The Therapeutic Value of Hysteroscopic Assessment of Uterine Cavity in Cases of Implantation Failure in IVF Programs

Transcription

1 Med. J. Cairo Univ., Vol. 78, No. 1, March: , The Therapeutic Value of Hysteroscopic Assessment of Uterine Cavity in Cases of Implantation Failure in IVF Programs HOSSAM M. ALKADY, M.D. The Department of Obstetrics and Gynecology, Faculty of Medicine, Al-Azhar University. Abstract Objective: To evaluate if the diagnosis and treatment of uterine abnormalities by hysteroscopy in patients undergoing IVF program is of any value in improving clinical pregnancy outcome. Study Design: Prospective, randomized observational clinical trial. Setting: Kuwait Maternity Hospital. Subjects and Methods: A total of 100 patients with prior history of failed IVF cycles after transfer of good-quality embryos, were randomized in two groups. Group I without hysteroscopy. Group II had hysteroscopy and was sub classified into group IIa and group IIb. Group IIa (n=32) had normal hysteroscopic findings whereas Group IIb (n=18) had abnormal hysteroscopy findings which were corrected at the same time. Intervention (s): Standard hysterosalpingography and diagnostic and therapeutic hysteroscopy. Main Outcome Measure (s): Pregnancy and live birth rates after IVF cycles that followed diagnostic and therapeutic hysteroscopy. Results: There was no difference in the mean number of oocytes retrieved, fertilization rate and number of embryos transferred among the patients in different groups. Statistically significant difference was observed in terms of clinical pregnancy rates between group I and group IIa (24 and 40.6%, p<0.05), and group 1 and group 2b 24 and 38.8%, p<0.05), respectively. Conclusion: Patient with recurrent IVF embryo transfer failure after normal hysterosalpingography findings should also be evaluated using hysteroscopy prior to further commencing IVF-embryo transfer cycles in order to enhance the clinical pregnancy rates. The incidence of pathologic findings on hysteroscopy is high in patients with repeated failures of IVF-ET. Evaluation of endometrial integrity by hysteroscopy is highly valuable and should be applied to all such cases. Key Words: IVF-ET Implantation failure Uterine cavity Hysteroscopy Correspondence to: Dr. Hossam M. Alkady, Dept. of Obst. & Gyn., Fac. of Medicine, Al-Azhar Univ., Cairo. Introduction TREATMENT of infertile couples has progressed immensely during recent years. The successful pregnancy outcome of patients undergoing ovarian stimulation for in vitro fertilization (IVF) depends on several factors. Among these, embryo quality and intra uterine environment plays a major role for the achievement and further continuation of pregnancy [1]. However, the significance of embryo quality in determining the pregnancy and implantation rates should not be considered apart from other factors, including endometrial receptivity and uterine integrity. Thus, benign endometrial abnormalities such as chronic endometritis, endometrial polyps, submucous leiomyomata and intrauterine adhesions, may negatively affect endometrial receptivity and implantation [2,3]. Uterine evaluation is usually accomplished with the help of hysterosalpingography (HSG) or hysteroscopy (HSC). Historically and till today, most of the clinicians prefer HSC as a first line approach to evaluate the intrauterine pathology in infertile patients, but it has been proven to have certain drawbacks [4]. Studies by Wang et al. [5] and Golan et al. [6] reported that HSG has a false positive rate of 15.6% and flase negative rate of 35.4%. Hysteroscopic evaluation of uterine cavity for women with infertility has recently become a routine procedure. Hysteroscopy also offers great assistance for the interpretation of uncertain findings from other diagnostic methods. Further it enables direct visualization of the cervical canal and uterine cavity, and increases the precision and accuracy in the diagnosis of intrauterine conditions [7,8]. Aim of the work: The main objective of this study is to assess the improvement in pregnancy outcome in patients undergoing IVF-ET who 149

