Rkk16

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Rkk16

  1. 1. TinjauanPustaka Kimia Klinik<br />PemeriksaanLaboratoriumpadaInfertilitasWanita<br />DiahPuspitaRini/SidartiSoehita SFHS<br />1<br />
  2. 2. I. PENDAHULUAN<br />2<br />
  3. 3. Definisi<br />Infertilitas: pasutritidakmampuhamilsetelahsatutahunmelakukanhubunganseksualteraturtanpakontrasepsi<br />Infertilitassekunder: pernahhamil, tidakhamillagidalam 12 bulantanpakontrasepsi<br />3<br />
  4. 4. PenyebabInfertilitas<br />1. Pria: abnormalitassperma<br />2. Wanita: <br /><ul><li>Disfungsiovulasi
  5. 5. Kelainanpada tuba</li></ul>3. Gabunganpriadanwanita<br />4. Unexplained infertility: penyebabinfertilitas yang pastitidakdiketahui<br />4<br />
  6. 6. 5<br />II. AnatomidanFisiologi<br />SistemReproduksiWanita<br />
  7. 7. AnatomiFungsional<br />Gambar 1. Organ reproduksiwanita<br />6<br />
  8. 8. AksisHipotalamus-Pituitari-Ovarium<br />7<br />Gambar 2. Interaksiendokrinpadaaksis HPO danendometrium . E2, Estradiol; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; InhA, inhibin-A; InhB,inhibin-B; LH, luteinizing hormone; P, progesteron. <br />
  9. 9. SintesisHormonOvarium<br />Ovariummensekresi : <br /> Estrogen<br />Progesteron<br /> Androgen<br />Folikel -> sumberproduksihormonovarium<br />Folikelterdiridari :<br />Seltheka->produksi androgen<br />Selgranulosa -> <br />produksi estrogen<br />3. Oosit primer<br />8<br />Gambar 3. Perubahanovariumselamamasasiklus<br />
  10. 10. RegulasiHormonReproduksi<br />Gambar 4. Siklusmenstruasi<br />9<br />
  11. 11. ImplantasiEmbrio<br />Implantasi : terjadi 5-7 harisetelahfertilisasi, saatfasesekretoriendometrium<br />Masareseptivitasendometrium : <br /><ul><li>hari 16-22 (siklus 28 hari)
  12. 12. hari 16-19 dgnstimulasigonadotropineksogen</li></ul>Hilangnyasinkronisasiantaraendometriumdanembrio -> keguguranberulang<br />10<br />
  13. 13. Gambar 5. Tahapanimplantasi, dimulaidenganovulasidandiikutifertilisasidanperpindahankeendometrium. <br />11<br />
  14. 14. 12<br />III. Penyebabinfertilitaspada<br />wanita<br />
  15. 15. KelainanOvulasi<br />Hiperprolaktinemia<br />Gangguanfungsi tuba falopii<br />Endometriosis<br />13<br />
  16. 16. KelainanOvulasi<br />Kegagalanhipotalamus-pituitari<br />FSH & LH  -> Hipoestrogenemia<br />Disfungsihipotalamuspituitari<br />Estrogen normal, kelainangonadotropin<br />Terbanyak : PCOS (Polycystic Ovary syndrome)<br />Kriteria: <br />oligo - danatauanovulasi<br />hiperandrogenism yang dibuktikansecaraklinisataulaboratorium<br />ovariumpolikistik, denganmenyingkirkanpenyebab lain <br />Kegagalanovarium<br /> FSH, amenorea, hipogonadism, estrogen rendah<br />14<br />
  17. 17. 2.Hiperprolaktinemia<br />galaktorea, estrogen rendah, anovulasi, siklusmenstruasitidakteratur-> infertilitas<br />3. Gangguanpada tuba falopii<br />dialami 25%pasangan <br />perlekatanringansampaisumbatan total<br />terapi: pembedahan<br />4. Endometriosis<br />Kelenjarendometriumataustromadiluarkavitasendometriumdan uterus<br />Patogenesis: belumjelas, mungkinadesi<br />15<br />
  18. 18. 16<br />iv. Pemeriksaanlaboratorium<br />
