To the Editor:
The article by Mollo et al. (1) reporting the benefit of hysteroscopic septum resection supports the recent literature about the topic. We congratulate the authors for their contribution to the relevant literature.
Uterine septum is a Müllerian anomaly existing in differing degrees. Infertile patients (6.3%) had a significantly higher incidence of Müllerian anomalies, compared with fertile (3.8%) and sterile (2.4%) women. Septate (33.6%) and arcuate (32.8%) uteri were the most common malformations observed (2).
Previously, it has been documented that septate uterus could be related to spontaneous abortion, early miscarriage and recurrent fetal loss (3,4). Early miscarriages (25-38%) and preterm deliveries (25-47%) were quite common in Müllerian anomalies (2). Especially in infertile patients and those with a history of early miscarriages, hysterosalpingography is routinely performed to diagnose uterine anomalies and pathologies. Because uterine septum was believed to be a cause of subfertility, surgical treatment was necessary. Recently, hysteroscopic resection of the uterine septum has become the most common surgical treatment modality.
On the other hand, in patients for whom IVF-ET is indicated, septum resection is required before the beginning of the cycle in order to minimize the adverse effect of the septum on fecundity and early pregnancy. It is also known, however, that many women with septate uterus are not infertile and have term pregnancies and deliveries without complications. Incidence of uterine septum in a fertile population was documented as 3-4% in reports (2). These women were diagnosed coincidentally during gynecological evaluation (2,5). Because some women have a normal obstetric history despite having a uterine septum, we are not sure about the effect of the septum on fertility. It must be mentioned, though, that many studies have reported the positive effect of surgical treatment of the septum in infertile women and patients with a history of spontaneous abortion and preterm delivery (3).
In conclusion, uterine anomalies are relatively frequent in fertile women, and more frequent in infertile patients. Uterine septum is associated with both normal and adverse reproductive outcomes, and while women with uterine septum and otherwise unexplained infertility might benefit from hysteroscopic septum resection, management in infertile women remains controversial (5).
Fatma Bahar Cebesoy, MD, Asst.Prof.Obstetrics and Gynecology Department Gaziantep University Faculty of Medicine
Gaziantep, Turkey
References
1. Mollo A, De Franciscis P, Colacurci N, Cobellis L, Perino A, et al. Hysteroscopic resection of the septum improves the pregnancy rate of women with unexplained infertility: a prospective controlled trial. Fertil Steril. 2008 Jun 18. In press.
2. Raga F, Bauset C, Remohi J, Bonilla-Musoles F, Simón C, Pellicer A. Reproductive impact of congenital Müllerian anomalies. Hum Reprod. 1997;12:2277-81.
3. Colacurci N, De Placido G, Mollo A, Carravetta C, De Franciscis P. Reproductive outcome after hysteroscopic metroplasty. Eur J Obstet Gynecol Reprod Biol. 1996;66:147-50.
4. Bradley LD. Complications in hysteroscopy: prevention, treatment and legal risk.
Curr Opin Obstet Gynecol. 2002;14:409-15.
5. Rackow BW, Arici A. Reproductive performance of women with müllerian anomalies.
Curr Opin Obstet Gynecol. 2007;19:229-37.
Published online in Fertility and Sterility DOI: 10.1016/j.fertnstert.2008.12.073
The Authors Respond:
We thank Dr. Cebesoy for the interest in our manuscript (1) and for the opportunity we have to better explain some thoughts related to our work.
We are aware that the presence of the septum is compatible with ongoing pregnancies and that some observational trials failed to show any relationship between this common malformation and sterility (2). Most studies investigating this association were retrospective. As a consequence, women with other possible causes of sterility were included. Conversely, only women with unexplained fertility comprised our prospective trial population.
