Abstract
Background
A yield of fewer than five oocytes is associated with a sharp drop in success rates, making each oocyte extremely valuable and demanding highly efficient utilization. Therefore, we aimed to explore the optimal fertilization method for these patients.
Methods
This retrospective cohort single-center study included 424 C-IVF cycles and 90 ICSI cycles from 2016 to 2023. All patients were in their first ART cycle, with 3 or 4 oocytes retrieved. The study subjects were primarily divided into two groups: the IVF-LN (C-IVF with a 50% lower-than-expected oocyte yield) group and the ICSI-LN (ICSI with a 50% lower-than-expected oocyte yield) group.
Results
We observed no significant differences in the day 3 available embryo (87.0 versus 84.8%; p = 0.41), blastocyst formation (61.2 versus 57.9%; p = 0.69), day 5 blastocyst (56.9 versus 54.5%; p = 0.83) or good quality blastocyst (45.4 versus 50.0%; p = 0.83) rates between the IVF-LN and ICSI-LN groups. However, the day 3 good quality embryo rate was significantly higher in the IVF-LN group than in the ICSI-LN group (59.76% vs. 47.46%; p < 0.01). There were no significant differences in the pregnancy (61.8 versus 57.7%; p = 0.50), clinical pregnancy (59.1 versus 53.8%; p = 0.40), ongoing pregnancy (52.2 versus 47.4%; p = 0.45) or live birth (48.6 versus 44.9%; p = 0.55) rates between the IVF-LN and ICSI-LN groups.
Conclusion
For patients with <5 Oocytes and a predicted yield of ≤50%, ICSI did not demonstrate a significant advantage over C-IVF.
Keywords: C-IVF, ICSI, oocyte yield, reproductive outcomes
Background
A common phenomenon during in vitro fertilization (IVF) treatment is a significant discordance between anticipated and actual oocyte yield. This is empirically defined as a shortfall of ≥30% from the predicted number, with predictions derived from either ultrasound-based antral follicle count (AFC) or serum anti-Müllerian hormone (AMH) levels. Such discrepancies are observed in approximately 15–25% of clinical cases which may compromise subsequent embryo development and pregnancy outcomes [1].
When the number of collected oocytes is limited (e.g. ≤4), optimizing the fertilization strategy to maximize usable embryos becomes critical. While conventional IVF (C-IVF) remains standard practice, it carries risks of total fertilization failure or low fertilization rates in cycles with poor oocyte yield. Although intracytoplasmic sperm injection (ICSI) can theoretically improve fertilization efficiency, its use in non-male factor infertility cases remains controversial [2,3]. Multiple researches have demonstrated that low oocyte number is not an indication to perform ICSI in the presence of normal semen parameters [4,5]. However, recent studies have indicated that patients with fewer than five oocytes are at a risk of fertilization failure after undergoing C-IVF [6–8]. The reproductive outcomes of patients experiencing fertilization failure following C-IVF have not been extensively documented.
The lower-than-expected oocyte yield may primarily result from asynchronous follicular development, along with inherent limitations in AMH/AFC-based predictions. It remains uncertain whether oocyte competence and maturation status are adversely affected in these cases. In this study, we aim to determine the optimal fertilization method for patients with fewer than five retrieved oocytes and an oocyte retrieval rate ≤50%.
Materials and methods
Study participants
This study was a retrospective cohort analysis which included 424 C-IVF cycles and 90 ICSI cycles at the Northwest Women’s and Children’s Hospital from January 2016 to December 2023. All patients were during their first assisted reproductive technologies (ART) cycle with 3 or 4 retrieved oocytes. For each initiated cycle, only the first embryo transfer was compared. The number of motile sperm (a + b) in the semen sample was not less than 5 × 106 for ICSI cycles in this study. The exclusion criteria were as follows: (1) Rescue ICSI cycles; (2) Preimplantation genetic testing (PGT) cycles; (3) Testicular sperm aspiration (TESA) cycles; (4) Microscopic testicular sperm extraction (Micro-TESE) cycles. The study subjects were primarily divided into two groups: the IVF-LN group (C-IVF cycles with a 50% lower-than-expected oocyte yield) and the ICSI-LN group (ICSI cycles with a 50% lower-than-expected oocyte yield). The IVF-LN group was considered as a control group. This study was approved by the Ethics Committee of Northwest Women’s and Children’s Hospital (No. 2023003).
