Ovarian function and fertility preservation for young people treated for cancer

Further advances in the treatment of young people with cancer have led to improved survival, with 85.6% 5-year relative survival for ages 0–14 in the USA for the years 2010–2016 [18]. However, successful cancer treatment during childhood can cause infertility and premature ovarian insufficiency (POI) in some patients [20, 33]. The risk of developing POI is dependent on a number of factors, which include the nature of the underlying disease and the planned therapy. Both chemotherapy and radiotherapy have been shown to affect ovarian function either directly by depleting the primordial follicle pool or indirectly via effects on hormonal regulation of ovarian function.Postprin

Fertility preservation in pre-pubertal girls with cancer : the role of ovarian tissue cryopreservation

Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.With increasing numbers of survivors of cancer in young people future fertility and ovarian function are important considerations that should be discussed before treatment commences. Some young people, by nature of the treatment they will receive, are at high risk of premature ovarian insufficiency and infertility. For them, ovarian tissue cryopreservation (OTC) is one approach to fertility preservation that remains both invasive and for young patients experimental. There are important ethical and consent issues that need to be explored and accepted before OTC can be considered established in children with cancer. In this review we have discussed a framework for patient selection which has been shown to be effective in identifying those patients at high risk of premature ovarian insufficiency (POI) and who can be offered OTC safely.PostprintPeer reviewe

Human ovarian reserve from conception to the menopause

Current understanding is that the human ovary contains a fixed number of several million non-growing follicles (NGF), established by five months of gestational age, that declines with increasing age to the menopause when approximately 1,000 NGF remain at an average age of 50-51 years. With approximately 450 ovulatory monthly cycles in the normal human reproductive lifespan, this progressive decline in NGF numbers is attributed to follicle death by apoptosis. Individual histological studies have quantified NGF numbers over limited age ranges. However, no model describing the rate of establishment and decline of the NGF population from conception to menopause has been previously reported. Here we describe the best fitting model of the age-related NGF population in the human ovary from conception to menopause. Our model matches the log-adjusted NGF population to a five-parameter asymmetric double Gaussian cumulative (ADC) curve (r2 = 0.81). Furthermore we found that the rate of NGF recruitment into growing follicles for all women increases from birth until approximately age 14 years (coinciding with puberty) then decreases towards the menopause. The explanation for this new finding remains unclear but is likely to involve both paracrine and endocrine factors. We describe and analyse the best fitting model for the establishment and decline of human NGF; our model extends our current understanding of human ovarian reserve

The effect of radiotherapy on the human reproductive system

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Family size and duration of fertility in female cancer survivors : a population based analysis

Funder: R.A.A. reports grant from Medical Research Council for the submitted work (Grant No. MR/N022556/1). T.W.K. has nothing to disclose. D.S.M. has nothing to disclose. W.H.B.W. has nothing to disclose.Objective: To assess family size and timescale for achieving pregnancy in women who remain fertile after cancer. Design: Population-based analysis. Setting: National databases. Patient(s): All women diagnosed with cancer before the age of 40 years in Scotland, 1981–2012 (n = 10,267) with no previous pregnancy; each was matched with 3 population controls. Intervention(s): None. Main Outcome Measure(s): The number and timing of pregnancy and live birth after cancer diagnosis, to 2018. Result(s): In 10,267 cancer survivors, the hazard ratio for a subsequent live birth was 0.56 (95% confidence interval, 0.53–0.58) overall. In women who achieved a subsequent pregnancy, age at live birth increased (mean ± SD, 31.2 ± 5.5 vs. 29.7 ± 6.1 in controls), and the family size was lower (2.0 ± 0.8 vs. 2.3 ± 1.1 live births). These findings were consistent across several diagnoses. The interval from diagnosis to last pregnancy was similar to that of controls (10.7 ± 6.4 vs. 10.9 ± 7.3 years) or significantly increased, for example, after breast cancer (6.2 ± 2.8 vs. 5.3 ± 3.3 years) and Hodgkin lymphoma (11.1 ± 5.1 vs. 10.1 ± 5.8 years). Conclusion(s): These data quantify the reduced chance of live birth after cancer. Women who subsequently conceived achieved a smaller family size than matched controls, but the period of time after cancer diagnosis across which pregnancies occurred was similar or, indeed, increased. Thus, we did not find evidence that women who were able to achieve a pregnancy after cancer had a shorter timescale over which they have pregnancies.Publisher PDFPeer reviewe

