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Successful pregnancy after four-step hysteroscopic technique for the treatment of atypical polypoid adenomyoma
stress condition, involved in both endometriosis and preeclampsia. Martina Montagnana, M.D.a Giuseppe Lippi, M.D.a Alessandro Albiero, M.D.b Massimo Franchi, M.D.b Cesare Gian Guidi, M.D.a a Sezione di Chimica Clinica, Dipartimento di Patologia, and b Unita` di Ostetricia, Dipartimento Materno ed Infantile Universita` di Verona, Verona, Italy February 4, 2008 REFERENCES 1. Lambrinoudaki IV, Augoulea A, Christodoulakos GE, Economou EV, Kaparos G, Kontoravdis A, et al. Measurable serum markers of oxidative stress response in women with endometriosis. Fertil Steril. Published online January 17, 2008. 2. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005;365: 785–99. 3. Patil SB, Kodliwadmath MV, Kodliwadmath SM. Role of lipid peroxidation and enzymatic antioxidants in pregnancy-induced hypertension. Clin Exp Obstet Gynecol 2007;34:239–41. 4. Gidenne S, Ceppa F, Fontan E, Perrier F, Burnat P. Analytical performance of the albumin cobalt binding (ACB) test on the Cobas MIRA Plus analyzer. Clin Chem Lab Med 2004;42:455–61. 5. Dery MA, Michaud MD, Richard DE. Hypoxia-inducible factor-1: regulation by hypoxic and non-hypoxic activators. Int J Biochem Cell Biol 2005;37:535–40. 6. Lippi G, Montagnana M, Guidi GC. Albumin cobalt binding and ischemia modified albumin generation: an endogenous response to ischemia? Int J Cardiol 2006;108:410–1.
doi:10.1016/j.fertnstert.2008.02.151
Reply of the Authors: We would like to thank Dr. Montagnana and her colleagues for their kind comments on our work (1). Ischemia modified albumin (IMA) is a new promising biomarker reflecting myocardial ischemia, which increases early in the process of acute coronary events and may thus contribute to an early and accurate diagnosis (2). Beyond ischemic cardiac events, however, IMA may increase in any condition associated with ischemia. Pregnancy per se is associated with increased circulating IMA levels. First trimester circulating IMA is significantly higher compared to nonpregnant controls, possibly due to ischemia induced by trophoblast development (3). Furthermore, fetal IMA from complicated deliveries is 50% higher compared to uneventful deliveries and may increase by more than 300% in cases of severe fetal hypoxia, serving thus as a biomarker of fetal distress (4). Preeclampsia is a severe obstetric complication posing serious threats to both mother and fetus. We read with great interest the results of Dr. Montagnana and her colleagues showing that preeclamptic women have higher circulating IMA compared to normotensive women. A clinical research protocol is currently in progress in our Department evaluating among other factors Fertility and Sterility
circulating IMA in preeclamptic women stratified by the severity of the hypertensive disease. The aim of the protocol is to identify circulating biomarkers that may serve as early diagnostic tests predicting subsequent development of hypertensive disease in pregnancy. Irene Lambrinoudaki, M.D.a George Kaparos, Ph.D.b Areti Augoulea, M.D.a Emmanuel Economou, Ph.D.b Maria Creatsa, M.D.a Konstantinos Papadias, M.D.a a Second Department of Obstetrics and Gynecology b Hormonal and Biochemical Laboratory University of Athens, Aretaieio Hospital Athens, Greece February 25, 2008 REFERENCES 1. Lambrinoudaki I, Augoulea A, Economou E, Kaparos G, Kontoravdis A, Papadias C, et al. Measurable serum markers of oxidative stress response in women with endometriosis. Fertil Steril. In press. 2. Lippi G, Montagnana M, Salvagno GL, Guidi GC. Potential value for new diagnostic markers in the early recognition of acute coronary syndromes. CJEM 2006;8:27–31. 3. Perfumo F, Gaze DC, Papageorghiou AT, Collinson PO, Thilaganathan B. First trimester maternal serum ischemia-modified albumin: a marker of hypoxia-ischemia-driven early trophoblast development. Hum Reprod 2007;22:2029–32. 4. Gugliucci A, Hermo R, Monroy C, Numaguchi M, Kimura S. Ischemiamodified albumin levels in cord blood: a case-control study in uncomplicated and complicated deliveries. Clin Chim Acta 2005;362:155–60.
