REVIEW URRENT C OPINION

Hysteroscopic polypectomy for women undergoing IVF treatment: when is it necessary? Pinar H. Kodaman

Purpose of review The objectives of the present review are to discuss the role of endometrial polyps in infertility and to analyze the evidence for hysteroscopic polypectomy prior to IVF. Recent findings Endometrial polyps are frequently found during routine workup for infertility and are known to negatively impact endometrial receptivity through various mechanisms. Overall, most studies to date point to a favorable effect of hysteroscopic polypectomy on subsequent fertility. A recent meta-analysis showed a four-fold increase in expected pregnancy rates following hysteroscopic polypectomy in women planning to undergo intrauterine insemination, and although there are no randomized controlled trials specifically addressing hysteroscopic polypectomy prior to IVF, several large studies suggest a beneficial effect of hysteroscopy both prior to initial IVF and after failed IVF as intrauterine abnormalities, mostly endometrial polyps, are found in a significant proportion of the infertile population. There may be an added benefit of hysteroscopy itself in facilitating subsequent embryo transfer via dilation of the cervix or by increasing endometrial receptivity through endometrial injury. Summary Hysteroscopic polypectomy is a minimally invasive procedure with little risk of complication and therefore should be performed prior to IVF to optimize chances for successful implantation. Keywords endometrial polyp, endometrial receptivity, hysteroscopy, IVF

INTRODUCTION Endometrial polyps are localized overgrowths of endometrial glands and stroma within the uterine cavity. Although polyps can cause abnormal uterine bleeding (AUB), they are frequently asymptomatic and therefore may remain undetected [1]. They can be found incidentally on imaging, particularly during the infertility workup, which includes evaluation of the endometrial cavity. Whether endometrial polyps directly cause infertility remains uncertain; yet the presence of such growths is known to alter several salient markers of endometrial receptivity [2,3]. Thus, it is plausible that endometrial polyps may adversely affect fertility by impairing implantation. This review analyzes the evidence to date for hysteroscopic resection of endometrial polyps in women who are planning to undergo IVF.

BACKGROUND As outgrowths of the surrounding endometrium, endometrial polyps consist of a central basalis core www.co-obgyn.com

supplied by a single feeding vessel and covered by a functional endometrium [4]. There are conflicting data about the normal versus abnormal distribution of estrogen and progesterone receptors within polyps [5,6]; however, the functional layer is often asynchronous with the normal endometrium, which may predispose these growths to AUB, often in the form of intermenstrual spotting [7]. Bleeding may also occur following apical necrosis of the polyp as a result of underlying stromal congestion and diminished blood flow [8,9]. The polyps may be millimeters to centimeters in size, single or multiple, Yale University School of Medicine, Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology and Infertility, Yale Fertility Center, New Haven, Connecticut, USA Correspondence to Pinar H. Kodaman, MD, PhD, Yale University School of Medicine, Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology and Infertility, Yale Fertility Center, 150 Sargent Drive, 2nd Floor, New Haven, CT 06511, USA. Tel: +1 203 785 3725; e-mail: [email protected] Curr Opin Obstet Gynecol 2016, 28:184–190 DOI:10.1097/GCO.0000000000000277 Volume 28  Number 3  June 2016

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Hysteroscopic polypectomy for women undergoing IVF Kodaman

KEY POINTS  Endometrial polyps are prevalent among women with infertility and should be investigated with sonohysterography or hysteroscopy as other diagnostic modalities are inferior.  Hysteroscopic polypectomy should be performed prior to fertility treatments because polyps have negative effects on endometrial receptivity and can diminish successful implantation.  The timing of hysteroscopic polypectomy prior to IVF does not matter, though there may be an added benefit of hysteroscopy with associated cervical dilatation/ endometrial injury in the cycle preceding the embryo transfer in terms of subsequent implantation.