  19. 19. 1. Penilaiancadanganoosit<br />Pemeriksaan FSH hari ke-3 siklus<br />17<br />
  20. 20. 2. PenilaianOvulasi<br />Membuktikanadanyaovulasi -> terpentingdalamevaluasifertilitas<br />Mengetahuiovulasi:<br />Sesudahovulasi<br />Suhu basal tubuh<br />USG: ukuranfolikel <, hilangnyadeveloped folikel<br />Progesteron<br />Sebelumovulasi : deteksilonjakan LH -> 12-36 <br /> jam ovulasi<br />18<br />
  21. 21. Progesteron<br /><ul><li>Indikasi:</li></ul>riwayatunexplained infertility / keguguranberulang<br />curigaadanyadefek/inadekuatfaseluteal<br /><ul><li>Interpretasi:
  22. 22. Kadar > 3 μg/L -> indikatortelahterjadiovulasi</li></ul>kadar < 10 ng/mL , 2 dari 3 sampeldalamsatuminggusebelumawalmenstruasiatau 7 harisetelahovulasi -> defekfaseluteal<br /><ul><li>Nilairujukan: </li></ul>Fasefolikular 0,1 – 0,7 ng/mL<br />Faseluteal 2 – 25 ng/mL<br />19<br />
  23. 23. Pemeriksaan LH urine<br />Menggunakanstrip->perubahankadar LH<br />Pemeriksaandimulai 2 harisebelumovulasi<br />♀ siklus 28 hari : ovulasi 13-15<br />♀ siklus 27-34: ovulasi 13-20 -> tesdimulaihari 11 sampai 20/sampaiovulasiterjadi<br />Ovulasi (-) 2 siklusberurutan -> masalahovulasi<br />20<br />
  24. 24. 3. Hormon Lain<br />A. FSH<br />Nilairujukan: <br />Fasefolikular 1,68 – 15,0 IU/ml<br />Faseovulasi 21,9 - 56,6 IU/ml<br />Faseluteal 0,61 - 16,3 IU/ml<br />Fase menopause 14,2 - 52,3 IU/ml<br />Meningkat: hipogonadisme, pubertasprekoks, menopause dansidroma Turner<br />Menurun : keadaaninsufisiensihipotalamus, disfungsi gonad, anovulasi, insufisiensihipofisis, dan tumor ovarium.<br />21<br />
  25. 25. B.LH<br />Nilairujukan:<br />Fasefolikular 1,37 – 9,9 IU/L<br />Faseovulasi 6,17 – 17,2 IU/L<br />Faseluteal 1,09 – 9,2 IU/L<br />Fase menopause 19,3 – 100,6 IU/L<br />Indikasipemeriksaan FSH dan LH<br /><ul><li>bagiandarievaluasidasarinfertilitas
  26. 26. menilaiaksis gonad-pituitarijikaadakecurigaankekuranganestrogenisasi
  27. 27. amenoreasentralataufertilitas yang berkurangsetelahkemoterapikanker
  28. 28. diagnosis kegagalanovariumatau gonad usia <40 tahun</li></ul>22<br />
  29. 29. C. ESTRADIOL<br />estrogen endogen utama yang paling aktif<br />Indikasipemeriksaan: wanitatdkhamil:<br /><ul><li>amenoreaatausiklusmenstruasi yang abnormal
  30. 30. akanmenjalaniinduksiovulasi
  31. 31. kemungkinanmengalamikegagalanovariumsebelumumur 40
  32. 32. pubertasprekoks</li></ul>NilairujukanPremenopause : 30 - 400 pg/mL<br />Postmenopause : 0 - 30 pg/mL<br />Interpretasi<br />kadartinggi > 100 pg/mLdankadar FSH < 10 IU/L hari 2 sampai 4 siklusmenstruasi -> tandadisfungsiovulasidanresponterapiinfertilitas yang buruk<br />23<br />
  33. 33. Nilairujukan : testosteron total     15-70 ng/mL<br />Interpretasi<br />Kadar testosteron >200 ng/ml ->tumor ovarium /adrenal<br />PCOS <150 ng/ml <br />Nilairujukanwanitatidakhamil 3-30 ng/mL<br />Interpretasi<br />Peningkatanprolaktinnyata (> 100 μg/L [normal< 25 μg/L]):<br />hipogonadisme, galaktoreadanamenorea<br />Peningkatanprolaktinmoderat (51–75 μg/L) : oligomenorea<br />Peningkatanprolaktinsedang (31–50 μg/L) : faseluteal yang pendek, penurunan libido daninfertilitas<br />24<br />D. TESTOSTERON<br />E.PROLAKTIN<br />
