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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."

"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. "

"Ketidaktepatan dalam pemberian obat pada pasien balita dapat menimbulkan adanya masalah terkait obat dikarenakan adanya perbedaan farmakokinetika dan farmakodinamika dengan pasien dewasa. Obat kortikosteroid merupakan salah satu obat yang prevalensi diresepkan kepada balita cukup tinggi karena dianggap memiliki banyak manfaat. Namun terdapat beberapa efek samping yang perlu diwaspadai yaitu imunosupresan dan retardasi pertumbuhan. Penelitian ini bertujuan untuk menganalisis adanya masalah terkait obat kortikosteroid oral terhadap pasien anak di Puskesmas Kecamatan Tebet yang meliputi ketepatan pemilihan obat, kesesuaian dosis, ketepatan durasi pengobatan, dan juga adanya potensi interaksi obat. Penelitian ini dilakukan secara restrospektif dari resep pasien dan teknik total sampling. Sampel pada penelitian ini menggunakan resep obat deksametason dan prednsison pada pasien balita Puskesmas Kecamatan Tebet periode September-Desember 2019 sebanyak 523 sampel. Dari 523 resep didapatkan jumlah pengobatan kortikosteroid oral yang paling banyak adalah 63% dengan indikasi terbanyak berupa Infeksi Saluran Pernafasan Atas (ISPA) sebanyak 70,7%. Hasil analisis masalah terkait obat menunjukkan adanya ketidaktepatan pemilihan obat sebanyak 382 (73,1%) dan ketidaksesuaian dosis sebanyak 7 (1,3%). Dari hasil analisis statistik didapatkan adanya korelasi antara pemilihan obat dengan ketepatan indikasi pasien (p=0,006). Tingginya potensi masalah terkait obat yang ditemukan membutuhkan kewaspadaan bagi tenaga kesehatan dalam pelayanan resep kortikosteroid oral pada pasien balita.

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Inaccuracy in drug administration in under-five patients can lead to drug-related problems due to differences in pharmacokinetics and pharmacodynamics with adult patients. Corticosteroid drugs are one of the drugs whose prevalence is quite high because they are considered to have many benefits. However, there are some side effects that need to be watched out for, namely immunosuppression and growth retardation. This study aims to analyze the existence of problems related to oral corticosteroid drugs in pediatric patients at the Tebet District Health Center which include the accuracy of drug selection, appropriate dosage, accuracy of treatment duration, and also the potential for drug interactions. This study was conducted retrospectively from patient prescriptions and total sampling technique. The sample in this study used prescription drugs for dexamethasone and prednison in toddler patients in Puskesmas Kecamatan Tebet for the period September-December 2019 with a total of 523 samples. Of the 523 prescriptions, the highest number of oral corticosteroid treatment was 63% with the most indication being Upper Respiratory Tract Infection (URTI) of 70.7%. The results of drug-related problem analysis showed that there were 382 (73.1%) drug selection inaccuracies and 7 (1.3%) dose inaccuracies. From the results of statistical analysis, it was found that there was a correlation between drug selection and the accuracy of patient indications (p=0.006). The high potential for drug-related problems that are found requires special attention for health workers in prescribing oral corticosteroid drugs in toddler health services."

"Endocrinologists have engaged in thisnew method and have thus acquired many new and sophisticated tools. Withoutthese advances in molecular biological tools, could we have imagined, for example,that variants of the leptin receptor missing the part for signal transductionmight stillserve as a vehicle for leptin uptake through the blood–brain barrier? In this book, we aim to integrate such new results into an enhanced understanding of endocrinology."

"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."

"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)."

