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dr. Risman Felix Kaban, SpOG dr. Indra Gunasti Munthe, SpOG (K)

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KORELASI ANTARA ALIRAN DARAH CORPUS LUTEUM<br />

DENGAN KONSENTRASI SERUM PROGESTERON<br />

PADA WANITA INFERTIL<br />

TESIS<br />

OLEH :<br />

BOY RIVAI PANDAPOTAN SIREGAR<br />

DEPARTEMEN OBSTETRI DAN GINEKOLOGI<br />

FAKULTAS KEDOKTERAN UNIVERSITAS SUMATERA UTARA<br />

RUMAH SAKIT UMUM PUSAT H. ADAM MALIK<br />

MEDAN<br />

2011<br />

Universitas Sumatera Utara


PENELITIAN INI DIBAWAH BIMBINGAN TIM-5<br />

PEMBIMBING: <strong>dr</strong>. Binarwan Halim, <strong>SpOG</strong> (K)<br />

<strong>dr</strong>. Muhammad Rusda, <strong>SpOG</strong> (K)<br />

PENYANGGAH : <strong>dr</strong>. <strong>Risman</strong> <strong>Felix</strong> <strong>Kaban</strong>, <strong>SpOG</strong><br />

<strong>dr</strong>. In<strong>dr</strong>a <strong>Gunasti</strong> <strong>Munthe</strong>, <strong>SpOG</strong> (K)<br />

Prof. <strong>dr</strong>. M. Fauzie Sahil, <strong>SpOG</strong> (K)<br />

Diajukan untuk melengkapi tugas-tugas<br />

dan memenuhi salah satu syarat untuk<br />

mencapai keahlian dalam bidang Obstetri dan Ginekologi<br />

Universitas Sumatera Utara


LEMBAR HALAMAN PENGESAHAN<br />

Penelitian ini telah disetujui oleh Tim 5 ( Lima )<br />

PEMBIMBING :<br />

Dr. Binarwan Halim, <strong>SpOG</strong> (K) ……………………<br />

Pembimbing I ....…. MEI 2011<br />

Dr. Muhammad Rusda, <strong>SpOG</strong> (K) ……………………<br />

Pembimbing II .…… MEI 2011<br />

PENYANGGAH :<br />

Dr. <strong>Risman</strong> <strong>Felix</strong> <strong>Kaban</strong>, <strong>SpOG</strong> .……………………<br />

Universitas Sumatera Utara


Divisi Feto Maternal ……. MEI 2011<br />

Dr. In<strong>dr</strong>a <strong>Gunasti</strong> <strong>Munthe</strong>,<strong>SpOG</strong> (K) …………………….<br />

Divisi Fertilisasi, Endokrinologi .…… MEI 2011<br />

& Reproduksi<br />

Prof. Dr. M. Fauzie Sahil, <strong>SpOG</strong> (K) …………………….<br />

Divisi Onko- Ginekologi ……. MEI 2011<br />

Universitas Sumatera Utara


“ Ya Allah ya Tuhan kami, … bagi-Mu lah segala pujipujian,<br />

pujian sepenuh langit, pujian sepenuh bumi<br />

dan sepenuh apapun yang Engkau kehendaki<br />

setelah itu …“<br />

( H.R. Muslim )<br />

Kupersembahkan untuk yang Terkasih dan Tercinta<br />

Kedua orangtua-ku,<br />

Drs.H.Amir Hood Siregar, Apt, MHA<br />

Dan<br />

(Almh.) Hj. Yunidar Anas<br />

Universitas Sumatera Utara


KATA PENGANTAR<br />

Dengan nama Allah Yang Maha Pengasih Lagi Maha Penyayang,<br />

Segala Puji dan Syukur saya panjatkan ke hadirat Allah Subhanahu Wata’ala, Tuhan Yang Maha<br />

Kuasa, berkat Rahmat,Ridho dan Karunia-Nya lah penulisan tesis ini dapat diselesaikan dengan<br />

baik.<br />

Tesis ini disusun untuk melengkapi tugas-tugas dan memenuhi salah satu syarat untuk<br />

memperoleh keahlian dalam bidang Obstetri dan Ginekologi. Sebagai manusia biasa, saya<br />

menyadari bahwa tesis saya ini masih banyak kekurangannya dan masih jauh dari sempurna,<br />

namun demikian besar harapan saya kiranya tulisan sederhana ini dapat bermanfaat dalam<br />

menambah perbendaharaan bacaan khususnya tentang :<br />

“ KORELASI ANTARA ALIRAN DARAH CORPUS LUTEUM DENGAN<br />

KONSENTRASI SERUM PROGESTERON PADA WANITA INFERTIL ”<br />

Dengan selesainya laporan penelitian ini, perkenankanlah saya menyampaikan rasa terima kasih<br />

dan penghargaan yang setinggi-tingginya kepada yang terhormat :<br />

1. Rektor Universitas Sumatera Utara Prof.Dr.<strong>dr</strong>.Syahril Pasaribu, DTM&H, MSc (CTM),<br />

SpA(K) dan Dekan Fakultas Kedokteran Universitas Sumatera Utara, Prof.<strong>dr</strong>.Gontar<br />

Alamsyah Siregar, SpPD (K-GEH) yang telah memberikan kesempatan kepada saya untuk<br />

mengikuti Program Pendidikan Dokter Spesialis di Fakultas Kedokteran USU Medan.<br />

2. Prof.<strong>dr</strong>.Delfi Lutan, MSc, <strong>SpOG</strong>(K), Ketua Departemen Obstetri dan Ginekologi FK-USU<br />

Medan ; dan <strong>dr</strong>. M. Fidel Ganis Siregar, <strong>SpOG</strong>, Sekretaris Departemen Obstetri dan<br />

Ginekologi FK-USU Medan<br />

3. <strong>dr</strong> Henry Salim Siregar, <strong>SpOG</strong>(K), Ketua Program Studi Pendidikan Dokter Spesialis<br />

Obstetri dan Ginekologi FK-USU Medan ; <strong>dr</strong>. M. Rhiza Z. Tala, <strong>SpOG</strong>(K), Sekretaris<br />

Program Studi Pendidikan Dokter Spesialis Obstetri dan Ginekologi FK-USU Medan<br />

4. Prof. <strong>dr</strong>. R. Haryono Roeshadi, <strong>SpOG</strong>(K), selaku Kepala Bagian Obstetri dan Ginekologi<br />

pada saat saya diterima untuk mengikuti pendidikan spesialis di Departemen Obstetri dan<br />

Universitas Sumatera Utara


Ginekologi FK-USU Medan ; Prof. M. Jusuf Hanafiah, <strong>SpOG</strong>(K) ; Prof. <strong>dr</strong>. Hamonangan<br />

Hutapea, <strong>SpOG</strong>(K) ; Prof. DR. <strong>dr</strong>. M. Thamrin Tanjung, <strong>SpOG</strong>(K) ; Prof. <strong>dr</strong>. Djafar Siddik,<br />

<strong>SpOG</strong>(K) ; Prof. <strong>dr</strong>. T.M. Hanafiah, <strong>SpOG</strong>(K) ; Prof. <strong>dr</strong>. Budi R. Hadibroto, <strong>SpOG</strong>(K) ;<br />

Prof. <strong>dr</strong>. Daulat H. Sibuea, <strong>SpOG</strong>(K) dan Prof. <strong>dr</strong>. M. Fauzie Sahil, <strong>SpOG</strong>(K) yang telah<br />

bersama-sama berkenan menerima saya untuk mengikuti Program Pendidikan Dokter<br />

Spesialis di Departemen Obstetri dan Ginekologi di FK-USU Medan.<br />

5. <strong>dr</strong>. Binarwan Halim, <strong>SpOG</strong>(K) yang telah memberikan idenya yang cemerlang kepada saya<br />

untuk melakukan penelitian ini dan sekaligus sebagai Pembimbing Utama Tesis saya<br />

,bersama-sama dengan <strong>dr</strong>. Muhammad Rusda, <strong>SpOG</strong>(K) yang juga sebagai pembimbing<br />

tesis saya, yang telah dengan sabar meluangkan waktu dan pikiran yang sangat berharga dan<br />

juga sebagai nara sumber untuk membimbing, mengkoreksi, dan melengkapi penulisan dan<br />

penyusunan tesis ini hingga dapat diselesaikan dengan baik.<br />

6. <strong>dr</strong>. <strong>Risman</strong> <strong>Felix</strong> <strong>Kaban</strong>, <strong>SpOG</strong> ; <strong>dr</strong>.In<strong>dr</strong>a <strong>Gunasti</strong> <strong>Munthe</strong>, <strong>SpOG</strong>(K) ; dan Prof. <strong>dr</strong>. M.<br />

Fauzie Sahil, <strong>SpOG</strong>(K), sebagai penyanggah tesis saya, yang juga merupakan nara sumber<br />

yang telah dengan penuh kesabaran meluangkan waktu yang sangat berharga untuk<br />

membimbing, memeriksa, dan melengkapi penulisan tesis ini hingga dapat diselesaikan<br />

dengan baik.<br />

7. Dr Ichwanul Adenin, <strong>SpOG</strong>(K), selaku Ketua Divisi Fertilisasi dan Endokrinologi<br />

Reproduksi atas kesempatan yang diberikan kepada saya untuk dapat melakukan penelitian<br />

di Bidang Fertilisasi dan Endokrinologi Reproduksi di Departemen Obstetri dan Ginekologi<br />

FK-USU .<br />

8. Ucapan Terimakasih yang tak terhingga kepada <strong>dr</strong>. Binarwan Halim, <strong>SpOG</strong>(K) beserta<br />

seluruh Staff ,Paramedis dan Karyawan / ti “Halim Fertility Center” Medan yang telah<br />

mengizinkan saya dan banyak sekali memberikan bantuan kepada saya, selama saya<br />

melakukan penelitian di “Halim Fertility Center” Medan. Semoga Tuhan membalas<br />

kebaikan anda semua.<br />

Universitas Sumatera Utara


9. Kepada <strong>dr</strong>. Surya Dharma, MPH, Drs.Abdul Jalil Amri,M.Kes dan <strong>dr</strong>.Arlinda Sari<br />

Wahyuni,M.Kes, sebagai pembimbing statistik Tesis saya ,yang telah dengan penuh<br />

kesabaran meluangkan waktu dan pikiran untuk membimbing dan membantu saya dalam<br />

penyelesaian uji statistik tesis ini.<br />

10. <strong>dr</strong>.Yusuf R Surbakti, <strong>SpOG</strong>(K), selaku pembimbing Referat Fetomaternal saya yang<br />

berjudul ”Penatalaksanaan Thrombo Emboli Vena dalam Kehamilan” ; Kepada <strong>dr</strong>.<br />

