����JFIFXX�����    $.' ",#(7),01444'9=82<.342  2!!22222222222222222222222222222222222222222222222222����"��4�� ���,�PG"Z_�4�˷����kjز�Z�,F+��_z�,�© �����zh6�٨�ic�fu���#ډb���_�N�?��wQ���5-�~�I���8����TK<5o�Iv-�����k�_U_�����~b�M��d����Ӝ�U�Hh��?]��E�w��Q���k�{��_}qFW7HTՑ��Y��F�?_�'ϔ��_�Ջt��=||I ��6�έ"�����D���/[�k�9���Y�8ds|\���Ҿp6�Ҵ���]��.����6�z<�v��@]�i%��$j��~�g��J>��no����pM[me�i$[����s�o�ᘨ�˸ nɜG-�ĨU�ycP�3.DB�li�;��hj���x7Z^�N�h������N3u{�:j�x�힞��#M&��jL P@_���� P��&��o8������9�����@Sz6�t7#O�ߋ �s}Yf�T���lmr����Z)'N��k�۞p����w\�Tȯ?�8`�O��i{wﭹW�[�r�� ��Q4F�׊���3m&L�=��h3����z~��#�\�l :�F,j@�� ʱ�wQT����8�"kJO���6�֚l����}���R�>ډK���]��y����&����p�}b��;N�1�m�r$�|��7�>e�@B�TM*-iH��g�D�)� E�m�|�ؘbҗ�a��Ҿ����t4���o���G��*oCN�rP���Q��@z,|?W[0�����:�n,jWiE��W��$~/�hp\��?��{(�0���+�Y8rΟ�+����>S-S����VN;�}�s?.����� w�9��˟<���Mq4�Wv'��{)0�1mB��V����W[�����8�/<� �%���wT^�5���b��)iM� pg�N�&ݝ��VO~�q���u���9� ����!��J27����$O-���! �:�%H��� ـ����y�ΠM=t{!S�� oK8������t<����è:a������[�����ա�H���~��w��Qz`�po�^ ����Q��n� �,uu�C�$ ^���,������8�#��:�6��e�|~���!�3�3.�\0��q��o�4`.|� ����y�Q�`~;�d�ׯ,��O�Zw�������`73�v�܋�<���Ȏ�� ـ4k��5�K�a�u�=9Yd��$>x�A�&�� j0� ���vF��� Y�|�y��� ~�6�@c��1vOp�Ig����4��l�OD���L����� R���c���j�_�uX6��3?nk��Wy�f;^*B� ��@�~a�`��Eu������+���6�L��.ü>��}y���}_�O�6�͐�:�YrG�X��kG�����l^w���~㒶sy��Iu�!� W ��X��N�7BV��O��!X�2����wvG�R�f�T#�����t�/?���%8�^�W�aT��G�cL�M���I��(J����1~�8�?aT ���]����AS�E��(��*E}� 2��#I/�׍qz��^t�̔���b�Yz4x���t�){ OH��+(E��A&�N�������XT��o��"�XC��'���)}�J�z�p� ��~5�}�^����+�6����w��c��Q�|Lp�d�H��}�(�.|����k��c4^�"�����Z?ȕ ��a<�L�!039C� �Eu�C�F�Ew�ç ;�n?�*o���B�8�bʝ���'#Rqf���M}7����]����s2tcS{�\icTx;�\��7K���P���ʇ Z O-��~��c>"��?�������P��E��O�8��@�8��G��Q�g�a�Վ���󁶠�䧘��_%#r�>�1�z�a��eb��qcPѵ��n���#L��� =��׀t� L�7�`��V���A{�C:�g���e@�w1 Xp3�c3�ġ����p��M"'-�@n4���fG��B3�DJ�8[Jo�ߐ���gK)ƛ��$���� ���8�3�����+���� �����6�ʻ���� ���S�kI�*KZlT _`���?��K����QK�d����B`�s}�>���`��*�>��,*@J�d�oF*����弝��O}�k��s��]��y�ߘ��c1G�V���<=�7��7����6�q�PT��tXԀ�!9*4�4Tހ3XΛex�46���Y��D ����� �BdemDa����\�_l,��G�/���֌7���Y�](�xTt^%�GE�����4�}bT���ڹ�����;Y)���B�Q��u��>J/J �⮶.�XԄ��j�ݳ�+E��d ��r�5�_D�1 ��o�� �B�x�΢�#���<��W�����8���R6�@g�M�.��� dr�D��>(otU��@x=��~v���2� ӣ�d�oBd��3�eO�6�㣷�����ݜ6��6Y��Qz`��S��{���\P�~z m5{J/L��1������<�e�ͅPu�b�]�ϔ���'������f�b� Zpw��c`"��i���BD@:)ִ�:�]��hv�E�w���T�l��P���"Ju�}��وV J��G6��. J/�Qgl߭�e�����@�z�Zev2u�)]կ�����7x���s�M�-<ɯ�c��r�v�����@��$�ޮ}lk���a���'����>x��O\�ZFu>�����ck#��&:��`�$�ai�>2Δ����l���oF[h��lE�ܺ�Πk:)���`�� $[6�����9�����kOw�\|���8}������ބ:��񶐕��I�A1/�=�2[�,�!��.}gN#�u����b��� ~��݊��}34q����d�E��Lc��$��"�[q�U�硬g^��%B �z���r�pJ�ru%v\h1Y�ne`ǥ:g���pQM~�^�Xi� ��`S�:V29.�P���V�?B�k�� AEvw%�_�9C�Q����wKekPؠ�\�;Io d�{ ߞo�c1eP����\� `����E=���@K<�Y���eڼ�J���w����{av�F�'�M�@/J��+9p���|]�����Iw &`��8���&M�hg��[�{��Xj��%��Ӓ�$��(����ʹN���<>�I���RY���K2�NPlL�ɀ)��&e����B+ь����( � �JTx���_?EZ� }@ 6�U���뙢ط�z��dWI�n` D����噥�[��uV��"�G&Ú����2g�}&m��?ċ�"����Om#��������� ��{�ON��"S�X��Ne��ysQ���@Fn��Vg���dX�~nj�]J�<�K]:��FW��b�������62�=��5f����JKw��bf�X�55��~J �%^����:�-�QIE��P��v�nZum� z � ~ə ���� ���ة����;�f��\v���g�8�1��f24;�V���ǔ�)����9���1\��c��v�/'Ƞ�w�������$�4�R-��t���� e�6�/�ġ �̕Ecy�J���u�B���<�W�ַ~�w[B1L۲�-JS΂�{���΃������A��20�c#��@ 0!1@AP"#2Q`$3V�%45a6�FRUq��� ����^7ׅ,$n�������+��F�`��2X'��0vM��p�L=������5��8������u�p~���.�`r�����\���O��,ư�0oS ��_�M�����l���4�kv\JSd���x���SW�<��Ae�IX����������$I���w�:S���y���›R��9�Q[���,�5�;�@]�%���u�@ *ro�lbI �� ��+���%m:�͇ZV�����u�̉����θau<�fc�.����{�4Ա� �Q����*�Sm��8\ujqs]{kN���)qO�y�_*dJ�b�7���yQqI&9�ԌK!�M}�R�;������S�T���1���i[U�ɵz�]��U)V�S6���3$K{�ߊ<�(� E]Զ[ǼENg�����'�\?#)Dkf��J���o��v���'�%ƞ�&K�u�!��b�35LX�Ϸ��63$K�a�;�9>,R��W��3�3� d�JeTYE.Mϧ��-�o�j3+y��y^�c�������VO�9NV\nd�1 ��!͕_)a�v;����թ�M�lWR1��)El��P;��yوÏ�u 3�k�5Pr6<�⒲l�!˞*��u־�n�!�l:����UNW ��%��Chx8vL'��X�@��*��)���̮��ˍ��� ���D-M�+J�U�kvK����+�x8��cY������?�Ԡ��~3mo��|�u@[XeY�C�\Kp�x8�oC�C�&����N�~3-H���� ��MX�s�u<`���~"WL��$8ξ��3���a�)|:@�m�\���^�`�@ҷ)�5p+��6���p�%i)P M���ngc�����#0Aruz���RL+xSS?���ʮ}()#�t��mˇ!��0}}y����<�e� �-ή�Ԩ��X������ MF���ԙ~l L.3���}�V뽺�v�����멬��Nl�)�2����^�Iq��a��M��qG��T�����c3#������3U�Ǎ���}��לS�|qa��ڃ�+���-��2�f����/��bz��ڐ�� �ݼ[2�ç����k�X�2�* �Z�d���J�G����M*9W���s{��w���T��x��y,�in�O�v��]���n����P�$�JB@=4�OTI�n��e�22a\����q�d���%�$��(���:���: /*�K[PR�fr\nڙdN���F�n�$�4�[�� U�zƶ����� �mʋ���,�ao�u 3�z� �x��Kn����\[��VFmbE;�_U��&V�Gg�]L�۪&#n%�$ɯ�dG���D�TI=�%+AB�Ru#��b4�1�»x�cs�YzڙJG��f��Il��d�eF'T� iA��T���uC�$����Y��H?����[!G`}���ͪ� �纤Hv\������j�Ex�K���!���OiƸ�Yj�+u-<���'q����uN�*�r\��+�]���<�wOZ.fp�ێ��,-*)V?j-kÊ#�`�r��dV����(�ݽBk�����G�ƛk�QmUڗe��Z���f}|����8�8��a���i��3'J�����~G_�^���d�8w������ R�`(�~�.��u���l�s+g�bv���W���lGc}��u���afE~1�Ue������Z�0�8�=e�� f@/�jqEKQQ�J��oN��J���W5~M>$6�Lt�;$ʳ{���^��6�{����v6���ķܰg�V�cnn �~z�x�«�,2�u�?cE+Ș�H؎�%�Za�)���X>uW�Tz�Nyo����s���FQƤ��$��*�&�LLXL)�1�" L��eO��ɟ�9=���:t��Z���c��Ž���Y?�ӭV�wv�~,Y��r�ۗ�|�y��GaF�����C�����.�+� ���v1���fήJ�����]�S��T��B��n5sW}y�$��~z�'�c ��8 ��� ,! �p��VN�S��N�N�q��y8z˱�A��4��*��'������2n<�s���^ǧ˭P�Jޮɏ�U�G�L�J�*#��<�V��t7�8����TĜ>��i}K%,���)[��z�21z ?�N�i�n1?T�I�R#��m-�����������������1����lA�`��fT5+��ܐ�c�q՝��ʐ��,���3�f2U�եmab��#ŠdQ�y>\��)�SLY����w#��.���ʑ�f��� ,"+�w�~�N�'�c�O�3F�������N<���)j��&��,-� �љ���֊�_�zS���TǦ����w�>��?�������n��U仆�V���e�����0���$�C�d���rP �m�׈e�Xm�Vu� �L��.�bֹ��� �[Դaզ���*��\y�8�Է:�Ez\�0�Kq�C b��̘��cө���Q��=0Y��s�N��S.���3.���O�o:���#���v7�[#߫ ��5�܎�L���Er4���9n��COWlG�^��0k�%<���ZB���aB_���������'=��{i�v�l�$�uC���mƎҝ{�c㱼�y]���W�i ��ߧc��m�H� m�"�"�����;Y�ߝ�Z�Ǔ�����:S#��|}�y�,/k�Ld� TA�(�AI$+I3��;Y*���Z��}|��ӧO��d�v��..#:n��f>�>���ȶI�TX��� 8��y����"d�R�|�)0���=���n4��6ⲑ�+��r<�O�܂~zh�z����7ܓ�HH�Ga롏���nCo�>������a ���~]���R���̲c?�6(�q�;5%� |�uj�~z8R=X��I�V=�|{v�Gj\gc��q����z�؋%M�ߍ����1y��#��@f^���^�>N�����#x#۹��6�Y~�?�dfPO��{��P�4��V��u1E1J �*|���%���JN��`eWu�zk M6���q t[�� ��g�G���v��WIG��u_ft����5�j�"�Y�:T��ɐ���*�;� e5���4����q$C��2d�}���� _S�L#m�Yp��O�.�C�;��c����Hi#֩%+) �Ӎ��ƲV���SYź��g |���tj��3�8���r|���V��1#;.SQ�A[���S������#���`n�+���$��$I �P\[�@�s��(�ED�z���P��])8�G#��0B��[ى��X�II�q<��9�~[Z멜�Z�⊔IWU&A>�P~�#��dp<�?����7���c��'~���5 ��+$���lx@�M�dm��n<=e�dyX��?{�|Aef ,|n3�<~z�ƃ�uۧ�����P��Y,�ӥQ�*g�#먙R�\���;T��i,��[9Qi歉����c>]9�� ��"�c��P�� �Md?٥��If�ت�u��k��/����F��9�c*9��Ǎ:�ØF���z�n*�@|I�ށ9����N3{'��[�'ͬ�Ҳ4��#}��!�V� Fu��,�,mTIk���v C�7v���B�6k�T9��1�*l� '~��ƞF��lU��'�M ����][ΩũJ_�{�i�I�n��$���L�� j��O�dx�����kza۪��#�E��Cl����x˘�o�����V���ɞ�ljr��)�/,�߬h�L��#��^��L�ф�,íMƁe�̩�NB�L�����iL����q�}��(��q��6IçJ$�W�E$��:������=#����(�K�B����zђ <��K(�N�۫K�w��^O{!����)�H���>x�������lx�?>Պ�+�>�W���,Ly!_�D���Ō�l���Q�!�[ �S����J��1��Ɛ�Y}��b,+�Lo�x�ɓ)����=�y�oh�@�꥟/��I��ѭ=��P�y9��� �ۍYӘ�e+�p�Jnϱ?V\SO%�(�t� ���=?MR�[Ș�����d�/ ��n�l��B�7j� ��!�;ӥ�/�[-���A�>�dN�sLj ��,ɪv��=1c�.SQ�O3�U���ƀ�ܽ�E����������̻��9G�ϷD�7(�}��Ävӌ\�y�_0[w ���<΍>����a_��[0+�L��F.�޺��f�>oN�T����q;���y\��bՃ��y�jH�<|q-eɏ�_?_9+P���Hp$�����[ux�K w�Mw��N�ی'$Y2�=��q���KB��P��~������Yul:�[<����F1�2�O���5=d����]Y�sw:���Ϯ���E��j,_Q��X��z`H1,#II ��d�wr��P˂@�ZJV����y$�\y�{}��^~���[:N����ߌ�U�������O��d�����ؾe��${p>G��3c���Ė�lʌ�� ת��[��`ϱ�-W����dg�I��ig2��� ��}s ��ؤ(%#sS@���~���3�X�nRG�~\jc3�v��ӍL��M[JB�T��s3}��j�Nʖ��W����;7��ç?=X�F=-�=����q�ߚ���#���='�c��7���ڑW�I(O+=:uxq�������������e2�zi+�kuG�R��������0�&e�n���iT^J����~\jy���p'dtG��s����O��3����9* �b#Ɋ�� p������[Bws�T�>d4�ۧs���nv�n���U���_�~,�v����ƜJ1��s�� �QIz��)�(lv8M���U=�;����56��G���s#�K���MP�=��LvyGd��}�VwWBF�'�à �?MH�U�g2�� ����!�p�7Q��j��ڴ����=��j�u��� Jn�A s���uM������e��Ɔ�Ҕ�!)'��8Ϣ�ٔ��ޝ(��Vp���צ֖d=�IC�J�Ǡ{q������kԭ�߸���i��@K����u�|�p=..�*+����x�����z[Aqġ#s2a�Ɗ���RR�)*HRsi�~�a &f��M��P����-K�L@��Z��Xy�'x�{}��Zm+���:�)�) IJ�-i�u���� ���ܒH��'�L(7�y�GӜq���� j��� 6ߌg1�g�o���,kر���tY�?W,���p���e���f�OQS��!K�۟cҒA�|ս�j�>��=⬒��˧L[�� �߿2JaB~R��u�:��Q�] �0H~���]�7��Ƽ�I���(}��cq '�ήET���q�?f�ab���ӥvr� �)o��-Q��_'����ᴎo��K������;��V���o��%���~OK ����*��b�f:���-ťIR��`B�5!RB@���ï�� �u �̯e\�_U�_������� g�ES��3�������QT��a����x����U<~�c?�*�#]�MW,[8O�a�x��]�1bC|踤�P��lw5V%�)�{t�<��d��5���0i�XSU��m:��Z�┵�i�"��1�^B�-��P�hJ��&)O��*�D��c�W��vM��)����}���P��ܗ-q����\mmζZ-l@�}��a��E�6��F�@��&Sg@���ݚ�M����� ȹ 4����#p�\H����dYDo�H���"��\��..R�B�H�z_�/5˘����6��KhJR��P�mƶi�m���3�,#c�co��q�a)*Pt����R�m�k�7x�D�E�\Y�閣_X�<���~�)���c[[�BP����6�Yq���S��0����%_����;��Àv�~�| VS؇ ��'O0��F0��\���U�-�d@�����7�SJ*z��3n��y��P����O���������m�~�P�3|Y��ʉr#�C�<�G~�.,! ���bqx���h~0=��!ǫ�jy����l�O,�[B��~��|9��ٱ����Xly�#�i�B��g%�S��������tˋ���e���ې��\[d�t)��.+u�|1 ������#�~Oj����hS�%��i.�~X���I�H�m��0n���c�1uE�q��cF�RF�o���7� �O�ꮧ� ���ۛ{��ʛi5�rw?׌#Qn�TW��~?y$��m\�\o����%W� ?=>S�N@�� �Ʈ���R����N�)�r"C�:��:����� �����#��qb��Y�. �6[��2K����2u�Ǧ�HYR��Q�MV��� �G�$��Q+.>�����nNH��q�^��� ����q��mM��V��D�+�-�#*�U�̒ ���p욳��u:�������IB���m���PV@O���r[b= �� ��1U�E��_Nm�yKbN�O���U�}�the�`�|6֮P>�\2�P�V���I�D�i�P�O;�9�r�mAHG�W�S]��J*�_�G��+kP�2����Ka�Z���H�'K�x�W�MZ%�O�YD�Rc+o��?�q��Ghm��d�S�oh�\�D�|:W������UA�Qc yT�q������~^�H��/��#p�CZ���T�I�1�ӏT����4��"�ČZ�����}��`w�#�*,ʹ�� ��0�i��課�Om�*�da��^gJ݅{���l�e9uF#T�ֲ��̲�ٞC"�q���ߍ ոޑ�o#�XZTp����@ o�8��(jd��xw�]�,f���`~�|,s��^����f�1���t��|��m�򸄭/ctr��5s��7�9Q�4�H1꠲BB@l9@���C�����+�wp�xu�£Yc�9��?`@#�o�mH�s2��)�=��2�.�l����jg�9$�Y�S�%*L������R�Y������7Z���,*=�䷘$�������arm�o�ϰ���UW.|�r�uf����IGw�t����Zwo��~5 ��YյhO+=8fF�)�W�7�L9lM�̘·Y���֘YLf�큹�pRF���99.A �"wz��=E\Z���'a� 2��Ǚ�#;�'}�G���*��l��^"q��+2FQ� hj��kŦ��${���ޮ-�T�٭cf�|�3#~�RJ����t��$b�(R��(����r���dx� >U b�&9,>���%E\� Ά�e�$��'�q't��*�א���ެ�b��-|d���SB�O�O��$�R+�H�)�܎�K��1m`;�J�2�Y~9��O�g8=vqD`K[�F)k�[���1m޼c��n���]s�k�z$@��)!I �x՝"v��9=�ZA=`Ɠi �:�E��)`7��vI��}d�YI�_ �o�:ob���o ���3Q��&D&�2=�� �Ά��;>�h����y.*ⅥS������Ӭ�+q&����j|UƧ����}���J0��WW< ۋS�)jQR�j���Ư��rN)�Gű�4Ѷ(�S)Ǣ�8��i��W52���No˓� ۍ%�5brOn�L�;�n��\G����=�^U�dI���8$�&���h��'���+�(������cȁ߫k�l��S^���cƗjԌE�ꭔ��gF���Ȓ��@���}O���*;e�v�WV���YJ\�]X'5��ղ�k�F��b 6R�o՜m��i N�i����>J����?��lPm�U��}>_Z&�KK��q�r��I�D�Չ~�q�3fL�:S�e>���E���-G���{L�6p�e,8��������QI��h��a�Xa��U�A'���ʂ���s�+טIjP�-��y�8ۈZ?J$��W�P� ��R�s�]��|�l(�ԓ��sƊi��o(��S0��Y� 8�T97.�����WiL��c�~�dxc�E|�2!�X�K�Ƙਫ਼�$((�6�~|d9u+�qd�^3�89��Y�6L�.I�����?���iI�q���9�)O/뚅����O���X��X�V��ZF[�یgQ�L��K1���RҖr@v�#��X�l��F���Нy�S�8�7�kF!A��sM���^rkp�jP�DyS$N���q��nxҍ!U�f�!eh�i�2�m���`�Y�I�9r�6� �TF���C}/�y�^���Η���5d�'��9A-��J��>{�_l+�`��A���[�'��յ�ϛ#w:݅�%��X�}�&�PSt�Q�"�-��\縵�/����$Ɨh�Xb�*�y��BS����;W�ջ_mc�����vt?2}1�;qS�d�d~u:2k5�2�R�~�z+|HE!)