"Sindrom ovarium polikistik (SOPK) adalah salah satu kelainan endokrin yang paling umum terjadi pada wanita usia reproduktif. Patogenenesis SOPK berhubungan langsung dengan resistensi insulin. Beberapa studi menyimpulkan bahwa akupunktur dapat meningkatkan sensitivitas insulin sehingga dapat memperbaiki gejala SOPK. Uji klinis acak tersamar ganda dilakukan pada 44 penderita SOPK yang dibagi secara acak ke dalam dua kelompok, yakni kelompok elektroakupunktur kombinasi medikamentosa (n=22) dan kelompok elektroakupunktur sham kombinasi medikamentosa (n=22). Elektroakupunktur dilakukan 3 kal seminggu, sebanyak 12 kali, selama 4 minggu, pada titik CV3 Zhongji, CV4 Guanyuan, CV6 Qihai, ST25 Tianshu, ST28 Shuidao, ST36 Zusanli, SP6 Sanyinjiao, dan BL57 Chengsan. Pemeriksaan gula darah puasa dan insulin puasa dilakukan untuk mengukur indeks HOMA-IR sebagai luaran primer. Hasil penelitian menunjukkan adanya perbedaan yang bermakna. Median indeks HOMA-IR pada kelompok elektroakupunktur kombinasi medikamentosa sebelum dan sesudah terapi menunjukkan perbedaan bermakna secara statistik (p=0,014). Sedangkan median indeks HOMA-IR pada kelompok elektroakupunktur sham kombinasi medikamentosa sebelum dan sesudah terapi tidak terdapat perbedaan bermakna (p=0,592). Kesimpulan penelitian ini elektroakupunktur kombinasi medikamentosa efektif untuk meningkatkan sensitivitas insulin.

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Polycystic ovary syndrome (SOPK) is one of the most common endocrine disorders in women of reproductive age. The pathogenesis of SOPK is directly related to insulin resistance. Several studies have concluded that acupuncture can increase insulin sensitivity to improve symptoms of PCOS. Double-blind randomized clinical trials were performed on 44 patients with SOPK who were randomly divided into two groups, the electroacupuncture with medication group (n=22) and the electroacupuncture sham with medication group (n=22). Electroacupuncture was given 3 times a week, 12 times, for 4 weeks, at the point of CV3 Zhongji, CV4 Guanyuan, CV6 Qihai, ST25 Tianshu, ST28 Shuidao, ST36 Zusanli, SP6 Sanyinjiao, and BL57 Chengsan. Fasting blood glucose and fasting insulin were performed to measure the HOMA-IR index as the primary outcome. The results showed a significant difference. The median HOMA-IR index in the electroacupuncture with medication group before and after therapy showed statistically significant differences (p = 0.014). While median HOMA-IR index in electroacupuncture sham with medication group before and after therapy there was no significant difference (p = 0.592). The conclusion of this study electroacupuncture combination with medication is effective to improve insulin sensitivity. "

