To the Editor:
We would like to make some comments on the paper by Onalan et al (1). In this paper, the authors found that obesity could be a factor in initiating the growth of an endometrial polyp because they identified obesity as the only independent risk factor using logistic regression analysis.
The authors examined only infertile patients underwent routine diagnostic hysteroscopy before in vitro fertilization and embryo transfer. In addition, the authors did not take patients with polycystic ovary syndrome (PCOS) into consideration in the logistic regression model, even though these patients represent at least half of their sample. Since the authors themselves report that PCOS is a risk factor for endometrial polyps, it would have been logical to include this factor in the logistic regression model. Therefore, we wish to point out that the results of Onalan et al (1) should not be generalized to the entire population, within which endometrial polyps could be caused by risk factors other than obesity (2).
The results of Onalan et al (1) are very interesting when considered in the scope of infertility’s complex pathogenesis. In particular, as reported by Horcajadas et al (3), endometrial receptivity is a very delicate process linked with the cyclic expression of gene sets during the menstrual cycle. On one hand, an anomaly in expression can lead to unsuccessful embryo transfers. On the other hand, perhaps, it can result in the growth of endometrial polyps. While it may be true that the growth of endometrial polyps is related to the expression of the Bcl-2 gene (4), it has not been demonstrated that this expression is linked to a hyperestrogenism (as Onalan’s study demonstrates) even though a hormonal implication seems possible [e.g., the results of Maia et al (5)]. Therefore, the effect of estrogens on the expression of the Bcl-2 gene could be indirect, induced by mediators influenced sometimes, but not always, by the obesity of many infertile patients.
In order to give the correct prognosis to a patient with endometrial polyps concerning infertility and/or hypothetical malignant potential, it would be necessary to conduct a prospective study on a wide population of symptomatic and asymptomatic women in which an in-office diagnostic hysteroscopy is carried out, followed by a multivariate analysis of as many factors as possible. This could prove very difficult.
Giorgio Gentile, M.D., Ph.D.
Department of Internal Medicine
University of Perugia
Ugo Indraccolo, M.D., Ph.D.
Department of Surgical Sciences
University of Foggia
1. Onalan R, Onalan G, Tonguc E, Ozdener T, Dogan M, Mollamahmutoglu L. Body mass index is an independent risk factor for the development of endometrial polyps in patients undergoing in vitro fertilization. Fertil Steril. 2008 Mar 4. [Epub ahead of print]
2. Nappi L, Indraccolo U, Sardo AD, Gentile G, Palombino K, Castaldi MA, Spinelli M, Greco P. Are Diabetes, Hypertension, and Obesity Independent Risk Factors for Endometrial Polyps? J Minim Invasive Gynecol. 2009 Jan 20. [Epub ahead of print]
3. Horcajadas JA, Pellicer A, Simon C. Wide genomic analysis of human endometrial receptivity: new times, new opportunities. Hum Reprod Update. 2007 13 (1): 77-86.
4. Taylor LJ, Jackson TL, Reid JG, Duffy SRG. The difference expression of oestrogen receptors, progesterone receptors, Bcl-2 and Ki67 in endometrial polyps. BJOG 2003; 110(9): 794-798.
5. Maya H Jr, Maltez A, Studard E, Athayde C, Coutinho EM. Gynecol Endocrinol. 2004; 18 (6): 299-304.
Published online in Fertility and Sterility doi: 10.1016/j.fertnstert.2009.03.015
The Authors Respond:
Thank you for the interesting and appreciated comments on our article entitled “Body mass index is an independent risk factor for the development of endometrial polyps in patients undergoing in vitro fertilization”.
Our study was based on our hypothesis that hysteroscopy before IVF program on a merely selected subgroup of patient protocols could be recommended as a routine procedure and was not seeking pathogenesis of endometrial polyp (in accordance with over-expression of genes such as Bcl-2).
Furthermore we included patients with polycystic ovary syndrome (PCOS) in the logistic regression model; however at third step of stepwise model PCOS was excluded from the model. According to the model, obesity was the only independent prognostic factor for the development of endometrial polyps.
As no data exist for this issue, our study may be accepted as a feasibility study. The modest aim of the current study was to provide an estimate of incidence of endometrial polyp in selected subgroups, to identify a group of patients to routinely investigate before IVF program on a relatively large patient population; and to be included in a future meta-analysis focusing on routine use of office hysteroscopy prior IVF-ICSI cycles. As a pilot study, we hope our results provoke larger prospective randomize studies.
Gogsen Onalan, M.D.
Baskent University School of Medicine
Published online in Fertility and Sterility doi: 10.1016/j.fertnstert.2009.03.016