This document discusses fertility preservation options for young women diagnosed with gynecologic cancers. It covers cervical, endometrial, and ovarian cancers. For early-stage cervical cancer, conization or radical trachelectomy can allow fertility preservation. For early-stage endometrial cancer, hormonal treatment with progesterone may induce remission and allow attempted pregnancy. For early-stage ovarian cancers including borderline tumors and germ cell tumors, fertility-sparing surgery such as unilateral salpingo-oophorectomy may be an option. Patient selection is crucial to balance oncologic and fertility outcomes.
Fertility Preservation for Gynecologic Cancer Patients
1. Shaukat Khanum Memorial Cancer Hospital and Research Centre
Iqra Yasin
Fertility Preservation for
Gynecologic Cancer Patients
Fellow Gynecologic Oncology
SKMCH & RC, Lahore
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Shaukat Khanum Memorial Cancer Hospital and Research Centre
Outline
Introduction
Cervical Cancer
Endometrial Cancer
Ovarian Cancer
Conclusion
References
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Shaukat Khanum Memorial Cancer Hospital and Research Centre
Introduction
Overall cancer risk in females <39 years (1:39)
In young women
Cervical cancer 2%
Endometrial cancer 5%
Ovarian cancer 12 %
5 year survival
46% in ovarian cancer to 80% in endometrial cancer
Over 90% in borderline ovarian tumor
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Introduction
Gynecologic Malignancies – Often diagnosed in postmenopausal
age
Rise in a trend seen in premenopausal age
Traditional management = TAH + BSO (permanent sterility)
Fertility preservation: important at young age
Patient selection: Crucial
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Cervical Cancer
Incidence: 1.5 – 14.9 per 100,000 (20 – 49 years)
45 % of early-stage IB surgically removed:
< 40 years of age.
Standard management:
Radical hysterectomy + systematic pelvic LND
Ovarian preservation and upper transposition:
Pelvic RT in young age
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Cervical Cancer
Fertility sparing procedures
1. Excisional conization of the cervix
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Shaukat Khanum Memorial Cancer Hospital and Research Centre
Cervical Cancer
Indications of cervical conization (microscopic disease)
Stage DOI Horizontal
Spread
Cervical
Conization
Risk of LN
metastases
Systemic
Pelvic LND
IA1 < 3 mm < 7 mm + 0.5 – 1.5 % -
IA2 < 5 mm < 7 mm + 5 – 8 % +
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Cervical Cancer
Fertility sparing procedures
2. Radical Trachelectomy/cervicectomy (Greek: trachelos – neck)
Approaches
a. Vaginal
b. Abdominal
a. Pediatric, nullipara
b. distorted anatomy
c. Cervical stump tumor
d. Exophytic cervical tumor
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Shaukat Khanum Memorial Cancer Hospital and Research Centre
Cervical Cancer
Fertility sparing procedures
2. Radical Trachelectomy (Patient Selection)
1. Strong desire to preserve fertility
2. Histopathological diagnosis with proven diagnosis of cervical cancer by
expertise
3. SCC / AdenoCA / Adenosquamous CA
4. Stage IA1 with LVSI , IA2 and IB1
5. Tumor size < 2 cm
6. No evidence of pelvic LN or distant metastases
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Cervical Cancer
Fertility sparing procedures
2. Radical Trachelectomy (Preoperative assessment)
1. Colposcopy
2. Histopathology review by second expertise (type, depth, LVSI)
3. MRI
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Cervical Cancer
Fertility sparing procedures
2. Radical Trachelectomy (steps)
a) Systemic Pelvic Lymphadenectomy
b) Excision of cervix + Para cervix + 1-2 cm of vagina
c) Upper cervical or isthmic cerclage
d) Reconstruction of uterine corpus to upper vagina
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Cervical Cancer
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Shaukat Khanum Memorial Cancer Hospital and Research Centre
Cervical Cancer
Fertility sparing procedures
Radical Trachelectomy (Follow-up)
Cytologic (vaginal +isthmic smear) and colposcopic
evaluation
0-2 years ( every 3-4 months) , > 2 years (every 6 months)
Yearly MRI
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Cervical Cancer
Fertility sparing procedures
Radical Trachelectomy
Obstetrical Outcomes
2nd trimester miscarriage
Preterm birth
Oncologic Outcomes
5 years survival 98.4 %
Relapse rate 4.5 %
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Cervical Cancer
Fertility sparing procedures
Radical vaginal Trachelectomy vs radical hysterectomy
Same or less morbidity
No significant difference in intra and post operative
complications
No difference in 5-year OS, RFS, PFS
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Cervical Cancer
Fertility sparing procedures
Radical Trachelectomy (Conclusion)
Radical hysterectomy, the “gold standard” traditional treatment
for patients with early stage cervical cancer has been recently
replaced by radical trachelectomy – vaginal or abdominal route
– for young women with strong desire for fertility preservation.
