Effects of sequential cleavage and blastocyst embryo transfer on pregnancy outcomes in patients with poor ovarian response

With the development of economy, delaying childbearing has become a social norm. As a result, the proportion of patients with poor ovarian response (POR) has increased in in vitro fertilization-embryo transfer (IVF-ET) cycle in recent years. The estimated incidence of POR varies worldwide from 9% to 24% (Ubaldi et al., 2014, Ubaldi et al., 2005). To date, the management of POR patients remains a major challenge for fertility specialists in IVF. POR patients are mainly characterized by diminished ovarian reserve, inadequate response to controlled ovarian stimulation (COS), and a low number of harvested oocytes and available embryos (Giannelou et al., 2020, Abu-Musa et al., 2020). Consequently, they are less likely to achieve an ideal clinical pregnancy rate and cumulative live birth rate (Youssef et al., 2017, Bastu et al., 2016).

Different interventions have been proposed to deal with the challenges posed by POR to IVF, but few have targeted embryo transfer (ET) strategies (Vaiarelli et al., 2018, Drakopoulos et al., 2020). Extending the culture time to day 5 is beneficial for improving embryo selection. Therefore, blastocyst transfer is associated with a higher implantation rate compared with cleavage-stage ET (Dai et al., 2021). However, this procedure is rarely used to treat poor responders (Goto et al., 2005). Prolonged culture of all the embryos in patients with POR may result in no embryo transfer due to the failure in obtaining blastocysts. This can increase the risk of ET cycle cancellation, bringing great psychological and spiritual stress to the patients. In order to take advantage of both cleavage-stage ET and blastocyst transfer, some scientists have proposed a sequential transfer procedure; that is, the two-step interval transfer of a cleavage-stage embryo (day 3) followed by a blastocyst (day 5/6) in one treatment cycle (Ashkenazi et al., 2000, Kyono et al., 2003). Several studies have reported the effectiveness of sequential transfer in increasing the treatment success rate for some special subgroups of patients (Almog et al., 2008, Machtinger et al., 2006, Tehraninejad et al., 2019). However, in the current clinical practice, sequential transfer is mostly performed to treat patients with repeated implantation failure (RIF). Whether it is applicable to a larger population of infertile patients remains to be confirmed.

Therefore, in this current study, we aimed to evaluate the effectiveness of sequential transfer on pregnancy outcomes in patients with POR. Our findings would help in the management of POR patients.

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