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"Penelitian ini bertujuan untuk mengevaluasi dampak liraglutide terhadap kadar gula darah serta gen penanda diabetes GLUT4, IRS1, TCF7L2, BCL2, dan BAX menggunakan hewan model sindrom ovarium polikistik yang diinduksi diabetes mellitus gestasional. Liraglutide dipilih karena memiliki efek insulinotropik paling baik dibandingkan agen lain serta bersifat glucose-dependent. Penelitian ini juga bertujuan untuk mengetahui pengaruh jalur pentosa fosfat (PPP) terhadap maturasi oosit dan ekspresi gen GDF9, BMP15, CDCA8, dan TRIP13 serta pengaruh inhibisi PPP oleh 6-nicotinamide (6AN) terhadap kedua parameter tersebut menggunakan oosit babi. 6AN digunakan sebagai inhibitor karena secara langsung menghentikan aktivitas enzim utama PPP. Aktivitas PPP dinilai dengan pewarnaan brilliant cresyl blue (BCB) dimana BCB+ menunjukkan aktivitas PPP rendah sedangkan BCBsebaliknya. Analisis menunjukkan kadar gula darah kelompok eksperimen yang diberi liraglutide pada gestational day (GD)12 dan GD20 lebih rendah dibandingkan kelompok kontrol dan sham. Ekspresi GLUT4, TCF7L2, dan BCL2 pada kelompok eksperimen lebih tinggi dibandingkan kelompok kontrol dan kelompok sham. Ekspresi BAX pada kelompok eksperimen lebih rendah dibandingkan kelompok kontrol dan sham. Ekspresi IRS1 tidak berubah pada seluruh kelompok. Laju maturasi oosit pada kelompok BCB+ lebih tinggi dibandingkan kelompok BCB-. Ekspresi GDF9 dan BMP15 serta ekspresi CDCA8 dan TRIP13 pada 20 dan 44 jam IVM lebih tinggi pada kelompok BCB+. Inhibisi PPP menurunkan ekspresi GDF9 dan BMP15 serta ekspresi seluruh gen pada 20 dan 44 jam IVM. Hasil penelitian menunjukan bahwa liraglutide menurunkan kadar gula darah dan memperbaiki profil gen penanda diabetes. PPP mempengaruhi laju maturasi dan ekspresi gen penanda maturasi dan inhibisinya menurunkan kedua parameter tersebut.

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This present study aims to evaluate the effect of liraglutide on blood sugar levels and diabetes-associated genes GLUT4, IRS1, TCF7L2, BCL2, and BAX using gestational diabetes mellitus-induced polycystic ovary syndrome model. Liraglutide was selected as having the best insulinotropic properties and is glucose-dependent. This study also aims to determine the effect of the pentose phosphate pathway (PPP) on oocyte maturation and the expression of GDF9, BMP15, CDCA8, and TRIP13 as well as the impact of its inhibition by 6-nicotinamide (6AN) on these two parameters using porcine oocytes. 6AN is used as it directly inhibits the main PPP enzyme. PPP activity was assessed by brilliant cresyl blue (BCB) staining where BCB+ reflected low PPP and vice versa. Results showed that blood sugar levels in the experimental group treated with liraglutide at gestational day (GD)12 and GD20 were lower compared to the control and sham groups. GLUT4, TCF7L2, and BCL2 expression were elevated in the experimental group while BAX expression was declined. IRS1 expression was unaltered in all groups. The BCB+ group had a higher maturation rate. The expression of GDF9 and BMP15 as well as CDCA8 and TRIP13 at 20 and 44 hours of IVM were higher in the BCB+ group. Inhibition of PPP reduced GDF9 and BMP15 expression with all examined genes at 20 and 44 hours of IVM. Our study suggests that liraglutide reduced blood sugar levels and improved diabetes-associated genes profile. PPP influences the oocyte maturation rate and expression of maturation-related genes where inhibition of PPP decreases both parameters."

