CONTACT Jennifer Roberts jennifer_3.roberts@boehringer-ingelheim.com © 2025 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http:// creativecommons.org/licenses/by-nc/4.0/), permitting all noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Citation: Clinical Theriogenology 2025, 17, 11644, http://dx.doi.org/10.58292/CT.v17.11644 Review Report Anovular conditions impacting fertility in dairy cattle and considerations for clinical management Jennifer Roberts,a Clare Scullyb aBoehringer Ingelheim Animal Health, Duluth, GA, USA bDepartment of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA Abstract Reproductive performance is a primary driver of herd profitability and reproductive failure or infertility is one of the main causes of culling in USA dairy herds. Nearly ⅓ of dairy cows in USA experience anovulation in early lactation leading to increases in days open and reductions in first service conception rates. Anestrus and anovulation in dairy cows can be attributed to many causes including parity, postpartum uterine or systemic diseases, nutritional deficiencies, body condition loss, and stress. Identification and management of anovular cows, including strategies to reduce the incidence of anovulation, are critical to the overall reproduc- tive performance of the herd. The aim of this review is to highlight causes, recent research on anovulatory conditions, and clinical approaches to management to improve dairy herd reproductive outcomes.  Keywords: Anovulation, anestrus, dairy cattle, infertility  Introduction Optimizing profitability is a primary focus of producers and veterinarians in the USA dairy industry. One of the drivers of maintaining profitability within a dairy herd is the ability to achieve optimal reproductive performance and minimize the number of days open after calving. Many factors influence the number of days open or the calving to conception interval including, but not limited to, herd management, nutrition, metabolic disease during early lactation, uterine health, and ovarian function. Failure of cyclicity in early lactation or anovulation has been a focus of researchers and clinical veter- inarians for decades. In cattle, anovulation is broadly defined as lack of ovulation during the normal 21-day estrous cycle. The term anovulation is often used interchangeably with anestrus; however, it is important to distinguish anovulation from anestrus as it is not uncommon for cows in the postpartum period to have a silent estrus at first postpartum ovulation. Four types of anovulation have been described in cattle. Type I involves fol- licle growth only to emergence, Type II is characterized by fol- licle growth to deviation with failure to reach ovulatory size, Type III is follicle growth to ovulatory size or larger and may be referred to as persistent or cystic follicles, and Type IV is anovulation as a result of a prolonged luteal phase1,2 In dairy production, postpartum anovulation of any type can delay cows’ ability to conceive and result in economic losses due to increases in the number of days open or culling due to subfertility.  Incidence of anovulation in the USA varies by region, farm, and parity; analysis of data across 4 geographical regions iden- tified 28.5% anovulation rate (8.1-49.6% among farms).3 The ranges emphasized the variability of the condition across var- ious management systems. In addition, there is also opportu- nity for veterinarians to influence herds’ reproductive health and performance by focusing on diagnostics and interven- tions to reduce the economic impact of anovular conditions. Postpartum anovulation Uneventful calving followed by normal uterine involution and return to cyclicity are critical milestones in the postpar- tum period of dairy cows. Although this appears simple, in theory, the return to cyclicity depends upon an intricate series of events involving an array of molecular and cellular signal- ing, with the production and release of hormones throughout the hypothalamic-pituitary-ovarian axis. The modern dairy cow experiences many stressors in the postpartum transition period that can disrupt the delicate balance of this complex mailto:jennifer_3.roberts@boehringer-ingelheim.com http://creativecommons.org/licenses/by-nc/4.0/ http://creativecommons.org/licenses/by-nc/4.0/ http://dx.doi.org/10.58292/CT.v17.11644 Citation: Clinical Theriogenology 2025, 17, 11664, http://dx.doi.org/10.58292/CT.v17.11664 3 biological phenomenon. On average, the first postpartum ovulation occurs around 30 days in milk (DIM); however, this can be impacted by nutritional status, uterine health, and presence or absence of concurrent diseases.4-7 During the post- partum period, it is common to observe a voluntary waiting period (VWP) during which, despite cows exhibiting estrous signs, producers elect to delay insemination to allow uterine involution completion to ensure uterine environment readi- ness for subsequent pregnancy. Length of VWP varies depend- ing on farm management but is