Recent research published in the Journal of Assisted Reproduction and Genetics has revealed a significant breakthrough in the treatment of recurrent implantation failure (RIF) in IVF embryo transfer procedures. This comprehensive study explores the effectiveness of combining acupuncture with gonadotropin-releasing hormone agonists (GnRHa) for improving endometrial receptivity and overall pregnancy outcomes.

The Challenge of Recurrent Implantation Failure (RIF)

For many couples undergoing in vitro fertilization (IVF), RIF is a major hurdle. It is defined as the absence of clinical pregnancy despite the transfer of multiple high-quality embryos. The emotional and physical toll of repeated failures can be overwhelming, prompting many to seek alternative therapies that could tip the scales in their favor.

Study Insights: Acupuncture made a significant difference

The investigation focused on 164 patients experiencing recurrent implantation failure (RIF) during their IVF-embryo transfer processes. The participants were systematically categorized into two groups: a control group, which continued with the standard hormone replacement therapy (HRT) for endometrial preparation, and a study group, which received an innovative combination of acupuncture, gonadotropin-releasing hormone agonists (GnRHa), and HRT. The findings from this comparative analysis revealed notable enhancements in the study group:

  • Endometrial Thickness: The study group, treated with acupuncture in conjunction with GnRHa, showed a significant increase in endometrial thickness compared to the control group. This factor is crucial as a thicker endometrium is often associated with higher rates of embryo implantation.
  • Morphological Improvements: There was a higher prevalence of favorable endometrial morphologies, specifically linear endometrium (A + B type), in the study group. Such morphological features are considered beneficial for embryo implantation, indicating a receptive uterine environment.
  • Blood Flow Enhancement: The study group also demonstrated enhanced submucosal uterine blood flow, particularly with an increase in type III flow patterns. Improved blood flow to the uterus is essential for creating a nourishing environment that supports embryo implantation and growth.

These results underscore the potential benefits of integrating acupuncture with GnRHa in the treatment protocol for patients undergoing IVF, especially those with a history of RIF, by improving endometrial receptivity and overall pregnancy outcomes.

 

Acupuncture improves embryo implantation rate in recurrent implantation failure (RIF) patients undergoing IVF

Adding acupuncture as an adjunct to IVF improved embryo implantation rate in recurrent implantation failure (RIF) patients

As you can see the embryo implantation rate was much higher when acupuncture was used. Consequently this also resulted in much higher pregnancy rate. How can the pregnancy be higher than implantation rate? This difference due to more than one embryo being transferred in both control group (approximately 1.82 per cycle) and acupuncture group (1.76 per cycle). Effectively, there were fewer embryos transferred in the control group, but it still resulted in much higher pregnancy rate.

 

Acupuncture improves IVF success rates in patients with RIF

IVF success rates in patients with Recurrent Implantation Failure (RIF) were improved significantly with acupuncture

 

Why  is recurrent implantation failure such a challenging diagnosis?

Emotional Impact: RIF can be emotionally and psychologically draining for patients. For instance, the repeated failure despite having high-quality embryos transferred can lead to significant stress, anxiety, and depression, which can, in turn, impact overall health and potentially interfere with treatment outcomes.

  • Complex Etiology: RIF maybe influenced by a multitude of factors including embryo quality, genetic issues, anatomical problems of the uterus, immunological factors, and the endometrial environment. Each of these factors can vary significantly from patient to patient, making it difficult to pinpoint the exact cause of implantation failure in each case.
  • Treatment Challenges: Because RIF can be caused by many different factors, there isn’t a one-size-fits-all treatment. Health professionals must often use a trial-and-error approach to find the most effective treatment for an individual, which can be time-consuming and frustrating for both the patient and the clinician.
  • Financial Strain: IVF cycles and additional interventions to address RIF can quickly add up.  Many IVF cycles may be needed before a successful pregnancy is achieved. This financial burden can be significant, especially as most insurance plans do not cover the full costs of multiple IVF attempts.
  • Impact on Future Fertility Decisions: The challenges and uncertainties associated with RIF can influence future fertility decisions. Couples may reconsider their options, weighing the emotional and financial impacts against the desire to continue trying for a biological child.

