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"LATAR BELAKANG: Anti Mullerian Hormon (AMH) adalah anggota dari golongan Transforming Growth Factor-β yang berperan dalam pengaturan folikuligenesis pada reproduksi wanita. Peningkatan kadar AMH 2 sampai 3 kali dijumpai pada pasien SOPK (Sindrom Ovarium Polikistik) daripada wanita dengan ovulasi normal. Pada penelitian ini dideteksi varian sekuen disepanjang daerah promoter gen AMH. Adanya variasi promoter gen AMH diduga mempengaruhi proses transkripsi gen AMH yang selanjutnya berimplikasi pada pembentukan protein AMH. Apabila terjadi gangguan pada pembentukan protein AMH maka akan berpengaruh terhadap kadar protein tersebut di dalam darah. BAHAN DAN CARA KERJA: Sampel penelitian ini berjumlah 114 pasien yang terdiri dari 60 pasien SOPK dan 54 pasien non SOPK (Kontrol). Kadar AMH dan Jumlah folikel antral didapatkan dari data rekam medik pasien Klinik IVF Yasmin, RSCM Kencana Jakarta. Analisis molekuler dan genotyping dilakukan dengan teknik PCR dan sekuensing kemudian dilanjutkan dengan analisis bioinformatika. HASIL : Dari penelitian ini ditemukan 60 titik varian mutasi promoter gen AMH. Jenis varian mutasi terbesar yang ditemukan adalah -674 G/A (100 %), -245 C/CT (88,2 %), dan -444 A/G (17,9 %) dari seluruh sampel. Berdasarkan hasil uji Wilcoxon Signed Ranks, pada kelompok SOPK ditemukan jumlah mutasi yang terjadi berpengaruh secara bermakna terhadap kadar AMH dan jumlah folikel antral (p<0,05). Pada kelompok kontrol ditemukan bahwa jumlah mutasi tidak berpengaruh secara bermakna terhadap kadar AMH (p>0,05), tetapi berpengaruh secara bermakna terhadap jumlah folikel antral (p<0.05). Ditemukan 60 titik varian pada promoter gen AMH. Jumlah mutasi pada promoter gen AMH berpengaruh terhadap kadar AMH dan jumlah folikel antral pada SOPK. Mutasi pada titik -674 G/A merupakan titik mutasi baru yang belum pernah dilaporkan oleh NCBI, ditemukan pada seluruh subyek penelitian baik kelompok SOPK maupun non SOPK.

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INTRODUCTION : Anti-Mullerian Hormone (AMH) is a member of the Transforming Growth Factor-β group which plays an important role in the regulation of the female reproductive folliculogenesis. A 2-3 fold increase in AMH levels was found in patients with PCOS (Polycystic Ovary Syndrome) compared to women with normal ovulation. This study detected sequence variants in the AMH gene promoter region. The AMH gene promoter variation is thought to affect AMH gene transcription process implicated in the formation of proteins. In the event of disruption in the formation of these AMH proteins, the levels of these proteins in the blood will be affected. The purpose of this study was to detect variants of AMH gene promoter sequences.

MATERIALS AND METHODS: The sample size was 114 patients consisting of 60 PCOS patients and 54 non-PCOS patients as control. The AMH levels and anthral follicle number obtained from the patients? medical records of the Yasmin IVF Clinic, RSCM Kencana Hospital, Jakarta. Molecular analysis and genotyping were performed by PCR and sequencing was followed by bioinformatics analysis.

RESULTS: There were 60 point mutations in the AMH gene promoter variants. The highest variant types of mutations found was -674 G/A (100%), followed by -245 C/CT (88.2%), and -444 A/G (17.9%) in the entire sample. Based on the results of the Wilcoxon Signed Rank test, the number of mutations in the PCOS group were significant to effect the serum AMH level and the anthral follicle number (p<0.05). In the control group, the number of mutations had no significant effect on the levels of AMH (p>0.05), but significantly affected the number of anthral follicles (P<0.05). There were 60 point variances in the AMH gene promoter. The number of mutations in the gene promoter affected serum AMH levels and the number of anthral follicles in PCOS. A new point mutation was found in all subjects at position -674 G/A, which have not been reported by the NCBI."

