**3. Results**

35 cycles were started and all had retrievals. 22 cycles involved use of intra-cytoplasmic sperm injection (ICSI) due to male factor problems. Endometrial thickness varied between 7 and 16 mm. 22 cycles had transfers on day 2 and 13 cycles had transfers on day 3. There were 16 positive β hCG's greater than 5 IU/ml twelve days after embryo transfer. Of these, 2 had biochemical pregnancies, and 12 had clinical pregnancies as evidenced by presence of gestational sac by ultrasound examination at five weeks of gestation and presence of the fetus and a heart beat at six weeks of gestation. There were 5 first trimester spontaneous abortions at 7-8 weeks of gestation. Seven(7) patients have delivered healthy babies at term; there were 2 ectopic pregnancies (Table 1).


Table 1. Results from HEED on day2 and day 3 transfers

#### **4. Discussion**

82 Ectopic Pregnancy – Modern Diagnosis and Management

"feel" for the scope. The transfer catheter (Precision Reproduction, LLC, LA, CA USA) is

Fig. 3. Placement of embryo(s) under hysteroscopic guidance; arrow points to the tip of the

35 cycles were started and all had retrievals. 22 cycles involved use of intra-cytoplasmic sperm injection (ICSI) due to male factor problems. Endometrial thickness varied between 7 and 16 mm. 22 cycles had transfers on day 2 and 13 cycles had transfers on day 3. There were 16 positive β hCG's greater than 5 IU/ml twelve days after embryo transfer. Of these, 2 had biochemical pregnancies, and 12 had clinical pregnancies as evidenced by presence of gestational sac by ultrasound examination at five weeks of gestation and presence of the fetus and a heart beat at six weeks of gestation. There were 5 first trimester spontaneous abortions at 7-8 weeks of gestation. Seven(7) patients have delivered healthy babies at term;

catheter; catheter entry at 8 o'clock position.

there were 2 ectopic pregnancies (Table 1).

**3. Results** 

polycarbonate based with a tapered tip (to 500 m), beveled to 60o.

As may have been expected, the average age of patients for transfers on day 3 versus day 2 was lower (35 vs. 38 years of age), as they had better quality embryos which made it more feasible to continue embryo culture 1 day longer. Interestingly enough, the live pregnancy rate was also higher in day 3 transfers (31% vs. 15% ).

Advantages of hysteroscopic guided direct embryo delivery include objectivity and replicability of the procedure. This unique and significant aspect of the procedure increases the reliability of correct entry into the uterine cavity with direct visual confirmation. Furthermore, placement and subsequent implantation at a precise location, with minimal volume of transfer media, provides an obvious benefit to patients with distorted uterine cavities, myomas, and adenomyosis and uterine adhesions. Visualization also provides the advantage of maneuvering along the contours of the uterus, thus decreasing the rate of trauma to the endometrial lining. In addition, performing gas distension of the uterus by an inert gas (N2), the catheter tip is less likely to come into contact with the uterine fundus which has been associated with

stimulating uterine contractions and creating an unfavorable environment for implantation (Kovacs 1999, Lesny 1998). It has been reported that high frequency uterine contractions are associated with a lower ongoing clinical pregnancy rate and complete expulsion of the embryo (Fanchin 1998). It has also been postulated that the expulsion of the embryo into the lower uterine segment may result in higher rates of cervical ectopic pregnancy and placenta previas (Romundstad 2006; Schoolcraft 2001).

Witnessing uterine contractions hysteroscopically can also guide the clinician to abort and defer the procedure, thus decreasing costs, multiple failed attempts of ET, embryo loss, and risk of cervical ectopics and placenta previas. Direct visualization of the catheter tip ensures that the embryos are not retained in the catheter or lost. Viser et al. found a lower pregnancy rate when retained embryos were present (3% vs. 20.3%). In addition, catheter tip visualization allowed us to deliver smaller aliquot volumes for ET (5µl) as opposed to routine volumes (30µl). Smaller volume allows better handling of the embryo for proper orientation to the uterine lining, stabilizing the position and has been reported to increase pregnancy and implantation rates (Meldrum 1987). It may also contribute to the reduced

Hysteroscopic Endometrial Embryo Delivery (HEED) 85

Fanchin R, Righini C, Olivennes F, Taylor S, de Ziegler D, Frydman R. Uterine contractions

Garcia-Velasco J, Isaza V, Martinez-Salazar J, Landazabal A, RequenaA, Remohi J, PellicerA,

Ghazzawi IM, Al-Hasani S, Karaki R, Souso S. Transfer technique and catheter choice

Kamrava M, Yin M. Hysteroscopic Subendometrial Embryo Delivery (SEED), Mechanical

Knutzen.V., Scoto-Albors,C.E., Fuller,D., Sher.G., Shynock.K. and Behr,B. (1989) Mock

Kovacs GT.What factors are important for successful embryo transfer after in-vitro

Marcus S, Brinsden P. Analysis of the incidence and risk factors associated with ectopic

Meldrum DR, Chetkowski R, Steingold KA, de Ziegler D, Cedars MI, Hamilton M.