"Insufisiensi ovarium primer (IOP) adalah sindrom klinik yang ditandai dengan hilangnya aktivitas ovarium sebelum usia 40 tahun, disertai gangguan menstruasi, peningkatan gonadotropin dan rendahnya kadar estradiol. Kondisi tersebut menyebabkan infertilitas. Diagnosis IOP ditegakkan berdasarkan hormon FSH, tetapi memerlukan 2 kali pemeriksaan dalam waktu 4-6 minggu, sehingga digunakan persentil wiweko untuk mengetahui kadar AMH sebagai prediktor cadangan ovarium. Kadar AMH rendah menunjukkan cadangan ovarium juga rendah; diduga karena ada mutasi gen AMH sehingga perlu dilakukan penelitian untuk mengetahui hubungan antara mutasi gen dengan hormon AMH. Penelitian potong lintang ini dilakukan di Rumah Sakit dr Cipto Mangunkusumo (RSCM) Jakarta dalam kurun waktu Juni 2021-Maret 2022. Subjek penelitian adalah pasien yang dikonsulkan ke RSCM untuk masalah gangguan menstruasi. Subjek dibagi tiga kelompok yaitu kelompok IOP, SOPK dan kontrol, kemudian dilakukan uji karyotiping dengan G-banding untuk mengetahui normalitas kromosom. Selanjutnya diperiksa urutan gen AMH dan SNP menggunakan sanger sekuensing, sedangkan kadar AMH diperiksa dengan uji ELISA. Data diolah dengan SPSS versi 20 dan uji statistik yang digunakan adalah Uji Mann Whitney, chi square, exact fisher dan uji korelasi spearman. Dari total 31 subjek penelitian, 8 subjek masuk dalam kelompok IOP, 16 subjek SOPK, dan 7 subjek kontrol. Terdapat 30 mutasi dengan 2 mutasi novel pada promoter gen AMH dan 3 mutasi novel pada struktur gen AMH. Terdapat 14 SNP pada kelompok IOP dan 15 SNP pada kelompok SOPK, dengan nilai LDI > 0,8 yang berarti kemunculan satu mutasi diikuti oleh mutasi di titik lain. Mutasi struktural gen AMH, SNP P247Q, menyebabkan perubahan prolin menjadi glutamin. Mutasi itu mengubah folding pada model prediksi 3D protein AMH. Mutasi pada kelompok IOP memiliki nilai HW 0,014; artinya, mutasi tidak diwariskan ke generasi selanjutnya. Terdapat perbedaan bermakna distribusi frekuensi mutasi promoter gen AMH antara kelompok IOP dengan SOPK, pada titik mutasi 19:g.2249146T>G (p=0,007) dengan rasio prevalens RP (95%CI) = 5(1,6-14,9) terhadap SOPK, sehingga genotipe TG 5 kali lebih besar kemungkinan menjadi IOP. Disimpulkan terdapat mutasi pada promoter dan struktural gen AMH pada semua kelompok, yang menyebabkan perbedaan urutan basa; namun tidak bermakna. Model prediksi struktur 3D AMH menunjukkan perubahan folding di titik P247Q yang mengalami mutasi, sehingga mengakibatkan perubahan struktur protein. Jumlah dan jenis mutasi pada struktural gen AMH tidak berhubungan dengan kadar AMH. Jumlah mutasi di promoter gen AMH tidak memengaruhi kadar AMH pada semua kelompok.

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Primary ovarian insufficiency (POI) is a clinical syndrome characterized by the loss of ovarian function before the age of 40, resulting in menstrual irregularities, elevated gonadotropin levels, and decreased estradiol levels. It leads to infertility. Diagnosis of POI requires two FSH hormone tests within a 4-6 week period. To predict ovarian reserve, AMH levels are measured using the Wiweko percentile. Low AMH levels indicate diminished ovarian reserve, possibly due to AMH gene mutations. Hence, a study was conducted at Cipto Mangunkusumo Hospital (RSCM) in Jakarta from June 2021 to March 2022.

The study included three groups: POI, polycystic ovary syndrome (PCOS), and control. G-banding karyotyping determined chromosomal normality, while Sanger sequencing examined AMH gene sequence and single nucleotide polymorphisms (SNPs). ELISA was used to measure AMH levels. Statistical analysis employed SPSS version 20, including tests like Mann-Whitney, chi-square, exact Fisher, and Spearman correlation.

Out of 31 subjects, 8 had POI, 16 had PCOS, and 7 were controls. The study identified 30 mutations, including 2 novel promoter mutations and 3 novel missense mutations in the AMH gene structure. The POI group had 14 SNPs, while the PCOS group had 15, with an LDI value > 0.8 indicating multiple mutations. The SNP P247Q caused a proline to glutamine change, impacting the protein structure. The HW value of POI mutations was 0.014, suggesting no inheritance.

There was a significant difference in the distribution of AMH gene promoter mutation frequencies between the IOP and PCOS groups, at the mutation point 19:g.2249146T>G (p=0.007) with a prevalence ratio of RP (95%CI) = 5(1.6-14.9) to PCOS, so that the TG genotype is 5 times more likely to become IOP.. In conclusion, mutations occurred in both promoter and structural regions of the AMH gene but did not significantly impact AMH levels. The 3D model predicted structural changes at the P247Q mutation point. The number and type of structural mutations were unrelated to AMH levels. The number of promoter gene mutations did not affect AMH levels in any group."

