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Hysteroscopic metroplasty in patients with a uterine septum and otherwise unexplained infertility
International Journal of Gynecology and Obstetrics 113 (2011) 128–130
Contents lists available at ScienceDirect
International Journal of Gynecology and Obstetrics j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j g o
CLINICAL ARTICLE
Hysteroscopic metroplasty in patients with a uterine septum and otherwise unexplained infertility Esra A. Tonguc ⁎, Turgut Var, Sertac Batioglu Department of Reproductive Endocrinology, Zekai Tahir Burak Woman's Health Education and Research Hospital, Ankara, Turkey
a r t i c l e
i n f o
Article history: Received 29 August 2010 Received in revised form 24 November 2010 Accepted 25 January 2011 Keywords: Hysteroscopic metroplasty Pregnancy rate Primary infertility Reproductive outcome Uterine septum
a b s t r a c t Objective: To evaluate the reproductive outcomes of patients with a uterine septum and otherwise unexplained infertility who underwent hysteroscopic metroplasty, and to compare them with those of patients with the same diagnosis who did not have hysteroscopic metroplasty. Methods: The present retrospective study included 127 patients with diagnosis of a uterine septum and otherwise unexplained infertility. The reproductive outcomes of 102 patients who underwent hysteroscopic metroplasty (group 1) and 25 patients who rejected the operation (group 2) were compared. Results: Of the 102 patients who underwent hysteroscopic metroplasty, 44 (43.1%) were able to achieve pregnancy, as compared with 5 (20%) of the 25 patients who did not undergo the operation (P = 0.03). The abortion rate was 11.4% (5/44) in group 1, compared with 60% (3/5) in group 2 (P = 0.02). The live birth rate was 35.3% (36/102) in group 1, as compared with 8% (2/25) in group 2 (P = 0.008). Conclusions: The results indicate that hysteroscopic metroplasty improves reproductive outcome for patients with a uterine septum and otherwise unexplained infertility. © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction A uterine septum is the most commonly encountered congenital Müllerian anomaly [1,2]. It is associated with poor reproductive outcome and obstetric problems. Spontaneous miscarriage is the most commonly seen obstetric complication, affecting more than 60% of women with a uterine septum [3–6]. Although patients with a uterine septum are usually asymptomatic and are able to conceive and deliver without difficulty, the presence of a uterine septum can frequently lead to habitual abortion. Some authors have suggested that a uterine septum is a potential cause of infertility [3]. Patients with otherwise unexplained primary infertility and with a septate uterus have been described in many studies; however, the role of the uterine septum in infertility and the indications for metroplasty remain controversial [7–12]. A hysteroscopic approach is the standard treatment modality for a uterine septum. Hysteroscopic metroplasty is an expeditious, efficient, and safe method. The ideal way demonstrate a relationship between a uterine septum and infertility would be to carry out a prospective randomized study between 2 groups—1 that underwent metroplasty and 1 that did not— after other factors leading to infertility have been excluded. However, it is not ethically possible to carry out such a study because a uterine septum leads to abortion. Attending the infertility clinic of Zekai Tahir Burak Woman's Health Research and Education Hospital, however, are patients who have been diagnosed with a uterine septum but have ⁎ Corresponding author at: Tunalihilmi cad, Binnaz sok, no.1/5 Kavaklidere, Ankara, Turkey. Tel.: + 90 5324144889. E-mail address: [email protected] (E.A. Tonguc).
