Reply of the Authors

Preoperative treatment for hysteroscopic surgery To the Editor: We want to comment on the article by Triolo et al. (1). We congratulate the authors for their contribution to the relevant literature. Hysteroscopic surgery is a commonly used surgical treatment method in the management of endometrial pathologies. It is not only used in pathologies, such as endometrial polyp or myomas, but also in Müllerian anomalies such as uterine septum; it is also an alternative to hysterectomy in menometrorrhagias amenable to medical treatment. As stated in the authors’ study, some agents can be used for pretreatment to ease the surgical procedure and to enable postoperative effectivity (1). Several studies have been performed to evaluate the effectivity of these agents. The most studied agents are GnRHanalogue (GnRH-a) danazol, and progesterone derivatives. In this study, the authors state that gestrinone pretreatment is effective (1). In the literature, endometrial polyps ⬎2 cm (2), myomas ⬎3 cm, with or without an intramural component, and vaginal bleeding causing anemia reportedly benefit from pretreatment (3). On the contrary, numerous reports state the ineffectivity or even disadvantages of pretreatment (4). Postoperative long-term amenorrhea secondary to pretreatment is a serious handicap, especially in infertile patients. In some studies, pretreatment reportedly lacks a positive effect on short- and long-term results, causes difficulties in cervical dilatation, and lengthens the operation time for hysteroscopic myomectomy candidates (5). Pretreatment is reportedly unnecessary, even for patients who will undergo hysteroscopic endometrial resection (4). In conclusion, it is important to set the criteria to determine the patients who are likely to benefit from pretreatment before hysteroscopic surgery. Using these criteria, pretreatment will only be given to the suitable patients, and overtreatment will be prevented. Fatma Bahar Cebesoy, M.D. Irfan Kutlar, M.D. Obstetrics and Gynecology Gaziantep University Gaziantep, Turkey May 10, 2006

REFERENCES 1. Triolo O, De Vivo A, Benedetto V, Falcone S, Antico F. Gestrinone versus danazol as preoperative treatment for hysteroscopic surgery: a prospective, randomized evaluation. Fertil Steril 2006;85(4):1027–31.

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Letters to the Editor

2. Porreca MR, Pansini N, Bettocchi S, Loverro G, Selvaggi L. Hysteroscopic polypectomy in the office without anesthesia. J Am Assoc Gynecol Laparosc 1996;3(Suppl 4):S40. 3. Romer T. Benefit of GnRH analogue pretreatment for hysteroscopic surgery in patients with bleeding disorders. Gynecol Obstet Invest 1998; 45(Suppl 1):12–20. 4. Rai VS, Gillmer MD, Gray W. Is endometrial pre-treatment of value in improving the outcome of transcervical resection of the endometrium? Hum Reprod 2000;15(9):1989 –92. 5. Campo S, Campo V, Gambadauro P. Short-term and long-term results of resectoscopic myomectomy with and without pretreatment with GnRH analogs in premenopausal women. Acta Obstet Gynecol Scand 2005; 84(8):756 – 60.

doi:10.1016/j.fertnstert.2006.06.004 Reply of the Authors We thank Dr. Cebesoy and Dr. Kutlar for appreciating our randomized evaluation of gestrinone and danazol as pretreatment for hysteroscopic surgery (1). As reported in our article, we agree with their opinion that polyps ⬎2 cm and myomas ⬎3 cm benefit from a long-term pretreatment to either reduce the thickness of the endometrium and its vascularity or to decrease the size of endouterine pathologies. However, because lesions with these characteristics had been excluded from our series, a short-term pretreatment (4 –5 weeks instead of 2–3 months) was considered more useful and adequate to obtain a good preparation of the endometrium, thus avoiding side effects and preventing over treatment. The short-term pretreatment and the administration of gestrinone—a drug that had not been used for this scope— make our study incomparable with previous studies conducted on the basis of long-term GnRH-analogue (GnRH-a) or danazol treatments. These two factors may justify the discordant findings, such as the absence of long-term amenorrhea secondary to pretreatment and the absence of difficulty in cervical dilatation, as reported in other studies (2, 3). Gestrinone, with its antiestrogenic activity, may determine endometrial atrophy and inhibition of ovulation, but it does not completely abolish ovarian steroidogenesis like danazol (4). The mean serums of LH, FSH, PRL, androstendione, and DHEAS do not change during gestrinone treatment, and this may guarantee normal posttreatment endocrine function (4). Nevertheless, the cited study conducted by Rai et al. (3) also reported a nonsignificant difference in the amenorrhea rate among pretreated women and untreated patients. Although no improvements in short- and long-term clinical outcomes were reported (2–3, 5), other benefits, such as a decreased fluid absorption, a reduced operating time, and better operative conditions, which were the main objectives of our study, were widely confirmed in the literature (1, 5). Moreover, our data suggest that a short gestrinone pretreatment appears to offer some advantages in terms of dosage (twice weekly), surgical time, incidence of hemorrhage, volume of infusion liquid, and side effects. Given these results, this kind of preparation could always be taken into consideration before hysterVol. 86, No. 4, October 2006

