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Abstrak :
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

Abstrak :
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. ...... 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.

Abstrak :
Latar Belakang: Sejalan dengan kemajuan terapi agresif kanker, angka kesintasan hidup pasien kanker juga meningkat. Namun, peningkatan kesintasan hidup ini tidak berjalan paralel dengan peningkatan kualitas hidup, khususnya fungsi reproduksi. Sebanyak 68 survivor kanker usia reproduksi pasca kemoterapi atau radiasi menderita amenorrhea, pengurangan cadangan ovarium dan kegagalan ovarium dini. Namun, apakah fungsi reproduksi pasien kanker usia reproduksi sebelum mendapat terapi memang sudah menurun, masih terus diperdebatkan. Saat ini, salah satu untuk menilai fungsi reproduksi adalah dengan mengukur cadangan ovarium. Sedangkan, parameter terbaik untuk mengukur cadangan ovarium adalah dengan pengukuran kadar serum Anti Mullerian Hormone AMH . Selain mendapatkan prediksi cadangan ovarium, kadar AMH juga dapat digunakan untuk mengetahui usia biologis seseorang, dimana fungsi reproduksi lebih dipengaruhi oleh usia biologis. Tujuan: Mengetahui cadangan ovarium pasien kanker usia reproduksi sebelum mendapat terapi Metode: Penelitian potong lintang, dilakukan di tiga tempat, Poliklinik Ginekologi, Poliklinik Hematologi Onkologi - Departemen Ilmu Penyakit Dalam RSUPN Cipto Mangunkusumo, dan Poliklinik Ginekologi dan Unit Rawat Inap RS Kanker Dharmais, pada bulan Juni 2015 hingga Desember 2017. Sebanyak 88 subyek penelitian, terdiri dari 44 pasien kanker usia reproduksi sebelum mendapat terapi dan 44 pasien non-kanker berhasil direkruit pada penelitian ini. Pada subyek penelitian dilakukan pengambilan serum darah dan kemudian diperiksakan kadar AMH-nya. Hasil: Dari 88 subyek penelitian yang berhasil dikumpulkan. Rerata usia pada kedua kelompok didapatkan sama, yaitu 28 tahun. Kadar AMH kelompok kanker sebelum mendapat terapi didapatkan lebih rendah dibanding kelompok non kanker, yaitu 1.11 0.08-4.65 ng/ml vs 3.99 1.19-8.7 ; p: Background:. ......In line with advance cancer therapy, survival rate of cancer patients is also increase. Unfortunately, this condition doesn rsquo;t run parallel with increase quality of life, especially reproductive function. Sixty-six per cent cancer survivors in reproductive age suffered from amenorrhea, premature ovarian failure and decreased ovarian reserved, after cancer therapy. But, does ovarian reserve in cancer patient already decreased before treatment, still being debated. Nowadays, the best parameter to measure ovarian reserve is by measuring serum Anti Mullerian Hormone AMH . Therefore, we can also predict biological age, that is more crucial to assess reproductive function. Objective:To study whether AMH level in cancer patient in reproductive age is already decreased before cancer therapy.Method:This cross-sectional study was conducted in Gynecology Policlinic, Hematology-Oncology Policlinik Departement of Internal Medicine Cipto Mangunkusumo Hospital and Dharmais Hospital, from June 2015 to December 2017. We enrolled 88 subjects, consist of 44 cancer patients in reproductive age before cancer treatment and 44 non-cancer patients. Blood serum was collected and level of AMH was measured.Results:The median age in both groups were 28 years. AMH level in the cancer group patients before cancer treatment were found significantly lower than the non-cancer group, 1.11 0.08-4.65 ng / ml vs 3.99 1.19- 8.7 ; p:

Abstrak :
Pendahuluan: Angka keberhasilan FIV di Indonesia sekitar 32-35%. Salah satu penyebab pencapaian yang rendah ini adalah mutu oosit yang dinilai secara mi­kros­kopik pada saat panen oosit. Dari sekian banyak faktor yang berperan dalam pembentukan oosit matang bermutu baik diduga yang paling menentukan per­olehan oosit ma­tang, jumlah fertilisasi, dan jumlah embrio yang dipindahkan ke ute­rus pada FIV adalah AMH, inhibin-B, IGF-2 dan nisbahnya. Bahan dan metoda: Kajian analitik potong-lintang pengukuran berulang dilaku­kan pada bu­lan September 2013-Agustus 2014 di Rumah Sakit Anak dan Bunda Harapan Kita, Jakarta. Sebanyak 38 pasien berumur 26-42 tahun yang mengikuti program FIV diukur kadar AMH, inhibin-B, IGF-2 saat basal, pencetus, panen oosit dalam serum dan dalam zalir folikel. Analisis regresi linear digunakan untuk memperoleh faktor penduga jumlah perolehan oosit matang, jumlah fertilisasi, dan jumlah embrio yang dipindahkan. Hasil: Parameter penduga perolehan oosit matang adalah inhibin-B serum panen oosit dan folikel antral basal (FAB) total. Parameter penduga jumlah fertilisasi adalah FAB to­tal, nisbah inhibin-B pencetus terhadap inhibin-B basal, dan nisbah IGF-2 pen­cetus terhadap inhibin-B pencetus. Parameter penduga jumlah embrio yang dipin­dahkan adalah FAB total, inhibin-B panen oosit, dan nisbah inhibin-B panen oosit terhadap inhi­bin-B pencetus. Pada analisis bivariat area under curve (AUC) terbesar (77,4%) ditemukan pada titik-potong in­hi­bin-B serum panen oosit. Kadar inhibin-B panen oosit yang lebih tinggi dari 131,16 ng/ mL adalah akurat untuk menetapkan kematangan oosit de­ngan ke­pe­­kaan (sensiti­vitas) 84% dan kekhasan (spesifisitas) 69,2%. Simpulan: Inhibin-B serum saat panen oosit berhubungan dengan pembentukan oo­sit matang dan normal sehingga dapat dijadikan parameter penduga perolehan oosit ma­tang dan jum­lah em­brio yang terbentuk. Ditemukan parameter-parameter baru, yaitu (1) nisbah inhibin-B pen­ce­tus terhadap inhibin-B basal serum, dan nisbah IGF-2 pen­cetus terhadap in­hibin-B pencetus serum untuk menduga jumlah fertili­sasi; (2) nisbah inhibin-B pa­nen terhadap inhibin-B pen­­cetus serum untuk menduga jumlah em­brio yang dipindahkan ke uterus pada FIV. ......Background: The success rate of IVF in Indonesia was 30-35%. This low rate was caused by the microscopically evaluated oocyte quality that was obtained by ovum pick-up (OPU). The determinatively contributing factors for the formation of good quality mature oocytes, which are considered to be used as predictive parameter for mature oocytes recovery, number of fertilization, and number transferrable embryos in IVF, are AMH, inhibin-B, IGF-2, and their ratios. Therefore, the study to determine the correlation of those factors with the formation of ferti­li­zable mature oocyte in IVF program is necessary. Materials and methods: An analytic cross-sectional repeated measurements study was conducted from September 2013 until August 2014 at Harapan Kita Mother and Chil­d Hospital, Jakarta. There were 38 patients aged between 26-42 years who par­ticipated in the IVF program; all of them underwent measurement for serum AMH, inhibin-B, and IGF-2 levels at basal, trigger, and OPU times. Predictive parameters for the number of mature oocytes, fertilizable oocytes, number of embryos transferred were analysed using linear regression. Results: Predictive parameter for the number of mature oocytes are inhibin-B at OPU and total basal antral follicle (BAF) count. Predictive factors for the number of fertili­za­tion are total BAF count, the ratio of inhibin-B at triggering to inhibin-B at basal ti­mes. Predic­ti­ve factors for the number of embryos transferred are total BAF, inhibin-B at OPU, and the ratio of inhibin-B at OPU to inhibin-B at triggering time. Using bivariate analysis, at the largest area under the curve (AUC) which was as high as 77.4%, the cut-off point of serum inhibin-B at OPU was found. The serum inhibin-B level at OPU higher than 131.16 ng/mL is accurate for determining the oocyte ma­turity (84% sensitivity and 69.2% spe­cificity). Conclusions: Serum inhibin-B at OPU correlates with the formation of both mature and normal oocytes, thus it can be used as a predictor for the number of mature oo­cytes recovered and the number of embryos transferred. New parameters are found, those are: (1) the ratio of inhibin-B at triggering to inhi­bin-B in serum at basal times; and the ratio of IGF-2 at triggering to inhibin-B in serum at triggering times to pre­dict the number of fer­tilization; (2) the ratio of inhibin-B at OPU to inhibin-B in se­rum at triggering times to pre­dict the number of embryos transferred.

Abstrak :
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. ......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).