2 150 Hysteroscopic Assessment in IVF Programs repeatedly failed to conceive despite transfer of good- quality embryos, by diagnosing and treating intrauterine abnormalities using hysteroscopy. Subjects and Methods This study was a prospective, randomized observational clinical trial which was approved by the ethical committee of Kuwait Maternity Hospital during the period January 2007 March One hundred patients who had undergone two or more failed ICSI cycles, in which two or more goodquality embryos were transferred per procedure, were recruited. All the participating patients had primary infertility and normal appearance of the uterine cavity on hysterosalpingography. Informed consent was also taken from them prior to the study. The patients age ranged from years and duration of infertility ranged from 6-8 years. Patients were randomly allocated to one of two groups (I & II) using computer generated random numbers. Patients were blinded to which procedure to they underwent. Group I without hysteroscopic evaluation prior to ovarian stimulation for ICSI treatment. Group II had hysteroscopy. Group II were subcategorized into group IIa and group IIb. Those in group IIa (n=32) had normal hysteroscopic findings whereas Group IIb (n=18) had abnormal hysteroscopic findings which were corrected at the same time. Hysteroscopy: All procedures were performed under general anesthesia on a day case basis which is the standard in our unit. All hysteroscopies were performed in early proliferative phase of the cycle using hysteroscopy (Karl Storz, SC-SX19-AIAII, Germany) whose diagnostic sheath had an outer diameter of 3.5 mm. uterine distension was accomplished with glycine and 80 mmhg constant intrauterine pressure was maintained using an electronic pump (endoflator). Light source was (Xenon Nova 300). The endocervical canal, uterine cavity, endometrium, tubal ostea, were inspected methodically. Filmy and dense intrauterine adhesions involving at least one third of the uterine cavity were classified as mild to moderate. Surgical video. assisted hysteroscopy was performed by using a bipolar electric resectoscope (Karl Storz) that had a surgical sheath with an outer diameter of 9 mm. The uterine cavity was distended with glycine. At the end of diagnostic hysteroscopy, an endometrial sample was obtained for histopathological examination by using a Novak curette. If polyps, leiomyomas or adhesions were found, the patient underwent immediate hysteroscopic resection or adhesolysis. Chronic endometritis at hysteroscopy was defined as areas of red endometrium that were flushed with a white central point and were localized or scattered out the cavity (the strawberry aspect). Prophylactic antibiotic (Rocephin (cephtriaxone) Roche, Basel Switzerland) was routinely given during induction of anaesthesia. The patients were discharged in the same day of the procedure and no further complications were observed. Ovarian stimulation protocol: Long protocol down-regulation was commenced using Triptorelin (Decapeptyl, Ferring, Kiel, Germany) 0.1 mg subcutaneously daily on day 21 of the cycle. Adequacy of down regulation was confirmed by measuring E2 (<50 pg/ml) and LH levels (<1 miu/ml). Controlled ovarian stimulation was achieved using human menopausal gonadotrophin (HMG) (Merional, IBSA, Lugano, Switzerland) and the dose was adjusted on the basis of individual response. Follow-up using transvaginal ultrasound and serum estradiol was commenced on day 6 of stimulation and repeated as indicated. Human chorionic gonadotrophin (hcg) at a dose of IU was given after a three follicles of 18 mm or more were visualized in the ultrasound scan. Oocyte retrieval was scheduled 36 hours later using double lumen catheter (Cook, Ireland). After successful fertilization, embryo transfer was performed on day 3 using a Wallace catherter (Sims Portex Ltd, United Kingdom) under ultrasonographic guidance). Two to three embryos of good quality were transferred. Luteal support was given constant in all patient groups by progesterone vaginal suppositories (cyclogest). Two weeks after embryo transfer, serum human chorionic gonadotrophin (hcg) was measured for confirmation of pregnancy and a diagnosis of clinical pregnancy was made after visualization of foetal heart pulsation four weeks later by transvaginal ultrasonography (TVS). Our main outcome measures were pregnancy and live birth rates after the IVF cycle. Statistical analysis: Patient s age, body mass index (BMI), duration of infertility, number of oocytes, fertilization rate (%), and the number of embryos transferred were compared by one way analysis of variance (ANOVA). Mean number of failed transfer cycles, clinical pregnancy (%) and live births (%) were compared using (hi-square test and student s t-test. A p value of <0.05 was taken as a cut-off for statistical significance.

