Shift in sleep apnoea type in heart failure patients in the CANPAP trial.

In patients with heart failure (HF), the predominant type of sleep apnoea can change over time in association with alterations in circulation time. The aim of this study was to determine whether, in some patients with HF, a spontaneous shift from mainly central (>50% central events) to mainly obstructive (>50% obstructive events) sleep apnoea (CSA and OSA, respectively) over time coincides with improvement in left ventricular ejection fraction (LVEF). Therefore, sleep studies and LVEFs of HF patients with CSA from the control arm of the Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure (CANPAP) trial were examined to determine whether some converted to mainly OSA and, if so, whether this was associated with an increase in LVEF. Of 98 patients with follow-up sleep studies and LVEFs, 18 converted spontaneously to predominantly OSA. Compared with those in the nonconversion group, those in the conversion group had a significantly greater increase in the LVEF (2.8% versus -0.07%) and a significantly greater fall in the lung-to-ear circulation time (-7.6 s versus 0.6 s). In patients with HF, spontaneous conversion from predominantly CSA to OSA is associated with an improvement in left ventricular systolic function. Future studies will be necessary to further examine this relationship.

Risk and severity of motor vehicle crashes in patients with obstructive sleep apnoea/hypopnoea.

BACKGROUND: Obstructive sleep apnoea/hypopnoea (OSAH) appears to be associated with an increased risk of motor vehicle crashes (MVCs). However, its impact on crash patterns, particularly the severity of crashes, has not been well described. A study was undertaken to determine whether OSAH severity influenced crash severity in patients referred for investigation of suspected sleep-disordered breathing. METHODS: Objective crash data (including the nature of crashes) for 783 patients with suspected OSAH for the 3 years prior to polysomnography were obtained from provincial insurance records and compared with data for 783 age- and sex-matched controls. The patient group was 71% male with a mean age of 50 years, a mean apnoea-hypopnoea index (AHI) of 22 events/h and a mean Epworth Sleepiness Scale score of 10. RESULTS: There were 375 crashes in the 3-year period, 252 in patients and 123 in controls. Compared with controls, patients with mild, moderate and severe OSAH had an increased rate of MVCs with relative risks of 2.6 (95% CI 1.7 to 3.9), 1.9 (95% CI 1.2 to 2.8) and 2.0 (95% CI 1.4 to 3.0), respectively. Patients with suspected OSAH and normal polysomnography (AHI 0-5) did not have an increased rate of MVC (relative risk 1.5 (95% CI 0.9 to 2.5), p = 0.21). When the impact of OSAH on MVC associated with personal injury was examined, patients with mild, moderate and severe OSAH had a substantially higher rate of MVCs than controls with relative risks of 4.8 (95% CI 1.8 to 12.4), 3.0 (95% CI 1.3 to 7.0) and 4.3 (95% CI 1.8 to 8.9), respectively, whereas patients without OSAH had similar crash rates to controls with a relative risk of 0.6 (95% CI 0.2 to 2.5). Very severe MVCs (head-on collisions or those involving pedestrians or cyclists) were rare, but 80% of these occurred in patients with OSAH (p = 0.06). CONCLUSION: Patients with OSAH have increased rates of MVCs, and disproportionately increased rates of MVCs are associated with personal injury.

Cost-effectiveness of continuous positive airway pressure therapy in patients with obstructive sleep apnea-hypopnea in British Columbia.

BACKGROUND: Obstructive sleep apnea-hypopnea (OSAH) is a common disorder characterized by recurrent collapse of the upper airway during sleep. Patients experience a reduced quality of life and an increased risk of motor vehicle crashes (MVCs). Continuous positive airway pressure (CPAP), which is the first-line therapy for OSAH, improves sleepiness, vigilance and quality of life. OBJECTIVE: To assess the cost-effectiveness of CPAP therapy versus no treatment for OSAH patients who are drivers. METHODS: A Markov decision analytical model with a five-year time horizon was used. The study population consisted of male and female patients, between 30 and 59 years of age, who were newly diagnosed with moderate to severe OSAH. The model evaluated the cost-effectiveness of CPAP therapy in reducing rates of MVCs and improving quality of life. Utility values were obtained from previously published studies. Rates of MVCs under the CPAP and no CPAP scenarios were calculated from Insurance Corporation of British Columbia data and a systematic review of published studies. MVCs, equipment and physician costs were obtained from the British Columbia Medical Association, published cost-of-illness studies and the price lists of established vendors of CPAP equipment in British Columbia. Findings were examined from the perspectives of a third-party payer and society. RESULTS: From the third-party payer perspective, CPAP therapy was more effective but more costly than no CPAP (incremental cost-effectiveness ratio [ICER] of $3,626 per quality-adjusted life year). From the societal perspective, the ICER was similar ($2,979 per quality-adjusted life year). The ICER was most dependent on preference elicitation method used to obtain utility values, varying almost sixfold under alternative assumptions from the base-case analysis. CONCLUSION: After considering costs and impact on quality of life, as well as the risk of MVCs in individuals with OSAH, CPAP therapy for OSAH patients is a highly efficient use of health care resources. Provincial governments who do not provide funding for CPAP therapy should reconsider.

