EMBRYO TRANSFER Dr. M. Hakan ÖZÖRNEK EUROFERTIL Reproductive Health Center Istanbul, Turkey

Variables affecting pregnancy rates Uterine receptivity Embryo quality Transfer efficiency

ET is the final and most crucial step in IVF ET technique has been given little attention and the published data on the subject are minimal. But it is not as simple as it looks

Variables affecting ET success Trial transfer Cervical mucus Catheter typ Difficult ET Ultrasound quidance

Embryo transfer

Significant differences were observed in pregnancy rates after the embryo transfer was performed by different clinicians Hearn-Stokes, et al., Fertil Steril, 2000

Trial transfer A trial transfer in a cycle preceding IVF for the purpose of measuring the uterine cavity depth and direction apperars to be of value.

Trial transfer 335 patients Pregnancy rates Trial group 22.8% No trial group 13.1% Mansour, et al., Hum Reprod, 1994

Trial transfer Because of the great variability in cervical and uterine anatomy a trial transfer is beneficial.

Cervical mucus Mucus plugging of the catheter tip can cause Retained embryos Damage to the embryos Improper embryo placement

Cervical mucus Cervical lavage before ET to remove all visible mucus 55% pregnancy rate with lavage 41% pregnancy rate without lavage Mac Namee

Cervical mucus Embryos may be retained in the catheter owing to plugging of the tip with mucus or uterine tissue. Visser (1993) found a decrease in pregnancy rates from 20% to 3% when embryos were retained.

Cervical mucus Cervical mucus can plug the tip of the catheter The embryos can stick to the cervical mucus around the catheter and be dragged outside during the withdrawal of the catheter.

Cervical mucus In a retrospective study analysing 1204 embryo transfer procedures, it was shown that the embryos were much more likely to be retained when the embryo transfer catheter was contaminated with mucus or blood. Nabi, et al., Hum Reprod, 1997

Catheters The ideal embryo transfer catheter should be soft enough to avoid any trauma to the endocervix or endometrium and malleable enough to find its way into the uterine cavity

Catheter type Although stiff catheters and use of a rigid outer sheath make catheter placement easier, they may result in more bleeding, trauma, mucus plugging and stimulation of uterine contractions.

Catheter type Soft catheters allow the tip to follow the contour of the cervical and uterine axis and minimize trauma to the endometrium.

Catheter type Pregnancy rate with different catheters Frydman 32% Wallace 19% TDT 19% Wisanto, et al., Fertil Steril, 1989

Catheter type Pregnancy rate with different catheters 518 IVF cycles Frydman 31% Wallace 30% Al-shawaf, et al., J Assist Reprod Genet, 1993 518 IVF cycles Soft catheter 36% Hard catheter 17% Wood, et al., Hum Reprod, 2000

Catheter type Pregnancy rate with different catheters Tomcat 35% Wallace 63% M-Wallace 69% Schoolcraft, et al., 2003

Catheter type A large volume (60μl) of transfer media and a large air interface have been shown to result in embryos which were expelled into the cervix on the speculum or adherent to the catheter Removing the air column minimized such complication

Avoiding any uterine contractility Use soft catheters Avoid touching the uterine fundus Try to gentle manipulation

Uterine contractility It was demonstrated that only 45% of embryos were present within the uterine cavity 1 h after the transfer. Menezo, et al., Acta Europ Fertil, 1985 Stimulation of the cervix causes the release of oxytocin, thus increasing uterine contractility.

Touching the uterine fundus It is a fact that if the tip of the catheter touches the uterine fundus the patients experience immediate discomfort followed by suprapubic pain Touching the fundus with the catheter stimulated junctional zone contactions that can reduce the chances of pregnancy Lesny, et al., Hum Reprod, 1998

Touching the fundus Yes 24% PR No 46% PR Waterstone, et al., Lancet, 1991

Touching the fundus Distance between the tip of the catheter and the uterine fundus 10 mm 20.6% 15 mm 31.3% 20 mm 33.3% implantation rate Coroleu, et al., Lancet, 1991

Gentle manipulation Gentle manipulation should be the rule even in introducing the speculum to avoid unnecessary pushing of the cervix. Studies have shown that technically difficult embryo transfers are associated with reduced pregnancy rates Sharif, et al., Hum Reprod, 1995

Gentle manipulation Some authors suggest that it is preferable to wait for the release of embryos from the catheter or to wait before withdrawal of the catheter. Wisanto, et al., Fertil Steril, 1989 It was reported no differences in the pregnancy rate between withdrawal of the catheter immediately after embryo deposit or after a 30 s wait Martinez, et al., Hum Reprod, 2001

Blood When blood was noted outside the transfer catheter, the chance of conception was reduced significantly by sixfold to sevenfold Goudas, et al., Fertil Steril, 1998

Ultrasound Guidance The full bladder required to perform transabdominal ultrasound examinations is itself helpful in straightening the cervico-uterine axis and improving pregnancy rates Lewin et al., J Assisted Reprod Genet, 1987

Ultrasound Guidance is especially helpful with the insertion of “soft” catheters. When placement is difficult, the problem may be visualized and modification of the angle between the cervix and uterus can be accomplished with manipulation of the speculum.

Ultrasound Guidance Better pregnancy rate No significant difference Wood, et al., Hum Reprod, 2000 Coroleu, et al., Hum Reprod, 2000 No significant difference Al-Shawaf, et al., J Assisted Reprod Genet, 1993 Kan, et al., Hum Reprod, 1999

Meta-analysis of ultrasound-guided ET Buckett, Fertil Steril, 2003

Bedrest Standing shortly after embryo transfer does not play a significant role in the final position of the embryos. Woolcott, et al., Hum Reprod, 1998 In a study that had > 1000 cycles the results strongly suggested that bedrest was not necessary following embryo transfer Sharif, et al., Fertil Steril, 1998

Protocol for ET Full bladder, US guidance Wash cervix and lavage with culture media Trial transfer to internal os Wallace catheter, 30μl continious column Gentle insertion – manipulate cervix with speculum Examination of catheter following transfer for retained embryos

The goal Atraumatic placement of the embryos 1.5 cm proximal to the fundus without pain, bleeding, trauma to the endometrium or embryos and with the absence of uterine contractions.