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Patient cases workshop

PATIENTS CASES WORKSHOP. By Prof. Dr. Mohammed Khaled Professor Of OB-Gyn Alazhar University Head of IVF Center Dr. Erfan And Bagedo Hospital. Patient cases workshop. “IBSA LINK ELITE Meeting for Iraq” ; Istanbul 26-28 January 2012. CASE 1 OUR DIAGNOSTIC APPROACH.

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Patient cases workshop

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  1. PATIENTS CASES WORKSHOP By Prof. Dr. Mohammed Khaled Professor Of OB-Gyn Alazhar University Head of IVF Center Dr. Erfan And Bagedo Hospital Patient cases workshop “IBSA LINK ELITE Meeting for Iraq”; Istanbul26-28 January 2012

  2. CASE 1 OUR DIAGNOSTIC APPROACH UNEXPLAINED INFERTILITY Age of patient (35 years old) + Duration of infertility (>3 years) = ACTIVE ATTITUDE Start IUI cycles

  3. CASE 1 OUR THERAPEUTIC APPROACH FOR OI and IUI • Patient age: 35 years old • Duration of infertility: 4 years • FSH (3th day): 5,6 mIU/ml • LH (3th day): 3,5 mIU/m • 17-β-Estradiol (3th day): 32 pgr/ml • PROGESTERONE (21st day): 16,0 ngr/ml • BMI: 24. Normal distribution of hair and body fat. • AFC: 8 antral follicles in RO; 7 antral follicles in LO.

  4. 16mm CASE 1 Day 2 of cycle • TRANSVAGINAL ULTRASOUND SCAN (2th day): RIGHT OVARY AFC: 8 Follicles <10mm. LEFT OVARY AFC: 7 Follicles <10mm.

  5. Lutenized Unruptured FollicleLUF SYNDROME • Firstdescribed in 1975 byJewelewicz: Lack of ovulationdueto a failure of collapse of the follicle. Eggs ripen but do not release from the follicle, althoughthere are allovulatorychanges: LH surge,  plasma progesterone and secretoryendometrium. • Recorded in 5-10% cycles of normo-ovulatorywomen. • - Biological variable or true syndrome? • -Single processorrecurringphenomenon in unexplainedinfertility? • More frecuent in womentakingNonsteroidal Anti-InflammatoryDrugs. Jewelewicz R et al. Am J ObstetGynecol 1975; 122 (8): 909-20

  6. Lutenized Unruptured FollicleLUF SYNDROME • Prospectivestudy: increasedpercentage of LUF in unexplainedthan in tubalinfertility(Koninckx et al; 1978). • Ifincreasedincidence and recurrence of LUF in subsequentcycles of IUI: lower PR, and itissuggestedto try IVF-ICSI in these cases(Qublan et al; 2006). • The CC protocol was shown to be associated with LUF in 25% of first cycles in unexplained infertility (Qublan et al., 2006). • With Gonadotropins was shown in 15% of first cycles in PCOS (Ghanem et al; 2009), and up to 25% of sucessivecycles in womenwith endometriosis (Romeu et al; 2001). Jewelewicz R et al. Am J ObstetGynecol 1975; 122 (8): 909-20

  7. Lutenized Unruptured FollicleLUF SYNDROME • While most authors reported low LH levels as pathophysiological fator, other postulated the possiblity of a decrease in the concentration of LH receptors, which acquires special meaning in relation to the occurrence of LUF in stimulated cycles. • A particular aspect related to the lack of follicular rupture is the pharmacological induction of ovulation, in which the above condition may be caused by a defective conduction of treatment or early hCG administration while still rate of receptors is low. In these cases can be corrected by changing stimulation in the next cycle.

  8. Lutenized Unruptured FollicleLUF SYNDROME SHOULD WE REQUEST NOW Ca 12.5? • CA-12.5 has limitedvalue in the diagnosis of endometriosis stages I-II. (28% sensitivity; 90% specificity) • (Recommendation grade A) • Itis more useful in the diagnosis of stages III-IV. • (47% sensitivity; 89% specificity) • Is a markerwiththegreatestpredictivevalue in the diagnosis of recurrences, once itiscompletedthesurgicaltreatment. • (EvidencelevelIb)