sessile or pedunculated, and can occur anywhere in the endometrial cavity, though most are found in the fundal region [9,10]. The prevalence of endometrial polyps reported in the literature is quite variable depending on the diagnostic modality used, the population studied, and the presence or absence of symptoms [11]. Among premenopausal women with AUB, the prevalence of endometrial polyps was 33% compared with 10% among those without symptoms [12]. Although polyps most often present with AUB, now designated as AUB-P by the new International Federation of Gynecology and Obstetrics (FIGO) classification system [13], polyp size, number, and location do not correlate with the presence of symptoms [1]. Unopposed or excess estrogen exposure appears to underlie many of the risk factors for endometrial polyps, including obesity, polycystic ovary syndrome [14], and use of gonadotropins for fertility treatments [9,15 ]. Other risk factors included advancing age [16], tamoxifen use [17], hypertension [18], and the presence of cervical polyps [19] or atypical glandular cells on Pap smear [20]. A recent meta-analysis also established endometriosis as a significant risk factor for the presence of endometrial polyps (response rate, RR 2.81; 95% CI, 2.48–3.18) [21]. Although over 95% of endometrial polyps are benign, the risk of malignancy is greater with postmenopausal status, abnormal bleeding [22], and size greater than 1.5 cm [23]. However, asymptomatic polyps with complex hyperplasia and atypia can be found in the premenopausal population, and nonsurgical predictors of malignancy are limited [1,24 ,25]. In a study of 230 infertile women who underwent hysteroscopic polypectomy, endometrial hyperplasia was found in 6.9% [26]. Endometrial polyps less than 1 cm in diameter may &

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spontaneously shed or regress over time, whereas those greater than 1 cm and multiple polyps are unlikely to resolve on their own [27]. Therefore, expectant management has been suggested for the small, incidentally found polyp in asymptomatic women without risk factors for malignancy [16]. Endometrial polyps are diagnosed by various modalities, including transvaginal ultrasound, hysterosalpingogram, sonohysterogram, and the gold standard hysteroscopy. More recently, 3D sonography has been utilized, but its marginal benefit for diagnosis of endometrial polyps compared with 2D sonography is questionable both with and without isotonic saline infusion [28]. A large meta-analysis recently showed that sonohysterography is comparable to hysteroscopy for the detection of endometrial polyps [29], whereas hysterosalpingography has high sensitivity, but low specificity [30]. Almost 20% of women with normal hysterosalpingogram are found to have endometrial polyps upon hysteroscopic evaluation of the endometrial cavity [31].

ENDOMETRIAL POLYPS AND INFERTILITY There is a paucity of randomized controlled trials (RCTs) looking at a causal relationship between endometrial polyps and infertility; however, based on the available data, including the potential negative effects of polyps on endometrial receptivity, polyp resection is generally recommended for infertile women prior to fertility treatments [32,33].

Prevalence of endometrial polyps in infertility As with the general population, the true prevalence of endometrial polyps among infertile women is unknown as many are asymptomatic, and identification depends on the sensitivity and specificity of the diagnostic modality used [30]. Although isolated uterine factor represents only 2–3% of infertility cases [34], intrauterine abnormalities, such as polyps, are frequently found during evaluation of the endometrial cavity. When compared with women with a history of tubal ligation, polyps are more common among women with unexplained infertility, 3.2 versus 15.6%, respectively [7]. They are also prevalent among women with repeated implantation failure following IVF, representing up to 20–25% of the intrauterine anomalies found in this setting [35,36 ]. For asymptomatic women undergoing IVF, the prevalence of endometrial polyps as determined by hysteroscopy was reported between 6 and 8% [37,38], though a prospective analysis of 1000 consecutive infertile women undergoing office hysteroscopy prior to IVF found that

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32% had endometrial polyps [39]. Although the variability in polyp prevalence in the infertile population may have to do with the heterogeneity of the patients studied or the diagnostic modality used, polyps are a fairly common finding in this group.

