Letter to the editor regarding “The status of public reporting of clinical outcomes in assisted reproductive technology”

23 07 2013

To the Editor:

We commend Kushnir et al. for their detailed analysis of the publicly available Society for Assisted Reproductive Technology (SART) report in the article “The status of public reporting of clinical outcomes in assisted reproductive technology” (1). SART continues to believe that any use of the ART report to make direct comparisons of outcomes between clinics is not valid and is inappropriate. The goal of the report is to facilitate reasonable estimation of the success rate at a given clinic. Unfortunately, recent evolution of clinical practice has made the reasonable estimation of success per cycle start much more difficult.

The exclusion of “banking” cycles from the denominator of the report is an unintended consequence of our common sense handling of true “fertility preservation” cycles. The outcomes report would be misleading if it included cycles with no intention for embryo transfer in the near future (for example, cycles conducted to obtain eggs or embryos prior to chemotherapy). SART has identified the need to distinguish fertility preservation from “short-term” banking. The indications for short-term banking (such as PGD, endometrial receptivity) are outlined in the manuscript; however, other indications for short-term banking exist (for example, risk for OHSS, polyps, etc.). We fully agree that the outcomes of these cycles should be accounted for in the Clinic Summary Report. The SART Registry Committee and SART Executive Council have discussed this at length, and we have sought input from our members. We do not believe that simply indicating the number of embryo banking cycles is adequate. SART has met with the Centers for Disease Control and Prevention (CDC), with whom we have a long-standing collaboration, to discuss what our options are for including banked cycles in outcome reports. Read the rest of this entry »





Letter to the editor on “Trophectoderm grade predicts outcomes of single-blastocyst transfers”

23 07 2013

To the Editor:

Hill and colleagues (1) and others (2) found that trophectoderm morphology grading but not inner cell mass morphology grading significantly correlated with implantation and live birth after single-blastocyst transfer. This could reflect a positive embryonic condition in the interaction with the endometrium at the implantation site. In this respect our findings on the localization of prostaglandin H (PGH) synthase or cyclooxygenase, the key enzyme in prostaglandin synthesis, in the preimplantation mouse embryo might be of interest (2). Intracytoplasmic PGH synthase, localized in the endoplasmic reticulum, was found from the two-cell stage onward. In the blastocyst, PGH synthase was abundant in the trophectoderm, but only minimal background activity was observed in the inner cell mass. The involvement of prostaglandins in the interaction between embryo and endometrium at the time of human implantation has been established (3).

Robin M. F. van der Weiden, M.D., Ph.D.
Sint Franciscus Gasthuis, Department of Obstetrics and Gynecology, Rotterdam, The Netherlands

References

1. Hill MJ, Richter KS, Heitmann RJ, Graham JR, Tucker MJ, DeCherney AH, et al. Trophectoderm grade predicts outcomes of single-blastocyt transfers. Fertil Steril 2013;99:1283-9.

2. Ahlström A, Westin C, Reismer E, Wikland M, Hardarson T. Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer. Hum Reprod 2011;26:3289-96.

3. Van der Weiden RMF, Wisse LJ, Helmerhorst FM, Keirse MJNC, Poelmann RE. Immunohistochemical and ultrastructural localization of prostaglandin H synthase in the preimplantation mouse embryo. J Reprod Fert 1996;107:161-6.

4. Van der Weiden RMF, Helmerhorst FM, Keise MJNC. Influence of prostaglandins and platelet activating factor on implantation. Hum Reprod 1991;6:436-42.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.07.1986

The authors respond:

