Serum thyroid-stimulating hormone receptor antibody levels and thyroid dysfunction after hysterosalpingography: a case-control study.

OBJECTIVE: Hysterosalpingography (HSG) performed with an iodine contrast media can cause thyroid dysfunction, including thyrotoxicosis and hypothyroidism. We investigated the association between the serum levels of thyroid-stimulating hormone receptor antibody (TRAb), an indicator of Graves' disease, and abnormal thyroid function after performing HSG. METHODS: The screening of TRAb was conducted in 362 patients who first visited the Tawara IVF Clinic between April and September 2018. The association between TRAb levels and the effects of HSG examinations on thyroid function were evaluated. RESULTS: Of the 362 patients, 2 (0.55%) had high levels (>2.0 IU/L) of TRAb, whereas 18 (5.0%) had intermediate TRAb levels, ranging from 0.3 to 1.9 IU/L. Of the 98 women (including 7 of the 18 women with TRAb level 0.3-1.9 IU/L, and 91 of the 342 women with TRAb level <0.3 IU/L) who had undergone HSG, two women developed overt thyrotoxicosis after HSG, and the frequency was significantly higher (p = .0044) in the group with intermediate levels of TRAb (28.6%, 2 of 7) than that in the group with low TRAb levels (<0.3 IU/L; 0.0%, 0 of 91). CONCLUSIONS: These findings indicate that increased serum levels of TRAb are significantly associated with the development of thyrotoxicosis after HSG.

Predictive Factors of Conception and the Cumulative Pregnancy Rate in Subfertile Couples Undergoing Timed Intercourse With Ultrasound.

The aim of this study was to determine predictive factors for pregnancy and assess the cumulative pregnancy rate (CPR) and live birth rate (CLBR) in subfertile couples undergoing timed intercourse (TI) using ultrasound. This retrospective cohort study included 285 women (854 cycles) who started TI with ultrasound between January 2017 and October 2019. The overall clinical pregnancy rate was 28.1% (80/285) per couple and 9.4% (80/854) per cycle. Pregnant women had a higher body mass index (BMI), higher percentage of irregular menstrual cycles, a shorter duration of subfertility, lower serum follicle-stimulating hormone levels, and higher anti-Müllerian hormone levels than non-pregnant women. A longer duration of subfertility (≥24 months vs. <12 months; odds ratio: 0.193; 95% confidence interval: 0.043-0.859) and endometriosis (vs. ovulatory factors; odds ratio: 0.282; 95% confidence interval: 0.106-0.746) as causes of subfertility were unfavorable factors that independently affected clinical pregnancy. In subgroup analysis, old age ≥ 35 years [vs. < 35 years; odds ratio: 0.279; 95% confidence interval: 0.083-0.938), a longer duration of infertility ≥24 months (vs. <24 months; odds ratio: 0.182; 95% confidence interval: 0.036-0.913) and a higher BMI ≥ 25 kg/m2(vs. >25 kg/m2; odds ratio: 3.202; 95% confidence interval: 1.020-10.046) in couples with ovulatory factor and a longer duration of infertility ≥24 months (vs. <24 months; odds ratio: 0.185; 95% confidence interval: 0.042-0.819) in couples with non-ovulatory factors were significant independent predictive factors for pregnancy. No significant differences were found in the cycle characteristics between pregnant and non-pregnant women. The CPR substantially increased during the first three cycles and significantly increased until the sixth cycle. No significant increase was observed in the CPR after the sixth cycle. The CLBRs substantially increased during the first three cycles and significantly increased until the fourth cycle. No significant increase was observed in the CLBRs after the fifth cycle. When comparing CPRs and CLBRs according to subfertile causes, CRPs was significantly different and CLBRs was different with borderline significance. Our findings may indicate that women with a longer duration of subfertility or subfertility due to endometriosis have poor outcomes during TI with ultrasound. Women who failed to achieve conception by the fourth or fifth cycle of TI with ultrasound may be encouraged to consider advancing to the next treatment strategy.