typically 60-80 days postpartum. As many as 20-30% of cows may be anovular at the end of the VWP, which can decrease conception rates after first artificial insemination (AI) and increase days open.8 Postpartum diseases have substantial impact on ovular sta- tus of dairy cows. Among anovular cows, 63.8% were diag- nosed with at least 1 postpartum health problem.7 Prevalence of retained fetal membranes, metritis, ketosis, and digestive disease (e.g. displaced abomasum) and lame- ness were significantly higher among anovular compared to cyclic cows. Additionally, cows experiencing 1 health event had 2-fold increase in risk of anovulation whereas cows with 2 or more health events were 3 times more likely to be anovular compared to cows that remained healthy in the postpartum period.7  Nutritional status also has an important role in return to cyclicity in the postpartum period. The transition from the dry period to early lactation involves a major shift in energy requirements as milk production commences whereas dry matter intake does not increase as rapidly to keep up with the demand for increased energy. Consequently, dairy cows in early lactation experience a state of negative energy bal- ance (NEB) that can result in diversion of nutritional resources away from the reproductive tract.2 The mecha- nism by which NEB delays onset of first postpartum ovula- tion has been attributed to low blood concentrations of glucose, insulin and insulin-like growth factor-I, and inhi- bition of LH pulse frequency.4 In addition, increases in cir- culating non-esterified fatty acids (NEFA) and ketone bodies that are often associated with NEB in cows can have negative effects on oocytes and granulosa cells9 and high NEFA concentrations have been associated with higher risk of anovulation around 63 DIM.6 A study evaluating blood metabolites and activity data in cows ovulating early or late in the postpartum period, defined as before or after 33 DIM, implied that earlier ovulating cows had lower serum concentrations of free fatty acids, beta-hydroxybutyrate, and haptoglobin and spent more time eating and less time resting in the first 3 weeks after calving compared to cows that ovulated later. Additionally, early ovulating cows lost less body condition in the first 9 weeks postpartum.5 In a study evaluating 942 Holstein primiparous and multipa- rous cows, those with a lower body condition score (BCS) at 35 DIM were more likely to be anovular compared to those with higher BCS.7 The interconnectedness of nutri- tion, postpartum health, and reproductive performance underscores the importance of focusing on the postpartum period when working up cases of poor reproductive perfor- mance in dairy herds.  Diagnosis of postpartum anovulation is via transrectal pal- pation or ultrasonographic examination or measurement of serum or milk progesterone concentrations. The most practi- cal and commonly implemented methods in commercial dairies are transrectal ultrasonography or palpation. Absence of corpus luteum at either of 2 ultrasonographic examina- tions performed at a 14-day interval has been used as criteria for determining an anovular state.7 Anovular cows diagnosed with small ovaries via transrectal palpation alone may be referred to as static; however, even in the case of small ova- ries, there may still be follicular activity and growth beyond emergence of the deviation stage of development, making ultrasonography a more reliable means to assess the ovarian activity of anovular cows.1 Despite the apparent lack of ovar- ian activity in cows with small ovaries on transrectal palpa- tion or ultrasonography, follicles that have reached the deviation stage may be capable of responding to exogenous gonadotropin releasing hormone (GnRH) and presynchro- nization protocols using timed injections of GnRH and pros- taglandin have been successful in reducing the prevalence of anovular cows in early lactation.1,10-12  Resolution of anovular conditions can be achieved using progesterone exposure to reinitiate the hypothalamic respon- siveness to estradiol to stimulate an LH surge from the ante- rior pituitary. In anovular cows, a minimum of 3 days of progesterone exposure improved ovulation.13 From a practi- cal standpoint when designing protocols to be implemented on farm, 7 days of progesterone exposure is more commonly used to reduce labor associated with additional handling of synchronized cows. Although exogenous progesterone sources are available for use in lactating dairy cows, a more widely adopted strategy to increase circulating progesterone involves a presynchronization protocol that induces ovula- tion with subsequent formation of a CL and increase in endogenously produced progesterone. Presynch-Ovsynch and Double Ovsynch are presynchronization protocols used in many dairy herds. Multiple studies have implied that GnRH and prostaglandin (PGF)-based presynchronization like Double Ovsynch is more effective for inducing ovulation and decreasing the number of anovular cows prior to the breeding Ovsynch portion of the protocol as compared to a PGF-based presynchronization like Presynch-Ovsynch.14 Cows with progesterone concentrations < 1 ng/ml at the final PGF injection of Ovsynch are more likely to experience a short luteal phase and significantly lower pregnancy rate per AI (P/AI) than cows with serum progesterone > 1 ng/ml.8 Therefore, an important component in management of anovular cows in the postpartum period should be imple- mentation of presynchronization protocols capable of achieving higher serum progesterone concentrations at final PGF injection of the protocol.  