Detrimental effects of polyps on fertility Whether there is a direct cause and effect relationship between polyps and infertility remains incompletely understood. Several potential mechanisms have been proposed, including mechanical obstruction of the ostium such that sperm and/or embryo transport is hindered [7], inflammatory changes [40,41], AUB-P [42 ], and alterations in markers of endometrial receptivity [2,43,44]. With respect to endometrial receptivity, HOXA10 and HOXA11 mRNA expression are decreased in endometrium obtained from uterine cavities containing polyps compared with normal cavities, and these findings were independent of polyp size (<8 versus >8 mm) and polyp number [2]. Other markers of endometrial receptivity, such as IGFBP-1 and glycodelin are also altered in women with endometrial polyps, and their levels normalize following hysteroscopic polypectomy [3]. The elevated glycodelin levels found in uterine flushings of women with endometrial polyps may impair sperm binding to the zona pellucida [45]. &

Hysteroscopic polypectomy and fertility Given that over 70% of polyps persist at 1 year with expectant management [46] and because time is of the essence in the infertility patient, most of whom are going to undergo gonadotropin stimulation, hysteroscopic polypectomy is generally recommended to restore normal anatomy prior to fertility treatments [46,47]. In fact, endometrial polyps may be an underlying cause for unexplained infertility as shown in a retrospective study by Stamatellos et al. [48] in which spontaneous pregnancy rates in women with both primary and secondary unexplained infertility reached 61.4% after hysteroscopic intervention. Interestingly, there was no difference in the pregnancy rate based on size (<1 cm or >1 cm) or number of polyps present. Removal of polyps at the uterotubal junction results in the greatest chance of pregnancy (57.4%) based on a retrospective study of polyp location in 230 infertile women [26]. The best evidence for polyps as a cause for infertility comes from a well designed RCT of 215 infertile women with polyps planning to undergo intrauterine insemination (IUI) [49]. Significantly higher pregnancy rates were demonstrated in women who had hysteroscopic polypectomy 186

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compared with diagnostic hysteroscopy with just polyp biopsy (63 versus 28%) [49]. Furthermore, the majority of women in the polypectomy group (65%) conceived spontaneously prior to the first IUI, whereas every pregnancy in the second group was achieved with IUI [49]. Of note, the mean polyp size in this study was 16 mm leaving the generalizability of the findings to smaller polyps in question, though other studies have shown restoration of fertility following polypectomy regardless of polyp size [50,51]. Similarly, a previous retrospective study showed that natural conception rates were increased among infertile women who had hysteroscopic polypectomy compared with those who had hysteroscopy, but were found to have a normal cavity (78 versus 42.1%) [52]. In a recent systematic review of this topic, Bosteels et al. [53 ] found that hysteroscopic polypectomy results in a greater than fourfold increase in clinical pregnancy among subfertile or infertile women who subsequently undergo IUI. &

Considerations for hysteroscopy Direct visualization and resection of polyps via hysteroscopy is the gold standard for diagnosis and concomitant treatment. There are few risks of hysteroscopy and hysteroscopic polypectomy in particular. In a large, prospective study of over 13 000 hysteroscopic procedures, the overall complication rate was only 0.28%, and the majority of these were related to more difficult procedures such as myomectomy, endometrial ablation, or lysis of adhesions [54]. There is a negligible risk of intrauterine synechiae formation after hysteroscopic polypectomy, and therefore, anti-adhesion barriers or postoperative hormonal treatments are not necessary [55]. The overall risk of recurrence following polypectomy is very low, approximately 3%, with most of the recurrences occurring following use of hysteroscopic forceps versus the resectoscope [51]. With respect to the latter, the potential detrimental effect of electrosurgery on subsequent endometrial thickness (1.2 mm decrease) should be taken into consideration, though there was no difference in the live birth rate despite this decrease in endometrial thickness postoperatively [56 ]. Although traditionally hysteroscopy has been performed in the surgical suite for both diagnostic and operative indications, office hysteroscopy has been gaining popularity in recent years because of new, smaller caliber scopes, reduced cost, lack of need for general anesthesia, and convenience [57]. A recent randomized, controlled multicenter study showed that hysteroscopy under local anesthesia in the outpatient setting was noninferior to hospitalbased hysteroscopy with general anesthesia [58 ]. &

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Polyps less than or equal to 2 cm can be removed successfully in the office setting regardless of menopausal status or parity [59].

