Early Embryonic Mortality in Bovines: Current Insights and Interventions
DOI:
https://doi.org/10.48165/aru.2025.5.2.1Keywords:
Early embryonic mortality, Early Pregnancy Factor, Endometrial receptor modulators, Luteal phase defects, Preimplantation factor, Recombinant interferon-tauAbstract
Early embryonic mortality (EEM) is a critical reproductive challenge in bovines, significantly impacting fertility, milk production, and farm economics. Despite high fertilization rates, embryonic losses during the first 24 days of gestation remain a major bottleneck in achieving optimal conception rates. This review synthesizes current understanding of the multifactorial aetiology of EEM, encompassing genetic, endocrine, immunological, nutritional, environmental, and managerial factors. Species, breed, age, parity, milk yield, and stress are all associated with increased embryonic loss. Endocrine disruptions such as luteal phase defects and inadequate progesterone levels are frequently implicated. Immune system dysfunction, including maternal fetal immunological incompatibility and subclinical infections, further compromises embryo viability. Diagnostic tools such as early pregnancy factor, preimplantation factor, progesterone assays, ultrasonography, and pregnancy-associated glycoproteins (PAGs) allow early detection of EEM. Therapeutic interventions include hormonal supplementation (GnRH, hCG, progesterone, kisspeptin), immunomodulators, endometrial receptor modulators, and nutritional strategies such as omega-3 fatty acid supplementation and insulin-based regimens. Assisted reproductive technologies like embryo transfer and embryo co-transfer offer promising alternatives for repeat breeder animals. Preventive strategies emphasize precise AI timing, estrus detection, heat stress mitigation, and improved nutritional management to enhance uterine receptivity and embryo survival. This review underscores the need for integrated, individualized approaches to managing EEM, combining diagnostics with targeted therapeutic and environmental interventions. Future research directions include identifying novel biomarkers, refining genomic selection for fertility traits, and leveraging AI-based tools for real-time reproductive monitoring. A comprehensive understanding of EEM pathophysiology, coupled with evidence-based interventions, is essential to improve reproductive efficiency and sustainability in dairy production systems.
References
1. Abdelli A, Benabdelaziz A, Khelili R, Belabdi I, Mebarki M, Kaidi R. Effect of treatment with GnRH or hCG on day 5 after artificial insemination on luteal activity of dairy cows. J Appl Biol Sci. 2020;14(2):225-232.
2. Abubakar M, Adeyeye A, Baraya Y, Ahmed A. Comparative diagnosis of pregnancy wastage in cows at slaughter using pregnancy specific protein-B and post slaughter inspection diagnostic procedures. Anim Reprod Sci. 2019; 211:106233. https://doi.org/10.1016/j.anireprosci.2019.106233.
3. Akbarinejad V, Gharagozlou F, Vojgani M, Ranji A. Evidence for quadratic association between serum anti-Müllerian hormone (AMH) concentration and fertility in dairy cows. Anim Reprod Sci. 2020; 218:106457.
https://doi.org/10.1016/j.anireprosci.2020.106457
4. Akköse M. Comparative evaluation of two commercial pregnancy-associated glycoproteins tests for early detection of pregnancy in dairy cattle. Theriogenology. 2023;200:11-17. https://doi.org/10.1016/j.theriogenology.2023.01.022.
5. Almería S, López-Gatius F. Bovine neosporosis: clinical and practical aspects. Res Vet Sci. 2013;95(2):303-309.
https://doi.org/10.1016/j.rvsc.2013.04.008
6. Basavaraja R, Przygrodzka E, Pawliński B, Gajewski Z, Kaczmarek M, Meidan R. Interferon-tau promotes luteal endothelial cell survival and inhibits specific luteolytic genes in bovine corpus luteum. Reproduction. 2017;154(5):559-568. https://doi.org/10.1530/REP-17-0290.
7. Berg DK, van Leeuwen J, Beaumont S, Berg M, Pfeffer PL. Embryo loss in cattle between Days 7 and 16 of pregnancy. Theriogenology. 2010;73(2):250-260.
https://doi.org/10.1016/j.theriogenology.2009.09.005
8. Betteridge KJ, Eaglesome MD, Randall GC, Mitchell D. Collection, description and transfer of embryos from cattle 10–16 days after oestrus. J Reprod Fertil. 1980;59(1):205-216.
https://doi.org/10.1530/jrf.0.0590205
9. Boakari Y, Ali E, Dini P, Loux S, Fernandes C, Scoggin K, Esteller-Vico A, Lawrence L, Ball B. Elevated blood urea nitrogen alters the transcriptome of equine embryos. Reprod Fertil Dev. 2020;32(2):156-167. https://doi.org/10.1071/RD20088.
10. Bulman DC. Milk progesterone levels in relation to conception, repeat breeding and factors influencing acyclicity in dairy cows. J Reprod Fertil. 1979;54(2):447-458. https://doi.org/10.1530/jrf.0.0540447.
11. Campanile G, Neglia G, Gasparrini B, et al. Embryonic mortality in buffaloes synchronized and mated by AI during the seasonal decline in reproductive function. Theriogenology. 2005;63(8):2334-2340.
https://doi.org/10.1016/j.theriogenology.2004.10.012
12. Campanile G, Neglia G, Vecchio D, Gasparrini B, Prandi A, Di Palo R, D'Occhio MJ, Zicarelli L. Embryonic mortality in buffaloes synchronized and mated by AI during the seasonal decline in reproductive function. Theriogenology. 2007;63(8):2334-2340. https://doi.org/10.1016/j.theriogenology.2004.10.012.
13. Campanile G, Neglia G. Embryonic mortality in buffalo cows. Ital J Anim Sci. 2007;6(Suppl 2):119-129.
14. Caton J, Crouse M, McLean K, Dahlen C, Ward A, Cushman R, Grazul-Bilska A, Neville B, Borowicz P, Reynolds L. Maternal periconceptual nutrition, early pregnancy, and developmental outcomes in beef cattle. J Anim Sci. 2020;98(12):skaa358. https://doi.org/10.1093/jas/skaa358.
