Assisted Reproductive Technology Outcomes Unaffected By Presence of Liver Disease

Tatyana Kushner, MD, BSCE

Credit: Tatyanakushner.com

Assisted reproductive technology may be a viable treatment option for women with liver disease experiencing impaired fertility, according to findings from a retrospective study comparing treatment outcomes in patients with and without liver disease.

Although some differences were observed in baseline characteristics, hormone levels, and in vitro fertilization (IVF) laboratory outcomes, IVF treatment and pregnancy outcomes were not significantly different in response to controlled ovarian stimulation, embryo fertilization rate, or ploidy outcome in patients with liver disease compared to controls.¹

“To date, the literature about [assisted reproductive technology] treatment outcomes in women with liver disease has been limited,” wrote investigators.¹ “This study expands on the previous work by comparing [assisted reproductive technology] treatment outcomes in women with and without liver disease in a large patient cohort evaluated and treated at a single fertility practice.”

Several factors associated with liver disease are thought to contribute to decreased fertility, including alterations in estrogen metabolism, changes in the hypothalamic-pituitary axis, lower serum luteinizing hormone and follicle stimulating hormone, increased circulating estrogen, and malnutrition. Assisted reproductive technology may offer a potential solution for those struggling with fertility, although research regarding its efficacy in this patient population is limited and merits further exploration.²

To compare assisted reproductive technology treatment outcomes in patients with and without liver disease, Tatyana Kushner, MD, BSCE, associate professor of medicine in the division of liver diseases at the Icahn School of Medicine at Mount Sinai, and a team of investigators collected electronic medical record data for patients who underwent treatment in a high-volume fertility practice from 2002 to 2021.¹

The study included women with liver disease who underwent IVF, embryo biopsy for genetic testing, and embryo cryopreservation, as well as a subanalysis of patients who subsequently underwent a single embryo transfer with a thawed euploid embryo. Controls included all women without liver disease who received assisted reproductive technology treatment due to male factor infertility, which investigators noted was indicative of these patients having normal ovarian reserve and being fertile.¹

Investigators identified 295 women with liver disease who underwent 1033 assisted reproductive technology treatment cycles. Among the cohort, the mean age was 37.8 (Standard deviation [SD], 5.2) years and 281 (95.3%) had chronic liver disease, including hepatitis B virus (46.5%), hepatitis C virus (34.5%), nonalcoholic fatty liver disease (14.8%), autoimmune hepatitis (2.5%), and primary biliary cholangitis (1.4%).¹

Of the 1033 treatment cycles, 425 were IVF and the remaining 519 were other forms of reproductive endocrinology, including mild ovarian stimulation and intrauterine insemination. The final study population included 115 women with liver disease who underwent 186 IVF cycles. Investigators identified an additional 624 control patients who underwent 868 IVF cycles with embryo biopsy for genetic testing for comparison.¹

Compared to the control group, patients with liver disease were older (37.3 vs 35.9 years; P < .05), had a higher BMI (25.7 vs 23.9 kg/m2; P < .05), and differences in selected baseline hormone levels, including FSH, BAFC, and estradiol surge (all P < .05). Investigators also pointed out patients with liver disease had a significantly lower number of oocytes retrieved (12.3 vs 16.5; P < .05), number of mature oocytes (9.1 vs 12.6; P < .05), number of fertilized embryos (7.0 vs 9.9; P < .05), number of embryos biopsied (3.4 vs 5.1; P < .05), and number of euploid embryos (1.6 vs 2.7; P < .05) compared to controls.¹

Despite these differences, investigators observed similar mature oocyte rates, fertilization per mature oocyte rates, and embryo ploidy rates between the liver disease and control groups. Of note, liver disease was not found to be significantly associated with any of these outcomes on univariable and multivariable linear regression analyses.¹

Investigators pointed out similar trends for single embryo transfer, with no significant differences in rates of clinical pregnancy (70.3% vs 65.5%; P = .55), clinical pregnancy loss (7.1% vs 8.8%, P = .76), or live birth (64.9% vs 58.6%, P = .45) observed between liver disease and control patients. Again, liver disease was not found to be significantly associated with any of these outcomes.¹

Among postliver transplantation and chronic liver disease patients, investigators noted statistically significant differences in the number of oocytes retrieved (21.0 vs 12.6; P < .05), number of mature oocytes (17.7 vs 9.1; P < .05), and number of fertilized embryos (14.7 vs 6.8; P < .05) for the liver disease and control groups, respectively, although there were no statistically significant differences in the mature oocyte rate and fertilization per mature oocyte rate among the groups.¹

“Our study showed that patients with liver disease have similar IVF treatment outcomes compared with patients without liver disease. Based on our findings, women with liver disease and impaired fertility should be counseled about contemporary, standard IVF treatment, and the presence of liver disease should not prevent them from seeking IVF as an option due to concerns about efficacy,” investigators concluded.¹

References:

1. Lee JD, Gounko D, Lee, JA, et al. Assisted Reproductive Technology Treatment Outcomes in Women With Liver Disease. The American Journal of Gastroenterology doi:10.14309/ajg.0000000000002252
2. Kaletnbach, M. Why is it recommended to provide reproductive health counseling to women with cirrhosis? Liver Fellow Network. January 16, 2023. Accessed January 3, 2024. https://www.aasld.org/liver-fellow-network/core-series/why-series/why-it-recommended-provide-reproductive-health