1. Surgical Procedures that enhance Fertility?
Cleveland Clinic
Tommaso Falcone,M.D.
Professor & Chair
Obstetrics &Gynecology

2. Surgical Procedures that enhance Fertility?
Enhance Spontaneous Pregnancy
Enhance IVF outcomes
Fertility preserving surgery versus fertility enhancing surgery

3. The Most Common Causes: in Western Society
Tubal disease: 15%
Male factor: 25% (40%)
Ovulation disorders: 25%
Endometriosis: 10%
Unexplained: 20%

4. Multiple Gestation Epidemic

5. Changing IVF paradigm Guidelines for number of embryos to transfer
Typically 1 embryo

6. Tubal Disease: Result of Treatment
Depends on severity of disease
Distal tubal disease
Preserved mucosal folds
Microsurgical technique for repair
CO2 laser makes no difference

7. Salpingostomy: Result of Treatment
Dubuisson et al HR1994
Canis et al F&S 1991
Donnez et al J Gynecol Surg 1989
Taylor et al F&S 2001
Milingos et al J Am Assoc Gynecol Laparosc 2000
N=81 PR% 37
N=87 PR% 40
N=25 PR % 20
N=139 PR% 25
N=61 PR% 21

8. Fimbrioplasty: Results of Treatment:
Dubuisson et al F&S 1990
Saleh & Dlugi F&S 1997
N=31 PR% 35
N=88 PR 40%

9. Proximal Tubal obstruction
Hysteroscopic surgery 48% PR

10. Peri-tubal adhesions No laparoscopic study
One prospective study of open treatment
n-=69 Tulandi et al 1990 Am J Obstet Gynecol
Pregnancy rates at 12 and 24 months
Treated 32 and 45%
Control 11 and 16%

11. When is it feasible? Importance of other pathologies Age of patient
Patient preference
Desire for “natural” procreation
Insurance coverage
Results of ART program

13. Treatment effect
Treatment effect large enough to be clinically relevant?
Number needed to treat (NNT): number of subjects that must be treated to achieve one more outcome with intervention than control
NNT=1/Risk difference
Risk difference: Event rate treated group- Event rate control

14. Stage 1 & 2 endometriosis Canadian study Italian study
N=172 treated & N=169 untreated
PR% 29% treated & 17% untreated
NNT= 1/.12=8.3
NNT=9, 95 % CI, 5,33
Italian study
N=54 treated & N=47 no treatment
PR% 22% & 28%

15. Treatment Effect
Canadian study PR for pregnancies more than 20 weeks of gestation, Italian study reported any pregnancies
Combine the studies for pregnancies over 20 weeks: 27% (treated) & 18% ( non treated): NNT=12 ( 95% CI 6,112)
20% prevalence of endometriosis
60 diagnostic laparoscopies to get an extra pregnancy

17. Endometriomas Drainage has a high recurrence rate
Need to excise the cyst
Cochrane database 2005 Hart R et al
Excision of cyst associated with a reduced rate of recurrence; reduced symptom recurrence and increased spontaneous pregnancy rates compared with ablative surgery

18. Endometriomas Unresponsive to medical therapy
Surgery required to remove them
Jones & Sutton 2002; Alborzi et al 2004
Surgical removal
40-50 % young women will conceive spontaneously
Laparoscopic removal of endometrioma represents the first line treatment for infertile women

19. Stage III&IV Endometriosis: reoperation or IVF Pagidas, Falcone et al Fertility & Sterility 1996
Previously operated patients with infertility
Reoperation PR were
6% at 3 months
18% at 7 months
24 % at 9 months

20. Reoperation for Stage III&IV Endometriosis
Reoperation for Stage III&IV Endometriosis ? Pagidas et al Fertility & Sterility 1996

21. Stage III&IV endometriosis
After initial unsuccessful operative procedure to restore fertility , IVF-ET appears to be a superior alternative to re-operation
In patients with chronic pain reoperation is a viable alternative

