Role of pre IVF hysteroscopy in women with unexplained infertility for detecting unsuspected intrauterine lesions and effect on pregnancy outcome

INTRODUCTION

The cause of infertility is unexplained in up to one-third of all couples, undergoing in-vitro fertilization (IVF) treatment, where no specific contributors to infertility are detected after completing standard fertility investigations.^[1] The assessment of intrauterine abnormalities is a core part of infertility evaluation as it impacts the complex process of embryo implantation.^[2]

There has been seen high prevalence of (40%–50%) unsuspected intrauterine lesions like synechiae, septum, endometritis and polyps in asymptomatic women, diagnosed by pre IVF hysteroscopy, in numerous studies conducted in various IVF clinics.^[3,4,5,6,7] The presence of such intrauterine lesions can significantly compromise spontaneous fertility as well as pregnancy outcome in women after fertility treatment.^{[2,8,9,10,11]}

The gold standard technique for evaluating the uterine cavity is hysteroscopy.^[2,12] Compared to transvaginal ultrasonography (TVS), hysteroscopy allows for a direct visualization of the unsuspected lesions and treatment in the same sitting.^[7,13] According to the international guidelines of American Society for reproductive medicine (ASRM), hysteroscopy should be reserved for further evaluation after finding abnormalities on transvaginal ultrasonography and hysterosalpingography (HSG) considering cost effectiveness.^[14] However new endoscopical advancements have made diagnostic and operative hysteroscopy cost effective, safe, time saving and useful as fertility enhancing minimal invasive surgery.^[15]

The relevance of routine hysteroscopy before IVF is debatable and there is no consensus on the effectiveness of hysteroscopic surgery in improving pregnancy outcome. A number of studies have shown increased pregnancy rates after pre IVF hysteroscopy,^[3,4,5] whereas some have showed no potential benefits.^[19,20,21]

This study is aimed to assess the role of pre IVF hysteroscopy in women with unexplained infertility in detecting unsuspected intrauterine lesions and also to assess the effect of treating such lesions on pregnancy outcome.

AIMS AND OBJECTIVES

The purpose of this study is to determine the role of pre IVF hysteroscopy in women with unexplained infertility for detecting unsuspected intrauterine lesions and effect on pregnancy outcome.

MATERIALS AND METHODS

This is a retrospective observational study, conducted in women undergoing IVF treatment at Medicover Fertility Center, New Delhi over the period from January 2018 to January 2020. The study was approved by the institutional Ethics Board.

RESULTS

The baseline characteristics including age, body mass index (BMI), duration and type of infertility were similar in both study and control groups. The mean age of the women was 31.50 ± 6.30 years in study group and 30.26 ± 5.89 years in control group (P value = 0.109). The mean BMI was 25.47 ± 5.64 in study group and 25.20 ± 4.32 in control group (P-value = 0.671). There was no significant difference between the groups regarding duration of infertility (P-value = 0.126). Majority of the women had primary infertility in both the groups [Table 1].

Table 1 Demographic characteristics

Among 60 women who underwent hysteroscopy, intrauterine abnormalities were found in 19 (31.6%) of them. Intrauterine adhesions were present in 6 women (10%), tubular cavity in 3 (5%), septum in 3 (5%), endometritis in 2 (3.3%) and endometrial focal thickening/ polyp was present in 5 (8.3%) of them [Table 2]. Adhesions noted were mild and flimsy, septum was partial (1.5–3 cm) and size of endometrial polyps varied from 5 to 7mm. Operative hysteroscopy procedure was done to correct intrauterine abnormalities accordingly. The procedure was well tolerated in almost all the patients. No intraoperative complication occurred. The majority of women didn’t feel any significant pain after the procedure, only five women (8.3%) had mild lower abdominal cramps like pain and managed with oral analgesics. Two (3.3%) women had irregular mild bleeding per vaginum for one to two weeks that was managed with oral tranexamic acid.

Table 2 Hysteroscopy findings in the study group

The clinical pregnancy rate was 48.3% (29/60) in study group and 36.7% (22/60) in control group. The clinical pregnancy rate (CPR) was observationally higher in women with pre IVF hysteroscopy, but the difference was not statistically significant (P-value = 0.193) [Table 3]. This difference was seen in women who underwent operative hysteroscopy for correction of intrauterine abnormalities as well as who had normal findings after hysteroscopy. 29 women (48.3%) out of 60 conceived after hysteroscopy. 9/19 (47.3%) pregnancies occurred in women with corrected intrauterine abnormalities [Table 4]. In the study group, out of 29 women who conceived, 14 (48.2%) have delivered, 4 (13.8%) aborted, and 11 (37.9%) have ongoing pregnancy. In the control group, among 22 who conceived, 11 (50%) have delivered, 3 (13.6%) aborted and 8 (36.3%) have ongoing pregnancy. [Table 5]

Table 3 The comparison of clinical pregnancy rate between study and control group

Table 4 Clinical pregnancy rate in study (Hysteroscopy) group (N = 60)

