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Induction of successive follicular waves by gonadotropin-releasing hormone and prostaglandin F2α to improve fertility of high-producing cows during the summer and autumn

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Reduced conception rate during the hot summer and subsequent autumn is a well-documented phenomenon. Evaporative cooling systems greatly increase milk production but only slightly improve reproductive performance; hence, additional approaches to improving fertility during the hot season are required. The purpose of the present study was to examine whether the combination of an efficient cooling system and hormonal manipulation (GnRH+PGF(2α)) might improve fertility during the summer and autumn. The experiment was conducted from July to December in 2 commercial herds in Israel and included 382 healthy Holstein cows. Cows (50 to 60 d in milk) were hormonally treated to induce 3 consecutive 9-d follicular waves, with GnRH administration followed by PGF(2α) injection 7 d later. Both control (n=187) and treated (n=195) cows were inseminated following estrus, and pregnancy was determined by palpation 45 d post-insemination. Data revealed an interaction between treatment and primiparous cows, reflected by a 16% increase in conception rate [odds ratio (OR) 2.32, 95% confidence interval (CI): 0.96-5.61] and 14% increase in pregnancy rate at 120 d in milk (OR 3.16, 95% CI: 0.93-10.47). Interaction between treatment and high body condition score was reflected by a 14% increase in pregnancy rate at 90 d in milk (OR 3.02, 95% CI: 1.14-7.96). About 60% of the treated cows expressed estrus at the expected time (normal response within 5 d following the third PGF(2α) injection); the remaining 40% that manifested estrus later (late response) had higher milk yield and lower body condition score. Additional analyses indicated that treatment interacted with normal response to raise conception rates and pregnancy rates of primiparous cows and cows with high body condition score. On the other hand, treatment by late-response interaction lowered conception rate during the summer. Implementation of such hormonal treatment in combination with an efficient cooling system may improve reproductive performance of dairy cows during the summer and subsequent autumn.
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... Such treatments would not be expected to be effective in the summer because follicles emerging into the growing pool would also be damaged by heat stress. Consistent with this idea was the observation that treatment of lactating cows in the summer and autumn with three rounds of a GnRH and PGF 2α protocol to hasten removal of follicles did not improve pregnancy rate at first AI in multiparous cows, although it tended to improve pregnancy rate in primiparous cows [143]. Perhaps greater responses would have been seen if the study was limited to the late summer or autumn. ...
Chapter
A useful term to describe the reproductive function of a herd of cows is 21‐day pregnancy rate. Heat stress is among the most consequential changes in the environment of the cow that can reduce 21‐day pregnancy rate. This chapter focuses on effects of heat stress on reproductive events important for establishment of pregnancy. It describes what is known about the physiological and cellular mechanisms by which heat stress compromises reproductive function. The chapter addresses strategies for minimizing heat stress effects on reproduction. Consequences of heat stress on the physiology and productive potential of the cow depend on both physiological changes that an animal engages to regulate body temperature and the direct negative effects of elevated body temperature on cellular function.
... These were found to hasten the restoration of oocyte competence to some extent, but none has been implemented in the summer reproductive management. Conversely, the induction of three consecutive 9-day follicle waves by GnRH and prostaglandin improved conception rate during the summer and autumn in primiparous cows (37% vs 53% for control vs treated cows respectively), but did not affect that of multiparous cows (Friedman et al. 2011). The treatment has been more effective for cows with a high body condition score (BCS) or low somatic cell count (SCC) than for cows with a low BCS or high SCC. ...
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The ovarian pool of follicles, and their enclosed oocytes, is highly sensitive to hyperthermia. Heat-induced changes in small antral follicles can later manifest as impaired follicle development and compromised competence of the enclosed oocytes to undergo maturation, fertilisation and further development into an embryo. This review describes the main changes documented so far that underlie the oocyte damage. The review discusses some cellular and molecular mechanisms by which heat stress compromises oocyte developmental competence, such as impairment of nuclear and cytoplasmic maturation and mitochondrial function, changes in the expression of both nuclear and mitochondrial transcripts and the induction of apoptosis. The review emphasises that although the oocyte is exposed to heat stress, changes are also evident in the developed embryo. Moreover, the effect of heat stress is not limited to the summer; it carries over to the cold autumn, as manifest by impaired steroid production, low oocyte competence and reduced fertility. The spontaneous recovery of oocytes from the end of the summer through the autumn until the beginning of winter suggests that only subpopulations of follicles, rather than the entire ovarian reserve, are damaged upon heat exposure.