Syamsul Arifin Nasution, <strong>SpOG</strong>(K) selaku pembimbing Referat Fertilitasi, Endokrinologi<br />

dan Reproduksi saya yang berjudul ”Penggunaan Selective Progesterone Receptor<br />

Modulator pada Pengobatan Endometriosis dan Myoma Uteri” dan kepada <strong>dr</strong>. John S.<br />

Khoman, <strong>SpOG</strong>(K) selaku pembimbing Referat Onko-Ginekologi saya yang berjudul<br />

”Pseudomyxoma Peritonei”. Terimakasih atas bimbingan dan arahan yang diberikan<br />

kepada saya , selama saya menyelesaikan referat referat saya tersebut.<br />

11. <strong>dr</strong>. Einil Rizar, <strong>SpOG</strong>(K), selaku Bapak Angkat saya ,selama saya menjalani masa<br />

pendidikan di Departemen Obstetri dan Ginekologi FK-USU, yang telah banyak<br />

mengayomi, membimbing dan memberikan nasehat-nasehat yang bermanfaat kepada saya<br />

dalam menghadapi masa-masa sulit selama masa pendidikan.<br />

12. Seluruh Staf Pengajar di Departemen Obstetri dan Ginekologi FK-USU Medan / RSUP<br />

H.Adam Malik / RSUD Dr.Pirngadi Medan, yang secara langsung telah banyak<br />

membimbing dan mendidik saya sejak awal hingga akhir pendidikan.<br />

13. Kepada Sekretariat Bersama Fakultas Kedokteran se-Indonesia (CHS) dan Kepala Dinas<br />

Kesehatan Propinsi Sumatera Utara, atas izin yang telah diberikan kepada saya untuk<br />

mengikuti Program Pendidikan Dokter Spesialis Obstetri dan Ginekologi di Fakultas<br />

Kedokteran Universitas Sumatera Utara Medan.<br />

Universitas Sumatera Utara


14. Direktur RSUP. H. Adam Malik Medan ; dan Ketua SMF Kebidanan dan Penyakit<br />

Kandungan RSUP H.Adam Malik , beserta seluruh staf ,para Bidan dan seluruh paramedis<br />

yang telah memberikan kesempatan dan sarana serta bantuan kepada saya untuk bekerja<br />

selama mengikuti pendidikan dan selama saya bertugas di SMF Kebidanan dan Penyakit<br />

Kandungan RSUP H.Adam Malik Medan.<br />

15. Direktur RSUD Dr. Pirngadi Medan ; dan Ketua SMF Kebidanan dan Penyakit Kandungan<br />

RSUD Dr.Pirngadi Medan <strong>dr</strong>. Rushakim Lubis, <strong>SpOG</strong> beserta seluruh staff-nya ,para Bidan<br />

dan seluruh paramedis yang telah memberikan kesempatan dan sarana serta bantuan kepada<br />

saya untuk bekerja selama mengikuti pendidikan dan selama saya bertugas di SMF<br />

Kebidanan dan Penyakit Kandungan di RSUD Dr.Pirngadi Medan.<br />

16. Direktur RS. PTPN 2 Tembakau Deli Medan ;dan Kepala SMF Kebidanan dan Penyakit<br />

Kandungan RS PTPN 2 Tembakau Deli Medan <strong>dr</strong>. Sofian Abdul Ilah, <strong>SpOG</strong> dan juga <strong>dr</strong>.<br />

Nazaruddin Jaffar, <strong>SpOG</strong>(K) ; beserta staf ,para Bidan dan Paramedis yang telah<br />

memberikan kesempatan dan sarana kepada saya dan membantu saya selama bertugas di<br />

Rumah Sakit tersebut.<br />

17. Direktur RS Haji Mina Medan ;dan Kepala SMF Kebidanan dan Penyakit Kandungan RS<br />

Haji Mina Medan ,<strong>dr</strong> Muslich Peranginangin, <strong>SpOG</strong> beserta seluruh staff ,para Bidan dan<br />

seluruh paramedis yang telah memberikan kesempatan dan sarana serta membantu saya<br />

untuk bekerja selama bertugas di Rumah Sakit tersebut.<br />

18. Direktur RS Sundari Medan dan Kepala SMF Kebidanan dan Penyakit Kandungan RS<br />

Sundari Medan <strong>dr</strong> Muhammad. Haidir, <strong>SpOG</strong> beserta staff, dan Ibu Hj.Sundari,Amkeb<br />

beserta para Bidan dan seluruh paramedis yang telah memberikan kesempatan dan sarana<br />

kepada saya untuk bekerja selama bertugas di Rumah Sakit tersebut.<br />

19. Ka. RUMKIT Tk. II KesDam II / Bukit Barisan ” Puteri Hijau” ; dan Kepala SMF<br />

Kebidanan dan Penyakit Kandungan di RUMKIT Tk.II KesDam II / Bukit Barisan Mayor<br />

CKM <strong>dr</strong> Gunawan Rusuldi, <strong>SpOG</strong> beserta seluruh staff, para Bidan dan seluruh paramedis<br />

Universitas Sumatera Utara


di RUMKIT Tk.II KesDam II / Bukit Barisan ”Puteri Hijau” yang telah memberikan<br />

kesempatan dan sarana serta bantuan kepada saya untuk bekerja selama bertugas di Rumah<br />

Sakit tersebut.<br />

20. Distrik Manager PTPN 3 Distrik Pamela dan Manager RS PTPN 3 Sri Pamela, Tebing<br />

Tinggi, dan Kepala SMF Kebidanan dan Penyakit Kandungan RS PTPN 3 Sri Pamela,<br />

Tebing Tinggi, beserta seluruh staf,para Bidan dan seluruh paramedis yang telah<br />

memberikan kesempatan kerja ,memberikan bantuan sarana dan bantuan moril selama saya<br />

bertugas di rumah sakit tersebut.<br />

21. Dinas Kesehatan Kota Tebing Tinggi ,IDI dan POGI Kota Tebing Tinggi atas bantuan dan<br />

perlindungan kepada saya selama saya bertugas di Tebing Tinggi. Khusus kepada <strong>dr</strong>.Budi<br />

Santoso, <strong>SpOG</strong> ,<strong>dr</strong>.Rosnaliza Harahap, <strong>SpOG</strong> dan <strong>dr</strong>.Maria Novita Adelina Pardede, <strong>SpOG</strong><br />

,saya menghaturkan banyak terimakasih atas bantuan dan bimbingan selama saya bertugas<br />

di Tebing Tinggi. Semoga Tuhan membalas kebaikan anda.<br />

22. Ketua Departemen Anestesiologi dan Reanimasi FK USU / RSUP H.Adam Malik Medan<br />

beserta seluruh staff, atas kesempatan dan bimbingan yang telah diberikan selama saya<br />

bertugas di Departemen tersebut.<br />

23. Ketua Departemen Patologi Anatomi FK-USU beserta seluruh staf, atas kesempatan dan<br />

bimbingan yang telah diberikan selama saya bertugas di Departemen tersebut.<br />

24. Kepada senior-senior saya, Terimakasih banyak atas segala bimbingan, bantuan dan<br />

dukungannya yang telah diberikan kepada saya selama ini. Semoga Allah SWT membalas<br />

budi baik yang saya terima dari mereka selama ini.<br />

25. Teman-teman seangkatan saya: <strong>dr</strong>. Muhammad Jusuf Rachmatsyah, <strong>SpOG</strong>; <strong>dr</strong>. Teuku<br />

Jeffrey Abdillah, <strong>SpOG</strong>; <strong>dr</strong>.Sri Jauharah Laily, <strong>SpOG</strong>; <strong>dr</strong>. Made Surya Kumara, <strong>SpOG</strong>; <strong>dr</strong>.<br />

Muhammmad Rizki Yaznil, <strong>SpOG</strong>; dan <strong>dr</strong>. Yuri An<strong>dr</strong>iansyah, Terima kasih untuk<br />

kebersamaan dan kerjasama kita selama pendidikan ini.<br />

Universitas Sumatera Utara


26. Kepada yunior-yunior saya, saya menyampaikan sedalam-dalam terima kasih dan rasa<br />

syukur alhamdulillah atas segala dukungan dan bantuan yang diberikan selama ini serta<br />

kebersamaan kita selama pendidikan. Semoga kebersamaan dan kerjasama kita tetap<br />

terpelihara dan Allah SWT melindungi kita semua.<br />

27. Kepada yang tersayang ,tim Jaga ku. Tiada saat yang paling indah selain di waktu jaga kita<br />

bersama selama ini. Rasa Syukur dan Terimakasih yang sebesar-besarnya atas bantuan dan<br />

kerjasama yang kompak diantara kita selama ini. Semoga kebersamaan dan kekompakan<br />

kita tetap terpelihara, dan kita semua senantiasa dalam lindungan Allah SWT.<br />

28. Seluruh teman sejawat PPDS yang tidak dapat saya sebutkan satu persatu, terima kasih atas<br />

kebersamaan, dorongan semangat dan doa yang telah diberikan .<br />

29. Seluruh Teman Sejawat Dokter Muda, para Bidan, seluruh Paramedis, serta para pasien di<br />

Departemen Obstetri dan Ginekologi FK USU / RSUP. H. Adam Malik – RSU. Dr. Pirngadi<br />

Medan dan RS Jejaring yang daripadanya saya banyak memperoleh pengetahuan baru,<br />

terima kasih atas kerja sama dan saling pengertian yang baik, yang diberikan kepada saya<br />

selama ini ,sehingga saya dapat sampai pada akhir program pendidikan ini.<br />

30. Para karyawan / karyawati yang banyak membantu saya selama menjalani masa pendidikan<br />

di Departemen Obstetri dan Ginekologi FK-USU, Ibu Asnawati Hasibuan, Ibu Sosmalawati<br />

