TINJAUAN PUSTAKA
5.6 Keterbatasan dan kekuatan penelitian serta saran untuk penelitian selanjutnya. selanjutnya
Keterbatasan dari penelitian ini adalah tidak adanya pemeriksaan ROS dan proses metilasi yang dilakukan bersamaan dengan pemeriksaan homosistein dan fragmentasi DNA sperma. Jadi, dampak homosistein terhadap fragmentasi DNA tidak dapat diketahui dengan jelas. Kami menggunakan studi sebelumnya yang relevan dengan konteks di atas sebagai dasar teori untuk menjelaskan hubungan ini.
Studi lebih lanjut untuk menyelidiki kadar ROS pada semen dalam hiperhomosisteinemia dan keguguran berulang masih diperlukan. Universitas Sumatera Utara
untuk keguguran berulang harus berbeda dan sampai sekarang tidak ada studi yang meneliti tentang batas bawah untuk kasus keguguran berulang. Kami menggunakan ≥ 30, ini dianggap terlalu tinggi, karena penelitian sebelumnya menyatakan bahwa DFI ≥ 30 berkorelasi dengan kegagalan fertilisasi yang tinggi. Studi di masa mendatang dengan penelitian sampel yang lebih besar diperlukan untuk mencari nilai untuk kasus keguguran berulang.
Demikian pula, penelitian untuk meneliti kadar homosistein dalam populasi normal semen tidak pernah ada, apakah itu memiliki efek positif atau negatif masih belum diketahui.
Kelebihan penelitian ini adalah sampel yang dipilih dengan kriteria eksklusi yang ketat untuk mencari korelasi kadar homosistein pria dan fragmentasi DNA sperma dengan kejadian keguguran berulang idiopatik dini dan sejauh ini, sampai penelitian ini dilakukan, dan sepanjang pengetahuan peneliti masih belum ada studi yang mencari hubungan antara hiperhomosisteinemia dengan fragmentasi DNA sperma dan keguguran berulang idiopatik dini.
76 6.1 Kesimpulan
1. Faktor penentu yang ditemukan dalam penelitian ini mengungkapkan bahwa homosistein serum pria dan DFI memiliki korelasi yang signifikan dalam kejadian keguguran berulang idiopatik dini.
2. Hiperhomosisteinemia menyebabkan fragmentasi DNA sperma dan berkorelasi dengan keguguran berulang idiopatik dini.
6.2 Saran
1. DFI dapat digunakan sebagai salah satu parameter dalam menyelidiki faktor pria dalam pasangan dengan keguguran berulang idiopatik dini. 2. Hiperhomosisteinemia bukanlah kondisi yang jarang dan dapat
ditelusuri pada pria dari pasangan dengan keguguran berulang idiopatik dini dan ini harus menjadi perhatian untuk dijadikan bagian dari penyelidikan untuk diagnosis dan pengobatan.
77
Levalle, O., 2002. Overt and subclinical hypothyroidism complicating pregnancy. Thyroid, 12(1), pp.63-8.
Agarwal, A., Ikemoto, I. and Loughlin, K.R.,1994. Relationship of parameters with levels of reactive oxygen species in semen specimens. The J of Urol, 152, pp.107-10.
Agarwal, A. and Said, T.M., 2003. Role of sperm chromatin abnormalities and DNA damage in male infertility. Hum Reprod Update, 9, pp.331-45.
Agarwal, A., Erenpreiss, J. and Sharma, R., 2009. Sperm chromatin assessment. In: Gardner, D.K. and Weissman, A., ed. Textbook of assisted reproductive technologies. 3rd ed. London: Informa, pp.70-84.
Ahmadi, A. and Ng, S.C.,1999. Fertilizing ability of DNA-damaged spermatozoa. J Exp Zool, 284, pp.696-700.
Aitken, R.J. and West, K.M.,1990. Analysis of relationship between reactive oxygen species production and leucocyte infiltration in fractions of human semen separated on Percoll gradients. Int J of Androl, 13, pp.433-51.
