**4. Role of hysteroscopy prior to assisted reproduction**

Failure of IVF treatment can be broadly attributed to embryonic, uterine or transfer factors, but remains unexplained in most cases (18). A number of interventions have been proposed to improve IVF outcome, many of which are not strictly evidence-based and their efficacy in improving pregnancy rates remains controversial (19,20). One of the main causes of failure of implantation after proper embryo transfer is intrauterine pathology. Whether to perform hysteroscopic evaluation of the endometrial cavity prior to IVF/ICSI especially in patients with repeated failures is a controversial issue that is open for criticism and deserves further studies (21).

In a systematic review (Level Ia evidence), 5 reliable studies were included (22). Two RCT showed a statistically significant improvement in the clinical pregnancy rate in the group who had office hysteroscopy (pooled RR = 1.57, 95% CI 1.29–1.92, *P* < 0.00001). The miscarriage rate was not statistically different between the office hysteoscopy and control groups in either study (24% versus 29%, respectively, RR = 0.83, 95% CI 0.56–1.21, *P* = 0.33). Three non-randomized controlled studies suggests that office hysteroscopy improves the pregnancy rate in the subsequent IVF cycle (pooled RR = 2.01, 95% CI 1.60–2.52, *P* < 0.00001). In addition to the well known diagnostic as well as therapeutic advantages of performing hysteroscopy, even if the endometrial cavity was completely free, high pregnancy rate was achieved after diagnostic hysteroscopy since uterine instrumentation during hysteroscopy would inevitably cause a degree of endometrial injury and provokes a posttraumatic reaction that involves release of cytokines and growth factors (23,24), which in turn may influence the likelihood of implantation (25). Commencing IVF treatment soon after hysteroscopy may take advantage of this immunological response (26). Performing diagnostic hysteroscopy before assisted reproductive technologies (ART) may be advisable not only from the clinical but also from the economic point of view (27). Enhanced clinical pregnancy rates would be achieved on adding office hysteroscopy as a complementary step prior to IVFspecially patients with recurrent IVF embryo transfer failures even after normal hysterosalpingography findings. Some abnormal intrauterine findings that would affect the prognosis of IVF/ICSI can be easily diagnosed by hysteroscopy like chronic endometritis, Müllerian anomalies, retained fetal bones, or endocervical ossification. Moreover, contact hysteroscopy may reveal addition valuable findings such as polyposis, strawberry pattern,

hypervascularisation, irregular endometrium with endometrial defects, or cystic haemorrhagic lesion which are commonly seen with adenomyosis (28). Future high-quality randomized trials are needed to confirm the favorable effect of standard hysteroscopy in different IVF populations and examine whether newer and less invasive techniques of uterine cavity evaluation such as mini-hysteroscopy (29) or hysterocontrast sonography (30) would have an equally beneficial effect when compared with no intervention before IVF.

Endoscopy versus IVF: The Way to Go 35

 In cases of failed IVF once, hysteroscopy is valuable and recommended. In cases with recurrent implantation failure, hysteroscopy is mandatory.

**4.2. Office hysteroscopy versus saline-infusion sonography (SIS)** 

only with office hysteroscopy as we recently published (41).

**5. Role of hysteroscopy after embryo transfer** 

**6. Hysteroscopic embryo transfer** 

was selected in difficult cases of embryo transfer (44).

significantly higher than that in conventional ET (45).

In 1999, we published our first series of SIS for screening in infertile patients utilizing 0.9% saline as an infusion solution and Nelaton catheters for injection (39). We reported satisfactory results. One year later, we published a study (40) on the efficacy of SIS for the detection of endometrial polyps in comparison to the conventional hysteroscopy. These studies compared SIS versus conventional hysteroscopy with excellent results in favor of SIS. Later on, we introduced office hysteroscopy (I use it since 2002 utilizing 2.6 mm telescope). With the advent of vaginoscopic approach, the procedure gained more acceptability among our patients. Now, after these years of experience we changed our mind and strongly say that office hysteroscopy can easily replace indirect diagnostic tools like SIS or 4D ultrasonography. Moreover, more detailed description of the endometrial cavity particularly the blood vessels would be obtained

In a study evaluating the incidence of endometrial injury following embryo transfer, office hysteroscopy was performed immediately following embryo transfer and demonstrated marked endocervical and endometrial damage following rigid catheters more than soft catheters (42). Even for cases of early abortion following IVF/ICSI, hysteroscopy was proved to be very valuable. In one study (43), among 84 early abortion patients after IVF-ET, it succeeded to diagnose intrauterine abnormalities in 58 (69.05%) of the patients, including intrauterine adhesion in 32 (32/84, 38.10%), endometrial polyps in 12 (12/84, 14.29%), endometritis in 10

As a trial of improving implantation rate following IVF/ICSI, some scattered papers described hysteroscopically-guided embryo transfer. Principally, hysteroscopic approach

Catheterization was performed in 60 patients at hysteroscopic insemination into tube, using 3 French catheters, in which the distal 3,4, and 5 cm tapered to 2 French. Hysteroscopic tubal embryo transfer and conventional IVE-ET were performed in 30 patients with normal tubes, who failed to achieve pregnancy after 2 IVF-ET trials. The success rate of complete insertion with the catheter tapering at the distal 3 cm was significantly higher than that at the distal 5 cm. Since we obtained the highest success rate of insertion with the catheter tapering at the distal 3 cm, we selected this catheter for the h-TEST. The rate of pregnancy in h-TEST was

(10/84, 11.90%), submucous leiomyoma in 3 (3/84, 3.57%) and septa in 1 (1/84, 1.19%).

**6.1. A new hysteroscopic tubal embryo transfer catheter was developed** 

With the advent of technical refinements and advancement in hysteroscopic surgery, it is expected that preoperative hysteroscopic evaluation of uteri prior to IVF/ICSI would be widely performed. Unfortunately, many of studies on this topic focus on the central role of hysteroscopic examination of the endometrial cavity in cases with recurrent failures (28,31,32). This concept should be reviewed since office hysteroscopy or minihysteroscopy is a simple outpatient conscious procedure (33-34) that provides excellent information on the implantation site in the endometrial cavity in a very short time. Relying on hysterosalpingography alone may be fallacious in some cases of fine intrauterine adhesions that may be masked by dye especially oily dye. Likewise, transvaginal ultrasonography as well as sonohysterograohy may miss some important fine intrautrerine lesions thatwould simply contribute for failures (3). In one study, hysteroscopy succeeded to diagnose and treat intrauterine lesions in 26% of patients prior to starting trials of assisted reproduction (31). In a big sample sized study (36), intrauterine pathology was diagnosed in about 23% of 2500 cases prior to IVF trial. Another study diagnosed abnormalities in only 11 out of 678 cases. On reevaluation of DVD records of hysteroscopy by an experienced team, the same team reported perfect diagnosis in 77.6% of cases (37).

Following recurrent IVF failure there is some evidence of benefit from hysteroscopy in increasing the chance of pregnancy in the subsequent IVF cycle, both in those with abnormal and normal hysteroscopic findings. Various possible mechanisms have been proposed for this beneficial effect, but more randomized controlled trials are needed before its routine use in the general subfertile population can be recommended (38).
