1. Fertility Sparing Surgery (FSS) in Gynecologic Oncology
Ali AYHAN, MD.
Baskent University School of Medicine Department of Obstetrics & Gynecology Division of Gynecologic Oncology

2. The Main Purpose of Cancer Therapy
High cure
Low morbidity
High level of quality of life
(as a mood, sexuel life, cosmetic appearence, fertility preservation...)

3. All Therapeutic Modalities in Female Cancer
Are associated with infertility
(radiation, radical surgery, chemo...)

4. is performed by different centers
Therefore
Fertility saving surgery instead of radical in early stage selected gyn/cancer
is performed by different centers

5. FSS Objectives
Similiar oncologic outcomes to standard therapy
Favorable obstetric outcome
Benefits > risks
Low morbidity and cost

6. Benefits-Risks of FSS Risks Benefits
Increase in probability of recurrence and death
Additional surgery
Benefits
Preservation of fertility
Maintanence of endocrine function

7. The Main Requirement of FSS
Preserving of the uterus
Preserving at least one ovary

8. Fertility Saving Surgery Depends on
Type and origions of tumor
Stage, grade, histology
Age, performance
Fertility desire
Previous infertility problems
Close follow up

9. Indications for Fertility Saving Surgery
All germ cell
Sex cord stromal (early stage)
Borderline ovarian tumor
Invasive EOC
Cervical Carcinoma
Endometrial Carcinoma

10. Adequate surgical staging Removal of affected ovary and tube
Fertility Saving Surgery in Ovarian Tumors (EOC, BOT,MOGCT, Sex Cord Stromal)
Adequate surgical staging
Removal of affected ovary and tube
Preservation of uterus and contralateral ovary
Finally evaluation of normal appearing contralateral ovary* and endometrium (D&C)**
* For occult metastases
* Endometrioid type of epithelial tumors

11. SO TODAY; PROBLEM IS SMALL
FSS in EOC
25-30% of all EOC are early stage at the diagnosis
14% of EOC will occur under 40 years
Of these 62% will be stage I and IIa
Not all, many of these desire to preserve fertility
SO TODAY; PROBLEM IS SMALL

12. Indication for Fertility Sparing Surgery in EOC
1. Stage Ia Grade 1
Stage Ia Grade 2 (limited)
2. Stage Ic, Grade 3, Clear cell +
Chemotherapy

13. Main Problems in FSS in EOC
A) In preserved ovary
1) occult metastasis
2) Relapse in spared ovary
B) Is there any relationship between relapse, death and preservation of ovary, uterus or other risk factors
C) Is there a place of complementary surgery after childbearing

14. Occult Metastasis in Normal Appearing Ovaries
Varies from 7-33% in old literature
In new literature, this figures are lower than older (about 2.5%)

15. (ICON1 and ACTION Studies)
Survival
925 patients with early stage disease were subjected to Radical Surgery +Chemo
(ICON1 and ACTION Studies)
5 yrs DFS
76%
5 yrs OS
82%
J Natl Cancer Inst, 2003:95:

16. FSS Does Not Affect Survival in Early Stage EOC
Survival after FSS in patients with early ovarian cancer
Without chemo is about 94%

17. Recurrence, Death and Pregnancy After FSS in EOC
Author
Recurrences
Ovary / Total
Deaths
Pregnancy
Colombo
n=152
11 /18
9 (5.9%)
53 (35%)
Brown
n=16
2 / 2 2 ?
Schilders
n=52
3 / 5 26
UK Study
n=56
12%
Colombo N et al IJGC 2005, Monk BJ, DiSaia PJ, IJGC 2005, Farthing A, BJOG 2006

18. Obstetric Outcome After Fertility Saving Surgery in EOC
Author
% Pregnancy
Term Delivery
Abort.
Ectopic
Anomaly
Colombo 1994
100 (25/25) 16 4 2
Zanetta 1997
56 (20/36) 17
Duska
1999
33.3 (2/6) 1
Morice
2001
22.2 (4/18) 3
Schilder 2002
71 (17/24) 26 5
Total
56.5 (68/109) 64 14

19. Fertility –Sparing Surgery in Borderline Tumors of the Ovary:
15% of all EOC
Young age
Early stage
95% serous - mucinous
Overall survival 95 %

20. Fertility Sparing Surgery in Borderline Ovarian Tumors
Staging
Leaving the uterus
Some functional ovarian tissue in place
Evaluation of endometrial cavity?

