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Citation: Salman, L.; Covens, A.
Fertility Preservation in Cervical
Cancer—Treatment Strategies and
Indications. Curr. Oncol. 2024,31,
296–306. https://doi.org/
10.3390/curroncol31010019
Received: 26 November 2023
Revised: 28 December 2023
Accepted: 2 January 2024
Published: 4 January 2024
Copyright: © 2024 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Review
Fertility Preservation in Cervical Cancer—Treatment Strategies
and Indications
Lina Salman 1and Allan Covens 1, 2, *
1Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Toronto,
Toronto, ON M5G 2M9, Canada; lina.salman@uhn.ca
2Division of Gynecologic Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre,
Toronto, ON M4N 3M5, Canada
*Correspondence: al.covens@sunnybrook.ca
Abstract: Cervical cancer is frequently diagnosed in women during their reproductive years, and
fertility preservation is an essential part of their cancer treatment. In highly selected patients with
early stage, low-risk cervical cancer and a tumor size
≤
2 cm, several treatment strategies can be
offered for patients wishing to preserve fertility, including radical/simple trachelectomy or conization
with pelvic lymph node assessment. Trachelectomy can be performed through a vaginal, abdominal,
or minimally invasive approach and has been shown to have an equivalent oncologic outcome
compared to radical hysterectomy. All surgical approaches for radical trachelectomy seem to have
excellent survival with comparable oncologic outcomes. Nevertheless, patients undergoing vaginal
trachelectomy have better obstetric outcomes compared to the other routes. In patients with larger
tumors (2–4 cm), neoadjuvant chemotherapy followed by fertility-sparing surgery is an alternative
option. Several chemotherapy regimens have been used for this indication, with a pathologic complete
response rate of 17–73%. For locally advanced diseases that require radical hysterectomy or primary
chemoradiation, fertility preservation can be performed using oocyte, embryo, or ovarian tissue
cryopreservation, as well as ovarian transposition. For these patients, future pregnancy is possible
through surrogacy. In addition to fertility preservation, ovarian transposition, where the ovaries are
repositioned outside of the radiation field, is performed to maintain ovarian hormonal function and
prevent premature ovarian failure. In summary, fertility-preservation treatment strategies for patients
with early stage cervical cancer are continuously evolving, and less radical surgeries are becoming
more acceptable. Additional and ongoing evidence is helping determine the impact of conservative
procedures on oncologic and obstetric outcomes in these patients.
Keywords: cervical cancer; fertility preservation; trachelectomy; ovarian transposition
1. Introduction
Cervical cancer is the fourth most common cancer in women worldwide [1].
It is frequently diagnosed in women aged 35–44, and it is the second leading cause of
cancer death in women aged 20–39 [
2
]. Treatment of cervical cancer is based on the stage of
the disease [
3
]. The standard treatment for patients with early stage disease (stage IA2-IB1)
is/has been radical hysterectomy with pelvic lymph node dissection, while patients with
locally advanced and metastatic disease are treated with primary radiation therapy (RT)
+/
−
systemic treatment [
3
,
4
]. As 37% of patients with newly diagnosed cervical cancer are
under the age of 45 [
5
], fertility preservation treatment options are often desired. Surgical
treatment modalities include radical and simple trachelectomy as well as cervical conization.
In certain cases of locally advanced disease where uterine preservation is not an option,
fertility preservation can be maintained through assisted-reproduction technologies (ART)
and ovarian transposition, which also have the advantage of preserving ovarian hormonal
function [
6
–
8
]. In this review, we present fertility preservation treatment strategies for early
Curr. Oncol. 2024,31, 296–306. https://doi.org/10.3390/curroncol31010019 https://www.mdpi.com/journal/curroncol
Curr. Oncol. 2024,31 297
stage cervical cancer, including indications, oncologic, and obstetric outcomes. In addition,
we present evidence supporting conservative management of these patients.