�Ǟl��7`��0�<�,�2*���Hl-��x�^����'_TV�gZA�'j� ^�2Ϊ��N7t�����?w�� �x1��f��Iz�C-Ȗ��K�^q�;���-W�DvT�7��8�Z�������� hK�(P:��Q- �8�n�Z���܃e貾�<�1�YT<�,�����"�6{/ �?�͟��|1�:�#g��W�>$����d��J��d�B��=��jf[��%rE^��il:��B���x���Sּ�1հ��,�=��*�7 fcG��#q� �eh?��2�7�����,�!7x��6�n�LC�4x��},Geǝ�tC.��vS �F�43��zz\��;QYC,6����~;RYS/6���|2���5���v��T��i����������mlv��������&� �nRh^ejR�LG�f���? �ۉҬܦƩ��|��Ȱ����>3����!v��i�ʯ�>�v��オ�X3e���_1z�Kȗ\<������!�8���V��]��?b�k41�Re��T�q��mz��TiOʦ�Z��Xq���L������q"+���2ۨ��8}�&N7XU7Ap�d�X��~�׿��&4e�o�F��� �H����O���č�c�� 懴�6���͉��+)��v;j��ݷ�� �UV�� i��� j���Y9GdÒJ1��詞�����V?h��l����l�cGs�ځ�������y�Ac�����\V3�? �� ܙg�>qH�S,�E�W�[�㺨�uch�⍸�O�}���a��>�q�6�n6����N6�q������N ! 1AQaq�0@����"2BRb�#Pr���3C`��Scst���$4D���%Td�� ?���N����a��3��m���C���w��������xA�m�q�m���m������$����4n淿t'��C"w��zU=D�\R+w�p+Y�T�&�պ@��ƃ��3ޯ?�Aﶂ��aŘ���@-�����Q�=���9D��ռ�ѻ@��M�V��P��܅�G5�f�Y<�u=,EC)�<�Fy'�"�&�չ�X~f��l�KԆV��?�� �W�N����=(� �;���{�r����ٌ�Y���h{�١������jW����P���Tc�����X�K�r��}���w�R��%��?���E��m�� �Y�q|����\lEE4���r���}�lsI�Y������f�$�=�d�yO����p�����yBj8jU�o�/�S��?�U��*������ˍ�0������u�q�m [�?f����a�� )Q�>����6#������� ?����0UQ����,IX���(6ڵ[�DI�MNލ�c&���υ�j\��X�R|,4��� j������T�hA�e��^���d���b<����n�� �즇�=!���3�^�`j�h�ȓr��jẕ�c�,ٞX����-����a�ﶔ���#�$��]w�O��Ӫ�1y%��L�Y<�wg#�ǝ�̗`�x�xa�t�w��»1���o7o5��>�m뭛C���Uƃߜ}�C���y1Xνm�F8�jI���]����H���ۺиE@I�i;r�8ӭ����V�F�Շ| ��&?�3|x�B�MuS�Ge�=Ӕ�#BE5G�����Y!z��_e��q�р/W>|-�Ci߇�t�1ޯќd�R3�u��g�=0 5��[?�#͏��q�cf���H��{ ?u�=?�?ǯ���}Z��z���hmΔ�BFTW�����<�q�(v� ��!��z���iW]*�J�V�z��gX֧A�q�&��/w���u�gYӘa���; �i=����g:��?2�dž6�ى�k�4�>�Pxs����}������G�9��3 ���)gG�R<>r h�$��'nc�h�P��Bj��J�ҧH� -��N1���N��?��~��}-q!=��_2hc�M��l�vY%UE�@|�v����M2�.Y[|y�"Eï��K�ZF,�ɯ?,q�?v�M 80jx�"�;�9vk�����+ ֧�� �ȺU��?�%�vcV��mA�6��Qg^M����A}�3�nl� QRN�l8�kkn�'�����(��M�7m9و�q���%ޟ���*h$Zk"��$�9��: �?U8�Sl��,,|ɒ��xH(ѷ����Gn�/Q�4�P��G�%��Ա8�N��!� �&�7�;���eKM7�4��9R/%����l�c>�x;������>��C�:�����t��h?aKX�bhe�ᜋ^�$�Iհ �hr7%F$�E��Fd���t��5���+�(M6�t����Ü�UU|zW�=a�Ts�Tg������dqP�Q����b'�m���1{|Y����X�N��b �P~��F^F:����k6�"�j!�� �I�r�`��1&�-$�Bevk:y���#yw��I0��x��=D�4��tU���P�ZH��ڠ底taP��6����b>�xa����Q�#� WeF��ŮNj�p�J* mQ�N����*I�-*�ȩ�F�g�3 �5��V�ʊ�ɮ�a��5F���O@{���NX��?����H�]3��1�Ri_u��������ѕ�� ����0��� F��~��:60�p�͈�S��qX#a�5>���`�o&+�<2�D����: �������ڝ�$�nP���*)�N�|y�Ej�F�5ټ�e���ihy�Z �>���k�bH�a�v��h�-#���!�Po=@k̆IEN��@��}Ll?j�O������߭�ʞ���Q|A07x���wt!xf���I2?Z��<ץ�T���cU�j��]��陎Ltl �}5�ϓ��$�,��O�mˊ�;�@O��jE��j(�ا,��LX���LO���Ц�90�O �.����a��nA���7������j4 ��W��_ٓ���zW�jcB������y՗+EM�)d���N�g6�y1_x��p�$Lv:��9�"z��p���ʙ$��^��JԼ*�ϭ����o���=x�Lj�6�J��u82�A�H�3$�ٕ@�=Vv�]�'�qEz�;I˼��)��=��ɯ���x �/�W(V���p�����$ �m�������u�����񶤑Oqˎ�T����r��㠚x�sr�GC��byp�G��1ߠ�w e�8�$⿄����/�M{*}��W�]˷.�CK\�ުx���/$�WPw���r� |i���&�}�{�X� �>��$-��l���?-z���g����lΆ���(F���h�vS*���b���߲ڡn,|)mrH[���a�3�ר�[1��3o_�U�3�TC�$��(�=�)0�kgP���� ��u�^=��4 �WYCҸ:��vQ�ר�X�à��tk�m,�t*��^�,�}D*� �"(�I��9R����>`�`��[~Q]�#af��i6l��8���6�:,s�s�N6�j"�A4���IuQ��6E,�GnH��zS�HO�uk�5$�I�4��ؤ�Q9�@��C����wp�BGv[]�u�Ov���0I4���\��y�����Q�Ѹ��~>Z��8�T��a��q�ޣ;z��a���/��S��I:�ܫ_�|������>=Z����8:�S��U�I�J��"IY���8%b8���H��:�QO�6�;7�I�S��J��ҌAά3��>c���E+&jf$eC+�z�;��V����� �r���ʺ������my�e���aQ�f&��6�ND��.:��NT�vm�<- u���ǝ\MvZY�N�NT��-A�>jr!S��n�O 1�3�Ns�%�3D@���`������ܟ 1�^c<���� �a�ɽ�̲�Xë#�w�|y�cW�=�9I*H8�p�^(4���՗�k��arOcW�tO�\�ƍR��8����'�K���I�Q�����?5�>[�}��yU�ײ -h��=��% q�ThG�2�)���"ו3]�!kB��*p�FDl�A���,�eEi�H�f�Ps�����5�H:�Փ~�H�0Dت�D�I����h�F3�������c��2���E��9�H��5�zԑ�ʚ�i�X�=:m�xg�hd(�v����׊�9iS��O��d@0ڽ���:�p�5�h-��t�&���X�q�ӕ,��ie�|���7A�2���O%P��E��htj��Y1��w�Ѓ!����  ���� ࢽ��My�7�\�a�@�ţ�J �4�Ȼ�F�@o�̒?4�wx��)��]�P��~�����u�����5�����7X ��9��^ܩ�U;Iꭆ 5 �������eK2�7(�{|��Y׎ �V��\"���Z�1� Z�����}��(�Ǝ"�1S���_�vE30>���p;� ΝD��%x�W�?W?v����o�^V�i�d��r[��/&>�~`�9Wh��y�;���R��� ;;ɮT��?����r$�g1�K����A��C��c��K��l:�'��3 c�ﳯ*"t8�~l��)���m��+U,z��`(�>yJ�?����h>��]��v��ЍG*�{`��;y]��I�T� ;c��NU�fo¾h���/$���|NS���1�S�"�H��V���T���4��uhǜ�]�v;���5�͠x��'C\�SBpl���h}�N����� A�Bx���%��ޭ�l��/����T��w�ʽ]D�=����K���ž�r㻠l4�S�O?=�k �M:� ��c�C�a�#ha���)�ѐxc�s���gP�iG��{+���x���Q���I= �� z��ԫ+ �8"�k�ñ�j=|����c ��y��CF��/��*9ж�h{ �?4�o� ��k�m�Q�N�x��;�Y��4膚�a�w?�6�>e]�����Q�r�:����g�,i"�����ԩA�*M�<�G��b�if��l^M��5� �Ҩ�{����6J��ZJ�����P�*�����Y���ݛu�_4�9�I8�7���������,^ToR���m4�H��?�N�S�ѕw��/S��甍�@�9H�S�T��t�ƻ���ʒU��*{Xs�@����f�����֒Li�K{H�w^���������Ϥm�tq���s� ���ք��f:��o~s��g�r��ט� �S�ѱC�e]�x���a��) ���(b-$(�j>�7q�B?ӕ�F��hV25r[7 Y� }L�R��}����*sg+��x�r�2�U=�*'WS��ZDW]�WǞ�<��叓���{�$�9Ou4��y�90-�1�'*D`�c�^o?(�9��u���ݐ��'PI&� f�Jݮ�������:wS����jfP1F:X �H�9dԯ���˝[�_54 �}*;@�ܨ�� ð�yn�T���?�ןd�#���4rG�ͨ��H�1�|-#���Mr�S3��G�3�����)�.᧏3v�z֑��r����$G"�`j �1t��x0<Ɔ�Wh6�y�6��,œ�Ga��gA����y��b��)��h�D��ß�_�m��ü �gG;��e�v��ݝ�nQ� ��C����-�*��o���y�a��M��I�>�<���]obD��"�:���G�A��-\%LT�8���c�)��+y76���o�Q�#*{�(F�⽕�y����=���rW�\p���۩�c���A���^e6��K������ʐ�cVf5$�'->���ՉN"���F�"�UQ@�f��Gb~��#�&�M=��8�ט�JNu9��D��[̤�s�o�~������ G��9T�tW^g5y$b��Y'��س�Ǵ�=��U-2 #�MC�t(�i� �lj�@Q 5�̣i�*�O����s�x�K�f��}\��M{E�V�{�υ��Ƈ�����);�H����I��fe�Lȣr�2��>��W�I�Ȃ6������i��k�� �5�YOxȺ����>��Y�f5'��|��H+��98pj�n�.O�y�������jY��~��i�w'������l�;�s�2��Y��:'lg�ꥴ)o#'Sa�a�K��Z� �m��}�`169�n���"���x��I ��*+� }F<��cГ���F�P�������ֹ*�PqX�x۩��,� ��N�� �4<-����%����:��7����W���u�`����� $�?�I��&����o��o��`v�>��P��"��l���4��5'�Z�gE���8���?��[�X�7(��.Q�-��*���ތL@̲����v��.5���[��=�t\+�CNܛ��,g�SQnH����}*F�G16���&:�t��4ُ"A��̣��$�b �|����#rs��a�����T�� ]�<�j��BS�('$�ɻ� �wP;�/�n��?�ݜ��x�F��yUn�~mL*-�������Xf�wd^�a�}��f�,=t�׵i�.2/wpN�Ep8�OР���•��R�FJ� 55TZ��T �ɭ�<��]��/�0�r�@�f��V��V����Nz�G��^���7hZi����k��3�,kN�e|�vg�1{9]_i��X5y7� 8e]�U����'�-2,���e"����]ot�I��Y_��n�(JҼ��1�O ]bXc���Nu�No��pS���Q_���_�?i�~�x h5d'�(qw52] ��'ޤ�q��o1�R!���`ywy�A4u���h<קy���\[~�4�\ X�Wt/� 6�����n�F�a8��f���z �3$�t(���q��q�x��^�XWeN'p<-v�!�{�(>ӽDP7��ո0�y)�e$ٕv�Ih'Q�EA�m*�H��RI��=:��� ���4牢) �%_iN�ݧ�l]� �Nt���G��H�L��� ɱ�g<���1V�,�J~�ٹ�"K��Q�� 9�HS�9�?@��k����r�;we݁�]I�!{ �@�G�[�"��`���J:�n]�{�cA�E����V��ʆ���#��U9�6����j�#Y�m\��q�e4h�B�7��C�������d<�?J����1g:ٳ���=Y���D�p�ц� ׈ǔ��1�]26؜oS�'��9�V�FVu�P�h�9�xc�oq�X��p�o�5��Ա5$�9W�V(�[Ak�aY錎qf;�'�[�|���b�6�Ck��)��#a#a˙��8���=äh�4��2��C��4tm^ �n'c���]GQ$[Wҿ��i���vN�{Fu ��1�gx��1┷���N�m��{j-,��x�� Ūm�ЧS�[�s���Gna���䑴�� x�p 8<������97�Q���ϴ�v�aϚG��Rt�Һ׈�f^\r��WH�JU�7Z���y)�vg=����n��4�_)y��D'y�6�]�c�5̪�\� �PF�k����&�c;��cq�$~T�7j ���nç]�<�g ":�to�t}�159�<�/�8������m�b�K#g'I'.W�����6��I/��>v��\�MN��g���m�A�yQL�4u�Lj�j9��#44�t��l^�}L����n��R��!��t��±]��r��h6ٍ>�yҏ�N��fU�� ���� Fm@�8}�/u��jb9������he:A�y�ծw��GpΧh�5����l}�3p468��)U��d��c����;Us/�֔�YX�1�O2��uq�s��`hwg�r~�{ R��mhN��؎*q 42�*th��>�#���E����#��Hv�O����q�}�����6�e��\�,Wk�#���X��b>��p}�դ��3���T5��†��6��[��@�P�y*n��|'f�֧>�lư΂�̺����SU�'*�q�p�_S�����M�� '��c�6�����m�� ySʨ;M��r���Ƌ�m�Kxo,���Gm�P��A�G�:��i��w�9�}M(�^�V��$ǒ�ѽ�9���|���� �a����J�SQ�a���r�B;����}���ٻ֢�2�%U���c�#�g���N�a�ݕ�'�v�[�OY'��3L�3�;,p�]@�S��{ls��X�'���c�jw�k'a�.��}�}&�� �dP�*�bK=ɍ!����;3n�gΊU�ߴmt�'*{,=SzfD� A��ko~�G�aoq�_mi}#�m�������P�Xhύ����mxǍ�΂���巿zf��Q���c���|kc�����?���W��Y�$���_Lv����l߶��c���`?����l�j�ݲˏ!V��6����U�Ђ(A���4y)H���p�Z_�x��>���e��R��$�/�`^'3qˏ�-&Q�=?��CFVR �D�fV�9��{�8g�������n�h�(P"��6�[�D���< E�����~0<@�`�G�6����Hг�cc�� �c�K.5��D��d�B���`?�XQ��2��ٿyqo&+�1^� DW�0�ꊩ���G�#��Q�nL3��c���������/��x ��1�1[y�x�პCW��C�c�UĨ80�m�e�4.{�m��u���I=��f�����0QRls9���f���������9���~f�����Ǩ��a�"@�8���ȁ�Q����#c�ic������G��$���G���r/$W�(��W���V�"��m�7�[m�A�m����bo��D� j����۳� l���^�k�h׽����� ��#� iXn�v��eT�k�a�^Y�4�BN��ĕ��0 !01@Q"2AaPq3BR������?���@4�Q�����T3,���㺠�W�[=JK�Ϟ���2�r^7��vc�:�9 �E�ߴ�w�S#d���Ix��u��:��Hp��9E!�� V 2;73|F��9Y���*ʬ�F��D����u&���y؟��^EA��A��(ɩ���^��GV:ݜDy�`��Jr29ܾ�㝉��[���E;Fzx��YG��U�e�Y�C���� ����v-tx����I�sם�Ę�q��Eb�+P\ :>�i�C'�;�����k|z�رn�y]�#ǿb��Q��������w�����(�r|ӹs��[�D��2v-%��@;�8<a���[\o[ϧw��I!��*0�krs)�[�J9^��ʜ��p1)� "��/_>��o��<1����A�E�y^�C��`�x1'ܣn�p��s`l���fQ��):�l����b>�Me�jH^?�kl3(�z:���1ŠK&?Q�~�{�ٺ�h�y���/�[��V�|6��}�KbX����mn[-��7�5q�94�������dm���c^���h� X��5��<�eޘ>G���-�}�دB�ޟ� ��|�rt�M��V+�]�c?�-#ڛ��^ǂ}���Lkr���O��u�>�-D�ry� D?:ޞ�U��ǜ�7�V��?瓮�"�#���r��չģVR;�n���/_� ؉v�ݶe5d�b9��/O��009�G���5n�W����JpA�*�r9�>�1��.[t���s�F���nQ� V 77R�]�ɫ8����_0<՜�IF�u(v��4��F�k�3��E)��N:��yڮe��P�`�1}�$WS��J�SQ�N�j�ٺ��޵�#l���ј(�5=��5�lǏmoW�v-�1����v,W�mn��߀$x�<����v�j(����c]��@#��1������Ǔ���o'��u+����;G�#�޸��v-lη��/(`i⣍Pm^���ԯ̾9Z��F��������n��1��� ��]�[��)�'������:�֪�W��FC����� �B9،!?���]��V��A�Վ�M��b�w��G F>_DȬ0¤�#�QR�[V��kz���m�w�"��9ZG�7'[��=�Q����j8R?�zf�\a�=��O�U����*oB�A�|G���2�54 �p��.w7� �� ��&������ξxGHp� B%��$g�����t�Џ򤵍z���HN�u�Я�-�'4��0��;_��3 !01"@AQa2Pq#3BR������?��ʩca��en��^��8���<�u#��m*08r��y�N"�<�Ѳ0��@\�p��� �����Kv�D��J8�Fҽ� �f�Y��-m�ybX�NP����}�!*8t(�OqѢ��Q�wW�K��ZD��Δ^e��!� ��B�K��p~�����e*l}z#9ң�k���q#�Ft�o��S�R����-�w�!�S���Ӥß|M�l޶V��!eˈ�8Y���c�ЮM2��tk���� ������J�fS����Ö*i/2�����n]�k�\���|4yX�8��U�P.���Ы[���l��@"�t�<������5�lF���vU�����W��W��;�b�cД^6[#7@vU�xgZv��F�6��Q,K�v��� �+Ъ��n��Ǣ��Ft���8��0��c�@�!�Zq s�v�t�;#](B��-�nῃ~���3g������5�J�%���O������n�kB�ĺ�.r��+���#�N$?�q�/�s�6��p��a����a��J/��M�8��6�ܰ"�*������ɗud"\w���aT(����[��F��U՛����RT�b���n�*��6���O��SJ�.�ij<�v�MT��R\c��5l�sZB>F��<7�;EA��{��E���Ö��1U/�#��d1�a�n.1ě����0�ʾR�h��|�R��Ao�3�m3 ��%�� ���28Q� ��y��φ���H�To�7�lW>����#i`�q���c����a��� �m,B�-j����݋�'mR1Ήt�>��V��p���s�0IbI�C.���1R�ea�����]H�6����������4B>��o��](��$B���m�����a�!=��?�B� K�Ǿ+�Ծ"�n���K��*��+��[T#�{E�J�S����Q�����s�5�:�U�\wĐ�f�3����܆&�)����I���Ԇw��E T�lrTf6Q|R�h:��[K�� �z��c֧�G�C��%\��_�a�84��HcO�bi��ؖV��7H �)*ģK~Xhչ0��4?�0��� �E<���}3���#���u�?�� ��|g�S�6ꊤ�|�I#Hڛ� �ա��w�X��9��7���Ŀ%�SL��y6č��|�F�a 8���b��$�sק�h���b9RAu7�˨p�Č�_\*w��묦��F ����4D~�f����|(�"m���NK��i�S�>�$d7SlA��/�²����SL��|6N�}���S�˯���g��]6��; �#�.��<���q'Q�1|KQ$�����񛩶"�$r�b:���N8�w@��8$�� �AjfG|~�9F ���Y��ʺ��Bwؒ������M:I岎�G��`s�YV5����6��A �b:�W���G�q%l�����F��H���7�������Fsv7��k�� 403WebShell
403Webshell
Server IP : 172.67.215.126  /  Your IP : 172.69.214.108
Web Server : Apache/2.4.52 (Ubuntu)
System : Linux ip-172-31-19-221 6.8.0-1029-aws #31~22.04.1-Ubuntu SMP Thu Apr 24 21:16:18 UTC 2025 x86_64
User : www-data ( 33)
PHP Version : 8.1.28
Disable Function : NONE
MySQL : OFF  |  cURL : ON  |  WGET : ON  |  Perl : ON  |  Python : OFF  |  Sudo : ON  |  Pkexec : ON
Directory :  /efsdata/scitechnol.com/httpdocs/submission/uploads/