"Sindrom Ovarium Polikistik (SOPK) saat ini merupakan salah satu kelainan dengan keberhasilan kehamilan terendah di antara berbagai penyebab infertilitas. Penelitian ini bertujuan untuk menilai ultrasonografi (USG) sebagai prediktor diagnosis reseptivitas endometrium perempuan infertil Sindrom Ovarium Polikistik. Penelitian ini merupakan studi diagnostik observasional dengan disain potong lintang. Tiga puluh empat perempuan usia reproduksi (32,5 ± 3,8 tahun), mengalami infertilitas primer 4,9 ± 3,1 tahun dengan siklus anovulasi mendapat klomifen sitrat 100 mg perhari H2?6; perkembangan folikel dan ovulasi dikonfirmasi dengan pemeriksaan ultrasonografi (USG) H12?17. Pemeriksaan USG yang diikuti biopsi endometrium dan hormon progesteron dilakukan pada H19?21 atau pasca ovulasi H+5?+7. USG digunakan untuk menilai Zona Vaskularisasi menurut kriteria Sonai, Volume Endometrium menurut kriteria Zollner, dan Indeks Vaskularisasi-Arus Darah menurut kriteria Wu. Biopsi endometrium dinilai berdasarkan penanggalan histopatologis menurut kriteria Noyes, dan pemeriksaan imunohistokimia VEGF dan VEGFR-1 dengan penilaian secara H-Score. Kadar VEGF serum diperiksa dengan metode Elisa. Analisis statistik menggunakan uji chi-square, uji-t dan nilai ROC. Dihasilkan titik potong komposit endometrium sebagai baku emas reseptivitas endometrium berdasarkan pemeriksaan penanggalan histopatologis endometrium. Pemeriksaan USG berdasarkan pemeriksaan komposit endometrium ini akhirnya menghasilkan baku emas USG penetapan reseptivitas endometrium. Pemeriksaan USG H19?21 menunjukkan rerata tebal endometrium 10,47 ± 1,85 mm, Volume Endometrium 3,70 ± 1,31 ml, Indeks Vaskularisasi?Arus Darah Indeks Vaskularisasi?Arus Darah 0,08 (0,00-3,21) dan Zona Vaskularisasi di lapis 1,2,3 dan 4 masing-masing 14,7%, 41,2%, 35,3% dan 8,8%. Pemeriksaan histopatologis endometrium mendapatkan 58,8% in-phase dan 41,2% out-phase. Pemeriksaan VEGF endometrium mendapatkan ekspresi tertinggi di endotel (2,34 ± 0,26), kemudian di epitel luminal (2,23 ± 0,37), sel stroma (2,1±1,9), terendah di epitel kelenjar (2,00 ± 0,68). VEGFR-1 endometrium tertinggi di epitel kelenjar (2,85 ± 0,30), diikuti di epitel luminal (2,83 ± 0,54), endotel (2,70 ± 0,42) dan terendah di sel stroma (2,58 ± 0,42). Secara statistik, ditemukan hubungan bermakna antara Zona Vaskularisasi dengan VEGF sel stroma (p = 0,018), Volume Endometrium dengan VEGF endotel (p = 0,000), epitel luminal (p = 0,029) dan total sel (0,043) serta Penanggalan Histologis Endometrium dengan VEGFR-1 sel stroma (p = 0,009). Penetapan reseptivitas endometrium hasil penilaian Komposit USG berdasarkan baku emas komposit endometrium adalah ditemukannya Zona Vaskularisasi lapis 3?4, Volume Endometrium ≥ 3,090 ml dan Indeks Vaskularisasi-Arus Darah ≥ 0,253 yang menunjukkan spesifisitas 77,4%. Ultrasonografi dapat digunakan sebagai prediktor diagnosis reseptivitas endometrium masa jendela implantasi embrio perempuan infertil SOPK.