15. Chandrika T, Radhika V, Srikanth N, Srihari J, Rao M, Praveen S, Manoranjan I. Artificial insemination in cattle and buffalo: An update. Int J Vet Sci Anim Husb. 2024;9(5):1690. https://doi.org/10.22271/veterinary.2024.v9.i5d.1690.
16. Chaudhari RK, Mahla AS, Singh AK, Singh SK, Pawde AM, Gandham RK, Singh G, Sarkar M, Kumar H, Krishnaswamy N. Effect of dietary n-3 polyunsaturated fatty acid rich fish oil on the endometrial prostaglandin production in the doe (Capra hircus). Prostaglandins Other Lipid Mediat. 2018;135:27-35. https://doi.org/10.1016/j.prostaglandins.2018.02.001
17. Chełmońska-Soyta A. Interferon tau and its immunobiological role in ruminant reproduction. Arch Immunol Ther Exp. 2002;50(1):47-52.
18. Cheon YP, Xu X, Bagchi MK, Bagchi IC. Immune-responsive gene 1 is a novel target of progesterone receptor and plays a critical role during implantation in the mouse. Endocrinology. 2003;144(12):5623-5630. https://doi.org/10.1210/en.2003-0585
19. Chetoui C, Slimane N. Embryonic and fetal mortality risk factors in dairy cattle in the mountainous and forested areas of Northwestern Tunisia. J Anim Sci Adv. 2012;2:596-607.
20. Chikkagoudara K, Singh P, Bhatt N, Barman D, Selvaraj R, Lathwal S, Singh S, Choudhary S, Uddin J. Effect of heat stress mitigations on physiological, behavioural, and hormonal responses of Buffalo calves. Int J Biometeorol. 2022;66:995-1003. https://doi.org/10.1007/s00484-022-02255-9
21. Committee on Bovine Reproductive Nomenclature. Recommendations for standardizing bovine reproductive terms. Cornell Vet. 1972;62:216-237.
22. Cooke RF, Bohnert DW, Cappellozza BI, Mueller CJ, DelCurto T. Effects of temperament and acclimation to handling on reproductive performance of Bos taurus beef females. J Anim Sci. 2009;87(12):4125-4133.
https://doi.org/10.2527/jas.2009-2186
23. Corpron M, Huo Q, Rezamand P, Ahmadzadeh A. Relationship between beef cow fertility and maternal immunity. Appl Anim Sci. 2021;37(5):1-10.
https://doi.org/10.15232/aas.2021-02214
24. Curran S, Pierson RA, Ginther OJ. Ultrasonographic appearance of the bovine conceptus from days 20 through 60. J Am Vet Med Assoc. 1986;189(10):1295-1302.
25. da Silva M, Gambonini F, Oli N, Ott TL. Effects of parity and early pregnancy on peripheral blood leukocytes in dairy cattle. bioRxiv. 2024.
https://doi.org/10.1101/2024.05.06.592827
26. Davies CJ, Hill JR, Edwards JL, et al. Major histocompatibility antigen expression on the bovine placenta: its relationship to abnormal pregnancies and retained placenta. Anim Reprod Sci. 2004;82-83:267-280.
https://doi.org/10.1016/j.anireprosci.2004.05.016
27. Decleer W, Osmanagaoglu K, Devroey P. The role of oxytocin antagonists in repeated implantation failure. Facts Views Vis ObGyn. 2012;4(4):227.
28. Diskin MG, Morris DG. Embryonic and early foetal losses in cattle and other ruminants. Reprod Domest Anim. 2008;43(Suppl 2):260-267.
https://doi.org/10.1111/j.1439-0531.2008.01171.x
29. Diskin MG, Murphy JJ, Sreenan JM. Embryo survival in dairy cows managed under pastoral conditions. Anim Reprod Sci. 2006;96(3-4):297-311.
https://doi.org/10.1016/j.anireprosci.2006.08.008
30. Dobson H, Walker SL, Morris MJ, Routly JE, Smith RF. Why is it getting more difficult to successfully artificially inseminate dairy cows? Animal. 2008;2(8):1104-1111. https://doi.org/10.1017/S175173110800236X.
31. Ebdalabadi M, Valizadah R, Moussavi A, Mesgaran M, Tahmoorespour M, Ehsani A. Effects of timing to start lipogenic diet on productive and reproductive responses in periparturient dairy cows. Livest Sci. 2014; 162:104-114. https://doi.org/10.1016/j.livsci.2014.01.010
32. Eshete T, Demisse T, Yilma T, Tamir B. Repeat Breeding and Its' Associated Risk Factors in Crossbred Dairy Cattle in Northern Central Highlands of Ethiopia. Vet Med Int. 2023; :1176924. https://doi.org/10.1155/2023/1176924.
33. Fedele A, Check J, Bollendorf A, Katsoff D. The use of chymotrypsin/galactose to treat spermatozoa bound with anti-sperm antibodies prior to intra-uterine insemination. Hum Reprod. 1994;9(3):484-488. https://doi.org/10.1093/oxfordjournals.humrep.a138532
34. Fontes P. Contributions of sire diet to pregnancy establishment in cattle. J Anim Sci. 2024;102(Suppl. 1): skae234.116. https://doi.org/10.1093/jas/skae234.116.
35. Funeshima N, Noguchi T, Onizawa Y, Yaginuma H, Miyamura M, Tsuchiya H, Iwata H, Kuwayama T, Hamano S, Shirasuna K. The transfer of parthenogenetic embryos following artificial insemination in cows can enhance pregnancy recognition via the secretion of interferon tau. J Reprod Dev. 2019; 65:443-450. https://doi.org/10.1262/jrd.2019-026
36. Gates MC, Woolhouse ME, Gunn GJ, Humphry RW. Relative associations of cattle movements, local spread, and biosecurity with bovine viral diarrhoea virus (BVDV) seropositivity in beef and dairy herds. Prev Vet Med. 2013;112(3-4):285-295.
https://doi.org/10.1016/j.prevetmed.2013.07.017
37. Givens MD, Marley MS. Infectious causes of embryonic and fetal mortality. Theriogenology. 2008;70(3):270-285.
https://doi.org/10.1016/j.theriogenology.2008.04.018
38. Gupta J, Prajapati M, Chaudhari J, Pawar M, Patel P, Bhatt T, Purohit P. Unravelling the impact of heat stress on daughter pregnancy rate in Mehsana buffalo through innovative breeding interventions. J Therm Biol. 2024; 123:103922. https://doi.org/10.1016/j.jtherbio.2024.103922
39. Gupta PS, Selvaraju S, Pal DT, Ravikiran G, Ravindra JP. Amelioration of reproductive problems in crossbred cattle with high blood urea nitrogen levels by ragi (finger millet) supplementation—a field study. Indian J Anim Sci. 2008;78(9):987-990.
