Importance of patient selection to analyze in vitro fertilization outcome with transplanted cryopreserved ovarian tissue

Importance of patient selection to analyze in vitro fertilization outcome with transplanted cryopreserved ovarian tissue


Go to the profile of Ina Marie Dueholm Hjorth
almost 2 years ago

Comment to the Editorial by Dolmans et al., 2020:

The aim of our study, Dueholm Hjorth et al., 2020, was to evaluate the pregnancy rate (PR) and live birth rate (LBR) per cycle and embryo transfer in a cohort of Danish women undergoing ovarian tissue transplantation (OTT) and IVF in order to compare results with the general IVF-population. In the current editorial by Dolmans et al., 2020, the authors argue that our reported LBR is not comparable to current literature and significantly lower than previously reported. However, the literature referred to in the editorial by Dolmans et al., 2020 importantly, also includes spontaneous conceptions and subsequent live births. As our LBR is based on IVF outcomes only, the discussion of our results in the context of LBRs including transplanted women conceiving spontaneously is inappropriate and mistaken.

The poor IVF outcomes in our cohort of Danish patients undergoing OTT and IVF are not surprising or contradicting in light of our recently published systematic review, reporting PR and LBR of 14.4% and 10.3% per cycle, respectively, in 40 transplanted women undergoing OTT and IVF worldwide (Andersen et al., 2019). The low LBR (7.1% per cycle) reported in our cohort is mainly caused by very poor IVF outcomes in older (>35 years) breast cancer patients which corroborates previous studies, highlighting that age at OTC is a determining factor, which  affects reproductive outcomes in transplanted women. For other diagnoses than breast cancer in which patients were younger at OTC we found a higher LBR of 29%.

Further, the authors of the current editorial argue that skewed patient selection and incomplete data collection may leave the readers with doubts on the efficacy of OTT. However, by including all patients undergoing OTT and IVF from 2012-2019 in a single center our cohort represent an unselected population of patients which in the last two decades have been offered OTC as a fertility preserving measure. It is well known that transplanted women have a reduced ovarian reserve due to the huge loss of ovarian follicles after OTT and it is not surprising that this cohort of patients undergoing IVF after OTT belongs to the poor prognosis clientele (Andersen et al., 2019).

 Our results in Dueholm Hjorth et al., 2020, indeed reflect outcomes from patients with poor prognosis, but unfortunately this is ‘real life’ – this is the situation for these patients and for daily clinical practice, and as highlighted, this is indeed a very heterogeneous population in which we were not able to extrapolate clinical results according to individual patients and their reproductive history, cancer treatment, personal choices, etc. This cohort of Danish patients was referred to IVF treatment when spontaneous conception failed and as such our study adds very valuable information and insight into the IVF-treatment (ovarian stimulation regimes, fresh versus FET etc.) of these patients transplanted with cryopreserved tissue.

Reporting negative as well as positive outcomes for transplanted women in a whole cohort including a diverse population of patients is of great clinical importance to pinpoint which patients benefit the most from the procedure – and importantly, who does not benefit in terms of reproductive outcomes. We agree that the current results should be interpreted with caution due to the heterogeneity, but at the same time readers should be aware that the reproductive outcomes of OTT patients who do not conceive spontaneously, and thus have to rely on IVF treatment are not very favorable and that further optimization of OTC-OTT is warranted

In conclusion, we agree with Dolmans et al., that OTC and OTT have indeed proven to be efficient for some patient categories, that the OTC-OTT technique is a well-established and should be offered to primarily patients as a valid way of preserving and subsequently restoring ovarian function. However, we question the  efficacy of the procedure in older patients, and in OTTwomen who do not conceive spontaneously. When IVF is the only alternative after OTT, the reproductive outcomes are poor and patients should be counseled accordingly.

/ Ina Marie D Hjorth, Stine Gry Kristensen, Margit Dueholm and Peter Humaidan.