Abstract
Purpose
To evaluate the embryological and pregnancy outcomes of women who failed in their first IVF treatment if they attempted a second cycle.
Methods
For evaluating the embryological outcomes, the study cohort included 1,227 women who failed to obtain a live birth after the initial IVF cycle from September 2018 to August 2021 and returned for a second attempt. To evaluate reproductive outcomes including live birth rates (LBRs), 1227 women who returned for a second attempt were compared with 13,195 women undergoing their first oocyte retrieval with blastocyst culture attempted during the same study period.
Results
In women who had a second cycle, the median number of oocyte retrieved (11 vs 9), fertilized oocytes (7 vs 5), usable embryos (6 vs 4) and blastocysts (3 vs 1) was higher in the second cycle compared to the first cycle (All p < 0.001). Blastocyst formation rates were significantly increased from 33% in the first cycle to 50% in the second cycle across the age group (p < 0.001). However, the primary transfer LBRs were significantly lower in the second cycle than that in the initial cycle (40.82% versus 51.79%, aOR: 0.74 [0.65, 0.84]). LBRs in the second cycle were 42.26%, 42.68%, 25.49% and 16.22% in women aged < 35, 35–37, 38–40, and > 40 years.
Conclusion
There was a notable enhancement in laboratory outcomes following the second attempt in women whose initial IVF cycles were unsuccessful. However, the uncertainty inherent in the successful implantation and the consequent progression to live birth remains a significant challenge.
Keywords: Live birth rate, Second attempt, Blastocyst formation, Failed first cycle, In vitro fertilization
Introduction
Assisted reproductive technologies (ART) have significantly advanced over the past decade, including embryonic endometrial synchrony, the extended culture, and vitrification. However, many couple will not conceive or achieve a live birth in their first full cycle of IVF or intracytoplasmic sperm injection (ICSI) [1, 2]. The pregnancy rates per transfer in fresh cycles remained at 32 to 34% for IVF or ICSI, as did delivery rates per transfer 26.1% for IVF and 23.9% for ICSI [2]. After completion of their first IVF cycles, couples who are unsuccessful may choose to undergo further treatment.
While some studies suggest that repeated rounds of IVF cycles lead to compromised oocyte competence and laboratory outcomes [3–5], other studies deny such an effect [6]. Furthermore, evidence on the transfer outcomes in the subsequent IVF cycles is also highly controversial. Several publications have suggested a lower implantation and pregnancy rates in the additional treatment if the first cycle fails [4]; however, data on live birth rates and how these are affected by women’s age are not well described in repeated IVF cycles [7]. Yet, this information is critical to counsel couples before embarking on their subsequent cycle, especially to prevent treatment discontinuation due to a history of reproductive failure.
The aim of this study was to determine the prognosis of women who underwent their second IVF cycles following the initial failure and how these could be affected by age. We hypothesized that a history of IVF failure would have a negative impact on the embryo development and subsequent implantation potential in the second attempt. The age-specific data could inform couples about their chance of success after previous adverse reproductive events and help them to make an informed decision about whether they want to continue IVF.
Materials and methods
Study design
This study was a noninterventional retrospective cohort study to explore the outcomes of second cycles in patients who underwent an initial failed IVF cycle at a single large reproductive medicine center from September 2018 to August 2021. This time frame was selected because extending culture to the blastocyst stage was routinely performed if at least two good embryos were available at day 3 at this center from September 2018 and no major changes in culture media or laboratory equipment were made during this time period. All data were prospectively entered into our internal IVF program database, and our retrospective analysis of these data was approved by the Women’s and Children’s Hospital Internal Review Board (2,022,018). Due to the retrospective nature of the study, written informed consent was not required from the participants.