Harahap, Ibu Nur Asmawati, Ibu Zubaedah, Ibu Jas, Ibu Nurmawan, Mimi Rahmi ,Rifda<br />

Astuti, Winta, Yus Sari Asih. Terimakasih atas bantuan dan kerjasamanya selama saya<br />

menjalani pendidikan di Departemen Obstetri dan Ginekologi FK-USU / RSUP H.Adam<br />

Malik / RSU Dr. Pirngadi Medan.<br />

Sembah sujud, setinggi-tinggi hormat dan sedalam-dalam terima kasih yang tidak terhingga dari<br />

lubuk hati sanubari yang paling dalam ,saya sampaikan kepada kedua Orang Tua saya yang saya<br />

cintai dan saya sayangi, Ayahanda Drs.H.Amir Hood Siregar, Apt, MHA dan Ibunda (Almh.)<br />

Hj. Yunidar Anas, tiada kata terindah yang dapat saya ucapkan melainkan rasa syukur dan<br />

terimakasih saya kepada Allah SWT yang tidak terhingga, karena telah menitipkan saya kepada<br />

Universitas Sumatera Utara


orangtua yang telah membesarkan, membimbing, mendoakan, serta mendidik saya dengan penuh<br />

kasih sayang dari sejak saya kecil hingga saat ini, memberi contoh yang baik dalam menjalani<br />

hidup ,serta memberikan motivasi dan semangat serta dukungan kepada saya selama saya<br />

mengikuti pendidikan ini. Semoga Allah SWT melindungi kita semua.<br />

Kepada abangku tersayang Rachmad Saleh Siregar, ST ; dan kakak iparku Rika Yulisa<br />

Rachmad Saleh, S.IP, M.HRD Science ( Hons.) dan adikku tersayang Fifi Savitri Siregar,<br />

B.Comp Science ( Hons,), M.M .Dan juga kepada ibunda Siti Rodiah, S.E .Terima kasih atas<br />

dorongan semangat serta doa yang diberikan kepada saya ,sehingga saya dapat menyelesaikan<br />

program pendidikan ini. Tanpa pengorbanan, doa, dorongan ,semangat dan dukungan dari kalian<br />

semua, tidak mungkin tugas tugas ini semua dapat saya selesaikan.<br />

Kepada yang terhormat, Om <strong>dr</strong>.H.Sjahrial Refli Anas, MHA dan Tante Hj. Getrina Fezienty<br />

Sjahrial. Terimakasih yang sebesar-besarnya atas dukungan, bantuan, doa dan semangat yang<br />

diberikan kepada saya selama ini.Tiada kata terindah selain ungkapan rasa syukur dan<br />

terimakasih yang teramat dalam atas bantuan Om dan Tante selama saya menjalani masa<br />

pendidikan ini. Semoga Allah SWT membalas kebaikan Om dan Tante.<br />

Akhirnya kepada seluruh keluarga besar saya, Keluarga besar Alm.Bokar Siregar glr Sutan<br />

Pandapotan Muda dan Keluarga besar Anas Sofyan glr Datuak Rajo Sutan, serta seluruh handai<br />

taulan semua yang tidak dapat saya sebutkan namanya satu persatu, baik secara langsung<br />

maupun tidak langsung, yang telah banyak memberikan bantuan,doa dan dukungan, baik moril<br />

maupun materiil, saya ucapkan banyak terima kasih.<br />

Semoga Allah Subhanahu wa Ta’ala senantiasa melimpahkan rahmah dan barokah-Nya kepada<br />

kita sekalian. Amin<br />

Medan, Mei 2011<br />

<strong>dr</strong>. BOY RIVAI PANDAPOTAN SIREGAR<br />

Universitas Sumatera Utara


KORELASI ANTARA ALIRAN DARAH CORPUS LUTEUM DENGAN KONSENTRASI SERUM<br />

PROGESTERON PADA WANITA INFERTIL<br />

Siregar B R P, Halim B, Rusda M<br />

Departemen / SMF Obstetri dan Ginekologi<br />

Fakultas Kedokteran Universitas Sumatera Utara / RSUP H. Adam Malik /<br />

Unit/Sub-Divisi Teknologi Reproduksi Bayi Tabung, Divisi FER,Dept Obgyn FK-USU<br />

”Halim Fertility Centre” Medan<br />

---------------------------------------------------------------------------------------------------------------------------------<br />

ABSTRAK<br />

Tujuan : Tujuan penelitian ini adalah untuk mengetahui Adakah Korelasi yang signifikan antara Aliran darah<br />

Corpus Luteum dengan Konsentrasi serum Progesteron pada Fase Luteal wanita infertil.Dan untuk menilai<br />

parameter manakah dari Aliran Darah Corpus Luteum yang menjadi Prediktor terbaik untuk menegakkan diagnosa<br />

Defek Fase Luteal sebagai parameter diagnostik alternatif selain melalui penilaian Kadar Serum Progesteron<br />

Rancangan Penelitian : Penelitian ini merupakan suatu penelitian survei analitik dengan menggunakan rancangan<br />

potong lintang (cross sectional study),dilaksanakan di Unit / Sub-Divisi Teknologi Reproduksi Bayi Tabung, Divisi<br />

FER, Dept Obgin ,FK-USU “Halim Fertility Centre”, Medan,berlangsung dimulai dari 1 November 2010 sampai<br />

dengan 30 April 2011. Sampel penelitian adalah semua wanita infertil yang merupakan wanita usia reproduksi ( 15 –<br />

45 tahun ) yang yang dilakukan dengan Consecutive Sampling diseleksi menurut kriteria inklusi dan eksklusi yang<br />

datang memeriksakan diri ,kemudian yang memenuhi kriteria inklusi dan bersedia ikut serta,diambil sebagai sampel<br />

penelitian. Dengan rumus Korelasi Pearson (r = 0.433) dari liteartur, didapatkan sebanyak 41 sampel. Data – data<br />

yang dikumpulkan dibuat dalam Tabulasi Induk, diolah secara komputerisasi dengan menggunakan SPSS versi<br />

19.0. Data disajikan dengan nilai Rata-rata ± Standar Deviasi . Data disajikan dalam bentuk Grafik Scattered Dot.<br />

Untuk melihat hubungan signifikansi antar variabel dilakukan dengan analisis korelasi Pearson dan dinyatakan<br />

bermakna jika nilai p < 0.05, dan dengan menggunakan nilai r untuk melihat kuatnya hubungan antar variabel<br />

penelitian. Hubungan akan semakin kuat jika mendekati nilai +1 atau -1Arah korelasi dinyatakan positif (+) jika<br />

ditemukan variabel yang satu berbanding lurus dengan variabel yang lainnya dan negatif (-) jika ditemukan variabel<br />

yang satu berbanding terbalik dengan variabel yang lainnya<br />

Material dan Metode Penelitian : Tiap responden yang memenuhi kriteria inklusi masing masing diberikan Chart<br />

Suhu Basal Badan untuk dicatat suhu basal badannya pada pagi hari setiap hari selama 28 hari. Hari ke 14<br />

diperkirakan merupakan suhu terendah selama siklus, dan dinyatakan sebagai hari ovulasi. Setelah ovulasi,<br />

terbentuk Corpus Luteum yang memproduksi Progesteron. Puncak fase Luteal yaitu 7 hari setelah ovulasi. Pada hari<br />

ke 21 pasien diminta datang untuk dilakukan pemeriksaan konsentrasi serum progesteron,dan selanjutnya dilakukan<br />

USG Power Doppler Transvaginal untuk menilai Aliran darah Corpus Luteum (PSV,EDV,PI,RI,Volume Corpus<br />

Luteum), kemudian data dikumpulkan sampai 41 sampel terpenuhi dan ditabulasi, lalu dilakukan Uji Korelasi<br />

Pearson.<br />

Hasil Penelitian : Dengan uji korelasi Pearson, secara statistik ditemukan hubungan yang bermakna antara kadar<br />

serum Progesterone dan Peak Systolic Velocity (PSV) pada Corpus Luteum dengan nilai p=0.000 (p


dengan nilai r = 0.002. Diperoleh nilai cut off point dari Pulsatility Index (PI) sebagai alat diagnostik yang paling<br />

baik nilai AUC-nya (AUC=70,1%) dibandingkan dengan variabel-variabel prediktor (alat diagnostik ) lainnya<br />

pada defek fase luteal adalah 1,085 dengan sensitivitas 73,3 % dan spesifisitas 66,7 %.<br />

Kesimpulan : Ada korelasi yang bermakna antara Peak Systolic Velocity (PSV) Aliran Darah Corpus Luteum<br />

dengan Konsentrasi Serum Progesteron dan ditemukan hubungan korelasi positif dengan Kekuatan Korelasi sedang.<br />

Ada korelasi yang bermakna antara End Diastolic Velocity (EDV) Aliran Darah Corpus Luteum dengan Konsentrasi<br />

Serum Progesteron dan ditemukan hubungan korelasi positif dengan Kekuatan Korelasi kuat. Ada korelasi yang<br />

bermakna antara Pulsatility Index Aliran Darah Corpus Luteum dengan Konsentrasi Serum Progesteron dan<br />

ditemukan hubungan korelasi negatif dengan Kekuatan Korelasi lemah .Ada korelasi yang bermakna antara<br />

Resistance Index Aliran Darah Corpus Luteum dengan Konsentrasi Serum Progesteron dan ditemukan hubungan<br />

Korelasi negatif dengan Kekuatan Korelasi sedang. Ada Korelasi yang tidak bermakna antara Volume Corpus<br />

Luteum (mm 3 ) dengan Konsentrasi Serum Progesteron dan ditemukan hubungan korelasi positif dengan kekuatan<br />

Korelasi sangat lemah Diperoleh nilai Pulsatility Index (PI) sebagai nilai untuk alat diagnostik yang paling baik ,<br />

dimana nilai AUC-nya (AUC=70,1%) dibandingkan dengan variabel-variabel prediktor (alat diagnostik ) lainnya<br />

pada defek fase luteal ,dengan nilai cut-off point nya adalah 1,085 dengan sensitivitas 73,3 % dan spesifisitas 66,7<br />

