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BJOG: An International Journal of Obstetrics & Gynaecology, 2025; 132:167–177
https://doi.org/10.1111/1471-0528.17954
167
BJOG: An International Journal of Obstetrics & Gynaecology
RESEARCH ARTICLE OPEN ACCESS
Fertility and Miscarriage Incidence After Cervical
Intraepithelial Neoplasia Treatment by Thermal Ablation:
A Cohort Study
AniaWisniak1,2 | VirginieYakam3 | SophieEvinaBolo2 | AlidaMoukam2,3 | JessicaSormani1,4 | PierreVassilakos1 |
BrunoKenfack3,5 | PatrickPetignat1
1Department of Gynecology, Obstetrics and Pediatrics, Geneva University Hospitals, Geneva, Switzerland | 2Institute of Global Health, Faculty of
Medicine, University of Geneva, Geneva, Switzerland | 3Department of Gynecology and Obstetrics, Dschang Regional Hospital A nnex, Dschang,
Cameroon | 4Geneva School of Health Sciences, HES- SO University of Applied Sciences and Arts, Geneva, Switzerland | 5Department of Biomedical
Sciences, University of Dschang, Dschang, Cameroon
Correspondence: Ania Wisniak (ania.wisniak@hcuge.ch)
Received: 25 March 202 4 | Revised: 15 August 2024 | Accepted: 28 August 2 024
Funding: This study was funded by the Nuovo Soldati Foundation for Cancer Research, Swiss Societ y for Gynecology and Obstetrics, Humanitarian Affairs
Commission of Geneva University Hospitals, and Swiss Cancer Research.
Keywords: cervical cancer| fertility| miscarriage| pregnancy| screening| thermal ablation
ABSTRACT
Objective: To assess the impact of thermal ablation (TA) for the treatment of cervical dysplasia on fertility and pregnancy out-
comes among women screened for cer vical cancer in Cameroon.
Design: Retrospective cohort study.
Setting: Dschang health district, Cameroon.
Population: Participants aged 30–45 years from two screening trials conducted between 2015 and 2020 in Dschang District
Hospital.
Methods: Participants were primarily screened for human papillomavirus infection, triaged by visual inspection and treated
by TA if needed. Between October 2021 and March 2022, interviews on subsequent fertility were conducted with participants
treated by TA and a control group of untreated women.
Main Outcome Measures: Pregnancy and miscarriage after screening/treatment.
Results: A total of 760 participants (219 treated and 541 untreated) completed the survey, with a mean follow- up time of
1297 days. Sixty- two women (28.3%) treated by TA reported a pregnancy postscreening versus 165 (30.5%) in the control group
(p = 0.550). Adjusted for potential confounders, the hazard ratio of pregnancy for treated compared with untreated women was
0.82 (0.54–1.24, p = 0.350). Among women reporting pregnancies with a known outcome and which were not voluntarily termi-
nated, 18 (35.3%) treated participants had a miscarriage versus 31 (21.4%) in the control group (p = 0.048). In the adjusted model,
no association remained between TA and miscarriage (1.04, 0.39–2.78, p = 0.935) .
Conclusions: In our study population, TA did not significantly impact fertility nor miscarriage risk. Our results support the
widespread use of TA as a treatment of choice for precancerous cervical lesions in low- income settings.
This is a n open access ar ticle under the terms of t he Creative Commons Attr ibution-NonCommercial Lice nse, which permit s use, distribut ion and reproduction in a ny medium, provide d the
origin al work is properly cited a nd is not used for commer cial purpose s.
© 2024 T he Author(s). BJOG: An Inter national Jour nal of Obstetr ics and Gyna ecology publi shed by John Wiley & So ns Ltd.
Bruno Ken fack and Patrick Pet ignat joint senior aut horship.
168 BJOG: An International Journal of Obstetrics & Gynaecology, 2025
1 | Introduction
Cervical cancer (CC) is the second most frequent cancer in
sub- Saharan Africa and the most deadly, despite being largely
preventable [1]. Significant global disparities in this prevent-
able cancer prompted the World Health Organization (WHO) to
launch a global initiative in 2020 aiming to eliminate CC as a
public health issue [2]. The WHO initiative was designed to meet
the following targets by 2030: (i) 90% of girls vaccinated against
HPV, (ii) 70% of women screened with a high- performance test
and (iii) 90% of women with precancerous/cancerous lesions re-
ceiving treatment.
WHO guidelines for CC prevention recommend several suit-
able options for treating precancerous lesions in low- and
middle- income countries (LMICs). Recommended therapies
include ablative or excisional methods, depending on the ex-
tent and visibility of the lesion. Among available ablative ther-
apies, thermal ablation (TA) with a heated metallic probe is
recommended as an alternative to cryotherapy since 2019 [3].
