol: +25.2% and +12.1%, respectively; HDL2 cholesterol: +47.4% and +23.5%, respectively; HDL3 cholesterol: +18.1% and +11.2%, respectively; apolipoprotein A-I: +23.0 and +14.8%, respectively. Comparing the two study groups no significant differences were found in lipid changes during the study period, except for HDL2 cholesterol., Conclusion: Supplementation with conjugated estrogens, with and without medrogestone, and given for a longer period, demonstrated a beneficial influence on serum lipoproteins with almost no differences between the two treatment regimens.

Background: In a prospective study the effect of the behavioral risk factors of both partners on fecundability was studied., Methods: Information was collected on smoking habits, alcohol consumption, and caffeine intake (e.g. coffee, tea, and cola consumption) by interviewing 259 female nonmedical hospital workers, i.e., clerical staff, cleaners, kitchen and restaurant workers, and their partners, who were planning a pregnancy. The occurrence of pregnancy was tested prospectively during the 12 months after enrollment., Results: Among the participants as well as among their partners, smoking a moderate number of cigarettes (1-10/day) was associated with higher fecundability (i.e., the probability of becoming pregnant each month) than among those not smoking (participant: OR = 1.4 (95% CI, 0.9-2.2); partner: OR = 2.1 (95% CI, 1.2-3.5)). The level of alcohol consumption in the female partner was not related to fecundability. However, in the male partner, there was a positive influence for drinking more than 10 alcoholic drinks per week compared with that observed for those drinking less than 5 (OR = 1.6; 95% CI, 1.0-2.4). Participants with a moderate caffeine intake (400-700 mg/day) showed a higher fecundability than those with a lower intake level (ORadjusted = 2.1 (95% CI, 1.2-3.7)). Heavy caffeine intake (> 700 mg/day) among partners was negatively related to fecundability when compared with the lowest intake level (ORadjusted = 0.6 (95% CI, 0.3-0.97))., Conclusions: This study does not support the hypothesis that moderate cigarette smoking, caffeine intake, and alcohol consumption have an adverse influence on fecundability.

We examined the influence of the level of occupational physical activity per working hour (intensity score) and per working day (fatigue score) on menstrual function and fecundability in a population of 260 nonmedical female workers who were employed at 39 Dutch hospitals and were planning a pregnancy. We studied the influence of the intensity and fatigue scores as such and in combination with unfavorable working hours (before 8:00 am or after 6:00 pm) and high working speed (working at high speed for more than 50% of the time). The data did not reveal a clear relation between the occupational physical activity levels (representing an estimated energy requirement of up to 3 times the basal metabolic rate) and menstrual function, but the presence of a small effect could have been missed. The fecundability of women with a high fatigue score, particularly in association with unfavorable working hours, was lower than that of women with a low fatigue score (fecundability odds ratio = 0.37; 95% confidence interval = 0.18-0.77). Moderate levels of physical activity, as found in cleaners, kitchen staff, and clerical workers at hospitals, appear to affect the female reproductive system. Fecundability, as measured by the time to pregnancy, seems to be a more sensitive parameter for these biological changes than menstrual function.

Introduction: Postmenopausal hormone replacement therapy (HRT) has been described to reduce the risk of developing cardiovascular disease (CVD), which can be attributed at least in part to beneficial effects of oestrogens on serum lipoproteins. Little is known about a possible counteracting effect by the progestogen integrated in modern HRT regimens., Objective: To study the possible changes in serum lipids, lipoproteins and apolipoproteins during HRT with special emphasis on the possible progestational effect., Study Design: In an open-label longitudinal non-comparative study 23 healthy non-hysterectomized postmenopausal women were treated with continuous micronized 17 beta-oestradiol, 2 mg daily, in combination with cyclic dydrogesterone, 10 mg daily, the first 14 days of each 28-day treatment cycle. The women were followed for up to 2 years., Results: After 2 years serum total cholesterol and low-density lipoprotein cholesterol had decreased by 9.0% and 18%, respectively (P < 0.01), while high-density lipoprotein cholesterol had increased by 13% (P < 0.01). The latter change was accompanied with similar increases in apolipoprotein A-I (+16%; P < 0.01) and A-II (+13%; P < 0.01), while apolipoprotein B remained unchanged. Serum very low-density lipoprotein (VLDL) cholesterol and VLDL-triglycerides increased by 28% and 21%, respectively, the latter reflecting the slight increase in serum triglycerides by 21%. These values, however, remained within the normal range. Serum lipoprotein(a) decreased by 16% (P < 0.01). All calculated atherogenic indices decreased (P < 0.01) during the study period. Serum lipids and (apo)lipoproteins did not change after withdrawal of dydrogesterone for 14 days during the combination therapy in the last cycle studied. Serum fibrinogen decreased by 8.4% (P < 0.01) in the first 12 cycles, after which it increased to 13% above baseline value (P < 0.01 vs. baseline). Antithrombin III did not change and serum glucose decreased by 5.7%., Conclusions: This HRT regimen induces (and also when given for a longer period) beneficial changes in the lipid profile, without affecting important indicators of thrombosis. Also, the glucose metabolism does not seem to be interfered with. Cyclic administration of dydrogesterone does not unfavourably affect serum lipids and (apo)lipoproteins when combined with 17 beta-oestradiol supplementation. Therefore, this combination hormone regimen can be recommended for use in HRT.

