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IVF Clinical

Frozen embryo transfers in a natural cycle: how to do it right

Accepted: May 11, 2023


In the recent years of assisted reproductive technol-ogy (ART), treatments have seen a significant shift in the embryo transfer strategy from fresh (fresh embryo transfers) to FET cycles. This fact has even being formulated as a paradigm shift with the absence of an indication for fresh embryo transfers [1].

Endometrial preparation for a FET cycle can be performed either in an artificial, medicated cycle with or without downregulation, in which estrogens and progesterone are sequentially administered to mimic the hormonal course of the natural cycle, as modified natural cycle (mNC) with or without hor-monal stimulation of the follicle growth and ovu-lation induction to plan the embryo transfer and as a ‘pure’ natural cycle (pNC), without any interference through exogenously administered hormones with the timing of the embryo transfer depending on the ovulation and progesterone rise [2].

Recent evidence suggests that the endometrial preparation for FET has important implications on the pregnancy itself, hence the question of how to prepare the endometrium for FET has gained even more importance and taken on a new dimension as it should not simply be reduced to the basic question of ‘which approach will result in superior pregnancy rates?’ but instead ‘which approach will result in the best pregnancy rates and the safest outcome for mother and baby?’ [3].

Compared with artificial, medicated cycles, pNC cycles have a significantly lower incidence for bleeding and miscarriages in early pregnancy [4&].

In later pregnancy, artificial, medicated cycle cycles exhibit an increased risk of hypertensive disorders, preeclampsia and delivery via Caesarean section and natural cycle lead to a significantly higher live birth rate [4& ,5–9]. Table 1 summarizes the different approaches forendometrial preparation and the advantages and disadvantages/risks.

The pNC approach is limited to women with undisturbed follicle growth, ovulation and an adequate luteal phase. However, even in women with regular cycles, there is a distinct variation amongst women and from cycle to cycle [10,11]. So, the challenge and the ‘real ART’ in the pNC- approach is to correctly identify ovulation and adequate progesterone rise, inducing the secretory transformation of the lining. The aim of this review it to summarize recent evidence and to elucidate the question of ‘How to do it right?’.