Pig farming constitutes one of the most significant contributors to global animal protein supply, accounting for more than 30% of the total meat production worldwide (Kim et al., 2023). The pig production sector holds considerable importance in sustaining the livelihoods, food and nutritional securities of the economically disadvantaged communities in many countries (Roesel, 2019; Singh et al., 2019). Contemporary pig production systems must prioritize both farm efficiency and environmental sustainability, particularly given the mounting challenges posed by climate change. Pig farming systems span a wide spectrum- from subsistence-level backyard farming to mechanized and modern commercial pig farms-and are undergoing continuous transformation driven by rapid urbanization and rising consumer demand for livestock-derived products (Singh et al., 2023; Hasan et al., 2024; Wang and Li, 2024). On a global scale, pig industry is highly dynamic and rapidly expanding sector, increasingly driven by technological innovations. Productivity in commercial pig farming have witnessed sustained enhancement and currently, pig enterprises are aiming for annual production target of 30 to 35 piglets per sow with an average farrowing of 2.2 per year mostly in European and North American countries (Sanz-Fernández et al., 2024; Pierozan et al., 2020). These gains are attributable primarily to progressive genetic selection programmes and the widespread adoption of advanced reproductive biotechnologies (Knox, 2014; Whitworth et al., 2022).
       
Reproductive soundness of pre-pubertal females and weaned sows as well as adequate pool of eligible breeding females are critical requisites to achieve optimal herd productivity. The availability of sufficient pool of cyclic gilt and weaned sows for breeding lend predictability to the breeding programme (Kirkwood and De Rensis, 2016). The key reproductive goal is to achieve early age of breeding in gilts thereby maintaining high lifetime prolificacy; and minimizing weaning-to-estrus interval in multiparous sows.                

Furthermore, successful and large-scale adoption of Artificial Insemination (AI) necessitates precise management of ovarian function and cyclicity in the breeding herd.  Reproductive efficiency is a multi-faceted indicator and it varies with the level of management and climatic factors. The factors which influence the reproductive processes in pigs include housing and environment, genotype, male stimulation, heat stress, nutrition and duration of lactation. Genetic background has a measurable impact on reproductive traits such as litter size, age at first farrowing and farrowing interval, as demonstrated in crossbred pig populations (Reddy et al., 2013). Breed-specific variability in reproductive efficiency has been documented, indicating the importance of genetic resource selection and conservation strategies in optimizing sow productivity (Nevrkla et al., 2017; Kadirvel et al., 2020). For optimal efficiency, gilts should be bred by 8 to 10 months of age and the average litter size of the farm should be 10- 12 piglets per farrowing. Piglets should be weaned at 25 to 35 days of age depending upon the level of management. At least 80% weaned sows should display estrus within 7 days of weaning and after breeding, 90% should settle down and repeat breeding cases should be less than 10 percent. Piglets weaned per sow per year should be minimum of 25 to 30 piglets and abortion rate should be less than 2%.
       
In different pig production systems, controlled breeding and strategic manipulation of ovarian function through reproductive technologies like estrus induction, synchronization, Fixed-Time Artificial Insemination (FTAI) and planned farrowing are considered as valuable reproductive management tools for improving reproductive efficiency and productivity (Brüssow et al., 1996; Baishya et al., 2018; Singh et al., 2020). Controlled breeding approaches can be used to improve submission rates by inducing estrus in a larger proportion of eligible animals. This can also enable pig farmers to plan different aspects of breeding programme on time-basis. For a group of animals, having synchronized oestrus at an early stage and at the same time is beneficial since it allows for simultaneous breeding and delivery of progenies at the same time, thereby generating litters of uniform age; off spring from synchronized groups grow at comparable rates, simplifying feed management, housing allocation and marketing decisions. Moreover, estrus synchronization can facilitate FTAI which is a highly effective way of achieving pregnancy without reference to estrus (Knox, 2014). Further, controlled farrowing induction can serve as a useful tool for improving piglet survival and allowing batch management (Gokuldas et al., 2015; Vallet and Miles, 2017). Overall, different reproductive strategies targeting optimal regulation of ovarian activity can be of great benefit to pig rearers and commercial pig enterprises. In this backdrop, an overview of different methods of regulation of ovarian activity and their applications, recent trends and future prospects in pig breeding are compiled and discussed in this article.
 