2. Radical Trachelectomy with Lymph Node Assessment
Selected patients with early stage cervical cancer wishing to preserve fertility might
be eligible for trachelectomy [
9
]. Radical trachelectomy was first described by Dargent
in 1987 [
10
], and it consists of the removal of the cervix, vaginal margins, and parame-
tria. Historical indications for trachelectomy included stage IA1 with lymphovascular
space invasion (LVSI), stage IA2-IB1 (tumor size
≤
2 cm), negative nodal metastasis, and
the absence of deep stromal invasion [
3
,
11
]. Excluding nodal disease prior to fertility
preservation treatment is crucial, as positive lymph nodes are a poor prognostic factor
and can determine the appropriate treatment [
12
]. The feasibility of sentinel lymph node
mapping led to a paradigm shift in lymph node assessment in cervical cancer [
3
]. Ac-
cording to the NCCN guidelines, sentinel lymph node biopsy can replace pelvic lymph
node dissection in FIGO 2018 stage IA1 with LVSI and stage IA2-IB1 [
3
,
13
], whereas in
the 2023 ESGO guidelines, pelvic lymph node dissection should be performed in stage
IB1 with negative sentinel nodes frozen [
4
]. Although data from the prospective SENTI-
COL I and SENTICOL II studies showed that omitting full pelvic lymphadenectomy for
patients with stage IA-IIA with bilateral negative sentinel lymph nodes does not seem to
be associated with an increased recurrence rate, evidence on the accuracy and oncologic
safety of sentinel lymph node biopsy in cervical cancer is still evolving, and additional
prospective data are needed [
14
]. Nica et al. evaluated the outcome of patients with early
stage cervical cancer (tumor size
≤
2 cm) undergoing cervical conization with laparoscopic
sentinel lymph node assessment [
15
]. Of the 44 patients included in the analysis, 93%
had negative sentinel nodes and did not require further nodal procedures, while 6.8% of
patients had micrometastases detected in the sentinel nodes and underwent ipsilateral
lymphadenectomy. All the remaining non-sentinel lymph nodes were negative. After a
median follow-up of 44 months, no recurrences were documented. Another retrospective
study included 36 patients with stage IA2-IBI cervical cancer [
16
]. All patients underwent
FSS and laparoscopic sentinel lymph node dissections. Of those, 50% underwent sentinel
lymph node dissection alone, and 50% underwent sentinel lymph node followed by full
pelvic lymph node dissection. In total, there were four recurrences: two in the sentinel and
two in the pelvic lymphadenectomy groups. The results of these studies are promising,
but larger prospective studies are required to assess the accuracy of sentinel lymph node
dissection in early stage cervical cancer and to evaluate the safety of minimally invasive
surgeries for lymph node assessment.
Radical trachelectomy originally combined vaginal approaches. Since then, the proce-
dure has been modified and is currently performed via a vaginal, abdominal, or minimally
invasive approach, based on the surgeon’s preference and experience [
17
]. Several studies
evaluated the oncologic outcome of radical trachelectomy and found it to have comparable
survival and recurrence rates compared to radical hysterectomy [
18
–
20
], making it a safe
alternative for patients wishing to preserve fertility.
The question of whether one surgical approach is superior to the other has been eval-
uated in several retrospective studies. A systematic review by Smith et al. compared the
surgical, oncologic, and obstetric outcomes of radical trachelectomy according to the surgi-
cal route: vaginal, abdominal, and laparoscopic [
17
]. Out of 2566 patients included in the
analysis, 75% had stage IB1 (tumor size < 2 cm). The majority of patients underwent vaginal
radical trachelectomy (58%), 37% had abdominal procedures, and only 4.7% underwent
laparoscopic trachelectomy. The vaginal approach had a shorter median operative time
compared to the abdominal and laparoscopic routes, and had lower rates of positive mar-
gins. The post-operative pregnancy rate was found to be highest in the vaginal approach
(38%) compared to abdominal and laparoscopy (10% and 9%, respectively), in addition
to lower rates of preterm delivery. It should be noted that the group undergoing vaginal
trachelectomy had a longer follow-up time, which might explain the higher pregnancies
Curr. Oncol. 2024,31 298
reported. While this review included a large number of patients, it is based on published
retrospective data; therefore, selection and publication biases should be taken into account
when interpreting these findings.
