Fertility treatments for women older than 40 years of age

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Fertility options for women after age of 40 years:
what is realistic, what is not?
Tevfik Yoldemir MD BSc MA
Prof. Marmara University, School of Medicine,
Dept. of Obs Gyn, Istanbul, Turkey
Adjunct Prof. Eastern Mediterranean University, School of
Medicine, Dept. of Obs Gyn, Famagusta, North Cyprus
Photo
(compulsory)
I have no financial relationships to disclose.
I have no conflict of interest.
Kaplan Meier curves for cumulative probability of pregnancy
across cycles of pregnancy attempt by age group
Fertil Steril. 2016 June ; 105(6): 1584–1588.e1. doi:10.1016/j.fertnstert.2016.02.028
Fecundability and cumulative pregnancy rates for the cohort as
calculated from survival analysis
Fertil Steril. 2016 June ; 105(6): 1584–1588.e1. doi:10.1016/j.fertnstert.2016.02.028
Fecundability and cumulative pregnancy rates by history of
prior pregnancy as calculated from survival analysis
Fertil Steril. 2016 June ; 105(6): 1584–1588.e1. doi:10.1016/j.fertnstert.2016.02.028
Which is better for live birth prediction in patients aged over
40 with their first IVF treatment?
European Journal of Obstetrics & Gynecology and Reproductive Biology 221 (2018) 151–155

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Survey done with 196 IVF centers
Reproductive BioMedicine Online (2015) 30, 581–592 Reproductive BioMedicine Online (2015) 30, 581–592
Reproductive BioMedicine Online (2015) 30, 581–592
Frequency of various ‘poor responder’ definitions appearing in
randomized trials
Human Reproduction Update, Vol.0, No.0 pp. 1–14, 2016
doi:10.1093/humupd/dmw001

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Live birth rate per started cycle
J Assist Reprod Genet (2015) 32:931–937
Cycle cancellation per initiated cycle
Clin Exp Reprod Med 2017;44(2):111-117
https://doi.org/10.5653/cerm.2017.44.2.111
Bologna Criteria
• At least two of the following three criteria must be met to be
considered as a poor responder to COS:
(1) age 40 years or any other risk factor for poor response,
(2) a previous poor response (3 oocytes in a conventional COS cycle),
(3) an abnormal ovarian reserve test (defined as AFC < 5–7 or serum
AMH level <0.5–1.0 ng/mL)
Subgroups of POSEIDON
Reproductive Biology and Endocrinology (2018) 16:20
https://doi.org/10.1186/s12958-018-0342-1

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Human Reproduction Update, pp. 1–10, 2017
doi:10.1093/humupd/dmw047
Human Reproduction Update, pp. 1–10, 2017
doi:10.1093/humupd/dmw047
Freeze-all?
J Assist Reprod Genet (2017) 34:179–185
Freeze all
Human Reproduction, Vol.33, No.5 pp. 924–929, 2018
after the first complete cycle among 20 687 women

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accumulation of vitrified oocytes
J Assist Reprod Genet (2017) 34:479–486
accumulation of vitrified oocytes
Reproductive BioMedicine Online (2012) 24, 424– 432
Cumulative live birth rate
JAMA. 2015;314(24):2654-2662. doi:10.1001/jama.2015.17296
Strategies for women of 40+ years of age
• Tailored ovarian stimulation
• Protocol/ Gn dose & type
• Larger cohort
• Synchronous cohort
• Dual stim
• Modification of intraovarian environment
• Androgen / GH
• Embryo selection
• BT / PGS, Time-lapse
• Oocyte donation
Estimated mean number of metaphase II oocytes required to
obtain at least one euploid blastocyst
Curr Opin Obstet Gynecol 2018, 30:000–000
DOI:10.1097/GCO.0000000000000452
Human Reproduction Update, Vol.0, No.0 pp. 1–14, 2016
doi:10.1093/humupd/dmw001

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Human Reproduction Update, Vol.0, No.0 pp. 1–14, 2016
doi:10.1093/humupd/dmw001
Androgens or androgen modulating agents
Tarlatsis B, ISGE 2018
Urman B, 12th Turkish German Gynecologic Congress 2018
Future - Alternative sources of autologous oocytes
Human Reproduction, Vol.32, No.4 pp. 725–732, 2017
Future Hormonal regulation of preantral follicle growth
Endocrine Reviews, February 2015, 36(1):1–24

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Future
Endocrine Reviews, February 2015, 36(1):1–24
Future
Future Future
J Clin Endocrinol Metab, November 2016, 101(11):4405– 4412
Future
Endocrine Reviews, February 2015, 36(1):1–24
Future
JFIV Reprod Med Genet 2015, 3:3 http://dx.doi.org/10.4172/2375-4508.1000154