3 Hossam M. Alkady 151 Results There was no significant difference in the mean age, body mass index (BMI), duration of infertility and number of failed cycles in either group ( p> 0.05) Table (1). Considering the causes of infertility, there was no significant difference between the studied groups (p>0.05) except for the uterine factor which was found in all patients of group (IIb). The different causes are summarized in Table (2). Among the 50 patients (group II) who had hysteroscopy, 18 patients (36%) were found to have uterine cavity abnormalities Table (3). Among these, 6 (34%) had polyps, 2 (11%) had adhesions, 1 (5.5%) had submucous leiomyoma, 3 (16.6%) had emdometritis, 2 (11%) had septate uterus, 3 (16.6%) had cervical stenosis, and 2 (11%) had endometrial hyperplasia. All these abnormalities were treated during the hysteroscopic procedures and were accomplished in a maximum of 30 minutes without any difficulty and without complications. In 32 patients (64%), no abnormality was observed during hysteroscopy. The number of eggs collected, fertilization rates and the number of resultant embryos were comparable in the studied groups Table (4). The mean (±SD) number of eggs collected were 8.34±3.40, 9.6±4.31 and 8.41 ±4.37 in group I, group IIa and group IIb, respectively (p>0.05). There was statistically significant difference in the rate of chemical pregnancy in favor of group IIa and group IIb (14 [43.7%] and 8 [44%], respectively) versus 13 (26%) in group I, (p<0.05). There was a statistically significant difference in the rate of chemical pregnancy in favor of group IIa and group IIb (14 [43.7%] and 8 [44%], respectively) versus 13 (26%) in group I, (p<0.05). There was statistically significant difference in the rate of chemical pregnancy in favor of group IIa and group IIb (14 [43.7%] and 8 [44%], respectively) versus 13 (26%) in group I, (p*< 0.05). Significant difference was found in the clinical pregnancy rates between patients in group I and group IIa (24 vs. 40.6%, p<0.05), and group I and group IIb (24 vs. 38.8%, p<0.05). There was no significant difference in the clinical pregnancy rates in patients in group IIa and group IIb (p>0.05). The incidence of live birth rate was significantly higher in group IIa 9 (28%) and group IIb 5 (27.7%) than in group I 8 (16%) (p*<0.05). The incidence of twin and triplet pregnancy did not differ significantly between the studied groups ( p>0.05). There were no significant differences observed in terms of miscarriage rates in all groups ( p>0.05). Table (1): Clinical characteristics of patients in the studied groups. Variables Group I Group IIa (n=32) Group IIb (n=18) P value Age 24.32± ± ±082 Body mass index (Kg/m2) Duration of infertility Mean number of failed transfer cycles 25.71± ± ± ± ± ± ± ± ±0.40 Values are presented as mean ± SD., NOT significant (p>0.05). Table (2): Causes of infertility and indications for IVF in the studied groups. Ovulatory PCOD (% of ovulatory) Ovarian reserve (% of ovulatory) Endometriosis Tubal factor Uterine factor Male factor Unexplained Combined male and female factor Group I 10 (20) 8 (80) 2 (20) 3 (6) 10 (20) Not Performed 18 (36) 3 (6) 6 (12) Group IIa Group IIb P (n=32) (n=18) value 7 (22) 6 (82) 1 (8) 2 (7) 5 (16) Nil 11 (34) 2 (6) 5 (16) 4 (22) 3 (81) 1 (9) 1 (5) 2 (14) 18 6 (32) 1 (5) 4 (22) Values are presented as n (%)., not significant ( p>0.05). Table (3): Findings on hysteroscopy in 50 patients undergoing ICSI. Findings No. of cases confirmed by hysteroscopy (%) Polyps 6 (34) Adhesions 2 (11) Submucous leiomyoma 1 (5.5) Endometritis 3 (16.6) Septate uterus 1 (5.5) Cervical stenosis 3 (16.6) Endometrial hyperplasia 2 (11) Normal cavity 32 (64) Values are presented as n (%).

