Cumulative Live Birth Rate in Patients With Subtle Distal Fallopian Tube Abnormalities: A Retrospective Cohort Study

In: Reproductive Medicine and Biology · 2025 · vol. 24(1) , pp. e12677 · doi:10.1002/rmb2.12677 · PMID:40950645 · PMC12423111 · W4414137929
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Abstract

Purpose: Compare reproductive outcomes between patients with subtle distal fallopian tube abnormalities (SDFTA) and unexplained infertility (UI) undergoing in vitro fertilization (IVF), exploring influencing factors. Methods: This retrospective study analyzed 447 women undergoing their first IVF cycle after laparoscopic evaluation for UI between January 2019 and December 2021. Based on laparoscopic findings, 162 women were classified into the SDFTA group and 285 into the UI group. Propensity score matching (PSM) created 160 matched pairs. The primary outcome was the cumulative live birth rate (CLBR) over 24 months. Results: = 0.033). Independent predictors of CLBR were age at retrieval, the number of oocytes retrieved, and the number of IVF cycles. Conclusions: In conclusion, despite an increased risk of ectopic pregnancy, patients with SDFTA undergoing IVF exhibit favorable cumulative reproductive outcomes.
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Ethics

The study protocol received approval from the Ethics Committee of the First Hospital of Lanzhou University (No. LDYYLL‐2025‐750).

