embryo transfer: factors involved in optimizing the success doç. dr. erdal aktan Özel ege tüp...

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Embryo transfer: Embryo transfer: factors involved in factors involved in optimizing the optimizing the success success Doç. Dr. Erdal Aktan Doç. Dr. Erdal Aktan Özel Ege Tüp Bebek Merkezi, Özel Ege Tüp Bebek Merkezi, IVF Center- Izmir IVF Center- Izmir 20.4.2008 20.4.2008 Çeşme Çeşme

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Embryo transfer: factors Embryo transfer: factors involved in optimizing involved in optimizing

the success the success

Doç. Dr. Erdal AktanDoç. Dr. Erdal AktanÖzel Ege Tüp Bebek Merkezi,Özel Ege Tüp Bebek Merkezi,

IVF Center- IzmirIVF Center- Izmir20.4.200820.4.2008

ÇeşmeÇeşme

2nd v 3rd day ET2nd v 3rd day ET

►3rd day ET increased PR3rd day ET increased PR(OR 1.26 %95 CI 1.06-1.51) (OR 1.26 %95 CI 1.06-1.51) 10 RCT10 RCT

►Groups are similar regarding OPR and Groups are similar regarding OPR and LBR LBR (OR 1.05 %95 CI 0.83-1.32 ve OR 1.07 %95 (OR 1.05 %95 CI 0.83-1.32 ve OR 1.07 %95 CI 0.84-137 )CI 0.84-137 )

3 RCT3 RCT

Cochrane Database Syst Rev 2004; 2:CD004378Cochrane Database Syst Rev 2004; 2:CD004378

Blastocyst v Cleavage ETBlastocyst v Cleavage ET

►LBR per couple LBR per couple (OR 1.16, 95% (OR 1.16, 95% CI 0.74 -CI 0.74 -1.441.44 ) ) 2/3 day 34.3% vs 5/6 day 35.4%2/3 day 34.3% vs 5/6 day 35.4% 7 RCT7 RCT

►PR per couple PR per couple (OR 1.05, 95% (OR 1.05, 95% CI 0.88 -1.26CI 0.88 -1.26)) 2/3 day 38.8% vs 5/6 day 40.3%2/3 day 38.8% vs 5/6 day 40.3% 15 RCT15 RCT

►Groups are similar regarding multiple Groups are similar regarding multiple pregnancy rate pregnancy rate (OR 0.85, 95% (OR 0.85, 95% CI 0.63 - 1.13CI 0.63 - 1.13) ) 12 RCT12 RCT

Cochrane Database Syst Rev 2005 Oct 19;Cochrane Database Syst Rev 2005 Oct 19;

(4):CD002118(4):CD002118

Blastocyst v Cleavage ETBlastocyst v Cleavage ET

►n of Couples with spare embryos to freezen of Couples with spare embryos to freeze

more in cleavage ET groupmore in cleavage ET group

►ET cancellation: more in blastocyst ET ET cancellation: more in blastocyst ET groupgroupSubgroups with good prognostic criteria are similar Subgroups with good prognostic criteria are similar regarding ET cancellation rateregarding ET cancellation rate

Cochrane Database Syst Rev 2005 Oct 19;(4):CD002118Cochrane Database Syst Rev 2005 Oct 19;(4):CD002118

n of embryos transferred:n of embryos transferred:2 v 3 embryos2 v 3 embryos

►Retrospective cohort studyRetrospective cohort study►1448 women & 4004 embryos 1448 women & 4004 embryos

transferredtransferred►Only 1Only 1stst IVF cycles IVF cycles►At least 6 embryos eligible for ET in At least 6 embryos eligible for ET in

every cycleevery cycle

Salha O et al, J Assist Reprod Genet. 2000 Jul;17(6):335-43 Salha O et al, J Assist Reprod Genet. 2000 Jul;17(6):335-43

n of embryos transferred:n of embryos transferred:2 v 3 embryos2 v 3 embryos

►Women <35 y Women <35 y withwith good quality spare good quality spare embryos: embryos: PR are similarPR are similar LBR (total) are similarLBR (total) are similar Twins and triplets are more frequent in 3 Twins and triplets are more frequent in 3

