The effect of nutritional management of the dairy cow on reproductive efficiency

Animal Reproduction Science 96 (2006) 282–296

The effect of nutritional management of the dairy cow on reproductive efficiency夽 James F. Roche UCD, School of Agriculture, Food Science and Veterinary Medicine, College of Life Sciences, University College Dublin, Belfield, Dublin 4, Ireland Available online 3 August 2006

Abstract The cause of low fertility in dairy cows is multifactorial. Poor nutrition during the dry and early postpartum periods results in reduced glucose, insulin, insulin-like growth factor (IGF-I) and low LH pulse frequency with concomitant increases in ␤-hydroxy butyrate, non-esterified fatty acids (NEFA) and triacylglycerol. Cows must mobilize large lipid, but also some protein reserves, with a consequent increased incidence of such metabolic disorders as hypocalcaemia, acidosis, ketosis, fatty liver and displaced abomasums. The occurrence of milk fever and ketosis affects uterine contractions, delays calving and increases the risk of retained foetal membranes (RFM) and endometritis. The nutritional risk factors that cause RFM are hypocalcaemia, high body condition score (BCS) at calving and deficiencies in Vitamin E and selenium. The risk factors for endometritis are hypocalcaemia, RFM, high triacylglycerol and NEFA. Thus, metabolic disorders predispose cows to gynaecological disorders, thereby reducing reproductive efficiency. Cows that are overconditioned at calving or those that lose excess body weight are more likely to have a prolonged interval to first oestrus, thereby prolonging days open. Nutritionally induced postpartum anoestrus is characterized by turnover of dominant follicles incapable of producing sufficient oestradiol to induce ovulation due to reduced LH pulse frequency. High nutrition can also increase metabolic clearance rate of steroid hormones such as progesterone or oestradiol. Lower concentrations of oestradiol on the day of oestrus are highly correlated with the occurrence of suboestrus, thereby making the detection of oestrus in high yielding cows even more difficult. Nutrition also affects conception rate (CR) to AI. Cows that develop hypocalcaemia, ketosis, acidosis or displaced abomasums have lower CRs and take longer to become pregnant. Excessive loss of BCS and excess protein content of the ration can reduce CR while supplemental fats that attenuate the production of F2␣ can improve CR. The increased metabolic clearance rate of progesterone (P4), which decreases blood concentrations during early embryo cleavage up to the blastocyst stage is associated with decreased CRs.

夽 This paper is part of the special issue entitled Nutrition and Fertility in Dairy Cattle, Guest Edited by A. Evans and F.J. Mulligan. E-mail address: [email protected].

0378-4320/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.anireprosci.2006.08.007

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In conclusion, poor nutritional management of the dairy cow, particularly before and after calving, is a key driver of infertility. © 2006 Elsevier B.V. All rights reserved. Keywords: Fertility; Dairy cow; Metabolic disorders; Negative energy; Body condition; Retained placenta; Anoestrus; Conception rate; Endometritis; Progesterone; LH; Transition period; Postpartum; Reproductive management

1. Introduction The cause of low fertility in the modern Holstein Friesian cow is multifactorial involving genetic improvement, inadequate nutrition, poor reproductive management, an increased incidence of disease and overall poor cow welfare (Lucy, 2001). The partitioning of the relative impact of these various factors on infertility is not well understood. It is also clear that there are interactions between these factors and different contributions from individual farm factors depending on the specific farm management strategy. It is becoming increasingly clear that good reproductive management is dependent on proper attention to the optimum nutrition of the cow, whose nutrient requirements vary depending on physiological state and the specific nutrient demands to prevent metabolic disorders in the peri-parturient period (Boland et al., 2001; Overton and Waldron, 2004). Thus, increasingly emphasis must be placed on the nutritional management of the cow before and during the dry period, the length of the dry period and the actual body condition score (BCS on a scale of 1–5) targets and rate of BCS loss to be met. The underlying theme of this paper is that poor nutritional management of the cow, particularly before calving, is the key driver of low reproductive efficiency in high yielding dairy cows, when fed to allow her meet her genetic potential for milk production. High reproductive efficiency is necessary for efficient milk production and it, therefore, has an important influence on herd profitability (Pryce et al., 2004). Low reproductive efficiency decreases herd profitability by: (i) prolonging the calving interval, which results in less milk produced per cow and fewer calves born per year; (ii) increasing culling due to infertility and therefore, increased replacement costs; (iii) increased labour, semen costs and veterinary bills; (iv) an extended low production or dry period can result in over conditioned cows calving in too high a BCS (>3.5) which results in a subsequent prolonged period of negative energy balance (NEB) and low reproductive efficiency. The two key components of high reproductive efficiency are: • High submission rate of cows for insemination. • High conception rate to each service. Submission rate is defined as the percent eligible cows (e.g. calved >42 days so that the majority should be cyclic) presented for artificial insemination (AI) in a 24-day period (representing an oestrous cycle). The two key factors that affect it are: • Percent cows that are anoestrus. • Heat detection efficiency in the herd. The target is to achieve >80% of cows inseminated in a 24-day period of the breeding season. Therefore, to obtain high submission rate to AI, it is necessary to obtain proper uterine involution by day 50 or so postpartum and get >90% of cows resuming cyclicity with normal oestrous cycles