%.<br />

Kata Kunci : Suhu Basal Badan, Volume Corpus Luteum, Peak Systolic Velocity, End Diastolic Velocity,<br />

Pulsatility Index, Resistance Index, Konsentrasi serum Progesteron,Defek Fase Luteal.<br />

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DAFTAR ISI<br />

PEMBIMBING PENELITIAN………………………………………………………………. i<br />

LEMBAR PENGESAHAN PENELITIAN…………………………………………………..ii<br />

KATA PENGANTAR………………………………………………………………………...iv<br />

ABSTRAK TESIS……………………………………………………………………………xiii<br />

DAFTAR ISI……………………………………………………………………………….…xv<br />

DAFTAR GAMBAR………………………………………………………………………....xix<br />

DAFTAR TABEL…………………………………………………………………………….xx<br />

DAFTAR GRAFIK…………………………………………………………………………..xxi<br />

DAFTAR SKEMA…………………………………………………………………………. .xxii<br />

DAFTAR SINGKATAN………………………………………………………………….....xxiii<br />

DAFTAR LAMPIRAN…………………………………………………………………...….xxv<br />

BAB I PENDAHULUAN<br />

I.1 LATAR BELAKANG...........................................................................................................1<br />

I.2 RUMUSAN MASALAH……………………………………………………. .....................7<br />

I.3 TUJUAN PENELITIAN .......................................................................................................7<br />

I.3.1 TUJUAN UMUM……………………………………………………………………..7<br />

I.3.2 TUJUAN KHUSUS.......................................................................................................7<br />

I.4 HIPOTESIS PENELITIAN...................................................................................................8<br />

I.5 MANFAAT PENELITIAN ..................................................................................................8<br />

BAB II TINJAUAN KEPUSTAKAAN<br />

II.1 CORPUS LUTEUM.............................................................................................................9<br />

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II.2 TUMBUH KEMBANG CORPUS LUTEUM .....................................................................9<br />

II.3 PATHWAY STEROIDOGENIK LUTEAL .....................................................................10<br />

II.4 REGULASI FUNGSI LUTEAL ........................................................................................12<br />

II.5 ANGIOGENESIS CORPUS LUTEUM ............................................................................13<br />

II.5.1 PENDAHULUAN......................................................................................................13<br />

II.5.2 FAKTOR-FAKTOR YANG MEMPENGARUHI ANGIOGENESIS<br />

CORPUS LUTEUM...................................................................................................14<br />

II.5.2.1 PERUBAHAN DALAM JUMLAH PERISIT ..............................................14<br />

II.5.2.2 STABILISASI PEMBULUH DARAH.........................................................15<br />

II.5.3 FAKTOR ANGIOGENIK..........................................................................................15<br />

II.5.3.1 FAKTOR PERTUMBUHAN ENDOTELIAL ................................................15<br />

II.5.3.2 ANGIOPOEITIN..............................................................................................15<br />

II.5.4 REGULASI MOLEKULER ANGIOGENESIS CORPUS LUTEUM ......................17<br />

II.5.5 ANGIOGENESIS DAN FUNGSI LUTEAL .............................................................18<br />

II.6 DETEKSI ALIRAN DARAH LUTEAL PADA CORPUS LUTEUM .............................19<br />

II.7 PENILAIAN ANGIOGENESIS CORPUS LUTEUM......................................................19<br />

II.7.1 VOLUME CORPUS LUTEUM.................................................................................20<br />

II.7.2 PEAK SYSTOLIC VELOCITY (PSV) DAN EDV<br />

(END DIASTOLIC VELOCITY) ALIRAN DARAH CORPUS LUTEUM...........20<br />

II.7.3 INDEKS PULSATILITAS (PI=PULSATILITY INDEX)........................................20<br />

II.7.4 INDEKS RESISTENSI (RI= RESISTANCE INDEX) .............................................21<br />

II.8 KONSENTRASI SERUM PROGESTERON....................................................................22<br />

II.8.1 PERAN PROGESTERON PADA SUMBU HIPOTHALAMUS-HIPOFISIS..........22<br />

II.8.2 PERAN PROGESTERON DALAM SISTEM REPRODUKSI ................................24<br />

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II.8.3 DEFEK FASE LUTEAL............................................................................................25<br />

II.9 PENENTUAN DEFISIENSI SEKRESI PROGESTERON OLEH CORPUS LUTEUM<br />

PADA FASE LUTEAL .....................................................................................................25<br />

II.9.1 SAAT OVULASI DAN PEMBENTUKAN CORPUS LUTEUM ............................25<br />

II.9.2 PENGUKURAN SUHU BASAL BADAN<br />

(BBT=BASAL BODY TEMPERATURE).................................................................26<br />

II.9.3 PENENTUAN PANJANG FASE LUTEAL .............................................................28<br />

II.9.4 PEMERIKSAAN KONSENTRASI SERUM PROGESTERON FASE LUTEAL...28<br />

II.9.5 PEMANTAUAN DENGAN ULTRASONOGRAFI.................................................29<br />

II.9.6 BIOPSI ENDOMETRIUM ........................................................................................29<br />

II.10 HUBUNGAN ALIRAN DARAH CORPUS LUTEUM DENGAN<br />

KONSENTRASI SERUM PROGESTERON .................................................................30<br />

II.10.1 HUBUNGAN PEAK SYSTOLIC VELOCITY (PSV) DENGAN<br />

KONSENTRASI SERUM PROGESTERON PADA FASE MID-LUTEAL .........31<br />

II.10.2 HUBUNGAN END DIASTOLIC VELOCITY (EDV) DENGAN<br />

KONSENTRASI SERUM PROGESTERON PADA FASE MID-LUTEAL .........32<br />

II.10.3 HUBUNGAN PULSATILITY INDEX (PI) DENGAN KONSENTRASI<br />

SERUM PROGESTERON PADA FASE MID-LUTEAL ......................................33<br />

II.10.4 HUBUNGAN RESISTANCE INDEX (RI) DENGAN KONSENTRASI<br />

SERUM PROGESTERON.......................................................................................34<br />

II.10.5 HUBUNGAN VOLUME CORPUS LUTEUM DENGAN KONSENTRASI<br />

SERUM PROGESTERON.......................................................................................36<br />

BAB III METODE PENELITIAN<br />

III.1 DESAIN PENELITIAN....................................................................................................39<br />

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III.2 TEMPAT DAN WAKTU PENELITIAN.........................................................................39<br />

III.3 POPULASI DAN SAMPEL PENELITIAN<br />

III.3.1 POPULASI PENELITIAN .......................................................................................39<br />

III.3.2 SAMPEL PENELITIAN...........................................................................................39<br />

III.3.3 BESAR SAMPEL PENELITIAN.............................................................................40<br />

III.3.4 KRITERIA SAMPEL<br />

III.3.4.1 KRITERIA INKLUSI .....................................................................................41<br />

III.3.4.2 KRITERIA EKSKLUSI..................................................................................41<br />

III.4 MATERIAL DAN METODE PENELITIAN<br />

III.4.1 MATERIAL ALAT PENELITIAN .........................................................................41<br />

III.4.2 MATERIAL BAHAN PENELITIAN.......................................................................42<br />

III.4.3 METODE/ CARA KERJA PENELITIAN ...............................................................42<br />

III.5 ALUR PENELITIAN .......................................................................................................51<br />

III.6 VARIABEL PENEITIAN ................................................................................................52<br />

III.7 KERANGKA KONSEP PENELITIAN ...........................................................................52<br />

III.8 BATASAN OPERASIONAL PENELITIAN...................................................................54<br />

III.9 PENGOLAHAN DATA ...................................................................................................56<br />

III.10 ETIKA PENELITIAN ....................................................................................................57<br />

BAB IV HASIL PENELITIAN DAN PEMBAHASAN..........................................................59<br />

BAB V KESIMPULAN DAN SARAN<br />

V.1 KESIMPULAN..................................................................................................................89<br />

V.II SARAN .............................................................................................................................90<br />

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DAFTAR GAMBAR<br />

Gambar 1 Penyebab infertilitas pada pasangan suami-istri ......................................................... 1<br />

Gambar 2 Fase Proliferasi Endometrium / Fase Folikuler Ovarium ,Ovulasi dan Fase Sekresi<br />

Endometrium / Fase Luteal Ovarium Siklus Menstruasi Wanita ............................... 3<br />

Gambar 3 Sel Theca Lutein dan Sel Granulosa Lutein.............................................................. 10<br />

Gambar 4 Tumbuh Kembang Corpus Luteum........................................................................... 10<br />

Gambar 5 Pathway Biosintesis Progesteron dalam Sel-sel Luteal ............................................ 11<br />

Gambar 6 Siklus Hidup Corpus Luteum.................................................................................... 12<br />

Gambar 7 Hipotesis Regulasi perubahan pembuluh darah oleh VEGF, Angiopoietin-1, dan<br />

Angiopoietin-2 selama perkembangan dan regresi Corpus Luteum .......................................16<br />

Gambar 8 Mekanisme biomolekuler Angiogenesis dalam Corpus Luteum selama siklus<br />

Menstruasi dan pada Awal Kehamilan ...................................................................................18<br />

Gambar 9 Hasil Scaning Aliran Darah (Angiogenesis) Corpus Luteum dalam Ovarium......... 21<br />

Gambar 10Interpretasi Hasil Scanning Aliran Darah ( Angiogenesis ) Corpus Luteum Dalam<br />

Ovarium Pada USG Doppler Transvaginal..................................................................... 22<br />

Gambar 11Gambaran Mekanisme Hipothalamus Hipofisis Ovarium dalam Mempengaruhi<br />

Corpus Luteum Memproduksi Progesteron.............................................................. 23<br />

Gambar 12Representasi Skematik perubahan vaskularisasi selama hidup Folikel tunggal yang<br />

diseleksi untuk menjadi matang dan ber-Ovulasi ..................................................... 25<br />

Gambar 13Rekaman Suhu Basal Badan Ideal ............................................................................ 26<br />

