Abstract
Objective: To evaluate the effect of prior uterine cavity procedures on clinical and neonatal outcomes in patients undergoing first-time in vitro fertilization-embryo transfer with donor sperm (IVF-ET with DS). Methods: This retrospective cohort study included 599 infertility patients receiving their first IVF-ET with DS. Patients were categorized into two groups: those with a history of uterine cavity operation group (n=457) and the group with no history (n=142). The former was further subdivided into curettage (n=67), hysteroscopy (n=292), and complex uterine operations (n=98). Primary outcomes included clinical pregnancy outcomes (implantation rate, clinical pregnancy rate, miscarriage rate, and live birth rate) and neonatal outcomes (gestational age, birth weight and length, incidence of being small for gestational age [SGA], large for gestational age [LGA], and preterm birth). Results: No significant differences were found in clinical pregnancy outcomes between the non-operative, curettage, and complex operation groups (all P > 0.05). However, the hysteroscopy group showed significantly lower miscarriage rates and higher implantation, clinical pregnancy, and live birth rates (all P < 0.05). Multivariate analysis confirmed that hysteroscopy history was independently associated with improved pregnancy outcomes and reduced miscarriage rates, particularly in both age groups (< 35 and ≥ 35 years). No significant differences in neonatal outcomes were observed across all groups (all P > 0.05). Conclusion: A history of hysteroscopy is associated with improved implantation, clinical pregnancy, and live birth rates, and a lower miscarriage rate in patients undergoing first IVF-ET with DS, without affecting neonatal outcomes.
Keywords: History of intrauterine operation, in vitro fertilization-embryo transfer, pregnancy outcome, neonatal outcome
Introduction
In vitro fertilization and embryo transfer (IVF-ET) is a widely used clinical treatment for infertility. Successful clinical pregnancy after IVF-ET depends on multiple factors, among which the uterine environment plays a critical role. An abnormal uterine environment can impair embryo implantation and pregnancy maintenance, leading to poor outcomes after embryo transfer [1,2].
Uterine surgery is a common gynecological intervention used for diagnosis and treatment, including procedures such as dilation and curettage (D&C), surgical abortion, diagnostic curettage, and hysteroscopic surgery [3]. Procedures like surgical abortion may increase the risk of pelvic inflammatory disease (e.g., salpingitis) and damage the endometrial environment, thereby contributing to infertility [4,5]. Some studies suggest that a history of uterine surgery is associated with reduced success rates in assisted reproduction [6]. However, the impact of prior uterine manipulation on pregnancy and neonatal outcomes after IVF-ET remains controversial. For example, a study by Ozgur et al. [7] reported that surgical abortion adversely affects pregnancy outcomes within six months of the procedure, while other studies found no significant impact of uterine evacuation history on subsequent IVF-ET outcomes [8].
Therefore, the effect of different types of uterine interventions on clinical and neonatal outcomes in IVF-ET cycles remains unclear. This study aims to minimize the confounding effects of male age and sperm quality by focusing on IVF-ET cycles using donor sperm (IVF-ET with DS), to assess the influence of various uterine procedures on clinical pregnancy and neonatal outcomes, and to explore potential mechanisms, thereby providing theoretical support for improving IVF-ET success rates and neonatal health.
Materials and methods
General information
This retrospective study included 599 infertility patients who underwent first-time IVF-ET with DS between January 2015 and December 2023 at the Third Affiliated Hospital of Guangxi Medical University and the Second People’s Hospital of Nanning City. The study was approved by the Ethics Committee of the Second People’s Hospital of Nanning City (Ethics Approval No. Y2022015).
Inclusion criteria
(1) patients who received the gonadotropin-releasing hormone (GnRH) agonist long protocol for controlled ovarian hyperstimulation; (2) first-time fresh embryo transfer; (3) complete clinical, diagnostic, treatment, embryo, and outcome data.
Exclusion criteria
(1) congenital uterine anomalies (e.g., septate, bicornuate, unicornuate, or hypoplastic uterus); (2) adenomyosis or endometrial tuberculosis; (3) tubal effusion; (4) sonographic evidence of endometrial polyps; (5) intrauterine fluid, adhesions, etc.; (6) positive serology for hepatitis B, hepatitis C, HIV, or syphilis; (7) ovarian hyperstimulation syndrome; (8) chromosomal abnormalities.