Ovarian stimulation protocol
Two types of controlled ovarian hyperstimulation (COH) protocols were used: GnRH agonist and GnRH antagonist. Stimulation medication dosage was decided and adjusted considering patients’ characteristics and treatment response. The starting dosage of gonadotropin, ranging from 100 IU to 300 IU, was primarily determined by the antral follicle count. Human chorionic gonadotropin injection (HCG, Ovidrel, Merck Serono, Italy) was administered once the leading follicle reached 18 mm, followed by oocyte retrieval 36 h post-injection [9].
Oocyte retrieval, C-IVF and ICSI procedure
Oocyte retrieval was performed 36 h after triggering final oocyte maturation. During the study period, all retrieval procedures were conducted according to a standardized protocol. Follicular flushing was performed in all unselected women with no more than 5 follicles with a diameter above 12 mm. Additionally, flushing was performed in women with a poor oocyte retrieval rate to maximize oocyte recovery. In cases where no cumulus–oocyte complex (COC) was obtained from the initial aspirate, follicular flushing was repeated until a COC was retrieved, up to a maximum of five attempts.
For C-IVF, semen processing was performed using density gradient centrifugation combined with the swim-up method. For ICSI, semen processing was performed using density gradient centrifugation combined with simple washing. Oocyte retrieval was followed by a 2–2.5-hour interval before initiating C-IVF. During this procedure, natural fertilization was achieved by exposing each oocyte to approximately 40,000 motile sperm. After a short incubation period lasting 4–4.5 h, mechanical removal of cumulus cells was performed. For ICSI, mature (MII) oocytes were injected by the direct penetration technique. Gametes were prepared in separate microdroplets: oocytes in 5 µL G-MOPS medium (Vitrolife, Goteborg, Sweden) and sperm in polyvinylpyrrolidone solution, both maintained under with paraffin oil (Ovoil; Vitrolife, Gothenburg, Sweden). During the study period, no changes were made to the indications for different fertilization methods at our center. Nevertheless, a minor proportion of patients might have opted for a specific method based on individual preference. The injection procedure followed established methodology [10].
Embryo culture and embryo grading
The oocyte–cumulus complexes were cultured in the medium (G-IVF; Vitrolife, Gothenburg, Sweden) after retrieval. The zygotes were shifted to the cleavage medium (G-1 plus; Vitrolife, Gothenburg, Sweden) 5 h after fertilization. The embryos to culture blastocyst on day 3 were transferred to the blastocyst medium (G-2 plus; Vitrolife, Gothenburg, Sweden) until day 6. All medium were covered with paraffin oil (Ovoil; Vitrolife, Gothenburg, Sweden) in a humidified atmosphere at 37 °C, in 6% CO2, 5% O2, and 89% N2 for prior 24 h.
Normal fertilization was confirmed 18–19 h post-insemination through identification of two pronuclei (2PN) accompanied by second polar body extrusion. After 64–68 h of culture, the morphology of day-3 embryos was evaluated using a scoring system that considered blastomere count, blastomere consistency, and the severity of cytoplasmic fragmentation. Blastocysts were observed on the fifth and sixth morning after oocyte retrieval, and the scoring system for blastocyst evaluation was a combination of the stage of development from 1 to 6 (early, blastocyst, full blastocyst, expanded, hatching/hatched) and of the grade of the inner cell mass (ICM; A, tightly packed, many cells; B, loosely grouped, several cells; or C, very few cells.) and of the trophectoderm (TE; A, many cells forming a cohesive epithelium; B, few cells forming a loose epithelium; or C, very few large cells.). The detailed scoring criteria were based on our published literature [11]. The day 3 (D3) good quality embryos were graded I and II. The D3 available embryos were graded I, II, and III. The blastocyst scored ≥3BB was defined as good quality blastocyst.
