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Collège Marocain de Fertilité Rabat , Mars , 2019

Collège Marocain de Fertilité Rabat , Mars , 2019. Monitoring the IVF cycles Pieraldo Inaudi, MD,PhD. Center for Reproductive Health Diagnosys and Treatment of Infertility Florence, Italy. Monitoring definition. close observation of a patient’s characteristics

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Collège Marocain de Fertilité Rabat , Mars , 2019

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  1. Collège Marocain de Fertilité Rabat, Mars , 2019 Monitoring the IVF cycles Pieraldo Inaudi, MD,PhD Center for Reproductive Health Diagnosys and Treatment of Infertility Florence, Italy

  2. Monitoringdefinition closeobservationof a patient’scharacteristics and the ovarianresponseto stimulation, butalsothe eventsafterthe stimulation

  3. Why monitor the patient? ithelps the physicianfor the choice of the mostsuitablestimulationprotocol, or to modify the dose and/or the approachin an attempt to obtain the best possibleoutcomeand avoidcomplications(OHSS and lowresponse) of therapy and to find the optimal time for hCGadministration.

  4. Beforediscussingdifferentmethods of monitoring, itisbetter to divide monitoringintothreestages: Before During After the ovarianstimulation

  5. Beforestarting the OS Duringthisperiod, the physicianhas to thinkaboutwhichprotocolshould be offered to the patient. Thisdepends on manyfactors patient’s endocrine profile general health age previouscycles

  6. Ifgonadotropintherapyischosen, itis of utmostimportance to excludeovarianinsufficiencybecausethistype of treatment isveryexpensive and isnot free of complications. Abnormallyhigh serumlevelsof FSH and LH with lowestradiollevelsor AntimullerianHormone of lessthan 0.1 indicate ovarianfailurewhichprecludesa multiple folliculardevelopment.

  7. Non-endocrine problemsshould be treatedbeforestarting the therapy (Vaginalinfections, uterine congenitalmalformations, endometriosis ) . Hypogonadotropicfunctionwith galactorrhearequiresevaluation for an intracraniallesion. Thyroidproblems Ultrasonographyshould be done to exclude the presence of ovariancystsand/or to identifie a condition of polycysticovarydisease (PCO) whichrequire special care.

  8. Ifitisdecided to prescribethe long termGnRHaprotocol, the patientshould be monitored for the criteria of pituitary and ovariansuppression. Complete suppressionisverified by the onset of menstruationassociatedwith a plasmaLH <2 IU/L, estradiol (E2) <50 pg/ml and better <30 pg/ml, and progesterone of < 1.0 ng/mland by the absence of anyovarianfollicles >10 mm in diameter. Ifallthesecriteria are notmet, GnRHashould be continued and the patientassessedatweeklyintervalsuntilsuppressionis complete, theninduction can be started.

  9. Basalhormonalvalues westart with stimulationwhen: LH <2 IU/L, E2 <50pg/ml Pg<1.0pg/ml absence of anyovariancyst or follicles>10 mm in diameter.

  10. STANDARD STIMULATION PROTOCOL start of stimulation at 225/150 IU FSH/LH day REGIMEN ADAPTATION GnRHa depot 36 h LATER OPU d23 d6 d8 d10 MENSES hCG ADMINISTRATION ULTRASOUND + HORMONE • MONITORING

  11. Methods of monitoring of IVF cycle • Ultrasoundsscans folliclesize and number endometrialthickness and texture • Hormoneassay • Estradiol • LH • Progesterone

  12. TVUS

  13. Monitoring of IVF/ICSI cycles: • 6 RCTs, 781 women TVUS vs TVUS and estradiolmonitoring • No difference in clinicalpregnancyratesbetween TVUS vs. TVUS +E2 (OR) 1.10; 95% CI 0.79 to 1.54; fourstudies; N = 617; I2 = 5%; lowqualityevidence). • CPR in TVUS+E2 34%, TVUS only from 29-44% • No difference in OHSS between the twoarms (OR 1.03; 95% CI 0.48 to 2.20; sixstudies; N = 781; I2 = 0%; lowqualityevidence), • 4% chance of OHSS TVUS +E2, 2-8% with TVUS only Cochranereview , Kwan et al., 2014

  14. Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI)Kwan I, BhattacharyaS, Kang A, Woolner A.Cochranewww.cochranelibrary.com 2014 Clinical pregnancy per woman Cochrane Database of Systematic Reviews24 AUG 2014 DOI: 10.1002/14651858.CD005289.pub3http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005289.pub3/full#CD005289-fig-00101

  15. Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI)Kwan I, BhattacharyaS, Kang A, Woolner A.Cochranewww.cochranelibrary.com 2014 Mean number of oocytes retrieved per woman Cochrane Database of Systematic Reviews24 AUG 2014 DOI: 10.1002/14651858.CD005289.pub3http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005289.pub3/full#CD005289-fig-0005

  16. Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI)Kwan I, BhattacharyaS, Kang A, Woolner A.Cochranewww.cochranelibrary.com2014 OHSS rate (mild, moderate or severe) per woman Cochrane Database of Systematic Reviews24 AUG 2014 DOI: 10.1002/14651858.CD005289.pub3http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005289.pub3/full#CD005289-fig-00104

  17. Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI)Kwan I, BhattacharyaS, Kang A, Woolner A.Cochranewww.cochranelibrary.com 2014 Cyclecancellation rate per woman Cochrane Database of Systematic Reviews24 AUG 2014 DOI: 10.1002/14651858.CD005289.pub3http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005289.pub3/full#CD005289-fig-00104

  18. Cyclemonitoring with both TVUS and estradiolmeasurementis likely to involve highercosts (to cover technicians and laboratory costs, outpatientattendance) whencompared with TVUS alone. Hormonalassays involve repeatedvenepuncture, whichmay cause stress and anxiety to women. However, itisunclearifwomenwouldbe more satisfied with combinedmonitoring and because of a placebo effect with the perceptionthatthey are beingmonitored more closely. In future researchitwould be useful to knowwhich monitoringprotocolwomenwere more satisfied with.

