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"Tujuan : Untuk mengetahui hubungan antara GDF-9 dan BMP-15 Serum dan cairan folikel, untuk memprediksi kualitas oosit pada wanita yang menjalani siklus fertilisasi in vitro (FIV). Metode : Studi  Potong Lintang dengan jumlah sampel penelitian sebanyak 30 darah sérum dan 30 sampel cairan folikel yang diambil saat petik telur (OPU), dilakukan pemeriksaan GDF-9 dan BMP-15 menggunakan kit ELISA. Dilakukan analisa dengan uji korelasi Pearson dan Spearman  untuk melakukan analisa hubungan antara GDF-9 dan BMP-15 serum dan cairan folikel dengan parameter-parameter kualitas oosit seperti laju maturasi dan laju fertilisasi. Hasil : rerata usia subyek penelitiann adalah 35,0(26,0-39,0) tahun. Kadar GDF-9 cairan folikel adalah 163,0 pg/ml (48,0-537) dan kadar GDF-9 serum 260,33 pg.ml ± 121,82) sedangkan kadar rerata BMP-15 cairan folikel adalah 58,30 pg/ml ± 31,54 dan kadar BMP-15 serum 74,20 pg/ml (1,0-610). Tidak terdapat hubungan yang bermakna antara kadar GDF-9 serum dan GDF-9 cairan folikel (p =0,245) sedangkan antara BMP 15 serum dan BMP-15 cairan folikel  terdapat hubungan bermakna (p =0,001). Simpulan : Terdapat sebaran yang tidak normal kadar GDF-9 serum dan cairan folikel, keduanya tidak berkorelasi. Terdapat korelasi positif kadar BMP-15 serum dan BMP-15 cairan folikel. Terdapat  korelasi yang kuat. antara BMP-15 serum dengan laju maturasi. Tidak terdapat korelasi antara kadar GDF-9 serum, GDF-9 cairan folikel dan BMP-15 cairan folikel dengan laju maturasi dan laju fertilisasi. GDF-9 serum-cairan folikel dan BMP-15 serum-cairan folikel tidak dapat memprediksi kualitas oosit.

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Aim : To determine the relationship between GDF-9 and BMP-15 serum within follicular fluid in order to predict the quality of oocytes in women undergoing In Vitro Fertilisation (IVF). Method : We collected 30 samples of blood serum and 30 samples of follicular fluid on the day of ovum pickup (OPU), and we examined GDF-9 and BMP-15 using ELISA kits. Analysis by Pearson and a partial-correlation was conducted to analyse the correlation between the concentration of GDF-9 and BMP-15 in serum and follicular fluid with general physiological parameters, such as maturation rates and fertilisation rates.Results : The mean age of the subjects was 35,0 (26,0-39,0) years. The level of GDF-9 in the follicular fluid was 163,0 pg/ml (48,0-537), and the level in the serum was 260.33 pg/ml±121,82. The level of BMP-15 in the follicular fluid was 58,30 pg/ml ± 31,54, and the level in the serum was 74,20 pg/ml (1,0-610). There was no correlation between GDF-9 serum and follicular fluid (P = 0.245) but any correlation  between BMP-15 and follicular fluid (p = 0.001). Conclusion : There was an abnormal distribution of GDF-9 serum and follicular fluid levels, both of them not correlate. There was a positive correlation between BMP-15 serum and BMP-15 follicular fluid. There was strong correlation between BMP-15 serum and maturation rates. No correlation between levels of GDF-9 serum-follicular fluid, and BMP-9 follicular fluid with maturation and fertilization rates. GDF-9 serum-follicular fluid, BMP-15 serum-follicular fluid are not able to predict the quality of oocytes."