The influence of occupational physical activity on early pregnancy failure was examined in a population of 24 cleaners, 36 kitchen staff and 110 clerical workers from 39 Dutch hospitals who were enrolled before becoming pregnant between August 1987 and January 1989. The occupational energy expenditure was defined by an intensity and a fatigue score, which were studied alone and in combination with working hours and working speed. The occupational biomechanic load was defined by a peak and a chronic pressure score. The intensity and the fatigue score of the work, whether or not in combination with working hours and working speed, were not related to the occurrence of spontaneous abortion. Work involving a high biomechanic load, in particular high peak pressure scores, showed an odds ratio (OR) for spontaneous abortion of 3.1 (95% confidence interval [CI]: 1.1-8.9). There were strong indications that work involving bending (OR = 3.2; 95% CI: 1.3-9.8) rather than lifting (OR = 1.1; 95% CI: 0.3-3.4) was the main cause.

Objective: To test non-hysteroscopic thermodestruction of the endometrium for safety and efficiency., Design: Prospective pilot study from February 1991 to July 1992., Setting: University Hospital Nijmegen., Patients and Method: There were 68 patients aged 30-55 years with menorrhagia, who did not want children but wished to retain the uterus. There were two patients with a subserous myoma but with a normal uterine cavity. Patients with hypergonadotropism, a markedly enlarged uterus, abnormalities at cytological examination of the cervix, adnexal lesions, prolapse, intrauterine lesions and coagulation disorders were excluded. By way of preparation, danazol was administered for 4 weeks before the intervention (36 patients). Three patients with side effects were given lynestrenol. From January 1992, an LH-RH analogue was administered (29 patients) for 6 weeks prior to the intervention or in the patients with a subserous myoma for 12 weeks. Thermodestruction of the endometrium by means of radio waves was carried out according to a standard protocol under general or epidural spinal anaesthesia. The intracavitary temperature measured was 62-65 degrees C, mean duration of the treatment 20 minutes., Results: The patients were discharged 10-24 hours after the intervention. A non-disturbing watery discharge of 3-6 weeks' duration was reported. Normal activities were resumed after one week. Success (duration of follow-up 3-21 months) was defined as amenorrhoea (6 patients; 9%) or a markedly reduced menstruation or duration of menstruation (48 patients; 70%). Six patients (9%) reported no improvement and of eight patients (12%) with slight, unsatisfactory improvement three were treated again, with success (4%). During the trial period the method was further adjusted and perfected. There were no complications., Conclusion: This preliminary experience shows that thermodestruction with radio waves is simple, safe and efficient.