"Pendahuluan: Sindrom Ovarium Polikistik SOPK merupakan gangguan endokrin tersering penyebab infertifilitas pada wanita usia reproduktif. Wanita-wanita dengan SOPK diketahui memiliki tingkat apoptosis yang rendah dibandingkan dengan wanita tanpa SOPK dan memiliki kadar Anti-Muellerian Hormone AMH yang lebih tinggi dibandingkan dengan wanita tanpa SOPK. Akan tetapi, belum ada penelitian yang menghubungkan kadar AMH dengan apoptosis yaitu adanya atresia folikel pada ovarium wanita penderita SOPKTujuan: Untuk mengetahui hubungan antara kadar AMH yang tinggi dengan tingkat apoptosis sel granulosa yang terjadi pada pasien SOPK sehingga dapat diketahui salah satu patogenesis kelainan folikulogenesis pada pasien SOPKMetodologi: Studi cross sectional dengan mengambil sampel sel granulosa wanita SOPK dan tanpa SOPK atau kelainan ovarium yang mengikuti program Fertiisasi In Vitro FIV di Yasmin dan SMART-IVF, klinik dr. Sander B Jakarta. Jumlah sampel yaitu 40 sampel yang terdiri dari 20 wanita dengan SOPK dan 20 wanita tanpa SOPK. Tingkat apoptosis dievaluasi dengan mengukur ekspresi mRNA dari gen pengkode protein keluarga apoptotic Bcl2 Bax dan Bcl2 menggunakan metode kuantitatif absolut qPCR. Pengukuran kadar AMH di serum dilakukan dengan metode ELISA.Hasil: Terdapat perbedaan bermakna secara statistik antara kadar AMH wanita SOPK dan kontrol pABSTRACT Background Polycystic Ovary Syndrome PCOS is a common endocrine abnormality in causing infertility in reproductive aged women. Women with PCOS were reported have lower apoptosis rate compared to women without PCOS and have higher level Anti Muellerian Hormone compared to women without PCOS. However, there are no reported studies which directly study to know correlation between AMH level in serum and apoptosis result in follicle atresia in ovarium of PCOS patients.Objective To analysis correlation between serum AMH level and apoptosis in granulosa cell in PCOS pasien that may underlie the folliculogenesis abnormality in PCOS.Methods Cross sectional study of sample from granulose cells women with PCOS and without PCOS or with ovarian abnormalities that following Fertility In Vitro FIV program in Yasmine and SMART ndash IVF, dr. Sander B clinic, Jakarta. Sample number were 40 consisting 20 women with PCOS and 20 women without PCOS. Apoptosis level were evaluated with measuring mRNA expression from gene that of coding apoptotic Bcl2 family Bax and Bcl2 using quantitave absolute method qPCR. AMH level in serum were measured using ELISA method.Results There was a statistical significance difference AMH level between PCOS group and control group p"

"Sindrom Ovarium Polikistik (SOPK) didefinisikan sebagai kelainan hormonal multifaktorial yang ditandai dengan berlebihnya jumlah hormon androgen, menstruasi yang irregular dan atau morfologi ovarium yang berukuran besar serta berkista-kista. SOPK dapat berujung pada berbagai komplikasi, seperti penyakit kardiovaskular, resistensi insulin, serta infertilitas. Studi-studi sebelumnya menunjukkan bahwa patogenesis SOPK dapat berkaitan dengan faktor genetik, non-genetik, maupun epigenetik. Salah satu faktor epigenetik yang diduga berperan adalah metilasi dari DNA gen Anti-Mulerian Hormone (AMH). Gen AMH menghasilkan suatu produk berupa hormon, yakni hormon AMH yang terbukti ditemukan meningkat secara signifikan pada serum pasien SOPK. Untuk mengevaluasi peranan faktor epigenetik berupa metilasi DNA gen AMH pada patogenesis SOPK, dilakukan suatu penelitian potong lintang menggunakan sampel dari jaringan granulosa ovarium. Sampel diperoleh dari 14 wanita dengan SOPK dan 9 kontrol. DNA dari sampel diisolasi untuk kemudian dikonversi bisulfit dan diamplifikasi menggunakan metode Methyl Specific PCR (MSP). Hasil amplifikasi kemudian diamati dengan menggunakan gel elektroforesis dan intensitas pita yang tampak dibawah sinar ultraviolet dikuantifikasi dengan cara konversi kedalam bentuk numerik menggunakan perangkat lunak ImageJ. Data yang diperoleh dianalisis secara statistik menggunakan uji Mann-Whitney dengan signifikansi ditetapkan apabila p<0.05. Dari hasil analisis ditemukan perbedaan yang signifikan antara persentase metilasi DNA pada pasien SOPK dengan kontrol (p=0.002), dimana pasien SOPK cenderung memiliki tingkat metilasi DNA gen AMH yang lebih rendah dibandingkan dengan kontrol. Hasil tersebut mengindikasikan bahwa rendahnya tingkat metilasi DNA gen AMH pada pasien SOPK dapat meningkatkan ekspresi dan produksi AMH. Peningkatan AMH tersebut diduga berkontribusi dalam patogenesis SOPK.