  9. Lutenized Unruptured FollicleLUF SYNDROME SHOULD BE LAPAROSCOPY ALWAYS INDICATED IN PATIENTS WITH UNEXPLAINED INFERTILITY TO TRY TO DIAGNOSE ENDOMETRIOSIS STAGE I…? “Laparoscopy may reveal minimal or mild endometriosis or peritubal adhesions. In these cases either surgery or medical treatment has not been proven to improve fecunditity”. RCOG; 2004 “No difference in cycle pregnancy rate and in cumulative live-birth rate between women with surgically treated minimal to mild endometriosis and women with unexplained infertility, after controlled ovarian hyperstimulation and intrauterine insemination”. Werbrouck E et al. FertilSteril 2006; 86(3): 566-71

  10. FSH ui/day CASE 1 (I) Step up protocol 0 6 9 14 C 7mm C 11mm C 8mm C 6mm End Lineal Lineal 18 16 14 12 <10 E2 75 150 234 495 75 75 Gn 75 75 75 75 75 112.5? 112.5 8 9 14 15 12 13 Days 1 2 3 4 … 7 10 11

  11. 0 6 9 14 210 330 640 37.5 37.5 9 10 FSH ui/day CASE 1 (II) Step down protocol C 7mm C 12mm C 9mm B-C 6mm End Lineal Lineal 18 16 14 12 <10 E2 125 75 75 37,5? 37.5? Gn 112.5 112.5 112.5 112.5 112.5 7 8 13 14 11 12 Days 1 2 3 4 5 6

  12. CASE 2 • FEMALE: 39 years old, blood type O Rh Positive, referring primary infertility of 7 months of evolution. • FAMILY HISTORY: Without interest for current process. • PERSONAL HISTORY: She reportsthattwoyearsagosheunderwent a laparoscopy and thatsurgeons removed somecysts in bothovaries. She has lostthesurgeryreport and thereis a lack of histologicalfindings. Non smoker. No known drugs allergies. • OBSTETRIC HISTORY: Nulligravida.

  13. CASE 2 • GYNECOLOGIC HISTORY: Men: 13 MT: 3/21-22. Intense and progressive dysmenorrhea during the last 9 months. • GENERAL EXAMINATION: Weight: 60 Kg. Height: 164 cm. BMI: 22.5 Normal distribution of hair and body fat. • GYNAECOLOGICAL EXAMINATION: Normal EG; Normal V; NulliparousCxnormallyepithelialized. Anteverteduterus, with normal shape, size and consistency, withpain at mobilization. Bothannexeswith normal size and verypainful. • MALE: 45 years old, blood type A Rh Positive. Personal history without interest for current process. No known allergies or toxic habits. No adverse reproductive history. No genitourinary clinic. 1 child with a previous partner.

  14. CASE 2 • TRANSVAGINAL ULTRASOUND SCAN (done on 17th day of natural cycle): Right Ovary Left Ovary

  15. CASE 2 With only this available data… Would you try an OI with IUI or would you advise the patients directly to an IVF cycle?

  16. CASE 2 OUR DIAGNOSTIC APPROACH FEMALE FACTOR Age of patient (39 years old) + Endometriosis Start IVF cycles

  17. CASE 3 • FEMALE: 26 years old, blood type O Rh Negative, referring primary infertility of 18 months of evaluation. • FAMILY HISTORY: Mother diabetic (insulin-dependent). Father without interest for current process. • PERSONAL HISTORY: Without interest for current process. Non smoker. No known drugs allergies. • OBSTETRIC HISTORY: Nulligravida.

  18. CASE 3 • GYNECOLOGYC HISTORY: Men: 13 MT: 5/irregular (amenorrheic intervals up to 4 months). No dysmenorrhea. • GENERAL EXAMINATION: Weight: 68 Kg. Height: 165 cm. BMI: 25. Severe hirsutism. BP: 115/75. • GYNAECOLOGICAL EXAMINATION: normal EG; normal V; Nulliparous Cx, normally epithelialized. Anteverted uterus, with normal shape, size and consistency, mobile and painless mobilization. Both annexes are enlarged but not painful. • MALE: 30 years old, blood type A Rh Positive. Personal history without interest for current process. No known allergies or toxic habits. No genitourinary clinic. No erectile dysfunction. No previous children.