Reproductive physiology of pigs
 
Estrous cycle of pig ranges from 18 to 24 days with an average duration of 21 days and is composed of generally prolonged luteal phase and a brief follicular phase (Soede et al., 2011). Estrus generally last for 36 to 48 hours in gilts and for 48 to 72 hours in sows. The hypothalamus controls the estrous cycle by secreting gonadotropin releasing hormone (GnRH) which in turns act on the anterior pituitary gland. In response, the pituitary gland secretes follicle stimulating hormone (FSH) and luteinizing hormone (LH) and these endocrine factors subsequently act on ovary and regulates the follicular growth and ovulation (Coffey et al., 1997; Soede et al., 2011; Knox, 2023). During the luteal phase, progesterone regulates follicular development and effectively suppress the onset of estrus. At about 12-14 days of luteal phase, PGF₂ α causes CL regression and leading to a decline in systemic progesterone which stimulate secretion of gonadotropins like LH and FSH allowing follicular development to be completed with estrogen production and onset of estrus (Coffey et al., 1997; Knox, 2019; De Rensis et al., 2012). Restoration of normal uterine physiology following parturition is typically achieved within 20 to 25 days postpartum. Duration of oestrus will be longer for sows with a shorter weaning-to-estrus interval (e.g., 4-5 days) and shorter for sows with a longer interval (6-12 days). Sows with a shorter weaning-to-estrus (WEI) will ovulate later after oestrus detection (late ovulators) than sows with a longer WEI (early ovulators), as ovulation happens at roughly 70% during oestrus regardless of its duration. The fertility of sows inseminated following a long WEI is less than that of sows inseminated following shorter WEI which likely involves a relatively poor synchrony between times of sperm deposition and ovulation. From a management perspective, efforts should be directed at minimizing prolonged WEI, a concern particularly relevant in first-parity sows (Almeida et al., 2000; Poleze et al., 2006).
 
Management strategies for control of ovarian function
 
Suitable non-pharmacological management strategies can be applied to modulate ovarian function in pigs and these include biostimulation through boar exposure, transportation of a group of females, relocation or mixing of breeding females and group weaning (Walton, 1986; Knox et al., 2014; Gokuldas et al., 2023). The visual and olfactory stimuli, pheromones from boar and stress are external cues that the female hypothalamus translates into GnRH secretion, which eventually leads to ovarian stimulation and estrus onset. Studies indicated that olfactory stimuli from sexually mature boar and concurrent exposure to tactile, visual and auditory stimuli can be used to stimulate onset of puberty in gilts (Patterson et al., 2002). Precocious puberty can be induced in gilts through boar exposure and active boar can be used at a ratio of 1 boar per 12-15 females. The direct physical contact with the boar for 15 minutes daily can stimulate healthy female pigs so that they can be bred when between 210 and 260 days of age. Fully grown gilts should be removed from the breeding program if they are unable to exhibit oestrus within 30 days of coming into contact with a boar. Research also suggests that shifting females to boar shed or vice versa improves estrus induction and detection efficiency. Similarly, mixing and relocation of gilts from different pens or transporting in a truck can also induce estrus within 7 to 10 days, if gilts have adequate nutrition. Due to relocation or mixing from different groups, fighting occurs to re-form the hierarchy causing stress in gilts and subsequent stimulation of cyclic activity. If the age of gilts at the time of transport or relocation is close to normal onset of puberty, 25-35% of animals may display estrus within one week after transport (Kouamo and Kamga-waladjo, 2013). Proper sow management during lactation and weaning can also be beneficial in synchronizing estrus for rebreeding as well as for incorporation in fixed AI protocols. Under adequate body condition and nutritional status, most sows return to fertile estrus within 4 to 7 days following weaning. Batch or group weaning is a successful practical method for estrus synchronization in sows in good body condition. This is because of hormonal interplay influencing post-weaning follicle development and resumption of cyclicity. However, this mechanism becomes ineffective in sows weaned in summer as well as in sows that entered weaning with depleted body condition or diminished feed intake during lactation. Administration of combination of 300 IU of equine chorionic gonadotropin (eCG) and 150 IU of human chorionic gonadotropin (hCG) per 3 ml dose given as a single IM injection within 12 hours after weaning can improve estrus induction within 7 days of weaning and further tighten the synchronization of estrus (Knox, 2021). The success rate of most of these management methods is inherently variable and their implementation tends to be both labour-intensive and time-consuming. Integration of these methods with other estrus control schedules has been found to enhance the overall efficiency. Boar exposure in conjunction with P.G. 600 (a hormonal cocktail of gonadotropins containing Pregnant Mare Serum Gonadotropin and human Chorionic Gonadotropin) is effective in pre-pubertal gilts in inducing fertile synchronized estrus (Flowers et al., 2006 and Breen et al., 2006; Bartlett et al., 2009). Combined application of transport stress or boar exposure with exogenous gonadotropin treatment can be beneficial in inducing and synchronizing estrus in gilts (Breen et al., 2006; Kraeling and Webel, 2015).
 