Re-implantation of cryopreserved ovarian cortex resulting in restoration of ovarian function, natural conception and successful pregnancy after haematopoietic stem cell transplantation for Wilms tumour

With the improvement of long-term cancer survival rates, growing numbers of female survivors are suffering from treatment-related premature ovarian insufficiency (POI). Although pre-treatment embryo and oocyte storage are effective fertility preservation strategies, they are not possible for pre-pubertal girls or women who cannot delay treatment. In these cases, the only available treatment option is ovarian cortex cryopreservation and subsequent re-implantation. A 32-year-old woman had ovarian cortex cryopreserved 10 years previously before commencing high-dose chemotherapy and undergoing a haematopoietic stem cell transplant for recurrent adult Wilms tumour, which resulted in POI. She underwent laparoscopic orthotopic transplantation of cryopreserved ovarian cortex to the original site of biopsy on the left ovary. She ovulated at 15 and 29 weeks post-re-implantation with AMH detectable, then rising, from 21 weeks, and conceived naturally following the second ovulation. The pregnancy was uncomplicated and a healthy male infant was born by elective Caesarean section at 36(+4) weeks gestation. This is the first report of ovarian cortex re-implantation in the UK. Despite the patient receiving low-risk chemotherapy prior to cryopreservation and the prolonged tissue storage duration, the re-implantation resulted in rapid restoration of ovarian function and natural conception with successful pregnancy

Fertility preservation for girls and young women with cancer: population-based validation of criteria for ovarian tissue cryopreservation

This study was partly funded by the UK Medical Research Council grant G1100357 (to RAA). Open Access funded by Department of Health UK.Background: Ovarian tissue cryopreservation with later reimplantation has been shown to preserve fertility in adult women, but this approach remains unproven and experimental in children and adolescents. We aimed to assess the use of the Edinburgh selection criteria for ovarian tissue cryopreservation in girls and young women with cancer to determine whether we are offering this invasive procedure to the patients who are most at risk of premature ovarian insufficiency. Methods: Cryopreservation of ovarian tissue has been selectively offered to girls and young women with cancer who met the Edinburgh selection criteria since 1996. Between Jan 1, 1996, and June 30, 2012, 410 female patients younger than 18 years at diagnosis were treated for cancer (including leukaemia and brain tumours) at the Edinburgh Children's Cancer Centre, which serves the whole South East of Scotland region. We determined the ovarian status of these patients from review of clinical records and classified them as having premature ovarian insufficiency or not, or as unable to be determined. Patients younger than 12 years at time of data cutoff (Jan 31, 2013) were excluded from the analysis. Findings: 34 (8%) of the 410 patients met the Edinburgh selection criteria and were offered ovarian tissue cryopreservation before starting cancer treatment. 13 patients declined the procedure and 21 consented, and the procedure was completed successfully in 20 patients. Of the 20 patients who had ovarian tissue successfully cryopreserved, 14 were available for assessment of ovarian function. Of the 13 patients who had declined the procedure, six were available for assessment of ovarian function. Median age at the time of follow-up for the 20 assessable patients was 16·9 years (IQR 15·5-21·8). Of the 14 assessable patients who had successfully undergone ovarian cryopreservation, six had developed premature ovarian insufficiency at a median age of 13·4 years (IQR 12·5-14·6), one of whom also had a natural pregnancy. Of the six assessable patients who had declined the procedure, one had developed premature ovarian insufficiency. Assessment of ovarian function was possible for 141 of the 376 patients who were not offered cryopreservation; one of these patients had developed premature ovarian insufficiency. The cumulative probability of developing premature ovarian insufficiency after treatment was completed was significantly higher for patients who met the criteria for ovarian tissue cryopreservation than for those who did not (15-year probability 35% [95% CI 10-53] vs 1% [0-2]; pPublisher PDFPeer reviewe