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Cervical Cancer (NCCN / Summary)
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Endometrial Cancer
Most common gynecologic malignancy
Median age of diagnosis: 61 years
Incidence: 1.2 – 24 per 100,000 (25 – 49 years)
Standard management: TAH +BSO + PLND +/- Para-aortic
LND
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Endometrial Cancer
Fertility preserving options
Hormonal treatment
Patient selection
Well-differentiated endometrioid AdenoCA confirm by expert
pathology review
Disease limited to endometrium without myometrium
Absence of any suspicious or metastatic disease
Absence of LVSI
No contraindication to medical therapy
Strong desire to preserve fertility (understanding of fertility-
preserving – not standard of care)
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Endometrial Cancer
Fertility preserving options
Hormonal treatment
Oral Progesterone (Megestrol acetate,
medroxypogesterone acetate)
LNG – IUD
MOA: inhibit estrogen receptor function and endometrial
cell mitosis, promote apoptosis
Duration: at least 6 months
Meta-analysis: improved outcomes (IUD LNG > oral
progesterone)
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Endometrial Cancer
Fertility preserving options
Hormonal treatment
Follow up
Every 3-6 months (endometrial sampling)
Oncologic Outcomes
Persistent disease (25 %): Hysterectomy
Partial response (25%): Medication for additional 3 – 6
months
Complete response (50 %) : Encourage fertility treatment
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Endometrial Cancer
Fertility preserving options
Hormonal treatment
Recurrence rate: 40 % (15 months)
Encourage to have pregnancy using ART
Obstetrical Outcomes:
Successful pregnancy significant reduced risk of
recurrence
IVF doesn’t increase the risk of recurrence
5 DFS (ovulation induction = spontaneous conception)
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Endometrial Cancer
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Endometrial Cancer
(NCCN / Summary)
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Ovarian Cancer
Leading cause of death from gynecologic malignancies in western countries
Majority in postmenopausal age
Incidence
20 – 49 year = 1.6 -16 per 100,000
< 20 years = 0.7 – 1.4 per 100,000
Standard management:
Exploratory laparotomy + FS of ovarian tumor
If invasive – TAH + BSO + debulking omentectomy + PLND + Para-
aortic LND, multiple peritoneal washings and biopsies
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Ovarian Cancer
Fertility preserving options
Comprehensive surgical staging –a mainstay of the
conservative surgical approach
Removal of ipsilateral adnexa
Preservation of uterus and contralateral adnexa
Omentectomy and multiple peritoneal biopsies
Evaluation of retroperitoneal space through pelvic and para-
aortic lymphadenectomy
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Ovarian Cancer
Fertility preserving options
Indications:
Epithelial ovarian cancer
Stage IA, grade I, Serous/mucinous/endometrioid variety
Not for
clear cell, small cell and anaplastic tumors,
high grade serous/mucinous/endometrioid variety
Hereditary syndrome (BRCA)
Synchronous endometrial cancer
Stage > 1 or grade 3
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Ovarian Cancer
Borderline / low malignant potential tumors (BOT)
10-15 % EOC (1/3rd of ovarian cancer < 40 years)
Suitable candidate for FSS (excellent prognosis even at an advanced
stage)
Recurrence (0-25 %, not affect survival rate)
Fertility preserving procedures
Cystectomy: Not recommended (40 % relapse rate)
Bilateral BOT: unilateral SO + contralateral cystectomy
Routine biopsy of a contralateral healthy ovary is not
recommended
LND: lymphadenomegaly or peritoneal spread
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Ovarian Cancer
Borderline / low malignant potential tumors (BOT)
Follow up
Every 6 months (0-3 years), then yearly
Prolong F/U: Late recurrence
Oncologic outcomes
Survival rate: 99 % (stage 1) to 89 % (stage 3)
Recurrence rate: 0 - 25 %
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Ovarian Cancer
Germ-Cell Tumor (GCT)
3 -5 % of ovarian tumor
Age: < 20 years
Good prognosis (even for extraperitoneal spread),
Good response to chemotherapy (good candidate for FS options)
OS: not affected by FS options
Relapse: Grade II/III, Advanced stages
Adjuvant therapy (BEP):
excellent cure rate 95 % for early stage,
less toxic to ovaries,
endocrine function intact
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Ovarian Cancer
Sex-cord Stromal tumors
Rare neoplasms
Common at a young age
Fertility-Preserving Procedure:
Unilateral salpino-oophorectomy + peritoneal surgical staging (safe
alternative to radical surgery)
LND: not favorable according to literature
Further studies are required to evaluate the safety of the conservative
approach and to define obstetrical outcomes
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Conclusion
Fertility preservation options for early-stage gynecological cancers indicate
oncological safety.
Enables cancer patients at a young age to complete their family without
compromising the oncological outcome
Patient selection and counseling are crucial.
Further studies are needed to investigate the role of fertility-sparing treatment
in high-grade cancers and obstetrical outcomes in rare gynecologic tumors.
