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Long term pregnancy outcomes of women with cancer following fertility preservation: A systematic review and meta-analysis

Published:December 09, 2022DOI:https://doi.org/10.1016/j.ejogrb.2022.12.016

      Highlights

      • Only 8% of women returned to use their frozen reproductive material (558/7037, 8.0%), resulting in 210 live births in total, including assisted conceptions following EC/OC/OTC and natural conceptions following OTC.
      • The cumulative live birth rate following any fertility preservation treatment was 0.046 (95 %CI 0.029–0.066).
      • The overall LBR was highest in women who had EC (OR 0.45, 95 %CI 0.14–0.76), followed by OTC group (OR 0.37, 95 %CI 0.22–0.53) and OC group (OR 0.31, 95 %CI 0.15–0.47).
      • There was limited reporting on other important reproductive outcomes in this cohort including miscarriages, ectopic pregnancies and Caesarean sections rate.

      Abstract

      Objective

      As cancer survivorship increases, there is higher uptake of fertility preservation treatments among affected women. However, there is limited evidence on the subsequent use of preserved material and pregnancy outcomes in women who underwent fertility preservation (FP) before cancer treatments. We aimed to systematically review the long-term reproductive and pregnancy outcomes in this cohort of women.

      Patients

      Women who underwent any type of the following FP treatments: embryo cryopreservation (EC), oocyte cryopreservation (OC) and ovarian tissue cryopreservation (OTC)) before any planned cancer treatment.

      Evidence review

      We searched electronic databases (MEDLINE, Embase, Cochrane CENTRAL, and HTA) from inception until May 2021 for all observational studies that met our inclusion criteria. We extracted data on reproductive and pregnancy outcomes in duplicate and assessed the risk of bias in included studies using the ROBINS-I tool. We pooled data using a random-effects model and reported using odds ratios (OR) with 95% confidence intervals (CI).

      Main outcome measures

      Our primary outcome was live birth rate and other important reproductive and pregnancy outcomes.

      Results

      Of 5405 citations, we screened 103 and included 26 observational studies (n = 7061 women). Hematologic malignancy was the commonest cause for seeking FP treatments, followed by breast and gynecology cancers. Twelve studies reported on OTC (12/26, 46 %), eight included EC (8/26, 30 %), and twelve reported on OC (12/26, 46 %). The cumulative live birth rate following any FP treatment was 0.046 (95 %CI 0.029–0.066). Only 8 % of women returned to use their frozen reproductive material (558/7037, 8.0 %), resulting in 210 live births in total, including assisted conceptions following EC/OC/OTC and natural conceptions following OTC. The odds for live birth was OR 0.38 (95 %CI 0.29–0.48 I2 83.7 %). The odds for live birth was the highest among women who had EC (OR 0.45, 95 %CI 0.14–0.76, I2 95.1 %), followed by the OTC group (OR 0.37, 95 %CI 0.22–0.53, I2 88.7 %) and OC group (OR 0.31, 95 %CI 0.15–0.47, I2 78.2 %).

      Conclusions

      Fertility preservation treatments offered good long-term reproductive outcomes for women with cancer with a high chance to achieve a live birth. Further research is needed to evaluate the long-term pregnancy and offspring outcomes in this cohort.