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Table 1 The postpartum (pp) reproductive targets to be met to obtain high reproductive efficiency and the associated key risk factors affecting these targets Reproductive process

Target to be achieved

Risk factors affecting targets

Normal uterine involution

Day 50 pp

Dystocia RFM Uterine infection

Resumption of ovulation

90% by day 42

Loss of > 0.5 BSC unit Low feed intake Uterine health

High oestrous detection

85% per cycle

Infrequent checks Sub-oestrus High yield

High conception rate to AI

50% per breeding

Excess BCS loss Prior uterine problems Low P4 days 4–7 of pregnancy

before breeding. The postpartum reproductive targets to aim for are presented in Table 1. Thus high reproductive efficiency is dependent on obtaining normal uterine involution, early resumption of ovulation, high efficiency of oestrous detection and high conception rates per service. 2. Uterine involution Following calving, there is a rapid decrease in size and weight of the uterus due to vasoconstriction and reduction in size of the cotyledons within 9 days (Gier and Marion, 1968). There is dissolution and detachment of superficial layers of the cotyledons with increased cellular debris and fluid production. Most of the necrotic layer has been removed by 10–14-day (Gier and Marion, 1968). Peristaltic contractions of the uterus continue for the first few days, presumably under the influence of the prostaglandin (PG) F2␣, which remains elevated, but declines over the next 20 days after calving (Lindell and Kindahl, 1982). Changes in the cervix resulted in decrease in size and cervical diameter from about 15 cm after calving, to 9–11, 7–8 and 5–6 cm by days 10, 20 and 60 after calving (Gier and Marion, 1968). Physical involution, i.e. return to its normal nonpregnant size is completed by 30–40 days post-calving but the endometrium may not be capable of normal embryonic development and maternal recognition of pregnancy until day 60 or so after calving. The key factors that affect progression of involution are retained placenta, dystocia and the occurrence of metabolic disorders such as milk fever (Gier and Marion, 1968; Marion et al., 1968; Morrow et al., 1966). Therefore, delayed uterine involution will reduce reproductive efficiency. There are no effective ways to speed it up although some authors use multiple injections of PGF2␣ in the early postpartum period. Results of its efficiency are not clear cut and this is partially related to the high but declining concentrations of PGF2␣ in the early postpartum period (Lindell and Kindahl, 1982) and the short half life of PGF. Postpartum uterine health plays a central role in determining the reproductive efficiency of dairy herds. Postpartum local infections of the uterus delay uterine involution, cause inflammation of the endometrium, may delay the interval to first ovulation postpartum, reduce conception rate (CR) to first insemination and increase the risk of culling for infertility (Sheldon, 2004). Uterine problems can also have a negative effect on dry matter intake of cows, cause poor welfare and increased stress, probably resulting in high cortisol secretion (Wischral et al., 2001).

