1. Dr. Shavi Fernando MBBS (Hons.) BMedSc (Hons.)
Outcomes of Assisted Reproductive Technology (ART) in women with endometriosis
Dr. Shavi Fernando
MBBS (Hons.) BMedSc (Hons.)
Funded by FSA and The BUPA Foundation

2. Endometriosis 20% of infertile women Commonly on ovaries
Fig 1. Normal ovarian follicle
20% of infertile women
Commonly on ovaries
Pelvic side-wall
Recto-vaginal
Ovarian endometriomata can be reliably differentiated on US
89% specificity
Brosens et al, Fertil Steril, 2004
Garcia-Velasco et al, Fertil Steril, 2004
Stratton et al, Fertil Steril, 2005
Fig 2. Ovarian endometrioma
Source:

3. Current knowledge
Reduced uterine receptivity and pregnancy rate after ART
Little known about perinatal outcomes
Barnhart et al, Fertil Steril, 2002
Olivennes, J Gynecol Obstet Biol Reprod (Paris), 2003
Omland et al, Hum Reprod, 2005
Eutopic endometrium in endometriosis is abnormal
Pritts et al, Endocrinol Metab Clin NorthAm, 2003
Taylor et al, Hum Reprod, 1999
Braun et al, Curr Opin Obstet Gynecol, 1998
Ovarian endometriosis is molecularly different to other forms of endometriosis
De Placido et al, Hum Reprod, 2001
Nisolle et al, Fertil Steril, 1997

4. Aim To determine whether women with:
Ovarian endometriomata undergoing ART have increased perinatal adverse outcomes compared with:
ART non-ovarian endometriosis
ART other aetiologies of infertility
Subfertile women
Fertile women

5. Definition of Subfertile
Registered for ART for infertility:
But did not receive ART treatment; OR
Had unsuccessful ART
AND
Subsequently conceived without ART (IVF/ICSI/GIFT)
Are adverse outcomes due to ART or infertility?
FSA Poster: Jaques et al, 2006

6. Outcome Measures Singleton live births (≥20 weeks):
Low birthweight (LBW)
<2500g
Preterm
<37 wks
Small for gestational age (SGA)
<10th percentile

7. Data Sources Monash IVF database
Victorian Perinatal Data Collection Unit (PDCU)
Mandated data collection of all births ≥ 20 weeks’ gestation (850,000 )
Includes:
Perinatal data for live births, still births, neonatal deaths and terminations of pregnancy for birth defects
Maternal demographics, reproductive history and obstetric complications
Record linkage (LinkageWiz v4.1) matched Monash IVF records to PDCU births

8. 4,113 Monash IVF records of women with singletons
( )
850,000 PDCU birth records
1,987 medical records accessed
2,126 medical records not accessed
1,201 other aetiology controls
156 subfertile controls
630 cases of endometriosis
Subgroup of 95 cases of ovarian endometriomata
1,140 fertile controls (1:12)
1,260 fertile controls (1:2)
Matched on maternal age and year of birth

9. 4,113 Monash IVF records of women with singletons
( )
1,987 medical records accessed
2,126 medical records not accessed
1,201 other aetiology controls
156 subfertile controls
850,000 PDCU birth records
630 cases of endometriosis
Subgroup of 95 cases of ovarian endometriomata
In total, there were 4,387 singleton babies included in the retrospective cohort
Matched on maternal age and year of birth
1,260 fertile controls (1:2)
1,140 fertile controls (1:12)

10. Diagnosis Dx of Ovarian endometriomata Dx of Non-ovarian endometriosis
US report
Dx of Non-ovarian endometriosis
Laparoscopy and/or histology report

11. Results – Ovarian Endometriomata
SPSSTM v.13 Binomial logistic regression
Only significant or close to significant results are shown OR
95% CI p*
Ovarian endometriomata vs
Non-ovarian Endometriosis
LBW
2.55
1.26 – 5.18
.009
SGA
1.20
1.04 – 3.83
.040
Other aetiologies
2.87
1.49 – 5.55
.002
1.95
1.06 – 3.61
.050
* Adjusted for maternal age, parity, smoking, year of birth and sex