ET groupET group

Salha O et al, J Assist Reprod Genet. 2000 Jul;17(6):335-43Salha O et al, J Assist Reprod Genet. 2000 Jul;17(6):335-43

n of embryos transferred:n of embryos transferred:2 v 3 embryos2 v 3 embryos

►Women <35 y Women <35 y withoutwithout good quality good quality spare embryos:spare embryos:In 3 ET groupIn 3 ET group PR PR (39.3 vs 28.8%; P = 0.04)(39.3 vs 28.8%; P = 0.04)

Total LBR Total LBR (32.7 vs 19.4%; P = 0.02) (32.7 vs 19.4%; P = 0.02)

LBR (single) LBR (single) Multiple PR are similarMultiple PR are similar

Salha O et al, J Assist Reprod Genet. 2000 Jul;17(6):335-43Salha O et al, J Assist Reprod Genet. 2000 Jul;17(6):335-43

n of embryos transferred:n of embryos transferred:2 v 3 embryos2 v 3 embryos

►Women >35 y Women >35 y with or withoutwith or without good good quality spare embryos: quality spare embryos: Clinical results are better in 3 ET groupClinical results are better in 3 ET group Multiple PR are similarMultiple PR are similar

Salha O et al, J Assist Reprod Genet. 2000 Jul;17(6):335-43Salha O et al, J Assist Reprod Genet. 2000 Jul;17(6):335-43

n of embryos transferred:n of embryos transferred:2 v 3 embryos2 v 3 embryos

►Conclusion: Optimal n of embryos for Conclusion: Optimal n of embryos for transfer depends ontransfer depends on Quality of embryosQuality of embryos Age of womenAge of women Presence of good quality spare embryosPresence of good quality spare embryos

Salha O et al, J Assist Reprod Genet. 2000 Jul;17(6):335-43Salha O et al, J Assist Reprod Genet. 2000 Jul;17(6):335-43

n of embryos transferred:n of embryos transferred:2 v 3 embryos2 v 3 embryos

►Retrospective analysisRetrospective analysis►ET policies during two different periodsET policies during two different periods►Morphologic scoring, best embryos for Morphologic scoring, best embryos for

ETET►<36 y, 2ET v 3ET:<36 y, 2ET v 3ET:

PR 42.5% v 55.7% (p<0.01)PR 42.5% v 55.7% (p<0.01) Twin rates are similarTwin rates are similar Triplets 0 v 6.8%Triplets 0 v 6.8%

Setti PE et al, Reprod Biomed Online. 2005 Jul;11(1):64-70Setti PE et al, Reprod Biomed Online. 2005 Jul;11(1):64-70

eSET v DETeSET v DET

►3 RCT3 RCT►Meta-analysis:Meta-analysis:

PR per woman DETPR per woman DET(OR 2.08 %95 CI 1.24-3.50)(OR 2.08 %95 CI 1.24-3.50)

LBR per woman DETLBR per woman DET (OR 1.90 %95 CI 1.12-3.22)(OR 1.90 %95 CI 1.12-3.22)

Multiple PR DETMultiple PR DET(OR 9.97 %95 CI 2.61-38.19)(OR 9.97 %95 CI 2.61-38.19)

Cochrane Database Syst Rev 2004; 4:CD003416Cochrane Database Syst Rev 2004; 4:CD003416

eSET v DETeSET v DET

►4 RCT meta-analysis (fresh cycles)4 RCT meta-analysis (fresh cycles)

eSET: LBR , MPReSET: LBR , MPR eSET + 1 FET (subsequent cycle): groups are eSET + 1 FET (subsequent cycle): groups are similar regarding cumulative LBR and CPRsimilar regarding cumulative LBR and CPRPandian Z et al. Hum Reprod 2005; 20:2681-2687Pandian Z et al. Hum Reprod 2005; 20:2681-2687

►Single blast v single cleavage ET (<36 y)Single blast v single cleavage ET (<36 y) %32 v 26.1 RR 1.48 %95CI 1.04-2.11 RCT%32 v 26.1 RR 1.48 %95CI 1.04-2.11 RCT

Papanikolau EG et al. N Engl J Med. 2006 Mar 16;354(11):1139-46Papanikolau EG et al. N Engl J Med. 2006 Mar 16;354(11):1139-46

Economic evaluations of eSET v DET Economic evaluations of eSET v DET

► It can be concluded that DET is the most It can be concluded that DET is the most expensive strategy. expensive strategy.