Study population
All IVF and ICSI patients using ejaculated sperm with extending culture to the blastocyst stage were included. Women who failed to conceive or achieve a live birth after the completion of their first IVF or ICSI and returned to undergo a second cycle within 1 year were included as the study cohort. Women with infertility undergoing their first ART cycle who qualified for extended embryo culture (two or more good quality cleavaged embryos) during the same study period were included as entire patient cohort. If patients completing three or more cycles of IVF or ICSI, charts corresponding to the 1st and 2nd cycle were reviewed and data of other cycles were excluded from this analysis. Patients with a progestin-primed ovarian stimulation as well as natural cycle were not included. Cycles including preimplantation genetic testing (PGT), testicular sperm extraction (TESE), cryopreserving oocytes and oocyte/sperm donation cycles were also excluded from the analysis. To minimize the known effect of aging on IVF outcomes, the study restricted to patients who had repeated stimulation within 1 year. Cycles in which fertilization changed from conventional IVF to ICSI in the second attempts (ICSI could also be directly proposed to couples without male factor in the case of previous low fertilization rate, representing < 5% of all consecutive cycles in this center) were also excluded.
Conventional ovarian stimulation was performed based on GnRH agonist or antagonist protocols as we previously reported [8]. Ovarian stimulation was achieved by several types of FSH (Gonal-F®, Serono, Switzerland; Puregon®, N. V. Organon, Netherlands; Urofollitropin®, Livzon, China) or by FSH combined with LH activity (hMG®, Livzon, China). Stimulation medication dosage was decided and adjusted considering patients’ characteristics and treatment response. Fertilization was implemented by using either conventional IVF or ICSI. Assessment of fertilization was carried out about 16–18 h (Day 1) after insemination. Embryo culture protocols and media remained stable in the laboratory throughout the study period. Embryos were cultured in G1.5TM PLUS (Vitrolife, Sweden) to Day 3 and then graded according to the criteria described before [9]. When there were at least two good quality embryos, all embryos were cultured in G2.5TM PLUS to Day 5 or 6 [10]. For some couples who have no usable blastocyst or failed to implant in an earlier IVF attempt, in accordance with patient preference after detailed discussion, one or two embryos were transferred or frozen at day 3 and the other embryos were further cultured to the day 5/6. The number transferred adhered to national guidelines.
Outcome measures
The primary outcome was the primary transfer live birth rate (LBR), which defined as a live birth from the first fresh or frozen-thawed embryo transfer associated with the retrieval [11]. Live birth was defined as delivery of a live infant born after 24 completed weeks of gestation. Secondary outcomes were changes in laboratory outcomes between cycles including numbers of oocyte retrieved, two pronuclei (2PNs), usable embryos and blastocysts, as well as the blastocyst formation rates per embryo in prolonged culture at day 3. The average rate of blastocyst formation was determined as the arithmetic average of blastulation rate for stimulation cycles. To analyze whether maternal age has an impact on outcomes, The LBRs were stratified into the four groups based on women’s age at the start of the first cycle (< 35, 35–37, 38–40, and > 40 years).
Comparisons
Two separate analyses were performed. Firstly, a within-group comparison was made between the first and second cycles within the study cohort, focusing on laboratory outcomes such as oocyte yield and parameters of embryo development. Secondly, we compared the primary transfer of LBRs after the second retrieval in women of the study cohort to the rates of the entire patient population undergoing first cycle with blastocyst culture during the study period.
Statistical analyses
Exploratory data analysis and Shapiro–Wilk tests were performed to determine the normality of the data distribution (Shapiro–Wilk tests < 0.01). Therefore, non-parametric tests were adopted for the investigations. Continuous variables are expressed as medians with interquartile ranges (IQR); for categorical variables, counts and percentages are presented. Wilcoxon signed ranks tests were performed between first and second stimulation cycles among women in the study cohort. Multivariate regression was used to assess the association between the stimulation cycles and the outcomes after adjusting for known potential covariates. The comparisons between the study cohort and the entire patient cohort were tested with Kruskal–Wallis tests or the χ2 test. We used a Generalized Estimating Equation (GEE) model for statistical analysis to account for repeated treatments. In analyses of live birth rates we adjusted for women’s age as a continuous variable, numbers of oocyte retrieved as well as number and stage of embryo transferred. The odd risk (OR) was calculated, with 95% confidence intervals (CIs). All statistical analyses were performed using the R statistical package (R version 3.4.3; R Foundation for Statistical Computing, Vienna, Austria). p values were considered significant if < 0.05.