  19. CASE 3

  20. CASE 3 TRANSVAGINAL ULTRASOUND SCAN (done on 21st day of natural cycle):

  21. CASE 3 Which of the following diagnostic tests would be more suitable on the first visit?: A.- Karyotype of maleB.- Basal cortisol and ACTHC.- Pelvic MRID.- Insulin resistance screening in women

  22. CASE 3 MALE ANALYTICAL DATA • SEROLOGIES: HIV (-); Hepatitis B y C (-) • SEMINOGRAM + TSC: Normozoospermia Vol Viscosity Total Nº A+B Mov Normal Agglutination pH 2.5cc No 85 x 106 52% 14% No 7.2 TNSC 12 x 106

  23. CASE 3 FEMALE ANALYTICAL DATA • SMEAR TEST: Negative for malignant cells. • BLOOD SAMPLE: Normal (Toxoplasmosis, syphilis, Hepatitis B-C, and HIV negatives; Rubella immunity). • FSH (3rd day): 5.6 mIU/ml • LH (3rd day): 13.5 mIU/ml • 17-β-Estradiol (3rd day): 72 pgr/ml • PRL: 10 ngr/ml (<25)

  24. CASE 3 FEMALE ANALYTICAL DATA • TSH: 1.4 uIU/ml (0.4 to 3.8 uIU/ml). T3 and T4 into normal ranges. • Progesterone (21st day): 0.16 ngr/ml • Free Testosterone: 4.2 pg/ml (0.7-3.6)and Total Testosterone: 85 ng/dl (6.0-89) • DHEA-S: 45 UG/DL (35-430) • Androstenedione: 3.0 ng/ml (0.7-3.1) • SHBG: 0.6 ng/ml (0.80-3.0)

  25. CASE 3 FEMALE ANALYTICAL DATA • 17-Hydroxyprogesterone: 1.2 ng/ml  (0.80-3.0) • Basal Insuline: 16.4 µU/ml (17.4 ± 7.4) • Basal Glucose: 123 mgr/dl • HOMA Test: 4.9 • HSG: Normal uterine cavity, patent tubes, normal peritoneal dissemination of contrast.

  26. METFORMIN prior OI…? Metabolism1994 May;43(5):647-54. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Velazquez Mendoza EM, Hamer T, Sosa F, Glueck CJ.

  27. METFORMIN prior OI…? Evidence for the effectiveness of metformin alone for ovulation induction vs. Placebo or no therapy Norman RJ. JCEM 2004; 89: 4797-4800.

  28. METFORMIN prior OI…? Evidence for the effectiveness of metformin combined with Clomid vs. Clomid alone Lord JM et al. Cochrane database of systematicreviews Online (2003); Issue 3: CD003053

  29. METFORMIN prior OI…? AUTHORS' CONCLUSIONS: In agreementwiththepreviousreview, metforminisstill of benefit in improvingclinicalpregnancy and ovulationrates. However, thereis no evidencethatmetforminimproveslivebirthrateswhetheritisusedaloneor in combinationwithclomiphene, orwhencomparedwithclomiphene. Tang T et al. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane database of systematic reviews Online (2010); Issue 1: CD003053.

  30. METFORMIN prior OI…? Metformintreatmentbefore and duringassistedreproductivetechnology (ART) amongwomenwith PCOS showedthattherisk of ovarian hyperstimulation syndrome (OHSS) wasreduced. Tso LO et al.Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2009; 2:CD006105.

  31. METFORMIN prior OI…? Kjøtrød SB et al. Hum Reprod 2011; 26 (8): 2045-53

  32. METFORMIN prior OI…? In conclusion, currentevidencesuggeststhatthe use of metforminortheaddition of metforminto CC therapydoesnotincreasethe chances of pregnancy in infertilewomenwith PCOS. However, thelack of a universal agreementonthecriteria of diagnosing PCOS and thelack of a screeningprocedureforinsulinresistancemaycontributetothisfailure. Thus, whethermetforminwouldbehelpful in a subgroup of patientswho show evidence of insulinresistanceornotisnotclearyet and awaitsfurtherevidence. Attia A. MEFSJ 2008; 13 (1): 16-19

  33. CASE 3 • Becauseclinical and analytical data suggestanovulation…Whatisthemostlikely diagnosis of thispatient? • A. - 21-Hydroxylase DeficiencyB. - FunctionalOvarianHyperandrogenism (PCOS)C. - HiperperolactinemiaD. - Hypogonadotropichypogonadism

  34. CASE 3 • Becauseclinical and analytical data suggestanovulation…Whatisthemostlikely diagnosis of thispatient? • A. - B. - FunctionalOvarianHyperandrogenism (PCOS)C. - D. -

  35. CASE 3 OUR DIAGNOSTIC APPROACH PCOS Age of patient (26 years old) + Duration of infertility (<3 years) + Anovulation Start IUI cycles

  36. CASE 3 OUR THERAPEUTIC APPROACH FOR OI and IUI • Patient age: 26 years old • FSH(3rd day): 5,6 mUL/ml • LH (3rd day): 13,5 mUl/m • 17-β-Estradiol (3rd day): 62 pgr/ml • BMI: 19. • AFC: 18 Follicles in RO; 14 Follicles in LO.