... For example, the induction of three consecutive follicular waves by GnRH and PGF 2α improved the conception rate during the summer and autumn. The most prominent effect was in first-calving cows and cows with high body condition score postpartum (Friedman et al., 2011). ...
... Induction of three consecutive follicular waves improved the conception rate during the summer and autumn. In particular, an increase of 15 and 16 percentage units was recorded in first-calving cows and cows with high body condition score post-partum, respectively (Friedman, Voet, Reznikov, Dagoni, & Roth, 2011). Hormonal treatment before (GnRH + PG) and after (CIDR) AI combined with efficient cooling system improved fertility in subpopulations of dairy cows during the summer and autumn (Friedman, Voet, Reznikov, Wolfenson, & Roth, 2014; Figure 2). ...
Article
Reduced reproductive performance of lactating cows during the summer is associated mainly with intensive genetic selection for high milk production, which places a great load on the thermoregulatory mechanism. In the last decades, a big effort has been made to explore the mechanism by which heat stress compromises fertility. The data gained so far revealed that the effect of thermal stress on the female reproductive tract is multifactorial in nature. Based on this understanding, new strategies to mitigate the effect of heat stress have been developed. The review summarizes some of the physiological responses of the cow to elevated temperature and discusses its limitations to maintain normothermia. The review emphasizes that cooling is the predominant strategy used today to alleviate the effects of heat stress. Findings from the Israeli dairy herd indicate that efficient cooling management can improve milk production during the summer to a similar level of the winter, expressed by summer to winter ratio of 0.98. However, cooling as a singular approach cannot eliminate the decline in reproduction. Nonetheless, an efficient cooling system is a prerequisite for any other strategy. The review suggests additional hormonal treatments to improve reproductive performance during the summer. Given the complexity of heat‐stress effects on reproduction, comprehensive reproductive management during the summer is suggested i.e. combining two or more strategies in a program, might be more beneficial.
... Such treatments would not be expected to be effective in the summer because follicles emerging into the growing pool would also be damaged by heat stress. Consistent with this idea was the observation that treatment of lactating cows in the summer and autumn with three rounds of a GnRH and PGF 2α protocol to hasten removal of follicles did not improve pregnancy rate at first AI in multiparous cows, although it tended to improve pregnancy rate in primiparous cows [143]. Perhaps greater responses would have been seen if the study was limited to the late summer or autumn. ...
Chapter
Depending on its severity, heat stress can have moderate to severe effects on many aspects of reproductive function in both females and males. Among the most notable effects of heat stress are reduced intensity of behavioral estrus, low fertility and compromised fetal development in females, and compromised sperm output and increased sperm abnormalities in males. Lactation increases the sensitivity of females to heat stress because the associated increase in heat production makes regulation of body temperature more difficult. Among the strategies to reduce the magnitude of heat stress effects are the provision of housing that contains shade, sprinklers or misters, and fans. Effects of heat stress on estrus detection can be eliminated by the implementation of timed artificial insemination programs. However, such programs do not improve fertility. The most effective means for enhancing pregnancy rate during heat stress is to perform embryo transfer. The embryo transferred at day 7 after estrus has escaped deleterious effects of heat stress and is more resistant to subsequent heat stress than embryos at earlier stages of development. Opportunities also exist for changing cattle genetically to increase their ability for thermoregulation and cellular resistance to elevated temperature.
... Induction of three consecutive follicular waves by GnRH and PGF 2a, improved the conception rate during the summer and autumn. The most prominent effect was in first-calving cows and cows with high body condition score postpartum [64]. ...