Estrus induction and synchronization strategies in pigs
 
Fertile estrus can be induced in gilts and sows with the use of exogenous hormonal agents, provided that they are of suitable age and in satisfactory body condition. Hormonal therapy can be used to prevent anestrus incidence or delayed estrus in less fertile sows, particularly during summer period. Hormonal methods are based on regulating events leading to follicular maturation and ovulation or altering the luteal phase. Most of the strategies for control of estrus and ovarian activity include use of exogenous hormonal agents to delay follicle development (progesterone analogues), to control follicle development (PMSG or FSH-analogues) or to trigger ovulation at a predetermined time (LH or GnRH-analogues).
 
Use of progesterone and synthetic progestogens
 
Extended treatment with progestogens can effectively suppress the final stages of follicular development and subsequent withdrawal can stimulate follicular growth (Kouamo and Kamga-waladjo, 2013). These agents can be fed orally at a daily dose rate of 15-20 mg for 14-18 days period to suppress estrus in order to facilitate induction of normal estrous cycle activity (Fig 1). Subsequent onset of estrus can be expected around 3-8 days after progestogen withdrawal. Orally active synthetic progestins or progestogens like Altrenogest or Allyltrenbolone (Regumate®, Matrix®) have been evaluated and validated for effective control of estrus and ovulation in pigs (Kirkwood and De Rensis, 2016).


       
Altrenogest treatment has been reported to achieve estrus synchronization in excess of 80% of treated females within 4 to 8 days of the final dose. Since estrus suppression is required only during the time of luteal regression, costs can be minimized by feeding Altrenogest from approximately 13 days after estrus detection until 5 days before scheduled breeding. Altrenogest is indicated for estrus synchronization in sows and gilts that have had at least one estrous cycle (Kraeling and Webel, 2015). The preparation may additionally serve as an alternative therapeutic approach in the management of anestrus conditions in swine. Matrix® is a 0.22% Altrenogest solution mostly used in gilts. Oral administration of Altrenogest does not inhibit normal luteolysis, but it can block the onset of estrus after luteolysis. Even though a marginally higher dose of the agent is not risky, but under-dosing of Altrenogest (<13 mg/day) may cause cystic follicles and therefore, correct dose regime is important for successful outcome.
 