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Polycystic Ovarian Syndrome (PCOS) defined as a multifactorial hormonal disorder that is characterized by androgen excess, irregular periods, and or enlarged ovarium with cystics morfology. PCOS leads to many complications, such as cardiovascular disease, insulin resistance, and infertility. Previous studies showed that the pathogenesis of PCOS correlated with genetic, non-genetic, and epigenetic factors. One of epigenetic factors that is suspected to play a role is the DNA methylation of Anti-Mullerian Hormone (AMH) gene. AMH gene produces a hormone, called AMH, of which found to elevate in the serum of PCOS patient. To evaluate the contribution of AMH gene DNA methylation in the pathogenesis of PCOS, this cross-sectional study using ovarian granulose cells sample was performed. Samples were obtained from 14 PCOS patient and 9 control. The DNA from each sample was isolated, converted by bisulfite conversion, and amplificated by Methyl Specific PCR (MSP) method. After being amplificated, samples then were observed by using electrophoresis gel and the band intensity that was appeared under ultraviolet was quantified by conversion to numeric form by using ImageJ software. The obtained data statistically analyzed by Mann-Whitney test with significant result considered to p<0.05. The analysis result showed that there was a significant difference between DNA methylation percentage in PCOS group and control group (P=0.002), of which PCOS patient tend to have a lower AMH gene DNA methylation compared to control. This finding indicates that the lower AMH gene DNA methylation in PCOS patient may increase the expression and production of AMH. This elevation of AMH suspected to play a role in the pathogenesis of PCOS."

"Latar Belakang: SOPK dijumpai pada 5-20% perempuan usia reproduksi. AMH digunakan sebagai penanda SOPK karena pada penderita SOPK salah satu gejalanya adalah terjadinya anovuasi yang menyebabkan peningkatan kadar AMH. SOPK juga berkaitan dengan adanya resistensi insulin dan hiperandrogen yang berkorelasi dengan obesitas dan inflamsi kronik yang dapat menyebabkan risiko terjadinya sindrom metabolik.Tujuan: Mengetahui hubungan peningkatan kadar AMH pada penderita SOPK dan fenotip SOPK dengan kejadian Sindrom Metabolik.Metode: Penelitian ini menggunakan disain potong lintang di RSUPN Cipto Mangunkusumo pada penderita SOPK pada bulan Januari 2013 hingga Desember 2017. Data penderita SOPK yang memenuhi kriteria inklusi dicatat dan dilakukan analisis statistik.Hasil: Dari pengumpulan data Januari 2013 hingga Desember 2017 di RSUPN Cipto Mangunkusumo didapati 109 kasus SOPK yang memenuhi kriteria inklusi. Penderita SOPK tesebut memiliki median kadar AMH 7.10 ng/ml (3.11-34.06) dan yang mengalami sindrom metabolik 21% dengan median kadar AMH 7.21ng/ml (2.83-20.20) yang lebih tinggi dibandingkan yang tidak sindrom metabolik (p=0.387). Sedangkan untuk fenotip yang terbanyak adalah fenotip 4 (OA dan PCOM) yaitu 41.3% dan yang mengalami sindrom metabolik terbanyak adalah fenotip 1 (OA+PCOM+HA)  sebanyak 56.5% dengan median kadar AMH  yang tertinggi sebesar 13.92ng/ml.Kesimpulan: Kadar AMH pada penderita SOPK yang mengalami sindrom metabolik  trend nya lebih tinggi dibandingkan yang tidak sindrom metabolik. Fenotip 1 (OA+PCOM+HA) adalah kelompok fenotip yang paling banyak mengalami sindrom metabolik.