rejected the operation for various reasons. Thus, it is possible to follow those patients who reject hysteroscopic metroplasty and to monitor their reproductive outcomes. In Turkey, most young women (particularly in rural areas) do not receive gynecologic examinations even if they have gynecologic problems until they get married. Even those women who have had indications for an operation do not want to undergo the operation until after marriage, or even until after the first birth if possible. They are anxious about the removal of their uterus, ovaries, or tubes during the operation and subsequent infertility owing to intraoperative complications. Because fertility has prime importance in Turkish society, such women postpone their operation. Married couples are pressured by their families and society to have children immediately after marriage. These attitudes and the reluctance to have an operation can facilitate a comparison of the outcomes of those patients who undergo surgery with those who do not. The aim of the present study was to compare the reproductive outcomes of patients with unexplained infertility and a uterine septum who accepted hysteroscopic metroplasty surgery with those of patients with the same diagnosis who rejected the surgery. 2. Materials and methods In a retrospective study, the records of all patients with a uterine septum on hysterosalpingography who attended the Infertility Unit of Zekai Tahir Burak Women's Health Research and Education Hospital with the diagnosis of primary infertility between January 10, 2006, and January 3, 2009, were evaluated. From the records, the basal hormone levels, endocrinologic profile, vaginal ultrasonography,
0020-7292/$ – see front matter © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2010.11.023
E.A. Tonguc et al. / International Journal of Gynecology and Obstetrics 113 (2011) 128–130
office hysteroscopy, and sexually transmitted disease status of these patients, in addition to the spermiogram examination of their husbands, were checked. Patients who had a history of tuberculosis or endometriosis, an endocrinologic problem (e.g. diabetes mellitus, thyroid disease, hyperandrogenemia, or polycystic ovarian syndrome), a history of abdominal surgery, a husband with mild or severe oligospermia (defined as volume b2 mL, count b20 million per mL, motility b50%, and a normal shape in b30% of sperm), as revealed by the spermiogram, were excluded from the study. The study protocol was approved by the Ethics Committee of the hospital. A total of 127 patients between the ages of 20 and 35 years who had normal basal hormone profiles, who were not diagnosed with non-septum pathology in their vaginal and abdominal ultrasonography and office hysteroscopy, and who had bilateral tubal patency on hysterosalpingography were enrolled in the study. All septa were classified according to the American Society for Reproductive Medicine classification: 35 patients had a complete uterine septum (class Va), and 92 had a partial uterine septum (class Vb). Patients with both a complete uterine septum and a double cervix, with or without a vaginal septum, were excluded from the study. All participants provided informed consent. It was documented in the patient records that each woman was informed of their uterine septum and was advised to undergo hysteroscopic metroplasty. The details of the operation and the potential complications were also explained to each patient. The records showed that 25 patients rejected the operation owing to fear of surgery, or financial or social reasons. These 25 patients, who had primary infertility, were not treated with hysteroscopic metroplasty and were followed for 14 months; the remaining 102 patients underwent hysteroscopic metroplasty. Before every operation, antibiotic prophylaxis was provided with 1 g of cefazolin sodium (Sefamax, Nobel, Istanbul, Turkey), and the operation was performed during the early proliferative phase of the menstrual cycle. All patients were operated on by the same surgical team, and all operations were performed under general anesthesia. Diagnostic laparoscopy was carried out first, followed by operative hysteroscopy. A rigid hysteroscope (26-Fr resectoscope, 30 ° lens; Storz endoscope, Tuttlingen, Germany) was used. After a cervical dilatation of 11 mm was achieved, the uterine cavity was distended with 1.5% glycine solution at an inflow pressure of 60–90 mm Hg. The cutting current was set at 50–70 watts. The procedure was performed with a monopolar 90° angle knife electrode. After visualizing both tubal ostia, incision of the septa was started at the lower margin and continued upward with a horizontal section until the hysteroscope could be moved freely from 1 tubal ostium to the other without obstruction. The procedure was considered to be complete when a normal cavity was obtained and both tubal ostia became equally visible. Intrauterine devices and estrogen supplementation were not used after the operation [13]. All patients were re-evaluated for a residual septum by office hysteroscopy 2 months after the initial operation. A retained septum of more than 1 cm in length was considered a residual septum and defined as inadequate treatment. Patients with a residual septum underwent a second operation. Those patients who did not undergo the operation were followed for a period of 14 months after the diagnosis of a septum was made; those who did undergo the operation were followed for 14 months after normal office hysteroscopy. The reproductive outcomes of all patients were evaluated by examining the patient obstetric files in the hospital and by contacting those patients who had not returned to the hospital. The reproductive outcomes of the 102 patients who underwent hysteroscopic metroplasty and the 25 patients who rejected the operation were compared. Data analysis was performed by using SSPS for Windows (SPSS, Chicago, IL, USA). χ2 and Fisher exact tests were used to compare frequencies and percentages between the 2 groups. Variables that were continuous and normally distributed were compared via 2-tailed t test. P b 0.05 was considered to be statistically significant.