HYSTEROSCOPY AND IVF Given the significant prevalence of intracavitary abnormalities among infertile women, hysteroscopy should be considered before IVF and is recommended after one, otherwise unexplained, failed IVF cycle [29]. Several studies have looked at the role of hysteroscopy before IVF and incorporate, albeit indirectly, the effect of hysteroscopic polypectomy on subsequent IVF outcome. To date, there are no RCTs addressing the specific role of hysteroscopic polypectomy prior to IVF.

Routine hysteroscopy prior to IVF Based on a recent meta-analysis of five RCTs, there appears to be a modest benefit of routine hysteroscopy prior to IVF in terms of clinical pregnancy rate (RR 1.44; 95% CI, 1.08–1.92) [60]. According to these data, the number of hysteroscopy procedures needed prior to IVF to achieve one additional clinical pregnancy is 10, and interestingly, the benefit with respect to the clinical pregnancy rate was irrespective of whether or not intrauterine disease was found and corrected, suggesting a therapeutic effect of the diagnostic procedure itself [60]. In a recent RCT looking at the use of routine hysteroscopy prior to assisted reproductive technology with intracytoplasmic sperm injection (ICSI), Al Elsetohy et al. [24 ] found a 43% rate of abnormal hysteroscopic findings in the hysteroscopy group, and clinical pregnancy rate was significantly higher in this group compared with the control group that went straight to ICSI (odds ratio, OR 2.77; 95% CI, 1.53–5.00). Of note, the most common finding in the hysteroscopy group was endometrial polyp (9.3%), but other findings, including cervical stenosis, fibroids, adhesions, and septa were also found and treated prior to ICSI, making this study less applicable to the management of polyps specifically.

abnormalities compared with women who have no history of failed attempts at IVF (42 versus 23.7%) and restoration of normal anatomy results in equivalent outcomes following subsequent IVF [63]. Endometrial polyps were the most common (14.7%) intrauterine abnormality found among the group that had previously failed IVF [63]. For patients with repeated implantation failure, it also appears that hysteroscopy itself, regardless of whether abnormalities are found, results in greater subsequent clinical pregnancy and implantation rates compared with those who did not undergo hysteroscopy (41.9 versus 32.3 and 23.8 versus 18.6%, respectively) [36 ]. The findings of this study and others [60,64] raise the question of whether dilation of the cervix during the hysteroscopy and stimulation of the endometrial cavity with any manipulation provide separate and/or additional benefit to the operative procedure, such as polypectomy. It is possible that hysteroscopy and not specifically the polypectomy is responsible for the increased clinical pregnancy rates either by facilitating subsequent embryo transfer or by enhancing endometrial receptivity by inducing endometrial stimulation through injury [45]. The main argument against this hypothesis is derived from the previously discussed RCT in which hysteroscopy with polyp resection resulted in a significantly increased pregnancy rate compared with just diagnostic hysteroscopy with polyp biopsy [48], though it should be reiterated that this study encompassed couples undergoing IUI and not IVF. &

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Hysteroscopy after failed IVF There are two meta-analyses on hysteroscopy after failed IVF prior to another IVF cycle, both of which showed approximately a 1.6-fold increase in clinical pregnancy rate following hysteroscopy and resection of lesions if found [61,62]. The number of procedures needed to achieve one additional pregnancy in this case is about 7 [60,61]. Other data further support a role for hysteroscopy, particularly after failed IVF, as these women are more likely to have intrauterine