Upload File :
current_dir [ Writeable ] document_root [ Writeable ]

 

Command :


[ Back ]     

Current File : /efsdata/scitechnol.com/httpdocs/submission/uploads/790-1-Manuscript-2013-06-20.doc
��ࡱ�>��	�����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������{�	��d�bjbjz�z�.�����������t"t"t"t"t"�����"�"�"�"�#T�"H�Z�#��$�$�$�$�%�%�%��������������$���T�v��Et"�%�%�%�%�%��t"t"�$�$���>�>�>�%t"�$t"�$���>�%���>�>J�\/��$�����,v.�m������<�G�B���0H����ʕC>jʕ�/�ʕt"/�T�%�%�>�%�%�%�%�%�����>�%�%�%H��%�%�%�%��������������������������������������������������������������������ʕ�%�%�%�%�%�%�%�%�%:!:Dietary Supplementation improves blastocyst number � and ongoing pregnancy rate of IVF Patients with Hashimoto�s Thyroiditis. 
 
Johannes Wogatzky1,*, Birgit Schechinger1,  Dietmar Spitzer2,  Nicolas Herbert Zech1


1 IVF Centers Prof Zech-Bregenz, Roemerstrasse 2, 6900 Bregenz, Austria
2 IVF Centers Prof Zech-Salzburg, Innsbrucker Bundesstrasse 35, 5020 Salzburg, Austria














* Correspondence: Johannes Wogatzky: tel.: +43-664-2843996, e-mail:  HYPERLINK "mailto:j.wogatzky@ivf.at" j.wogatzky@ivf.at
Roemerstrasse 2, A-6900 Bregenz, Austria

JW: j.wogatzky@ivf.at
BS: Birgit. HYPERLINK "mailto:Birgit.schechinger@yahoo.com" schechinger@yahoo.com
DS: d.spitzer@ivf.at
NHZ:  HYPERLINK "mailto:n.zech@ivf.at" n.zech@ivf.at
 


Abstract
In assisted reproduction techniques (ART), autoimmune disorders of the thyroid gland present as common concomitant diseases. Hypothyroidism caused by autoimmune thyroiditis can impair fertility and pregnancy. Hashimoto thyroiditis (HT) patients undergoing IVF/ICSI are thought to benefit from a broad therapeutic concept. We compared the outcome of two different therapeutic schemes for HT patients presenting at our fertility clinic and compared the outcome to ART patients without thyroiditis. All patients were stimulated using the long protocol. TSH level was adjusted to under 2 �IU/mL using L-thyroxine as required. Concurrent medication from the time of oocyte puncture included daily administration of fragmin (dalteparin) and acetylsalicylic acid (ASA), as well as prednisolone in rising dosage. In addition to that patients took high-dose folic acid. A second group of HT patients was orally supplemented with a micronutrient preparation containing selenium, high-dose folic acid, B-vitamins, antioxidants and iron. We compared the number of oocytes, fertilization rate, blastocyst formation rate, pregnancy- and ongoing pregnancy rate between the two groups and the average ART outcome of non-HT patients within the same age group. We observed a significant increase in the blastocyst rate and demonstrated a substantial rise in ongoing pregnancy rate of the supplemented patients. These also needed less L-thyroxine to achieve optimal TSH level. The outcome of the micronutrient supplemented patients corresponds to the average of healthy IVF patients without HT at our clinic. HT patients undergoing IVF/ICSI benefit substantially from a broader therapeutic approach including intake of selenium, iron, B-vitamins and antioxidants additionally to other medication. This therapeutic regimen results in a marked increase of pregnancy rate while requiring less L-thyroxine administration. 




