Nitrofurantoin for the treatment of uncomplicated urinary tract infection in female patients: the impact of dosing regimen, age, and renal function on drug exposure.

PURPOSE: The aim of this study is to determine nitrofurantoin exposure in female patients with different age and renal function with complaints of an uncomplicated UTI. Also the nitrofurantoin exposure in relation to the dosage regimen will be studied. METHODS: Eight general practitioners (GP) participated in the study and included 38 patients with symptoms of an uncomplicated UTI, treated either with a dose of 50 mg q6h or 100 mg q12h, upon the discretion of the GP. Nitrofurantoin exposure was quantified in the patient's 24-h urine samples by UHPLC-UV and the area under the curve was calculated. RESULTS: The 38 patients provided a range of 2-17 urine samples. The urine nitrofurantoin exposure was 1028 mg h/L for the patients receiving 50 mg q6h and 1036 mg h/L for those treated with 100 mg q12h (p = 0.97) and was not affected by age and eGFR (p = 0.64 and p = 0.34, respectively). CONCLUSION: The data obtained do not support the discouragement of nitrofurantoin use in the elderly and in patients with impaired renal function. Since only a small number of patients were included, a larger study with more patients is warranted to evaluate nitrofurantoin exposure and adverse effects.

Lactating dairy cows managed for second and greater artificial insemination services with the Short-Resynch or Day 25 Resynch program had similar reproductive performance.

The objective of this randomized controlled experiment was to evaluate reproductive performance and reproductive physiological outcomes of lactating Holstein cows managed for second and greater artificial insemination (AI) services with the Short-Resynch or Day 25 Resynch program. Cows from 2 commercial farms were randomly assigned after first service to the Short-Resynch (SR; n = 870) or Day 25 Resynch (D25R; n = 917) program in which they remained until 210 d after first service or left the herd. Cows in D25R received GnRH 25 ± 3 d after AI, whereas cows in SR did not. Cows not reinseminated at detected estrus (AIE) by 32 ± 3 d after AI underwent nonpregnancy diagnosis (NPD) through transrectal ultrasonography (TUS). Nonpregnant cows from both treatments with a corpus luteum (CL) ≥15 mm and an ovarian follicle ≥10 mm (hereafter, CL cows) received 2 PGF2α treatments 24 h apart, GnRH 32 h after the second PGF2α, and timed AI 16 to 18 h later. Cows that did not meet the criteria to be included in the CL group (NoCL cows) received a modified Ovsynch protocol with progesterone (P4) supplementation [P4-Ovsynch; GnRH and controlled internal drug-release device (CIDR) in, 7 d later CIDR removal and PGF2α, 24 h later PGF2α, 32 h later GnRH, and 16 to 18 h later timed AI]. In a subgroup of cows, blood samples were collected and TUS conducted at each treatment to evaluate ovarian responses to resynchronization. Binary data were analyzed with logistic regression, continuous data by ANOVA, and time-to-event data by Cox's proportional hazard regression. A greater proportion (mean; 95% CI) of cows were AIE before NPD in the SR (60.5%; 57.0-63.8; n = 3,416) than the D25R (50.1%; 46.5-53.7; n = 3,177) treatment, whereas pregnancy per AI (P/AI) at 32 d for AIE services before NPD was greater for the D25R (41.3%; 38.8-43.8; n = 1,560) than the SR (37.6%; 35.5-39.8; n = 1,961) treatment. At NPD, a greater proportion of cows in the D25R (84.3%; 82.2-86.2) than the SR (77.0%; 74.4-79.4) treatment were considered CL cows. Pregnancy per AI at 32 d was greater for the D25R than the SR treatment for all timed AI services (D25R = 43.0%; 40.2-45.9 vs. SR = 36.8%; 33.8-39.8) and for CL cows (D25R = 42.8%; 39.7-45.9 vs. SR = 33.8%; 30.6-37.2) but did not differ for NoCL cows (D25R = 39.4%; 32.1-47.3 vs. SR = 44.0%; 36.8-51.4). The hazard ratio for time to pregnancy (1.03; 0.93-1.14) and the proportion of cows not pregnant at the end of the observation period (D25R = 5.9%; 4.4-7.8 vs. SR = 6.7%; 5.0-8.7) did not differ between SR and D25R treatments. The GnRH treatment 25 d after AI resulted in more cows with P4 >1 ng/mL (D25R = 80.5%; 75.3-84.9 vs. SR = 63.6%; 57.3-69.4) and smaller follicle diameter at NPD 32 ± 3 d after AI for D25R (16.2 ± 0.4 mm) than for SR (17.5 ± 0.4 mm); however, it did not affect follicle diameter and luteal regression risk (CL cows only) before TAI. We concluded that the use of reproductive management programs including SR and D25R for CL cows and the P4-Ovsynch protocol for NoCL cows resulted in similar hazard of pregnancy and proportion of nonpregnant cows for up to 210 d after first service.

The effectiveness of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in relation to renal function.

OBJECTIVES: We evaluated the effect of renal function on clinical failure rates of nitrofurantoin, fosfomycin and trimethoprim for the treatment of cystitis in primary care. METHODS: Data were retrospectively obtained from 78 Dutch general practitioner (GP) practices between 2013 and 2019. Eligible episodes in patients (>11 years) were those requiring 5 days of nitrofurantoin (NF5), single-dose fosfomycin-trometamol (FT1), 3 days of trimethoprim (TMP3) for uncomplicated cystitis, or 7 days of nitrofurantoin (NF7) or trimethoprim (TMP7) for complicated cystitis. Clinical failure was defined as second antibiotic prescription for cystitis or pyelonephritis within 28 days post-prescription. Mixed effects regression analysis was used, with patient and GP practice as random effects and demography, comorbidity, and cystitis history as fixed effects. RESULTS: Adjusted odds ratios (aORs) for clinical failure per 10mL/min decrease in estimated glomerular filtration rate (eGFR) were 1.05 (95% CI: 1.01-1.09) for NF5 (n = 24,591), 0.96 (95% CI: 0.92-1.01) for FT1 (n = 5359), 0.98 (95% CI: 0.89-1.08) for TMP3 (n = 1064), 1.05 (95% CI: 1.02-1.09) for NF7 (n = 10,628) and 1.02 (95% CI: 0.93-1.14) for TMP7 (n = 831). In uncomplicated cystitis and eGFR ≥60 mL/min, clinical failures occurred in 14.6% (1895/12 980) of NF5-treated, 20.7% (266/1283) of FT1-treated (aOR versus NF5 1.37, 95% CI 1.18-1.59) and 20.8% (66/318) of TMP3-treated patients (aOR 1.42, 95% CI 1.07-1.87 versus NF5). In uncomplicated cystitis and eGFR <60 mL/min, FT1 resulted in 16.0% (39/244) and NF5 in 23.3% clinical failures (110/472), aOR: 0.61, 95% CI: 0.39-0.95). CONCLUSIONS: In eGFR ≥60 mL/min treatment with fosfomycin or trimethoprim for uncomplicated cystitis was associated with more clinical failure than treatment with nitrofurantoin, while in eGFR <60 mL/min nitrofurantoin was associated with more clinical failure than fosfomycin-trometamol. Renal function, if known, should be considered in the clinical decision-making for cystitis treatment.

