ART Outcomes in Endometriosis and Adenomyosis Patients.pdf

ART outcomes for women with endometriosis, adenomyosis, and both

1. ART Outcomes
Endometriosis & Adenomyosis
Tevfik Yoldemir MD, BSc, MA, PhD
[email protected]
profdr.tevfikyoldemir
Co-chair of the Council of Affiliated Menopause Societies- CAMS
Associate Editor of Climacteric, Gynecological Endocrinology,
European Gynecology and Obsterics
Full Professor of Obs & Gyn @ Marmara University, Istanbul

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. Impact of moderate-to-severe endometriosis on IVF
cumulative live birth rate
RBMO VOLUME 47 ISSUE 3 2023 103186
doi:10.1016/j.rbmo.2023.02.012

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

7. 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.

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

9. 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

N=4416

10. 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

11. 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

12. Journal of Ovarian Research (2022) 15:116
doi.10.1186/s13048-022-01042-9



Endometriosis patients with and without prior surgery

13. Unoperated OMAs according to the cyst size


Journal of Ovarian Research (2022) 15:116
doi.10.1186/s13048-022-01042-9

14. Cumulative pregnancy rate in women with current,
resected, or recurred endometrioma
Taiwanese Journal of Obstetrics & Gynecology 62 (2023) 677-681
Doi: 10.1016/j.tjog.2023.07.008

15. qualitative and quantitative assessment of
ovarian response and embryo development
RBMO VOLUME 45 ISSUE 2 2022
doi:10.1016/j.rbmo.2022.04.010

16. qualitative and quantitative assessment of
ovarian response and embryo development
RBMO VOLUME 45 ISSUE 2 2022
doi:10.1016/j.rbmo.2022.04.010

17. 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

18. 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

19. deferred embryo transfer strategy
PLoS ONE 14(8): e0220256.
doi.10.1371/journal.pone.0194800

20. 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

21. 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).

22. 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

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

24. Oocyte donation outcomes in endometriosis with multiple failures
RBMO VOLUME 47 ISSUE 2 2023 103236
10.1016/j.rbmo.2023.05.008

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

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

27. 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

28. 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

29. 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

30. 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.

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

32. 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

33. 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%).

34. Live birth rate in women without and with adenomyosis
Reproductive Sciences (2022) 29:3177–3193
doi.10.1007/s43032-021-00818-6
40% reduction in LBR

35. Comparisons of Live Birth Rate between the adenomyosis
and non-adenomyosis populations
BMJ Open 2024;14:e077025.
doi:10.1136/bmjopen-2023-077025
35% reduction in LBR

36. Reproductive outcomes calculated per fresh ET cycle.
Front. Endocrinol. 13:865358.
doi: 10.3389/fendo.2022.865358

37. Pregnancy outcomes after frozen–thawed embryo transfer
Archives of Gynecology and Obstetrics (2021) 304:1089–1096
doi. 10.1007/s00404-021-06011-z

38. Subgroup comparisons of LBR with Fresh ET between the
adenomyosis and non-adenomyosis populations
BMJ Open 2024;14:e077025.
doi:10.1136/bmjopen-2023-077025
The first subgroup received long-acting GnRHa pretreatment (ultralong protocol).
The second subgroup received non-GnRHa pretreatment (long/antagonist/short
protocols).
The LBR was 30.82% (470/1525) in the adenomyosis and
52.13% (1956/3752) in the non-adenomyosis groups
LBR of adenomyosis group was very poor (24.07% vs 50.82%)

39. Subgroup comparisons of LBR with FET protocols between the
adenomyosis and non- adenomyosis populations
BMJ Open 2024;14:e077025.
doi:10.1136/bmjopen-2023-077025
The third subgroup assessed the effect of long-acting GnRHa pretreatment.
The fourth subgroup assessed the effect of non-GnRHa pretreatment
(long/antagonist/short protocols) on FET cycles.

40. Comparisons of LBR with long acting GnRHa vs nonGnRHa in the
adenomyosis population
BMJ Open 2024;14:e077025.
doi:10.1136/bmjopen-2023-077025
Following sensitivity analysis, we observed that the LBR in the long-acting GnRHa group was
higher than that in the non-long GnRHa group (seven studies, 2009 women, 42.54% vs 30.20%,
OR: 0.08, 95% CI: 0.03 to 0.12, p=0.002). Therefore, long-acting GnRHa therapy may improve LBR.
fresh ET and FET cycles

41. Subgroup comparisons of adenomyosis population in
fresh embryo transfer cycles
BMJ Open 2024;14:e077025.
doi:10.1136/bmjopen-2023-077025
Because of the intragroup heterogeneity in LBR, we made sensitivity analysis and the results
indicated that the benefit of ultralong protocol on LBR (3 studies, 1202 women, 46.04% vs 36.93%,
OR: 1.40, 95% CI: 1.06 to 1.86, p=0.02).
Ultralong protocol may be beneficial for fresh ET cycles.