Since the publication of the Laparoscopic Approach to Cervical Cancer (LACC)
trial [
21
], the safety of minimally invasive surgery (MIS) for radical trachelectomy has
raised some concerns. The LACC trial was a randomized controlled trial that evaluated
disease-free survival in patients undergoing MIS versus open radical hysterectomy for
early stage cervical cancer. The results demonstrated increased recurrence and death rates
in patients undergoing radical hysterectomy via the MIS approach in patients with stage
IB2, as these comprised the majority of the study cohort. Prospective data on MIS versus
open surgeries for stage IA2/IB1 cervical cancer are limited, as is the safety of MIS for
lymph node assessment in these patients. A retrospective study using the National Cancer
Database evaluated the trends, characteristics, and survival outcomes of patients with stage
IA2-IB cervical cancer undergoing radical trachelectomy via MIS versus laparotomy [
22
].
Of the 246 people included in the study, 144 underwent surgery via the MIS approach.
Patients undergoing vaginal trachelectomy were excluded. The authors found a significant
increase in using the MIS approach throughout the years (increasing from 29% in 2010
to 75% in 2015). Death events were 7.6% in the laparotomy group compared to 3.5% in
the MIS (p= 0.025). The absolute number of events in the study was very low, and the
authors conclude that although no survival difference was found, the effect of MIS radical
trachelectomy on survival remains unknown.
A further comparison of MIS versus open radical trachelectomy was published by
the International Radical Trachelectomy Assessment (IRTA) [
23
]. In this retrospective
study,
646 patients
were included in the analysis. 358 underwent open surgery, and
288 underwent
MIS. At 4.5 years, 4.8% had a recurrence in the open surgery and 6.3%
in the MIS, but this was not statistically significant. In addition, there was no difference in
overall survival between groups (99.2% in open surgery vs. 99.0% in MIS). As this is not a
common procedure, the feasibility of performing a randomized clinical trial to evaluate
survival outcomes in MIS versus open trachelectomy is unlikely, and clinical practice will
be based on the best available evidence.
Regardless of the surgical approach, the radicality of the procedure is continuously
being refined for more conservative surgeries. Based on tumor factors, patients may
undergo simple trachelectomy or cervical conization rather than radical trachelectomy with
similar oncologic outcomes [24].
3. Simple Trachelectomy and Cone Biopsy
The rationale for performing more conservative surgeries is supported by the re-
sults of several studies evaluating the risk of parametrial involvement in patients with
early stage cervical cancer who have favorable pathologic features (tumor
≤
2 cm, depth
of
invasion ≤10 mm
, and negative pelvic nodes) [
25
,
26
]. In this well-defined cohort of
patients, the risk of parametrial involvement is lower than <1%, putting the benefit of
removing the parametria in doubt. While cervical conization is typically performed to
treat high-grade premalignant lesions of the cervix [
27
], the above evidence led to studies
evaluating the performance of cone biopsy as a treatment for cervical cancer. The ConCerv
trial was the first prospective study to evaluate the feasibility and oncologic outcomes of
conization alone or simple hysterectomy in early stage low-risk cervical cancer [
28
]. In this
study, they included patients with FIGO 2009 stage IA2-IB1 cervical cancer [
29
] who meet
the following criteria: squamous cell or adenocarcinoma, tumor size
≤
2 cm, no LVSI, depth
of invasion
≤
10 mm, negative imaging for metastatic disease, and negative conization
margins. Patients were allowed to undergo a repeated cone if the first one had positive
margins. Patients desiring fertility underwent a second conization with pelvic lymph node
assessment, and those not desiring fertility preservation underwent a simple hysterectomy
with pelvic lymph node assessment. In total, 44 patients were enrolled in the fertility
preservation arm. Of those, two patients had positive lymph nodes, and one patient had
Curr. Oncol. 2024,31 299
recurrent disease. The one patient with recurrent disease had a stromal invasion of 13 mm
on the first conization with positive margins. Repeated conization was negative for cancer,
but margins were positive for high-grade dysplasia. This had led the investigators to
amend the protocol and exclude patients with positive margins not only for invasive cancer
but also for intra-epithelial neoplasia. Data from Bogani et al. on 32 patients with FIGO
2018 stage IA2, IB1, and IB2 undergoing conization with pelvic lymph node assessment
showed 5-year disease-free survival and overall survival to be 94% and 97%, respectively.