Liv Bente Romundstad, Pal R.Romundstad, Arne Sunde, Vidar von Düring, Rolv Skjærven

Sallam HN, Saad-el-Din S. Performing embryo transfer under ultrasound guidance- A meta

Schoolcraft WB, Surrey ES, Gardner DK. Embryo transfer: techniques and variables affecting

Sieck UV, Jaroudi KA, Hollanders JM, Hamilton CJ. Ultrasound guided embryo transfer

Strandell, J. Thorburn and L. Hamberger, Risk factors for ectopic pregnancy in assisted

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Embryo Implantation. IJFS, Vol 4, No 1, Apr-Jun 2010

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at the time of embryo transfer alter pregnancy rates after in-vitro fertilization. Hum

SimonC.Transabdominal ultrasoundguided embryo transfer does not increase pregnancy rates in oocyte recipients. Fertility and Sterility 2002;78(3):534–539 Gardner DK, Lane M. Culture of viable human blastocysts in defined sequential serum-free

influence the incidence of transcervical embryo expulsion and the outcome of IVF.

embryo transfer (MET) in early luteal phase, the cycle prior to in-vitro fertilisation and embryo transfer. Presented at the 45th Annual Meeting of the American Fertility Society, San Francisco, California, 13-16 November 1989. Published by the American Fertility Society in the program supplement, p. S152 (Abstract P. 229). Kosmas IP, R.Janssens R, De Munck L, Al Turki H, Van der Elst J, Tournaye H and Devroey

P. Ultrasound-guided embryo transfer does not offer any benefit in clinical outcome: a randomized controlled trial. Human Reproduction Vol.22, No.5 pp.

pregnancy following in-vitro fertilization and embryo transfer. Hum Reprod

Evolution of a highly successful in vitro fertilization embryo transfer program.

and Lars J.Vatten. Increased risk of placenta previa in pregnancies following IVF/ICSI; a comparison of ART and non-ART pregnancies in the same mother.

analysis of randomized trials. Fertility and Sterility. 2002; Vol. 78, issue 3 (Suppl

does not prevent ectopic pregnancies after in-vitro fertilization. Hum Reprod

ectopic pregnancy rates, as larger volumes have been associated with increased ectopic pregnancy risk (Marcus 1995). Expulsion of this low volume of transfer media, carrying the embryo(s), from the tip of the catheter can only now be verified under direct visualization. In the "blind" procedure there is a real concern that this tiny droplet can be dragged into the lower uterine segment or into the cervical canal or out of the uterus along with the catheter during the final withdrawal of the catheter after embryo transfer.

The potential disadvantage and risk of this technique is disruption of the uterine lining, however the risk is postulated to be less than "blind" and ultrasound guided transfers due to the advantage of direct visualization of the uterine lining and not requiring movement of the catheter to facilitate identification during ultrasound (Garca-Velasco 2002). In addition, visualization allows one to place the embryo at a different location if trauma ensues. The major drawback to its acceptance is that hysteroscopy is an invasive procedure. However, as opposed to rigid endoscopes which may cause trauma to the uterus, the hysteroscope used in this study is a mini hysteroscope with a 3 mm diameter and flexible tip that allows one to easily follow the curvature of the uterus. The catheter used is semi-rigid to prevent kinkage as it passes through the endoscope yet with flexibility to bend with the endoscope. In our study, no disruption to the uterine lining or uterine bleeding occurred. Increased cost is another drawback, however utilizing a hysteroscope will decrease the costs from multiple failed IVF-ET attempts and improve patient satisfaction.

#### **5. Conclusion**

Hysteroscopic endometrial embryo delivery (HEED) is a beneficial technique in increasing clinical pregnancy rates, especially in patients with repeated failed IVF-ET attempts. Due to the objective and replicable nature of the hysteroscopic procedure along with increased accuracy of placement of embryo(s), efforts in reducing multiple pregnancies should now be more focused on increasing our knowledge of selecting embryo(s) with high survival potential for embryo transfer. Ectopic pregnancies from IVF will be minimized by using lower transfer volumes of 5 µl and visually confirmed positional placement of embryos away from the uterine cornu. Ectopics are almost eliminated when using the SEED technique for blastocyst embryo transfer.

#### **6. Acknowledgment**

Supported by: West Coast IVF Clinic, Inc. and LA IVF LAB, LLC. LA, CA USA

#### **7. References**


ectopic pregnancy rates, as larger volumes have been associated with increased ectopic pregnancy risk (Marcus 1995). Expulsion of this low volume of transfer media, carrying the embryo(s), from the tip of the catheter can only now be verified under direct visualization. In the "blind" procedure there is a real concern that this tiny droplet can be dragged into the lower uterine segment or into the cervical canal or out of the uterus along with the catheter