TA has the advantage of being particularly adapted to low-
resource settings, as it requires simple reusable equipment
and little training, while achieving high cure rates of pre-
cancerous lesions [4, 5], with mainly minimal side effects [6].
However, the safety of TA for future fertility and pregnancy
outcomes is still unclear.
Assessing the effect of cervical treatment on future fertility
is essential in LMICs, as the primary target population for
CC screening are women aged 30–49 years with reproduc-
tive potential [7]. In this population, adherence to treatment
and screening coverage may be reduced by fear of infertility
[8, 9]. 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]. 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].
The risk of adverse effects on fertility and early pregnancy out-
comes after local cervical treatment has mostly been studied
for excisional therapies and did not show evidence for affected
fertility [12]. The effect on fertility of ablative therapies such as
cryotherapy or laser vaporisation was assessed only in three
studies in high- income countries [13–15]. To date, long- term
post- operative fertility and pregnancy outcomes following TA
have not been evaluated in resource- constrained settings. Our
objective was to assess the impact of TA on fertility and preg-
nancy outcomes among women screened for CC in Cameroon.
2 | Methods
2.1 | Study Design
The TaCCare (‘Evaluation of Thermal ablation in Cervical
Cancer screening on reproductive outcomes’) study was a ret-
rospective cohort study conducted with participants from
two previous CC screening trials taking place at the Dschang
District Hospital (now renamed Dschang Regional Hospital
Annex) since 2015.
2.2 | Setting and Screening Procedure
Since 2015, a collaboration between the Geneva University
Hospitals (HUG), Dschang District Hospital, the University of
Dschang and the Cameroonian Ministry of Health, has given
rise to a CC screening programme in the health district of
Dschang, in the West Region of Cameroon. The screening pro-
gram has been part of two clinical trials evaluating the real-
life effectiveness of a same- day test- triage- and- treat approach
to CC screening in Cameroon. The first trial was conducted
between 2015 and 2016 [16], and the second trial started in
2018 and was still ongoing at the time of the TaCCare study
[17]. Participants aged 30 –49 years were primarily screened
for HPV infection; HPV- positive women were triaged by vi-
sual inspection after application of acetic acid (V IA) and
Lugol's iodine (VILI), and treated on the same day by TA if
VIA/VILI positive. V IA/VILI was assessed by naked eye en-
hanced by smartphone digital photography, using the previ-
ously developed ABCD criteria for VIA evaluation [18]. HPV
status was determined by a point- of- care HPV assay (Xpert
HPV, GeneXpert technology, Cepheid, Sunnyvale, CA), which
identifies 14 high- risk genotypes. PAP- tests, endocervical
brushing and cervical biopsies were performed on all HPV-
positive participants for quality control and were analysed
at the Pathology Division of Geneva University Hospitals,
Switzerland. Participants with suspected cancer were referred
to a gynaecologist or gynaecologic oncologist for further eval-
uation. HPV- negative women were advised to repeat screening
after 5 years, respectively, 3 years if HIV- positive, while HPV-
positive women were invited for a follow- up visit after 1 year.
Following local guidelines, HPV- positive participants were
advised to avoid pregnancy until their 12- month follow- up
visit, and those treated by TA were additionally advised to
refrain from penetrative intercourse for 4 weeks. If the labo-
ratory analyses identified a high- grade lesion that was missed
upon visual examination, patients were called back for treat-
ment by TA or large loop excision of the transformation zone
(LLETZ), depending on the site of the lesion. Patients were
eligible for TA if the lesion did not extend into the endocer-
vix beyond reach of the thermal probe. TA was performed by
trained midwives using a WISAP probe (Medical Technology
GmbH, Brunnthal/Hofolding, Germany) heated at 100°C and
applied for 60 s on the cervical transformation zone and sus-
pected lesion when present. The treatment depth achieved in
these conditions is between 3 and 4 mm [19, 20]. If necessary,
the application was repeated several times until the entire ab-
normal area and transformation zone were covered.
2.3 | Recruitment Procedure and Data Collection
Participants were eligible for the TaCCare study if they had
been screened in one of the trials conducted in Dschang District
Hospital between 2015 and 2020 and were aged 30– 45 years at
the time of screening. Women having received cervical treat-
ment other than TA, as well as women having undergone a
169
hysterectomy, were excluded from the study. Women constitut-
ing the ‘treatment group’ were all pa rticipants treated by thermal
ablation within one of the two source trials, while participants of
the control group were untreated women from the source trials,
both HPV- positive and - negative.