Results

Between January 2019 and December 2021, 8477 patients underwent IVF treatment at our institution. Among them, 2966 patients (35.0%) had undergone prior laparoscopic surgery. The primary indications for laparoscopy were categorized as follows: tubal factors ( n  = 1189, 40.1%), ovarian endometriomas ≥ 4 cm detected by ultrasound ( n  = 848, 28.6%), UI ( n  = 638, 21.5%), and recurrent IVF failure ( n  = 291, 9.8%). From the UI subgroup ( n  = 638), 191 patients were excluded based on preoperative diagnoses of endometriosis, bilateral distal tubal obstruction, or other exclusionary diseases. Consequently, 447 women with pure UI constituted the final cohort. Among the 447 women, 162 were diagnosed with SDFTA (36.24%), while the remaining 285 women were classified in the UI group. Among the 162 SDFTA cases, fimbrial agglutination (35.8%; n  = 58) was the most common abnormality, followed by morgagni hydatids (MH) (24.7%; n  = 40), fimbrial phimosis (22.8%; n  = 37), tubal diverticula (8.6%; n  = 14), accessory fallopian tube (4.9%; n  = 8), and tubal accessory ostium (3.1%; n  = 5). After PSM, 160 women were included in each group. During the 24‐month follow‐up period, the SDFTA group completed 193 ovulation stimulation cycles while the UI group completed 205 cycles. A total of 33 women with remaining embryos discontinued follow‐up (SDFTA: 19; UI: 14), primarily due to loss to contact ( n  = 22), divorce ( n  = 6), or spontaneous pregnancy ( n  = 5) (Figure  1 ). Patient flowchart. Demographic characteristics of the cohort before and after PSM. Note: Non‐Gaussian as median (interquartile range). Categorical variables expressed as (%). Abbreviations: AFC, antral follicle count (2–10 mm); AMH, anti‐Müllerian hormone (ng/mL); BMI, body mass index; FSH, follicle‐stimulating hormone; PSM, propensity score matching; SDFTA, subtle distal fallopian tube abnormalities; UI, unidentified infertility. Mann–Whitney U test. Pearson's chi‐squared test or Fisher's exact test. Table  1 presents the baseline demographics of patients before (left column) and after (right column) PSM. Before matching, the SDFTA group had significantly higher AMH levels (median [IQR]: 3.83 ng/mL [2.53–5.95] vs. 3.25 ng/mL [2.32–5.40], p  = 0.03), and a longer duration of infertility (median [IQR]: 3.00 [2.00–4.00] vs. 3.00 [2.00–4.00], p  = 0.044) compared to the UI group. After PSM, all baseline characteristics were comparable between the groups, with no statistically significant differences observed ( p  > 0.05). Cycle stimulation characteristics of couples who completed treatment. Note: Continuous data are expressed as medians (interquartile ranges). Non‐Gaussian as median (interquartile range). Categorical variables expressed as (%). Abbreviations: MII, metaphase II mature oocyte; SDFTA, subtle distal fallopian tube abnormalities; UI, unidentified infertility. Pearson's chi‐squared test or Fisher's exact test. Mann–Whitney U test. No notable variances were observed in the Stimulation protocol, total Gn dose, or FSH stimulation days between the two groups. Nevertheless, on the trigger day, progesterone levels were markedly elevated in the UI group (median [IQR]: 1.13 ng/mL [0.78–1.79] vs. 0.95 ng/mL [0.65–1.4], p  = 0.03), while peak estradiol levels showed no significant difference ( p  > 0.05). No significant differences were observed in the number of oocytes retrieved, MII oocytes, number of usable embryos on Day 3, or the number of good quality embryos between the two groups. Comparison of pregnancy outcomes between the two groups. Note: Categorical variables expressed as (%). Abbreviations: CLBR, cumulative live birth rate; ET, embryo transfer; FET, frozen–thawed embryo transfer; HCG, human chorionic gonadotropin; LBR, live birth rate; SDFTA, subtle distal fallopian tube abnormalities; UI, unidentified infertility. Pearson's chi‐squared test or Fisher's exact test. Calculation of LBRs and CLBRs for the completed cycles. Note: Categorical variables expressed as number (%). Abbreviations: CLBR, cumulative live birth rate; LBR, live birth rate; SDFTA, subtle distal fallopian tube abnormalities; UI, unidentified infertility. Pearson's chi‐squared test or Fisher's exact test. A total of 257 embryo transfer cycles (129 fresh, 128 frozen) in the SDFTA group and 270 cycles (128 fresh, 142 frozen) in the UI group were analyzed. The CLBR per oocyte retrieval cycle did not differ significantly between the two groups (65.8% vs. 60.0%, p  = 0.231). Similarly, no significant differences were observed in β‐hCG positivity rate, biochemical pregnancy rate, CPR, LBR per transfer, or preterm birth rate ( p  > 0.05). Notably, the early miscarriage rate was significantly lower in the SDFTA group compared to the UI group (8.3% vs. 16.1%, p  = 0.036). Conversely, the ectopic pregnancy rates were significantly higher in the SDFTA group (5.8% vs. 1.3%, p  = 0.033), including tubal diverticula (1/9, 11.1%), fimbrial agglutination (2/9, 22.2%), tubal accessory ostium (4/9, 44.4%), and fimbrial phimosis (2/9, 22.2%). Furthermore, Kaplan–Meier analysis revealed no significant difference in CLBRs over four IVF cycles between the groups (Log‐rank test: χ 2  = 1.054, p  = 0.304), as shown in Figure  2 . Kaplan–Meier curves of cumulative live birth rates for two groups. The curves show the cumulative live birth rates (CLBRs) the number of embryo transfer cycles increased. Regression analysis of factors predicting a cumulative live birth in an oocyte retrieval cycle. Abbreviations: AFC, antral follicle count (2–10 mm); AMH, anti‐Müllerian hormone (ng/mL); BMI, body mass index; ET, embryo transfer; FET, frozen–thawed embryo transfer; FSH, follicle‐stimulating hormone; IVF, in vitro fertilization; SDFTA, subtle distal fallopian tube abnormalities; UI, unidentified infertility. A multivariable Poisson regression analysis of factors predicting the cumulative LBR of the oocyte retrieval cycle is shown in Table  5 . Univariate and multivariate analyses revealed no significant association between SDFTA and CLBR ( p  > 0.05). Additionally, this model demonstrated that female age at oocyte retrieval (adjusted RR = 0.98, 95% CI: 0.96–1.00; p  = 0.018), the number of oocytes retrieved (adjusted RR = 1.01, 95% CI: 1.00–1.02; p  = 0.008), and the number of IVF cycles (adjusted RR = 0.88, 95% CI: 0.79–0.97; p  = 0.011) were significantly associated with the cumulative LBR.