doi:10.1016/j.fertnstert.2008.02.152 Successful pregnancy after four-step hysteroscopic technique for the treatment of atypical polypoid adenomyoma To the Editor: We read with interest the report by Wong et al. (1) describing the successful conservative management of a patient suffering from 5 years of primary infertility and persistent atypical polypoid adenomyoma (APA). The management proposed by the authors included a close surveillance of the APA by means of regular hysteroscopic examinations and uterine curettages (every 4–6 months) as well as the administration of the traditional Chinese herbal medication Danggui (Angelica sinensis), which acts as an ovulation inducer. Given the unfavorable outcome of the first pregnancy, lowdose aspirin was also administered to the patient as soon as she achieved her second pregnancy. Recently, we have reported an innovative hysteroscopic technique for the treatment of APA in a 35-year-old infertile woman desiring pregnancy (2). This technique includes four steps, each one being characterized by a pathological analysis: [1] the removal of the APA, [2] the removal of 1283
endometrium adjacent to the APA, [3] the removal of the myometrium underlying the APA, and [4] multiple random endometrial biopsies. Whenever any of the specimens collected from steps 2–4 is positive for neoplastic lesion, the conservative treatment should be converted into a radical approach (hysterectomy). Two months after the procedure, our patient achieved a pregnancy by means of a superovulation induction treatment (an injection containing FSH and hCG) and IVF. The gestation was complicated early on by moderate ovarian hyperstimulation syndrome, which was successfully treated with an inpatient regimen of bed rest, close fluid and electrolyte balance monitoring, and albumin infusions. Neither lowdose aspirin nor progestogen agents were administered during gestation. The course of her pregnancy was otherwise uncomplicated and terminated by a cesarean section performed at 39 weeks of gestation with the delivery of a healthy baby weighing 3850 g and with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. Follow-up hysteroscopic examinations with random biopsies performed 3 and 6 months later revealed a normal appearance of the uterus with neither visual nor pathological signs of APA. Our experience seems to suggest that the four-step approach is highly effective and convenient for the conservative treatment of APA in that it has three great advantages: [1] it provides for the complete removal of the lesion, [2] it saves most of the endometrium within the uterine cavity, and [3] it differentiates APA from endometrial carcinoma (EC) with myometrial invasion. In addition, we are firmly convinced that a diagnostic hysteroscopy with target-eye biopsy in an outpatient setting (without anesthesia) may be an adequate tool for the surveillance of such patients after surgery.
1284
Letters to the Editor
Furthermore, we believe that the blunt curettage should not be performed either for the surveillance or for the treatment of APA for two main reasons: [1] it has been well demonstrated that even when a direct visualization of the uterine cavity is available (as was the case reported by Wong et al.) focal lesions might be missed or not completely removed; and [2] the differential diagnosis between APA and EC with myometrial invasion may be difficult in a curettage specimen. Finally, we consider that blunt curettage should be avoided especially in patients with APA who desire pregnancy. Indeed, it cannot be excluded that the poor outcome of the first pregnancy achieved in the patient managed by Wong and colleagues might be related to the extensive damage to the endometrium from repeated blunt curettages. Guida Maurizio, M.D. Elena Greco, M.D. Attilio Di Spiezio Sardo, M.D. Costantino Di Carlo, M.D. Giada Lavitola, M.D. Francesco Tarsitano, M.D. Carmine Nappi, M.D. Departments of Gynaecology and Obstetrics and of Pathophysiology of Human Reproduction, University of Naples ‘‘Federico II,’’ Italy January 25, 2008 REFERENCES 1. Wong AY, Chan KS, Lau WL, Tang LC. Pregnancy outcome of a patient with atypical polypoid adenomyoma. Fertil Steril 2007;88: 1438.e7–9. 2. Di Spiezio Sardo A, Mazzon I, Gargano V, Di Carlo C, Guida M, Mignogna C, et al. Hysteroscopic treatment of atypical polypoid adenomyoma diagnosed incidentally in a young infertile woman. Fertil Steril 2008;89:456.e9–12.
doi:10.1016/j.fertnstert.2008.01.093
Vol. 89, No. 5, May 2008
doi:10.1016/j.fertnstert.2008.02.151
Reply of the Authors: We would like to thank Dr. Montagnana and her colleagues for their kind comments on our work (1). Ischemia modified albumin (IMA) is a new promising biomarker reflecting myocardial ischemia, which increases early in the process of acute coronary events and may thus contribute to an early and accurate diagnosis (2). Beyond ischemic cardiac events, however, IMA may increase in any condition associated with ischemia. Pregnancy per se is associated with increased circulating IMA levels. First trimester circulating IMA is significantly higher compared to nonpregnant controls, possibly due to ischemia induced by trophoblast development (3). Furthermore, fetal IMA from complicated deliveries is 50% higher compared to uneventful deliveries and may increase by more than 300% in cases of severe fetal hypoxia, serving thus as a biomarker of fetal distress (4). Preeclampsia is a severe obstetric complication posing serious threats to both mother and fetus. We read with great interest the results of Dr. Montagnana and her colleagues showing that preeclamptic women have higher circulating IMA compared to normotensive women. A clinical research protocol is currently in progress in our Department evaluating among other factors Fertility and Sterility
circulating IMA in preeclamptic women stratified by the severity of the hypertensive disease. The aim of the protocol is to identify circulating biomarkers that may serve as early diagnostic tests predicting subsequent development of hypertensive disease in pregnancy. Irene Lambrinoudaki, M.D.a George Kaparos, Ph.D.b Areti Augoulea, M.D.a Emmanuel Economou, Ph.D.b Maria Creatsa, M.D.a Konstantinos Papadias, M.D.a a Second Department of Obstetrics and Gynecology b Hormonal and Biochemical Laboratory University of Athens, Aretaieio Hospital Athens, Greece February 25, 2008 REFERENCES 1. Lambrinoudaki I, Augoulea A, Economou E, Kaparos G, Kontoravdis A, Papadias C, et al. Measurable serum markers of oxidative stress response in women with endometriosis. Fertil Steril. In press. 2. Lippi G, Montagnana M, Salvagno GL, Guidi GC. Potential value for new diagnostic markers in the early recognition of acute coronary syndromes. CJEM 2006;8:27–31. 3. Perfumo F, Gaze DC, Papageorghiou AT, Collinson PO, Thilaganathan B. First trimester maternal serum ischemia-modified albumin: a marker of hypoxia-ischemia-driven early trophoblast development. Hum Reprod 2007;22:2029–32. 4. Gugliucci A, Hermo R, Monroy C, Numaguchi M, Kimura S. Ischemiamodified albumin levels in cord blood: a case-control study in uncomplicated and complicated deliveries. Clin Chim Acta 2005;362:155–60.
