Impact of cervical intraepithelial neoplasia and treatment on IVF/ICSI outcomes

Abstract

Study question: Does treatment selection for cervical lesions affect the outcome of IVF/ICSI?

Summary answer: There was no difference in pregnancy outcome between treated and untreated groups, or between different types of IVF/ICSI treatment.

What is known already: Human papillomavirus (HPV) infection and HPV-induced cervical lesions are associated with decreased fertility, and cervical intraepithelial neoplasia (CIN) treatment may increase the risk of adverse pregnancy outcomes.

Study design, size, duration: Between 2018 and 2020, 190 women with infertility who had abnormal HPV screening or cytology results prior to IVF/ICSI, and were diagnosed with CIN2/CIN3 by colposcopy biopsy at a tertiary hospital, were enrolled in a retrospective cohort study with follow-up until 31 December 2021.

Participants/materials, setting, methods: Patients with infertility who were diagnosed with CIN2/CIN3 by colposcopy biopsy were divided into the treatment and expectant management groups. The treatment group was divided into two intervention subgroups: the ablative therapy group and the surgical treatment group. The baseline data, number of oocytes retrieved, and rates of fertilization, high-quality embryos, positive serum HCG, clinical pregnancy, abortion, live birth, and cumulative pregnancy were compared among groups.

Main results and the role of chance: Among the 190 patients included in the study, 152 were diagnosed with CIN2, and 38 patients had CIN3. There was no significant difference in the baseline data between the treatment and expectant groups. The time from confirmed lesions to the onset of gonadotrophin administration in the surgical treatment group was significantly longer than in the ablative therapy group and the expectant group (P = 0.007 and P = 0.024, respectively). For the treatment and expectant groups, respectively, the average number of oocytes retrieved (12.95 ± 8.77; 13.32 ± 9.16), fertilization rate (71.01 ± 23.86; 64.84 ± 26.24), and high-quality embryo rate (48.93 ± 30.72; 55.17 ± 34.13) did not differ, and no differences were detected between the different treatment subgroups. There were no differences among groups in rates of HCG positivity, clinical pregnancy, miscarriage, live birth, or cumulative pregnancy. The live birth rate in the surgical treatment group was slightly higher than that in the expectant groups (77.78% versus 66.67%), but the difference was not statistically significant. The 3-year cumulative pregnancy rates in the surgical treatment and expectant groups were 58.19% and 64.00%, respectively.

Limitations, reasons for caution: This is a retrospective study, which by nature can include selection bias, and the number of cases in the expectant group was <30, which may result in a false-negative result owing to the small sample size.

Wider implications of the findings: For patients with CIN2/CIN3, the treatment of cervical lesions does not affect the outcome of IVF/ICSI. Patients with CIN2 can enroll for IVF/ICSI cycles, with close follow-up to prevent the progression of cervical lesions, in order to avoid further delay in starting ART. For patients with CIN3, ovulation induction and embryo cryopreservation can be initiated as soon as possible after cervical lesions are treated, and frozen-thawed embryo transfer can be carried out 9-12 months later.

Study funding/competing interest(s): This work was funded by the Key Clinical Projects of the Peking University Third Hospital (to Y.W., BYSYZD2021014). The authors declare no conflicts of interest.

Trial registration number: N/A.

Keywords: IVF; ablative therapy; cervical intraepithelial neoplasia; embryo transfer; expectant treatment; human papillomavirus infection; surgical treatment.