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Outcomes of ovarian stimulation after treatment with chemotherapy

  • Fertility Preservation
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Chemotherapeutic agents have a known gonadotoxic effect; however, it is difficult to predict the impact they may have on ovarian stimulation. The objective of this study was to evaluate response to ovarian stimulation in patients exposed to chemotherapy compared with patients who were chemotherapy-naïve.

Methods

A retrospective cohort study of 130 patients with cancer or autoimmune disease was performed. Demographics, ovarian reserve, ovarian response and stimulation parameters, and oocyte data were compared between patients who were pre- and post-chemotherapy. Logistic regression modeling was performed to identify risk factors for cancellation and low oocyte yield, adjusting for confounders as appropriate.

Results

Antral follicle count (AFC) was significantly lower in post-chemo patients (9 vs. 17, p < 0.001). Post-chemotherapy patients were more likely to be cancelled during stimulation (23 vs. 4 %, p = 0.003). Among those that went to retrieval, there was no difference in total number of oocytes (10 vs. 10, p = 0.31) or mature oocytes retrieved (8 vs. 8, p = 0.38), despite higher starting (300 vs. 450 IU, p < 0.001) and total gonadotropin (3075 vs. 4612.5 IU, p = 0.008) doses in post-chemotherapy patients. Low AFC (≤6) was associated with cycle cancellation (OR 7.7, 95 % CI 1.8–33.2) and low oocyte yield (<6) (OR 5.4, 95 % CI 1.6–17.7).

Conclusions

Patients post-chemotherapy have lower AFC compared with the chemotherapy-naïve and have higher cancellation rates. Among those who underwent oocyte retrieval, oocyte yield was similar in both groups. Low AFC was most strongly associated with cycle cancellation and oocyte yield. Post-chemotherapy patients had higher rates of cycle cancellation but did equally well as pre-chemotherapy patients if they reached retrieval.

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References

  1. Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol: Off J Am Soc Clin Oncol. 2009;27(16):2677–85. doi:10.1200/JCO.2008.20.1541.

    Article  CAS  Google Scholar 

  2. Miller 3rd JJ, Williams GF, Leissring JC. Multiple late complications of therapy with cyclophosphamide, including ovarian destruction. Am J Med. 1971;50(4):530–5.

    Article  PubMed  Google Scholar 

  3. Nicosia SV, Matus-Ridley M, Meadows AT. Gonadal effects of cancer therapy in girls. Cancer. 1985;55(10):2364–72.

    Article  CAS  PubMed  Google Scholar 

  4. Familiari G, Caggiati A, Nottola SA, Ermini M, Di Benedetto MR, Motta PM. Ultrastructure of human ovarian primordial follicles after combination chemotherapy for Hodgkin's disease. Human Reprod (Oxford, England). 1993;8(12):2080–7.

    CAS  Google Scholar 

  5. Gracia CR, Sammel MD, Freeman E, Prewitt M, Carlson C, Ray A, et al. Impact of cancer therapies on ovarian reserve. Fertil Steril. 2012;97(1):134–40. doi:10.1016/j.fertnstert.2011.10.040. e1.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Hensley ML, Reichman BS. Fertility and pregnancy after adjuvant chemotherapy for breast cancer. Crit Rev Oncol/Hematol. 1998;28(2):121–8.

    Article  CAS  Google Scholar 

  7. Wallace WH, Blacklay A, Eiser C, Davies H, Hawkins M, Levitt GA, et al. Developing strategies for long term follow up of survivors of childhood cancer. BMJ. 2001;323(7307):271–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Damewood MD, Grochow LB. Prospects for fertility after chemotherapy or radiation for neoplastic disease. Fertil Steril. 1986;45(4):443–59.

    CAS  PubMed  Google Scholar 

  9. Mok CC, Chan PT, To CH. Anti-mullerian hormone and ovarian reserve in systemic lupus erythematosus. Arthritis Rheum. 2013;65(1):206–10. doi:10.1002/art.37719.

    Article  CAS  PubMed  Google Scholar 

  10. Clowse ME, Copland SC, Hsieh TC, Chow SC, Hoffman GS, Merkel PA, et al. Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's). Arthritis Care Res. 2011;63(12):1777–81. doi:10.1002/acr.20605.

    Article  CAS  Google Scholar 

  11. Hodgson DC, Pintilie M, Gitterman L, Dewitt B, Buckley CA, Ahmed S, et al. Fertility among female hodgkin lymphoma survivors attempting pregnancy following ABVD chemotherapy. Hematol Oncol. 2007;25(1):11–5. doi:10.1002/hon.802.

    Article  PubMed  Google Scholar 

  12. Harel S, Ferme C, Poirot C. Management of fertility in patients treated for Hodgkin's lymphoma. Haematologica. 2011;96(11):1692–9. doi:10.3324/haematol.2011.045856.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Blumenfeld Z. Chemotherapy and fertility. Best Pract Res Clin Obstet Gynaecol. 2012;26(3):379–90. doi:10.1016/j.bpobgyn.2011.11.008.

