Time and Frequency Repolarization Domains in Elderly Candidates to Transcatheter Aortic Valve Replacement.

Background and aim: Aortic valve stenosis (AVS) is a well-known risk factor for sudden cardiac death. Therefore, some non-invasive, electrocardiographic markers are capable to stratify the risk of sudden death at rest and during light mental challenge [mini-mental state examination (MMSE) administration]. Method: We compared short period RR, QT and Te intervals variability in 42 candidates to and 12 age-matched hypertensive control patients at rest and during mental challenge. Results: At rest, AVS patients showed a higher QT standard deviation (sd), QT low frequency power (LF), QT High Frequency (HF), Tpeak-Tend intervals sd (Te sd) and Te HF than the control group. During mental challenge AVS group showed a decrease of RR mean and RR HF, expressed in normalized units (NU), and an increase of RR total power (TP), RR LF, RR LF NU, RR LF, HF ratio (LF/HF). During this same mental test, QT sd, QT LF, QT HF, Te sd, Te LF, Te HF, QT variability index (VI), TeVI, QT normalized variance (VN) were higher in AVS patients than the control group. During mental challenge Te LF (r:0.825, p<0.05) was significantly associated to: serum albumin (ß:-0.473, p<0.001), MMSE (ß:-0.267, p:0.038), diastolic blood pressure (ß:-0.443, p:0.03) and cardiac index (ß:-0.303, p:0.029). Conclusion: AVS patients showed temporal dispersion of ventricular repolarization phase, useful maker to individuate high risk patients. MMSE administration induced a sympathetic sinus activation and vagal deactivation in AVS subjects. Frailty and mental function influenced Te HF and Te LF.

Relationship between plasma aldosterone levels and arterial stiffness parameters in hypertensive patients with subclinical vascular damage.

Purpose: Aldosterone plays important role in cardiovascular damage. Aim was to evaluate arterial subclinical damage through arterial stiffness parameters in patients with Essential Hypertension (EH) and Primary Aldosteronism (PA). Methods: From 2018 to 2019 we consecutively enrolled 82 subjects (37 males and 45 women), distinguished in two groups: 60 EH [systolic blood pressure (SBP) 143.4 ± 16.7 mmHg, diastolic blood pressure (DBP) 89.5 ± 12.1 mmHg] and 22 PA (SBP 149 ± 19.5 mmHg, DBP 92.7 ± 12.4 mmHg) [5 with aldosterone-secreting adrenal adenoma(APA), 17 with idiopathic aldosteronism(IHA)]; 40 matched normotensive subjects (NS) were enrolled (SBP 109.7 ± 6.2 mmHg, DBP 71.3 ± 9.7 mmHg). We used non-invasive applanation tonometer to acquire pressure waveform. Results: PA patients showed higher µ-Albuminuria (UAE) (65.7 ± 11.0mg/24 h) than EH and NS (21.5 ± 7.0 mg/24 h and 21.5 ± 7.0 mg/24 h, respectively); APA group showed increased levels of arterial stiffness index (11.7 ± 4.8 m/s; p < 0.02) compared to EH subjects (8.3 ± 3 m/s) and NS subjects (7.2 ± 1.7 m/s) as well as higher carotid intima-media thickness (c-IMT); APA patients showed significant reduction of subendocardial viability ratio (SEVR) and travel time of the reflected waves (TI) respect EH and NS. PA groups showed high percentage of augmented "worsening age" (60%), compared to EH (38%) and NS (37%). PAC was positively correlated with Arterial Stiffness Index. Performing multiple linear regression analysis (evaluating anthropometric and biochemical parameters), we found UAE as predictor of Augmentation Index, Arterial Stiffness Index and Travel Time of reflected waves in the enrolled population. Conclusion: PA patients showed higher cardiovascular subclinical damage respect to EH; UAE excretion had significant correlation with aldosterone, resulting best marker of subclinical vascular remodeling.

Short-Period Temporal Dispersion Repolarization Markers in Elderly Patients with Decompensated Heart Failure.