  19. OVARIAN STIMULATION FOR IVF Estradiol plasma levels Estradiol (nmol/L) 6 PCO 5 4 CONTROLS 3 2 1 0 days -

  20. OVARIAN STIMULATION FOR IVF Endometrial Thickness ETh (mm) PCO 12 CONTROLS 9 6 3 0

  21. Predictors of hyper-response Estradiol …the cascade of eventsthatleads to the development of OHSS isalmostalwaysaccompanied by elevated E2 levels but ..acceptablesensitivity (83%) and specificity (84%) is achievedonlyat high cut-off level (5000 pg/ml) (Papanicolaou 2006) then ..modestsensitivity and high false-positive rateslimits the clinical use (Hendriks 2004, Papanicolaou 2006)

  22. TVUSand Estradiolare usefull for the evaluation of the ovary(position, totalsize, folliclenumber and size, hormonalactivity)presence and diffusion of ascites, and • permit the monitoring of progression or regression of symptoms.

  23. Cautionwith: rapidlyrising E2 levels, E2 >2500 pg/ml and large number of intermediate sizedfollicles (10-14 mm) Whereas the sonographicfinding of enlargedovaries with multiple immature folliclesmaysuggest the possibility of hyperstimulation, extremely high levels of E2 (over 3000 pg/ml) can be a more accurate predictor of thissyndrome.

  24. Predictors of hyper-response Coasting Initiatedwhenfollicles are 15 to 16 mm in diameter and serum E2 levels > 3000pg/ml Large follicleshave high FSH sensitivity and can toleratefewdayswithoutgonadotrophinswhile Immature folliclesenter atresia E2 <3000pg/ml limitbelowwhichcoasting can be terminated and hCGadministered

  25. Elevated progesterone on the day of hCG Meta analysis of more than 60 000 cycles In fresh IVF cycles, a decreasedprobabilityof pregnancywaspresent in womenwith elevatedP(whenelevatedPwasdefinedusinga threshold≥ 0.8 ng/ml) whencomparedwith thosewithoutPelevation. Venetis et al., 2013

  26. Elevated progesterone on the day of hCG freezeall, and ET in naturalcycle

  27. Basal progesterone levelas the maindeterminant of progesteroneelevation on the day of hCGtriggering in controlledovarianstimulationcycles Papaleo et al., 2014

  28. Basal progesterone levelas the maindeterminant of progesteroneelevation on the day of hCGtriggering in controlledovarianstimulationcycles Fratarelli et al 2013

  29. Fratarelli et al 2013

  30. FolliclesizeiscrucialbecausehCGis best administered once folliclesreach 15 to 18 mm in size For IVF, follicles are typicallyaspiratedwhentheyreach16 to 18 mm in averagediameter and when the E2 levelisapproximately300 pg/ml per large follicle. Whenfollicles >16 mm are aspirated, oocytesare all mature. Thereforeone can rely on folliculardiameters alone if the patient’spreviouscycles and her E2 response are known.

  31. Timing of human chorionic gonadotropin (hCG) hormone administration in IVF/ICSI protocols using GnRH agonist or antagonists: a systematic review and meta-analysis. Chen Y1, Zhang Y, Hu M, Liu X, Qi H. Gynecol Endocrinol. 2014 Jun;30(6):431-7. OBJECTIVE: To evaluate the effect of altering the timing of human chorionic gonadotropin (hCG) administration on the clinical outcome of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) using gonadotropic hormone releasing hormone (GnRH) agonist or antagonist. METHODS: We systematically searched six databases. Randomized controlled trials (RCTs) of the effects of altering the timing of hCG administration on the clinical outcome of IVF and ICSI using GnRH agonist or antagonist were included. A meta-analysis was conducted following a quality evaluation performed with Cochrane collaboration

  32. a total of 1295 participants were included. Significant difference was observed regarding estradiol and progesterone levels on the day of hCG administration and oocyte retrieval between early hCG and late hCG administration group and in favor of the latter. The fertilization rate was not statistically different between early and 24-h late hCG groups, but it is significantly higher in the 48-h late hCG group. The pooled results showed no significant differences in the ongoing pregnancy rate per oocyte pick-up, the miscarriage rate and the live birth rate. CONCLUSION: • The prolongation of follicular phase by delaying hCG administration could increase estradiol, progesterone levels and oocyte retrieval, which will not influence ongoing pregnancy rate per oocyte pick-up, miscarriage rate and live birth rate. • Postponing hCG may enable increased flexibility of cycle scheduling to avoid weekend procedures.

  33. Oocytepick-up

  34. Complications of oocyte pick-up Ovarianaccess Vaginalbleeding Injury of pelvicstructures Anesthesia/sedation Pain Infections Adnexaltorsion Endometrioma rupture

  35. Nyboe Andersen et al 2005

  36. 7,098 transvaginaloocyteretrieval Fourcases of severe peritonealbleedingrequiringsurgery 0,06% And twopelvicabscesses 0,03% total of sixcases of severe clinicalcomplications 0,08%

  37. CONCLUSION closeobservation of patient’scharacteristicsand the ovarianresponseto stimulation, butalso the eventsafter the stimulation Hormones and ultrasoundis the best choice to help for best treatment decisions and to help for ovarianhyperstimulationsyndromeprevention

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