infertility centre delhi

Endometrial scratch final

Prof. Abha Majumdar
Director, Center of IVF and Human
Reproduction Sir Ganga Ram Hospital,
New Delhi, INDIA

President’s Medal for best medical graduate of year1970-75
Award from DMA on Dr. B.C Roy’s birthday: outstanding contribution to
medicine,1999
Vikas Ratan Award by Nations economic development & growth society 2002

President’s Medal for best medical graduate of year1970-75
Award from DMA on Dr. B.C Roy’s birthday: outstanding contribution to medicine,1999
Vikas Ratan Award by Nations economic development & growth society 2002
Chitsa Ratan Award by International Study Circle in 2007
Life time Medical excellence award Obs & Gyne by Hippocrates foundation 2014
Abdul Kalam gold medal 2015 & Rashtriya Gaurav Gold Medal award 2017 by Global Economic Progress & Research Association.
Distinguished teacher of excellence award for PG medical education by ANBAI & NBE 2017 and Inspiring Gynecologists of India by Economic Times 2017. Felicitated by highest Merck Serono honor award at times healthcare achievers award 2018
Course director for post-doctoral Fellowship in Reproductive Medicine by NBE, since 2007, IFS since 2014, ISAR 2014 and by FOGSI for basic & advanced infertility training since 2008.
Member of Editorial board of ‘IVF Worldwide’, peer reviewer for ‘Journal of Human Reproductive Sciences’, and member of advisory board for ‘Journal of Fertility Science & Research’.
Field of interest: Infertility, ART, Reproductive endocrinology, Endoscopic surgery for pelvic resurrection. and ART.
IVF Specialist Delhi

Endometrial scratch

Every single menstrual cycle aims at endometrial growth & receptivity which is a steroid-dependent phenomenon & is targeted to create a ‘window of implantation’ which spans from day 20 to 24 of a 28-day cycle.

Endometrial

Embryo implantation

  • The probability of an embryo successfully implanting is approximately 30%.
  • Implantation failure can be multifactorial
  • Recurrent implantation failures (RIF) may occur in 5–10% of women undergoing IVF cycles
  • Significant proportion of RIF is related to endometrial receptivity.

What does recurrent implantation failure mean?

  • ≥8 of 8cell or = >5 blastocyst transferred  Rinehart  J 2004
  • Failure of 3 cycles with reasonably good embryos  transferred. Margolioth et al; 2006
  • Failure to achieve a clinical pregnancy after transfer of at least 4 good-quality embryos in a minimum of 3 fresh or frozen cycles in a woman under the age of 40 years C Coughlan et al., 2014 –
  • Recently if 2 good morphology euploid embryos fail to implant it is considered as recurrent implantation failure

Endometrials centre

Endometrial scratch (ES)

Barash was the first to introduce the concept of endometrial scratch where he observed that local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing IVF. Fertil. Steril. 2003, 79, 1317–1322

What is the biological process that may lead to an increased probability of pregnancy?

Endometrials centre india

Endometrial scratch (ES)

  • Endometrial regeneration
  • Slowing down of disproportionate endometrial development often associated with OS cycle to restore embryonic-endometrial synchrony.

Endometrial centre india

The trauma can be achieved simply by a pipelle, biopsy curette, or hysteroscope at low cost and with no need of analgesia or anaesthesia

Hysteroscopy as an intervention for ES

Hysteroscopy is used to treat endometrial pathologies that can interfere with embryo implantation. Benefits of hysteroscopy are beyond the possible ‘injury’ effect only:

  • Correction of unsuspected intrauterine abnormalities in asymptomatic previously failed IVF patients.
  • Assessment of cervical conditions to achieve an easier ET.

Therefore, studies based on hysteroscopy should not be combined with those exclusively based on endometrial biopsy to analyse the scratching effect

Carlos and Bellver Hum Rep.2014, Pundir et al., 2014

Endometrial scratch

Endometrial scratch

  1. Pipelle is inserted until it reaches the fundus.
  2. The inner plunger is withdrawn to apply a suction force to the endometrial cavity.
  3. Endometrial scratch of the superficial layer of endometrium is performed with the use of a ‘hoovering’ movement, combining a rotational and in-and-out movement of the pipelle sampler several times

Endometrial scratch How safe is it?

