Fertility and Miscarriage Incidence After Cervical Intraepithelial Neoplasia Treatment by Thermal Ablation: A Cohort Study

May combine two claims.

Most women with a positive primary HPV test are overtreated because 90% of HPV-positive women do not have high-grade cervical lesions.

“The drawback of this strategy is that most women with a positive primary HPV test are overtreated, since 90% of HPV‐positive women do not have high‐grade cervical lesions, although they could develop them in the next years [10, 11].”

• cites [10] J. Cuzick, A. Szarewski, H. Cubie, et al., “ Management of Women Who Test Positive for High‐Risk Types of Human Papillomavirus: The HART Study,” Lancet 362, no. 9399 (2003): 1871– 1876. 14667741 sourceNot checked — no full text of the source
• cites [11] C. Broquet, P. Vassilakos, F. M. Ndam Nsangou, et al., “ Utility of Extended HPV Genotyping for the Triage of Self‐Sampled HPV‐Positive Women in a Screen‐and‐Treat Strategy for Cervical Cancer Prevention in Cameroon: A Prospective Study of Diagnostic Accuracy,” BMJ Open 12, no. 12 (2022): e057234. PMC9791451 36549727 sourcePartly supported

  The Results report that 44 of 382 HPV-positive women (11.5%) had CIN2+, supporting the approximate claim that 90% did not have high-grade lesions. The Introduction says a single HPV test can lead to overtreatment, but the study used triage rather than treating every HPV-positive woman; it does not show that most HPV-positive participants were actually overtreated. The copy also does not establish whether women without lesions developed them in subsequent years. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

In this population, adherence to treatment and screening coverage may be reduced by fear of infertility.

“In this population, adherence to treatment and screening coverage may be reduced by fear of infertility [8, 9].”

• cites [8] C. O. Chigbu and U. U. Aniebue, “ Non‐Uptake of Colposcopy in a Resource‐Poor Setting,” International Journal of Gynecology & Obstetrics 113, no. 2 (2011): 100– 102. 21349518 sourceNot checked — no full text of the source
• cites [9] N. Buchanan Lunsford, K. Ragan, J. Lee Smith, M. Saraiya, and M. Aketch, “ Environmental and Psychosocial Barriers to and Benefits of Cervical Cancer Screening in Kenya,” Oncologist 22, no. 2 (2017): 173– 181. 28167567 PMC5330703 sourcePartly supported

  The Results (page unavailable) report that some women feared speculum use during screening could cause infertility, supporting fear of infertility as a potential screening barrier. The paper does not link that fear to treatment adherence or measure its effect on screening coverage. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

The risk of adverse effects on fertility and early pregnancy outcomes after local cervical treatment has mostly been studied for excisional therapies and did not show evidence for affected fertility.

“The risk of adverse effects on fertility and early pregnancy outcomes after local cervical treatment has mostly been studied for excisional therapies and did not show evidence for affected fertility [12].”

• cites [12] M. Kyrgiou, A. Mitra, M. Arbyn, et al., “ Fertility and Early Pregnancy Outcomes After Treatment for Cervical Intraepithelial Neoplasia: Systematic Review and Meta‐Analysis,” BMJ 349 (2014): g6192. 25352501 PMC4212006 sourceSupported

May combine two claims.

A meta-analysis published in 2014 assessing fertility and early pregnancy outcomes after treatment of patients with suspected cervical precancerous disease identified only three studies assessing ablative methods, none of which included patients treated by thermal ablation.

“A meta‐analysis published in 2014 [12] assessing fertility and early pregnancy outcomes after treatment of patients with suspected cervical precancerous disease identified only three studies assessing ablative methods [13, 14, 23], none of which included patients treated by TA.”

• cites [12] M. Kyrgiou, A. Mitra, M. Arbyn, et al., “ Fertility and Early Pregnancy Outcomes After Treatment for Cervical Intraepithelial Neoplasia: Systematic Review and Meta‐Analysis,” BMJ 349 (2014): g6192. 25352501 PMC4212006 sourceSupported
• cites [13] C. N. Spracklen, K. K. Harland, B. J. Stegmann, and A. F. Saftlas, “ Cervical Surgery for Cervical Intraepithelial Neoplasia and Prolonged Time to Conception of a Live Birth: A Case–Control Study,” BJOG: An International Journal of Obstetrics & Gynaecology 120, no. 8 (2013): 960– 965. 23489374 PMC3691952 sourceSupported
• cites [14] I. Kalliala, A. Anttila, T. Dyba, T. Hakulinen, M. Halttunen, and P. Nieminen, “ Pregnancy Incidence and Outcome Among Patients With Cervical Intraepithelial Neoplasia: A Retrospective Cohort Study,” BJOG: An International Journal of Obstetrics & Gynaecology 119, no. 2 (2012): 227– 235. 21790950 sourceNot checked — no full text of the source
• cites [23] M. Spitzer, J. Herman, B. A. Krumholz, and M. Lesser, “ The Fertility of Women After Cervical Laser Surgery,” Obstetrics and Gynecology 86, no. 4 Pt 1 (1995): 504– 508. 7675369 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Less frequent pregnancy outcomes such as preterm birth, late miscarriages, premature membrane rupture, low birthweight or ectopic pregnancy have been associated with excisional cervical treatment.