Gambar 14Contoh TABEL BBT ( BASAL BODY TEMPERATURE ) IDEAL..................... 44<br />

Gambar 15Ilustrasi Penggunaan Usg Doppler Transvaginal …………………………………..47<br />

Gambar 16Aliran Darah ( Angiogenesis ) Corpus Luteum Di Dalam Ovarium Pada USG<br />

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Doppler Transvaginal………………………………………………………………49<br />

Gambar 17Hasil Scanning Aliran Darah ( Angiogenesis ) Corpus Luteum Dalam<br />

Ovarium Pada USG Doppler Transvaginal…………………………………………50<br />

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DAFTAR TABEL<br />

Tabel 2.1 Peran Progesteron untuk Implantasi dan Perkembangan Folikel ................................ 23<br />

Tabel 4.1 Hubungan peak systolic velocity (PSV) aliran darah corpus luteum dengan konsentrasi<br />

serum progesteron.......................................................................................................59<br />

Tabel 4.2 Hubungan end diastolic velocity (EDV) aliran darah corpus luteum dengan konsentrasi<br />

serum progesteron.......................................................................................................62<br />

Tabel 4.3Hubungan pulsatility index (PI) alirandarah corpus luteum dengan konsentrasi serum<br />

progesteron..................................................................................................................63<br />

Tabel 4.4Hubungan resistance index (RI) aliran darah corpus luteum dengan konsentrasi serum<br />

progesteron..................................................................................................................67<br />

Tabel 4.5 Hubungan volume corpus luteum dengan konsentrasi serum progesteron....................69<br />

Tabel 4.6.1 Sebaran subyek penelitian berdasarkan karakteristik umur…………………………72<br />

Tabel 4.6.2 Sebaran subyek penelitian berdasarkan karakteristik BMI…………………………72<br />

Tabel 4.6.3 Sebaran subyek penelitian berdasarkan karakteristik kadar serumProgesteron…….73<br />

Tabel 4.7 Distribusi perbedaan rata – rata dari variabel-variabel prediktor terjadinya defek fase luteal<br />

yang dikategorikan berdasarkan kadar serum progesterone < 10 ng/ml dan >10ng/dl……74<br />

Tabel 4.8 Hubungan variabel-variabel prediktor terhadap kadar serum progesteron pada subyek<br />

Penelitian……………………………………………………………………………..76<br />

Tabel 4.9 Nilai Adjusted R Square dari variabel-variabel prediktor kadar serum<br />

Progesteron.………………………………………………………………………….77<br />

Tabel 4.10 Nilai sensitivitas dan spesifisitas serta cut off point dari pemeriksaan Kadar Serum<br />

Progesteron pada defek fase luteal……………………………………………………..79<br />

Tabel 4.10.1 Nilai sensitivitas dan spesifisitas serta cut off point dari pemeriksaan Pulsatility Index (PI)<br />

pada defek fase luteal……………………………………………………………………..85<br />

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DAFTAR GRAFIK<br />

Grafik 1 Korelasi antar Peak Systolic Velocity (PSV) Aliran Darah Corpus Luteum dengan<br />

Konsentrasi Serum Progestereon……………………………………………………..60<br />

Grafik 2 Korelasi antar End Diastolic Velocity (EDV) Aliran Darah Corpus Luteum dengan<br />

Konsentrasi Serum Progestereon……………………………………………………..63<br />

Grafik 3 Korelasi antar Pulsatility Index (PI) Aliran Darah Corpus Luteum dengan<br />

Konsentrasi Serum Progestereon……………………………………………………..64<br />

Grafik 4 Korelasi antar Resistance Index (RI) Aliran Darah Corpus Luteum dengan<br />

Konsentrasi Serum Progestereon……………………………………………………..67<br />

Grafik 5 Korelasi antar Corpus Luteum dengan Konsentrasi Serum Progestereon…………...70<br />

Grafik 6 Receiver Operating Characteristic (ROC) dari kadar serum progesterone pada<br />

defek fase luteal…………………………………………………………..…………….78<br />

Grafik 7 Receiver Operating Characteristic (ROC) dari Peak Systolic Velocity (PSV) pada<br />

defek fase luteal…………………………………………………………………………81<br />

Grafik 8 Receiver Operating Characteristic (ROC) dari End Diastolic Velocity (EDV) pada<br />

defek fase luteal……………………………………………………………………………82<br />

Grafik 9 Receiver Operating Characteristic (ROC) dari Pulsatility Index (PI) pada defek fase<br />

Luteal……………………………………………………………………………………….,83<br />

Grafik 10 Receiver Operating Characteristic (ROC) dari Resistance Index (RI) pada defek<br />

fase luteal………………………………………………………………………….…………87<br />

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DAFTAR SKEMA<br />

Skema 1. KERANGKA TEORI PENELITIAN .......................................................................38<br />

Skema 2. ALUR PENELITIAN ...............................................................................................51<br />

Skema 3. KERANGKA KONSEP PENELITIAN…………………………………………..52<br />

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α-SMA α Smooth Muscle Actin<br />

Ang 1 Angiopoeitin 1<br />

Ang 2 Angiopoeitin 2<br />

DAFTAR SINGKATAN<br />

HSD Hy<strong>dr</strong>oxysteroid Dehy<strong>dr</strong>ogenase<br />

BBT Basal Body Temperature<br />

CL Corpus Luteum<br />

COS Controlled Ovarian Stimulation<br />

CTGF Connective Tissue Growth Factor<br />

EDTA Ethylene Diamine Tetraacetic Acid<br />

EDV End Diastolic Velocity<br />

FER fertilitas endokrinologi<br />

FSH Follicle Stimulating Hormone<br />

GH Growth Hormone<br />

GnRH Gonadotrophin Releasing Hormone<br />

hCG human Chorionic Gonadothropin<br />

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HDL High Density Lipoproteinm<br />

IGF-I Insulin Like Growth Factor I<br />

IVF In Vitro Fertilization<br />

LDL Low Density Lipoprotein<br />

LH Luteinizing Hormone<br />

LLC Large Luteal Cells<br />

LPD Luteal Phase Defect<br />

mRNA messenger ribo nucleic acid<br />

OHSS Over Hyper Stimulation Syn<strong>dr</strong>ome<br />

PCOS Poly Cistic Ovarium Syn<strong>dr</strong>ome<br />

PGE2 Prostaglandin E2<br />

PGI 2 Prostaglandin I2<br />

PI Pulsatility Index<br />

PIBF progesteron induced blocking factor<br />

PSV Peak Systolic Velocity<br />

RI Resistance Index<br />

ROC Receiver Operating Characteristic Curve<br />

SLC Small Luteal Cells<br />

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StAR Steroidogenic acute regulatory protein<br />

USG Ultasonography<br />

VEGF Vascular Endotelial Growth Factor<br />

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DAFTAR LAMPIRAN<br />

Lampiran 1. LEMBAR INFORMASI PASIEN…………………………………………………..<br />

Lampiran 2. LEMBAR PERSETUJUAN PASIEN………………………………………………<br />

Lampiran 3. KUESIONER PESERTA PENELITIAN…………………………………………..<br />

Lampiran 4. PERSETUJUAN DAN PENGESAHAN KOMITE ETIK PENELITIAN………..<br />

Lampiran 5. TABEL INDUK PESERTA PENELITIAN………………………………………..<br />

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CORRELATION BETWEEN CORPUS LUTEUM BLOOD FLOW AND<br />

PROGESTERONE SERUM CONCENTRATION IN INFERTILE WOMEN<br />

Boy Rivai Pandapotan Siregar, Binarwan Halim, Muhammad Rusda<br />

Departement of Obstetrics and Gynecology<br />

Medical School, University of Sumatera Utara / H. Adam Malik General Hospital /<br />

Sub-Division of Reproduction Technology of IVF, Division of FER,Dept of Obgyn, Medical<br />

School-USU<br />

”Halim Fertility Centre” Medan<br />

ABSTRACT<br />

Objective : The purpose of this study is to assess wether any significant correlation between<br />

corpus luteum blood flow and progesterone serum concentration on lutheal phase in infertile<br />

women. And to determine which parameter of corpus luteum blood flow would be the best<br />

predictor to diagnose the lutheal phase defect, as an alternative diagnostic parameter beside the<br />

Progesteron Serum Level.<br />

Study Design : This was an analytic survey study research with cross sectional study design,<br />

which performed in Sub-Division of Reproduction Technology of IVF, Division of FER, Obgyn<br />

Departement ,Medical School-USU “Halim Fertility Centre”, Medan, since November 1 st 2010<br />

until April 30 th 2011. The samples of this study were obtained of all infertile women of<br />

reproductive age (15 - 45 years old) which collected by Consecutive Sampling, who is being<br />

selected according to inclusion and exclusion criteria which came to pursue medical check up,<br />

then fulfilled the inclusion criterias and willing to participate on this research. By Correlation<br />

Pearson Formula (r = 0.433) from literature, 41 samples were obtained to participate. The 41<br />

samples data which completely collected , composed in a master of tabulation, then<br />

computerized by using Computer Statistic Program. Data presented on average<br />

values (Mean)± standard deviation. The presented data described in a scattered Dot graph form.<br />

To assess the significance of the relationship between the two variables were used Pearson<br />

correlation analysis and expressed significant if p value


asked to come and pursue the progesterone serum concentration examination, and then<br />

performed ultrasound Transvaginal Power Doppler to assess corpus luteum blood flow (PSV,<br />

EDV, PI, RI, Volume Corpus Lutem). Each patient which completely examined were recorde on<br />

a medical record ,then the Medical Record data collected until completely 41 samples ,and the<br />

data were tabulated , then the tabulated data were examined on Pearson correlation test.<br />

Results : By Pearson correlation test, statistically significant correlation was found between<br />

serum level of Progesterone (ng/ml) and Peak Systolic Velocity (PSV) of the corpus luteum<br />

(cm/s) with p = 0.000 (p


Key Words : Body Basal Temperature, Corpus Luteum Volume, Peak Systolic Velocity, End<br />

Diastolic Velocity, Pulsatility Index, Resistance Index, Progesteron Serum Concentration, Luteal<br />