Hysteroscopy for polyps found in cycle The diagnosis of endometrial polyps in midst of an IVF cycle represents a unique clinical challenge with respect to management, and the data to date are controversial. Although oocyte retrieval followed by embryo cryopreservation and subsequent thaw transfer after polypectomy is a viable option, studies specifically looking at this issue do not necessarily support such a conservative approach. For example, when patients with polyps less than 2 cm in size were divided between fresh transfer and subsequent thaw transfer following polypectomy, there were no differences in pregnancy rates compared with the expected fresh and thaw transfer success rates; however, there was a nonsignificant trend towards increased risk of miscarriage in the fresh transfer group [65]. Similar findings with respect to comparable pregnancy rates, but possible increased risk of miscarriage were found in a subsequent retrospective analysis of patients with polyps undergoing ICSI [66], and a recent retrospective cohort analysis showed a two-fold increase in biochemical

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pregnancy rates when polyps were left in situ for embryo transfer compared with patients without polyps (18.3 versus 9.6%, respectively); however, again there were no differences in clinical pregnancy or live birth rates [65]. Another retrospective study came to the same conclusion and even raised the question if polyps should be removed at all given that pregnancy rates were similar between patients with treated and untreated polyps and their respective matched controls [67]. A novel approach to polyps found in cycle is described in a small case series of hysteroscopic polypectomy in cycle prior to oocyte retrieval and followed by fresh embryo transfer [68]. There is potential utility to this management approach with three of the six patients conceiving [68]; however, additional, larger studies are required before this practice can be considered. Taken together, patients diagnosed with polyps during an IVF cycle should be counseled regarding increased risk of biochemical pregnancy and possible increased risk of miscarriage, but if the pregnancy progresses, outcomes are overall good [65]. The decision to bypass a fresh embryo transfer due to a newly diagnosed endometrial polyp should be individualized to the patient specific factors, including polyp number, size and location, the number and quality of embryos available, available insurance coverage for IVF, and the IVF center’s frozen embryo transfer success rates [15 ,65]. &

Timing of hysteroscopic polypectomy prior to IVF Although the current data overall support resection of endometrial polyps prior to fertility treatments, the optimal timing for surgical intervention is not clear. One study looking at greater than 6 months and less than 6 months interval between hysteroscopic polypectomy and IVF found no difference in outcomes, including clinical pregnancy rate [69]. Similarly, a more recent study demonstrated that starting IVF after one, two, or more than three menstrual cycles following hysteroscopic polypectomy made no difference in terms of clinical pregnancy or live birth rates [70 ]. This lack of a time-dependent effect of hysteroscopic polyp resection argues against a nonspecific effect of hysteroscopy on IVF success because the robust data for endometrial injury as a mechanism for enhancing implantation are based on biopsy in the menstrual cycle prior to IVF [71]. &

Cost effectiveness of hysteroscopy prior to IVF The cost effectiveness of office hysteroscopy prior to a first IVF cycle is currently the subject of an ongoing 188

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prospective RCT [72]. In a preliminary study, Kasius et al. [73] showed a potential cost benefit of routine hysteroscopy prior to IVF compared with hysteroscopy after failed IVF or no hysteroscopy, though in the analysis where only patients found to have an intrauterine abnormality benefited, there was a cost to routine hysteroscopy that could preclude widespread use. The monetary cost of IVF, particularly when there is limited or no insurance coverage, is substantial; yet, this does not take into account the emotional and physical toll of repeated IVF cycles, which should also be factored into the cost of not optimizing an IVF cycle by evaluating for and treating intrauterine pathology prior to embryo transfer. It has been shown that even when insurance covers three or more cycles, almost 40% of patients drop out prior to utilizing their full benefit as a result of the impact of stress [74]. Although hysteroscopy for polypectomy prior to IVF appears to be a reasonable approach, routine diagnostic hysteroscopy prior to IVF requires additional study to determine if there is a generalizable benefit for all women planning to undergo IVF [75].