Addressing the Complex Etiology of RIF: Further thoughts why acupuncture may be helpful with Recurrent Implantation Failure

RIF’s complexity stems from various factors, including embryo quality, genetic issues, anatomical and immunological factors, and the endometrial environment. Acupuncture has been shown to benefit numerous and diverse diagnoses such as endometriosis, PCOS, back pain, hayfever and migraines to name a few. It offers a multifaceted therapeutic approach that addresses several underlying causes:

  • Endometrial Receptivity: Enhances blood flow and thickness of the endometrium.
  • Immunological Factors: Modulates immune responses, potentially reducing inflammation.
  • Hormonal Regulation: Influences hormonal balance crucial for fertility.
    Stress Reduction: Lowers stress levels, which can negatively impact fertility.
  • Stress Reduction: Lowers stress levels, which can impact fertility.

This study highlights the benefits of integrating acupuncture with IVF in managing RIF, offering a more effective and holistic approach to overcoming this fertility challenge. For many couples, this could mean a renewed hope and a higher chance of achieving the dream of parenthood.

Study abstract:

J Assist Reprod Genet
. 2024 Jun 7. doi: 10.1007/s10815-024-03140-7. Online ahead of print.

Acupuncture combined with gonadotropin-releasing hormone agonists improves endometrial receptivity and pregnancy outcome in patients with recurrent implantation failure of in vitro fertilization-embryo transfer

Jingya Yang # 1, Yan Lu # 2, Yuan Zhang 1, Cuijuan Zhou 1, Qin Liang 1, Ting Liang 3
Affiliations expand
PMID: 38847932 DOI: 10.1007/s10815-024-03140-7
Abstract
Objective: Gonadotropin-releasing hormone agonists (GnRHa), combined with other auxiliary treatments, can improve pregnancy outcomes in in vitro fertilization-embryo transfer (IVF-ET). This research investigated the effect of acupuncture combined with GnRHa in patients with recurrent implantation failure (RIF) of IVF-ET.

Methods: A total of 164 patients who intended to undergo frozen-thawed embryo transfer after RIF of IVF-ET were selected for experiments and then divided into the control (received conventional hormone replacement therapy (HRT) for endometrial preparation) and study groups (received a combination of acupuncture, GnRHa, and HRT for endometrial preparation) (n = 82). Endometrial thickness (EMT), endometrial morphological classification, submucosal uterine blood flow classification, clinical pregnancy rate, embryo implantation rate, and early abortion rate for each transfer cycle were compared between the two groups.

Results: EMT of the study group was higher than that of the control group 1 day before transfer. There were more patients with linear endometrium (A + B type) in the study group on the day of endometrial transformation than in the control group. The number of patients with type I submucosal uterine blood flow in the study group was decreased and the number of patients with type III was increased compared with the control group on the day of endometrial transformation. The clinical pregnancy rate and embryo implantation rate of the study group were higher than those of the control group.

Conclusion: Acupuncture combined with GnRHa improves the endometrial receptivity of patients with RIF of IVF-ET, thereby increasing clinical pregnancy rates and improving pregnancy outcomes.

Keywords: In vitro fertilization-embryo transfer; Acupuncture; Endometrial receptivity; Gonadotropin-releasing hormone agonists; Pregnancy outcome; Recurrent implantation failure.

© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

PubMed Disclaimer

References
Suzuki M. In vitro fertilization in Japan – early days of in vitro fertilization and embryo transfer and future prospects for assisted reproductive technology. Proc Jpn Acad Ser B Phys Biol Sci. 2014;90(5):184–201. – PubMed – PMC – DOI
Johnson MH. A short history of in vitro fertilization (IVF). Int J Dev Biol. 2019;63(3-4–5):83–92. – PubMed – DOI
Franasiak JM, et al. A review of the pathophysiology of recurrent implantation failure. Fertil Steril. 2021;116(6):1436–48. – PubMed – DOI
For the participants to the Lugano, RIFW, et al. Recurrent implantation failure: reality or a statistical mirage?: consensus statement from the July 1, 2022 Lugano Workshop on recurrent implantation failure. Fertil Steril. 2023;120(1):45–59. – DOI
Coughlan C, et al. Recurrent implantation failure: definition and management. Reprod Biomed Online. 2014;28(1):14–38. – PubMed – DOI
Xia Q, et al. Effectiveness of herb-partitioned moxibustion on the navel for pregnancy outcomes in patients with recurrent implantation failure undergoing in vitro fertilization and embryo transfer: a study protocol for a randomized controlled trial. Trials. 2022;23(1):217. – PubMed – PMC – DOI
Ma YJ, et al. The mechanism of traditional Chinese medicine based on semi-targeted metabolomics to improve IVF outcomes in senile patients. Evid Based Complement Alternat Med. 2021;2021:6696305. – PubMed – PMC – DOI
Gu YE, et al. The effects of acupuncture on pregnancy outcomes of in vitro fertilization with embryo transfer: an interdisciplinary systematic review. J Gynecol Obstet Hum Reprod. 2019;48(8):677–84. – PubMed – DOI
Guven PG, Cayir Y, Borekci B. Effectiveness of acupuncture on pregnancy success rates for women undergoing in vitro fertilization: a randomized controlled trial. Taiwan J Obstet Gynecol. 2020;59(2):282–6. – PubMed – DOI
Wang X, et al. An overview of systematic reviews of acupuncture for infertile women undergoing in vitro fertilization and embryo transfer. Front Public Health. 2021;9:651811. – PubMed – PMC – DOI
Dehghani AS, et al. The effect of acupuncture on the day of embryo transfer on the in vitro fertilization outcomes: An RCT. Int J Reprod Biomed. 2020;18(3):209–14. – PubMed – PMC
Hullender Rubin LE, Anderson BJ, Craig LB. Acupuncture and in vitro fertilisation research: current and future directions. Acupunct Med. 2018;36(2):117–22. – PubMed – DOI
Wu L, et al. Influence of different gonadotropin-releasing hormone agonist administration methods on pregnancy outcomes of patients undergoing in-vitro fertilization-embryo transfer. Curr Med Sci. 2019;39(3):437–41. – PubMed – DOI
Guo YH, et al. Comparative study on the pregnancy outcomes of in vitro fertilization-embryo transfer between long-acting gonadotropin-releasing hormone agonist combined with transvaginal ultrasound-guided cyst aspiration and long-acting gonadotropin-releasing hormone agonist alone. Contemp Clin Trials. 2012;33(6):1206–10. – PubMed – DOI
Pan D, et al. Gonadotropin-releasing hormone agonist downregulation combined with hormone replacement therapy improves the reproductive outcome in frozen-thawed embryo transfer cycles for patients of advanced reproductive age with idiopathic recurrent implantation failure. Reprod Biol Endocrinol. 2022;20(1):26. – PubMed – PMC – DOI
Depalo R, et al. GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET). Reprod Biol Endocrinol. 2012;10:26. – PubMed – PMC – DOI
Zhu YC, et al. Effect of intrauterine perfusion of granular leukocyte-colony stimulating factor on the outcome of frozen embryo transfer. World J Clin Cases. 2021;9(30):9038–49. – PubMed – PMC – DOI
Pang C, et al. A comparison of pregnancy rate between natural cycle and hormone replacement cycle in patients who underwent frozen embryo transfer using 2 consecutive hormone replacement regiments: a STROBE-compliant retrospective study. Medicine (Baltimore). 2020;99(37):e22163. – PubMed – DOI
Dong M, et al. Gonadotropin-releasing hormone agonist combined with hormone replacement therapy does not improve the reproductive outcomes of frozen-thawed embryo transfer cycle in elderly patients: a retrospective study. Reprod Biol Endocrinol. 2020;18(1):73. – PubMed – PMC – DOI
Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26(6):1270–83. – DOI
Gonen Y, Casper RF. Prediction of implantation by the sonographic appearance of the endometrium during controlled ovarian stimulation for in vitro fertilization (IVF). J In Vitro Fert Embryo Transf. 1990;7(3):146–52. – PubMed – DOI