Sensitivity analyses
The primary transfer LBRs were stratified into fresh or frozen-thawed transfer. Considering some women in the study cohort with primary transfer of day 3 embryo in their second retrieval, the primary transfer LBRs were further investigated by restricting to per cycle of blastocyst-stage embryo transfer.
Results
Cohort and cycle characteristics
Throughout the study period, a cohort of 13,195 women undergoing their first oocyte retrieval with blastocyst culture (entire patient cohort), and a separate cohort of 1,227 women (Study cohort) embarked on a second attempt after their first failing treatment within 1 year (Fig. 1). The demographics and treatment information are detailed in Table 1. Of these women in the study cohort, 79.22% were age < 35, 13.45% were age 35–37, 4.24% were age 38–40, and 3.10% were age > 40 at the time of their first retrieval, with a relatively older median age of 32 years. Primary infertility was present in 57.54% and 51.11% of women in study and entire cohort, respectively. Tubal infertility and male factor were the most common infertility causes. As expected, the study cohort had significantly poorer laboratory outcomes in their first attempts compared to the entire cohort.
Fig. 1.
Study sample selection process
Table 1.
Characteristics at the start of the first IVF treatment for women in the study cohort and the entire patient cohort
| Characteristic | Entire patient cohort | Study cohort | p-value |
|---|---|---|---|
| Number | 13,195 | 1227 | |
| Female age, years | 31 (28–33) | 32 (29–35) | < 0.001 |
| Female age group, n (%) | < 0.001 | ||
| < 35 | 10,914 (82.71) | 972 (79.22) | |
| 35–37 | 1562 (11.84) | 165 (13.45) | |
| 38–40 | 512 (3.88) | 52 (4.24) | |
| > 40 | 207 (1.57) | 38 (3.10) | |
| Male age, years | 32 (29–35) | 32 (30–35) | < 0.001 |
| BMI (kg/m2) | 21.78 (19.84–24.14) | 22.10 (20.20–24.22) | 0.192 |
| Infertility duration, years | 3.00 (2.00–4.00) | 3.00 (2.00–4.50) | 0.727 |
| Smoking | 267 (2.02) | 27 (2.20) | 0.675 |
| Gravidity, n (%) | < 0.001 | ||
| 0 | 6744 (51.11) | 706 (57.54) | |
| 1 | 3161 (23.96) | 241 (19.64) | |
| ≥ 2 | 3290 (24.93) | 280 (22.82) | |
| No. of prior live births, n (%) | 0.275 | ||
| 0 | 10,947 (82.96) | 1046 (85.25) | |
| 1 | 1936 (14.67) | 163 (13.28) | |
| ≥ 2 | 312 (2.36) | 18 (1.47) | |
| No. of prior miscarriages, n (%) | < 0.001 | ||
| 0 | 9559 (72.44) | 944 (76.94) | |
| 1 | 2750 (20.84) | 223 (18.17) | |
| ≥ 2 | 886 (6.71) | 60 (4.89) | |
| Causes of infertility, n (%) | < 0.001 | ||
| Tubal factor | 6675 (50.59) | 589 (48.00) | |
| Ovulatory disorder | 1151 (8.72) | 99 (8.07) | |
| Endometriosis | 503 (3.81) | 80 (6.52) | |
| Diminished ovarian reserve | 382 (2.90) | 30 (2.44) | |
| Male factor | 3271 (24.79) | 325 (26.49) | |
| Unexplained | 1105 (8.37) | 101 (8.23) | |
| Others | 108 (0.82) | 3 (0.24) | |
| Basal FSH, IU | 6.72 (5.60–8.00) | 6.67 (5.41–8.09) | 0.304 |
| Antral follicle counts | 12 (9–17) | 12 (9–16) | 0.003 |
| Type of treatment, n (%) | < 0.001 | ||
| IVF | 10,676 (80.91) | 920 (74.98) | |
| ICSI | 2519 (19.09) | 307 (25.02) | |
| Stimulation protocol, n (%) | |||
| GnRH agonist based | 9475 (71.81) | 832 (67.81) | 0.003 |
| GnRH antagonist based | 3720 (28.19) | 395 (32.19) | |
| Total gonadotrophin dosage (IU) | 2100 (1650–2700) | 2100 (1800–2650) | 0.734 |