      Keywords

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      References

        • Griffiths M.J.
        • Winship A.L.
        • Hutt K.J.
        Do cancer therapies damage the uterus and compromise fertility?.
        Hum Reprod Update. 2019; 26: 161-173
        • van Dorp W.
        • Haupt R.
        • Anderson R.A.
        • Mulder R.L.
        • van den Heuvel-Eibrink M.M.
        • van Dulmen-den B.E.
        • et al.
        Reproductive Function and Outcomes in Female Survivors of Childhood, Adolescent, and Young Adult Cancer: A Review.
        J Clin Oncol. 2018; 36: 2169-2180
        • Arnold M.
        • Rutherford M.J.
        • Bardot A.
        • Ferlay J.
        • Andersson T.M.
        • Myklebust T.
        • et al.
        Progress in cancer survival, mortality, and incidence in seven high-income countries 1995–2014 (ICBP SURVMARK-2): a population-based study.
        Lancet Oncol. 2019; 20: 1493-1505
        • Anderson R.A.
        • Brewster D.H.
        • Wood R.
        • Nowell S.
        • Fischbacher C.
        • Kelsey T.W.
        • et al.
        The impact of cancer on subsequent chance of pregnancy: a population-based analysis.
        Hum Reprod. 2018; 33: 1281-1290
        • Ruddy K.J.
        • Gelber S.I.
        • Tamimi R.M.
        • Ginsburg E.S.
        • Schapira L.
        • Come S.E.
        • et al.
        Prospective study of fertility concerns and preservation strategies in young women with breast cancer.
        J Clin Oncol. 2014; 32: 1151-1156
        • Ruggeri M.
        • Pagan E.
        • Bagnardi V.
        • Bianco N.
        • Gallerani E.
        • Buser K.
        • et al.
        Fertility concerns, preservation strategies and quality of life in young women with breast cancer: Baseline results from an ongoing prospective cohort study in selected European Centers.
        Breast. 2019; 47: 85-92
        • Bastings L.
        • Baysal Ö.
        • Beerendonk C.C.
        • IntHout J.
        • Traas M.A.
        • Verhaak C.M.
        • et al.
        Deciding about fertility preservation after specialist counselling.
        Hum Reprod. 2014; 29: 1721-1729
        • Niederberger C.
        • Pellicer A.
        • Cohen J.
        • Gardner D.K.
        • Palermo G.D.
        • O'Neill C.L.
        • et al.
        Forty years of IVF.
        Fertil Steril. 2018; 110: 185-324.e5
        • Pfeifer S.
        Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion.
        Fertil Steril. 2013; 100: 1214-1223
        • Oktay K.
        • Harvey B.E.
        • Partridge A.H.
        • Quinn G.P.
        • Reinecke J.
        • Taylor H.S.
        • et al.
        Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update.
        J Clin Oncol. 2018; 36: 1994-2001
        • Kazer R.
        • Penzias A.
        • Bendikson K.
        • Falcone T.
        Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion.
        Fertil Steril. 2019; 112: 1022-1033
        • Anderson R.A.
        • Amant F.
        • Braat D.
        • D'Angelo A.
        • de Sousa C.
        • Lopes S.M.
        • et al.
        ESHRE guideline: female fertility preservation†.
        Hum Reprod Open. 2020; 2020
        • Cobo A.
        • García-Velasco J.
        • Domingo J.
        • Pellicer A.
        • Remohí J.
        Elective and Onco-fertility preservation: factors related to IVF outcomes.
        Hum Reprod. 2018; 33: 2222-2231
        • Mascarenhas M.
        • Mehlawat H.
        • Kirubakaran R.
        • Bhandari H.
        • Choudhary M.
        Live birth and perinatal outcomes using cryopreserved oocytes: an analysis of the Human Fertilisation and Embryology Authority database from 2000 to 2016 using three clinical models.
        Hum Reprod. 2021; 36: 1416-1426
        • Shenfield F.
        • de Mouzon J.
        • Scaravelli G.
        • Kupka M.
        • Ferraretti A.P.
        • Prados F.J.
        • et al.
        Oocyte and ovarian tissue cryopreservation in European countries: statutory background, practice, storage and use†.
        Hum Reprod Open. 2017; 2017
        • Alikani M.
        • Parmegiani L.
        Human Reproductive Cell Cryopreservation, Storage, Handling, and Transport: Risks and Risk Management.
        Semin Reprod Med. 2018; 36: 265-272
        • Klipstein S.
        • Fallat M.E.
        • Savelli S.
        Fertility Preservation for Pediatric and Adolescent Patients With Cancer: Medical and Ethical Considerations.
        Pediatrics. 2020; 145
        • Liberati A.
        • Altman D.G.
        • Tetzlaff J.
        • Mulrow C.
        • Gøtzsche P.C.
        • Ioannidis J.P.
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
        PLoS Med. 2009; 6: e1000100
        • Sterne J.A.
        • Hernán M.A.
        • Reeves B.C.
        • Savović J.
        • Berkman N.D.
        • Viswanathan M.
        • et al.
        ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions.