"Pendahuluan : Infertilitas merupakan salah satu gejala pada endometriosis dengan prevalensi mencapai 40-50%. Endometriosis memiliki dampak merugikan terhadap kualitas oosit, sementara sampai saat ini belum ada biomarker baik dari serum ataupun cairan folikel yang dapat dijadikan acuan penilaian kualitas oosit untuk dapat digunakan pada pasien endometriosis yang menjalani fertilisasi in vitro (FIV). Telah ditemukan bahwa pada serum pasien endometriosis terjadi perubahan ekspresi microRNA dimana miRNA-125b memiliki peningkatan yang paling signifikan dengan sensitifitas dan spesifisitas yang paling tinggi. Pada cairan folikel, miRNA-125b berperan saat transisi fase folikular-luteal dengan mempengaruhi ekspresi leukemia inhibitory factor (LIF). LIF diketahui dapat menginduksi sel kumulus yang kemudian mempengaruhi maturasi oosit.Tujuan: Tujuan penelitian ini adalah untuk mencari apakah terdapat hubungan antara miRNA-125b serta LIF dengan kualitas oosit pada pasien infertil dengan endometriosis.Desain: Studi Analitik korelatif dengan desain potong lintang.Material dan Metode: Sampel penelitian didapatkan dari 31 pasien infertil dengan endometriosis yang menjalankan program FIV di Klinik Yasmin RSCM Kencana, dan Klinik Melati RSAB Harapan Kita. Sesaat sebelum petik ovum, sebanyak 5cc sampel darah dari setiap pasien akan diambil untuk penilaian ekspresi miRNA-125b. Pada saat petik ovum, sebanyak 10cc dari total cairan dari folikel yang didapat akan diambil untuk penilaian ekspresi miRNA-125b dan kadar LIF. Oosit yang didapat dinilai oleh embriolog. Pemeriksaan ekspresi miRNA dilakukan dengan RT-PCR, dan kadar LIF menggunakan metode sandwich ELISA.Hasil:Terdapat korelasi negatif antara miRNA-125b serum dengan LIF cairan folikel (p=0,042; r=-0,34). Tidak terdapat korelasi antara miRNA-125b serum dengan miRNA-125b cairan folikel. Tidak terdapat korelasi antara miRNA-125b cairan folikel dengan LIF cairan folikel. Tidak terdapat korelasi antara miRNA-125b serum, miRNA-125b cairan folikel, dan LIF cairan folikel dengan kualitas oosit. Terdapat hubungan yang bermakna antara kadar ekspresi miRNA-125b cairan folikel dengan angka kehamilan biokimia.Kesimpulan: Terdapat ekspresi miRNA-125b pada serum dan cairan folikel pada pasien endometriosis, namun miRNA-125b belum dapat dijadikan sebagai parameter yang kuat untuk pemeriksaan kualitas oosit pada pasien endometriosis yang menjalani FIV.

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Introduction : Infertility is one of the symptoms in endometriosis with prevalence reaching 40-50%. Endometriosis is known to have detrimental effect on oocyte quality, yet until now there is no biomarker derived from either serum, or even follicular fluid, which can be used as reference for oocyte quality assessment in endometriosis patients going through in vitro fertilization (IVF) procedures. Changes of some microRNAs expression has been found in serum of endometriosis patients, with miRNA-125b showing the most significant increase with the highest sensitivy and specificity. In follicular fluid, miRNA-125b play role during follicular-lutheal phase transition by targeting the expression of Leukemia Inhibitory Factor (LIF). LIF has been studied to have the ability to induce cumulus cell expansion which in turn will affect the oocytes maturation.

Purpose: The purpose of this study is to observe the correlation between miRNA-125b, LIF, and oocyte quality in infertile patient with endometriosis.

Design: this is a cross-sectional study with correlation analysis method.

Materials and Methods: in this study, samples were collected from 31 infertile women with endometriosis undergoing in vitro fertilization procedure at Yasmin Clinic of Dr. Cipto Mangunkusumo Hospital, and Melati Clinic of Harapan Kita Mother and Child Hospital. Shortly prior to ovum pick up (OPU) procedure, 5cc of blood sample from each patients was collected, and 10 cc of total follicular fluid was obtained during OPU. Harvested oocytes during the procedure were assessed and scored by embryologist. MiRNA-125b expressions from serum and follicular fluid samples were analyzed using RT-PCR, and LIF levels were analized using ELISA sandwich method.

Result: negative correlation was found between the expression of miRNA-125b serum and LIF follicular fluid (p=0,042; r=-0,34). No correlation was found between the expression of miRNA-125b in serum and in follicular fluid, as well as the expression of miRNA-125b in follicular fluid and LIF in follicular fluid. No correlation was found between the expression of miRNA-125b in serum, follicular fluid, also LIF in follicular fluid, with oocyte quality. Significant result was found between the expression of miRNA-125b in follicular fluid and biochemical pregnancy rate.

Conclusion: This study found miRNA-125 expression represented in serum and follicular fluid in endometriosis patient, but it still cannot be used as a strong parameter for assessing the oocyte quality in infertile women with endometriosis"