  37. CASE 3 Day 2 of cycle • TRANSVAGINAL ULTRASOUND SCAN (2th day): RIGHT OVARY AFC: 18 Follicles <10mm. LEFT OVARY AFC: 14 Follicles <10mm.

  38. 0 6 9 14 FSH ui/day CASE 3 (II) Step down regimen B-C 7mm B 10mm A 13mm End Lineal Lineal 18 16 14 12 <10 E2 196 920 490 IVF? CANCELLATION? hCG? COASTING? 112.5 Gn 75? 37.5? Days 1 2 3 4 5 6 7 8 11 12 9 10

  39. C 8mm C 7mm 190 242 150? 75? 75? 112.5? 112.5? 8 … 10 … 13 12 FSH ui/day CASE 3 (III) Step up regimen 0 6 9 14 C 11mm B-C 5mm End Lineal Lineal 18 16 14 12 <10 E2 105 410 Gn 37.5 37.5 37.5 37.5 37.5 13 14 Days 1 2 3 4 … 7

  40. Definitely...

  41. It's a game that you invented 1400 years ago... In some way, we are like chess players... But every game is different ... Even against the same player... Even if you begin with the same opening...

  42. The only problem is that we play with black pieces... Ovaries always plays with the whites...

  43. THANK YOU VERY MUCH FOR YOUR ATTENTION شكرا جزيلا لكم على اهتمامكم

  44. CASE 1 • FEMALE: 35 years old, blood type AB Rh Positive, referring primary infertility of 4 years of evolution. • FAMILY HISTORY: Without interest for current process. • PERSONAL HISTORY: Without interest for current process. Smoker (10 cigarettes/day). No known drugs allergies. One month ago 1 cycle of OI with Clomid and TI without pregnancy. • OBSTETRIC HISTORY: Nulligravida. • GYNECOLOGYC HISTORY: Men: 13 MT: 3/28. Slight dysmenorrhea treated with conventional analgesics.

  45. CASE 1 • GENERAL EXAMINATION: Weight: 73 Kg. Heigh: 172 cm. BMI: 24. Normal distribution of hair and body fat. • GYNAECOLOGICAL EXAMINATION: normal EG; normal V; Nulliparous Cx with periorificial erythroplasia. Anteverted uterus, with normal shape, size and consistency, mobile and painless mobilization. Both annexes with normal size and not painful. • MALE: 33 years old, blood type A Rh Positive. Tonsillectomy. Refers a testicular trauma at age 14. No known allergies or toxic habits. No genitourinary clinic. No erectile dysfunction. No previous children.

  46. CASE 1 • TRANSVAGINAL ULTRASOUND SCAN (done on 12th day of her natural cycle):

  47. CASE 1 What diagnostic test should NOT be requested at this moment? A.- Seminogram. B. - Serology for HBV, HCV and HIV in both partners. C. – Hysterosalpingography. D. - FSH, LH and 17-β-Estradiol on 3th day of cycle.

  48. CASE 1 What diagnostic test should NOT be requested for the moment? A.- B.- C.- Hysterosalpingography. D.-

  49. CASE 1 MALE ANALYTICAL DATA • SEROLOGIES: HIV (-); Hepatitis B y C (-) • SEMINOGRAM + TSC: Normozoospermia Vol Viscosity Total Nº A+B Mov Normal Agglutination pH 3,5cc No 110 x 106 60% 15% No 7,2 TNSC 22 x 106

  50. CASE 1 • FEMALE ANALYTICAL DATA • SMEAR TEST: Negative for malignant cells. • BLOOD SAMPLE: Normal (Toxoplasmosis, syphilis, Hepatitis B-C, and HIV negatives; Rubella immunity). • FSH(3th day): 5,6 mUI/ml • LH (3th day): 3,5 mUl/ml • 17-β-Estradiol (3th day): 32 pgr/ml • PRL: 12.2 ngr/ml • TSH: 1.2 mIU/ml • PROGESTERONE (21st day): 16,0 ngr/ml • ¿Ca 12.5? • ¿HSG?

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