Data collection took place between October 2021 and March
2022, during which women from both original screening trials
were invited to answer a phone survey (Figure1). Interviews
were led by two Cameroonian medical anthropologists trained
in CC screening and a Cameroonian physician, based on a
paper questionnaire structured along the following sections: (i)
update of CC screening and treatment, (ii) medical history and
risk factors, (iii) obstetrical history since CC screening and (iv)
obstetrical history prior to screening. 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.
Sociodemographic data, previous screening results and treat-
ment received, contraception use, tobacco consumption and
human immunodeficiency virus (HIV) status, were retrieved
from the data sets of the original screening trials. Participants
who did not answer their phone on the first try were called
again at least twice, at different times of the day and week. If
no answer was received after three tries, a text message was
sent inviting the participant to call back, and a relative indi-
cated by the participant as ‘additional contact’ was called to
update the participant's contact information. All participants
provided informed oral consent over the phone to participate
in the study.
2.4 | Statistical Analyses
The primary outcome was pregnancy since screening/treat-
ment, and the secondary outcome was miscarriage. Only the
first pregnancy occurring after screening/treatment for each
participant was considered in the analysis. Core outcome sets
were not considered at the time of trial design.
The sample size was determined based on the number of eligible
participants treated by TA (N = 296) with an estimated partici-
pation rate of 80%. 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. Considering a slightly lower
participation rate of 70% in the control group, approximately
670 participants were considered necessary to be recruited. To
reach this sample size, all eligible untreated HPV- positive par-
ticipants (N = 159) were included, as well as 505 additional HPV-
negative participants (rounded to obtain a total sample of 960
participants).
Descriptive statistics summarised categorical variables as per-
centages stratified by exposure group and compared using the
chi- squared test, and numerical variables as means with their
standard deviations and compared using the t- test. Because of
the high number of participants who did not know their HIV
status and body mass index (BMI) and their unequal distribu-
tion across exposure groups, unknown HIV status and BMI
were kept in the analyses as distinct categories. p values were
considered statistically significant at <0.05.
Reverse Kaplan–Meier survival curves were plotted to graph
the probability of pregnancy by exposure group and com-
pared using the log rank test. Having a cervical treatment
other than TA after initial screening was treated as censored
data. Pregnancy incidence rates and their 95% CI were calcu-
lated per 100 person- years. Cox regression models were used
to examine the effect of TA on pregnancy rates, expressed as
hazard ratios (HR). Potential confounders of the association
FIGUR E | Kaplan–Meier curve for pregnancy probability by treatment received.
170 BJOG: An International Journal of Obstetrics & Gynaecology, 2025
between TA and subsequent pregnancy were identified a pri-
ori based on published literature and clinical experience, and
included age, gravidity, parity, relationship status, tobacco
consumption, reported infertility prior to initial screening,
contraception use, BMI, suffering from a chronic disease, his-
tory of gynaecologic disease/surgery, HIV status, HPV status
and presence of cervical intraepithelial neoplasia grade 2 or
higher (CIN2+) at initial screening. Among these, variables
showing no strong association (p > 0.1) with TA or with preg-
nancy rates were excluded from the adjusted model. CIN2+ at
initial screening was excluded from the adjusted model due
to low counts across categories. Gravidity was also excluded
due to collinearity with parity. As the primary analysis did not
consider participants' desire for pregnancy, a subanalysis was
conducted excluding participants without any reported preg-
nancies and who did not attempt to get pregnant during the
follow- up period.
For the secondary outcome of miscarriage, analyses included par-
ticipants reporting at least one pregnancy after initial screening/
treatment. Participants still pregnant at the time of the survey and
those reporting voluntary abortion were excluded from the analy-
sis. Considering that miscarriage was a common outcome in our
study population (>10%), risk ratios (RR) were calculated for the
crude analysis. Logistic regression models were used to examine
the association between TA and miscarriage adjusted for poten-
tial confounders. As odds ratios (OR) are known to overestimate
(if OR > 1) or underestimate (if OR < 1) the effect when the inci-
dence 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 etal. [21] 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. As for the pri-
mary analysis, the presence of CIN2+ and variables showing no
strong association (p > 0.1) with TA or with subsequent miscar-
riage were excluded from the adjusted model.
2.5 | Patient and Public Involvement
Patients and the general public did not play a direct role in shap-
ing the study's design or its implementation. Nevertheless, the
research question took into consideration patient priorities and
experiences. Notably, in both source studies, over 50% of women
who underwent thermal ablation expressed a desire for future
pregnancies.
To ensure that participants felt at ease when responding to the
study survey, the questions were administered by a local anthro-
pologist and physician who were well- versed in the local culture
and vocabulary. The survey was also collaboratively developed
with local researchers, ensuring that the questions were cultur-
ally appropriate.