Luteal support and embryo transfer
Three methods of luteal support are implemented in our center. I. Vaginal progesterone gel (90 mg q.d; Crinone, Serono, Hertfordshire, UK); II. Vaginal progesterone soft capsules (0.2 g t.i.d; Utrogestan, Besins, France); III. Intramuscular progesterone (60 mg q.d; Xianju, Zhejiang, China). Patients from both groups could select one of these three luteal support methods and receive oral progesterone (10 mg t.i.d; Dydrogesterone, Abbott Biologicals B.V., Amsterdam, Netherlands) simultaneously. The luteal support was maintained until week 10 of gestation.
The mucus in the cervical os was cleaned in advance with a cotton swab soaked in warm and humid saline. Embryos were transferred under ultrasound guidance with a transfer catheter (Limerick, Ireland). Pregnancy was defined as β-HCG value more than 50 mIU/ml after 12 days of transfer. Clinical pregnancy was characterized as the presence of an intrauterine gestational sac on ultrasonography during the first trimester. Ongoing pregnancy was defined as a clinical pregnancy that continued for a minimum of 12 weeks. Live birth was defined as the delivery of a live-born infant (>24 weeks of gestation). During the study period, the embryo transfer strategy at our center was modified. Prior to 2020, patients with at least four good quality embryos on day 3 were generally advised to undergo elective blastocyst culture for all embryos. From 2020 onward, the threshold was reduced to two or more good-quality embryos on day 3. A subset of patients opted to accept or decline this strategy according to their individual preferences.
Statistical analysis
Statistical analysis between groups in the case of continuous variables was performed with Student’s t test for data with normal distribution. Non-parametric Mann–Whitney U test was performed for data with skewed distribution. Statistical analysis between groups in the case of categorical variables was expressed as number and percentage and Chi-square test or Fisher exact test was performed. The statistical analysis was performed with SPSS version 23 (IBM Corp.; NY, USA). A p value of less than 0.05 was considered to indicate statistical significance.
Results
Patients’ baseline clinical characteristics and reproductive outcomes
A total of 514 cycles were analyzed in this study, comprising 424 IVF-LN cycles and 90 ICSI-LN cycles. Our data showed no significant differences in general characteristics between the two groups (p > 0.05) (Table 1). We observed that there were no significant differences in the 2PN (61.8 vs. 57.1%; p = 0.12) or 1PN (2.3 vs. 1.6%; p = 0.44) rates between the IVF-LN and ICSI-LN groups. Following ICSI, a total multiple pronuclei (MPN) rate of 2.3% was achieved, which was significantly lower than that of 9.3% after C-IVF (p < 0.01). There were no significant differences in the D3 available embryo (87.0 vs. 84.8%; p = 0.41), blastocyst formation (61.2 vs. 57.9%; p = 0.69), D5 blastocyst (56.9 vs. 54.5%; p = 0.83) or good quality blastocyst (45.4 vs. 50.0%; p = 0.83) rates between the IVF-LN and ICSI-LN groups. The D3 good quality embryo rate was significantly higher following C-IVF compared to ICSI (59.8 vs. 47.5%; p < 0.01) (Table 2).
Table 1.
General characteristics of the enrolled patients.