The impact of obstructive sleep apnea and daytime sleepiness on work limitation.

BACKGROUND: Many patients with obstructive sleep apnea (OSA) participate in the work force. However, the impact of OSA and sleepiness on work performance is unclear. METHODS: To address this issue, we administered the Epworth Sleepiness Scale (ESS), the Work Limitations Questionnaire (WLQ), and an occupational survey to patients undergoing full-night polysomnography for the investigation of sleep-disordered breathing. Of 498 patients enrolled in the study, 428 (86.0%) completed the questionnaires. Their mean age+/-standard deviation (SD) was 49+/-12 years, mean body mass index (BMI) was 31+/-7 kg/m(2) mean apnea hypopnea index (AHI) was 21+/-22 events/h, and mean ESS score was 10+/-5. Subjects worked a mean of 39+/-18 h per week. The first 100 patients to complete the survey were followed up at two years. RESULTS: In the group as a whole, there was no significant relationship between severity of OSA and the four dimensions of work limitation. However, in blue-collar workers, significant differences were detected between patients with mild OSA (AHI 5-15/h) and those with severe OSA (AHI>30/h) with respect to time management (limited 23.1% of the time vs. 43.8%, p=0.05) and mental/personnel interactions (17.9% vs. 33.0%, p=0.05). In contrast, there were strong associations between subjective sleepiness (as assessed by the ESS) and three of the four scales of work limitation. That is, patients with an ESS of 5 had much less work limitation compared to those with an ESS 18 in terms of time management (19.7% vs. 38.6 %, p<0.001), mental-interpersonal relationships (15.5% vs. 36.0%, p<0.001) and work output (16.8% vs. 36.0%; p<0.001). Of the group followed up, 49 returned surveys and 33 who were using continuous positive airway pressure (CPAP) showed significant improvements between the initial and second follow-up in time management (26% vs. 9%, p=0.0005), mental-interpersonal relationships (16% vs. 11.0%, p=0.014) and work output (18% vs. 10%; p<0.009). CONCLUSION: We have demonstrated a clear relationship between excessive sleepiness and decreased work productivity in a population referred for suspected sleep-disordered breathing. Screening for sleepiness and sleep-disordered breathing in the workplace has the potential to identify a reversible cause of low work productivity.

Oral appliances for obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea-hypopnoea (OSAH) is a syndrome characterised by recurrent episodes of partial or complete upper airway obstruction during sleep that are usually terminated by an arousal. Nasal continuous positive airway pressure (CPAP) is the primary treatment for OSAH , but many patients are unable or unwilling to comply with this treatment. Oral appliances (OA) are an alternative treatment for OSAH. OBJECTIVES: The objective was to review the effects of OA in the treatment of OSAH in adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register. Searches were current as of June 2005. Reference lists of articles were also searched. SELECTION CRITERIA: Randomised trials comparing OA with control or other treatments in adults with OSAH . DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Study authors were contacted for missing information. MAIN RESULTS: Sixteen studies (745 participants) met the inclusion criteria. All the studies had some shortcomings, such as small sample size, under-reporting of methods and data, and lack of blinding. OA versus control appliances (six studies): OA reduced daytime sleepiness in two crossover trials (WMD -1.81;95%CI -2.72 to -0.90), and improved apnoea-hypopnoea index (AHI) (-10.78; 95% CI-15.53 to -6.03 parallel group data - five studies). OA versus CPAP (nine studies): OA were less effective than CPAP in reducing apnoea-hypopnoea index (parallel group studies: WMD 13 (95% CI 7.63 to 18.36), two trials; crossover studies: WMD 7.97; (95% CI 6.38 to 9.56, seven trials). However, no significant difference was observed on symptom scores. CPAP was more effective at improving minimum arterial oxygen saturation during sleep compared with OA. In two small crossover studies, participants preferred OA therapy to CPAP. OA versus corrective upper airway surgery (one study): Symptoms of daytime sleepiness were initially lower with surgery, but this difference disappeared at 12 months. AHI did not differ significantly initially, but did so after 12 months in favour of OA. AUTHORS' CONCLUSIONS: There is increasing evidence suggesting that OA improves subjective sleepiness and sleep disordered breathing compared with a control. CPAP appears to be more effective in improving sleep disordered breathing than OA. The difference in symptomatic response between these two treatments is not significant, although it is not possible to exclude an effect in favour of either therapy. Until there is more definitive evidence on the effectiveness of OA in relation to CPAP, with regard to symptoms and long-term complications, it would appear to be appropriate to recommend OA therapy to patients with mild symptomatic OSAH, and those patients who are unwilling or unable to tolerate CPAP therapy. Future research should recruit patients with more severe symptoms of sleepiness, to establish whether the response to therapy differs between subgroups in terms of quality of life, symptoms and persistence with usage. Long-term data on cardiovascular health are required.