40. Gustavsson I. Distribution and effects of the 1/29 Robertsonian translocation in cattle. J Dairy Sci. 1979;62(5):825-835.
https://doi.org/10.3168/jds.S0022-0302(79)83335-5
41. Guzel E, Kaya N, Tektemur A, Ulker N, Yardimci A, Akkoc RF, Ozan IE. Chronic effects of maternal tobacco-smoke exposure and/or α-lipoic acid treatment on reproductive parameters in female rat offspring. Syst Biol Reprod Med. 2020;66(6):387-399.
42. Hadef A, Sebihi H, Miroud K. Relationship between retained placenta and body condition changes during the transition period in Holstein dairy cows in north-eastern Algeria. SPERMOVA. 2021;11(1):1-8.
https://doi.org/10.18548/aspe/0009.03
43. Hafez ESE, Hafez B. Reproduction in Farm Animals. 7th ed. Wiley-Blackwell; 2013.
44. Hai Fan Yu, Chen Y, Li X, et al. HB-EGF promotes endometrial stromal cell proliferation and decidualization via ErbB4 during early pregnancy. Reproduction. 2019;158(5):441-451.
https://doi.org/10.1530/REP-19-0148
45. Hansen T, Sinedino L, Spencer T. Paracrine and endocrine actions of interferon tau (IFNT). Reproduction. 2017;154(5):F45-F59. https://doi.org/10.1530/REP-17-0315.
46. Hansen TR, Imakawa K, Polites HG, et al. Interferon RNA of embryonic origin is expressed transiently during early pregnancy in the ewe. J Biol Chem. 1988;263(26):12801-12804.
47. Haugejorden G, Waage S, Dahl E, Karlberg K, Beckers JF, Ropstad E. Pregnancy associated glycoproteins (PAG) in postpartum cows, ewes, goats and their offspring. Theriogenology. 2006;66(8):1976-1984. https://doi.org/10.1016/j.theriogenology.2006.05.016.
48. Hawk H, Kidder H, Wiltbank J, Casida L. Embryonic Mortality Between 16- and 34-Days Post-Breeding in Cows of Low Fertility. J Dairy Sci. 1955;38:673-676. https://doi.org/10.3168/jds.S0022-0302(55)95023-2.
49. Hitesh HS, Kansal G. Application of GnRH modulators in controlling reproductive cycle in farm animals: a review. Pharm J. 2022;7:4288-301.
50. Huang QY, Rong MH, Lan AH, Lin XM, Lin XG, He RQ, Li MJ. The impact of atosiban on pregnancy outcomes in women undergoing in vitro fertilization-embryo transfer: A meta-analysis. PLoS One. 2017;12(4):e0175501.
51. Hughes JP, Couto MA. Endometritis in mare. 11th Int Congr Anim Reprod AI. 1988;5:91-99.
52. Huynh L, L'Haridon R, Lantier F, et al. Recent developments and potentialities for reducing embryo mortality in ruminants: the role of IFN-tau and other cytokines in early pregnancy. Reprod Fertil Dev. 1997;9(3):355-380.
https://doi.org/10.1071/R96083
53. Inskeep EK, Dailey RA. Embryonic death in cattle. Vet Clin North Am Food Anim Pract. 2005;21(2):437-461.
https://doi.org/10.1016/j.cvfa.2005.02.002
54. Janowski T, Kaleczyc J, Zdunczyk S, Podlasz P, Baranski W. Preliminary studies on the expression of macrophages (CD14) and lymphocytes (CD4, CD8) in the endometrium of repeat breeder cows. Reprod Biol. 2013;13(1):51-56.
https://doi.org/10.1016/j.repbio.2013.01.177
55. Jawor P, Mee JF, Stefaniak T. Role of Infection and Immunity in Bovine Perinatal Mortality: Part 2. Fetomaternal Response to Infection and Novel Diagnostic Perspectives. Animals. 2021;11(7):2102.
https://doi.org/10.3390/ani11072102
56. Jisna KS. Luteal insufficiency and its effect on conceptus development in buffalo (Bubalus bubalis) [Doctoral dissertation]. Indian Veterinary Research Institute; 2024.
57. Kaneda S, Horii Y, Minamino T, Honkawa K, Sasaki Y. Effects of parity, calving season, and previous lactation's milk yield on fertility of dairy cows on a commercial farm. Anim Sci J. 2024;95(1):e13998.
https://doi.org/10.1111/asj.13998
58. Kasimanickam R, Kasimanickam V, Kastelic JP. Mucin 1 and cytokines mRNA in endometrium of dairy cows with postpartum uterine disease or repeat breeding. Theriogenology. 2014;81(7):952-958.
https://doi.org/10.1016/j.theriogenology.2014.01.018
59. Kastelic JP, Bergfelt DR, Ginther OJ. Ultrasonic detection of the conceptus and characterization of intrauterine fluid on days 10 to 22 in heifers. Theriogenology. 1991;35(3):569-581. https://doi.org/10.1016/0093-691x(91)90453-k.
60. Katagiri Y, Takahashi T, Kato S. Heparin-binding epidermal growth factor-like growth factor is essential for development of the bovine placenta. Reproduction. 2004;128(6):661-669.
https://doi.org/10.1530/rep.1.00310
61. Katsoff D, Check J. Two methods of achieving pregnancies despite subnormal hypo-osmotic swelling test scores. Fertil Steril. 1997;68(3):549-551. https://doi.org/10.1016/S0015-0282(97)00234-3
62. Kim IH, Kang HG, Jeong JK, Kim SH, Hur TY, Jung YH. Risk factors for late embryonic mortality in dairy cows. J Vet Clin. 2017;34(2):82-86.
https://doi.org/10.17555/JVC.2017.04.34.2.82
63. Kimura M, Nakao T, Moriyoshi M, Kawata K. Luteal phase deficiency as a possible cause of repeat breeding in dairy cows. Br Vet J. 1987;143(6):560-566.
https://doi.org/10.1016/0007-1935(87)90017-6
64. Krishnan BB. Effect of immunomodulators on the recovery of subclinical endometritis in crossbred cows [Doctoral dissertation]. IVRI, Izzat Nagar; 2011.