22. Endometrial Polyps
Afifi K et al Eur J Obstet Gynecol Reprod Biol- 2010
Meta-analysis management of endometrial polyps in subfertile women: a systematic review
Significantly improved PR in women undergoing IUI

23. Leiomyomas & Infertility:
Submucosal fibroids
PR after hysteroscopic resection up to 43%
Goldberg F&S 1995
Hart Br J Obstet & Gynecol 1999
Bernard Eur J Obstet Gynecol Reprod Biol 2000
Intramural fibroids distort the uterine cavity

24. Myomectomy: Indications
Shokeir et al 2010 Fertil Steril 2010
Randomized matched trial;
Unexplained infertility
Type 0 and Type 1 myomas
Hysteroscopic surgery was performed
PR significantly improved ( 63 % vs 28 %)

25. Ideal Candidate for Hysteroscopic procedure
Single intracavitary myoma or one involving less than 50 % of the myometrium (Type 0 or 1) and up to 3cm in diameter.
Uterine size less than weeks
Normal hemoglobin and normal electrolytes

26. General Assumptions
The pregnancy rate 1-2 years following laparosocpic or laparotomy myomectomy in an infertile woman ( with no other problems) is approximately
40-60%
Laparoscopic Surgery is superior to laparotomy
Challenges are

27. Reproductive Outcome: Pregnancy rates
Seracchioli et al 2000
RCT (only study Cochrane database)
Pregnancy rate: over 3 years
AM:56% LM:54%
Spont Ab: AM 20% LM:12%
Preterm labor:AM:7% LM:5%
C/S: AM: 77% & LM:65%
No ruptures

29. EndoWristTM Instrumentation
Modeled after the human wrist. Full range of motion
High-strength cable system
Transpose fingers to instrument tips

30. Summary of Literature on Robotic Myomectomy Surgery
Number Removed
of Robotic Type of Myomas
Author Year Cases Study Weight Results
Advincula Preliminary Mean = Robotic myomectomy
AP et al experience g is new promising
approach
Mao SP Case report Not Successful
et al available robotically-assisted excision of large
uterine myoma
measuring 9x8x7cm
Bocca S Case report Not Achievement of
et al available uncomplicated full term pregnancy
after robotic myomectomy

31. Summary of Literature on Robotic Myomectomy Surgery
Number Removed
of Robotic Type of Myomas
Author Year Cases Study Weight Results
Advincula Retrospective Mean = Robotic myomectomy
AP, et al case matched g approach is
between comparable to open robotic and approach regarding
open short term surgical
myomectomy outcome and costs
Nezhat C Retrospective Mean = 116g Robotic myomectomy
et al case matched (min 25-max 350)g had significant longer
between surgical time without robotic and offering any major
laparoscopic advantages
myomectomy

32. Cleveland Clinic- Obstet Gynecol 2011
Abdominal
(n=393)
Laparoscopic (n=93)
Robotic (n=89)
p value
Age years
36.93
( 5.61)
39.57
( 9.17)
36.62
( 5.18)
< 0.001
Weight Kg
75.5
(62.8,90.7)
64.8 (59.1, )
68.04
( 57.6, 82.5)
Height cm
163.92
( 13.17)
164.02
( 6.19)
163.63
(6.62)
0.97
BMI kg/m2
27(23,32)
24.1 ( 22, 28.1)
25.1 ( 22.1, 29.4)
The mean (SD) age of patients in the LM group was {39.57(9.17)} years which was significantly higher than that OM {36.93(5.61)} and that of the RM group {36.62(5.18); (P < 0.001)}. Similarly, the median (IQR) weights were (62.85, 90.72), (59.10, 76.66) and (57.65, 82.56) kg in the OM, LM and RM groups respectively. Patients in the OM group were significantly heavier than patients in the LM and RM groups, (P < 0.001; table I). All three groups were comparable regarding the patients heights, (P=0.97). Due to the significant differences in the patients weight the median BMI (IQR) was significantly higher in OM (23.40, 32.88) kg/ (m2) compared to (22, 28.01) kg/ (m2) in the LM as well as the RM group (22.14, 29.44) kg/ (m2), (P < 0.001). No significant differences were seen among the three groups regarding their parity (P=0.13) (Table I). 32