| Parameter | IVF-LN | ICSI-LN | P value |
|---|---|---|---|
| Cycles (oocyte retrievals) | 424 | 90 | / |
| Female age (y) | 32.2 ± 4.3 | 31.7 ± 3.5 | 0.28 |
| COH protocol | / | / | 0.68 |
| GnRH agonist (%, n) | 59.9 (254/424) | 62.2 (56/90) | / |
| GnRH antagonist (%, n) | 40.1 (170/424) | 37.8 (34/90) | / |
| Infertility duration (years) | 3.8 ± 2.7 | 4.2 ± 3.0 | 0.20 |
| Primary infertility (%, n) | 50.2 (213/424) | 54.4 (49/90) | 0.47 |
| BMI for women (kg/m²) | 24.1 ± 3.35 | 23.9 ± 3.5 | 0.59 |
| Basal FSH(IU/L) | 6.7 ± 2.4 | 6.5 ± 2.4 | 0.74 |
| Total Gn dosage (IU) | 2620.5 ± 974.2 | 2621.3 ± 1025.3 | 0.99 |
| Stimulation duration (days) | 10.8 ± 2.6 | 11.2 ± 2.8 | 0.26 |
| AFC (n) | 8.7 ± 2.9 | 8.8 ± 2.9 | 0.87 |
| Number of oocytes retrieved (n) | 3.4 ± 0.5 | 3.4 ± 0.5 | 0.95 |
IVF-LN: C-IVF cycles with a 50% lower-than-expected oocyte yield; ICSI-LN: ICSI cycles with a 50% lower-than-expected oocyte yield; COH: Controlled ovarian hyperstimulation; GnRH: Gonadotropin-releasing hormone; BMI: Body mass index; FSH: Follicle-stimulating hormone; AFC: Antral follicle count.
Table 2.
Comparison of embryo development after C-IVF and ICSI cycles in patients with <5 oocytes and ≤50% predicted yield.
| Parameter | IVF-LN | ICSI-LN | P value |
|---|---|---|---|
| Cycles (oocyte retrievals) | 424 | 90 | / |
| 2PN (2PN/oocytes) (%, n) | 61.8 (902/1459) | 57.1 (177/310) | 0.12 |
| 1PN (1PN/oocytes) (%, n) | 2.3 (34/1459) | 1.6 (5/310) | 0.44 |
| MPN (MPN/oocytes) (%, n) | 9.3 (135/1459) | 2.3 (7/310) | <0.01 |
| D3 good quality embryo rate (D3 good quality embryos/2PN) | 59.8 (539/902) | 47.5 (84/177) | <0.01 |
| D3 available embryo rate (D3 embryos/2PN) | 87.0 (785/902) | 84.8 (150/177) | 0.41 |
| Extended culture to blastocyst-stage (n) | 353 | 38 | / |
| Blastocyst formation rate (%, n) | 61.2 (216/353) | 57.9 (22/38) | 0.69 |
| D5 blastocyst rate (D5 blastocyst/blastocyst) | 56.9 (123/216) | 54.5 (12/22) | 0.83 |
| Good quality blastocyst rate (Good quality blastocyst/blastocyst) | 45.4 (98/216) | 50.0 (11/22) | 0.83 |
2PN: Two pronuclei; 1PN: One pronuclei; MPN: Multiple pronuclei; D3: Day3; D5: Day 5.
We further compared embryo development by different fertilization method between the patients with expected oocyte yield and those with lower-than-expected oocyte yield. Regardless of the fertilization method, the patients with a lower-than-expected oocyte yield had a significantly lower 2PN rate than those with an expected oocyte yield (p < 0.01). Among ICSI cycles, the patients with lower-than-expected oocyte yield had a significantly lower D3 good quality embryo rate than those with expected oocyte yield (47.5 vs. 55.4%; p = 0.04). Among C-IVF cycles, the cancellation rate of cycles with no transferable embryos was significantly higher in the patients with lower-than-expected oocyte yield than those with expected oocyte yield (13.4 vs. 9.4%; p = 0.02). In addition, the results for other parameter comparisons were also shown in Supplemental Table 1.
We further compared the embryo development and clinical outcomes in the patients with different age. We observed that the IVF-LN and ICSI-LN groups showed similar outcomes in terms of fertilization, embryo quality and clinical outcomes in the patients aged 35 years or older (p > 0.05). In the patients younger than 35 years old, the IVF-LN group showed higher MPN (10.2 vs. 1.7%; p < 0.01) and D3 good quality embryo (60.3 vs. 44.5%; p < 0.01) rates compared to the ICSI-LN group (Supplemental Table 2).
