To the Editor: Cesarean delivery is the most common major surgery used to address complications during pregnancy or childbirth, and optimizing its use is essential to reducing mortality and morbidity.[1] However, growing evidence shows that the overuse of cesarean delivery, particularly non-medically indicated cesarean delivery, can be harmful to maternal and child health, and its continued rise has become a significant global public health concern.[2]
Research has shown that cesarean delivery is associated with increased risks of childhood obesity and asthma, as well as higher maternal risks of adverse pregnancy outcomes such as stillbirth, preterm birth, uterine rupture, and abnormal placentation.[3] Additionally, cesarean delivery may increase the risk of low fecundability.[4] Nevertheless, with ongoing shifts in fertility patterns and greater emphasis on fertility preservation, the relationship between cesarean delivery and fecundability in subsequent pregnancy requires further investigation and clarification. Moreover, many studies have used the interpregnancy interval in the general population rather than the time to pregnancy (TTP) to assess fecundability,[5] even though the interpregnancy interval is largely influenced by the couple’s pregnancy intentions and planning. Spontaneous abortion (SA), an important indicator of fecundability, has also been largely overlooked in most of these studies. Due to the limited data in the literature, the associations between cesarean delivery and fecundability across diverse populations, potential synergistic factors, and changes in post-cesarean fecundability over time remain unclear.
We therefore conducted a large population-based cohort study using data from the National Free Pre-pregnancy Check-ups Project (NFPCP) to examine the association between cesarean delivery and TTP as well as SA. We also aimed to identify population-specific and potential synergistic factors underlying this relationship and to explore whether there is an optimal time interval from operation to attempting subsequent pregnancy that minimizes the risks of prolonged TTP and SA, thereby providing more personalized support for women.
The NFPCP is a national public health service project jointly organized by the National Health Commission and Ministry of Finance of China in 2010. The project was approved by the Institutional Research Review Board of the National Research Institute for Family Planning in Beijing, China (IRB-201001, December 23, 2009). Written informed consent was acquired from each participant.
In total, 314,050 couples with female participants aged 20–49 years who had participated in the NFPCP twice between January 1, 2013 and December 31, 2019 were enrolled. Females who were pregnant during the interval between two enrollments or at the second enrollment were excluded due to a lack of reliable TTP data. We also excluded participants who were not planning to conceive and those with reproductive system malformations or viral infections that could affect fecundability. Finally, a total of 227,907 female participants were included for 1:3 propensity score matching by delivery mode. Details of the exclusion criteria are presented in Supplementary Figure 1, http://links.lww.com/CM9/C723.
The exposure factor in this study was the delivery mode (vaginal or cesarean) as recorded during the initial participation in the NFPCP among female participants who completed both enrollments. Two primary outcomes were assessed during the 2-year follow-up period. First, TTP, measured in cycles, was calculated using this formula: TTP = (date of the last menstrual period [for pregnant women] or date of the most recent follow-up [for nonpregnant women] − date of enrollment) / mean menstrual cycle length + 1.[6] Second, SA was defined as pregnancy loss or fetal death occurring before 28 weeks of gestation. All analyses were carried out with the use of R software (version 4.2.2, The R Foundation for Statistical Computing, Vienna, Austria, https://www.r-project.org/). P-values were considered to be statistically significant if they were <0.05. Further details on data collection, covariable definitions, and statistical analyses are provided in the Supplementary Methods, http://links.lww.com/CM9/C723.
After propensity score matching, 196,532 females (49,133 cesarean vs. 147,399 vaginal) were included in TTP analysis, and 69,080 females (17,270 cesarean vs. 51,810 vaginal) were included in SA analysis. Baseline characteristics were well balanced between the two delivery mode groups [Supplementary Tables 1 and 2, http://links.lww.com/CM9/C723]. The characteristics of participants included in the TTP and SA analyses are presented in Supplementary Tables 3 and 4, http://links.lww.com/CM9/C723, respectively.