Phase Defect.<br />

Universitas Sumatera Utara


CORRELATION BETWEEN CORPUS LUTEUM BLOOD FLOW AND<br />

PROGESTERONE SERUM CONCENTRATION IN INFERTILE WOMEN<br />

Boy Rivai Pandapotan Siregar, Binarwan Halim, Muhammad Rusda<br />

Departement of Obstetrics and Gynecology<br />

Medical School, University of Sumatera Utara / H. Adam Malik General Hospital /<br />

Sub-Division of Reproduction Technology of IVF, Division of FER,Dept of Obgyn, Medical<br />

School-USU<br />

”Halim Fertility Centre” Medan<br />

THESIS SUMMARY<br />

INTRODUCTION<br />

Infertility in the clinical sense is defined as an inability of one person or a couple to produce<br />

conception after one year of regular having sex without using protection, or a woman's inability<br />

to maintain pregnancy until term pregnancy. Forecast found in some literature suggests that the<br />

incidence of infertility in the United States the incidence ranges from 10-15%. From some<br />

literature, other causes of infertility incidence,such as: Male Factor 30-40%, Ovulation Disorders<br />

(Diminished Ovarian Reserve, Polycystic Ovaries, hyperprolactinemia, Dysfunction Thyroid)<br />

15%, 5-10% cervical mucus factor, Tuba adhesions 20%, 10% luteal phase defect, Unknown<br />

10%, Other (autoimmune diseases, tumors / Endocrine, Endometriosis) 1<br />

A woman's menstrual cycle is influenced by many hormones, In the first half of the menstrual<br />

cycle, GnRH in the hypothalamus induce the Anterior pituitary to release FSH. This FSH<br />

stimulates the maturation of follicles in the ovary (follicular phase), resulting in the synthesis of<br />

estrogen hormone in large quantities. The estrogen causes the proliferation of endometrium cells,<br />

known as Proliferation in the Endometrium or also known as the follicular phase in ovary.<br />

Proliferation phase lasts not fixed, can range from 7 to 21 days. This high estrogen signs the<br />

pituitary to release the LH. Estrogen in high quantity on mid-menstrual cycle causes ovulation.<br />

And then in the second half of Menstrual Cycle, corpus luteum formed then developed, to<br />

synthesize progesterone. Progesterone causes changes in the secretory of endometrium, known<br />

as Secretion phase in Endometrium which also known as luteal phase in the ovary. Luteal phase<br />

lasts 14 days and usually remains on the same length. 2,21,22<br />

Angiogenesis in the corpus luteum occurrs during the menstrual cycle and is functionally<br />

important for the maintenance of early pregnancy. After ovulation, as the luteinizing granulosa<br />

cell layer become thicker, the basement membrane that separates the granulosa cell layer from<br />

the theca cell layer breaks down. Blood vessels from the Theca interna invaded the cavity of the<br />

ruptured follicle and form a network that supplies neovascularization luteal cells. Corpus luteum<br />

being one of the most powerful organ in the body experiencing vascularization 3,4,5,6,7,8. Blood<br />

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flow in the corpus luteum is important for the development itself and the maintenance of luteal<br />

function 3,4,5,6,7,8<br />

This neovascularization is essential for the delivery of luteal steroid to the general circulation, as<br />

well as for the provision of the circulating substrate, Low Density Lipoprotein,that is used by<br />

luteal cells in the biosynthesis of progesterone (Carr et al,1982). Therefore it is likely that blood<br />

flow to the ovary and to the corpus luteum, may be important in the regulation of the function of<br />

the Corpus Luteum. Blood flow to the ovary bearing Corpus Luteum increases three to seven<br />

fold during luteal phase and then decreases markedly as the Corpus Luteum regresses<br />

(Niswender et al, 1976). 3,4,5,6,7,8 If the corpus luteum does not produce progesterone in sufficient<br />

quantities and not on time, then the difficulty arises from multiple interactions of focus-focus on<br />

the reproductive cycle. 1<br />

Transvaginal colour Power Doppler ultrasound imaging- has been used to determine indices of<br />

echogenicity index and intrafollicular blood flow (Collins et al, 1991) and to evaluate serial<br />

indices of echogenicity, vascularity and blood flow throughout the life span of the corpus luteum<br />

(Bourne et al, 1996). Furthermore, color flow pulsed Doppler has been used to predict a luteal<br />

phase defect (Tinkannen, 1994: Glock and Brumsted, 1995). Previous studies using colour<br />

Power Doppler imaging have measured indices of blood flow in the Ovary and the corpus<br />

luteum. 3,10,11,14,15,16,17,18,19,20,21,24<br />

Changes in the Corpus luteum blood flow in the luteal phase and close relationship with luteal<br />

function are interesting topics to be discussed. Interestingly, luteal blood flow correlated<br />

significantly with progesterone serum concentration during mid-luteal phase, and luteal blood<br />

flow is significantly lower in women with luteal phase defect than women with normal luteal<br />

function, which indicates that the low blood flow to the corpus luteum associated with the<br />

incidence of luteal phase defect. 12,13<br />

Luteal phase defect is a state of recurrent post-ovulation deficiency to produce progesterone from<br />

the corpus luteum that result in infertility and recurrent miscarriage. In these circumstances, the<br />

corpus luteum is unable to produce an adequate progesterone, causing disturbances in the<br />

endometrium such as unsynchronized endometrium stroma and endometrial glands which builds<br />

the endometrium. Which in turn caused the disruption of implantation. So a woman is unable to<br />

maintain pregnancy until term pregnancy and resulted in the incidence of recurrent<br />

miscarriage. 1,2,15,20,21,22<br />

The literature estimates that 10% incidence of Luteal Phase Defect was found in the normal<br />

population in the United States. In Indonesia, the incidence of Luteal Phase Defect is 3-4% of all<br />

infertile women, and 5% in women with recurrent miscarriage. However, this reference is less<br />

accurate due to the lack of homogenous standardized criteria which used to evaluate and<br />

diagnose luteal phase defect. 1,2,15,20,21,22<br />

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Many clinical trials have been performed to diagnose luteal phase defect and various<br />

combinations have been used to investigate this situation, including measurement of Basal Body<br />

Temperature Chart, endometrial biopsy, pelvic ultrasound to measure the pre-ovulatory follicle<br />

diameter pre-ovulation, serum progesterone levels of mid-luteal phase, luteal phase length.<br />

Growing discrepancy in the literature that when should we recommend the most optimal time in<br />

the menstrual cycle to obtain sampling to determine the luteal phase defect, varied from between<br />

1 to 2 days before the onset of the next menstrual period, up to 9 days after ovulation. However,<br />

the most optimal time is at Mid luteal phase, ie at 7 days after the LH surge or 7 days before<br />

onset of next menstruation. Categorized as luteal phase defect wether found Serum Progesterone<br />

Levels


This research is expected to gain more knowledge and understanding of the corpus luteum blood<br />

flow and its effect on the production of progesterone in the luteal phase of infertile women.<br />

Transvaginal colour Power Doppler Ultrasound imaging examination was able to help to<br />

diagnose blood flow of the corpus luteum in the luteal phase of infertile women and could be an<br />

alternative non-invasive diagnostic to diagnose the Luteal Phase Defect beside The examination<br />

of Progesterone serum concentration.<br />

MATERIAL AND METHODS<br />

This was an analytic survey study research with cross sectional study design, which performed in<br />

Sub-Division of Reproduction Technology of IVF, Division of FER, Obgyn Departement<br />

,Medical School-USU “Halim Fertility Centre”, Medan, since November 1 st 2010 until April<br />

30 th 2011. The samples of this study were obtained of all infertile women of reproductive age (15<br />

- 45 years old) which collected by Consecutive Sampling, who is being selected according to<br />

inclusion and exclusion criteria which came to pursue medical check up, then fulfilled the<br />

inclusion criterias and willing to participate on this research.<br />

Each respondent who fulfilled the inclusion criteria are given respectively a Basal Body<br />

Temperature Chart to record their basal body temperature in the morning every day for 28 days<br />

recorded. Day 14 has been estimated as the lowest temperature during the menstrual<br />

cycle, and declared as the day of ovulation. After ovulation, corpus luteum would be formed and<br />

developed then started to produces progesterone. Peak of the luteal phase has been estimated<br />

on 7 days after ovulation. On day 21 patients were asked to come and pursue the progesterone<br />

serum concentration examination, and then performed<br />

ultrasound Transvaginal Power Doppler to assess corpus luteum blood flow (PSV, EDV, PI, RI,<br />

Volume Corpus Lutem). Each patient which completely examined were recorde on a medical<br />

record ,then the Medical Record data collected until completely 41 samples ,and the data were<br />

tabulated , then the tabulated data were examined on Pearson correlation test.<br />

By Correlation Pearson Formula (r = 0.433) from literature, 41 samples were obtained to<br />

participate. The 41 samples data which completely collected , composed in a master of<br />

tabulation, then computerized by using Computer Statistic Program. Data presented on average<br />

values (Mean)± standard deviation. The presented data described in a scattered Dot graph form.<br />

To assess the significance of the relationship between the two variables were used Pearson<br />

correlation analysis and expressed significant if p value < 0.05 and by using the r<br />

value to described the strength of the relationship between the two variables of this study. The<br />

relationship would be stronger if closer to the value of +1 or-1. The correlation would be<br />

positive (+) if found that one variable is directly proportional to the other variable and would be<br />

negative (-) if found that one variable varies inversely with the other variable.<br />

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RESULTS<br />

After 6 months duration of this study, from November 1 st , 2010 to April 30th, 2011, which<br />

performed at Sub-Division of Reproductive Technology IVF,Division of FER, Department of<br />

Obgyn FK-USU "Halim Fertility Centre" obtained 42 infertile women who admitted to<br />

performed examination, who fulfilled the inclusion criteria .<br />

Table 4.1 . Correlation between Peak Systolic Velocity (PSV) of Corpus Luteum blood flow<br />

and progesterone serum concentration in the mid-luteal phase<br />

Peak Systolic Velocity<br />

(PSV) (cm/s)<br />

Serum Progesteron<br />

(ng/ml)<br />

*Pearson correlation test<br />

Mean SD P r<br />

12.75 7.30 0.000* 0.567*<br />

13.06 4.77<br />

The Average level of Progesterone serum concentration of the participants on this study is 13.06<br />