►DET is also most effective if performed in DET is also most effective if performed in one fresh cycle. one fresh cycle.

► eSET is only preferred from a cost-eSET is only preferred from a cost-effectiveness point of view when performed effectiveness point of view when performed in good prognosis patients and when in good prognosis patients and when frozen/thawed cycles are included. frozen/thawed cycles are included.

► If frozen/thawed cycles are excluded, the If frozen/thawed cycles are excluded, the choice between eSET and DET depends on choice between eSET and DET depends on how much society is willing to pay for one how much society is willing to pay for one extra successful pregnancy. extra successful pregnancy. Fiddelers AA et al. Hum Reprod Update. 2007 Jan-Feb;13(1):5-13Fiddelers AA et al. Hum Reprod Update. 2007 Jan-Feb;13(1):5-13. .

ET CathetersET Catheters

ET CathetersET CathetersTight Difficult Transfer (TDT) Tight Difficult Transfer (TDT)

CatheterCatheter(Hard catheter), The Worst One(Hard catheter), The Worst One

ET CathetersET CathetersSoft Catheters: Cook v WallaceSoft Catheters: Cook v Wallace

ET CathetersET Catheters

Abou-Setta A et al. Hum Reprod 2005; 20:3114-Abou-Setta A et al. Hum Reprod 2005; 20:3114-31213121

Mock embryo transfer Mock embryo transfer

►During the luteal phase of previous During the luteal phase of previous cyclecycle

►On the day of oocyte retrievalOn the day of oocyte retrieval► Just before the real transferJust before the real transfer►To choose the right catheter and To choose the right catheter and

determine the axis of the uterusdetermine the axis of the uterus

Mock embryo transferMock embryo transfer

► Reduces the risk of difficult transfer, Reduces the risk of difficult transfer, increases IR and PRincreases IR and PRMansour R et al, Fertil Steril 1990; 54:678-681Mansour R et al, Fertil Steril 1990; 54:678-681

► Uterus at mock embryo transfer will often Uterus at mock embryo transfer will often change position at real embryo transfer change position at real embryo transfer

(RV AV)(RV AV)Henne MB, Milki AA, Human Reprod 2004; 19:570-572Henne MB, Milki AA, Human Reprod 2004; 19:570-572

►Moulding the catheter according to the Moulding the catheter according to the uterocervical angle measured by ultrasound uterocervical angle measured by ultrasound increases CPR & IRincreases CPR & IRSallam HN et al, Human Reprod 2002; 17:1767-1772Sallam HN et al, Human Reprod 2002; 17:1767-1772

Endometrial assessmentEndometrial assessment

►Endometrial thickness in pregnant and Endometrial thickness in pregnant and nonpregnant groups are similarnonpregnant groups are similar Rashidi BH et al. Eur J Obstet Gynecol Reprod Biol 2005 Rashidi BH et al. Eur J Obstet Gynecol Reprod Biol 2005 1;120(2):179-84 1;120(2):179-84

Schild RL et al. Hum Reprod 1999; 14:1255-1258Schild RL et al. Hum Reprod 1999; 14:1255-1258

Laasch C, Puscheck E. Assist Reprod Genet 2004; 21:47-50Laasch C, Puscheck E. Assist Reprod Genet 2004; 21:47-50

Endometrial assessmentEndometrial assessment

► In oocyte recipients who shared oocytes In oocyte recipients who shared oocytes from the same donor and showed from the same donor and showed discordant pregnancy outcome:discordant pregnancy outcome: Endometrial thickness in pregnant and non-Endometrial thickness in pregnant and non-

pregnant groups are similarpregnant groups are similar

(Matched pair analysis)(Matched pair analysis)

Garcia-Velasco JA et al. Fertil Steril 2003;80:54-60Garcia-Velasco JA et al. Fertil Steril 2003;80:54-60

Endometrial assessmentEndometrial assessment

►Endometrial thickness predicts PR in Endometrial thickness predicts PR in IVF cyclesIVF cycles

McWilliams GD et al. Fertil Steril 2007;88:74-81McWilliams GD et al. Fertil Steril 2007;88:74-81

Kovacs P et al. Hum Reprod. 2003;18:2337-2341Kovacs P et al. Hum Reprod. 2003;18:2337-2341