| Estradiol on the day of trigger (pg/mL) | 3038.00 (1917.11–4557.75) | 2994.00 (1872.16–4602.00) | 0.739 |
| Number of oocytes retrieved | 10 (8–13) | 9 (7–13) | < 0.001 |
| Number of M II oocytes | 9 (7–12) | 8 (4–7) | < 0.001 |
| Number of 2PNs | 7 (5–9) | 5 (4–7) | < 0.001 |
| IVF fertilization rate per oocyte retrieval (%) | 71 (60–83) | 64 (50–75) | < 0.001 |
| ICSI fertilization rate per M II (%) | 77 (67–88) | 70 (57–82) | < 0.001 |
| Number of embryos available | 6 (4–8) | 4 (3–6) | < 0.001 |
| Number of blastocysts | 4 (2–6) | 1 (1–2) | < 0.001 |
| Blastulation rate per cultured (%) | 67 (50–83) | 33 (10–60) | < 0.001 |
| Cycles without usable blastocyst (%) | 365 (2.78) | 302 (24.61) | < 0.001 |
Data expressed as median (interquartile range) or percentage of outcome. BMI, Body mass index; M II, Metaphase II, 2PN, two pronuclear
Laboratory outcomes
Within the study cohort, there were some significant differences in stimulation characteristics such as types of stimulation, days of stimulation and dosage of gonadotrophin, which were higher in the second cycle of stimulation (Table 2). The average of oocyte yields, 2pn oocytes, and numbers of usable embryo and blastocysts were significantly improved in the second cycle. The median rates of blastocyst formation were also greatly increased from 33 to 50%.
Table 2.
Cycle data and embryological outcomes from the 1227 women in the study cohort
| 1st cycle | 2nd cycle | p-value | |
|---|---|---|---|
| Stimulation protocol, n (%) | < 0.001 | ||
| GnRH agonist based | 832 (67.81) | 492 (40.10) | |
| GnRH antagonist based | 395 (32.19) | 735 (59.90) | |
| Total gonadotrophin dosage (IU) | 2100 (1800–2650) | 2250 (1800–2700) | 0.012 |
| E2 at triggering (pg/mL) | 2994.00 (1872.16–4602.00) | 2940.00 (1929.57–4546.57) | 0.891 |
| Number of oocytes retrieved | 9 (7–13) | 11 (8–15) | < 0.001 |
| Number of M II oocytes | 8 (4–7) | 9 (6–13) | < 0.001 |
| Number of 2PN | 5 (4–7) | 7 (5–10) | < 0.001 |
| Mean IVF fertilization rate per oocyte retrieval (%) | 64 (50–75) | 71 (58–82) | < 0.001 |
| Mean ICSI fertilization rate per M II (%) | 70 (57–82) | 75 (62–86) | < 0.001 |
| Number of embryos available | 4 (3–6) | 6 (4–8) | < 0.001 |
| Number of blastocysts | 1 (1–2) | 3 (1–4) | < 0.001 |
| Blastulation rate per cultured (%) | 33 (10–60) | 50 (33–75) | < 0.001 |
| Cycles without usable blastocyst (%) | 302 (24.61) | 184 (15.00) | < 0.001 |
Data are expressed as Median (Interquartile range); M II, Metaphase II, 2PN, two pronuclear
Specifically, the changes in laboratory outcomes following the first and second ovarian stimulation cycles varied on maternal age. Oocyte yield and embryo development outcomes were increased significantly in the second cycles compared to their initial cycles. The same trend was observed in younger women (< 35 and 35–37 years), but not women with advanced age (38–40 and > 40 years) (Fig. 2 and Fig. 3). In the younger age groups (< 35 and 35–37 years), there was statistically significant differences in median blastocyst formation rates between the second and first stimulation cycles (< 35 years: 56% vs 38%, p < 0.001; 35–37 years: 58% vs 39%, p < 0.001); whereas, for women women older than 37 years, the changes were not significantly different (38–40 years: 48% vs 40%, p = 0.981; > 40 years: 45% vs 42%, p = 0.831) (Fig. 2).
