Ce diaporama a bien été signalé.
Nous utilisons votre profil LinkedIn et vos données d’activité pour vous proposer des publicités personnalisées et pertinentes. Vous pouvez changer vos préférences de publicités à tout moment.

EMPTY FOLLICLE SYNDROME

3 675 vues

Publié le

EMPTY FOLLICLE SYNDROME

Publié dans : Santé & Médecine

EMPTY FOLLICLE SYNDROME

  1. 1. EMPTY FOLLICLE SYNDROME Aboubakr Elnashar Benha University, Egypt ABOUBAKR ELNASHAR
  2. 2. 1. INTRODUCTION First described: Coulam et al. [1986]. Define: Failure to aspirate or retrieve mature oocytes from mature ovarian follicles following ovulation induction for in vitro fertilization (IVF) treatment in spite of meticulous aspiration and repeated flushing No oocytes retrieved in good responder patients undergoing ovarian stimulation with at least 5 mature follicles (≥15 mm) on the day of hCG (Coskun et al. 2010) ABOUBAKR ELNASHAR
  3. 3. Borderline form of EFS Very few mature or immature oocytes are recovered from several mature follicles (Isik and Vicdan, 2000; Nikolettos et al., 2004; Duru et al.,2007; Desai et al., 2009; Vutyavanich et al., 2010). ABOUBAKR ELNASHAR
  4. 4. Types: 1. Genuine: 33% Failure to retrieve oocytes despite optimal hCG levels on the day of OR. it does not respond to the rescue protocol. 2. False: 67% Failure to retrieve oocytes in the presence of low hCG (<40 IU/L) due to an error in the administration or bioavailability of hCG (Stevenson and Lashen, 2008) ABOUBAKR ELNASHAR
  5. 5. Impact frustrating complication of IVF: cycle cancellation stress and anxiety for both patients and physicians ABOUBAKR ELNASHAR
  6. 6. Incidence uncommon event 0.05% to 7% of patients undergoing OR. {different inclusion criteria}. In some studies, patients with a poor ovarian response or premature ovulation were included while in others they were not. No specific stimulation or triggering protocol is related to the occurrence of EFS. (Castillo et al., 2012) GEFS: 0–1.1%. (Beck-Fruchter et al, 2012) ABOUBAKR ELNASHAR
  7. 7. 2. MECHANISM I. FALSE EFS 1. hCG-related faults: main mechanism. •hCG injection later than scheduled (11 h before retrieval) •Failure of the hCG injection, confirmed by the undetectable hCG serum concentrations. . 1. Forgott to dissolve the powder in the solvent , and taken only the inert solvent 2. Taken an HMG injection instead of the hCG 3. Mis-timed it 4. Spilled the drug ABOUBAKR ELNASHAR
  8. 8. 2. Rapid metabolic clearance 3. Manufacturer defects in hCG production: Reduced in vivo biological activity of some batches: EFS is pharmaceutical industry syndrome (Zegers-Hochschild et al.1995). 4. Low bioavailability of hCG after bariatric surgery. {Hirshfeld-Cytron and Kim, 2008] Abdominal skin redundancy alter absorption of SC hCG: IM is recommended. 5. individual variation in the threshold for the follicular response to urinary hCG, [Abdalla et al, 1987] ABOUBAKR ELNASHAR
  9. 9. II. GENUINE EFS Early oocyte atresia (Awonuga et al.2003) Absence of oocytes might be due to increased apoptotic gene expression and reduction of transcripts whose products are responsible for healthy follicular growth. (Inan et al. 2006) Associated with ovarian ageing (Lorusso et al, 2005) manifestation of low ovarian reserve [Baum et al, 2001]. ABOUBAKR ELNASHAR
  10. 10. Does genuine EFS really exist?  Some suggest that genuine EFS does exist and that it might be a real cause of infertility. 1. Microscopic evidence of genuine EFS with a case of borderline EFS. (Desai et al.2009) 2. Borderline form of EFS: very few mature or immature oocytes are recovered from several mature follicles [Duru et al, 2007 Desai et al, 2009 Vutyavanich et al, 2010 ]. 3. The genetic basis for EFS provides strong evidence for the existence of genuine EFS [Yariz et al,2011]. ABOUBAKR ELNASHAR
  11. 11. Genetic causes 1. Presence of a pericentric inversion of chromosome 2:46, XX,inv(2)(p11q21) in a patient who had multiple failed OR. (Vujisic et al. 2005) 2. An inherited condition of EFS with moderate sensorineural deafness affecting two sisters. (Onalan et al. 2003) 3. An inherited mutation of LH/hCG receptor was identified in two sisters with EFS (Vujisic et al, 2005). ABOUBAKR ELNASHAR