Group classification
Patients were grouped based on their history of intrauterine procedures, including induced abortion, curettage, dilation and curettage, hysteroscopic surgery, or intrauterine device placement/removal. The cohort was divided into a history of uterine cavity operation group (n=457) and a no history group (n=142). The operation group was further classified into three subgroups: Curettage group (n=67): patients who underwent induced abortion, curettage, or dilation and curettage; Hysteroscopy group (n=292): patients with hysteroscopic surgery only; Complex uterine operation group (n=98): patients with multiple types of intrauterine procedures.
Sperm source
Sperm samples were obtained from the following certified sperm banks: Xiangya Reproductive and Genetic Specialty Hospital, the Zhejiang Provincial Institute of Family Planning Science and Technology, Renji Hospital Affiliated to Shanghai Second Medical University, the First Affiliated Hospital of Guangxi Medical University, the Third Affiliated Hospital of Zhengzhou University, and the Affiliated Hospital of Nanchang Medical Science Research Institute. All institutions are licensed by the National Health Commission of China. All sperm donation procedures strictly adhered to national laws, ethical standards, and relevant regulations.
Methods
Controlled ovarian hyperstimulation protocol
All patients received the luteal phase long protocol using GnRH-a (Diphereline, 1.2-1.5 mg). After 14-18 days of downregulation, ovarian stimulation began when downregulation criteria were met: LH < 5 IU/L, estradiol (E2) < 50 pg/mL, endometrial thickness < 4-5 mm, and absence of functional cysts. Gonadotropins (Gonal-F or Ovidrel) were initiated at 150-300 IU/day depending on antral follicle count, age, AMH, and BMI. When follicles reached 13-14 mm, LH (HMG or recombinant LH) was added based on follicular growth, LH and E2 levels, and follicle count. Trigger was performed using human chorionic gonadotropin (8000-10000 IU) or Ovidrel (250 U), and oocyte retrieval was conducted 36-38 hours later under transvaginal ultrasound guidance.
In vitro fertilization and embryo transfer
Oocytes were fertilized with donor sperm. Embryo quality was assessed by two experienced embryologists based on blastomere development, cell number, uniformity, and fragmentation rate. The highest-quality day 3 cleavage embryos or day 5 blastocysts were selected for fresh transfer. A transvaginal ultrasound was performed 28 days post-transfer to confirm clinical pregnancy, defined as the presence of a gestational sac. Intrauterine pregnancy was confirmed if the gestational sac was located within the uterus. Miscarriage was defined as pregnancy loss before 28 weeks of gestation [9,10].
Observational indicators and data collection
(1) Basic information: Age, duration of infertility, body mass index (BMI), basal follicle-stimulating hormone (bFSH), basal estradiol (bE2), basal luteinizing hormone (bLH), endometrial thickness on the trigger day, number of oocytes retrieved, number of high-quality embryos, and number of embryos transferred.
(2) Pregnancy outcomes [9,10]: ① Clinical pregnancy rate: calculated as the number of clinical pregnancies divided by the total number of embryo transfer cycles. ② Embryo implantation rate: calculated as the number of implanted embryos divided by the number of embryos transferred. Implanted embryos were defined as those with gestational sacs identified by transvaginal ultrasound 28 days post-transfer. ③ Miscarriage rate: calculated as the number of miscarriages divided by the number of clinical pregnancies. ④ Live birth rate: calculated as the number of live births divided by the total number of embryo transfer cycles.
(3) Neonatal outcomes: Gestational age (weeks at delivery), birth weight, birth length, incidence of being small for gestational age (SGA), large for gestational age (LGA), and preterm birth. In this study, SGA and LGA were defined based on birth weight percentiles [11], with SGA referring to neonates whose birth weight was below the 10th percentile, and LGA to those above the 90th percentile for the corresponding gestational age. Preterm birth was defined as delivery before 37 weeks of gestation.
A total of 599 patients undergoing IVF-ET with DS were included, of which 261 resulted in live births. Among them, 201 were singleton live births and 60 were twin live births. Due to the complex and heterogeneous factors influencing twin births, neonatal outcome analysis was limited to singleton live births.
Data collection: Basic demographic and treatment-related information was extracted from the electronic medical record system and laboratory information management system of the Third Affiliated Hospital of Guangxi Medical University.