Aitken, R.J., Harkiss, D. and Buckingham, D., 1993. Relationship between iron-catalysed lipid peroxidation potential and human sperm function. J Reprod Fertil, 98, pp.257-65.
Aitken, R.J., Fisher, H., 1994. Reactive oxygen species generation and human spermatozoa. The balance of benefit and risk. BioEssays, 16, pp.259-67.
Aitken, R.J., Fisher, H., Fulton, N., Gomez, E., Knox, W., Lewis, B., and Irvine, S., 1997. Reactive oxygen species generation by human spermatozoa
inhibitors diphenylene iodonium and quinacrine. Mol Reprod and Develop, 47, pp.468-82.
Aitken, R.J., Gordon, E., Harkiss, D., Twigg, J.P., Milne, P., Jenning, Z. et al, 1998. Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod, 59, pp.1037-46.
Aitken, R.J. and Luliis, G.N.D., 2007. Origins and consequences of DNA damage in male germ cells. RBM Online, 14, 727-33.
American College of Obstetricians and Gynaecologists ACOG educational bulletin, 1990. Management of isoimmunisation in pregnancy. Int. J Gyn Obst, 155, pp.183-90.
American Society of Reproductive Medicine (ASRM), 2005. Recurrent pregnancy loss, [online] Available at: <http://www.asrm.org/patient/factsheet/fact.html>
[Accessed 9 January 2008].
Apedaile, A.E., Garret C.; Liu D.Y.; Clarke G.N.; Johnston SA.; Baker H.W.G., 2004. Flow cytometry and microscopic acridine orange test. In: Relationship with standard semen analysis. RBMOnline, 8, pp.398-407.
Armstrong, J.S., Rajasekaran, M., Chamulitrat, W., Gatti, P., Hellstrom, W., Sikka, S.C.,1999. Characterization of reactive oxygen species induced effects on human spermatozoa movement and energy metabolism. Free Rad Bio Med, 26, pp.869-80.
Aubard, Y., Darodes, N., Cantaloube, M., 2000. Hyperhomocysteinemia and pregnancy-review of our present understanding and therapeutic implications. EU J Obstet Gynecol and Rep Bio, 93, pp.157-65.
Kelahiran tidak diinginkan (aborsi) dalam kesejahteraan reproduksi remaja, Palembang, 25 Juni 2002.
Balhorn, R., 1998. A model for the structure of chromatin in human sperm. J Cell Bio, 2(93), pp.298-305.
Banks, S., King, S.A., Irvine, D.S., Saunders, P.T.K., 2005. Impact of a mild scrotal heat stress on DNA integrity in murine spermatozoa. Society for Reprod and Fertil, 129, pp.505-14.
Baziad, A., Sumapraja, K. and Santoso, B. eds., 2011. Panduan tata laksana keguguran berulang. Jakarta: Himpunan Endokrinologi-Reproduksi dan Fertilitas Perkumpulan Obstetri dan Ginekologi Indonesia (HIFERI-POGI).
Bentivoglio, G., Melica, F., Cristoforoni, P.,1993. Folic acid in the treatment of human male infertility. Fertil Steril, 60, pp.698-701.
Bezold, G., Lange, M., Peter, R.U., 2001. Homozygous methylenetetrahydrofolate reductase C677T mutation and male infertility. New Engl J Med, 344, pp.1172-73.
Bian, Q., Xu, L.C., Wang, S.L., Xia, Y.K., Tan, L.F., Chen, J.F., et al., 2004. Study on relation between occupational fenvalerate exposure and spermatozoa DNA damage of pesticide factory workers. Occupational and environmental medicine, 61, pp.999-1005.
Bohlmann, M.K., Rossmann, H., Von Wolff, M., 2004. A role for “acquired”
activated protein C resistance in recurrent fetal loss. Fertility & Sterility, 81, pp.1427-28.
Borini, A., Tarozzi, N., Bizarro, D., Bonu, M.A., Fava, L., Flamigni, C. et al., 2006. Sperm DNA fragmentation. Paternal effect on early post-implantation embryo development in ART. Hum Reprod, 21, pp.2876-81.