    Article  PubMed  Google Scholar 

  14. Letourneau JM, Ebbel EE, Katz PP, Katz A, Ai WZ, Chien AJ, et al. Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer. Cancer. 2012;118(6):1710–7. doi:10.1002/cncr.26459.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Barton SE, Najita JS, Ginsburg ES, Leisenring WM, Stovall M, Weathers RE, et al. Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol. 2013;14(9):873–81. doi:10.1016/S1470-2045(13)70251-1.

    Article  PubMed  Google Scholar 

  16. Friedler S, Koc O, Gidoni Y, Raziel A, Ron-El R. Ovarian response to stimulation for fertility preservation in women with malignant disease: a systematic review and meta-analysis. Fertil Steril. 2012;97(1):125–33. doi:10.1016/j.fertnstert.2011.10.014.

    Article  PubMed  Google Scholar 

  17. Domingo J, Guillen V, Ayllon Y, Martinez M, Munoz E, Pellicer A, et al. Ovarian response to controlled ovarian hyperstimulation in cancer patients is diminished even before oncological treatment. Fertil Steril. 2012;97(4):930–4. doi:10.1016/j.fertnstert.2012.01.093.

    Article  PubMed  Google Scholar 

  18. Senapati S, Morse CB, Sammel MD, Kim J, Mersereau JE, Efymow B, et al. Fertility preservation in patients with haematological disorders: a retrospective cohort study. Reprod Biomed Online. 2014;28(1):92–8. doi:10.1016/j.rbmo.2013.07.014.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Klock SC, Zhang JX, Kazer RR. Fertility preservation for female cancer patients: early clinical experience. Fertil Steril. 2010;94(1):149–55. doi:10.1016/j.fertnstert.2009.03.028.

    Article  PubMed  Google Scholar 

  20. Johnson LN, Dillon KE, Sammel MD, Efymow BL, Mainigi MA, Dokras A, et al. Response to ovarian stimulation in patients facing gonadotoxic therapy. Reprod Biomed Online. 2013;26(4):337–44. doi:10.1016/j.rbmo.2013.01.003.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Conaway MR. A random effects model for binary data. Biometrics. 1990;46(2):317–28. doi:10.2307/2531437.

    Article  Google Scholar 

  22. Johnson LN, Sammel MD, Dillon KE, Lechtenberg L, Schanne A, Gracia CR. Antimullerian hormone and antral follicle count are lower in female cancer survivors and healthy women taking hormonal contraception. Fertil Steril. 2014;102(3):774–81. doi:10.1016/j.fertnstert.2014.05.026. e3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Larsen EC, Muller J, Schmiegelow K, Rechnitzer C, Andersen AN. Reduced ovarian function in long-term survivors of radiation- and chemotherapy-treated childhood cancer. J Clin Endocrinol Metab. 2003;88(11):5307–14. doi:10.1210/jc.2003-030352.

    Article  CAS  PubMed  Google Scholar 

  24. Lutchman Singh K, Muttukrishna S, Stein RC, McGarrigle HH, Patel A, Parikh B, et al. Predictors of ovarian reserve in young women with breast cancer. Br J Cancer. 2007;96(12):1808–16. doi:10.1038/sj.bjc.6603814.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Almog B, Azem F, Gordon D, Pauzner D, Amit A, Barkan G, et al. Effects of cancer on ovarian response in controlled ovarian stimulation for fertility preservation. Fertil Steril. 2012;98(4):957–60. doi:10.1016/j.fertnstert.2012.06.007.

    Article  PubMed  Google Scholar 

  26. Ginsburg ES, Yanushpolsky EH, Jackson KV. In vitro fertilization for cancer patients and survivors. Fertil Steril. 2001;75(4):705–10.

    Article  CAS  PubMed  Google Scholar 

  27. Chang MY, Chiang CH, Hsieh TT, Soong YK, Hsu KH. Use of the antral follicle count to predict the outcome of assisted reproductive technologies. Fertil Steril. 1998;69(3):505–10.

    Article  CAS  PubMed  Google Scholar 

  28. Frattarelli JL, Levi AJ, Miller BT, Segars JH. A prospective assessment of the predictive value of basal antral follicles in in vitro fertilization cycles. Fertil Steril. 2003;80(2):350–5.

    Article  PubMed  Google Scholar 

  29. Hsu A, Arny M, Knee AB, Bell C, Cook E, Novak AL, et al. Antral follicle count in clinical practice: analyzing clinical relevance. Fertil Steril. 2011;95(2):474–9. doi:10.1016/j.fertnstert.2010.03.023.

    Article  PubMed  Google Scholar 

  30. Melo MA, Garrido N, Alvarez C, Bellver J, Meseguer M, Pellicer A, et al. Antral follicle count (AFC) can be used in the prediction of ovarian response but cannot predict the oocyte/embryo quality or the in vitro fertilization outcome in an egg donation program. Fertil Steril. 2009;91(1):148–56. doi:10.1016/j.fertnstert.2007.11.042.

    Article  PubMed  Google Scholar 

  31. Bentzen JG, Forman JL, Pinborg A, Lidegaard O, Larsen EC, Friis-Hansen L, et al. Ovarian reserve parameters: a comparison between users and non-users of hormonal contraception. Reprod Biomed Online. 2012;25(6):612–9. doi:10.1016/j.rbmo.2012.09.001.