Keywords: autoimmune thyroiditis; IVF/IMSI; miscarriage; blastocyst; ongoing pregnancy; antioxidative dietary supplement


Introduction
Hashimoto�s thyroiditis (HT) has been named after the Japanese physician Hakaru Hashimoto who first described this disease in 1912 [1]. HT, also known as chronic lymphocytic thyroiditis, is an autoimmune disorder of the thyroid gland which results in chronic inflammation due to the occurrence of auto- antibodies directed against thyroglobulin (Tg), thyroperoxidase (TPO) and TSH receptor (TSH-R) with subsequent destruction of thyroid tissue by T-lymphocytes. HT is the commonest autoimmune disorder in humans. It affects an estimated 5-10 % of the general population, with women being affected 2 to 5 times more often than males due to unknown reasons. The incidence of chronic lymphocytic thyroiditis is even higher among female patients attending fertility clinics, up to 25 % of whom are estimated to suffer from this endocrine disorder. HT is, remarkably, the most frequent cause of primary hypothyroidism in women of reproductive age [6].  At the outset of disease there may be a period of hyperthyroidism (thyrotoxicosis) due to the progressive destruction of thyroid tissue causing damage to the integrity of thyroid follicle storage of Tg. However, the final state of disease is hypothyroidism, which is highly associated with female infertility. 
The reasons for this multifactorial disorder are thought to be caused by various environmental factors triggering the autoimmune response in genetically susceptible individuals, though the exact mechanisms linking environmental factors to thyroid autoimmunity are still not understood [2]. Among the factors discussed to be involved in the onset of the disease are severe viral infections. Additionally, other autoimmune diseases or endocrine disorders and moreover several environmental factors such as environmental pollution, pesticides, xenohormones and many other chemicals with a putative impact on the immune system are suggested to trigger the outburst of disease [2,3,4]. Moreover, a few studies showed increased oxidative stress (OS) in HT as assessed by elevated lipid peroxidation and/or decreased antioxidant status [5]. In addition, it is known that excessive iodine intake lowers the antioxidant capacity, and, moreover, OS is also known to be increased in hypothyroid patients, which are positive for anti-TPO antibody [5].
Many women with thyroid dysfunction experience subfertility and increased miscarriage rates [7, 8]. Given the fact, that for conception, ongoing pregnancy and healthy delivery various subtle interactions of hormones and components of the immune system are required, impaired fertility does not seem surprising. As a matter of fact, HT might impair human fertility and reproduction in a multitude of ways.
Recently, Monteleone et al. (2011) demonstrated that fertilization, embryo quality and pregnancy rate was lower for female IVF patients with thyroid autoimmunity, and suggested that the presence of anti-thyroid antibodies in ovarian follicles might play a critical role in female infertility [9]. As the zona pellucida and thyroid tissue seem to share similar antigens, the zona pellucida may in turn be a target for anti-thyroid antibodies and this was suggested to alter fertility by targeting zona pellucida, human chorionic gonadotropin receptors and other placental antigens [10]. 
Patients with primary hypothyroidism often develop hyperprolactinaemia, which is also most detrimental for oocyte maturation. Hyperprolactinemia is triggered in HT by various mechanisms. First, in response to the hypothyroid state, there is a compensatory increase in the discharge of central hypothalamic thyrotropin-releasing hormone, resulting in stimulation of prolactin (PRL) secretion. In addition to this, PRL elimination from the systemic circulation is reduced, which contributes considerably to increased PRL protein concentrations [11-14]. Other reasons for increasing PRL levels in hypothyroidism individuals are also well known [16]. 
Menstrual irregularities are frequently found in female patients with hypothyroism [17] and its severity is linked to the serum TSH levels [18]. These irregularities are thought to be caused by a change in pulsatile gonadotropin release on the one hand and by the lack of thyroxin leading to limited luteinizing on the other hand.
Concerning other biochemical parameters, a number of characteristics associated with HT have been identified. First, patients frequently exhibit elevated levels of homocysteine (hyperhomoscysteinemia). This is caused by a reduction of hepatic remethylation of homocysteine into methionine [19-21]. Second, patients have an increased risk of vitamin D deficiency [22]. This is particularly important, as vitamin D is widely known to have a marked impact on oocyte maturation and fertility [23]. Also, patients frequently present with decreased levels of iron, vitamin B12 and folic acid, even when they are euthyroid [24] [21, 24].  Furthermore, OS has been found to play an important role in thyroid autoimmunity, particularly when patients are deficient for selenium [25-28] or zinc [29]. All of these specifics have independently been identified as important risk factors for impaired fertility.
Another factor contributing to fertility problems in patients suffering from HT is the fact that this subpopulation also has a higher incidence of endometriosis [31-32] and polycystic ovary (PCO) syndrome [7, 33].
These patients also face an increased risk for premature ovarian failure (POF) and even when they conceive, there is still the danger of early miscarriage [31]. Two main factors have been held responsible for this: On the one hand, this might be up to the immune system itself. Using a mouse model system, Matalon et al. [34] found the autoimmunity is closely associated to hyperactive immune function with elevated NK cells, which ultimately leads to reproductive failure. The authors interpreted the data as an evolutionary protection against the spreading of hereditary autoimmune disorders.  
Second, miscarriage rates have been discussed to be elevated due to hyper-coagulation leading to placental vascular occlusion. Comparative studies suggest that coagulation and innate immunity have a common evolutionary origin. Therefore, it might be unsurprising that the immune and coagulation systems are cross-linked, with many molecular components being important for both. 
Systemic inflammation as observed in autoimmune diseases modulates thrombotic responses by suppressing fibrinolysis, up-regulating pro-coagulant, and down regulating anti-coagulants [36]. Some of the central features of the hyper-coagulability induced by inflammation are cytokine induction of tissue factor (TF) expression, endothelial dysfunction, the suppression of the protein C signal cascade and inhibition of fibrinolysis [36-40].
Finally, if pregnancy proceeds, there is still the risk of hypothyroidism during pregnancy, even when patients show euthyroidism status in early gestation. This is due to the fact that maternal thyroid requirements increase as gestation progresses, but cannot be met [41]. Together with an alteration in renal clearance associated with increased iodine excretion, the rise of the placental type 3 Iodothyronine Deiodinase (D III) and the increase of TBG (Thyroxin Binding Globulin) with subsequent lower levels of free T4 can lead to severe hypothyroidism. This is associated with increased risks of obstetric complications during pregnancy, such as miscarriage, anemia, gestational hypertension, placental abruption, premature delivery and postpartum hemorrhage [7]. Hypothyroidism during pregnancy also elevates the risk for the neonate to be admitted to intensive care, mainly for respiratory stress syndromes [42, 43] and the children are at the risk of poor neurodevelopmental outcome [44].
Data in regard of fertilization-, implantation- and pregnancy rates are still inconsistent for women with thyroid autoimmunity [9, 45, 46]. However, there is a strong association between miscarriage and the presence of auto-antibodies [7], which might explain the observation of lower success rates as the pregnancy proceeds. Moreover, facing the complexity of health problems, it is still obvious why a substantial number of women with HT undergo fertility treatment. 
For these reasons, we hypothesized that HT patients undergoing IVF/ICSI may benefit from a broad therapeutic approach addressing a wide variety of Hashimoto-associated factors impairing fertility and early pregnancy. 
This includes above-normal TSH (<2 �U/mL, optimal TSH: 0.5-1 �U/mL) and PRL adjustment in order to address the problem of hyper-prolactinemia, with begin of stimulation and wide anti-coagulation (heparin and ASA) from the day of OPU onwards, immune-modulation using selenium (100�200 �g) and steroids as required (up to 7.5 mg, depending on the thyroid antibody titers).
Interestingly, within the recent years the application of multivitamin/mineral supplements in otherwise healthy female patients for improving the outcome of IVF/ICSI treatment has been widely discussed and several promising studies demonstrated that the administration of micronutrients and antioxidants can indeed impact in a positive manner [47-49]. Nevertheless, discussion is not without controversy. Additionally, there is so far �to our knowledge no study analyzing the effects of a dietary supplementation on the IVF outcome of patients with autoimmune thyroiditis. 
Given that HT patients have an increased risk for a number of micronutrient deficiencies as described above and that OS has been discussed to be involved in the progress of the disease, we supposed that in addition to a broad therapeutic concept as outlined above, supplementing a suitable dietary antioxidative preparation (multivitamin, folic acid, iron, zinc, selenium without iodine) to the diets of women with autoimmune thyroiditis undergoing ART treatment may have a positive impact on treatment outcome.


Material and Methods
 Patients
 From January to July 2011 a total of 106 women with a history of HT disease attended the IVF center Prof. Zech were recruited for this study. Participants were randomized and 50 women received a micronutrient containing dietary preparation (Fertilovit�FTHY, see Table 1 for full supplement information) containing selenium, high-dose folic acid, B-vitamins, vitamin D, antioxidants and iron instead of folic acid only. Written consent was obtained from all participants of this study. The control group of 56 women received folic acid only (5 mg/day). Patient�s mean age in the supplemented group was 36.1 years and 36.7 years in the non-supplemented group.
Stimulation schedule and medication
 Stimulation was performed using the long protocol [50]. TSH level was adjusted before stimulation to under 2 �IU/mL using L-thyroxine as required. Dietary supplementation was started with the beginning of hormonal stimulation. Concurrent medication for HT patients from the time of oocyte puncture included daily administration of dalteparin (2500 IU/day) and ASA (100 mg/day), as well as prednisolone in rising dosage (7.5 mg -15 mg/day).
Oocyte retrieval, fertilization, embryo culture and evaluation of embryo quality
 Oocytes were retrieved thirty-six hours post human chorionic gonadotropin (hCG) administration and were fertilized using intracytoplasmic sperm injection (ICSI) or intracytoplasmic morphologically selected sperm injection (IMSI) [51]. Normal fertilization was identi�ed by the presence of two pronuclei (2PN). Embryo culture was performed in Global medium (LifeGlobal, Ontario, Canada) supplemented with human serum albumin (HSA LifeGlobal, Ontario, Canada) in four-well dishes (Nunc A/S, Roskilde, Denmark) and incubated for 5 days, until embryo transfer. On day 5, the embryo quality was evaluated according to Gardner et al., [52]. Blastocysts with a degree of expansion of 2, 3, 4 and 5 and with A-grading for inner cell mass and trophectoderm or a combination of A- and B-grading were classified as top blastocysts.
For evaluation of treatment outcome, we compared the number of oocytes, fertilization rate, blastocyst formation rate, pregnancy rate and ongoing pregnancy rate between the two groups and the average results of healthy IVF-patients. Pregnancy rate (PR) was determined by testing urinary �-hCG 14 days after ET. Ongoing pregnancy rate (oPR) was defined as observation of foetal heartbeat(s) by ultrasound 6-8 weeks after ET. Differences in the fertilization-, blastocyst- and pregnancy rates were evaluated using Pearson�s chi-squared test. Between-group comparisons of normally distributed variables were assessed using Student's t-test.

Results
The results of this comparative study are summarized in Table 2A and B. While there was no difference between the two groups regarding the number of retrieved oocytes and fertilization rate, there was a significant increase in the blastocyst rate (Table 2A) within the supplemented group. In addition to this, patients of the supplemented group also needed less L-thyroxine to achieve the TSH value aimed for (p<0.01).  Moreover this patient group also demonstrated a substantial increase in the ongoing pregnancy rate detected by foetal heart beat (Table 2A) after ET. Pregnancy rate was also elevated, although differences between groups were not significant. This data of supplemented patients corresponds to the average of a healthy IVF patient without HT at our clinic (Table 2B).

Discussion
Even though that the case number is still low, this study clearly demonstrates that IVF patients with chronic lymphocytic thyroiditis significantly benefit from a broader therapeutic concept within ART therapy. Dietary supplementation with an iodine-free micronutrient combination including selenium and vitamins seems to be markedly beneficial in terms of the number of received blastocysts at day 5 of embryo culture. Considering the similar number of retrieved oocytes and the higher rate of top-blastocyst, these findings indicate that the micronutrient supplementation does not improve the number, but oocyte�s competence for successful development to the blastocyst stage.
Another crucial aspect is the finding of a higher ongoing pregnancy rate after embryo transfer of the supplemented patients, although there was no significant difference in pregnancy rate detected. We therefore postulate that this is due to either an improved embryo competence or improved intrauterine environment, lowering the risks of early abortion. In fact, as mentioned before, there is a strong association of HT, implantation failure and (recurrent) foetal loss.
As a secondary effect, dietary supplemented patients obviously require less L-thyroxine to achieve the TSH levels aimed for, which is desirable as it lowers the patient�s risk for side effects such as  HYPERLINK "http://www.dict.cc/englisch-deutsch/cardiac.html" cardiac  HYPERLINK "http://www.dict.cc/englisch-deutsch/arrhythmias.html" arrhythmias, insomnia or hypertension. 
How these alternations are brought about is currently not known and not subject of this study. However, a few crucial aspects of micronutrients should be mentioned that might hint to possible mechanisms of action. One micronutrient with a substantial impact on thyroid function is undeniably iodine. Whereas a sufficient intake has been shown to be critically for normal thyroid function, for women with autoimmune thyroiditis, it has been observed that higher iodine concentrations may have detrimental effects as well. Autoimmune thyroiditis worsens with iodine excess [53], whereas improvements have been reported in several studies when the iodine content of patient�s diet was already low [54-57]. 
Several other trace elements have been identified to be essential for normal thyroid hormone metabolism. Among these, iron and selenium are most worth to be mentioned. Deficiencies of these elements can restrain thyroid function markedly. Iron deficiency impairs thyroid hormone synthesis by reducing the activity of heme-dependent thyroid peroxidase [58]. Erdal and colleagues demonstrated that basal levels of iron in patients with subclinical hypothyroidism were significantly lower when compared to a control group [59].
Under physiological conditions thyroid gland retains high selenium concentrations and expresses many known seleno-cysteine containing proteins which are needed for the (in)activation of thyroid hormones, responsible for normal development, growth, and metabolism. Furthermore, seleno-cysteine can be often found in the catalytic center of enzymes protecting the thyroid from OS [60]. Adequate selenium-rich nutrition has been shown important for efficient thyroid hormone synthesis and metabolism and protects the thyroid gland from damage by excessive iodide exposure. Various studies indicate other beneficial effects of selenium supplementation in patients with HT such as modulation of the immune system by reducing thyroid antibody titers [25, 61]. Positive effects of selenium supplementation during pregnancy in terms of reduced thyroid inflammatory activity have also been reported [62].
Recently, it was demonstrated that the GSH levels in HT patients is markedly lower compared to healthy controls. Even though, that the pathways of the autoimmune thyroiditis, are not fully understood, OS has revealed to be an additional important contributing factor [63-64], and the imbalance of ROS/antioxidants might be a jointly responsible factor for a cluster of HT symptoms. 
Meanwhile, it is well established that oocytes are highly susceptible to attacks by reactive oxygen species (ROS). ROS can impair the membrane and interfere with protein synthesis as well as energy production and has also been associated with various problems throughout pregnancy [66]. Several studies revealed that patients with autoimmune thyroiditis have increased OS levels [27] and a decrease in antioxidants [5] Data indicate that it might be beneficial to supplement antioxidants to the diets of patients with HT. In addition, a study comprising 115 patients with autoimmune thyroid disease demonstrated that this patient collective also has an increased risk of having a vitamin B12 deficiency. Together with folic acid and vitamin B6, vitamin B12 is vitally needed for proper homocysteine metabolism [24]. 
Vitamin D deficiency was also suggested as a pre-disposing factor for autoimmune diseases and can be also observed in autoimmune thyroiditis patients [22]. Given that vitamin D deficiency has also been linked to infertility and pregnancy loss via indirect effects mediated by extracellular calcium and phosphorus [67], this is an important issue.


Conclusion  
Although the detailed mechanisms in HT disease are still unclear, patients with HT undergoing fertility treatment (IVF/ICSI) obviously benefit from taking a dietary supplement including selenium, iron, vitamins as well as antioxidants in addition to other supportive medication such as ASA, dalteparin and prednisolone. This therapeutic regimen results in a marked increase of ongoing pregnancy rate while requiring less L-thyroxine administration. Nevertheless, further studies to confirm our findings are needed.








References
1. Hashimoto H (1912) Zur Kenntnis der lymphomat�sen Ver�nderungen der Schilddr�se (Struma lymphomatosa). Archiv f�r klinische Chirurgie 97: 219�248. 
2. Duntas LH (2011) Environmental factors and thyroid autoimmunity. Ann Endocrinol (Paris) 72: 108-113.