  • Pain, vasovagal attack, demand of anaesthesia, difficult entry into uterine cavity, intermittent bleeding are procedural side-effects.
  • Possibility of chronic endometrial inflammation, may be detrimental for embryo implantation and development, potentially leading to infertility and recurrent pregnancy loss.
  • Pelvic abscess especially in women with adnexal masses
  • Solid evidence is needed to draw any conclusions about the benefits of such iatrogenic inflammation on implantation before using it routinely as treatment for RIF.

Cicinelli E, Matteo M, Tinelli R, Lepera A, Alfonso R, Indraccolo U, et al. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod 2015; 30:323–30. (49–51).

Endometrial scratch in IVF

Endometrial scratch (ES)

ES has been used in IVF cycles with variability:

  • First or previous IVF failures (1 or more)
  • Timing of scratch
    • luteal or follicular
    • Once or twice
    • previous cycle or same cycle
  • Type of embryo transfer cycles
    • Fresh embryo transfer in stimulated cycle
    • FET in artificial cycle using HRT
    • FET in natural cycle

Fresh embryo transfer cycles (Barash et al., 2003; Baum et al., 2012; Gibreel et al., 2015; Guven et al., 2014; Inal et al., 2012; Karimzadeh et al., 2009; Mahran et al., 2016; Narvekar et al., 2010; Nastri et al., 2013; Raziel et al., 2007; Shohayeb and El-Khayat, 2012; Singh et al., 2015; Yeung et al., 2014) FET in HRT cycles (Aflatoonian et al., 2016; Dunne and Taylor, 2014) natural FET cycles (Jennifer Sze Man Mak et al.,2017)

Endometrial scratch (ES)

Meta-analysis and systematic reviews

Endometrials india

In total, 901 participants included in 2 randomized (n = 193) and six non-randomized controlled studies (n = 708). The quality of studies was variable. Meta-analysis showed that clinical pregnancy rate was significantly improved after LEI in both randomized & non-randomized studies.

Pooling of 7 controlled studies (four randomized and three non-randomized), with 2062 participants, showed that local endometrial injury induced in the cycle preceding ovarian stimulation is 70% more likely to result in a clinical pregnancy as opposed to no intervention

endometrial india

Authors’ conclusions Endometrial injury performed prior to the embryo transfer cycle improves clinical pregnancy and live birth rates in women undergoing ART.

This opinion paper, analysed the methodological and plausibility problem beneath ‘the Scratching Case’.

It has been suggested not to dilute evidence-based medicine by a vicious circle created by the over-exploitation of inadequate or insufficient data to compute incorrect or incomplete conclusions through systematic reviews and meta-analysis.

To summarize > 300 publications can be found on this topic, but only four RCTs with poor quality were analysed in 3 meta-analyses published in the same year with the same conclusion.

ES was first suggested a decade ago by Barash as a simple intervention to improve endometrial receptivity in patients undergoing ART. A decade later, this intervention is being widely advertised by some of our colleagues on their web pages, and patients are paying to undergo the ‘scratching cycle’ before their ART treatment cycle.

This intervention must not be advertised as an established practice to improve implantation until real good data demonstrates that it does. We, doctors, have to remind ourselves of the Hippocratic Oath of Primum non nocere  which means first, do not harm.

Though more studies are still needed one should consider this evidence is probably better than that existing for all other interventions aiming to improve the reproductive outcomes of women with RIF with fortunately several new studies on the horizon.

Why are the authors compelled to convince readers against endometrial scratching?
Is endometrial scratching expensive and/or risky?
Endometrial biopsy using a Pipelle is an affordable procedure, and millions have been performed per year for diagnostic indications for decades as a safe and well-tolerated procedure.

Although current evidence suggests some benefit of ES, we need evidence from well-designed trials that avoid instrumentation of the uterus in the preceding three months, do not cause endometrial damage, stratify the results for women with and without recurrent implantation failure (RIF) and report live birth.

<p>Key results
ES performed sometime during the month before the start of OS improves chances that a woman will achieve live birth and clinical pregnancy.
Moderate-quality evidence suggests that if 26% of women achieve live birth without endometrial injury, between 28% and 48% will achieve live birth with this intervention.
Contrary to this, endometrial injury performed on the day the eggs are picked up reduces the chances of pregnancy.