doi:10.1016/j.fertnstert.2008.02.152 Successful pregnancy after four-step hysteroscopic technique for the treatment of atypical polypoid adenomyoma To the Editor: We read with interest the report by Wong et al. (1) describing the successful conservative management of a patient suffering from 5 years of primary infertility and persistent atypical polypoid adenomyoma (APA). The management proposed by the authors included a close surveillance of the APA by means of regular hysteroscopic examinations and uterine curettages (every 4–6 months) as well as the administration of the traditional Chinese herbal medication Danggui (Angelica sinensis), which acts as an ovulation inducer. Given the unfavorable outcome of the first pregnancy, lowdose aspirin was also administered to the patient as soon as she achieved her second pregnancy. Recently, we have reported an innovative hysteroscopic technique for the treatment of APA in a 35-year-old infertile woman desiring pregnancy (2). This technique includes four steps, each one being characterized by a pathological analysis: [1] the removal of the APA, [2] the removal of 1283
endometrium adjacent to the APA, [3] the removal of the myometrium underlying the APA, and [4] multiple random endometrial biopsies. Whenever any of the specimens collected from steps 2–4 is positive for neoplastic lesion, the conservative treatment should be converted into a radical approach (hysterectomy). Two months after the procedure, our patient achieved a pregnancy by means of a superovulation induction treatment (an injection containing FSH and hCG) and IVF. The gestation was complicated early on by moderate ovarian hyperstimulation syndrome, which was successfully treated with an inpatient regimen of bed rest, close fluid and electrolyte balance monitoring, and albumin infusions. Neither lowdose aspirin nor progestogen agents were administered during gestation. The course of her pregnancy was otherwise uncomplicated and terminated by a cesarean section performed at 39 weeks of gestation with the delivery of a healthy baby weighing 3850 g and with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. Follow-up hysteroscopic examinations with random biopsies performed 3 and 6 months later revealed a normal appearance of the uterus with neither visual nor pathological signs of APA. Our experience seems to suggest that the four-step approach is highly effective and convenient for the conservative treatment of APA in that it has three great advantages: [1] it provides for the complete removal of the lesion, [2] it saves most of the endometrium within the uterine cavity, and [3] it differentiates APA from endometrial carcinoma (EC) with myometrial invasion. In addition, we are firmly convinced that a diagnostic hysteroscopy with target-eye biopsy in an outpatient setting (without anesthesia) may be an adequate tool for the surveillance of such patients after surgery.
1284
Letters to the Editor
Furthermore, we believe that the blunt curettage should not be performed either for the surveillance or for the treatment of APA for two main reasons: [1] it has been well demonstrated that even when a direct visualization of the uterine cavity is available (as was the case reported by Wong et al.) focal lesions might be missed or not completely removed; and [2] the differential diagnosis between APA and EC with myometrial invasion may be difficult in a curettage specimen. Finally, we consider that blunt curettage should be avoided especially in patients with APA who desire pregnancy. Indeed, it cannot be excluded that the poor outcome of the first pregnancy achieved in the patient managed by Wong and colleagues might be related to the extensive damage to the endometrium from repeated blunt curettages. Guida Maurizio, M.D. Elena Greco, M.D. Attilio Di Spiezio Sardo, M.D. Costantino Di Carlo, M.D. Giada Lavitola, M.D. Francesco Tarsitano, M.D. Carmine Nappi, M.D. Departments of Gynaecology and Obstetrics and of Pathophysiology of Human Reproduction, University of Naples ‘‘Federico II,’’ Italy January 25, 2008 REFERENCES 1. Wong AY, Chan KS, Lau WL, Tang LC. Pregnancy outcome of a patient with atypical polypoid adenomyoma. Fertil Steril 2007;88: 1438.e7–9. 2. Di Spiezio Sardo A, Mazzon I, Gargano V, Di Carlo C, Guida M, Mignogna C, et al. Hysteroscopic treatment of atypical polypoid adenomyoma diagnosed incidentally in a young infertile woman. Fertil Steril 2008;89:456.e9–12.
doi:10.1016/j.fertnstert.2008.01.093
Vol. 89, No. 5, May 2008