4 152 Hysteroscopic Assessment in IVF Programs Table (4): Laboratory data from 100 subsequent IVF-ET cycles in the studied groups. Variables Group I Group IIa (n=32) Group IIb (n=18) Group IIb (n=18) p value No. of eggs collected ± ±4.37 Fertilization rate (%) (63) (60) (64) No. of embryos transferred: Mean ± SD Values are presented as mean ± SD or n (%)., not significant (p>0.05) Table (5): Pregnancy outcome in the studied groups. Variables p value Chemical pregnancy 13 (26) 14 (43.7)* 8 (44)* p<0.05 Clinical pregnancy Group I 12 (24) 13 (40.6)* 7 (38.8)* p<0.05 Miscarriage rate (% of 4 (33.3) 4 (30.7) 2 (28.5) clinical pregnancies) Live birth rate 8 (16) 9 (28) 5 (27.7)* p<0.05 Singleton 6 (75) 7 (79) 4 (75) Multiple pregnancies 2 (25) 2 (21) 1 (25) Values are presented as n (%)., not significant ( p>0.05). p*<0.05 when compared to group I. Discussion Group IIa (n=32) The evaluation of the couple with recurrent implantation failure is very complex and to a large extent it mainly depends on two important factors which include embryo quality and uterine integrity. At present, ovarian stimulation and predictive outcome of embryo quality have developed in a standardized manner whereas reliable parameters for uterine receptivity are still in the infancy [1,9]. It is a very frustrating problem for both the patient and the medical team, especially after all the preceding steps leading up to obtaining good embryos have been successful [10]. One such parameter for uterine receptivity is the morphological assessment of the uterine cavity by hysteroscopy. A thorough evaluation of the uterine cavity forms an important part of screening process before starting any assisted reproduction technique [3]. Further, it is also mandatory particularly in patients with good quality embryos who fail to conceive [7]. Hysterosalpingogram (HSG) has been the most commonly used for the evaluation of uterine cavity before undergoing IVF treatment. Since last decade, its sensitivity and specificity have been questioned by several studies. Studies by Kessler and Lancet [11] reported that more than two thirds of the cases diagnosed by HSG did not correlate with hysteroscopic findings and results show that 54.3% of intrauterine adhesions diagnosed on HSG were not found on hysteroscopic examinations [6]. Another study comparing the diagnostic value of HSG and HSC by Wang et al. [5]. Reported that HSG has false negative rate of 35.4% and false positive rate of 15.6%. This study is further supported by Valle [12], Golan, et al. [6] and Prevedourakis, et al. [4]. Therefore, HSC interpreted as normal in more than one third of the cases given a false reassurance. Small intrauterine lesions such as adhesions, polyps and submucous myomas which may be of greater significance in causing of implantation failure are diagnosed more accurately by using hysteroscopy in comparison with HSG. The present study demonstrated that 36% of patients with normal HSG had abnormal hysteroscopy findings and this concurs with the results reported by Kirsop, et al. [13] and Cunha, et al. [14]. A recent study by Cincenilli, et al. [15] reported that HSG has a false negative rate of 59% in case of intrauterine abnormalities which is higher than that reported by Balmaceda & Ciuffrdi [16]. This is further supported by studies done by Meyer et al. [17]. These data further strengthen the role of hysteroscopy in the management of infertile patients in detecting endometrial pathologies that were never revealed by HSG. The importance of embryo quality in determining pregnancy outcome should not be considered independent of endometrial receptivity and uterine integrity [18]. In our study, patients had had replacement with good-quality embryos, yet repeated implantation failure occurred. At present, although ovarian stimulation and assessment of embryo quality have developed in standardized manner, reliable predictors of uterine receptivity are still needed. Neither endometrial thickness nor Doppler evaluation of uterine perfusion has been consistently predictive of pregnancy outcome [19]. Endometrial integrity is the only variable that can be studied n a large scale by using hysteroscopy and endometrial biopsy but this has not yet been done [20]. In the current study, the endouterine abnormalities diagnosed with hysteroscopy in 18 of 50 (36%) patients were significant and were not seen by hysterosalpingography preformed prior to the study.