Another published study by Plante et al. evaluated the obstetric and oncologic outcomes
of simple vaginal trachelectomy/conization in patients with low-risk, early stage cervical
cancer. The 5-year progression-free survival and overall survival were 97.9% and 97.6%,
respectively [30].
A systematic review looking into obstetrics and oncologic outcomes following fertility
preservation treatment for early cervical cancer included 347 cases that underwent coniza-
tion [
31
]. In this group, the recurrence rate was 0.4%, and the pregnancy rate was 36.1%
with no death events. A more recent systematic review published by Nezhat et al. evaluated
reproductive and oncologic outcomes after fertility-sparing surgery (FSS) for stage IA1-IB1
cervical outcomes [
32
]. They included patients who underwent conization/simple trach-
electomy, or radical trachelectomy via different surgical approaches. Of the 3044 patients
included, the pregnancy rate was 55.4% in patients attempting to conceive, with the highest
clinical pregnancy rate after vaginal trachelectomy (67.5%). After a median follow-up of
39.7 months, the mean cancer recurrence rate was 3.2%, and the cancer death rate was
0.6%. These data highlight the excellent oncologic outcome and safety of performing these
procedures in these patients.
Another aspect that should be considered when choosing a treatment modality is the
impact of such treatment on quality of life. The Gynecologic Oncology Group (GOG)-0278
is a phase I/II study evaluating physical function and quality of life in patients with cervical
cancer stage IA1 with LVSI and IA2-IB1 (
≤
2 cm) who underwent simple hysterectomy or
cone biopsy with pelvic lymphadenectomy (ClinicalTrials.gov/NCT01649089). This study
will look into urinary, gastrointestinal, and sexual function following non-radical surgery.
The study completed accrual, and results are anticipated to be presented in early 2024.
4. Oncologic Safety of Fertility-Preservation Surgeries in Different Histologic Types
Squamous cell carcinoma (SCC) is the most common histological type of cervical cancer,
followed by adenocarcinoma, which accounts for approximately 25% of all cases [
33
]. The
incidence of adenocarcinoma in developed countries has increased in the last decade,
whereas the incidence of SCC has been decreasing [
34
]. Studies on patients with early stage
cervical cancer undergoing definitive treatment showed conflicting results regarding the
oncologic outcome of adenocarcinoma compared to SCC [
35
–
37
]. Concerns were raised
regarding the oncologic safety of FSS in patients with adenocarcinoma or adenosquamous.
Zusterzeel et al. looked at recurrence risk following radical vaginal trachelectomy in early
stage cervical cancer [
38
]. In this retrospective study of 132 patients, 72% had SCC, 24.2%
had adenocarcinoma, and 3.8% had adenosquamous. The majority of patients in this study
had FIGO 2009 stage IB1 disease. The overall recurrence rate was 6.8%, with a median
time to recurrence of 21 months. Adenosquamous carcinoma had the highest recurrence
rate of 20%, followed by 12.5% for adenocarcinoma and 4.2% for SCC. Additional studies
failed to show a difference in oncologic outcome in adenocarcinoma compared to SCC for
patients undergoing radical trachelectomy [
39
,
40
]. A recently published multicenter study
evaluated risk factors for recurrence in patients with early stage cervical cancer treated
with FSS [
41
]. They included 733 patients who underwent any type of FSS. The majority
of patients (70%) had SCC, and 24% had adenocarcinoma. A total of 49% of patients had
FIGO 2018 stage IB1 disease. After a median follow-up of 72 months, histologic subtype
was not found to be a risk factor for recurrence. In fact, the only significant risk factor was
tumor size >2 cm.
Curr. Oncol. 2024,31 300
While some histological types have a worse prognosis than SCC, it is not evident
that FSS increases the risk of recurrence. Although additional adjuvant therapy might
be indicated based on pathology to decrease the risk of recurrence, FSS should not be a
contraindication to its administration.