► In “<8 mm endometrial thickness In “<8 mm endometrial thickness group” PR is significantly decreasedgroup” PR is significantly decreasedNoyes N et al. Fertil Steril 2001; 76:92-97Noyes N et al. Fertil Steril 2001; 76:92-97

Zenke U et al. Fertil Steril 2004; 82:850-856Zenke U et al. Fertil Steril 2004; 82:850-856

Ardaens Y et al. Gynecol Obstet Fertil 2002; 30:663-672Ardaens Y et al. Gynecol Obstet Fertil 2002; 30:663-672

Endometrial assessmentEndometrial assessment

►The chances of achieving a thick The chances of achieving a thick endometrium for patients >40 years of age endometrium for patients >40 years of age are lower than for younger patients. are lower than for younger patients.

►A thicker endometrium is correlated with a A thicker endometrium is correlated with a higher PR only for patients >35 years of higher PR only for patients >35 years of ageage

Amir W et al. Fertil Steril 2007;87:799-804Amir W et al. Fertil Steril 2007;87:799-804 ►Endometrial thickness is independently and Endometrial thickness is independently and

significantly related to higher pregnancy significantly related to higher pregnancy rates in IVF cycles of women 40 y and olderrates in IVF cycles of women 40 y and olderTsafrir A et al. Reprod Biomed Online Tsafrir A et al. Reprod Biomed Online 2007 Mar;14(3):348-552007 Mar;14(3):348-55

Endometrial assessmentEndometrial assessment

► Endometrial pattern is similar in pregnant and Endometrial pattern is similar in pregnant and non-pregnant groupsnon-pregnant groupsNoyes N et al. Fertil Steril 2001; 76:92-97Noyes N et al. Fertil Steril 2001; 76:92-97

Rashidi BH et al. Eur J Obstet Gynecol Reprod Biol 2005 1;120(2):179-84Rashidi BH et al. Eur J Obstet Gynecol Reprod Biol 2005 1;120(2):179-84

► Triple-line pattern group had significantly Triple-line pattern group had significantly higher PR campared with homogenous patternhigher PR campared with homogenous pattern

Jarvela IY et al. Ultrasound Obstet Gynecol. 2005;26:765-769Jarvela IY et al. Ultrasound Obstet Gynecol. 2005;26:765-769 ► The effect of pattern on the day of OPU is The effect of pattern on the day of OPU is

more important than the one on hCG daymore important than the one on hCG day Sharara FI et al. J Assist Reprod Genet. 1999;16:523-528 Sharara FI et al. J Assist Reprod Genet. 1999;16:523-528

Effect of “provider at ET” Effect of “provider at ET”

►10 different providers had significantly 10 different providers had significantly different PRs during 854 fresh ETs.different PRs during 854 fresh ETs. Hearns-Stokes RM et al. Fertil Steril 2000; 74:80-86Hearns-Stokes RM et al. Fertil Steril 2000; 74:80-86

►Appropriately trained nurses and Appropriately trained nurses and doctors had similar IR/PR doctors had similar IR/PR Barber D et al,Hum Reprod. 1996; 11:105-108 Barber D et al,Hum Reprod. 1996; 11:105-108

Sinclair L et al, Hum Reprod. 1998; 13:699-702 Sinclair L et al, Hum Reprod. 1998; 13:699-702 Bjuresten K et al, Acta Obstet Gynecol Scand 2003; 82:462-Bjuresten K et al, Acta Obstet Gynecol Scand 2003; 82:462-466 (RCT)466 (RCT)

Effect of “provider at ET”Effect of “provider at ET”

►Experienced (training completed) and Experienced (training completed) and inexperienced (training ongoing) nurses inexperienced (training ongoing) nurses are compared:are compared: Nurses in a given group are similar Nurses in a given group are similar

regarding resultsregarding results Groups are significantly different regarding Groups are significantly different regarding

results (29.5% v 19.5%, p<0.02)results (29.5% v 19.5%, p<0.02)

Barber D et al, Hum Fertil (Camb) 2000; 3:181-185Barber D et al, Hum Fertil (Camb) 2000; 3:181-185

Effect of “provider at ET”Effect of “provider at ET”

►Learning curve:Learning curve: ET trainees can reach an acceptable PR ET trainees can reach an acceptable PR

after the first 25-30 ETs.after the first 25-30 ETs. Clinical pregnancy rates of fellows-in-Clinical pregnancy rates of fellows-in-

training were indistinguishable statistically training were indistinguishable statistically from those of experienced staff by 50 from those of experienced staff by 50 transfers. transfers.