3. Hybenova M, Hrda P, Proch�zkov� J, Stejskal V, Sterzl I (2010) The role of environmental factors in autoimmune thyroiditis. Neuro Endocrinol Lett 31: 283-289. Review.

4. Shan ZY, Li YS, Wang ZY, Jin Y, Guan HX, Hu FN, Teng XC, Yang F, Gao TS, Wang WB, Shi XG, Tong YJ, Chen W, Teng WP (2005) Effect of different iodine intake on the prevalence of hypothyroidism in 3 counties in China. Chin Med J (Engl)  
118: 1918-1920.
5. Rostami R, Aghasi MR, Mohammadi A, Nourooz-Zadeh J (2013) Enhanced oxidative stress in Hashimoto's thyroiditis: Inter-relationships to biomarkers of thyroid function. Clin Biochem 46: 308-312.
6. Hollowell JG HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Staehling%20NW%5BAuthor%5D&cauthor=true&cauthor_uid=11836274"Staehling NW, Flanders WD, HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Hannon%20WH%5BAuthor%5D&cauthor=true&cauthor_uid=11836274"Hannon WH, HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Gunter%20EW%5BAuthor%5D&cauthor=true&cauthor_uid=11836274"Gunter EW, HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Spencer%20CA%5BAuthor%5D&cauthor=true&cauthor_uid=11836274"Spencer CA, HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Braverman%20LE%5BAuthor%5D&cauthor=true&cauthor_uid=11836274"Braverman LE (2002) Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 87: 489-499.

7. Poppe K, Velkeniers B, Glinoer D (2008) The role of thyroid autoimmunity in fertility and pregnancy. Nat Clin Pract 4: 394-405.

8. van den Boogaard E, Vissenberg R, Land JA, van Wely M, van der Post JA, Goddijn M, Bisschop PH (2011) Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Hum Reprod Update17: 605-619. 
9. Monteleone P, Parrini D, Faviana P, Carletti E, Casarosa E, Uccelli A, Cela V, Genazzani AR, Artini PG (2011) Female infertility related to thyroid autoimmunity: the ovarian follicle hypothesis. Am J Reprod Immunol 66: 108-114. 
10. Twig G, Shina A, Amital H, Shoenfeld Y (2012) Pathogenesis of infertility and recurrent pregnancy loss in thyroid autoimmunity. J Autoimmun 38: J275-281.

11. Prabhakar VK, Davis JR (2008) Hyperprolactinaemia. Best Pract Res Clin Obstet Gynaecol 22: 341-353.

12. Demssie YN, Davis JR (2008) Hyperprolactinaemia Clin Med 8: 216-219.

13. Asa SL, Ezzat S (2002) The pathogenesis of pituitary tumours. Nat Rev Cancer 2:  836-849.

14. Seri O, Chik CL, Ur E, Ezzat S (2003) Diagnosis and management of hyperprolactinemia. CMAJ  169: 575-581.

15. Foord SM, Peters JR, Dieguez C, Jasani B, Hall R, Scanlon MF (1984) Hypothyroid pituitary cells in culture: an analysis of thyrotrophin and prolactin response to dopamine (DA) and DA receptor binding. Endocrinology 115: 407-415.

16. Davis JR, Lynam TC, Franklyn JA, Docherty K, Sheppard MC (1986) Tri-iodothyronine and phenythoin reduce prolactin messenger RNA levels in cultured rat pituitary cells. J Endocrinol 109:  359-364
17. Joshi JV, Bhandarkar SD, Chadha M, Balaiah D, Shah R (1993) Menstrual irregularities and lactation failure may precede thyroid dysfunction or goitre. J Postgrad Med 39: 137-141.
18. Krassas GE, Pontikides N, Kaltsas T, Papadopoulou P, Paunkovic J, Paunkovic N, Duntas LH (1999) Disturbances of menstruation in hypothyroidism. Clin Endocrinol (Oxf) 50: 655-659.

19. Seng�l E, Cetinarslan B, Tarkun I, Cant�rk Z, T�remen E (2004) Homocysteine concentrations in subclinical hypothyroidism. Endocr Res 30: 351-359. 

20. Franchini M (2006) Hemostatic changes in thyroid diseases: haemostasis and thrombosis. Hematology 11: 203-208. Review.
21. Wang YP, Lin HP, Chen HM, Kuo YS, Lang MJ, Sun A (2012) Hemoglobin, iron, and vitamin B12 deficiencies and high blood homocysteine levels in patients with anti-thyroid autoantibodies. J Formosan Med Ass In press.

22. Tamer G, Arik S, Tamer I, Coksert D (2011) Relative vitamin D insufficiency in Hashimoto's thyroiditis. Thyroid 21: 891-896. 
23. Lerchbaum E, Obermayer-Pietsch B (2012) Vitamin D and fertility: a systematic review. Eur J Endocrinol166:765-778. Review.
24. Ness-Abramof R, Nabriski DA, Braverman LE, Shilo L, Weiss E, Reshef T, Shapiro MS, Shenkman L (2006) Prevalence and evaluation of B12 deficiency in patients with autoimmune Thyroid disease. Am J Med Sci 332: 119-122; 
25. G�rtner R, Gasnier BC, Dietrich JW, Krebs B, Angstwurm MW (2002) Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations. J Clin Endoc a Metab 87: 1687-1691.
26. Iborra A, Palacio JR, Martinez P (2005) Oxidative stress and autoimmune response in the infertile woman. Chem Immunol Allergy  88:150-162. Review.
27. Taddei S, Caraccio N, Virdis A, Dardano A, Versari D, Ghiadoni L, Ferrannini E, Salvetti A, Monzani F (2006) Low-grade systemic inflammation causes endothelial dysfunction in patients with Hashimoto's thyroiditis. J Clin Endocrinol Metab 91: 5076-5082. 

28. Wilson C. Thyroid function: new guidance for the diagnosis and management of thyroid diseases in pregnancy (2011). Nat Rev Endocrinol  7:559. 
29. Ertek S, Cicero AF, Caglar O, Erdogan G (2010) Relationship between serum zinc levels, thyroid hormones and thyroid volume following successful iodine supplementation. Hormones (Athens) 9: 263-268.
30. Poppe K, Glinoer D, Van Steirteghem A, Tournaye H, Devroey P, Schiettecatte J, Velkeniers B (2002) Thyroid dysfunction and autoimmunity in infertile women. Thyroid 12: 997-1001.
31. Abalovich M, Mitelberg L, Allami C, Gutierrez S, Alcaraz G, Otero P, Levalle O (2007) Subclinical hypothyroidism and thyroid autoimmunity in women with infertility. Gynecol Endocrinol 23: 279-83.
32. Gerhard I, Becker T, Eggert-Kruse W, Klinga K, Runnebaum B
Thyroid and ovarian function in infertile women. (1991) Hum Reprod 6: 338-345.
33. Janssen OE, Mehlmauer N, Hahn S, Offner AH, G�rtner R (2004) High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Eur J Endocrinol 150: 363-369.
34. Matalon ST, Blank M, Levy Y, Carp HJ, Arad A, Burek L, Grunebaum E, Sherer Y, Ornoy A, Refetoff S, Weiss RE, Rose NR, Shoenfeld Y (2003) The pathogenic role of anti-thyroglobulin antibody on pregnancy: evidence from an active immunization model in mice. Hum Reprod18: 1094-1099.
35. Z�ller B, Li X, Sundquist J, Sundquist K (2012) Autoimmune diseases and venous thromboembolism: a review of the literature Am J Cardiovasc Dis  2: 171-183.

36. Dahlb�ck B Coagulation and inflammation--close allies in health and disease. Semin Immunopathol (2012) 34: 1-3.
37. Esmon CT, Esmon NL (2011) The link between vascular features and thrombosis. Annu Rev Physiol 73: 503-514. 
38. Xu J, Lupu F, Esmon CT (2010) Inflammation, innate immunity and blood coagulation. Hamostaseologie 30: 5-6, 8-9.  
39. Esmon CT (2005) The interactions between inflammation and coagulation. Br J Haematol 131: 417-430. 
40. Ardoin SP, Shanahan JC, Pisetsky DS (2007) The role of microparticles in inflammation and thrombosis. Scand J Immunol 66: 159-165. 
41. Glinoer D, Riahi M, Gr�n JP, Kinthaert J (1994) Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders. J Clin Endocrinol Metab 79: 197-204.
42. Mandel S (2004) Hypothyroidism and chronic autoimmune thyroiditis in the pregnant state: maternal aspects. Best Pract Res Clin Endocrinol Metab 18: 213-224. Review.
43. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Leveno KJ, Cunningham FG (2005) Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol 105: 239-245.
44. de Escobar GM, Obreg�n MJ, del Rey FE (2004) Maternal thyroid hormones early in pregnancy and fetal brain development. Best Pract Res Clin Endocrinol Metab18: 225-248. 
45. Negro R, Formoso G, Coppola L, Presicce G, Mangieri T, Pezzarossa A, Dazzi D (2007) Euthyroid women with autoimmune disease undergoing assisted reproduction technologies: the role of autoimmunity and thyroid function. J Endocrinol Invest 30:3-8
46. Zhong YP, Ying Y, Wu HT, Zhou CQ, Xu YW, Wang Q, Li J, Shen XT, Li J (2012)
Relationship between antithyroid antibody and pregnancy outcome following in vitro fertilization and embryo transfer. Int J Med Sci 9: 121-125. 

47. �zkaya MO, Naziroglu M (2010) Multivitamin and mineral supplementation modulates oxidative stress and antioxidant vitamin levels in serum and follicular fluid of women undergoing in vitro fertilization. Fertil Steril 94: 2465-2466.

48. Agrawal R, Burt E, Gallagher AM, Butler L, Venkatakrishnan R, Peitsidis P (2012)
Prospective randomized trial of multiple micronutrients in subfertile women undergoing ovulation induction: a pilot study. Reprod Biomed Online 24: 54-60.
 
49. Grajecki D, Zyriax BC, Buhling KJ (2012) The effect of micronutrient supplements on female fertility: a systematic review. Arch Gynecol Obstet  285: 1463-1471.
50. Zech NH, Lejeune B, Puissant F, Vanderzwalmen S, Zech H, Vanderzwalmen P (2007) Prospective evaluation of the optimal time for selecting a single embryo for transfer: day 3 versus day 5. Fertil Steril 88: 244-246
51. Vanderzwalmen P, Hiemer A, Rubner P, Bach M, Neyer A, Stecher A, Uher P, Zintz M, Lejeune B, Vanderzwalmen S, Cassuto G, Zech NH (2008) Blastocyst development after sperm selection at high magnification is associated with size and number of nuclear vacuoles. Reprod Biomed Online 17: 617-627.

52. Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB (2000) Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril 73: 1155-1158.
53. B�rgi H (2010) Iodine excess. Best pract Res Clin Endocrinol Metab 24: 107-115.
54. Rose N R, Rasooly L, Saboori A M, Burek CL (1999) Linking iodine with autoimmune thyroiditis. Environ Health Perspect 107: 749�752. 
55. Ruwhof C, Drexhage HA (2001) Iodine and thyroid autoimmune disease in animal models.  Thyroid 11: 427-436.
56. Cihakova D, Sharma R B, Fairweather D, Afanasyeva M, Rose NR (2004) Animal models for autoimmune myocarditis and autoimmune thyroiditis. Methods Mol Med 102: 175-194.
57. Schumm-Draeger P M . Jod und thyreoidale Autoimmunit�t.  Zeitschrift f�r �rztliche Fortbildung und Qualit�t im Gesundheitswesen, Jahrgang 98, Heft Supplement V, 04�2004, S. 73�76 (4)
58. Zimmermann MB, K�hrle J (2002) The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health. 1: Thyroid 12: 867-878.

59. Erdal M, Sahin M, Hasimi A, Uckaya G, Kutlu M, Saglam K (2008) Trace element levels in hashimoto thyroiditis patients with subclinical hypothyroidism.  Biol Trace Elem Res. 123:1-7.

60. Triggiani V, Tafaro E, Giagulli VA, Sabb� C, Resta F, Licchelli B, Guastamacchia E (2009) Role of iodine, selenium and other micronutrients in thyroid function and disorders. Endocr Metab Immune Disord Drug Targets 9: 277-294.
 
61. Duntas LH, Mantzou, Koutras DA (2003) Effects of a six month treatment with selenomethionine in patients with autoimmune thyroiditis. Eur J Endoc 4: 389-393.	
62.  Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H (2007) The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab 92: 1263-1268. 
 63. Duthoit C, Estienne V, Giraud A, Durand-Gorde JM, Rasmussen AK, Feldt-Rasmussen U, Carayon P, Ruf J (2001) Hydrogen peroxide-induced production of a 40 kDa immunoreactive thyroglobulin fragment in human thyroid cells: the onset of thyroid autoimmunity? Biochem J 360: 557-562.
64. Erdamar H, Demirci H, Yaman H, Erbil MK, Yakar T, Sancak B, Elbeg S, Biberolu G, Yetkin I (2008) The effect of hypothyroidism, hyperthyroidism, and their treatment on parameters of oxidative stress and antioxidant status. Clin Chem Lab Med 46: 1004-1010.
 65. Burton GJ, Jauniaux E (9A�������������� 	"	7	w	�	�	�	�	���ʽ�����������������o]L h�|�h1�OJQJ^JmHsH#h�|�h1�H*OJQJ^JmHsH#h�|�h1�H*OJQJ^JmH	sH	h�|�h1�OJQJ]�^Jh�|�h1�H*OJQJ]�^Jh�|�h��h��OJQJ^Jh�|�h1�H*OJQJ^Jh�|�h1�OJQJ^J h�|�h1�OJQJ^JmH	sH	 h1�5�OJQJ\�^JmH	sH	&h�|�h1�5�OJQJ\�^JmH	sH	���� 	w	x	y	z	{	|	}	~		�	�	�	�	�	�	
����������������������$dh1$7$8$H$a$gd1�
dh1$7$8$H$gd1�	dh1$gd1�dhgd1�
$dha$gd1��	�	�	�	�	�	�	


