Embryo transfer is a key step for successful pregnancy of women through assisted reproduction, but this process may face cycle cancellation because of no oocyte retrieved, no normal zygote formed, or no available embryos. Considering the inherent poor outcomes, most studies have excluded patients with cycle cancellation at the beginning of research (1–3). The ESPART study reported the prevalence of cycle cancellation was 4.7% in poor responders (4), and another survey showed the risk of cycle cancellation caused by poor ovarian response was about 20% (5). However, the prevalence in the general population receiving in vitro fertilization (IVF) is obscure. A French study examined medical factors associated with early cessation of IVF in 5135 couples and found that couples who did undergo no embryo transfer during the first IVF cycle attempt were more likely to stop treatment early (6). Other studies (7–10) have found that the psychological burden of failure in non-pregnancy treatment is the reason for withdrawing from further treatment. There are currently few reports on the clinical outcome of follow-up treatment in these patients, but it is necessary to provide these patients with information about the final clinical outcome in all institutions carrying out the artificial reproduction technology (ART).

Based on the above observational studies and to answer the consultation of patients with no transplantable embryo in their first IVF cycle attempt, this study was performed to investigate the outcome of future fertility of patients undergoing their first IVF cycle attempt with no embryos transplanted as well as to identify factors that might affect the possibility to get a baby in subsequent IVF cycle attempt.

This study evaluated the chance of a live birth in women with no embryo transfer at their first IVF cycle attempt over their subsequent IVF treatment course and factors affecting the live birth.

In our center, the total cycle cancellation rate was nearly 10%, and the cancellation rate of the first cycle was 4.9%. This may be related to embryo transfer strategies as well as the ovarian stimulation protocols used in our hospital. For example, the cycle cancellation rate of low ovarian response with minimal stimulation was 10% while that with long protocol was 2.9% (12). A meta-analysis in 2021 showed that the cycle cancellation rate of mild stimulation was higher than that of conventional ovarian stimulation in the low ovarian response group (13). Siristatidis et al (14) also found that the cycle cancellation rate of mild stimulation was significantly higher than that of long-term and antagonist regimens (36.4% vs 12%). A recent study showed that participants experienced an overall feeling of “loss and loneliness” when they had no experience of embryo transfer. The situation was described as a shock unprepared for them. Their need for relevant information has not been met (15). The results of the present study showed that some data could provide these patients with some information in terms of no embryo transfer in their first IVF cycle attempt.

In the group with no egg retrieved, the proportion of the patients in the first IVF cycle cancellation was 21.54% [(121 + 50)/(496 + 298)], and 22 of these women achieved a live birth in their subsequent cycles. Furthermore, there was no significant difference in the cycle source and the mode of fertilization through analysis of the original data. In patients with no eggs being retrieved in our study, the ovarian response was low, and their average age was higher than those in the other two groups. In the end, a 18% cumulative live birth rate was achieved in these patients after the 5th IVF cycle, which was similar to that of the study by Raoul Orvieto et al. (16). For these patients, the reproductive outcome will not change after the 5th IVF OPU cycle being tried, and the next ovulation stimulation cycle is suggested to be abandoned. Nonetheless, the patient’s own decision should always be respected.

The proportion of women with no normal zygotes formed in the first IVF cycle cancellation was 23.43% [(138 + 48)/(496 + 298)], and 40 of the 138 patients achieved a live birth eventually. In our hospital, when the number of eggs retrieved was less than or equal to 3, ICSI was not rescued. The majority of these patients had fewer eggs retrieved, which might be one reason for fertilization failure. Even though there was no significant difference in the fertilization methods (IVF vs ICSI) in the live birth cycle (9.46%vs13.27%), 54 cases were changed to ICSI after the first cycle of IVF, and 13 cases obtained a live birth, with the live birth rate of 24.07%. According to these outcomes, changing the mode of insemination in the second cycle may bring a better outcome. Some scholars (17) found that compared with the hCG single trigger group, the oocyte fertilization rate (73.1% vs 58.6%), clinical pregnancy rate (33% vs 20.7%), live birth rate (26.9% vs 14.5%), abortion rate (17.4% vs 37.0%), and embryo transfer elimination rate (6.1% vs 15.4%) in the double trigger group were significantly different. This may suggest that changing the trigger scheme, grasping the correct trigger time so as to get the target follicles as far as possible, and getting the MII (mature) eggs may improve the pregnancy outcomes. Furthermore, some patients may improve the clinical outcomes by using some new techniques like AOA (assisted oocyte activation), IVM (in vitro maturation), and testing for associated genes. A retrospective study (18) showed that AOA intervention after ICSI fertilization failure significantly increased the normal fertilization rate (52.1%), the cumulative clinical pregnancy rate (47.1%) and the live birth rate (29.4%).

The proportion of patients with the cancellation cycle caused by poor embryo quality in the first IVF cycle was 55.04% [(237 + 200)/(496 + 298)]. These patients are more challenging for the ART. In our study, these patients’ age was not high, they had more eggs, but the CLBR was low. In the ovulation induction of these patients, 25 cases with the antagonist regimen obtained a live birth, whereas 23 cases with other protocols did not. It seems that the antagonist regimen had a trend of increasing the live birth rate, but no significant difference was found in our study (10.25% vs 6.28%, P =0.07). Similarly, the fertilization mode of the live birth cycle was not signfiicantly different. Moreover, although no differences were found in various infertility factors among these patients in our study, a recent study (19) reported that AOA could improve the clinical pregnancy and live birth rate in patients with male factors (oligoasthenospermia [OAT]), advanced age, polycystic ovary syndrome (PCOS), and unexplained infertility. In current literature, blastocyst transfer after ICSI-AOA according to different infertility factors may help to improve the clinical outcome of these patients. Besides, shortening the embryo culture time to the first or second day and carrying out gamete transfer or zygote transfer may be a goodway to improve the reproductive outcome of patients with embryonic development block from the embryologists’ point of view.

Female age and ovarian reserve are still the main factors influencing the live birth of patients with first IVF cycle cancellation. However, clinical quality control, personalized treatment, or changes in ovulation induction and fertilization mode may help them achieve a live birth. Therefore, for patients with good financial resources, the findings of the present study suggest extending the number of OPU cycles up to the 3rd, 5th, or 7th cycle even if the reasons for cancellation of the first IVF cycle are different.

Some limitations existed in this study, including the retrospective and one-center design, a small cohort of patients, and Chinese patients enrolled only. Moreover, the reasons for patient cycle cancellation are multifarious and complex, and patients with non-fertilization, fertilization failure and abnormal fertilization might have been assigned to one group for analysis, which limits the ability to control for potential unknown confounding factors. All these factors may affect the generalization of the outcome of this study. Future studies will have to resolve all these issues for better outcomes.

In conclusion, future clinical outcomes may be better in women with no normal zygotes than those with no oocyte retrieved or no available embryo at their first IVF cycle attempts. The main factors influencing the live birth are age and ovarian reserve.

The raw data supporting the conclusions of this article will be made available by the authors without undue reservation.

The studies involving human participants were reviewed and approved by Ethics Committee of The Second Hospital of Hebei Medical University. The patients/participants provided their written informed consent to participate in this study.

Study design: ZZ and GH. Data collection: XZ, MC, ZY, and PL. Data analysis: XZ and MC. Supervision: YX. Writing the original article: MC. Revision: ZZ. All authors contributed to the article and approved the submitted version.

This study was supported by S&T Program of Hebei (22377742D), Natural Science Foundation of Hebei Province(Beijing-Tianjin-Hebei Cooperation Special Project) (H2019206712).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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