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Background: PCOS is present in 5-20% women of reproductive age. AMH is used as a marker because one of the sign is anovulation that cause elevated AMH level. PCOS is also associated with the presence of insulin resistance and hyperandrogen that correlate with obesity and chronic inflammation that will increase the risk of metabolic syndrome.Purpose: To evaluate the correlation between AMH level in PCOS patients with the incidence of Metabolic Syndrome.Method: This research used cross sectional design with consecutive sampling. Data that fulfilled the inclusion criteria were collected and analyzed.Result: Data collection from January 2013 to December 2017 at RSUPN Cipto Mangunkusumo found 109 cases of PCOS meet the inclusion criteria. Patients with PCOS have median level of AMH 7.10 ng/ml (3.11-34.06). Twenty one percent of the patient had metabolic syndrome with median level of AMH 7.21ng/ml (2.83-20.20) higher than non-metabolic syndrome (p = 0.387). The largest number of phenotypes on PCOS patients is phenotype 4 (OA and PCOM) which is 41.3%. Most metabolic syndrome is phenotype 1 (OA + PCOM + HA) as much as 56.5% with median highest AMH level of 13.92 ng/ml.Conclusion: AMH levels in patients with PCOS who have metabolic syndrome are higher than non-metabolic syndrome. Phenotype 1 (OA + PCOM + HA) is a group of phenotypes with the most metabolic syndrome."

"Sindrom ovarium polikistik (SOPK) merupakan suatu kondisi umum endokrinopati yang ditandai dengan adanya oligoovulasi atau anovulasi, produksi androgen berlebih, dan adanya kista ovarium kecil multipel yang diidentifikasi secara sonografis (kriteria Rotterdam, 2004). SOPK ditemukan pada 10% populasi wanita usia reproduksi dan berhubungan erat dengan disfungsi ovulasi sehingga menurunkan angka fertilitas. Tujuan penelitian ini adalah untuk mengetahui pengaruh terapi kombinasi elektroakupunktur dan medikamentosa terhadap SOPK. Uji klinis acak tersamar ganda dengan kontrol dilakukan terhadap 44 subjek dengan SOPK yang dialokasikan secara acak ke dalam kelompok elektroakupunktur sejati dan medikamentosa (n=22), serta kelompok elektroakupunktur sham dan medikamentosa (n=22). Penilaian menggunakan pencitraan USG transvaginal dan perhitungan panjang siklus menstruasi sebelum dan sesudah perlakuan. Hasil penelitian menunjukkan terdapat perbedaan bermakna rerata volume ovarium antara kedua kelompok sebelum dan sesudah perlakuan (p=0,002); penurunan jumlah folikel antral (p=0,005); angka kejadian menstruasi (p=0,001); dan pemendekan siklus menstruasi (p=0,003). Kesimpulan penelitian ini elektroakupunktur dan medikamentosa memberikan perbaikan terhadap keluhan dan gambaran ovarium pada pasien SOPK.

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Polycystic Ovarian Syndrome (PCOS) is a general endocrinopathy condition that signed with oligoovulation or anovulation cycle, excess androgen production, and an image of multiple small cysts identified by transvaginal ultrasound (Rotterdam criteria, 2004). PCOS found in 10% of reproductive women and highly corresponded with ovulation dysfunction and finally decrease the fertility rate. The goal of this study is to know the effect of electroacupuncture combined with medical treatment in PCOS. A double blind randomized controlled trial is performed in 44 subjects with PCOS and divided into true electroacupuncture combined with medical treatment group (n=22) and sham electroacupuncture combined with medical treatment group (n=22). Ovarian volume and antral follicle are evaluated with transvaginal ultrasound and the length of menstrual cycle is counted before and after the treatment. The results show there are significant mean differences between ovarian volume in two groups before and after treatment (p=0,002); antral follicle count (p=0,005); menstrual incidence during the treatment (p=0,001); and shortened menstrual cycle (p=0,003). The conclusion of this study is electroacupuncture combined with medical treatment could improve PCOS patients’ compaint and ovarian image."

