Methods
This retrospective cross-sectional study aimed to identify women with unexplained infertility who underwent IUI at the University of Health Science, assisted reproductive technologies center, Adana City Hospital from January 2022 to October 2024. The study included 374 women with unexplained infertility who underwent 533 IUI cycles. Some patients were retrospectively identified with minimal or asymptomatic endometriosis through ultrasound. These cases were initially categorized under unexplained infertility due to the absence of prior clinical diagnosis. This classification has been acknowledged as a methodological limitation. The study received ethical approval (No: 06/02/2025 − 365) and informed consent from all participants. The population was divided into two IUI cycle groups based on the presence of adenomyosis: 139 women with cycle with adenomyosis and 394 women without adenomyosis. While most patients underwent up to two IUI cycles, a minority underwent up to four cycles, based on individualized clinical assessment.
The inclusion criteria were women aged ≤ 40 years, unexplained infertility for at least 12 months, normal uterine cavity and at least one patent fallopian tube, normal endocrine and metabolic profiles, basal FSH levels < 12 mIU/mL, and male partners with a minimum of 5 million total progressive motile sperm counts.
This study excluded women with a body mass index (BMI) ≥ 40 kg/m², recent uterine surgery, resence of uterine and adnexal diseases, uterine myomas, breast disease incompatible with gonadotropin stimulation. Mild, incidental, or subclinical endometriosis identified retrospectively by ultrasound was not considered a primary exclusion from the unexplained infertility classification.
Adenomyosis was identified using 2D transvaginal and 3D transabdominal ultrasonography (Mindray, DC-80 2022 2D, 3D Diagnostic Ultrasound System, Shenzhen, China). The Morphological Uterus Sonographic Assessment (MUSA) criteria were used, evaluating direct (myometrial cysts, hyperechogenic islands, and echogenic subendometrial lines and buds) and indirect characteristics (globular uterus, asymmetrical myometrial thickness, fan-shaped shadowing, translesional vascularity, and an inconsistent or interrupted junctional zone) [ 8 ]. Color Doppler analysis was conducted to assess trans- or intralesional vascularization of myometrial tissue and differentiate between a myometrial cyst and a vascular component. The morphological features of adenomyosis have been thoroughly documented in each patient’s electronic file, and their reliability is widely agreed upon.
Each partner supplied a semen sample following a minimum of three days of sexual abstinence, obtained through masturbation and collected in sterile containers. Semen samples intended for insemination were processed within one hour post-ejaculation, utilizing density gradient centrifugation followed by washing with culture medium. The volume of the prepared semen sample utilized for insemination was 0.5 ml.
Ovulation induction was conducted using letrozole (Novartis Health, Food and Agricultural Products Industry, Beykoz, İstanbul) in combination with gonadotropins (recombinant FSH (rFSH), follitropin alpha; Gonal-F, (Merck Serono Laboratories, Bari, İtaly), or gonadotropins rFSH alone or rFSH plus recombinant luteinizing hormon (rLH) (Pergoveris; recombinant FSH 150 IU plus recombinant luteinizing hormone 75 IU), (Merck Serono Laboratories, Bari, İtaly). Letrazole and gonadotropin stimulation began on cycle day 3 following either spontaneous menstruation or progesterone-induced menstrual bleeding. Evaluating the patient’s ovarian reserve and the ovarian response to previous treatments, gonadotropins were started at a dose ranging from 37.5 to 250 IU per day. According to our institutional protocol, mild-to-moderate stimulation is preferred, especially for patients over 35 or with diminished ovarian reserve, to optimize follicular recruitment while minimizing Ovarian hyperstimulation syndrome (OHSS) risk. Letrozole is administered at a dosage of 2.5-5 mg per day, commencing on day 3 of either spontaneous or progestin-induced menstruation, for a duration of 5 days. Treatment response was assessed using repeated transvaginal ultrasounds and serum estradiol (E2) measurements. The dosage of gonadotrophins and the duration of ovulation induction were established based on the patient’s response to stimulation. Cycle characteristics recorded at each visit included follicle counts and sizes for each ovary (mm), endometrial thickness (mm) and endometrial morphology.