Carbohydrate source offered in the prepartum diet did not affect postpartum metabolic status or milk yield in dairy cows.

Increasing the provision of non-fibrous carbohydrates (NFC) during the prepartum period is a feeding strategy that has been recommended to facilitate the transition to the onset of lactation and improve dairy cow performance, but results are contradictory, probably because most studies have confounded the effects of level and source of energy. The objective of this experiment was to evaluate the effect of the source of carbohydrate offered in the prepartum diet on postpartum cow performance. Holstein dairy cows (n=24) were assigned to receive diets with either low (LNFC), or high (HNFC) levels of NFC during the last 3 weeks before expected calving date according to a randomized complete block design. Soybean hulls and corn grain were the main energy ingredients in the LNFC and HNFC total mixed rations (TMR), respectively, and diets were designed to be isocaloric and isoproteic. After calving, all cows were managed as a single group until day 56 postpartum and grazed on improved pastures and were supplemented with a TMR. Body condition score evaluation and blood sampling were performed weekly throughout the experimental period to monitor the metabolic status of the animals. Prepartum glucose concentrations tended to be greater in HNFC than LNFC, but there was no effect on prepartum or postpartum insulin concentrations. Although nutrient intake was greater in the immediate week after calving in HNFC than LNFC, treatment did not affect milk yield and composition. In conclusion, increasing the NFC intake during the prepartum period, at a similar level of energy and protein intake, had a marginal residual effect on postpartum intake, and did not affect metabolic status or milk production.

Profitability of dairy cows submitted to the first service with the Presynch-Ovsynch or Double-Ovsynch protocol and different duration of the voluntary waiting period.

The objective of this study was to compare cash flow and parameters of economic performance for dairy cows submitted to the first service using a combination of insemination at detected estrus and timed AI (TAI) in cows synchronized with the Presynch-Ovsynch (PSOv) protocol versus all TAI after synchronization of ovulation with the Double-Ovsynch (DO) protocol with different durations of the voluntary waiting period. A secondary objective was to calculate the variation in cash flow under different input pricing scenarios through stochastic Monte Carlo simulation. Lactating Holstein cows from a commercial dairy farm were randomly assigned to 3 first-service management programs. Cows in the PSOv treatment (n = 450) received first service through a combination of insemination at detected estrus after a voluntary waiting period of 50 d in milk (DIM; i.e., after second PGF2α treatment of the protocol) and TAI at 72 ± 3 DIM. Cows in the DO60 (n = 458) and DO88 (n = 462) treatments received first service by TAI at 60 ± 3 and 88 ± 3 DIM, respectively. Individual cow cash flow was calculated for the calving interval after enrollment and for an 18-mo period after calving. Cash flow was the aggregation of daily income over feed cost, replacement cost, calf value, recombinant bovine somatotropin treatment cost, reproductive cost, and other operating expenses. All analyses were conducted separately for primiparous and multiparous cows. Continuous, binomial, and time to event outcomes were analyzed using ANOVA, logistic regression, and Cox's proportional hazard regression in SAS (SAS Institute Inc., Cary, NC). Treatments affected the dynamics of pregnancy creation, which affected time to pregnancy during lactation. As a result, we observed differences in the proportion of nonpregnant cows at the end of lactation, herd exit dynamics, lactation length, calving interval, and proportion of cows that calved again. Some of these effects varied by parity, affecting the direction and magnitude of treatment differences within parity group. For primiparous cows, maximum cash flow differences per slot for the 18-mo period were in the range of $26 (PSOv > DO60) to $29 (DO88 > DO60) but did not differ statistically. For multiparous cows, maximum cash flow differences per slot for the 18-mo period were in the range of $122 (PSOv > DO88) to $155 (DO60 > DO88) but did not differ statistically. Despite the substantial differences in cash flow (in particular for multiparous cows) caused by the effect of treatments on reproductive performance, herd exit dynamics, and calving interval, large variability in overall cash flow among individual cows and compensation between multiple outcomes resulted in lack of statistical differences in cash flow. Outcomes from the stochastic analysis indicated that similar trends for differences between treatments would be observed under varying scenarios for economic input values. In conclusion, we did not detect statistically significant cash flow differences between the PSOv, DO60, and DO88 treatments, but numerical trends and stochastic simulation indicated that the DO88 and PSOv treatments were more economically favorable than the DO60 treatment for primiparous cows. For multiparous cows, the DO60 and PSOv treatments were more economically favorable than the DO88 treatment.

Economic performance of lactating dairy cows submitted for first service timed artificial insemination after a voluntary waiting period of 60 or 88 days.

