Determination of Escherichia coli phylogroups in elderly patients with urinary tract infection or asymptomatic bacteriuria

ObjectivesDistinguishing between urinary tract infection (UTI) and asymptomatic bacteriuria (ABU) is difficult in the geriatric population since specific symptoms are often lacking. Escherichia coli is the most frequent UTI pathogen in this population but also a common urine colonizer. We hypothesized that detecting E. coli phylogroups B2 or D, which were previously associated with virulent strains responsible for extra-intestinal infections outside elderly patients, could help in distinguishing UTI from ABU.MethodsConsecutive cases of E. coli bacteriuria diagnosed in hospitalized patients >75 years old during 3 months were investigated for E. coli phylogroups. Multiplex PCR was used to search for several virulence genes as previously described. Characteristics of UTI and ABU cases, assessed retrospectively according to definitions and geriatric expertise, were compared.ResultsOut of 233 bacteriuria cases, 60 were assessed to be UTI and 163 to be ABU, with 10 cases unclassified. E. coli strains belonging to the phylogroups B2 and D were significantly more frequent in UTI (48/60, 80%) than in ABU (101/163, 62%) by univariate and multivariate analyses (OR 3.05, 1.44–6.86, p 0.005). Out of all the host and bacterial characteristics studied, falls (p 0.032), comorbidities (p 0.041), and altered autonomy evaluated by a low activity of daily living score (p 0.027) were also associated with UTI using univariate and multivariate analysis.ConclusionsDetermination of the E. coli phylogroup, in addition to some host characteristics, can help to distinguish UTI from ABU in elderly patients with bacteriuria. If this hypothesis is confirmed by prospective studies, then inappropriate use of antibiotics may be reduced in ABU cases.     

Herbal treatment with uva ursi extract versus fosfomycin in women with uncomplicated urinary tract infection in primary care: a randomized controlled trial

ObjectiveWe explored whether initial treatment with the herbal drug uva ursi (UU) reduces antibiotic use in women with uncomplicated urinary tract infection (UTI) without increasing symptom burden and complication frequency compared with antibiotic treatment.MethodsA double-blind randomized controlled trial was conducted in 42 family practices in Germany. The participants were adult women with suspected uncomplicated UTIs receiving either UU 105 mg 3 × 2 tablets for 5 days (intervention) or fosfomycin a 3-g single dose (control), and their respective placebos. Participants and investigators were blinded. The primary outcome included (1) antibiotic courses day 0–28 as superiority, and (2) symptom burden (sum of daily symptom scores) day 0–7, as non-inferiority outcome (margin 125%). Clinicaltrials.gov: NCT03151603.ResultsOverall, 398 patients were randomly allocated to groups receiving UU (n = 207) and fosfomycin (n = 191). The number of antibiotic courses was 63.6% lower (95% CI 53.6%–71.4%; p < 0.0001) in the UU group than in the fosfomycin group. The ratio of total symptom burden in the UU group compared with control was 136.5% (95% CI 122.7–151.9; p 0.95), failing non-inferiority. Eight women developed pyelonephritis in the UU group compared with two in the fosfomycin group (mean difference 2.8; 95% CI 0.2–5.9; p 0.067). Adverse events were similar between the groups.DiscussionIn women with uncomplicated UTIs, initial treatment with UU reduced antibiotic use but led to a higher symptom burden and more safety concerns than fosfomycin.     

Oral decontamination with colistin plus neomycin in solid organ transplant recipients colonized by multidrug-resistant Enterobacterales: a multicentre,randomized, controlled,open-label,parallel-group clinical trial

ObjectivesTo evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients.MethodsMulticentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum β-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed.ResultsMDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24–2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea.ConclusionsDT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously.     