Ovulation was triggered with a subcutaneous injection of recombinant hCG at a dosage of 6500 IU (Ovitrelle 250 Mikrograms/0.5 mL (Merck Serono Laboratories, Bari, Italy) once the leading follicle reached a minimum size of 17 mm. It was recommended that couples cancel the cycle if the presence of more than three dominant follicles was observed.
Insemination was performed 36–38 h post-hCG injection using a Soft-Pass Coaxial Insemination catheter (Cook Incorporated Bloomington, USA). Women underwent bed rest for thirty minutes following insemination. Luteal phase support was administered with progesterone soft capsules 200 mg (Koçak Farma Pharmaceutıcal and Chemical Industry Inc. Company, Istanbul, Türkiye) once daily for 14 days following the determination of ovulation. A serum hCG assay was conducted on the 14th day post-insemination to evaluate the occurrence of pregnancy. Following a positive result, an ultrasound examination was conducted after a period of 20 to 25 days. Clinical pregnancy was characterized by the detection of a fetus with a heartbeat at six weeks of intrauterine gestation.
Data were analyzed using SPSS 26.0. Continuous variables were presented as mean ± SD, and categorical variables as percentages. The Mann-Whitney U test, Fisher’s exact test, Pearson Chi-Square test, and multivariable logistic regression analysis were performed to determine statistical significance, with p < 0.05 considered significant.
Results
The study involved 374 women, with 95 (25.4%, 95% CI 21.2–30.5) having adenomyosis and 279 (74.6%) having without adenomyosis, and performed 533 IUI cycles, with 139 for adenomyosis and 394 for without adenomyosis. Our data show that there are no significant differences between the two groups in terms of body mass index, duration of infertility, pregnancy history, abortion history, serum day 3 FSH, LH, E2, Anti-müllerian hormone (AMH), antral follicle count (AFC), and total progressive motile sperm count (TPMSC). However, women’s age, diagnosis of concomitant endometriosis, infertility type, birth history, and live birth history showed significant differences. The demographic characteristics and laboratory measurements for both groups are summarized in Table 1 .
Table 1 Demographic characteristics and laboratory measurements adenomyosis and non-adenomyosis groups Variable Adenomyosis cycle ( n = 139) Non-adenomyosis cycle ( n = 394) p value Age (years) 30.63 ± 5.54 29.52 ± 5.06 0.018 BMI (Kg/m 2 ) 25.10 ± 3.94 24.99 ± 3.21 0.726 History of gravida ( n ) 0 [0–3] 0 [0–5] 0.190 History of parity ( n ) 0 [0–3] 0 [0–2] 0.006 History of abortion ( n ) 0 [0–3] 0 [0–5] 0.872 History of live birth ( n ) 0 [0–3] 0 [0–2] 0.007 History of İnfertility type Primary 113 (81.29%) a 354 (89.84%) b 0.008 Secondary 26 (18.71%) a 38 (10.15%) b Concomitant Endometriosis Yes 30 (21.58%) a 33 (8.38%) b 0.001 No 109 (78.42%) a 361 (91.62%) b Duration of infertility (mounts) 47.72 ± 31.14 45.08 ± 27.98 0.392 Total progressive motile sperm count (million) 43.80 ± 26.07 43.55 ± 31.53 0.722 Number of antral follicle count (AFC) ( n ) 13.70 ± 6.51 14.25 ± 7.33 0.055 Anti-Mullerian hormone (AMH) ng/mL 2.64 [0.48–24.65] 3.33 [0.16-24] 0.075 Day 3 Follicle-stimulating hormone (FSH). mIU/mL 6.63 ± 2.04 6.60 ± 2.00 0.184 Day 3 Luteinizing hormone (LH). mIU/mL 5.70 ± 3.80 6.44 ± 3.84 0.763 Day 3 Estradiol (E2). pg/mL 36.47 ± 14.12 34.97 ± 14.12 0.832 Continuous data were summarized with mean ± standard deviation and median [min.-max.]. Categorical variables were collected as numbers and percentages. The Chi-square or Fisher’s exact tests were used to compare proportions between groups Independent Samples T-test was used to compare continuous variables with normal distribution. and Mann-Whitney U test was used for non-normal variables. p < 0.05 was consider to be statistically significant. Different superscripts indicate significant mean differences