Our results suggest that, at least in this subset of women, resection of the septum significantly increases the fecundity rate. This observation is consistent with data emphasized by Dr. Bahar, demonstrating that in patients in whom in vitro fertilization (IVF-ET) is indicated, the treatment of the uterine septum improves both fecundity and evolution of the pregnancy (3). Taken together, these lines of evidence suggest that, in some cases, the presence of the septum may condition early stages of implantation.
The process of human reproduction is complex and depends on a numbers of factors: effective ovulation, transport of viable spermatozoa and ovum in the genital tract, and successful interaction between embryo and endometrium (4,5). In this context, the endometrium plays an active role in the reproductive process, and it is crucial that some ultrastructural and molecular modifications take place in order to obtain embryo implantation (6,7). As we have already reported in our paper, some ultrastructural modifications have been described in the literature regarding the endometrium covering the septum.
We hypothesize that these alterations can negatively influence the multifaceted mechanisms of implantation and reduce the chances of pregnancy. Otherwise, it is unlikely that endometrial abnormality of the septum condition implantation in a “on-off” manner. For instance, despite the well-known association between septum and higher risk of recurrent miscarriage, in clinical practice we daily see full-term pregnancies in patients affected by such malformations. In this complex scenario, investigating the relationship between uterine septum and reproductive performance is complicated, and retrospective analyses do not allow adequate management of confounders.
In conclusion, our study, together with other data from the literature, suggest that metroplasty is indicated in patients with otherwise unexplained infertility and in patients undergoing ART cycles. These results underline the need for prospective randomized trials aimed at clarifying the impact of the septum in different subsets of sterile patients.
Antonio Mollo, M.D.
Carlo Alviggi, M.D.
Giuseppe De Placido, M.D.
Department of Obstetrics, Gynecology, Urology, and Reproductive MedicineFederico II University of Naples
Naples, Italy
Pasquale De Franciscis, M.D.
Luigi Cobellis, M.D.
Nicola Colacurci N, M.D.
Department of Gynecology, Obstetrics and Reproductive Sciences
Second University of Naples
Naples, Italy
Antonio Perino, M.D.
Renato Venezia, M.D.
Department of Obstetrics, Gynecology and Reproductive Medicine
University of Palermo
Palermo, Italy
References
1. Mollo A, De Franciscis P, Colacurci N, Cobellis L, Perino A, et al. Hysteroscopic resection of the septum improves the pregnancy rate of women with unexplained infertility: a prospective controlled trial. Fertil Steril. 2008; Jun 18. In press.
2. Raga F, Bauset C, Remohi J, Bonilla-Musoles F, Simón C, Pellicer A. Reproductive impact of congenital Müllerian anomalies. Hum Reprod. 1997;12:2277-81.
3. Lavergne N, Aristizabal J, Zarka V, Erny R, Hedon B. Uterine anomalies and in vitro fertilization: what are the results? Eur J Obstet Gynecol Reprod Biol 1996;68:29–34.
4. Clinical Guideline Fertility: assessment and treatment for people with fertility problems. National Collaborating Centre for Women’s and Children’s Health Commissioned by the National Institute for Clinical Excellence. 2004 February RCOG Press.
5. te Velde ER, Eijkemans R, Habbema HDF. Variation in couple fecundity and time to pregnancy, an essential concept in human reproduction. Lancet. 2000;355:1928–9.
6. Lindhard A, Bentin-Ley U, Ravn V, Islin H, Hviid T, Rex S, Bangsbøll S, Sørensen S. Biochemical evaluation of endometrial function at the time of implantation. Fertil Steril. 2002; 78(2):221-33.
7. Diedrich K, Fauser BC, Devroey P, Griesinger G; Evian Annual Reproduction (EVAR) Workshop Group. The role of the endometrium and embryo in human implantation. Hum Reprod Update. 2007. 13(4):365-77.
Published online in Fertility and Sterility DOI: 10.1016/j.fertnstert.2008.12.074
Fertility and Sterility eLetters to the Editor 
Leave a comment