        BMJ. 2016; 355i4919
        • Schünemann H.J.
        • Higgins J.P.
        • Vist G.E.
        • Glasziou P.
        • Akl E.A.
        • Skoetz N.
        • et al.
        Completing ‘Summary of findings’ tables and grading the certainty of the evidence.
        Cochrane Handbook for Systematic Reviews of Interventions. 2019; : 375-402
        • Laird N.M.
        • Ware J.H.
        Random-Effects Models for Longitudinal Data.
        Biometrics. 1982; 38: 963-974
        • Miller J.J.
        The Inverse of the Freeman – Tukey Double Arcsine Transformation.
        Am Stat. 1978; 32(4):138-
        • Higgins J.P.
        • Thompson S.G.
        • Deeks J.J.
        • Altman D.G.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Sterne J.A.
        • Egger M.
        Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis.
        J Clin Epidemiol. 2001; 54: 1046-1055
        • Egger M.
        • Davey Smith G.
        • Schneider M.
        • Minder C.
        Bias in meta-analysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        • Oktay K.
        • Turan V.
        • Bedoschi G.
        • Pacheco F.S.
        • Moy F.
        Fertility Preservation Success Subsequent to Concurrent Aromatase Inhibitor Treatment and Ovarian Stimulation in Women With Breast Cancer.
        J Clin Oncol. 2015; 33: 2424-2429
        • Lotz L.
        • Barbosa P.R.
        • Knorr C.
        • Hofbeck L.
        • Hoffmann I.
        • Beckmann M.W.
        • et al.
        The safety and satisfaction of ovarian tissue cryopreservation in prepubertal and adolescent girls.
        Reprod Biomed Online. 2020; 40: 547-554
        • Rodriguez-Wallberg K.A.
        • Tanbo T.
        • Tinkanen H.
        • Thurin-Kjellberg A.
        • Nedstrand E.
        • Kitlinski M.L.
        • et al.
        Ovarian tissue cryopreservation and transplantation among alternatives for fertility preservation in the Nordic countries - compilation of 20 years of multicenter experience.
        Acta Obstet Gynecol Scand. 2016; 95: 1015-1026
        • Courbiere B.
        • Decanter C.
        • Bringer-Deutsch S.
        • Rives N.
        • Mirallié S.
        • Pech J.C.
        • et al.
        Emergency IVF for embryo freezing to preserve female fertility: a French multicentre cohort study.
        Hum Reprod. 2013; 28: 2381-2388
        • Beckmann M.W.
        • Dittrich R.
        • Lotz L.
        • van der Ven K.
        • van der Ven H.H.
        • Liebenthron J.
        • et al.
        Fertility protection: complications of surgery and results of removal and transplantation of ovarian tissue.
        Reprod Biomed Online. 2018; 36: 188-196
        • Hulsbosch S.
        • Koskas M.
        • Tomassetti C.
        • De Sutter P.
        • Wildiers H.
        • Neven P.
        • et al.
        A Real-Life Analysis of Reproductive Outcome after Fertility Preservation in Female Cancer Patients.
        Gynecol Obstet Invest. 2018; 83: 156-163
        • Pretalli J.B.
        • Frontczak Franck S.
        • Pazart L.
        • Roux C.
        • Amiot C.
        Development of Ovarian Tissue Autograft to Restore Ovarian Function: Protocol for a French Multicenter Cohort Study.
        JMIR Res Protoc. 2019; 8: e12944
        • Poirot C.
        • Fortin A.
        • Lacorte J.M.
        • Akakpo J.P.
        • Genestie C.
        • Vernant J.P.
        • et al.
        Impact of cancer chemotherapy before ovarian cortex cryopreservation on ovarian tissue transplantation.
        Hum Reprod. 2019; 34: 1083-1094
        • Martinez M.
        • Rabadan S.
        • Domingo J.
        • Cobo A.
        • Pellicer A.
        • Garcia-Velasco J.A.
        Obstetric outcome after oocyte vitrification and warming for fertility preservation in women with cancer.
        Reprod Biomed Online. 2014; 29: 722-728
        • Abel M.K.
        • Wald K.
        • Sinha N.
        • Letourneau J.M.
        • Simbulan R.
        • Mok-Lin E.
        • et al.
        Conception after chemotherapy: post-chemotherapy method of conception and pregnancy outcomes in breast cancer patients.
        J Assist Reprod Genet. 2021; 38: 1755-1765
        • Alvarez R.M.
        • Ramanathan P.
        Fertility preservation in female oncology patients: the influence of the type of cancer on ovarian stimulation response.
        Hum Reprod. 2018; 33: 2051-2059
        • Cobo A.
        • García-Velasco J.A.
        • Coello A.
        • Domingo J.
        • Pellicer A.
        • Remohí J.
        Oocyte vitrification as an efficient option for elective fertility preservation.
        Fertil Steril. 2016; 105: 755
        • Anderson R.A.
        • Kelsey T.W.
        • Morrison D.S.
        • Wallace W.H.B.
        Family size and duration of fertility in female cancer survivors: a population-based analysis.
        Fertil Steril. 2022; 117: 387-395
      1. Zaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2021;2(2):Cd011184.