Demographic characteristics and laboratory measurements adenomyosis and non-adenomyosis groups
Continuous data were summarized with mean ± standard deviation and median [min.-max.]. Categorical variables were collected as numbers and percentages. The Chi-square or Fisher’s exact tests were used to compare proportions between groups Independent Samples T-test was used to compare continuous variables with normal distribution. and Mann-Whitney U test was used for non-normal variables. p < 0.05 was consider to be statistically significant. Different superscripts indicate significant mean differences
There were 99 pregnancies, resulting in cumulative pregnancy rates (CPRs) in the entire population per cycle of 18.57% and per couple of 26.47%. Among women with adenomyosis, 18 clinical pregnancies resulted from IUI cycles, whereas 81 clinical pregnancies were achieved from IUI cycles in women without adenomyosis. The pregnancy rates per cycle were 12.94% in women with adenomyosis, compared to 20.55% in those without adenomyosis. Figure I illustrates the pregnancy rates in patients with adenomyosis compared to those without, alongside the overall pregnancy rate per cycle throughout all cycles. Our investigation revealed that pregnancy rates per cycle were statistically considerably elevated in women without adenomyosis p < 0,05. The distribution of pregnancy rates and pregnancy outcomes in IUI cycles among women with and without adenomyosis is presented in Table 2 . Table 2 : Pregnancy rates and outcomes with adenomyosis and without adenomyosis. Figure I illustrates the pregnancy rates in patients with adenomyosis compared to those without, alongside the overall pregnancy rate per cycle throughout all cycles.
Fig. 1 Pregnancy rates per cycle with adenomyois, without adenomyois and total cycle
Pregnancy rates per cycle with adenomyois, without adenomyois and total cycle
Table 2 Pregnancy rates and outcomes adenomyosis and non-adenomyosis groups With adenomyosis ( n = 139) Without adenomyosis ( n = 394) p value Pregnancy n (%) 18 (12.94%) a 81 (20.55%) b 0.047 Pregnancy outcome Miscarriage per cycle 5/18 (27.8%) 8/81 (9.9%) 0.011 Intrauterine ex n (%) 0 (0%) 2 (2,02%) 0.147 Ectopic pregnancy 1 (0.72%) 1 (0.25%) Ongoing pregnancy 5 (3.60%) 41 (10.40%) Single term delivery 6 (4.32%) 21 (5.33%) Twin term delivery 0 (0%) 6 (1.52%) Preterm delivery 1 (0.72%) 2 (0.50%) Categorical variables were collected as numbers and percentages. The Chi-square or Fisher’s exact tests were used to compare proportions between groups. p < 0.05 was consider to be statistically significant. Different superscripts indicate significant mean differences
Pregnancy rates and outcomes adenomyosis and non-adenomyosis groups
Categorical variables were collected as numbers and percentages. The Chi-square or Fisher’s exact tests were used to compare proportions between groups. p < 0.05 was consider to be statistically significant. Different superscripts indicate significant mean differences
The average gonadotropin dose used for IUI in the without adenomyosis was 650.15 IU, whereas in the adenomyosis, it was 748.71 IU. Although the dose was higher in the group with adenomyosis, this difference was not statistically significant ( p = 0.211). Table 3 presents the clinical features, laboratory and ultrasound data, the distribution of pharmacological agents utilized for ovulation induction in both with adenomyosis and without adenomyosis. Table 3 : Clinical characteristics, laboratory and ultrasound data and the distribution of pharmacological drugs utilized in ovulation induction in groups with adenomyosis and without adenomyosis.