Discussion

Traditionally, SDFTA have been regarded as anatomical variants without clinical significance. However, emerging research indicates that these lesions are more prevalent in infertile populations, suggesting a potential role in the etiology of infertility [ 17 ]. Notably, there is a high rate of comorbidity between SDFTA and early‐stage endometriosis (EMs), with a co‐occurrence rate of up to 90.5%. This implies that the inflammatory microenvironment associated with EMs may contribute to early tubal dysfunction. However, several critical questions remain regarding SDFTA: (1) the role of early laparoscopy in UI for detecting SDFTA; (2) criteria for selecting UI patients benefiting from surgery versus direct IVF; (3) natural pregnancy rates post‐intervention; and (4) comparative reproductive outcomes between SDFTA and actual UI following IVF. High‐quality evidence and consensus on these pivotal clinical questions are currently lacking. This study provides new insights to address these questions and justifies the rationale for laparoscopic evaluation before IVF. Although laparoscopy is not routinely recommended for all patients before IVF, it may be considered in certain conditions to improve the success rate of IVF by diagnosing and treating underlying pelvic abnormalities [ 18 , 19 , 20 ]. Laparoscopy enables doctors to visualize and evaluate the pelvic organs directly, which can help identify conditions such as endometriosis, adhesions, or tubal abnormalities that may not be detectable through non‐invasive tests [ 18 ]. In addition, laparoscopy can achieve simultaneous diagnosis and treatment of specific conditions, such as endometriosis lesions and adhesions, which may improve fertility outcomes [ 19 ]. Furthermore, laparoscopy, either alone or combined with other treatments, can potentially improve the success rates of subsequent IVF cycles [ 20 ]. Therefore, laparoscopy before IVF can be a viable option to improve fertility outcomes, with careful patient selection and strict adherence to institutional protocol and guidelines [ 20 , 21 ]. Specifically, patients with the following conditions are potential candidates for laparoscopic evaluation before IVF: (1) younger patients (< 27 years old) with prolonged infertility (over 2 years); (2) patients diagnosed with UI after a basic infertility workup; (3) patients with symptoms suggestive of endometriosis (dysmenorrhea, dyspareunia), distal tubal occlusion, previous pelvic infections, or surgeries; (4) patients with a history of recurrent IVF failure [ 20 , 21 ]. In our study, the detection rate of SDFTA among women originally classified as UI was 36.24%, which was comparable to that reported in most previous studies. A prospective cohort study found that 28.65% of infertile patients undergoing laparoscopy exhibited SDFTA [ 22 ]. Notably, in a multicenter prospective observational study, a significantly higher prevalence of SDFTA was reported in the infertile group (50.1%) [ 23 ]. Shoukry et al. reported that among 120 UI patients, 58% were diagnosed with subtle fallopian tube abnormalities [ 24 ]. The discrepancies in the detection rate of SDFTA across studies may be attributed to multiple factors, including differences in study regions, participant selection, study design, and measurement tools. However, all these findings highlight the importance of recognizing and addressing SDFTA in the evaluation of female infertility. Additionally, our study demonstrates favorable clinical outcomes for patients with SDFTA undergoing IVF. Our findings indicated that patients with SDFTA achieved CLBR comparable to those with UI (65.8% vs. 60.0%, p  = 0.231), despite a significantly elevated risk of ectopic pregnancy (5.8% vs. 1.3%, p  = 0.033). Notably, the early miscarriage rate was significantly lower in the SDFTA group than in the UI group (8.3% vs. 16.1%, p  < 0.05), even though both rates fell within the range reported in prior literature (approximately 15%). This discrepancy may be related to the multifactorial, synergistic effects present in UI patients that are difficult to detect through conventional testing; however, this hypothesis requires mechanistic validation. In contrast, the cause of infertility in the group with SDFTA is straightforward and relatively simple. When lesions are mild, patients' ovarian function, embryonic developmental potential, and