Conclusion(s)

The ESI may improve IVF success in patients with two or more previous ET failures undergoing fresh ET. The ESI timing and technique seem to play a crucial role in determining its effect on embryo implantation.

Result(s):10 studies included (1,468 participants).

Intervention group higher LBR (RR 1.38, 95% CI 1.05–1.80)  and clinical PR (RR 1.34, 95% CI 1.07–1.67)

No difference in multiple PR, miscarriage rate, and EPR.

Double luteal ESI with flexible pipelle had greatest effect on LBR (RR 1.54, 95% CI 1.10–2.16) and clinical PR (RR 1.30, 95% CI 1.03–1.65).

ESI was beneficial for patients with two or more previous ET failure, but not for women with single previous failed ET.

No effect seen in women with frozen-thawed ET cycles

This Cochrane review included 9 RCT’s (1512 women) who underwent endometrial scratching and were trying to get pregnant from intercourse or IUI with unexplained subfertility.

Overall the results suggest a benefit from ES. However, all the studies have significant limitations and so the results may be biased. Thus not possible to say with any confidence whether ES can increase the probability of pregnancy in this group of women.

ESI is expected to be safe, although clear evidence about its short-term and long-term complications is warranted.

ESI lead to higher CPR (OR 2.27) & OPR (OR 2.04) vs controls. Not higher risk of multiple pregnancy (OR 1.09), MR (OR 0.80), or EPR (OR 0.82).
Subgroup analysis based on ESI timing showed higher clinical pregnancy rate (OR 2.57) and ongoing pregnancy rate (OR 2.27) in patients receiving ES in same cycle of before hCG but not in patients in previous cycle.

Poor evidence quality (GRADE of evidence: low) that ESI improves CPR (OR 2.27, P<00001) and OPR (OR 2.04, P=.004) in patients undergoing IUI without increasing the risk of multiple pregnancy, miscarriage, or ectopic pregnancy (GRADE score: low/very low).

Results support clinicians by providing an updated summary on ESI use in IUI and advising about the uncertainties in the real chances of ESI improving CPR and OPR.

Despite the novel evidence provided by our analysis, there is still a need for further robust, high-quality RCTs to confirm the effectiveness and safety ESI before routinely recommending its use in patients undergoing IUI cycles.

Methods/design: The PIP trials are 3 multi-centre, RCTs designed to test 3 separate hypotheses:
Whether endometrial injury increases the probability of live birth in women or couples

  1. Who are undergoing autologous embryo transfer as part of an IVF cycle (PIP-IVF),
  2. With unexplained infertility who are attempting to conceive naturally (PIP-UE) and
  3. With subfertility related to polycystic ovarian syndrome (PCOS) who are on ovulation induction medication and attempting to conceive (PIP-PCOS).

The PIP study: design

Design

  • Pragmatic, multi-centre, randomized controlled trial
  • Endometrial scratch vs. no procedure (open – label)

Eligibility

  • Autologous embryo transfer (fresh or frozen)
  • No disruptive instrumentation in three preceding months (e.g. hysterosalpingogram, hysteroscopy)
  • No contraindication to pipelle biopsy

Sample size

Anticipated effect of endometrial scratching considered separately in two sub groups (80% power, α=0.05)

Recurrent implantation failure (≥1 prior unsuccessful embryo transfers)

  • 15 percentage point difference in live birth (31% vs 16%)
  • 280 women required

Non-recurrent implantation failure (no prior unsuccessful embryo transfers)

  • 8 percentage point difference in live birth (33% vs 25%)
  • 1002 women required

Overall target: 1300

Primary analyses performed on the whole trial population

Conclusion

  • Luteal ES in previous cycle improves CPR in RIF in IVF cycles (better in 2 failed ET compared to 1 failed ET)
  • Better effectivity seen in fresh IVF cycles vs cryo ET
  • ES in IUI cycles or in women with unexplained infertility in the same cycle also offers some benefit towards CPR
  • This procedure is very simple and inexpensive hence its abuse more likely & introduction of iatrogenic chronic endometritis is a real possibility with substantial procedural pain .
  • More robust data with adequately powered studies are still desirable to establish the real benefit and the PIP study with adequately powered RCTs appears to throw some more light on the scratch.
  • Solid evidence is needed to draw any conclusions about the benefits before adopting it as a routine procedure

dr abha majumdar ivf specilist


Sir Ganga Ram Hospital

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