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2.1. Retained foetal membranes Retained foetal membranes occur due to any interference with the normal detachment of cotyledons from the caruncle resulting in its failure to be expelled within 12 h of calving. The enzymes involved in tissue remodelling such as collagenases and proteases play an important role in concert with myometrial contractions in the early postpartum period. Decreased neutrophil function, manifest as reduced placental attraction, is implicated as a primary cause (Kimura et al., 2002). Interleukin-8, a potent chemoattractant and the immune status were reduced in cows that develop RFM. Increased metabolic stress could be implicated in the earlier but reduced synthesis of cortisol, the reduced oestradiol and prostaglandin PGE and F metabolites before parturition in cows with RFM’s (Wischral et al., 2001). RFM delay uterine involution, predispose cows to endometritis or metritis and decrease fertility (Gr¨ohn and Rajala-Schultz, 2000; Maizon et al., 2004). Nutrition plays an important role in causing RFM. The factors involved are: high BCS at calving, dietary deficiencies of Vitamins A, D and E and deficiencies in selenium, iodine and perhaps zinc (Laven and Peters, 1996; Gupta et al., 2004; Han and Kim, 2005). Hypolcalcaemia is also a key risk factor for RFM (Houe et al., 2001). Thus, maintenance of normal uterine physiology by good nutritional management during the dry and transition periods is important to reduce the incidence of RFM, which is an important risk factor for endometritis. Hence, its occurrence has a negative effect on reproduction. 2.2. Endometritis Endometritis is a superficial inflammation of the endometrium without systemic or overt signs of illness that often occurs before first ovulation (Sheldon, 2004). The presence of pathogens trigger an innate immune response including neutrophil migration, cytokine release, macrophage and serum compliment increases to overcome the local infection. The uterus of most cows is exposed to bacterial contamination after calving; the proportion of uteri contaminated with bacteria declined from 78% by days 16–30 to 50% by days 31–45 and 9% by days 46–60 postpartum (Sheldon, 2004). The problem arises where pathogenic bacteria multiply due both to the suppressed immune system around parturition and the resultant decrease in migration and the functional capacity of neutrophils to eliminate uterine bacteria. The incidence of endometritis is affected by the method used to diagnose it because of perceived insensitivity and lack of specificity of rectal examination of the uterus and observation of a genital discharge (Gilbert et al., 2005; Sheldon et al., 2006). Current evidence suggests the most efficacious methods for its diagnosis are the presence of a muco-purulent discharge following vaginoscopy, the presence of an enlarged cervix and/or the presence of inflammatory cells in uterine aspirates. The prevalence of endometritis varies with method of diagnosis used, production system employed, yield and parity of cows being examined. The incidence of clinical/subclinical endometritis in Canada, Ireland and the US, has been reported as 17% of 1865 cows, 24% of 6500 cows and 54% of 141 cows, respectively (Mee and Buckley, 2003; LeBlanc et al., 2002; Gilbert et al., 2005). It causes damage to the endometrium, histological lesions, and may delay uterine involution. The consequences of it on reproductive efficiency are partly dependent on when it occurs, its severity in the herd and the prevalence of the key risk factors on a herd basis. However, its incidence is such that it can have serious negative effects on herd reproductive efficiency. It can decrease submission rate by: prolonging the interval to first ovulation, reducing the growth rate of the first postpartum dominant follicle and decreasing the secretion of oestradiol from dominant follicles in the early postpartum period (LeBlanc et al., 2002; Sheldon and Dobson, 2004). This, therefore,

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increases the chances that the dominant follicles that develop will produce insufficient oestradiol to induce GnRH release, the LH/FSH preovulatory surge and ovulation, with a consequent delay to first ovulation. The production of endotoxins can also suppress LH pulse frequency, which will reduce oestradiol secretion from dominant follicles thereby increasing the chances of dominant follicle artesia, rather than ovulation. Endometritis can also have detrimental effects on first service conception rates if it occurs between 20 and 33 days postpartum (LeBlanc et al., 2002) and it increases the number of inseminations per pregnancy (Gilbert et al., 2005). Thus, it will prolong the calving to first service interval, the calving to conception interval, days open and increase the risk of cows being culled for infertility. There are many risk factors for the establishment of endometritis previously reviewed (Sheldon and Dobson, 2004; Sheldon, 2004). Those that relate to nutritional involvement are RFM, high triacylglycerol concentrations associated with liver disease (Zerbe et al., 2000), overconditioned cows at calving, high non-esterified fatty acid levels as an indicator of NEB (Jorritsma et al., 2003) and hypolcalcemia (Whiteford and Sheldon, 2005). The incidence of metabolic disorders is inter-related and the occurrence of one can predispose cows to related disorders (Laven and Peters, 1996). Milk fever and ketosis affect uterine muscle contractions, delay the process of calf delivery and also the ability of the uterus to expel the placenta within 12 h of calving. Thus, endometritis is prevalent in the postpartum period, its incidence is affected by nutrition and it is a serious cause of reduced reproductive efficiency in the modern Holstein Friesian dairy cow. 3. Resumption of ovulation and oestrus Following calving, the negative feedback effects of the high steroid concentrations in late pregnancy on gonadotrophin releasing hormone (GnRH) are removed. This is followed by an increase in FSH concentrations for 3–5 days between days 7 and 14 postpartum (Fig. 1). The increase in FSH results in the emergence of the first postpartum follicle wave (Savio et al., 1990a).

Fig. 1. Follicular dynamics, ovulation and concentrations of FSH, progesterone, oestradiol (E2) and LH pulse (in panels) in cows that resume ovulation early postpartum (cyclic cow) or in those that fail to ovulate (anoestrous cow) within 30–40 days after calving.

