Is endometrial stimulation considered a viable In Vitro Fertilization (IVF) Treatment (TTT) option?

Endometrial Stimulation in IVF: Current Evidence and Recommendations

Endometrial stimulation is not considered a standard or recommended treatment option for IVF based on current guidelines and evidence. 1, 2

Current Guidelines on Endometrial Factors in IVF

The European Society of Human Reproduction and Embryology (ESHRE) guidelines explicitly state that decisions to perform double embryo transfer (DET) instead of elective single embryo transfer (eSET) should not be based on endometrial characteristics in either fresh or frozen embryo transfer cycles 1. This strong recommendation indicates that endometrial factors, including stimulation techniques, are not considered decisive factors in embryo transfer decisions.

The guidelines emphasize:

• Endometrial characteristics should not guide the decision between DET and eSET in fresh embryo transfer cycles 1
• Endometrial characteristics should not guide the decision between DET and eSET in frozen embryo transfer cycles 1
• No mention of endometrial stimulation as a standard treatment approach in IVF protocols

Research on Endometrial Stimulation

The research on endometrial stimulation shows mixed and largely unconvincing results:

• A 2019 double-blind randomized controlled trial found that endometrial mechanical stimulation (EMS) in the luteal phase prior to embryo transfer did not improve clinical outcomes in an unselected subfertile population 3
• This study was terminated after futility analysis showed no difference in clinical pregnancy rates between EMS versus control (47.2% vs 61.7%) 3
• Concerningly, there was a trend toward lower live birth rates with endometrial stimulation (43.4% vs 61.7%) 3

While some older studies suggested potential benefits:

• A 2010 study indicated that endometrial stimulation might improve endometrial receptivity and boost clinical pregnancy rates for patients with repeated implantation failure 4
• A 2009 study suggested that stimulation of endometrium embryo transfer (SEET) might improve implantation rates for first-time ART patients with high-grade blastocysts 5

Potential Mechanisms and Concerns

Ovarian stimulation for IVF may already impact endometrial receptivity:

• Analysis of protein profiles in endometrial secretions shows significant differences between natural cycles and stimulated cycles 6
• These findings suggest that additional endometrial manipulation may further disrupt the intrauterine environment at the time of embryo transfer 6

Clinical Approach to IVF Treatment

Current best practices for IVF focus on:

1. Elective single embryo transfer (eSET) for most patients to minimize the risk of multiple pregnancies 2
2. Appropriate ovarian stimulation protocols tailored to specific patient conditions (such as endometriosis) 7
3. Consideration of embryo quality and patient factors rather than endometrial stimulation techniques

Conclusion for Clinical Practice

Based on the most recent and highest quality evidence, endometrial stimulation should not be considered a standard treatment option in IVF. The 2019 randomized controlled trial 3 showed no benefit and a concerning trend toward lower live birth rates with endometrial stimulation.

For patients with repeated implantation failure, clinicians should focus on:

• Optimizing embryo quality
• Considering genetic testing of embryos
• Evaluating for anatomical factors affecting implantation
• Addressing any underlying immunological issues

Routine use of endometrial stimulation in IVF treatment is not supported by current evidence and guidelines and may potentially reduce live birth rates in some populations. 3