Use of exogenous gonadotropin preparations
 
Exogenous gonadotropins including eCG, hCG, LH, GnRH and porcine LH (pLH) are capable of inducing follicular development, estrus and ovulation in swine (De Rensis and Kirkwood, 2016). Among these, eCG improves the control of weaning-to-oestrus interval (WEI), but lacks the capacity to precisely control the interval from oestrus-to ovulation. In contrast, hCG, LH, GnRH and pLH controls the timing of ovulation and are effectively used in fixed time AI protocols. If the cyclic status is unknown, exogenous gonadotropins can be used to control ovarian activity and synchronize estrus (Rogozarski et al., 1996). The eCG administration during lactation can stimulate development of preovulatory follicles and dose range of 500 to 750 IU administered within 24 hrs of weaning can aid in early onset of estrus. P.G. 600 is a commonly used gonadotropin formulation, containing 400 IU of Pregnant Mare Serum Gonadotropin (PMSG) and 200 IU of human Chorionic Gonadotropin (hCG) in each administered dose. This preparation can be used to induce ovarian activity in pre-pubertal gilts and synchronize estrus in sows (Fig 2).


       
A summary of various studies indicated that 50-70% of gilts expressed estrus within 5-7 days of treatment (Kirkwood, 1999; Knox, 2014). Gilts within 30 days of natural onset of puberty, will respond to treatment with gonadotropins by expressing estrus (Coffey et al., 1997). However, cycling gilts will not respond to P.G. 600 during the luteal phase due to the negative feedback of progesterone.
       
P.G. 600 has also demonstrated efficacy in addressing post-weaning anoestrus in sows. Treatment can enhance estrus expression and ovulation in weaned sows but, breeding methods may need to be optimized for ovulation time based on the time interval from weaning to estrus. As an alternative to P.G. 600, a cost-effective lower dose gonadotropin combination regime has been found to be effective in synchronizing estrus as well as in managing post-weaning anestrus in sows (Singh, et al., 2023b; Gokuldas et al., 2014). A combination of agents like Prostaglandins, PMSG and hCG can also be used to treat delayed puberty as well as sows with post-weaning anestrus. Mating at first-detected or hormonally induced estrus in gilts is generally discouraged; protocols that facilitate synchronization of the subsequent second estrus are therefore considered more advantageous. In these cases, prepubertal gilts can be given P.G. 600 injection (Fig 3) to induce puberty and subsequent luteolytic dose of PGF₂α on day 18 for re-synchronization (Coffey et al., 1997).


       
PMSG is another effective agent for induction of follicular growth, estrus and ovulation in pigs (Driancourt, 2013). Its predominant FSH-like bioactivity qualifies it for therapeutic use in inducing fertile estrus in anoestrous animals through effective follicle-stimulating action. When using PMSG alone, higher dose (1200 IU) given on the day after weaning is also effective in inducing early return to estrus in weaned primiparous sows (Kouamo and Kamga-waladjo, 2013). GnRH and porcine Luteinizing Hormone (pLH) have luteinizing effect and can be used to stimulate or synchronize ovulation after estrus induction or at the first sign of estrus (Tummaruk et al., 2011). Administration of GnRH or hCG enables more precise prediction of ovulation timing, thereby facilitating optimized insemination scheduling relative to ovulation and contributing to enhanced fertility outcomes. In addition to GnRH analogues, human chorionic gonadotropin and pLH can also induce ovulation. Synthetic GnRH agonists have been explored as agents to promote follicular development in swine and can be used as potential substitutes for PMSG in certain protocols. Also, combination of exogenous gonadotropins can be administered on the day of withdrawal of oral progesterone feeding to better synchronize estrus. In case of longer and variable wean-to-estrus intervals, gonadotropins can also be used at weaning for shorter and more synchronous onset of post-weaning estrus.
       
More recently, the administration of Buserelin, a GnRH analogue, 86 h after weaning induced ovulation 32 to 44 h after treatment in majority of multiparous sows but in only about 50% of primiparous sows, possibly reflecting a parity effect on follicle maturity at the time of treatment (Driancourt, 2013). A novel GnRH administration protocol has been developed whereby the GnRH analogue triptorelin in a methyl cellulose carrier is deposited onto the vaginal luminal mucosa 96 h after weaning. This generated normal LH surges and ovulation between 36 and 48 h after deposition followed by fixed time AI at 22 to 24 hr (Knox et al., 2014; Knox, 2019). It is important to note that, gonadotropin administration may also carry risks, especially if females are having silent estrus and are actually cyclic as cystic follicles may develop after gonadotropin treatment.
 