Lindermans, J. et al., 2011. Low folate in seminal plasma is associated with increase sperm DNA damage. Fertil steril, 92(2), pp.548-56.
Branch, D.W., Heuser, C., 2010. Recurrent miscarriage. In: Carrel, D.T., Petterson, C.M., ed. Reproductive endocrinology and infertility. Integrating Modern Clinical and Laboratory Practice. New York: Springes, p.281-93.
Brattstrom, L.E., Lingdren, A., Israelsson, B., Anderson, A., Hultberg, B., 1994. Homocysteine and cysteine. Determinant of plasma levels in middle aged and elderly subjects. J Intern Med, 236, pp.633-41.
Brattstrom, L., Wilcken, D.E., Ohrvik, J., Brudin, L., 1998. Common methylene tetrahydrofolate reductase gene leads to hyperhomocysteinemia but not to vascular disease. Results of a meta analysis. Circulation, 98, pp.2520-26.
Bricker, L., Farquharsson, R.G., 2002. Types of pregnancy loss in recurrent miscarriage. Implications for research and clinical practice. Hum Reprod, 17, pp.1345-50.
Brigham, S.A., Conlon, C., Farquaharson, R.G., 1999. A longitudinal study of pregnancy outcomes following idiopathic recurrent miscarriage. Hum Reprod, 14, pp.2868-71.
Brinkworth, M.H., Nieschlag, E., 2000. Association of cyclophosphamide-induced male mediated, fetal abnormalities with reduced paternal germ-cell apoptosis. Mutat res, 447, pp.149-54.
Bungum, M., Humaidan, P., Spano, M., Jepson, K., Bungum, L., Giwercman, A., 2004. The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination, IVF and ICSI. Hum Reprod, 19, pp.1401-08.
Intrauterine growth retardation, perinatal death, and maternal homocysteine levels. New Engl J Med, 326, pp.69-70.
Burton, G.J., Watson, A.L., Hempstock, J., Skipper, J.N., Jauniaux, E., 2002. Uterine glands provide histeotrophic nutrition for the human fetus during the first trimester of pregnancy. J Clin Endocrinol Metab, 87, pp.2954-59.
Cahill, M., Karabatzaki, M., Meleady, R., Refsum, H., Ueland P., Shields D. et al, 2000. Raised plasma homocysteine as a risk factor for retinal vascular occlusive disease. Bristish J of Opht, 84, pp.154-7.
Carreil, D.T., Liu, L., Peterson, C.M., Jones, K.P., Hatasaka, H.H., Erickson, L. et al, 2003. Sperm DNA Fragmentation is increated in couples with unexplained recurrent pregnancy loss. Arch of Androl, 49, pp.49-55.
Champe, P.C., Harvey, R.A.,2008. Biochemistry. Lippincott’s Illustrated reviews. 4th ed. Lippincott: Williams and Wilkins.
Charles, D., Larsen, B., 1990. Spontaneous abortion as a result of infection. In: Huisjes, H.B. and Lind, T., eds. Early pregnancy l failure. Edinburgh: Chruchill Livingstone, pp.161-76.
Cho, C., Jung-Ha, H., Willis, W.D., Goulding, E.H., Stein, P., Xu, Z. et al, 2003. Protamine 2 deficiency leads to sperm DNA damage and embryo death in mice. Bio Reprod, 69, pp.211-7.
Clark, A.M., Thornley, B., Tomlinson, L., Gattetly, C., Norman, R.J., 1998. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod, 13, pp.1502-5.
suppressing luteinizing hormone secretion reduce the miscarriage rate? Results of a randomized controlled trial. BMJ, 312, pp.1508-11.
Cristiansen, O.B., Anderson, A.M.N., Bosch, E., Daya, S., Delves, P.J., Hviid, T.V. et al, 2005. Evidenced-based investigations and treatments of recurrent pregnancy loss. Fertil Steril, 83, pp.821-39.
Crow, J.F., 1997. The high spontaneous mutation rate. Is it a health risk? Proc Natl Acad Sci, 94, pp.8380-6.
