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Preventing Chemotherapy Induced Ovarian
Failure
Dr Alok Gupta
MD, DM,
Consultant Medical Oncologist
Max Super Speciality Hospital, Saket
Ex-Asst. Professor, AIIMS, New Delhi
Premature Ovarian Failure (POF)
1. Definition
2. Magnitude of problem
3. Implications of POF
4. Methods to Prevent POF
Definition of Ovarian Failure
 Amenorrhea & Postmenopausal levels of both FSH & E2
at 1 year after the end of chemotherapy
 Amenorrhea for the preceding 6 months and FSH levels
in the postmenopausal range at 2 years
Magnitude of problem
 Majority of pre-menopausal women taking chemotherapy
stop menstruating, at least temporarily.
 However, the risk of POF varies widely depending on
age and treatment regimen and dose of chemotherapy.
 Even after resumption of regular menses after
chemotherapy, patients are still at risk of developing
early menopause
Effect of Different Cytotoxic Agents on Ovarian Function
Probability of Ovarian Failure with Combination Chemotherapy
Implications of Ovarian Failure
1. Menopause tends to come on suddenly, so
symptoms—including vaginal dryness, hot flashes,
sleep disturbance, and mood changes—may be more
intense.
2. Negatively impacts global health of young cancer
survivors
3. Infertility
4. Can also influence treatment decisions
Premature Ovarian Failure (POF)
1. Definition
2. Magnitude of problem
3. Implications of POF
4. Methods to Prevent POF
Methods to preserve
hormonal function
1. Cryopreservation of ovarian
tissue
2. Temporary ovarian
suppression with LHRHa
during chemotherapy
Methods for fertility
preservation
1. Cryopreservation of embryos
or oocytes
2. Cryopreservation of ovarian
tissue
3. Temporary ovarian
suppression with LHRHa
during chemotherapy
Cryopreservation of Ovarian tissue vs
Cryopreservation of embryo/oocyte
1. Ovarian tissue cryopreservation can save not only
fertility but also hormonal gonadal function.
 Expected pregnancy rate – 25%
 Ovarian function recovery > 90% of the cases within 3.5–6.5
months after reimplantation
2. Can be performed at any time during the menstrual
cycle
3. No hormonal stimulation is required, thus no delay in
chemotherapy
Drawbacks of Ovarian tissue cryopreservation
1. Expensive technique requiring two surgical procedures
2. Significant high risk of empty follicles (29%)
3. Abnormal/immature oocytes (38%)
4. Low rate (24%) of embryo transfer
5. Potential risk of reintroducing malignant cells when the
tissue is reimplanted
Temporary ovarian suppression with GnRHa
 Advantages
 Widely available option
 No delay in the initiation of anticancer treatments
 No surgical procedure
Evidence Available
 20 studies [five prospective randomized, controlled trials
(RCTs) and 15 non-RCTs] report benefit
 9 studies not supporting the effectiveness of GnRH-a (6
of them RCT) report no benefit
 Two recent large randomized trials report benefit
 POEMS-SWOG S0230
 PROMISE-GIM6 study
Prevention of Early Menopause Study<br />(POEMS)-S0230<br /> Phase III trial of LHRH analog during chemotherapy to reduce ovarian failure in early stage, hormone receptor-
negative breast cancer: an international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance)
Presented By Halle Moore at 2014 ASCO Annual Meeting
POEMS study design
POEMS Objectives and Endpoints
POEMS Outcome Measures
POEMS Consort Diagram
POEMS Evaluable Patients
POEMS Ovarian Failure
POEMS Ovarian Failure Rate
POEMS Pregnancy
POEMS Pregnancy Outcomes
POEMS Disease Free Survival
POEMS Disease Free Survival
POEMS Overall Survival
POEMS Overall Survival
Endocrine Toxicity
POEMS Endocrine Toxicity
POEMS
POEMS Critical Analysis
Conclusions
POEMS Conclusion
PROMISE-GIM6 Study design
Thank You
Dr Alok Gupta MD, DM,
Consultant Medical Oncologist
Max Super Speciality Hospital, Saket
Phone No. 9167164364
Email: alokgupta16@yahoo.co.in