Uterine health and anovulation Uterine involution and clearance of uterine contamination in the postpartum period is another critical factor in return to cyclicity. Reproductive challenges of cows experiencing retained fetal membranes, puerperal metritis, and delayed involution have been well documented.3,15-19 Effects of post- partum uterine diseases on fertility and cyclicity have been attributed to bacterial uterine contamination leading to sys- temic inflammation and endotoxins in follicular fluid and systemically. The inflammatory process may lead to a decrease in LH secretion, slower follicular growth and reduced size of the dominant follicle, and reduced ste- roidogenesis within the follicle, all of which negatively impact return to cyclicity.3 The intimate association of the uterine vein and ovarian artery that allow for countercurrent exchange of prostaglandin from http://dx.doi.org/10.58292/CT.v17.11664 4 Citation: Clinical Theriogenology 2025, 17, 11664, http://dx.doi.org/10.58292/CT.v17.11664 the uterus to the ovary also has the potential to transport endotoxins and other proinflammatory cytokines from an infected postpartum uterus to the ovary. Endotoxins reach fol- licular fluid causing inflammation, oxidative stress, and ulti- mately, delayed oocyte development and ovulation.20 Anovular cows had higher concentrations of endotoxin in fol- licular fluid and a greater degree of systemic inflammation as measured by serum haptoglobin compared to ovular cows in the early postpartum period.21 However, it is important to note that a robust local inflammatory response within the uterus on the day of calving is positively correlated with return to cyclicity.21 The reported benefits of inflammation on the day of calving are consistent with other research indicating that dysregulation of the inflammatory process in the immediate postpartum period contributed to retained fetal membranes.22 Consequently, some degree of inflammation is beneficial to postpartum uterine health whereas increased inflammation associated with increased bacterial contamination of the uterus is detrimental to fertility.  Clinical endometritis or subclinical endometritis, identi- fied clinically as cows with purulent vaginal discharge (PVD) or abnormal endometrial cytology after 21 days postpartum, respectively, also result in negative effects on postpartum fertility and cyclicity.3,23 Cytological endometri- tis (CE) is often used as a proxy for subclinical endometri- tis. Cows with subclinical endometritis may go undiagnosed by farm personnel due to lack of visible clinical signs. In contrast, cows with PVD, or clinical endometritis, are easily identified and may be managed more aggressively to address uterine inflammation. Clinically, these conditions are often considered less severe compared to puerperal metritis but any postpartum condition that results in pro- longed inflammation has the potential to reduce first ser- vice conception rates, increase days open and reduce fertility, thereby contributing to increased risk of culling and decrease in productive life of dairy cows.  Cows diagnosed with CE experience significantly prolonged postpartum anovulation (OR = 1.52) compared to cows that are not diagnosed with CE.6 Combined with anovulation, effects of CE are even more substantial. Individual and com- bined effects of anovulation and cytological endometritis in 1,569 cows across 3 states were evaluated.23 Cyclicity was determined via serial transrectal ultrasonographic examina- tions at 35 and 49 DIM. Cows without a corpus luteum at both time points were diagnosed as anovular. Cows that were anovular and were diagnosed with CE had a first service pregnancy per AI (P/AI) of 21.3% compared to healthy cyclic cows that achieved P/AI of 46.7% whereas cows that were healthy but anovular had a P/AI of 37.9%.23 In addition, cows that were anovular, with or without CE, had more days open compared to healthy cows with or without CE. Although this study demonstrated that uterine disease com- bined with anovulation has an additive negative effect on reproductive performance, the reduction in P/AI for healthy, anovular cows in this study reinforced the importance of return to cyclicity and its impact on fertility.  