"Latar Belakang: Growth Differentiation Factor 9 (GDF9) adalah salah satu anggota dari superfamili TGF-β yang merupakan salah satu oocyte-secreted factor (OSF). GDF9 memainkan peran penting dalam folikulogenesis ovarium, kompetensi perkembangan oosit, serta sebagai molekul esensial yang mengontrol berbagai proses sel granulosa dan laju ovulasi. GDF9 merupakan OSF yang memainkan peran penting dalam menjaga fertilitas wanita. Penelitian ini bertujuan untuk mengetahui apakah ekspresi GDF9 berkorelasi dengan kualitas oosit dan laju fertilisasi pada pasien fertilisasi in vitro.Tujuan: Mengetahui korelasi ekspresi GDF-9 dengan kualitas oosit dan laju fertilisasi pada pasien Fertilisasi In VitroMetode: Penelitian ini adalah penelitian potong lintang yang dilaksanakan di Klinik Yasmin, Rumah Sakit dr. Cipto Mangunkusumo, Jakarta sejak bulan Juli 2019 sampai bulan Juli 2020. Terdapat 26 wanita berusia 25-40 tahun pasien Fertilisasi In Vitro tanpa penyakit endometriosis maupun Sindrom Ovarium Polikistik yang menjadi subjek penelitian ini. Cairan folikel pasien diambil, kemudian dilakukan pengukuran ekspresi gen GDF9. Setelah itu, dilakukan evaluasi pada data ekspresi gen GDF9 serta diuji korelasinya dengan kualitas oosit dan laju fertilisasi pasien menggunakan aplikasi SPSS.Hasil: Sebanyak 26 pasien IVF berpartisipasi dalam penelitian ini. Median jumlah ekspresi gen GDF9 adalah sebanyak 2.47 x 10-5 ng/μl dengan median kualitas oosit dan laju fertilisasi pasien IVF sebesar 3.00 dan 0.60. Berdasarkan hasil uji korelasi, terdapat korelasi negatif antara ekspresi GDF9 terhadap laju fertilisasi dengan kekuatan korelasi sedang (r = -0.443, p = 0.012). Sementara, ditemukan korelasi tidak bermakna antara ekspresi GDF9 terhadap kualitas oosit (r = -0.306, p = 0.064).Kesimpulan: Terdapat korelasi negatif dengan kekuatan korelasi sedang antara ekspresi GDF9 dengan laju fertilisasi, sementara hubungan ekspresi GDF-9 dengan kualitas oosit memiliki korelasi tidak bermakna.

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Background: Growth Differentiation Factor 9 (GDF9) is a member of the TGF-β superfamily which is one of the oocyte-secreted factor (OSF). GDF9 plays an important role in ovarian folliculogenesis, the competence of oocyte development, as well as an essential molecule that controls various granulosa cells process and the rate of ovulation. GDF9 is an OSF which plays an important role in maintaining female fertility. This study is conducted to see the correlation between the expression of GDF9 gene with the oocyte quality and the fertilization rate in the IVF patients.

Aim: To find out the correlation between the expression of GDF9 with the oocyte quality and the rate of fertilization of IVF Patients

Methods: This study is a cross-sectional study which was conducted at Klinik Yasmin dr. Cipto Mangunkusumo General Hospital, Jakarta since July 2019 to July 2020. 26 IVF patients aged 25-40 years without the conditions of endometriosis or Polycystic Ovary Syndrome (PCOS) participated in this study. Follicular fluids are taken from the patients and the GDF9 gene expression were measured. The data were then evaluated for its correlation with the oocyte quality and the fertilization rate using the SPSS application.

Results: Abour 26 IVF patients were participated in this study. The median amount of GDF9 gene expression was 2.47 x 10-5 ng/μl. The median of the oocyte quality and the fertilization rate was 3.00 and 0.60. According to the correlation test, there is a negative correlation between the expression of GDF9 gene and the fertilization rate with a moderate statistical correlation (r = -0.443, p = 0.012). Meanwhile, the expression of GDF9 gene has no significance correlation with the oocyte quality (r = -0.306, p = 0.064).

Conclusion: This study showed a negative correlation between the expression of GDF9 gene and the fertilizatio rate, while the relation between the GDF9 expression and the occyte quality has no significance correlation."

"Pendahuluan: Endometriosis berkaitan dengan adanya inflamasi  kronik,  gangguan  maturasi  oosit,  peningkatan stress  oksidatif  radikal,  dan  apoptosis  yang  kemudian  mendasari  terjadinya  infertilitas pada wanita usia subur.  Fertilisasi In Vitro (FIV)  merupakan  salah  satu  teknik  yang dapat menangani  infertilitas  dengan  tingkat  keberhasilannya  bergantung  dengan  kualitas  oosit  yang diambil  untuk  menjadi  embrio.  Kualitas oosit dipengaruhi  oleh  nutrisi. Profil  mikronutrien  seperti  vitamin  D  dan  zink  dianggap mempengaruhi  fungsi  reproduksi  melalui aktivitas  anti-inflamasi,  anti-apoptosis dan  anti-oksidan  yang dimiliki. Sayangnya, urgensi untuk menjaga adekuasi nutrisi  ini  sering diabaikan. Selain itu juga hingga saat ini  belum  ada  acuan  untuk  memprediksi  kadar  profil  vitamin  D  dan  zink  dalam serum  dan  cairan  folikular  yang  berhubungan  pada  pasien  endometriosis  itu  sendiri.Tujuan: Penelitian ini membandingkan kadar vitamin D dan zink di serum dan cairan folikular pada pasien endometriosis dan non-endometriosis.Metode: Studi ini merupakan studi potong lintang yang dilaksanakan pada pasien Fertilisasi In Vitro (FIV) di Klinik Yasmin, RSCM Kencana selama Juli –  Desember 2020. Data klinis diperoleh melalui rekam medis dan wawancara pasien. Data laboratorium diperoleh melalui sampel darah dan cairan folikuler yang diperoleh bersamaan dengan prosedur Ovum Pick Up (OPU). Sampel kemudian dikelompokkan menjadi kelompok endometriosis dan non-endometriosis. Setelah itu data disajikan dalam tabel dan dianalisis dengan uji parametrik, yaitu uji-t berpasangan bila sebaran data normal atau uji non parametrik, yaitu uji Mann-Whitney bila sebaran data tidak normal. Data dianalisis dengan SPSS 24.Hasil: Dari jumlah sampel 26 pasien pada studi ini, didapatkan tidak adanya perbedaan bermakna dari vitamin D serum pada pasien endometriosis (22,83 (5,00 – 40,00)) dan non endometriosis (30,11 (10,40-76,10)), namun secara rerata kadar vitamin D serum pada pasien endometriosis lebih rendah. Kadar vitamin D cairan folikular pada pasien endometriosis (15,33 (4,50-36,32)) dan non-endometriosis (23,64 (4,98-60,22)) tidak berbeda bermakna (P>0,05). Kadar zink serum pada pasien endometriosis (75,23 ± 11,58) dan non-endometriosis (79,46 ± 12,09) tidak berbeda bermakna (P>0,05). Konsentrasi zink paada cairan folikular tidak menunjukkan perbedaan bermakna antara pasien endometriosis (39,00 (22,00 – 49,00)) dan tanpa endometriosis (51,00 (19,00-95,00)) (P>0,05). Kesimpulan: Tidak ditemukan perbedaan bermakna antara kadar vitamin D serta zink serum dan cairan folikular pada pasien endometriosis dan non-endometriosis. 

