FERTILITY AND STERILI~

Copyright B 1997 American Society for Reproductive Medicine

Published by Elsevier Science Inc.

Reply to the Reply on IUI

To the Editor:

We read with surprise the recent Letter-to-the- Editor by Karande et al (1) in regard to a report by our team on a new technique of tubal sperm perfu- sion (2). Their letter was supposed to reply to our original Letter-to-the-Editor (3), which aimed at an- alyzing some of the possible reasons for the frank discrepancy between their results (41, obtained with a new method for IUI inadequately called tubal sperm perfusion by these authors, and our own (2).

We cannot accept the strange accusations brought by Karande et al. against the reliability of our data, suggesting that a “relationship between authors and the device maker” could explain the twofold higher PRs obtained with our tubal sperm perfusion method in comparison to standard IUI (1). These authors clumsily add that data reported by others are “much more credible” than ours, which are “un- realistic” in that we have selected “an unusually fer- tile infertility population” (1). We would like to make clear three points, First, these authors are expressly invited to consult our files and verify the authentic- ity of our results. Second, we have stated in our arti- cle that the patients included in the trial have been carefully selected according to strict inclusion and exclusion criteria to reduce the possible influence of confounding variables (2). Yet, the duration of infer- tility ranged from 2 to 6 years in that series (2). This design explains the overall high PRs obtained and stresses that the 2:l ratio between tubal sperm per- fusion and standard IUI PRs is likely to be technique related. Finally, it is sorrowful to observe that Ka- rande et al. did not notice that both insemination methods have been performed with devices provided by the same “device maker,” namely, the FAST Sys- tem (CCD Laboratories, Paris, France) and the Fryd- man’s Catheter (CCD Laboratories, Paris, France), information that disables by itself any commercial interest of this laboratory in the results of the our study.

In the last two paragraphs of their letter, we could finally welcome Karande et al. back again to the scientific discussion. These authors refuse here to understand why tubal sperm perfusion requires cer- vical seal and pressure injection and that this might be the key point for its success. They recognize that

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Vol. 67, No. 6, June 1997

Printed on acid-free paper in U. S. A

they are “unaware of any literature” that would sup- port this. We would like, therefore, to invite Karande et al. to read the first paragraph of the Discussion of the paper by T.C. Li (5) more carefully. Yet, all three reported techniques for tubal sperm perfusion judged it pertinent to achieve a cervical seal to avoid sperm reflux and to improve sperm concentration in the Fallopian tubes. Furthermore, it is very impres- sive that, in their “own radiogynecologic experience,” Karande et al. have been performing hysterosalpin- gography according to the same technique used in their reported “high-volume-slow-release IUI.” If one considers the virtual lack of pressure of their system and the unavoidable reflux . . . What a waste of contrast material!

Ultimately, as it has been stated in our letter of October 1995 (3), we would like to confirm that, in 556 controlled ovarian hyperstimulation cycles un- dertaken in an unselected infertile population in our Institution between November 1993 and October 1995, the 2:l ratio between tubal sperm perfusion (n = 290) and standard IUI (n = 266) on clinical (20.3% versus 9.7%, respectively, P < 0.011 and on- going (18.1% versus 8.5%, respectively, P < 0.01) PRs persisted, confirming the clear trend for a better effectiveness of the new artificial insemination method. At the present time, all IUI candidates are being treated routinely by tubal sperm perfusion in our Institution.

Renato Fcznchin, M.D. Franqois Olivennes, M.D. Claudia Righini, M.D. Rem? Frydman, M.D. Department of Obstetrics and Gynecology Hdpital Antoine B&?dre Clamart, France August 1, 1996

REFERENCES

Karande VC, Rao R, Pratt DE, Balin M, Levrant S, Morris R, Dudkeiwicz A, Gleicher N. The efficacy of “Tubal Sperm Perfusion?” [Letter]. Fertil Steril 1996;66:169-70. Fanchin R, Olivennes F, Righini C, Hazout A, Schwab B, Frydman R. A new system for fallopian sperm perfusion leads to pregnancy rates twice as high as intrauterine insemina- tion. Fertil Steril 1995;64:505-10. Fanchin R, Olivennes F, Righini C, Frydman R. The efficacy of “Tubal Sperm Perfusion?” [Letter]. Fertil Steril 1996; 66:169.