Objectives: Aging and chronic heart failure (CHF) are responsible for the temporal inhomogeneity of electrocardiogram (ECG) repolarization phase. In the past, short period repolarization-dispersion parameters were used as makers of mortality risk in different heart diseases, yet. Aim of this work was to evaluate risk of mortality or worsening condition in CHF elderly subjects by mean of these repo-larization variables. Method: An observational, prospective cohort study was performed, collecting 5 minutes ECG recordings to assess the mean and standard deviation (SD) of the following variables: QT end (QTe), QT peak (QTp) and T peak to T end (Te) in 117 decompensated CHF (age range: from 49 to 103 years). 30-day mortality and high levels of NT-pro BNP (<75 percentile) were considered markers of decompensated CHF. Results: A total of 27 patients (23%) died during the 30-day follow-up (overall mortality rate 23%). Te mean (odd ratio (OR): 1.04, 95% confidence limit (Cl 7u): 1.02-1.09, p<0.01), NT-pro BNP (OR: 1.00, 95% cl: 1.00-1.00, p<0.01) and LVMI (OR : 0.98, 95% cl: 0.96-0.10, p<0.05) were associated to risk of mortality at the multivariable logistic analysis. On the contrary, the same statistical analysis selected TeSD (OR: 1.36, 95% cl: 1.16-1.59, p<0.001) and LVEF (OR: 0.91, 95% cl: 0.87-0.95, p<0.001) as marker of decompensated CHF. Conclusion: In decompensated CHF elderly subjects, Te mean seem be associated to mortality and TeSD could be considered a risk factor for CHF worsening and complications. These evidences could provide useful tools for telemonitoring CHF elderly patients, amelio-rating treatments and outcomes.

[Para-arortic lymhadenectomy and pelvic gynecological cancers: Extraperitoneal or transperitoneal laparoscopy?] / Curage lombo-aortique et cancers gynécologiques pelviens : cœlioscopie rétroperitonéale ou transpéritonéale ?

INTRODUCTION: Para-aortic lymphadenectomy plays a fundamental role in the surgical management of pelvic gynecological cancers. Two laparoscopic approaches exist: the transperitoneal (TP) and the extraperitoneal (EP). The aim of this study was to compare these 2 approaches in terms of surgical outcomes, specially the number of removed lymph nodes according to the surgical technique, and morbidity. MATERIALS AND METHOD: A single-center retrospective study was carried out at the Lariboisiere University Hospital between January 2011 and March 2020 including all patients who underwent para-aortic lymphadenectomy for the management of a pelvic gynecological cancer (cervix, endometrium, ovary). Univariate and multivariate analysis (logistic regression) were performed to compare the TP and the EP groups. RESULTS: 143 patients were included: 74 in the TP group and 69 in the RP group. The total duration of surgery was 220.8minutes in the TP group and 166.4minutes in the EP group (P<0.001 in multivariate analysis). No significant difference between groups were found in the average total number of lymph nodes removed but there was a statistically significant difference in the average latero-aortic number of lymph nodes removed: 8.5 lymph nodes in the TP group and 11.3 lymph nodes in the group RP (P<0.001 in multivariate analysis). There was no difference between groups in peri and postoperative morbidity. CONCLUSION: EP para-aortic lymphadenectomy reduces duration of surgery and increases the average latero-aortic number of lymph nodes removed with same morbidity compared to TP para-aortic lymphadenectomy, this confirming its preferred indication in endometrial and in cervical cancers.

Management of borderline ovarian tumours during pregnancy: Results of a French multi-centre study.