33. Maximum Diameter of the Resected Myoma (in cm) by Surgical Approach30 20
Significantly larger myomas were removed in the OM and the RM groups compared to the LM group (P=0.036).
The median (IQR) of the maximum diameter of the removed myoma in cm as measured by preoperative ultrasound or MRI examination was 7.50 (5.05, 10.20) cm in the OM group, 6.70 (4.20, 10) cm in the LM group and 7.70 (5.40, 10.50) cm in the RM group Figure (1) and table II. 10
(P=0.036)
Abdominal
Laparascopic
Robotic 33

34. Weight of the Resected Myomas (in grams) by Surgical Approach
2,500
2,000
Overall
P < 0.001
RM vs LM < 0.001
1,500
1,000
The weight of the removed myomas is comparable between both robotic and open groups while being significantly lower in the laparoscopic group. In addition, significant heavier myomas weight were removed in the RM group when compared the LM (P < 0.001).
The median (IQR) weight of the removed myomas in grams as measured postoperatively during the pathological examination showed significantly heavier myomas in the OM group 263 (90.43, ) gram, than in the LM group (49.50, ) gram and in the RM group 223 (85.25, ) gram with (p < 0.001) Figure (2).
500
Abdominal
Laparascopic
Robotic 34

35. The Actual Operative Time (in minutes) by Surgical Approach
350
300
Overall
P < 0.001
RM vs LM NS
250
200
The actual surgical time was significantly less with the OM group than the in both other groups (P < 0.001; Figure 5) where the median and IQR was 126 (95, 177), 155 (98, 200) and 181 (151, 265) minutes for the OM, LM and RM groups respectively. Only when the OM group was compared to the RM group, the actual surgical times were significantly higher in the RM group (P < 0.001). There were no significant differences upon comparing the OM versus the LM group or the LM versus the RM groups. The actual surgical time is defined as the time from the incision to the closure. It reflects the absolute time of the surgical procedure.
150
100 50
Abdominal
Laparascopic
Robotic 35

36. The Intra−operative Blood Loss (mL) by Surgical Approach
2,500
2,000
Overall
P < 0.001
RM vs LM NS
1,500
1,000
Over all, a significantly higher blood loss was reported in the OM compared to the other two groups with the median (IQR) of the blood loss of 200 (100, ) mL, 150 (100, 200) mL and 100 (50, ) mL in the OM, LM and RM groups respectively (P < 0.001); Figure (3). On comparing the different groups; a significant higher blood loss was reported in the OM group compared to the LM group (P < 0.001), OM compared to the RM group (P < 0.001), while there was no significant difference blood loss between the RM group and LM group (P = 0.065).
500
Abdominal
Laparascopic
Robotic 36

37. The Postoperative Hemoglobin Drop (gm/dL) by Surgical Approach7 6
Overall
P < 0.001
RM vs LM NS 5 4 3
The hemoglobin drop was significantly lower in the RM group compared to the other 2 groups (p < 0.001). Significantly less Hb drop was detected in RM group compared to the OM group (P < 0.001), and in the OM group compared to the LM group (P =0.002). On the other side the 2 minimally invasive approaches (LM&RM) were comparable regarding the postoperative Hb drop (P = 0.36). 2 1
Abdominal
Laparascopic
Robotic 37

39. 8-10 cm
45°

41. Solution: Side Docking – 4 arm41

47. Surgical Procedures that will improve IVF outcome

48. Hydrosalpinx: meta-analysis
Zeyneloglu et al Fert Steril 1998
13 published studies, 10 abstracts
Pregnancy rate decreased by half compared to controls (fresh & frozen cycles)
50% lower implantation rate
Higher miscarriage rates
Strandell et al HR 1999
Prospective RCT
204 patients
Salpingectomy group: 36.6%
No surgery: 24%