"TUJUAN: Mengetahui efek metformin atau DLBS3233 terhadap kadar AMH. LATAR BELAKANG: SOPK merupakan sindrom yang diketahui berkaitan dengan resistensi insulin dalam patofisiologi dan peranan AMH dalam patogenesis. Maka salah satu bagian dari tatalaksana SOPK adalah dengan pemberian insulin sensitizing agent ISA. ISA yang telah banyak digunakan yaitu metformin yang terbukti dalam memperbaiki siklus haid, namun obat ini juga menimbulkan efek samping seperti keluhan gastrointestinal yang cukup berat. Sehingga perkembangan obat herbal seperti fraksi bioaktif DLBS3233 memberikan harapan akan ISA yang efektif, namun memiliki efek samping minimal. Peranan ISA dalam efek perubahan AMH masih kontroversial, dan hanya ditemui penelitian yang meneliti metformin. DESAIN DAN METODE: Penelitian ini menggunakan desain uji klinis acak tersamar ganda yang berlangsung pada bulan Maret 2013 hingga Juni 2015 di klinik Yasmin, RSCM Kencana dan RS Hasan Sadikin, Bandung. Subjek penelitian akan mendapatkan metformin sebanyak 2x750mg atau DLBS3233 1x100mg per hari selama enam bulan. Evaluasi kadar AMH akan dilakukan sebanyak dua kali, sebelum dan sesudah pengobatan. HASIL: Sebanyak 20 subjek mendapati metformin dan 18 subjek mendapati DLBS3233. Rerata kadar AMH sebelum pengobatan didapati 9,30 5,06 ng/mL dan 11,27 6,47 ng/mL. Pasca pengobatan, didapati penurunan kadar AMH yang signifikan sebesar 1,52 0,07 p < 0,001. Penurunan kadar AMH didapati lebih tinggi pada grup metformin bila dibandingkan dengan DLBS3233 ? AMH = 1,83 ng/mL vs 1,15 ng/mL. Namun, metformin menimbulkan efek samping yang lebih signifikan dibandingkan DLBS3233 p=0,01. Sebanyak 7 pasien 18,42 hamil selama penelitian ini. Namun efek samping pengobatan jauh dirasakan oleh subjek yang mendapatkan metformin dibandingkan DLBS3233 p=0,01. KESIMPULAN: Baik metformin atau fraksi bioaktif DLBS3233 dapat menurunkan kadar AMH, dan DLBS3233 merupakan pilihan terapi SOPK dengan efek samping yang minimal.

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OBJECTIVE: To determine the effect of metformin and DLBS3233 on serum AMH level.

BACKGROUND: PCOS is known to be associated with insulin resistance in the pathophysiology and Anti Mullerian Hormone AMH in the pathogenesis. Thus, one of management of PCOS is to give insulin sensitizing agent ISA. Type of ISA which has been widely used is metformin which proven to improve menstrual cycle, but this medication cause major side effect such as gastrointestinal problems. So, the development of herbal medicine such as Bioactive Fraction DLBS3233, offer effective medicine, with minimal side effects. To date, the role of ISA to effects the changes in AMH still controversial, and studies only examine the effect of metformin to the level of AMH.

METHOD: Double blind randomized controlled trial was conducted in Yasmic Clinic, Cipto Mangunkusumo General Hospital, Kencana and Hasan Sadikin hospital, Bandung within March 2013 until June 2015. PCOS patient diagnosed using Rotterdam All participant get daily dose of metformin 2x750mg or DLBS3233 1x100mg for six months. Evaluation of serum AMH level was conducted twice prior therapy and after the completion of the therapy. Protocol analysis was carried out upon differences of AMH using SPSS 20.

RESULTS: 20 subjects received metformin, while 18 subject received DLBS3233. Level of AMH prior medication was known to be 9,30 5,06 ng mL and 11,27 6,47 ng mL. After six months of therapy, there is significant decrease of AMH level of 1,52 0,07 p 0,001. The decrease level of AMH was observed higher in metformin group compared to DLBS3233 AMH 1,83 ng mL vs 1,15 ng mL. However, metformin causing more side effects compared to DLBS3233 p 0,01. There are total of 7 subjects 18,42 pregnant during the studies.

CONCLUSION: There rsquo s a significant decrease of AMH level after administration of either metformin or DLBS3233. "