The findings of the study will be conveyed to community mem-
bers in a simplified manner through a biannual newsletter
published by our research group. This newsletter is a result of
collaboration between our Swiss and Cameroonian teams. It is
distributed to local partners within the healthcare system and
throughout the community with the assistance of community
health workers and women's associations.
3 | Results
Out of 2508 participants from both source trials aged
30–45 years, 16 patients meeting exclusion criteria, 11 included
in the pretest and two with no contact information were re-
moved from the sampling frame (FigureS1). Of the remaining
eligible participants, 296 had received treatment by TA and
2183 had not, among which all 159 HPV- positive women were
included in the study and 505 HPV- negative women were ran-
domly selected. 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). Follow- up duration was similar
between treated (mean 1273 days, SD ± 683), untreated HPV-
positive (mean 1113 ± 637) and untreated HPV- negative (mean
1366 ± 696) women. Baseline characteristics of responders ver-
sus nonresponders are available in the supplement (TableS1).
Participants had a mean age of 36.9 years (SD ± 4.9) in the treated
group and 37.5 (±4.8) in the control group (p = 0.102) (Table1).
Treated participants were more frequently without a partner at
the time of initial screening (16.0% vs. 10.2%, p = 0.026). There
was a larger proportion of HIV- positive participants in the
treated group (8.2% vs. 3.9%, p < 0.001), as well as participants
with a BMI <25 kg/m2 (18.7% vs. 10.7%), and a lower proportion
with a BMI >30 kg/m2 (27.4% vs. 37.2%, p = 0.0 01). Treated par-
ticipants had had less pregnancies prior to screening (mean 4.8
vs. 5.3, p = 0.007) and less children (mean 3.8 vs. 4.2, p = 0.023).
A higher proportion of women in the treated group reported past
infertility (22.9% vs. 15.4%, p = 0.014), whereas past caesarean
sections were less frequent (9.2% vs. 14.4%, p = 0.0 50).
Two- hundred and twenty- seven participants reported having
at least one pregnancy since screening or treatment. Twenty-
eight per cent (n = 62) of treated women reported a pregnancy
compared with 30.5% (n = 165) in the control group (p = 0.550)
(Table S2). Time to first pregnancy postscreening/treatment
ranged between 0 and 65 months, with a median of 12 months
(interquartile range 6–18). Distribution of time to pregnancy
varied according to HPV status and treatment group (FigureS2),
with a peak of pregnancies observed after 1 year among un-
treated HPV- positive women, mirroring the recommendations
given by healthcare providers to this group of participants to
avoid pregnancy until their follow- up visit.
The Kaplan–Meier curves showed no significant difference in
probability of pregnancy between treatment groups (p = 0.543)
(Figure 1). The adjusted hazard ratio of pregnancy for treated
women was 0.82 (95% CI: 0.54–1.24, p = 0.350) ( Table2). When
excluding women who did not attempt pregnancy, the probabil-
ity of pregnancy appeared to be slightly higher in the control
group on the Kaplan–Meier curves with borderline significance
(p = 0.072) (F igure S3). However, the adjusted analysis showed
no significant association (aHR 0.92 [0.60 –1.40], p = 0.689)
(TableS3). To account for the high proportion of missing values
for BMI and HIV status, a sensitivity analysis was conducted
excluding participants with missing values, which did not sig-
nificantly affect the results (TableS4).
171
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 (TableS2). In the crude analysis,
the proportion of miscarriages was higher among pregnant
women who had been treated (35.3%) compared with the con-
trol group (21.4%, p = 0.048) (Fig ure2A). However, when fur-
ther stratified by HPV status, the proportion of miscarriages
did not differ between HPV- positive women treated or not
(Figure 2). After adjusting for potential confounders includ-
ing HPV status, there remained no association between treat-
ment by TA and subsequent miscarriage (aOR 1.04 [0.39–2.78],
p = 0.935) (Table3).
4 | Discussion
4.1 | Main Findings
In this cohort of women screened for CC in the West Region
of Cameroon, TA did not significantly impact fertility (aHR
0.82 [0.54–1.24], p = 0.350) or risk of miscarriage (aOR 1.04
[0.39–2.78], p = 0.935) after adjusting for potential confounders.
Interestingly, HPV- positive women were twice as likely to have
a miscarriage than HPV- negative women.