65. Kubovičová E, Makarevič A, Stádnik L, Holásek R. Effect of body condition and season on the yield and quality of cattle embryos. J Microbiol Biotechnol Food Sci. 2013;2(Special Issue 2):1426-1435.
66. Kumar A, Verma A, Rahal A. Mycoplasma bovis, a multi-disease producing pathogen: An overview. Asian J Anim Vet Adv. 2011;6(6):537-546.
https://doi.org/10.3923/ajava.2011.537.546
67. Kumar H, Singh B, Goswami TK, Rawat M. Use of neem preparations for the treatment of endometritis in cows. Indian J Anim Sci. 2013;83(10):1027-1033.
68. Kumar S, Charpe B, Kumbhar U. Bovine embryonic mortality with special reference to mineral deficiency, heat stress and endocrine factors: A review. Int J Bio-Resour Stress Manag. 2021;12(1):1-10.
https://doi.org/10.23910/1.2021.2139A
69. Kumar S, Charpe B, Kumbhar U. Bovine Embryonic Mortality with Special Reference to Mineral Deficiency, Heat Stress and Endocrine Factors: A Review. Int J Bio-Resour Stress Manag. 2021;12(1):1-10. https://doi.org/10.23910/1.2021.2139A.
70. Lean IJ, Rabiee AR, Stevenson MA. Proceedings of the Society of Dairy Cattle Veterinarians of the NZVA. 2003; 20:327-351.
71. Leeuw AM. Number and viability of embryos collected in vivo or from the excised uteri of slaughtered donor cows. Theriogenology. 1992;37(4):907-913.
72. Lehimcioğlu NC, Öztürkler Y, Yıldız S, Arı UÇ. The Effect of intrauterine infusion of carvacrol after insemination on conception rate in repeat breeder cows subjected to progesterone based estrus synchronization protocol. Kafkas Univ Vet Fak Derg. 2019;25(5):643-650.
73. Lemaster JW, Seals RC, Hopkins FM, Schrick FN. Effects of administration of oxytocin on embryonic survival in progestogen supplemented cattle. Prostaglandins Other Lipid Mediat. 1997;57(4):259-268.
74. Lepesheva I, Bolgov A, Grishina N. Factors of early embryo mortality incidence in dairy cows. E3S Web Conf. 2020;161:01083.
https://doi.org/10.1051/e3sconf/202016101083
75. Leroy JL, Bie J, Jordaens L, Desmet K, Smits A, Marei W, Bols P, Hoeck V. Negative energy balance and metabolic stress in relation to oocyte and embryo quality: an update on possible pathways reducing fertility in dairy cows. Anim Reprod. 2017;14(3):497-506. https://doi.org/10.21451/1984-3143-AR992
76. Lobodin A, Mikhalev V, Lozovaya E, Safonov V, Nezhdanov A. Pathophysiological aspects of embryonic mortality in dairy cows. Agrobiology. 2017;52(2):338-348.
https://doi.org/10.15389/AGROBIOLOGY.2017.2.338ENG
77. Lonergan P. The importance of progesterone in pregnancy establishment in cattle. Livestock. 2023;28(6):271-276. https://doi.org/10.12968/live.2023.28.6.271.
78. López-Gatius F, García-Ispierto I. Ultrasound and endocrine findings that help to assess the risk of late embryo/early foetal loss by non-infectious cause in dairy cattle. Reprod Domest Anim. 2010;45(Suppl. 3):15-24. https://doi.org/10.1111/j.1439-0531.2010.01620.x.
79. López-Gatius F, Hunter RHF. Spontaneous reduction of advanced twin embryos: its occurrence and clinical relevance in dairy cattle. Theriogenology. 2005;63(1):118-125.
https://doi.org/10.1016/j.theriogenology.2004.03.006
80. López-Gatius F, Saleri R, De Rensis F, Llobera-Balcells M, Garcia-Ispierto I. Transfer of a single fresh in vitro-produced embryo may prevent twin pregnancy without compromising the fertility of the cow. Reprod Domest Anim. 2022;57(11):1418-1427. https://doi.org/10.1111/rda.14079
81. Mahla AS, Chaudhari RK, Verma AK, Singh AK, Singh SK, Singh G, Sarkar M, Dutta N, Kumar H, Krishnaswamy N. Effect of dietary supplementation of omega-3 polyunsaturated fatty acid (PUFA) rich fish oil on reproductive performance of the goat (Capra hircus). Theriogenology. 2017; 99:79-89. https://doi.org/10.1016/j.theriogenology.2017.05.023
82. Maillo V, Duffy P, O'Hara L, Frutos C, Kelly A, Lonergan P, Rizos D. Effect of human chorionic gonadotropin (hCG) administration on days 1, 2, 3, or 4 post-oestrus on corpus luteum development and circulating progesterone concentrations in beef heifers. Reprod Fertil Dev. 2013;25(1):202-203. https://doi.org/10.1071/RDV25N1AB110.
83. Malmo J, Beggs D. Reproduction management programs for seasonal calving dairy herds. Aust Vet J. 2000;78(9):608-614.
84. Manoj M, Gupta A, Mohanty T, et al. Non-genetic factors influencing fertility problems in Murrah buffaloes. Indian J Anim Sci. 2015;85(5):485-488.
https://doi.org/10.56093/ijans.v85i5.48570
85. Marai I, Haeeb A. Buffalo's biological functions as affected by heat stress - A review. Livest Sci. 2010;127(2-3):89-109. https://doi.org/10.1016/j.livsci.2009.08.001
86. McDonald RJ, McKay GW, Thomson JD. The use of organic iodine in the treatment of repeat breeder cows. Can Vet J. 1962;3(12):321-325.