Dahlan, M.S, 2009. Besar sampel dan cara pengambilan sampel. Jakarta: Salemba Medika, hal 101.
Dawood, F., Farquharson, R., Qenby, S., Toh, C.H., 2003. Acquired activated protein C resistance maybe a risk factor for recurrent fetal loss. Fertil Steril, 80, pp.649-50.
De Vries, J.L.P., Dekker, G.A., Huijgens, P.C., Jakobs, C., Blomber, B.M.E., Hyperhomocysteinemia and protein S deficiency in complicated pregnancies. Br J Obstet Gynecol, 104, pp.1248-54.
Donelly, E.T., O’Connell, M., McClure, N., Lewis, S.E.M., 2000. Differences in nuclear DNA fragmentation and mitochondrial integrity of semen and prepared human spermatozoa. Hum Reprod, 15(7), pp.1552-61.
Ebisch, I.M., Van Heerde, W.L., Thomas, C.M. et al, 2003. C677T methylenetetrahydrofolate reductase polymorphism interferes with the effects of folic acid and zinc sulfate on sperm concentration. Fertil Steril, 80, pp.1190-4.
Empson, M., Lassere, M., Craig, J., Scoot, J., 2002. Recurrent pregnancy loss with antiphospolipid antibody. A systematic review of therapeutic trials. Obstet Gynaecol, 99, pp.135-44.
support on pregnancy rates in intrauterine insemination cycles. A prospective randomized study. Fertil Steril, 91(6), pp.2508-13.
Evenson, D.P., Jost L.K., Marshall, D., Zinaman, M.J., Clegg, E., Purvis, K. et al, 1999. Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in Human Fertility Clinic. Hum Reprod, 14, pp.1039-49.
Evenson, D.P., Wixon, R., 2005. Comparison of the Halosperm test kit with the sperm chromatin structure assay (SCSA) infertility test in relation to patient diagnosis and prognosis. Fertil Steril, 84(4), pp.846-9.
Evenson D.P.; Wixon R., 2006. Clinical aspect of sperm DNA fragmentation detection and male infertility. Theriogenology, 65, pp.979-91.
Fenech, M., Aitken, C., Rinaldi, J., 1998. Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. PubMed, 19, pp.1163-71.
Fernandez, J.L., Goyanes, V.J., Ramiro-Diaz, J., Gosalvez, J., 1998. Application of FISH for in situ detection and quantification of DNA breakage. Cytogenet Cell Genet, 82, pp.251-6.
Fernandez, J.L., Muriel, L., Goyanes, V., Segrelles, E., Gosalves, J., Enciso, M. et al, 2005. Halosperm is an easy, available and cost-effective alternative for determining sperm DNA fragmentation. Fertil Steril, 84, pp.860.
Forges, T., Barbarino, P.M., Alberto, J.M., Rodriguez, R.M.G., Daval, J.L., Guent, J.L., 2007. Impact of folate and homocysteine metabolism on human reproductive health. Hum Reprod Update, pp.1-14.
Fox, H., 1993. Histological classification of tissue from spontaneous abortions: a valueless exercise? Histopathol, 22, pp.599-600.
A.C., Gerssen-Schoorl, K.B.J. et al, 2005. Selective chromosome analysis in couples with two or more miscarriages. Case control study. BMJ, 331, pp.137-9.
Fritz, M.A., Speroff, L., 2005. Recurrent pregnancy loss. In: Fritz, M.A., Speroff, L., ed. Clinical gynaecologic endrocrinology and infertility. Philadelphia: Lippincott William S Wilkin, pp.1191-220.
Gagnon, C.; Iwasaki, A.; Lamirande, E.D.; Kovalski, N., 1991. Reactive oxygen species and Human spermatozoa. Ros and Human Spermatozoa. Ann. NY Acad. Sci., 637, pp.436-44.
Gardella, J.R., Hill, J.A., 2000. Enviromental toxins associated with recurrent pregnancy loss. Semin Reprod Med, 18, pp.137-9.