OBJECTIVE: To assess the diagnostic and prognostic characteristics of borderline ovarian tumours (BOTs) detected during pregnancy, and to establish an inventory of French practices. MATERIALS AND METHODS: A retrospective multi-centre case study of 14 patients treated for BOTs, diagnosed during pregnancy between 2005 and 2017, in five French pelvic cancerology expert centres, including data on clinical characteristics, histological tumour characteristics, surgical procedure, adjuvant treatments, follow-up and fertility. RESULTS: The mean age of patients was 29.3 [standard deviation (SD) 6.2] years. Most BOTs were diagnosed on ultrasonography in the first trimester (85.7 %), and most of these cases (78.5 %) also underwent magnetic resonance imaging to confirm the diagnosis (true positives 54.5 %). Most patients underwent surgery during pregnancy (57 %), with complete staging surgery in two cases (14.3 %). Laparoscopy was performed more frequently than other procedures (50 %), and unilateral adnexectomy was more common than cystectomy (57.5 %). Tumour size influenced the surgical approach significantly (mean size 7.5 cm for laparoscopy, 11.9 cm for laparoconversion, 14 cm for primary laparotomy; P = 0.08), but the type of resection did not. Most patients were initially diagnosed with International Federation of Gynecology and Obstetrics stage IA (92.8 %) tumours, but many were upstaged after complete restaging surgery (57.1 %). Most BOTs were serous (50 %), two cases had a micropapillary component (28.5 %), and one case had a micro-invasive implant. BOTs were bilateral in two cases (14.2 %). Mean follow-up was 31.4 (SD 14.8) months. Recurrent lesions occurred in two patients (14.2 %) and no deaths have been recorded to date among the study population. CONCLUSION: BOTs remain rare, but this study - despite its small sample size - supports the hypothesis that BOTs during pregnancy have potentially aggressive characteristics.

[Guidelines for surgical management of gynaecological cancer during pandemic COVID-19 period - FRANCOGYN group for the CNGOF]. / Prise en charge chirurgicale des cancers gynécologiques en période de pandémie COVID-19 ­ Recommandations du Groupe FRANCOGYN pour le CNGOF.

INTRODUCTION: Recommendations for the management of patients with gynecological cancer during the COVID-19 pandemic period. MATERIAL AND METHOD: Recommendations based on the consensus conference model. RESULTS: In the case of a COVID-19 positive patient, surgical management should be postponed for at least 15 days. For cervical cancer, the place of surgery must be re-evaluated in relation to radiotherapy and Radio-Chemotherapy-Concomitant and the value of lymph node staging surgeries must be reviewed on a case-by-case basis. For advanced ovarian cancers, neo-adjuvant chemotherapy should be favored even if primary cytoreduction surgery could be envisaged. It is lawful not to offer hyperthermic intraperitoneal chemotherapy during a COVID-19 pandemic. In the case of patients who must undergo interval surgery, it is possible to continue the chemotherapy and to offer surgery after 6 cycles of chemotherapy. For early stage endometrial cancer, in case of low and intermediate preoperative ESMO risk, hysterectomy with bilateral annexectomy associated with a sentinel lymph node procedure should be favored. It is possible to consider postponing surgery for 1 to 2 months in low-risk endometrial cancers (FIGO Ia stage on MRI and grade 1-2 endometrioid cancer on endometrial biopsy). For high ESMO risk, it ispossible to favor the MSKCC algorithm (combining PET-CT and sentinel lymph node biopsy) in order to omit pelvic and lumbar-aortic lymphadenectomies. CONCLUSION: During COVID-19 pandemic, patients suffering from cancer should not lose life chance, while limiting the risks associated with the virus.

Prediction of tumor grade and lymphovascular space invasion in endometrial adenocarcinoma with MR imaging-based radiomic analysis.