Statistical analysis
All statistical analyses were performed using SPSS version 23.0. Continuous variables with normal distribution are presented as mean ± standard deviation; those with non-normal distribution are reported as median (interquartile range), denoted as M (P25, P75). Group comparisons were performed using independent sample t-tests, one-way ANOVA, or non-parametric tests, as appropriate. Categorical variables are expressed as n (%), and group differences were analyzed using chi-square or Fisher’s exact tests. Multivariable logistic regression was conducted to assess the association between a history of uterine cavity procedures and pregnancy or neonatal outcomes. A p-value < 0.05 was considered statistically significant.
Results
Comparison of general information
Endometrial thickness on the trigger day was significantly lower in the complex group compared to the no history and hysteroscopy groups (P < 0.05). No significant differences were observed among the groups in terms of age, duration of infertility, number of oocytes retrieved, number of high-quality embryos, number of embryos transferred, BMI, bFSH, bE2, or bLH levels (all P > 0.05). For details, see Table 1.
Table 1.
Comparison of General information [x̅±s, M (P25, P75), n (%)]
| General information | No history of uterine cavity operation group (n=142) | Uterine cavity operation history group (n=457) | Curettage group (n=67) | Hysteroscopy group (n=292) | Complex uterine operation group (n=98) |
|---|---|---|---|---|---|
| Age (years) | 32.91±4.73 | 32.55±4.15 | 32.28±4.46 | 32.33±4.11 | 33.31±4.00 |
| Duration of infertility (years) | 6.00 (5.00, 8.00) | 5.00 (4.00, 8.00) | 5.00 (4.00, 7.00) | 5.00 (3.00, 8.00) | 6.00 (4.00, 8.00) |
| BMI (kg/m2) | 21.51±2.57 | 21.24±2.91 | 21.57±3.05 | 21.16±2.82 | 21.23±3.08 |
| bFSH (mIU/ml) | 5.58±1.52 | 5.72±1.86 | 5.64±1.50 | 5.76±1.83 | 5.64±2.07 |
| bE2 (pg/ml) | 30.00 (22.00, 42.75) | 33.00 (24.00, 47.00) | 33.00 (23.50, 51.50) | 33.00 (24.00, 47.25) | 32.00 (22.00, 46.00) |
| bLH (mIU/ml) | 3.06 (2.42, 4.14) | 3.28 (2.48, 4.63) | 3.24 (2.49, 4.96) | 3.42 (2.54, 4.60) | 3.16 (2.31, 4.64) |
| Endometrial thickness on the trigger day (mm) | 12.43±2.66 | 12.06±2.56 | 12.00±2.41 | 12.32±2.69 | 11.41±2.20*,a |
| Number of oocytes retrieved | 10.00 (8.00, 12.25) | 10.00 (7.00, 13.00) | 10.00 (7.00, 12.00) | 10.00 (7.00, 13.00) | 10.00 (7.00, 12.00) |
| Number of high-quality embryos | 3.00 (1.00, 5.00) | 4.00 (2.00, 6.00) | 4.00 (2.00, 5.00) | 4.00 (2.00, 6.00) | 3.00 (2.00, 5.00) |
| Number of embryos transferred | 1.92±0.27 | 1.86±0.36 | 1.90±0.31 | 1.84±0.38 | 1.89±0.32 |
P < 0.05: compared to the No history of uterine cavity operation group;
P < 0.05: compared to the hysteroscopy group;
BMI: Body mass index, bFSH: Basal Follicle-Stimulating Hormone, bE2: Basal Estradiol, bLH: Basal Luteinizing Hormone.
Comparison of pregnancy outcomes of IVF-ET with DS
There were no statistically significant differences in embryo implantation rate, clinical pregnancy rate, miscarriage rate, or live birth rate between the history of uterine cavity operation group and the no history group (all P > 0.05). However, the hysteroscopy group demonstrated significantly higher embryo implantation, clinical pregnancy, and live birth rates, and a significantly lower miscarriage rate compared to the no history, curettage, and complex groups (all P < 0.05). For details, see Table 2.
Table 2.