endometrial microenvironment are typically not significantly impaired. Bypassing tubal functional defects via IVF technology minimizes disruptions to embryo implantation and development, resulting in miscarriage risks closer to those observed in natural pregnancies. The incidence of ectopic pregnancy was notably higher in the SDFTA group (5.8%) compared to the UI group (1.3%, p  = 0.033). This suggests that functional tubal impairment may pose a greater risk for ectopic implantation. Prior research also supports this hypothesis: Schmidt et al. reported that patients with intact tubal mucosa achieved pregnancy rates up to 100% after IVF with no ectopic pregnancies, whereas those with bilateral mucosal lesions had a lower intrauterine pregnancy rate (35%) and experienced ectopic implantation after IVF [ 25 ]. Furthermore, prospective data show that when < 50% of the tubal mucosa is normal, the chance of intrauterine pregnancy is only 7% [ 26 ]. This chance significantly increases to 50%–69% when 50%–70% of the mucosa is preserved [ 26 ]. Although laparoscopic surgery can alleviate adhesions, it cannot reverse mucosal fibrosis. Pre‐IVF laparoscopic assessment is therefore critical in patients with hydrosalpinx. Thin‐walled hydrosalpinx with preserved ampullary mucosa is associated with higher intrauterine pregnancy rates and lower ectopic pregnancy risk, whereas thickened, fibrotic tubes confer poor outcomes [ 26 ]. However, due to the limited number of cases ( n  = 9), we were unable to conduct a detailed analysis of the different subtypes of tubal minimal lesions or to clarify the impact of surgical methods on pregnancy outcomes in these patients. Age remains one of the most pivotal predictors of success in assisted reproductive technology such as IVF. A previous retrospective comparative study reported CLBRs of 62.9% and 51.4% for women under 35 years old and those aged 35–37 years, respectively [ 27 ]. Our Poisson's analysis has established female age as an independent negative predictor of CLBR, with a 2% decline in CLBR for every 1‐year increase in age (adjusted RR = 0.98, 95% CI: 0.96–1.00; p  = 0.018). The number of retrieved oocytes stands as a core positive predictor of CLBR, with each additional oocyte retrieved correlating to a 1% increase in CLBR. A study encompassing 400 135 treatment cycles demonstrated that the CLBR rises in tandem with the number of recovered oocytes [ 28 ]. However, it is important to note that while this dose–response relationship highlights the critical role of oocyte quantity, the quality of oocytes—often influenced by factors such as maternal age and ovarian reserve—also significantly impacts CLBR [ 29 ]. Given the irreversible decline in ovarian reserve function with age and its critical impact on IVF outcomes, it is recommended that all patients undergoing pelvic surgery undergo routine preoperative ovarian reserve assessment (AMH/AFC) and follow‐up examinations 3–6 months postoperatively to monitor changes in ovarian function dynamically. If reserve indicators decline significantly (AMH decrease > 50%), it is recommended to initiate fertility preservation counseling and adjust assisted reproductive strategies promptly. From a methodological standpoint, our study employed PSM to reduce baseline imbalances between groups, enhancing the robustness of our findings [ 30 ]. However, several limitations remain. First, the retrospective study design is susceptible to multiple biases, including selection bias, information bias, confounding bias, and measurement bias. For instance, the presence of unrecorded confounding factors may create spurious correlations or mask true causal relationships, thereby leading to inaccurate or misleading conclusions. Future prospective, longitudinal study designs are needed for a more robust assessment. Second, ovarian reserve parameters were not comprehensively assessed, which could influence reproductive potential [ 31 ]. Third, while we stratified tubal abnormalities by type and number, mucosal integrity was not directly assessed. Future studies should incorporate dynamic functional assessments, such as imaging‐based evaluations of tubal peristalsis and secretory function, to better characterize subtle lesions. Animal models and molecular profiling of the tubal epithelium may further elucidate the pathophysiological impact of these abnormalities [ 32 ].