        • Loren A.W.
        • Mangu P.B.
        • Beck L.N.
        • Brennan L.
        • Magdalinski A.J.
        • Partridge A.H.
        • et al.
        Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update.
        J Clin Oncol. 2013; 31: 2500-2510
        • Rosendahl M.
        • Andersen M.T.
        • Ralfkiær E.
        • Kjeldsen L.
        • Andersen M.K.
        • Andersen C.Y.
        Evidence of residual disease in cryopreserved ovarian cortex from female patients with leukemia.
        Fertil Steril. 2010; 94: 2186-2190
        • Gellert S.E.
        • Pors S.E.
        • Kristensen S.G.
        • Bay-Bjørn A.M.
        • Ernst E.
        • Yding A.C.
        Transplantation of frozen-thawed ovarian tissue: an update on worldwide activity published in peer-reviewed papers and on the Danish cohort.
        J Assist Reprod Genet. 2018; 35: 561-570
        • Segers I.
        • Bardhi E.
        • Mateizel I.
        • Van Moer E.
        • Schots R.
        • Verheyen G.
        • et al.
        Live births following fertility preservation using in-vitro maturation of ovarian tissue oocytes.
        Hum Reprod. 2020; 35: 2026-2036
        • Anderson R.A.
        • Amant F.
        • Braat D.
        • D'Angelo A.
        • de Sousa C.
        • Lopes S.M.
        • et al.
        ESHRE guideline: female fertility preservation.
        Hum Reprod Open. 2020;2020(4):hoaa052.;
        • Melville J.
        • Stringer A.
        • Black N.
        • Quenby S.
        • Keay S.D.
        • David A.L.
        • et al.
        The impact of assisted reproductive technology treatments on maternal and offspring outcomes in singleton pregnancies: a review of systematic reviews.
        F&S Reviews. 2021; 2: 287-301
        • Nijagal M.A.
        • Wissig S.
        • Stowell C.
        • Olson E.
        • Amer-Wahlin I.
        • Bonsel G.
        • et al.
        Standardized outcome measures for pregnancy and childbirth, an ICHOM proposal.
        BMC Health Serv Res. 2018; 18: 953
        • Harrison C.
        • Gameiro S.
        • Boivin J.
        Patient willingness, preferences and decision-making about planning for three complete cycles of IVF/ICSI treatment.
        Hum Reprod. 2021; 36: 1339-1352
        • Daly C.
        • Micic S.
        • Facey M.
        • Speller B.
        • Yee S.
        • Kennedy E.D.
        • et al.
        A review of factors affecting patient fertility preservation discussions & decision-making from the perspectives of patients and providers.
        Eur J Cancer Care (Engl). 2019; 28: e12945
        • Lawson A.K.
        • Klock S.C.
        • Pavone M.E.
        • Hirshfeld-Cytron J.
        • Smith K.N.
        • Kazer R.R.
        Psychological counseling of female fertility preservation patients.
        J Psychosoc Oncol. 2015 Jul 4; 33: 333-353
        • Mulder R.L.
        • Font-Gonzalez A.
        • van Dulmen-den Broeder E.
        • Quinn G.P.
        • Ginsberg J.P.
        • Loeffen E.A.
        • et al.
        Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.
        Lancet Oncol. 2021; 22: e68-e80
        • Khattak H.
        • Malhas R.
        • Craciunas L.
        • Afifi Y.
        • Amorim C.A.
        • Fishel S.
        • et al.
        Fresh and cryopreserved ovarian tissue transplantation for preserving reproductive and endocrine function: a systematic review and individual patient data meta-analysis.
        Hum Reprod Update. 2022 May; 28: 400-416