In another study, the combined effect of anovulation and purulent vaginal discharge (PVD) in 10,995 cows in 16 herds across USA were evaluated.3 Diagnosis of PVD was made at 28 DIM and anovulation was diagnosed via tran- srectal ultrasonographic examinations at 40 and 54 DIM. The mean prevalence of anovulation and PVD was 28.5 and 25.7%, respectively.3 Cows diagnosed with both PVD and anovulation had decreased first service conception rates and increased days open compared to healthy cows or cows with either PVD or anovulation alone.  Cows that are pregnant at 130 DIM are more likely to main- tain or gain body condition in the first 30 days of the next lactation, leading to a greater chance of pregnancy and reduced pregnancy losses after insemination.24 This con- cept, referred to as the high fertility cycle, relies on prompt insemination of cows in early lactation with the goal of maintaining health and fertility in each subsequent lacta- tion. Anovulation and uterine disease in the postpartum period have the potential to make this goal unattainable, leading to farm reproductive losses. Therefore, manage- ment practices should be aimed at optimizing postpartum uterine health and reducing the herd prevalence of metritis and endometritis, as the effects of these conditions com- bined with anovulation are detrimental to herd reproduc- tive performance. Large ovary syndrome and anovulation Large ovary syndrome (LOS) is a collection of conditions that may cause anovulation in the cow and includes ovarian cysts, abscesses, hematomas, and neoplasia. Among LOS cases referred to a veterinary teaching hospital, 60% were granulosa theca cell tumors (GTCT).25 Although rare, GTCT is the most common ovarian neoplasm reported in cattle and leads to anovulation via production of anti-Müllerian hormone (AMH), inhibin, and estradiol that arrest follicu- lar development on the contralateral ovary through nega- tive feedback to the hypothalamus and pituitary.26 The predominance of GTCT cases in referral centers is most likely related to the fact that other causes of LOS, particu- larly ovarian cysts, are managed on farm by the clinician and not referred. In a commercial dairy, it is unlikely that GTCT cases would be treated as it is more economical to cull these animals from the herd. However, in animals of high value or genetic merit, the clinician may be requested to investigate or treat an animal with suspected GTCT. The diagnosis of GTCT can be presumptively made via transrec- tal ultrasonography and confirmed via hormonal assays or histopathology; AMH and inhibin may be used to confirm GTCT diagnosis versus other causes of LOS.26,27 Unilateral ovariectomy to remove the affected ovary can lead to favor- able outcomes including return to fertility in the majority of cases; however, other reproductive comorbidities such as pneumovagina or urovagina may contribute to culling.25 Therefore, it is important to consider all factors, including economics and genetic value of the animal, prior to invest- ing in GTCT treatment to resolve anovulation in these cases.  Cystic ovarian disease Cystic ovarian disease (COD), another condition broadly classified within LOS, represents a significant challenge in dairy cattle management, impacting reproductive efficiency and economic sustainability within the industry. This section aims to elucidate the complexities of COD, from its etiology to its diagnosis and management strategies. Cystic ovarian disease is defined as the presence of anovula- tory follicles > 17 mm in diameter in the ovaries that interfere with cyclicity and persist for more than 6 days, with low to intermediate concentrations of progesterone http://dx.doi.org/10.58292/CT.v17.11664 Citation: Clinical Theriogenology 2025, 17, 11664, http://dx.doi.org/10.58292/CT.v17.11664 5 indicative of the absence of a corpus luteum.28,29 The flu- id-filled structures in the ovaries are classified as follicular or luteal cysts based on steroid production. The disease eti- ology and progression are not entirely understood; how- ever, environmental and hereditary factors are speculated that affect clinical outcomes. The most consistent hypothe- sis for occurrence of COD is a dysfunction of the neuroen- docrine system, specifically in the hypothalamic-pituitary axis. Cystic ovarian disease is caused by a disturbance of the estrogen positive feedback on the hypothalamus that leads to failure of preovulatory LH surge and consequently leads to anovulation.1 The disturbance is associated with an unre- sponsiveness of the hypothalamus, caused by either decreased estradiol or abnormal progesterone concentra- tions. Another factor that can predispose cows to develop ovarian cysts is increased milk production and associated stress, through the adrenocorticotropic hormone (ACTH) and cortisol secretion. The secretion of both ACTH and cor- tisol suppresses the preovulatory LH surge and increased ACTH can downregulate the expression of LH receptor mRNA in the ovarian follicle.30 Additionally, delayed uter- ine involution, retained fetal membranes, and peripartum hypocalcemia can have a role in the development of