An open-label randomized clinical trial to evaluate the efficacy of everolimus versus tacrolimus in triple maintenance immunosuppressive therapy for kidney transplant patients

Tacrolimus (TAC), a calcineurin inhibitor, and everolimus (EVL), an mTOR inhibitor, have been used as immunosuppressive (ISS) drugs in post-kidney transplantation therapy. The objective of this study was to compare the efficacy of EVL vs TAC in the ISS maintenance triple therapy. Ninety-seven kidney transplant patients, who received triple maintenance therapy with TAC, mycophenolate mofetil (MMF), and methyl prednisone (PRED), were evaluated. After four months of post-kidney transplant therapy, 30 patients enrolled in a randomized controlled clinical trial, in which 16 patients received TAC+MMF+PRED (cohort 1), and 14 patients switched to EVL+MMF+PRED (cohort 2). The patients were followed-up for 36 months. Two patients from cohort 1 lost their grafts after one year due to non-adherence. Two patients from cohort 2 had intolerance to mTOR inhibitors and were switched back to TAC from EVL. One case (6.25%) in cohort 1 and three cases (21.43%) in cohort 2 of acute T-cell-mediated rejection was observed. Antibody-mediated acute rejection (ABMAR) was observed in four patients (25.0%) in cohort 1, and antibody-mediated chronic rejection (ABMCR) was observed in two patients (12.50%). One patient from cohort 2 lost the graft after 15 months due to polyomavirus infection. The graft survival rate was 87.50% in cohort 1 and 92.86% in cohort 2. This clinical trial showed that the EVL+MMF+PRED triple maintenance therapy was efficacious compared with TAC during 32 months of follow-up. However, further studies are needed to confirm the efficacy of this regimen for long-term graft survival.     

A comparison of mycophenolate mofetil and calcineurin inhibitor as maintenance immunosuppression for kidney transplant recipients: A meta-analysis of randomized controlled trials

Background/aim We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the comparison and its timing between mycophenolate mofetil (MMF) and calcineurin inhibitor (CNI) as maintenance immunosuppression for kidney transplant recipients. Materials and methodsThe RCTs of MMF versus CNI as maintenance immunosuppression for kidney transplant recipients were searched from PubMed, Embase, Cochrane Central Register of Controlled Trials (CCRCT), and ClinicalTrials.gov. After screening relevant RCTs, two authors independently assessed the quality of included studies and performed a meta-analysis using RevMan5.3. Relative risk (RR) was used to report dichotomous data, while mean difference (MD) with 95% confidence interval (CI) was used to report continuous outcomes. The analysis was conducted using the random-effect model due to the expected heterogeneity among different studies. Four subgroups were allocated to compare MMF with CNI as maintenance immunosuppression: (1) after 3 months of CNI-based therapy, (2) after 6 months of CNI-based therapy, (3) after 12 months of CNI-based therapy, and (4) in recipients with allograft dysfunction.Results Twelve RCTs with 950 renal transplant recipients were included. This meta-analysis presented the following results upon comparison between MMF and CNI as maintenance immunosuppression for kidney transplant recipients: (1) MMF significantly improved the glomerular filtration rate (GFR) not only in the comparison performed after 3, 6, or 12 months of CNI-based therapy but also in the comparison of recipients with allograft dysfunction, (2) MMF may increase the risk of acute rejection in the comparison performed after 3 months of CNI-based therapy, but no increase was noted in the comparison performed after 6 or 12 months of CNI-based therapy. Conclusion Our present meta-analysis suggested that MMF followed at least 6 months of CNI-based therapy is an effective maintenance immunosuppressive regimen for kidney transplant recipients to improve renal function but not increase rejection.     

Comparison of ertapenem and ceftriaxone therapy for acute pyelonephritis and other complicated urinary tract infections in Korean adults: a randomized, double-blind, multicenter trial