As shown in Kaplan–Meier plot, the cumulative pregnancy probabilities for participants with previous cesarean delivery were 14.68%, 22.59%, and 32.79% at 3, 6, and 12 cycles, respectively. In contrast, the corresponding probabilities for participants with previous vaginal delivery were 23.30%, 33.91%, and 45.05%, respectively. A statistically significant difference in cumulative pregnancy probability was observed between cesarean and vaginal delivery groups (log-rank P <0.001) [Supplementary Figure 2, http://links.lww.com/CM9/C723].
The multivariable-adjusted hazard ratios (HRs) for TTP and odds ratios (ORs) for SA, along with their corresponding 95% confidence intervals (CIs), are presented in Supplementary Table 5, http://links.lww.com/CM9/C723. Compared to women with previous vaginal delivery, those with previous cesarean delivery had a 33% lower likelihood of becoming pregnant (HR, 0.67; 95% CI, 0.66–0.69). Additionally, women with cesarean delivery had a 1.64-fold higher risk of SA (OR, 1.64; 95% CI, 1.47–1.82) than those with previous vaginal delivery. Similar results were obtained after excluding females with multiple births and those who had two or more previous deliveries before the second enrollment.
In the interaction analysis, significant synergistic effects were observed between cesarean delivery and several factors, including being underweight (relative excess risk index [RERI], 0.12; 95% CI, 0.07–0.16), tobacco exposure (RERI, 0.08; 95% CI, 0.02–0.13), hypertension (RERI, 0.10; 95% CI, 0.01–0.21), impaired fasting glucose (RERI, 0.11; 95% CI, 0.03–0.19), decreased thyrotropin level (RERI, 0.11; 95% CI, 0.03–0.20), and a history of adverse pregnancy outcomes (RERI, 0.11; 95% CI, 0.07–0.14) in relation to prolonged TTP [Supplementary Table 6, http://links.lww.com/CM9/C723]. Subgroup analyses indicated that the association was not modified across populations with different characteristics [Supplementary Figures 3 and 4, http://links.lww.com/CM9/C723].
As shown in Supplementary Figure 5, http://links.lww.com/CM9/C723, HRs and ORs were recalculated using a time interval of 25–36 months after vaginal delivery as the control group. Among women with prior cesarean delivery, an interval of 25–36 months was associated with a higher pregnancy rate (HR, 0.70; 95% CI, 0.68–0.73) and a lower risk of SA (OR, 1.68; 95% CI, 1.36–2.08). These results remained consistent among participants aged 20–29 years and those aged 30 years or older [Supplementary Tables 7 and 8, http://links.lww.com/CM9/C723].
This large-scale pregnancy-planning cohort comprehensively examined the association between cesarean delivery and fecundability, including TTP and SA. Compared with women who had vaginal deliveries, those with prior cesarean deliveries showed a 33% reduction in the odds of pregnancy and a 64% increase in the risk of SA. Synergistic effects were also observed between cesarean delivery and maternal lifestyle or health factors on subsequent fecundability. Moreover, a time interval of 25–36 months between cesarean delivery and attempting the next pregnancy was associated with optimal fecundability.
The association between cesarean delivery and prolonged TTP found in this study aligns with previous researches.[4,5] Although some studies based on smaller cohorts compared SA rates between cesarean and vaginal delivery groups,[4] few have thoroughly examined the impact of cesarean delivery on the risk of SA in subsequent pregnancies. The present study expands on this evidence, demonstrating that women with prior cesarean delivery face a significantly increased risk of SA, providing new insights into the relationship between cesarean delivery and fecundability.