12. Results – Ovarian EndometriomataOR
95% CI p
Ovarian endometriomata vs
Subfertile
LBW
2.29
1.02 – 5.16
.05*
SGA
2.11
0.99 – 4.53
.06*
Fertile
Preterm
1.93
1.03 – 3.62
.04†
1.84
0.99 – 3.44
.06†
* Adjusted for maternal age and parity
† Adjusted for parity and sex

13. Limitations
Women with endometriosis may have > 1 cause of infertility
Endometriosis stage and treatment status unknown
Women with ovarian endometriomata may have also had other forms of endometriosis
Unlikely that those with other forms of endometriosis had ovarian endometriomata

14. Conclusion
ART patients with ovarian endometriomata have increased likelihood of having:
A baby of LBW or SGA compared with:
Non-ovarian endometriosis following ART
Other aetiologies of infertility following ART
A preterm baby compared with:
Fertile women
Suggests independent effect of ovarian endometriomata on perinatal outcomes

15. Discussion Ovarian endometriomata Severe form of endometriosis
Reduction in uterine receptivity/placentation
Khong et al, Br J Obstet Gynaecol, 1986
Eutopic endometrium may be more abnormal → more adverse outcomes
Lessey, Fertil Steril, 2000
Kuivasaari et al, Hum Reprod, 2005
Genetic differences?
Oocyte quality differences?

16. Acknowledgements Monash IVF Prof. David Healy Ms. Sue Breheny
Murdoch Children’s Research Institute
& Perinatal Data Collection Unit
A/Prof. Jane Halliday
Dr. Alice Jaques
Melbourne IVF
A/Prof. Gordon Baker

17. Additional Slides

18. Future Directions
Ovarian endometriomata are associated with more adverse outcomes than other forms of endometriosis after ART
Reduction in uterine receptivity/oocyte quality
= ? spectrum
Lessey, Fertil Steril, 2000
Kuivasaari et al, Hum Reprod, 2005
Should ovarian endometriomata be surgically removed prior to ART?
Will this improve outcomes?
Prospective studies

19. Adjustments LBW Not LBW Ovarian endometriomata Other endometriosis 16
All fertile groups were matched for age and YOB
Depends on sample size and minimum number of each outcome
Continuous - Age, YOB – count for 1 point
Categorical - Sex, Parity – count for (Ncat – 1) point(s)
Eg.
Parity (2) + smoking (1) + year of birth (1) + sex (1) + age (1) = (6)
LBW
Not LBW
Ovarian endometriomata
Other endometriosis 16 48 79
487
Totals 64
566

20. Fertile Population Representative of Victorian population
All Endometriosis (RR 1.10, 95% CI 0.90 – 1.34, p=.4)
Ovarian Endometriomata RR (1.13, 95% CI 0.92 – 1.39, p=.3)
Ovarian endometriomata may genuinely have increased likelihood of LBW and SGA:
Sample of ovarian endometriomata too small
Need at least n=150 to detect differences in LBW and SGA
Ovarian endometriomata may have no increased chances of LBW and SGA:
Other endometriosis, other aetiologies and subfertile may have abnormally lower rates of LBW/SGA

21. Further Recommendations
Prospective study - time
Ascertain treatment status of endometriosis patients
Larger sample of subfertile patients
Combine with Melbourne IVF - larger sample of ovarian/other endometriosis:
Allow adjustment for the presence of other aetiologies of infertility

22. Methods Epiinfo™ and SPSS™ v13.0
Multivariate analysis - Binomial regression
Adjustments:
Parity
Gender
Year of birth
Maternal age
Smoking
BMI

23. Omland et al Retrospective cohort
Endometriosis (n=212) vs Idiopathic infertility (n=274) following IVF:
Lower pregnancy rate in endometriosis compared with idiopathic infertility.
Omland et al, Hum Reprod, 2005 OR
95% CI p
Birthweight
1.03
.36
Gestation
2.6
.178

24. Abbreviations
BUPA (British United Provident Association)

25. Unsuccessful ART treatment:
Failed to conceive with ART
Couples who conceived with ART but pregnancy loss <20 weeks gestation