Gatewood, J.M., Cook, G.R., Balhorn, R., Schmid, C.W., Bradbury, E.M., 1990. Isolation of four core histones from human sperm chromatin representing a minor subset of somatic histones. J Biol Chem, 265, pp.20662-6.
Genesca, A., Caballin, M.R., Miro, R., 1992. Repair of human sperm chromosome aberrations in the hamster egg. Hum Genet, 89, pp.181-6.
Gill-Guzman, E., Ollero, M., Lopez, M.C., Sharma, R.K., Alvarez, J.G., Thomas, A.J., Agarwal, A., 2001. Differential production of reactive oxygen species by subsets of human spermatozoa at different stages of maturation. Hum Reprod, 16(9), pp.1922-30.
Gill Villa, A.M., Cardona-Maya, W.D., Cadavid, A., Jaramillo, A.P., 2007. Early embryo death: does the male factor play a role? Arch Esp Urol, 60, pp.1057-68.
2008. Role of male factor in early recurrent embryo loss: do antioxidants have any effect? Fertil Steril, 92, pp.565-71.
Gill Villa, A.M., Cardona-Maya, W.D., Agarwal, A., Sharma, R., Cadavid, A., 2010. Assessment of sperm factors possibly involved in early recurrent pregnancy loss. Fertil Steril, 94, pp.1465-72.
Goddijn-Wessel, T.A., Wouters, M.G., Van deMolen, E.F., 1996. Hyperhomocysteinemia: a risk factor for placental abruption or infarction. Eur J Obstet Gynecol Reprod Biol, 66, pp.23-9.
Graham, I.M., 1997. Plasma Homocysteine as a Risk Factor for Vascular Disease. JAMA, 277, pp.1775-81.
Griveau, J.F.; Dumont, E.; Renard, P.; Callegari, J.P.; Lannou, D.L., 1995. Reactive oxygen species, lipids peroxidation and enzymatic defence systems in human spermatozoa. J of Reprod and Fertil, 103, pp.17-26.
Griveau, J.F., Lannou, D.L., 1997. Reactive oxygen species and human spermatozoa: physiology and pathology. Int J of Androl., 20, pp.60-9.
Guttmacher Institute, 2008. Abortion in Indonesia. New York: Guttmacher In Brief, 2, pp.1-6.
Hadijanto, B., 2008. Perdarahan pada kehamilan muda. In: Prawirohardjo, S. and Saifuddin, A.B., eds., 2011. Ilmu Kebidanan. Jakarta: PT Bina Pustaka Sarwono Prawirohardjo. Ch. 37.
Hales, B.F., Barton, T.S., Robaire, B., 2005. Impact of Paternal Exposure to Chemotherapy on offspring in the rat. J Nat Cancer Inst Monograph, 34, pp.28-31.
sperm chromatin condensation (aniline blue staining) in the assessment of male fertility. Arch Androl, 46, pp.99-104.
Hankel, R., Hajimohammad, M., Stafl, T., Hoogendjik, C., Mehnert, C., Menkveld, R. et al., 2004. Influence of deoxyribonucleic acid damage on fertilization and pregnancy. Fertile Steril, 81, pp.965-72.
Hankey, G.J., Eikelboom, J.W., 1999. Homocysteine and vacular disease. Lancet, 354, pp.407-13.
Harlap, S., Shionop, Ramcharan, S., 1980. A life table of spontaneous abortion and the effects of age, pasity and other variables. In: Porter, I. and Hook, E., Eds. Human Embrionic and fetal death. New York: Academic, pp.145.
Hay, P.E., Lamont, R.F., Robinson, T.D., Morgan, D.J., Ison, C. and Pearson, J., 1994. A Longitudinal study of bacterial vaginosis during pregnancy. Br JObstet Gynecol, 101, pp.1048-53.
Hikim, A.P.S., Swerdloff Rs., 1999. Hormonal and genetic control of germ cell apoptosis in the testis. Rev Repro, 4, pp.38-47.
HFC, 2011. Halim fertility center company profile. Medan, pp.5.