Comparison of pregnancy outcomes of IVF-ET with DS [%, (n)]
| Group | Embryo implantation rate | Clinical pregnancy rate | Miscarriage rate | Live birth rate |
|---|---|---|---|---|
| No history of uterine cavity operation group (n=142) | 30.40 (83/273) | 44.37 (63/142) | 19.05 (12/63) | 35.92 (51/142) |
| Uterine cavity operation history group (n=457) | 38.09 (323/848) | 52.08 (238/457) | 11.76 (28/238) | 45.95 (210/457) |
| Curettage group (n=67) | 32.28 (41/127) | 44.78 (30/67) | 16.67 (5/30) | 37.31 (25/67) |
| Hysteroscopy group (n=292) | 41.79 (224/536)*,# | 57.19 (167/292)*,# | 8.38 (14/167)*,# | 52.40 (153/292)*,# |
| Complex uterine operation group (n=98) | 31.35 (58/185)a | 41.84 (41/98)a | 21.95 (9/41)a | 32.65 (32/98)a |
P < 0.05: compared to the No history of uterine cavity operation group;
P < 0.05: compared to the curettage group;
P < 0.05: compared to the Hysteroscopy group;
IVF-ET with DS: In Vitro Fertilization-Embryo Transfer with Donor Sperm.
Comparison of neonatal outcomes in IVF-ET with DS
There were no significant differences in gestational age, incidence of preterm birth, neonatal birth weight, SGA, LGA, or birth length between patients with or without a history of uterine procedures, or among the uterine operation subgroups (all P > 0.05). See Table 3 for details.
Table 3.
Comparison of neonatal outcomes in IVF-ET with DS [x̅±s, n (%)]
| Neonatal outcome | No history of uterine cavity operation group (n=42) | Uterine cavity operation history group (n=159) | Curettage group (n=23) | Hysteroscopy group (n=106) | Complex uterine operation group (n=30) |
|---|---|---|---|---|---|
| Gestational age (weeks) | 38.26±1.73 | 38.27±1.47 | 38.48±1.83 | 38.16±1.46 | 38.50±1.20 |
| Preterm infants | 5 (11.90) | 12 (7.55) | 2 (8.70) | 7 (6.60) | 3 (10.00) |
| Birth weight (g) | 3070.24±372.63 | 3067.64±505.88 | 3224.78±481.71 | 3039.48±500.27 | 3196.67±400.12 |
| SGA | 6 (14.29) | 10 (6.29) | 2 (8.70) | 7 (6.60) | 1 (3.33) |
| LGA | 3 (7.14) | 15 (9.43) | 3 (13.04) | 10 (9.43) | 2 (6.67) |
| Birth length (cm) | 49.76±1.43 | 50.05±2.08 | 49.82±2.46 | 50.11±1.95 | 50.07±2.14 |
Note: SGA: small for gestational age, LGA: large for gestational age, IVF-ET with DS: In Vitro Fertilization-Embryo Transfer with Donor Sperm.
Impact of history of uterine operation on clinical outcomes in IVF-ET with DS
A multivariate logistic regression model was constructed to assess the impact of different types of uterine operations on pregnancy and neonatal outcomes, with endometrial thickness on the trigger day included as a covariate. The results indicated that, both before and after adjustment, a history of hysteroscopic surgery was independently associated with improved clinical pregnancy, implantation, and live birth rates, and with a reduced miscarriage rate (all P < 0.05). See Table 4 for details.
Table 4.
Analysis of the impact of different types of uterine operation history on clinical outcomes of IVF-ET with DS
| Clinical outcomes | Model 1 [OR (95% CI)] | Model 2 [OR (95% CI)] | ||||||
|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||
| No history of uterine cavity operation | History of curettage | History of hysteroscopy | History of Complex uterine operation | No history of uterine cavity operation | History of curettage | History of hysteroscopy | History of Complex uterine operation | |
| Clinical pregnancy/embryo implantation rate | 1 | 1.017 (0.567-1.824) | 1.675 (1.118-2.510)* | 0.902 (0.536-1.518) | 1 | 1.015 (0.565-1.821) | 1.673 (1.117-2.507)* | 0.995 (0.935-1.059) |
| Miscarriage rate | 1 | 0.850 (0.270-2.679) | 0.389 (0.169-0.895)* | 1.195 (0.453-3.155) | 1 | 0.854 (0.271-2.693) | 0.390 (0.169-0.898)* | 1.235 (0.456-3.340) |
| Live birth rate | 1 | 1.062 (0.582-1.940) | 1.964 (1.300-2.967)* | 0.865 (0.502-1.490) | 1 | 1.060 (0.580-1.936) | 1.961 (1.298-2.964)* | 0.862 (0.499-1.487) |
P < 0.05;
Model 1: no adjustment factor added; Adjustment 2: endometrial thickness on the trigger day was used as an adjustment factor. Because both implantation and clinical pregnancy occurred in this study, the regression analysis parameters for implantation and clinical pregnancy rates were the same, and therefore, only 1 row of the table is presented to show the data; IVF-ET with DS: In Vitro Fertilization-Embryo Transfer with Donor Sperm, OR: Odds Ratio, 95% CI: 95% Confidence Interval.