oscopic surgery. Nonetheless, further studies are necessary to set possible criteria that would distinguish patients who need gestrinone-based treatments from patients who can directly undergo operative hysteroscopies. Onofrio Triolo, M.D. Antonio De Vivo, M.D. Vincenzo Benedetto, M.D. Salvatore Falcone, M.D. Francesco Antico, M.D. Department of Gynecological, Obstetrical Sciences and Reproductive Medicine University Hospital “G. Martino” Messina, Italy June 1, 2006

REFERENCES 1. Triolo O, De Vivo A, Benedetto V, Falcone S, Antico, F. Gestrinone versus danazol as preoperative treatment for hysteroscopic surgery: a prospective, randomized evaluation. Fertil Steril 2006;85:1027–31. 2. Rai VS, Gillmer MD, Gray W. Is endometrial pre-treatment of value in improving the outcome of transcervical resection of the endometrium? Hum Reprod 2000;15:1989 –92. 3. Campo S, Campo V, Gambadauro P. Short-term and long-term results of resectoscopic myomectomy with and without pre-treatment with GnRH analogs in premenopausal women. Acta Obstet Gynecol Scand 2005;84: 756 – 60. 4. Venturini PL, Bertolini S, Brunenghi MCM, Daga A, Fasce V, Marcenaro A, et al. Endocrine, metabolic, and clinical effects of gestrinone in women with endometriosis. Fertil Steril 1989;52:589 –95. 5. Kriplani A, Manchanda R, Nath J, Takkar D. A randomized trial of danazol pretreatment prior to endometrial resection. Eur J Obstet Gynecol Reprod Biol 2002;103:68 –71.

doi:10.1016/j.fertnstert.2006.06.005

The authors suggest from this article that DNA fragmentation is a significant finding to warrant evaluation with a sperm analysis in patients with infertility. We would appreciate answers from the authors to the following questions, which are disturbing in this article: 1. If the varicocele leads to a decrease in testicular size, why do patients with varicocele have only a decrease in the size of the left testicle and not the right testicle compared with controls? 2. The issue is also DNA fragmentation, as a result of the varicocele. We wonder if the authors took into consideration other aspects that lead to DNA changes, including smoking, marijuana use, various drugs, alcohol, and febrile illnesses. These were not mentioned in the exclusion criteria cited in the article. 3. The number of patients (20) included in this study and a control group of 20 may not be a high enough number to give the study a strong enough statistical power to draw such conclusions. This also affects the various group numbers, which makes it very, very small for any reasonable conclusions. Shawky Z.A. Badawy, M.D. Frances Shue, M.D. Kazim Chohan, Ph.D. Brian Hearn, M.D. Division of Reproductive Endocrinology and Infertility SUNY Upstate Medical University Syracuse, New York April 25, 2006

REFERENCE 1. Bertolla RP, Cedenho AP, Hassun Filho PA, Lima SB, Ortiz V, Srougi M. Sperm nuclear DNA fragmentation in adolescents with varicocele. Fertil Steril 2006;85(3):625– 8.

Varicoceles and sperm nuclear fragmentation?

doi:10.1016/j.fertnstert.2006.05.005

To the Editor: The authors of this article (1) evaluated 20 patients with bilateral varicoceles, as documented by clinical evaluation by one of the authors, and 20 patients without varicoceles. Both groups of patients were between 15 and 17 years old. These patients were between Tanner stages IV and V. The exclusion criteria included urogenital diseases, leukocytospermia, and current or previous systemic diseases that would lead to testicular alterations, such as cancer, chemotherapy, and endocrinopathies. The results showed a higher percentage of cells with no DNA fragmentation in the nonvaricocele group, compared with the varicocele group. The percentage for the varicocele group was higher for classes I, III, and IV. The results additionally indicated that there is a decrease in the size of the left testicle; however, there was no decrease in the size of the right testicle compared with the controls. Fertility and Sterility姞

Reply of the Authors: We appreciate Drs. Badawy, Shue, Chohan, and Hearn’s interest in our article. However, we would like to clarify a few of their concerns regarding our study and interpretations that may derive thereof. Our study concludes that although varicocele causes a progressive decrease in sperm characteristics, DNA fragmentation increases at an early age, suggesting that DNA fragmentation evaluation could be an important factor in deciding treatment options for adolescent patients (1). We do not conclude from this study that DNA fragmentation should be assessed in patients undergoing infertility evaluation, as stated in the letter. In addition, the percentage of DNA fragmentation was higher for classes III and IV (high DNA 1031