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A cohort of oestrogen active antral follicles is detectable by ultrasound scanning on the ovaries. The follicles produce both oestradiol and inhibin, which in turn suppress FSH secretion. Thus, the growing follicles are now faced with a decline in FSH. However, one follicle (generally the largest of the cohort) develops increased amounts of LH receptors and insulin-like growth factor (IGF-I) binding protein proteases, which allow the maintenance of high levels of bioactive IGF-I by degrading the IGF binding proteins. Thus, this follicle is selected to continue growing due to these local paracrine changes within the follicle in spite of declining systemic concentrations of FSH, which prevents other FSH-dependent cohort members developing. This dominant follicle (DF) is now mainly LH-responsive and thus, its fate is determined by the LH pulse frequency it is exposed to at this time. The fate of the first postpartum DF based on recent research (Savio et al., 1990b; Beam and Butler, 1997; Sartori et al., 2004; Sakaguchi et al., 2004) is one of the following: • it ovulates in 30–80% of cows; • it undergoes atresia in 15–60% of cows; • it becomes cystic in 1–5% of cows. The occurrence of the first transient 3–4 days increase in FSH concentrations is not affected by plane of nutrition or presence of a calf (Stagg et al., 1998). The incidence of anoestrus in dairy cows based on twice weekly assay of progesterone in milk has increased from 7% in 1986 (Fagan and Roche, 1986) to 11–22% in UK and Netherlands (Lamming and Darwash, 1998; Opsomer et al., 2000). There are significant metabolic changes associated with parturition and early lactation. The transient but crucial period of NEB in the early postpartum period induces significant metabolic changes, which have a negative impact on reproductive efficiency (Jorritsma et al., 2003). The ability of each cow to adapt physiologically to these metabolic changes and limit the amount of body tissue mobilization has an important influence on inherent cow fertility (Jorritsma et al., 2003). Following calving, concentrations of growth hormone (GH) are increased which induces lipolysis and suppresses peripheral tissue insulin responsiveness. The increased GH induces a catabolic state and results in loss of BCS and weight of cows (Lucy, 2003). There are also reduced GH receptors in the liver, which results in declining IFG-I concentrations despite the increased GH concentrations in the early postpartum period (Vandehaar et al., 1995; Lucy, 2001). This decline in IGF-I is an important indicator of nutritional status on the hypothalamic-pituitary-ovarian axis in the early postpartum period. It has been hypothesized that measurement of serum concentrations of IGF-I could be a useful predictor of nutritional status and hence reproductive efficiency in dairy cows (Zula et al., 2002a). 3.1. First ovulation The key factors determining whether or not the first DF ovulates are: size of the DF, the LH pulse frequency it is exposed to and the systemic concentrations of IGF-I. Follicles less than 1 cm in diameter rarely ovulate. The LH pulse frequency required for ovulation is about 1 pulse per hour. This pulse frequency ensures there is a significant increase in oestradiol concentrations necessary to induce positive feedback and ovulation to occur. If the first postpartum DF ovulates, oestrous behaviour is not generally expressed and the ovulation is silent (Kyle et al., 1992). This is because ruminants require prior exposure to progesterone in order for them to express oestrous behaviour in response to the pre-ovulatory increase in oestradiol (Kyle et al., 1992) that causes

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first postpartum ovulation. Thus, it is necessary to pre-treat anoestrous cows with progesterone in order to increase the chances of behavioural oestrus being shown at first ovulation. In addition, the length of the first luteal phase is also often short, due to the premature release of PGF2␣ arising from the increased oestradiol produced from the formation of the post-ovulatory DF on days 5–8 of the cycle. Thus, the CL regresses prematurely at days 8–10 of the cycle and the DF from the first post-ovulatory follicle wave ovulates around days 9–11 after the first ovulation. The second ovulation is generally accompanied by oestrous behaviour and a normal length luteal phase. Prior exposure to progesterone also plays a key role in determining whether or not a short cycle occurs. Treatment of anoestrous cows with progesterone and oestradiol induces oestrous and shortens the postpartum interval to conception (Rhodes et al., 2003). Cows can have two, three or four follicle waves during the oestrous cycles that recur in the early postpartum period (Savio et al., 1990a; Sartori et al., 2004). Holstein cows tend to have two follicle waves per 18–23 days cycle (Sartori et al., 2004). Certain factors that regulate LH pulse frequency such as progesterone concentration may affect the duration of dominance of the sequential DFs that develop during the luteal phase of the oestrous cycle. Holstein cows have lower concentrations of progesterone during the cycle than cyclic heifers (Sartori et al., 2004; Wolfenson et al., 2004). Thus, the lower concentrations of progesterone may allow a subtle increase in LH pulse frequency and allow the DF to continue to grow rather than undergoing atresia, thereby preventing the development of a third follicle wave. Cows with longer than normal luteal phases can have a fourth follicle wave (Savio et al., 1990a). Follicle waves also continue during early pregnancy (Savio et al., 1990a). The number of follicle waves will affect the duration of dominance of the DF and, in general, the shorter the duration of dominance of the pre-ovulatory follicle, the higher conception rate to AI will be, where all other factors are consistent (Austin et al., 1999). Thus, nutrition by altering metabolic clearance rates of progesterone can affect the number of follicle waves per cycle, and hence, indirectly, conception rates. 3.2. Failure of first postpartum DF to ovulate The factors that influence whether the first postpartum DF ovulates are BCS, yield, parity season and disease (Beam and Butler, 1997; Stagg et al., 1998). Cows that calve down in poor BCS (<2.5) are more likely to have a prolonged anoestrous period (Fig. 1) due, presumably, to low LH pulse frequency and subsequent reduced concentrations of oestradiol, which are ineffective to induce an LH surge and ovulation. Cows in poor BCS after calving have decreased diameter of the DF, reduced insulin and IGF-I concentrations and low LH pulse frequency. Current evidence suggests cows should calve down in a BCS of 2.75–3 and not lose more than 0.5 of a unit of BCS between calving and first service (Overton and Waldron, 2004) rather than the previous higher recommendations of 3–3.5 (Buckley et al., 2003). Cows that lose ≥1 unit BCS have a longer postpartum interval to first ovulation. Thus, monitoring of BCS score from calving to first service is an important aspect of good reproductive management. Current Holstein cows produce very high yields of milk. This high yield in the early postpartum period forces the cow to mobilize mainly fat but also protein to meet the energetic demands of milk production. Cows can lose 50–75 kg body weight. It is necessary to prevent a steep decline in NEB and to shorten its duration postpartum by increasing dry matter intake (DMI) in the early postpartum period. Cows that are mobilizing tissue at a high rate have increased blood concentration of non-esterified fatty acids, ␤-hydroxy butyrate, triacylglycerol but reduced concentrations of insulin, glucose and IGF-I (Grummer et al., 2004). This metabolic status increases the risk of hypocalcaemia, acidosis, ketosis, fatty liver and displaced abomasums (Gr¨ohn and Rajala-