Conclusions

Prior to undergoing IVF treatment, all patients provided written informed consent for the collection of anonymized clinical data.

Introduction

Subtle distal fallopian tube abnormalities (SDFTA) represent a group of diseases characterized by inconspicuous anatomical alterations located at the end of the fallopian tube, a vital structure for transporting eggs from the ovaries to the uterus for fertilization [ 1 ]. These include tubal diverticula, hydatids of Morgagni, accessory fallopian tubes, accessory ostium, phimosis, tubal sacculation, and fimbrial agglutination [ 1 ]. While structurally subtle, these abnormalities can significantly impair tubal function, leading to infertility [ 1 ]. Recent epidemiological studies reported that the prevalence of SDFTA among infertile women reached 28.7% [ 2 ], highlighting their clinical relevance. While the precise pathogenic mechanisms remain partially understood, existing evidence associates these anomalies with functional impairments affecting ovum pickup and transport [ 3 ], potentially reducing endometrial receptivity [ 4 ]. Diagnostic challenges arise from their frequent preservation of tubal patency and lack of overt symptoms, often leading to misclassification as unexplained infertility (UI) and consequent delays in intervention. Laparoscopy is considered the “gold standard” for evaluating pelvic pathology and tubal patency, which can provide a detailed anatomical assessment and perform concurrent surgical correction (e.g., salpingoplasty) [ 5 , 6 ]. However, the American Society for Reproductive Medicine (ASRM) guidelines do not endorse the routine use of diagnostic laparoscopy for evaluating UI due to its invasive nature, high cost, long recovery time, and potential complications [ 7 ]. In today's clinical landscape, especially for aging populations, there is a growing trend to favor in vitro fertilization (IVF) over laparoscopy as an initial approach for infertility treatment [ 8 ]. IVF is considered a more pragmatic option because it offers a potentially quicker path to pregnancy by addressing various infertility issues and allowing for controlled ovarian stimulation to maximize pregnancy chances [ 9 ]. IVF is widely employed for tubal infertility, with pregnancy rates reaching 50% per embryo transfer cycle [ 10 ]. However, 25% of patients require ≥ 5 cycles, and 12% need ≥ 7 attempts to achieve success [ 11 ]. Moreover, tubal infertility is associated with elevated risks of miscarriage, preterm birth, and placenta previa versus other infertility etiologies [ 12 , 13 ]. In this case, laparoscopic evaluation before IVF may be considered a valuable approach to address underlying fertility issues and improve IVF success rates. So far, it remains debatable whether laparoscopic evaluation should be conducted before IVF, and whether patients with SDFTA should be managed differently from typical UI patients. There is a noted gap in systematic data on IVF outcomes for patients with SDFTA, especially those failing spontaneous conception after laparoscopic procedures. Zheng et al. ( n  = 59) observed reduced full‐term delivery rates and increased preterm and multiple births in patients with SDFTA undergoing IVF; however, predictive factors for outcomes in this population remain undefined [ 2 ]. Hence, the study aimed to compare pregnancy outcomes, particularly cumulative live birth rates (CLBRs), between individuals diagnosed with SDFTA and those diagnosed with UI following laparoscopy. By combining propensity score matching (PSM) and robust (modified) Poisson regression, our study can address confounding bias and directly estimate risk ratios, thus offering a powerful approach to investigating the complex relationships between UI, SDFTA, and reproductive health outcomes. Our findings hold promise for providing new insights regarding treatment strategies and pregnancy monitoring for patients with infertility.