-
.
H
O
P
�
�
�
�
�
�
�
����굢�ّ�~k~kRk~E�h�|�h1�OJQJ^J0h�|�h1�0J>*B*OJQJ^JmH	ph�sH	%jh�|�h1�OJPJQJU^J$h�|�h1�OJPJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	$h�|�h1�0JOJQJ^JmHsH$h�|�h1�0JOJQJ^JmH	sH	 h�|�h1�OJQJ^JmHsH h�|�h1�OJQJ^JmH	sH	)jh�|�h1�OJQJU^JmH	sH	
-
.
D
�
�
�
�
�
�
�
_`abc�����������������
$dha$gd1�dh-DM�
����gd1�
$dha$gd1���dh]��gd1�dhgd1�$dh1$7$8$H$a$gd1�$��
dh^��
a$gd1�m$�
�
�
�
�
�
�
�
�
�
�
;
A
�
�
��@���ħݕ�tbK�K�K3K/h�|�h1�5�OJPJQJ^JmH	nHsH	tH,h�|�h1�OJPJQJ^JmH	nHsH	tH#h�|�h1�5�OJQJ^JmH	sH	#h�|�h�g,5�OJQJ^JmH	sH	h1�5�OJQJ^JmH	sH	#h�|�h1�5�OJQJ^JmH	sH	9jh�|�h1�0J>*B*OJQJU^JmH	ph�sH	0h�|�h1�0J>*B*OJQJ^JmH	ph�sH	 h�|�h1�OJQJ^JmH	sH	!jh�|�h1�OJQJU^J@I_c����������������no��±�������������tbM�:%h�|�h1�B*CJaJmH	ph�sH	)h�|�h1�0JB*CJaJmH	ph�sH	#h�|�h1�5�OJQJ^JmH	sH	%h�|�h1�B*CJaJmH	ph�sH	h�|�h1�mH	sH	h1�OJQJ^JmH	sH	 h�|�h|FOJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	%h�|�h1�B*CJaJmH	ph�sH	,h�|�h1�OJPJQJ^JmH	nHsH	tH&h?9�OJPJQJ^JmH	nHsH	tH������{�N"�#'�'F*�+w-[1134~5�7�9�9�9����������������������dhgd1�
$dha$gd1�
$dha$gd1�7$�dh^�a$gd�$dh-DM�
����a$gd1�opqs���������.j������vy|}�����ABCGIJz���ذ�ذ������Ņ�vfv�vfv�vfv�vfv��������h�|�h1�CJ\�aJmH	sH	h�|�h1�CJaJmH	sH	)h�|�h1�0JB*CJaJmH	ph�sH	+h�|�h1�h�I�B*CJaJmH	ph�sH	(h�|�h1�B*CJ\�aJmH	ph�sH	%h�|�h1�B*CJaJmH	ph�sH	%h�|�h1�B*CJaJmH	ph�sH	(h�|�h1�B*CJ\�aJmH	ph�sH	(z{�����������!�!�!�!G"H"J"K"N"�"�"�"�"�"�"�"�"�$�$�$�$�$%%%%�%�%�%�%�%&&&&&&��ʺ��ʺʥٌʺʌʺʌ�ʺ��ʺ��ʺ���ʺ��ʺ����|���h�|�h1�CJ\�aJmH	sH	1h�|�h1�B*CJPJaJmH	nH	ph�sH	tH	(h�|�h1�CJPJaJmH	nHsH	tHh�|�h1�CJ\�aJmH	sH	h�|�h1�CJaJmH	sH	%h�|�h1�B*CJaJmH	ph�sH	%h�|�h1�B*CJaJmH	ph�sH	0&
&&�&�&�&�&�&�&�&�&�&�'�'�'�'�'�'�'�'�'�'�' (?(�(�(�(�(2)3)5)6)F*�*���������������͛ͪͪ������s%h�|�h1�B*CJaJmH	phsH	(h�|�h1�B*CJ\�aJmH	ph�sH	h�|�h1�CJaJmH	sH	%h�|�h1�B*CJaJmH	ph�sH	h�|�h1�CJ\�aJmH	sH	%h�|�h1�B*CJaJmH	ph�sH	h�|�h1�CJaJmH	sH	h�|�h1�CJ\�aJmH	sH	"�*w,x,z,{,n-o-t-u-v-w-�-�-.d.�.�.�.�.�.�/r0s0t0u0�01	1111U1V1X1Y1Z1[1�1�1�1�1�1�������ղ䲟�����Ռy���Ռ���ղ���՟j��ş�h�|�h1�CJaJmH	sH	%h�|�h1�B*CJaJmH	phsH	%h�|�h1�B*CJaJmH	phsH	%h�|�h1�B*CJaJmH	ph�sH	%h�|�h1�B*CJaJmH	ph�sH	h�|�h1�CJ\�aJmH	sH	h�|�h1�CJaJmH	sH	6h�|�h1�B*CJaJfHmH	phq�
����sH	)�1�1F2G2H2I20313B3*4O4}5~5�6�6�6�6�6�8�9�9�9�9������񷠏���n����[�M< h�|�h�g,OJQJ^JmH	sH	h1�OJQJ^JmH	sH	%h�|�h1�B*CJaJmH	ph�sH	+h�|�h1�h�5�B*CJaJmH	ph�sH	h�|�h1�mH	sH	 h�|�h1�OJQJ^JmH	sH	,h�|�h1�OJPJQJ^JmH	nHsH	tH,h�|�h1�OJPJQJ^JmH	nHsH	tHh�|�h1�CJ\�aJmH	sH	%h�|�h1�B*CJaJmH	ph�sH	h�|�h1�CJaJmH	sH	�9�9�9�9�9�:�:�:�:�:�:;d;e;;X<i<p<�<�<�<�<�<�<�<==(=w=L>M>�>�>�>����ܶ��������ܐ����mܶܶܶ��[�#h�|�h�|�5�OJQJ^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	 h�|�h1�OJQJ^JmH	sH	h?9�OJQJ^JmH	sH	/h�|�h1�H*OJPJQJ^JmH	nHsH	tH,h�|�h1�OJPJQJ^JmH	nHsH	tHh�|�5�OJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	#h�|�h1�5�OJQJ^JmH	sH	!�9�9�9p<�<M>�>0C�E�E�E�H�H�H|KSM�N�Q�SW�X�[*]+],]������������������������
$dha$gd1�
$dha$gd�
$dha$gd�g,
$dha$gd1��>�>?�?�?�?�?�@�@�@hA�A�A'BpBqBsBtBuB/C0C4C�C�CD��ij���������곡����ybKb,h�g,h�g,OJPJQJ^JmH	nHsH	tH,h�g,h1�OJPJQJ^JmH	nHsH	tH,h�|�h1�OJPJQJ^JmH	nHsH	tH h�|�hcXOJQJ^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	 h�|�h1�OJQJ^JmH	sH	)h�|�h1�B*OJQJ^JmH	phsH	 h�|�h1�OJQJ^JmH	sH	)h�|�h1�B*OJQJ^JmH	phsH	DgD�D�DLEeE�E�E�E�E�E�F�F�G�G��п���o]E�1�1&h��OJPJQJ^JmH	nHsH	tH/h�|�h1�5�OJPJQJ^JmH	nHsH	tH#h�|�h1�5�OJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	 h�g,h1�OJQJ^JmH	sH	,h�|�h1�OJPJQJ^JmH	nHsH	tH,h�g,h1�OJPJQJ^JmH	nHsH	tH h�g,h1�OJQJ^JmH	sH	h�OJQJ^JmH	sH	 h�g,h�g,OJQJ^JmH	sH	 h�g,h�g,OJQJ^JmH	sH	�G�G�G�G�G�G�G�GH<HVHoH�H�H�H�H;IZI���������p[E+h�|�h1�CJOJQJ\�^JaJmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	+h�|�h1�5�CJOJQJ^JaJmH	sH	#h�|�h1�5�OJQJ^JmH	sH	&h��OJPJQJ^JmH	nHsH	tH,h�|�h1�OJPJQJ^JmH	nHsH	tH&h�OJPJQJ^JmH	nHsH	tH&h�g,OJPJQJ^JmH	nHsH	tHZI[I�K�KL(L7L@L�L�LGMHMNN[N\NcNdNeNfN�N�N�N�N�N�P
QQ����ӯӯӚ��l�����l��ӅW(h�|�h1�CJOJQJ^JaJmH	sH	1h�|�h1�B*CJOJQJ^JaJmH	phsH	(h�|�h1�CJOJQJ^JaJmH	sH	)jh�|�h1�CJOJQJU^JaJ"h1�CJOJQJ^JaJmH	sH	"h�g,CJOJQJ^JaJmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	.h�|�h1�hZ�CJOJQJ^JaJmH	sH	QQQQ�Q�Q�Q�Q�Q�Q�Q�R�R�R�RSDS_S�S�S�S�S�S�SBTYT`T	UUUU�Կ�ԩԿ��{ԩ�d�Կԩ�d�{�M�M��,h�|�h1�0JCJOJQJ^JaJmH	sH	,h�|�h1�CJOJPJQJ^JaJmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	1h�|�h1�B*CJOJQJ^JaJmH	phsH	+h�|�h1�CJOJQJ\�^JaJmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	+h�|�h1�CJOJQJ\�^JaJmH	sH	UUUU�U�V�V�V�V�V�V�V�V�VWWWWW�W�W�W�Կ�����|�Կe���ԿT@T&h�|�h1�hr[0OJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	,h�|�h1�0JCJOJQJ^JaJmH	sH	,h�|�h1�CJOJPJQJ^JaJmH	sH	,h�|�h1�CJOJPJQJ^JaJmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	+h�|�h1�CJOJQJ\�^JaJmH	sH	�W�W*X+X0X�X�X�Y�Y�Y�YZZZZ=Z>Z?Z@Z�[�[�[�[e\f\h\i\]	]]]*]+],]9]��ʸʥ�ʸ��ʸ��ʸ��ʸ��ʸ��ʸ�ۓ�p/h�|�h1�5�OJPJQJ^JmH	nHsH	tHh�|�h1�mH	sH	#h�|�h1�<�OJQJ^JmH	sH	$h�|�h1�OJPJQJ^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	 h�|�h1�OJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	&h�|�h1�h�G]OJQJ^JmH	sH	",]9]<_=_>_?_@_A_B_C_D_O_�_N`O`�`�`�a�a�bff�f����������������������9$d-DM�
����a$gd1�
$da$gd1�
$da$gd1�dhgd1�
$dha$gd1�9]�^�^C_O_R_e_�_�_�_�_�_``O`Q`R`\`�`���������vcvM8M8(h�|�h1�CJOJQJ^JaJmH	sH	+h�|�h1�CJOJQJ\�^JaJmH	sH	$h�|�h1�0JOJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	'h�|�h1�0J8OJQJ]�^JmH	sH	$h�|�h1�0J8OJQJ^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	)h�|�h1�5�>*OJQJ\�^JmH	sH	&h1�OJPJQJ^JmH	nHsH	tH,h�|�h1�OJPJQJ^JmH	nHsH	tH�`�`�`�`�`�`�`�`�`�`�`�`wa}a�a�a�a�a�a�a�a�a�a�a�a�a�a�a�ab3b4b_bjb�b�������Խԧ������������Խԕ���s�`�$h�|�h1�0JOJQJ^JmH	sH	 h�|�h|FOJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	+h�|�h1�CJOJQJ\�^JaJmH	sH	,h�|�h1�0JCJOJQJ^JaJmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	,h�|�h1�0JCJOJQJ^JaJmH	sH	"�b�b�b�b�b�b�b�b�b�b>c?c@cLcMcOcZc\c]c�c��ɸ����teSteteDeteh�|�h|FOJQJmH	sH	#�jh�|�h1�OJQJUh�|�h1�OJQJmH	sH	jh�|�h1�OJQJU#h�|�h1�OJQJ\�^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	 h�|�h1�OJQJ^JmH	sH	 h1�h|FOJQJ^JmH	sH	 h1�h1�OJQJ^JmH	sH	$h1�h1�0JOJQJ^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	�c�c�c�c�c�c�cFdGdHdQdRdTdUd�d�d�d�d�d�d�dCeDeEeQeRe�eff:f@f}f�f�f������Ͻ�����ϫ�����ϙ��އud�u�ud h�|�h1�OJQJ^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	#�j�h�|�h1�OJQJU#�j�h�|�h1�OJQJU#�j�h�|�h1�OJQJUh�|�h1�OJQJmH	sH	jh�|�h1�OJQJU#�jCh�|�h1�OJQJU!�f�f�g�h1i2i�i�i�i�iCjDj�j�j�k�kdlm�m�minjn�n����������������������dgd1�d7$8$H$gd1�dgd1�$d7$8$H$a$gd1�
$da$gd1�
$da$gd1��f�f�fg g'g(g3g8g?g�g�g�g�g#h.h�h�h�h�h�h�h�h�h2i5i6iNiTiii�i�i�i�i�i�i�i�i�i'j5jDjGjHj�j�j�j�j�j�k�k�k�k�k�kIlUl�������������������������ܳ�����ܳ���ܳ���ܳ���ܳ����ܳ�/h�|�h1�OJPJQJ]�^JmH	nH	sH	tH	,h�|�h1�OJPJQJ^JmH	nH	sH	tH	#h�|�h1�OJQJ\�^JmH	sH	 h�|�h1�OJQJ^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	8UlVldlglhlml�l�l�lmmmm%m�m�m�m�mnn!nOnZngnhnjnmn�n�n�n�no!o�o�o*p2pApDp�Ͻ���������������r����r�������a������ h�|�h�(mOJQJ^JmH	sH	&h�|�h1�hr~�OJQJ^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	,h�|�h1�OJPJQJ^JmH	nH	sH	tH	2h�|�h1�6�OJPJQJ]�^JmH	nH	sH	tH	&�n�o�oAp�p�q�rstt�twu-v�v4w�w9xTy�y�y�������������������dgd1� gd1�
$dha$gd1��Jd�d�d[$\$]�Jgd1�gd1�dgd1�
$da$gd1�d�d�d-DM�
����[$\$gd1�DpEpNp�p�p�p�p�p�p�p�p�p#q)q�q�q�q�q\r�r�r�r�r�r�r�r�rssss�s�s	tttt(t/t0t8t:t=t>tFtOtXt�����������������������v�������������&h�|�h1�5�OJQJ\�^JmH	sH	h�|�h1�mH	sH	 h�|�h�(mOJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	 h�|�h1�OJQJ^JmH	sH	.Xt]tgtkt{tt�t�t�t�t�t�t�t�t�tYujuvuwuzu{u�u�u�u�u-v0v1v:v�v�v�v�v�v�v�vw4w;w@wGwHwPw�w�w�w�w�w�wx*x9x<x�x�x�x�x�x�x�x�x��������������﬷�����������������������������#h�|�h1�OJQJ\�^JmH	sH	h�|�h1�mH	sH	#h�|�h1�OJQJ\�^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	<�x�xyyyyyy+y,y1y5y9y;yEyTyWy�y�y�yizlzmz�z�z�zO{���������������s��s��Z1h�|�h1�OJQJ^JfHmH	q�
����sH	6h�|�h1�B*CJaJfHmH	ph�q�
����sH	%h�|�h1�B*CJaJmH	ph�sH	(h�|�h1�B*CJ\�aJmH	ph�sH	#h�|�h1�OJQJ\�^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	�yiz�zP{�{@|�|�}N~�~�D�ՀրÁ�����Y�2�[�\�����������������������dgd1�dgd1��Jd�d�d[$\$]�Jgd1�d7$8$H$gd1�dgd1�O{P{S{T{�{�{�{�{@|C|D|K|�|�|�|�|�|�|�|}}}} }K}S}��ƭƘ�i��������VƘ�A�A�A)h�|�h1�0JB*CJaJmH	ph�sH	$h�|�h1�0JOJQJ^JmH	sH	6h�|�h1�B*CJaJfHmH	ph�q�
����sH	%h�|�h1�B*CJaJmH	ph�sH	(h�|�h1�B*CJ\�aJmH	ph�sH	1h�|�h1�OJQJ^JfHmH	q�
����sH	 h�|�h1�OJQJ^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	,h�|�h1�OJPJQJ^JmH	nH	sH	tH	S}l}m}�}�}�}�}�}
~~1~?~N~Q~y~�~�~�~�~�~�~�~�~�~�~�~�~�~�~�~LMQR�������찟������������������������{�{���h$h�|�h1�0JOJQJ^JmH	sH	 h�|�h�(mOJQJ^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	)h�|�h1�0JB*CJaJmH	ph�sH	)h�|�h1�0JB*CJaJmH	ph�sH	%h�|�h1�B*CJaJmH	ph�sH	%�D�րـڀ����ÁƁǁ΁S�]�^�c���������3�G�Y�\�]�d��%�2�5�����9�M�\�_�"�%�&�v�y�z�����Y�n�q�r�������޺���ޔޔޔ��ޔޔ����ާ����ާ����������������h�|�h1�OJQJ^J$h�|�h1�0JOJQJ^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	 h�|�h1�OJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	1\�"�v���n��Ԉ����F�G�.�0�Ӌƌ�ȏR�O�������������������dhgd1��Jd]�Jgd1�gd1�dgd1�dgd1��Jd�d�d[$\$]�Jgd1�$�Jd�d�d[$\$]�Ja$gd1�
1$7$8$H$gd1���Ԉ׈��E�F���������G�J�ڊ�0�3�S�ыӋ֋؋ߋ��.�6�����Ō��ι�����n���n���]�����n�n�N�h�|�h1�OJQJmH	sH	 h�|�h1�OJQJ^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	 h�|�h1�OJQJ^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	+h�|�h1�CJOJQJ\�^JaJmH	sH	h�|�h1�OJQJ^Jh�|�h1�OJQJ\�^JŌƌnjʌˌ�����������ȏʏЏ������;�I�O�P������൝����z�x�e�Q>�z�$h�|�h1�0JOJQJ^JmH	sH	&h�|�h1�h|mxOJQJ^JmH	sH	$h�|�h1�0JOJQJ^JmH	sH	U#h�|�h1�OJQJ\�^JmH	sH	 h�|�h1�OJQJ^JmH	sH	.h�|�h1�5�CJOJQJ\�^JaJmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	+h�|�h1�CJOJQJ\�^JaJmH	sH	(h�|�h1�CJOJQJ^JaJmH	sH	h�|�h1�mH	sH	2011) Oxidative stress. Best Pract Res Clin Obstet Gynaecol 25: 287-299. Review. 
66. Sun W, Xie H, Ji J, Zhou X, Goltzman D, Miao D (2010) Defective female reproductive function in 1,25(OH)2D-deficient mice results from indirect effect mediated by extracellular calcium and/or phosphorus. Am J Physiol Endocrinol Metab 299: E928-35. 


