**Hysteroscopic Endometrial Embryo Delivery (HEED)**

M.M. Kamrava, L. Tran and J.L. Hall *1West Coast IVF Clinic 2LA Center for Embryo Implantation 3UCLA, the Geffen School of Medicine USA* 

### **1. Introduction**

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It has been over 30 years since the first successful pregnancy using in vitro fertilization (IVF). There have been major advancements in the different components of IVF such as ovulation induction protocols, oocyte retrieval techniques, and culture medium tailored to improving embryo quality (Gardner 1998). However, the discrepancy between women undergoing IVF with normal embryo development and live pregnancy rates continues to exist. It is estimated that up to 85% of replaced embryos fail to implant despite the selection of apparently normal embryos for transfer (Sallam 2002). This failure rate suggests that the embryo transfer stage is a key step to successful live pregnancy rates in assisted reproductive technology (ART) (Meldrum 1987).

Embryo transfer is traditionally performed by "blindly" replacing the embryos into the uterine cavity utilizing a transcervical catheter at approximately 2-5 days of development. This technique relies highly on the skill and tactile senses of the clinician. Many clinicians will transfer the embryos at a fixed distance (6 cm) from the external os; however, with varying cervical lengths and uterine anatomy, this often does not ensure optimal placement (Brown 2007). Recently, there have been many studies proposing potential embryo transfer related factors to the low success rate in pregnancy outcomes such as uterine contractions, expulsion of embryos, blood or mucus on the catheter tip, bacterial contamination of the catheter, and retained embryos (Schoolcraft 2001). Ultrasound guided embryo transfer (UGET) is currently suggested as the standard clinical practice and appears to improve the chances of live/ongoing and clinical pregnancies compared with clinical touch methods (Brown 2007). However, controversies still remain regarding the actual benefit of UGET in successful clinical pregnancy rates (Kosmas 1999). The subendometrial embryo delivery (SEED) technique has been previously reported to increase pregnancy rates and eliminate ectopic pregnancies associated with ART (KAMRAVA 2010). In this study, we set out to use a similar technique which utilized a mini-hysteroscope with a flexible catheter for direct delivery of embryo(s) at the 4-12 cell stage onto the endometrium under direct visualization. The hysteroscopic visual guidance ensures more precise and reliable placement at the desired location of the endometrium.

Hysteroscopic Endometrial Embryo Delivery (HEED) 81

The cervix is grasped with an allis clamp and stabilized. Nitrogen gas is used as the distention media throughout the procedure via a hysteroscopic insufflator. A 3 mm flexible hysteroscope (Figure 1) loaded with embryo catheter containing the embryos (Figure 2) is then gently inserted through the cervical os under direct visualization of the cervical canal into the uterine cavity. Once the cavity is visualized, it is then further advanced to the fundus of the uterus. The loaded embryo transfer catheter (Precision Reproduction, LA, CA USA) is then advanced to 1.5 cm from the tip of the hysteroscope and placed over the point of embryo deposition, half way between the lowest point of the fundus in the midline and the tubal opening into the uterus (Figure 3). The embryos are then gently released by the embryologist. Our results show that hysteroscopic guided early embryo transfer results in a high pregnancy outcome, 2-3x greater than "blind" transfer technique rates. Direct visualization provides an objective, visually confirmed, replicable technique for embryo transfer. The end result is less operator dependent and in contrast to routine ET techniques in which operator experience may account for the variable overall pregnancy rates (Garcia 2002). Hysteroscopic direct embryo delivery may circumvent many of the known and previously reported embryo transfer related factors associated with poor outcomes. Many

of our patients had failed prior IVF-ET attempts due to multiple etiologies.

Fig. 2. The flexible catheter for embryo delivery (Precision Reproduction, LLC. LA, CA USA) A light weight flexible minihysteroscope was used for visualization of the endometrial cavity (Figure 1d) (Storz®, LA, CA USA). The scope incorporates a flexible distal end of 3mm in diameter with a straight through operating channel. In addition, the optic filter is directly connected to a light source, decreasing the weight of the scope and giving a better