5. Neoadjuvant Chemotherapy
Neoadjuvant chemotherapy (NACT) is an alternative option for patients with bulky
cervical cancer (tumor size > 2 cm) wishing to preserve fertility. The rationale for administer-
ing chemotherapy is to shrink the tumor and make an FSS feasible. Different chemotherapy
regimens were studied in small case series, including paclitaxel/cisplatin/ifosphamide
(TIP) [
42
,
43
], paclitaxel/cisplatin [
44
], and carboplatin/paclitaxel [
45
], with varying num-
bers of cycles (Table 1).
Table 1. Summary of several studies evaluating neoadjuvant chemotherapy followed by fertility-
sparing surgery for cervical cancer.
Study # of Patients Stage of Disease aChemotherapy Regimen # of Chemo
Cycles
Complete
Pathologic
Response to NACT
FSS after NACT
Maneo et al., 2008
[43]21 IB1 (tumor size
< 3 cm)
Cisplatin 75 mg/m2, paclitaxel
175 mg/m2, and ifosfamide
5 g/m2
3 24% PLND + conization
Vercellino et al.,
2012 [46]18 IB1-IB2 (tumor size
2–5 cm)
Ifosphamide 5 g/m2, cisplatin
100 mg/m2, and paclitaxel
200 mg/m2
2–3 17% PLND + RVT
Lanowska et al.,
2014 [47]18 IB1-IB2 (tumor size
2–5 cm)
Ifosphamide 5 g/m2, cisplatin
100 mg/m2, and paclitaxel
200 mg/m2
2–3 50% PLND + RVT
Robova et al., 2014
[48]28 IB1-IB2 (tumor size
1.5–4 cm)
1.Cisplatin 75 mg/m2and
ifosfamide (2 g/m2)
OR
2. Cisplatin (75 mg/m2) and
doxorubicine (35 mg/m2)
3 21% PLND + SVT
Salihi et al., 2015
[49]11 IB1-IB2 (tumor size
1.2–5.2 cm)
1.Paclitaxel 90 mg/m2and
carboplatin AUC 4
OR
2. Ifosphamide 5 g/m2, cisplatin
75 mg/m2, and paclitaxel
175 mg/m2
OR
3. Dose-dense paclitaxel
60 mg/m2
and carboplatin AUC 2
3–9 73% Conization
Tesfai et al., 2020
[45]19 IB1-IIA (tumor size
3.5–6 cm)
Weekly cisplatin 70 mg/m2and
paclitaxel 70 mg/m26 47% ART
Zusterzeel et al.,
2020 [50]18 IB2 b(tumor size
2.2–4 cm)
Weekly cisplatin 70 mg/m2and
paclitaxel 70 mg/m26 39% RVT
a
According to 2009 FIGO staging;
b
according to 2018 FIGO staging. #—Number; NACT—Neoadjuvant
Chemotherapy; FSS—Fertility-Sparing Surgery; PLND—Pelvic Lymph Node Dissection; RVT—Radical Vaginal
Trachelectomy; SVT—Simple Vaginal Trachelectomy; and ART—Abdominal Radical Trachelectomy.
The results of several case series investigating the oncologic and obstetric outcomes
of NACT followed by fertility preservation surgery in patients with tumor sizes 2–4 cm
have been summarized in a systematic review by Gwacham et al. [
51
]. All patients in-
cluded in this review (n = 114) had FIGO 2018 stage IB2 cervical cancer. The most common
chemotherapy regimen was TIP (89.5% of patients). Pelvic lymphadenectomy was per-
formed in 49% of patients prior to starting NACT, whereas 51% underwent NACT without
nodal assessment. FSS was performed on 99.1% of patients. The most common procedure
performed was radical vaginal trachelectomy (40.7%). The response to treatment was high,
with a complete pathologic response reported to be 39.5% and a partial response of 45.6%.