Endometrial thickness is not predictive for live birth after embryo transfer, even without a cutoff.

OBJECTIVE: To investigate the predictive value of endometrial thickness (EMT) for live birth when a lower threshold of EMT is not employed for embryo transfer (ET). DESIGN: Retrospective study SETTING: Academic assisted reproduction center PATIENT(S): All women who underwent fresh or frozen-thawed ET at the Koç University Hospital Assisted Reproduction Unit between October 2016 and August 2019 INTERVENTION(S): After ruling out endometrial pathology, blastocyst transfer was planned regardless of the EMT in the absence of increased serum progesterone level on the trigger day in fresh embryo transfer cycles or before commencing progesterone treatment in artificially prepared frozen-thawed ET cycles. MAIN OUTCOME MEASURE(S): The primary outcome was live birth. Live birth and miscarriage rates per ET were stratified according to fresh and frozen-thawed ET cycles for each millimeter of endometrial thickness. Receiver operator characteristic curve analyses were performed to evaluate the predictive value of EMT for live birth. RESULT(S): A total of 560 ET cycles, 273 fresh and 287 frozen-thawed, were included in the study. Relevant patient characteristics as well as EMTs were similar between women who achieved a live birth and those who did not after fresh or frozen-thawed ET. There was no linear association between EMT and live birth or miscarriage rates. Area under the curve values for EMT to predict live birth after fresh, frozen-thawed, and all ETs were 0.56, 0.47, and 0.52, respectively. CONCLUSION(S): Our results showed that the EMT was not predictive for live birth in either fresh or frozen-thawed ET cycles. Once intracavitary pathology and inadvertent progesterone exposure were excluded, women with thinner EMTs should not be denied their potential for live birth because it is comparable to that of those with thicker EMT.

Endometrial osseous metaplasia in a patient with secondary infertility referred for hysterosalpingogram with ultrasound.

Endometrial osseous metaplasia is a rare entity resulting in the formation of trabecular bone fragments within the uterine cavity and frequently presents as secondary infertility with a history of previous pregnancy loss or termination. The unusual transvaginal ultrasound appearances are important to recognise, as fertility is often restored after hysteroscopic removal of the bone fragments from the uterine cavity.

Optimal lead follicle size for human chorionic gonadotropin trigger in clomiphene citrate and intrauterine insemination cycles: an analysis of 1,676 treatment cycles.

OBJECTIVE: To identify the optimal lead follicle size for hCG trigger in clomiphene citrate (CC)-intrauterine insemination (IUI) cycles. DESIGN: Retrospective cohort study. SETTING: University-affiliated center. PATIENT(S): Patients <40 years of age with ovulatory dysfunction or unexplained infertility undergoing their first CC-IUI cycle. INTERVENTION(S): Ovulation induction, hCG trigger, and IUI. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (CPR) was the primary outcome and was plotted against lead follicle size in increments of 1 mm. Odds ratios with 95% confidence intervals for associations between lead follicle size and CPR were calculated from a multivariable logistic regression model. A receiver operating characteristic (ROC) curve was generated for CPR as a function of lead follicle size. RESULT(S): 1,676 cycles were included. The overall CPR was 13.8% (232/1,676). There was no difference in baseline demographics or ovulation induction parameters of patients who did or did not conceive. The odds of clinical pregnancy were 2.3 and 2.2 times higher with lead follicle sizes of 21.1-22.0 mm and >22.0 mm, respectively, compared with the referent category of 19.1-20.0 mm. Lead follicle size was an independent predictor of CPR, even after accounting for confounders. A lead follicle size of 22.1 mm corresponded to a sensitivity and specificity of 80.1% and 90.4% for clinical pregnancy, respectively, with an area under the ROC curve of 0.89. CONCLUSION(S): hCG administration at a lead follicle size of 21.1-22.0 mm is associated with higher odds of clinical pregnancy in patients undergoing their first CC-IUI cycles for ovulatory dysfunction or unexplained infertility.