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Future
Hum Reprod 2001 Mar;16(3):513-6.
Case 1
• 43 year-old woman
• Recently married, BMI 20 kg/m2
• CD3 FSH 8.08 IU/L, AMH 0.8 ng/ml, AFC 10
• Curious about her fertility potential.
• What would you advise her ?
Live birth rate
Clin Exp Reprod Med 2017;44(2):111-117
https://doi.org/10.5653/cerm.2017.44.2.111
Cumulative live birth rate
Clin Exp Reprod Med 2017;44(2):111-117
https://doi.org/10.5653/cerm.2017.44.2.111
Case 2
• 40 year-old woman
• Married for 3 years, BMI 28.5 kg/m2
• CD3 FSH 8.85 IU/L, AMH 0.73 ng/ml, AFC 6
• Had 2 ICSI cycles; with poor ovarian response.
• She wants to know what might happen in the next trial?
Reproductive BioMedicine Online (2017),
doi: 10.1016/j.rbmo.2017.03.009

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Reproductive BioMedicine Online (2017),
doi: 10.1016/j.rbmo.2017.03.009
Reproductive BioMedicine Online (2017),
doi: 10.1016/j.rbmo.2017.03.009
High-dose gonadotropin stimulation with estradiol priming
Semin Reprod Med 2015;33:169–178
The protocol of double stimulation during the follicular and
luteal phases in patients with poor ovarian response
Reproductive BioMedicine Online (2014) 29, 684–691
Case 3
• 42 year-old woman
• Nulliparous, BMI 24.5 kg/m2
• Newly married ( 4 months)
• Cycle length longer than it is used to be
• CD3 FSH 17.03 IU/L, AMH 0.4 ng/ml, AFC 5
• She is worried about her chances for conception.
• How would you counsel her?
Novel POSEIDON (Patient-Oriented Strategies Encompassing
Individualized Oocyte Number) Stratification
(1) Group 1: patients younger than 35 with sufficient ovarian reserve parameters
(AFC ≥ 5, AMH ≥ 1.2 ng/ml) and with an unexpected poor or suboptimal ovarian
response;
(2) Group 2: patients older than 35 with sufficient ovarian reserve parameters (AFC
≥ 5, AMH ≥ 1.2 ng/ml) and with an unexpected poor or suboptimal ovarian
response;
(3) Group 3: patients younger than 35 with poor ovarian reserve parameters (AFC
<5, AMH <1.2ng/ml);
(4) Group 4: patients older than 35 with poor ovarian reserve parameters (AFC <5,
AMH <1.2ng/ml).
Curr Opin Obstet Gynecol 2018, 30:000–000
DOI:10.1097/GCO.0000000000000452

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“DELAYED START” PROTOCOL WITH GNRH ANTAGONIST
Obstet Gynecol Sci 2018;61(1):102-110
https://doi.org/10.5468/ogs.2018.61.1.102
Luteal phase stimulation
Semin Reprod Med 2015;33:169–178
Minimal stimulation protocol
Semin Reprod Med 2015;33:169–178
The protocol of double stimulation during the follicular and
luteal phases in patients with poor ovarian response
Reproductive BioMedicine Online (2014) 29, 684–691
Live birth rates are satisfactory following multiple IVF
treatment cycles in poor prognosis patients
Reprod Biol (2016), http://dx.doi.org/10.1016/j.repbio.2016.11.004
Group A, 20/30/40 follicles;
group B, 13–19 follicles;
group C, 9–12 follicles;
group D, 5–8 follicles;
group E, ≤4 follicles).
Groups B and C were combined
(B/C, 9–19 follicles)
Women with FSH> 20 mIU/ml
Reproductive Sciences 1-6, 2017
DOI: 10.1177/1933719117697130

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Case 4
• 41 year-old woman
• Married for 2 years, BMI 26.5 kg/m2
• CD3 FSH 9.8 IU/L, AMH 0.08 ng/ml, AFC 4
• Has started COH for ART; only 2 follicles developed.
• She wants to know what will happen next?
In vitro fertilization versus conversion to intrauterine
insemination in Bologna-criteria poor responders
Fertil Steril2014;102:1596–601
Double ovarian stimulation protocol: both follicular and luteal
phase ovarian stimulation in the same cycle
Zhang Reproductive Biology and Endocrinology (2015) 13:76
DOI 10.1186/s12958-015-0076-2.
Case 5
• 40 year-old woman
• Married for 2 years, BMI 21 kg/m2
• CD3 FSH 4.89 IU/L, AMH 0.64 ng/ml, AFC 4
• During her previous ICSI cycle; 7 oocytes were collected, 5 were
injected and 3 fertilized and 2 embryos were transfered on D2.
• She wants to know if the next trial may be better?
tailored mode and timing of final follicular maturation
Journal of Ovarian Research (2015) 8:69
DOI 10.1186/s13048-015-0198-3
Triggering final follicular maturation- hCG,
GnRH-agonist or both, when and to whom?
Journal of Ovarian Research (2015) 8:60
DOI 10.1186/s13048-015-0187-6
GnRHa is now offered concomitant to the
standard hCG trigger dose, to improve
oocyte/embryo yield and quality.
GnRHa and hCG may be offered concomitantly,
34–37 h prior to oocyte retrieval (dual trigger)
or
40 h and 34 h prior to oocyte retrieval,
respectively (double trigger) in patients with
abnormal final follicular maturation.

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Thank you for your attention
Tevfik Yoldemir MD BSc MA
tevfik.yoldemir@marmara.edu.tr
Photo
(compulsory)