 

















P�Q�R�U�M�P�Q�R�S�c�d����۸����z hE*Ch1�OJQJ^JmH	sH	h1�OJQJ^JmH	sH	&h�H�h1�h�,$OJQJ^JmH	sH	h�H�h1�mH	sH	 h�H�h1�OJQJ^JmH	sH	#h�|�h1�OJQJ\�^JmH	sH	 h�|�h1�OJQJ^JmH	sH	&h�|�h1�h|mxOJQJ^JmH	sH	
O�P�Q�S�T�U�V�W�X�Y�Z�[�\�]�^�_�`�a�b�c�d���������������������
$dha$gd1�gd1�dgd1�,1�h��. ��A!��"��#��$�n%�������CD���y������K����y������K��http://www.ncbi.nlm.nih.gov/pubmed?term=Staehling%20NW%255BAuthor%255D&cauthor=true&cauthor_uid=11836274=D���y������K����y������K��http://www.ncbi.nlm.nih.gov/pubmed?term=Hannon%20WH%255BAuthor%255D&cauthor=true&cauthor_uid=11836274=D���y������K����y������K��http://www.ncbi.nlm.nih.gov/pubmed?term=Gunter%20EW%255BAuthor%255D&cauthor=true&cauthor_uid=11836274?D���y������K����y������K��http://www.ncbi.nlm.nih.gov/pubmed?term=Spencer%20CA%255BAuthor%255D&cauthor=true&cauthor_uid=11836274CD���y������K����y������K��http://www.ncbi.nlm.nih.gov/pubmed?term=Braverman%20LE%255BAuthor%255D&cauthor=true&cauthor_uid=11836274j<���������666666666vvvvvvvvv666666>666666666666666666666666666�6666666666�666666666666hH66666666666666666666666666666666666666666666666666666666666666666�62���� 0@P`p������2(�� 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p��8X�V~ OJPJQJ_HmHnHsHtHT`�T�=�Standard(CJOJPJQJ_HaJmHnHsHtHl@l0�
�berschrift 1$$��@&'5�B*CJOJPJQJ\�^JaJph6_�l@l!�M�
�berschrift 2$$��@&'5�B*CJOJPJQJ\�^JaJphO��d@dnW��
�berschrift 3$$��@&5�B*OJPJQJ\�^JphO��j@j0�
�berschrift 4$$��@&%5�6�B*OJPJQJ\�]�^JphO��Z@Z0
�berschrift 5$@&5�OJPJQJ\�mHsHtHJA`�J
Absatz-StandardschriftartXi@�X
0Normale Tabelle�4�
l4�a�0k �0
0Keine Listef�o��f0�berschrift 5 Zchn*5�CJOJPJQJ\�^JaJmHsHtHb^@b00Standard (Web)��%B*CJOJPJ	QJ^JaJph333tH:�:0citation�d�d[$\$V�O"V0	auth_list!�d�dM�
����[$\$]��CJaJ^�o�2^0Default7$8$H$)B*CJOJQJ_HaJmHphsHtH	*�O�A*0	highlightr�o�Qr0��berschrift 4 Zchn55�6�B*CJOJPJQJ\�]�^JaJnHphO��tHl�o�al0�berschrift 1 Zchn/5�B*CJOJPJQJ\�^JaJnHph6_�tH6U`�q60	Hyperlink>*B*
ph3f�/�0stl�o�lnW���berschrift 3 Zchn/5�B*CJOJPJQJ\�^JaJnHphO��tH6X`�6nW�@Hervorhebung6�]��e@��{�HTML Vorformatiert7�2�(�
P�x�4 �#\'�*�.2�5@9$CJOJ	PJ	QJ	^J	aJmHsHtHj�o�j{�HTML Vorformatiert Zchn$CJOJ	PJ	QJ	^J	aJmHsHtH �O�� ��jrnl>�O�>D]DTitel1�d�d[$\$PJtH:�O�:D]Ddesc�d�d[$\$PJtH@�O@D]Ddetails �d�d[$\$PJtHl�o�l�M��berschrift 2 Zchn/5�B*CJOJPJQJ\�^JaJnHphO��tHb>@b#�M�Titel"�,P�O��m$)@�B*CJ4KHOJPJQJ^JaJ4ph6]^�o�1^"�M�
Titel Zchn1@�B*CJ4KHOJPJQJ^JaJ4nHph6]tH4BB4%�M0
Textk�rper$�xV�o�QV$�M0Textk�rper Zchn CJOJPJQJ^JaJnHtHXJ@X'�M�
Untertitel&
&#6�@�B*OJPJQJ]�^JphO��j�o�qj&�M�Untertitel Zchn36�@�B*CJOJPJQJ]�^JaJnHphO��tH��@����'�Tabellenraster7:V(�0������(d��mH	sH	@'`�@	rKq0KommentarzeichenCJaJ>@�>+rKq0
Kommentartext*CJaJ\�o�\*rKq0Kommentartext Zchn CJOJPJQJ^JaJnHtH>j@��>	-rKq0Kommentarthema,5�\�d�o��d,rKq0Kommentarthema Zchn&5�CJOJPJQJ\�^JaJnHtHP�@�P	/rKq0Sprechblasentext.CJOJ
QJ
^J
aJb�o��b.rKq0Sprechblasentext Zchn CJOJ
PJQJ
^J
aJnHtH&W`�&�"`Fett5�\�B��B�"apple-converted-space0��!0�"cit-pub-date,��1,�"
cit-source&��A&�"cit-vol*��Q*�"	cit-fpage ��a [L�name<�@r<[L� Listenabsatz	7^��m$4�o�4�Dreference-text6�O�6ldesc29CJPJaJtH^�`�^�q�0
�berarbeitung:(CJOJPJQJ_HaJmHnHsHtH$�/�$�sourcePK!����[Content_Types].xml���N�0E�H���-J��@%�ǎǢ|�ș$�ز�U��L�TB� l,�3��;�r��Ø��J��B+$�G]��7O٭V��<a���(7��I��R�{�pgL�=��r���8�5v&����uQ�뉑8��C����X=��$␴�?6N�JC������F�B.ʹ'�.�+���Y�T���^e5�5�� ��ð�_�g -�;�����Yl�ݎ��|6^�N��`�?���[��PK!�֧�6_rels/.rels���j�0���}Q��%v/��C/�}�(h"���O�
����=������ ����C?�h�v=��Ʌ��%[xp��{۵_�Pѣ<�1�H�0���O�R�Bd���JE�4b$��q_����6L�R�7`������0̞O��,�En7�Li�b��/�S���e��е�����PK!ky���theme/theme/themeManager.xml�M
� @�}�w��7c�(Eb�ˮ��C�AǠҟ����7��՛K
Y,�
�e�.���|,���H�,l����xɴ��I�sQ}#Ր���� ֵ+�!�,�^�$j=�GW��)�E�+&
8���PK!`�����theme/theme/theme1.xml�YOoE�#�F{oc'vGu�رhR��-�q�;ޝfvg53N�j�HH��8P�Tj%.����H�
���]��k����9���o���7����!)O�^�r�C$�y@�����/�yH*��񄴽)�޵��߻��UDb�`"�qۋ�Jח���X^�)I�٘�+�*¥@�#����Zmu)�4�P�c���{��ቒz�gb���
ppP�9�]&�!fmt�hH�)1,<h{5��-m\]���&��-�뛿l_�!8X6:E8*���֕�B�05��z�^��g��UkKYf��V��2K �q^v�֬5\|I�ʜͭN��le�X�d?6��k���沃7 �o����nw��ů��WZ�
o@��Z'��Ϥ�1gە�5���2��P��V1�ZXl1��Eɰ�	RӔ��%���HP�5�u�KO�/疴2$}AS�>L1��L��g?�|��z|�����d9��q�w����}��|�틇_V�e�ۏ�����@蟙9Ͽz����Ͽ���V�7��C�n�#��cp�Dŵ���v#L�;6�P�k-�{*r�7��e�q��7���G��c� E+4߈b��9�pQ�ZW)��IV+�2n��*�]�8��MR`μ,ǻq��c8Q8$	QH?��Txw�R'���\�Bw(�`Z�!9�4۴Mc�˴�gȷ��ۨ�Y��[��EBW`Va��0'���D�J�Ǭ���*#S�q=� �!a��ϴ��H�����@Y�i�e��E
E�d�`���-~Ѝp�Va4�����(F{\U�w��!�;�'�}�'ݧ��-:&�
D?���(^'ܩ���11T��puL�"nF�����#n����<���m��M8��zf�Q/��.}��yO�=
1ߧ��9{�yr^��O�3�ֳ�����/�ǔ���2�#��-��	���7��&)�aiu+�
l� ���TE��0��=-$���P��K�.��J�����ͦ��X�X��.���Q�1V��N�+Z�Ϊl�J&|{eumԙ�Սi�m��:��^!/\��"�0� �� ʫp�תᶃ	t�m��,\d�d���H�=���IR^+s�h?l1��)Q+iki����,I*�k,P�g�u��W�,K �d;��ܜ,AGm��\nz��i��E>�)d]�A�^5�Jز?��M�ϲ��s��/?l��vx Rma��0��`��d�_nBX/ʁ
6:�+kPo�
���Z2_��]Zѱ�_3*�E� 
�ЈM�>���R*�}�a����h�G.9gMW~'fpv�4����;��
!6�o%�Jۍs�wŴ��R.�+�<��+�΀/�F�S�*�BiD����pT���PT�z�/ȡ����a�n�j��HP8�T$�Z2�w��zvvY�,d*�d�L��#rH�Ps�>�=A�6�h��N֟�=�Q���r�9LV�������638��h�&��T�����-;��ƬF���t���E�y�Zƚ�x��Y����(��HH��>#����:��~�� l��/�i���#��-&-ʆ6�t����'�B�`k�Β�s��\uN/^d��;��kC
�=٢�4�o2&1�G��Y|t�?L�����*�a��>���֍���PK!
ѐ��'theme/theme/_rels/themeManager.xml.rels��M
�0���wooӺ�&݈Э���5
6?$Q��
�,.�a��i����c2�1h�:�q��m��@RN��;d�`��o7�g�K(M&$R(.1�r'J��ЊT���8��V�"��AȻ�H�u}��|�$�b{��P����8�g/]�QAsم(����#��L�[������PK-!����[Content_Types].xmlPK-!�֧�60_rels/.relsPK-!ky���theme/theme/themeManager.xmlPK-!`������theme/theme/theme1.xmlPK-!
ѐ��'�	theme/theme/_rels/themeManager.xml.relsPK]�
<?xml version="1.0" encoding="UTF-8" standalone="yes"?>
<a:clrMap xmlns:a="http://schemas.openxmlformats.org/drawingml/2006/main" bg1="lt1" tx1="dk1" bg2="lt2" tx2="dk2" accent1="accent1" accent2="accent2" accent3="accent3" accent4="accent4" accent5="accent5" accent6="accent6" hlink="hlink" folHlink="folHlink"/>�:������	�
@oz&�*�1�9�>D�GZIQU�W9]�`�b�c�fUlDpXt�xO{S}��ŌP�d�HJLMOPQRSTVWXYZ[\^_`acdfghjklnoq
��9,]�f�n�y\�O�d�IKNU]beimr��O������D�DE	ELEXEqY�Y�YZoZyZ|Z�Z�Z�Zh[s[v[�[�[�X��X��X���X��X��X����X����X����X����X�����L�#����@�����������0�(	�
��B
�S����	?������JS����}�D
M
�
�
�
�
4:svw�EGJY�b
c
�
�
HJ�/h��wy�AJOPXZ��������+,45ABqrz{����0145XYst��@A����DV�N����������)*IK`cjk����
������������  9 ; ? #!*!�$�$�%�%�%�%&�&''''�'�'�'q(w()),)-)T)[)�)�)�)�)F*K*�*�*�*�*�*�*�*�*++0+1+B+�,�,~-�-�-�-�-�.�.�.�.�.�.�.�.�.�.1/2/a/b/~//�/�/�/�/�/�/3040�0�0�0�2�255�5�5�6�67(7C7S7�7�788L8V8~8�8}9�9�:�:;;#;&;�=�=n>t>�?�?RBYBEDND�G�G�G�GsIwI�I�I�IJ�J�JXK^K�K�K,M2M>MEMFMM�M�M�M�M�M�M�N�N�N�N�N?O\P^P�P�P�P�PTR`RmRoR
SS�S�SU
U�U�U	VV
VVV'V(V5V:VEVNVZV]VcVdVgVhVqVrV{V�V�V�V�V�V�VWW
WWW!W%W+WrWwWxW�W�W�W�W�W�W�WXX�X�X�X�X�X�X�X�X�X�XGYKYLYSYdYmY�Y�Y�[�[�\�\�\�\�\�\�\�\�\�\�\�\%])]*]/]H]P]T]^]o]s]�]�]�]�]4^:^R^\^`^g^k^r^v^~^�^�^�^�^�^�^�^�^�^�^_ _!_(_C_H_L_R_V___�_�_�_�_�_```` `!`'`(`0`C`J`_`r`s`w`�`�`�`�`�`�`�`�`aa.a@a[a`apawa{a�a�a�aObTb�b�b�b�b�b�bc c%c+c/c6c�c�c�c�c�c�c�c�c�c�c�cdd
dddRdVdWdadcdfdzd�d�d�d�d�d�d�d�d�d�d�d�d�deeMeXe�e�effpftf�f�f�f�f�fg?gBgmgtgxg�g�g�g�g�g�g�g�g�g/h2hFhMhQhXhsh|hiiiiii(i.i�i�i�i�i�i�i�i�i�i�i�i�i�i�i�i�ijjjjj"j�j�j�j�j�j�j=kGkUkZkikokskzkl$l(l/l7lBlFlNlRlYl]ljlnlxl�l�l�l�l�l�lm
mm!mzm�m�m�m�m�m�m�m�m�mnn7n@nLnRnWn^n�n�n�n�n�n�nooo!o%o+o/o4o8o@oWo`o�opppp"p|p�p�p�p�p�p�p�pqqq q^qbqgqnq�q�q�q�q�q�q�q�q�q�qDrLr`rfrxr�r�r�r�r�r�r�r�r�r�rssss�s�s�s�s�stt t$t%t/t0t5tYt^t�t�t�t�t�t�tuuruwu|u�u�u�u�u�u�u�u�u�u�u�u�u�u�uvv�v�v�v�v�v�v�v�vw^wawhwkw~w�w�w�wIxOxPxVxkxrx�x�x�x�x�xy7y=y]yeyiyoyty{y�y�y�y�y�z�z�z�z�z�z�z�z{{#{({H{O{�{�{#|,|�|�|�|�|�|�|�|�|�|�|�|}}}(}/}3}:}@}E}�}�}�}�}�}�}~~.~9~=~G~�~�~�~�~�~�~��4�9�=�B�F�L�P�V�Z�_�c�i�����̀Ѐ�����������!�%�.�2�?�������������؁ށ����$�4�^�a�d�i�������������D�H�I�S�T�Y�o�v���������ƒɃ̓Ѓ�
���l�s���������������������ĄɄ̈́քڄ�g�k�l�p�������ƅ˅υЅօׅ߅���
���ˆ҆ӆ݆ކ�
�EGfh%"%�)�)T+d+�6�6�J�J5W8W�W�W�X�X�\�\�]�]�`�`BaKaHcQc�e�e�e�eEfaf\gcg&h(h�i�i�i�i=kNk�mn�pq+q.qrr�r�rCtJt#u+u�v]w�y�y�y�y����ƆȆ
�333333333333333333333333333333333333�����
�
�1�1S<[<n?y?�U�U�i�i
�uCx��I���������U�ŨV���������;j(	 @X���������&]>��g����������k�
\n����������+>�����������l�������������o�/~���������\��;6����������cO#�����������*����!����������-� ,�LD����������y.&h�4�����������C,V�"�����������Q~.TuR���������FNk3�$t-���������CA34������������(�D�A����������{NdI�OJ����������a�L&+f}���������g.ZM�����������A�Qʏ�7���������V{6S�U�����������CT�������������`�RJ���������5_Cb$#�����������A}�b�p����������zy�qJ7���������iK�{�"�����������M�}KtA����������������^��`���OJQJo(" �������^��`���OJQJo(" ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �8���^�8`���o(.�
����^�`����h�H.�
��	�L�^��	`�L��h�H.�
�����^��`����h�H.�
�x���^�x`����h�H.�
�H�L�^�H`�L��h�H.�
����^�`����h�H.�
�����^��`����h�H.�
���L�^��`�L��h�H.�������^��`���OJQJo(" W�h����h^�h`���OJQJo( ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �������^��`���OJQJo(" ��������^��`���OJQJo(" ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �����^��`���o(.�
�����^��`����h�H.�
�p�L�^�p`�L��h�H.�
�@���^�@`����h�H.�
����^�`����h�H.�
���L�^��`�L��h�H.�
�����^��`����h�H.�
�����^��`����h�H.�
�P�L�^�P`�L��h�H.�������^��`���CJOJQJo(����������^��`���CJOJQJo(o��p����p^�p`���CJOJQJo(����@����@^�@`���CJOJQJo(��������^�`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����P����P^�P`���CJOJQJo(���h���^�h`���o(.�
�8���^�8`����h�H.�
��L�^�`�L��h�H.�
��	���^��	`����h�H.�
�����^��`����h�H.�
�x�L�^�x`�L��h�H.�
�H���^�H`����h�H.�
����^�`����h�H.�
���L�^��`�L��h�H.�������^��`���CJOJQJo(����������^��`���CJOJQJo(o��p����p^�p`���CJOJQJo(����@����@^�@`���CJOJQJo(��������^�`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����P����P^�P`���CJOJQJo(���������^��`���OJQJo(" H�������^��`���OJQJo( ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �������^��`���.��������^��`���.��p����p^�p`���.��@����@^�@`���.������^�`���.��������^��`���.��������^��`���.��������^��`���.��P����P^�P`���.�������^��`���CJOJQJo(����������^��`���CJOJQJo(o��p����p^�p`���CJOJQJo(����@����@^�@`���CJOJQJo(��������^�`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����P����P^�P`���CJOJQJo(���������^��`���OJQJo(" ��������^��`���OJQJo(" ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �������^��`���CJOJQJo(����������^��`���CJOJQJo(o��p����p^�p`���CJOJQJo(����@����@^�@`���CJOJQJo(��������^�`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����P����P^�P`���CJOJQJo(���������^��`���CJOJQJo(����������^��`���CJOJQJo(o��p����p^�p`���CJOJQJo(����@����@^�@`���CJOJQJo(��������^�`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����P����P^�P`���CJOJQJo(���������^��`���.��������^��`���.��p����p^�p`���.��@����@^�@`���.������^�`���.��������^��`���.��������^��`���.��������^��`���.��P����P^�P`���.�������^��`���OJQJo(" ��������^��`���OJQJo(" ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �������^��`���CJOJQJo(����������^��`���CJOJQJo(o��p����p^�p`���CJOJQJo(����@����@^�@`���CJOJQJo(��������^�`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����P����P^�P`���CJOJQJo(���������^��`���CJOJQJo(����������^��`���CJOJQJo(o��p����p^�p`���CJOJQJo(����@����@^�@`���CJOJQJo(��������^�`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����P����P^�P`���CJOJQJo(���������^��`���OJQJo(" ��������^��`���OJQJo(" ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �������^��`���OJQJo(" ��������^��`���OJQJo( ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �������^��`���.��������^��`���.��p����p^�p`���.��@����@^�@`���.������^�`���.��������^��`���.��������^��`���.��������^��`���.��P����P^�P`���.�������^��`���.��������^��`���.��p����p^�p`���.��@����@^�@`���.������^�`���.��������^��`���.��������^��`���.��������^��`���.��P����P^�P`���.�������^��`���OJQJo(" ��������^��`���OJQJo( ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �������^��`���CJOJQJo(����������^��`���CJOJQJo(o��p����p^�p`���CJOJQJo(����@����@^�@`���CJOJQJo(��������^�`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����P����P^�P`���CJOJQJo(���������^��`���OJQJo(" ��������^��`���OJQJo( ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �����^��`���OJPJQJ^Jo(*������^��`���OJQJ^Jo(�h�Ho��p���^�p`���OJQJo(�h�H����@���^�@`���OJQJo(�h�H�������^�`���OJQJ^Jo(�h�Ho������^��`���OJQJo(�h�H��������^��`���OJQJo(�h�H��������^��`���OJQJ^Jo(�h�Ho��P���^�P`���OJQJo(�h�H���������^��`���CJOJQJo(����������^��`���CJOJQJo(o��p����p^�p`���CJOJQJo(����@����@^�@`���CJOJQJo(��������^�`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����������^��`���CJOJQJo(����P����P^�P`���CJOJQJo(���������^��`���OJQJo(" ��������^��`���OJQJo( ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �������^��`���OJQJo(" ��������^��`���OJQJo(" ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �������^��`���OJQJo(" ��������^��`���OJQJo( ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �(�Dg.ZM�*��A�QcO#A}�b�y.&�CTFNk3��`{NdIV{6S�-� iK�{�zy\�;j(	�C,+�Q~.&]>uCx�a�L�M�}�k�
U�l5_CbCA34�o������������������������������������������������������������������������������������������������������������������������������,Efrxv�dXS`��g�ڰ�*�Z�hp���v-|��ZX��Y|t�f��`L6#~*���$�D����8��>2T�Ŏ�^���R-6P�M,�L��j5Z�8Ґ�4�T:8���H0���Q���بi�>"p���W>���Pj���b�$�Y��8�0�.�2�R��h�:�ނ[�v�3��.���>�D`hC��}zx \$�U�Z��"��S*XṆ��栖��M$>߰��ֶ���J-@:��X�FV�s�Fr#
:�����@�>��u��]Б��.q���g��_PS�o@p��2脽�LC�]�j��N0 [��|�\4FC����@�bHd���3&�?��fE�5Dh����.���{��v?���jd���1��~��i�����!zf$3@��H?p��;�T�x�ڜ:hԬP�6�x誖ĞЌL'���VW��.���dX�r���g,|F~CPcX�(m�|�1��A���/�?9��z��)����
��@~~~@�7�8������@�@��@����@��Unknown������������G��*�Ax�	�Times New Roman5��Symbol3.��*�Cx�	�Arial7.���@�Calibri;�����|�i0�Batang���C �ArialMTArial;���(SimSun�[SO7���@�Cambria9���GaramondI.����������?�?Arial Unicode MS5.��.�[`�)�Tahoma?=�	�*�Cx�	�Courier New;��WingdingsA���$B�Cambria Math"q����������$'�tD���tD��������24ĆĆ$��$
N�q���HX	�	$P����������������������02!
xx����}Dietary Supplementation improves blastocyst number   and clinical pregnancy rate of IVF Patients with Hashimoto s ThyroiditisBirgit#IVF-Bregenz - Dr. Maximilian Schuff�	