The efficacy and safety of ertapenem, 1 g once daily, were compared with that of ceftriaxone, 2 g once daily, for the treatment of adults with acute pyelonephritis (APN) and complicated urinary tract infections (cUTIs) in a prospective, multicenter, double-blinded, randomized study. After ≥ 3 days of parenteral study therapy, patients could be switched to an oral agent. Of 271 patients who were initially stratified by APN (n = 210) or other cUTIs (n = 61), 66 (48.9%) in the ertapenem group and 71 (52.2%) in the ceftriaxone group were microbiologically evaluable. The mean duration of parenteral and total therapy, respectively, was 5.6 and 13.8 days for ertapenem and 5.8 and 13.8 days for ceftriaxone. The most common pathogen was Escherichia coli. At the primary efficacy endpoint 5-9 days after treatment, 58 (87.9%) patients in the ertapenem group and 63 (88.7%) in the ceftriaxone had a favorable microbiological response. When compared by stratum and severity, the outcomes in the two groups were equivalent. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. The results indicate that ertapenem is highly effective and safe for the treatment of APN and cUTIs.     

Factors associated with asymptomatic infection in health-care workers with severe acute respiratory syndrome coronavirus 2 infection in Wuhan,China: a multicentre retrospective cohort study

ObjectivesTo describe the fraction of asymptomatic health-care workers (HCWs) in two designated hospitals for coronavirus disease 2019 (COVID-19) treatment in Wuhan and explore the factors associated with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.MethodsAll HCWs in Wuhan Union Hospital and Wuhan Red Cross Hospital with either positive SARS-CoV-2 nucleic acid or positive antibody test before 18 April 2020 were included. Exposure, epidemiological and demographic information were retrospectively collected by a structured questionnaire. Medical records were also reviewed for clinical characteristics and CT images of HCWs.ResultsAs of 18 April 2020, a total of 424 HCWs were identified. Among them, 276 (65.1%) were symptomatic and 148 (34.9%) were asymptomatic. Fifty-five (19.9%) families of the symptomatic HCWs and 16 (10.8%) families of the asymptomatic HCWs were infected with SARS-CoV-2. HCWs with infected family members tended to be symptomatic (OR 2.053, 95% CI 1.130–3.730; p 0.018). Multivariable logistic regression analysis exhibited that performing tracheal intubation or extubation (OR 4.057, 95% CI 1.183–13.909; p 0.026) was associated with an increased likelihood of symptomatic SARS-CoV-2 infection, whereas consistent use of N95 respirators (OR 0.369, 95% CI 0.201–0.680; p 0.001) and eye protection (OR 0.217, 95% CI 0.116–0.404; p < 0.001) were associated with an increased likelihood of asymptomatic SARS-CoV-2 infection.ConclusionsAsymptomatic SARS-CoV-2 infection in HCWs comprised a considerable proportion of HCW infections during the pandemic of COVID-19. Those who performed tracheal intubation or extubation were most likely to develop related symptoms, whereas those taking aggressive measures, including consistent use of N95 masks and eye protection, tended to be asymptomatic cases.     

Tacrolimus (FK506) versus cyclosporin A microemulsion (Neoral) maintenance immunosuppression: effects on graft survival and function,infection, and metabolic profile following kidney transplantation (KT)

We reviewed two groups of kidney transplant patients receiving neoral (Group I, 27 patients) or FK506 (Group II, 25 patients) as maintenance immunosuppression between December 1998 and May 2002. The recipient and donor demographics and induction therapy were comparable in both groups except for more highly sensitized patients in Group II. Acute rejection (AR) rate and timing were similar in both groups except for more steroid resistant AR in Group II (P=0.04). Infections rate was similar in both groups (25.9% in Group I and 36% in Group II; P=N.S.), but there were less viral infections in Group I (0%) than Group II (29%; 4 CMV). CMV infections were related to the presence in Group II of more CMV-negative recipients getting kidneys from CMV-positive donors. The metabolic profile was comparable between the two groups, except for a better HDL in Group II (48.2+/-7.6) versus Group I (45+/-2.2; P=0.021). Mean serum creatinine levels upon discharge, at 1, 3 and 6 months were: 1.62+/-0.32, 1.4+/-0.17, 1.39+/-0.14 and 1.4+/-0.14 in Group I and 2.15+/-0.5, 1.48+/-0.23, 1.41+/-0.21 and 1.23+/-0.11 in Group II, respectively. The 6 months actuarial patient and graft survival were identical in both groups (100 and 100%). Both calcineurin inhibitors are effective and safe in KT. The higher rate of AR in Group II was related to more highly sensitized patients and the higher CMV infections was due to the presence of more CMV-negative recipients receiving kidneys from CMV-positive donors. The same study will be continued to evaluate the long term effects of both drugs.     