129
Table 1 Patient characteristics at first attendance at clinic.a
Age, years BMI Septum Incomplete Complete Duration of infertility, years
Group 1 (n = 102)
Group 2 (n = 25)
P value
24.6 ± 3.5 24.2 ± 3.1
23.8 ± 2.5 23.4 ± 2.0
0.3 0.2 0.7
74 (72.5) 28 (27.5) 5.5 ± 2.2
19 (76) 6 (24) 5.9 ± 1.7
0.4
Abbreviation: BMI, body mass index (calculated as weight in kilograms divided by the square of height in meters). a Values are given as mean ± SD or number (percentage) unless otherwise indicated.
3. Results The mean ± SD (range) age of the study patients at presentation at the clinic was 24.4 ± 3.3 years (19–35 years). The mean infertility period was found to be 5.6 ± 2.1 years (1–18 years), and the average body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) was 24.0 ± 2.9. There was no difference between the 2 groups in age, infertility period, BMI, or septum classification (Table 1). In the postoperative office hysteroscopy examination, a minor fundal notch (b1 cm) was found in 55 patients, whereas a normal uterine cavity was observed in 41 patients. The remaining 6 patients had a septal remnant larger than 1 cm and underwent a second operation. Pregnancy was obtained in 44 (43.1%) of the 102 patients who underwent hysteroscopic metroplasty, and 5 (20%) of the 25 patients who did not. This difference in clinical pregnancy rate was significant (P = 0.03). The abortion rate was 11.4% (5/44) in group 1, and 60% (3/5) in group 2 (P = 0.02). In group 1, 8 (18.2%) patients delivered preterm and 31 (70.5%) patients delivered at term, whereas 1 (20%) patient delivered preterm and 1 (20%) patient delivered at term in group 2. There was no difference between the 2 groups in preterm birth rate (P N 0.99), but the difference in term birth rate was significant (P = 0.04). The live birth rate was 35.3% (36/102) in group 1, and 8% (2/25) in group 2 (P = 0.008) (Table 2). 4. Discussion Although it is known that a uterine septum leads to early and late pregnancy losses, the relationship between uterine septum and infertility remains controversial. Most studies have been performed in sample populations where patients with abortion and those with infertility are grouped together. A significant improvement in reproductive outcome has been reported to occur after hysteroscopic metroplasty in patients with abortion. In a review of published studies, Homer et al. [8] found that abortion rates decreased from 71%–100% to 6%–29% after hysteroscopic metroplasty. In addition, the term birth rates increased from 0%–7% to 73%–100% after the operation [8]. Thus, metroplasty is clearly beneficial in patients with abortion, although its efficacy in infertile patients is undefined. Some researchers recommend hysteroscopic metroplasty for infertility [12,14–16], whereas others do not [11,17,18]. Table 2 Comparison of reproductive outcome between the 2 groups.a
Pregnancies Abortions Preterm deliveries Term deliveries Live birth rate a
Group 1 (n = 102)
Group 2 (n = 25)
P value
44 (43.1) 5 (11.4) 8 (18.2) 31 (70.5) 36 (35.3)
5 (20) 3 (60) 1 (20) 1 (20) 2 (8)
0.03 0.02 N 0.99 0.04 0.008
Values are given as number (percentage) unless otherwise indicated.