  34. 34. 4. Penilaianinteraksimukusserviks & spermatozoa<br />Post Coital Test/Sim'satauHunner'stest<br /><ul><li>Prinsip: mengevaluasiinteraksi spermatozoa – mukusserviksdanmenilaijumlah spermatozoa yang aktifsertasurvivalnyabeberapa jam setelahkoitus
  35. 35. Waktu: sedekatmungkindenganovulasi
  36. 36. Persiapanpasien: </li></ul>Tidakkoitusdalam 48 jam<br />Koitus 2-8 jam sebelumke lab<br />Tidakmenggunakan gel yang bersifatspermisidaataulubrikan<br />- Pemeriksaan lab: 9-14 jam post coital<br />25<br />
  37. 37. Peralatan : <br />spekulum vagina <br />sarungtangan<br />lidikapas<br />spuittuberkulintanpajarum<br />obyekglasdancover glass<br />kertas pH<br />Cara PengambilanSpesimen<br /><ul><li>posisipasienlitotomi
  38. 38. sampeldiambildiserviks & vagina
  39. 39. 3 obyekglas: “fern”, “endoserviks”, “vagina”
  40. 40. Fern: mukusserviksdiambildenganswab->obyekglas -> kering</li></ul>Endoserviks & Vagina : mukusdiambilmenggunakanspuittuberkulin->tutupdengancover glass<br />26<br />
  41. 41. 1. EvaluasiMukusServiks<br /> Volume <br />Viskositas<br />Ferning<br />Spinnbarkeit<br />Selularitas<br /> pH<br />27<br />SKOR : 0,1,2,3<br />2. Evaluasi Spermatozoa<br />
  42. 42. 28<br />Gambar 6. TehnikSpinnbarkeit<br />Gambar 7. Bentukgambaranferning<br />
  43. 43. 1. EvaluasiMukus<br />29<br />
  44. 44. pH mukus : tidaktermasukdalamskor, determinanpentingdalaminteraksimukus-sperma<br />asam -> immobilisasi spermatozoa<br /> alkali -> meningkatkanmotilitas<br /> pH optimum : 7 - 8,5 (pH mukus normal pertengahansiklus)<br />Skormukusserviks > 10 -> kualitasmukusbagus, memudahkanpenetrasisperma<br />30<br />
  45. 45. 2. EvaluasiSperma<br /><ul><li>2-3 jam setelahkoitus, akumulasi spermatozoa dikanalserviksbagianbawah
  46. 46. Konsentrasi spermatozoa dihitungdalamjumlah spermatozoa/μL
  47. 47. Motilitasnya : </li></ul>PR (progressive motility) : spermaaktif, gerakan linier/membentuklingkaranbesar<br />NP (non-progressive motility): tidakmaju, lingkarankecil, hanyagerakanflagela<br />IM (immotile spermatozoa): tidakadapergerakan<br />31<br />
  48. 48. 32<br />Gambar 8. Contohformulirhasilpost coital test<br />
  49. 49. Interpretasi<br />Tesdianggapnegatifbilatidakditemukan spermatozoa <br /> Spermatozoa denganmotilitasprogresifmenyingkirkanfaktorserviksdanautoimunterhadapspermasebagaipenyebabinfertilitas<br /> Spermatozoa motilitas non progresif, fenomenashaking -> antibodidimukusataudi spermatozoa<br />33<br />
  50. 50. Hasilawalnegatif, tesharusdiulang<br />Tes yang negatifdapatdisebabkankarenawaktu yang tidaktepat<br />Masaovulasitidakdapatdiprediksi, post coital test diulangbeberapa kali dalamsatusiklusmenstruasi<br />Post coital test padawaktu yang optimal, hasilnegatifmenunjukkanfaktorservikssebagaikemungkinanpenyebabinfertilitas<br />34<br />
  51. 51. 35<br />Terimakasih<br />
  52. 52. Causes of Female Infertility<br />36<br />
  53. 53. 37<br />
