Surgical Procedures that enhance
Fertility?
Cleveland Clinic
Tommaso Falcone,M.D.
Professor & Chair
Obstetrics &Gynecology
Surgical Procedures that enhance
Fertility?
Enhance Spontaneous Pregnancy
Enhance IVF outcomes
Fertility preserving surgery versus
fertility enhancing surgery
The Most Common Causes: in
Western Society
Tubal disease:
15%
Male factor:
25% (40%)
Ovulation disorders: 25%
Endometriosis:
10%
Unexplained:
20%
Multiple Gestation Epidemic
Changing IVF paradigm
Guidelines for number of embryos to
transfer
– Typically 1 embryo
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
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
Fimbrioplasty: Results of
Treatment:
Dubuisson et al F&S
1990
Saleh & Dlugi F&S
1997
N=31 PR% 35
N=88 PR 40%
Proximal Tubal obstruction
Hysteroscopic surgery 48% PR
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
Control
32 and 45%
11 and 16%
When is it feasible?
Importance of other pathologies
Age of patient
Patient preference
Desire for “natural” procreation
Insurance coverage
Results of ART program
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
Stage 1 & 2 endometriosis
Canadian 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%
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
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
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
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
Reoperation for Stage III&IV
Endometriosis ?
Pagidas et al
Fertility & Sterility 1996
Stage III&IV endometriosis
After initial unsuccessful operative
procedure to restore fertility , IVF-ET
appears to be a superior alternative to reoperation
In patients with chronic pain reoperation is
a viable alternative
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
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
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 %)
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 12-14 weeks
Normal hemoglobin and normal
electrolytes
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
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
EndoWrist Instrumentation
TM
Modeled after the
human wrist. Full
range of motion
High-strength cable
system
– Transpose fingers to
instrument tips
Summary of Literature on Robotic Myomectomy Surgery
Author
Number
of Robotic
Year
Cases
Advincula 2004
AP et al
Type of
Study
Removed
Myomas
Weight
35
Preliminary
experience
Mean =
223.2 + 244.1g
Results
Robotic myomectomy
is new promising
approach
Mao SP
et al
2007
1
Case report
Not
available
Successful
robotically-assisted
excision of large
uterine myoma
measuring 9x8x7cm
Bocca S
et al
2007
1
Case report
Not
available
Achievement of
uncomplicated full
term pregnancy
after robotic
myomectomy
Summary of Literature on Robotic Myomectomy Surgery
Author
Number
of Robotic
Year
Cases
Type of
Study
Advincula 2007
AP, et al
29
Retrospective
case matched
between
robotic and
open
myomectomy
Nezhat C
et al
15
Retrospective
case matched
between
robotic and
laparoscopic
2009
myomectomy
Removed
Myomas
Weight
Mean =
227.86 + 247.54g
Results
Robotic myomectomy
approach is
comparable to open
approach regarding
short term surgical
outcome and costs
Mean = 116g
Robotic myomectomy
(min 25-max 350)g had significant longer
surgical time without
offering any major
advantages
Cleveland ClinicObstet 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,
76.66)
68.04
( 57.6, 82.5) < 0.001
Height cm
163.92
( 13.17)
164.02
( 6.19)
163.63
(6.62)
27(23,32)
25.1 ( 22.1,
24.1 ( 22, 28.1) 29.4)
BMI kg/m2
0.97
< 0.001
Maximum Diameter of the Resected
Myoma (in cm) by Surgical Approach
30
20
10
(P=0.036)
0
Abdominal
Laparascopic
Robotic
Weight of the Resected Myomas
(in grams) by Surgical Approach
2,500
2,000
Overall
P < 0.001
1,500
RM vs LM
< 0.001
1,000
500
0
Abdominal
Laparascopic
Robotic
The Actual Operative Time (in minutes)
by Surgical Approach
350
300
Overall
P < 0.001
250
200
RM vs LM
NS
150
100
50
Abdominal
Laparascopic
Robotic
The Intra−operative Blood Loss (mL)
by Surgical Approach
2,500
2,000
Overall
P < 0.001
1,500
RM vs LM
NS
1,000
500
0
Abdominal
Laparascopic
Robotic
The Postoperative Hemoglobin Drop
(gm/dL) by Surgical Approach
7
6
Overall
P < 0.001
5
4
RM vs LM
NS
3
2
1
0
Abdominal
Laparascopic
Robotic
8-10 cm
45°
Solution: Side Docking – 4 arm
Surgical Procedures that will
improve IVF outcome
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%
Hydrosalpinx: effect of
salpingectomy
Subgroup analysis: Hydrosalpinges visible
at ultrasound appeared to benefit the most
(Strandell et al)
Hydrosalpinx: alternative
treatment
Proximal tubal cauterization
Surrey & Schoolcraft F&S 2001
– Salpingectomy: 57%
– Bipolar proximal tubal occlusion: 46%; P=NS
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.
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
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.
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
Oocytes retrieved: previously operated endometriomas
adapted from review Somigliana et al 2006
Endometriosis
Controls-No endo
Al-Azemi et al 2000
6.9+0.7
7.1+0.5
Canis et al 2001
9.4+6.2
10.9+6.5
Donnez et al 2001
10.6+4.2
8.6+6.3
Marconi et al 2002
7.5+3.9
8.7+5.1
Geber et al 2002
9.8+5.4**
12.0+5.9
Pabucco et al 2004
5.7+1.3**
7.2+1.5
Esinler et al 2006
Uni (10.8) Bi (7.1)**
11.1+6.1
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
Oocytes retrieved: operated vs. nonoperated normal ovary
Control ovary
Operated ovary
Nargund et al 1996 8.9+5.1
6.3+5.2*
Loh et al 1999
3.6
4.6
Donnez et al 2001
6.6+3.5
5.2+3.0
Ho et al 2002
6.1+4.1
2.9+2.6*
Somigliana et al
2003
4.2+2.5
2.0+1.5*
Wong et al 2004
5.2+0.8
5.6+0.9
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%)
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?
Endometrioma surgery
Outcome is dependent on technique
Minimize damage to the surrounding
tissue
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
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