“which have been associated with excisional cervical treatment [12, 22].”

• cites [12] M. Kyrgiou, A. Mitra, M. Arbyn, et al., “ Fertility and Early Pregnancy Outcomes After Treatment for Cervical Intraepithelial Neoplasia: Systematic Review and Meta‐Analysis,” BMJ 349 (2014): g6192. 25352501 PMC4212006 sourceSupported
• cites [22] H. Zhuang, S. Hong, L. Zheng, et al., “ Effects of Cervical Conisation on Pregnancy Outcome: A Meta‐Analysis,” Journal of Obstetrics and Gynaecology 39, no. 1 (2019): 74– 81. 29884103 sourceNot checked — no full text of the source

May combine two claims.

Two cohort studies in North America assessed pregnancy rates following ablative treatment, showing either increased pregnancy rates for grouped ablative procedures including thermal cautery, or no significant effect for laser treatment and cryotherapy.

“More recently, two cohort studies in North America assessed pregnancy rates following ablative treatment, showing either increased pregnancy rates for grouped ablative procedures, including thermal cautery [24], or no significant effect for laser treatment and cryotherapy [15].”

• cites [24] A. L. Naleway, S. Weinmann, G. Krishnarajah, et al., “ Pregnancy After Treatment for Cervical Cancer Precursor Lesions in a Retrospective Matched Cohort,” PLoS One 10, no. 2 (2015): e0117525. 25671561 PMC4324989 sourceSupported
• cites [15] L. A. Wise, S. K. Willis, R. B. Perkins, et al., “ A Prospective Study of Treatments for Cervical Intraepithelial Neoplasia and Fecundability,” American Journal of Obstetrics and Gynecology 223, no. 1 (2020): 96.e1– 96.e15. PMC8041134 31887271 sourceSupported

May combine two claims.

The association between HPV infection and spontaneous abortions has rarely been investigated, with existing studies limited by small sample sizes and showing conflicting results.

“The association between HPV infection and spontaneous abortions has rarely been investigated in the literature to date, with existing studies being limited by small sample sizes and showing conflicting results [29, 30].”

• cites [29] S. D. Popescu, A. G. Boiangiu, R. M. Sima, L. Bilteanu, S. Vladareanu, and R. Vladareanu, “ Maternal HPV Infection and the Estimated Risks for Adverse Pregnancy Outcomes—A Systematic Review,” Diagnostics 12, no. 6 (2022): 1471. 35741280 PMC9221727 sourcePartly supported

  The Results (§3.2.1, Miscarriage) say the published data are contradictory and limited by small sample size, supporting the claim about conflicting findings and study limitations. The review identifies nine studies investigating the link and says many studies have examined HPV as a possible miscarriage risk factor; it does not establish that the association has rarely been investigated. (LLM, conf=0.83)

  Experimental — accuracy not yet measured
• cites [30] A. Basonidis, A. Liberis, A. Daniilidis, S. Petousis, and K. Dinas, “ Human Papilloma Virus Infection and Miscarriage: Is There an Association?,” Taiwanese Journal of Obstetrics & Gynecology 59, no. 5 (2020): 656– 659. 32917313 sourcePartly supported

  The Abstract reports conflicting findings and says the studies are limited by small sample sizes and/or methodological limitations. The section on studies evaluating HPV infection and miscarriage likewise says most studies were small. The paper does not establish the stronger claim that the association has rarely been investigated. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Pregnancy rate was higher among patients treated by laser ablation than an untreated control group, and time to conception was not significantly associated with any ablative treatment.

“Pregnancy rate was higher among patients treated by laser ablation than an untreated control group, and time to conception was not significantly associated with any ablative treatment.”

• cites [12] M. Kyrgiou, A. Mitra, M. Arbyn, et al., “ Fertility and Early Pregnancy Outcomes After Treatment for Cervical Intraepithelial Neoplasia: Systematic Review and Meta‐Analysis,” BMJ 349 (2014): g6192. 25352501 PMC4212006 sourceSupported

May combine two claims.