87. McDowell RE, Hooven NW, Camoens JK. Effect of climate on performance of Holsteins in first lactation. J Dairy Sci. 1976;59(5):965-971.
88. McGeady T, Roche J, Bolandl M. Reproductive wastage following artificial insemination of heifers. Vet Rec. 1981;109(18):401-404. https://doi.org/10.1136/vr.109.18.401.
89. Mee J. Invited Review: Bovine neonatal morbidity and mortality—causes, risk factors, incidences, sequelae and prevention. Reprod Domest Anim. 2023;58(Suppl 1):1-15.
https://doi.org/10.1111/rda.14369
90. Mellado M, López R, de Santiago Á, et al. Climatic conditions, twinning and frequency of milking as factors affecting the risk of fetal losses in high-yielding Holstein cows in a hot environment. Trop Anim Health Prod. 2016;48(6):1247-1252.
https://doi.org/10.1007/s11250-016-1085-7
91. Merrill ML, Ansotegui RP, Burns PD, MacNeil MD, Geary TW. Effects of flunixin meglumine and transportation on establishment of pregnancy in beef cows. J Anim Sci. 2007;85(6):1547-1554.
92. Methai A. Efficacy of lipopolysaccharide and plasma in the treatment of endometritis in cows [Doctoral dissertation]. TANUVAS; 1999.
93. Meyer C, Berger P. Perinatal mortality in Holsteins. Anim Ind Rep. 2004;650(1):57.
https://doi.org/10.31274/ans_air-180814-783
94. Meyer MD, Hansen PJ, Thatcher WW, Drost M, Badinga L, Roberts RM, Li J, Ott TL, Bazer FW. Extension of corpus luteum lifespan and reduction of uterine secretion of prostaglandin F2 alpha of cows in response to recombinant interferon-tau. J Dairy Sci. 1995;78(9):1921-1931. https://doi.org/10.3168/jds.S0022-0302(95)76817-5
95. Michi AN, Favetto PH, Kastelic J, Cobo ER. A review of sexually transmitted bovine trichomoniasis and campylobacteriosis affecting cattle reproductive health. Theriogenology. 2016;85(5):781-791.
https://doi.org/10.1016/j.theriogenology.2015.10.037
96. Mikulková K, Illek J, Kadek R. Glutathione redox state, glutathione peroxidase activity and selenium concentration in periparturient dairy cows, and their relation with negative energy balance. J Anim Feed Sci. 2020;29(1):19-26. https://doi.org/10.22358/jafs/117867/2020.
97. Mohapatra S, Dang A, Kamboj A, Panda B, Verma A, Alhussien M. A comparative study on various immunological parameters influencing embryo survivability in crossbred dairy cows. Theriogenology. 2020; 157:140-148.
https://doi.org/10.1016/j.theriogenology.2020.05.041
98. Mohapatra S, Kamboj A, Panda B, et al. Indoleamine 2, 3-dioxygenase 1 mediated alterations in the functionality of immune cells, decipher the pregnancy outcomes in crossbred dairy cows. bioRxiv. 2022.
https://doi.org/10.1101/2022.08.01.502424
99. Moqbel M, Al-Ramadan S. MUC1 regulation in the left and right uterine horns and conceptus trophectoderm during the peri-implantation period of dromedary camel. Theriogenology. 2024;218:244-253.
https://doi.org/10.1016/j.theriogenology.2024.02.009
100. Moraloglu O, Tonguc E, Var T, Zeyrek T, Batıoglu S. Treatment with oxytocin antagonists before embryo transfer may increase implantation rates after IVF. Reprod Biomed Online. 2010;21(3):338-343.
101. Neglia G, Natale A, Esposito G, et al. Effect of prostaglandin F2α at the time of AI on progesterone levels and pregnancy rate in synchronized Italian Mediterranean buffaloes. Theriogenology. 2008;69(8):953-960.
https://doi.org/10.1016/j.theriogenology.2007.12.012
102. Nenova R, Ilieva Y, Penchev P, Vasilev N, Fasulkov I, Nikolova G, Karamalakova Y, Gadjeva V. Pregnancy Rates Associated with Oxidative Stress after Estrus Synchronization of Bulgarian Murrah Buffaloes in Breeding and Non-Breeding Season. J Buffalo Sci. 2023;12(1):1-10. https://doi.org/10.6000/1927-520x.2023.12.05.
103. Nestor C, Bedenbaugh M, Hileman S, Coolen L, Lehman M, Goodman RL. Regulation of GnRH pulsatility in ewes. Reproduction. 2018;156(3): R83-R99.
https://doi.org/10.1530/REP-18-0127
104. Nitta A, Shirasuna K, Haneda S, Matsui M, Shimizu T, Matsuyama S, Kimura K, Bollwein H, Miyamoto A. Possible involvement of IFNT in lymphangiogenesis in the corpus luteum during the maternal recognition period in the cow. Reproduction. 2011;142(6):879-892. https://doi.org/10.1530/REP-11-0157
105. Nivetha P. Unraveling luteal insufficiency and its mitigation using GnRH analogue, hCG and synthetic Kisspeptin in crossbred cows [Doctoral dissertation]. Indian Veterinary Research Institute; 2024.
106. Noakes DE, Parkinson TJ, England GCW. Veterinary reproduction and obstetrics. Elsevier; 2019.
107. Nowicki A. Embryo Transfer as an Option to Improve Fertility in Repeat Breeder Dairy Cows. J Vet Res. 2021;65(2):231-237. https://doi.org/10.2478/jvetres-2021-0018
108. Oliveira LJ, Barreto RSN, Perecin F, Mansouri-Attia N, Pereira FTV, Meirelles FV. Modulation of maternal immune system during pregnancy in the cow. Reprod Domest Anim. 2012;47(3):384-393.
https://doi.org/10.1111/j.1439-0531.2011.01893.x
109. Oliveira LJ, Mansourri-Attia N, Fahey AG, et al. Characterization of the Th profile of the bovine endometrium during the oestrous cycle and early pregnancy. PLoS One. 2013;8(10):e75571.
https://doi.org/10.1371/journal.pone.0075571
110. Ott T. Symposium review: Immunological detection of the bovine conceptus during early pregnancy. J Dairy Sci. 2019;102(4):3766-3777.
https://doi.org/10.3168/jds.2018-15668
111. Ouedraogo A, Kalandi M, Nyabinwa P, Mouliom M, Sawadogo G, Adama S. Detection of embryonic mortality using progesterone and bovine pregnancy associated glycoprotein assays following artificial insemination of Gobra Zebu cattle in Senegal. J Anim Sci Biotechnol. 2016;7(1):1-8.