Age-stratified analysis: clinical characteristics and outcomes by age group
To assess age-related differences, patients were stratified into age-appropriate (< 35 years) and advanced age (≥ 35 years) groups. In the age-appropriate group, endometrial thickness on the trigger day was significantly lower in the complex group compared to the no history group (P < 0.05). The hysteroscopy group had a significantly lower miscarriage rate and higher live birth rate compared to the complex and no history groups (both P < 0.05). See Table 5 for details.
Table 5.
Comparison of clinical characteristics and outcomes among different groups of age-appropriate patients [x̅±s, M (P25, P75), n (%)]
| Clinical features and clinical outcomes | No history of uterine cavity operation group (n=91) | Uterine cavity operation history group (n=310) | Curettage group (n=37) | Hysteroscopy group (n=218) | Complex uterine operation group (n=55) |
|---|---|---|---|---|---|
| Age (years) | 30.18±3.13 | 30.28±2.87 | 29.92±3.06 | 30.49±2.82 | 30.38±2.58 |
| Duration of infertility (years) | 5.00 (4.00, 7.00) | 5.00 (3.00, 7.00) | 4.00 (3.00, 6.00) | 5.00 (3.00, 7.00) | 5.00 (4.00, 8.00) |
| BMI (kg/m2) | 21.66±2.69 | 21.16±2.77 | 21.13±3.12 | 21.10±2.73 | 21.41±2.74 |
| bFSH (mIU/ml) | 5.48±1.45 | 5.80±2.11 | 5.68±1.64 | 5.82±1.99 | 5.79±2.75 |
| bE2 (pg/ml) | 29.00 (22.00, 45.50) | 33.00 (24.00, 46.00) | 28.00 (21.25, 39.75) | 34.00 (24.00, 49.00) | 32.00 (23.00, 47.00) |
| bLH (mIU/ml) | 3.16 (2.49, 4.10) | 3.42 (2.58, 4.65) | 3.24 (2.55, 4.96) | 3.53 (2.56, 4.70) | 3.18 (2.22, 4.97) |
| Endometrial thickness on the trigger day (mm) | 12.64±2.73 | 12.08±2.53 | 12.02±2.45 | 12.31±2.61 | 11.63±2.29* |
| Number of oocytes retrieved | 11.00 (8.00, 13.00) | 10.00 (7.00, 13.00) | 11.00 (6.50, 14.50) | 10.00 (7.00, 13.00) | 10.00 (8.00, 14.00) |
| Number of high-quality embryos | 3.00 (1.00, 5.00) | 4.00 (2.00, 6.00) | 4.00 (2.50, 6.00) | 4.00 (2.00, 6.25) | 3.00 (1.00, 5.00) |
| Number of embryos transferred | 1.92±0.27 | 1.84±0.37 | 1.84±0.37 | 1.83±0.38 | 1.85±0.36 |
| Clinical pregnancy rate (%) | 48.35 (44/91) | 55.81 (173/310) | 51.35 (19/37) | 58.72 (128/218) | 47.27 (26/55) |
| Embryo implantation rate (%) | 35.43 (62/175) | 41.83 (238/569) | 38.23 (26/68) | 43.86 (175/399) | 36.27 (37/102) |
| Miscarriage rate (%) | 15.91 (7/44) | 8.09 (14/173) | 10.53 (2/19) | 5.47 (7/128)* | 19.23 (5/26)a |
| Live birth rate (%) | 40.66 (37/91) | 51.29 (159/310) | 45.95 (17/37) | 55.50 (121/218)* | 38.18 (21/55)a |
P < 0.05: compared to the No history of uterine cavity operation group;
P < 0.05: compared to the Hysteroscopy group.
BMI: Body mass index, bFSH: Basal Follicle-Stimulating Hormone, bE2: Basal Estradiol, bLH: Basal Luteinizing Hormone.
In the advanced age group, endometrial thickness on the trigger day was significantly lower in the complex group compared to the hysteroscopy group (P < 0.05). The hysteroscopy group showed significantly higher rates of embryo implantation, clinical pregnancy, and live birth than the other three groups (all P < 0.05). See Table 6 for details.
Table 6.