As for obstetric outcomes, 69.4% had full-term delivery, 9.7% had preterm delivery, and
16.1% had miscarriages. Although these data are obtained from small retrospective studies,
these findings are promising. As mentioned earlier, different chemotherapy regimens were
used, and it is not clear whether one regimen is superior to the other. In addition, there
Curr. Oncol. 2024,31 301
was no consistency between studies in the timing of performing lymph node dissection.
While some studies performed lymph node dissection after NACT, one would argue that it
should be performed prior to starting NACT, as positive nodes are associated with a poor
prognosis and these patients would require adjuvant treatment with chemotherapy and
radiation [52].
The outcome of NACT, followed by FSS, is currently being investigated by the CoN-
tESSA trial. This is a prospective multi-center trial evaluating NACT followed by FSS for
premenopausal patients with cervical cancer, FIGO 2018 stage IB2, wishing to preserve
fertility [
53
]. Participants are treated with NACT, consisting of platinum-based chemother-
apy (cisplatin or carboplatin) with paclitaxel. Those with a complete/partial response will
undergo fertility-sparing surgery. The primary end point of this study is to assess the rate
of functional uterus defined as successful fertility-sparing surgery and no adjuvant therapy.
The study is recruiting, and results are expected in 2025.
6. Ovarian Transposition
In patients with locally advanced cervical cancer, treatment includes external beam
radiation (EBRT) +/
−
brachytherapy +/
−
chemotherapy [
3
,
54
]. The standard dose used
in EBRT for cervical cancer is lethal to the ovaries and leads to ovarian failure [
55
]. In
premenopausal patients, this can result in a post-menopausal state with its associated symp-
toms and manifestations such as vasomotor symptoms, urogenital atrophy, osteoporosis,
and long-term cardiovascular complications [
56
,
57
]. In patients receiving EBRT, ovarian
transposition (OT) can be offered prior to treatment initiation to preserve ovarian function
in addition to fertility preservation. In this procedure, the ovaries are transposed laterally,
well above the pelvic brim, avoiding tension or torsion of the gonadal vessels [
58
,
59
]. When
OT is considered, it should be performed as soon as possible and with a minimally invasive
approach to enhance recovery, as a longer duration of time from diagnosis to treatment
negatively affects prognosis [
60
]. In a systemic review by Buonomo et al. [
61
], looking into
the outcomes of 1377 patients with cervical cancer undergoing OT followed by RT, it was
found that ovarian function was preserved in 61.7% (range 16.6–100%). Several factors
could explain the low rate of ovarian function preservation noted in that study: First, there
are surgical techniques, as the transposed ovaries might not be situated far enough from the
radiation borders, therefore exposing the ovaries to significant amounts of scatter radiation.
Second, the patient’s age at the time of the procedure plays an important factor. Although
this procedure is performed in premenopausal patients, the more advanced the patient’s
age, the higher the likelihood of ovarian failure [
62
]. Smaller doses of exposure to radiation
in these patients can lead to ovarian insufficiency as the effective sterilizing radiation dose
decreases with increasing age [63].
In addition to preserving hormonal function, ovarian transposition plays a role in
fertility preservation, and there have been reports of successful pregnancies following
this procedure [
6
]. In patients with preserved ovarian function, ovulation induction and
transabdominal oocyte retrieval can be performed, with successful pregnancies reported
through surrogacy [61,64].
7. Cryopreservation of Oocytes, Embryos and Ovarian Tissue
For young patients who are not eligible for any of the fertility preservation options
discussed above, it is important to refer them to fertility specialists to discuss other options
using ART. Fertility preservation can be performed through mature oocyte cryopreserva-
tion, embryo cryopreservation, or, in cases where chemotherapy cannot be delayed, ovarian
tissue cryopreservation (OTC) [
7
] (Table 2). Controlled ovarian hyperstimulation with
gonadotropins, followed by oocyte retrieval and cryopreservation of oocytes or embryos,
can be performed before initiating gonadotoxic treatments [
8
]. The stimulation can have a
“random start” regardless of the phase of the menstrual cycle, which facilitates the process
without impacting the quality or number of retrieved oocytes [
65
]. A study looking at
the long-term reproductive outcome of controlled ovarian stimulation in patients with
Curr. Oncol. 2024,31 302
gynecologic malignancies found that 17 out of 68 patients (25%) returned to the clinic
to claim their oocytes/embryos in a median time of 36 months. Out of this sample, the
successful livebirth rate was 58.8% [
66
]. While oocyte and embryo cryopreservation are
well-established techniques for fertility preservation, OTC is considered an innovative
technique [
67
]. In OTC, the cortex of harvested ovarian tissue is separated and cryopre-
served. Once gonadotoxic treatment is completed, the ovarian tissue can be thawed and
transplanted back to the patient to regain ovarian hormonal function and fertility [
68
].