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Polycyctic ovary syndrome has been recognized as one of the lowest successful pregnancy rates in infertile women. This studi aimed to assess ultrasound as predictor of endometrial receptivity in PCOS infertile women.

Diagnostic observational study in cross sectional design was conducted. Thirty-four subjects suffered anovulatory cycles in a average 32,5 ± 3,8 years of age and primary infertility for 4,9 ± 3,1 years, receiving 100 mg/d clomiphene citrate therapy on D2?6 . Follicular development and ovulation were confirmed by tranasvaginal USG examination on D12?17 . Repeated USG procedures followed by endometrial biopsy and serum progesterone test were conducted on either D 19?21 or D+5?+7 post ovulatory. The use of USG was to assess Vascularization Zone by Sonai criteria, Endometrial Volume by Zollner criteria and Vascularization Flow Index (VFI) by Wu criteria. Endometrial biopsy was performed and dated, based on endometrial histological dating by Noyes citeria. Immunohistochemistry of VEGF and VEGFR-1 were done and counted by H-Score formula. VEGF serum was tested by Elisa method. Statistical analysis of Chi-squre test, student t-test and ROC value were used. Immunohistochemistry composite formation was based on histological dating of endometrium. Ultrasound composite based on immunohistochemistry composite was finally resulting the new cut-off of endometrial reseptivity. Ultrasound findings on D19?21 showed the average endometrial thickness 10,47± 1,85 mm, Endometrium Volume 3,70 ± 1,31 ml, Vascularization?Flow Index (VFI) 0,08 (0,00?3,21 ) and Vascularization Zone (ZV) of zone 1,2,3 and 4 were 14,7%, 41,2%, 35,3% and 8,8%. Endometrial dating was 58,8% in-phase and 41,2% out-phase. Endometrial VEGF staining showed the highest expression in endothel (2,34 ± 0,26), followed by luminal epithelium (2,23 ± 0,37), stromal cells (2,1 ± 1,9) and the lowest in glandular epithelial (2,00 ± 0,68); meanwhile the highest VEGFR-1 expression was seen in glandular epithelial (2,85 ± 0,30), followed by luminal epithelial (2,83 ± 0,54), endothelial (2,70 ± 0,42) and the lowest at the stromal cells (2,58 ± 0,42). Statistically, ZV was correlated to the VEGF stromal cells (p = 0,018) and Endometrial Volume was correlated to VEGF endothelial (p = 0,000) and VEGF luminal epithelium (p = 0,029) and VEGF total cells (p = 0,043); meanwhile Histological Dating of Endometrium was correlated to VEGFR-1 stromal cells (p = 0,009). Endometrial receptivity predictor determined by Ultrasound Composite based on immunohistochemistry composite was Vascularization Zone of layer 3?4, Endometrial Volume of ≥ 3,090 ml and endometrial VFI of 0,253 with a specificity of 77,4%. Ultrasound was the useful tools for diagnostic predictor of endometrial receptivity diagnosis during the implantation windows period of PCOS infertile female."

"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. "

"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."