PURPOSE: To evaluate the capabilities of two-dimensional magnetic resonance imaging (MRI)-based texture analysis features, tumor volume, tumor short axis and apparent diffusion coefficient (ADC) in predicting histopathological high-grade and lymphovascular space invasion (LVSI) in endometrial adenocarcinoma. MATERIALS AND METHODS: Seventy-three women (mean age: 66±11.5 [SD] years; range: 45-88 years) with endometrial adenocarcinoma who underwent MRI of the pelvis at 1.5-T before hysterectomy were retrospectively included. Texture analysis was performed using TexRAD® software on T2-weighted images and ADC maps. Primary outcomes were high-grade and LVSI prediction using histopathological analysis as standard of reference. After data reduction using ascending hierarchical classification analysis, a predictive model was obtained by stepwise multivariate logistic regression and performances were assessed using cross-validated receiver operator curve (ROC). RESULTS: A total of 72 texture features per tumor were computed. Texture model yielded 52% sensitivity and 75% specificity for the diagnosis of high-grade tumor (areas under ROC curve [AUC]=0.64) and 71% sensitivity and 59% specificity for the diagnosis of LVSI (AUC=0.59). Volumes and tumor short axis were greater for high-grade tumors (P=0.0002 and P=0.004, respectively) and for patients with LVSI (P=0.004 and P=0.0279, respectively). No differences in ADC values were found between high-grade and low-grade tumors and for LVSI. A tumor short axis≥20mm yielded 95% sensitivity and 75% specificity for the diagnosis of high-grade tumor (AUC=0.86). CONCLUSION: MRI-based texture analysis is of limited value to predict high grade and LVSI of endometrial adenocarcinoma. A tumor short axis≥20mm is the best predictor of high grade and LVSI.

[Vaginal gas: Review]. / Gaz vaginaux : revue de la littérature.

OBJECTIVE: The aim of this article was to review the literature about vaginal winds (VW). METHODS: A literature review (Medline database, Cochrane Library and Google scholar) with no time limit was performed using keywords "vaginal winds", "vaginal noise", "vaginal gaz", "flatus vaginalis", "vaginal flatus", "colpophony", "Garrulitas vulvae", "vaginal laxity". RESULTS: From 412 articles about VW, 15 have been selected and 99 from 110 about vaginal laxity. VW occurs during physical exercises but also during and just after coïtus. The prevalence is about 20%. The pathophyiology of VW is probably a vaginal hyperlaxity itself secondary to pelvic floor muscles weakness and thus increased diameter of vaginal hiatus. VW alter sexual function in female patients but this sexual function seems not influenced in male partners. Tampons or pessaries are currently the most commonly proposed treatment (but naturally impossible to use during sexual intercourse), but some results from vaginal laser therapy are encouraging. CONCLUSION: Data from the literature suggest that vaginal winds are frequent and seriously impact quality of life of female patients. Childbirth and more generally vaginal laxity are the main causes. Pelvic-floor exercises, tampons, pessaries, surgery and laser can be proposed in order to improve sexual function in patients seeking treatment.

[Use of botulinum toxin A in pelvic floor dysfunctions in the elderly: A review]. / Intérêt de la toxine botulinique A dans le traitement des troubles pelvi-périnéaux de la personne âgée.

INTRODUCTION: The present article is the final report of a multi-disciplinary meeting supported by the GRAPPPA (group for research applied to pelvic floor dysfunctions in the elderly). The objective was to conduct a comprehensive review on the role of botulinum toxin A (BonTA) in the treatment of pelvic floor dysfunctions in the elderly. METHODS: The present article, written as a comprehensive review of the literature, combines data issued from the scientific literature with expert's opinions. Review of the literature was performed using the online bibliographic database MedLine (National Library of Medicine). Regarding intra-detrusor BonTA injections, only articles focusing on elderly patients (>65 yo) were included. Regarding other localizations, given the limited number of data, all articles reporting outcomes of BonTA were included, regardless of studies population age. In case of missing or insufficient data, expert's opinions were formulated. RESULTS: Although, available data are lacking in this specific population, it appears that BonTA could be used in the non-fraily elderly patients to treat overactive bladder or even neurogenic detrusor overactivity, with a success rate comparable to younger population at 3 months (88.9% vs. 91.2%), 6 months (49.4% vs. 52.1%) and 12 months (23.1% vs. 22.3%), as well as a significant decrease in number of voids per day (11.4 vs. 5.29 P<0.001) and in the number of pads per day (4.0 vs. 1.3, P<0.01). Furthermore, BonTA is likely to be offered in the future as a treatment of fecal incontinence and obstructed defecation syndrome symptoms. Concerning bladder outlet obstruction/voiding dysfunction symptoms, intra-urethral sphincter BonTA should not be recommended. CONCLUSION: BonTA injections are of interest in the management of various pelvic floor dysfunctions in the elderly, and its various applications should be better evaluated in this specific population in order to further determine its safety and efficacy.

