9. Acupuncture
Four meta-analyses showed no evidence of the overall benefit of acupuncture for improving live birth rates regardless of whether acupuncture was performed around the time of oocyte retrieval or around the day of embryo transfer. Consequently, acupuncture cannot be recommended routinely to improve IVF outcomes.11
10. Immunologic tests/treatments
Given the “foreign” genetic nature of a fetus, attempts to suppress the maternal immunologic response to sustain the pregnancy have been made for decades, especially for recurrent miscarriage and recurrent implantation failure with IVF. Testing has included natural killer (NK) cells, human leukocyte antigen (HLA) genotypes, and cytokines. While NK cells can be examined by endometrial biopsy, levels fluctuate based on the cycle phase, and no correlation between peripheral blood testing and uterine NK cell levels has been shown. Further, no consensus has been reached on reliable normal reference ranges in uterine NK cells.12
Several treatments have been proposed to somehow modulate the immune system during the implantation process thereby improving implantation and live birth, including lipid emulsion (intralipid) infusion, intravenous immunoglobulin, leukocyte immunization therapy, tacrolimus, anti–tumor necrosis factor agents, and granulocyte colony-stimulating factor. A recent systematic review and meta-analysis cited low-quality studies and did not recommend the use of any of these immune treatments.13 Further, immunomodulation has many known side effects, some of which are serious (including hepatosplenomegaly, thrombocytopenia, leukopenia, renal failure, thromboembolism, and anaphylactic reactions). Excluding women with autoimmune disease, taking glucocorticoids or other immune treatments to improve fertility has not been proven.13
Conclusion
To quote the New York Times opinion piece, “IVF remains an under-regulated arena, and entrepreneurial doctors and pharmaceutical and life science companies are eager to find new ways to cash in on a growing global market that is projected to be as large as $40 billion by 2024.” While this bold statement compels a huge “Ouch!”, it reminds us of our obligation to provide evidence-based medicine and to include emotional and financial harm to our oath of Primum non nocere.
References
1. The News York Times. 2019 Dec 12. Opinion.
2. Wilkinson J et al. Fertil Steril. 2019;112(6):973-7.
3. Lensen S et al. N Engl J Med. 2019 Jan 24;380(4):325-34.
4. Practice Committee of the American Society for Reproductive Medicine. Fertil Steril. 2020;113(2):305-22.
5. Miyakis S et al. J Thromb Haemost. 2006;4(2):295-306.
6. Kamath MS et al. Cochrane Database Syst Rev. 2019 Apr 16;4(4):CD012856.
7. Bosteels J et al. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD009461.
8. Munne S et al. Fertil Steril. 2019;112(6):1071-9.
9. Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. Fertil Steril. 2020;114(2):239-45.
10. Lacey L et al. Cochrane Database Syst Rev. March 7 2021;3:2199.
11. Coyle ME et al. Acupunct Med. 2021;39(1):20-9.
12. Von Woon E et al. Hum Reprod Update. 2022;30;28(4):548-82.
13. Achilli C et al. Fertil Steril. 2018;110(6):1089-100.