"Latar Belakang: Sindrom ovarium polikistik (SOPK) merupakan kelainan endokrin dan metabolisme dengan prevalensi tinggi. Salah satu akibat dari SOPK merupakan infertilitas. Fertilisasi In Vitro (FIV) merupakan salah satu alternatif dari masalah tersebut. Akan tetapi, belum terdapat penelitian yang mendeskripsikan hubungan SOPK dengan komplikasi obstetri pada pasien yang menjalani FIV dibandingkan dengan pasien lainnya. Tujuan: Penelitian ini bertujuan untuk mengetahui hubungan komplikasi obstetri pada wanita yang menjalani program FIV dengan SOPK Metode: Penelitian ini merupakan penelitian kohort retrospektif yang dilakukan di RSUPN Dr. Cipto Mangunkusumo sejak tahun 2013-2019. Subjek penelitian merupakan seluruh wanita berusia diatas 18 tahun yang menjalani program FIV tanpa kelainan ginekologis lain selain SOPK. Luaran dalam penelitian ini adalah komplikasi obsteri berupa abortus dan IUFD. Analisa dilakukan dengan menggunakan cox-regresi untuk mendapatkan nilai Risk Ratio (RR) setelah dilakukan control terhadap confounding Hasil: Penelitian ini mengikutsertakan 355 wanita, dimana 72 diantaranya memiliki SOPK (20,3%). Komplikasi obstetri yang didapatkan pada subjek dengan SOPK adalah preterm (2,78%), IUFD (17,24%), abortus (9,72%), dan kehamilan ektopik (1,39%). Tidak dijumpai hubungan antara SOPK dengan IUFD pada wanita yang menjalani program FIV (RR: 1.07, 95%CI: 0.52-2.20, p-value: 0.864). Didapatkan adanya hubungan antara interaksi antara SOPK dengan pembelahan nisbah < 6 terhadap terjadinya abortus pada wanita yang menjalani program FIV. (RR: 7.32, 95%CI: 2.10-25.45, P-value: 0.002). Simpulan: SOPK tidak memengaruhi terjadinya IUFD dan abortus pada wanita yang menjalani program FIV.

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Introduction: Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with a high prevalence. One result of PCOS is infertility. In Vitro Fertilization (FIV) is one of the alternatives to the problem. However, there are no study describing the differences in obstetric complications of PCOS patients undergoing FIV compared to other patients. Aim: This study aims to determine the relationship of obstruction complications in women undergoing FIV programs with PCOS.

Methods: This was a retrospective cohort study conducted at Dr. RSUPN. Cipto Mangunkusumo since 2013-2019. The study subjects were all women aged over 18 years who underwent FIV programs without other gynecological abnormalities besides PCOS. The outcomes in this study were obstetric complications in the form of abortion and IUFD. Analysis is done by using cox-regression to get the value of Risk Ratio (RR) after controlling for confounding Results: This study included 355 women, of whom 72 had PCOS (20.3%). Complications found in subjects with PCOS were preterm preterm were found in (2.78%), IUFD (17.24%), abortion (9.72%) and ectopic pregnancy (1.39%). No association was found between PCOS and IUFD in women undergoing FIV programs (RR: 1.07, 95% CI: 0.52-2.20, p-value: 0.864). Interaction between PCOS and ratio <6 had higher probability of having abortion in women

undergoing FIV program obtained. (RR: 7.32, 95% CI: 2.10-25.45, P-value: 0.002). Conclusion: PCOS does not affect the occurrence of IUFD and abortion in women undergoing FIV programs."