Use of prostaglandins and analogues
 
Artificially shortening the luteal phase is important for control of inter-estrous interval in cyclic pigs. Luteolytic compounds like prostaglandin F₂α can be used for estrus synchronization, but a major constraint is that the CL in pig is refractory to exogenous prostaglandin-induced luteolysis prior to day 12 of the cycle. A single injection of PGF₂α or its analogues is mostly ineffective in synchronizing estrus before day 12 of cycle. Dinoprost tromethamine (Lutalyse®) is a natural prostaglandin and is one of the first estrus synchronization agent approved for pigs (Moreira and Hammon, 2012). A double intra-muscular injection of Dinoprost at 12-14 days interval has demonstrated efficacy in synchronization in cyclic gilts and sows (Kouamo and Kamga-waladjo, 2013). In contrast to the CL before day 12 of cycle, the CL of early pregnant pig easily reacts to exogenous administration of PGF₂α and prompt estrus can be induced between 4 and 7 days after treatment; however, exogenous PGF₂α is associated with abortion in pregnant pigs. A combination of PGF₂α analogues with estradiol dipropionate (EDP) can be effectively used to synchronize estrus in pseudopregnant gilts (Noguchi et al., 2010). In cases of delayed return to estrus after weaning especially in early weaned animals, PGF₂α can be administered within 24 hours after farrowing followed by an injection of P.G. 600 at the time of weaning to induce prompt return to estrus (Fig 4).


 
Planned induction of farrowing and lactational estrus in pigs
 
Farrowing performance and neonatal piglet viability are key determinants of overall pig enterprise efficiency. Litter size and weight at weaning, being the most important criteria for profitability, are adversely affected due to perinatal mortality and reduced piglet viability (Quinton et al., 2006). Moreover, cases of prolonged gestation are commonly observed in especially exotic breeds leading to higher incidences of stillbirths and perinatal mortality. Planned induction of farrowing using prostaglandin analogues can be a valuable tool in improving piglet survival and allowing batch management especially in sows with prolonged gestation (Gokuldas et al., 2015). When integrated into sow management protocols, this approach permits closely supervised farrowing events, yielding improvements in both the number of viable piglets born and their higher weaning weights. Farrowing can be induced by administration of 10-15 mg of natural PGF₂α or equivalent dose of synthetic analogues. Farrowing generally occurs 18-36 hours later in 80-90% of sows when PGF₂α is given at or after 113-114 days gestation. PGF₂α must be used within 72 hours of the expected farrowing date to prevent an increase in stillbirths. Farrowing may be induced into an even shorter period by injecting 20 IU of oxytocin, IM, 15-24 hours after the PGF₂α injection (Balogh and Bilkei, 2003).
       
Following farrowing, sows typically enter a period of lactational anoestrus, mediated by the neuroendocrine inhibitory effects of suckling stimulus on the hypothalamo-pituitary-ovarian axis. In order to shorten the inter-farrowing interval and maximize number of litters per sow, early weaning is being followed in many farms (at 21 days) but this has welfare implications due to stress of maternal separation and nutritional demands. More beneficial approach is to stimulate lactational estrus and the common strategies include use of exogenous hormones, boar exposure, intermittent or split suckling (Langendijk et al., 2009; Soede et al., 2012; van Wettere et al., 2013). Combination or individual uses of PGF₂α, hCG and P.G. 600 has been reported to be beneficial in stimulating lactational estrus (Hausler et al., 1980; Armstrong et al., 1999).