"Ketimpangan antara kadar vitamin D25(OH) rendah dan keadaan resistensi insulin pada penderita SOPK dengan anovulasi kronik menarik untuk digali lebih jauh. Anovulasi kronik pada SOPK diyakini disebabkan terhentinya pertumbuhan folikel di ovarium. Pada resistensi insulin, vitamin D diperkirakan berperan di sel sasaran dengan menambah substrat reseptor insulin. Perlu diungkap pengaruh vitamin D terhadap pertumbuhan folikel ovarium dengan mengukur kadar AMH, kemudian diperbandingkan antara penderita S-OPK-RI dan SOPK-nir-RI berdasarkan perubahan kadar reseptor insulin darah. Penelitian ini bertujuan menentukan pengaruh pemberian vitamin D3 terhadap pertum-buhan folikel ovarium dan penurunan kadar AMH melalui jalur reseptor insulin dan resep-tor vitamin D darah. Penelitian dua tahap dilakukan dari 14 Agustus 2018 hingga 25 Fe-bruari 2019 terhadap 35 subjek SOPK-RI dan 35 subjek SOPK-nir-RI di Poliklinik Infer-tilitas dan Endokrinologi Departemen Obstetri dan Ginekologi RSPAD Gatot Soebroto (RSGS), Jakarta. Tahap pertama adalah iris-silang antara SOPK-RI dan nir-RI untuk mem-bandingkan kadar vitamin D25(OH), AMH, reseptor insulin dan reseptor vitamin D darah. Tahap kedua adalah uji kuasi-eksprimental untuk mengetahui pengaruh pemberian vitamin D3 12.000 IU per minggu selama tiga bulan terhadap pertumbuhan folikel dengan peman-tauan USG-transvaginal atau transrektal sebulan sekali dan kadar AMH pada SOPK-RI dan nir-RI. Kadar glukosa puasa, insulin puasa, vitamin D25(OH), AMH diukur dari darah. Reseptor vitamin D darah dan reseptor insulin darah diperiksa dari sel mononukleus darah tepi (SMDT). Hasil penelitian memperlihatkan bahwa: (1) prapemberian vitamin D3 nilai yang berbeda bermakna antara SOPK-RI dan SOPK-nir-RI adalah kadar glukosa puasa (84 vs. 78 mg/dL; p = 0,016), insulin puasa (20,3 vs. 7,49 μIU/mL; p < 0,001) (2) pascapemberian vitamin D3 yang berbeda bermakna adalah kadar glukosa puasa (82 vs. 79 mg/dL; p = 0,049), insulin puasa (23,19 vs. 10,54; p < 0,001), reseptor insulin lebih tinggi pada SOPK-RI diban-dingkan SOPK-nir-RI (18,80 vs. 14,78 ng/mL; p = 0,020), reseptor vitamin D pada SOPK-nir-RI menurun bermakna (63,29%); (3) pascapemberian vitamin D3 ditemukan: (a) delta perubahan kadar vitamin D25(OH) pasca (8,38 ng/mL (63,4%) [SD 4,06] SOPK-RI vs. 12,31 ng/mL (10,29%) SOPK-nir-RI, p < 0,001); (b) delta perubahan penurunan kadar AMH pasca SOPK RI 10,29 vs. SOPK-nir-RI 14,61%; p = 0,492); (c) delta peningkatan diameter folikel antara dua kelompok SPOK meningkat pada bulan pertama (14,3% vs. 50%), kedua (33,3% vs. 66,7%), dan ketiga (50% vs. 66,7%), tetapi yang berbeda bermak-na (p < 0,05) hanya pada bulan pertama, yaitu lebih besar pada SOPK-nir-RI. Disimpulkan bahwa vitamin D3 menurunkan kadar AMH pada SOPK-RI dan SOPK-nir-RI, serta meningkatkan pertumbuhan folikel pada kededua kelompok SOPK, pada bulan pertama perubahan diameter folikel lebih besar pada SOPK nir-RI. Prapemberian vitamin D3 tidak ditemukan perbedaan kadar reseptor insulin dan reseptor vitamin D pada kededua kelompok SOPK, sedangkan pascapemberian vitamin D3 terdapat penurunan kadar reseptor vitamin D pada SOPK-nir-RI.