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Schultz, 2000; Overton and Waldron, 2004; Maizon et al., 2004). The occurrence of subclinical hypocalcaemia increases the risk of reproductive problems associated with parturition viz such as dystocia and retained placenta while the occurrence of metabolic disorders after calving can affect uterine functions viz endometritis. Cows thus affected are more prone to mastitis, lameness, anoestrus and reduced conception rate to AI (Fourichon et al., 1999; Gr¨ohn and Rajala-Schultz, 2000; Lucy, 2001; L´opez-Gatius et al., 2005; Maizon et al., 2004). This, in turn, means these cows are more likely to be culled for infertility. Therefore, high yielding cows must be nutritionally managed to ensure only a mild, but not severe, NEB deficit post calving occurs, have adequate Ca mobilization in the peri parturient period and are given the appropriate vitamin and mineral allowances, particularly selenium, iodine, vitamins A, D and E to maintain their health, welfare and reproductive status. Current strategies to mimimize BCS loss involve keeping cows in BCS 2.75–3.00 at calving, shortening the dry period and maintenance of normal rumen function. 3.3. Formation of a cystic follicle These occur when the first DF that develops in the early postpartum period fails to ovulate and continues to grow to diameters >25 mm over a 10–40 days period in the absences of a corpus luteum (CL) in the dairy cow (Savio et al., 1990a; G¨umen et al., 2002; Hatler et al., 2003). The continuation of the growth of the cyst seems to be due to lack of positive feedback induced by oestradiol and thus failure of occurrence of an LH/FSH pre-ovulatory surge. Thus, progesterone concentrations are low but oestradiol concentrations are elevated much above normal proestrous concentrations (Savio et al., 1990b; Hatler et al., 2003). This elevation in oestradiol affects their behaviour, and cows with follicular cysts tend to be members of the sexually active group, and thus can facilitate oestrous detection. The secretion of high concentrations of oestradiol from the cyst and also presumably inhibin, result in the suppression of FSH recurrent increases; hence no new follicle wave emerges during this period. It then appears that the cyst becomes oestrogen inactive while still morphologically present and still detectable by ultrasound examination. This is followed by new follicle wave emergence and subsequent ovulation often when the original large physiologically active cyst is still present. This difference in functionality is important in deciding whether or not to treat a cow with a cystic follicle. Multiple cysts can develop simultaneously and these are often accompanied by very high concentrations of oestradiol being produced during their early physiologically active phase. Many cysts that occur in the early postpartum period self correct but some persist and further cysts can develop which may be hard to eliminate. Cows with ovarian cysts take 6–11 days longer to first service and 20–30 more days to conception (Fourichon et al., 1999). The metabolic risk factors involved in the pathogenesis of cysts are overconditioned cows, a reduction in insulin and IGF-I and increased non-esterified fatty acids (Vanholder et al., 2005; Zula et al., 2002b). Cows with an abnormal puerperium were 1.9 times more likely to develop cysts while an increase of 1 unit of BCS increased the risk 8.4 times; thereby indirectly implicating nutrition as a secondary causative factor (L´opez-Gatius et al., 2002). 3.4. Manifestation of irregular cycle lengths Some cows have irregular cycles, either shorter or longer than 3 weeks in the absence of the embryo. These irregular cycles generally relate more to premature or prolonged CL regression. The risk factors associated with irregular cycles are dystocia, RFM, abnormal vaginal discharge and metritis (Opsomer et al., 2000). Cows with atypical ovarian progesterone patterns before first service had longer intervals to conception, a higher number of services per conception and lower