21. Ovarian procedures in BOT
BSO (very rare)
USO
Cystectomy
Partial excision
Cortical ovarian biopsy for cryopreservation

22. After FSS Recurrence 7.7-31 % Disease related death 0
Donnez, 2003
Morriu, 2001
Cutlieb, 1998
Disease related death 0
Pregnancy rates 31.8, 38.5 and 63.3 % Donnez, 2003

23. Ovarian Tumors of Low Malignant Potential
Study
No. Pts.
Stage
No. Pregn.
Lim-Tam 1988 35
IA-III 8
Gotlieb 1998 39
22 in 15
Morris 2000 43
25 in 12
Zanetta 2001
189
44 in 44
Morice 2001 44
17 in 14
Rao 2005 38
6 in 5
Boran 2005 62
10 in 10

24. FSS in MOGCTs 20-25 % of all ovarian neoplasm
Only 3 % of these are malignant
Young age
Early stage
Generally unilateral (Dysgerminoma 12%)

25. Fertility Sparing Surgery In early and selected advanced stage
Full staging
Removal of affected ovary
Preserving the contraleral ovary
Preserving of the uterus
+ Chemo
In early and selected advanced stage

26. The survival in FSS is similar to radical surgery in MOGCTs
Survival in MOGCTs
The survival in FSS is similar to radical surgery in MOGCTs

27. Pregnancy after surgery in MOGCTs
Number of patients
Pregnancy rate
29/32
76 %
19/20
95 % (Surg +Chemo)
16/20
80 % (Surg +Chemo)
12/12
100 % (Only surgery)
Low et al, Zanette et al Gerhenson et al

28. Obstetric Outcome in MOGCT
Author
% Pregnancy
Term Delivery
Abort.
Ektopic
Anomaly
Gershenson 1988
100 (12/16) 22
Perrin
1999
------ 8 --
Low
2000
95 (19/20) 16
Zanetta
2001
80 (16/20) 26 9 3
Tangir 2003
76 (25/33) 38 2
Toplam
87.75 (72/89)
110 11

29. After Fertility Sparing Surgery:
Oncologic Outcome:
After Fertility Sparing Surgery:
EOC
MOGCTs
BOT
Survival is
similiar to radical surgery

30. FSS in LMS 25% of uterine sarcomas 1% of all uterine malignancies
0.29 of all myomectomies
(6815 myoma)
25% premenopausal

31. FSS in LMS
Local excision
(at least 0.5-1cm
tumor free border )

32. Endometrial Cancer Most frequent Gyn.Ca 25% premenopausal
5% under 40 age
Type I good prognosis (PCOS)
Grade I, EPR +
Cure rate %95

33. Pretreatment Evaluation
History (infertility...)
Physicial Examination
TVUSG
D&C
Abdominopelvic/ endovajinal coil MRI
Ca-125
Laparoscopic evaluation
Response to Progesterone or
Staging Laparotomy

34. MRI Sensitivity %80 Specifity %100 Before and After Treatment

35. Progestogenic Agents MPA 200-600 /mg/ day Megace 40-160 /mg/day
IUD / Prog
Response Rate
Hyperplasia with Atypia %83-94
End. Ca %
Duration of Treatment
Range months
Median months
Recurrens
Hyperplasia with Atypia % 13
End. Ca %

36. Response Rates to Progesterones in Endometrial Cancer
Drug
Time
Regr.
Recur.
Pregnancy 7 MA
3 ay 4 2 14
MA/ MPA
1 yıl 9 1 3 12
MA / MPA
3-18 ay
MPA
2-14 ay
MA / Tam - 8 13
3.5 ay 6 67 16 15
*26
%55 IVF 31
Kım 1997, Randal-Kurman 1997, Kaku 2001, Wang 2002, Gotlieb 2003
*Jadoul-Donnez Fertil Steril 2005;84; 1564