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E.A. Tonguc et al. / International Journal of Gynecology and Obstetrics 113 (2011) 128–130
When patients with infertility and those with abortion were analyzed separately, the pregnancy rate was 29%–-71% after the operation [8]. For example, Fedele et al. [9] reported a 3-year cumulative pregnancy rate of 39% in the infertile patient group and 62% in the abortion group; however, there were additional factors that might have caused infertility in 13 of the 31 infertile patients in that study. Saygili et al. [19] found an 18-month cumulative pregnancy rate of 23.3% in the infertile group and 83.1% in the habitual abortion group. In addition, Litta et al. [20] reported a term pregnancy rate of 83% in patients with 1 or more abortion, and 53.3% in the infertile group [20]. Pabuccu and Gomel [15] published a prospective observational study of 61 patients with uterine septum and primary infertility that was otherwise unexplained. They found a pregnancy rate of 41% and a live birth rate of 29.5% after hysteroscopic metroplasty. This pregnancy rate is lower than that reported for patients in abortion groups after metroplasty. Pabuccu and Gomel [15] suggested the reason for this low rate was the presence of an insidious factor able to improve implantation in patients in abortion groups. Many histopathologic studies have been carried out to research the effect of uterine septum on reproductivity, and various theories have been suggested. For example, Candiani et al. [21] claimed that implantation might be affected by changes in the vascularization pattern in the decidua basalis of the septum. Another opinion is that the presence of a septum causes irregular uterine contractions and blocks normal reproductive functions by disturbing sperm migration and transport [22]. In a histologic study, Dabirashrafi et al. [23] found that the muscular tissue of the septum is more than fibroelastic connective tissue and contains abnormal vascularization. In a comparison of endometrial specimens from the covering of the septum and the corresponding uterine lateral wall, Fedele et al. [24] found that the septal endometrium showed a reduced number of glandular ostia, irregular non-ciliated cells with rare microvilli, incomplete ciliogenesis on the ciliated cells, and a decrease in the ratio of the ciliated to non-ciliated cells. Their results indicated a decrease in the sensitivity of the septal endometrium to preovulatory hormonal changes and suggested that this could play a role in the pathogenesis of primary infertility in patients with a uterine septum [24]. Mollo et al. [16] recently compared patients with unexplained infertility and a uterine septum to those with unexplained infertility patients without a uterine septum. They reported a pregnancy rate of 20.4% and a live birth rate of 18.9% in the unexplained infertility group, as compared with 38.6% and 34.1%, respectively, in patients with a uterine septum who underwent hysteroscopic metroplasty. The difference in both rates was significant. According to these outcomes, hysteroscopic metroplasty increased the pregnancy rate in women with unexplained infertility and uterine septum [16]. In the present study, the pregnancy rate was 43.1%, the term birth rate was 70.5%, and the live birth rate was 35.3% for patients with a uterine septum who underwent hysteroscopic metroplasty. These percentages were significantly higher than those for patients who refused the operation. Furthermore, the abortion rate was found to be higher in the non-operated group than in the operated group (60% versus 11%), as expected. The insufficient number of patients in the non-operated group is a limitation of the present study. Nonetheless,
the results indicate that hysteroscopic metroplasty improves reproductive outcomes for patients with a uterine septum and otherwise unexplained infertility, and might be considered for all patients with primary infertility. Conflict of interest The authors have no conflicts of interest. References [1] Raga F, Bauset C, Remohi J, Bonilla- Musoles F, Simon C, Pellicer A. Reproductive impact of congenital müllerian anomalies. Hum Reprod 1997;12(10):2277–81. [2] Nasri MN, Setchell ME, Chard T. Transvaginal ultrasound for diagnosis of uterine malformations. Br J Obstet Gynaecol 1990;97(11):1043–5. [3] Heinonen PK, Saarikoski S, Pystynen P. Reproductive performance of women with uterine anomalies. Acta Obstet Gynecol Scand 1982;61(2):157–60. [4] Green LK, Harris RE. Uterine anomalies. Frequency of diagnosis and associated obstetric complications. Obstet Gynecol 1976;47(4):427–9. [5] Harger JH, Archer DF, Marchhese SG, Muracca-Clemens M, Garver KL. Etiology of recurrent pregnancy losses and outcome of subsequent pregnancies. Obstet Gynecol 1983;62(5):547–81. [6] Golan A, Langer R, Bukovsky I, Caspi E. Congenital anomalies of the müllerian system. Fertil Steril 1989;51(5):747–55. [7] Perino A, Mencaglia L, Hamou J, Cittadini E. Hysteroscopy for metroplasty of uterine septa: Report of 24 cases. Fertil Steril 1987;48(2):321–3. [8] Homer HA, Li TC, Cooke ID. The septate uterus: A review of management and reproductive outcome. Fertil