cysts.31 The heritability of this disease is speculated to be low but breeds and certain bloodlines selected for higher milk pro- duction had increased incidence of ovarian cysts.32,33 Prevalence of COD varies; follicular cysts occurred in 6 to 19% of lactating dairy cows1 and was 4.6% in abattoir sourced tracts.34 Ovarian cysts develop more commonly in dairy cattle, specifically during the early postpartum period and before the first ovulation. Presence and development of these fluid-filled structures affect fertility by increasing the calving intervals, delaying the first postpartum ovulation and estrus, and subsequently increasing the days to first AI.35,36  Although through the years transrectal palpation has been the most common method of diagnosing COD, the diagnostic accuracy of palpation alone, as well as the ability to differenti- ate follicular versus luteal cysts, is relatively poor.37 As a way of improving diagnosis and management of cystic cows, other tests can be performed to better assess ovarian cysts. Ultrasonography is the most reliable tool in diagnosing COD since native anatomical ovarian structures can be differenti- ated from true cysts. These cysts are distinguished via ultraso- nography by their wall thickness. Follicular cysts have a wall thickness of ≤ 3 mm whereas luteal cysts are ≥ 3 mm thick.38 To further differentiate cystic ovarian structures, color doppler ultrasonography (CDU) was used to measure ovarian vascular function; follicular cysts had notably lower blood flow values than luteal cysts and the diagnostic accuracy of CDU was superior to B-mode ultrasonography.39 The combination of wall thickness measurement and blood flow area measure- ments increased the sensitivity to differentiate a follicular from a luteal cyst. The evaluation of progesterone concentra- tions in combination with the ultrasonography analysis may also aid in differentiation of the type of cyst, as progesterone concentration thresholds for follicular and luteal cysts are < 1 ng/ml and ≥ 1 ng/ml, respectively.39 Some behavioral abnormalities that might be observed in cattle with COD are related mostly to the neuroendocrine imbalance. One abnormality the cow may present with is  nymphomania, a frequent, irregular, and prolonged estrus. Other clinical signs at evaluation include elevation of tail-head, relaxation of pelvic ligaments, and even masculine phenotype in chronic cases.38 Although all of these are possible clinical signs of the disease, prolonged anestrus due to failure of ovulation is the most commonly observed manifestation of COD in dairy cattle. It is recom- mended to perform transrectal palpation or transrectal ultrasonography for evaluation of the cyst wall thickness and plasma progesterone concentrations to have a more accurate diagnosis of COD.  For many years, the treatment of COD was manual rupture of the cysts via transrectal palpation. However, this treat- ment is no longer recommended due to the potential nega- tive effects including ovarian trauma, hemorrhage, and an increased risk of ovariobursal adhesions.31 Fortunately, many studies have reported that approximately 60% of cys- tic cows undergo spontaneous recovery and cyst regression by the first postpartum ovulation.31 The mechanism by which the cysts regress spontaneously is still unknown. Nowadays the most common treatment for COD involves the use of gonadotropin releasing hormone (GnRH) to stimulate an LH surge from the anterior pituitary, resulting in luteinization of the cyst.40 The efficacy of these treat- ments varies across studies and the significance, or lack thereof, of reported rates of resolution is likely attributed to small numbers of cows in each study. Human chorionic gonadotropin hormone (hCG) has also been used in the treatment of COD as it has LH-like activity and luteinizes the cysts, leading to increased progesterone concentra- tions;31,41 the resulting luteal cysts are then treated with prostaglandin F2α (PGF2α) that cause the structure to regress, resulting in expression of estrus within 2-5 days.  Treatment with GnRH and PGF2α in combination is benefi- cial for luteal and follicular cyst regression and early return to estrus.31 The use of exogenous progesterone with or with- out the Ovsynch protocol are other options for the treat- ment of COD in cows. Exogenous progesterone treatment can reestablish the hypothalamic response to the estrogen positive feedback mechanism and return the animal to nor- mal cyclicity. Single controlled internal drug release device (CIDR) for 14 days in cows with endocrinologically active cysts (determined via circulating estradiol concentrations) initiated emergence of a new follicular wave within 3 days after CIDR insertion.42 However, this treatment was ineffective for cysts that were not estrogen producing. The Ovsynch artificial insemination protocol has also been used successfully on cows with cystic ovaries. In a study comparing Ovsynch to an exogenous progesterone source for 7 days followed by an injection of PGF2α (with estrus detection as an option) for treatment of cystic cows, the use of the Ovsynch protocol increased the percentage of cows inseminated, but the conception rates and pregnancy rates did not differ across groups.35 Using the findings of this  study, an economic analysis was conducted showing that treatment of COD with a timed AI protocol had an $11.39 advantage over a CIDR-based protocol.43 Ultimately, the decision on which protocol to implement for manage- ment of COD depends on the farm’s ability to achieve pro- tocol compliance, value of the cow, stage of lactation at diagnosis, and the cost benefit ratio of each treatment option.  