We read with interest the comments of Dr. van der Weiden in regard to our recent publication demonstrating that trophectoderm morphologic grading was significantly correlated with implantation and live birth in single-blastocyst transfers (1). We agree that favorable trophectoderm morphology likely reflects embryonic capacity to interact with the endometrium and thus results in improved implantation. It is known that the trophectoderm is actively involved in implantation and produces numerous compounds including hCG, progestamedins, inteferons, and, as Dr. van der Weiden suggests, prostaglandin synthesis, all of which modulate embryonic-endometrial communication (2). The trophectoderm morphology has also been correlated with aneuploidy, is the first occurring specialized tissue distinguished from the embryo mass, and may be a more static measure than the assessment of the inner cell mass (3). It remains to be determined whether trophectoderm morphology is more accurately assessing trophectoderm function or aneuploidy or both. While assessing the mechanisms of the interaction between the endometrium and the trophectoderm was not the focus of our work, it would be reasonable to speculate that favorable morphologic characteristics of the trophectoderm would reflect improved biochemical function of the trophectoderm, including the production of prostaglandin H synthase and the importance of prostaglandins in human implantation and thus result in improved pregnancy outcomes (4, 5).

Micah J. Hill, D.O.a
Ryan J. Heitmann, D.O.a
Eric D. Levens, M.D.b
a Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
b Shady Grove Fertility Reproductive Science Center, Rockville, Maryland

References

1. Hill MJ, Richter KS, Heitmann RJ, Graham JR, Tucker MJ, DeCherney AH, Browne PE, Levens ED. Trophectoderm grade predicts outcomes of single blastocyt transfers. Fertil Steril 2013; 99: 1283-9.

2. Bazer FW, Spencer TE, Johnson GA, Burghardt RC, Wu G. Comparative aspects of implantation. Reprod 2009;138:195-209.

3. Krupinski P, Chickarmane V, Peterson C. Simulating the mammalian blastocyst- molecular and mechanical interactions pattern the embryo. PLoS Comput Biol 2011;7: e1001128.

4. Van der Weiden RMF, Wisse LJ, Helmerhorst FM, Keirse MJNC, Poelmann RE. Immunohistochemical and ultrastructural localization of prostaglandin H synthase in the preimplantion mouse embryo. J Reprod Fert 1996; 107: 161-6.

5. Van der Weiden RMF, Helmerhorst FM, Keise MJNC. Influence of prostaglandins and platelet activating factor on implantation. Hum Reprod 1991; 6: 436-42.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.07.1989





Letter regarding Reflections on “Successful testicular sperm retrieval in adolescents with Klinefelter syndrome treated with at least 1 year of topical testosterone and aromatase inhibitor”

18 07 2013

To the Editor:

The authors thank Dr. Oates for his insightful comments (1) on our article, “Successful testicular sperm retrieval in adolescents with Klinefelter syndrome (KS) treated with at least 1 year of topical testosterone and aromatase inhibitor,” which summarize the key messages of the article (2). First of all, the goal of this study was not to advocate for the routine use of testosterone therapy in affected adolescents, and our results should not be used as this clinical approach in the absence of more data. Secondly, the study was not designed to compare rates of surgical sperm retrieval in adolescence versus adulthood, or in the setting of hormone therapy versus without it. And thirdly, the viability and utility of the retrieved and cryopreserved sperm remain to be determined. We acknowledge these limitations in the manuscript. Nevertheless, our results suggest that surgical sperm retrieval is possible in adolescents with KS, despite receiving treatment with aromatase inhibitor and topical testosterone therapy, offering additional information for patients interested in future fertility. Read the rest of this entry »





Letter regarding “Acupuncture—help, harm, or placebo?”

17 07 2013

To the Editors:

We read with interest the recent article, “Acupuncture—help, harm, or placebo?” by Meldrum et al. (1). We have one observation and one area of concern regarding the authors’ conclusions. The observation is focused on the dismissal of the efficacy of any impact of acupuncture on pregnancy rates as a placebo effect. First of all, the placebo effect is not to be taken lightly, and in fact may well be responsible for the efficacy of antidepressant medications, which appear to positively impact the psychological well-being of millions of Americans (2). Second, many of the randomized controlled trials on acupuncture do show a statistically significant impact on pregnancy rates. It is quite possible that acupuncture may only be effective with specific patient populations, analogous to assisted hatching (3). Finally, authors may influence the conclusions of any meta-analysis by shifting the criteria to include/exclude certain studies.