112. Parmar S, Dhami A, Hadiya K, Parmar C. Early embryonic death in bovines: an overview. Raksha Tech Rev. 2016;6(1):6-12.
113. Parra-Bracamonte G, Gómez-Guzmán J, Velazquez M. Impact of Heat Stress on Oocyte Developmental Competence and Pre-Implantation Embryo Viability in Cattle. Animals. 2024;14(15):2280. https://doi.org/10.3390/ani14152280.
114. Paul D, Chandel BS, Ray J. Quantity and value of milk losses due to technical constraints—a case of crossbred cows in North-Eastern states of India. Indian J Agric Econ. 2013;68(4):562-572.
115. Peters AR. Embryo mortality in the cow. Anim Reprod Sci. 1996;42(1-4):1-11.
https://doi.org/10.1016/0378-4320(96)01530-4
116. Peterson AJ, Tervit HR, Fairclough RJ, et al. Maternal recognition of pregnancy in the ewe, cow and sow: effects of conceptus removal and conceptus products. J Reprod Fertil Suppl. 1985; 34:185-195.
117. Plante C, Thatcher WW, Hansen PJ. Alteration of oestrous cycle length, ovarian function and oxytocin-induced release of prostaglandin F-2α by intrauterine and intramuscular administration of recombinant bovine interferon-α to cows. Reproduction. 1991;93(2):375-384.
118. Pohler K, De Melo G, Holton M, Fontes P, Oosthuizen N, Lamb G, Stewart R, Davis D. Luteal Color doppler ultrasonography and pregnancy associated glycoproteins as early pregnancy diagnostic tools and predictors of pregnancy loss in Bos taurus postpartum beef cows. J Anim Sci. 2022;100(1):skac018. https://doi.org/10.1093/jas/skac018.
119. Prandi A, Galiero G, Di Palo R, Campanile G, Zicarelli L, Gasparrini B, Neglia G, D'Occhio M. Embryonic mortality in buffaloes synchronized and mated by AI during the seasonal decline in reproductive function. Theriogenology. 2005;63(8):2334-2340. https://doi.org/10.1016/j.theriogenology.2004.10.012.
120. Puglisi R, Cambuli C, Capoferri R, et al. Differential gene expression in cumulus oocyte complexes collected by ovum pick up from repeat breeder and normally fertile Holstein Friesian heifers. Anim Reprod Sci. 2013;141(1-2):26-33.
https://doi.org/10.1016/j.anireprosci.2013.07.004
121. Puklová P, Šubrt J, Skrip D, Filipčík R. Embryonic mortality in Holstein cows. Acta Univ Agric Silvic Mendel Brun. 2011;59(1):23-30.
122. Rajkumar R, Singh SK, Agarwal SK, Mahmood S, Shankar U. Effect of selective COX-2 inhibitor on conception rate, progesterone and PGFM profile in buffalo (Bubalus bubalis). J Appl Anim Res. 2010;38(2):209-212.
123. Rasmussen A, Holtenius K, Båge R, Strandberg E, Åkerlind M, Kronqvist C. Customized voluntary waiting period before first insemination in primiparous dairy cows. Effect on milk production, fertility and health. J Dairy Sci. 2024;107(1):1-15. https://doi.org/10.3168/jds.2023-24593
124. Rizzo A, Minoia G, Trisolini C, Manca R, Sciorsci RL. Concentrations of free radicals and beta-endorphins in repeat breeder cows. Anim Reprod Sci. 2007;100(3-4):257-263.
https://doi.org/10.1016/j.anireprosci.2006.08.013
125. Robinson JL, Dombrowski DB, Harpestad GW, Shanks RD. Detection and prevalence of UMP synthase deficiency among dairy cattle. J Hered. 1984;75(4):277-280.
126. Rodriguez-Campos S, Hirsbrunner G, Mock T, et al. Evaluation of an investigative model in dairy herds with high calf perinatal mortality rates in Switzerland. Theriogenology. 2020;148:48-59.
https://doi.org/10.1016/j.theriogenology.2020.02.039
127. Roy KS, Prakash BS. Seasonal variation and circadian rhythmicity of the prolactin profile during the summer months in repeat-breeding Murrah buffalo heifers. Reprod Fertil Dev. 2007;19(4):569-575. https://doi.org/10.1071/rd06093.
128. Ryan DP, Godke RA, Prichard JF, Kopel E. Comparing early embryo mortality in dairy cows during hot and cool seasons of the year. Theriogenology. 1993;39(3):719-737.
https://doi.org/10.1016/0093-691X(93)90257-6
129. Sahu UK, Gupta AK, Kumar M, Sahu L, Sharma R. Breeding the future: How sexed semen is transforming India's dairy industry. The Scientific Frontiers. 2025;1(1):6-8. https://doi.org/10.5281/zenodo.14830174.
130. Sahu UK, Singh M, Warghat C, Khan MH. Post-partum prolapse of genitalia in a cow. Indian J Anim Reprod. 2024;45(2):93-95.
131. Sahu UK. Uterine haemodynamics, follicular-luteal attributes and developmental competence of OPU derived oocytes in subclinical endometritic dairy cows [Doctoral dissertation]. Indian Veterinary Research Institute; 2025.