The objective of this study was to evaluate the economic performance of dairy cows managed with a voluntary waiting period (VWP) of 60 or 88 d. A secondary objective was estimating variation in cash flow under different input pricing scenarios through stochastic Monte Carlo simulations. Lactating Holstein cows from 3 commercial farms were blocked by parity group and total milk yield in their previous lactation and then randomly assigned to a VWP of 60 (VWP60; n = 1,352) or 88 d (VWP88; n = 1,359). All cows received timed-artificial insemination (TAI) for first service after synchronization of ovulation with the Double-Ovsynch protocol. For second and greater services, cows received artificial insemination (AI) after detection of estrus or the Ovsynch protocol initiated 32 ± 3 d after AI. Two analyses were performed: (1) cash flow per cow for the calving interval of the experimental lactation and (2) cash flow per slot occupied by each cow enrolled in the experiment for an 18-mo period after calving in the experimental lactation. Extending the VWP from 60 to 88 d delayed time to pregnancy during lactation (∼20 d) and increased the risk of leaving the herd for multiparous cows (hazard ratio = 1.21). As a result, a smaller proportion of multiparous cows calved again and had a subsequent lactation (-6%). The shift in time to pregnancy combined with the herd exit dynamics resulted in longer lactation length for primiparous (22 d) but not multiparous cows. Longer lactations led to greater milk income over feed cost and a tendency for greater cash flow during the experimental lactation for primiparous but not multiparous cows in the VWP88 group. On the other hand, profitability per slot for the 18-mo period was numerically greater ($68 slot/18 mo) for primiparous cows but numerically reduced (-$85 slot/18 mo) for multiparous cows in the VWP88 treatment. For primiparous cows most of the difference in cash flow was explained by replacement cost, whereas for multiparous cows it was mostly explained by differences in replacement cost and income over feed cost. Under variable input pricing conditions generated through stochastic simulations, the longer VWP treatment always increased cash flow per 18 mo for primiparous and reduced cash flow for multiparous cows. In conclusion, extending the duration of the VWP from 60 to 88 d numerically increased profitability of primiparous cows and reduced profitability of multiparous cows. Such an effect depended mostly on the herd replacement dynamics and milk production efficiency.

A resynchronization of ovulation program based on ovarian structures present at nonpregnancy diagnosis reduced time to pregnancy in lactating dairy cows.

Our objective was to evaluate time to pregnancy after the first service postpartum and pregnancy per artificial insemination (P/AI) in dairy cows managed with 2 resynchronization of ovulation programs. After first service, lactating Holstein cows were blocked by parity (primiparous vs. multiparous) and randomly assigned to the d 32 Resynch (R32; n = 1,010) or short Resynch (SR; n = 1,000) treatments. Nonpregnancy diagnosis (NPD) was conducted 32 ± 3 d after AI by transrectal ultrasonography. Nonpregnant cows in R32 received the Ovsynch protocol: GnRH, PGF2α 7 d later, GnRH 56 h later, and timed AI (TAI) 16 to 18 h later. Cows in SR with a corpus luteum (CL) ≥15 mm and a follicle ≥10 mm at NPD received PGF2α, PGF2α 24 h later, GnRH 32 h later, and TAI 16 to 18 h later. Cows in SR without a CL ≥15 mm or a follicle ≥10 mm at NPD received a modified Ovsynch protocol with 2 PGF2α treatments and progesterone (P4) supplementation (GnRH plus CIDR, PGF2α and CIDR removal 7 d later, PGF2α 24 h later, GnRH 32 h later, and TAI 16 to 18 h later). Blood samples were collected from a subgroup of cows at the GnRH before TAI (R32 = 114; SR = 121) to measure P4 concentration. Binomial outcomes were analyzed with logistic regression and hazard of pregnancy (R32 = 485; SR = 462) with Cox's proportional regression in SAS (SAS Institute, Cary, NC). For P/AI analysis, the TAI service was the experimental unit (R32 = 720; SR = 819). Models included treatment and parity as fixed effects and farm as random effect. The hazard of pregnancy was greater for the SR treatment (hazard ratio = 1.18; 95% confidence interval: 1.01-1.37). Median time to pregnancy was 95 and 79 d for the R32 and SR treatments, respectively. At NPD, 71.3 and 71.2% of cows had a CL for the R32 and SR treatments, respectively. Treatment did not affect overall P/AI 32 ± 3 d after AI (R32 = 31.0% vs. SR = 33.9%) or for cows with a CL at NPD (R32 = 32.7% vs. SR = 32.8%). For cows with no CL at NPD, P/AI was greater for the SR treatment (36.9%) than for the R32 treatment (28.6%). Pregnancy loss from 32 to 63 d after AI was similar for all services combined (R32 = 8.3% vs. SR = 10.4%) and for cows with no CL at NPD (R32 = 13.2% vs. SR = 7.2%) but tended to be affected by treatment for cows with a CL at NPD (R32 = 6.8% vs. SR = 11.9%). Treatment affected the proportion of cows with P4 ≤0.5 ng/mL at the GnRH before TAI for all cows (R32 = 68.4% vs. SR = 81.8%), tended to have an effect among cows with a CL (R32 = 70.0% vs. SR = 81.8%), and had no effect for cows with no CL (R32 = 64.7% vs. SR = 81.8%). We concluded that the SR program reduced time to pregnancy because of a reduction of the interbreeding interval for cows with a CL at NPD and greater P/AI in cows with no CL at NPD.

Reproductive performance and herd exit dynamics of lactating dairy cows managed for first service with the Presynch-Ovsynch or Double-Ovsynch protocol and different duration of the voluntary waiting period.

The objective of this experiment was to evaluate the reproductive performance and herd exit dynamics of dairy cows managed for first service with programs varying in method of submission for insemination and voluntary waiting period (VWP) duration. Holstein cows from a commercial farm in New York were randomly allocated to receive timed artificial insemination (TAI) after the Double-Ovsynch protocol (GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later GnRH, 7 d later PGF2α, 56 h later GnRH, and 16 to 18 h later TAI) at 60 ± 3 d in milk (DIM) (DO60 = 458), TAI after Double-Ovsynch at 88 ± 3 DIM (DO88 = 462), or a combination of AI at detected estrus (starting at 50 ± 3 d in milk) and TAI with the Presynch-Ovsynch protocol (PGF2α, 14 d later PGF2α, 12 d later GnRH, 7 d later PGF2α, 56 h later GnRH, and 16 to 18 h later TAI; PSOv = 450). Subsequent artificial insemination (AI) services were conducted at detected estrus or the Ovsynch protocol (32 ± 3 d after AI GnRH, 7 d later PGF2α, 56 h later GnRH, and 16 to 18 h later TAI) for cows not reinseminated at detected estrus. In a subgroup of cows, cyclicity (based on progesterone concentration), uterine health (vaginal discharge and uterine cytology), and BCS were evaluated at baseline (DO60 and DO88 = 33 ± 3 DIM; PSOv = 34 ± 3 DIM), beginning of the synchronization protocol (DO60 = 33 ± 3 DIM; DO88 = 61 ± 3 DIM; PSOv = 34 ± 3 DIM), and within -5 (PSOv) or -10 d (DO) of the VWP end (DO60 = 50 ± 3 DIM; DO88 = 78 ± 3 DIM; PSOv = 45 ± 3 DIM). Effects of treatments were assessed with multivariable statistical methods relevant for each outcome variable. Cows in the DO88 treatment had delayed time to pregnancy during lactation (DO60 vs. DO88 hazard ratio = 1.53, 95% confidence interval = 1.32 to 1.78; PSOv vs. DO88 hazard ratio = 1.37, 95% confidence interval = 1.19 to 1.61) and, within multiparous cows, the DO88 and PSOv treatments had greater risk of leaving the herd than cows in the DO60 treatment (DO88 vs. DO60 hazard ratio = 1.49, 95% confidence interval = 1.11 to 2.00; PSOv vs. DO60 hazard ratio = 1.39, 95% confidence interval = 1.03 to 1.85). Cows in the DO88 treatment had improved uterine health, greater BCS, and reduced incidence of anovulation than cows in DO60 and PSOv; however, overall pregnancy per AI 39 ± 3 d after AI was similar for the 3 treatment groups. In summary, reproductive management strategies that led to similar average DIM to the first service (∼60 d) through a combination of AI at estrus with TAI (PSOv) or all TAI (DO60) resulted in reduced time to pregnancy after calving when compared with an all TAI program (DO88) with a VWP of 88 d. Within the multiparous cow group, those that received all TAI with a VWP duration of 60 d were less likely to leave the herd than cows in the other treatments.

