Abstract

This study investigated the combination of an unstimulated IVF cycle with in-vitro maturation (IVM) of additional immature cumulus–oocyte–complexes (COC) from the same cycle collected at the same time as the spontaneous preovulatory follicle. This could potentially improve rates of embryo transfer and pregnancy/live births compared with conventional unstimulated IVF treatment and at the same time eliminate the risk of ovarian hyperstimulation syndrome. This prospective trial included 77 women with regular menstrual cycles. Age at inclusion was between 20 and 37 years. Results showed a retrieval rate of mature oocytes of 50/80 (62.5%) per cycle started and immature COC were collected in 74/80 (92.5%) cycles. The embryo transfer rate was 28/80 (35.0%) with mature oocytes and increased in total to 43/80 (53.8%) with IVM oocytes. Corresponding birth rates per transfer were 3/28 (10.7%) and 4/43 (9.3%). Birth rates per aspiration were 3/76 (3.9%) and 4/76 (5.3%). It is concluded that the protocol described here shows proof of concept, but the impact of the IVM procedure only reached a significant level regarding embryo transfer, not with live births. The reason for this is yet unclear, but asynchrony between endometrial factors and IVM oocytes together with unknown competence of IVM embryos is suspected. For some time, there has been an increasing interest in mild approaches for fertility treatment, in particular IVF. In-vitro maturation (IVM) of immature eggs outside the ovaries followed by IVF is one of the potential treatments which eliminates the risk of ovarian hyperstimulation syndrome and minimizes the side-effects of medication. At the same time, natural-cycle IVF without hormonal stimulation is also experiencing a revival. By combining IVM and natural-cycle IVF, we aimed for to improve success rates in terms of more fertilized eggs to transfer and higher number of pregnancies and live births compared with sole natural-cycle IVF. At the same time, this project was a pilot study of eggs retrieved at this particular stage of the spontaneous menstrual cycle. Their reproductive capacity might be different from eggs retrieved in an earlier phase regarding maturation and fertilization capacity. The results showed that outcome was not better in the protocol combining IVM and natural-cycle IVF compared with natural-cycle IVF only. The reproductive capacity of the retrieved immature eggs seems less than reported in other IVM protocols. Though the combined concept of IVM and natural-cycle IVF is possible and there are ongoing pregnancies from both IVM and in-vivo matured eggs, we recommend either optimizing an IVM programme or using natural-cycle IVF rather than our original approach.

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