    Article  CAS  PubMed  Google Scholar 

  32. Reichman DE, Goldschlag D, Rosenwaks Z. Value of antimullerian hormone as a prognostic indicator of in vitro fertilization outcome. Fertil Steril. 2014;101(4):1012–8.e1. doi:10.1016/j.fertnstert.2013.12.039.

    Article  CAS  PubMed  Google Scholar 

  33. Arce JC, La Marca A, Mirner Klein B, Nyboe Andersen A, Fleming R. Antimullerian hormone in gonadotropin releasing-hormone antagonist cycles: prediction of ovarian response and cumulative treatment outcome in good-prognosis patients. Fertil Steril. 2013;99(6):1644–53. doi:10.1016/j.fertnstert.2012.12.048.

    Article  CAS  PubMed  Google Scholar 

  34. Lekamge DN, Barry M, Kolo M, Lane M, Gilchrist RB, Tremellen KP. Anti-Mullerian hormone as a predictor of IVF outcome. Reprod Biomed Online. 2007;14(5):602–10.

    Article  CAS  PubMed  Google Scholar 

  35. La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, et al. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010;16(2):113–30. doi:10.1093/humupd/dmp036.

    Article  PubMed  Google Scholar 

  36. Jayaprakasan K, Campbell B, Hopkisson J, Johnson I, Raine-Fenning N. A prospective, comparative analysis of anti-Mullerian hormone, inhibin-B, and three-dimensional ultrasound determinants of ovarian reserve in the prediction of poor response to controlled ovarian stimulation. Fertil Steril. 2010;93(3):855–64. doi:10.1016/j.fertnstert.2008.10.042.

    Article  CAS  PubMed  Google Scholar 

  37. Lee RK, Wu FS, Lin MH, Lin SY, Hwu YM. The predictability of serum anti-Mullerian level in IVF/ICSI outcomes for patients of advanced reproductive age. Reprod Biol Endocrinol : RB&E. 2011;9:115. doi:10.1186/1477-7827-9-115.

    Article  CAS  Google Scholar 

  38. Cakmak H, Katz A, Cedars MI, Rosen MP. Effective method for emergency fertility preservation: random-start controlled ovarian stimulation. Fertil Steril. 2013;100(6):1673–80. doi:10.1016/j.fertnstert.2013.07.1992.

    Article  PubMed  Google Scholar 

  39. von Wolff M, Thaler CJ, Frambach T, Zeeb C, Lawrenz B, Popovici RM, et al. Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase. Fertil Steril. 2009;92(4):1360–5. doi:10.1016/j.fertnstert.2008.08.011.

    Article  Google Scholar 

  40. Sonmezer M, Turkcuoglu I, Coskun U, Oktay K. Random-start controlled ovarian hyperstimulation for emergency fertility preservation in letrozole cycles. Fertil Steril. 2011;95(6):2125 e9–11. doi:10.1016/j.fertnstert.2011.01.030.

    Article  PubMed  Google Scholar 

  41. Green DM, Sklar CA, Boice Jr JD, Mulvihill JJ, Whitton JA, Stovall M, et al. Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol: Off J Am Soc Clin Oncol. 2009;27(14):2374–81. doi:10.1200/jco.2008.21.1839.

    Article  Google Scholar 

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Acknowledgments

This research was supported by the National Institutes of Health (Grant numbers: R01-HD-062797-05- Dr. Gracia, T32 HD007440- Drs. Chan and Johnson).

Conflicts of interest

The authors declare that they have no conflicts of interest.

Statement of human rights and informed consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this retrospective cohort study, formal consent is not required.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Pennsylvania, 3701 Market Street, Suite 800, Philadelphia, PA, 19104, USA

    Jessica L. Chan, Lauren N. C. Johnson, Brenda L. Efymow & Clarisa R. Gracia

  2. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, 423 Guardian Drive, 605 Blockley Hall, Philadelphia, PA, 19104, USA

    Mary D. Sammel

Authors
  1. Jessica L. Chan
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  2. Lauren N. C. Johnson
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  3. Brenda L. Efymow
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  4. Mary D. Sammel
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  5. Clarisa R. Gracia
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Corresponding author

Correspondence to Jessica L. Chan.

Additional information

Capsule Chemotherapy has a known gonadotoxic effect, however the specific impact on ovarian stimulation parameters/outcomes is unclear. Though post-chemotherapy patients had lower AFC and higher risk of cancellation, those who reached retrieval had similar oocyte yield as those who were pre-chemotherapy. It is reasonable to offer fertility preservation/treatment after chemotherapy with individualized protocols.

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Chan, J.L., Johnson, L.N.C., Efymow, B.L. et al. Outcomes of ovarian stimulation after treatment with chemotherapy. J Assist Reprod Genet 32, 1537–1545 (2015). https://doi.org/10.1007/s10815-015-0575-2

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  • DOI: https://doi.org/10.1007/s10815-015-0575-2

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