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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).

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.