42. Subgroup comparisons of adenomyosis population in
frozen embryo transfer cycles
BMJ Open 2024;14:e077025.
doi:10.1136/bmjopen-2023-077025
LBR with long-acting GnRHa pretreatment seemed higher than those without GnRHa pretreatment; however,
no statistical differences were observed (28.57% vs 23.1%, OR: 1.25, 95% CI: 0.86 to 1.82, p=0.25)

43. Subgroup comparisons of adenomyosis population
between fresh and frozen embryo transfer cycles
BMJ Open 2024;14:e077025.
doi:10.1136/bmjopen-2023-077025
GnRHa pretreatment combined with FET appears to be more
attractive. (one study, 50.93% vs 33.91%, p=0.003)

44. Assisted reproduction technology (ART) outcomes in the
fresh and freeze-all groups
Fertil Steril 2024;121:460-9.
10.1016/j.fertnstert.2023.11.039

45. ART outcomes in the fresh and freeze-all groups in patients with
adenomyosis with and without associated endometriosis
Fertil Steril 2024;121:460-9.
10.1016/j.fertnstert.2023.11.039

46. RBMO VOLUME 38 ISSUE 1 2019
10.1016/j.rbmo.2018.09.014

47. European Journal of Obstetrics and Gynecology 271 (2022) 223–234
doi:10.1016/j.ejogrb.2022.02.026

48. Pregnancy outcomes of 1st frozen-thawed embryo
transfer cycles (FET)
Scientific Reports | (2023) 13:6741
doi: 10.1038/s41598-023-34045-7

49. Cumulative live birth rates per retrieval cycle
Scientific Reports | (2023) 13:6741
doi: 10.1038/s41598-023-34045-7

50. Studies on adenomyosis, endometriosis, and pregnancy outcomes
Scientific Reports | (2023) 13:6741
doi: 10.1038/s41598-023-34045-7

51. Impact of adenomyosis on in vitro fertilization outcomes
in women undergoing donor oocyte transfers
Fertil Steril 2024;121:480-8.
10.1016/j.fertnstert.2023.11.034

52. Pregnancy outcomes with donor oocyte embryos in
patients diagnosed with adenomyosis
Fertil Steril 2023;119:484-9
doi:10.1016/j.fertnstert.2022.12.021

53. Association between uterine volume and pregnancy outcomes in
adenomyosis patients undergoing frozen-thawed embryo transfer
RBMO VOLUME 42 ISSUE 2 2021
doi:10.1016/j.rbmo.2020.10.002
Group A,
uterine volume
≤98.81 cm3
Group B,
uterine volume
>98.81 cm3

54. Clinical outcomes of initiated stimulation cycles by
presence of sonographic evidence of adenomyosis -SEOA
Human Reproduction Open, 2021
doi:10.1093/hropen/hoab015

55. Comparison of outcomes of fresh and frozen embryo
transfers by presence of sonographic evidence of
adenomyosis - SEOA
Human Reproduction Open, 2021
doi:10.1093/hropen/hoab015

56. Take Home Messages -1
Endometriosis
1.Endometriosis is unremarkable to ovarian response.
A reduction in the response to ovarian stimulation can be detected only for
endometriomas larger than 4 cm. The follicular steroidogenesis is unaffected.
2.Oocyte quality is preserved.
Fertilization rate is similar, making ICSI unjustifiable. Embryological development
does not differ from other forms of infertility, with no surge in aneuploidy rate.
3. Endometrial receptivity is not or minimally reduced.
To note, the most informative studies supporting this perspective did not exclude
women with adenomyosis, a main confounder that was expected to lower the
success of the procedure. This further strengthens the idea that women with
endometriosis should not be considered at increased risk of implantation
failure

Reproductive Biology and Endocrinology (2023) 21:107
doi: 10.1186/s12958-023-01157-8

57. Take Home Messages -2
Endometriosis
4.Encourage fertility preservation, particularly when
endometriomas are present.
5.Pre-treatment with GnRH agonists is not recommended to
improve outcomes in fertility treatments.
6.Stimulation protocols with GnRH antagonists are preferred.
7.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

58. Take Home Messages -3
Adenomyosis
1.The principal problem is related to the heterogenity of the patients with different
degrees of the disease, and patients with focal and diffuse adenomyosis were often
included in the same group.
2.An ultralong protocol is usually used in patients with adenomyosis and good ovarian
function. In fresh ET cycles, the ultralong protocol seemed to improve pregnancy
outcomes; however, increased gonadotropin duration and dosage increased the
economic burden.
3.In patients with poor ovarian function, an ultralong protocol should be adopted with
caution.
4.Long/short/antagonist protocols in fresh ET cycles combined with
a flexible FET strategy might be a viable choice for patients with
adenomyosis and poor ovarian reserve
Reproductive Sciences (2022) 29:3177–3193
BMJ Open 2024;14:e077025. doi: 10.1136/bmjopen-2023-077025

59. Thank you for your attention.

[email protected]
TevfikYoldemirMDBBAM profdrtevfikyoldemir Tevfik-
Yoldemir
profdr.tevfikyoldemir