Article
The effects of environmental heat-stress on production and reproduction in dairy cows have been intensively studied throughout the past few decades. In light of climate changes and global warming, this issue has gained attention worldwide. So far, most of the documentations are related to warmer-climate regions, however, environmental thermal stress has recently been reported in cooler regions, such as Europe. The review attempts to present the experiences from the past years and lessons for the present. The review highlights some of the environmental characterizations and provides some practical approaches to estimate the level of heat load on farms. For instance, the intensity of heat stress can be evaluated by the temperature humidity index (THI). Other environmental parameters, such as the increased number of consecutive hot days or the increased frequency of extremely hot days, can be also used to estimate the level of heat load on farms. Exposure of dairy cows to environmental thermal stress results in multiple behavioral changes, physiological responses and endocrinological alterations, which in sequence, lead to reduced reproductive performance. Multiple in-vitro studies have been performed for better understanding the mechanism by which heat stress impairs reproductive processes. However, the current review focuses mainly on animal reactions and on the limitations of physiological and behavioral responses in maintaining normothermia, without human intervention. The review provides evidence that thermal stress induces alterations in the hypothalamus–pituitary–ovarian axis. For instance, impaired gonadotropin secretion, attenuation of follicular development, reduced steroid production and progesterone concentration in the plasma. These were found to be associated with impaired estrus behavior, reduced oocyte developmental competence and embryo survival. Heat stress also has direct and indirect effects on the preimplantation embryo. The review summarizes the thermo-sensitivity of the embryo and the acquisition of its thermotolerance through early developmental stages.Understanding the effects of environmentally elevated temperature on the reproductive physiology of lactating cows is extremely important for the development of new strategies in order to mitigate the effects of heat stress on farms. The review also provides various types of management and practical tools, in order to alleviate the effects of thermal stress. It introduces some approaches that have been developed during recent years, ones that have been practically used to alleviate the effect of the environmental heat load and suggested to be implanted. Cooling is the predominant strategy used nowadays in order to alleviate the effects of heat stress. It includes indirect cooling of the environment surrounding the animal, by providing shed and ventilation (with or without water) or direct evaporative cooling of the cow with water and fans. Using an efficient cooling system can improve milk production during the hot season, but it cannot eliminate the decline in reproduction. The review also discusses some additional approaches such as timed artificial insemination, hormonal treatment and embryo transfer, which have already been developed. These are suggested to be examined, adapted and implemented in dairy farms located in new regions that have recently suffered from environmental heat stress. The review also discusses unclear points and open questions some of which might lead new research directions.
... Progress in dairy breeding and the application of novel technologies has dramatically increased per-cow milk yields over the past decades [1]. However, this progress has negatively affected the reproductive efficiency of lactating cows by decreasing the rate of established successful conceptions from more than 50% in the 1950s [1][2][3] to only approximately 35% recently [4], and even to approximately 25% in summer and autumn [5,6]. Improving the conception rate has become a major challenge in dairy cow reproduction. ...
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This study was conducted to investigate the feasibility of improving fertility in dairy cows via immunization against inhibin. Thirty-two cows were divided into Control (n = 11), Low-dose (n = 10) and High-dose (n = 11) groups. The High-dose and Low-dose cows were treated with 1 and 0.5 mg of the inhibin immunogen, respectively. All the cows were subjected to the Ovsynch protocol from the day of antigen administration and were artificially inseminated. Blood samples were serially collected over a 24-day period from the start of the Ovsynch protocol to 14 days after insemination. The results showed that immunization against inhibin dose-dependently increased the plasma concentrations of follicle-stimulating hormone (FSH), estradiol (E2), and activin A, but decreased progesterone (P4) concentrations in the luteal phase. Immunization also increased the plasma interferon (IFN)-τ concentrations in pregnant cows on day 14 after initial insemination. The conception rates in High-dose (45.5%) and Low-dose (40%) cows marginally increased compared to that in Control cows (27.3%), but the increases were not significant (p > 0.05). In conclusion, a single immunization against inhibin has the potential to improve conception rates, despite impaired luteal development. To further improve the reproductive performance of dairy cows, additional luteal-stimulating treatments are suggested in combination with immunization against inhibin and Ovsynch techniques.
... Supplementation of exogenous progesterone during summer heat stress has the potential to improve fertility. b) Friedman et al., 2011;Das, 2017 reported that heat synchronization with GnRH and PGF2α also improves fertility. iii. ...
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Low fertility of cattle during the cool autumn is mostly associated with exposure to thermal stress in the previous summer. This study examined carry-over effects of summer heat stress and induction of enhanced follicular turnover, on the characteristics of preovulatory follicles during autumn. Holstein cows were treated with PGF2α and GnRH to induce six successive 9-day follicular waves during autumn. Intact cows served as controls. Follicular fluid concentrations of androstenedione were higher in treated cows, but those of IGF-I and progesterone did not differ between groups. The concentration of estradiol at the end of the treatment was higher, and the content per follicle increased with time and was numerically higher in treated cows. The volume of follicular fluid increased during the autumn and was greater in treated cows. A delayed effect of heat stress on preovulatory follicles was noted, and induction of follicular waves by GnRH was able to improve follicular characteristics in autumn.