  54. 54. Luteal Phase Defect<br />Three causes of LPD include poor follicle production, premature demise of the corpus luteum, and failure of the uterine lining to respond to normal levels of progesterone. <br />Once a diagnosis of LPD is suspected, a serum progesterone test will often be performed at about seven days past ovulation. A level less than 14 ng/ml indicates that progesterone production in the luteal phase is inadequate.<br />Should progesterone levels prove to be low, the temptation is often to "treat the symptom" by giving the patient progesterone supplementation during the luteal phase. In the case of inadequate corpus luteum performance, progesterone support may indeed be the appropriate solution. However, inadequate follicle development may also be causing the low progesterone levels. Thus, it is important to measure midcycle follicle size (via ultrasound) and estradiol levels (via a blood test).<br />38<br />
  55. 55. FERNING<br />As ovulation nears, estrogen increases and causes the body's sodium levels to rise. Saliva is affected by the increased salinity. This is noticeable when allowing samples of saliva to dry. Near ovulation the higher salt content causes the dried saliva to form crystallization patterns. Both saliva and cervical mucus have shown these patterns.<br />39<br />
  56. 56. in vitro sperm mucus penetration test <br />This is performed simply by putting a drop of freshly removed mucus next to a drop of freshly ejaculated semen on a microscope slide. The interface between the two drops is examined for about a quarter of an hour, and it is then possible to see if the sperm are penetrating the mucus and swimming actively in it. If this does not occur, then it is likely that there is some form of immune response between the sperm and the mucus, and further tests should be conducted to examine this.<br />Another simple test for antisperm antibodies in the mucus is called the sperm cervical mucus contact test (SCMC for short) where the sperm and mucus are mixed together. If, under the microscope, the sperm are seen to be shaking in a characteristic way, this means that there are anti-bodies present<br />40<br />
  57. 57. Treatment on poor cervical mucus<br />Cervical problems can be corrected depending upon what the cause is. For example, if the reason for the poor mucus is:<br />lack of ovulation, then ovulation can be induced <br />cervical infection, then this can be treated by cauterising or freezing the abnormal cervical tissue, so that this is destroyed, and is then replaced by healthy cervical glands <br />thick or viscous mucus can occasionally be treated by cough medicines (expectorants, which contain guaifensin ( Robitussin) in a dose of 1-2 tsp per day, beginning three to four days prior to when you want to conceive.) Just like guaifensin helps to thin the thick phlegm if you have a cough, it also helps to thin the cervical mucus. <br />scanty mucus, then mucus production can be enhanced by supplemental low-dose estrogens<br />41<br />
