Live birth rate after female fertility preservation for cancer or haematopoietic stem cell transplantation: a systematic review and meta-analysis of the three main techniques; embryo, oocyte and ovarian tissue cryopreservation

Abstract STUDY QUESTION What are the chances of achieving a live birth after embryo, oocyte and ovarian tissue cryopreservation (OTC) in female cancer survivors? SUMMARY ANSWER The live birth rates (LBRs) following embryo and oocyte cryopreservation are 41% and 32%, respectively, while for IVF and spontaneous LBR after tissue cryopreservation and transplantation, these rates are 21% and 33%, respectively. WHAT IS KNOWN ALREADY Currently, fertility preservation (FP) has become a major public health issue as diagnostic and therapeutic progress has made it possible to achieve an 80% survival rate in children, adolescents and young adults with cancer. In the latest ESHRE guidelines, only oocyte and embryo cryopreservation are considered as established options for FP. OTC is still considered to be an innovative method, while it is an acceptable FP technique in the American Society for Reproductive Medicine guidelines. However, given the lack of studies on long-term outcomes after FP, it is still unclear which technique offers the best chance to achieve a live birth. STUDY DESIGN, SIZE, DURATION We performed a systematic review and meta-analysis of published controlled studies. Searches were conducted from January 2004 to May 2021 in Medline, Embase and the Cochrane Library using the following search terms: cancer, stem cell transplantation, FP, embryo cryopreservation, oocyte vitrification, OTC and reproductive outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 126 full-text articles were preselected from 1436 references based on the title and abstract and assessed via the Newcastle–Ottawa Quality Assessment Scale. The studies were selected, and their data were extracted by two independent reviewers according to the Cochrane methods. A fixed-effect meta-analysis was performed for outcomes with high heterogeneity. MAIN RESULTS AND THE ROLE OF CHANCE Data from 34 studies were used for this meta-analysis. Regarding cryopreserved embryos, the LBR after IVF was 41% (95% CI: 34–48, I2: 0%, fixed effect). Concerning vitrified oocytes, the LBR was 32% (95% CI: 26–39, I2: 0%, fixed effect). Finally, the LBR after IVF and the spontaneous LBR after ovarian tissue transplantation were 21% (95% CI: 15–26, I2: 0%, fixed-effect) and 33% (95% CI: 25–42, I2: 46.1%, random-effect), respectively. For all outcomes, in the sensitivity analyses, the maximum variation in the estimated percentage was 1%. LIMITATIONS, REASONS FOR CAUTION The heterogeneity of the literature prevents us from comparing these three techniques. This meta-analysis provides limited data which may help clinicians when counselling patients. WIDER IMPLICATIONS OF THE FINDINGS This study highlights the need for long-term follow-up registries to assess return rates, as well as spontaneous pregnancy rates and birth rates after FP. STUDY FUNDING/COMPETING INTEREST(S) This work was sponsored by an unrestricted grant from GEDEON RICHTER France. The authors have no competing interests to declare. REGISTRATION NUMBER CRD42021264042.

[1]  G. Gullo,et al.  Oncofertility and Reproductive Counseling in Patients with Breast Cancer: A Retrospective Study , 2022, Journal of clinical medicine.

[2]  A. Coomarasamy,et al.  Fresh and cryopreserved ovarian tissue transplantation for preserving reproductive and endocrine function: a systematic review and individual patient data meta-analysis , 2022, Human reproduction update.

[3]  A. Lanes,et al.  Oocyte cryopreservation review: outcomes of medical oocyte cryopreservation and planned oocyte cryopreservation , 2022, Reproductive Biology and Endocrinology.

[4]  F. Gumy-Pause,et al.  Pregnancy and pregnancy outcomes after hematopoietic stem cell transplantation in childhood: a cross-sectional survey of the EBMT Pediatric Diseases Working Party. , 2021, Human reproduction.

[5]  E. Bosch,et al.  Individualized luteal phase support normalizes live birth rate in women with low progesterone levels on the day of embryo transfer in artificial endometrial preparation cycles. , 2021, Fertility and sterility.

[6]  A. Karger,et al.  Cancer and Relationship Dissolution: Perspective of Partners of Cancer Patients , 2021, Frontiers in Psychology.