(45.5% v 47.3%)(45.5% v 47.3%)

Papageorgiou TC et al. Hum Reprod 2001; 16:1415-1419 Papageorgiou TC et al. Hum Reprod 2001; 16:1415-1419

Effect of difficult ETEffect of difficult ET

Sallam HN. Curr Opin Obstet Gynecol 2005; 17:289-298Sallam HN. Curr Opin Obstet Gynecol 2005; 17:289-298

Effect of difficult ETEffect of difficult ET

►ETs in 584 IVF cycles, only GI, II or ETs in 584 IVF cycles, only GI, II or blastocysts transferred, 10 physiciansblastocysts transferred, 10 physicians

►ParametersParameters Blood on catheter (10.3%)Blood on catheter (10.3%) Mucus on catheter (20.7%)Mucus on catheter (20.7%) Retention of embryos in catheter (5%)Retention of embryos in catheter (5%) Aborted first attempt at ET (8.9%)Aborted first attempt at ET (8.9%) Difficult ET as judged by provider (10%)Difficult ET as judged by provider (10%) Need for mock embryo transfer Need for mock embryo transfer

immediately before the actual transfer immediately before the actual transfer (6.7%)(6.7%)

Alvero R et al, Hum Reprod. 2003;18:1848-1852Alvero R et al, Hum Reprod. 2003;18:1848-1852

Effect of difficult ETEffect of difficult ET

►Presence of blood on or in the catheter Presence of blood on or in the catheter negatively affected the IR and PR.negatively affected the IR and PR.

(31.3% v 19.5% p=0.015) and (51.7% v 31.7% p=0.004)(31.3% v 19.5% p=0.015) and (51.7% v 31.7% p=0.004) ►None of the other factors significantly None of the other factors significantly

affected PR.affected PR.

Alvero R et al, Hum Reprod. 2003;18:1848-1852Alvero R et al, Hum Reprod. 2003;18:1848-1852

Tenaculum placement Tenaculum placement

►Tenaculum placement during ET Tenaculum placement during ET increases oxytocin concentration and increases oxytocin concentration and “junctional zone” contractions“junctional zone” contractionsDorn C et al, Eur J Obstet Gynecol Reprod Biol 1999; 87:77-80Dorn C et al, Eur J Obstet Gynecol Reprod Biol 1999; 87:77-80

Lesny P et al, Hum Reprod 1999; 14:2367-2370Lesny P et al, Hum Reprod 1999; 14:2367-2370 ►Frequency of uterine contractions is Frequency of uterine contractions is

negatively correlated to IR & PRnegatively correlated to IR & PR(embryos are expelled ?)(embryos are expelled ?)

Fanchin R et al. Contracept Fertil Sex. 1998; 26:498-505 Fanchin R et al. Contracept Fertil Sex. 1998; 26:498-505

Tenaculum placementTenaculum placement

►Tenaculum (volsellum) placement Tenaculum (volsellum) placement during ET did not have any significant during ET did not have any significant effect on PR & IReffect on PR & IR

Tenaculum placement ET v easy transfer Tenaculum placement ET v easy transfer

(PR & IR)(PR & IR)

OR=0.71 (95% OR=0.71 (95% CI 0.31-1.63CI 0.31-1.63) & OR=0.97 (95% ) & OR=0.97 (95% CI 0.53-CI 0.53-1.771.77))

Sallam HN et al. J Assist Reprod Genet. 2003 Apr;20(4):135-142Sallam HN et al. J Assist Reprod Genet. 2003 Apr;20(4):135-142

Ultrasound-guided embryo Ultrasound-guided embryo transfer: immediate withdrawal transfer: immediate withdrawal

of the catheter versus a 30 of the catheter versus a 30 second wait second wait

►Does failing to withdraw catheter Does failing to withdraw catheter immidiately after ET causes uterine immidiately after ET causes uterine contractions which can lower PR?contractions which can lower PR?