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Discrepancy between low-level vitamin 25(OH)D and insulin resistance in PCOS patients with chronic anovulation required to be further explored. Chronic anovulation in PCOS is believed to be caused by the follicular arrest in the ovary. In insulin resistance the vitamin D is thought to play a role in target cell by adding the insulin receptor substrate. It is nec-essary to elucidate the effect of vitamin D on the ovarian folliculogenesis by measuring the AMH levels, which are then compared between patients with IR-PCOS and non-IR-PCOS based on the changes in blood insulin receptor levels. The aim of this study is to determine the effect of vitamin D3 administration on ovarian follicular growth and reduction of AMH through insulin receptor and blood vitamin D re-ceptor pathways. The two stages study was carried out from 14th August 2018 to 25th February 2019 on 35 IR-PCOS and 35 non-IR-PCOS subjects at the Infertility and Endo-crinology Out-patient Clinic, Department of Obstetrics and Gynecology, Gatot Soebroto Central Army Hospital (RSGS), Jakarta. The first stage was a cross-section study between IR-PCOS and non-IR-PCOS to compare levels of vitamin 25(OH)D, AMH, blood insulin receptors and vitamin D receptors; the second is a quasi-experimental test to determine the effect of 12,000 IU vitamin D3 administration per week for 3 months on follicular growth with transvaginal or transrectal ultrasound monthly and AMH levels on IR-PCOS-and non-IR-PCOS. Fasting glucose, fasting insulin, vitamin D25(OH), AMH levels are measured from the blood. Blood vitamin D receptor and insulin receptor were measured from the peripheral blood mononuclear cells (PBMC). The results of the study demonstrated that: (1) before administration of vitamin D3, there were differences in fasting glucose (84 vs. 78 mg/dL; p = 0.016) and fasting insulin (20.3 vs. 7.49 μIU/mL; p < 0.001) between the two groups; (2) after vitamin D3 administration, significant differences were found between the two groups for the levels of fasting glucose (82 vs. 79 mg / dL; p = 0.049), fasting insulin (23.19 vs. 10.54; p < 0.001); higher insulin receptors was found in IR-PCOS compared to non-IR-PCOS (18.80 vs. 14.78 ng / mL; p = 0.020), the vitamin D receptors in non-IR-PCOS decreased significantly (63.29%); (3) vitamin 25(OH)D levels before vitamin D3 administration were not significantly different in the two groups (13.84 vs. 10.97 ng/mL; p = 0.327), while after vitamin D3 administration the levels increased significantly (8.38 ng/mL (63.4%) [SD 4.06] in IR-PCOS vs. 12.31 ng/mL (10.29%) in non-IR-PCOS, p < 0.001); (4) AMH levels decreased in the both groups after vitamin D3 admin-istration but the ratio of the decrease was not significantly different (10.29 vs. 14.61%; p = 0.492); (5) follicular diameter between the two groups increased in the first month (14.3% vs. 50%), the second month (33.3% vs. 66.7%), and the third month (50% vs. 66.7% ) after vitamin D3 administration, but the significant difference (< 0.05) was demonstrated only in the first month, which was greater in non-IR-PCOS than that in the IR-PCOS. It is concluded that vitamin D3 decreases AMH levels in both IR-PCOS and non-IR-PCOS. It increases folliculogenesis in both PCOS groups; in the first month, the changes in follic-ular diameter are greater in non-IR-PCOS. Before vitamin D3 administration, there is no difference in the levels of insulin receptors and vitamin D receptors between the two groups, whereas after vitamin D3 administration there is a decrease in the levels of vitamin D re-ceptors in non-IR-PCOS. Keywords: AMH, IR-PCOS, non-IR-PCOS, PBMC, vitamin D receptor, insulin receptor, vitamin D25(OH)."

"ABSTRAK Latar Belakang: Sindroma ovarium polikistik (SOPK) merupakan kelainan kompleks endokrin terbanyak pada usia reproduksi. Ketidakseimbangan hormonmerupakan salah satu temuan SOPK yang terkait dengan patofisiologinya.Adanya perbedaan kejadian resistensi insulin mungkin terkait dengan perbedaankarakteristik hormon pada pasien SOPK pada berbagai fenotipe, salah satunyaHormon Anti-Mullerian (HAM). Metode: Desain penelitian potong lintang (cross sectional), pengambilan subjekdimulai dari identifikasi kelompok dengan SOPK menggunakan titik potongHAM >4,45 ng/dl, lalu akan dikelompokkan menjadi empat kelompok sesuaidengan fenotipnya berdasarkan kriteria Rotterdam 2003, di klinik Yasmin danMakmal Endokrinologi di bagian Obstetri dan Ginekologi RSUPN Dr.CiptoMangunkusumo selama tahun 2011 ?2014. Resistensi insulin dinilaimenggunakan homeostatic model assessment for insulin resistance (HOMA IR). Hasil: Didapatkan 125 subjek SOPK dengan kadar HAM cenderung lebih tinggipada fenotipe 1 dan lebih rendah pada fenotipe 4 (p<0,05). Selain itu, ditemukanperbedaan kadar LH dan rasio LH/FSH pada keempat fenotipe (p<0,05). NilaiHOMA IR juga lebih tinggi pada fenotipe 1 (p<0,05). Berdasarkan analisis regresilinear, didapatkan indeks massa tubuh dan HAM berkorelasi positif dengan nilaiHOMA IR (r=0,19 p=0,015 dan r=0,53 p<0,001, berturut-turut). Kesimpulan: Terdapat korelasi positif kadar HAM terhadap nilai HOMA IR.Pada keempat fenotipe SOPK didapatkan kadar HAM dan HOMA IR lebih tinggipada fenotipe 1 dan semakin rendah pada fenotipe 4. ABSTRACT Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder that is

the most complex in the reproductive age. Hormonal imbalance remains a part of

its pathophysiology. Insulin resistance might be linked with difference in

hormonal parameter across four phenotypes of PCOS, especillay in AMH level.