The potential disadvantage and risk of this technique is disruption of the uterine lining, however the risk is postulated to be less than "blind" and ultrasound guided transfers due to the advantage of direct visualization of the uterine lining and not requiring movement of the catheter to facilitate identification during ultrasound (Garca-Velasco 2002). In addition, visualization allows one to place the embryo at a different location if trauma ensues. The major drawback to its acceptance is that hysteroscopy is an invasive procedure. However, as opposed to rigid endoscopes which may cause trauma to the uterus, the hysteroscope used in this study is a mini hysteroscope with a 3 mm diameter and flexible tip that allows one to easily follow the curvature of the uterus. The catheter used is semi-rigid to prevent kinkage as it passes through the endoscope yet with flexibility to bend with the endoscope. In our study, no disruption to the uterine lining or uterine bleeding occurred. Increased cost is another drawback, however utilizing a hysteroscope will decrease the costs from multiple

Hysteroscopic endometrial embryo delivery (HEED) is a beneficial technique in increasing clinical pregnancy rates, especially in patients with repeated failed IVF-ET attempts. Due to the objective and replicable nature of the hysteroscopic procedure along with increased accuracy of placement of embryo(s), efforts in reducing multiple pregnancies should now be more focused on increasing our knowledge of selecting embryo(s) with high survival potential for embryo transfer. Ectopic pregnancies from IVF will be minimized by using lower transfer volumes of 5 µl and visually confirmed positional placement of embryos away from the uterine cornu. Ectopics are almost eliminated when using the SEED

Supported by: West Coast IVF Clinic, Inc. and LA IVF LAB, LLC. LA, CA USA

Baba K, Ishihara O, Hayashi N, Saitoh M, Taya J, Kinoshita K. Where does the embryo implant after embryo transfer in humans? Fertil Steril 2001;73:123–5 Brown JA, Buckingham K, Abou-Setta A, Buckett W. Ultrasound versus 'clinical touch' for

Coroleu et al., 2002 Increased risk of placenta previa in pregnancies following IVF/ICSI; a

catheter guidance during embryo transfer in women. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD006107. DOI: 10.1002/

comparison of ART and non-ART pregnancies in the same mother. Romundstad

during the final withdrawal of the catheter after embryo transfer.

failed IVF-ET attempts and improve patient satisfaction.

technique for blastocyst embryo transfer.

14651858.CD006107.pub2.

**6. Acknowledgment** 

**7. References** 

**5. Conclusion** 

LB, Romundstad PR, Sunde A, von Düring V, Skjaerven R, Vatten LJ. Hum Reprod. 2006 Sep;21(9):2353-8. Epub 2006 May 25.


**5** 

*Germany* 

**Ectopic Pregnancy Following** 

**Reconstructive, Organ-Preserving** 

Cordula Schippert, Philipp Soergel and Guillermo-José Garcia-Rocha

Disease or damage of the fallopian tubes accounts for 25% to 35% of reported cases of infertility (Pandian at al., 2008). Decreased fecundity may be caused by tubal occlusion, fimbrial damage, and/or peritubal adhesions, usually related to previous pelvic inflammatory disease, endometriosis, pelvic surgery, salpingitis isthmica nodosa or otherwise unknown causes. A special group of women affected by tubal infertility are those who have undergone intentional sterilization; 5% to 25% of these women (Neuhaus et al.; 1995; Kim et al.; 1997; Schippert et al., 2004) later regret having undergone this surgery. Some of them desire an operation to restore fertility, the most frequent reason for this is the desire to have a child with a new partner. The diagnosis of "tubal infertility" is a serious and

In the presence of a functional impairment of the fallopian tubes, the desire to have a child is (if at all) only possible through complicated, risky and cost-intensive therapies: on the one hand through reconstructive surgery or – on the other hand - by means of assisted reproductive technology procedures (ART). The limitations of surgical repair in many cases have been the driving force behind the rising numbers of ART. However, the success of either treatment - even when attempted multiple times - cannot be guaranteed. Outpatient in-vitro fertilization (IVF) can be repeated several times which results in an overall higher success rate. Unfortunately, a large number of couples is not be able to afford multiple IVF cycles. An IVF therapy also is not without risks and is associated with physical and mental

Problems of IVF therapy in many countries, e.g. in Germany, are found in the low birth rates of at most 21% despite a clinical pregnancy rate of approximately 28-30% per embryo transfer, but it is the large number of multiple pregnancies at approximately 20% with occasionally significant maternal and child morbidity and mortality rates. The overall average pregnancy rate in Germany for all IVF cycles in 2009 was 29.5%, compared with a rate of 28.6% for the ICSI cycles (Bühler et al., 2010). Because of German legal restrictions, no embryo selection is permitted and the German Embryo Protection Act, passed in 1991, permits no more than three embryos to be transferred. Oocyte donation as well as surrogate

**1. Introduction** 

motherhood is illegal.

burdensome diagnosis for the affected woman.

stresses which not infrequently lead to a discontinuation of therapy.

*Medical School of Hannover, Department of Gynecology and Obstetrics Division of Reproductive Medicine; Carl-Neuberg-Str. 1, 30625 Hannover,* 

**Microsurgery in Tubal Infertility** 

Visser DS, Fourie FL, Kruger HF. Multiple attempts at embryo transfer: effects on pregnancy outcome in an in vitro fertilization and embryo transfer program. J Assist Reprod Genetics 1993;10:37–43.