►PR: PR: %60.8 v 69.4% %60.8 v 69.4% p>0.05p>0.05 RCTRCT

Martinez F et al. Hum Reprod. 2001 May;16(5):871-4Martinez F et al. Hum Reprod. 2001 May;16(5):871-4

Time interval between embryo Time interval between embryo catheter loading and catheter loading and

discharging discharging

►The longer the duration, the lower the The longer the duration, the lower the PR and IR. PR and IR.

►The decrease in PR and IR is gradual The decrease in PR and IR is gradual until a duration of 120 s, and until a duration of 120 s, and decreases sharply afterwards. decreases sharply afterwards.

Matorras R et al, Hum Reprod. 2004; 19:2027-2030Matorras R et al, Hum Reprod. 2004; 19:2027-2030

Impact of retained embryos on Impact of retained embryos on the outcomethe outcome

►2.8-3.9% of all transfers2.8-3.9% of all transfers►Retained embryos in the transfer Retained embryos in the transfer

catheter and immediate retransfer of catheter and immediate retransfer of them have no adverse impact on them have no adverse impact on clinical pregnancy*, implantation**, and clinical pregnancy*, implantation**, and live birth rates***live birth rates***

Vicdan K et al. Eur J Obstet Gynecol Reprod Biol. 2007;134:79-82 */**Vicdan K et al. Eur J Obstet Gynecol Reprod Biol. 2007;134:79-82 */**Lee HC et al. Fertil Steril 2004;82:334-7*/**/***Lee HC et al. Fertil Steril 2004;82:334-7*/**/***Alvero R et al. Hum Reprod. 2003;18:1848-1852**Alvero R et al. Hum Reprod. 2003;18:1848-1852**Tur-Kaspa I et al. Hum Reprod. 1998;13:2452-5*Tur-Kaspa I et al. Hum Reprod. 1998;13:2452-5*Nabi A et al. Hum Reprod. 1997;12:1188-90*Nabi A et al. Hum Reprod. 1997;12:1188-90*

Impact of retained embryos on Impact of retained embryos on the outcomethe outcome

►Retained embryos in the transfer Retained embryos in the transfer catheter and immediate retransfer of catheter and immediate retransfer of them have adverse effect on CPR.them have adverse effect on CPR.

Visser DS et al, J Assist Reprod Genet. 1993 Jan;10(1):37-43Visser DS et al, J Assist Reprod Genet. 1993 Jan;10(1):37-43

US Guided ETUS Guided ET

►Observation of ET catether tipObservation of ET catether tip►Observation of the embryo discharge Observation of the embryo discharge

sitesite►Observation of the air bubbleObservation of the air bubble►Prevents touch to fundus (contractions Prevents touch to fundus (contractions

?)?)►Discharge 1-2 cm to fundusDischarge 1-2 cm to fundus

US guided v clinical touchUS guided v clinical touch

►5968 ET in 20 RCT5968 ET in 20 RCT►Meta-analysisMeta-analysis

Abou-Setta AM et al. Fertil Steril. 2007;88:333-41Abou-Setta AM et al. Fertil Steril. 2007;88:333-41

US guided v clinical touchUS guided v clinical touch

Abou-Setta AM et al. Fertil Steril. 2007;88:333-41 Abou-Setta AM et al. Fertil Steril. 2007;88:333-41

US guided v clinical touchUS guided v clinical touch

US guided v clinical touchUS guided v clinical touch

US guided v clinical touchUS guided v clinical touch

US guided v clinical touchUS guided v clinical touch

In US guided ET group:In US guided ET group:►IRIR OR = 1.35, 95% CI = 1.22-1.50OR = 1.35, 95% CI = 1.22-1.50

►Difficult ETR Difficult ETR OR = 0.68, 95% CI = 0.58-OR = 0.68, 95% CI = 0.58-0.81 0.81

►Similar for MPR, ectopic & miscarriage Similar for MPR, ectopic & miscarriage ratesrates

Abou-Setta AM et al. Fertil Steril. 2007;88:333-41Abou-Setta AM et al. Fertil Steril. 2007;88:333-41

Influence of embryo transfer Influence of embryo transfer depth depth

►For every additional millimeter For every additional millimeter embryos embryos are depositedare deposited away from the fundus, the away from the fundus, the odds of clinical pregnancy increased by odds of clinical pregnancy increased by 11%11%(OR=1.11 by multivariable logistic regression model)(OR=1.11 by multivariable logistic regression model)

