ART outcomes of women with endometriosis

1. Endometriosis
ART Outcomes
Tevfik Yoldemir MD, BSc, MA, PhD
Marmara University, School of Medicine, Istanbul, Turkiye
tevfik.yoldemir@marmara.edu.tr

2. I have no financial relationships to disclose.

3. Key confounders in different steps of the IVF procedure
Reproductive Biology and
Endocrinology (2023) 21:107
doi.10.1186/s12958-023-01157-8
Ovarian response
Egg retrieval
Fertilization
Implantation

4. Endometriosis and live birth
Human Fertility, DOI: 10.1080/14647273.2023.2200979

5. Reproductive BioMedicine Online (2023), doi:
https://doi.org/10.1016/j.rbmo.2023.02.012
Impact of moderate to severe endometriosis on IVF
cumulative live birth rate

6. Live birth rate - Women with and without Endometriosis
J Gynecol Obstet Hum Reprod 51 (2022) 102446

7. Live birth rate
Women with III/IV and without Endometriosis
J Gynecol Obstet Hum Reprod 51 (2022) 102446

8. The Latin America Network of Assisted Reproduction
(REDLARA)
Reproductive Biology and Endocrinology (2017) 15:8
DOI 10.1186/s12958-016-0217-2
145 centers

9. Journal of Assisted Reproduction
and Genetics (2019) 36:1649–1656
doi.10.1007/s10815-019-01519-5
Endometriosis
OSI which refers to the number of
oocytes retrieved for
gonadotrophins administered is a
measure of ovarian responsiveness.

10. Journal of Assisted Reproduction
and Genetics (2019) 36:1649–1656
doi.10.1007/s10815-019-01519-5
Endometrioma

11. Cumulative live birth rate after fresh and frozen IVF cycles
with single embryo transfer
Journal of Assisted Reproduction and Genetics (2019) 36:1649–1656
doi.10.1007/s10815-019-01519-5

12. Conventional IVF performs similarly in women
with and without endometriosis
Journal of Assisted Reproduction
and Genetics (2023) 40:599–607
doi.10.1007/s10815-022-02700-z

13. IVF/ICSI outcomes in the endometrioma and control groups
Journal of Ovarian Research (2022) 15:116
doi.10.1186/s13048-022-01042-9
The matched
variables included
maternal age,
maternal BMI, and
duration of infertility
2067 patients undergoing their first IVF/ICSI cycles with autologous oocytes

14. Journal of Ovarian Research (2022) 15:116
doi.10.1186/s13048-022-01042-9
Endometriosis patients with and without prior surgery

15. Unoperated OMAs according to the cyst size
Journal of Ovarian Research (2022) 15:116
doi.10.1186/s13048-022-01042-9

16. Presence of endometrioma
Archives of Gynecology and Obstetrics (2023) 307:2011–2020
https://doi.org/10.1007/s00404-023-07036-2
N= 89 OMA
N=119 ENDO
N=624 CONTROL

17. Presence of endometrioma
Archives of Gynecology and Obstetrics (2023) 307:2011–2020
https://doi.org/10.1007/s00404-023-07036-2
N= 89 OMA
N=119 ENDO
N=624 CONTROL
There is no significant difference in terms of CPR, LBR and cumulative LBR

18. Fertility Outcomes of
Freeze-All vs. Fresh Embryo Transfer
endometriosis by laparoscopy and
classified stage III to IV according to
the revised ASRM scoring system
Front. Endocrinol. 10:770.
doi: 10.3389/fendo.2019.00770
16 covariates:
age,
BMI,
duration of infertility,
gravidity,
parity,
endocrinological profile (basal
FSH, LH, E2, P, and AFC),
concomitant infertility factors
(tubal factors and male factors),
procedure,
number of oocytes retrieved,
number of embryos available,
number of embryos transferred

19. Fertility Outcomes of
Freeze-All vs. Fresh Embryo Transfer
the number of oocytes retrieved
Front. Endocrinol. 10:770.
doi: 10.3389/fendo.2019.00770
endometriosis by laparoscopy and
classified stage III to IV according to
the revised American Society for
Reproductive Medicine (ASRM)
scoring system

20. deferred embryo transfer strategy
PLoS ONE 14(8): e0220256.
doi.10.1371/journal.pone.0
194800

21. Endometriosis is associated with a
lowered cumulative live birth rate
Journal of Reproductive Immunology 151 (2022) 103631
doi.10.1016/j.jri.2022.103631

22. Endometrial receptivity in women with endometriosis
FET cycles
RBMO VOLUME 47 ISSUE 6 2023
doi.10.1016/j.rbmo.2023.103414
N=101
N=101

23. Endometriosis and oocyte quality
donor oocyte recipients vs autologous
Human Reproduction Open, pp. 1–8, 2022
doi.10.1093/hropen/hoac025
women with endometriosis undergoing
758 donor oocyte recipient were compared
with 12856 autologous IVF cycles
Live birth outcomes- fresh and frozen
*Adjustment for confounders (number of previous IVF cycles, previous live birth, period of treatment, day of embryo transfer,
number of embryo transferred, fresh and frozen cycle for combined fresh/frozen).
*Adjustment for confounders (number of previous IVF cycles, previous live birth, year of treatment, day of embryo transfer, number
of embryo transferred, fresh and frozen cycle for combined fresh/frozen).