Fig. 2.
Boxplots reporting the laboratory outcomes within study cohort in their first (open box) and second cycle (filled box) according to different ranges of women’s age. Data are shown as the median and the interquartile range
Fig. 3.
Blastocyst development rate per cohort of embryos in prolonged culture at day 3 from each patient of the study cohort among different ranges of age based on treatment cycle (1st /2nd) Open and stripe boxes identify the 1st and 2nd cycle, respectively
Reproductive outcomes
The primary LBRs after the second IVF treatment in the study cohort were 42.26%, 42.68%, 25.49% and 16.22% for women aged < 35, 35–37, 38–40, and > 40 years, respectively. The LBRs per first embryo transfer were significantly lower in women with a history of initial IVF failure than in controls (40.82% versus 51.79%) and the differences were statistically significant (adjusted OR: 0.74 [0.65, 0.84], p = < 0.001 for both) (Table 3).
Table 3.
Primary transfer LBRs between the study cohort and entire patient cohorts stratified by maternal age
| Study cohort | Entire patient cohort | Multivariate OR (95% CI) | Adjusted p value | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Live birth | Transfer cycle | LBR (%) | Live birth | Transfer cycle | LBR (%) | ||||
| Total | 496 | 1215 | 40.82 | 6639 | 12,820 | 51.79 | 0.74 (0.65 to 0.84) | < 0.001 | |
| Age category, years | |||||||||
| < 35 | 407 | 963 | 42.26 | 5753 | 10,622 | 54.16 | 0.71 (0.61 to 0.82) | < 0.001 | |
| 35–37 | 70 | 164 | 42.68 | 686 | 1512 | 45.37 | 0.92 (0.64 to 1.32) | 0.660 | |
| 38–40 | 13 | 51 | 25.49 | 169 | 492 | 34.35 | 0.82 (0.38 to 1.79) | 0.623 | |
| > 40 | 6 | 37 | 16.22 | 31 | 194 | 15.98 | 1.25 (0.45 to 3.49) | 0.666 | |
LBR: live birth rate
Primary transfer live birth rates defined as the live birth of the first transfer that occurs after retrieval
adjusted for female age, numbers of oocyte retrieved as well as number and stage of embryo transferred
Sensitivity analyses
Similar trends were also observed when primary transfer LBRs were stratified by cycles with fresh or frozen-thawed transfers (Table 4).
Table 4.