Method: The study design was cross-sectional (cross-sectional). Subject retrieval

starts from the identification of the group with PCOS (with cutt-off AMH serum

>4.45 ng/dl), and will be grouped into four groups according to their phenotype

based on the criteria of Rotterdam in 2003, in the clinic Yasmin and

Endocrinology Laboratory at the Obstetrics and Gynecology RSUPN Dr.Cipto

Mangunkusomo during 2011 -2014. Insulin resistance was counted using

homeostatic model assessment for insulin resistance (HOMA IR).

Result: A total of 125 PCOS patients were recruited with AMH serum

significantly higher among phenotype 1 and lower among phenotype 4 (p<0.05).

Besides, Lh serum and LH/FSH ratio were also different across four phenotypes

(p<0.05). The value of HOMA IR tend to be higher among phenotype 1 (p<0.05).

Using multivariable linear regression analysis, body mass index and AMH serum

were positively correlated with HOMA IR (r=0.19 p=0.015 and r=0.53 p<0.001,

respectively).

Conclusion: There was a positive correlation between AMH serum and HOMA

IR value. The four PCOS phenotypes had significantly different value of HAM

serum and HOMA IR with phenotype 1 possed higher value among the others.

;Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder that is

the most complex in the reproductive age. Hormonal imbalance remains a part of

its pathophysiology. Insulin resistance might be linked with difference in

hormonal parameter across four phenotypes of PCOS, especillay in AMH level.

Method: The study design was cross-sectional (cross-sectional). Subject retrieval

starts from the identification of the group with PCOS (with cutt-off AMH serum

>4.45 ng/dl), and will be grouped into four groups according to their phenotype

based on the criteria of Rotterdam in 2003, in the clinic Yasmin and

Endocrinology Laboratory at the Obstetrics and Gynecology RSUPN Dr.Cipto

Mangunkusomo during 2011 -2014. Insulin resistance was counted using

homeostatic model assessment for insulin resistance (HOMA IR).

Result: A total of 125 PCOS patients were recruited with AMH serum

significantly higher among phenotype 1 and lower among phenotype 4 (p<0.05).

Besides, Lh serum and LH/FSH ratio were also different across four phenotypes

(p<0.05). The value of HOMA IR tend to be higher among phenotype 1 (p<0.05).

Using multivariable linear regression analysis, body mass index and AMH serum

were positively correlated with HOMA IR (r=0.19 p=0.015 and r=0.53 p<0.001,

respectively).

Conclusion: There was a positive correlation between AMH serum and HOMA

IR value. The four PCOS phenotypes had significantly different value of HAM

serum and HOMA IR with phenotype 1 possed higher value among the others.

;Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder that is

the most complex in the reproductive age. Hormonal imbalance remains a part of

its pathophysiology. Insulin resistance might be linked with difference in

hormonal parameter across four phenotypes of PCOS, especillay in AMH level.

Method: The study design was cross-sectional (cross-sectional). Subject retrieval

starts from the identification of the group with PCOS (with cutt-off AMH serum

>4.45 ng/dl), and will be grouped into four groups according to their phenotype

based on the criteria of Rotterdam in 2003, in the clinic Yasmin and

Endocrinology Laboratory at the Obstetrics and Gynecology RSUPN Dr.Cipto

Mangunkusomo during 2011 -2014. Insulin resistance was counted using

homeostatic model assessment for insulin resistance (HOMA IR).

Result: A total of 125 PCOS patients were recruited with AMH serum

significantly higher among phenotype 1 and lower among phenotype 4 (p<0.05).

Besides, Lh serum and LH/FSH ratio were also different across four phenotypes

(p<0.05). The value of HOMA IR tend to be higher among phenotype 1 (p<0.05).

Using multivariable linear regression analysis, body mass index and AMH serum

were positively correlated with HOMA IR (r=0.19 p=0.015 and r=0.53 p<0.001,

respectively).

Conclusion: There was a positive correlation between AMH serum and HOMA

IR value. The four PCOS phenotypes had significantly different value of HAM

serum and HOMA IR with phenotype 1 possed higher value among the others.

"