Of the 227 first postscreening pregnancies reported, 11 were voluntarily terminated, 49 ended in spontaneous abortion, 147 were delivered (livebirth or stillbirth), and 20 were ongoing at the time of data collection.

“Of the 227 first postscreening pregnancies reported, 11 were voluntarily terminated, 49 ended in spontaneous abortion, 147 were delivered (livebirth or stillbirth), and 20 were ongoing at the time of data collection (Table S2).”

Probably not a substantial claim: may not pass S3 (load-bearing).

A total of 760 participants (219 treated by thermal ablation and 541 untreated) completed the survey.

“A total of 760 participants (219 treated and 541 untreated) completed the survey, with a mean follow‐up time of 1297 days.”

• Also stated in: § Results · plain

  “A total of 760 participants (219 treated by TA) completed the survey and were followed up for an average of 1297 days (range 244–2432).”

May combine two claims.

Distribution of time to pregnancy varied according to HPV status and treatment group, with a peak of pregnancies observed after 1 year among untreated HPV-positive women.

“Distribution of time to pregnancy varied according to HPV status and treatment group (Figure S2), with a peak of pregnancies observed after 1 year among untreated HPV‐positive women, mirroring the recommendations given by healthcare providers to this group of participants to avoid pregnancy until their follow‐up visit.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The mean follow-up time was 1297 days (range 244-2432).

“A total of 760 participants (219 treated by TA) completed the survey and were followed up for an average of 1297 days (range 244–2432).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The questionnaire was pretested on 10 participants and further adapted.

“The questionnaire was designed by a team of physicians specialised in gynaecology‐obstetrics and public health, and medical anthropologists, and was further adapted after being pretested on 10 participants.”

Probably not a substantial claim: may not pass S4 (based).

The safety of thermal ablation for future fertility and pregnancy outcomes is still unclear.

“However, the safety of TA for future fertility and pregnancy outcomes is still unclear.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In both source studies, over 50% of women who underwent thermal ablation expressed a desire for future pregnancies.

“Notably, in both source studies, over 50% of women who underwent thermal ablation expressed a desire for future pregnancies.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The peak of pregnancies after 1 year among untreated HPV-positive women mirrors the recommendations given by healthcare providers to this group to avoid pregnancy until their follow-up visit.

“Distribution of time to pregnancy varied according to HPV status and treatment group (Figure S2), with a peak of pregnancies observed after 1 year among untreated HPV‐positive women, mirroring the recommendations given by healthcare providers to this group of participants to avoid pregnancy until their follow‐up visit.”

Probably not a substantial claim: may not pass S4 (based).

Potential confounders of the association between thermal ablation and miscarriage were identified a priori based on published literature and clinical experience.

“A priori potential confounders of the association between TA and miscarriage included age, tobacco consumption, BMI, suffering from a chronic disease, history of gynaecologic disease/surgery, history of miscarriage, HIV status, HPV status and presence of CIN2+ at time of initial screening.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Thermal ablation with a heated metallic probe is recommended as an alternative to cryotherapy since 2019.

“Among available ablative therapies, thermal ablation (TA) with a heated metallic probe is recommended as an alternative to cryotherapy since 2019 [3].”

• cites [3] World Health Organization, “WHO Guidelines for the Use of Thermal Ablation for Cervical Pre‐Cancer Lesions,” 2019, https://www.who.int/publications‐detail‐redirect/guidelines‐use‐of‐thermal‐ablation‐for‐cervical‐pre‐cancer‐lesions. 31661202Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

As odds ratios are known to overestimate or underestimate the effect when the incidence of an outcome is common, adjusted ORs of more than 2.5 or less than 0.5 were corrected based on the formula proposed by Zhang et al.

“As odds ratios (OR) are known to overestimate (if OR > 1) or underestimate (if OR < 1) the effect when the incidence of an outcome is common, adjusted ORs of more than 2.5 or less than 0.5 were corrected based on the formula proposed by Zhang et al. [21]”

• cites [21] J. Zhang and K. F. Yu, “ What's the Relative Risk? A Method of Correcting the Odds Ratio in Cohort Studies of Common Outcomes,” Journal of the American Medical Association 280, no. 19 (1998): 1690– 1691. 9832001 sourceNot checked — no full text of the source

May combine two claims.

Thermal ablation did not significantly impact fertility nor miscarriage risk in the study population.

“In our study population, TA did not significantly impact fertility nor miscarriage risk.”