The site of transplant can be on the remaining ovary, pelvic side walls, subcutaneously, or
intramuscularly [
67
]. In a systematic review and individual patient data meta-analysis of
ovarian tissue transplants, 87 studies and 735 women were included [
68
]. In this review,
most patients underwent ovarian transplant via laparoscopy, either to the remaining ovary
or pelvic side wall/peritoneum. Pooled rates for pregnancy were 37%, and the live birth
rate was 28%. The median time of graft function was 2.5 years (range 0.7–5 years). In the
cohort included in this study, it was not surprising but worth noting that no pregnancies
were achieved in patients with cervical cancer. This has been demonstrated in other studies
showing that patients with cervical cancer have a lower chance of pregnancy compared to
other types of cancer [69]. This is secondary to radiation-induced uterine fibrosis [70].
Table 2. Comparison of different artificial reproductive technologies used in fertility preservation for
cervical cancer.
Artificial Reproductive
Technology
Indication in Cervical
Cancer Advantages Reported Pregnancy
Rate
Reported Livebirth
Rate
Ovarian transposition
Prior to pelvic radiation
Preserves ovarian
hormonal function 75–89% [59] -
Oocyte and embryo
cryopreservation
Prior to systemic
chemotherapy
Well-established
technique with high
success rate
- 58.8% [66]
Ovarian tissue
cryopreservation
Prior to systemic
chemotherapy
Can be performed in
any patient irrespective
of age, without delays
in cancer treatment
37% [68] 28% [68]
While this seems to be a promising option for fertility preservation, there are some
concerns regarding this approach, mainly the risk of recurrence. Ovarian tissue from
cancer patients may have microscopic disease, and auto-transplantation of this tissue can
theoretically lead to cancer recurrence [
71
]. Although the harvested tissue is examined for
cancer cells, the strip of tissue examined is not used for cryopreservation, and one could
argue that ovarian tissue that is actually cryopreserved has cancer cells. More research is
required in this field, as there is no consensus regarding the size of ovarian tissue used for
auto-transplants or the ideal site of transplantation [68].
8. Summary
Several fertility preservation modalities are available for patients with early stage cer-
vical cancer. Radical trachelectomy has an excellent survival outcome with low recurrence
rates when compared to radical hysterectomy, regardless of the surgical approach. The low
risk of parametrial involvement in early stage disease justifies the performance of less radi-
cal procedures such as simple trachelectomy and cone biopsy for highly selected patients.
For patients with large tumors not eligible for primary surgery, NACT is associated
with a good response, making an FSS more feasible.
In cases where uterine preservation is not possible, fertility preservation can be per-
formed using cryopreservation of oocytes, embryos, and ovarian tissues, as well as ovar-
ian transposition. These methods enable patients to have future fertility through ART
and surrogacy.
Curr. Oncol. 2024,31 303
Great advances have been made in treating cervical cancer; however, evidence on
treatment options for fertility preservation should be interpreted with caution as it is extrap-
olated from retrospective and prospective single-arm studies. Since randomized clinical
trials are unlikely to be feasible due to the rarity of these procedures, multi-institutional
collaboration is needed to continuously evaluate patients’ outcomes, especially in an era of
less radicality.
Author Contributions: L.S.—conceptualization; methodology; resources; writing—original draft
preparation; writing—review and editing; and visualization. A.C.—conceptualization; methodology;
resources; writing—review and editing; visualization; and supervision. All authors have read and
agreed to the published version of the manuscript.
Funding: This research received no external funding.
Conflicts of Interest: The authors declare no conflicts of interest.
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