Comparison of clinical characteristics and outcomes among different groups of age-advanced patients [x̅±s, M (P25, P75), n (%)]
| Clinical features and clinical outcomes | No history of uterine cavity operation group (n=51) | Uterine cavity operation history group (n=147) | Curettage group (n=30) | Hysteroscopy group (n=74) | Complex uterine operation group (n=43) |
|---|---|---|---|---|---|
| Age (years) | 37.78±2.38 | 37.03±2.07 | 36.50±1.38 | 37.42±2.41 | 36.74±1.69 |
| Duration of infertility (years) | 7.00 (6.00, 9.00) | 6.00 (5.00, 9.00) | 7.00 (5.00, 10.00) | 6.00 (5.00, 9.00) | 6.00 (4.00, 9.00) |
| BMI (kg/m2) | 21.25±2.32 | 21.46±3.12 | 22.11±2.91 | 21.35±3.07 | 21.20±3.35 |
| bFSH (mIU/ml) | 5.76±1.64 | 5.50±1.28 | 5.59±1.34 | 5.60±1.21 | 5.50±1.33 |
| bE2 (pg/ml) | 33.00 (24.00, 41.00) | 34.00 (25.00, 50.25) | 40.00 (30.00, 69.50) | 28.00 (24.00, 37.00) | 34.00 (18.50, 47.00) |
| bLH (mIU/ml) | 2.34 (2.82, 4.43) | 3.13 (2.30, 4.58) | 2.92 (2.31, 5.01) | 3.13 (2.35, 4.29) | 2.96 (2.34, 4.52) |
| Endometrial thickness on the trigger day (mm) | 12.06±2.50 | 11.98±2.63 | 11.99±2.40 | 12.36±2.92 | 11.34±2.13a |
| Number of oocytes retrieved | 9.00 (8.00, 12.00) | 9.00 (6.50, 12.00) | 9.00 (6.75, 12.00) | 10.00 (6.75, 13.00) | 10.00 (7.00, 12.00) |
| Number of high-quality embryos | 3.00 (1.00, 5.00) | 3.00 (2.00, 5.00) | 3.00 (1.00, 5.00) | 3.00 (1.00, 6.00) | 3.00 (2.00, 5.00) |
| Number of embryos transferred | 1.92±0.27 | 1.90±0.33 | 1.97±0.18 | 1.85±0.39 | 1.93±0.26 |
| Clinical pregnancy rate (%) | 37.25 (19/51) | 44.22 (65/147) | 36.67 (11/30) | 52.70 (39/74)*,# | 34.88 (15/43)a |
| Embryo implantation rate (%) | 21.43 (21/98) | 30.47 (85/279) | 25.42 (15/59) | 35.77 (49/137)*,# | 25.30 (21/83)a |
| Miscarriage rate (%) | 26.32 (5/19) | 21.54 (14/65) | 27.27 (3/11) | 17.95 (7/39) | 26.67 (4/15) |
| Live birth rate (%) | 27.45 (14/51) | 34.69 (51/147) | 26.67 (8/30) | 43.24 (32/74)*,# | 35.58 (11/43)a |
P < 0.05: compared to the No history of uterine cavity operation group;
P < 0.05: compared to the curettage group;
P < 0.05: compared to the Hysteroscopy group.
BMI: Body mass index, bFSH: Basal Follicle-Stimulating Hormone, bE2: Basal Estradiol, bLH: Basal Luteinizing Hormone.
Impact of different uterine operation types on clinical outcomes by age
Among women < 35 years of age, those with a history of hysteroscopic surgery had a significantly lower miscarriage rate (Odds Ratio [OR] =0.308, 95% Confidence Interval [CI]: 0.101-0.935) and a significantly higher live birth rate (OR =1.840, 95% CI: 1.118-3.028) compared to those without such a history.
Among women ≥ 35 years of age, those with a history of hysteroscopic surgery had significantly higher clinical pregnancy (OR =2.124, 95% CI: 1.021-4.416), embryo implantation (same OR as above), and live birth rates (OR =2.289, 95% CI: 1.061-4.941) than those without a hysteroscopy history. See Tables 7 and 8 for details.
Table 7.
