Research on The Impacts of Anesthesia on IVF Outcome

In the modern world, more and more people are choosing to give birth at later ages. However, peak female reproductive years are between the late teens and late 20s. By age 30, fertility begins to decline, with a higher risk of diminished ovarian function, endometriosis, recurrent pregnancy loss, and ovulatory or uterine dysfunction.¹ First introduced in the late 1970s, in vitro fertilization (IVF) allows some of those who struggle with infertility to conceive through technological assistance. IVF procedures work through four critical steps: ovarian stimulation, oocyte retrieval, fertilization in the laboratory, and transfer back into the uterus.² The second step, ultrasound-directed oocyte retrieval, is a painful and stressful process that benefits from the use of anesthesia.^2,3 An important research question is whether anesthesia impacts the outcome of IVF.

Since 1987, researchers around the world have investigated the effect of anesthesia on IVF outcome. As one of the first research teams to examine this procedure, Dr. Maria Hayes and her team in Michigan collected data from 276 ovum retrieval laparoscopies.⁴ Anesthesia was induced with either thiopental or thiamylal and maintained with the use of fentanyl and nitrous oxide/oxygen, isoflurane/oxygen, or a combination of these agents. A total of 692 mature oocytes and 228 immature oocytes were included in the investigation, with the average length of anesthesia exposure for one oocyte being ~37 minutes. There was a strong correlation found between length of anesthesia exposure and oocyte fertilization or cleavage, where prolonged exposure to anesthesia was linked to a lower likelihood of an oocyte fertilizing, or of a fertilized oocyte going on to cleave.⁴

In a 2023 retrospective study, a research team from Tel Aviv University in Israel collected data from 245 IVF cycles, where 129 oocytes were retrieved under general anesthesia (with propofol) and 116 were retrieved without anesthesia.⁵ While the total quantity of oocytes retrieved was higher for women under anesthesia compared to the number of oocytes retrieved from women without anesthesia, fertilization was lower in oocytes retrieved under anesthesia compared to without anesthesia. Researchers also observed a trend toward lower pregnancy and delivery rates among the patients who underwent anesthesia.⁵

One proposed explanation for this negative association between anesthesia and IVF outcome lies with the oxygen consumption requirements of healthy human oocytes. Induction of general anesthesia can result in apnea, where tissue oxygenation can only be maintained by consumption of the oxygen reserve. In most surgical cases, preoxygenation and continuous oxygen administration are necessary for maintaining adequate oxygen levels.⁶ A 2011 study conducted in Spain collected data from 349 human oocytes and used oxygen microsensors to characterize oxygen consumption rates. This prospective study observed higher oxygen consumption in human oocytes that underwent healthy fertilization compared to unfertilized oocytes. The researchers also found high consumption rates among oocytes that produced embryos that implanted successfully, compared to those that did not.⁷ Therefore, it is concluded that anesthesia-related reduced oxygen levels may contribute to suboptimal fertilization, embryo development and implantation.^5,7

The role of the anesthesiologist in IVF procedures is to provide sufficient comfort and pain relief to patients during the oocyte retrieval and embryo transfer processes. Current research has explored the effect of different types of anesthesia on human participants; however, best practices can vary drastically depending on patient comorbidities, or the type of anesthetic drug or technique applied. While the extant literature largely suggests that anesthesia may lower fertilization and transfer rates, further research can help solidify this conclusion and examine strategies for mitigating any negative effects.

References

1. Affairs (ASPA), Assistant Secretary for Public. Fact Sheet: In Vitro Fertilization (IVF) Use Across the United States. 13 Mar. 2024, https://www.hhs.gov/about/news/2024/03/13/fact-sheet-in-vitro-fertilization-ivf-use-across-united-states.html
2. Sharma, Ankur, et al. “Anesthesia For In Vitro Fertilization.” Journal of Obstetric Anaesthesia and Critical Care, vol. 5, no. 2, Dec. 2015, p. 62. https://doi.org/10.4103/2249-4472.165132
3. Kwan, Irene, et al. “Pain Relief For Women Undergoing Oocyte Retrieval For Assisted Reproduction.” Cochrane Database of Systematic Reviews, no. 5, 2018. https://doi.org/10.1002/14651858.CD004829.pub4
4. Hayes, Maria F., et al. “Effect of General Anesthesia on Fertilization and Cleavage of Human Oocytes In Vitro.” Fertility and Sterility, vol. 48, no. 6, Dec. 1987, pp. 975–81. https://doi.org/10.1016/S0015-0282(16)59594-6.
5. Haikin Herzberger, Einat, et al. “General Anesthesia With Propofol During Oocyte Retrieval and In Vitro Fertilization Outcomes: Retrospective Cohort Study.” Scientific Reports, vol. 13, no. 1, May 2023, p. 8021. https://doi.org/10.1038/s41598-023-35224-2
6. Hedenstierna, G. “Oxygen and Anesthesia: What Lung do we Deliver to The Post‐operative Ward?” Acta Anaesthesiologica Scandinavica, vol. 56, no. 6, July 2012, pp. 675–85. https://doi.org/10.1111/j.1399-6576.2012.02689.x
7. Tejera, Aberto, et al. “Oxygen Consumption is a Quality Marker For Human Oocyte Competence Conditioned by Ovarian Stimulation Regimens.” Fertility and Sterility, vol. 96, no. 3, Sept. 2011, pp. 618-623.e2. https://doi.org/10.1016/j.fertnstert.2011.06.059