Treated
(n = 219),
N (%)
Not treated
(n = 541),
N (%) p
Past infertilityd0.014
Yes 49 (2 2.9) 83 (15.4)
No 165 (7 7.1) 457 (84.6)
Premature birth 0.525
Yes 1 3 (6 .0) 39 (7.3)
No 20 4 (94.0) 496 (92.7)
Caesarean section 0.050
Yes 2 0 (9.2) 78 (14. 4)
No 198 (90. 8) 462 (85.6)
Adverse obstetrical
outcomes
0.100
No 201 (92.2) 475 (88 .1)
Yes 17 (7. 8) 64 (11.9)
Stillbirth 10 (4.6) 54 (10.0)
Peripartum
haemorrhage
2 (0.9) 6 (1.1)
Othere5 (2.3) 4 (0.7)
aAt the fir st screening visit (or at the time of thermal ablation for age).
bIncludes past consumption (n = 3).
cCurrent or in the period of time since the first screening visit or date of thermal
ablation.
dDefined as self- repor ted failure to achieve pregnanc y after 12 months of
unprotected sexual intercourse.
eCervical tear (n = 3), uterine rupture (n = 1) or not specified (n = 5).
TABLE | (Continued)TABLE | Participants' characteristics stratified by exposure to
thermal ablation.
Treated
(n = 219),
N (%)
Not treated
(n = 541),
N (%) p
Agea (mean ± SD) 36.9 ± 4.9 37.5 ± 4.8 0.102
Relationship status 0.026
With partner 184 (84.0) 48 3 (8 9. 8)
Without partner 35 (16 .0) 55 (10.2)
Tobacco
consumption
0.626
Yes b8 (3.7) 24 (4.4)
No 211 (96. 3) 517 (95.6)
Chronic disease 0.299
Yes 33 (15.2) 67 (12. 4)
No 184 (84.8) 474 (8 7.6)
HIV status <0.001
Positive 18 (8 .2) 21 (3.9)
Negative 112 (51.1) 2 09 (3 8.6)
Unknown 89 (4 0.6) 311 (57.5)
Gynaecological
disease
0.801
Yes 74 (3 4.4) 180 (33.5)
No 141 (65.6) 358 (66.5)
BMI 0.001
<25 41 (18.7) 58 (10.7)
25–30 50 (2 2.8) 149 (27.5)
>30 60 (27.4) 201 (37.2)
Unknown 6 8 (31.1) 133 (2 4.6)
Contraception usec0.157
No 92 (42 .0) 196 (3 6.5)
Yes 127 (58.0) 341 (63 .5)
Obstetrical history at initial screening
Graviditya
(mean ± SD)
4.8 ± 2.3 5.3 ± 2 .5 0.007
0–4 93 (42 .5) 191 (36.0) 0.099
≥5126 (5 7.5) 339 (6 4.0)
Paritya (mean ± SD) 3 .8 ± 2.0 4.2 ± 2.0 0.023
0–4 128 (58.5) 282 (53.3) 0.199
≥591 (41.5) 2 47 (46.7)
Past miscarriage(s) 0.738
Yes 8 4 (38 .7) 202 (37. 4)
No 133 (62. 2) 338 (62. 6)
(Continues)
172 BJOG: An International Journal of Obstetrics & Gynaecology, 2025
TABLE | Incidence rates and hazard ratios of pregnancy, crude and adjusted for participants' sociodemographic and medical characteristics.
Var iables
Number of pregnancies
(% of category) Person- years
Pregnancy IRa
(95% CI) Crude HR (95% CI) p
Adjusted HR
(95% CI) p
Thermal ablation
No 165 (30. 5) 1509 10 .9 (9.4–12 .7) Ref Ref
Yes 6 2 (28 .3) 618 10.0 (7.8–12.9) 0.91 (0.68–1.22) 0.547 0.82 (0.54–1.24) 0.350
Age (years)b
<35 147 (58. 8) 484 30.3 (25.8–35.7)
35–40 64 (23.5) 807 7.9 (6.2 –10.1) 0.81 (0.78–0.84) <0.001 0.82 (0.79–0.85) <0.001
>40 16 (6.6) 843 1.9 (1.2–3.1)
Relationship status
Without partner 25 (27.8) 196 12.7 (8.6–18.9) Ref Ref
With partner 201 (30 .1) 1921 10.5 (9.1–12.0) 1.03 (0.68–1.56) 0.886 1.10 (0.71–1.72) 0.668
HPV statusb
Negative 124 (29.4) 1216 10.2 (8.5–12.2) Ref Ref
Positive 103 (30.4) 910 11.3 (9.3–13.7) 1.04 (0.80–1.35) 0.768 0.96 (0.66–1.42) 0.852
CIN2+b
No 22 3 (30 .3) 2057 10.8 (9.5 –12.4) Ref —