Stratification of the primary transfer LBRs into fresh or frozen-thawed transfer
| Study cohort | Entire patient cohort | Multivariate OR (95% CI) | Adjusted p value |
|||||
|---|---|---|---|---|---|---|---|---|
| Live birth | Transfer cycle | LBR (%) | Live birth | Transfer cycle | LBR (%) | |||
| Primary transfer | 496 | 1215 | 40.82 | 6639 | 12,820 | 51.79 | 0.74 (0.65, 0.84) | < 0.001 |
| Fresh | 322 | 796 | 40.45 | 4403 | 8614 | 51.11 | 0.76 (0.65, 0.89) | 0.001 |
| Frozen-thawed | 174 | 419 | 41.53 | 2236 | 4206 | 53.16 | 0.72 (0.58, 0.89) | 0.003 |
LBR: live birth rate
Primary transfer live birth rates defined as the live birth of the first transfer that occurs after retrieval
adjusted for female age, numbers of oocyte retrieved as well as number and stage of embryo transferred
These results also remained consistent when the analysis was confined to cycles following the transfer of blastocysts (Table 5).
Table 5.
Primary transfer LBRs stratified by maternal age and limited to blastocyst-stage embryos
| Study cohort | Entire patient cohort | Multivariate OR (95% CI) |
adjusted p value | |||||
|---|---|---|---|---|---|---|---|---|
| Total | Live birth | Transfer cycle | LBR (%) | Live birth | Transfer cycle | LBR (%) | ||
| Number | 432 | 1041 | 41.50 | 6639 | 12,820 | 51.79 | 0.79 (0.70 to 0.90) | 0.002 |
| Age category, years | ||||||||
| < 35 | 359 | 834 | 43.05 | 5753 | 10,622 | 54.16 | 0.77 (0.67 to 0.89) | 0.002 |
| 35–37 | 57 | 139 | 41.01 | 686 | 1512 | 45.37 | 0.97 (0.69 to 1.37) | 0.851 |
| 38–40 | 10 | 37 | 27.03 | 169 | 492 | 34.35 | 0.71 (0.36 to 1.41) | 0.331 |
| > 40 | 6 | 31 | 19.35 | 31 | 194 | 15.98 | 1.06 (0.38 to 2.93) | 0.917 |
LBR: live birth rate
adjusted for female age, numbers of oocyte retrieved and number embryo transferred
Discussion
Prognostic information is critical for women who failed in their initial cycles about to embark on their second cycle of IVF or ICSI. While the oocyte yields and embryonic outcomes were significantly improved in the second stimulation, we found a decline in the overall primary transfer LBRs following the second retrieval when compared the control cohort in the same study period.
Interpretation of findings
Change in oocyte yield after repeated IVF cycles has been discussed before. Some studies noted a significantly decline in the number of oocyte retrieved after consecutive stimulations [12], whereas others reported that oocyte yield remained stable or increased slightly between cycles [5]. In the present study, we found a significantly increase in the number of oocytes retrieved in the second cycle compared with the first treatment attempt, which is consistent with previous report. The improvement may be attributed to the more total gonadotrophin consumption in the second cycle, which may reflect the usual adjustments in clinic practice when the numbers of oocytes retrieved are lower in the first cycle.
The decline of fertility and pregnancy outcomes with advancing age is well documented [13] but few reports of the combined effect of prior IVF failure and age on the subsequent outcomes [14, 15]. Here, we provided reliable age specific data to better understanding whether a failed IVF cycle is a particular poor prognosis on the development and transfer of blastocysts in the subsequent second attempts. Our findings have shown improved blastocyst formation from first stimulation cycles to the second ones in an age-dependent manner. In the second cycle, there was a significant enhancement in the median rate of blastocyst formation, which markedly increased from 33 to 50%. However, this trend was not evidence in women of advanced age, specifically those aged between 38–40 and above 40 years. For younger women (< 35 and 35–37 years), there was a remarkable improvement in blastocyst formation, significantly increasing from 38 to 56% and 39 to 58%, along with the higher oocyte yields in the second retrieval, potentially suggesting an iatrogenic etiology resulting from different stimulation cycles. Such significant biological variation in oocyte quantity and quality from cycle to cycle has been shown in previous studies of women who have completed two consecutive IVF cycles. We assumed that factors such as ovarian stimulation protocol, follicle size at ovulatory trigger could be considered when poor embryo development occurred [1].