Comparison of clinical and neonatal outcomes between the IVF-LN and ICSI-LN groups
We observed that there were no significant differences in the pregnancy (61.8 vs. 57.7%; p = 0.50), clinical pregnancy (59.1 vs. 53.8%; p = 0.40), ongoing pregnancy (52.2 vs. 47.4%; p = 0.45) or live birth (48.6 vs. 44.9%; p = 0.55) rates between the IVF-LN and ICSI-LN groups (Table 3). We also observed no significant disparities in the neonatal outcomes, including multiple birth rates, sex ratio, gestational age, birth weight, preterm birth or neonatal anomalies (p > 0.05, for all) (Table 4).
Table 3.
Comparison of clinical outcomes after C-IVF and ICSI in patients with <5 oocytes and ≤50% predicted yield.
| Parameter | IVF-LN | ICSI-LN | P value |
|---|---|---|---|
| Cycles (oocyte retrievals) | 424 | 90 | / |
| Cycles (Embryo transfers) | 364 | 78 | / |
| Oocyte retrievals with fresh or frozen embryo transfer (ET/initiated cycle) | 85.9 (364/424) | 86.9 (78/90) | 0.84 |
| Type of embryo (%, n) | / | / | 0.64 |
| Fresh | 73.1 (266/364) | 75.6 (59/78) | / |
| Thawed | 26.9 (98/364) | 24.4 (19/78) | / |
| Stage of embryo (%, n) | / | / | 0.88 |
| Cleavage-stage | 72.3 (263/364) | 73.1 (57/78) | / |
| Blastocyst-stage | 27.8 (101/364) | 26.9 (21/78) | / |
| Pregnancy rate (%, n) | 61.8 (225/364) | 57.7 (45/78) | 0.50 |
| Clinical pregnancy rate (%, n) | 59.1 (215/364) | 53.8 (42/78) | 0.40 |
| Ongoing pregnancy rate (%, n) | 52.2 (190/364) | 47.4 (37/78) | 0.45 |
| Live birth rate (%, n) | 48.6 (177/364) | 44.9 (35/78) | 0.55 |
Table 4.
Comparison of neonatal outcomes after C-IVF and ICSI in patients with <5 oocytes and ≤50% predicted yield.
| Parameter | IVF-LN (n = 177) | ICSI-LN (n = 35) | P value |
|---|---|---|---|
| Singleton or multiple pregnancy (n, %) | / | / | 0.76 |
| Singleton | 87.6 (155/177) | 85.7 (30/35) | / |
| Twins | 12.4 (22/177) | 14.2 (5/35) | / |
| Gender (%, n) | / | / | |
| Singleton | / | / | 0.45 |
| Male | 54.1 (84/155) | 46.7 (14/30) | / |
| Female | 45.8 (71/155) | 53.3 (16/30) | |
| Twins | / | / | 0.41 |
| Male | 45.5 (20/44) | 60.0 (6/10) | / |
| Female | 54.5 (24/44) | 40.0 (4/10) | / |
| Gestational age (week) | / | / | / |
| Singleton | 38.8 ± 1.5 | 38.6 ± 1.4 | 0.82 |
| Twins | 36.2 ± 2.2 | 35.9 ± 2.1 | 0.77 |
| Birth weight (g) | / | / | / |
| Singleton | 3178.2 ± 526.6 | 3142.7 ± 499.7 | 0.62 |
| Twins | 2752.5 ± 368.1 | 2676.5 ± 323.4 | 0.49 |
| Prematurity (n, %) | / | / | / |
| Singleton | 8.4 (13/155) | 10.0 (3/30) | 0.77 |
| Twins | 50.0 (22/44) | 60.0 (6/10) | 0.57 |
| Neonatal anomaly (n, %) | / | / | / |
| Singleton | 8.4 (2/155) | 3.3 (1/30) | 0.42 |
| Twins | 4.6 (2/44) | 0 (0/10) | 0.49 |
Discussion
Based on the findings of this study, ICSI demonstrates no superiority over C-IVF in patients with <5 oocytes and a predicted yield of ≤50%. Hence, in the presence of normal semen parameters, C-IVF should be regarded as the first-line fertilization method for such patients.
