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"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"

"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: 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."

"Pengantar: Endometriosis merupakan salah satu penyebab infertilitas dan menjadi indikasi fertilisasi in vitro (FIV). Laju apoptosis dan stress oksidatif yang tinggi pada pasien endometriosis diyakini menimbulkan efek negatif terhadap peluang keberhasilan FIV. Namun, pengaruh endometriosis terhadap keberhasilan FIV menunjukkan bukti yang inkonsisten dan belum banyak studi yang menilai langsung efek endometriosis terhadap kualitas oosit sebagai parameter keberhasilan FIV.Tujuan: Untuk menilai laju apoptosis pada sel granulosa pasien endometriosis dibanding pasien non-endometriosis melalui rasio ekspresi mRNA BAX/BCL-2 dan menilai korelasinya dengan kualitas oosit yang didapatkan saat petik ovum.Hasil: Sampel didapatkan dari 15 subjek dengan endometriosis dan 15 subjek kontrol. Dosis rekombinan FSH total yang diterima pada kelompok endometriosis untuk stimulasi ovarium lebih tinggi dibandingkan kelompok kontrol (p=0.005). Terdapat perbedaan bermakna kadar ekspresi BAX (p=0.029) dan BCL-2 (p<0.001) pada kedua kelompok, tetapi perbedaan rasio keduanya tidak signifikan (p=0.787). Korelasi antara rasio BAX/BCL-2 dengan parameter kualitas oosit tidak menunjukkan hubungan bermakna di kedua kelompok.Kesimpulan: Tidak terdapat perbedaan signifikan pada rasio kadar BAX/BCL-2 di kedua kelompok dan tidak ditemukan hubungan bermakna antara rasio tersebut dengan kualitas oosit. 

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Introduction: Endometriosis is one of common conditions causing infertility and an indication to undergo in vitro fertilization (IVF). High apoptosis rate and oxidative stress in patient with endometriosis is believed to cause negative effect on IVF success rate. However, there has been conflicting results on endometriosis effect to IVF success and there have been limited studies that directly assess endometriosis and its effect on oocyte quality.

Aim: To assess apoptosis rate on granulosa cells in patients with endometriosis compared to non-endometriosis patients through mRNA BAX/BCL-2 ratio and how it correlates with oocyte quality collected during ovum pick up.

Results: Samples were collected from 15 subjects with endometriosis and 15 control subjects. Total dose of recombinant FSH received by endometriosis group is significantly higher compared to control (p=0.005). There is difference in BAX level (p=0.029) and BCL-2 level (p<0.001) in both groups. However, the ratio does not differ significantly (p=0.787). No significant correlation is found in BAX/BCL-2 ratio and any of the oocyte quality parameters.

Conclusion: We found no significant difference in BAX/BCL-2 ratio between endometriosis and control group as well as significant correlation between the ratio and oocyte quality."

"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."

"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."

"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."

"Pemilihan oosit merupakan salah satu tahap penting dalam fertilisasi in vitro (FIV) sebab semakin banyak jumlah oosit yang masuk kualifikasi, maka semakin besar kesempatan oosit tersebut untuk difertilisasi. Growth Differentiation Factor 9 (GDF9) dan Bone Morphogenetic 15 (BMP15) yang merupakan anggota dari superfamili protein Transforming Growth Factor β (TGF-β), memiliki peranan penting terhadap folikulogenesis. Gen gdf9 dan bmp15 diketahui tidak hanya terekspresikan pada oosit, namun juga pada sel granulosa dan cairan folikel. Oleh karena itu, dilakukan penelitian mengenai ekspresi gen gdf9 dan bmp15 pada sel granulosa dan cairan folikel untuk mengetahui pengaruhnya terhadap kualitas oosit. Lima belas sampel sel granulosa dan cairan folikel dikumpulkan untuk mengukur ekspresi gen gdf9 dan bmp15 secara kuantitatif. Metode kuantifikasi absolut digunakan untuk mengukur tingkat ekspresi gen. Uji korelasi Pearson digunakan untuk menganalisis korelasi antara ekspresi gen gdf9 dan bmp15 terhadap parameter umum fisiologis. Ekspresi gen gdf9 pada sel granulosa memiliki korelasi lemah searah tak signifikan (P>0,05) terhadap umur, tingkat kematangan oosit, tingkat fertilisasi normal, dan tingkat pembelahan. Ekspresi gen bmp15 memiliki korelasi lemah searah tak signifikan (P>0,05) terhadap umur serta memiliki korelasi lemah tak searah tak signifikan (P>0,05) terhadap tingkat kematangan oosit, tingkat fertilisasi normal, dan tingkat pembelahan. Ekspresi gen gdf9 dan bmp15 pada cairan folikel tidak dapat dianalisis sebab kurva standar tidak terkonstruksi.