Pope et al, Fertil Steril 2004; 81:51-58Pope et al, Fertil Steril 2004; 81:51-58

►Better IR & PR are obtained when the Better IR & PR are obtained when the catheter tipcatheter tip is positioned close to the is positioned close to the middle area of the endometrial cavitymiddle area of the endometrial cavity Oliveira JB et al, Reprod Biomed Online 2004; 9:435-441Oliveira JB et al, Reprod Biomed Online 2004; 9:435-441

Influence of embryo transfer Influence of embryo transfer depthdepth

►PR in 1 cm depth group was PR in 1 cm depth group was significantly lower than in 1.5 cm and significantly lower than in 1.5 cm and 2 cm depth groups2 cm depth groups

Coroleu B et al. Hum Reprod. 2002;17:341-6Coroleu B et al. Hum Reprod. 2002;17:341-6

►The IR & PR were similar whether the The IR & PR were similar whether the embryos were deposited in the upper embryos were deposited in the upper or lower half of the endometrial cavityor lower half of the endometrial cavity

Franco JG Jr et al. Hum Reprod. 2004 ;19:1785-90Franco JG Jr et al. Hum Reprod. 2004 ;19:1785-90

Influence of embryo transfer Influence of embryo transfer depthdepth

►PR, OPR, and IR are higher when the PR, OPR, and IR are higher when the air bubble is at the upper half of the air bubble is at the upper half of the endometrial lengthendometrial length

Schats R et al. Hum Reprod 2006; 21(Supp 1):i82 Schats R et al. Hum Reprod 2006; 21(Supp 1):i82

ESHRE 2006 Abstracts Book (O-210)ESHRE 2006 Abstracts Book (O-210)

Bed rest versus free Bed rest versus free mobilisation following ETmobilisation following ET

► Immediate ambulation following the ET Immediate ambulation following the ET procedure has no adverse influence on the procedure has no adverse influence on the ability to conceive.ability to conceive.Bar-Hava I et al. Fertil Steril. 2005 Mar;83(3):594-7Bar-Hava I et al. Fertil Steril. 2005 Mar;83(3):594-7

Sharif K et al. Fertil Steril 1998; 69:478-481Sharif K et al. Fertil Steril 1998; 69:478-481

►One-hour*/20’** and 24-hour rest post-One-hour*/20’** and 24-hour rest post-embryo transfer result in comparable rates embryo transfer result in comparable rates of clinical pregnancy. of clinical pregnancy. Amarin ZO, Obeidat BR. BJOG 2004; 111:1273-1276* RCTAmarin ZO, Obeidat BR. BJOG 2004; 111:1273-1276* RCT

Botta G, Grudzinskas G. Hum Reprod 1997; 12:2489-2492** RCTBotta G, Grudzinskas G. Hum Reprod 1997; 12:2489-2492** RCT

The effect of peri-transfer The effect of peri-transfer intercourse on pregnancy rates intercourse on pregnancy rates

►Multicenter RCTMulticenter RCT►There was no significant difference There was no significant difference

between the intercourse and abstain between the intercourse and abstain groups in relation to PRgroups in relation to PR

►Hence exposure to semen around the Hence exposure to semen around the time of embryo transfer increases IRtime of embryo transfer increases IROR 1.48, %95 CI 1.01-2.19OR 1.48, %95 CI 1.01-2.19

Tremellen KP et al. Hum Reprod 2000; 15:2653-2658Tremellen KP et al. Hum Reprod 2000; 15:2653-2658

PIROXICAMPIROXICAM

►RCTRCT►10 mg Piroxicam v placebo 1-2 h before 10 mg Piroxicam v placebo 1-2 h before

ETET► IR IR (18.7% v 8.6% )(18.7% v 8.6% ) and PR and PR (46.8% v 27.6% )(46.8% v 27.6% )

<40 y, fresh and frozen ET<40 y, fresh and frozen ET

Moon HS et al, Fertil Steril. 2004 Oct;82(4):816-20Moon HS et al, Fertil Steril. 2004 Oct;82(4):816-20

Antibiotic prophylaxis & Antibiotic prophylaxis & IVF/ETIVF/ET

► Amoxicilline + clavulanic acid prophylaxis Amoxicilline + clavulanic acid prophylaxis Only RCT on AB prophylaxis & IVF/ETOnly RCT on AB prophylaxis & IVF/ETIR (36.9% v 36.5%; p>0.95)IR (36.9% v 36.5%; p>0.95)Peikrishvili R et al. J Gynecol Obstet Biol Reprod (Paris). 2004;33:713-719Peikrishvili R et al. J Gynecol Obstet Biol Reprod (Paris). 2004;33:713-719

► Failure to conceive in ART is significantly Failure to conceive in ART is significantly associated with bacterial colonization of the associated with bacterial colonization of the uterine cervix uterine cervix Salim R et al. Hum Reprod 2002; 17:337-340.Salim R et al. Hum Reprod 2002; 17:337-340.