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Background: Endometriosis associates with chronic inflammation, dysfunction of oocyte maturation, increase of oxidative stress, and apoptosis which underlie infertility problem in reproductive female. In-Vitro Fertilization (IVF) is a technique used to treat infertility with the success rate depending on the quality of the oocytes extracted to become embryos. Oocyte quality is influenced by nutrition. Micronutrient profiles such as vitamin D and zink are thought to influence reproductive function through their anti-inflammatory, anti-apoptotic and anti-oxidant activities. However, the urgency of maintaining nutritional adequacy is often overlooked. In addition, until now there is no reference for predicting levels of vitamin D and zink in serum and follicular fluid associated with endometriosis.

Method: This study is a cross-sectional study conducted on In Vitro Fertilization (FIV) patients at the Yasmin Clinic, RSCM Kencana during July – December 2020. Clinical data were obtained through medical records and patient interviews. Laboratory data were obtained through blood and follicular fluid samples obtained in conjunction with the Ovum Pick Up (OPU) procedure. The samples were then grouped into endometriosis and non-endometriosis groups. After that the data are presented in tables and analyzed by parametric test, namely paired t-test if the data distribution is normal or non-parametric test, namely the Mann-Whitney test if the data distribution is not normal. Data were analyzed by SPSS 24.

Result: From a total sample of 26 patients in this study, there was no significant difference in serum vitamin D in patients with endometriosis (22.83 (5.00 – 40.00)) and non-endometriosis (30.11 (10.40-76.10). )), but the mean serum vitamin D level in endometriosis patients was lower. Follicular fluid vitamin D levels in patients with endometriosis (15.33 (4.50-36.32)) and non-endometriosis (23.64 (4.98-60.22)) were not significantly different (P>0.05) . Serum zink levels in patients with endometriosis (75.23 ± 11.58) and non-endometriosis (79.46 ± 12.09) were not significantly different (P>0.05). Zink concentration in follicular fluid did not show a significant difference between endometriosis patients (39.00 (22.00 – 49.00)) and without endometriosis (51.00 (19.00-95.00)) (P>0.05) .

Conclusion: There was no significant difference between the levels of vitamin D and serum zink and follicular fluid in patients with endometriosis and non-endometriosis."