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References
Abu-Rustum NR, Sonoda Y, Black D, Levine DA, Chi DS, Barakar RR. Fertility-sparing radical abdominal trachelectomy for
cervical carcinoma: Technique and review of the literature. Gynecol Oncol 2006;103(3):807-13.
Chiva L, Lapuente F, Gonzalez-Cortijo L, Carball N, Garcia JF, Rojo JF, Gonzalez-Martin A. Sparing fertility in young patients
with endometrial cancer. Gynecol Oncol 2008;111(2 suppl):S101-104.
Cibula D, Slama J, Fiscerova D. Update on abdominal radical trachelectomy. Gynecol Oncol 2008;111(2 Suppl):111-115.
Erkanli S, Ayhan A. Fertility-sparing therapy in young women with endometrial cancer. Int J Gynecol Cancer 2010;20:1170-1177.
Gershenson DM. Contemporary treatment of borderline ovarian tumors. Cancer Invest 1999;17(3):206-10.
Gershenson DM. Management of ovarian germ cell tumors. J Clin Oncol 2007;25(20):2938-43.
Gien LT, Covens A. Fertility-sparing options for early stage cervical cancer. Gynecol Oncol 2010;117(2):350-357.
Lai CH, Chang TC, Hsueh S et al. Outcome and prognostic factors in ovarian germ cell malignancies. Gynecol Oncol
2005;96:784-791.
Larson DM, Johnson KK, Broste SK et al. Comparison of D&C and office endometrial biopsy in predicting final histopathologic
grade in endometrial cancer. Obstet Gynecol 1995;86:38-42.
Leitao MM, Chi DS. Fertility-sparing options for patients with gynaecologic malignancies. Oncologist 2005;10(8):613-22.
Maltaris T, Boehm D, Dittrich R, Seufert R, Koelbl H. Reproduction beyond cancer: a message of hope for young women.
Gynecol Oncol 2006;103(3):1109-21.
Milliken DA, Shepherd JH. Fertility preserving surgery for carcinoma of the cervix. Curr Opin Oncol 2008;20(5):575- 80.
Muruyaesu N, Schmid P, Dancey G et al. Malignant ovarian germ cell tumors : Identification of noval prognostic markers and
long-term outcome after multimodality treatment. J Clin Oncol 2006;24:4862-4866.
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References
Oark TJ, Voit D, Gupta JK et al. Accuracy of hysterescopy in the diagnosis of endometrial cancer and hyperplasia: A systematic quantitative
review. JAMA 2002;288:1610-1621.
Rob L, Pluta N, Skapa P, Robora H. Advances in fertilitysparing surgery for cervical cancer. Expert Rev Anticancer Ther 2010;10(7):1101-
1114.
Tangjitgamol S, Manusizivithaya S, Hanprassertpong J. Fertility sparing in endometrial cancer. Gynecol Obstet Invest 2009;67:250-268.
Ramirez PT, Pareja R, Rendon GJ, Millan C, Frumovitz M, Schmeler KM. Management of low-risk early-stage cervical cancer: should
conization, simple trachelectomy, or simple hysterectomy replace radical surgery as the new standard of care? Gynecol Oncol. 2014
132(1):254-9.
Rob L, Pluta M, Skapa P, Robova H. Advances in fertilitysparing surgery for cervical cancer. Expert Rev Anticancer Ther. 2010;10(7):1101-
14.
Rob L, Skapa P, Robova H. Fertility-sparing surgery in patients with cervical cancer. Lancet Oncol. 2011;12(2):192-200.
Reade CJ, Eiriksson LR, Covens A. Surgery for early stage cervical cancer: how radical should it be? Gynecol Oncol. 2013;131(1):222-30.
Gien LT, Covens A. Fertility-sparing options for early stage cervical cancer. Gynecol Oncol. 2010;117(2):350-7.
Rodolakis A, Biliatis I, Morice P, Reed N, Mangler M, Kesic V, Denschlag D. European Society of Gynaecological Oncology Task Force for
Fertility Preservation: Clinical Recommendations for Fertility-Sparing Management in Young Endometrial Cancer Patients. Int J Gynecol
Cancer. 2015;25(7):1258-65.
Morice P, Denschlag D, Rodolakis A, Reed N, Schneider A, Kesic V, Colombo N; Fertility Task Force of the European Society of
Gynaecologic Oncology. Recommendations of the Fertility Task Force of the European Society of Gynaecologic Oncology about the
conservative management of ovarian malignant tumors. Int J Gynecol Cancer. 2011;21(5):951-63.
Denschlag D, von Wolff M, Amant F, Kesic V, Reed N, Schneider A, Rodolakis A. Clinical recommendation on fertility preservation in
borderline ovarian neoplasm: Ovarian stimulation and oocyte retrieval after conservative surgery. Gynecol Obstet Invest. 2010;70(3):160-5.
Thomakos N, Trachana SP, Rodolakis A, Bamias A, Antsaklis A. Less Radical Surgery for Fertility Preservation in Patients with Early-Stage
Invasive Cervical Cancer Contemporary Problematics. Gynecol Obstet 2013;3:165.
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