  12. 12. Risk factors 1) Advanced age (37.7±6.0 y vs. 34.2±6.0 y, p< 0.001), 2) longer infertility duration (8.8±10.6 y vs. 6.3±8.4 y, p<0.05), 3) higher baseline FSH levels (8.7±4.7 IU/L vs. 6.7±2.9 IU/L, p<0.001), 4) lower E2 levels before the hCG injection (499.9± 480.9 pg/mL vs. 1,516.3±887.5 pg/mL, p<0.001)  EFS may be a gradual biological occurrence related to ovarian ageing. ABOUBAKR ELNASHAR
  13. 13. Prognosis after EFS Sporadic event with good clinical outcomes in most of the cases except the 15% that are recurrent cases. (Aktas et al., 2005; Baum et al. 2012) Poor outcome in subsequent cycles. (Lorusso et al., 2005; Coskun et al., 2010) ABOUBAKR ELNASHAR
  14. 14. Risk of recurrence. 20% (Zreik et al., 2000) had a poor success rate. 2 consecutive cases of EFS: no further pregnancies or successful OR ABOUBAKR ELNASHAR
  15. 15. Risk factors of recurrence 1. Advanced age: 35 to 39y: 24% recurrence rate >40: 57% 2. Prolonged infertility 3. Lower E2 levels: consistent with the risk factors of poor ovarian response. Recurrent EFS may be a variant phenotype of poor response. ABOUBAKR ELNASHAR
  16. 16. 3. THERAPEUTIC APPROACH False EFS: Readministering hCG and reaspiration -24-36 h after this second hCG shot. ABOUBAKR ELNASHAR
  17. 17. PREVENTATION 1. Assessment of serum hCG the day after the trigger if the βhCG concentration is <100 mIU/ml [Zreik et al, 2000] or <40 mIU/ml [Stevenson, Lashen,2008] second bolus of hCG: OR 24–36 h later 2. Prolonging the interval between ovulation triggering and OPU. the strategy little evidence to be generally recommended. 3. Increase the dose of hCG to 20000 IU (instead of the standard 10000 IU we use routinely) ABOUBAKR ELNASHAR
  18. 18. 4. Prolonging the interval between ovulation triggering and OPU and inducing ovulation using GnRHa. in a GnRH antagonist cycle ovulation was triggered using GnRHa 40 h prior to OPU and hCG was added 6 hours after the first trigger. (Beck-Fruchter et al, 2012) 5. Use recombinant hCG (Ovitrelle) or LH (Luveris) to trigger ovulation ABOUBAKR ELNASHAR
  19. 19. GEFS can be managed in subsequent cycles by using recombinant hCG, recombinant LH, or triggering oocyte maturation with the GnRH agonist in an antagonist cycle ABOUBAKR ELNASHAR
  20. 20. MANAGEMENT  if the embryologist does not get any eggs after flushing 3 mature follicles: 1. stop the procedure 2. ensure patient has taken the trigger injection at the right time 3. rapid home urine pregnancy test (obtained by catherisation) for the presence of hCG (Instead of urine, it’s also possible to do the test on the aspirated follicular fluid) 4. If the patient has taken her hCG properly: positive pregnancy test is expected. This rules out the diagnosis of EFS, and we can then continue with the egg collection. ABOUBAKR ELNASHAR
  21. 21. 5. if the pregnancy test is negative: diagnosis of EFS is confirmed: stop the procedure, leaving the rest of the follicles intact, and wheel the patient out of the OR . a. Give the patient an additional HMG injection to support follicular growth ; and do a blood test to measure estrogen and Hcg levels. (Remember that we will get the results of the blood tests only after a few hours. ) b. Give the patient another hCG injection , and reschedule the egg collection 36h after this second hCG shot. ABOUBAKR ELNASHAR
  22. 22. c. If we are worried about the quality of the hCG injection, we may use recombinant hCG ( such as Ovitrelle) to trigger ovulation ; and we may also increase the dose of hCG to 20000 IU (instead of the standard 10000 IU we use routinely) . d. The next day, we review the blood test results. We would expect the estradiol levels to be high; and the hCG level to be less than 100 mIU/ml, thus confirming the diagnosis of EFS. An ultrasound scan at this time confirms that the follicles are still intact. e. At the time of the second egg retrieval , which is planned 36 hours after the second hCG shot , ABOUBAKR ELNASHAR
  23. 23. we expect to see intact follicles ; and expect to retrieve eggs from each of these follicles. In order to document the diagnosis , we repeat the blood hCG level again , and expect this to be more than 100 mIU/ml. ABOUBAKR ELNASHAR
  24. 24. ABOUBAKR ELNASHAR INVITATION

×