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Oocyte selection is one of important steps in in vitro fertilization (IVF) procedures, because more number of qualified oocyte will bring its chance to be fertilized bigger. Growth Differentiation Factor 9 (GDF9) dan Bone Morphogenetic 15 (BMP15) are members of protein superfamily Transforming Growth Factor β (TGF-β) which have important role in folliculogenesis. Gdf9 dan bmp15 genes are not only expressed in oocyte, but in granulosa cell and follicular fluid too. Research has been conducted about gdf9 and bmp15 gene expression in granulosa cell and follicular fluid to know their association with oocyte quality. Fifteen samples of granulosa cell and follicular fluid were collected to measure gdf9 and bmp15 gene expression quantitatively. Absolute quantification method were used to measure gene expression levels. Pearson correlation was used to analize correlation between both gene expression levels and general physiological parameters. The expression levels of gdf9 in granulosa cell had weak positive unsignificant (P>0,005) correlation with age, oocyte maturity rate, normal fertilization rate, and cleavage rate. The expression levels of bmp15 in granulosa cell had weak positive unsignificant (P>0,005) correlation with age, but had weak negative unsignificant (P>0,005) correlation with oocyte maturity rate, normal fertilization rate, and cleavage rate. Gdf9 and bmp15 gene expression in follicular fluid cannot be analized because the standard curve could not be constructed."

"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."

"Endometriosis merupakan penyakit ginekologi kronis yang ditandai dengan sel-sel kelenjar dan stroma endometrium yang tumbuh di luar rongga uterus dan dapat mengganggu reseptivitas endometrium. Standar emas untuk diagnosis endometriosis adalah dengan melakukan operasi laparoskopi. Prosedur ini merupakan prosedur invasif yang memiliki risiko melukai endometrium. Oleh karena itu, dibutuhkan diagnosis noninvasif untuk endometriosis yang dapat mengurangi ketidaknyamanan penderita. Salah satu metode noninvasif yang dapat digunakan adalah deteksi biomarker. Salah satu biomarker yang menandakan reseptivitas endometrium adalah Leukemia Inhibitory Factor (LIF). Penelitian ini bertujuan untuk mendeteksi ekspresi gen LIF dari sampel darah perifer pada wanita penderita endometriosis dan wanita normal yang sedang menjalani program in-vitro fertilization (IVF) sebagai penanda reseptivitas endometrium. Penelitian ini dilakukan dengan menganalisis 15 sampel darah wanita pengidap endometriosis dan 15 sampel darah wanita normal menggunakan metode RT-qPCR absolut dengan kurva standar. Kurva standar dibuat dengan fragmen gen LIF, didapatkan nilai efisiensi sebesar 117,74% dan nilai R2 sebesai 0,880345. Kedua nilai tersebut tidak masuk ke dalam kriteria yang baik. Sementara itu, Uji-U Mann-Whitney menunjukkan tidak terdapat perbedaan nyata pada ekspresi gen LIF dari sampel darah wanita penderita endometriosis dan gen LIF dari sampel darah wanita normal. Ekspresi gen LIF terdeteksi pada darah perifer sehingga gen LIF memiliki potensi kuat untuk menjadi biomarker reseptivitas endometrium pada wanita penderita endometriosis. Namun, ekspresi gen LIF pada sampel darah wanita penderita endometriosis dan sampel darah wanita tanpa endometriosis tidak menunjukkan perbedaan nyata.

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Endometriosis is a gynecological disease characterized by endometrial glandular and stromal cells that grow outside the uterine cavity and can interfere with endometrial receptivity. The gold standard for the endometriosis diagnosis is laparoscopic surgery. This procedure is an invasive procedure that carries the risk of injuring the endometrium. Therefore, a noninvasive diagnosis of endometriosis is needed which can reduce the number of sufferers. One of the non-invasive methods that can be used is biomarker detection. One of the biomarkers that indicates endometrial receptivity is Leukemia Inhibitory Factor (LIF). This study aims to detect LIF gene expression from blood samples in women with endometriosis and normal women undergoing in-vitro fertilization (IVF) as a marker of endometrial receptivity. This study was conducted by analyzing 15 blood samples of women with endometriosis and 15 normal women blood samples using absolute RT-qPCR method with standard curves. The standard curve was made with the LIF gene fragment, getting an efficiency value of 117.74% and an R2 value of 0.880345. Both values do not fit into a good criterion. Meanwhile, the Mann-Whitney U-test showed no significant difference in the expression of the LIF gene from blood samples of women with endometriosis and the LIF gene from blood samples of normal women. Expression of LIF was detected in peripheral blood so that the LIF has a strong potential to be a biomarker of endometrial receptivity in women with endometriosis. However, the expression of the LIF in blood samples of women with endometriosis and blood samples of women without endometriosis did not show significant differences."