Extending the duration of the voluntary waiting period from 60 to 88 days in cows that received timed artificial insemination after the Double-Ovsynch protocol affected the reproductive performance, herd exit dynamics, and lactation performance of dairy cows.

This experiment evaluated the reproductive performance, herd exit dynamics, and lactation performance of dairy cows managed with a voluntary waiting period (VWP) of 60 or 88 d. Secondary objectives were evaluating VWP effect on cyclicity status, uterine health, systemic inflammation, and body condition score (BCS) before first service. Lactating Holstein cows from 3 commercial farms in New York State cows were blocked by parity group and total milk yield in their previous lactation and then randomly assigned to VWP of 60 (VWP60; n = 1,352) or 88 (VWP88; n = 1,359) days in milk (DIM). All cows received the Double-Ovsynch protocol (GnRH-7 d-PGF2α-3 d-GnRH-7 d-GnRH-7 d-PGF2α-56 h-GnRH-16 to 20 h-timed artificial insemination; TAI) for synchronization of ovulation and TAI. For second and greater artificial insemination (AI), cows received AI after detection of estrus or the Ovsynch protocol (GnRH-7 d-PGF2α-56 h-GnRH-16 to 20 h-TAI) initiated 32 ± 3 d after AI for cows not re-inseminated at detected estrus. Cyclicity status (progesterone concentration), uterine health (vaginal discharge and uterine cytology), BCS, and systemic inflammation (haptoglobin concentration) were evaluated at baseline (33 ± 3 DIM for both treatments), beginning of the Double-Ovsynch protocol, and 10 d before TAI. Effects of treatments were assessed with multivariable statistical methods relevant for each outcome variable. Extending duration of VWP from 60 to 88 DIM increased pregnancies per AI (P/AI) to first service (VWP60 = 41%; VWP88 = 47%). Nonetheless, the greatest benefit of extending VWP on first-service P/AI was for primiparous cows (VWP60 = 46%; VWP88 = 55%), as P/AI did not differ within the multiparous cow group (VWP60 = 36%; VWP88 = 40%). Physiological status more conducive to pregnancy-characterized by improved uterine health, greater BCS, reduced systemic inflammation, and to a lesser extent more time to resume ovarian cyclicity-explained the increment in P/AI to first service. Our data also indicated that despite having greater P/AI to first service, cows with the longer VWP had delayed time to pregnancy during lactation (hazard ratio = 0.72; 95% confidence interval 0.69-0.98) and greater risk of leaving the herd, particularly for multiparous cows (hazard ratio = 1.34; 95% confidence interval 1.23-1.47). This shift in pregnancy timing led to an overall extension of the lactation length (+13 d), which resulted in greater total milk yield per lactation (+491 kg) but not greater milk yield per day of lactation. In conclusion, data from this experiment highlight the importance of considering the complex interactions between reproductive performance, herd exit dynamics, and lactation performance as well as the effects of parity at the time of defining the duration of the VWP for lactating dairy cows.

High interindividual variability in urinary fosfomycin concentrations in healthy female volunteers.

OBJECTIVES: Fosfomycin is increasingly being prescribed for treatment of uncomplicated urinary tract infections in an era of emerging drug resistance. Surprisingly, little is known of the urinary concentrations of fosfomycin and its interindividual variation after the standard single 3-g oral dose. We aimed to gain more insight into urinary fosfomycin pharmacokinetics to evaluate its effectiveness. METHODS: Three grams of fosfomycin trometamol was administered to 40 healthy female volunteers with an estimated mean glomerular filtration rate of >90 mL/min/1.73m2. Urine samples were collected from every urination during 48 hours, and then twice daily for up to 7 days. Time, volume, and pH were recorded. Concentrations were quantified with UPLC-MS/MS. Effectiveness was evaluated based on urinary concentrations and the target MIC of E. coli, the most common uropathogen. RESULTS: A high interindividual variability was found. Peak concentration was 1982.0 ± 1257.4 mg/L, urinary half-life 12.4 ± 5.7 hours, and excretion rate over 48 hours 29.9 ± 7.1 mg/h. Recovery was 44.5 ± 12.6% after 48 hours and 47.0 ± 10.4% after 7 days. Concentrations remained above the EUCAST breakpoint of 32 mg/L in 100% of the volunteers over the first 24 hours, 67.5% for 48 hours, and 30% for 72 hours. A high urinary output was associated with low urinary concentrations and consequently reduced time > MIC, AUC0-7days/MIC, and Cmax/MIC values. CONCLUSIONS: Considerable interindividual variability observed in the pharmacokinetics of fosfomycin signifies a risk for inadequate drug exposure in a significant proportion of the population. The current dosing regimen should therefore be reevaluated.

Resynchronization of ovulation protocols for dairy cows including or not including gonadotropin-releasing hormone to induce a new follicular wave: Effects on re-insemination pattern, ovarian responses, and pregnancy outcomes.