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The well-documented phenomenon of reduced conception rate in dairy cows during the hot season involves impaired functioning of the ovarian follicles and their enclosed oocytes. Three experiments were performed to examine the administration of low doses of follicle-stimulating hormone (FSH) to induce turnover of follicles that are damaged upon summer thermal stress and to examine whether this FSH administration has beneficial effects on preovulatory follicles. In experiment 1, synchronized heifers were treated with 100 mg of Folltropin-V (n = 7) or 4.4 mg of Ovagen (n = 6) on day 3 of the estrous cycle. Treatment with both FSH sources resulted in greater (P < 0.05) numbers of follicles than in control animals (n = 12) on day 6 of the estrous cycle, indicating that low doses of FSH can increase the number of emerging follicles in a follicular wave. In experiment 2, milking cows were assigned to a control group (n = 4) or treated with 2.2 mg (FSH-2.2; n = 6) or 4.4 mg (FSH-4.4; n = 5) Ovagen. Follicle-stimulating hormone was administrated on day 3 or 4 and day 10 or 11 of the estrous cycle, coinciding with emergence of the first and second follicular waves, respectively. The number of follicles emerging during the first wave tended to be higher (P < 0.1) in FSH-4.4-treated cows than in controls. The second-wave dominant follicles emerged 2 d later in the treated cows and were smaller in diameter (P < 0.05) than controls, 2 d before aspiration. Despite being younger, the preovulatory follicles of FSH-4.4 cows expressed a steroidogenic capacity that was similar to controls with a tendency toward greater insulin concentrations (P < 0.09). In experiment 3, milking cows were assigned to a control group (n = 6) or treated with 4.4 mg Ovagen (FSH-4.4; n = 6). Follicle-stimulating hormone was administrated on day 3 and day 12 or 13 of the estrous cycle. The number of emerging follicles was higher (P < 0.05) in the treated vs control cows. However, the features of the preovulatory follicle developed in the subsequent cycle did not differ between groups. In summary, low doses of FSH can efficiently induce follicular turnover accompanied by a modest effect on the preovulatory follicle of the treated cycle. It appears that the administration of low doses of FSH, precisely timed to synchronize with the emergence of follicular waves, might have a beneficial effect on the preovulatory follicle and its enclosed oocyte.
Article
The effects of naturally occurring subclinical chronic or clinical short-term mastitis on time of ovulation, plasma steroid and gonadotropin concentrations, and follicular and luteal dynamics were examined in 73 lactating Holstein cows. Cows were sorted by milk somatic cell count and bacteriological examination into an uninfected group (n=22), a clinical mastitis group (n=9; events occurring 20+/-7 d before the study), and a subclinical chronic mastitis group (n=42). In addition, uninfected and mastitic cows were further sorted by their estrus to ovulation (E-O) interval. About 30% of mastitic cows (mainly subclinical) manifested an extended E-O interval of 56+/-9.2h compared with 28+/-0.8h in uninfected cows and 29+/-0.5h in the other 70% of mastitic cows. In mastitic cows with extended E-O interval, the concentration of plasma estradiol at onset of estrus was lower than that of uninfected cows or mastitic cows that exhibited normal E-O intervals (3.1+/-0.4, 5.8+/-0.5, and 5.5+/-0.5 pg/mL, respectively). The disruptive effect of mastitis on follicular estradiol probably does not involve alterations in gonadotropin secretion because any depressive effects of mastitis on pulsatile LH concentrations were not detected. Cortisol concentrations did not differ among groups. The preovulatory LH surge in mastitic cows with delayed ovulation varied among individuals, being lower, delayed, or with no surge noted compared with the normal LH surge exhibited by uninfected cows or mastitic cows with normal E-O interval (6.8+/-0.7 ng/mL). The diameter of the second-wave dominant follicle was larger and the number of medium follicles was smaller in uninfected and subclinical cows with normal intervals compared with subclinical cows with extended intervals (13.4+/-0.5 vs. 10.9+/-0.9mm, and 3.8+/-0.2 vs. 6.7+/-0.14 follicles, respectively). Mid-luteal progesterone concentrations were similar in uninfected and mastitic cows. These results indicate for the first time that around 30% of cows with subclinical chronic mastitis exhibit delayed ovulation that is associated with low plasma concentrations of estradiol and a low or delayed preovulatory LH surge.