A high proportion of empty follicles, potentially the main cause of a lower-than-expected oocyte yield, can often be attributed to suboptimal trigger timing [12]. Triggering too early results in the retrieval of developmentally incompetent oocytes. As a result, the cumulus-oocyte complex remains tightly adhered to the follicular wall. Consequently, the oocyte fails to detach even during aspiration, thereby resulting in oocyte retention and the observed phenomenon of an “empty follicle.” Delayed trigger administration is associated with an increased risk of oocyte over-maturity. The oocytes may either be spontaneously released from the follicle or suffer a loss of viability. In either situation, the oocytes remain irretrievable at the time of collection. Optimal trigger timing is critical, as both premature and delayed administration can impair oocyte maturity and quality, thereby directly influencing the competence of subsequent embryos and final clinical outcomes [13].
In such patients, insufficient follicular flushing may also lead to a suboptimal oocyte retrieval rate. Multiple researches demonstrated that follicular flushing significantly increased the number of cumulus-oocyte complexes (COCs) retrieved compared to single aspiration [14,15]. Flushing each follicle four times was identified as the optimal regimen to achieve maximal oocyte retrieval in poor ovarian responders. As our center adhered to a protocol of at least three flushing cycles per follicle for these patients, insufficient flushing should not be considered a contributing factor to the low yield. Nevertheless, repeated flushing posed two main risks to oocyte quality: first, the mechanical stress from flushing could physically disturb the cumulus-oocyte complex, despite its protective layers; second, it prolonged in vitro exposure, thereby increasing the risk of diminished oocyte viability and impaired developmental potential. Thus, a markedly low oocyte yield may reflect an underlying compromise in overall oocyte quality.
Berntsen et al. indicated that ICSI could not improve cumulative live birth rate compared to C-IVF and support C-IVF as the preferred first-line treatment for patients with normal or nonseverely decreased sperm quality [16]. Accordingly, Fancsovits et al. showed that ICSI had no advantage over C-IVF in terms of fertilization, embryo quality, implantation or pregnancy rates for couples with low oocyte number [17]. Nevertheless, recent studies demonstrated that the patients with fewer than five oocytes were at increased risk of fertilization failure following C-IVF [6–8]. Tian et al. reported that semen parameters offer limited predictive value for total fertilization failure (TFF) in unselected populations, whereas oocyte yield serves as a more significant predictor [6]. De Souza et al. also identified a low oocyte retrieval count as the most critical factor associated with TFF in cases of non-male factor infertility [7]. Therefore, it is essential to optimize the fertilization strategy for this poor-prognosis patient cohort.
We observed that the rate of MPN was significantly higher in the IVF-LN group than in the ICSI-LN group, whereas the 2PN rate was comparable between the two groups. Typically, ICSI yield a higher 2PN rate and a lower MPN rate compared to C-IVF. Since our primary focus was the 2PN rate in both groups, these results suggested that ICSI did not improve fertilization outcomes in such patients compared to C-IVF. Our results demonstrated that C-IVF yielded a significantly higher D3 good quality embryo rate than ICSI, while the D3 available embryo rate was comparable between the two groups. It might be due to a relative increase in the proportion of day 3 embryos with 8–10 blastomeres (data not shown). After all, the number of blastomeres is the most important factor affecting day 3 embryo grading. Our data showed that this difference existed only in younger patients by age-stratified analysis, likely owing to the small sample size in the older group. Nevertheless, we observed that there were no significant differences in the blastocyst formation and good quality blastocyst rates between the two groups. And the two groups had a similar proportion of day 5 blastocysts, likely because most patients underwent cleavage-stage embryo transfer. It was important to note that the clinical outcomes were comparable between the two groups.