Pleuropulmonary disease during bromocriptine treatment of Parkinson's disease.

Pleuropulmonary disease has been observed in eight patients with Parkinson's disease treated with bromocriptine or its related compound, mesulergine. The pleuropulmonary changes included pleural effusions, pleural thickening, and parenchymal lung disease. The patients developed symptoms from nine months to four years after starting treatment with bromocriptine that varied in dosage from 22 to 50 mg daily, while the patient receiving mesulergine was taking 6 mg daily. No other cause was found for the pleuropulmonary changes. In six patients the medication was discontinued with subsequent clinical, physiologic, and radiologic improvement. In two patients bromocriptine treatment was continued for one to two years, and in one patient there was further physiologic and radiologic progression of the pleuropulmonary changes. These findings suggest a causal relationship between bromocriptine treatment and pleuropulmonary disease. We recommend a chest roentgenogram and pulmonary function evaluation prior to bromocriptine treatment with follow-up studies if the patient develops respiratory symptoms. Physicians prescribing bromocriptine should be aware of this side effect to ensure early recognition and prompt withdrawal of bromocriptine therapy.

Production and characterization of monoclonal antibodies to embryo-associated immunosuppressor factor (EASF) produced by human pre-implantation embryo.

Balb/c mice were immunized with pre-implantation embryo-associated immunosuppressor factor (EASF) (purified from embryo growth media of in vitro fertilized human ova). Hybridoma clones were produced by fusing their spleen cells with NS1 and P3X653 myeloma cell lines. The presence of specific anti-EASF monoclonal antibodies (mAb) in the hybridoma culture supernatants were tested by enzyme-linked immunosorbent assay. A total of 15 hybridoma clones were selected, and their products were purified and characterized. Each mAb bound specifically to its antigen in a dose-dependent manner. The affinity-purified EASF from embryo growth media demonstrated immunosuppressive activity on Concanavalin A-induced lymphocytes and the presence of 14 kDa, 24 kDa and 37 kDa factors. No such activity or similar molecules were identified when control growth media were analyzed. This clearly demonstrates that these mAb are indeed EASF-specific and are able to recognize biologically active immunosuppressive components in embryo growth media. These mAbs are presently being tested for the development of EASF-specific assay system.

The predictive accuracy of home oximetry in patients with suspected obstructive sleep apnea.

To evaluate the predictive accuracy of home oximetry, we have performed a questionnaire, physical examination and home oximetry on 96 patients with suspected obstructive sleep apnea (OSA) within 2 weeks of laboratory polysomnography. We have developed a predictive equation that includes questionnaire, anthropometric and home oximetry data to diagnose OSA. We could confidently diagnose OSA in 20% of patients and exclude OSA in 5% of patients based on this prediction model and the population distribution.

Periodic movements of the legs during sleep associated with rises in systemic blood pressure.

We report the relationship between periodic leg movements during sleep and recurrent rises in systemic blood pressure in a patient with narcolepsy. The mean increase in systolic blood pressure following leg movements was 23%, which is of the same order as the rises seen in patients with obstructive sleep apnea. Following treatment with temazepam, the swings in blood pressure were unchanged despite considerably less electroencephalographic evidence of cortical arousal.