Cystic ovarian disease remains as a substantial concern in dairy cattle management, demanding ongoing research efforts and collaborative initiatives. Preventing COD neces- sitates a multifaceted approach encompassing genetic http://dx.doi.org/10.58292/CT.v17.11664 6 Citation: Clinical Theriogenology 2025, 17, 11664, http://dx.doi.org/10.58292/CT.v17.11664 selection, nutritional management, prioritization of animal welfare, and evidence-based reproductive protocols. By enhancing our understanding of its etiology, refining diag- nostic techniques, and implementing effective manage- ment strategies, clinicians can work with dairy clients to minimize the economic burden of COD and optimize reproductive outcomes. Technology for identification of anovular cows The availability and affordability of agricultural technolo- gies has been increasing over the past decade. The use of automated activity monitors (AAM) on dairy farms has enabled producers to gather more data on health and repro- ductive parameters than ever before. Automated activity monitor systems use sensor technology incorporated into ear tags, neck collars, leg bands, or boluses allowing dairy producers to monitor cow activity and rumination. The associated software determines baseline data for each cow and monitors daily movement facilitating detection of changes in activity patterns that are associated with behav- ioral estrus. The challenge with increasing amounts of data is determining how to best use the available data to make management decisions to improve production at the herd level. With respect to anovulation, the use of AAM in the postpartum period may enable farmers to identify anovular cows and act more promptly to improve reproductive outcomes.  Anovular cows in the postpartum period were identified via AAM; 35.9% were in the first 30 DIM,44 20.8% at 60 DIM,45 and 17% at 80 DIM.46 Although the rates decreased as DIM increased, these studies were consistent with previous data indicating that, on average, > 20% of cows remain anestrus at the end of VWP. Lack of estrus expression before 60 DIM is negatively associated with reproductive performance with cows that did not express estrus had prolonged interval to first AI, reduced estrus duration and intensity, longer days to pregnancy, and reduced first service pregnancy per AI (P/AI) compared to cows that were detected in estrus.45,47 Furthermore, cows that had 2 or more estrus events prior to the end of VWP were more likely to be inseminated by 100 DIM with a higher first service P/AI, and increased likelihood of pregnancy by 200 DIM compared to cows with 0 or 1 estrus event in the same period.45  Lack of estrus expression may not always coincide with lack of ovulation. From a clinical perspective, at the herd level, methods to assess the true ovarian status of individual cows are rarely practical. Blood progesterone measurements are expensive, require additional labor, and samples must be submitted to an outside laboratory. In-line milk progester- one monitoring is not widely available, and serial ultraso- nography of ovarian structures requires additional time, labor, and veterinary cost. However, the use of confirmatory tests is crucial in understanding the validity of the on-farm AAM systems that many producers use to identify anovular or anestrous cows.  Based on blood progesterone to assess resumption of cyclic- ity, 9% of cows were truly anovular despite 17% diagnosed as anestrus.46 In an assessment of sensitivity and specificity of AAM to detect resumption of cyclicity compared to serum progesterone, AAM had a sensitivity and specificity of 34.1 and 84.0%, respectively.44 The authors attributed the low sensitivity for identification of cyclic cows to the silent estrus often observed in early postpartum cows. However, the higher specificity indicated that the AAM sys- tem was able to correctly identify a majority of the anovular cows. Although this means that some cows diagnosed as anovular may be cyclic and could be enrolled into a syn- chronization protocol aimed at managing anovular cows, there is little risk in doing so. Enrollment in a synchroniza- tion protocol in early lactation improves P/AI to first ser- vice, reduces days open, and improves overall reproductive performance, regardless of ovular status.48 It is noteworthy to consider a