Our objectives were to evaluate the pattern of re-insemination, ovarian responses, and pregnancy per artificial insemination (P/AI) of cows submitted to different resynchronization of ovulation protocols. The base protocol started at 25 ± 3 d after artificial insemination (AI) and was as follows: GnRH, 7 and 8 d later PGF2α, GnRH 32 h after second PGF2α, and fixed timed AI (TAI) 16 to 18 h after GnRH. At 18 ± 3 d after AI, cows were randomly assigned to the G25 (n = 1,100) or NoG25 (n = 1,098) treatments. The protocol for G25 and NoG25 was the same, except that cows in NoG25 did not receive GnRH 25 ± 3 d after AI. At nonpregnancy diagnosis (NPD), 32 ± 3 d after AI, cows from G25 and NoG25 with a corpus luteum (CL) ≥15 mm in diameter and a follicle ≥10 mm completed the protocol (G25 CL = 272, NoG25 CL = 194), whereas cows from both treatments that did not meet these criteria received a modified Ovsynch protocol with P4 supplementation [controlled internal drug release insert plus GnRH, controlled internal drug release insert removal, and PGF2α 7 and 8 d later, GnRH 32 h after second PGF2α, and TAI 16 to 18 h after GnRH (G25 NoCL = 53, NoG25 NoCL = 78)]. Serum concentrations of progesterone (P4) were determined and ovarian ultrasonography was performed thrice weekly from 18 ± 3 d after AI until 1 d after TAI (G25 = 46, NoG25 = 44 cows). A greater percentage of NoG25 cows were re-inseminated at detected estrus (NoG25 = 53.5%, G25 = 44.6%), whereas more cows had a CL at NPD in G25 than NoG25 (83.7 and 71.3%). At 32 d after AI, P/AI was similar for G25 and NoG25 for inseminations at detected estrus (38.4 and 42.9%), TAI services for cows with no CL (40.4 and 36.7%), and for all services combined (39.6 and 39.0%). However, P/AI were greater for cows with a CL in G25 than NoG25 (40.6 and 32.8%) that received TAI. More cows ovulated spontaneously or in response to GnRH for the G25 than the NoG25 treatment (70 and 36%) but a similar proportion had an active follicle at NPD (G25 = 91% and NoG25 = 96%). The largest follicle diameter at NPD (G25 = 15.0 ± 0.4 mm, NoG25 = 16.5 ± 0.6 mm) and days since it reached ≥10 mm (G25 = 4.0 ± 0.3 d, NoG25 = 5.8 ± 0.6 d) were greater for the NoG25 than G25 treatment. For cows with a CL at NPD, CL regression after NPD, ovulation after TAI, and ovulatory follicle diameter did not differ. In conclusion, removing the first GnRH of a modified Resynch-25 protocol for cows with a CL at NPD and a modified Ovsynch protocol with P4 supplementation for cows without a CL at NPD resulted in a greater percentage of cows re-inseminated at detected estrus and a similar proportion of cows pregnant in spite of reduced P/AI for cows with a CL at NPD.

Intravaginal instillation of gonadotropin-releasing hormone analogues with an absorption enhancer induced a surge of luteinizing hormone in lactating dairy cows.

Our objectives were to evaluate circulating LH concentrations after intravaginal (IVG) instillation of GnRH analogs in lactating dairy cows. In 2 experiments, lactating Holstein cows (experiment 1: n = 32; experiment 2: n = 47) received the experimental treatments 48 h after the first of 2 PGF2α treatments given 12 h apart and 7 d after a modified Ovsynch protocol (GnRH at -7 d, PGF2α at -24 h, PGF2α at -56 h, GnRH at 0 h). In experiment 1, cows were stratified by parity and randomly allocated to receive the following treatments: 2 mL of saline IVG (SAL, n = 6), 100 µg of gonadorelin (Gon) i.m. (G100-IM, n = 5), and 100 (G100, n = 7), 500 (G500, n = 8), or 1,000 µg of Gon IVG (G1000, n = 7). In experiment 2, treatments were SAL (n = 8), G100-IM (n = 8), G1000 (n = 7), 1,000 µg of Gon plus 10% citric acid (CA) IVG (G1000CA, n = 8), 80 µg of buserelin IVG (B80, n = 8), and 80 µg of buserelin plus 10% CA IVG (B80CA, n = 8). In both experiments, blood was collected every 15 min from -15 min to 4 h, and every 30 min from 4 to 6 h after treatment. Data for area under the curve (AUC), mean LH concentrations, and time to maximum LH concentration were analyzed by ANOVA with (mean LH only) or without repeated measures using PROC MIXED of SAS (version 9.4, SAS Institute Inc., Cary, NC). The proportion of cows with a surge of LH was evaluated with Fisher's exact test using PROC FREQ of SAS. In both experiments, LH concentrations were affected by treatment, time, and the treatment by time interaction. In experiment 1, the AUC for LH and maximum LH concentration were greatest for the G100-IM treatment and were greater for the G1000 than for the SAL and G500 treatments. The proportion of cows with an observed surge of LH was 100 and 0% for cows that received Gon i.m. and IVG, respectively. In experiment 2, the AUC and maximum LH concentrations were greater for the G100-IM, G1000CA, and B80CA treatments than for the other IVG treatments. The proportion of cows with a surge of LH differed by treatment (SAL = 0%, G100-IM = 100%, G1000 = 14%, G1000CA = 88%, B80 = 13%, and B80CA = 100%). For the treatments with a surge of LH, time to maximum concentration of LH was the shortest for the G100-IM treatment, intermediate for the G1000CA treatment, and the longest for cows in the B80CA treatment. In conclusion, Gon (up to 1,000 µg) absorption through intact vaginal epithelium after a single IVG instillation was insufficient to elicit a surge of LH of normal magnitude. Conversely, IVG instillation of 1,000 µg of Gon and 80 µg of buserelin with the addition of citric acid as absorption enhancer resulted in a surge of LH of similar characteristics than that induced after i.m. injection of 100 µg of Gon.

Use of rumination and activity monitoring for the identification of dairy cows with health disorders: Part II. Mastitis.