Homonnai, Z.T., Paz, G.F., Weiss, J.N, David, M.P., 1980. Relation between semen quality and fate of pregnancy: retrospective study on 534 pregnancies. Int J Androl, 3, pp.574-84.
Inna, I.K. et al., 2000. Homocysteine Elicits a DNA damage Response in Neurons That Promotes Apoptosis and Hypersensitivity to Excitotoxicity. J of Neuros, 20(18), pp.6920-6.
2000. DNA integrity in human spermatozoa: relationship with semen quality. J Androl, 21, pp.33-44.
Jacques, P.F., Selhub, J., Bostom, A.G., Wilson, P.W.F., Rosenberg, I.H., 1999. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. The New England Journal of Medicine, pp.1449-54.
Jauniaux, E., Watson, A.L., Hempstock, J., Sleeper, J.N., Buston, G.J., 2006. Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure. Am J Pathol, 157(6), pp.2111-2.
Kang, S.S. et al., 1992. Hyperhomocyst(e)inemia as a risk factor for occular disease. Annual Review of Nutrition, 12, pp.279-98.
Karamadian, L., Griomes, D., 1994. Luteal phase deficiency: effect of treatment on pregnancy rates. Am j Obstet gynecol, 70, pp.958-9.
Kazerooni, T., Asadi, N., Jadid, L., Kazerooni, M., Ghanadi, A., Ghaffarpasand, F. et al., 2009. Evaluation of sperm’s chromatin quality with acridine orange test, chromomycin A3 and aniline blue staining in couples with unexplained recurrent abortion. J Assist Reprod Genet, 26, pp.591-6.
Kessopoulou, E., Tomlinson, M.J., Barrat, C.L.R., Bolton, A.E., Cooke, I.D., 1992. Origin of reactive oxygen species in human semen: spermatozoa or leucocytes?. J Reprod Fert, 94, pp.463-70.
Khosrowbeygi, A., Zarghami, N., Deldar, Y., 2004. Correlation between sperm quality parameters and seminal plasma antioxidant status. Iranian J of Reprod Med, 2, pp.58-64.
2001. Association of DDT with spontaneous abortion: a Case control study. AEP, 11(7), pp.491-6.
Kunzle, R., Mueller, M.D., Hanggi, W., Birkhauser, M.H., Drescher, H., Bersingger, N.A., 2003. Semen quality of male smokers and non-smokers in infertile couples. Fertil Steril, 79, pp.287-91.
Landau, B., Singer, R., Klein, T., 1978. Folic acid levels in blood and seminal plasma of normo- and oligospermic patients prior and following folic acid treatment. Experientia, 34, pp.1301-2.
Law, B.Jr., 2005. Evaluation and management of hyperprolactinemia. Revista de Endoc Nutri, 13(supp 1), s.56-9.
Leeda, M., Riyazi, N., Devries, J.I.P., Jakobs, C., 1997. Effects of folic acid and vitamin B6 supplementation on women with hyperhomocysteinemia and a history of preeclampsia or fetal growth resriction. Am J Obstet Gynecol, 179, pp.135-9.
Li, T.C., Makris, M., Tomsu, M., Tuckerman, E., Laird, S., 2002. Recurrent miscarriage: aetiology, management and prognosis. Hum Reprod Update, 8, pp.463-81.
Liu, C.C., Ho, W.Y., Leu, K.L., Tsai, H.M., Yang, T.H., 2008. Effect of S-adenosylhomocysteine and homocysteine on DNA damage cell cytotoxicity in murine hepatic and microglia cell lines. J of Biochem and Mol Toxic, 23(5), pp.349-56.
Lopes, S., Jurisicova, A., Sun, J.G., Casper, R.F., 1998. Reactive oxygen species: Potensial cause for DNA fragmentation in human spermatozoa. Hum Reprod, 13, pp.896-900.
Malinow, M.R., Nieto, F.J., Szklo, M., Chambless, L.E., Bond, G., 1993. Carotid artery intimal-medial wall thickening and plasma
communities study. Circulation, 87, pp.1107-13.