00150282/97/$17.00 PI1 SO0150282(97)0058-7

Rarande VC, Rao R, Pratt DE, Balin M, Levrant S, Morris R, Dudkeiwicz A, Gleicher N. A randomized prospective com- parison between intrauterine insemination and fallopian sperm perfusion for the treatment of infertility. Fertil Steril 1995;64:638-40. Li TC. A simple, non-invasive method of Fallopian tube sperm perfusion. Hum Reprod 1993;8:1848-50.

Reply of the Authors:

We appreciate the opportunity to respond to the letter “in response” by Fanchin et al. At the same time we do not wish to enter into “polemics” with these authors as to their subjective interpretation of our response to their letter to the editor in which they disputed results from our sperm perfusion study (1).

Whether the authors wish to acknowledge it or not, a commercial relationship with a device manu- facturer consciously or subconsciously can affect a study in many ways. We did not imply that this was the case here, rather, we raised the issue as one possible explanation for the discrepancy of results. As a side note, the fact that different devices from the same manufacurer were used in perfusion as well as IUI groups was noted. This does not disqual- ify our comment because why would anybody use a more costly device for IUI when the procedure can be done with basically any catheter at almost no cost? The potential motivation of any interested party in an outcome in favor of perfusion (and, there- fore, device use> is thus maintained. The authors’ obvious polemic in regard to this issue further vali- dates our inclusion of this matter in our earlier re- sponse and confirms it as a relevant part of a scien- tific discussion.

Finally, and most importantly, the main point of our earlier reply was that the most likely cause for the outcome difference between these two random- ized studies probably lies in patient selection. To obtain contradictory results in randomized studies is not uncommon in medicine. We cannot change our outcome as they cannot change theirs. Whatever the cause(s) for this discrepancy, in our hands and under our model fallopian, sperm perfusion does not in- crease pregnancy rates. Fanchin et al. obviously be- lieve that in their hands, using their model, it works. As so often in medicine, only time will tell!

Vishvanath C. Karande, M.D. Ramaa Rao, M.D. Donna E. Pratt, M.D. Martin Balin, M.D. Seth Levrant, M.D. Randy Morris, M.D. Alan Dudkiewicz, Ph.D. Norbert Gleicher, M.D. The Center for Human Reproduction Chicago, Illinois January 15, 1997

REFERENCES

The authors also misinterpret our gynecoradio- logic experience, which is widely published. All gyne- coradiologic procedures are, in fact, performed with catheters that prevent backflow of contrast by a vari- ety of balloon devices. It would exceed this letter format to go into any further detail, but the authors may obtain relevant references from a recently pub- lished review (2). They will discover in this literature that the resistance to flow into the fallopian tube (under normal tubal conditions) can be anywhere between 0 and approximately 250 mm Hg. No reflux occurs if contrast (or semen) is injected directly into the tube via a selective salpingography catheter. If the injection is transuterine, then reflux may be en- countered if the cavity is not occluded. However, such reflux will occur only rarely if cavity and fallo- pian tubes are normal and the injection pressure applied lies below the normal resistance of the fallo- pian tubes (< 250 mm Hg).

Rarande VC, Rao R, Pratt DE, Balin M, Levrant S, Morris R, Dudkiewicz A, Gleicher N. A randomized prospective com- parison between intrauterine insemination and fallopian and sperm perfusion for the treatment of infertility. Fertil Steril 1995;64:638-40. Gleicher N, Karande V. The diagnosis and treatment of proxi- mal tubal disease. Hum Reprod 1996; 11:1828-35.

Cause for Premature Luteinization?

To the Editor:

Ubaldi et al. (1) recently described the outcome of controlled ovarian hyperstimulation in 171 IVF-ET cycles performed with purified and recombinant FSH. They found that premature luteinization oc- curred in 13.4% of cycles and suggested that this may be due to FSH-induced increased LH receptivity in granulosa cells.

Of further interest is that fact that Fanchin et

Although this may be the case, I would like to suggest an alternative explanation. LH levels in the premature luteinization group of this study were in- creased, although not significantly; lack of statistical significance was likely due to the low number of pa-

Vol. 67, No. 6, June 1997 Letters-to-the-editor

al., in their initial comment to our paper, claimed a pregnancy rate of 40.1% per cycle. Their more recent letter, in contrast, reports on 556 patients with only a 20.31% pregnancy rate per cycle. Suffice to say, their most recent numbers are, interestingly, consid- erably closer to those reported by us than their origi- nal claims were.

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