Oral appliance therapy for the treatment of obstructive sleep apnea.

A variety of oral appliances (OA) are now available for the treatment of obstructive sleep apnea (OSA), OA therapy is effective in some patients with mild to moderate OSA and is associated with greater patient satisfaction than nasal CPAP. Adjustable OA are associated with improved treatment success and fewer compliance failures compared to non-adjustable OA. Large randomized clinical trials are necessary to further determine the precise indications, benefits, and risks of each OA in the treatment of OSA.

Portable recording in the assessment of obstructive sleep apnea. ASDA standards of practice.

The objective assessment of patients with a presumptive diagnosis of obstructive sleep apnea (OSA) has primarily used attended polysomnographic study. Recent technologic advances and issues of availability, convenience and cost have led to a rapid increase in the use of portable recording devices. However, limited scientific information has been published regarding the evaluation of the efficacy, accuracy, validity, utility, cost effectiveness and limitations of this portable equipment. Attaining a clear assessment of the role of portable devices is complicated by the multiplicity of recording systems and the variability of clinical settings in which they have been analyzed. This paper reviews the current knowledge base regarding portable recording in the assessment of OSA, including technical considerations, validation studies, potential advantages and disadvantages, issues of safety, current clinical usage and areas most in need of further study.

Treatment, airway and compliance effects of a titratable oral appliance.

STUDY OBJECTIVES: To measure the effects of a titratable anterior mandibular repositioner on airway size and Obstructive Sleep Apnea (OSA) and to evaluate its compliance. DESIGN: Before and after insertion sleep studies were obtained in a total of 38 OSA patients of varying severity from three different sites. Covert compliance was measured by means of a newly-developed, miniaturized, temperature-sensitive, imbedded monitor. Validity testing was completed in six adult volunteers who wore monitors imbedded into small acrylic appliances. MEASUREMENTS AND RESULTS: The mean RDI before treatment was 32.6 (SEM 2.1) and after the insertion of the appliance, the RDI was reduced to 12.1 (SEM 1.7, p<0.001). RDI was reduced to less than 15/hour in 80% of a group of moderate OSA patients (RDI 15 to 30) and in 61% of a group of severe OSA patients (RDI > 30) with respect to baseline RDI. Fiber optic video endoscopy was performed on 9 OSA patients with and without the appliance. No significant differences in hypopharynx or oropharynx cross sectional areas were found, but at the level of the velopharynx, the airway size was significantly increased (p<0.05). The index of agreement was 0.99 between the monitor clock time and the subject's log sheets. Compliance data from eight OSA subjects instructed to wear the appliance during sleep indicated that it was worn for a mean of 6.8 hours with a range of 5.6 to 7.5 hours per night. CONCLUSION: The titratable adjustable mandibular advancement appliance, made from thermoelastic acrylic, significantly reduces RDI in moderate to severe OSA patients, has a direct effect on airway size and is well worn throughout the night.

Respiratory dysrhythmias in patients with tardive dyskinesia.

Tardive dyskinesia (TD) is a disorder characterized by abnormal involuntary movements and associated with neuroleptic therapy. To determine whether the respiratory muscles are involved in this condition, we compared the breathing pattern of ten patients with TD with ten patients with chronic schizophrenia receiving neuroleptic therapy without evidence of TD, and ten age-matched normal control subjects during resting tidal breathing, forearm pronation-supination (a maneuver designed to elicit the abnormal movements of TD), and breathing to a set frequency. Breathing patterns were also assessed in seven patients with TD during a progressive incremental exercise test and an overnight polysomnogram. Patients with TD had an irregular tidal breathing pattern, with a greater variability in both tidal volume and time of the total respiratory cycle (TTOT). Both groups of patients receiving neuroleptic therapy had a rapid shallow breathing pattern when performing forearm pronation-supination compared with control subjects. There were no differences between any of the subject groups when breathing to a set frequency. The patients with TD had a normal response to progressive exercise and inspiratory time and TTOT values were less variable during non-rapid eye movement sleep compared with wakefulness. We conclude that patients with TD have irregular rapid shallow breathing which is less variable during sleep and does not limit their exercise performance.

Long-term survival of patients with obstructive sleep apnea treated by uvulopalatopharyngoplasty or nasal CPAP.