± 4.77 ng / ml with Average Peak Systolic Velocity (PSV) of the Corpus Luteum blood flow of<br />

the participants of this study is 12.75 ± 7.30 cm/s. By Pearson correlation test, found statistically<br />

significant correlation between Progesterone serum concentration and Peak Systolic Velocity<br />

(PSV) of the corpus luteum blood flow with p = 0.000 (p


= 0.567<br />

Graphic 1. Correlation between Peak Systolic Velocity (PSV) of Corpus Luteum blood flow<br />

and progesterone serum concentration in the mid-luteal phase<br />

From the scattered dot graph above described a positive correlation between the Progesterone<br />

serum concentration and Peak Systolic Velocity (PSV) of the corpus luteum blood flow with the<br />

strength value is moderate correlation r = 0.567.<br />

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Table 4.2 Correlation between End Diastolic Velocity (EDV) of Corpus Luteum blood flow and<br />

progesterone serum concentration in the mid-luteal phase<br />

End Diastolic Velocity<br />

(EDV)(cm/s)<br />

Serum Progesteron<br />

(ng/ml)<br />

*Pearson correlation test<br />

Mean SD p R<br />

4.54 3.95 0.000* 0.604*<br />

13.06 4.77<br />

The Average level of Progesterone serum concentration of the participants on this study is 13.06<br />

± 4.77 ng / ml with Average End Diastolic Velocity (EDV) of the Corpus Luteum blood flow of<br />

the participants of this study is 4.54 ± 3.95 cm/s. By Pearson correlation test, found statistically<br />

significant correlation between Progesterone serum concentration and End Diastolic Velocity<br />

(EDV) of the corpus luteum blood flow with p = 0.000 (p


Graphic 2. Correlation between End Diastolic Velocity (EDV) of Corpus Luteum blood flow<br />

and progesterone serum concentration in the mid-luteal phase<br />

From the scattered dot graph above described a positive correlation between the Progesterone<br />

serum concentration and End Diastolic Velocity (EDV) of the corpus luteum blood flow with the<br />

strength value is Strong correlation r = 0.604.<br />

s<br />

.<br />

r = 0.604<br />

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Table 4.3 Correlation between Pulsatility Index (PI) of Corpus Luteum blood flow and progesterone<br />

serum concentration in the mid-luteal phase<br />

Mean SD P r<br />

Pulsatility Index (PI) 1.12 0.51 0.032* - 0.332*<br />

Serum Progesteron<br />

(ng/ml)<br />

*Pearson correlation test<br />

13.06 4.77<br />

The Average level of Progesterone serum concentration of the participants on this study is 13.06<br />

± 4.77 ng / ml with Average Pulsatility Index (PI) of the Corpus Luteum blood flow of the<br />

participants of this study is 1.12 ± 0.51 cm/s. By Pearson correlation test, found statistically<br />

significant correlation between Progesterone serum concentration and Pulsatility Index (PI) of<br />

the corpus luteum blood flow with p = 0.032 (p


= ‐0.332<br />

Graphic 3. Correlation between Pulsatility Index (PI) of Corpus Luteum blood flow and<br />

progesterone serum concentration in the mid-luteal phase<br />

From the scattered dot graph above described a negative correlation between the Progesterone<br />

serum concentration and Pulsatility Index (PI) of the corpus luteum blood flow with the strength<br />

value is Weak correlation r = - 0.332<br />

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Table 4.4 Correlation between Resistance Index (RI) of Corpus Luteum blood flow and<br />

progesterone serum concentration in the mid-luteal phase<br />

Mean SD P R<br />

Resistance Index (RI) 0.71 0.36 0.005* - 0.423*<br />

Serum Progesteron<br />

(ng/ml)<br />

*Pearson correlation test<br />

13.07 4.77<br />

The Average level of Progesterone serum concentration of the participants on this study is 13.06<br />

± 4.77 ng / ml with Average Resistance Index (RI) of the Corpus Luteum blood flow of the<br />

participants of this study is 0.71 ± 0.36 cm/s. By Pearson correlation test, found statistically<br />

significant correlation between Progesterone serum concentration and Resistance Index (RI) of<br />

the corpus luteum blood flow with p = - 0.005 (p


= ‐0.423<br />

Graphic 4. Correlation between Resistance Index (RI) of Corpus Luteum blood flow and<br />

progesterone serum concentration in the mid-luteal phase<br />

From the scattered dot graph above described a negative correlation between the Progesterone<br />

serum concentration and Resistance Index (RI) of the corpus luteum blood flow with the strength<br />

value is Moderate correlation r = - 0.423<br />

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Table 4.5 Correlation between Volume Corpus Luteum and progesterone serum<br />

concentration in the mid-luteal phase<br />

Volume corpus luteum<br />

(cm 3 )<br />

Serum Progesterone<br />

(ng/ml)<br />

*Pearson correlation test<br />

Mean SD P r<br />

7.13 4.48 0.992* 0.002*<br />

13.14 4.65<br />

The Average level of Progesterone serum concentration of the participants on this study is 13.06<br />

± 4.77 ng / ml with Average Volume Corpus Luteum of the participants of this study is 7.13 ±<br />

4.48 cm/s. By Pearson correlation test, found no statistically significant correlation between<br />

Progesterone serum concentration and Volume corpus luteum with p = 0.992 and found a<br />

positive correlation between Progesterone serum concentration and Volume corpus luteum with<br />

the strength value is very weak, with r = 0.002.<br />

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= 0.002<br />

Graphic 5. Correlation between Volume Corpus Luteum and progesterone serum concentration<br />

in the mid-luteal phase<br />

From the scattered dot graph above described a positive correlation between the Progesterone<br />

serum concentration and Volume corpus luteum with the strength value is very weak correlation<br />

r = 0.002<br />

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DISCUSSION<br />

Corpus luteum becomes highly vascularized within a few days after ovulation so that, on a tissueto-weight<br />

basis, blood flow to the corpus luteum is among the greatest of any tissue in the body<br />

(Abdul-Karim and Bruce, 1973). This increased vascularity, in addition to providing a conduit for<br />

the delivery of luteal steroids to the general circulation, it also necessary for the provision of the<br />

cholesterol substrate in the form of Low Density Lipoprotein, for progesterone biosynthesis<br />

(Carr et al, 1982). Therefore, it seems likely that blood flow to the ovary and the corpus luteum<br />

may be important in regulating the function of the corpus luteum. 3<br />

Progesterone serum concentration peaked 6 to 8 days before the start of menstruation. The early<br />

luteal stage is characterized by the rapid proliferation of endothelial cells and invasion of<br />

capillaries from the cores of the luteal tissue infoldings, which contain connective tissue and<br />

blood vessels derived from the theca into the peripheral areas of the infoldings, which contain<br />

granulosa-derived luteal cells (Gaede et al. 1985). The mid-luteal stage is characterized by the<br />

formation of a dense microvascular network composed primarily of capillaries. The late luteal<br />

stage is characterized by the regression of the capillaries, a relative increase in connective tissue,<br />

an increased abundant of larger microvessels, and a regression and loss of luteal parenchymal<br />

cells (Azmi dan O’Shea, 1984; Jablonka Shariff dkk., 1993). 3<br />

In research of Bau and Bajo in Ma<strong>dr</strong>id, Spain in 2001, found the serum levels of progesterone<br />

was significantly lower in women with luteal phase defect than women with normal cycles. And<br />

the length of the luteal phase is found shorter in women with luteal phase defect than women<br />

with normal cycles. 16<br />

Kupesic and Kurjak Research in Zagreb, Croatia, 1996, found the average progesterone serum<br />

level was significantly lower in women with luteal phase defect compared to the control group (<br />

p < 0.01 ). 9,25<br />

Correlation between Peak Systolic Velocity (PSV) of Corpus Luteum blood flow and<br />

progesterone serum concentration in the mid-luteal phase<br />

Miyazaki et al, 1998, in Japan in their research, PSV found peaked at 8-6 days before the onset<br />

of the next menstrual period and declined until the late luteal phase. Serum concentrations of<br />

progesterone showed the same changes, increased from 12-16 days before the start of the next<br />

menstrual period and peaked at 6-8 days before onset of next menstruation. Although the PSV<br />

did not correlate with serum concentrations of progesterone in their study, but it showed the<br />

same pattern of changes in progesterone serum concentrations in accordance with a previous<br />

study conducted by Bourne et al., 1996. 3<br />

Bourne et al, 1996, showed a close relationship between the PSV of blood flow surrounding the<br />

Corpus luteum and Serum Concentration of progesterone in a spontaneous cycle. 3,13<br />

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Niswender et al, 1976 showed that blood flow to the ovary and the number and size of luteal<br />

cells may be important in the regulation of progesterone production by the ovary. Blood flow to<br />

the ovary bearing corpus luteum increases three to sevenfold during the luteal phase and then<br />

decreases markedly as the corpus luteum regresses. 3,7,8<br />

Hong-Ning Xie et al, Japan. In 2001 revealed that the blood flow of intra-Ovarial clearly show<br />

maximum velocity and low resistance index in the mid-luteal phase in normal menstrual cycle,<br />

suggesting that the blood vessels of the corpus luteum has a minimum flow of Resistance Index<br />

because they are maximally dilated, so it is not optimal for vasomotor motion. The same pattern<br />

was found in luteal blood flow and progesterone levels during developing corpus luteum,<br />

indicating that the corpus luteum of adequate vascularization is a physiological need for adequate<br />

luteal function. This research indicates that the increase in luteal blood flow is the impact of<br />

vascular dilatation in early luteal phase. PSV was found positively correlated with serum<br />

concentrations of progesterone. This supports the concept that luteal blood flow velocity is a<br />

complementary parameter that describes the luteal function in infertility. 19<br />

Relationship between PSV of Corpus Luteum blood flow and luteal phase deficiency, Bau and<br />