Coi Statement

The authors declare no conflicts of interest.

Materials And Methods

Data were retrieved from the Clinical Reproductive Medicine Management System at the Reproductive Medical Center, First Hospital of Lanzhou University. Prior to undergoing IVF treatment, all patients provided written informed consent for the collection of anonymized clinical data. The study protocol received approval from the Ethics Committee of the First Hospital of Lanzhou University (No. LDYYLL‐2025‐750). This retrospective cohort study included patients who initiated their first IVF cycle after undergoing laparoscopic evaluation for UI between January 2019 and December 2021. Inclusion criteria: (i) female aged 20–40 years; (ii) with a normal menstrual cycle; and (iii) ≥ 12 months of infertility after surgical therapy despite regular unprotected intercourse. Exclusion criteria: (i) chromosomal abnormalities or monogenic disorders (in either partner); (ii) history of recurrent spontaneous abortion or unhealthy progeny; (iii) autoimmune diseases; (iv) bilateral distal tubal obstruction; (v) endometriosis; (vi) congenital malformations of the female reproductive system; (vii) uterine fibroids; and (viii) cycles lacking accessible follow‐up data. All patients included in the study were followed up for 24 months from the date of first ovulation stimulation. Follow‐up concluded upon live birth or cryopreserved embryo exhaustion (utilization of all viable frozen embryos derived from retrieved oocytes). For this study, we included six types of SDFTA for analysis: Morgagni hydatids (MH), fimbrial agglutination, tubal diverticula, tubal accessory ostium, fimbrial phimosis, and accessory fallopian tube. MH are simple cysts that originate from the remnants of paramesonephric (müllerian) or mesonephric (Wolffian) ducts present during urogenital embryologic development, characterized by thin‐walled, smooth, pedunculated cysts arising from the fallopian tube, containing clear fluid. Fimbrial agglutination is defined as one or more adhesive bridges of fimbria across the opening of the fallopian tube (the ostium), which can be classified as either unilateral or bilateral. Tubal diverticula are described as small, concentric, localized, thin‐walled outpouches found in the ampullary or isthmic region of the fallopian tubes. Tubal accessory ostium refers to a finger‐like projection at the end of the fallopian tube (ectopic fimbria) that is located away from the normal fimbriated end of the tube. Fimbrial phimosis refers to a concentric stricture located at the infundibular fimbrial junction of the fallopian tube. An accessory fallopian tube is a rare congenital abnormality where a secondary tube is connected to the ampullary region of the main fallopian tube, but with a separate, open fimbriated end lacking communication with the main tube's lumen. Within our clinical framework, laparoscopy constitutes a secondary diagnostic approach for evaluating fallopian tube patency. This intervention is typically reserved for patients meeting specific criteria: (1) history of ≥ 3 unsuccessful intrauterine inseminations (IUIs); (2) UI with prior pelvic surgery; (3) UI persisting beyond 2 years; and (4) suggestive pelvic pathology identified via ultrasound/hysterosalpingography. For patients presenting with advanced maternal age, prolonged infertility duration, or diminished anti‐Müllerian hormone (AMH) levels, IVF may be prioritized as an initial treatment strategy. Laparoscopies were performed by two senior reproductive surgeons familiar with the diagnostic criteria of SDFTA, and each procedure was recorded on video. Laparoscopy was performed under endotracheal general anesthesia. A systematic laparoscopic evaluation was conducted to achieve an accurate depiction of the pelvic organs. The patency of the fallopian tubes was assessed by perfusion of diluted methylene blue dye. All SDFTA cases underwent tubal correction. Fimbrial agglutination was separated and removed using bipolar electrocoagulation. Tubal diverticula were first clamped with separation forceps and then closed