Testicular ultrasound inhomogeneity is an informative parameter for fertility evaluation.

Testicular volume (TV) is proposed to be a positive predictor of male fertility status, because of the relation known between the TV and the seminiferous tubule content. Independently of the measurement methodology, the role of TV and testicular ultrasound (US) assessments is still debated in andrological clinical practice. In this retrospective cohort study, we evaluated TV and testis US role in the diagnostic workup of andrological patients. All consecutive outpatients undergoing single-operator testis US (Modena, Italy) from March 2012 to March 2018 were enrolled, matching sonographic, hormonal, and seminal data. A total of 302 men were referred and evaluated for gynecomastia, suspected hypogonadism, couple infertility (CI), or sexual dysfunction. In the hypogonadal group, TV was lower compared to that in other groups (P < 0.001), and a significant, direct correlation between TV and testosterone level was observed in nonandrogen-treated patients (R = 0.911, P < 0.001), suggesting that testicular size could be related to the testosterone-secreting compartment. In the CI group, normozoospermic patients showed higher TV compared to men with impaired semen quality (P = 0.003) and azoospermia (P = 0.003). However, TV was not able to discriminate between patients presenting normal and altered semen quality. On the contrary, testis US inhomogeneity was more frequent in patients with impaired sperm quality (55.0%; P = 0.007) and azoospermia (40.0%; P = 0.012), compared to patients with normozoospermia (5%), identifying thereby the sonographic pattern as an informative parameter of the fertility status. Therefore, in the CI workup, US evaluation seems to be more informative than the TV assessment alone.

The Role of Endometrial Volume and Endometrial and Subendometrial Vascularization Parameters in a Frozen Embryo Transfer Cycle.

The role of three-dimensional power Doppler ultrasonography of the endometrium in assisted reproduction is still far from clear. In this retrospective cohort study, transvaginal three-dimensional power Doppler examinations were performed 30 min before frozen-thawed embryo transfer. After pregnancy tests, two cohorts were established: P (pregnant, n = 31) and NP (nonpregnant, n = 31). The study only included nullipara with no uterine abnormalities who were undergoing infertility treatment at the Department of Gynecology, Obstetrics and Gynecological Endocrinology, Kepler University Hospital, Linz, Austria. The main outcome measures were the vascularization flow index (VFI), flow index (FI), and vascularization index (VI) in the endometrium/subendometrium, assessed using Virtual Organ Computer-aided AnaLysis (VOCAL™), and the endometrial volume. A total of 62 patients were enrolled in the study, forming two cohorts (pregnant, P; nonpregnant, NP). There were no significant differences between the two cohorts with regard to demographic data, numbers of embryos transferred, or embryo grading, but there was a significant difference in endometrial volume (cohort P, 3.17 ± 0.84 mL; cohort NP, 2.36 ± 0.9 mL; P = 0.001) and the pregnancy rate rises with larger volume. No differences were observed in the vascularization parameters FI, VFI, and VI in the endometrium and subendometrium. In the cohort of pregnant patients, there were 26 (41.9%) live births, with 21 term deliveries (80.8%). The endometrial volume was larger in the cohort of pregnant patients. Measurements were performed 30 min before embryo transfer, and no differences were observed in vascularization parameters in the subendometrium and endometrium.

Reliability of testicular stiffness quantification using shear wave elastography in predicting male fertility: a preliminary prospective study.