Incidence,distribution and clinical relevance of microbial contamination of preservation solution in deceased kidney transplant recipients: a retrospective cohort study from China

ObjectivesTo determine whether microbial contamination of preservation solution (PS) in kidney transplantation is associated with donor-derived infections (DDIs).MethodsWe retrospectively analysed data from 1077 deceased kidney transplant recipients of 560 donors. In all, 1002 PS samples were collected for microbiological assessment to establish the incidence and distribution of contamination. Comparisons between patients with contaminated PS and those with sterile PS were performed to assess the impact of microbial contaminations in perfusate on probable donor-derived infections (p-DDIs), and potential risk factors for p-DDIs were examined.ResultsThe contamination rate of PS was 77.8% (402/517). Bacterial species accounted for 85.6% (887/1036) of the total 1036 isolated microorganisms and 26.5% (275/1002) of the recipients' PS were contaminated by ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.). Enterococcus predominated the microbiological pattern. The incidence of infection was significantly higher in patients with microbial contamination than in patients with sterile PS (13.8% (107/776) versus 7.1% (16/226), p 0.006). The prevalence of p-DDIs was significantly higher in patients with ESKAPE contamination than in patients with other bacterial contamination in PS (7.2% (18/251) versus 1.0% (4/405), p 0.000). Univariate analysis indicated that ESKAPE contamination increased the risk of p-DDIs (p 0.001, OR 3.610, 95% CI 1.678–7.764). Multivariate analysis determined ESKAPE contamination as the only independent risk factor associated with p-DDIs (OR 3.418, 95% CI 1.580–7.393).ConclusionsThe high rate of microbial contaminations in PS is unusual and probably due to poor surgical procedures. Patients whose PS are contaminated by ESKAPE pathogens could have a significantly increased risk of p-DDIs at early post-transplantation.     

Biofilm formation in long-term central venous catheters in children with cancer: a randomized controlled open-labelled trial of taurolidine versus heparin

Taurolidine has demonstrated inhibition of biofilm formation in vitro. The aim of this study was to compare the effect of catheter locking with taurolidine vs heparin in biofilm formation in central venous catheters. Forty‐eight children with cancer were randomized to catheter locking by heparin (n = 22) or taurolidine (n = 26), respectively. After removal, catheters were examined by standardized scanning electron microscopy to assess quantitative biofilm formation. Biofilm was present if morphologically typical structures and bacterial cells were identified. Quantitative and semi‐quantitative cultures were also performed. Biofilm was identified in 23 of 26 catheters from the taurolidine group and 21 of 22 catheters from the heparin group. A positive culture was made of six of the catheters locked with taurolidine and heparin, respectively (p = 0.78). The rate of catheter‐related bloodstream infections (CRBSI) was 0.1 per 1000 catheter‐days using taurolidine and 0.9 per 1000 catheter‐days using heparin (p = 0.03). This randomized trial confirmed that the use of taurolidine as catheter‐lock compared with heparin reduced the rate of CRBSIs; this reduction was not related to a reduction in the intraluminal biofilm formation and the rate of bacterial colonization detected by scanning electron microscopy in the two groups.     

Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre,randomized, double-blind controlled trial

ObjectivesTo determine if commercially available mouthwash with β-cyclodextrin and citrox (bioflavonoids) (CDCM) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral load.MethodsIn this randomized controlled trial, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive patients aged 18–85 years with asymptomatic to mild coronavirus disease 2019 (COVID-19) symptoms for <8 days were recruited. A total of 176 eligible patients were randomly assigned (1:1) to CDCM or placebo. Three rinses daily were performed for 7 days. Saliva sampling was performed on day 1 at 09.00 (T1), 13.00 (T2) and 18.00 (T3). On the following 6 days, one sample was taken at 15.00. Quantitative RT-PCR was used to detect SARS-CoV-2.ResultsThe intention-to-treat analysis demonstrated that, over the course of 1 day, CDCM was significantly more effective than placebo 4 hours after the first dose (p 0.036), with a median percentage (log₁₀ copies/mL) decrease T1–T2 of –12.58% (IQR –29.55% to –0.16%). The second dose maintained the low median value for the CDCM (3.08 log₁₀ copies/mL; IQR 0–4.19), compared with placebo (3.31 log₁₀ copies/mL; IQR 1.18–4.75). At day 7, there was still a greater median percentage (log₁₀ copies/mL) decrease in salivary viral load over time in the CDCM group (–58.62%; IQR –100% to –34.36%) compared with the placebo group (–50.62%; IQR –100% to –27.66%). These results were confirmed by the per-protocol analysis.ConclusionsThis trial supports the relevance of using CDCM on day 1 (4 hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7 days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva.     

Continuation therapy with lithium and amitriptyline in unipolar depressive illness: a randomized, double-blind, controlled trial

A detailed analysis of the results of a multi-centre clinical trial shows that, while the relapse rate following recovery from an operationally defined depressive illness was smaller among patients subsequently treated with either amitryptiline or lithium than with a placebo, there was no clinically significant difference between the prophylactic efficacy of the 2 antidepressants. An account is given of the relative adverse effects of the treatments, and the implications of the findings are discussed.     

Successful low-dose leflunomide treatment for ganciclovir-resistant cytomegalovirus infection with high-level antigenemia in a kidney transplant: A case report and literature review

Ganciclovir-resistant cytomegalovirus infection is sometimes life-threatening for organ transplant recipients. Foscarnet is an alternative, although it may potentially worsen the preexistent impaired renal function. Here we report the case of a successful low-dose leflunomide treatment in a kidney transplant recipient with very high viral replication, who underwent kidney transplantation 10 years before. Administering 10 mg leflunomide daily for 5 months without a loading dose completely cleared the ganciclovir-resistant cytomegalovirus strains.     

Skin disinfection with octenidine dihydrochloride for central venous catheter site care: a double-blind,randomized, controlled trial

To compare the efficacy of two commercially available, alcohol-based antiseptic solutions for preparation and care of central venous catheter (CVC) insertion sites, with and without octenidine dihydrochloride, a double-blind, randomized, controlled trial was undertaken in the haematology units and in one surgical unit of two university hospitals. Adult patients with a non-tunnelled CVC were randomly assigned to two different skin disinfection regimens at the insertion site: 0.1% octenidine with 30% 1-propanol and 45% 2-propanol, and as control 74% ethanol with 10% 2-propanol. Endpoints were (i) skin colonization at the insertion site; (ii) -positive culture from the catheter tip (≥15 CFU); and (iii) occurrence of CVC-associated bloodstream infection (defined according to criteria set by the CDC). Four hundred patients with inserted CVC were enrolled from May 2002 through April 2005. Both groups were similar in respect of patient characteristics and co-morbidities. Skin colonization at the CVC insertion site during the first 10 days was significantly reduced by octenidine treatment (relative difference octenidine vs. control: 0.21; 95%CI: 0.11–0.39, p <0.0001). -positive culture of the catheter tip was significantly less frequent in the octenidine group (7.9%) than in the control group (17.8%): OR = 0.39 (95%CI: 0.20–0.80, p 0.009). Patients treated with octenidine had a non-significant reduction in catheter-associated bloodstream infections (4.1% vs. 8.3%; OR = 0.44; 95%CI: 0.18–1.08, p 0.081). Side effects were similar in both groups. This randomized controlled trial supports the results of two observational studies demonstrating octenidine in alcoholic solution to be a better option than alcohol alone for the prevention of CVC-associated infections.     