Bajo ,Ma<strong>dr</strong>id, Spain in 2001, found that the PSV in mid-luteal phase of women with luteal<br />

phase defect is lower than PSV in women with normal cycles. And found a significant<br />

correlation between PSV and progesterone serum concentration in women with luteal phase<br />

defect ( r = 0,36 ). 16<br />

On this present study, found a significant correlation between the Peak Systolic Velocity (PSV)<br />

of Corpus luteum blood flow (cm/s) and Progesterone serum concentration (ng/ml) and found a<br />

positive correlation with the strength value was moderate.<br />

Correlation between End Diastolic Velocity (EDV) of corpus luteum blood flow and<br />

progesterone serum concentration in the mid-luteal phase<br />

Ottander et al., Sweden in 2004 showed that the End Diastolic Velocity (EDV) decreased<br />

significantly at the end-luteal phase than mid-luteal phase. It also found in the pattern of changes<br />

of PSV, where PSV showed a similar pattern of changes with the pattern of change of EDV. 10<br />

Relationship of EDV and luteal phase deficiency, Bau and Bajo in Ma<strong>dr</strong>id, Spain 2001, On this<br />

research found no difference between end diastolic blood flow velocity intra ovarial in women<br />

with luteal phase defect than women with normal ovulatoar cycle. 16<br />

On this present study, found a significant correlation between<br />

the End Diastolic Velocity (EDV) of corpus luteum blood flow (cm/s) and progesterone serum<br />

concentration (ng/ml) and found a positive correlation with the strength value was strong.<br />

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Correlation between Pulsatility Index (PI) of corpus luteum blood flow with progesterone<br />

serum concentration in the mid-luteal phase<br />

Miyazaki et al. In Japan, 1998 in his research found that the Pulsatility Index (PI) of<br />

ovarian artery reaches its nadir in the mid-luteal phase (3-8 days prior to the next menstrual<br />

cycle). Progesterone serum concentration showed similar changes, increased from 12-16 days<br />

before the start of the next menstrual period and peaked on 6-8 days before onset of next<br />

menstruation. In this study, intra-luteal PI are found to be associated with serum progesterone.<br />

Progesterone peaked in mid-luteal phase (8-6 days before onset of next menstruation), while<br />

intra-luteal PI began to decreased in the early luteal phase (11-9 days before the start of the next<br />

menstrual period) and then increased until the beginning of the next menstrual period. The<br />

difference between the maximum period of progesterone serum concentrations with lowest PI<br />

period point showing the fact that the increase in circulating hormone is inversely proportional to<br />

the increase in corpus luteum of structural vascularization. 3<br />

Hata et al, 1990; Glock et al, 1995 suggest that the low PI values associated with lower RI. The<br />

blood supply to the ovary bearing corpus luteum increased during the luteal phase, especially in<br />

the mid-luteal phase in line with increased consumption of Low-Density Lipoprotein to the luteal<br />

cells to produce progesterone in the corpus luteum. 3<br />

Tinkanen et al., Finland, 1994 in her research found no significant difference in terms of intra-<br />

Ovarial Pulsatility Index (PI) with Progesterone Serum Levels. However, inadequate number of<br />

patients and insuficient methods used for evaluation of luteal function in this study, have become<br />

limitations in this study. 9<br />

On this present study, found a significant correlation between the Pulsatility Index of<br />

Corpus Luteum blood flow and Progesterone Serum Concentration (ng/ml) and found a<br />

negative correlation with the strength value was weak.<br />

Correlation between Resistance Index (RI) of Corpus Luteum blood flow and Progesterone<br />

serum concentration in the Mid-Luteal Phase<br />

In the study of Kupesic and Kurjak in Croatia in 1996, their research found the lowest RI value<br />

at the mid-luteal phase, which then increased to higher values in the late luteal phase. The<br />

average progesterone level was significantly lower (P


detected in the mid-luteal phase in line with the peak of corpus luteum Angiogenesis. Increased<br />

RI is shown in the late luteal phase as the regression of the corpus luteum. 3,14<br />

In the study of Tamura et al. in Japan in 2008, found that luteal RI in the mid-luteal phase in<br />

women with luteal phase defect increased significantly compared with women with normal luteal<br />

function. Luteal RI was significantly correlated with progesterone serum concentrations in the<br />

mid-luteal phase. In this study, shows that the luteal RI decreased during the early luteal phase<br />

and increased during the regression phase. Furthermore, this study showed high luteal RI and<br />

low progesterone serum levels are found during the luteal phase. In fact, angiogenesis is essential<br />

for corpus luteum development and maintenance of luteal function. These findings indicate that<br />

blood flow is an important factor to regulate luteal function. Therefore, showing that the luteal<br />

phase defect is caused by defective regulation of blood flow during mid-luteal luteal phase. 11<br />

Study by Takasaki et al. in Japan in 2009 that conducts research on the corpus luteum blood<br />

flow associated with luteal function found a significant negative correlation between corpus<br />

luteum RI with progesterone serum concentrations during mid-luteal phase. 17<br />

Relationship between RI and luteal phase defect, both previous studies and the study of Takasaki<br />

et al, Japan,2009 support that the luteal phase defect associated with the presence of high RI in<br />

corpus luteum because luteal RI in women with luteal phase defects during mid-luteal phase<br />

increased significantly compared to women with normal luteal function and corpus luteum RI<br />

negatively correlated with progesterone serum concentrations during the Mid-luteal phase on<br />

women with normal cycles. 17<br />

On this present study, found a significant correlation between the Resistance Index of<br />

Corpus Luteum blood flow and Progesterone Serum Concentrations (ng/ml) and found<br />

negative correlation with the strength value was moderate..<br />

Correlation between the Volume of Corpus Luteum and Progesterone Serum Concentration in<br />

the Mid-Luteal Phase<br />

Miyazaki et al., 1998 in Japan showed the corpus luteum image with Doppler transvaginal<br />

ultrasound imaging during the luteal phase. Areas that seen increased vascularity in the time of<br />

periovulation to mid-luteal phase and declined until the next menstrual period. Volume of<br />

Corpus Luteum showed the same pattern as changes in Progesteron serum concentrations.<br />

Although the changes in volume corpus luteum is proportional to the change of Progesterone<br />

Serum Concentrations, but there is no significant correlation between the volume of the corpus<br />

luteum and Serum Concentrations of Progesterone. 3<br />

Jablonka Shariff et al., 1993 on their research found that the rapid growth of luteal<br />

vascularization is accompanied by a rapid increase in weight and size of the corpus luteum. 3<br />

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Bruce and Moor, 1976;. Niswender et al, 1976 found the luteal phase blood flow increased<br />

<strong>dr</strong>amatically in relation to the increase in corpus luteum tissue growth. 3,7,8<br />

Bourne et al, 1996 found a significant correlation between the size of the corpus luteum with<br />

progesterone production, shown in his research. 3,13<br />

Jokubkiene et al., Sweden 2006, in his study he found there was no significant relationship<br />

between volume corpus luteum on day-7 and progesterone level on day-7 after ovulation. The<br />

study found no correlation between serum progesterone levels with blood flow to the corpus<br />

luteum in the mid-luteal phase. Progestreron level is a description of the corpus luteum function,<br />

but blood flow does not depict progesterone production in the corpus luteum. Corpus luteum<br />

highest volume found in the early luteal phase and decreased significantly at the end of the luteal<br />

phase. 24<br />

Furthermore, the study of Singh et al 1997 found that the size of luteal cell increases during the<br />

formation of the corpus luteum and decreases during the regression of the corpus luteum. 3<br />

On this present study, found no significant correlation between the Volume of Corpus<br />

Luteum (mm3) and Progesterone Serum Concentration and found a positive correlation with<br />

the strength value was very weak.<br />

Retrieved the Pulsatility Index (PI) as the best diagnostic tool in this study. AUC value (AUC =<br />

70.1%) which compared to other predictor variables (diagnostic tools) to predict the luteal phase<br />

defect ,with cut off point value was 1.085 with a sensitivity of 73, 3% and a specificity of 66.7%.<br />

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CONCLUSION<br />

Based on the purpose of this study, results and discussion of this study, it can be concluded that :<br />

There is significant correlation between the Peak Systolic Velocity (PSV) of Corpus luteum<br />

blood flow (cm/s) and Progesterone serum concentration (ng/ml) and found a positive<br />

correlation with the strength value was moderate. There is significant correlation between<br />

the End Diastolic Velocity (EDV) of Corpus Luteum blood flow (cm/s) and Progesterone serum<br />

concentration (ng/ml) and found a positive correlation with the strength value was strong. There<br />

is significant correlation between the Pulsatility Index of Corpus Luteum blood flow<br />

and Progesterone Serum Concentration (ng/ml) and found a negative correlation with the<br />

strength value was weak. There is significant correlation between the Resistance Index of<br />

Corpus Luteum blood flow and Progesterone Serum Concentrations (ng/ml) and found<br />

negative correlation with the strength value was moderate. There was no significant<br />

correlation between the volume of Corpus Luteum (mm3) and Progesterone Serum<br />

Concentrations and found a positive correlation with the strength value was very weak. Retrieved<br />

the Pulsatility Index (PI) as the best diagnostic tool in this study. AUC value (AUC = 70.1%)<br />

which compared to other predictor variables (diagnostic tools) to predict the luteal phase defect<br />

,with cut off point value was 1.085 with a sensitivity of 73, 3% and a specificity of 66.7%.<br />

RECOMMENDATION<br />

Based on the advantages of this study, it can be suggested:<br />

By Power Doppler Transvaginal Ultrasound can also reflected the Progesterone serum<br />

concentration, without having to perform progesterone serum examination through the laboratory<br />

findings. Therefore Power Doppler Transvaginal Ultrasound can be used as an alternative noninvasive<br />

diagnostic tool to diagnose Luteal Progesterone Deficiency in the Luteal Phase with<br />

Pulsatility Index as the best predictor for determining the existence of Luteal Phase Defect.<br />

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REFERENCES<br />

1. Jacqueline P, Thomas N D, “Infertility due to Luteal Phase Defects : Option in<br />

Diagnosis, and Treatment with Bio-Identical Progesterone”<br />

2. Baziad Ali, “ Endokrinologi Ginekologi Edisi Ketiga Bab 8 defek Fase Luteal “ Media<br />

Auscaulapius. Fakultas Kedokteran Universitas Indonesia, Jakarta, 2008: 101-4<br />

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