The objectives of this study were to evaluate (1) the performance of an automated health-monitoring system (AHMS) to identify cows with mastitis based on an alert system (health index score, HIS) that combines rumination time and physical activity; (2) the number of days between the first HIS alert and clinical diagnosis (CD) of mastitis by farm personnel; and (3) the daily rumination time, physical activity, and HIS patterns around CD. Holstein cows (n=1,121; 451 nulliparous and 670 multiparous) were fitted with a neck-mounted electronic rumination and activity monitoring tag (HR Tags, SCR Dairy, Netanya, Israel.) from at least -21 to 80 d in milk (DIM). Raw data collected in 2-h periods were summarized per 24 h as daily rumination and activity. An HIS (0 to 100 arbitrary units) was calculated daily for individual cows with an algorithm that used rumination and activity. A positive HIS outcome was defined as an HIS of <86 units during at least 1 d from -5 to 2 d after CD. Blood concentrations of nonesterified fatty acids, ß-hydroxybutyrate, total calcium, and haptoglobin were also determined in a subgroup of cows (n=459) at -11±3, -4±3, 0, 3±1, 7±1, 14±1, and 28±1 DIM. The sensitivity of the HIS was 58% [95% confidence interval (CI): 49, 67] for all cases of clinical mastitis (n=123), and 55% (95% CI: 46, 64; n=114) and 89% (95% CI: 68, 100; n=9) for cases of mastitis alone or concurrent with other health disorders, respectively. Among clinical cases, sensitivity was 80.7% (95% CI: 67, 97) for cases caused by Escherichia coli (n=31) and ranged from 45 to 48% for cases caused by gram-positive bacteria (n=39; Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis, Streptococcus spp., Staphylococcus spp., and Trueperella pyogenes), Staphylococcus aureus (n=11), or cases with no bacterial growth (n=25). Days between the first HIS <86 and CD were -0.6 (95% CI: -1.1, -0.2) for all cases of mastitis. Cows diagnosed with mastitis had alterations of their rumination, activity, HIS patterns, and reduced milk production around CD depending on the type of mastitis case. Cows with mastitis also had some alterations of their calcium and haptoglobin concentrations around calving. The AHMS used in this study was effective for identifying cows with clinical cases of mastitis caused by E. coli and cows with another disease occurring during an event of mastitis, but it was less effective in identifying cows with mastitis not caused by E. coli.

Use of rumination and activity monitoring for the identification of dairy cows with health disorders: Part III. Metritis.

The objectives of this study were to evaluate (1) the performance of an automated health-monitoring system (AHMS) to identify cows with metritis based on an alert system (health index score, HIS) that combines rumination time and physical activity; (2) the number of days between the first HIS alert and clinical diagnosis (CD) of metritis by farm personnel; and (3) the daily rumination time, physical activity, and HIS patterns around CD. In this manuscript, the overall performance of HIS to detect cows with all disorders of interest in this study [ketosis, displaced abomasum, indigestion (companion paper, part I), mastitis (companion paper, part II), and metritis] is also reported. Holstein cattle (n=1,121; 451 nulliparous and 670 multiparous) were fitted with a neck-mounted electronic rumination and activity monitoring tag (HR Tags, SCR Dairy, Netanya, Israel) from at least -21 to 80 d in milk (DIM). Raw data collected in 2-h periods were summarized per 24 h as daily rumination and activity. An HIS (0 to 100 arbitrary units) was calculated daily for individual cows with an algorithm that used rumination and activity. A positive HIS outcome was defined as an HIS of <86 units during at least 1 d from -5 to 2 d after CD. Blood concentrations of nonesterified fatty acids, ß-hydroxybutyrate, total calcium, and haptoglobin were determined in a subgroup of cows (n=459) at -11±3, -4±3, 0, 3±1, 7±1, 14±1, and 28±1 DIM. The overall sensitivity of HIS was 55% for all cases of metritis (n=349), but it was greater for cows with metritis and another disorder (78%) than for cows with metritis only (53%). Cows diagnosed with metritis and flagged based on HIS had substantial alterations in their rumination, activity, and HIS patterns around CD, alterations of blood markers of metabolic and health status around calving, reduced milk production, and were more likely to exit the herd than cows not flagged based on the HIS and cows without disease, suggesting that cows flagged based on the HIS had a more severe episode of metritis. Including all disorders of interest for this study, the overall sensitivity was 59%, specificity was 98%, positive predictive value was 58%, negative predictive value was 98%, and accuracy was 96%. The AHMS was effective for identifying cows with severe cases of metritis, but less effective for identifying cows with mild cases of metritis. Also, the overall accuracy and timing of the AHMS alerts for cows with health disorders indicated that AHMS that combine rumination and activity could be a useful tool for identifying cows with metabolic and digestive disorders, and more severe cases of mastitis and metritis.

Use of rumination and activity monitoring for the identification of dairy cows with health disorders: Part I. Metabolic and digestive disorders.

The objectives of this study were to evaluate (1) the performance of an automated health-monitoring system (AHMS) to identify cows with metabolic and digestive disorders-including displaced abomasum, ketosis, and indigestion-based on an alert system (health index score, HIS) that combines rumination time and physical activity; (2) the number of days between the first HIS alert and clinical diagnosis (CD) of the disorders by farm personnel; and (3) the daily rumination time, physical activity, and HIS patterns around CD. Holstein cattle (n=1,121; 451 nulliparous and 670 multiparous) were fitted with a neck-mounted electronic rumination and activity monitoring tag (HR Tags, SCR Dairy, Netanya, Israel) from at least -21 to 80 d in milk (DIM). Raw data collected in 2-h periods were summarized per 24 h as daily rumination and activity. A HIS (0 to 100 arbitrary units) was calculated daily for individual cows with an algorithm that used rumination and activity. A positive HIS outcome was defined as a HIS of <86 during at least 1 d from -5 to 2 d after CD. Blood concentrations of nonesterified fatty acids, ß-hydroxybutyrate, total calcium, and haptoglobin were determined in a subgroup of cows (n=459) at -11±3, -4±3, 0, 3±1, 7±1, 14±1, and 28±1 DIM. The sensitivity of the HIS was 98% [95% confidence interval (CI): 93, 100] for displaced abomasum (n=41); 91% (95% CI: 83, 99) for ketosis (n=54); 89% (95% CI: 68, 100) for indigestion (n=9); and 93% (95% CI: 89, 98) for all metabolic and digestive disorders combined (n=104). Days (mean and 95% CI) from the first positive HIS <86 and CD were -3 (-3.7, -2.3), -1.6 (-2.3, -1.0), -0.5 (-1.5, 0.5), and -2.1 (-2.5, -1.6) for displaced abomasum, ketosis, indigestion, and all metabolic and digestive disorders, respectively. The patterns of rumination, activity, and HIS for cows flagged by the AHMS were characterized by lower levels than for cows without a health disorder and cows not flagged by the AHMS from -5 to 5 d after CD, depending on the disorder and parameter. Differences between cows without health disorders and those flagged by the AHMS for blood markers of metabolic and health status confirmed the observations of the CD and AHMS alerts. The overall sensitivity and timing of the AHMS alerts for cows with metabolic and digestive disorders indicated that AHMS that combine rumination and activity could be a useful tool for identifying cows with metabolic and digestive disorders.