"Pendahuluan: Sindroma ovarium polikistik (SOPK) merupakan masalah reproduksi yang sering terjadi pada perempuan usia reproduksi, namun hingga saat ini etiopatogenesis SOPK masih belum jelas. Penelitian ini bertujuan menganalisis peran sel granulosa folikel ovarium dalam etiologi SOPK, keterkaitan genotip FSHR Asn680Ser dengan patogenesis SOPK dan peran gen CYP19A1(aromatase) dalam patogenesis SOPK. Metode: Penelitian ini menggunakan desain penelitian analitik observasional berbentuk studi seran lintang (cross sectional study) dan dilakukan di Departemen Biologi FKUI, Klinik Yasmin-RSCM Kencana dan Laboratorium terpadu FKUI pada tahun 2011-2014. Sebanyak 142 subyek penelitian (66 pasien SOPK dan 76 pasien bukan SOPK) terlibat dalam penelitian ini. Sampel penelitian berupa darah tepi dan cairan folikel ovarium yang diaspirasi ketika proses ovum pick up sebagai sumber sel granulosa. Dilakukan isolasi DNA untuk analisis RFLP polimorfisme FSHR Asn680Ser, dilakukan kultur sel granulosa untuk mengetahui kemampuan proliferasi sel granulosa dan analisis ekspresi mRNA aromatase sel granulosa dengan metode RT-qPCR. Hasil: Indeks proliferasi sel dan ekspresi mRNA aromatase sel granulosa pada kelompok SOPK lebih rendah secara bermakna dibandingkan bukan SOPK (p<0,05). Tidak ditemukan perbedaan bermakna distribusi genotip FSHR Asn680Ser antara kelompok SOPK dan bukan SOPK (p>0,05), tidak ditemukan perbedaan bermakna antara kadar hormon FSH basal berdasarkan variasi genotip FSHR Asn680Ser pada kelompok SOPK dan bukan SOPK (p>0,05). Tidak ditemukan perbedaan yang bermakna indeks proliferasi sel granulosa berdasarkan variasi genotip FSHR Asn680Ser baik pada kelompok SOPK maupun bukan SOPK (p>0,05). Tidak terdapat korelasi antara indeks proliferasi sel granulosa dengan ekspresi mRNA aromatase (p>0,05). Kesimpulan: Indeks proliferasi sel dan tingkat ekspresi mRNA aromatase sel granulosa kelompok SOPK menurun dibandingkan kelompok bukan SOPK. Genotip FSHR Asn680Ser tidak menentukan kerentanan individu untuk menderita SOPK. Kadar hormon FSH basal dan indeks proliferasi sel granulosa tidak berbeda antara kelompok SOPK dan bukan SOPK berdasarkan variasi genotip FSHR Asn680Ser. Tidak ada korelasi antara indeks proliferasi sel dengan ekspresi mRNA aromatase sel granulosa pada penelitian ini.

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Introduction: Polycystic ovary syndrome (PCOS) is a common reproductive problem in women at reproductive age, but until now aetiopathogenesis of PCOS has not been fully understood. The objective of this study was to analyse interrelationship between proliferation of ovarian follicular granulosa cells, CYP19A1 expression and polymorphism at codon 680 of FSHR towards the etiology of PCOS.

Methods: Observational analytic in the form of cross-sectional study was used in this research. The study was carried out between 2011-2014 at the Department of Biology, Integrated laboratory of Faculty of Medicine University of Indonesia and Yasmin clinic at the Cipto Mangunkusumo Hospital. A total of 142 subjects (66 patients with PCOS and 76 patients without PCOS) were involved in this study. Granulosa cells for culture were obtained from ovarian follicular fluid and total RNA was isolated from the cells. DNA samples were extracted from peripheral blood. Granulosa cell proliferation index was determined by counting under a phase-contrast microscope. CYP19A1 expression was measured by qRT-PCR, whereas polymorphism at Asn680Ser FSHR was performed by RFLP.

Result: Cell proliferation index and CYP19A1 mRNA expression levels in the granulosa cells of the PCOS group was significantly lower than non-PCOS (p < 0.05). There was no significant difference found in Asn680Ser FSHR genotype distribution between PCOS and non-PCOS group (p > 0.05). Based on Asn680Ser FSHR genotype variation, no significant difference was found between basal FSH hormone levels in the PCOS and non- PCOS group (p > 0.05) and FSHR genotype variation did not correlate with granulosa cell proliferation index between PCOS and non-PCOS group (p > 0.05). Moreover, there was no correlation between the granulosa cell proliferation index with aromatase mRNA expression levels (p > 0.05).

Conclusion: Cell proliferation index and CYPA1 expression of granulosa cells in PCOS group were lower compared to the non PCOS group although no correlation was found between the two parameters. Asn680Ser FSHR genotype did not correlate with individual susceptibility to PCOS. FSHR genotype variation did not correlate with basal FSH levels and granulosa cell proliferation index between PCOS and non-PCOS."

