To the Editor:
We read the Modern Trends paper by Mains and Van Voorhis (1) in the August issue on “Optimizing the technique of embryo transfer” with great interest. Mains and Van Voorhis eloquently reviewed the evidence that certain methods in the embryo transfer (ET) are associated with improved outcomes after IVF, dispelling the historical notion that ET is an unimportant variable in the success of an ART treatment cycle (1). As such, they contend that there is no consensus on the optimal technique of ET.
The application of ultrasound guidance to ET has been described in more than 150 clinical trials, including 20 randomized clinical trials and three meta-analyses, including the most recent Cochrane review (2). These studies suggest that ultrasound-guided (UG) ET provides a benefit with respect to increases in pregnancy rates compared to blind, clinical touch method and is a critical factor in optimizing outcomes. It has been suggested that the ultrasound confirms the position of the tip of ET catheter and site of embryo deposition within the uterine cavity, increases the frequency of easy ETs, and avoids endometrial indentation. Most importantly, others argue that it allows for standardization of the transfer technique between physicians, thus minimizing variation.
They also suggest that UG-ET using transvaginal (TV) ultrasound has encouraging results, though most studies have utilized transabdominal (TA) UG-ET approach. This typically requires a full bladder carrying potential for cramping, which could impact on outcomes. In addition, TAS-guided ET also necessitates assistance to help with the ultrasound or placement of the embryo catheter. In contrast, TV-UG-ET does not require a full bladder, gives greater resolution of the utero-cervical angle, and can more clearly delineate the catheter tip than TAUG-ET.
TVUG-ET was originally reported by Hurley et al. (3) and subsequently in a few retrospective studies reporting improved outcomes (4-6). A recent, randomized trial directly compared TA and TVUG-ET, demonstrating no differences in overall pregnancy, clinical pregnancy, live-birth and implantation rates when randomized to either group (7).
While there were study limitations, the severely anteflexed uterus and multiparity seemed better served with a TAUG-ET as the bladder tended to straighten the cervico-uterine angle. Conversely, the retroflexed uterus appeared to be better served with a TVUG-ET. Lastly, a pre-transfer ultrasound the day of the ET (much like a mock-ET) served as a guide to decide the optimal ultrasound approach, particularly with hyperstimulated ovaries that may alter cervico-uterine angle following oocyte retrieval.
We wholeheartedly endorse the contention by Mains and Van Voorhis that a concerted attention to the embryo transfer technique is an important determinant of IVF success. Identifying the optimal approach (TA versus TV) to ultrasound-guided ET may further improve outcomes. Well-designed studies should address the optimal ultrasound approach with respect to extremes in transfer difficulty, uterine position, and degree of bladder distension that may further improve clinical outcomes.
Steven R. Lindheim, M.D.
Krystene DiPaola, M.D.
Department of Obstetrics and Gynecology
University of Cincinnati College of Medicine
1. Mains L, Van Voorhis BJ Optimizing the technique of embryo transfer Fertil Steril 2010;94(3):785-790.
2. Brown JA, Buckingham K, Abou-SettaA, Buckett W. Ultrasound versus “clinical touch” for catheter huidance during embryo transfer in women [review]. The Cochrane Database Syst Rev 2010; Jan 20(1):CD006107.
3. Hurley VA, Osborn JC, Leoni MA, et al. Ultrasound-guided embryo transfer: a controlled trial. Fertil Steril 1991;55:559-62.
4. Lindheim SR, Cohen MA, Sauer MV. Ultrasound guided embryo transfer significantly improves pregnancy rates in women undergoing oocyte donation. Int J Gynecol Obstet 1999;66:281-4.
5. Anderson RE, Nugent NL, Gregg AT, Nunn SL, Behr BR. Transvaginal ultrasound guided embryo transfer improves outcomes in patients with failed IVF cycles. Fertil Steril 2002;77:769-775.
6. Kojima K, Nomiyama M, Kumamoto T, Matsumoto Y, Iwasaka T. Transvaginal ultrasound guided-guided embryo transfer improves pregnancy and implantation rates after IVF. Hum Reprod 2001;16:2578-82.
7. Porat N, Boehnlein LM, Schouweiler CM, Kang J, Lindheim SR. Interim analysis of a randomized clinical trial comparing abdominal versus transvaginal ultrasound-guided embryo transfer. J Obstet Gynaecol Res. 2010 Apr;36(2):384-92.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2010.09.055
Response to Optimizing the Technique of Embryo Transfer
To the Editor:
I read with interest the article of Main and Van Voorhis, in which the authors managed to incorporate in few pages the up-to-date knowledge of the embryo transfer technique (1). I would like to make some comments in an effort to help their intention to improve it.
Minor doubt can be cast on the 3 factors influencing embryo transfer “success”: embryo quality, endometrial receptivity and the transfer technique itself. As much interest has been focused on the improvement of the first 2 – not managing to raise outcomes significantly – it is now logical for the 3rd to draw scientific attention as the mostly provider-related determinant of IVF success. It has changed little over the years, probably because there are few to change, but the attention has not been that little: for example, mostly senior staff are practicing it and, most importantly, educational organizations have implemented it in their training programs as a separate module from “Assisted Conception” (2).
Authors more than sufficiently mark the importance of confounding variables of the technique success, triggering reader’s curiosity to form a couple of questions: can everybody perform the transfers and is a standard technique appropriate for all or do particular patients need adapted technique?