Circulating progesterone dynamics after intravaginal instillation of prostaglandin-F2α to lactating dairy cows.

Our objectives were to evaluate circulating progesterone (P4) concentration dynamics and test the feasibility of inducing luteal regression after intravaginal (IVG) instillation of the PGF2α analogue dinoprost (PGF) in lactating dairy cows. In two experiments, cows were synchronized using the Ovsynch protocol to induce the formation of a corpus luteum (CL). Cows with at least one functional (P4 ≥1 ng/mL) CL ≥15 mm 7.5 days after Ovsynch remained in the studies. In experiment 1, cows (n = 31) were stratified by parity group and received 5 mL of saline IVG (SAL-IVG, n = 6), 25 mg of PGF intramuscular (IM) (PGF25-IM, n = 7), 25 mg of PGF IVG (PGF25-IVG, n = 6), 50 mg of PGF IVG (PGF50-IVG, n = 6), and 125 mg of PGF IVG (PGF125-IVG, n = 6). Experiment 2 was conducted to test the hypothesis that IVG instillation of two 25 mg doses of PGF 12 hours apart would be more effective than a 25- or 50-mg dose in a single application. Cows (n = 32) were stratified by parity and received SAL-IVG (n = 7), PGF25-IM (n = 7), PGF25-IVG (n = 6), and PGF50-IVG (n = 6) as in experiment 1, whereas another group received two IVG instillations of 25 mg of PGF 12 hours apart (PGF25-2X-IVG, n = 6). Blood was collected at -1 hour, every 6 hours from 0 hour to 24 hours, and every 12 hours up to 96 hours after treatment (trt). In experiment 1, there was an effect of trt (P < 0.01), time (P < 0.001), and an interaction between trt and time on P4 concentrations (P < 0.001). All PGF-treated groups had lower (P < 0.05) concentrations of P4 than cows in the SAL-IVG group from 12 to 96 hours after trt. Although an initial decline in P4 concentrations was induced in all PGF-treated cows, some cows in the IVG-treated groups presented a rebound in plasma P4, indicating CL recovery. More cows in the PGF25-IVG and PGF125-IVG groups than in the PGF50-IVG and PGF25-IM groups presented CL recovery, suggesting that greater doses of PGF may not necessarily improve CL regression. In experiment 2, there was an effect of trt (P < 0.001), time (P < 0.001), and an interaction between trt and time on P4 concentrations (P < 0.001). All PGF-treated groups had lower (P < 0.05) P4 than the SAL-IVG group from 12 to 96 hours after trt. Cows in the PGF25-2X-IVG group had a P4 profile that was similar to that of cows in the PGF25-IM group and the lowest P4 concentrations after treatment among the IVG-treated groups, and all cows presented complete CL regression (defined as P4 <0.4 ng/mL). We conclude that CL regression can be induced through IVG instillation of PGF in lactating dairy cows and that instillation of two IVG doses of 25 mg of PGF 12 hours apart was the most effective strategy.

Reproductive management strategies to improve the fertility of cows with a suboptimal response to resynchronization of ovulation.

The objective was to compare the reproductive performance of lactating Holstein cows managed with a strategy that included the Ovsynch protocol with exogenous progesterone (P4) supplementation or presynchronization with GnRH 7d before Ovsynch to treat cows without a corpus luteum (CL), a CL <15 mm, or cystic at the time of the PGF2α injection of Resynch (GnRH-7 d-PGF2α-56 h-GnRH-16 to 20 h-TAI). In a preliminary study, blood collection and transrectal ovarian ultrasonography were conducted (n=555) at the PGF2α of Resynch [coincident with nonpregnancy diagnosis (NPD)] to define a cutoff value for CL size that better predicted fertility after timed artificial insemination (TAI). A CL size of 15 mm was selected based on statistical differences in pregnancies per AI (P/AI) [33.2 vs. 10.3 P/AI for CL ≥15 mm (n=497) vs. no CL ≥15 mm (n=58; no CL, CL <15 mm, or cystic)]. Subsequently, in a completely randomized experiment, cows were enrolled in a management strategy that used Ovsynch with P4 supplementation [Ovsynch+P4; GnRH and controlled internal drug release device (CIDR)-7 d-PGF2α and CIDR removal-56 h-GnRH-16 to 20 h-TAI] or a PreG-Ovsynch protocol [PreG-Ovsynch; GnRH-7 d-GnRH-7 d-PGF2α-56 h-GnRH-16 to 20 h-TAI] to treat cows without a CL, a CL <15 mm, or cystic at NPD and the PGF2α of Resynch. Cows with a CL ≥15 mm at the PGF2α of Resynch completed the protocol and received TAI. Data were available from 212, 192, and 1,797 AI services after Ovsynch+P4, PreG-Ovsynch, and Resynch, respectively. At 39d after AI, P/AI tended to be greater for Ovsynch+P4 and PreG-Ovsynch combined (35.1%) than for Resynch cows (31.1%), whereas P/AI were similar for Ovsynch+P4 (34.4%) and PreG-Ovsynch (35.9%). The hazard of pregnancy for cows that received the experimental treatments at least once was similar for cows in the Ovsynch+P4 (n=124) and the PreG-Ovsynch (n=132) group (hazard ratio 1.15; 95% confidence interval: 0.87 to 1.53). Median days to pregnancy were 52 and 59 for cows in the Ovsynch+P4 and the PreG-Ovsynch groups, respectively. The presynchronizing GnRH injection of PreG-Ovsynch induced ovulation in 86.0% of the cows. At the first GnRH of Ovsynch, the proportion of cows with a CL based on ultrasound (86.6 vs. 15.0%), P4 >1 ng/mL (82.8 vs. 31.8%), a follicle ≥ 10 mm (98.0 vs. 84.4%), and P4 concentrations (3.7 vs. 1.1 ng/mL) was greater in PreG-Ovsynch than in Ovsynch+P4. Conversely, more cows ovulated in response to the first GnRH of Ovsynch in Ovsynch+P4 (71.9%) than PreG-Ovsynch (58.3%). At the PGF2α before TAI, more cows had a CL based on ultrasound (92.1 vs. 77.0%) and P4 concentrations were greater in PreG-Ovsynch than in Ovsynch+P4 (4.1 vs. 2.6 ng/mL); however, a similar proportion of cows had P4 >1 ng/mL (79.1 vs. 82.7%). We conclude that the Ovsynch+P4 and PreG-Ovsynch treatments for cows without a CL, a CL <15 mm, or cystic at the PGF2α injection of Resynch led to P/AI similar to that of cows with a CL ≥15 mm, and that both management strategies resulted in similar time to pregnancy.