Patients with obstructive sleep apnea (OSA) have decreased long-term survival. Treatment of OSA with either nasal continuous positive airway pressure (CPAP) or tracheostomy improves survival, but the effect of uvulopalatopharyngoplasty (UPPP) on survival is unclear. We attempted to contact all patients with OSA treated with either UPPP or nasal CPAP over a 6-year period to compare long-term survival between these two treatments. One hundred fifty-four patients had a UPPP during this period. Five of these patients were later treated with nasal CPAP and were excluded from the analysis. Twelve of the remaining 149 were unavailable for follow-up but were included in the analysis. Follow-up polysomnography was performed on 140 (94 percent) of these patients; 114 (81 percent) had either a postoperative apnea index < 5/h or > 50 percent reduction in apnea index. Two hundred eight patients were started on a regimen of nasal CPAP during the same period. Eighty-two patients discontinued nasal CPAP therapy and were excluded from analysis. Nine of the remaining 126 were unavailable for follow-up but were included in the analysis. Six patients treated with UPPP died. Three of these six patients had a 3-month follow-up polysomnogram that revealed apnea indices of 1/h, 5/h, and 23/h. Three patients treated with nasal CPAP died. There was no difference in the long-term survival between the two treatment groups. We conclude that there may be no difference in the long-term survival of patients with OSA between those treated with UPPP and those treated with nasal CPAP. This study emphasizes the importance of follow-up polysomnography in all patients after UPPP.

The acute effects of continuous positive airway pressure and oxygen administration on blood pressure during obstructive sleep apnea.

We have measured blood pressure continuously with a digital artery blood pressure monitor in eight patients with severe obstructive sleep apnea (OSA) during 30 min each of wakefulness, OSA, OSA with added oxygen to keep saturation above 96 percent at all times (OSA+O2), and nasal continuous positive airway pressure (CPAP) therapy. Mean blood pressures were not different between wakefulness, OSA, OSA+O2, and CPAP, although the variability in blood pressure was significantly greater during OSA and OSA+O2 than during wakefulness and CPAP. The addition of oxygen did not attenuate the variability in blood pressure. Using multiple linear regression modeling to further dissect out the principal variables determining the postapneic blood pressure rise, we found that only apnea length (r2 = 0.28, p less than 0.0001) and pulse rate changes (r2 = 0.15, p less than 0.0001) remained significantly related to SBPmax, while hypoxemia did not. We found the same trends in the other variables SBPten, DBPmax, and DBPten. Hypoxemia made a small contribution to the size of DBPmax, although this was small by comparison with apnea length. We conclude that CPAP treatment of OSA does not lower mean blood pressure acutely, although it significantly reduces the large oscillations in blood pressure seen in patients with untreated OSA. The rise in blood pressure following each apnea is not primarily due to arterial desaturation but is related to apnea length and may be caused by increased sympathetic activity secondary to arousal.

The relationship between obesity and craniofacial structure in obstructive sleep apnea.

STUDY OBJECTIVE: To evaluate the interaction between craniofacial structure and obesity in male patients with obstructive sleep apnea (OSA). DESIGN: Retrospective analysis of a cohort of OSA patients. The relationships between neck circumference (NC), body mass index, apnea severity, and craniofacial and upper airway soft-tissue measurements from upright lateral cephalometry were examined. Patients were divided into groups; small to normal NC (group A), intermediate NC (group B), or large NC (group C). SETTING: A university teaching hospital and tertiary sleep referral center. PATIENTS: A consecutive series of patients with OSA who underwent polysomnography and lateral cephalometry. MEASUREMENTS AND RESULTS: Group A patients were less obese and had more craniofacial abnormalities such as a smaller mandible and maxilla and a more retrognathic mandible. Group B patients had both upper airway soft-tissue and craniofacial abnormalities. Group C patients were more obese with larger tongues and soft palates, and an inferiorly placed hyoid. Group C patients also had fewer craniofacial abnormalities than group A or B patients. There was no difference in airway size among the three groups. CONCLUSIONS: We conclude that there is a spectrum of upper airway soft-tissue and craniofacial abnormalities among OSA patients: obese patients with increased upper airway soft-tissue structures, nonobese patients with abnormal craniofacial structure, and an intermediate group of patients with abnormalities in both craniofacial structure and upper airway soft-tissue structures.

A randomized crossover study of an oral appliance vs nasal-continuous positive airway pressure in the treatment of mild-moderate obstructive sleep apnea.