[Cardiovascular adverse effects of antimuscarinics used in the treatment of overactive bladder in the elderly : A review]. / Effets cardio-vasculaires des traitements anticholinergiques à visée vésicale chez la personne âgée : une revue.

AIM: The aim of this study was to review the evidence regarding the cardiovascular effects of urinary anticholinergic drugs in the elderly. METHODS: A literature review was conducted in October 2017 using the Medline/Pubmed database limiting the search to works in English or French. RESULTS: In total, 602 articles between March 1964 and October 2017 have been reported, 60 studies were analyzed, 19 were prospective trials. Geriatric population has a high prevalence of cardiovascular diseases (24.4% of heart diseases on 65-74years and 36.9% on ≥75years). More than 20% of the geriatric population has overactive bladder history and 41.43% of them use of antimuscarinic drugs. Evaluating the cardiovascular adverse effects of antimusarinics in the geriatric population is not easy because of exclusion of high-risk patients in trials. However, serious cardiovascular adverse effects were reported like atrial fibrillation, atrioventricular block or torsade de pointe. Further studies are needed especially in the "real life" in order to precise the exact prevalence of such cardiovascular alterations. CONCLUSION: Without conclusive evidence, potential cardiovascular adverse effects of anticholinergic agents used in overactive bladder must lead to a cautious prescription.

[Pathophysiology of detrusor underactivity in the elderly]. / Physiopathologie de l'hypoactivité détrusorienne de la personne âgée.

AIM: The aim of this study was to review the evidence regarding the pathophysiology of detrusor underactivity in the elderly. METHODS: A literature review was conducted in July 2016 using the Medline/Pubmed database limiting the search to works in English or French. RESULTS: The prevalence of detrusor underactivity has been reported to range from 8% to 48% depending on the definition used and the age of the population studied. Current data suggest that aging may itself be a causative factor of detrusor underactivity through myogenic dysfunctions (ultrastructural degeneration of the detrusor muscle) and neurogenic dysfunctions (by degeneration of efferent but mostly afferent innervation mechanisms). Beyond these inherently age-related mechanisms, many comorbidities whose prevalence increase with age (diabetes, bladder outlet obstruction, estrogen deficiency, atherosclerosis, etc.) may be implicated in the development of detrusor underactivity in the elderly. The role played by detrusor overactivity in the appearance of detrusor underactivity must be considered separately as both seem to be the expression of the same condition of the lower urinary tract responding to different stages and secondary to numerous etiopathogenic factors which modulate its progression and clinical expressions. CONCLUSION: Pathophysiology of detrusor underactivity remains poorly understood but seems to imply myogenic and neurogenic factors which are favored, besides the aging per se, by various and numerous comorbidities which prevalence increase with age (diabetes, bladder outlet obstruction…).

Low pressure gynecological laparoscopy (7mmHg) with AirSeal® System versus a standard insufflation (15mmHg): A pilot study in 60 patients.

OBJECTIVES: To evaluate feasibility of performing benign gynecologic pathology low pressure (7mmHg) laparoscopy (LPL) with AirSeal® system and to study benefits in terms of postoperative pain, when compared to a standard insufflation group (15mmHg). MATERIALS AND METHODS: In this prospective randomized pilot study, 60 patients had laparoscopy for gynecologic benign pathology: 30 with 7mmHg and AirSeal system, and 30 with 15mmHg standard insufflator. The primary endpoint was incidence of shoulder pain. A postoperative questionnaire was completed by each patient to assess shoulder pain (Numeric Rating Scale [NRS], from 0 to 10) at H4, H8, H24, and consumption of morphinics was notified. During each procedure, anesthesia parameters were collected (peak airway pressure, systolic blood pressure, end tidal CO2). RESULTS: Laparoscopy was performed on 30 patients in AirSeal®-LP group without need to increase pressure above 7mmHg, and no complication was reported. Incidence of shoulder pain was significantly lower in the AirSeal®-LP group (23.3% vs. 73.3%, P<0.001). NRS shoulder pain was significantly lower in AirSeal® LP group at hour 4, 8 and 24. Maximal values of ETCO2, systolic blood pressure, and peak airway pressure were significantly lower in AirSeal®-LP group. CONCLUSION: LP (7mmHg) laparoscopy with AirSeal® platform allows laparoscopic surgery with less postoperative shoulder pain. These results could facilitate the development of ambulatory laparoscopy.