37. FSS in Endometrial Cancer
At young age
Well differantiated End. Ca
Stage IA, Grade I-II
Progestin therapy
Evaluation of end with 3 months interval
Fertility desire

38. *Tumor <2 cm, Deep Stromal Inv. <1 cm
FSS in Cervical Cancer
%27.9 patients < 40 age (SEER)
Cx Ca most prevalant in years of age
Adenocarcinoma is a problem
Squam/ Adeno (except neuroendocrine type)
IA-IB1*
*Tumor <2 cm, Deep Stromal Inv. <1 cm

39. FSS in Cervical Cancer Cone Only Preinvazive Ia1 LVSI (-) 1a1 LVSI (+)
1b1 2 cm Der:1 cm
In selected cases with stage Ib-IIA ovarian transposition,oocyte and/or embryo criopreservation
Cone Only
Pelvic LND* + Radikal Trachelectomy**
*Endoscopic/ Laparotomy / Sentinel Node
**Vaginal /Abdominal

40. In IA1 LVSI (-) CONE RE-CONE
Tumor free margin and post-cone negative ECC
Positive margin or positive ECC
RE-CONE

41. Clinical importance of margin and ECC
Variables
Residual tumor
Margin
Negative 3%
Positive
22%
Margin and ECC 4%
33%

42. Pelvic Node Metastasis in Stage IA1
Depth of Invasion
LNM +
1mm or less
0,1
1-3 mm
0,5

43. Stage IA1 with LVSI (+) IA2
Pelvic lymphadenectomy
Radical trachelectomy* plus
Cervical cerclage
*Free margin >at least 5mm-1 cm

44. Why lymphadenectomy in Stage IA2
Variables
% LNM Metas.
LNM +
7.3
Invasive Rec
3.1
Death of Dis.
2.3
Van Nagell et al..... Creasman et al

45. Pelvic lymphadenectomy + Radical trachelectomy
FSS in Stage IB1
Lesion ≤ 2cm
Depth of Inv ≤ 1cm
LNM negative
Upper cervical involvement (-)
Pelvic lymphadenectomy +
Radical trachelectomy

46. Radical trachelectomy (1994 Dargent)
Removal of primary tumor
Parametrectomy
1/3 upper vaginectomy
Preserving uterine fundus
Pelvic lymphadenectomy

47. Radical trachelectomy
Abdominal
Vaginal
Lymphadenectomy (Open and Endoscopic)

48. Radical trachelectomy and
No difference between
Radical trachelectomy and
Radical hysterectomy
for
Recurrence and Death

55. Pregnancy Results after VRT
Fertility
Desire
No.of Pregn/
Patient
Livebirth 96 42
56/33 34 72
48/31 28 93 39
22/18 18 30 13
14/8 9 19 4
4/3 2 10
4/4
315
144
148/97
Mathevet 2003, Plante 2004, Steed-Covens 2003, Shephard 2001, Burnett 2003, Schlaerth 2003
Fertil Steril 2005;84:156

56. Reproductive Outcome after Trachelectomy
%25-43 infertility
Pre-operative (STD) ve post-operative (stenosis)
Loss of fertility desire in %25
Pregnancy rate %71
Delivery rate % 41
First trimester loss %21
Second trimester loss %8
Preterm delivery %20-%30
Cervical Insufficiency (Cerclage Saling Procedure, Ab, USG ??)
PPROM
Informed Consent !!!!!
Boss et al, Gynecol Oncol, 2005

57. Conclusion-I Fertility Preservation Options in Females
Conservative surgery
Embryo cryopreservation
Oocyte cryopreservation
Ovarian tissue cryopreservation
Ovarian supression (GnRH analogs)

58. Conclusion-II Fertility Preservation Strategies
Treatment can be delayed
Treatment cannot
be delayed
IVF-Embriyo
Freezing
Oocyte
freezing
Ovarian Tissue Freezing
In vitro maturation in high risk for ovarian involvement
Add TMX or Aromatase
Inhibitors for Est-sensitive

59. Thank you…