[7]  M. Weintraub,et al.  Chemotherapy-based gonadotoxicity risk evaluation as a predictor of reproductive outcomes in post-pubertal patients following ovarian tissue cryopreservation , 2021, BMC Women's Health.

[8]  C. Stern,et al.  Ovarian tissue grafting: Lessons learnt from our experience with 55 grafts , 2021, Reproductive medicine and biology.

[9]  A. Pellicer,et al.  Transplantation of cryopreserved ovarian tissue in a series of 285 women: a review of five leading European centers. , 2021, Fertility and sterility.

[10]  J. Remohi,et al.  Oocyte vitrification for fertility preservation for both medical and nonmedical reasons. , 2021, Fertility and sterility.

[11]  N. Frydman,et al.  Live birth rate after use of cryopreserved oocytes or embryos at the time of cancer diagnosis in female survivors: a retrospective study of ten years of experience , 2021, Journal of Assisted Reproduction and Genetics.

[12]  Y. Nagata,et al.  A multi-centre, retrospective case series of oocyte cryopreservation in unmarried women diagnosed with haematological malignancies , 2021, Human reproduction open.

[13]  A. Neuraz,et al.  Efficacy of assisted reproductive technology after ovarian tissue transplantation in a cohort of 11 patients with or without associated infertility factors , 2021, Journal of Assisted Reproduction and Genetics.

[14]  F. Amant,et al.  ESHRE guideline: female fertility preservation† , 2020, Human reproduction open.

[15]  J. Donnez,et al.  Fertility preservation in women for medical and social reasons: Oocytes vs ovarian tissue. , 2020, Best practice & research. Clinical obstetrics & gynaecology.

[16]  P. Humaidan,et al.  Reproductive outcomes after in vitro fertilization treatment in a cohort of Danish women transplanted with cryopreserved ovarian tissue. , 2020, Fertility and sterility.

[17]  Lifeng Lin,et al.  Meta-analysis of Proportions Using Generalized Linear Mixed Models , 2020, Epidemiology.

[18]  J. Bergh,et al.  Efficacy and safety of controlled ovarian stimulation using GnRH antagonist protocols for emergency fertility preservation in young women with breast cancer—a prospective nationwide Swedish multicenter study , 2020, Human reproduction.

[19]  Z. Nagy,et al.  Vitrification of the human embryo: a more efficient and safer in vitro fertilization treatment. , 2020, Fertility and sterility.

[20]  M. Gissler,et al.  Trends in the incidence, rate and treatment of miscarriage-nationwide register-study in Finland, 1998-2016. , 2019, Human reproduction.

[21]  C. Ronchetti,et al.  Oocyte Cryopreservation in Oncological Patients: Eighteen Years Experience of a Tertiary Care Referral Center , 2019, Front. Endocrinol..

[22]  L. Pazart,et al.  Development of Ovarian Tissue Autograft to Restore Ovarian Function: Protocol for a French Multicenter Cohort Study , 2019, JMIR research protocols.

[23]  C. Genestie,et al.  Impact of cancer chemotherapy before ovarian cortex cryopreservation on ovarian tissue transplantation. , 2019, Human reproduction.

[24]  M. Montag,et al.  Overnight ovarian tissue transportation for centralized cryobanking: a feasible option. , 2019, Reproductive biomedicine online.

[25]  L. Rienzi,et al.  A brief history of oocyte cryopreservation: Arguments and facts , 2019, Acta obstetricia et gynecologica Scandinavica.

[26]  J. Remohi,et al.  Elective and Onco-fertility preservation: factors related to IVF outcomes , 2018, Human reproduction.

[27]  Yuting Fan,et al.  Cryopreservation and transplantation of ovarian tissue: results from one center in the USA , 2018, Journal of Assisted Reproduction and Genetics.

[28]  J. Remohi,et al.  Oocyte vitrification versus ovarian cortex transplantation in fertility preservation for adult women undergoing gonadotoxic treatments: a prospective cohort study. , 2018, Fertility and sterility.

[29]  Kristin N. Smith,et al.  Long-term outcomes in cancer patients who did or did not pursue fertility preservation. , 2018, Fertility and sterility.