Yes 4 (16.7) 69 5.8 (2.2–15.4) 0.55 (0.20–1.48) 0.235
HIV status
Negative 1 29 (4 0.2) 803 16.1 (13.5 –19.1) Ref Ref
Positive 9 (23.1) 96 9.4 (4 .9–18.0) 0.58 (0.29–1.13) 0.110 1.71 (0.75–3.91) 0.204
Unknown 89 (22. 2) 1227 7.3 (5.9–8.9) 0.50 (0.38–0.66) <0.001 0.80 (0.60–1.07) 0.129
Gravidityb
0–4 116 (40.9) 725 16.0 (13.3–19.2) Ref —
≥5108 (23.2) 1390 7.8 (6.4–9.4) 0.51 (0.39–0.66) <0.001
Parityb
0–4 158 (38.5) 1063 14.9 (12 .7–17.4) Ref Ref
≥565 (19.2) 1049 6.2 (4.9–7.9) 0.44 (0.33–0.59) <0.001 0.78 (0.57–1.08) 0.137
(Continues)
173
Var iables
Number of pregnancies
(% of category) Person- years
Pregnancy IRa
(95% CI) Crude HR (95% CI) p
Adjusted HR
(95% CI) p
Past infertilityb,c
No 191 (30.7) 1733 11.0 (9.6–12.7) Ref Ref
Yes 3 6 (27. 3) 378 9.5 (6.9 –13. 2) 0.87 (0.61–1.25) 0.457 0.71 (0.47–1.06) 0.095
Chronic disease
No 204 (31.0) 1783 11.4 (10.0–13.1) Ref Ref
Yes 23 (23.0) 339 6.8 (4.5–10.2) 0.67 (0.44–1.03) 0.070 0.80 (0.48–1.35) 0.412
Gynaecological disease
No 134 (2 6.9) 1426 9. 4 (7.9 –11.1) Ref Ref
Yes 9 0 (35.4) 686 13.1 (10.7–16.1) 1.37 (1.05–1.79) 0.021 1.06 (0.80–1.41) 0.675
Contraception used
No 71 (24 .6) 888 8.0 (6.3–10.1) Ref Ref
Yes 1 56 (33. 3) 1234 12.6 (10.8–14.8) 1.44 (1.09–1.91) 0.011 0.99 (0.73–1.33) 0.945
BMI (kg/m2)
<25 33 (33.3) 239 13.8 (9.8–19.4) Ref Ref
25–30 66 (33.2) 538 12.3 (9.6–15.6) 0.97 (0.64–1.48) 0.895 1.19 (0.77–1.83) 0.433
>30 81 (31. 0) 811 10.0 (8.0–12.4) 0.87 (0.58–1.30) 0.496 1.10 (0.72–1.68) 0.658
Unknown 47 (23.4) 539 8.7 (6.6–11.6) 0.66 (0.42–1.03) 0.068 1.04 (0.65–1.66) 0.868
Tobacco consumption
No 221 (3 0.4) 2026 10.9 (9.6 –12.4) Ref —
Yes e6 (18.8) 100 6.0 (2.7–13.3) 0.55 (0.25–1.24) 0.152
Note: Signi ficant results at the p < 0.05 level in bold.
Abbreviations: BMI, body mass index; CI, confidence interval; CIN2+, cerv ical intraepithelial neoplasia of grade 2 or more; HIV, human immunodeficiency vir us; HPV, human papillomavirus; HR , hazard ratio; IR , incidence rate;
Ref, reference.
aPer 100 person- years.
bAt first screening visit.
cDefined as failure to achieve preg nancy after 12 months of unprotected sexual intercourse.
dCurrent or past, in the per iod of time since the first screening visit or date of thermal ablation.
eIncludes past tobacco consumption.
TABLE | (Continued)
174 BJOG: An International Journal of Obstetrics & Gynaecology, 2025
4.2 | Strengths and Limitations
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 misclassi-
fication. Further, a high participation rate of nearly 80% was
achieved thanks to a rigorous recall procedure, limiting the
risk of selection bias. 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 ac-
knowledged. First, women were included in the analysis irre-
spective of their desire of pregnancy at the time of screening,
which may have confounded the association with fertility due
to potentially unequal reproductive behaviours across study
groups. To mitigate this, a sensitivity analysis was conducted
considering retrospectively reported desire for pregnancy,
which did not differ substantially from the main analysis.