The provider’s factor has been emphasized long ago (3,4). Experienced physicians performing transfers according to a standardized method is the norm (5), currently accepted and eminently sensible, although robust data to support it are missing; nursing staff is an alternative (6, 7). Moreover, I have to point a strange phenomenon, even in the absence of published data, of cases in private practice that the “personal, not expert, gynecologist” performs transfers for “professional or communication reasons.” The rule here has to be clear: certified or at least properly trained medical staff should perform this most crucial step in an IVF cycle. Additionally, adequate training has to be ascertained by the IVF Units and/or related authorities.
Although truly randomized trials are difficult to recruit to in investigating alternative approaches and “old-fashioned” techniques are merely passed down to trainees, there are some algorithms in existence (8), which unfortunately have been few and are not universally accepted. What appears logically essential is for example a combination of pre-procedure evaluation of the patient’s physical history and anatomy and prediction of a subsequent potential difficulty, and ability to determine if alternative strategies are necessary. The strict follow-up of standarized procedures perfectly fitted on the patient’s needs may not induce the much-desired statistical significance but, at this point, results will be quite close to semantics.
Reviewing the literature trying to identify factors to significantly affect the ability of an embryo to transform into a child, the reader will be most probably disappointed: there are so many. Building up strict intervention algorithms, certified training and adequate maintenance of the providers’ skills and individualization according to and based on each Unit dynamics and previous success rates and mainly patient’s needs could be the next steps from the present, until more robust evidence changes the technique substantially.
Charalampos Siristatidis, Ph.D.
University of Athens
3rd Department of Obstetrics & Gynecology
1. Mains L, Van Voorhis BJ. Optimizing the technique of embryo transfer. Fertil Steril 2010;94:785-90.
3. Karande VC, Morris R, Chapman C, Rinehart J, Gleicher N. Impact of the “physician factor” on pregnancy rates in a large assisted reproductive technology program: do too many cooks spoil the broth? Fertil Steril 1999;71:1001–9.
4. Hearns-Stokes RM, Miller BT, Scott L, Creuss D, Chakraborty RK, Segars JH. Pregnancy rates after embryo transfer depend on the provider at embryo transfer. Fertil Steril 2000;74:80–6.
5. van Weering HG, Schats R, McDonnell J, Hompes PG. Ongoing pregnancy rates in in vitro fertilization are not dependent on the physician performing the embryo transfer. Fertil Steril 2005;83:316-20.
6. Barber D, Egan D, Ross C, Evans B, Barlow D. Nurses performing embryo transfer: successful outcome of in-vitro fertilization. Hum Reprod 1996;11:105–8.
7. Sinclair L, Morgan C, Lashen H, Afnan M, Sharif K. Nurses performing embryo transfer: the development and results of the Birmingham experience. Hum Reprod 1998; 13:699-702.
8. Schoolcraft WB, Surrey ES, Gardner DK. Embryo transfer: techniques and variables affecting success. Fertil Steril 2001;76:863-70.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2010.09.057
Other Alternatives for Difficult Embryo Transfer
In the August 2010 (Vol. 94, #3) journal, Mains and Van Voorhis present a well-documented review on embryo transfer. Surprisingly, they do not include ultrasound-guided transfer in their recommendations. Personal and institutional experience as well as enough evidence suggest it should only be done this way. Aspiration of cervical mucus is controversial. Our center made a comparison between both alternatives and no difference was found.
Also, they make no reference to tubal transfers. Although GIFT has been surpassed by conventional IFV in the last decade, when patent tubes are present (a large majority of current IVF cycles), tubal transfer of pronucleate oocytes or early embryos is an excellent option in cases of difficult cervical procedures, as published by authors from our center (IFER – Instituto de Ginecología y Fertilidad).
Edgardo D. Rolla, M.D.
Associated Physician/Director of Publications
IFER – Instituto de Ginecología y Fertilidad
Buenos Aires, Argentina
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2010.09.056
The Authors Respond:
We appreciate the interest in our review article. We agree with Dr. Rolla and Drs. Lindheim and DiPaola that ultrasound guidance has been shown to improve pregnancy rates with embryo transfer. Indeed, use of ultrasound guidance was one of our three evidence-based guidelines that we summarized at the conclusion of the manuscript. Although not yet proven by clinical trials, the use of transvaginal ultrasound guidance for embryo transfer may have some benefit for certain patients, particularly those with a retroflexed uterus. We appreciate these comments by Drs. Lindheim and DiPaola and agree that further study of transvaginal ultrasound for embryo transfer is indicated.
As with any procedure, we agree with Dr. Siristatiditis about the importance of experience with embryo transfer. The practitioner does not necessarily need to be a physician as evidenced by successful embryo transfers performed by nurses. However, the practitioner should be well versed in performing the manipulations necessary to achieve an atraumatic embryo transfer even when difficulties arise. Because the large majority of embryo transfers are relatively easy and occur without incident, many transfers must be done such that the rare, difficult case has been dealt with several times. We also agree that patients will benefit by individualization of care, especially when a difficult transfer is expected by the mock transfer. When transcervical transfer is impossible, laparoscopic transfer of embryos to the fallopian tubes is a viable alternative to transcervical transfer as mentioned in our paper.
We appreciate the interest and discussion that our paper has generated and hope that this spurs further improvements in this critical area contributing to the success of IVF for our patients.
Bradley J. Van Voorhis, M.D.
University of Iowa Carver College of Medicine
Department of Obstetrics & Gynecology
Iowa City, Iowa
Lindsay Mains, M.D.
Audubon Fertility & Reproductive Medicine
New Orleans, Louisiana
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2010.09.058