Fifty-four healthy women were studied during the follicular and the luteal phase of one menstrual cycle to determine possible cyclic influences on several parameters. After a 12-h overnight fast, blood samples were obtained between 08.00 h and 09.30 h and processed for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoproteins A-I and B and total triglycerides. In the same samples we also measured serum concentrations of follicle-stimulating hormone, luteinizing hormone, 17 beta-oestradiol, progesterone, sex hormone binding globulin and testosterone. Serum total cholesterol, low-density lipoprotein cholesterol and the related apolipoprotein B were decreased significantly with 0.35 mmol/l, 0.44 mmol/l and 15 mg/l, respectively, during the luteal phase as compared to the follicular phase (p < or = 0.01). The ratios of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and of total cholesterol/high-density lipoprotein cholesterol were also significantly lower (p < 0.01) in the luteal phase because high-density lipoprotein cholesterol and its major carrier apolipoprotein A-I as well as serum triglycerides remained unchanged in the two cycle phases compared. Sex hormone binding globulin was significantly higher (p < 0.001) in the luteal phase than in the follicular phase of the investigated cycles, whereas serum testosterone remained unchanged in the two cycle phases compared. Therefore, the free androgen index decreased in the luteal phase (p < 0.01). These results indicate the necessity to define the cycle phase in which blood has been collected during control cycles in studies concentrating on possible effects of oral contraceptives or other administered sex steroids on serum lipids, lipoproteins and androgen metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian stimulation in the treatment of infertility is far from physiological because patients and their ovaries are exposed to high concentrations of gonadotropins. Many studies have focused on the two most common side-effects of ovarian stimulation--ie, hyperstimulation and multiple pregnancy. We describe 12 patients in whom granulosa-cell tumour was discovered after ovarian stimulation treatment with clomiphene citrate and/or gonadotropins. Although we cannot prove a causal link between the tumour and the medication, investigations in animals have shown a relation between gonadotropin exposition and the development of granulosa-cell tumours. The possible relation of ovarian stimulation and granulosa-cell tumours in human beings has not been published before. We postulate three explanations for this finding; first, the granulosa-cell tumour is present in the ovary, waiting for a hormonal trigger; second, increased follicle stimulating hormone concentrations are oncogenic to granulosa cell; and third, the onset of the granulosa-cell tumour during ovarian stimulation is coincidental. We recommend that ovarian stimulation is done only if there is a valid indication after proper assessment of the ovaries, and that women who have had ovarian stimulation are followed for longer than at present.

Objective: The purpose of this study was to discriminate typical (type A) from atypical (type B) Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (congenital absence of vagina and uterus) and determine their association with renal anomalies and ovarian disease., Materials and Methods: The excretory urographic, sonographic, and laparoscopic findings in 91 patients with MRKH syndrome were compared retrospectively. Symmetric muscular buds and fallopian tubes were diagnostic of type A, and asymmetric muscular buds or abnormally developed fallopian tubes were diagnostic of type B., Results: On the basis of laparoscopic findings, type A was diagnosed in 40 patients (44%) and type B was diagnosed in 51 patients (56%). Renal anomalies were found in 34 (37%) of the 91 patients, all of whom had type B syndrome. Renal agenesis and a pelvic kidney were the most common findings in the upper part of the urinary tract. Ovarian abnormalities were seen in 14 patients (15%), all of whom had type B syndrome. Sonography did not allow discrimination between types A and B in patients with normal kidneys (17/51 = 33%), but it provided important information in patients with associated cyclic abdominal pain, in cases of diagnostic dilemma, and in patients with associated renal anomalies., Conclusion: Discrimination between type A and type B of MRKH syndrome is important because associated renal and ovarian abnormalities occur only in type B. Laparoscopy is still needed to discriminate between these two forms. Sonography is useful for diagnosing cyclic abdominal pain and associated renal anomalies.

To study the effects of sperm density on the results of computer-assisted semen analysis (CASA), 10 washed semen samples were diluted and measured with the CellTrak/S CASA system in a concentration range of 10-180 x 10(6) spermatozoa/ml. All sperm motility parameters were influenced to some extent by sperm density. The motility percentage was influenced significantly in 5 samples (P < 0.005), the straight line velocity in all samples (P < 0.0005 in 7 samples), the curvilinear velocity in 3 samples (P < 0.005), the linearity in 9 samples (P < 0.0005 in 6 samples) and the lateral head displacement in 9 samples (P < 0.005 in 6 samples). In general, the CellTrak/S data are influenced significantly if sperm density exceeds 50 x 10(6) spermatozoa/ml. The influence of sperm density on the motility parameters can be explained both by the accuracy of the CASA system and by actual changes in the motility of the spermatozoa. In the light of other published studies, it is concluded that sperm motility measurements with CASA systems should be assessed using 25-50 x 10(6) spermatozoa/ml, especially in studies concerning lateral head displacement and the linearity, as in sperm hyperactivation studies.