AIMS: To evaluate the reliability of testicular stiffness quantification using shear wave elastography in predicting the fertility potential of males and for the pre-diagnosis of disorders based upon sperm quantification. MATERIAL AND METHODS: One hundred males between the ages of 19-49 years (mean age of 28.77±6.11), ninety of whom with complaints of infertility, were enrolled in this prospective study. Scrotal grey-scale, Doppler ultrasound (US), and mean testicular shear wave velocity quantifications (SWVQs) were performed. The volumes of testes, as well as the grade of varicocele if present, were recorded. The mean shear wave velocity values (SWVVs) of each testis and a mean testicular SWVV for each patient were calculated. The semen-analyses of patients were consecutively performed. RESULTS: There were significant negative correlations between the mean testicular SWVVs of patients and their sperm counts or the testis volumes (r=-0.399, r=-0.565; p<0.01, respectively). A positive correlation was found between testicular volumes and sperm counts (r=0.491, p<0.01). The cut-off values regarding mean testicular SWVV to distinguish normal sperm count from azoospermia and oligozoospermia were 1.465 m/s (75.0% sensitivity and 75.0% specificity) and 1.328 m/s (64.3% sensitivity and 68.2% specificity), respectively, and the value to distinguish oligozoospermia from azoospermia was 1.528 m/s (66.7% sensitivity, 60.7% specificity). CONCLUSION: The mean testicular SWVQ using the ARFI shear wave technique was a reliable, non-invasive and acceptably stable method for predicting male infertility, especially related to sperm count issues.

Cycle day, estrogen level, and lead follicle size: analysis of 27,790 in vitro fertilization cycles to determine optimal start criteria for gonadotropin-releasing hormone antagonist.

OBJECTIVE: To determine the optimal criteria at which to start GnRH antagonists during controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). DESIGN: Retrospective clinical cohort. SETTING: IVF clinics. PATIENT(S): Women undergoing fresh autologous IVF using GnRH antagonist for ovulation suppression during COH. INTERVENTION(S): Measurement of lead follicle size, E2 level, and cycle day of stimulation on day of antagonist initiation. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (PR). RESULT(S): The highest clinical PR was achieved when the antagonist was started when a lead follicle reached 14-15.9 mm in size (mean clinical PR 21.3; 95% confidence interval [CI] 19.3, 23.6) on cycle day 6 (mean clinical PR 22.2; 95% CI 17, 28.4), or when the E2 level was between 500 and 599 pg/mL (mean clinical PR 25.4; 95% CI 19.5, 32.4). Starting antagonists when the E2 level was <300 or >1,100 pg/mL reduced the odds of clinical pregnancy by 40% (odds ratio 0.60, 95% CI 0.5, 0.7). CONCLUSION(S): Cycle day, E2 level, and follicle size at time of antagonist start are all independent predictors of a clinical pregnancy after IVF. Initiating antagonists when the E2 level is extremely low (<300 pg/mL) or extremely high (>1,100 pg/mL) significantly reduces the odds of pregnancy.

Use of atropine in four-dimensional hysterosalpingo-contrast sonography: Does it suppress pain during infertility examination?

This study aimed to ascertain if atropine is useful for suppressing the pain suffered during four-dimensional hysterosalpingo-contrast sonography (4D-HyCoSy) when assessing infertility in women. A total of 252 patients were divided into 2 groups to receive or not receive atropine (0.5 mg) injection 30 minutes before 4D-HyCoSy. Pain was evaluated using a numerical rating scale (NRS): during 4D-HyCoSy; upon 2-dimensional transvaginal sonography; before catheter insertion; upon insertion and fixation of the catheter into the uterine cavity; 30 minutes after 4D-HyCoSy. According to the degree of patency of Fallopian tubes, the 6 patterns observed were integrated further into 3 patient groups: all-negative (both Fallopian tubes were negative), positive-and-negative (one Fallopian tube showed patency and the other showed stenosis or non-patency), and all-positive (both Fallopian tubes showed stenosis or non-patency). We compared the NRS scores and prevalence of side-effects other than pain between the atropine-injection and non-atropine-injection groups within the three groups mentioned above. The NRS score showed no significant differences among the groups at any time point (all P > .05). The different prevalence of side-effects other than pain was significant between the atropine-injection and atropine-non-injection groups (P = .012). These data suggest that atropine does not reduce pain in patients during 4D-HyCoSy. However, atropine may reduce the prevalence of other side-effects during 4D-HyCoSy, which needs a further, large, prospective, multi-cohort study to verify.

Evaluation of the Cervix After Cervical Conization by Transvaginal Elastography.