Malinow, M.R., 1999. Homocysteine, Diet and Cardiovacular Disease: A Statement for Healthcare Professionals from Nutritional Committee American Heart Association. AHA Nutrition Committee, 77, pp.687-93.
Manicardi, G.C., Tombacco, A., Bizzaro, D., Bianchi, P.G., Sakkas, D., 1998. DNA strand breaks in ejaculated human spermatozoa: comparison of susceptibility to the nick translation and terminal transferase assays. Histoche J, 30, pp.33-9.
Micco, P.D., D’uva, M., 2009. Recurrent Pregnancy Loss and Thrombopholia. The open atherosclerosis & thrombosis Journal, 2, pp.33-5.
Mills, J.L., Simpson, J.L., Driscol, S.G., 1994. Incidence of spontaneous abortion among normal women and insulin dependent diabetic women whose pregnancies were identified within 21 days of conception. N Engl J Med, 319(25), pp.1617-23.
Morris, I.D., Ilott, S., Dixon, L., Brison, D.R., 2002. The spectrum of DNA damage in human sperm assessed by single cell gel electrophresis (Comet assay) and its relationship to fertilization and embryo development. Hum Reprod, 17, pp.990-8.
Nedrebo, B.G., Ericsson, U.B., Nygard, O., Refsum, H., Ueland, P.M., Aakvaag, A. et al., 1998. Plasma total homocysteine levels in hyperthyroid and hypothyroid patients. Metabolism,47, pp.89–93.
Nelen, W.L., 2001. Hyperhomocysteinaemia and human reproduction. Clin Chem Lab Med, 39, pp.758-63.
Nelson, D.L., Cox, M.M., 2000. Lehninger, Principales of Biochemistry. 3rd Ed. New York: Worth Publishing, ISBN 1-57259-13-6.
pasca abortus di rumah sakit Dr. Hasan Sadikin Bandung tahun 2004. Rofiqahmad.wordpress.com Ahmad rofiq, [blog] 24 January. Available at: <http://rofiqahmad.wordpress.com/2008/01/24/hasil-luaran-janin- pada-ibu-pasca-abortus-di-rumah-sakit-dr-hasan-sadikin-bandung-tahun-2004> [Accessed 12 October 2011]
Oliva, R., 2006. Protamines and male infertility. Hum Repro Update, 12, pp.417-435.
Ozgocmen, S., Sogut, S., Fadillioglu, E., Ardicoglu, A., Ardicoglu, O., 2003. Antioxidant status and lipid peroxidation in seminal plasma and spermatozoa of patients with ankylosing spondylitis. British Society for Rheumatology, pp.805-7.
Passwater, R.A., 2002. The Homocysteine Revolution: an interview with Dr. Kilmer McCully, [online] Available at:
<http://forum.lowcarber.org/archive/index.php/t-54420> [Accessed 10 March 2009].
Perry, I.J., Refsum, H., Morris, R.W., Ebrahim, S.B., Ueland, P.M., Shaper, A.G., 1995. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged Bristish men. Lancet, 346, pp.1395-8.
Piccinni, M.P., 2006. T cells in normal pregnancy and recurrent pregnancy loss. RBM Online, 13, pp.840-4.
Pritts, E.A., Atwood, A.K., 2002. Luteal phase support in infertility treatment: a meta-analysis of the randomized trials. Hum Reprod, 17(9), pp.2287-99.
Rai, R., Backos, M., Rushworth, F., Regan, L., 2000. Polycystic ovaries and recurrent miscarriage-a reappraisal. Hum Reprod, 15(3), pp.612-5.
hormone, infertility, and miscarriage. Lancet, 336, pp.1141-4.
Regan, L., Rai, R., 2006. Recurrent miscarriage. Lancet, 368(9535), pp.601-11.
Robinson, K., Gupta, A., Dennis, V., Arheart, K., Chaudhary, D., Green, R., Vigo, P., Mayer, E.L., Selhub, J., Kutner, M., Jacobsen, D.W., 1996. Hyperhomocysteinemia confers an independent increased risk of atherosclerosis in end-stage renal disease and is closely linked to plasma folate and pyridoxine concentrations. Circulation, 94, pp.2743– 8.