However, potential reporting bias due to stigma around infer-
tility may have led to misclassification of self- reported desire
for pregnancy. The study population also varied considerably
in the duration of follow- up, due to the 5- year screening pe-
riod and censoring of a limited number of participants hav-
ing received a different cervical treatment. These variations,
however, were accounted for in the survival analysis. Second,
differing recommendations regarding reproductive behaviour
were given to HPV- negative and HPV- positive women. Thus,
behaviour was likely to vary across study groups during the
first year of follow- up, which may have further confounded
the association with fertility. 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. 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. Fourth, generalisability of our results
cannot be assumed as the study was conducted in a specific
setting in the West Region of Cameroon where population
characteristics such as HPV and HIV prevalence, as well as re-
productive behaviour, may impact fertility outcomes. 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 exci-
sional cervical treatment [12, 22].
4.3 | Interpretation
To the best of our knowledge, this is the first study to specifically
assess the effect of TA on subsequent fertility. 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. 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. 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 ef-
fect for laser treatment and cryotherapy [15]. However, the effect
of TA was not individually assessed in either study. The safety
of cryotherapy on fertility and early pregnancy outcomes has
also been shown in older studies, albeit with low- grade quality
of evidence, contributing to its widespread use as a screen- and-
treat approach in low- resource settings before the advent of TA
[25, 26]. Despite some differences across studies, which may be
explained by heterogeneous study populations and adjustment
for different variables, none of the published research has show n
significantly reduced fertility following ablative treatment,
which is consistent with our findings. Our study is also the first
to assess the effect of an ablative treatment on fertility in a low-
income setting.
Although pregnant women treated by TA in our study had a
higher proportion of miscarriages, no association was observed
after adjusting for potential confounders. Previous literature
published on the topic is scarce and has provided conflicting re-
sults. Similar to our findings, a study led in the United Kingdom
[27] observed a higher overall rate of miscarriages in women
FIGUR E | Proportion of miscarriages in post- screening
pregnancies stratified by (A) treatment group and (B) treatment group
and HPV status. Error bars represent 95% confidence intervals. TA,
thermal ablation; HPV+, Human papillomavirus- positive participants,
HPV−, HPV- negative participants.
175
TABLE | Odds ratios of miscarriage according to pregnant participants' sociodemographic and medical characteristics (N = 196) .
Characteristics
Miscarriagea
Risk ratio (95% CI) pAdjusted ORb (95% CI) pNo, n (%) Yes , n (%)
Thermal ablation
No 114 (78.6) 31 (21.4) Ref Ref
Yes 33 (6 4.7) 18 (35 .3) 1.65 (1.02–2.68) 0.048 1.04 (0.39–2.78) 0.935
Age at pregnancy
<35 105 (81.4) 24 (18.6)
35–40 31 (62.0) 19 (38.0) 1.10 (1.02–1.20) 0.018 1.11 (1.02–1.21) 0.019
>40 11 (64.7) 6 (35. 3)
HPV statusc
Negative 93 (8 2.3) 20 (17.7) Ref Ref
Positive 54 (65.1) 2 9 (34 .9) 1.97 (1.20–3.24) 0.006 2.26 (1.15 –3.58)d0.021
Presence of CIN2+c
No 145 (75.1) 48 (24.9) Ref —
Yes 2 (66.7) 1 (33. 3) 1.34 (0.27–6.77) 0.737
HIV status
Negative 83 (76.9) 25 (23.1) Ref Ref
Positive 7 (87.5) 1 (12 .5) 0.54 (0.08–3.49) 0.486 0.44 (0.05–2.22)d0.392
Unknown 57 (7 1. 3) 23 (2 8.7) 1.24 (0.76 –2 .0 2) 0.384 1.41 (0.69 –2 .87) 0.350
Parityc
0–4 103 (74.1) 36 (25.9) Ref —
≥544 (80 .0) 11 (20.0) 0.77 (0.42–1.41) 0.387
Previous miscarriage
No 93 (75.6) 30 (2 4.4) Ref —
Yes 53 (73.6) 19 (26. 4) 1.08 (0.66–1.78) 0.756
Chronic disease
No 132 (75.9) 42 (2 4.1) Ref
Yes 15 (68.2) 7 (31.8) 1.32 (0.68–2.57) 0.433 —
Gynaecological disease
No 92 (79.3) 2 4 (20.7) Ref —
Yes 5 4 (70 .1) 23 (29.9) 1.44 (0.88–2.37) 0.146
BMI (kg/m2)
<25 19 (67.9) 9 (32.1) Ref Ref
25–30 42 (75.0) 14 (25.0) 0.78 (0.38–1.57) 0.489 0.73 (0.25–2.14) 0.568
>30 54 (76.1) 17 (23.9) 0.74 (0.38–1.47) 0.404 0.60 (0.22–1.67) 0.331
Unknown 32 (78.0) 9 (22 .0) 0.68 (0.31–1.50) 0.344 0.51 (0.18–1.19)d0.132
Tobacco consumption
No 145 (75.9) 46 (2 4.1) Ref Ref
Yes e2 (40.0) 3 (60.0) 2.49 (1.17–5.32) 0.067 2.53 (0.75 –3.81)d0.110
Note: Data presented does not include participants pregnant at the time of the sur vey or voluntary abor tions.