24. Live Birth After Oocyte Donation In Vitro Fertilization
Cycles in Women With Endometriosis
JAMA Network Open. 2024;7(1):e2354249.
doi:10.1001/jamanetworkopen.2023.54249

25. Live Birth After Oocyte Donation In Vitro Fertilization
Cycles in Women With Endometriosis
JAMA Network Open. 2024;7(1):e2354249.
doi:10.1001/jamanetworkopen.2023.54249

26. Live Birth After Oocyte Donation IVF Cycles in Women With
Endometriosis
JAMA Network Open. 2024;7(1):e2354249.
doi:10.1001/jamanetworkopen.2023.54249

27. Natural Cycle Endometrial Preparation
for Frozen-Thawed Embryo Transfer
Med Sci Monit, 2016; 22: 4596-4603
DOI: 10.12659/MSM.898044
If LH was <20 IU/L, 5000 IU of HCG
was administered at night (21:00) to
trigger ovulation, and the transfer
of 3-day-old embryos was
performed 5 days later.
If the LH value was >20 IU/L, 5000
IU HCG was injected the same
afternoon, and the embryo transfer
was conducted 4 days later.
Beginning on the third day after
HCG injection, 40 mg of
dydrogesterone (Duphaston™) was
given every day for luteal support

28. Natural Cycle Endometrial Preparation
for Frozen-Thawed Embryo Transfer
Med Sci Monit, 2016; 22: 4596-4603
DOI: 10.12659/MSM.898044

29. Endometrial Preparation for Frozen Embryo Transfer
The classic endometrium build-up preparation protocol started with 2 mg/day on days 1–4, 4 mg/day on days
5–8, and 6 mg/day from day 9 onward. Natural micronized progesterone was vaginally administered at a dose
of 400 mg/12 h for 3 or 5 complete days before embryo transfer.
Once a mean diameter of 17 mm had been reached, hCG (250 µg) was administered subcutaneously that
evening, and embryos were thawed and transferred 5 or 7 days later according to embryo stage (5 days for
day-3 embryos, and 7 days for day-5 blastocysts). Luteal phase support commenced 3 or 5 days before embryo
transfer (embryo age +0 days) by administering micronized vaginal progesterone at a dose of 200 mg/12 h
daily
Rambam Maimonides Med J
April 2017 Volume 8 Issue 2

30. Endometrial preparation protocols for frozen-thawed
embryo transfer cycles in women with endometriosis
Reproductive Biology and Endocrinology (2023) 21:83
Doi: 10.1186/s12958-023-01132-3

31. Reproductive Biology and Endocrinology (2023) 21:83
Doi: 10.1186/s12958-023-01132-3

32. Outcomes of IVF/ICSI-FET in studies about Endometriosis.
Front. Endocrinol. 2020;11:427.
doi: 10.3389/fendo.2020.00427

33. Outcomes of FET in the Endometriosis groups.
Front. Endocrinol. 2020;11:427.
doi: 10.3389/fendo.2020.00427

34. Single frozen-thawed embryo transfer
after preimplantation genetic testing
Journal of Assisted Reproduction and Genetics (2024) 41:429–435
doi.10.1007/s10815-023-02996-5

35. Clinical outcomes per vitrified-warmed euploid
single blastocyst transfer
European Journal of Obstetrics &
Gynecology and Reproductive
Biology 256 (2021) 205–210
doi.10.1016/j.ejogrb.2020.11.024
Patients affected from endometriosis (n = 210)
Controls (n = 420)
ICSI with qPCR and trophectoderm biopsy-based PGT-A

36. Cumulative live birth delivery rates (CLBdR)
among completed cycles
European Journal of Obstetrics &
Gynecology and Reproductive
Biology 256 (2021) 205–210
doi.10.1016/j.ejogrb.2020.11.024
Patients affected from endometriosis (n = 210)
Controls (n = 420)
ICSI with qPCR and trophectoderm biopsy-based PGT-A

37. Oocyte Cryopreservation in Women with Ovarian
Endometriosis
J. Clin. Med. 2023,12,6767. doi.10.3390/jcm12216767

38. Ovarian endometrioma increases the embryo aneuploid rate
An analysis of 7092 biopsied blastocysts
BMC Women's Health (2023) 23:244
doi.10.1186/s12905-023-02406-z

39. Patients with endometriosis have aneuploidy rates
equivalent to their age-matched peers
Fertil Steril 2017 Aug;108(2):284-288.
doi: 10.1016/j.fertnstert.2017.05.038.