5 Hossam M. Alkady 153 The sensitivity and specificity of hysterosalpingography for revealing abnormalities are about 80% and 70%, respectively [5]. Important unsuspected intrauterine abnormalities such as chronic endometritis (3 patients) and adhesions (2 patients) were found only on hysteroscopy in 27.5% of patients. This fact highlights the importance of the use of hysteroscopy as second level investigation independent of hysterosalpingographic examination. Previous studies have reported that hysteroscopy reveals undetected intrauterine abnormalities in 20% 50% of patients who are about to undergo or have undergone IVF- ET [21,22]. Consequently, some recommended routine hysteroscopy to characterize the uterine cavity as part of the standard evaluation of infertile women [23]. Nonetheless, most clinicians continue to rely on sonograph and hysterosalpingography for routine assessment of the uterine cavity in these patients. The prevalence of chronic endometritis in this group of patients with repeated IVF failures was 16.6% (3 of 18). There are two possible explanations for the relatively high incidence of endometritis among these patients. One is the sample size of the study. The other is related to the presence of cervical microorganisms on transfer catheters. Implantation and pregnancy rates are significantly lower in women with positive microbial cathetertip cultures [24,25]. Despite the lack of further testing to rule out an infectious cause of endometritis, we provided empirical treatment with doxycycline because we suspected that hysteroscopic endometritis were most likely caused by chlamydial or microplasma infection of the endometrium [26]. Nevertheless, in a prospective study of the aetiology of the endometritis by Polisinni, et al. [27], no correlation was observed between PCR for Chlamydia in endometrial biopsy specimens and endometritis diagnosed by hysteroscopy. The prevalence of endometritis was 12% (6 of 50 patients) among women who had been infertile for 1-18 years. Therefore, the presence of endometrial infection in hysteroscopic examination should be confirmed by another test and further studies are needed to establish the cause of chronic endometritis in infertile patients. The prevalence of submucous leiomyomata and polyps in this group of patients with repeated IVF- ET failures were about 5.5% and 34%, respectively. The prevalence of these conditions in patients with repeated failure of IVF-ET is not known. However, the effect of cavitary distortion from submucosal leiomyomata and polyps in implantation is readily understandable. Various theories have been proposed. Some investigators have suggested that uterine contractility and transportation of the embryo during the implantation phase is altered [28]. Others have proposed that the underlying leiomyomata may induce untoward inflammatory or vascular changes with aberrant growth factor release in the endometrium, thus leading to a less receptive implantation site [29]. Intrauterine adhesions were found in about 11 % (2 of 50) of this group of patients with repeated IVF-ET failure. Previous reports on the aetiology of intrauterine adhesions suggested that dilatation and curettage was responsible for 40% of the conditions [30]. However, no patient in this group had had previous abortions or uterine manipulation, such as dilatation and curettage. Therefore, other causes of intrauterine adhesions must be ruled out. In all patient groups, there was no significant difference in the parameters regarding age, duration of infertility and BMI (Table 1), whereas significant difference was observed in the pregnancy rates among the patients in Groups I, IIa, and IIb (24, 40.6, and 38.8%), respectively. There was no significant difference in miscarriages rate observed between the groups. This concurs with the results reported by Rama Raju, et al. [7] and Kadoch [31]. Our results suggest that the incidence of pathologic findings on hysteroscopy is relatively high in patients who have repeated IVF-ET failure despite transfer of good-quality embryos. Relevant therapeutic interventions before the third IVF-ET attempt significantly improved clinical pregnancy and implantation rates in patients with an abnormal uterine cavity compared with patients with a normal uterine cavity at hysteroscopy. In conclusion: Evaluation of uterine and endometrial integrity by hysteroscopy is valuable and reliable and should be preformed in all patients who have repeated IVF-ET failure after transfer of good-quality embryos as the multiple embryo transfer procedures may themselves induce certain endometrial pathologies like adhesions producing an unfavorable endometrial bed. Correction of these lesions reduces the implantation failure and enhances the clinical pregnancy outcome. References 1- MARGALIOTH E.J., BEN-CHERTI A.B., GAL M. and ELDAR-GEVA T.: Investigation and treatment of repeated implantation failure following IVF-ET. Hum Reprod, 21 (12): , 2006.