Table 3 Clinical characteristics, laboratory and ultrasound data and the distribution of Pharmacological drugs utilized in ovulation induction in groups adenomyosis and non-adenomyosis With adenomyosis cycle ( n = 139) Without adenomyosis cycle ( n = 394) P value İnitial gonadotrophin dose (IU) 80.89 ± 34.05 74.74 ± 32.01 0.135 Total gonadotrophin dose (IU) 748,71 ± 355,054 650,15 ± 370,53 0.211 Estradiol on day of hCG (pg/mL) 402,04 ± 359,79 381,91 ± 351,57 0.275 Duration of Gonadotrophin stimulation day 10,48 ± 2.19 10,66 ± 2.06 0.918 Endometrial thickness Hcg day (mm) 8.96 ± 1.95 8.91 ± 2.05 0.665 Menstruation pattern Regular 106 (76,25%) a 359 (91,11%) b < 0.001 İrregular 33 (23,74%) a 35 (8,88%) b Dysmenorrhea Yes 46 (33,09%) a 19 (4,82%) b < 0.001 No 93 (66,90%) a 375 (95,17%) b Ovarian stimulation LETROZOL + rFSH 46 (33,09%) a 183 (46,44%) b 0.022 rFSH 88 (63.30%) a 202 (51,26%) b rFSH + rLH 5(3,59%) a 9 (2,28%) a Continuous data were summarized with mean ± standard deviation and median [min.-max.]. Categorical variables were collected as numbers and percentages. The Chi-square or Fisher’s exact tests were used to compare proportions between groups Independent Samples T-test was used to compare continuous variables with normal distribution, and Mann-Whitney U test was used for non-normal variables. p < 0.05 was consider to be statistically significant. Different superscripts indicate significant mean differences
Clinical characteristics, laboratory and ultrasound data and the distribution of Pharmacological drugs utilized in ovulation induction in groups adenomyosis and non-adenomyosis
Continuous data were summarized with mean ± standard deviation and median [min.-max.]. Categorical variables were collected as numbers and percentages. The Chi-square or Fisher’s exact tests were used to compare proportions between groups Independent Samples T-test was used to compare continuous variables with normal distribution, and Mann-Whitney U test was used for non-normal variables. p < 0.05 was consider to be statistically significant. Different superscripts indicate significant mean differences
In the multivariate analysis, AMH levels and the presence of adenomyosis were the only independent factors significantly associated with IUI success, while other variables such as age, infertility duration, sperm count, and endometriosis did not show independent predictive value. In contrast, the presence of endometriosis was not independently associated with decreased pregnancy rates (OR 0.704, 95% CI: 0.335–1.478, p = 0.353). Furthermore, AMH levels were identified as another important independent predictor of IUI success (OR 1.212, 95% CI: 1.031–1.425, p = 0.020), indicating that higher AMH levels were positively correlated with improved pregnancy outcomes. Age, duration of infertility, and total motile sperm count did not show statistically significant associations with pregnancy outcomes, indicating that these factors may not be strong predictors in this context. The multivariable logistic regression analysis of factors affecting IUI success is shown in Table 4 .
Table 4 Multivariate logistic regression analysis of factors affecting IUI success Variables Odds Ratio (OR) 95% Confidence Interval p -value Adenomyosis (presence vs. absence) 0.575 0.335–0.998 0.049* Endometriosis (presence vs. absence) 0.704 0.335–1.478 0.353 Female Age (years) 1.020 0.995–1.045 0.114 Infertility Duration (mounts) 0.985 0.942–1.029 0.499 Antral Follicle Count (AFC) 1.054 0.999–1.111 0.052 AMH Level (ng/mL) 1.198 1.035–1.387 0.020* Total Progressive Motile Sperm Count (×10⁶) 1.002 0.989–1.016 0.742 *Note: p < 0.05 is considered statistically significant
Multivariate logistic regression analysis of factors affecting IUI success
*Note: p < 0.05 is considered statistically significant
Transvaginal Doppler ultrasound, utilizing 2D and/or 3D imaging, identified direct and indirect adenomyosis features. The prevalence of adenomyosis identified was 95 out of 374 women (25.40%, 95% CI 21.2–30.5). The direct features had a mean ± SD (2.12 ± 0.64, with a 95% CI of 1.99–2.25, while the indirect features had a mean ± SD (1.78 ± 1.54, with a 95% CI of 1.47–2.10. Table 5 shows the distribution of adenomyosis characteristics among women, while Table 6 shows number of direct and indirect features of adenomyosis in pregnancy results.