CONCLUSION Endometrial polyps are prevalent in the infertile population and are frequently asymptomatic. Despite advances in imaging modalities, hysteroscopy remains the gold standard for evaluation of the uterine cavity and has the added benefit of simultaneous treatment of intrauterine abnormalities, such as polyps, when found. Although routine diagnostic hysteroscopy prior to an initial IVF cycle remains controversial in terms of cost/benefit, there are sufficient data at this point to support hysteroscopy if a polyp is discovered incidentally or otherwise during the infertility workup. Similarly, hysteroscopy should be strongly considered after a failed IVF cycle and certainly pursued in the setting of recurrent implantation failure. Although additional studies are needed to better understand whether all polyps require resection prior to IVF, endometrial polyps negatively alter endometrial receptivity, and hysteroscopy with polypectomy enhances chances for conception. Leaving a known polyp in place while pursuing IVF with its significant emotional, physical, and financial costs, risks failed implantation. Even if the magnitude of this risk is small relative to other factors affecting implantation, given that hysteroscopic polypectomy is a minor surgical procedure with negligible intraoperative and postoperative complications and because it may have an added benefit due to cervical dilation and/or endometrial disruption, there is little reason, if any, to avoid this therapeutic intervention. Volume 28  Number 3  June 2016

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Acknowledgements None. Financial support and sponsorship None. Conflicts of interest There are no conflicts of interest.

REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Hassa H, Tekin B, Senses T, et al. Are the site, diameter, and number of endometrial polyps related with symptomatology? Am J Obstet Gynecol 2006; 194:718–721. 2. Rackow BW, Jorgensen E, Taylor HS. Endometrial polyps affect uterine receptivity. Fertil Steril 2011; 95:2690–2692. 3. Elbehery MM, Nouh AA, Mohamed ML, et al. Insulin-like growth factor binding protein-1 and glycodelin levels in uterine flushing before and after hysteroscopic polypectomy. Clin Lab 2011; 57:953–957. 4. Peterson WF, Novak ER. Endometrial polyps. Obstet Gynecol 1956; 8:40– 49. 5. Lopes RG, Baracat EC, de Albuquerque Neto LC, et al. Analysis of estrogenand progesterone-receptor expression in endometrial polyps. J Minim Invasive Gynecol 2007; 14:300–303. 6. Mittal K, Schwartz L, Goswami S, Demopoulos R. Estrogen and progesterone receptor expression in endometrial polyps. Int J Gynecol Pathol 1996; 15:345–348. 7. Shokeir TA, Shalan HM, El-Shafei MM. Significance of endometrial polyps detected hysteroscopically in eumenorrheic infertile women. J Obstet Gynaecol Res 2004; 30:84–89. 8. Jakab A, Ovari L, Juhasz B, et al. Detection of feeding artery improves the ultrasound diagnosis of endometrial polyps in asymptomatic patients. Eur J Obstet Gynecol Reprod Biol 2005; 119:103–107. 9. Salim S, Won H, Nesbitt-Hawes E, et al. Diagnosis and management of endometrial polyps: a critical review of the literature. J Minim Invasive Gynecol 2011; 18:569–581. 10. Kim KR, Peng R, Ro JY, Robboy SJ. A diagnostically useful histopathologic feature of endometrial polyp: the long axis of endometrial glands arranged parallel to surface epithelium. Am J Surg Pathol 2004; 28:1057–1062. 11. Dreisler E, Stampe Sorensen S, Ibsen PH, Lose G. Prevalence of endometrial polyps and abnormal uterine bleeding in a Danish population aged 20–74 years. Ultrasound Obstet Gynecol 2009; 33:102–108. 12. Clevenger-Hoeft M, Syrop CH, Stovall DW, Van Voorhis BJ. Sonohysterography in premenopausal women with and without abnormal bleeding. Obstet Gynecol 1999; 94:516–520. 13. Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet 2011; 113:3–13. 14. Kilicdag EB, Haydardedeoglu B, Cok T, et al. Polycystic ovary syndrome and increased polyp numbers as risk factors for malignant transformation of endometrial polyps in premenopausal women. Int J Gynaecol Obstet 2011; 112:200–203. 15. Pereira N, Petrini AC, Lekovich JP, et al. Surgical management of endometrial & polyps in infertile women: a comprehensive review. Surg Res Pract 2015; 2015:914390. This is an up-to-date, comprehensive review of endometrial polyp diagnosis and management in the setting of infertility. 16. American Association of Gynecologic Laparoscopists. AAGL practice report: practice guidelines for the diagnosis and management of endometrial polyps. J Minim Invasive Gynecol 2012; 19:3–10. 17. Hann LE, Kim CM, Gonen M, et al. Sonohysterography compared with endometrial biopsy for evaluation of the endometrium in tamoxifen-treated women. J Ultrasound Med 2003; 22:1173–1179. 18. Reslova T, Tosner J, Resl M, et al. Endometrial polyps. A clinical study of 245 cases. Arch Gynecol Obstet 1999; 262:133–139. 19. Vilodre LC, Bertat R, Petters R, Reis FM. Cervical polyp as risk factor for hysteroscopically diagnosed endometrial polyps. Gynecol Obstet Invest 1997; 44:191–195. 20. Kim TJ, Kim HS, Park CT, et al. Clinical evaluation of follow-up methods and results of atypical glandular cells of undetermined significance (AGUS) detected on cervicovaginal Pap smears. Gynecol Oncol 1999; 73:292–298.