49. Hydrosalpinx: effect of salpingectomy
Subgroup analysis: Hydrosalpinges visible at ultrasound appeared to benefit the most (Strandell et al)

50. Hydrosalpinx: alternative treatment
Proximal tubal cauterization
Surrey & Schoolcraft F&S 2001
Salpingectomy: 57%
Bipolar proximal tubal occlusion: 46%; P=NS

51. Impact of Fibroids on IVF
General observations
Submucosal fibroids & intramural leiomyoma that distort the cavity have an impact IVF outcome
Subserosal leiomyomas do not affect the on IVF fertility parameters
Although less clear, there is some evidence to support the concept that intramural leiomyomas without cavity distortion may affect IVF parameters such as pregnancy rates or implantation rates. However PR & delivery rates are still high.

52. Effect of intramural fibroids on IVF outcome
Sunkara et al HR 2010
Meta-analysis
Intramural fibroids without cavity distortion
19 studies-6087 cycles
Significant decrease in live birth and clinical pregnancy rates
This does not mean that removal will restor PR to the levels expected in women without fibroids

53. Impact of Fibroids on IVF
Generally if there is a distortion of the uterine cavity: remove the fibroids
Because of the lack of consistent or well designed studies, & high reported PR, prophylactic myomectomy pre-IVF if the cavity is normal should be individualized & not routine. No data for fibroids >5-7cm.

54. Impact of endometriosis on IVF outcome: Meta-analysis
22 studies ( 2377 with endometriosis & 4383 without endometriosis); Barnhart et al F&S 2002
Stage I & II- 21 % per cycle ( control 27.7%)
Decrease in implantation & fertilization rates
Stage III & IV –13.8 % per cycle ( control 27.7%)
Decrease in the number of oocytes retrieved

56. Oocytes retrieved: previously operated endometriomas adapted from review Somigliana et al 2006
Endometriosis
Controls-No endo
Al-Azemi et al 2000
Canis et al 2001
Donnez et al 2001
Marconi et al 2002
Geber et al 2002 **
Pabucco et al 2004 **
Esinler et al 2006
Uni (10.8) Bi (7.1)**

57. Oocytes retrieved: previously operated endometriomas
Endometrioma size >3cm but no upper limit given or mean diameter; others 2-5cm
Pregnancy rates:
Not different in most studies
Geber et al (in women over 35) & Pabucco decreased PR
Signs of decreased ovarian reserve
Marconi et al total dose of gonadotropin was higher
Esinler et al decreased antral follicle count & total dose of gonadotropin was higher

58. Oocytes retrieved: operated vs. non-operated normal ovary
Control ovary
Operated ovary
Nargund et al 1996 *
Loh et al 1999
3.6
4.6
Donnez et al 2001
Ho et al 2002 *
Somigliana et al 2003 *
Wong et al 2004

59. Bilateral Endometriomas
Somigliana et al HR 2008
Endometrioma group=68 patients
Control group ( no ovarian surgery)=136 patients
Day 3 FSH of cases> controls
Number follicles/oocytes/embryos decreased/Implantation rate-lower
PR/DR cases per transfer ( 14%/8%) vs. controls (28 %/25%)

60. General Consensus Reduced responsiveness in operated patients
Pregnancy rate not significantly affected-if unilateral but reduced if bilateral
Large number of variables that determine outcome ( size, age, duration of infertility etc)
CAUSE- surgical technique ?
Actual presence of the cyst?

61. Endometrioma surgery Outcome is dependent on technique
Minimize damage to the surrounding tissue

63. Will surgery improve IVF outcome?
Surgery within 6 months of IVF vs. 6 months to 5 years
No effect of the time interval between surgery & oocyte retrieval
Surrey & Schoolcraft

64. Endometriosis surgery prior to IVF: Conclusions
If patient symptomatic, there does not appear to be a deleterious affect on outcome if surgery performed
If patient asymptomatic: Case by Case