"Tujuan : Membandingkan dan menentukan perbedaan kadar homosistein dalam darah dan zalir folikel pada wanita infertil dengan dan tanpa endometriosis, kemudian menganalisis pengaruh kadar homosistein tersebut dengan mutu oosit.Metode : Penelitian ini merupakan penelitian potong lintang (cross sectional). Lima puluh sembilan subjek mengikuti program fertilisasi in-vitro yang masuk dalam kriteria penerimaan dibagi menjadi dua kelompok sama besar, yaknikelompok endometriosis dan tanpa endometriosis secara konsekutif (consecutive sampling). Masing-masing subjek diambil percontoh dari darah dan zalir folikel kemudian diukur kadar homosisteinnya dengan metode teraimun CMIA. Rerata masing-masing kelompok diuji statistik dengan uji t independen.Hasil : Rerata kadar homosistein dalam darah pada kelompok endometriosis lebih tinggi dibandingkan dengan tanpa endometriosis dan secara statisik berbeda bermakna (8,34 ±2,68 vs 6,71 ±1,56, p=0.007;95%CI: 0,02417-0,14657).Demikian pula dengan kadar homosistein dalam zalir folikel, kelompok endometriosis lebih tinggi dan secara statistik berbeda bermakna (6,19 ±1,67 vs 3,46 ±1,03; p= 0,000; 95% CI : 0,19310-0,32353). Semua mutu oosit baik padakedua kelompok, yakni derajat 3. Terdapat korelasi antara kadar homosistein di dalam darah dan zalir folikel pada kelompok endometriosis dan dinilai dengan uji Pearson didapatkan bermakna (p = 0,002) dan nilai korelasi 0,553 (kekuatan korelasi sedang) dan arah korelasi positif.Kesimpulan : Rerata kadar homosistein dalam darah dan zalir folikel pada wanita infertil dengan endometriosis lebih tinggi dibandingkan dengan tanpa endometriosis dan secara statistik berbeda bermakna. Kadar homosistein ini tidakberpengaruh terhadap mutu oosit. Terdapat korelasi positif antara kadar homosistein dalam darah dan zalir folikel pada kelompok endometriosis.

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Purpose : Compare and determine the differences in levels of homocysteine in

the blood and follicular fluid in infertile women with and without endometriosis, then analyze the effect of homocysteine levels with oocyte quality.

Method : This study was cross-sectional study. Fifty-nine subjects following the

in-vitro fertilization program are included in the admission criteria were divided into two equal groups, ie groups of endometriosis and without endometriosis consecutively (consecutive sampling). Each subject taken from the blood and follicular fluid then measured the levels of homocystein levels with immuoassay

method : The mean of each group was statistically tested with an independent t

test.

Results : The mean levels of homocysteine in the blood is higher in the endometriosis group than without endometriosis group and it was statisticaly significance (8,34 ±2,68 vs 6,71 ±1,56, p=0.007;95%CI: 0,02417-0,14657).

Similarly, the levels of homocysteine in follicular fluid , the endometriosis group

is higher and statisticaly significance (6,19 ±1,67 vs 3,46 ±1,03; p= 0,000; 95% CI : 0,19310-0,32353). All oocytes are in good quality in both groups, maturation grade 3. There is a correlation between the levels of homocysteine in the blood and follicular fluid in the endometriosis group and assessed with Pearson test, and it found significant (p = 0.002) and the correlation value 0.553 (moderate correlation strength) and direction of a positive correlation.

Conclusion : The mean levels of homocysteine in the blood and follicular fluid in infertile women with endometriosis is higher than without endometriosis and were statistically significantly different. These homocysteine levels does not affect the quality of oocytes. There is a positive correlation between the levels of homocysteine in the blood and follicular fluid in endometriosis group."

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Latar belakang: Suplementasi mikronutrien untuk wanita pada masa prakonsepsi, khususnya zinc dan kalsium, terbukti penting untuk maturasi oosit dan ovulasi. Namun, peran zinc dalam mempromosikan kualitas oosit dan potensi perkembangannya belum diketahui secara jelas. GDF9, anggota superfamili TGF b yang disekresikan dari oosit selama proses folikulogenesis, terbukti dapat menjadi biomarker maturasi nuklear oosit dan kualitas embrio. Tujuan: Studi potong lintang ini bertujuan untuk mengetahui apakah ada hubungan antara kadar zinc dan kalsium dalam serum dan cairan folikel dengan ekspresi GDF9 terhadap maturasi oosit. Selain itu, penelitian ini juga bertujuan untuk mengetahui apakah kadar zinc dan kalsium dalam serum dapat mewakili kadar zinc dan kalsium dalam cairan folikel. Metode: Studi ini dilakukan pada 25 subjek penelitian yang menjalani program fertilisasi in vitro di Poliklinik Yasmin RSUPN Cipto Mangunkusumo (RSCM) Kencana. Darah vena sebanyak 6 cc diambil pada hari ovum pick up (OPU) dan kemudian dianalisis di laboratorium untuk mengetahui kadar zinc, kalsium, dan protein GDF9. Cairan intrafolikuler dan sel granulosa juga akan diambil dan diperiksa kadar zinc dan kalsium dari cairan intrafolikuler serta ekspresi mRNA GDF9 dari sel granulosa. Hasil:  Dari 25 subjek penelitian, 12 subjek (48%) di antaranya dikategorikan ke dalam kelompok angka maturasi oosit baik (berdasarkan indikator oosit matur dari konsensus Vienna) serta 13 (52%) sisanya dikategorikan ke dalam kelompok angka maturasi oosit buruk. Dari uji korelasi antara kadar zinc dan kalsium dalam serum dengan cairan folikel, kadar zinc folikel terbukti berkorelasi secara signifikan dengan kadar zinc serum (p = 0,019). Kadar GDF9 serum juga terbukti berkorelasi secara signifikan dengan ekspresi GDF9 (p = 0,047). Tidak didapatkan korelasi yang bermakna antara kadar zinc dan kalsium serum dengan kadar GDF9 serum serta ekspresi mRNA GDF9 dari sel granulosa terhadap angka maturasi oosit (p > 0,05). Kesimpulan: Kadar GDF9 serum dapat menjadi pengganti biomarker untuk kualitas oosit. Tidak didapatkan hubungan antara kadar zinc dan kalsium dalam serum atau cairan folikel terhadap kadar GDF9 serum atau ekspresi mRNA GDF9 dari sel granulosa terhadap angka maturasi oosit.