"

Sindrom Ovarium Polikistik (SOPK) merupakan gangguan pada sistem reproduksi wanita yang menjadi penyebab umum terjadinya infertilitas pada usia reproduktif. Etiologi dari SOPK belum diketahui dengan pasti, namun lebih dari 50% wanita SOPK mengalami obesitas. Single Nucleotide Polymorphism (SNP) rs9939609 gen Fat Mass and Obesity Associated (FTO) merupakan kandidat genetik yang dapat memengaruhi perkembangan obesitas dan kerentanan terhadap SOPK. Tujuan dari penelitian ini untuk mengetahui asosiasi SNP rs9939609 gen FTO dengan SOPK. Penelitian ini menggunakan 120 sampel darah dengan masing-masing 30 sampel untuk setiap kelompok, yaitu kelompok wanita normal obesitas, normal non-obesitas, SOPK obesitas, dan SOPK non-obesitas. Metode yang digunakan yaitu amplifikasi sekuens target dengan Polymerase Chain Reaction (PCR), validasi dengan elektroforesis, dan sekuensing dengan menggunakan Automated Sanger. Hasil sekuensing dianalisis menggunakan perangkat lunak Bioedit dan FinchTV. Hasil penelitian ini menunjukkan adanya frekuensi minor alel A sebesar 29,6% serta frekuensi genotipe AA, AT, dan TT secara berurutan sebesar 10%, 39,20%, dan 50,80%. Studi ini juga menunjukkan hasil tidak adanya asosiasi (p>0,05) antara SNP rs9939609 gen FTO dengan sindrom ovarium polikistik.

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Polycystic Ovarian Syndrome (PCOS) is a female reproductive disorder which is a common cause of infertility at reproductive age. The etiology of PCOS is still unclear, however more than 50% of PCOS women are obese. Single Nucleotide Polymorphism (SNP) rs9939609 Fat Mass and Obesity Associated (FTO) gene is a genetic candidate that can affect the development of obesity and susceptibility to PCOS. This study aims to determine the association of FTO gene SNP rs9939609 with PCOS. Samples in this study was 120 blood samples divided into 30 samples for each group, normal with obesity, normal lean, PCOS with obesity, and PCOS lean. Amplification of target sequences using the PCR method, validation with electrophoresis, and sequencing was carried out using an Automated Sanger. Sequencing results were analyzed with Bioedit and FinchTV software. The results of this study showed that a minor allele A frequency was 29.6% and the genotype frequencies of AA, AT, and TT were 10%, 39.20%, and 50.80%, respectively. This study also showed no association (p>0.05) between SNP rs9939609 with polycystic ovarian syndrome.

 

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"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. "

"Sindrom ovarium polikistik (SOPK) merupakan kelainan reproduksi yang ditandai dengan anovulasi, menstruasi tidak teratur, dan hirsutisme yang seringkali menyebabkan infertilitas. Meski etiologinya belum sepenuhnya dipahami, namun telah diketahui bahwa sebagian besar wanita dengan SOPK mengalami obesitas dengan prevalensi mencapai 40—80%. Obesitas merupakan kelebihan akumulasi lemak tubuh yang dicirikan dengan hipertrofi. Salah satu gen yang diduga terkait dengan obesitas adalah gen fat mass and obesity associated (FTO). Gen FTO menyebabkan peningkatkan nilai BMI. Penelitian ini bertujuan untuk mengetahui perbedaan ekspresi mRNA gen FTO dan korelasinya dengan BMI pada wanita SOPK dan normal dengan obesitas dan non-obesitas. Jaringan darah digunakan sebagai sumber mRNA yang diambil pada 30 wanita non obesitas, 30 wanita normal obesitas, 30 wanita SOPK non-obesitas, dan 30 wanita SOPK obesitas. Kuantitas ekspresi mRNA gen FTO ditentukan dengan menggunakan quantitative real-time PCR. Hasil penelitian menunjukkan terdapat perbedaan ekspresi mRNA gen FTO pada kelompok wanita SOPK dan normal dengan obesitas, serta tidak terdapat korelasi antara ekspresi mRNA gen FTO dengan BMI. Gen FTO merupakan gen yang bertanggung jawab terhadap obesitas akan tetapi tidak memiliki keterkaitan dengan sindrom ovarium polikistik, serta tidak memiliki korelasi dengan BMI