Evaluation of sentinel lymph node biopsy after previous breast surgery for breast cancer: GATA study.

AIM: Sentinel lymph node (SLN) biopsy was recently recommended after prior breast tumour surgery and lymphadenectomy is not the gold standard anymore for nodal staging after a lesion's removal. The purpose of our study was to evaluate the good practices of use of SLN biopsy in this context. PATIENTS AND METHODS: From 2006 to 2012, 138 patients having undergone a surgical biopsy without prior diagnosis of an invasive carcinoma with a definitive histological analysis in favour of this diagnosis were included in a prospective observational multicentric study. Each patient had a nodal staging following SLN biopsy with subsequent systematic lymphadenectomy. RESULTS: The detection rate of SLN was 85.5%. The average number of SLNs found was 1.9. The relative detection failure risk rate was multiplied by 4 in the event of an interval of less than 36 days between the SLN biopsy and the previous breast surgery, and by 9 in the event of using a single-tracer detection method. The false negative rate was 6.25%. The prevalence of metastatic axillary node involvement was 11.6%. In 69% of cases only the SLN was metastatic. The post-operative seroma rate was 19.5%. CONCLUSION: Previous conservative breast tumour surgery does not affect the accuracy of the SLN biopsy. A sufficient interval of greater than 36 days between the two operations could allow to improve the SLN detection rate, although further studies are needed to validate this statement. CLINICAL TRIAL REGISTRATION NUMBER: NCT00293865.

[Assessment of the benefit-harm balance depending on gestationnal age to induce delivery for post-term pregnancies]. / Évaluation de la balance bénéfice/risque selon l'âge gestationnel pour induire la naissance en cas de grossesse prolongée.

OBJECTIVES: To attempt to determine for post-term pregnancies the optimal gestational age when the benefit-harm balance is in favor of induction labor in comparison with an expectative management including close monitoring. METHODS: Articles were searched using PubMed, Embase and Cochrane library. RESULTS: Current literature data are insufficient to demonstrate that routine labor induction is superior, inferior or equivalent to an expectant management to reduce maternal and perinatal mortality and morbidity (EL2). Although it is impossible to determine certainly a gestational age for which the benefit-harm balance is in favor of induction labor, epidemiological data regarding the perinatal mortality suggest that an expectant management is an unreasonable option after 42 completed weeks (EL3). Current data are insufficient to state positively or negatively that routine labor induction is associated significantly to a lower rate of cesarean delivery in comparison with an expectant management (EL2). There is no evidence of a statistically significant difference in the risk of cesarean section between the two policies for women with favorable cervices (Bishop score ≥ 5) (EL2). CONCLUSIONS: Induction of labor at 41(+0) to 42(+6)weeks should be proposed to women with uncomplicated post-term pregnancies (EL2). The optimal age gestionnal for induction will depend mainly on maternal characteristics (EL4), but also on women's preferences and organization of maternity cares, after having delivered information regarding the benefits and harms of both labor induction and expectant management (expert opinion). After 42(+0)weeks, expectant management is a possible option (expert opinion). Nevertheless, it may be associated with an increase of risks for the fetus, that must be explained to the patient and be weighed against the possible disadvantages of an induction of labor (expert opinion).

[Patient follow-up after treatment for breast cancer]. / Surveillance d'une femme traitée pour cancer du sein.