132. Sangsritavong S, Combs DK, Sartori R, Armentano LE, Wiltbank MC. High feed intake increases liver blood flow and metabolism of progesterone and estradiol-17β in dairy cattle. J Dairy Sci. 2002;85(11):2831-2842.
https://doi.org/10.3168/jds.S0022-0302(02)74370-1
133. Sanhueza JM, Heuer C, West D. Contribution of Leptospira, Neospora caninum and bovine viral diarrhea virus to fetal loss of beef cattle in New Zealand. Prev Vet Med. 2013;112(1-2):90-98.
https://doi.org/10.1016/j.prevetmed.2013.07.009
134. Santolaria P, López-Gatius F, García-Ispierto I, Bech-Sàbat G, Angulo E, Carretero T, Yániz J. Effects of cumulative stressful and acute variation episodes of farm climate conditions on late embryo/early fetal loss in high producing dairy cows. Int J Biometeorol. 2010;54(1):93-98.
135. Sartori R, Bastos MR, Wiltbank MC. Factors affecting fertilisation and early embryo quality in single- and superovulated dairy cattle. Reprod Fertil Dev. 2010;22(1):151-158.
https://doi.org/10.1071/RD09221
136. Scarlet D, Steufmehl M, Bollwein H, Ulbrich S, Honnens Ä. Presence of embryos increases uterine blood flow and affects endometrial gene expression in Holstein cows on day seven post-insemination. Reprod Biol. 2024;25(1):100986. https://doi.org/10.1016/j.repbio.2024.100986.
137. Schramm W, Friesen HG, Robertson HA, McCracken JA. Effect of exogenous ovine placental lactogen on luteolysis induced by prostaglandin F-2 alpha in sheep. J Reprod Fertil. 1984;70(2):557-565. https://doi.org/10.1530/jrf.0.0700557
138. Selvaraju S, Agarwal SK, Karche SD, Srivastava SK, Majumdar AC, Shanker U. Fertility responses and hormonal profiles in repeat breeding cows treated with insulin. Anim Reprod Sci. 2002;73(3-4):141-149.
139. Senger PL. Pathways to Pregnancy and Parturition. 3rd ed. Current Conceptions; 2012.
140. Serrano-Pérez B, Villalba D, Molina E, López-Helguera I, Casasús I, Sanz A. Maternal nutrient restriction in early pregnancy increases the risk of late embryo loss despite no effects on peri-implantation interferon-stimulated genes in suckler beef cattle. Res Vet Sci. 2019;128:69-75. https://doi.org/10.1016/j.rvsc.2019.10.023.
141. Silke V, Diskin MG, Kenny DA, et al. Extent, pattern and factors associated with late embryonic loss in dairy cows. Anim Reprod Sci. 2002;71(1-2):1-12.
https://doi.org/10.1016/S0378-4320(02)00123-8
142. Silva-del-Río N, Colloton J, Fricke PM. Factors affecting pregnancy loss for single and twin pregnancies in a high-producing dairy herd. Theriogenology. 2009;71(9):1462-1471.
https://doi.org/10.1016/j.theriogenology.2008.12.018
143. Singh A, Dash S, Upadhyay A, Chakravarty A, Singh M, Yousuf S. Effect of heat stress on reproductive performances of dairy cattle and buffaloes: A review. Vet World. 2016;9(3):235-244. https://doi.org/10.14202/vetworld.2016.235-244
144. Singh J, Dadarwal D, Honparkhe M, Kumar A. Incidences of various etiological factors responsible for repeat breeding syndrome in cattle and buffaloes. Indian J Anim Sci. 2008;6(1):1-5. https://doi.org/10.5580/2b9
145. Sood P, Zachut M, Dube H, Moallem U. Behavioral and hormonal pattern of repeat breeder cows around estrus. Reproduction. 2015;149(6):545-554.
https://doi.org/10.1530/REP-14-0598
146. Sousa NM, Ayad A, Beckers JF, Gajewski Z. Pregnancy-associated glycoproteins (PAG) as pregnancy markers in the ruminants. J Physiol Pharmacol. 2006;57(Suppl. 8):153-171.
147. Souto L, Geraldo A, Silva F. Effects of climatic heat stress on embryo mortality of grazing cattle in Azores. Reprod Fertil Dev. 2010;22(1):228. https://doi.org/10.1071/RDV22N1AB138.
148. Spencer TE, Bazer FW. Ovine interferon tau suppresses transcription of the estrogen receptor and oxytocin receptor genes in the ovine endometrium. Endocrinology. 1996;137(3):1144-1147.
149. Sreenan JM, Diskin MG. The extent and timing of embryonic mortality in the cow. In: Embryonic Mortality in Farm Animals. Springer; 1986:1-11.
150. Srivastava N, Pande M (Eds.). Protocols in semen biology (comparing assays). Springer; 2017.
151. Stangaferro ML, Wijma R, Masello M, Giordano JO. Reproductive performance and herd exit dynamics of lactating dairy cows managed for first service with the Presynch-Ovsynch or Double-Ovsynch protocol and different duration of the voluntary waiting period. J Dairy Sci. 2018;101(2):1673-1686. https://doi.org/10.3168/jds.2017-13425
152. Stewart HJ, Flint AP, Lamming GE, McCann SH, Parkinson TJ. Antiluteolytic effects of blastocyst-secreted interferon investigated in vitro and in vivo in the sheep. J Reprod Fertil. 1989;87(2):501-511.
https://doi.org/10.1530/jrf.0.0870501
153. Takahashi H, Haneda S, Kayano M, Matsui M. Differences in progesterone concentrations and mRNA expressions of progesterone receptors in bovine endometrial tissue between the uterine horns ipsilateral and contralateral to the corpus luteum. J Vet Med Sci. 2016;78(4):613-618.
154. Tamasaukas R, Rolo M, Roa N, Linares T. Reproductive Response of Crossbred Heifers (Bos indicus×Bos taurus) Used as Embryo Recipients in Venezuela. J Reprod Dev. 1998;44(4):367-370. https://doi.org/10.1262/JRD.44.367.