The area of concern is the recommendation, in the last paragraph, for patients to seek out education on lifestyle choices via a cited website rather than undergoing acupuncture treatment. There is a strong implication that the information provided on the website is more beneficial than acupuncture. It does not feel appropriate for an article in a peer-reviewed journal to be promoting a non-academic website. In addition, within the website are recommendations with links to purchase multiple products, including a wide range of supplements from a single manufacturer, such as fish oil, vitamin C, vitamin E, folic acid, green tea extract, and CoQ10, none of which have randomized controlled trials to support their efficacy to increase pregnancy rates in the infertile population. In the section on stress, the link is to a website that promotes a downloadable stress management program, which cites a pregnancy rate of 83%, despite the fact that there has never been a study utilizing the program. Read the rest of this entry »





Public reporting of clinical outcomes in assisted reproductive technology

10 07 2013

To the Editor:

We read the article “The status of public reporting of clinical outcomes in assisted reproductive technology” by Kushnir et al. (1) with great interest. As stewards of the National ART Surveillance System (NASS), we are always striving to improve data collection and public reporting of clinical outcomes of ART, as required by the Fertility Clinic Success Rates and Certification Act (FCSRCA) of 1992. The article refers to a recent but increasing trend of short-term embryo banking (cycles in which all embryos are created with the intent of cryopreservation for subsequent transfer in frozen/thawed cycle(s) in the next few months) following advances in cryopreservation techniques (2). Some of the potential reasons to delay embryo transfer include: embryo accumulation from several short-term embryo banking cycles to allow better choice of good-quality embryos, desire to avoid potentially negative effects of stimulation on implantation/pregnancy rates and fetal development, and need to wait for the results of preimplantation genetic screening. In contrast, long-term embryo banking cycles are generally used for fertility preservation for patients undergoing gonadotoxic medical treatments or for those who wish to delay childbearing for other reasons. Although NASS is currently unable to distinguish between short- and long-term banking cycles, we note that the total number and percent of embryo banking cycles in the U.S. has increased dramatically during recent years (Figure).

Click for larger view
Click for larger view

Since FCSRCA requires public reporting of ART success rates, embryo banking cycles (which by definition do not result in clinical outcome) are not shown in the national or clinic-specific pregnancy success rates tables. However, all embryo banking cycles fit the definition of ART and are required to be reported to the Centers for Disease Control and Prevention (CDC). Thus, we believe that the authors incorrectly assumed that embryo banking cycles are “unreported” or “excluded” by clinics. The outcomes of all frozen/thawed embryo transfers have been publicly reported for cycles started during or after 1995, the first year national ART surveillance began. In addition, reporting of embryo banking cycles is validated annually (3). Read the rest of this entry »





Biomarkers of endometriosis

8 07 2013

To the Editor:

We would like to thank Dr. Fassbender et al. for their fine article (1). The aim of the review study was to show the diagnostic performance of noninvasive or semi-invasive tests for endometriosis. This article provides an overview of various markers and their place in early detection. We greatly appreciated this paper, but there are also some other biomarkers that should be discussed.

Stem cell theory opens the latest advanced avenue for the etiology of many diseases, including endometriosis. Stem progenitor cells may serve as early markers and also detect recurrence. The endometrium contains endometrial/stem progenitor cells, and these stem cells are present in the peritoneal cavity in women that have retrograde menstruation. Bone marrow is another origin. Bone marrow mesenchymal stem cells (MSC) circulate to the endometrium and reprogram into the endometrial MSC. Positive immunostaining for stem cell markers such as CD9, CD34, c-Kit, Oct-4, Musashi-1 was detected in isolated epithelial and stromal cells in eutopic and ectopic endometrium (2). It has been reported that Oct-4 may stimulate the migration activity of endometrial cells (3). Moreover, these markers may also identify the patients that carry the risk of developing ovarian cancer. Read the rest of this entry »