Analysis of the effect of different types of uterine operation history on clinical outcomes of IVF-ET with DS in the age-appropriate group
| Clinical outcome | Model 1 [OR (95% CI)] | Model 2 [OR (95% CI)] | ||||||
|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||
| No history of uterine cavity operation | History of curettage | History of hysteroscopy | History of Complex uterine operation | No history of uterine cavity operation | History of curettage | History of hysteroscopy | History of Complex uterine operation | |
| Miscarriage rate | 1 | 0.622 (0.117-3.314) | 0.306 (0.101-0.928)* | 1.259 (0.355-4.465) | 1 | 0.625 (0.117-3.333) | 0.308 (0.101-0.935)* | 1.307 (0.354-4.823) |
| Live birth rate | 1 | 1.241 (0.574-2.679) | 1.821 (1.108-2.991)* | 0.901 (0.454-1.790) | 1 | 1.259 (0.582-2.725) | 1.840 (1.118-3.028)* | 0.920 (0.462-1.834) |
P < 0.05;
Model 1: no adjustment factor added; Adjustment 2: endometrial thickness on the trigger day was used as an adjustment factor; IVF-ET with DS: In Vitro Fertilization-Embryo Transfer with Donor Sperm, OR: Odds Ratio, 95% CI: 95% Confidence Interval.
Table 8.
Analysis of the effect of different types of uterine operation history on clinical outcomes of IVF-ET with DS in the age-advanced group
| Clinical outcome | Model 1 [OR (95% CI)] | Model 2 [OR (95% CI)] | ||||||
|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||
| No history of uterine cavity operation | History of curettage | History of hysteroscopy | History of Complex uterine operation | No history of uterine cavity operation | History of curettage | History of hysteroscopy | History of Complex uterine operation | |
| Clinical pregnancy rate/embryo implantation rate | 1 | 0.975 (0.383-2.483) | 2.093 (1.009-4.340)* | 0.902 (0.387-2.102) | 1 | 0.972 (0.381-2.478) | 2.124 (1.021-4.416)* | 0.875 (0.374-2.048) |
| Live birth rate | 1 | 0.961 (0.348-2.655) | 2.246 (1.044-4.834)* | 0.908 (0.362-2.281) | 1 | 0.958 (0.346-2.650) | 2.289 (1.061-4.941)* | 0.875 (0.347-2.207) |
P < 0.05;
Model 1: no adjustment factor added; Adjustment 2: endometrial thickness on the trigger day was used as an adjustment factor. Because both implantation and clinical pregnancy occurred in this study, the regression analysis parameters for implantation and clinical pregnancy rates were the same, and therefore, only 1 row of the table is presented to show the data; IVF-ET with DS: In Vitro Fertilization-Embryo Transfer with Donor Sperm.
Discussion
Donor sperm in vitro fertilization is indicated for men with azoospermia, severe oligozoospermia, or poor sperm quality, as well as for men with genetic disorders that render them unfit for childbearing [12]. Cryopreserved donor sperm is selected for fertility treatments, with all donors being under 45 years of age and meeting the semen quality standards established by the Ministry of Health. This ensures good sperm homogeneity, thereby minimizing male-related confounding factors. After excluding male-related factors, embryo quality and endometrial receptivity are critical determinants of IVF-ET success. While criteria for assessing embryo quality are well established, the impact of endometrial receptivity remains a major concern for reproductive physicians [13,14].
Endometrial receptivity refers to the endometrium’s ability to support embryo localization, adhesion, penetration, and implantation [15]. It is influenced by various factors, including sex hormone levels, controlled ovarian hyperstimulation regimens, uterine blood flow, and immune status, all of which affect embryo transfer outcomes. Endometrial thickness, blood flow, and volume are key indicators of endometrial receptivity.
Historically, researchers have sought to determine whether endometrial thickness can predict clinical pregnancy rates. Previous studies have shown that patients with thinner endometriums tend to experience lower implantation, clinical pregnancy, and live birth rates, and higher miscarriage rates in IVF-ET cycles [16]. In this study, we observed no significant difference in endometrial thickness between the hysteroscopy and curettage groups compared to the no history group. However, the Complex group had significantly thinner endometriums compared to the no history group. This finding aligns with Liu et al. [17], who reported that repeated and severe intrauterine procedures may cause endometrial damage and thinning.
Despite these findings, our study revealed no significant differences in embryo implantation rate, clinical pregnancy rate, miscarriage rate, or live birth rate between the no history group and the history group. Specific analysis of subgroups with a history of uterine procedures also showed no significant differences in these outcomes between the complex group and the no history group. Interestingly, the hysteroscopy group exhibited significantly higher rates of implantation, clinical pregnancy, and live birth, and significantly lower miscarriage rates compared to the no history, curettage, and complex groups. These findings are consistent with those of Tam et al. [18] and Vitale et al. [19]. A meta-analysis examining the relationship between endometrial thickness and pregnancy rates in artificial insemination [20] also found no significant correlation between the two. This suggests that, within a certain range, endometrial thickness may not have a direct impact on pregnancy outcomes.