OBJECTIVES: The purpose of this study was to investigate the stiffness of the cervix after the loop electrosurgical excision procedure (LEEP) by transvaginal elastography and its potential ability to predict future pregnancy. METHODS: A retrospective study included patients of reproductive age who underwent LEEP for cervical high-grade squamous intraepithelial lesions on the basis of colposcopic findings and who desired fertility. The characteristics on conventional transvaginal ultrasonography and elastography before and 6 months after LEEP were reviewed and analyzed. Each case had a 12-month follow-up, and the information on pregnancy and a cervical cytologic examination was recorded. RESULTS: Fifty-three patients who completed the 12-month follow-up were included in the analysis. Thirty-two cases (group 1) were pregnant during the follow-up, and the other 21 (group 2) had pregnancy failure. The cervical lengths of group 1 and 2 as measured by traditional transvaginal ultrasonography were similar before and 6 months after LEEP. The resistive index of group 1 was significantly higher 6 months after LEEP than before LEEP (mean ± SD, 0.88 ± 0.36 versus 0.42 ± 0.22; P = .007). The mean elasticity score for the cervix was statistically significantly lower after LEEP (2.21 ± 0.53) than before (3.46 ± 0.78; P = .001) in group 1. However, in group 2, the mean elasticity scores were similar after LEEP (3.19 ± 0.58) and before (3.25 ± 0.66; P = .75). CONCLUSIONS: Our results suggest that elastography was a useful technique for evaluating the stiffness of the cervix after LEEP. Elastography could provide a potential means to predict future pregnancy after LEEP.

Subfertility: What the Radiologist Needs to Know.

The role of imaging in subfertility is well established but is changing. In addition to traditional fertility assessments, there is an emerging role for the radiologist. The role of imaging in fertility-restoring procedures in benign disease and congenital malformations is evolving, and there is a growing need for accurate identification of young candidates suitable for fertility-preserving surgery in the oncologic setting. To facilitate this developing role, knowledge of the key imaging modalities used and potential therapeutic applications is important for accurate diagnosis and interpretation by the radiologist. ©RSNA, 2017.

MicroRNA expression profiling in endometriosis-associated infertility and its relationship with endometrial receptivity evaluated by ultrasound.

OBJECTIVE: To investigate the microRNA expression profiling in endometriosis-associate infertility, and relationship between the microRNA expression and endometrial receptivity evaluated by ultrasound. METHODS: First, miRNA expression profiling difference of ectopic endometrium between 8 endometriosis patients and 6 endometriosis-free patients were compared. Bioinformatics analyses detected 61 differentially expressed (DE) known miRNAs and 57 DE novel miRNAs. Next, other 24 patients were selected for checking the microRNAs in differential expression by RT-PCR. Among them, case and control groups include 14 endometriosis and 10 endometriosis-free infertility patients, respectively. Last, endometrial receptivity of other 20 endometriosis patients was evaluated by ultrasound. In this group of patients, 12 had high endometrial receptivity, in which infertility is caused by fallopian tube occlusion, and 8 had low endometrial receptivity. The study compared endometrial miRNAs expression between two groups, and also evaluated the relationship between the endometrial miRNAs expression and the endometrial receptivity. RESULTS: First, study indicated that "proteinaceous extracellular matrix," "laminin binding" and "extracellular matrix binding" were enriched in 6 up-regulated miRNA targets, while "cell proliferation" was enriched in the 4 down-regulated miRNA targets. Second, 10 miRNAs in different expression (miR-1304- 3p, miR-544b, miR-3684, miR-494-5p, miR-4683, miR-6747-3p; miR-3935, miR-4427, miR-652-5p, miR-205-5p) were detected by RT-PCR, and the results showed statistically significant differences between 2 groups in all 10 miRNAs. Third, the expression levels of miR-1304-3p, miR-494-5p, and miR-4427 were different between the two groups with different endometrial receptivity. But for the miR-544b, there was no statistically significant difference between two groups. CONCLUSIONS: The study provided a comprehensive understanding to the current knowledge in the field of miRNAs in endometriosis and the relationship between them and the endometrial receptivity. miRNAs could be used as diagnostic biomarkers and therapeutic agents for this disease. The combination of ultrasound and miRNAs detection could be a better choice for the diagnosis of infertility in the future.