Study Objective: To study the possible changes of reproductive hormones, sex hormone binding globulin, serum lipids and lipoproteins, lipoprotein (a) included, coagulation and glucose in postmenopausal women treated with 17 beta-oestradiol and cyclic dydrogesterone for 14 days per 28 days treatment cycle., Design: Open longitudinal prospective study., Duration: Twelve 28 days treatment cycles., Setting: Gynaecological department of university hospital., Subjects: 27 healthy postmenopausal women., Results: After treatment for six cycles serum concentrations of FSH and LH decreased significantly with 43.0% and 24.4%, respectively. Serum concentrations of 17 beta-oestradiol and oestrone increased significantly with 302% and 792%, respectively, and SHBG increased as well with 111% (P < 0.01). Serum total cholesterol decreased with 9.0% (P < 0.01). Serum VLDL-cholesterol did not change significantly. Serum LDL-cholesterol decreased with 16.3% (P < 0.01) and HDL-cholesterol increased with 8.0% (P < 0.01). This was accompanied with similar significant changes in the apolipoproteins: apolipoprotein A-I rose with 14.4% and apolipoprotein B decreased with 6.0%. Serum triglycerides and VLDL-triglycerides increased significantly with 14.4% and 17.9%, respectively. Lipoprotein (a) decreased with 17.5% (P < 0.01). These results more or less sustained at cycle 12 of treatment. Serum concentrations of antithrombin III and glucose did not change. Fibrinogen decreased slightly but significantly below the initial value., Conclusions: This combination replacement therapy gives beneficial changes in lipid-metabolism, indicating a reduced risk of developing coronary heart disease without unfavourably changing coagulation and glucose metabolism. The expected beneficial changes with oestradiol alone are not counteracted by the intermittent addition of dydrogesterone. Therefore this oestrogen/progestagen scheme can, indeed, be recommended for use in HRT.

A new system for co-culture in human in-vitro fertilization (IVF), using human skin fibroblasts, is described and tested pre-clinically. The first test involved the development of 1-cell mouse embryos which exhibit the 2-cell developmental block in vitro. Passage through this block (pb1-ratio) was determined by the ratio of compacted morula stages on day 4 of incubation. For nine human skin cell lines tested (fetal, neonatal and adult), the pb1-ratio was approximately 0.45 (0.07 in culture medium alone; P less than 0.0005). At the compacted morula stage, a second developmental block was observed. The ratio of passing this block (pb2-ratio) was 0.70 +/- 0.09 on skin fibroblasts obtained from fetal or neonatal tissue. On fibroblasts from adult patients the pb2-ratio was 0.30 +/- 0.04 (P less than 0.0005). The second test examined the influence of skin fibroblasts from fetal or neonatal tissue on human sperm motility. After 24 h of incubation, all skin cell lines had a positive influence (P less than 0.01) on the percentage motility compared to culture medium alone. The curvilinear velocity was not significantly increased. From the results we conclude that (i) human skin fibroblasts (especially from fetal tissue) have a positive influence on the development of mouse embryos in vitro, (ii) there is a positive influence of human skin fibroblasts on the percentage motility of human spermatozoa, and (iii) a clinical trial of co-culture with human skin fibroblasts can be justified.

Objective: To further elucidate the origin and significance of serum CA-125 in pelvic endometriosis., Design: Retrospective., Patients: Ninety-seven women with endometriosis who participated in two trials: (1) open-label study on buserelin acetate (n = 51) and (2) comparative, placebo-controlled study on nafarelin (n = 31) versus danazol (n = 15) (2:1 ratio)., Interventions: (1) Buserelin acetate 900 micrograms/d intranasally (IN); (2) nafarelin 400 micrograms/d IN versus danazol 400 mg/d orally during 6 months., Main Outcome Measure(s): Serum CA-125 and estradiol concentrations; severity of endometriosis-related symptoms; scores according to The American Fertility Society (AFS) classification for endometriosis and/or adhesions (before and on last day of therapy)., Results: Menstruation and adhesions appeared major factors influencing pretreatment serum CA-125 concentrations. Compared with nonmenstruating women without adhesions, both menses and adhesions induced a slight increase tending to significancy, whereas the elevating effect of adhesions and menses together was highly significant and more than expected. All three treatment regimens reduced CA-125 concentrations to the same extent; cessation of therapy was followed by restoration to pretreatment concentrations. Of the AFS scores for implants and/or adhesions, only pretreatment scores for adhesions correlated significantly with CA-125 concentrations. Severity scores for endometriosis-related complaints did not correlate., Conclusions: The findings indicate that adhesions play a major role in the presence of CA-125 in the systemic circulation and suggest that reductions of serum CA-125 concentrations during gonadotropin-releasing hormone agonist and danazol therapy are hormonally determined.