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Preventing chemotherapy induced ovarian failure

  • 1. Preventing Chemotherapy Induced Ovarian Failure Dr Alok Gupta MD, DM, Consultant Medical Oncologist Max Super Speciality Hospital, Saket Ex-Asst. Professor, AIIMS, New Delhi
  • 2. Premature Ovarian Failure (POF) 1. Definition 2. Magnitude of problem 3. Implications of POF 4. Methods to Prevent POF
  • 3. Definition of Ovarian Failure  Amenorrhea & Postmenopausal levels of both FSH & E2 at 1 year after the end of chemotherapy  Amenorrhea for the preceding 6 months and FSH levels in the postmenopausal range at 2 years
  • 4. Magnitude of problem  Majority of pre-menopausal women taking chemotherapy stop menstruating, at least temporarily.  However, the risk of POF varies widely depending on age and treatment regimen and dose of chemotherapy.  Even after resumption of regular menses after chemotherapy, patients are still at risk of developing early menopause
  • 5. Effect of Different Cytotoxic Agents on Ovarian Function
  • 6. Probability of Ovarian Failure with Combination Chemotherapy
  • 7. Implications of Ovarian Failure 1. Menopause tends to come on suddenly, so symptoms—including vaginal dryness, hot flashes, sleep disturbance, and mood changes—may be more intense. 2. Negatively impacts global health of young cancer survivors 3. Infertility 4. Can also influence treatment decisions
  • 8. Premature Ovarian Failure (POF) 1. Definition 2. Magnitude of problem 3. Implications of POF 4. Methods to Prevent POF
  • 9. Methods to preserve hormonal function 1. Cryopreservation of ovarian tissue 2. Temporary ovarian suppression with LHRHa during chemotherapy Methods for fertility preservation 1. Cryopreservation of embryos or oocytes 2. Cryopreservation of ovarian tissue 3. Temporary ovarian suppression with LHRHa during chemotherapy
  • 10. Cryopreservation of Ovarian tissue vs Cryopreservation of embryo/oocyte 1. Ovarian tissue cryopreservation can save not only fertility but also hormonal gonadal function.  Expected pregnancy rate – 25%  Ovarian function recovery > 90% of the cases within 3.5–6.5 months after reimplantation 2. Can be performed at any time during the menstrual cycle 3. No hormonal stimulation is required, thus no delay in chemotherapy
  • 11. Drawbacks of Ovarian tissue cryopreservation 1. Expensive technique requiring two surgical procedures 2. Significant high risk of empty follicles (29%) 3. Abnormal/immature oocytes (38%) 4. Low rate (24%) of embryo transfer 5. Potential risk of reintroducing malignant cells when the tissue is reimplanted
  • 12. Temporary ovarian suppression with GnRHa  Advantages  Widely available option  No delay in the initiation of anticancer treatments  No surgical procedure
  • 13. Evidence Available  20 studies [five prospective randomized, controlled trials (RCTs) and 15 non-RCTs] report benefit  9 studies not supporting the effectiveness of GnRH-a (6 of them RCT) report no benefit  Two recent large randomized trials report benefit  POEMS-SWOG S0230  PROMISE-GIM6 study
  • 14. Prevention of Early Menopause Study<br />(POEMS)-S0230<br /> Phase III trial of LHRH analog during chemotherapy to reduce ovarian failure in early stage, hormone receptor- negative breast cancer: an international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance) Presented By Halle Moore at 2014 ASCO Annual Meeting
  • 16. POEMS Objectives and Endpoints POEMS Outcome Measures
  • 17. POEMS Consort Diagram POEMS Evaluable Patients
  • 18. POEMS Ovarian Failure POEMS Ovarian Failure Rate
  • 20. POEMS Disease Free Survival POEMS Disease Free Survival
  • 21. POEMS Overall Survival POEMS Overall Survival
  • 26.
  • 27.
  • 28.
  • 29.
  • 30.
  • 31.
  • 32.
  • 33. Thank You Dr Alok Gupta MD, DM, Consultant Medical Oncologist Max Super Speciality Hospital, Saket Phone No. 9167164364 Email: alokgupta16@yahoo.co.in