presynchronization protocol such as Double Ovsynch over a basic Ovsynch protocol for synchronization of anovular cows as a management strategy. Although anovular cows ovulated in response to GnRH injections, conception rates were lower for anovular cows compared to ovular cows whether they are inseminated after detected estrus or Ovsynch.48 A combination strategy of AAM to detect anovular cows and enrollment in an appropriate syn- chronization protocol is likely most beneficial in improv- ing reproductive performance and the greatest return on investment of these technologies. Targeted reproductive management programs aim to make the best use of AAM along with customizing management protocols for groups of cows within a herd, particularly those that are anestrus and anovular. These programs typically involve allocation of cows to various management strategies for first service insemination based on estrus expression identified by automated activity alerts during the VWP and the use of these data as a proxy for cyclicity. The feasibility of implementing these programs is still a subject of research. For example, prioritization of AI after estrus detection based on estrus expression prior to the end of VWP resulted in sim- ilar proportion of cows pregnant around 150 DIM despite a lower first service P/AI compared to a Double Ovsynch pro- tocol.49 Targeted reproductive management using AAM may provide additional options to improve or at least maintain reproductive performance in herds whose goal is to reduce the cost and labor associated with enrolling all cows in a timed AI protocol for first service.  Future directions Until now, research on anovular conditions focused on the underlying mechanisms, contribution of postpartum dis- eases, and the use of commercially available formulations of various reproductive hormones to initiate resumption of ovarian activity. There are opportunities to explore hor- mones for management of anovular conditions that target the hypothalamic-pituitary-ovarian axis via different mech- anisms than current commercially available reproductive hormones. Synthetic kisspeptin, a peptide hormone, has a role in facilitation of the GnRH surge, and can stimulate ovulation in postpartum cows.50 A single injection of kiss- peptin was capable of inducing ovulation in postpartum anovular cows with a dominant follicle > 10 mm in diame- ter, followed by a normal length estrous cycle. Cows receiv- ing kisspeptin had significant increases in FSH and LH compared to controls but the ability of the kisspeptin-in- duced LH surge to cause ovulation was dependent on follic- ular size. Although this study only enrolled a limited number of cows, there is a potential for an alternate clinical tool in the management of anovulatory cows. Future stud- ies need to examine the effects of kisspeptin treatment on days open, first service P/AI, and pregnancy losses to deter- mine if this management tool has positive impact on fertil- ity in anovular postpartum cows. An additional hurdle for http://dx.doi.org/10.58292/CT.v17.11664 Citation: Clinical Theriogenology 2025, 17, 11664, http://dx.doi.org/10.58292/CT.v17.11664 7 kisspeptin use on a larger scale is that there is currently no commercially available product in the USA; however, the importance of reproductive performance to the USA dairy industry and high prevalence of anovulation in postpartum cows could make development of such a product a viable option for future application. Conclusion Regardless of cause, anovulation has substantial negative effects on reproductive performance and occurs at a rela- tively high rate in USA dairy cattle. Management practices to reduce within-herd rates of anovulation should be focused on maintaining nutritional status and minimizing body con- dition loss in the postpartum period, reducing risks for uter- ine and nonuterine diseases by supporting immune function and overall health, and reducing stress in the postpartum period. Early identification of anovular cows using activity monitoring systems, ultrasonographic examinations during routine herd health visits, or milk progesterone monitoring may allow for enrollment in targeted reproductive manage- ment programs to improve reproductive outcomes in this subgroup of cows. Clinical knowledge of the benefits and shortcomings of each management strategy will enable the reproductive practitioner to better assist dairy herd clients achieving their herd reproductive goals.  Conflict of interest Jennifer Roberts is employed by Boehringer Ingelheim Animal Health; authors have no other conflicts of interest to declare. Acknowledgements Authors acknowledge Paola N Colon Guerra’s contribution; assisted with editing and reference verification of the sec- tion on cystic ovarian disease. References 1. Wiltbank MC, Gümen A, Sartori R: Physiological classification of anovulatory conditions in cattle. Theriogenology 2002;57:21-52. doi: 10.1016/S0093-691X(01)00656-2 2. 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