  58. 58. Negative Post Coital Test<br />The PCT was not done at the best time. For example, the PCT may have been done too early or too late in the cycle. Wrong timing is the commonest reason for a negative test and can even cause repeatedly negative tests. <br />There was no ovulation the month of the test - perhaps because of the strain or stress of making love to order. <br />The sperm count was poor. Obviously, men with persistently low sperm counts, or men with poor motile sperm, may be responsible for a negative PCT. <br />There may be an abnormality of the cervix - for example, chronic infection in the cervix may prevent production of adequate mucus; and some women with a scarred cervix may not produce enough mucus.Patients who have had surgery on the cervix ( for example, cervical conisation, in which a cone of cervical tissue is removed to treat cervical dysplasia) often have this problem. <br />The cervix is producing antibodies to the sperm. <br />Medications such as clomiphene, tamoxifen, progesterones and danazol - all drugs used for infertility problems - can interfere with the production of good mucus. <br />42<br />
  59. 59. Endocrine and paracrine products of the endometrium<br />43<br />
  60. 60. 44<br />
  61. 61. FSH<br /> (+)<br />E2<br /> (-)<br />FSH=Follicle Stimulating Hormone<br />E2=Estradiol<br />Effects of Aging on the Ovary<br />
  62. 62. 46<br />
  63. 63. Sperm Count<br />Fresh sample (to lab within 30 mins.) –most sperm in initial ejaculate<br />Male should be abstinent for 48 to 72 hours<br />sperm concentration > 20 million per ml<br />total count > 60 million<br />ejaculate volume > 1.5 ml<br />total motile count > 30 million<br />viable sperm > 50%<br />normal shapes (morphology) > 60% <br />
  64. 64. Sperm Terms<br />Normozoospermia<br />Normal ejaculate <br />Asthenozoospermia<br />Teratozoospermia<br />Azoospermia<br />Aspermia<br />Normal ejaculate <br />Sperm concentration <20 × 106 /ml<br /><50% spermatozoa with forward progression<br /><30% spermatozoa with normal morphology<br />No spermatozoa in the ejaculate<br />No ejaculate<br />
  65. 65. Hook Effect<br />49<br />The prozone or (high-dose) hook effect, documented to cause false-negative assay results 50 years ago , still remains a problem in one-step immunometric assays , immunoturbidimetricassays , and immunonephelometricassays for immunoglobulins. To detect the prozone effect, samples are often tested undiluted and after dilution . If the result on dilution is higher than or the undiluted sample, then the undiluted sample most likely exhibited<br />the prozone effect.<br />
  66. 66. Diagnostic studies to confirm Ovulation<br />Basal body temperature<br />Inexpensive <br />Accurate<br />Endometrial biopsy<br />Expensive<br />Static information<br />Serum progesterone<br />After ovulation rises<br />Can be measured<br />Urinary ovulation-detection kits<br />Measures changes in urinary LH<br />Predicts ovulation but does not confirm it<br />
  67. 67. Basal Body Temperature<br />Excellent screening tool for ovulation<br />Biphasic shift occurs in 90% of ovulating women<br />Temperature <br />drops at the time of menses<br /> rises two days after the lutenizing hormone (LH) surge<br />Ovum released one day prior to the first rise<br />Temperature elevation of more than 16 days suggests pregnancy<br />
  68. 68.