Several studies reported that ICSI could improve both embryo quality and clinical outcomes over C-IVF in such couples with non-male factor infertility [18,19]. In contrast, other investigators demonstrated no significant benefit of ICSI on embryo quality and clinical outcomes in this population [20,21]. These discrepant findings might be attributed to variations in study design, sample size, statistical methodology and patient population characteristics. It was no doubt that the oocyte pre-incubation was critical for subsequent embryonic development, as it provided a stable environment for oocytes to recover from follicular aspiration stress and complete their final nuclear and cytoplasmic maturation. A study demonstrated that preincubating oocytes for at least 2.5 h benefited both C-IVF and ICSI outcomes through the enhancement of oocyte nuclear maturity [22]. In such patients with suboptimal oocyte yield, not only was the overall oocyte quality compromised, but a proportion of the retrieved oocytes were also likely derived from smaller follicles. Follicle size was predictive not only for oocyte maturity but also for the ability of a 2PN zygote to develop into a high-quality embryo [23]. Therefore, the sufficient incubation time was critically important for embryo quality and the duration of oocyte incubation consistently exceeded 2.5 h for all retrieved oocytes at our center. In this research, the difference in D3 good quality embryo rate might be independent of incubation time. It is speculated that the quality of these oocytes may be generally suboptimal, making them more susceptible to the detrimental effects of ICSI-induced mechanical damage, which could in turn adversely affect the D3 good quality embryo rate. And a recent study indicated that early rescue ICSI could achieve comparable embryological and clinical outcomes to ICSI for couples presenting with non-severe male factor infertility and a low oocyte yield [24]. We also observed the neonatal outcomes were similar between the IVF-LN and ICSI-LN groups which was consistent with a large body of existing literature [25–27]. These results suggested that ICSI might not offer benefits over C-IVF in this population.
There are certain weaknesses in the current study that should be underlined. First, the primary drawback is the retrospective design and limited sample size of ICSI cases. Second, there may be some potential bias and confounders that cannot be excluded. Lastly, the cumulative live birth rate may be a more significant indicator and it is hard to calculate in this study. Nevertheless, few researches have explored the embryo development and clinical outcomes of C-IVF and ICSI for such cases. Thus, the findings of the current study offer valuable insights for both clinicians and patients. Thus, these findings provide clinically actionable insights for optimizing treatment decisions.
In summary, ICSI showed no advantage over C-IVF in patients with <5 oocytes and a predicted yield of ≤50%. Therefore, C-IVF is strongly recommended as the treatment of choice for this population. Given the limited data and methodological constraints, further data accumulation is needed to obtain more reliable conclusions.
Supplementary Material
Acknowledgments
M.L. and J.S. designed the research; M.L. and W.C. performed the research. X.X. analyzed and prepared the data; all authors have reviewed the manuscript and agreed to be accountable for all aspects of the work.
Glossary
Abbreviations
- IVF
In vitro fertilization
- C-IVF
Conventional in vitro fertilization
- ICSI
Intracytoplasmic sperm injection
- AFC
Antral follicle count
- AMH
Anti-Müllerian hormone
- ART
Assisted reproductive technologies
- COH
Controlled ovarian hyperstimulation
- HCG
Human chorionic gonadotropin
- COCs
Cumulus–oocyte complexes
- TFF
Total fertilization failure
- FSH
Follicle-stimulating hormone
- GnRH
Gonadotropin-releasing hormone
- BMI
Body mass index
- PN
Pronuclei
- D3
Day 3
Funding Statement
This project was supported by China Association for Promotion of Health Science and Technology (No. 02008004).
Ethical approval and consent to participate
The study involving human participants was reviewed and approved by the Ethics Committee of Northwest Women’s and Children’s Hospital (No. 2023003). The study was complied with the Helsinki Declaration and the patient records were innominate ahead of the data analysis. Patient consent was waived due to the retrospective nature of the research.
Clinical trial number
Not applicable.
Human ethics and consent to participate declarations
Not applicable.
Consent for publication
Not applicable.
Disclosure statement
The authors declare no competing interests.
Data availability statement
Data available on request corresponding author due to privacy and ethical restrictions.
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