Age a significant factor in reproductive outcome of ovarian tissue freezing plus IVF

Published 11 August 2020

A little more cohort data helps nudge ovarian tissue freezing for medically indicated fertility preservation from the experimental towards the routine; live birth outcomes significantly affected by patient age.

Auto-transplantation of cryopreserved ovarian tissue is increasingly regarded as an important fertility preservation strategy, most frequently indicated in those with a good chance of overcoming diseases such as cancer and the toxic effects of their treatment, particularly prepubertal girls and younger women with insufficient time for egg freezing. As of June 2017, an estimated 130 live births had been recorded worldwide since the first successful delivery in 2004.

Now, two new small-scale retrospective cohort studies suggest that ovarian tissue freezing is moving from an experimental procedure to routine by confirming its efficacy in preserving and restoring fertility, including in cases of prior exposure to chemotherapy, and that the use of frozen embryo transfer versus fresh may enhance outcomes.(1,2) However, the same data raise questions over its efficacy/value in certain indications, notably among women of advanced maternal age, those diagnosed with certain cancers, and patients previously exposed to pelvic radiation.

The results from the first analysis come from three clinical centres (US, Israel and Belgium) and are based on data from 60 infertile patients returning for transplantation following ovarian tissue cryopreservation (age 14 to 39 years) with the aim of conceiving via IVF (n = 33) or spontaneously (n = 27).(1) The majority had had blood cancers.

Based on the findings, ovarian tissue cryopreservation is ‘a highly effective approach to fertility preservation’, write the authors, including for cases of recent chemotherapy, and add that repeat auto-transplantation should be considered for graft malfunction. The results show that menstruation returned in the majority of patients (94%) following 76 transplantations carried out between 2004 and 2018; 50 pregnancies (spontaneous 33, IVF 17) and 44 live births (spontaneous 29, IVF 15) were recorded; and half of the series achieved a least one pregnancy and two in five at least one delivery. Of the 12 patients who had more than one transplantation, three achieved live births, including two who had already delivered a baby successfully after their first transplantation.

Unsurprisingly, age was a key factor in failure to conceive - as was a diagnosis of cervical cancer. The study highlighted a trend towards a higher proportion of women aged 35 and above who were unsuccessful (53.3% vs 26.6%), and a significantly younger age at transplantation among those who became pregnant; the two cervical cancer patients neither recovered endocrine function or achieved pregnancy.

Once again, age proved a statistically significant factor in the second study, which used hospital and clinic records to investigate reproductive outcomes for 28 cancer patients having ovarian tissue freezing (mean age 24.6-35 years) at a single Danish centre between 2012 and 2017, followed by ovarian stimulation in local IVF fertility clinics.(2) However, pregnancy and live birth rates were low (15.2% and 7.1% respectively, with 60% miscarriage). Seven live births resulted from 15 pregnancies in 11 patients (39%) following restoration of ovarian function. Of those who did achieve a live birth (n = 5), the mean age at transplantation was significantly lower than found in unsuccessful patients, of whom 12 were aged 35 and above.

Older women treated for breast cancer appeared from the study to do worse than those with other diagnoses. Indeed, pregnancy and live birth rates for these patients were significantly lower (35% and 5% respectively) per embryo transfer than for others (50% and 37.5% respectively), and the only breast cancer patient who achieved a live birth was younger (age at transplantation 25.9 years). The findings also add to the debate over FET versus fresh, with the former resulting in more pregnancies (eight pregnancies/11 FETs vs seven pregnancies/25 fresh).

What neither study attempts to address is whether the auto-transplantation of cryopreserved ovarian tissue is preferable to egg freezing in post-pubertal patients who have sufficient time for ovarian stimulation before chemotherapy. That is a question, say the authors, that remains to be resolved. Low rates of patients returning for transplantation also limit the strength of the data, as acknowledged by the authors of the first study. However, the results will add a little more to what we know of this fertility preservation strategy as it emerges from its experimental phase, and allow a little better understanding of who benefits the most.

1. Moran S, Dolmans M, Silber S, Meirow D. Evaluation of ovarian tissue transplantation: results from three clinical centers. Fertil Steril 2020; doi: 10.1016/j.fertnstert.2020.03.037 
2. Hjorth I, Kristensen S, Dueholm M, Humaidan P. Reproductive outcomes after in vitro fertilization treatment in a cohort of Danish women transplanted with cryopreserved ovarian tissue. Fertil Steril 2020; doi.org/10.1016/j.fertnstert.2020.03.035

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