Objective: Diathermy loop excision was performed as a new diagnostic-treatment in patients with cervical cytologic diagnoses consistent with an epithelial abnormality., Study Design: A total of 424 patients with cervical cytologic diagnoses consistent with an epithelial abnormality, but macroscopically or colposcopically not consistent with invasive carcinoma, were subjected to diathermy loop excision to diagnose and treat cervical lesions in one procedure., Results: The diagnostic accuracy rate was 99%. In patients with histologically confirmed grade 3 cervical intraepithelial neoplasia, pretreatment cytologic diagnosis and subsequent histopathologic diagnosis corresponded in 73% of cases. In 91% of all patients the diathermy loop excision was sufficient for complete treatment. Cervical morphologic findings after treatment allowed adequate cytologic follow-up. There was no evidence that diathermy loop excision influenced fertility or pregnancy outcome., Conclusion: Diathermy loop excision is a reliable, well-tolerated, inexpensive, and efficient technique for the management of cervical intraepithelial neoplasia. This outpatient procedure is especially recommended in younger patients, because diathermy loop excision preserves the function of the cervix.

Objective: To study the reaction pattern of acrosome reaction in human semen and correlate it to the results of in vitro fertilization (IVF)., Design: The percentage of acrosome-reacted spermatozoa of 41 IVF semen samples was determined after 0, 2, 4, and 24 hours of incubation in human tubal fluid medium supplemented with 10% human pool serum., Setting: St. Radboud Hospital, Catholic University of Nijmegen, The Netherlands., Patients: Forty-one IVF couples., Interventions: None., Main Outcome Measure: Acrosome reaction was determined using fluorescein isothiocyanate conjugated concanavalin A lectin. To avoid false-positive signals from dead spermatozoa, the sperm viability was determined., Results: Three kinetic patterns of acrosome reaction could be distinguished: (1) normal reacting pattern (percentage of acrosome-reacted spermatozoa less than 10% at 2 hours and greater than 5% at 4 hours; 75% fertilization in IVF); (2) a quickly reacting pattern (percentage of acrosome-reacted spermatozoa greater than 10% at 2 hours; 22% fertilization in IVF); and (3) a nonreacting pattern (percentage of acrosome-reacted spermatozoa less than 5% at all time intervals studied; 15% fertilization in IVF)., Conclusions: The timing of acrosome reaction and the percentage of acrosome-reacted spermatozoa are very important parameters in IVF.

Objective: To determine CA-125 concentrations and total amounts in peritoneal fluid (PF) of women with various infertility-related factors throughout the menstrual cycle., Design: Peritoneal fluid was obtained at laparoscopy. CA-125 was determined using the assessed two-step immunoradiometric assay (IRMA) which, in contrast to the one-step IRMA, gives valid results., Setting: University Hospital Nijmegen, Nijmegen, The Netherlands., Patients: One hundred six infertile women with a regular and ovulatory cycle were included., Interventions: None., Main Outcome Measure(s): The mean PF CA-125 concentration and total amount were significantly lower during the luteal phase as compared with other phases of the menstrual cycle. No correlation was found with the presence or absence of endometriosis, adhesions, a male and/or cervical mucus infertility factor, and with patent or closed fallopian tubes., Results: Peritoneal fluid CA-125 concentrations varied from 630 to 12,000 arbitrary units/mL (mean +/- SD = 3,437 +/- 2,286). Total PF CA-125 amounts (concentration x PF volume) varied from 1,760 to 13,300 arbitrary units (mean +/- SD = 30,219 +/- 26,841)., Conclusions: CA-125 secretion into the abdominal cavity varies during the menstrual cycle. Retrograde menstruation is not the main source of CA-125 in PF.

A comparative immunocytochemical study was performed on endometriotic epithelial versus endometrial epithelial and normal mesothelial cells in order to obtain further evidence for either the endometrial implantation or mesothelial metaplasia theory. The three cell types could not be distinguished by keratin subtyping, using monoclonal antibodies (MAbs) to keratins 5, 7, 8, 14, 18, and 19. The epithelial markers HMFG-2 and BW 495/36, and a newly developed MAb NEND-3 (against endometrial cells) discriminated between generally negatively reacting mesothelial cells and positively reacting endometrial and endometriotic epithelial cells. The MAb NEND-3 appeared to be specific for endometrial (and endometriotic) epithelial cells since no reactivity with other epithelial cell types was found. Typing with MAbs against ovarian carcinoma related antigens (OV-TL 3, OV-TL 10 and OC 125) did not permit sufficient distinction. The marker profile of cultured endometrial, endometriotic and mesothelial cells confirmed the immunocytochemical findings on frozen sections. Although the data are consistent with the endometrial implantation theory, mesothelial metaplasia can not be excluded with regard to the histogenesis of endometriosis since metaplastic mesothelium may express different antigen markers.