► Positive microbiology cultures of embryo Positive microbiology cultures of embryo catheter tip is accociated with PR and IR catheter tip is accociated with PR and IR Prophylactic antibiotics are associated with Prophylactic antibiotics are associated with a reduction in positive microbiology cultures a reduction in positive microbiology cultures of embryo catheter tips of embryo catheter tips Egbase PE et al. Lancet 1999; 354:651-652Egbase PE et al. Lancet 1999; 354:651-652

Aspirin & IVF/ETAspirin & IVF/ET

►Currently available evidence does not Currently available evidence does not support the use of aspirin in IVF or ICSI support the use of aspirin in IVF or ICSI treatment.* (PR & LBR)treatment.* (PR & LBR)

►However, the noted However, the noted trendtrend of improvement of improvement in clinical pregnancy, and the lack of in clinical pregnancy, and the lack of power even when the studies were pooled power even when the studies were pooled highlight the need for a definitive trial.**highlight the need for a definitive trial.**Khairy M et al. Fertil Steril. 2007 Oct;88(4):822-31. Review/ Meta-Khairy M et al. Fertil Steril. 2007 Oct;88(4):822-31. Review/ Meta-analysis*/**analysis*/**

Gelbaya TA et al. Hum Reprod Update. 2007 Jul-Aug;13(4):357-64. Review/ Gelbaya TA et al. Hum Reprod Update. 2007 Jul-Aug;13(4):357-64. Review/ Meta-analysis* Meta-analysis*

PrednisolonePrednisolone

►Does not have any significant effect on Does not have any significant effect on IR & CPRIR & CPR

Lee KA et al. Hum Reprod 1994; 9:1832-1835Lee KA et al. Hum Reprod 1994; 9:1832-1835

Moffitt D et al. Fertil Steril 1995; 63:571-577 (RCT)Moffitt D et al. Fertil Steril 1995; 63:571-577 (RCT)

Motta GL et al. J Reprod Med 1996; 41:889-891 (RCT)Motta GL et al. J Reprod Med 1996; 41:889-891 (RCT)

Fridstrom M et al. Hum Reprod 1999; 14:1440-1444 (RCT)Fridstrom M et al. Hum Reprod 1999; 14:1440-1444 (RCT)

Ubaldi F et al. Hum Reprod 2002; 17:1544-1547 (RCT)Ubaldi F et al. Hum Reprod 2002; 17:1544-1547 (RCT)

Adjuvant therapy with Sildenafil Adjuvant therapy with Sildenafil in IVF for endometrial in IVF for endometrial

developmentdevelopment►While the use of adjuvant therapy did not While the use of adjuvant therapy did not

significantly improve ultrasonographic significantly improve ultrasonographic endometrial thickness, it did improve outcome endometrial thickness, it did improve outcome rates (PR&LBR).rates (PR&LBR).

Fratterelli JL et al. Reprod Biomed Online. 2006 Jun;12(6):722-9.Fratterelli JL et al. Reprod Biomed Online. 2006 Jun;12(6):722-9.

► Vaginal administration of sildenafil enhanced Vaginal administration of sildenafil enhanced endometrial development in 70% of patients with endometrial development in 70% of patients with previous poor (<9mm) endometrial development previous poor (<9mm) endometrial development High IR & OPR were achieved in group with High IR & OPR were achieved in group with enhanced development. Previous endometritis enhanced development. Previous endometritis may decrease the response to sildenafil.may decrease the response to sildenafil.Sher G and Fisch JD. Fertil Steril. 2002 Nov;78(5):1073-6.Sher G and Fisch JD. Fertil Steril. 2002 Nov;78(5):1073-6.

Thanks for your attentionThanks for your attention