Steril 2000;73(1):1–14. [9] Fedele L, Arcaini L, Parazzini F, Vercellini P, Nola G. Reproductive prognosis after hysteroscopic metroplasty in 102 women: Life-table analysis. Fertil Steril 1993;59(4):768–72. [10] Colacurci N, De Placido G, Mollo A, Carravetta C, De Franciscis P. Reproductive outcome after hysteroscopic metroplasty. Eur J Obstet Gynecol Reprod Biol 1996;66(2):147–50. [11] Marabini A, Gubbini G, Stagnozzi R, Stefanetti M, Filoni M, Bovicelli A. Hysteroscopic metroplasty. Ann NY Acad Sci 1994;734:488–92. [12] Mencaglia L, Tantini C. Hysteroscopic treatment of septate and arcuate uterus. Gynecol Endosc 1996;5:151–4. [13] Tonguc EA, Var T, Yilmaz N, Batioglu S. Intrauterine device or estrogen treatment after hysteroscopic septum resection. Int J Gynecol Obstet 2010;109(3):226–9. [14] Pabuccu R, Atay V, Urman B, Ergun A, Orhon E. Hysteroscopic treatment of septate uterus. Gynecol Endosc 1995;4:213–5. [15] Pabuccu R, Gomel V. Reproductive outcome after hysteroscopic metroplasty in women with septate uterus and otherwise unexplained infertility. Fertil Steril 2004;81(6):1675–8. [16] Mollo A, Franciscis P, Colacurci N, Cobellis L, Perino A, Venezia R, et al. Hysteroscopic resection of the septum improves the pregnancy rate of women with unexplained infertility: A prospective controlled trial. Fertil Steril 2009;91(6):2628–31. [17] Corson SL. Operative hysteroscopy for infertility. Clin Obstet Gynecol 1992;35(2): 229–41. [18] Daly DC, Mailer D, Soto-Alborz C. Hysteroscopic metroplasty: Six years’ experience. Obstet Gynecol 1989;73(2):201–5. [19] Saygili-Yilmaz E, Yildiz S, Erman-Akar M, Akyuz G, Yilmaz Z. Reproductive outcome of septate uterus after hysteroscopic metroplasty. Arch Gynecol Obstet 2003;268:289–92. [20] Litta P, Pozzan C, Merlin F, Sacco G, Saccardi C, Ambrossini G, et al. Hysteroscopic metroplasty under laparoscopic guidance in infertile women with septate uteri: follow-up of reproductive outcome. J Reprod Med 2004;49(4):274–8. [21] Candiani GB, Fedele L, Zamberletti D, De Virgillis D, Carinelli S. Endometrial patterns in malformed uteri. Acta Eur Fertil 1983;14(1):311–8. [22] Blum M. Comparative study of serum CAP activity during pregnancy in malformed and normal uterus. J Perinat Med 1978;6(3):165–8. [23] Dabirashrafi H, Bahadori M, Mohammad K, Alavi M, Moghadami-Tabrizi N, Zandinejad K. Septate uterus: New idea on the histologic features of the septum in this abnormal uterus. Am J Obstet Gynecol 1995;172(1Pt1):105–7. [24] Fedele L, Bianchi S, Marchini M, Franchi D, Tozzi L, Dorta M. Ultrastructural aspects of endometrium in infertile women with septate uterus. Fertil Steril 1996;65(4): 750–2.
Contents lists available at ScienceDirect
International Journal of Gynecology and Obstetrics j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j g o
CLINICAL ARTICLE
Hysteroscopic metroplasty in patients with a uterine septum and otherwise unexplained infertility Esra A. Tonguc ⁎, Turgut Var, Sertac Batioglu Department of Reproductive Endocrinology, Zekai Tahir Burak Woman's Health Education and Research Hospital, Ankara, Turkey
a r t i c l e
i n f o
Article history: Received 29 August 2010 Received in revised form 24 November 2010 Accepted 25 January 2011 Keywords: Hysteroscopic metroplasty Pregnancy rate Primary infertility Reproductive outcome Uterine septum
a b s t r a c t Objective: To evaluate the reproductive outcomes of patients with a uterine septum and otherwise unexplained infertility who underwent hysteroscopic metroplasty, and to compare them with those of patients with the same diagnosis who did not have hysteroscopic metroplasty. Methods: The present retrospective study included 127 patients with diagnosis of a uterine septum and otherwise unexplained infertility. The reproductive outcomes of 102 patients who underwent hysteroscopic metroplasty (group 1) and 25 patients who rejected the operation (group 2) were compared. Results: Of the 102 patients who underwent hysteroscopic metroplasty, 44 (43.1%) were able to achieve pregnancy, as compared with 5 (20%) of the 25 patients who did not undergo the operation (P = 0.03). The abortion rate was 11.4% (5/44) in group 1, compared with 60% (3/5) in group 2 (P = 0.02). The live birth rate was 35.3% (36/102) in group 1, as compared with 8% (2/25) in group 2 (P = 0.008). Conclusions: The results indicate that hysteroscopic metroplasty improves reproductive outcome for patients with a uterine septum and otherwise unexplained infertility. © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction A uterine septum is the most commonly encountered congenital Müllerian anomaly [1,2]. It is associated with poor reproductive outcome and obstetric problems. Spontaneous miscarriage is the most commonly seen obstetric complication, affecting more than 60% of women with a uterine septum [3–6]. Although patients with a uterine septum are usually asymptomatic and are able to conceive and deliver without difficulty, the presence of a uterine septum can frequently lead to habitual abortion. Some authors have suggested that a uterine septum is a potential cause of infertility [3]. Patients with otherwise unexplained primary infertility and with