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first service pregnancy rates (Lamming and Darwash, 1998). The incidence of prolonged cycles in non-pregnant cow has increased from 3% (Fagan and Roche, 1986) to 11–22% (Lamming and Darwash, 1998; Opsomer et al., 2000; Shrestha et al., 2004). 4. Detection of oestrus The efficiency of detection of oestrus in cows at farm level is variable but often low (Stevenson, 2001). This is a major limitation to achieving high submission rates to A1. The problem is due to the short duration of oestrus and exacerbated by the occurrences of low intensity oestrous behaviour. Continuous monitoring of dairy cows using pressure activated radiotelemetric devices showed that the duration of oestrus was 7.14 h (range of 5.5–10.6 h) with cows being mounted 8.5 times per oestrus (range of 6.4–12.8 times) (Dransfield et al., 1998). Similar results were reported by Xu et al. (1998) for dairy cows at pasture. The intensity of expression of oestrus is affected by housing, floor surface, yield, lameness and number of herd mates in oestrus simultaneously (Diskin and Sreenan, 2000). High ambient temperatures causing heat stress result in physical lethargy and reduced oestrous detection efficiency in cows (Peralta et al., 2005). Cows with high milk production (≥40 kg/day) have shorter duration of oestrus (6.2 ± 0.5 h versus 10.9 ± 0.7 h), less total mounts per cow (6.3 ± 0.4 s versus 8.8 ± 0.6 s) and overall shorter duration of total time standing to be mounted (21.7 ± 1.9 s versus 28.2 ± 1.9 s) than lower producing cows measured at the same postpartum interval (Lopez et al., 2004). Moreover, the high producing cows have more low intensity/short duration oestrus periods (53%) compared with low producing cows (32%). In Japan, it has been reported that 33% of cows apparently in oestrus, based on expression of secondary oestrous behavioural signs, were not detected to stand to be mounted when checked every 4 h (Yoshida and Nakao, 2005). Thus, as production levels of cows continue to increase, due to improved genetics and nutritional management, the duration and intensity of expression of oestrus have been reduced, thereby exacerbating the problems of oestrous detection, often in association with reduced labour input and sometimes associated with reduced technical knowledge of the stockmen hired. The physiological causes of these detrimental effects of high milk production on duration and expression of oestrus are in part related to a reduction in the concentrations of oestradiol on the day of oestrus (Lyimo et al., 2000). The increased milk production was associated with a corresponding increase in DMI, which increased liver blood flow and metabolic clearance rates of the key steroid hormones, progesterone and oestradiol (Sangsritavong et al., 2002). It is hypothesized that this increased metabolic clearance rate of the key reproductive steroid hormones is a major cause of the reduced oestradiol concentrations on the day of oestrus and thus it decreases the probability of detecting oestrous as DMI intake increases in high producing cows. Furthermore, heifers have higher concentrations of oestradiol than dairy cows (Sartori et al., 2004; Wolfenson et al., 2004) on the day of oestrus. The changes in peripheral steroid hormones during the oestrous cycles of high producing cows induced by high metabolic clearance rates of the key gonadotrophin regulating steroid hormones could alter the follicular wave patterns, duration of dominance and the time of ovulation relative to the onset of oestrus (Austin et al., 1999). The optimum time to inseminate cows has been reconfirmed to be within 4–12 h of observation of oestrus (Dransfield et al., 1998) since the cow generally ovulates 24–28 h after the onset of oestrus. Ovulation is induced by positive feedback of oestradiol on GnRH secretion, which results in the pre-ovulation LH/FSH surges and ovulation. Thus, the attenuation of the oestradiol increase on the day of oestrus could affect the timing of the LH/FSH surge, and hence the time of ovulation. This could potentially affect the optimum time to inseminate cows with reduced concentrations