Table 5 Number of direct and indirect features of adenomyosis according to pregnancy outcome on 2D/3D doppler ultrasonography ( n = 139) Ultrasound Feature Type Pregnancy Outcome Mean ± SD (95% CI) p Value Direct Features Pregnancy positive 1.94 ± 0.63 (1.62–2.23) 0.984 Direct Features Pregnancy negative 2.17 ± 0.64 (2.05–2.28) Indirect Features Pregnancy positive 1.38 ± 0.64 (0.66–2.15) 0.401 Indirect Features Pregnancy negative 1.82 ± 1.52 (1.55–2.21) Total Features Pregnancy positive 3.33 ± 1.68 (2.60–4.12) 0.656 Total Features Pregnancy negative 4.00 ± 1.82 (3.69–4.33) Values are presented as mean ± standard deviation and 95% confidence intervals. Comparison was made between pregnant and non-pregnant groups. p < 0.05 was considered statistically significant
Number of direct and indirect features of adenomyosis according to pregnancy outcome on 2D/3D doppler ultrasonography ( n = 139)
Values are presented as mean ± standard deviation and 95% confidence intervals. Comparison was made between pregnant and non-pregnant groups. p < 0.05 was considered statistically significant
Table 6 Prevalence of direct and /or indirect features of adenomyosis at 2D and/or 3D doppler ultrasonography ( n = 139)
n
Prevalence (%) 95% CI Myometrial cysts 118 85.5 82.6–93.7 Hyperechogenic islands 122 88.4 82.6–93.7 Echogenic sub endometrial lines and buds 56 40.6 32.4–48.9 Globular uterus 26 18.8 12.2–25.6 Asymmetrical myometrial thickening 44 31.9 23.8–40.2 Fan-shaped shadowing 49 35.5 27-43.9 Trans lesional vascularity 81 58.7 51-66.7 Irregular junctional zone 21 15.2 9.2–21.2 Interrupted junctional zone 26 18.8 12.2–25.6 Numbers are given as n (%) of the total cohort, with 95% CI. Women may have more than one feature of adenomyosis Abbreviations: 2D, two-dimensional; 3D, three-dimensional; CI, confidence interval; JZ, junctional zone
Prevalence of direct and /or indirect features of adenomyosis at 2D and/or 3D doppler ultrasonography ( n = 139)
Numbers are given as n (%) of the total cohort, with 95% CI. Women may have more than one feature of adenomyosis
Abbreviations: 2D, two-dimensional; 3D, three-dimensional; CI, confidence interval; JZ, junctional zone
Background
Intrauterine insemination (IUI) is a prevalent intervention for idiopathic infertility, providing ease, cost-effectiveness, and reduced intervention relative to more advanced assisted reproductive techniques such as in vitro fertilization (IVF) [ 1 , 2 ]. However, success rates vary widely due to factors like female age, ovarian reserve, sperm count, and the presence of gynecological conditions like endometriosis [ 3 – 5 ].
Adenomyosis, characterized by the ectopic presence of endometrial glands and stroma, is increasingly recognized as a contributing factor to infertility [ 6 – 8 ]. The prevalence of adenomyosis in reproductive-age women is estimated to be between 20% and 25% [ 9 , 10 ]. Studies suggest that transvaginal ultrasound (TVS) should be the primary imaging modality for diagnosing adenomyosis, as its sensitivity and specificity are comparable to histopathological examination of hysterectomy material [ 11 , 12 ]. Previous studies have primarily focused on IVF outcomes, with limited data on IUI success rates [ 13 , 14 ]. This study aims to evaluate pregnancy outcomes in women with unexplained infertility undergoing IUI treatment, comparing those with and without adenomyosis. The findings are expected to provide valuable insights for optimizing fertility treatment strategies and improving clinical outcomes.
Conclusion
A study reveals that adenomyosis significantly reduces IUI success rates in women with unexplained infertility, suggesting clinicians should include adenomyosis assessment in the standard workup. The study’s originality and robust methodology could influence clinical guidelines on managing adenomyosis. Future research should explore innovative therapeutic interventions and consider individualized approaches like hormonal therapies or advanced imaging techniques.