a septate uterus have been described in many studies; however, the role of the uterine septum in infertility and the indications for metroplasty remain controversial [7–12]. A hysteroscopic approach is the standard treatment modality for a uterine septum. Hysteroscopic metroplasty is an expeditious, efficient, and safe method. The ideal way demonstrate a relationship between a uterine septum and infertility would be to carry out a prospective randomized study between 2 groups—1 that underwent metroplasty and 1 that did not— after other factors leading to infertility have been excluded. However, it is not ethically possible to carry out such a study because a uterine septum leads to abortion. Attending the infertility clinic of Zekai Tahir Burak Woman's Health Research and Education Hospital, however, are patients who have been diagnosed with a uterine septum but have ⁎ Corresponding author at: Tunalihilmi cad, Binnaz sok, no.1/5 Kavaklidere, Ankara, Turkey. Tel.: + 90 5324144889. E-mail address: [email protected] (E.A. Tonguc).
rejected the operation for various reasons. Thus, it is possible to follow those patients who reject hysteroscopic metroplasty and to monitor their reproductive outcomes. In Turkey, most young women (particularly in rural areas) do not receive gynecologic examinations even if they have gynecologic problems until they get married. Even those women who have had indications for an operation do not want to undergo the operation until after marriage, or even until after the first birth if possible. They are anxious about the removal of their uterus, ovaries, or tubes during the operation and subsequent infertility owing to intraoperative complications. Because fertility has prime importance in Turkish society, such women postpone their operation. Married couples are pressured by their families and society to have children immediately after marriage. These attitudes and the reluctance to have an operation can facilitate a comparison of the outcomes of those patients who undergo surgery with those who do not. The aim of the present study was to compare the reproductive outcomes of patients with unexplained infertility and a uterine septum who accepted hysteroscopic metroplasty surgery with those of patients with the same diagnosis who rejected the surgery. 2. Materials and methods In a retrospective study, the records of all patients with a uterine septum on hysterosalpingography who attended the Infertility Unit of Zekai Tahir Burak Women's Health Research and Education Hospital with the diagnosis of primary infertility between January 10, 2006, and January 3, 2009, were evaluated. From the records, the basal hormone levels, endocrinologic profile, vaginal ultrasonography,
0020-7292/$ – see front matter © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2010.11.023
E.A. Tonguc et al. / International Journal of Gynecology and Obstetrics 113 (2011) 128–130
office hysteroscopy, and sexually transmitted disease status of these patients, in addition to the spermiogram examination of their husbands, were checked. Patients who had a history of tuberculosis or endometriosis, an endocrinologic problem (e.g. diabetes mellitus, thyroid disease, hyperandrogenemia, or polycystic ovarian syndrome), a history of abdominal surgery, a husband with mild or severe oligospermia (defined as volume b2 mL, count b20 million per mL, motility b50%, and a normal shape in b30% of sperm), as revealed by the spermiogram, were excluded from the study. The study protocol was approved by the Ethics Committee of the hospital. A total of 127 patients between the ages of 20 and 35 years who had normal basal hormone profiles, who were not diagnosed with non-septum pathology in their vaginal and abdominal ultrasonography and office hysteroscopy, and who had bilateral tubal patency on hysterosalpingography were enrolled in the study. All septa were classified according to the American Society for Reproductive Medicine classification: 35 patients had a complete uterine septum (class Va), and 92 had a partial uterine septum (class Vb). Patients with both a complete uterine septum and a double cervix, with or without a vaginal septum, were excluded from the study. All participants provided informed consent. It was documented in the patient records that each woman was informed of their uterine septum and was advised to undergo hysteroscopic metroplasty. The details of the operation and the potential complications were also explained to each patient. The records showed that 25 patients rejected the operation owing to fear of surgery, or financial or social reasons. These 25 patients, who had primary infertility, were not treated with hysteroscopic metroplasty and were followed for 14 months; the remaining 102 patients underwent hysteroscopic metroplasty. Before every operation, antibiotic prophylaxis was provided with 1 g of cefazolin sodium (Sefamax, Nobel, Istanbul, Turkey), and the operation was performed during the early proliferative phase of the menstrual cycle. All patients were operated on by the same surgical team, and all operations were performed under general anesthesia. Diagnostic laparoscopy was carried out first, followed