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Polycystic ovary syndrome (PCOS) is a reproductive disorder characterized by anovulation, irregular menstruation, and hirsutism which often causes infertility. Although the etiology is not fully understood, it is well known that most women with PCOS are obese with a prevalence of 40-80%. Obesity is an excess of body fat accumulation which is characterized by hypertrophy. Fat mass and obesity associated gene (FTO) is known to correlate with obesity. The study found that FTO gene causes an increase in the BMI. This reserach aim to determine the differences in FTO mRNA gene expression and its correlation with BMI in normal and PCOS woman with obesity and lean. This study used blood tissue as a source of mRNA taken in 30 normal lean woman, 30 normal obese women, 30 PCOS lean women, and 30 PCOS obese women. The quantity of FTO mRNA gene expression was determined using quantitative real-time PCR. The result shows that there is differences in FTO mRNA gene expression in PCOS and normal woman with obesity dan non-obesity. FTO mRNA expression in PCOS and normal obesity woman is higher than those in the PCOS and normal lean women, and there is no correlation between FTO gene mRNA expression and BMI. Thus, the FTO gene is a gene responsible for obesity but has no association with polycystic ovary syndrome, and does not have a correlation with BMI. "

"Sindrom ovarium polikistik (SOPK) adalah kelainan endokrin yang paling banyak ditemukan dan memengaruhi 5–20% perempuan pada usia reproduksi. Kadar LH dan rasio LH dengan FSH lebih tinggi pada pasien SOPK nir-obese dibandingkan obese. Sekresi LH dan FSH dipengaruhi oleh pulsatilitas GnRH neuron GnRH di hipotalamus. Kisspeptin diduga sebagai regulator utama sekresi GnRH, sedangkan neurokinin B (NKB) dan dinorfin mengatur sekresi kisspeptin neuron KNDy. Namun, patofisiologi gangguan neuroendokrin pada pasien SOPK nir-obese belum dipahami sehingga diperlukan penelitian untuk mengetahui hubungan kadar kisspeptin, NKB dan dinorfin dengan rasio LH/FSH serta hubungannya dengan polimorfisme dan metilasi DNA gen KISS1. Penelitian ini menggunakan desain potong lintang di Klinik Yasmin, RSUPN dr. Cipto Mangunkusumo Kencana dan klaster Human Reproduction, Infertility and Family Planning IMERI UI pada bulan September 2021 sampai Januari 2023 dengan subjek penelitian 120 pasien SOPK nir-obese. Dilakukan pengukuran parameter komposisi tubuh, skor Ferriman-Gallwey dan pemeriksaan kadar FSH, LH, rasio LH/FSH, kisspeptin, NKB, dinorfin, leptin, adiponektin, AMH, glukosa darah puasa, insulin puasa, HOMA-IR, testosteron, dan SHBG. Dilakukan analisis polimorfisme rs4889 dan rs5780218 gen KISS1 danmetilasi DNA gen KISS1. Analisis bivariat dan analisis jalur dilakukan untuk mengetahui hubungan antarvariabel. Terdapat hubungan negatif antara dinorfin dengan kisspeptin, sedangkan kadar NKB tidak berhubungan dengan kisspeptin. Tidak ada hubungan kadar kisspeptin dengan rasio LH/FSH; namun, dinorfin berhubungan positif dengan rasio LH/FSH pada pada analisis bivariat maupun analisis jalur. Kadar AMH berhubungan dengan rasio LH/FSH baik pada kedua analisis. Pada analisis jalur, terdapat hubungan positif antara HOMA-IR dengan FAI dan antara FAI dengan AMH. Pada analisis polimorfisme gen KISS1tidak terdapat hubungan antara frekuensi genotipe maupun frekuensi alel rs4889 dan rs5780218 gen KISS1 SOPK nir-obese dengan kadar kisspeptin dan rasio LH/FSH. Tidak terdapat perbedaan bermakna antara metilasi DNA dengan kadar kisspeptin dan rasio LH/FSH. Terdapat hubungan antara peningkatan dinorfin dengan penurunan kadar kisspeptin. Hubungan dinorfin dengan rasio LH/FSH kemungkinan disebabkan oleh rendahnya kadar progesteron. Peningkatan AMH berhubungan dengan peningkatan rasio LH/FSH pada pasien SOPK nir-obese. AMH merupakan variabel perantara HOMA-IR dan FAI terhadap rasio LH/FSH. Tidak ada hubungan polimorfisme rs4889 dan rs5780218 gen KISS1 serta metilasi DNA gen KISS1 dengan kisspeptin dan rasio LH/FSH pada pasien SOPK nir-obese. Perlu penelitian lebih lanjut untuk mengetahui potensi terapi terhadap dinorfin dan AMH dalam tatalaksana pasien SOPK nir-obese.