[30]  R. Álvarez,et al.  Fertility preservation in female oncology patients: the influence of the type of cancer on ovarian stimulation response , 2016, Human reproduction.

[31]  M. Ignatiadis,et al.  Reproductive potential and performance of fertility preservation strategies in BRCA-mutated breast cancer patients , 2018, Annals of oncology : official journal of the European Society for Medical Oncology.

[32]  V. Tjan-Heijnen,et al.  Abstract PD6-03: Preserving fertility in young women undergoing chemotherapy for early breast cancer; the Maastricht experience , 2017 .

[33]  L. Esserman,et al.  Fertility preservation with ovarian stimulation and time to treatment in women with stage II–III breast cancer receiving neoadjuvant therapy , 2017, Breast Cancer Research and Treatment.

[34]  M. Hernán,et al.  ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions , 2016, British Medical Journal.

[35]  S. Aviel-Ronen,et al.  Transplantations of frozen-thawed ovarian tissue demonstrate high reproductive performance and the need to revise restrictive criteria. , 2016, Fertility and sterility.

[36]  Morton B. Brown,et al.  Embryo banking among women diagnosed with cancer: a pilot population-based study in New York, Texas, and Illinois , 2016, Journal of Assisted Reproduction and Genetics.

[37]  M. Dolmans,et al.  Utilization rates and results of long-term embryo cryopreservation before gonadotoxic treatment , 2015, Journal of Assisted Reproduction and Genetics.

[38]  G. Bedoschi,et al.  Fertility Preservation Success Subsequent to Concurrent Aromatase Inhibitor Treatment and Ovarian Stimulation in Women With Breast Cancer. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  A. Pellicer,et al.  Obstetric outcome after oocyte vitrification and warming for fertility preservation in women with cancer. , 2014, Reproductive biomedicine online.

[40]  Y. Englert,et al.  Safety and usefulness of cryopreservation of ovarian tissue to preserve fertility: a 12-year retrospective analysis. , 2014, Human reproduction.

[41]  J. Donnez,et al.  Ovarian tissue cryopreservation followed by controlled ovarian stimulation and pick-up of mature oocytes does not impair the number or quality of retrieved oocytes , 2014, Journal of Ovarian Research.

[42]  D. de Ziegler,et al.  Emergency IVF for embryo freezing to preserve female fertility: a French multicentre cohort study. , 2013, Human reproduction.

[43]  K. J. Thong,et al.  Fifteen year follow-up of embryos cryopreserved in cancer patients for fertility preservation , 2013, Journal of Assisted Reproduction and Genetics.

[44]  A. Pellicer,et al.  Five years' experience using oocyte vitrification to preserve fertility for medical and nonmedical indications. , 2013, Fertility and sterility.

[45]  Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. , 2019, Fertility and sterility.

[46]  K. Oktay,et al.  Does higher starting dose of FSH stimulation with letrozole improve fertility preservation outcomes in women with breast cancer? , 2012, Fertility and sterility.

[47]  J. Goldman,et al.  Uptake and outcome of assisted reproductive techniques in long-term survivors of SCT , 2012, Bone Marrow Transplantation.

[48]  C. Farquhar,et al.  Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. , 2012, The Cochrane database of systematic reviews.

[49]  S. Missmer,et al.  Embryo yield after in vitro fertilization in women undergoing embryo banking for fertility preservation before chemotherapy. , 2011, Fertility and sterility.

[50]  Wolfgang Viechtbauer,et al.  Conducting Meta-Analyses in R with the metafor Package , 2010 .

[51]  A. Stang Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses , 2010, European Journal of Epidemiology.

[52]  K. Oktay,et al.  Ovarian cryopreservation and transplantation for fertility preservation for medical indications: report of an ongoing experience. , 2010, Fertility and sterility.

[53]  E. Porcu,et al.  Over 900 oocyte cryopreservation babies born with no apparent increase in congenital anomalies. , 2009, Reproductive biomedicine online.

[54]  Douglas G. Altman,et al.  Chapter 9: Analysing Data and Undertaking Meta-Analyses , 2008 .

[55]  L. Gianaroli,et al.  Birth following vitrification of a small number of human oocytes: case report. , 1999, Human reproduction.