Uterine contractility and elastography as prognostic factors for pregnancy after intrauterine insemination.

OBJECTIVE: To determine the impact of the frequency and intensity of uterine contractions (UCs) at the time of IUI on subsequent fertility. DESIGN: Observational pilot study. SETTING: University hospital. PATIENT(S): One hundred volunteer women scheduled for IUI between April 2011 and July 2013, in whom UCs were assessed during the ultrasound before IUI. INTERVENTION(S): A two-dimensional sagittal uterus elastography was recorded for 5 minutes. The elasticity index, defined as the mean ratio of elastographic measurements between the subendometrial area (of interest) and the endometrial area (control), was computed. UC frequency, endometrial thickness and volume, and subendometrial vascularisztion were also measured. MAIN OUTCOME MEASURE(S): These parameters, along with characteristics of the IUI cycle, were entered into a logistic regression model for predicting ongoing pregnancy. RESULT(S): The elasticity index was significantly higher (2.4 ± 1.3 vs. 1.5 ± 0.7, i.e., with stiffer myometrium), and the endometrium was significantly less echogenic in future pregnant women. Factors closely reaching significance were age, previous fertility, day 3 hormonal assessments, number of inseminated spermatozoa, endometrial thickness, and UC count. In multivariate analysis, low UC frequency (<2.8/minute; odds ratio [OR] = 0.039), high elasticity index (>1.7; OR = 63.26), high endometrial thickness on the ovulation triggering day (>8 mm; OR = 28.21), and low patient age (<32 years; OR = 0.001) were predictive of pregnancy after IUI. CONCLUSION(S): A low frequency and high intensity of UCs at the day of IUI appears associated with a higher pregnancy rate. Elastography provides a promising innovative tool for IUI monitoring.

Testicular Shear Wave Elastography in Normal and Infertile Men: A Prospective Study on 601 Patients.

Our aim in the study described here was to prospectively establish the feasibility of using and reproducibility of testicular shear-wave elastography in the assessment of testicular stiffness in 62 normal patients and 539 infertile men with obstructive azoospermia (OA), non-Klinefelter syndrome non-obstructive azoospermia (non-KS NOA), Klinefelter syndrome NOA (KS NOA), oligoasthenoteratozoospermia (OAT) or a left varicocele. The feasibility rate was 96.9%, with an intra-class correlation coefficient of 0.85 (95% confidence interval: 0.83-0.88). Median stiffness (interquartile range) values were 2.4 kPa (2.0, 2.9), 2.1 kPa (1.8, 2.5), 2.4 kPa (2.0, 2.7), 2.0 kPa (1.7, 2.4), 2.6 kPa (2, 3.2) and 2.2 kPa (1.8, 2.6) for men with a normal testis (n = 108), OAT (n = 689), OA (n = 119), non-KS NOA (n = 183), KS NOA (n = 70) and varicocele (n = 132), respectively. Testicular shear wave elastography is a feasible and reproducible technique. A significant positive association was found between stiffness and testis volume (p = 0.001). Testicular stiffness was higher in OA than in non-KS NOA populations (p = 1.e-10) and in KS NOA than in NOA populations (p = 2.0e-8), but the substantial number of overlapping values limited the clinical impact.

Medical Imaging and Infertility.

Infertility affects many couples, and medical imaging plays a vital role in its diagnosis and treatment. Radiologic technologists benefit from having a broad understanding of infertility risk factors and causes. This article describes the typical structure and function of the male and female reproductive systems, as well as congenital and acquired conditions that could lead to a couple's inability to conceive. Medical imaging procedures performed for infertility diagnosis are discussed, as well as common interventional options available to patients.