Discussion
Our study demonstrates that women with adenomyosis undergoing IUI have reduced pregnancy rates compared to those without adenomyosis. The per cycle pregnancy rate per couple was 12.94% in the group with adenomyosis compared to 20.55% in the without group with adenomyosis, with a statistically significant difference. Our findings reinforce and extend previous research primarily centered around IVF outcomes. This study is a pioneering work that explores the impact of adenomyosis on IUI success in women with unexplained infertility. Unlike previous studies that primarily focused on IVF outcomes, our research highlights the influence of adenomyosis on IUI, an important first-line treatment for unexplained infertility. IUI is an effective treatment option for women with unexplained infertility [ 1 ]. This study highlights a significant deficiency in literature about adenomyosis and the efficacy of IUI. A systematic review and meta-analysis reported that women with adenomyosis had a 9.3% reduction in the likelihood of clinical pregnancy following IVF/ICSI compared to those without the condition [ 15 ]. Adenomyosis is associated with higher miscarriage rates and lower live birth rates in IVF treatments [ 15 ]. The study highlights the influence of adenomyosis on IUI success in women with unexplained infertility, an important first-line treatment option. The mechanism by which adenomyosis affects fertility is not entirely understood but is believed to involve altered myometrial contractility, impaired endometrial receptivity, and disrupted implantation processes [ 6 , 7 , 9 , 16 – 19 ]. Structural anomalies in the endometrium may also reduce implantation potential in adenomyosis patients, obstructing sperm transmission [ 4 , 17 , 20 ].
Previous studies have consistently reported a detrimental effect of advanced maternal age, lower progressive sperm count, and endometriosis on IUI outcomes [ 5 ]. However, in our multivariate logistic regression model, only AMH and the presence of adenomyosis remained significant predictors of IUI success, while other variables such as age, sperm count, and endometriosis lost statistical significance. Several studies have documented lower IUI success rates with advancing female age due to a reduction in both oocyte quantity and quality [ 3 , 21 , 22 ]. Our investigation adds important evidence highlighting adenomyosis as an independent risk factor negatively affecting IUI success. This finding underscores the importance of thorough pre-treatment assessment and individualized counseling in patients diagnosed adenomyosis considering IUI treatment.
Notably, while AMH levels have been previously correlated with ovarian reserve and assisted reproductive technology outcomes, our logistic regression analysis further reinforced its significance as a predictor of IUI success, emphasizing the importance of AMH as part of routine infertility evaluations. Antral follicle count, another assessed variable, was found not to significantly affect pregnancy outcomes in our study, which differs from some previous studies that have suggested AFC as a critical factor in fertility success. This discrepancy may be due to variations in patient populations or the specific inclusion and exclusion criteria used in our study [ 23 ].
The study found that women with adenomyosis were significantly older than those without, suggesting that adenomyosis independently contributes to diminished fertility outcomes. However, there was no significant association between pregnancy outcomes and female age or infertility duration, which may be due to differences in patient selection, sample size, or statistical approaches. However, the persistence of lower pregnancy rates in the group with adenomyosis after adjusting for age suggests that adenomyosis independently contributes to diminished fertility outcomes. These findings diverge from previously published studies that have consistently shown female age and infertility duration as strong predictors of IUI success [ 3 , 24 ]. The reasons for these discrepancies might be attributed to differences in patient selection, sample size, or the specific statistical approaches employed. No statistically significant difference was observed between groups regarding BMI, which is consistent with the findings of Puente et al. and indicates that BMI may not directly affect IUI success in the context of adenomyosis [ 13 ].
The study reveals that IUI success generally declines after three cycles, but the limited number makes interpretations difficult. Doctors may prefer referring patients to IVF treatment if pregnancy doesn’t occur and limit IUI to less than three cycles. In cases of unexplained infertility, up to three cycles of IUI with ovarian stimulation may be viable therapy. The American Society for Reproductive Medicine recommends ovarian stimulation with oral medications combined with IUI for most couples, typically for three to four cycles, and if unsuccessful, in vitro fertilization is suggested [ 25 ]. A previous publication has stated that in the management of unexplained infertility, IUI should be limited to a maximum of three cycles [ 26 ]. In practice, patients adenomyosis might benefit from alternative ART strategies, particularly when IUI attempts have failed. For example, transitioning to IVF may be considered earlier in the treatment algorithm for these patients.