"Objektif : Untuk mengetahui asosiasi antara profil antropometri,dan lipid dengan kejadian resistensi insulin pada subjek SOPK.Latar belakang: Patofisiologi Hiperandrogen dan gangguan ovulasi pada SOPKadalah resistensi insulin (RI) dan kondisi hiperinsulinemia. kondisi tersebut dapatterjadi di ovarium dan kelenjar adrenal, kondisi ini dilaporkan terjadi pada 40%-70% pada subjek SOPK, SOPK pengukuran golden standar denganHyperinsulinaemic euglycaemic clamp technique,tehnik untuk menilai sekresi danresistensi insulin, namun tehnik tersebut kompleks serta membutuhkankemampuan ahli dan kurang tepat untuk praktik klinis. Penilaian Pengukuranresistensi insulin pengganti dengan homeostatik model assessment insulinresistance (HOMA-IR), disini digunakan titik potong 2,69. Subjek SOPKsebagian besar memiliki profil antropometri yang abnormal lebih dari delapanpuluh persen (> 80%), dan dengan kondisi dislipidemia (> 70%), peneliti inginmengetahui asosiasi profil antropometri, lipid terhadap resistensi Insulin padaSOPK.Metodologi: Penelitian ini merupakan penelitian lanjutan dari uji klinis DLBS3233 yang selesai pada bulan juni 2019, analisis data tambahan dilakukan sejakJuli-Desember 2019. Tempat pelaksanaan pengambilan sampel penelitian iniadalah di RSUPN Dr. Cipto Mangunkusumo dan Klinik Yasmin RSCM Kencana.Dilakukan analisis asosiasi antaraprofil antropometri dan profil lipid terhadapresistensi insulin.Hasil : Didapatkan faktor-faktor yang berhubungan dengan kejadian resistensiinsulin pada subjek SOPK, pada profil antropometri didapatkan variabel lingkarpinggang dan index masa tubuh berhubungan dengan kejadian resistensi insulin,pada metabolik didapatkan variabel GD2PP, insulin puasa, LDL, Tigliseridaberhubungan dengan.Didapatkan bahwa variabel Trigliserida memiliki pengaruhkuat pada resistensi insulin, dengan confounding faktor variabel IMT.Kesimpulan : didapatkan profil antropometri IMT dan dan profil lipidTrigliserida berhubungan dengan kejadian resistensi insulin di RSCM berdasarkangambaran profil pasien di RSCM.

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Objective: To determine the association between anthropometric and lipidprofiles with the incidence of insulin resistance among PCOS subjects.Background: Insulin resistance (IR) and hyperinsulinemia conditions is thekey of pathophysiology and ovulation disorders in PCOS. These conditions canoccur in the ovaries and adrenal glands, reported occur in 40%-70% amongPCOS subjects, golden standard measurement IR with hyperinsulinaemiceuglycaemic clamp technique, a technique to assess insulin secretion andresistance, but the technique is complex and requires expert ability and notappropriate for clinical practice. Assessment Measuring substitute insulinresistance with a homeostatic insulin resistance assessment model (HOMA-IR),we use cutoff point of 2.69. PCOS subjects mostly had an abnormalanthropometric profile (> 80%), and with dyslipidemia (>70%), researcherswanted to know the association of anthropometric profiles, lipids to Insulinresistance in PCOSMethodology: This study is a follow-up study of DLBS 3233 clinical trialcompleted in June 2019, additional data analysis was carried out since July-December 2019. The place for conducting the sample collection was atDr.Cipto Mangunkusumo Hospital and Yasmin Clinic RSCM Kencana. Anassociation analysis was performed between anthropometric profiles and lipidprofiles on insulin resistance.Result: Waist circumference and body mass index as antropometric factorassociated with insulin resistanc, 2 hour fasting glucose, fasting insulin, LDL,triglycerida as lipid factor associated with insulin resistance in PCOS. It wasfound that the triglyceride had a strong influence on insulin resistance, andbody mass index as confounding factor of insulin resistance in PCOSConclusions : Triglyceride and body mass index related to the incidence ofinsulin resistance in RSCM based on the profile of patients in RSCM."