Patient follow-up after treatment for a breast cancer is based on the local recurrence risk. Annual mammography remains the main point of this follow-up and tumor markers detection has still no interest. Absence of benefit of an intensive clinical, biological and radiological surveillance has been proved for a long time but expert recommendations still are a subject of discussion although they knew no evolution for more than 10 years. Evolution of those follow-up modalities will depend on the future indications of MRI and PET. About distant recurrence, a better knowledge of the risk is now possible thanks to the tumor biological profile study. Nevertheless, intensification of follow-up for some kind of high-risk tumors will have interest only if we can propose a therapeutic alternative in metastatic situation.

[Surgery for invasive breast cancer]. / Chirurgie des cancers invasifs du sein (à l'exception de la reconstruction mammaire).

As most solid tumors, surgery is often the first step of the multidisciplinary management for breast cancers. Although mastectomy and axillar lymphadenectomy still have indications, conservative treatment and sentinel node detection are commonly used. Thanks to induction chemotherapy and oncoplastic techniques, surgery is conservative in most cases, even for important tumors without overall survival prejudice. There is no consensus about resection margins status but a limit of 2 to 3 mm seems to be reasonable while oncoplastic surgery allows large resection and good cosmetic outcomes. In this overview, we present the state of the art for breast cancer surgery including conservative and radical treatments, axillar lymphadenectomy and sentinel lymph node detection, margins status, oncoplastic techniques.

Fertility impairment after mifepristone treatment to rats at proestrus. Actions on the hypothalamic-hypophyseal-ovarian axis.

Accumulated evidence indicates that the antigestagen mifepristone affects the reproductive axis acting on hypothalamic, pituitary, ovarian, and uterine tissues. The purpose of this study was to further investigate which reproductive functions are impaired by the antagonist, critically compromising the reproductive process, leading to unsuccessful pregnancy. Circulating pituitary and ovarian hormones, sexual receptivity, ovulation, and implantation rates were studied in cycling rats receiving a single dose of mifepristone (1 or 10 mg/kg subcutaneously) at 12:00 proestrus, before luteinizing hormone (LH) stimulation of the ovulatory process. Mifepristone-treated rats had decreased preovulatory surges of LH and prolactin (PRL), and hypersecretion of LH, PRL, and progesterone at estrus. The sexual receptivity was dramatically affected by the antagonist as indicated by the profound decrease in the lordosis response evaluated on the night of proestrus. The number of ovulating animals and the number of oocytes recovered from the oviduct on the morning of estrus were not affected by mifepristone. The low number of rats that succeeded in mating with potent males became pregnant. However, they delivered an average of only two pups at parturition, indicating a failure in the implantation of the fertilized ova, as ovulation was not affected by the antagonist at the dose used. We conclude that a dramatic inhibition of the sexual receptivity and unsuccessful implantation, preceded by a reduction on LH and PRL secretion, are the major components leading to fertility impairment after a single dose of mifepristone administered before the preovulatory surge of LH.

PIP: Mifepristone has been demonstrated to act on hypothalamic, pituitary, ovarian, and uterine tissue. To further investigate impairments in reproductive function triggered by this antagonist, circulating pituitary and ovarian hormones, sexual receptivity, ovulation, and implantation rates were studied in cycling Wistar rats receiving a single dose (1 or 10 mg/kg subcutaneously) of mifepristone at 12:00 proestrus, before luteinizing hormone (LH) stimulation of the ovulatory process. Treated rats had decreased preovulatory LH and prolactin (PRL) surges and hypersecretion of LH, PRL, and progesterone as estrus. A profound decrease in the lordosis response on the night of proestrus indicated a dramatic effect on sexual receptivity. There was no affect on the number of ovulating animals and the number of oocytes recovered from the oviduct on the morning of estrus. The few rats who succeeded in mating with potent males became pregnant, but they delivered an average of only two pups, indicating a failure in the implantation of the fertilized ova. These findings suggest that the dramatic inhibition of sexual receptivity and unsuccessful implantation, preceded by a reduction in LH and PRL secretion, are the major factors producing fertility impairment after a single dose of mifepristone before the preovulatory LH surge. factors such as smoking and parity.