Having chronic liver disease does not affect outcomes for women who undergo in vitro fertilization (IVF), new research suggests.
The study, published online April 13 in The American Journal of Gastroenterology, compared women with and those without chronic liver disease (LD) who had normal ovarian reserve and who underwent assisted reproductive technology (ART) treatment in a high-volume fertility practice from 2002 to 2021.
“IVF treatment and pregnancy outcomes were not significantly different compared to controls,” the researchers write.
Women with LD may experience impaired fertility, they note. For example, women with chronic liver disease, such as hepatitis C virus infection, may have premature ovarian insufficiency, while women with advanced liver disease, cirrhosis, and hepatic decompensation are known to have abnormally low gonadotropin levels.
The prevalence of LD in women of reproductive age is rising, they add, leading to “an immediate need for the clinical assessment of reproductive potential in women with chronic liver disease.”
Yet the literature about ART treatment outcomes for women with LD was limited and may not reflect current therapy protocols, the researchers note.
“To the best of our knowledge, this study is the largest to date to evaluate IVF efficacy in women with LD,” they write.
Similar Outcomes
Researchers identified 295 women with LD (mean age, 37.8 ± 5.2 years) who underwent 1033 contemporary, standard ART treatment cycles. Six patients (2%) had cirrhosis, eight (2.7%) had undergone liver transplantation, and 281 (95.3%) had chronic liver disease, of which viral hepatitis B and C infections were the most prevalent. The final study population consisted of 115 women who underwent 186 IVF cycles, as well as embryo biopsy for genetic testing.
The control group consisted of all the women at the treatment center without LD who received contemporary, standard ART treatment because of male factor infertility, which served as an indication that the women had normal ovarian reserve and were considered fertile. These 624 patients underwent 868 IVF cycles with embryo biopsy.
The mean age of the patients with LD was significantly higher than that of the control participants. Mean body mass index was also significantly higher for the patients with LD, and there were differences in baseline levels of selected hormones compared with control participants. In addition, among those with LD, the number of oocytes retrieved was significantly lower (12.3 ± 7.6 vs 16.5 ± 8.2; P < .05), as were the number of mature oocytes (9.1 ± 6.2 vs 12.6 ± 6.7; P < .05), the number of fertilized embryos (7.0 ± 5.2 vs 9.9 ± 5.9; P < .05), the number of embryos for which biopsy was performed (3.4 ± 2.2 vs 5.1 ± 3.5; P < .05), and the number of euploid embryos (1.6 ± 1.4 vs 2.7 ± 2.4; P < .05) compared with control participants.
Among the two groups, there were no statistically significant differences in mature oocyte rate (an indicator of response to controlled ovarian stimulation), fertilization per mature oocyte rate (an indicator of oocyte quality and ability to be fertilized), or embryo ploidy rate (an indicator of genetically normal embryos), as determined by embryo biopsy, the researchers write.
A subanalysis of women who went on to have a single thawed euploid (chromosomally normal) embryo transfer to achieve pregnancy found no statistically significant differences in rates of clinical pregnancy, clinical pregnancy loss, or live births between the LD group and the control group.
“Overall, women with chronic liver disease can be counseled that IVF treatment will not significantly differ in response to controlled ovarian stimulation, embryo fertilization rate, or ploidy outcome compared to women without liver disease,” the researchers write.
Data for Patient Counseling
The results could change the current common thinking among clinicians that IVF should not be conducted until liver disease is under optimal control, first author Jessica Lee, BS, a student at Icahn School of Medicine at Mount Sinai in New York City, told Medscape Medical News.
“There was a knowledge gap for studies in the United States, and we hope this study will not only help patients with liver disease but also providers with counseling,” she added.
The findings suggest that “even if you have chronic liver disease and it’s not fully optimized, that should not interfere with pursuing IVF,” said principal investigator Tatyana Kushner, MD, an associate professor of medicine in the Division of Liver Diseases at the Icahn School.
Women with LD whose fertility is impaired should receive counseling about fertility preservation options earlier to help access fertility care, the researchers write.
The study’s findings are “encouraging,” Monika Sarkar, MD, associate professor of medicine in the Division of GI/Hepatologyat at the University of California, San Francisco, told Medscape Medical News.
“With rising numbers of young adults with liver disease, it is encouraging to see dedicated studies that address a topic of importance to our patients, namely, their reproductive health,” she said. “The current study nicely expands beyond previous data to include a control population without liver disease.”
Differences in Oocyte Numbers
Although there were no differences in the success rate of embryo transfer, the researchers did see differences in the number of oocytes. Only 37 mature oocytes made it to transfer in the LD group, compared with 609 in the control group, noted Sarkar, who was not involved with the study.
“The challenge of ART is less at the level of embryo transfer, which is very successful once a euploid embryo is achieved, but rather at the earlier step of retrieval of mature oocytes,” Sarkar said. “Here, the authors found that patients with liver disease had a significantly lower number of oocytes retrieved, number of mature oocytes, and lower number of fertilized embryos.”
The data suggest that fewer eggs are retrieved per cycle from patients with LD, “which ultimately will lower the success per cycle,” Sarkar said.
“This suggests that referring women with chronic liver disease to ART sooner may help to optimize outcomes,” she added. “Larger data evaluating ability to achieve mature oocytes and subsequent fertilization will also be key for determining whether ART success differs by presence, severity, and type of liver disease.”
As more research on ART outcomes in women with LD is conducted, subspecialists in gastrointestinal and liver disease may gain confidence in counseling patients, Sarkar said.
Lee, Kushner, and Sarkar report no relevant financial relationships.
Am J Gastroenterol. Published online April 13, 2023. Abstract
Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and Nurse.com, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick.
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