Effect of extending the interval from Presynch to initiation of Ovsynch in a Presynch-Ovsynch protocol on fertility of timed artificial insemination services in lactating dairy cows.

The specific objective of this study was to determine if increasing the interval between the Presynch and Ovsynch portion of the Presynch-Ovsynch protocol (Presynch: PGF2α-14 d-PGF2α and Ovsynch: GnRH-7 d-PGF2α-56 h-GnRH-16-20 h-timed artificial insemination) from 12 to 14 d would reduce the fertility of lactating dairy cows not detected in estrus after Presynch that receive timed artificial insemination (TAI). Cows from 4 commercial dairy farms (n=3,165) were blocked by parity (primiparous vs. multiparous) and randomly assigned to a 12 (PSOv14-12; n=1,566) or 14 d (PSOv14-14; n=1,599) interval between the second PGF2α (PGF) injection of Presynch (P2) and the beginning of Ovsynch. Cows detected in estrus any time between P2 and the day of the TAI were inseminated (AIED group). From a subgroup of cows (177 and 150 in PSOv14-12 and PSOv14-14, respectively), ovarian parameters and ovulation were evaluated through determination of concentrations of progesterone (P4) in blood and transrectal ultrasonography at the time of the first GnRH (GnRH1) and the PGF injection of Ovsynch. Overall, 52.8% (n=1,671) of the cows were AIED, whereas 47.2% (n=1,494) received TAI. For cows that received TAI, pregnancies per artificial insemination 39 d after artificial insemination were similar for PSOv14-12 (36.3%) and PSOv14-14 (36.0%) but were greater for primiparous (41.5%) than multiparous cows (33.6%). Pregnancy loss from 39 to 105 d after artificial insemination was similar for PSOv14-12 (4.8%) and PSOv14-14 (8.6%), for primiparous (6.4%) and multiparous cows (7.0%), but a tendency for a treatment by parity interaction was observed. Both treatments had a similar proportion of cows with a follicle ≥ 10 mm and similar follicle size at GnRH1; however, the ovulatory response to GnRH was greater for PSOv14-12 (62.2%) than PSOv14-14 (46.4%). A greater proportion of cows with a functional corpus luteum (75.3 vs. 65.6%) and greater concentrations of P4 (3.9 vs. 3.3 ng/mL) at GnRH1 in PSOv14-14 than PSOv14-12 may have compensated for the reduction in fertility expected due to reduced ovulatory response to GnRH1. We concluded that extending the interval from Presynch to Ovsynch from 12 to 14 reduced ovulatory response to GnRH1 but did not reduce the fertility of cows that received TAI when cows were inseminated in estrus after presynchronization. Thus, farms that combine AIED and TAI during the Presynch-Ovsynch protocol may use a 14-d interval between Presynch and Ovsynch to simplify their management without reducing fertility of cows receiving TAI.

Reproductive performance of dairy cows managed with a program aimed at increasing insemination of cows in estrus based on increased physical activity and fertility of timed artificial inseminations.

The objective of this study was to compare the reproductive performance of lactating dairy cows using a treatment (TRT) program for second and subsequent artificial insemination (AI) services aimed at (1) increasing AI upon estrus detection based on increased physical activity (AIAct) and (2) increasing fertility of timed AI (TAI) services for cows not AIAct through presynchronization of the estrous cycle and improved physiological milieu before TAI. Cows in the control (CON) group were managed with a program that combined AIAct and TAI after the Ovsynch protocol. After nonpregnancy diagnosis (NPD) by transrectal ultrasonography at 31 ± 3 d after AI, cows received the following treatments: (1) CON (n=634), AIAct any time after a previous AI and resynchronization with the Ovsynch-56 protocol (GnRH-7d-PGF2α-56 h-GnRH-16 h-TAI) 1d after NPD, or (2) TRT (n = 616): cows with a corpus luteum (CL) ≥ 20 mm (TRT-CL) received a PGF2α injection 1d after NPD, whereas cows with no CL or a CL < 20 mm (TRT-NoCL) received a GnRH injection 3d after NPD. Cows in TRT-CL and TRT-NoCL not AIAct were enrolled in a 5-d Ovsynch + progesterone protocol (GnRH + controlled internal drug release-5d-PGF2α + controlled internal drug release removal-24 h-PGF2α -32 h-GnRH-16 h-TAI) 9 and 7d after the PGF2α or GnRH injection, respectively, to receive TAI. The hazard of pregnancy up to 270 DIM was similar for cows in the CON and TRT group (hazard ratio = 1.07, 95% CI = 0.95 to 1.21), but it was affected by parity (primiparous greater than multiparous cows). Median days to pregnancy for the CON and TRT group were 111 and 110 d, respectively. When evaluated after 104 DIM (first time point at which cows were affected by the treatments), the hazard of pregnancy was similar for the CON and TRT group (hazard ratio = 1.15, 95% CI = 0.95 to 1.39). Based on this analysis, median days to pregnancy for the CON and TRT group were 161 and 178 d, respectively. Thus, in spite of increasing the proportion of cows AIAct (29 and 10% for TRT and CON), median days to insemination after NPD were greater for cows in the TRT (17 d) than the CON (10 d) group, which coupled with similar fertility to AIAct, and TAI failed to improve overall reproductive performance. A low proportion of cows with a CL at NPD (65.2%) and a poor response to PGF2α may explain the poor estrus detection efficiency in the TRT group. We concluded that, when compared with a typical estrus detection and TAI program for cows failing to conceive to previous AI services, a program aimed at increasing the proportion of cows AIAct after NPD and fertility of TAI services increased the proportion of cows AIAct but failed to reduce days to pregnancy during lactation because of greater days to AI after NPD.