by operative hysteroscopy. A rigid hysteroscope (26-Fr resectoscope, 30 ° lens; Storz endoscope, Tuttlingen, Germany) was used. After a cervical dilatation of 11 mm was achieved, the uterine cavity was distended with 1.5% glycine solution at an inflow pressure of 60–90 mm Hg. The cutting current was set at 50–70 watts. The procedure was performed with a monopolar 90° angle knife electrode. After visualizing both tubal ostia, incision of the septa was started at the lower margin and continued upward with a horizontal section until the hysteroscope could be moved freely from 1 tubal ostium to the other without obstruction. The procedure was considered to be complete when a normal cavity was obtained and both tubal ostia became equally visible. Intrauterine devices and estrogen supplementation were not used after the operation [13]. All patients were re-evaluated for a residual septum by office hysteroscopy 2 months after the initial operation. A retained septum of more than 1 cm in length was considered a residual septum and defined as inadequate treatment. Patients with a residual septum underwent a second operation. Those patients who did not undergo the operation were followed for a period of 14 months after the diagnosis of a septum was made; those who did undergo the operation were followed for 14 months after normal office hysteroscopy. The reproductive outcomes of all patients were evaluated by examining the patient obstetric files in the hospital and by contacting those patients who had not returned to the hospital. The reproductive outcomes of the 102 patients who underwent hysteroscopic metroplasty and the 25 patients who rejected the operation were compared. Data analysis was performed by using SSPS for Windows (SPSS, Chicago, IL, USA). χ2 and Fisher exact tests were used to compare frequencies and percentages between the 2 groups. Variables that were continuous and normally distributed were compared via 2-tailed t test. P b 0.05 was considered to be statistically significant.
129
Table 1 Patient characteristics at first attendance at clinic.a
Age, years BMI Septum Incomplete Complete Duration of infertility, years
Group 1 (n = 102)
Group 2 (n = 25)
P value
24.6 ± 3.5 24.2 ± 3.1
23.8 ± 2.5 23.4 ± 2.0
0.3 0.2 0.7
74 (72.5) 28 (27.5) 5.5 ± 2.2
19 (76) 6 (24) 5.9 ± 1.7
0.4
Abbreviation: BMI, body mass index (calculated as weight in kilograms divided by the square of height in meters). a Values are given as mean ± SD or number (percentage) unless otherwise indicated.
3. Results The mean ± SD (range) age of the study patients at presentation at the clinic was 24.4 ± 3.3 years (19–35 years). The mean infertility period was found to be 5.6 ± 2.1 years (1–18 years), and the average body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) was 24.0 ± 2.9. There was no difference between the 2 groups in age, infertility period, BMI, or septum classification (Table 1). In the postoperative office hysteroscopy examination, a minor fundal notch (b1 cm) was found in 55 patients, whereas a normal uterine cavity was observed in 41 patients. The remaining 6 patients had a septal remnant larger than 1 cm and underwent a second operation. Pregnancy was obtained in 44 (43.1%) of the 102 patients who underwent hysteroscopic metroplasty, and 5 (20%) of the 25 patients who did not. This difference in clinical pregnancy rate was significant (P = 0.03). The abortion rate was 11.4% (5/44) in group 1, and 60% (3/5) in group 2 (P = 0.02). In group 1, 8 (18.2%) patients delivered preterm and 31 (70.5%) patients delivered at term, whereas 1 (20%) patient delivered preterm and 1 (20%) patient delivered at term in group 2. There was no difference between the 2 groups in preterm birth rate (P N 0.99), but the difference in term birth rate was significant (P = 0.04). The live birth rate was 35.3% (36/102) in group 1, and 8% (2/25) in group 2 (P = 0.008) (Table 2). 4. Discussion Although it is known that a uterine septum leads to early and late pregnancy losses, the relationship between uterine septum and infertility remains controversial. Most studies have been performed in sample populations where patients with abortion and those with infertility are grouped together. A significant improvement in reproductive outcome has been reported to occur after hysteroscopic metroplasty in patients with abortion. In a review of published studies, Homer et al. [8] found that abortion rates decreased from 71%–100% to 6%–29% after hysteroscopic metroplasty. In addition, the term birth rates increased from 0%–7% to 73%–100% after the operation [8]. Thus, metroplasty is clearly beneficial in patients with abortion, although its efficacy in infertile patients is undefined. Some researchers recommend hysteroscopic metroplasty for infertility [12,14–16], whereas others do not [11,17,18]. Table 2 Comparison of reproductive outcome between the 2 groups.a
Pregnancies Abortions Preterm deliveries Term deliveries Live birth rate a
Group 1 (n = 102)
Group 2 (n = 25)
P value
44 (43.1) 5 (11.4) 8 (18.2) 31 (70.5) 36 (35.3)
5 (20) 3 (60) 1 (20) 1 (20) 2 (8)
0.03 0.02 N 0.99 0.04 0.008
Values are given as number (percentage) unless otherwise indicated.