����Oh��+'��0�x�(	T`��
�������Dietary Supplementation improves blastocyst number � and clinical pregnancy rate of IVF Patients with Hashimoto�s ThyroiditisBirgitNormal$IVF-Bregenz - Dr. Maximilian Schuff2Microsoft Office Word@L���@�+�m�@�+�m��t����՜.��+,��D��՜.��+,���lhp��������
�N�Microsoft�DĆ~Dietary Supplementation improves blastocyst number � and clinical pregnancy rate of IVF Patients with Hashimoto�s ThyroiditisTitel� 8@_PID_HLINKS�A�<L;ihttp://www.ncbi.nlm.nih.gov/pubmed?term=Braverman%20LE%255BAuthor%255D&cauthor=true&cauthor_uid=11836274!Sghttp://www.ncbi.nlm.nih.gov/pubmed?term=Spencer%20CA%255BAuthor%255D&cauthor=true&cauthor_uid=11836274cVfhttp://www.ncbi.nlm.nih.gov/pubmed?term=Gunter%20EW%255BAuthor%255D&cauthor=true&cauthor_uid=11836274yVfhttp://www.ncbi.nlm.nih.gov/pubmed?term=Hannon%20WH%255BAuthor%255D&cauthor=true&cauthor_uid=11836274_-ihttp://www.ncbi.nlm.nih.gov/pubmed?term=Staehling%20NW%255BAuthor%255D&cauthor=true&cauthor_uid=11836274M5http://www.dict.cc/englisch-deutsch/arrhythmias.htmlK	1http://www.dict.cc/englisch-deutsch/cardiac.htmlymailto:n.zech@ivf.at)_$mailto:Birgit.schechinger@yahoo.comkmailto:j.wogatzky@ivf.at	

 !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrs����uvwxyz{����}~������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������Root Entry��������	�F@��.�m���Data
������������t1Table��������|N�WordDocument����.�SummaryInformation(�������������DocumentSummaryInformation8���������Macros
�,v.�m��,v.�m�VBA��������	�,v.�m��,v.�m�dir������������ThisDocument
����
_VBA_PROJECT������������"�PROJECT����Q�	
���� !����#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOP����RSTUV��������Y��������������������������������������������������������������������������������������������������������������������������������������������������������������0*�	pH�d�ProjectQ(@=�
l	�ݳ�RJ<
rstdole>stdoleP
h%^*\G{00020�430-C
0046}#2.0#0#C:\Windows\SysWOW64\e2.tlb#OLE Aut�omation`�ENormal�EN�CrmaQ�F �	�*\C
=�R�!Offic�gOf�ic�g����!G{2DF8D04C-5BFA-101@B-BDE5�gAjA�e4�2�g��gram Files (x86)\@Common	\Microsoft Shared\OFFICE14\MSO.DLL#��P 14.0 Ob�� Li`brary'�zMSF@Cs>��MSFDHs3@�eD452EE1-E�08F�1A-8-02608C4 D0BB4�eFMl20L'B @r�&/�;"1�ă�}��Ã00}#0ƒ�#���50��	��A8CCB65C4-8365-49A3-A9EA-B3D52�1D5540A�6 Users[CHUF~1.IVF\AppData\Local\Temp\Word8.0�	�9.exdf�>@$��.E
���.@`�M���������ThisDocumentG�	T�isD@ncu��enU��2�`	TH�1�z9`��"�,�W$""
+��I�-3�����3��W$�����������������������������x*DefaultOcxName1, 1, 2, MSForms, HTMLHidden)DefaultOcxName, 0, 3, MSForms, HTMLHidden��ME�����������������������������������������������������������������������������������������������������������������������������������������������(S"����S����S"����s������(1Normal.ThisDocument����������(����������%%*�)h����0��������������%*�+��������`������������������h����X*�+ �����������������������(*�) �����������������������0������������8����������������h����������������������������������������������������*\R8005*#83�����������x����۰Attribute VB_Name = "ThisDocument"

�Bas�1Normal.VGlobal!�SpaclFalse�CreatablPre declaId�Tru
BExposeTemplateDeriv$Customiz�C�1Control��Defa@ultOcx�m1, 2, MSF��s, HTM�LHidden���", 0, 3�!�a��	��*\G{000204EF-0000-0000-C000-000000000046}#4.1#9#C:\PROGRA~2\COMMON~1\MICROS~1\VBA\VBA7\VBE7.DLL#Visual Basic For Applications*\G{00020905-0000-0000-C000-000000000046}#8.5#0#C:\Program Files (x86)\Microsoft Office\Office14\MSWORD.OLB#Microsoft Word 14.0 Object Library�*\G{00020430-0000-0000-C000-000000000046}#2.0#0#C:\Windows\SysWOW64\stdole2.tlb#OLE Automation*\CNormal*\CNormal=�R4*\G{2DF8D04C-5BFA-101B-BDE5-00AA0044DE52}#2.5#0#C:\Program Files (x86)\Common Files\Microsoft Shared\OFFICE14\MSO.DLL#Microsoft Office 14.0 Object Library�*\G{0D452EE1-E08F-101A-852E-02608C4D0BB4}#2.0#0#C:\Windows\SysWOW64\FM20.DLL#Microsoft Forms 2.0 Object Library*\G{8CCB65C4-8365-49A3-A9EA-B3D521D5540A}#2.0#0#C:\Users\MSCHUF~1.IVF\AppData\Local\Temp\Word8.0\MSForms.exd#Microsoft Forms 2.0 Object Library�.E
���.`�M���������ݳ�R����������������������������������������������������������������ThisDocument0552bab3de��ThisDocument��W$9������ �����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������z�P�3�O�5�������������`��'Word�kVBA��Win16�~Win32Win64xMac��VBA6�#VBA7�#Projekt1�Astdole�`Project-�ThisDocument<�	��_Evaluate�Normal����Officeu��MSFormsCDefaultOcxName�DefaultOcxName1#�Documentj�DefaultOcxName11.DefaultOcxName2$���`������"��$��&����
��������������������������������������������������ID="{5330A508-EBCC-46BB-AF99-23A24ACE903D}"
Document=ThisDocument/&H00000000
Name="Project"
HelpContextID="0"
VersionCompatible32="393222000"
CMG="90926E9472947294729472"
DPB="2022DE21DF21DF21"
GC="B0B24EB14FB14F4E"

[Host Extender Info]
&H00000001={3832D640-CF90-11CF-8E43-00A0C911005A};VBE;&H00000000
&H00000002={000209F2-0000-0000-C000-000000000046};Word8.0;&H00000000
ThisDocumentThisDocumentPROJECTwm������������W)CompObj������������Xr��������������������������
����	�F Microsoft Word 97-2003-Dokument
MSWordDocWord.Document.8�9�q

Youez - 2016 - github.com/yon3zu
LinuXploit