• AssumptionRests on an assumption: The adjusted analyses control for all relevant confounders, so the estimated associations between thermal ablation and pregnancy/miscarriage are not biased by unmeasured confounding.
• AssumptionRests on an assumption: Self-reported pregnancy and miscarriage data collected by phone interview are accurate and complete.

Classified as probably not a substantial claim. May combine two claims.

The sample size was determined to obtain 80% power with 95% confidence for an estimated 10% difference in pregnancy rates between groups (30% control vs 20% thermal ablation) over an average of 3 years, giving a necessary control group of 441 participants and approximately 670 participants to be recruited.

“The size of the control group was calculated using Pearson's chi‐squared test to obtain 80% power with a 95% confidence level (95% CI) for an estimated 10% difference in pregnancy rates between both groups (30% in the control group vs. 20% in the TA group) over the full study period (estimated at an average of 3 years), giving a necessary sample size for the control group of 441 participants.”

• Also stated in: § Statistical Analyses · plain

  “Considering a slightly lower participation rate of 70% in the control group, approximately 670 participants were considered necessary to be recruited.”

May combine two claims.

International screening guidelines recommend a screen-and-treat approach in resource-constrained settings, leading to a high proportion of women of reproductive age receiving treatment.

“The safety of cervical treatment is especially relevant in resource‐constrained settings where international screening guidelines recommend a ‘screen‐and‐treat approach’ to avoid loss to follow‐up, leading to a high proportion of women of reproductive age receiving treatment [7].”

• cites [7] World Health Organization, WHO Guideline for Screening and Treatment of Cervical Pre‐Cancer Lesions for Cervical Cancer Prevention, 2nd ed. (Geneva, Switzerland: WHO, 2021), https://www.who.int/publications‐detail‐redirect/9789240030824. 34314129Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S2 (checkable).

Our findings provide essential information on the safety of thermal ablation on subsequent fertility and pregnancy outcomes in a sub-Saharan African population.

“Our findings provide essential information on the safety of TA on subsequent fertility and pregnancy outcomes in a sub‐Saharan African population.”

• AssumptionRests on an assumption: In low-resource contexts using a 'see and treat' approach, the risk of overtreatment is considerable.
• AssumptionRests on an assumption: Reassurance on the lack of negative impact of cervical treatment on future fertility improves screening coverage in a female target population of childbearing age.
• AssumptionRests on an assumption: Deleterious effects on fertility lead to major social and psychological impacts.

Probably not a substantial claim: may not pass S2 (checkable).

The study fills an important evidence gap on the safety of thermal ablation for women's fertility and pregnancy outcomes.

“Although our study fills an important evidence gap on the safety of TA for women's fertility and pregnancy outcomes, several study limitations should be acknowledged.”

• AssumptionRests on an assumption: In low-resource contexts using a 'see and treat' approach, the risk of overtreatment is considerable.

May combine two claims.

The study sample did not provide sufficient power to assess absolute differences in fertility of less than 10%, as well as less frequent pregnancy outcomes such as preterm birth, late miscarriages, premature membrane rupture, low birthweight or ectopic pregnancy.

“Finally, our study sample did not provide sufficient power to assess absolute differences in fertility of less than 10%, as well as less frequent pregnancy outcomes such as preterm birth, late miscarriages, premature membrane rupture, low birthweight or ectopic pregnancy, which have been associated with excisional cervical treatment [12, 22].”

May combine two claims.

Previous literature on miscarriage after thermal ablation is scarce and has provided conflicting results.

“Previous literature published on the topic is scarce and has provided conflicting results.”

May combine two claims.

An earlier cohort study of women treated by thermal ablation between 1975 and 1989 reported outcomes of 226 pregnancies without detecting an increase in miscarriage rates compared to expected figures, but did not include a control group.

“On the contrary, an earlier cohort study of women treated by TA between 1975 and 1989 reported the outcomes of 226 pregnancies without detecting an increase in miscarriage rates compared to expected figures [28]. However, the study did not include a control group.”

• cites [28] H. K. Gordon and I. D. Duncan, “ Effective Destruction of Cervical Intraepithelial Neoplasia (CIN) 3 at 100°C Using the Semm Cold Coagulator: 14 Years Experience,” BJOG: An International Journal of Obstetrics & Gynaecology 98, no. 1 (1991): 14– 20. 1998626 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

The study was not designed to assess the impact of HPV infection on pregnancy outcomes.

“Although this study was not designed to assess the impact of HPV infection on pregnancy outcomes, our results further indicate a strong association between HPV positivity and miscarriage rate.”

May combine two claims.

