‘The presence of blood in the transfer catheter negatively influences outcome at embryo transfer’

Karunakar Marikinti1 and Peter R. Brinsden2

1 Email: karunakar.marikinti{at}serono.com 2 Email: peter.r.brinsden{at}serono.com

Sir,

We read with interest the manuscript on the retrospective analysis of blood contamination of the embryo transfer catheter and its negative association with implantation and clinical pregnancy rates in assisted conception by Alvero et al. (2003)Go.

Our data suggest that, when the embryo transfer catheter is contaminated with blood at embryo transfer, there is a negative influence on pregnancy rates only when the transfers are difficult and no effect when the transfers are easy. We use the same technique for embryo transfer as Alvero and colleagues, except that we routinely try to remove cervical mucus and do not use ultrasound guidance for embryo transfer routinely. Blood or mucus contamination of the embryo transfer catheter is a regular occurrence, both after difficult and easy embryo transfers, but certainly more often after difficult transfers.

We wish to share our findings on the possible source of blood that contaminates the embryo transfer catheter based on our data from an ongoing observational study on hysteroscopic findings following mock embryo transfer (MET) in the luteal phase.

In the interim analysis of 34 cases (Marikinti et al., 2003aGo), we did not notice any endometrial bleeding into the uterine cavity following mock embryo transfer, although there were hysteroscopically visible traumatic lesions in the endometrium evident in 12 out of 31 cases as follows: sub-endometrial haemorrhage (n=5), endometrial grooving (n=4), vascular congestion (n=2), perforation of endometrium (n=1). There was no blood contamination of the MET catheter in any case and all the MET were easy.

Trauma to the endocervical mucosa was more common (18 out of 34 cases) following MET with the following findings: frank bleeding in seven, varying degrees of vascular congestion in 11. The MET catheter was contaminated with blood and/or mucus in four. Multiple passes even with a soft catheter, use of an outer sheath and or Allis forceps was frequently associated with mucosal bleeding from the endocervix but not from the endometrium. We have also reported (Marikinti et al., 2003bGo) a higher incidence of hysteroscopically visible anatomical abnormalities (23 out of 30) in the cervico-uterine canal (angulations, synechiae, false passages, cysts, polyps and hypertrophied endo-cervical mucosa) and a higher incidence bleeding from the endocervix following MET in those women who had a history of difficult embryo transfers.

In a similar but smaller study of 30 women following easy MET with a different but soft embryo transfer catheter, Murray et al. (2003)Go have reported the occurrence of moderate to severe endometrial damage, identified on hysteroscopy, in 37% of cases. They have also highlighted the lack of correlation between endometrial damage and degree of perceived difficulty of MET by the clinician. It is unclear from the report whether there was bleeding into the uterine cavity and whether there was blood contamination of MET catheter. We now have data from >100 hysteroscopies following MET and our findings clearly indicate that occult endocervical and endometrial trauma is common, even after easy MET, and that the presence of blood on the embryo transfer catheter represents only a small proportion of cases where there is actual bleeding into the cervical canal. The blood vessels underneath the cervical mucosa (which is relatively thinner than the endometrium in luteal phase) are distributed very superficially (even in the absence of inflammatory pathology) and are easily visible during hysteroscopic examination. This may explain their vulnerability to mechanical injury from the embryo transfer catheters, more so when the transfer warrants the use of an outer sheath, a stylet, a uterine sound, an os finder or multiple attempts. Unlike the cervical mucosa, luteal phase endometrium is thick and oedematous, with most of the superficial layers supplied by a sub-epithelial capillary plexus with sluggish blood flow (Rogers, 1996Go). This probably explains the occurrence of sub-endometrial haemorrhage and or grooving when there is trauma from the soft inner catheter. However, laceration of endometrium and bleeding into the endometrial cavity are likely to occur when a sharp device (such as the tip of the outer sheath) or other sharper material is used.

We believe that ultrasound-guided embryo transfer allows visualization of the tip of the catheter in relation to the depth of insertion, but is unlikely to prevent injury to the endometrium, which is caused by the impact and friction of the tip of the catheter on the endometrium. We have found endometrial lesions in the anterior uterine wall of women with retroverted uteri and in the posterior uterine wall of women with anteverted uteri. In addition, sub-endometrial haemorrhages were a common finding when there were polyps, polypoidal endometrium or submucus fibroids, and uterine anomalies such as septate uterus.

There are two possible explanations for the negative association of blood contamination and clinical pregnancy rates: (i) blood from the endocervix is drawn into the uterine cavity by the embryo transfer catheter and is deposited with the embryos, which may be detrimental to implantation; (ii) uterine contractions (Fanchin et al., 1998Go) and junctional zone contractions (Lesny et al., 1999Go) that have been shown to be associated with difficult embryo transfers may contribute to the reduced pregnancy rates by displacing or expelling the embryos, and the blood (from the cervix) contamination of the embryo transfer catheter in such cases is only a marker of difficult or traumatic embryo transfers.

References

Alvero R, Hearns-Stokes RM, Catherino WH, Leondires MP, Segars JH (2003) The presence of blood in the transfer catheter negatively influences outcome at embryo transfer. Hum Reprod 18, 1848–52.[Abstract/Free Full Text]

Fanchin R, Righini C, Olivennes F, de Zeigler D and Frydman R (1998) Uterine contractions at the time of embryo transfe alter pregnancy rates after in-vitro fertilization. Hum Reprod 13, 1968–1974.[Abstract]

Lesny P, Killick SR, Robinson J, Raven G and Maguiness SD (1999) Junctional zone contractions and embryo transfer: is it safe to use a tenaculum? Hum Reprod 14, 2367–2370.[Abstract/Free Full Text]

Marikinti K, Mathews T, Shuter S and Brinsden P (2003a) Hysteroscopic findings after mock embryo transfer. Hum Reprod 18 (Suppl 1), 139–140. (P413).

Marikinti K, Mathews T, Ball J and Brinsden P (2003b) Ultrasound and hysteroscopic findings in women with a history of difficult embryo transfers. Fertil Steril 80 (Suppl 3),125(P-12). Abstracts of the Scientific Oral and Poster Sessions Programme Supplement. 59th Annual meeting of the ASRM.

Murray AS, Healy DL and Rombauts L (2003) Embryo transfer: hysteroscopic assessment of transfer catheter effects on the endometrium. Reprod Biomed Online 7, 583–586.[Medline]

Rogers AW (1996) Structure and function of endometrial blood vessels. Hum Reprod Update 2, 57–62.[Abstract/Free Full Text]

Submitted on November 10, 2004; accepted on January 24, 2005.





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