Incidence,management and outcome of respiratory syncytial virus infection in adult lung transplant recipients: a 9-year retrospective multicentre study

ObjectivesTo analyse functional outcome parameters according to antimicrobial treatments after respiratory syncytial virus (RSV)-confirmed infection in adult lung transplant recipients.MethodsA 9-year retrospective multicentre cohort study (2011–19) included adult lung transplant recipients with RSV-confirmed infection. The first endpoint determined new allograft dysfunction (acute graft rejection and chronic lung allograft dysfunction (CLAD)) 3 months after infection. Then baseline and 3 months' postinfection forced expiratory volume in 1 second (FEV₁) values were compared according to antimicrobial treatment. Univariate logistic regression analysis was performed.ResultsRSV infection was confirmed in 77 of 424 lung transplant recipients (estimated incidence of 0.025 per patient per year; 95% confidence interval 0.018–0.036). At 3 months, 22 recipients (28.8%) developed allograft dysfunction: ten (13%) possible CLAD, six (7.9%) acute rejection and six (7.9%) CLAD. Recipients with the lowest preinfection FEV₁ had a greater risk of developing pneumonia (median (interquartile range) 1.5 (1.1–1.9) vs. 2.2 (1.5–2.4) L/s, p 0.003) and a higher odds of receiving antibiotics (1.6 (1.3–2.3) vs. 2.3 (1.9–2.5) L/s, p 0.017; odds ratio 0.52, 95% confidence interval 0.27–0.99). Compared to tracheobronchitis/bronchiolitis, RSV-induced pneumonia led more frequently to hospitalization (91.7%, 22 vs. 58.0%, 29, p 0.003) and intensive care unit admission (33.3%, 8 vs. 0, p < 10^-3). For ribavirin-treated recipients (24.7%, 19) and azithromycin prophylaxis (50.6%, 39), 3-month FEV₁ values were not different from untreated recipients. The overall mortality was 2.5% at 1 month and 5.3% at 6 months, unrelated to RSV.ConclusionsAt 3 months after RSV-confirmed infection, 22 recipients (28.8%) had new allograft dysfunction. Ribavirin treatment and azithromycin prophylaxis did not prevent FEV₁ decline.     

Recombinant human LH supplementation versus recombinant human FSH (rFSH) step-up protocol during controlled ovarian stimulation in normogonadotrophic women with initial inadequate ovarian response to rFSH. A multicentre, prospective, randomized controlled trial

BACKGROUND: In approximately 12-14% of young normogonadotrophic women treated with a depot GnRH agonist long protocol, the initial ovarian response to recombinant human FSH (rFSH) can be suboptimal. We have tested the hypothesis that these women may benefit from recombinant human LH (rLH) supplementation in a multicentre, prospective, randomized trial compared with patients treated with an rFSH step-up protocol. METHODS: A total of 260 young normogonadotrophic women undergoing controlled ovarian stimulation with a GnRH agonist long protocol for IVF/ICSI were enrolled. The starting dose of rFSH was 225 IU. One hundred and thirty patients with serum estradiol levels <180 pg/ml and with at least six follicles with a mean diameter >5 mm but none >10 mm on both day 5 and day 8 of stimulation were randomly allocated to two groups. From the eighth day of stimulation, women in group A (n=65) received 150 IU of rLH in addition to rFSH, while those in group B (n=65) had an increase of 150 IU in the daily dose of rFSH (step-up protocol). One hundred and thirty normally responding women continued monotherapy with rFSH and served as a further control population (group C). RESULTS: The mean number of cumulus-oocyte complexes retrieved in group A (9.0+/-4.3) was significantly higher (P<0.01) compared with group B (rFSH 6.1+/-2.6) but significantly lower compared with group C (10.49+/-3.7, P<0.05). Implantation and pregnancy rates were significantly lower (P<0.05) in the rFSH step-up group (10.5 and 29.3% respectively) when compared with normal responders (18.1 and 47.3% respectively). CONCLUSIONS: rLH supplementation is more effective than increasing the dose of rFSH in terms of ovarian outcome in patients with an initial inadequate ovarian response to rFSH alone.