155. Tameoka N, Izaike Y, Osawa T, et al. Association between energy status early postpartum and subsequent embryonic mortality in high-yielding recipient cows. Anim Sci J. 2012;83(4):284-290.
https://doi.org/10.1111/j.1740-0929.2011.00958.x
156. Teeli AS, Sheikh PA, Patra MK, Singh D, Kumar B, Kumar H, Singh SK, Verma MR, Krishnaswamy N. Effect of dietary n-3 polyunsaturated rich fish oil supplementation on ovarian function and interferon stimulated genes in the repeat breeding cow. Anim Reprod Sci. 2019; 211:106230. https://doi.org/10.1016/j.anireprosci.2019.106230
157. Thejaswini MP, Patra MK, Sharma R, Raza MR, Sasidharan JK, Karikalan M, Krishnaswamy N. Enhancement of progesterone biosynthesis via kisspeptin stimulation: Upregulation of steroidogenic transcripts and phosphorylated extracellular signal-regulated kinase (p-ERK1/2) expression in the buffalo luteal cells. Theriogenology. 2024; 220:108-115.
158. Van Haaften M, Wiegerinck MA, Poortman J, Haspels AA, Thijssen JH. Progesterone receptors in human oestrogen target tissues. Maturitas. 1982;4(1):57-66. https://doi.org/10.1016/0378-5122(82)90020-2
159. Van Knegsel AT, Brand H, Dijkstra J, Straalen WM, Jorritsma R, Tamminga S, Kemp B. Effect of glucogenic vs. lipogenic diets on energy balance, blood metabolites, and reproduction in primiparous and multiparous dairy cows in early lactation. J Dairy Sci. 2007;90(7):3397-3409. https://doi.org/10.3168/jds.2006-837
160. VanRaden PM, Miller RH. Effects of nonadditive genetic interactions, inbreeding, and recessive defects on embryo and fetal loss by seventy days. J Dairy Sci. 2006;89(7):2716-2721.
https://doi.org/10.3168/jds.S0022-0302(06)72347-5
161. Vanroose G, de Kruif A, Van Soom A. Embryonic mortality and embryo-pathogen interactions. Anim Reprod Sci. 2000;60-61:131-143.
https://doi.org/10.1016/S0378-4320(00)00098-1
162. Vasconcelos J, Pereira M, Edwards J, Reese S, Pohler K. Pregnancy diagnosis in cattle using pregnancy associated glycoprotein concentration in circulation at day 24 of gestation. Theriogenology. 2018; 106:178-185. https://doi.org/10.1016/j.theriogenology.2017.10.020.
163. Vasques MI, Pimenta J, Becker JD, Marques CC, Horta AE, Baptista MC, Pereira RM. Cyclooxygenase-2 (COX-2) expression by in vitro produced bovine embryos. Preliminary results. Reprod Domest Anim. 2005;40(4):321.
164. Verma AK, Mahla AS, Chaudhari RK, Singh AK, Khatti A, Singh SK, Dutta N, Singh G, Sarkar M, Kumar H, Yadav D, Krishnaswamy N. Effect of different levels of n-3 polyunsaturated fatty acids rich fish oil supplementation on the ovarian and endometrial functions in the goat (Capra hircus). Anim Reprod Sci. 2018; 195:153-161. https://doi.org/10.1016/j.anireprosci.2018.05.019
165. Verma S, Srivastava S, Verma RK, Kumar A, Yadav SK. Incidence of repeat breeding in cows in and around Kumarganj, Faizabad (Uttar Pradesh), India. Int J Curr Microbiol Appl Sci. 2018;7(10):4860-4870.
166. Villarroel A, Martino A, Bondurant R, Dèletang F, Sischo W. Effect of post-insemination supplementation with PRID on pregnancy in repeat-breeder Holstein cows. Theriogenology. 2004;61(7-8):1513-1520. https://doi.org/10.1016/j.theriogenology.2003.09.001.
167. Voljč M, Čepon M, Malovrh Š, Žgur S. The effect of dam breed on calf mortality in the first month of life in Slovenia. Agric Conspec Sci. 2017;82(2):69-73.
168. Vrisman D, Bastos N, Rossi G, Rodrigues N, Borges L, Taira A, De Paz C, Nogueira G, Teixeira P, Monteiro F, Oliveira M. Corpus luteum dynamics after ovulation induction with or without previous exposure to progesterone in prepubertal Nellore heifers. Theriogenology. 2018; 106:60-68. https://doi.org/10.1016/j.theriogenology.2017.10.018.
169. Wagener K, Gabler C, Drillich M. A review of the ongoing discussion about definition, diagnosis and pathomechanism of subclinical endometritis in dairy cows. Theriogenology. 2017; 94:21-30.
https://doi.org/10.1016/j.theriogenology.2017.02.005
170. Wang JY, Owen FG, Larson LL. Effect of beta-carotene supplementation on reproductive performance of lactating Holstein cows. J Dairy Sci. 1988;71(1):181-186.
171. Ximenes C, Bettencourt A, Schmitz B, Da Rosa D, Guimarães J, Da Cunha Borges B, Ghedini C, Fischer V. Physiological and behavioral indicators of water buffaloes with access to heat mitigation resources in a grazing system during the hot season in the subtropics. Appl Anim Behav Sci. 2024; 275:106409. https://doi.org/10.1016/j.applanim.2024.106409
172. Yaginuma H, Funeshima N, Tanikawa N, Miyamura M, Tsuchiya H, Noguchi T, Iwata H, Kuwayama T, Shirasuna K, Hamano S. Improvement of fertility in repeat breeder dairy cattle by embryo transfer following artificial insemination: possibility of interferon tau replenishment effect. J Reprod Dev. 2019;65(3):223-229. https://doi.org/10.1262/jrd.2018-121
173. Yáñez-Pizaña A, Cruz-Cruz L, Tarazona-Morales A, Roldán-Santiago P, Ballesteros-Rodea G, Pineda-Reyes R, Orozco-Gregorio H. Physiological and Behavioral Changes of Water Buffalo in Hot and Cold Systems: Review. J Buffalo Sci. 2020;9(1):110-120. https://doi.org/10.6000/1927-520x.2020.09.13
174. Yusuf M, Nakao T, Ranasinghe RBK, Gautam G, Long ST, Yoshida C, Hayashi A. Reproductive performance of repeat breeders in dairy herds. Theriogenology. 2010;73(9):1220-1229.
https://doi.org/10.1016/j.theriogenology.2010.01.017
175. Zhang L, Xia Y, Tang F, et al. The regulation of intrauterine immune cytokines and chemokines during early pregnancy in the bovine. Large Anim Rev. 2015;21(1):23-31.
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