A study in the United Kingdom observed a higher overall rate of miscarriages in women treated by thermal ablation than in untreated women, but the analysis was not adjusted for potential confounders.

“Similar to our findings, a study led in the United Kingdom [27] observed a higher overall rate of miscarriages in women treated by TA than in untreated women, but the analysis was not adjusted for potential confounders.”

• cites [27] D. Papoutsis, M. Underwood, W. Parry‐Smith, and J. Panikkar, “ Early and Late Pregnancy Outcomes in Women Treated With Cold‐Coagulation Versus LLETZ Cervical Treatment for Cervical Intraepithelial Neoplasia; a Retrospective Cohort Study,” Archives of Gynecology and Obstetrics 297, no. 4 (2018): 1015– 1025. 29404740 sourceNot checked — no full text of the source

May combine two claims.

The study had reliable data from previous clinical trials on cervical treatment received and HPV status, minimising the risk of misclassification.

“Strengths of this study include the availability of reliable data from previous clinical trials on cervical treatment received and HPV status, therefore minimising the risk of misclassification.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Potential reporting bias due to stigma around infertility may have led to misclassification of self-reported desire for pregnancy.

“However, potential reporting bias due to stigma around infertility may have led to misclassification of self‐reported desire for pregnancy.”

May combine two claims.

The study population varied considerably in duration of follow-up due to the 5-year screening period and censoring of a limited number of participants who received a different cervical treatment; these variations were accounted for in the survival analysis.

“The study population also varied considerably in the duration of follow‐up, due to the 5‐year screening period and censoring of a limited number of participants having received a different cervical treatment. These variations, however, were accounted for in the survival analysis.”

Classified as probably not a substantial claim. May combine two claims.

Thermal ablation is one of the main recommended methods by the WHO for the treatment of cervical precancerous lesions, due to its accessibility, affordability and effectiveness.

“This is particularly relevant in low‐income contexts where TA is one of the main recommended methods by the WHO for the treatment of cervical precancerous lesions, due to its accessibility, affordability and effectiveness [3, 6].”

• cites [3] World Health Organization, “WHO Guidelines for the Use of Thermal Ablation for Cervical Pre‐Cancer Lesions,” 2019, https://www.who.int/publications‐detail‐redirect/guidelines‐use‐of‐thermal‐ablation‐for‐cervical‐pre‐cancer‐lesions. 31661202Not checked yet

  Not checked in the free run.

• cites [6] C. Sauvaget, S. Bazikamwe, E. Lucas, A. Ndayikengurukiye, S. Harerimana, and P. Barango, “ Evaluation of Effectiveness, Acceptability and Safety of Thermal Ablation in the Treatment of Cervical Neoplasia in Burundi,” International Journal of Cancer 151, no. 7 (2022): 1120– 1126. 35567576 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

A study in the United States assessed the effect of laser vaporisation on pregnancy outcomes and found no significant effect on the rate of spontaneous abortions compared to a control group of untreated women.

“Another study conducted in the United States assessed the effect of laser vaporisation on pregnancy outcomes and found no significant effect on the rate of spontaneous abortions compared to a control group of untreated women [23].”

• cites [23] M. Spitzer, J. Herman, B. A. Krumholz, and M. Lesser, “ The Fertility of Women After Cervical Laser Surgery,” Obstetrics and Gynecology 86, no. 4 Pt 1 (1995): 504– 508. 7675369 sourceNot checked — no full text of the source

May combine two claims.

A high participation rate of nearly 80% was achieved through a rigorous recall procedure, limiting the risk of selection bias.

“Further, a high participation rate of nearly 80% was achieved thanks to a rigorous recall procedure, limiting the risk of selection bias.”

May combine two claims.

There were baseline differences between study groups, most notably roughly 50% higher prevalence of reported past infertility among women in the thermal ablation group; these disparities were included as potential confounders in the adjusted analysis.

“Third, there were some differences in baseline characteristics between the study groups, most notably the roughly 50% higher prevalence of reported past infertility among women in the thermal ablation group. These baseline disparities, however, were included as potential confounders in the adjusted analysis.”

May combine two claims.

The study attempted to account for potential imbalance by adjusting for HPV status at the initial screening visit, although residual confounding cannot be excluded.

“We have attempted to account for this potential imbalance by adjusting for HPV status at the initial screening visit, although residual confounding cannot be excluded.”

May combine two claims.

None of the published research has shown significantly reduced fertility following ablative treatment, which is consistent with our findings.

“Despite some differences across studies, which may be explained by heterogeneous study populations and adjustment for different variables, none of the published research has shown significantly reduced fertility following ablative treatment, which is consistent with our findings.”