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Background:  Micronutrient supplementation for women during preconception, especially zinc and calcium, is critical for oocyte maturation and ovulation. However, the role of Zinc in promoting quality of oocytes has not yet been elucidated. GDF9, one of oocyte sereting factor, has been proven to be a biomarker of maturation of nuclear oocyte and quality of embryo. Aim: to investigate any relationship between zinc and calcium levels in serum and follicular fluid and GDF9 expression towards maturation of oocytes. In addition, this study also aimed to determine whether zinc and calcium levels in serum could represent zinc and calcium levels in follicular fluid. Method: This cross-sectional study was conducted on 25 subjects who underwent IVF programs at the Yasmin Policlinic, RSCM Kencana. Six mililiters of venous blood was taken on the day of the ovum pick up (OPU) and then analyzed in the laboratory to determine the levels of zinc, calcium, and protein GDF9. In addition to venous blood, intrafollicular fluid and granulosa cells will also be taken and examined zinc and calcium levels from intrafollicular fluid and GDF9 mRNA expression from granulosa cells. Result: 12 (48%) out of 25 subjects were categorized into high oocyte maturation rate (based on Vienna consensus on oocyte maturation rate), and the other 13 (52%) were categorized into low oocyte maturation rate. Follicular zinc levels were significantly correlated with serum zinc levels (p = 0,019). Serum GDF9 levels were also significantly correlated with expressions of GDF9 mRNA (p = 0,047). No significant correlation was found between serum levels of zinc and calcium and serum GDF9 levels or GDF9 mRNA expression towards maturation of oocytes (p > 0,05). Conclusion: Serum GDF9 might substitute for follicular GDF9 as a biomarker of oocyte quality. There is no relationship between serum or follicular zinc/calcium levels and serum GDF9 levels or GDF9 mRNA expression from granulosa cells towards oocyte maturation rates.

 

 

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"Latar Belakang: Salah satu hipotesis yang menjelaskan hubungan endometriosis dengan infertilitas adalah endometriosis diyakini menyebabkan gangguan fisiologi ovarium, salah satunya dengan mempengaruhi folikulogenesis yang menyebabkan penurunan kualitas oosit. Oosit memainkan peran penting dalam mengatur dan mendukung pertumbuhan folikel, melalui produksi faktor pertumbuhan oosit. Beberapa faktor pertumbuhan telah diidentifikasi pada oosit manusia, termasuk growth differentiation factor-9 GDF-9 . Namun, sampai saat ini penelitian mengenai ekspresi GDF-9 pada sel granulosa pada wanita infertil dengan endometriosis masih belum banyak dilakukan. Tujuan: Untuk mengetahui ekspresi mRNA GDF-9 pada sel granulosa pasien endometriosis yang menjalani FIV dan untuk mencari adanya korelasi antara ekspresi GDF-9 dengan kualitas oosit. Metode: Penelitian potong lintang ini dilakukan di Klinik IVF Yasmin RSCM dan Klinik Sander B di Jakarta pada bulan Juli 2014 - Juli 2017. Sebanyak 50 sampel terdiri atas 25 wanita dengan endometriosis dan 25 kontrol. Sampel sel granulosa dikumpulkan pada saat petik oosit. Ekspresi mRNA GDF-9 dinilai menggunakan real time PCR. Hasil: Terdapat penurunan jumlah ambilan oosit, jumlah oosit matur dan skor morfologi oosit pada kelompok pasien dengan endometriosis dan bermakna secara statistik. Ekspresi GDF-9 secara kuantitatif lebih rendah pada kelompok endometriosis dibandingkan dengan kontrol 5.05 0.00002 ndash; 3523 ng/ l vs 81.93 1,47 ndash; 32450 ng/ l; p=0,01 . Pada penelitian ini tidak didapatkan korelasi antara ekspresi GDF-9 dan kualitas oosit dari skor morfologi oosit dan laju fertilisasi. Kesimpulan: Ekspresi GDF9 lebih rendah pada kelompok endometriosis dibandingkan kelompok kontrol. Namun, kami tidak menemukan korelasi antara ekspresi GDF-9 dengan kualitas oosit. Dibutuhkan studi dengan besar sampel yang lebih besar untuk mengkonfirmasi apakah perubahan ekspresi GDF-9 memiliki korelasi dengan kualitas oosit serta untuk membuktikan apakah GDF-9 dapat digunakan sebagai penanda molekuler baru untuk memprediksi kompetensi perkembangan oosit.