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of oestradiol on the day of oestrus. Acute reduction in the plane of nutrition of heifers attenuated both the proestrous increase in oestradiol and the magnitude of the LH surges (Mackey et al., 1999). There was a significant relationship between peak proestrous concentrations of oestradiol and pregnancy rates with reduced pregnancy rates occurring in heifers with attenuated oestradiol increases. This again highlights that nutrition can affect, indirectly, oestradiol concentrations on the day of oestrus, which, in turn, can affect the duration and intensity of oestrous behaviour and perhaps also fertility by affecting the time of ovulation in the cow. 5. Conception rate to AI The optimum time to inseminate the cow is 12–18 h before ovulation using viable fresh or frozen (thawed) semen. The fertile life span of bull spermatozoa is 24–30 h (Dalton et al., 2001) but the viable life span of the ovulated oocyte is only 6–12 h (Gordon, 1996). Breeding heifers based on the use of secondary signs of oestrus such as triggered heat mount detector, non-standing behavioural signs based on mounting and chin resting, or rectal palpation, resulted in significantly reduced conception rates (Donovan et al., 2003). The nutritional factors that affect conception rates include. 5.1. Disease status Cows that develop hypocalcemia, ketosis, acidosis or displaced abomasum can have lower CR to first service, require more inseminations per pregnancy, or take longer postpartum to become pregnant (LeBlanc et al., 2002; Kim and Kang, 2003; Gilbert et al., 2005). These metabolic diseases are key risk factors for the development of gynaecological problems during or after parturition and in the early postpartum period during the critical period of uterine involution. The key risk factors for delayed conception identified by Gr¨ohn and Rajala-Schultz (2000) were RFM, metritis and cysts while Maizon et al. (2004) found that days from first breeding to conception increased in cows with dystocia, stillbirth, RFM, metritis or ovulation dysfunction. Conception rates were reduced by 14, 15 and 21%, respectively, in cows with RFM, metritis or cysts compared with cows not diagnosed with these problems (Gr¨ohn and Rajala-Schultz, 2000). Other studies show that delayed conception can be related to sub-clinical disease, stressful environmental, social conditions and nutritional stress (L´opez-Gatius et al., 2005). Thus, it is clear that inadequate nutritional management of the cow in the dry period and after calving has a significant negative impact on subsequent conception rate, services per conception and interval from calving to conception. These effects of nutrition are manifest through different mechanisms including BCS changes, increase incidence of metabolic disease, the resultant abnormal metabolic profiles precipitated, the increased incidence of gynaecological problems with their attendant detrimental effects on the uterus and the abnormal profiles of cytokines and endotoxins produced which can act locally or systemically on the developing embryo. 5.2. Rate of BCS loss Dry matter intake and energy balance during the dry period and post calving transitional period have a crucial influence on herd health, productivity and reproductive efficiency. They affect endocrine parameters, metabolic hormones and key concentrations of metabolic factors. There is a normal decline in DMI prepartum in cows, as the foetus grows, which is exacerbated in cows that subsequently develop metabolic or gynaecological problems at or after parturition

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(Grummer et al., 2004). Thus, excessive drop in DMI prepartum could serve as an early warning signal of the propensity of cows to develop problems at or after parturition. Overconditioned cows have increased incidence of peri- and post-parturient problems (Zula et al., 2002b; Lacetera et al., 2005). However, it is becoming increasingly clear that massive increases in BCS followed by abrupt loss in the early postpartum period are not well tolerated by the cow. Overconditioned cows lose more BCS, have reduced DMI postpartum (Zula et al., 2002b; Jorritsma et al., 2003) and can be more difficult to get in calf. Accordingly, it may be more important to precondition the physiology and metabolism of the cow to moderate changes in NEB and minimal BCS loss (<0.5 unit) in order to attenuate the massive changes in metabolites and metabolic hormones that occur in the early postpartum period. Thus, minimizing BCS changes pre and post calving, maintenance of optimal rumen function and prevention strategies to prevent metabolic disorders are key management targets, in association with improved cow comfort and reduced stress, to improve health, productivity and reproductive efficiency of high yielding dairy cows. Furthermore, feeding high roughage diets at the start of the dry period to minimize BCS gain and maintaining change in BCS score of 0.5 of a unit are increasingly important goals to achieve for high conception rates and herd pregnancy rates (Overton and Waldron, 2004). 5.3. Dietary effects It is important to supply cows with the specific amino acid requirements for milk synthesis, reproduction and general body maintenance. These are derived from metabolizable proteins of either microbial or dietary origin. The protein content of the diet affects milk production and composition but many studies show that increasing the crude protein content of the diet reduces fertility (reviewed by Laven and Drew, 1999) by reducing conception rates to service, particularly in older cows, thereby prolonging days open. Some studies have shown that the degradability of the protein affects fertility, but this is conflicting (Laven and Drew, 1999; Westwood et al., 2000). Where excess protein is fed to cows in NEB, the energetic demands of excreting this as urea may exacerbate the effects of the NEB on reproduction, thereby decreasing fertility. This is supported by the fact that high crude protein diets with associated elevated urea levels, did not affect embryonic survival in heifers (Kenny et al., 2002). The source of rumen undegradable protein may be important. Where fish meal is used, improvements in fertility have been obtained in some studies but it is not clear if this effect is due to its protein content or fatty acid profile provided. There is increasing evidence that the fatty acid composition provided by feeding supplemental by-pass fats can alter the fatty acid profile in the blood of cows and increase linoleic acid (Thatcher et al., 2006). This results in increased arachadonic acid levels, which in turn result in increased PGF synthesis. PGF plays an important role in uterine involution, in upregulation of the immune system and neutrophil function in the early postpartum period. Thatcher et al. (2006) have hypothesized that a dietary strategy of feeding certain by-pass fats to increase PGF production in the uterus and enhance immune competency is a novel approach to reduce uterine infections and assist normal uterine involution in the transition period with consequent beneficial effects on fertility. The type of fat fed during the breeding season should provide increased levels of n − 3 fatty acids in order to reduce PGF␣ synthesis at the expense of increased PGE or other non-luteolytic PGs. This reduced or delayed synthesis of PGF␣ could be important in giving a longer period for maternal recognition of pregnancy (MRP) to take place from smaller embryos producing less interferon tau often in association with reduced progesterone concentrations before MRP (Mann et al., 2006). The feeding of fish oil reduces uterine PGF␣ synthesis and may benefit fertility in cows.