Roman, E., 1984. Fetal loss rates and their relation to pregnancy order. J Epidemiol Community Health, 38, pp.29.
Rousseaux, S., Caron, C., Govin, J., Lestrat, C., Faure, A.K., Khochbin, S., 2005. Establishment of male-specific epigenetic information. Gene, 345, pp.139-53.
Said, T.M., Agarwal, A., Sharma, R., Thomas, A.J., Sikka, S., 2005. Impact of sperm morphology on DNA damage caused oxidative stress induced by ß-nicotinamide adenine dinucleotide phosphate. Fertil Steril, 83(1), pp.95-103.
Sailer, B.L., Jost, L.K., Evenson, D.P., 1995. Mammalian sperm DNA susceptibility to in situ denaturation associated with the presence of DNA Strand breaks as measured by the terminal deoxynucleotidyl transferase assay. Journal of Andrology, pp.80-7.
Sakhi, S., Sun, N., Wing, L.L., Metha, P., Schreiber, S.S., 1996. Nuclear accumulation of p53 protein seizures. Neuro Report, 7, pp.493-6.
Sakkas, D., Seli, E., Bizarro, D., Tarozzi, N., Manicardi, G.C., 2003. Abnormal spermatozoa in the ejaculate; abortive apoptosis and faulty nuclear
32.
Saleh, R.A., Agarwal, A., Sharma, R.K., Said, T.M., Sikka, S.C., Thomas, A.J.Jr., 2003. Evaluation of nuclear DNA damage in spermatozoa from infertile men with varicocele. Fertil Steril, 80, pp.1431-6.
Salim, R., Woelfer, B., Backos, M., Regan, L. and Jurkovic, D., 2003. Reproducibility of three dimension ultrasound diagnosis of congenital uterine anomalies. Ultrasound Obstet and Gynaecol, 21, pp.578-82.
Saxena, P., Misro, M.M., Chaki, S.P., Chopra, K., Roy, S., Nandan, D., 2008. Is abnormal sperm function an indicator among couples with recurrent pregnancy loss? Fertil Steril, 90, pp.1854-7.
Sbracia, M., Cozza, G., Grasso, J.A., Mastrone, M., Scarpellini, F., 1996. Semen parameter and sperm morphology in men in unexplained recurrent spontaneous abortion, before and during a 3 year follow up period. Hum Repro, pp.117-2.
Selhub, J., Jacques, P.F., Rosenberg, I.H., Rogers, G., Bowman, B.A., Gunter, W. et al., 1999. Serum Total Homocysteine Concentrations in the Third National Helath and Nutrition Examination Survey (1991 -1994): Population Reference ranges and Contribution of Vitamin Status to High Serum Concentrations. Ann Intern Med, 131, pp.331-9.
Selhub, J., 1999. Homocysteine metabolism. Annual Review of Nutrition, 19, pp.217– 46.
Sergerie, M., Laforest, G., Bujan, L., Bissonnette, F., Bleau, G., 2005. Sperm DNA fragmentation: threshold value in male fertility. Hum Reprod, 20, pp.3446-51.
relevance in assessing reproductive outcome. Asian J Androl, 6, pp.139-48.
Shen, H.M., Ong, C.N., 2000. Detection of oxidative DNA damage in human sperm and its association with sperm function with sperm function and male infertility. Free Rad & Med, 28(4), pp.529-36.
Singh, N.P., Muller, C.H., Berger, R.E., 2003. Effects of agen on DNA double strand breaks and apoptosis in human sperm. Fertil Steril, 80, pp.1420-30.
Sonmez, M., Yuce, A., Turk, G., 2007. The protective effects of melatonin and Vitamin E on atioxidant enzyme activities and epididymal sperm characteristics of homocysteine treated male rats. Repro Toxic, pp.226-31.
Spadafora, C., 1998. Sperm cell and foreign DNA: a controversial; relation.