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Background: One of the hypothesis that explains the association between endometriosis and infertility is that endometriosis is believed to cause ovarian physiology disturbances, one of them by affecting folliculogenesis that cause decreased oocyte quality. The oocyte plays an important role in regulating and promoting follicle growth, by the production of oocyte growth factors. Several growth factors have been identified in human oocytes, including growth differentiation factor-9 GDF-9. However the studies on GDF-9 expression in granulosa cells of infertile women with endometriosis are sparse.

Objective: To investigate the expression of GDF-9 mRNA in granulosa cells of endometriosis patients undergoing IVF and to find the correlation between GDF-9 expression and oocyte quality.

Method: This cross sectional study was done at Yasmin IVF Clinic and dr. Sander B Clinic Jakarta in July 2014 - July 2017. A total fifty samples of 25 womens with endometriosis and 25 controls were included. We collect the granulosa cells sample at the time of oocyte retrieval. GDF-9 mRNA expression were investigated by Real-Time PCR.

Result: The number of oocytes retrieved, mature oocytes and the oocyte morphology score were lower in the group of patients with endometriosis and this was statistically significant. GDF-9 mRNA expression levels was quantitatively lower in endometriosis groups compared to control 5.05 0.00002 ndash; 3523 ng/ l vs 81.93 1,47 ndash; 32450 ng/ l; p=0,01. However, we did not find any correlation between GDF-9 expression levels and oocyte quality from oocyte morphology score and fertilization rate.

Conclusion: GDF9 mRNA level was lower in endometriosis group compared to control group. However, we did not find correlation between individual GDF-9 level and oocyte quality. Large-sample studies were needed to confirm whether the expression of GDF-9 had a correlation with oocyte quality as well as to prove whether GDF-9 could be used as a new molecular marker to predict the oocyte developmental competence."

"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.

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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 Latar belakang: Penilaian kualitas oosit merupakan bagian terpenting dan tersulit dalam fertilisasi in vitro (FIV). Metode yang saat ini tersedia tidak dapat menilai jumlah dan maturasi oosit secara optimal pada prosedur petik oosit pada FIV. Anti Mullerian Hormone (AMH) dalam cairan folikel dihasilkan langsung oleh sel granulosa, yang diharapkan dapat menjadi parameter alternatif untuk meramalkan kuantitas dan kualitas oosit pada program FIV.Tujuan: Mengembangkan metoda nir-invasif pada program FIV dengan mengetahui nilai prognostik kadar AMH serum dan cairan folikel sebagai parameter alternatif untuk meramalkan kualitas oosit pada program FIV.Metode: Penelitian ini merupakan uji prognostik dengan desain potong lintang selama periode April 2012 hingga Juni 2013 di Poliklinik Yasmin, RSCM, Jakarta. Subjek penelitian merupakan pasien infertilitas yang menjalani program IVF. Pengukuran kadar AMH dan estradiol serum dilakukan pada awal siklus, sementara kadar AMH cairan folikel, jumlah oosit total, jumlah oosit matur dan morfologi oosit dinilai pada saat hari petik ovum. Kualitas oosit dinilai dari skor morfologi oosit modifikasi Xia. Analisis data menggunakan korelasi Pearson dan analisis regresi linier untuk mencari nilai prognostik kadar AMH serum dan cairan folikel sebagai peramal kualitas oosit.Hasil: Didapatkan 102 pasien FIV dengan protokol stimulasi pendek, yang diperiksa kadar AMH serum, kadar AMH cairan folikel, kadar estradiol serum kemudian dinilai jumlah oosit total, jumlah oosit matur dan skor morfologi.Berdasarkan hasil analisis multivariat didapatkan bahwa usia dan AMH serum dapat digunakan dalam meramalkan kualitas oosit (r = - 0,038; r = 0, 183; p < 0,05).Kesimpulan: Kadar AMH serum dan cairan folikel berkorelasi dengan kuantitas oosit. Kadar AMH serum dapat digunakan sebagai parameter untuk meramalkan kualitas oosit, namun tidak untuk AMH cairan folikel

