Role of endometrial scratching among recurrent implantation failure patients undergoing in vitro fertilisation/ICSI

INTRODUCTION

One of the major cause of repeated in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) failure is related to failure of implantation.^[1,2,3,4] Implantation is defined as the attachment of good quality embryo or blastocyst to receptive endometrium in the window of implantation, which is during a specific period.^[5] Many reports suggested that scratching of endometrium with a pipelle catheter resulted in improved rate of implantation in next cycle.^[1,2,3,4] The current study was conducted with the aim to assess the effect of endometrial scratching to improve rate of implantation in repeated implantation failure patients and to evaluate the efficacy and safety of endometrial scratching when performed prior to embryo transfer in IVF patients.

MATERIALS AND METHODS

This prospective interventional study was conducted at the Department of Assisted Reproductive Technology of a fertility research center.

In this randomised control trial study, 100 patients each with at least two implantation failures were randomly assigned equally into two groups. In the case group, endometrial scratching was performed in mid-luteal phase of the cycle prior to controlled ovarian hyperstimulation with disposable pipelle catheter (Gynetics Medical Products N.V., Rembert Dodoensstraat, Lommel, Belgium) [Figure 1] and embryo transfer (day 3) performed in the next cycle. Implantation and clinical pregnancy rates were compared thereafter among patients in the non-interventional group.

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Figure 1

Pipelle catheter (GYNETICS).

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The present study was conducted among the patients attending the fertility center after fulfilling the following inclusion and exclusion criteria.

RESULTS

Table 1 shows the comparison of mean age between the two groups. It was observed that the mean age scratching group was 30.04 ± 4.41 years whereas mean age of non-scratching group was 29.40 ± 4.15 years. Further, it was observed that the difference in mean age between the two groups was not significant (P value of 0.457).

Table 1 Comparison of mean age between two groups

As per Table 2, maximum patients were of primary infertility in both the groups (Group A: 72%; Group B: 78%). Patients with secondary infertility in Group A were 28% and in Group B were 22%. No significant statistical difference was seen in the type of infertility between the two groups (P value of 0.488).

Table 2 Distribution of primary and secondary infertility between study groups

Table 3 shows that mean duration of infertility was almost similar in both the groups (P value 0.873).

Table 3 Comparison of mean duration of infertility between study groups

As per Table 4, maximum number of patients were suffering from polycystic ovarian Syndrome (PCOS), followed by unexplained infertility and male factor infertility in both the groups. But there was no significant statistical difference in both the groups regarding the cause of infertility (P value 0.166).

Table 4 Correlation between diagnosis and study groups

In Table 5, maximum number of patients were with two implantation failures in both the groups (Group A: 76%; Group B: 70%).

Table 5 Correlation between number of previous implantation failures and study groups

Only 10% of patients had mild complaints post scratching [minimal per vaginal (PV) spotting, mild discomfort and mild lower abdominal pain] [Table 6].

Table 6 Post-procedural complains in intervention group

According to Table 7, there was no significant difference observedno in mean endometrial thickness of patients in the study as well as the control group (P value 0.657).

Table 7 Comparison of endometrial thickness on the day of trigger between study groups

In both the groups, three embryos were transferred in majority of patients (Group A: 66%; Group B: 62%) [Table 8].

Table 8 Correlation between number of embryos transferred and study groups

Although biochemical pregnancy rate in endometrial scratching group and non-scratching group was 38% and 34%, respectively, it was statistically insignificant (P value 0.677) [Table 9].

Table 9 Correlation between biochemical pregnancy and study groups

According to Table 10, higher rates of clinical pregnancy was seen in endometrial scratching group (38%) compared to non-scratching group that was 30% as in group B (non-scratching); two biochemical pregnancies (4%) did not progress to clinical pregnancy.

Table 10 Correlation between clinical pregnancy and study groups

The difference in clinical pregnancies in both the groups was statistically insignificant (P value 0.581).

Table 11 shows that implantation rate was more in endometrial scratching group (15.8%) compared to the non-endometrial scratching group (11.5%). The difference was statistically insignificant (P value 0.304).