6 154 Hysteroscopic Assessment in IVF Programs 2- TAN B.K, VANDEKER P., KENNEDY R. and KEAY S.D.: Investigation and current management of recurrent IVF treatment failure in the UK. BJOG, 112: 773, OLIVERIA F.G., ABDELMASSIH V.G., DIAMOND M.P. and DZORTSEV D.: Uterine cavity findings and hysteroscopic interventions in patients undergoing in vitro fertilizat ion-embryo transfer who repeatedly cannot conceive. Fertil. Steril., 80 (6): , PREVEDOURAKIS C., LOUTRADIS D., KALIANIDIS C. and MARKIS N.: Hysterosalpingography and hysteroscopy in female infertility. Hum Reprod, 9: , WANG C.W., LEE C.H., LAI Y.M. and CHANG M.Y.: Comparison of hyterosalpingography and hysteroscopy in female infertility J. Am. Assoc Gynecol. Laparosc, 3: , GOLAN A., EILAT E., RON E.L., HERMAN A. and SOFFER Y.: Hysteroscopy is superior to hysterosalpingography in infertility investigation. Acta. Obstet. Gynecol. Scand, 9: , RAMA RAJU G.A., SHASHI K., KRISHNA K.M. and PRAKASH G.J.: Assessment of uterine cavity by hysteroscopy in assisted reproductive programme and its influence on pregnancy outcome Arch. Gynecol. Obstet., 274: , ARSLAN S., AYTAN H., TUNCAY G. and TAPISIZ O.L.: Office hysteroscopic evaluation of endometrium:can we hit the target? Arch. Gynecol. Obstet., 271: , DEMIROL A. and GURGAN T.: Effect of treatment of intrauterine pathologies with office hysteroscopy in patients with recurrent IVF failure. Reprod Biomed Online, 8: , BUSSO C.E., MELO M.A., FERNANDEZ M., PELLIC- ER: Implantation in IVF.Int Surg, 91 (suppl 5): S63-76, KESSLER I. and LANCET M.: Hysterography and hysteroscopy, acomparison. Ferti Steril, 46: , VALLE R.F.: Office hysteroscopy. Clin. Obstet. Gynecol., 42: , KIRSOP R., PORTER R.,TORODE H. and SMITH D.: The role of Hysteroscopy in patients having failed IVF/ GIFT transfer cycles. Aust NZ J. Obstet. Gynecol., 31: , CUNHA J.S., DE SOUZA C.A., SALAZAR C.C., FACIN A.C.: Accuracy of hysterosalpingography and hysteroscopy for diagnosis of intrauterine Lesions in infertile patients in an assisted fertilization program. Gynecol. Endosc, 10: 45-48, CINCINELLI E., ROMANO F., ANASTASSIO P.S. and BLASI N.: Transabdominal sonohysterography, transvaginal sonography and hysteroscopy in the evaluation of submucous myomas. Obstet. Gynecol. Scand., 85: 65-70, BALMACDA J.P. and CIUFFARDI I.: Hysterosalpingography and assisted reproductive technology. Obstet. Gynecol. Clin. North Am., 22: , MEYER W.R., CASTELBAUM A.J., SOMKUTI S., SAGOSKIN A.W., DOYLE M., HARRIS J.E. and LESSEY BA.: Hydrosalpinges adversely affect markers of endometrial receptivity. Hum. Reprod, 12: , SPIERS A.L., LOPATA A., GRONOW M.J. and KELLOW G.N.: Analysis of the benefits and risks of multiple embryo transfer. Fertil. Steril., 39: , SCHWARTZ L.B., CHIU A.S., COURTNEY M. and KREY L.: The embryo versus endometrium controversy revisited as it relates to predicting pregnancy outcome in in-vitro fertilization-embryo transfer cycles. Hum. Reprod, 12: 45-50, SHAMMA F.N., LEE G., GUTMANN J.N. and LAVY G.: The role of Office hysteroscopy in in-vitro fertilization. Fertil. Steril., 58: , GIATRAS K., BERKELEY A.S., NOYES N. and LIC- CIARDI F.: Fertility after hysteroscopic resection of submucous myomas. J. Am. Assoc Gynecol. Laparosc, 6: , FERNANDEZ H., SEFRIOUI O., VIRELIZIER C. and GERVAISE A.: Hysteroscopic resection of submucous myomas in patients with infertility. Hum. Reprod, 16: , LA SALA G.B., MONTANARI R., DESANTIL and CIGARINE C.: The role of diagnostic hysteroscopy and endometrial biopsy assisted reproductive technologies. Fertil. Steril., 70: , EGBASE P.E., UDO E.E. and GRUDZIKAS J.G.: Prophylactic antibiotics and endocervical microbial inoculation of endometriun at embryo transfer. Lancet, 21: 651-2, FANCHIN R., HARMAS A., LUMDKVIST U. and FRY- DMAN R.: Microbial flora of the cervix assessed at the time of embryo transfer adversely affects in vitro fertilization outcome. Fertil. Steril., 70: , CRAVELLO L., PORCU G., ROGER V. and BLANC B.: Identification and treatment of endometritis. Contracept Fertil. Sex., 25: 585-6, POLISSENI F., BAMBIRRA E.A. and CAMARGOS A.F.: Detection of chronic endometritis by diagnostic hysteroscopy in asymptomatic infertile patients. Fertil. Steril., 76 (suppl 3): S186, OLUFOWOBI O., SHARIF K., PAPAIONNON S. and AFNAN M.: Are the anticipated benefits of myomectomy achieved in womem of reproductive age? A 5-year review of the results at auk tertiary hospital. J. Obstet. Gynecol., 24: , SURREY E.S. and LIETZ A.K.: Schoolcraft WB. Impact of intramural leiomyomata in patients with normal endometrial cavity on in vitro fertilization-embryo transfer cycle outcome. Feril. Steril., 88: , SCHENKER J.G. and MARGALIOTH E.J.: Intrauterine adhesions: an up-dated appraisal. Fertil. Steril., 37: , KADOCH I.J.: Natural cycle IVF in women with implantation failure. J. Gynecol. Obstet. Biol. Reprod (Paris), 33: S33-S35, 2009.