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ABSTRAK Background: Assessment of oocyte quality is an important but difficult component in in vitro fertilization (IVF). Current methods available cannot predict ooctye number and maturation in oocyte pick-up optimally during IVF.Anti Mullerian Hormone (AMH) in follicular fluid is produced directly by granulosa cells, and it could be an alternative parameter to predict oocyte quantity and quality in IVF.Objective: To develop nir-invasif method in IVF program with knowing prognostic value of serum and follicular fluid AMH as alternative parameters to predict oocyte quality.Method: This is a prognostic study with cross sectional design, during a period of April 2012 until June 2013 in Yasmin Clinic, RSCM, Jakarta. The subjects of this study were infertile couples who underwent IVF. The measurement of serum AMH level and serum estradiol serum was done in the beginning of IVF cycles, while follicular fluid AMH, number of oocyte retrieved, number of mature oocyte, and oocyte morphology were measured at the day of ovum pick-up.Oocyte quality using morphological score modified from Xia criteria as parameter. Statistical analysis was done using Pearson correlation and linear regression analysis to measure predictive value of AMH as oocyte qualitypredictors.Result: We obtained 102 short protocol IVF patients. Serum AMH level, AMH level in follicular fluid, serum estradiol, oocyte count, number of mature ooctye, and morphological score were assessed. Based on multivariate analysis, we found that age and serum AMH level can be used to predict oocyte quality (r = - 0,038; r = 0, 183; p < 0,05).Conclusion: There were correlation between serum and follicular fluid AMH with oocyte quantity. AMH level in serum, but not follicular fluid, can be used as a parameter to predict oocyte quality."

"Latar belakang: Fertilisasi in vitro (FIV) merupakan salah satu tata laksana utama dalam penanganan infertilitas. Penyuntikan human Chorionic Gonadotropin (hCG)eksogen merupakan salah satu tahapan penting dalam proses FIV untuk proses maturasi oosit. Walaupun sudah terdapat penelitian sebelumnya mengenai korelasi kedua hal tersebut, namun belum didapatkan suatu model prediksi maturitas oosit. Tujuan: Mengetahui korelasi kadar serum hCG 12 jam pascapenyuntikan terhadap tingkat maturitas oosit pada FIV dan model prediksi maturitas oosit. Metode: Penelitian ini merupakan sebuah penelitian potong lintang yang dilakukan pada peserta program FIV di Klinik Yasmin, RSUPN dr. Cipto Mangunkusumo, Jakarta, Indonesia sejak Januari 2020 hingga Desember 2020. Pasien dengan riwayat prosedur pembedahan ovarium, kemoterapi, radioterapi, dan peserta poor responder dieksklusi dari penelitian. Dilakukan penyuntikan r-hCG 250 µg secara subkutan pada semua subjek. Kadar serum hCG 12 jam pascapenyuntikan dan tingkat maturitas oosit setiap subjek dikumpulkan dan dianalisis. Hasil: Didapatkan sebanyak 28 subjek yang diikutsertakan dalam penelitian. Didapatkan korelasi yang tidak bermakna antara kadar hCG 12 jam pascapenyuntikan dan tingkat maturitas oosit (r = 0,052, p = 0,788). Namun, didapatkan kadar serum hCG 12 jam pascapenyuntikan yang lebih tinggi pada subjek dengan tingkat maturitas >75% (mean diff 34.78,p = 0.046). Didapatkan titik potong kadar serum hCG 12 jam pascapenyuntikan sebesar 90.15 mIU/mL untuk memprediksi tingkat maturitas yang baik. (sensitivitas 68.2%, spesifisitas 83.3%). Prediksi tingkat maturitas oosit dapat dilakukan dengan mengetahui kadar serum hCG 12 jam pascapenyuntikan dan indeks massa tubuh (IMT) subjek (sensitivitas 83.3%, spesifisitas 68.2%). Simpulan: Kadar serum hCG 12 jam pascapenyuntikan yang lebih tinggi berhubungan dengan tingkat maturitas oosit yang lebih baik pada peserta program FIV. Tingkat maturitas oosit dapat diprediksi melalui kadar serum hCG 12 jam pascapenyuntikan dan IMT.

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Background: In vitro fertilization (IVF) is one of the main treatments of infertility. Exogenous Human chorionic gonadotropin (hCG) injection is an important process of IVF and thought to be vital in determining oocyte maturation.

Purpose: This study aims to determine the relationship between 12 hours post-injection serum hCG and oocyte maturation rate on IVF participants.

Method: This is a cross-sectional study on IVF participants on Yasmin Clinic, dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia, during the period of January 2020 to December 2020. Subjects with history of ovarian surgery, chemotherapy, radiotherapy, and poor responder subjects were excluded from the study. Subjects were injected with 250 µg of r-hCG subcutaneously. Twelve hours post-injection serum hCG level and oocyte maturation rate were collected and analyzed accordingly.

Result: A total of 28 subjects were included in the study. It was found that higher 12 hours post-injection serum hCG was related with subjects with >75% oocyte maturation rate (mean diff 23.78, p = 0.046). The cut-off point of 12 hours post-injection serum hCG in order to predict better oocyte maturation rate was found to be 90.15 mIU/mL (sensitivity 68.2%, specificity 83.3%). Oocyte maturation rate predicted may be calculated using body mass index and 12 hours post-injection serum hCG. (sensitivity 83,3%, specificity 68,2%).

Conclusion: Higher 12 hours post-injection serum hCG was associated with higher oocyte maturation rate on IVF subjects. Oocyte maturation rate may be predicted using body mass index and 12 hours post-injection serum hCG."