Recent trends in strategies for control of ovarian function
 
Multiple dose therapy of prostaglandin, newer forms of GnRH analogues to synchronize ovulation for use in fixed-time AI (FTAI), use of pheromonal agents and aerosol nano-drug delivery systems are some developments in this field. Recent investigations in swine have demonstrated that repeated PGF₂α injections are capable of inducing premature luteolysis before day 12 of the cycle, thereby opening new possibilities for the development of early-phase ovulation synchronization and timed-AI protocols. Administering PGF₂α at 24 or 36 hours intervals during days 6 to 10 of the cycle has been shown to curtail total cycle length by 2 to 5 days. However, the labor and cost factors preclude multiple PGF₂α regimen from practical application. Interestingly, administration of PGF₂α at the time of AI has been found to be useful especially when fertility is otherwise low, such as in summer stress or in repeat breeding cases. Efficacy of newer forms and routes of hormonal agents like OvuGel®, a proprietary gel formulation containing GnRH analogue called Triptorelin, have been explored. It can be administered intra-vaginally to female pigs 96 hours after weaning for synchronizing ovulation followed by fixed-time AI (Knox et al., 2018; Crespo and Gadea, 2024). All animals can be inseminated with a single dose of semen without regard to estrus 22-24 hours after 200 μg of triptorelin administration. Similarly, for FTAI, administration of 2.5 mg of pLH through vulvar submucosal route at the estrus onset in gilts and sows has been reported (Knox et al., 2018; Ulguim et al., 2016; Knox, 2021).
       
Advances have also been made in applications of pheromonal agents and aerosol nano-drug delivery systems. Priming pheromones are capable of triggering measurable physiological and neuroendocrine responses in recipient animals, operating through the hypothalamic-pituitary-ovarian axis (Fig 5). Porcine pheromones such as androstenone are now being used as active ingredient in aerosol spray like commercial products for stimulation of estrus behavior and enhancing AI success rate and also eliminating practical necessity for teaser boars.


               
Recent studies tested the effectiveness of a novel 3-molecule boar pheromonal preparation to improve the reproductive performance and mixture of boar salivary molecules like androstenone androstenol and quinoline has been found to be effective in eliciting sexual behavior in sows (McGlone et al., 2019; Sankarganesh et al., 2024). Aerosol nano drug delivery systems also represent an emerging and potentially transformative technology that could overcome some of the limitations of conventional delivery methods. Newer technologies in nano-encapsulation could optimize pheromone and hormone administration and bioavailability, potentially improving overall efficacy. When integrated with standard management practices, these strategies represent a new frontier of integrated reproductive management in modern swine production.

Controlled reproduction through regulation of ovarian follicular development and ovulation offers considerable potential for enhancing reproductive efficiency in pigs. The use of commercially available exogenous hormones enables modulation of the estrous cycle and synchroni-zation of estrus expression, facilitating fixed-time artificial insemination. However, the effective and judicious application of these agents requires an understanding of the sow’s current reproductive status and follicular development stage. Importantly, hormonal strategies should complement, rather than replace, standard management practices, as proper herd management remains critical for achieving optimal reproductive outcomes. Significant advances in controlled reproduction of pigs have been made in the past three decades. Nevertheless, more extensive research on influence of potential pharmaceutical agents, biologically-relevant pheromonal and other novel agents and targeted drug delivery on important reproductive processes is warranted to develop more efficient controlled strategies to enhance reproductive efficiency in pig breeding herd.

Authors are thankful to the Indian Council of Agricultural Research and the Director, ICAR-Central Coastal Agricultural Research Institute, Goa for the support and funding provided under institute research project.
 
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The views and conclusions expressed in this article are solely those of the authors and do not necessarily represent the views of their affiliated institutions. The authors are responsible for the accuracy and completeness of the information provided, but do not accept any liability for any direct or indirect losses resulting from the use of this content.
 
Informed consent
 
All animal procedures for experiments were approved by the Committee of Experimental Animal Care and Handling Techniques were approved by the University of Animal Care Committee.

The authors declare that there are no conflicts of interest regarding the publication of this article. No funding or sponsor- ship influenced the design of the study, data collection, analysis, decision to publish, or preparation of the manuscript.