Abbreviations: BMI, body mass index; CIN2+, cervical intraepithelial neoplasia grade 2 or worse; H IV, human immunodeficiency virus; HPV, human papillomavirus;
OR, odds ratio; Ref, reference.
aIncludes intrauterine fetal death (>24 gestational weeks).
bOR adjusted for thermal ablation, age, HPV status, HIV status, BMI category a nd tobacco consumption.
cAt first screening visit.
dAdjusted OR cor rected for common outcome (only for original adjusted ORs of >2.5 or <0.5).
eIncludes past tobacco consumption.
176 BJOG: An International Journal of Obstetrics & Gynaecology, 2025
treated by TA than in untreated women, but the analysis was
not adjusted for potential confounders. On the contrary, an ear-
lier 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. 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]. The association between HPV
infection and spontaneous abortions has rarely been investi-
gated in the literature to date, with existing studies being limited
by small sample sizes and showing conflicting results [29, 30].
To the best of our knowledge, ours is the first study to provide
insight into the association between vaginal HPV infection and
risk of miscarriage in a sub- Saharan African population.
5 | Conclusion
Our findings provide essential information on the safety of TA on
subsequent fertility and pregnancy outcomes in a sub- Saharan
African population. 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]. Safety of TA
is especially important in low- resource contexts using a ‘see and
treat’ approach where the risk of overtreatment is considerable.
Reassurance on the lack of negative impact of cervical treatment
on future ferti lity is para mount to improve screening coverage in a
female target population of childbearing age, as deleterious effects
on fertility may lead to major social and psychological impacts.
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.
This unexpected finding may prove useful to advocate for HPV
vaccination in sub- Saharan African countries where coverage re-
mains very low [31], as it highlights a potential additional benefit
of HPV vaccination in reducing the risk of miscarriage.
Further prospective studies with larger sample sizes should be
conducted in different settings, among women with a desire for
pregnancy, to conf irm the lack of association between TA and sub-
sequent fertility, and assess whether TA increases the risk of less
frequent adverse obstetrical outcomes. Multicenter prospective
studies comparing ablative to excisional methods may also offer
better insight into the differential effect on future pregnancies.
In conclusion, treatment of suspected cervical precancerous le-
sions by TA did not significantly impact subsequent fertility and
risk of miscarriage in a population of Cameroonian women. Our
results support the widespread use of TA as a treatment of choice
for precancerous cervical lesions in low- income settings.
Author Contributions
A.W., P.V., B.K. and P.P. designed the study. Data were collected by V.Y.,
S.E.B. and A.M. Data analysis was done by A.W. Data interpretation
was done by A.W., V.Y., J.S., P.V. and P.P. Data were accessed and veri-
fied by A.W. and J.S. This report was written by A.W. and was reviewed
and approved for publication by all co- authors. All authors had full ac-
cess to all data in the study and had final responsibility for the decision
to submit for publication.
Acknowledgements
We thank Prof. Nicole Schmidt for her insights into the course of the
study; Dr. Thomas Perneger for his expertise in statistical analyses; and
the collaborators of the Clinical Research Center, Geneva University
Hospitals and Faculty of Medicine, Geneva, for their contributions in
data management. We also would like to thank the clinical staf f of the
Dschang District Hospital (now Dschang Regional Hospital Annex), as
well as all women who participated in the study. Open access funding
provided by Universite de Geneve.
Ethics Statement
The protocol of the original clinical trial in which participants under-
went CC screening was amended to include TaCCare as a follow- up
study and was approved by the Cantonal Ethics Board of Geneva,
Switzerland (Commission cantonale d'éthique de la recherche,
No. 2017- 0110, amendment No. 4) and the Cameroonian National
Ethics Committee for Human Health Research (No. 2018/07/1083/
CE/CNERSH/SP and 2022/12/1518/CE/CNERSH/SP). Protocols
were carried out in accordance with the principles embodied in the
Declaration of Helsinki.
Conflicts of Interest
The authors declare no conflicts of interest.
Data Availability Statement
Individual participant data that underlie the results reported in this ar-
ticle (text, tables, figures and appendices) will be made available in a
data repositor y after de- identification, along with a data dictionary de-
fining each field in the set. The data will be available upon publication
of the article and for an indefinite period. The study protocol will be
made available upon request to the principal investigator (PP).
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Supporting Information
Additional supporting information can be found online in the
Supporting Information section.