  69. 69. Alteration in sex steroid metabolism-> attenuated release of gonadotropin-> anovulation<br />SHBG->free testosteron high normal<br />Increased visceral fat -> hiperinsulinemia->independent effect on ovulation<br />53<br />OBESITY and INFERTILITY<br />
  70. 70. Hypothyroid<br />bioactive estrogen :<br />decreased metabolism of estrogen in the liver (seen with both hypothyroidism and hyperthyroidism) <br />decreased levels of the protein that binds estrogen in the circulation. <br />Persistent elevations of bioactive estrogen can interfere with follicular growth and can disrupt the midcyclepreovulatory LH and FSH surges that are required for normal ovulation. <br /> TRH can "crosstalk" within the pituitary gland to release other pituitary hormones such as prolactin. Elevated prolactin levels are known to interfere with ovulation . <br />54<br />
  71. 71. Hyperthyroid<br />The mechanism for the ovulatory dysfunction associated with hyperthyroidism is not entirely clear. <br />There may be elevated bioactive estrogen concentrations either due to decreased liver metabolism of estrogens or due to an increase in the activity of the enzyme that forms estrogens (called aromatase). Persistent elevations of estrogen interfere with follicular growth and can disrupt the midcycle LH and FSH surges.<br />55<br />
  72. 72. Hyperprolactinemia<br />prolactin released from the pituitary gland ->brain's dopamine ->inhibit GnRH release from the hypothalamus -> FSH and LH secretion. A decrease in FSH may be the basis for most prolactin associated ovulatory problems. <br />There are prolactin receptors on the adrenal glands. The adrenal glands may respond to increased prolactin by increasing their own androgenic hormones. The adrenal androgenic hormones are known to interfere with ovulation. <br />Prolactin->progesterone production by granulosa cells. If there is a direct effect of prolactin on granulosa cell progesterone production in vivo (in a woman's ovaries) then this could also lead to an ovulatory dysfunction, called a luteal phase defect. <br />56<br />
  73. 73. AnovulationSymptoms Evaluation*<br />Irregular menstrual cycles<br />Amenorrhea<br />Hirsuitism<br />Acne<br />Galactorrhea<br />Increased vaginal secretions<br />Follicle stimulating hormone<br />Lutenizing hormone<br />Thyroid stimulating hormone<br />Prolactin<br />Androstenedione<br />Total testosterone<br />DHEAS<br /><ul><li>Order the appropriate tests based on the clinical indications</li></li></ul><li>PCOS<br />an increase in the hypothalamic GnRH pulse frequency and amplitude<br /> a continuously elevated pituitary LH concentration (with an exaggerated LH secretion and a normal FSH secretion in response to GnRH, resulting in an increase in the circulating LH:FSH ratio to about 3:1)<br /> increased circulating adrenal and ovarian androgen concentrations (testosterone, androstenedione and dehydroepiandrosterone sulfate [DHEAS]) in at least half the women<br /> decreased SHBG,so that bioactive forms of estrogen are increased (increased estrogen ->decrease in FSH ,GnRHpulsatility to further increase LH, either of which may further elevate the LH:FSH ratio) <br />ovarian inhibin secretion (inhibin specifically inhibits FSH secretion) to further suppress FSH and enhance the LH:FSH ratio. The elevation of LH and the relative abundance of LH with respect to FSH results in follicular growth that either becomes arrested in early to mid development or results in atresia (deterioration). Consequently, the ovaries become polycystic with numerous partially matured follicles.<br />58<br />
  74. 74. 59<br />PCOS<br />
  75. 75. Basic Steps in IVF<br /><ul><li>Ovary stimulation
  76. 76. Egg retrieval
  77. 77. Sperm retrieval-wash sperm
  78. 78. Fertilization
  79. 79. Embryo transfer
  80. 80. Progesterone</li></li></ul><li>Endometriosis<br />Occurs when the uterine tissue implants and grows outside of the uterus, affecting the function of the ovaries, uterus and fallopian tubes.<br />Scar tissue can block the fallopian tubes and prevent the egg from entering the uterus. <br />There is a 25-35% rate of infertility in moderate to severe cases of Endometriosis<br />
  81. 81. Anti Sperm Antibody<br />ASA in men are assumed to occur mainly as a consequence of trauma to the blood testis barrier, epididymis, or vas deferens (Gubin et al, 1998). The immunogenicity of the sperm antigens is indicated by the high incidence of ASA in the sera and accessory gland fluids of vasectomized men (Aitken et al, 1988). <br /> ASA may impair sperm function at various stages of reproduction, such as during the transport of spermatozoa in the female genital tract (Bronson et al, 1984), capacitation, acrosome reaction (Lansford et al, 1988; Wolf, 1989), and binding with zona or fusion with egg (Bronson et al, 1982; Alexander, 1984).<br />62<br />
  82. 82. 63<br />

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