STUDY OBJECTIVE: To compare efficacy, side effects, patient compliance, and preference between oral appliance (OA) therapy and nasal-continuous positive airway pressure (N-CPAP) therapy. DESIGN: Randomized, prospective, crossover study. SETTING: University hospital and tertiary sleep referral center. PATIENTS: Twenty-seven unselected patients with mild-moderate obstructive sleep apnea (OSA). INTERVENTIONS: There was a 2-week wash-in and a 2-week wash-out period, and 2 x 4-month treatment periods (OA and N-CPAP). Efficacy, side effects, compliance, and preference were evaluated by a questionnaire and home sleep monitoring. MEASUREMENTS AND RESULTS: Two patients dropped out early in the study and treatment results are presented on the remaining 25 patients. The apnea/hypopnea index was lower with N-CPAP (3.5 +/- 1.6) (mean +/- SD) than with the OA (9.7 +/- 7.3) (p < 0.05). Twelve of the 25 patients who used the OA (48%) were treatment successes (reduction of apnea/hypopnea to <10/h and relief of symptoms), 6 (24%) were compliance failures (unable or unwilling to use the treatment), and 7 (28%) were treatment failures (failure to reduce apnea/hypopnea index to <10/h and/or failure to relieve symptoms). Four people refused to use N-CPAP after using the OA. Thirteen of the 21 patients who used N-CPAP were overall treatment successes (62%), 8 were compliance failures (38%), and there were no treatment failures. Side effects were more common and the patients were less satisfied with N-CPAP (p < 0.005). Seven patients were treatment successes with both treatments, six of these patients preferred OA, and one preferred N-CPAP as a long-term treatment. CONCLUSIONS: We conclude that OA is an effective treatment in some patients with mild-moderate OSA and is associated with fewer side effects and greater patient satisfaction than N-CPAP.

Protein synthetic patterns in immature and mature human oocytes.

A preliminary study of protein synthesis and amino acid transport in human oocytes was initiated. Qualitative patterns or protein synthesis were examined in individual oocytes cultured in medium containing radiolabeled methionine. The protein synthetic profile of immature oocytes, resolved by one-dimensional electrophoresis and fluorography, was observed to change markedly following germinal vesicle breakdown and oocyte maturation. No further differences in the one-dimensional protein synthetic patterns were observed in mature oocytes maintained in culture from 10 hours up to as long as 50 hours. The protein synthetic pattern of follicular cells was observed to be distinct from that of oocytes and was characterized by the predominant synthesis of a polypeptide with Mr = 44,000. Based on the specific activity of the methionine precursor, the absolute rate of synthesis was calculated to be about 50 pg protein/oocyte/hour. Total protein content was measured to be about 150 ng/egg. Competition of methionine uptake by leucine, efflux of radiolabeled methionine from preloaded oocytes into medium containing methionine and uptake of methionine in medium with low sodium ion concentration was observed. These findings are consistent with the presence of an L (leucine-preferring) system for neutral amino acid transport, similar to that in mouse and rabbit eggs. These studies provide basic data for further analysis of oocytes and perhaps preimplantation-stage embryos in the future.

Effects of progesterone on luteinizing hormone release and estradiol/progesterone ratio in the luteal phase of women superovulated for in vitro fertilization and embryo transfer.

The present study extends the information on the effects of progesterone (P) on the luteinizing hormone (LH) release, and estradiol (E2)/P ratio in the luteal phase in women superovulated for in vitro fertilization and embryo transfer (IVF-ET). Two groups of 34 patients were induced for ovulation with clomiphene citrate and human menopausal gonadotropins. One group was given 25 mg P (Gesterol, Steris Laboratory Inc., Phoenix, AZ) at the time of, or 4 to 6 hours before human chorionic gonadotropin (hCG) administration and another group served as control (no Gesterol). Of the 34 patients in the Gesterol group, 10 had Gesterol 4 to 6 hours before the administration of hCG, 13 at the time of hCG, and 11 after the spontaneous LH surge. Administration of Gesterol 4 to 6 hours before hCG significantly increased the LH values (19.0 +/- 10.3) compared with those who had Gesterol at the time of hCG (6.8 +/- 2.8, P = 0.0006). A single dose of Gesterol (25 mg P) significantly reduced the E2/P ratio during the luteal phase (P = 0.0005). However, the outcome of IVF-ET was the same in the Gesterol and no-Gesterol groups. It is concluded that a significant increase in P triggers an LH surge and a single dose of Gesterol decreases E2/P ratio in the luteal phase of women after ovarian stimulation. The biochemical mechanisms are unclear.