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When patients with infertility and those with abortion were analyzed separately, the pregnancy rate was 29%–-71% after the operation [8]. For example, Fedele et al. [9] reported a 3-year cumulative pregnancy rate of 39% in the infertile patient group and 62% in the abortion group; however, there were additional factors that might have caused infertility in 13 of the 31 infertile patients in that study. Saygili et al. [19] found an 18-month cumulative pregnancy rate of 23.3% in the infertile group and 83.1% in the habitual abortion group. In addition, Litta et al. [20] reported a term pregnancy rate of 83% in patients with 1 or more abortion, and 53.3% in the infertile group [20]. Pabuccu and Gomel [15] published a prospective observational study of 61 patients with uterine septum and primary infertility that was otherwise unexplained. They found a pregnancy rate of 41% and a live birth rate of 29.5% after hysteroscopic metroplasty. This pregnancy rate is lower than that reported for patients in abortion groups after metroplasty. Pabuccu and Gomel [15] suggested the reason for this low rate was the presence of an insidious factor able to improve implantation in patients in abortion groups. Many histopathologic studies have been carried out to research the effect of uterine septum on reproductivity, and various theories have been suggested. For example, Candiani et al. [21] claimed that implantation might be affected by changes in the vascularization pattern in the decidua basalis of the septum. Another opinion is that the presence of a septum causes irregular uterine contractions and blocks normal reproductive functions by disturbing sperm migration and transport [22]. In a histologic study, Dabirashrafi et al. [23] found that the muscular tissue of the septum is more than fibroelastic connective tissue and contains abnormal vascularization. In a comparison of endometrial specimens from the covering of the septum and the corresponding uterine lateral wall, Fedele et al. [24] found that the septal endometrium showed a reduced number of glandular ostia, irregular non-ciliated cells with rare microvilli, incomplete ciliogenesis on the ciliated cells, and a decrease in the ratio of the ciliated to non-ciliated cells. Their results indicated a decrease in the sensitivity of the septal endometrium to preovulatory hormonal changes and suggested that this could play a role in the pathogenesis of primary infertility in patients with a uterine septum [24]. Mollo et al. [16] recently compared patients with unexplained infertility and a uterine septum to those with unexplained infertility patients without a uterine septum. They reported a pregnancy rate of 20.4% and a live birth rate of 18.9% in the unexplained infertility group, as compared with 38.6% and 34.1%, respectively, in patients with a uterine septum who underwent hysteroscopic metroplasty. The difference in both rates was significant. According to these outcomes, hysteroscopic metroplasty increased the pregnancy rate in women with unexplained infertility and uterine septum [16]. In the present study, the pregnancy rate was 43.1%, the term birth rate was 70.5%, and the live birth rate was 35.3% for patients with a uterine septum who underwent hysteroscopic metroplasty. These percentages were significantly higher than those for patients who refused the operation. Furthermore, the abortion rate was found to be higher in the non-operated group than in the operated group (60% versus 11%), as expected. The insufficient number of patients in the non-operated group is a limitation of the present study. Nonetheless,
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