Applebaum M. The uterine biophysical profile. Ultrasound Obstet Gynecol. 1995;5(1):67–8. – PubMed – DOI
Basatvat S, et al. Potential innate immunity-related markers of endometrial receptivity and recurrent implantation failure (RIF). Reprod Biol. 2021;21(4):100569. – PubMed – DOI
Zhao Y, et al. Expression and significance of miR-30d-5p and SOCS1 in patients with recurrent implantation failure during implantation window. Reprod Biol Endocrinol. 2021;19(1):138. – PubMed – PMC – DOI
Huang C, et al. Effect of recombinant LH supplementation timing on clinical pregnancy outcome in long-acting GnRHa downregulated cycles. BMC Pregnancy Childbirth. 2022;22(1):632. – PubMed – PMC – DOI
Lan J, et al. Ultra-long GnRH agonist protocol during IVF/ICSI improves pregnancy outcomes in women with adenomyosis: a retrospective cohort study. Front Endocrinol (Lausanne). 2021;12:609771. – PubMed – DOI
Ren J, et al. Does prolonged pituitary down-regulation with gonadotropin-releasing hormone agonist improve the live-birth rate in in vitro fertilization treatment? Fertil Steril. 2014;102(1):75–81. – PubMed – DOI
Wang T, et al. Comparison of luteal phase ovulation induction and ultra-short gonadotropin-releasing hormone agonist protocols in older patients undergoing in vitro fertilization. Libyan J Med. 2019;14(1):1597327. – PubMed – PMC – DOI
Segars JH, et al. The use of gonadotropin releasing hormone agonist (GnRHa) in good responders undergoing repeat in vitro fertilization/embryo transfer (IVF/ET). J In Vitro Fert Embryo Transf. 1990;7(6):327–31. – PubMed – DOI
Pan Y, et al. Correlation between different endometrial preparation protocols and pregnancy outcome of frozen embryo transfer in patients with polycystic ovary syndrome: a retrospective study. Gynecol Endocrinol. 2023;39(1):2217260. – PubMed – DOI
Liao Z, et al. The effect of endometrial thickness on pregnancy, maternal, and perinatal outcomes of women in fresh cycles after IVF/ICSI: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2021;12:814648. – PubMed – DOI
Lawrenz B, Fatemi HM. Editorial: endometrial thickness as a risk factor for pregnancy complications. Front Endocrinol (Lausanne). 2023;14:1216952. – PubMed – DOI
Yun L, et al. Acupuncture for infertile women without undergoing assisted reproductive techniques (ART): a systematic review and meta-analysis. Medicine (Baltimore). 2019;98(29):e16463. – PubMed – DOI
Yuan L, et al. Effects of erbuzhuyu decoction combined with acupuncture on endometrial receptivity are associated with the expression of miR-494-3p. Evid Based Complement Alternat Med. 2020;2020:9739672. – PubMed – PMC – DOI
Xing L, et al. Acupuncture improves endometrial angiogenesis by activating PI3K/AKT pathway in a rat model with PCOS. Evid Based Complement Alternat Med. 2022;2022:1790041. – PubMed – PMC – DOI
Qi Y, et al. Intracavitary physiotherapy combined with acupuncture mediated AMPK/mTOR signalling to improve endometrial receptivity in patients with thin endometrium. Eur J Obstet Gynecol Reprod Biol. 2022;277:32–41. – PubMed – DOI
Shuai Z, et al. Effect of transcutaneous electrical acupuncture point stimulation on endometrial receptivity in women undergoing frozen-thawed embryo transfer: a single-blind prospective randomised controlled trial. Acupunct Med. 2015;33(1):9–15. – PubMed – DOI
Cakmak YO, Akpinar IN, Yoldemir T. Decreasing the uterine blood flow with electroacupuncture: bidermatomal and monodermatomal applications. Gynecol Obstet Invest. 2017;82(2):151–6. – PubMed – DOI
Huang DM, et al. Acupuncture for infertility: is it an effective therapy? Chin J Integr Med. 2011;17(5):386–95. – PubMed – DOI
Wu JM, et al. Effects of acupuncture on endometrium and pregnancy outcomes in patients with polycystic ovarian syndrome undergoing in vitro fertilization-embryo transfer: a randomized clinical trial. Chin J Integr Med. 2022;28(8):736–42. – PubMed – DOI
Xie ZY, et al. The effects of acupuncture on pregnancy outcomes of in vitro fertilization: a systematic review and meta-analysis. BMC Complement Altern Med. 2019;19(1):131. – PubMed – PMC – DOI
Feng X, et al. Transcutaneous electrical acupoint stimulation improves endometrial receptivity resulting in improved IVF-ET pregnancy outcomes in older women: a multicenter, randomized, controlled clinical trial. Reprod Biol Endocrinol. 2022;20(1):127. – PubMed – PMC – DOI
Shao Y, et al. Predictive value of endometrial receptivity for pregnancy outcomes of in-vitro fertilization embryo transfer for patients of different ages. Altern Ther Health Med. 2023;29(4):210–7. – PubMed