Endometriosis is another common gynecological condition known to impair fertility, often through mechanisms such as chronic inflammation, altered peritoneal environment, and impaired folliculogenesis [ 27 , 28 ]. However, our study found that endometriosis did not independently affect IUI success rates when adjusting for the presence of adenomyosis. This result contrasts with some previous studies suggesting that endometriosis negatively influences fertility outcomes in ART [ 29 ]. One possible explanation for this discrepancy is that adenomyosis may have a more dominant impact on uterine function and endometrial receptivity, thereby overshadowing the effects of endometriosis [ 9 , 17 , 18 ]. Alternatively, the lack of significant impact of endometriosis in this study might reflect differences in the severity or stage of endometriosis among participants, as our study did not stratify endometriosis cases by severity.
Interestingly, the total motile sperm count and the presence of endometriosis did not significantly affect pregnancy outcomes in our multivariate analysis, consistent with several earlier studies indicating variability in these parameters’ predictive strength, emphasizing the complexity of infertility treatment outcomes [ 30 , 31 ].
The incidence of secondary infertility was notably higher in the group with adenomyosis. Advancing age may compromise the structural and physiological integrity of the uterus, contributing to infertility. This is supported by previous studies showing a higher rate of secondary infertility in women with adenomyosis [ 16 ].
The study assessed sonographic features associated with adenomyosis in infertile women undergoing IUI. Hyperechogenic islands and myometrial cysts were the most prevalent features, followed by echogenic sub-endometrial lines and budsand globular uterus. Each patient’s number and type of direct and indirect features were scored using the MUSA criteria. Although no formal staging system was used, this quantification is presented in Tables 5 and 6 to reflect disease severity. Other notable but less common features included irregularities and interruptions in the junctional zone. These findings align with previous research demonstrating the diversity of adenomyosis presentations through ultrasonographic features [ 11 , 32 ] The prevalence of hyperechogenic islands was 88.4%, while echogenic sub-endometrial lines and buds were 40.6%. The study found that globular uterine morphology (18.8%) might serve as a critical predictor for reproductive outcomes in adenomyosis patients undergoing assisted reproductive techniques. The study also found that indirect features and overall scores were not significantly associated with pregnancy outcomes. In the population of women with adenomyosis in our study, interrupted and irregular junctional zone were observed in one-third of the patients. Adenomyosis negatively impacts implantation due to altered endometrial receptivity, which is associated with changes in the junctional zone, as suggested by the Tissue Injury and Repair (TIAR) theory [ 6 , 33 ] Previous studies have similarly linked junctional zone abnormalities with diminished ART outcomes [ 34 , 35 ] Clinically, these findings support the utility of detailed ultrasonographic assessment of adenomyosis characteristics as prognostic markers in infertility treatments.
Regarding ovarian stimulation protocols, the group with adenomyosis used significantly less rFSH alone (63.30% vs. 51.26%, p = 0.022) and was less frequently treated with combination therapies rFSH + rLH. However, no significant difference in clinical pregnancy outcomes was found between the two groups across different treatment protocols. Consistent with our work, prior investigations did not reveal differences between pregnant and non-pregnant study groups, irrelevant to ovarian stimulation [ 36 , 37 ]. The study reveals that a lower initial dose of rFSH can reduce total ggonadotropin intake without compromising pregnancy success.
This study examines the impact of adenomyosis on IUI success rates in unexplained infertility. It has strengths like a well-defined patient population, rigorous diagnostic criteria, and comprehensive statistical analysis. However, limitations include a retrospective design, small sample size, and potential selection bias. Future research should focus on larger sample sizes and explore treatment modifications like hormonal therapies or personalized ovarian stimulation protocols. The study’s originality and robust methodology could influence clinical guidelines for managing infertility-associated adenomyosis.
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