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Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 5–20% of reproductive age women. LH levels and LH/FSH ratios are higher in lean PCOS patients than in obese patients. LH and FSH secretion are influenced by GnRH pulsatility of GnRH neurons in the hypothalamus. Kisspeptin is thought to be the main regulator of GnRH secretion, whereas neurokinin B (NKB) and dynorphin regulate kisspeptin secretion in KNDy neurons. However, the pathophysiology of neuroendocrine disorders in lean PCOS patients is not well established. This study aims to determine the relationship between kisspeptin, NKB and dynorphin levels with the LH/FSH ratio and the relationship between polymorphism and DNA methylation of the KISS1 gene. This study used a cross-sectional design at the Yasmin Clinic, RSUPN dr. Cipto Mangunkusumo Kencana and the IMERI UI Human Reproduction, Infertility and Family Planning cluster from September 2021 to January 2023 with 120 lean PCOS patients as subjects. Body composition parameters, Ferriman-Gallwey score, FSH, LH, LH/FSH ratio, kisspeptin, NKB, dynorphin, leptin, adiponectin, AMH, fasting blood glucose, fasting insulin, HOMA-IR, testosterone, and SHBG were measured. Analysis of KISS1 gene polymorphisms of rs4889 and rs5780218 and DNA methylation were performed. Bivariate analysis and path analysis were performed to determine the relationship between variables. There was a negative relationship between dynorphin and kisspeptin, while NKB levels was not related to kisspeptin. There was no relationship between kisspeptin levels and the LH/FSH ratio; however, dynorphin was positively related to the LH/FSH ratio in both bivariate and pathway analysis. AMH levels was positively correlated with the LH/FSH ratio in both analyses. In path analysis, there is a positive relationship between HOMA-IR and FAI as well as between FAI and AMH. In the analysis of the KISS1 gene polymorphism, there was no significant difference between the genotype and allele frequencies of rs4889 and rs5780218 of the lean KISS1 gene with kisspeptin levels and the LH/FSH ratio. There was no significant difference between DNA methylation with kisspeptin levels and LH/FSH ratio. There is a relationship between the increased dynorphin and decreased kisspeptin levels. The association of dynorphins with the LH/FSH ratio may be due to low levels of progesterone. Increased AMH is associated with increased LH/FSH ratio in lean PCOS patients. AMH is an intermediary variable between HOMA-IR and FAI with the LH/FSH ratio. There is no relationship between the rs4889 and rs5780218 KISS1 gene polymorphisms and KISS1 gene DNA methylation with kisspeptin and the LH/FSH ratio in lean PCOS patients. Further research is required to determine the therapeutic potential of dynorphin and AMH in the management of lean PCOS patients."