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6. Oocyte and embryo developmental capacity A major reason for reduced conception rates in dairy cows is the increased embryonic mortality prior to MRP (Sartori et al., 2004). This effect can be manifest as early as day 5 after AI. It is not yet clear whether this increased loss is due to ovulation of an incompetent oocyte capable of being fertilized but not able to develop or due to reduced embryonic development as a result of oviduct-uterine environmental aberrations. It is clear that progesterone concentrations are reduced by high DMI intake (Sangsritavong et al., 2002) and that embryonic loss is increased in cows with reduced progesterone concentrations days 4–7 post-insemination due in part to the presence of reduced interferon tau concentrations (Mann et al., 2006; Stronge et al., 2005). A reduction in oocyte competency in high yielding Holstein Friesian cows has been reported (Snijders et al., 2000; Leroy et al., 2005). Thus, it appears that both oocyte competency and embryonic survival are compromised. Nutrition is also implicated in oocyte competency because during NEB, the levels of non-esterified fatty acids are elevated which can compromise oocyte developmental capacity (Leroy et al., 2005) in the early postpartum period. 7. Conclusions Nutrition plays a pivotal role in determining fertility of postpartum cows. It affects submission rate of cows to AI during the breeding season by increasing the incidence of anoestrus due to its suppressive effect on LH pulse frequency, and reduced oestradiol production from the dominant follicle which then undergoes atresia rather than ovulation. The incidence of anoestrus in dairy cows has increased. The occurrence of metabolic disorders in their own right often delay the interval to first detected oestrus as well as predisposing cows to gynaecological disorders such as dystocia, RFM, endometritis and metritis. These disorders also reduce submission rate to AI. Their incidence is also increasing. There appears to be an interaction between the occurrence of metabolic diseases such as hypocalcemia, ketosis and fatty liver and an increased incidence of dystocia, RFM and endometritis. Thus, prevention of metabolic diseases is one important component of attaining high reproductive efficiency in dairy cows and points to the interaction of good nutritional management on fertility. Over conditioned cows (BCS >3.5) have reduced DMI post calving, lose excess BCS post calving, have lower fertility and increased risk of developing cystic follicles. Management of BCS is a critical component of nutritional management of cows for high fertility. Major increases in or loss of BCS are undesirable. It is clear that optimum reproductive efficiency is obtained when BCS loss is at or below 0.5 unit during the transition period. To achieve this important target, cows should be maintained at a BCS of 2.5–3.0 in association with maintenance of proper rumen function through adequate dietary fibre, shortening the dry period (6–8 weeks maximum), reduction in the incidence of subclinical metabolic disorders, particularly hypocalcemia and minimizing mobilization of body reserves in the early postpartum period. Nutrition and dietary factors also affect conception rate and the number of services per conception. Cows that have had metabolic disorders and/or gynaecological problems are more likely to have lower conception rates and to be culled due to infertility. The rate of BCS loss is also a critical component with cows losing most BCS and in low BCS at time of AI having reduced fertility. The energy status of the diet is, therefore, critical. However excess protein, particularly in cows in NEB can reduce conception rates to AI. In addition the fatty acid profile of the diet, the type of fat fed and the use of fish meal can affect uterine health and conception rates. Cows with high metabolic loads will metabolize progesterone faster resulting in reduced progesterone

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concentrations during early embryonic development, thereby reducing conception rates due to high embryonic loss in such cows. In order to meet the challenge of increasing fertility of the modern dairy cow, genetic strain selected, optimizing nutritional management, reduction in the incidence of metabolic and gynaecological disorders, and improved reproductive management in herds of increasing size with reduced labour are all critical components of fertility. Thus, multi-disciplinary approaches using the latest technology are fundamental to overcoming this major problem, which is a key component of determining the level of productivity, profitability and cow comfort in the herd.

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