In this study, interaction analysis was conducted for the first time to identify potential synergistic factors linking cesarean delivery and fecundability. Interestingly, we found that being underweight, tobacco exposure, hypertension, impaired fasting glucose, decreased thyrotropin, and a history of adverse pregnancy outcomes acted as synergistic factors influencing the relationship between cesarean delivery and TTP. Identifying these factors enables more targeted management of women who have undergone cesarean delivery, enabling personalized medical advice and interventions. Such a tailored approach may help reduce potential fertility barriers, improve the likelihood of successful conception, and optimize the use of clinical resources. However, further studies are needed to confirm the reliability and generalizability of these findings.
Several possible biological mechanisms have been proposed till date to explain the association between cesarean delivery and fecundability. First, cesarean delivery can trigger a local inflammatory response, leading to pelvic adhesions, tubal obstruction, or disruption of the placental bed, all of which may contribute to infertility.[4] Second, women with a cesarean scar diverticulum are at higher risk of infertility, possibly due to the accumulation of menstrual blood and inflammatory fluid within the uterine scar.[5] Further research is needed to clarify the biological mechanisms underlying the link between cesarean delivery and fecundability, as well as the role of associated synergistic factors.
Despite global efforts to reduce non-indicated cesarean delivery, medically necessary cesarean delivery remains indispensable for protecting maternal and neonatal health and continues to play a crucial role in reducing maternal mortality. For women who have undergone cesarean delivery, identifying the optimal time interval before the next pregnancy is essential to minimizing the risks associated with subsequent conception. Our study suggests that waiting 25–36 months after cesarean delivery before attempting another pregnancy is ideal, aligning with the World Health Organization recommendation of at least a 24-month interval.[7] Such an interval strategy promotes healthier outcomes for mothers and infants while also improving the likelihood of a successful pregnancy.
This study has several notable strengths. First, participants with strong or rare confounding factors were excluded from the pregnancy-planning cohort to ensure broader population representativeness and to more accurately examine the association between cesarean delivery and fecundability. Second, our study provides a key evidence of changes in fecundability across varying time intervals after cesarean delivery. Third, by incorporating SA and TTP as outcome indicators, we enhanced the precision of fecundability assessment.
However, several limitations should be acknowledged. Because data on pregnancy and childbirth complications were missing, we could not determine the extent to which these factors contributed to reduced post-cesarean fecundability. Additionally, the NFPCP database lacked detailed information related to fecundability, such as intercourse frequency and semen quality. As with previous studies, unmeasured or unknown covariables (e.g., socioeconomic status and healthcare accessibility) may also exist. Finally, some participants may have begun preparing for pregnancy before being enrolled in the project, potentially affecting TTP calculations and optimal interval estimations; thus, our findings should be interpreted with caution in clinical application.
In conclusion, this large retrospective cohort study in China found that cesarean delivery is associated with prolonged TTP and an increased risk of SA compared with vaginal delivery. We also identified an optimal time interval of 25–36 months for women planning a subsequent pregnancy after cesarean delivery. These findings suggest that minimizing unnecessary cesarean delivery may help preserve fertility, and clinicians should emphasize reproductive planning and optimal timing for women requiring cesarean delivery.
Acknowledgments
We thank all the health workers and countless participants throughout 31 provinces and cities for their considerable efforts and collaboration in the NFPCP.
Funding
This study was supported by grants from the National Key Research and Development Program of China (Nos. 2016YFC1000307 and 2025YFC2708303).
Conflicts of interest
None.
Supplementary Material
Footnotes
How to cite this article: Li JX, Jin YY, Zhao CY, Lyu XY, Tenzin T, Hu X, Liu MY, Wu HB, Lei JM, Cheng ZY, Fu WY, Xu JH, He Y, Wang YY, Zhang Y, Peng ZQ, Zhang HG, Wang QM, Shen HP, Zhang YP, Yan DH, Wei YM, Yang Y, Ma X. Association of cesarean delivery with time to pregnancy and risk of subsequent spontaneous abortion: A retrospective cohort study in China. Chin Med J 2026;139:623–625. doi: 10.1097/CM9.0000000000003954
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