Consistent with the previous data [7], this study indicated that the chance of having a live birth for patient in the second cycle was sustained lower than the entire cohort of women with infertility in their first attempts. The rationale behind this observation remains elusive, potentially attributing to the inherent potential of the embryo or compromised “reproductive competence” of the formed blastocysts. Despite the possibility of obtaining more blastocysts in subsequent treatment cycles, the uncertainty surrounding their potential for successful implantation and progression to delivery persists. Alternatively, this phenomenon might be linked to the asynchrony between the embryo and endometrium in terms of embryonic developmental speed. This finding underscores the imperative need for continued fundamental research to enhance our comprehension of oocyte functionality, with the ultimate objective of augmenting oocyte efficiency.
Strengths and limitations
This study has some limitations including its retrospective nature and the use of data generated in a single IVF center. Presence of multiple providers can lead to variability in practice including the use of different trigger medications. Also, ovarian stimulation cycles that did not extend culture to the blastocyst stage due to a lack of retrieved oocytes, mature oocytes or failure of fertilization were excluded from the study. Moreover, the data set lacks the known ploidy status of the embryos. The analysis should be performed also in PGT cycles and/or including patients who did not extend the culture to the blastocyst stage. Thus, these conclusions should not be generalized to the wide spectrum of infertile patients and further prospective studies are needed. Finally, the study was specifically designed to analyze data from the initial two cycles only. Nevertheless, there is a need for future research to extend the investigation to subsequent cycles, which would provide valuable insights into the long-term efficacy and patient adherence associated with the treatment.
The study was strengthened by the large sample size, which allowed us to properly evaluate the impact of age on the embryo development and reproductive potential of embryos generated in the second cycle. Another strength of the study was the assessment of the primary transfer live birth rate, which is more relevant to evaluate the couple’s outlook for success in their next cycle [11]. Furthermore, all blastocyst were cultured at a single reference laboratory, eliminating culture conditions or technical variation as a confounder of blastocyst formation.
Clinical importance
The experience of adverse reproductive history worsens the already frustrating condition of infertility; therefore, counseling couples after a failed cycle is sensitive and challenging. Based on our data, patients with first cycle failure should be informed of these less satisfied outcomes when consulted prior to another IVF treatment. After an unsuccessful first complete cycle of IVF, about 37% of women embark on a second cycle, suggesting many couples discontinuing treatment before having a baby [16]. The current data are critical to counsel women about their subsequent cycle, but even more so for older couples to prevent treatment discontinuation. The dropout rate after the first and second cycle for the older couples was even higher compared with younger couples [17]. We found that the LBRs of women with advanced maternal age categories (35 years and older) did not decline further with second IVF treatment. However, we need to be very cautious about the interpretation of this finding, due to the relatively small sample size of this subgroup. As increasing numbers of women delay childbearing until later years, information regarding the reproductive potential of women with advanced age is critical, especially to prevent treatment discontinuation.
Conclusion
The outcomes of oocyte yield and embryo development demonstrated significant improvement following the second attempt in women who experienced unsuccessful initial IVF cycles. Despite this, the uncertainty surrounding the success of implantation and eventual progression to live birth remains to be a significant challenge.
Acknowledgements
The authors thank all staff in the Department of Assisted Reproduction in Northwest Women’s and Children’s Hospital for their support and cooperation.
Author contribution
He Cai and Juanzi Shi designed the study. Dian Zhang and Xiaohua Liu conducted the statistical analyses. Wen Wen and He Cai drafted the manuscript. All authors contributed to the collection, analysis and discussion of the data and revised and approved the manuscript.
Declarations
Ethics approval and consent to participate
The Institutional Review Board of Northwest Women’s and Children’s Hospital approved the analysis of data obtained during routine clinical care (No.2022018). All participating patients provided informed written consent for the use of their clinical data in this analysis.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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