with 6‐0 absorbable purse‐string sutures. The tubal accessory ostium was removed after electrocoagulation. Fimbrial phimosis was corrected by laparoscopic fimbrioplasty. Tubal mesosalpinx cystectomy was performed for MH. If the cyst was pedunculated, it was resected using an electrocoagulation hook at its pedicle. Two experienced physicians with expertise in SDFTA diagnosis independently evaluated the patient's records and imaging studies. In cases of disagreement, a third senior physician was invited to discuss the discrepancies and reach a consensus diagnosis. Participants were stratified into two groups based on laparoscopic findings: (1) SDFTA group and (2) UI group (no apparent abnormalities observed). Two primary COS protocols were utilized according to patient characteristics: the GnRH antagonist protocol and the early follicular long‐acting GnRH agonist protocol [ 14 ]. On menstrual cycle days 2–3, transvaginal ultrasound and serum tests for FSH, luteinizing hormone (LH), estradiol (E 2 ), and progesterone were performed. Patients with no substantial follicular growth, cysts, or abnormal hormone levels proceeded to protocol‐specific interventions. In the early follicular long‐acting GnRH agonist protocol, down‐regulation was initiated with a single 3.75 mg dose of GnRH agonist. Patients returned 28 days later to repeat transvaginal ultrasound and serum hormone assessment. Once down‐regulation criteria were met (FSH < 5 mIU/mL, LH < 5 mIU/mL, E 2 < 30 pg/mL, progesterone < 0.6 ng/mL, antral follicle diameter 4–7 mm, endometrial thickness < 5 mm), ovarian stimulation commenced. Human menopausal gonadotropin (hMG; Lebaode, Lizhu, China) or recombinant FSH (Puregon, Organon, Dublin, Ireland; Gonal F, Merck Serono S.p.A., Modugno, Italy) was administered at a starting dose of 150–300 IU/day. This dose was determined based on the patient's age, baseline anti‐Müllerian hormone (AMH) level, antral follicle count (AFC), and body mass index (BMI), as outlined in the center's standard operating procedures. In the antagonist protocol, patients received recombinant FSH treatment on the second day of the cycle by once‐daily injection. After 5 days of this treatment, the antagonist regimen, ganirelix (Vetter Pharma‐Fertigung GmbH & Co. KG, Germany) 0.25 mg, was administered from the sixth day of ovulation until the trigger day. The gonadotropin (Gn) dose was adjusted according to individual ovarian response, which was assessed by ultrasound every 2–3 days. When 1–3 leading follicles reached ≥ 18 mm in diameter, final oocyte maturation was triggered using triptorelin (0.1 mg; Decapeptyl, Ferring Pharmaceuticals, Netherlands) co‐administered with either human chorionic gonadotropin (hCG, 2000 IU; Lizhu Pharmaceutical Trading Co., China) or recombinant hCG (Ovidrel, 250 μg; Merck Serono S.p.A., Modugno, Italy). Transvaginal ultrasound‐guided oocyte retrieval (TVOR) was performed 34–36 h after trigger administration. Oocytes were fertilized by conventional IVF. Normal fertilization was defined as the presence of two pronuclei, typically assessed approximately 16–18 h after insemination. Embryo quality was assessed on Days 3, 5, and 6. On Day 3, embryos with 7–9 blastomeres of uniform size and < 20% fragmentation, and originating from two pronuclei, were classified as high‐quality embryos; those with ≥ 5 blastomeres of uniform/relatively uniform size and  20% fragmentation were classified as abandoned embryos. Embryo quality was assessed at the blastocyst stage according to Gardner's classification [ 15 ]. For blastocysts graded as 3–6 (i.e., full blastocysts onward), the development of the inner cell mass was assessed as follows: (a) tightly packed, many cells; (b) loosely grouped, several cells; or (c) very few cells. The trophectoderm was assessed as follows: (a) many cells forming a cohesive epithelium; (b) few cells forming a loose epithelium; or (c) very few large cells. When the expansion degree was Grade 3–6 and the inner cell mass and trophectoderm were not (c), they were evaluated as high‐quality blastocysts. When both were (c), they