Table 5 Outcome of pregnancy among all women who conceived

DISCUSSION

A variety of factors can influence success rates after IVF. The uterine cavity is considered to be one of the key factors influencing the outcome of the fertility treatment.^[2] Hysteroscopy is the gold standard for the assessment of uterine cavity with an advantage to treat any detected uterine pathology.^[2,12] Elsetohy et al.^[3] and Bakas et al.^[7] have concluded that TVS is specific but not sensitive compared to hysteroscopy. In a study by Apirakviriya et al.^[22] 3D-TVS in comparison with hysteroscopy had 84.1% diagnostic accuracy, 68.2% sensitivity and 91.5% specificity. Several intrauterine lesions like intrauterine adhesions, septum and endometritis cannot be satisfactorily detected by transvaginal ultrasound.

Our results suggested a high prevalence (31.6%) of unsuspected intrauterine abnormalities in women with unexplained infertility with normal 2D-TVS findings who underwent pre IVF hysteroscopy. These intrauterine abnormal findings were intrauterine adhesions (10%), endometrial polyps (8.3%), uterine septum (5%), tubular cavity (5%) and endometritis (3.3%). Elsetohy et al.^[3] (43.3%), Cenksoy et al.^[4] (44.9%), Doldi et al.^[5] (40%), Ajayi et al.^[6] (61.1%) and Bakas et al.^[7] (31.8%) have also reported high prevalence of unsuspected intrauterine lesions like synechiae, septum, endometrial polyps in asymptomatic women undergoing infertility treatment. The evidence on the effectiveness of hysteroscopic surgeries in women with intrauterine abnormalities indicates a potential benefit. A Cochrane review by Bosteels et al.^[9] showed that hysteroscopic polypectomy prior to IUI increases clinical pregnancy rate. Perez-Medina et al.^[11] also demonstrated that hysteroscopy removal of endometrial polyps increases chance of pregnancy, suggesting its possible association with implantation failure. Bakas et al.^[16] found that hysteroscopy metroplasty in women with septate uterus and unexplained infertility improve clinical pregnancy rates and live births. A retrospective matched-control study by Tomazevic et al.^[23] evaluated the effect of uterine anomalies on pregnancy rates after 2481 embryo transfers and concluded that pregnancy rates after embryo transfer before hysteroscopy metroplasty were significantly lower in women with arcuate, subseptate and septate uterus compared with embryo transfer after corrected surgeries.

In this study, it was found that clinical pregnancy rate was higher (48.3% vs. 36.7%) in women with unexplained infertility who underwent hysteroscopy prior to first IVF cycle than who did not undergo hysteroscopy, but this difference was not statistically significant (P value = 0.193). 48.3% of women conceived after hysteroscopy, 47.3% pregnancies occurred in women with corrected intrauterine abnormalities. A systematic review and meta-analysis by Di Spiezio et al.^[17] showed beneficial effect of hysteroscopy for women undergoing their first IVF/ ICSI cycle and also for women with one or more implantation failures. A meta-analysis by Pundir et al.^[18] showed increased live birth rates when hysteroscopy was performed prior to first IVF cycle. The increased pregnancy rates after pre IVF hysteroscopy was also seen in studies by Elsetohy et al.,^[3] Censkoy et al.,^[4] and Doldi et al.^[5] The higher pregnancy rates in even those women who had normal findings after hysteroscopy can be because of immunological mechanism triggered by hysteroscopical mechanical manipulation or by the effect of distension medium on the endometrium. Irrigation of cavity with saline removes harmful anti-adhesive glycoprotein molecules (cyclooxygenase-2, mucin-1 & integrin aVβ3) on the endometrium thus improving endometrial receptivity.^[24,25,26] Sometimes visual assessment of cervical canal and adhesiolysis in case of cervical stenosis also helps further in embryo transfer. Some studies didn’t recommend hysteroscopy as a routine practice before ART, as the significance of treating unsuspected intrauterine lesions are not yet fully proven.^[19,20,21] The findings from a multicenter randomized clinical inSIGHT^[19] trial showed that hysteroscopy does not improve live birth rate in women with normal transvaginal ultrasound of uterine cavity before first IVF cycle. Another randomized controlled trial, TROPHY trial on the role of hysteroscopy in women with two to four failed IVF cycles also reported no improvement in live birth rates after hysteroscopy.^[20]

There is no consensus on the routine use of hysteroscopy before IVF, although many observational studies and meta-analysis suggest increased pregnancy rates after the hysteroscopical removal of such lesions.^{[3,4,5,10,16,17,18]} Hence, the importance of hysteroscopy as a routine in the management of infertile women still remains a matter of debate.

CONCLUSION

This study concluded that there was high prevalence rate of unsuspected intrauterine lesions in women with unexplained infertility diagnosed by pre IVF hysteroscopy. Pre IVF hysteroscopy increased clinical pregnancy rate, though the difference was not statistically significant. Limitation of this study was small sample size, further larger studies and randomized controlled trials are needed to verify the positive outcome of routine use of hysteroscopy prior to IVF.