Table 11 Comparison of implantation rates between study groups

In interventional group, singleton pregnancy was seen in 17 patients (34%) and twin pregnancy in two patients (4%). Similarly, in control group, singleton pregnancy was seen in 13 patients (26%) and twin pregnancy in just one patient (2%).

DISCUSSION

A lot of trials have been undertaken to establish the effect of endometrial scratching in patients undergoing IVF/ICSI cycles, but the significant variation remains in scratching technique, the type of patients chosen for scratching and the reliability of study. Due to these variations, the actual group of patient who can be benefitted by this method is still not confirmed.

Although this subgroup is well enumerated in literature, many parameters like different fertility treatments prior to IVF and different number of embryos transferred are still diverse. Generally, ‘implantation failure’ is a term in context with females who have at least failed thrice to implant good quality embryos which shifts the basis of this study to paramount the efficacy of assisted reproductive technology at early stages with utmost consideration to patient’s safety and comfort.

In the present study, endometrial scratching performed in the mid-luteal phase of previous cycle showed increase in chance of clinical pregnancy and implantation rate to some extent. Clinical pregnancy was 38% in the scratching group and 30% in the non-scratching group whereas implantation rate was 15.8% and 11.5% in the scratching and non-scratching group, respectively.

There has been a positive response in rate of clinical pregnancy and live births according to multiple previous trials.^{[6,7,8,9,10,11,12]} The initial demonstration of beneficial effect of endometrial scratching was done by Barash et al.^[6] which showed almost doubling of the rates of implantation, clinical pregnancy and live births in recurrent implantation failure patients.^[7] A study has shown its negative impact on clinical pregnancy when done at oocyte pickup time and not at the cycle preceding embryo transfer.^[13] Some studies have concluded endometrial scratching to be of no significant benefit.^[14,15,16] A study performed by Yeung et al.^[16] demonstrated endometrial scratching to be of no benefit in increasing chances of pregnancy when it was done in luteal phase of previous cycle rate.^[13]

The illustrated notable advantages of endometrial trauma in patients with repeated implantation failures has brought its existence into an interesting procedure which can be used in all patients prior to IVF treatments.

Suggestions have been made stating that nidation and pregnancy outcomes may be dependent on the timing and frequency of endometrial scratching performed and also on the extent of scratching done. The authors also suggested that endometrial scratching done on oocyte pickup day in same embryo transfer (ET) cycle had detrimental impact on pregnancy outcomes.^[13] Our study was based on endometrial scratching performed once in mid-luteal phase prior to IVF/ICSI cycle. However, the fact regarding ideal timing and number of times endometrial scratching required is not yet established. We selected the ‘window of nidation’ which is supposed to have maximum expression of cytokines, growth factors and other immune mediators in endometrium and thus the utmost impact of endometrial trauma is expected in this period.^[17]In the latest rational, multicenter, randomised controlled trial on endometrial scratching done on total of 1364 women, there was no difference in live birth rates after endometrial trauma when compared to control group.^[18] Live birth rate was 26.1% (180 out of 690 females) in test group and same 26.1% in the control group (176 out of 674 females).

Generally, endometrial scratching is being carried out as as an OPD procedure. Although, there are negative prospects which are based on previous studies stating that this intervention when performed on oocyte pickup day had led to decreased rates of implantation as well as pregnancy.^[18] However, it has not shown any detrimental effects when performed in cycle previous to IVF/ICSI, except for mild discomfort and mild lower abdominal pain. No other significant complains were observed in our study. Routine analgesics can be given prior to the procedure to reduce this. There is a potential risk for intrauterine infection while performing any intrauterine procedure. We know that patients with any type of vaginal or known pelvic infections are usually screened and treated before the commencement of IVF/ICSI cycle, thus minimizing the chances of any further spread of these infections during embryo transfer.

CONCLUSION

Endometrial scratching is very safe and cost effective outpatient procedure. It can also be done during diagnostic hysteroscopy.

Endometrial scratching performed once before IVF-ET increased the chance of clinical pregnancy and implantation rate to some extent; but as the study was performed on a smaller group, its reliability in clinical practice needs further research by randomised control trials on a larger study group.

Although reassurance of patients was done regarding post-procedural mild discomfort and PV spotting, in our study, none of the patients complained of any post-procedural infection, persistent bleeding or significant pain in lower abdomen.