Intracytoplasmic sperm injection hampers fertilization rate and pregnancy per initiated cycle in patients with extremely poor ovarian response

Archives of Gynecology and Obstetrics https://doi.org/10.1007/s00404-025-08033-3 RESEARCH Intracytoplasmic sperm injection hampers fertilization rate and pregnancy per initiated cycle in patients with extremely poor ovarian response Jinghua Chen1 · Lanlan Liu1,2 · Zhenfang Liu1 · Luxiang Pan1 · Liying Zhou1 · Kaijie Chen1 · Xiaolian Yang1 · Yurong Chen1 · Xiaoming Jiang1 · Jianzhi Ren1 · Jiali Cai1,2 Received: 26 October 2024 / Accepted: 8 April 2025 © The Author(s) 2025 Abstract Purpose To compare the clinical outcomes of extremely poor responders with one or two oocytes who receive in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Methods A retrospective study was carried out on 2572 patients with one or two oocytes retrieved from 2013 to 2022, of which 2159 patients were scheduled to receive IVF treatment and 413 patients were scheduled to receive ICSI treatment. The laboratory parameters and clinical outcomes were compared with adjusted multivariate regression and propensity score (PS) matching. Results In both matched and non-matched cohorts, The ICSI group had a significantly higher total fertilization failure (TFF) rate and lower multiple fertilization rate than the IVF group (P < 0.05). After matching, the cumulative pregnancy rate per initiated cycle in the IVF group was significantly higher than in the ICSI group (28.7% vs 21.7, P < 0.05). However, the difference in cumulative live births did not reach statistical significance (21.2% vs 17.2%, P > 0.05). The adjusted odds ratios for TFF, cumulative pregnancy, and cumulative live birth comparing ICSI versus IVF in multivariate models were 1.65(95% CI: 1.12, 2.43), 0.65(95% CI: 0.46, 0.91), and 0.76(95% CI: 0.55, 1.04), respectively. Conclusion In poor responders with one or two oocytes retrieved, ICSI insemination cannot avoid TFF, and it may hamper the cumulative pregnancy rate. Keywords IVF · ICSI · Normal fertilization rate · Total fertilization failure rate · Cumulative live birth rate · Poor responder What does this study add to the clinical work The use of ICSI in patients with extremely poor responders is usually driven by fear of total fertilization failure. However, our data suggest that using ICSI in these patients further hampers fertilization. * Jianzhi Ren * Jiali Cai 1 Reproductive Medicine Center, Xiamen University Affiliated Chenggong Hospital, Xiamen 361003, Fujian, China 2 School of Medicine, Xiamen University, Xiamen 361005, Fujian, China Introduction Since first described in 1992, intracytoplasmic sperm injection (ICSI) has become the gold standard for treating severe male factor infertility in assisted reproductive technologies (ART) [1]. Nowadays, over half of the ART cycles are inseminated with this technique according to the data of ICMART [2]. The fact that the number of ICSI cycles outnumbers the ART cycles involving male factor infertility [3] and varies across geographical regions[2] suggests that the use of ICSI may be driven by factors beyond male infertility, such as clinic-specific policy [4] or patients’ attitudes [5, 6]. Current evidence shows that ICSI does not improve pregnancy rates or live birth rates in non-male factor infertility [7–9]. The popularity of ICSI is possibly driven by the fear of an expected total fertilization failure during conventional IVF treatment. The fear might be irrational in patients with a normal ovarian response, as the absolute incidence of TFF Vol.:(0123456789) Archives of Gynecology and Obstetrics is rare in the general population [10]. For patients with only one or two oocytes retrieved, however, the chance of fertilization might be a game of all or none. An intracytoplasmic sperm injection could bypass several pre-fertilization hindrances, confirming the one selected spermatozoon reaches the oocyte, and be deemed as a method to overcome the frustrating TFF [11, 12]. However, successful fertilization is not only determined by the entry of the spermatozoon into the oocyte in ICSI cycles [13]. The developmental competence of the spermatozoon selected by the embryologist cannot be guaranteed, as it also bypasses the natural selection barriers. Additionally, mechanical damage to the oocytes is also a potential concern [14]. Practically, using ICSI in patients with one or two oocytes does not always promise a better fertilization rate. Poorer or equalized fertilization chances were reported along with improved fertilization rates among previous studies comparing ICSI and conventional IVF in patients with one or two oocytes [5, 15, 16]. The heterogeneity could be due to the low statistical power and high patient heterogeneity in such populations. Furthermore, meta-analyses focusing on advanced maternal age populations indicate that ICSI may not significantly enhance fertilization outcomes when oocyte yield is suboptimal [17, 18]. We postulate that the utilization of ICSI in patients with one to two oocytes may offer little substantial clinical advantages. Since a major reason for ICSI overuse is the pressure on the clinicians from the patients` intolerance to TFF, an informed consult would be essential. The present study aimed to provide further evidence concerning the association between ICSI and TFF in patients with one or two oocytes, with a larger sample size and matched indications. In addition, previous evidences were summarized and pooled for further reference. Materials and methods Study subjects A retrospective study of infertile patients treated at the Reproductive Medicine Center of Xiamen University Affiliated Chenggong Hospital, Xiamen, China, from 2013 to 2022, was included and analyzed. Inclusion criteria were poor responders with one or two oocytes retrieved in a cycle, patients with a complete cycle where live births had been achieved or no surplus frozen embryos left, and patients with a total motile sperm count (TMC) higher than 2 × 106 in their male counterparts. Exclusion criteria were severe male factor cases, frozen–thawed sperm, and surgical sperm collection. The reasons for ICSI in the included patients were borderline or suboptimal semen parameters. The suboptimal semen parameters were considered when the semen parameters were above the ICSI indications in our clinic (TMC ≤ 2 × 106), but lower than the WHO criteria [19] (concentration ≥ 15 million/ml, motility ≥ 40%, morphology ≥ 4%). Institutional review board approval for this study was obtained from the Ethical Committee of Xiamen University Affiliated Chenggong Hospital. Informed consent was not necessary because this retrospective research was based on non-identifiable records. Laboratory procedures and embryo assessment Oocyte retrieval was performed by transvaginal ultrasound, and follicles were aspirated by a 17 G needle (Cook Medical). Repeated follicular flushing was performed when the oocyte was not retrieved after the initial puncture to maximize the chances of recovery. On the same day, semen was collected in sterile c (...truncated)