were evaluated as abandoned blastocysts. Fresh embryo transfers were typically performed on either the third or fifth day following retrieval. The number of embryos to transfer (ranging from 1 to 2) was determined based on the quality of the embryos, the female's medical history, and the couple's preferences. In cases where there was a risk of ovarian hyperstimulation syndrome (OHSS), a comprehensive strategy for whole embryo cryopreservation was used. Embryo freezing adopts the high‐safety straw (Croy Bio System, La Igle, France) and vitrification cryopreservation technology (Irvine) (Scientific, Santa Ana, CA, USA). The frozen embryo transfer protocol depends on the ovulation status, such as a natural cycle regimen (for patients with normal ovulation) or a hormone replacement cycle regimen (for patients with anovulation). Intravaginal natural progesterone 600 mg/day combined with oral dydrogesterone 30 mg/day was used until 10–12 weeks of pregnancy (In fresh embryo transfer, luteal support starting on the day of oocyte retrieval). The primary outcome was the CLBR per oocyte retrieval cycle, calculated as the ratio of the number of first deliveries (> 24 weeks of gestation, including both fresh and frozen cycles) with at least one live birth to the number of retrieved oocyte cycles. Multiple births (singleton, twin, or multiple) were counted as one live birth event. The CLBR was computed with the completed cycles. A completed cycle was defined as an oocyte retrieval cycle that either resulted in at least one live birth or involved the transfer of all viable embryos without achieving a live birth. Secondary outcomes included biochemical pregnancy rate, clinical pregnancy rate (CPR), live birth rate (LBR), ectopic pregnancy rate, miscarriage rate, preterm birth rate, and laboratory parameters. Biochemical pregnancy was defined as a serum HCG concentration greater than 10 IU/L on the 13th–14th day after embryo transfer, but with no gestational sac observed later. Clinical pregnancy was identified as the presence of at least one gestational sac with or without fetal heart activity at seven gestational weeks. Live birth was defined as the delivery of a viable infant at 24 weeks or more of gestation. Ectopic pregnancy is described as a pregnancy outside the uterine cavity, diagnosed by ultrasound, surgical visualization, or histopathology. Early miscarriage was defined as spontaneous pregnancy termination prior to the gestational age of 12 weeks. Preterm birth was defined as delivery occurring between 28 +0 and 36 +6 weeks' gestation [ 16 ]. To address potential confounding, PSM was performed using a 1:1 matching ratio with a caliper width of 0.1. Propensity scores were calculated based on the following covariates: female age, BMI, duration of infertility, type of infertility, AMH level, AFC, and basal FSH level. Continuous data with normal distribution were presented as means ± standard deviations (SDs) and compared by Student's t test, while those with non‐normal distribution were presented as medians (interquartile ranges [IQRs]) and compared with the Mann–Whitney U test. Categorical variable data were expressed as the number of cases (%) and compared using the Pearson's chi‐squared test or Fisher's exact test, as appropriate. Kaplan–Meier curves, with live birth as the event of interest, were generated to illustrate the CLBRs across groups as the number of embryo transfers increased. A robust (modified) Poisson regression model was employed to assess the relationship between SDFTA type and CLBRs, yielding risk ratios (RRs) and adjusted risk ratios (aRRs) along with 95% confidence intervals (CIs). The variables in the regression model included cause of infertility, female age at oocyte retrieval, type and duration of infertility, female BMI, number of IVF cycles, number of oocytes retrieved, and number of usable embryos on Day 3. All analyses were conducted using SPSS version 25.0 (IBM Corp., Armonk, NY, USA). A two‐sided p ‐value < 0.05 was considered statistically significant.

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