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J Obstet Gynaecol Res 2015; 41:1569–1576. This prospective cohort study shows benefit of hysteroscopic evaluation for women with repeated implantation failure. 37. Fatemi HM, Kasius JC, Timmermans A, et al. Prevalence of unsuspected uterine cavity abnormalities diagnosed by office hysteroscopy prior to in vitro fertilization. Hum Reprod 2010; 25:1959–1965. 38. Karayalcin R, Ozcan S, Moraloglu O, et al. Results of 2500 office-based diagnostic hysteroscopies before IVF. Reprod Biomed Online 2010; 20:689–693. 39. Hinckley MD, Milki AA. 1000 office-based hysteroscopies prior to in vitro fertilization: feasibility and findings. JSLS 2004; 8:103–107. 40. Pinheiro A, Antunes A Jr, Andrade L, et al. Expression of hormone receptors, Bcl2, Cox2 and Ki67 in benign endometrial polyps and their association with obesity. Mol Med Rep 2014; 9:2335–2341. 41. Bozkurt M, Sahin L, Ulas M. Hysteroscopic polypectomy decreases NFkappaB1 expression in the mid-secretory endometrium of women with endometrial polyp. Eur J Obstet Gynecol Reprod Biol 2015; 189:96–100. 42. Cholkeri-Singh A, Sasaki KJ. Hysteroscopy for infertile women: a review. J & Minim Invasive Gynecol 2015; 22:353–362. A comprehensive review of the role of hysteroscopy in the management of infertility. 43. Hasegawa E, Ito H, Hasegawa F, et al. Expression of leukemia inhibitory factor in the endometrium in abnormal uterine cavities during the implantation window. Fertil Steril 2012; 97:953–958. 44. Ben-Nagi J, Miell J, Yazbek J, et al. The effect of hysteroscopic polypectomy on the concentrations of endometrial implantation factors in uterine flushings. Reprod Biomed Online 2009; 19:737–744. 45. Richlin SS, Ramachandran S, Shanti A, et al. Glycodelin levels in uterine flushings and in plasma of patients with leiomyomas and polyps: implications for implantation. Hum Reprod 2002; 17:2742–2747. 46. 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Volume 28  Number 3  June 2016

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.