40. Propensity Score Matched
Reproductive Biology and Endocrinology (2023) 21:107
doi.10.1186/s12958-023-01157-8
248 women with endometriosis and
an adequate ovarian reserve
(AMH>1.1 ng/ml) were meticulously
matched to 248 controls, according
to age, pharmacological regimen
(same drug, same initial dose), AMH
concentration and study period.
Cumulative clinical pregnancy and
live birth rates were almost
identical, even slightly favouring the
endometriosis group (50% and 40%
in endometriosis patients and 49%
and 36% in controls, respectively)

41. Oocyte vitrification for fertility preservation in women
with endometriosis
The number of oocytes retrieved and the number of MII oocytes finally vitrified, calculated
per cycle and per patient, was higher in women with no ovarian surgery before FP (P<.05).
The numbers were similar when we compared between surgically treated patients (unilateral
vs. bilateral surgery; not statistically significant [NS]).
Embryo quality was similar between the groups (NS).
The survival rate and CLBR were comparable in the three groups (NS).
Fertil Steril 2020;113:836–44.
doi:10.1016/j.fertnstert.2019.11.017

42. Oocyte vitrification for fertility preservation in women
with endometriosis
Fertil Steril 2020;113:836–44.
doi:10.1016/j.fertnstert.2019.11.017
Among patients aged %35 years, Surgery did not affect the survival rate (NS).
Similarly, the CLBR was statistically significantly higher in the nonsurgical group
(72.5%) compared with the group of patients who underwent surgery (52.8%).

43. Presence of adenomyosis at MRI reduces live birth rates
Human Reproduction, Vol.37, No.7, pp. 1470–1479, 2022
doi.10.1093/humrep/deac083

44. Impact of adenomyosis and endometriosis on IVF/ICSI
pregnancy outcome
Scientific Reports (2023) 13:6741
doi.10.1038/s41598-023-34045-7

45. Impact of adenomyosis and endometriosis on IVF/ICSI
pregnancy outcomes
Scientific Reports (2023) 13:6741
doi.10.1038/s41598-023-34045-7

46. Does presence of adenomyosis affect reproductive outcome
RBMO VOLUME 00 ISSUE 0 2018
doi.10.1016/j.rbmo.2018.09.014

47. Reproductive outcomes in women with endometriosis
Fertil Steril 2023;119:727–40
Doi. 10.1016/j.fertnstert.2023.03.018

48. Reproductive outcomes in women with adenomyosis
Fertil Steril 2023;119:727–40
Doi. 10.1016/j.fertnstert.2023.03.018

49. Limitations in many studies – lack of good evidence
• Lack of appropriate adjustment for the damage to the ovarian reserve
• The negligence of the strong association between adenomyosis and endometriosis
• Adjustment for additional confounders (besides previous surgeries and
adenomyosis)
• Diagnostic criteria across studies are highly heterogenous
• Most studies have not separately evaluated women with the lesions in situ and
those who have previously undergone lesion excision
• Endometriosis-related lesions are highly heterogeneous; even if studies attempt to
focus on specific types of endometriosis, they cannot avoid including women with
multiple forms of the disease in the same group
• Controls may have higher or lower chance of success, as not all causes of
infertility yield similar IVF success rates Reproductive Biology and Endocrinology (2023) 21:107
doi.10.1186/s12958-023-01157-8

50. Limitations in many studies – lack of good evidence
• Unless combined with matching for gonadotropins dose administered, matching
for the number of oocytes cannot be expected
• Maturity of oocytes is routinely established in case of ICSI and this selection bias
may contribute to a higher fertilization rate per oocyte compared with unselected
oocytes undergoing c-IVF
• Common tendence to prefer ICSI in cases of male infertility but also to avoid total
fertilization failure.
• Both embryo morphology and ploidy seem to be at some extent affected by the
ovarian reserve and the dose/duration of gonadotrophin regimen used for ovarian
stimulation
• Embryos obtained with higher doses of gonadotropins or lower number
of oocytes are at higher risk of aneuploidy.
Reproductive Biology and Endocrinology (2023) 21:107
doi.10.1186/s12958-023-01157-8

51. IVF stimulation protocols and outcomes
in women with endometriosis
Best Practice & Research Clinical Obstetrics & Gynaecology 92 (2024) 102429 .
doi. 10.1016/j.bpobgyn.2023.102429

52. IVF stimulation protocols and outcomes
in women with endometriosis
1. When treating young patients with endometriosis, it’s important to
take a multidisciplinary approach that involves fertility specialists.
2. Encourage fertility preservation, particularly when endometriomas
are present.
3. Pre-treatment with GnRH agonists is not recommended to improve
outcomes in fertility treatments.
4. Stimulation protocols with GnRH antagonists are preferred.
5. When no fresh transfer is planned, it’s advisable to consider using
PPOS as a pituitary suppressor, especially if PPOS are used just
before stimulation to control symptoms of endometriosis.
Best Practice & Research Clinical Obstetrics & Gynaecology 92 (2024) 102429 .
doi. 10.1016/j.bpobgyn.2023.102429

53. Thank you for your attention.
tevfik.yoldemir@marmara.edu.tr
TevfikYoldemirMDBBAM profdrtevfikyoldemir Tevfik-
Yoldemir