In this study, we found no significant differences in gestational age at delivery, birth weight, birth length, SGA, LGA, or preterm birth between the history group and its subgroups, compared to the no history group. These findings suggest that a history of uterine manipulation in infertile patients undergoing IVF-ET with DS cycles is not associated with adverse neonatal outcomes. Specifically, the presence or absence of a history of intrauterine manipulation does not appear to increase the risk of adverse neonatal outcomes. This is consistent with the findings of Tada et al. [21], who reported that uterine cavity operations, such as induced abortion, induced labor, and hysteroscopy, do not increase the likelihood of adverse outcomes like preterm birth or fetal growth restriction in pregnant women undergoing embryo implantation.
By performing multifactorial logistic regression analysis, we further explored the effects of different histories of uterine manipulation on embryo implantation rate, clinical pregnancy rate, miscarriage rate, and live birth rate. The results showed that, both before and after adjusting for endometrial thickness on the trigger day, a history of hysteroscopy improves the clinical pregnancy rate, implantation rate, and live birth rate in IVF-ET with DS cycles, while reducing the miscarriage rate. These findings are in agreement with a study by Kilic et al. [22].
Several potential mechanisms could explain these results. The detection rate of uterine cavity abnormalities is higher with hysteroscopy in patients who appear normal on vaginal ultrasound, particularly among older women [23,24]. These abnormalities may cause mechanical or inflammatory damage to the endometrium, interfering with its normal endocrine function and negatively impacting endometrial receptivity [25]. Hysteroscopy allows for the diagnosis and treatment of undetected uterine abnormalities, improving endometrial tolerance and, by extension, the uterine environment. This improvement may enhance overall treatment outcomes [26,27]. Additionally, some studies suggest that minor endometrial damage from hysteroscopy may stimulate proliferative endometrial metaplasia and alter the secretion of endometrial cytokines and growth factors, improving endometrial tolerance and reducing miscarriage rates [28,29]. Another theory proposes that hysteroscopy may induce immune system and gene expression changes that enhance endometrial receptivity and implantation [30]. However, studies by Ben et al. [31] and Marchand et al. [32] found no benefit of hysteroscopy for infertile women undergoing IVF-ET. Differences in study design, patient selection, surgical technique, and postoperative management may explain these divergent conclusions.
This study also demonstrated that hysteroscopy or hysteroscopic treatment significantly improves pregnancy outcomes in IVF-ET with DS, especially in women of advanced age. Specifically, hysteroscopy improved live birth rates in women of all ages, increased embryo implantation and clinical pregnancy rates in women aged ≥ 35 years, and reduced the miscarriage rate in women aged < 35 years. These findings suggest that hysteroscopy may offer greater benefits for women aged ≥ 35 undergoing IVF-ET with DS. One potential explanation is that older women have a higher detection rate of uterine abnormalities, and treatment of these abnormalities may improve embryo implantation rates and pregnancy outcomes by enhancing endometrial receptivity [27].
The study’s strength lies in its use of a standardized long protocol of gonadotropin-releasing hormone agonist for ovulation induction, which minimizes the impact of varying ovulation induction protocols on IVF-ET with DS outcomes. Additionally, stratified analyses by age group were conducted to assess clinical outcomes. However, this study has limitations: being a retrospective study, it is difficult to exclude all potential confounding factors. Moreover, as a single-center study, the generalizability of the results may be limited. Prospective, multicenter studies are needed to further validate these findings.
In conclusion, this study suggests that repeated and severe intrauterine surgery may lead to endometrial damage and thinning; however, no clear direct association was found between endometrial thickness and pregnancy or neonatal outcomes. A history of intrauterine operation does have an impact on IVF-ET with DS clinical outcomes. Hysteroscopy and hysteroscopic treatment can improve embryo implantation rates, clinical pregnancy rates, live birth rates, and reduce miscarriage rates. However, no association was found between a history of intrauterine manipulation and neonatal outcomes in IVF-ET with DS cycles.
Acknowledgements
This work was supported by the Health Commission of Guangxi Zhuang Autonomous Region Research Project (No. Z-A20221182).
Disclosure of conflict of interest
None.
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