What are the risks associated with lipiodol hysterosalpingography? A literature review.

INTRODUCTION: Hysterosalpingography is widely used as a first-line investigation for infertility, and may also be therapeutic, increasing pregnancy rates. Aqueous and oil-based contrast agents can be used. Some studies suggest Lipiodol hysterosalpingography has a greater therapeutic effect on fertility than aqueous contrast, though this is contentious. There are additionally safety concerns surrounding Lipiodol hysterosalpingography. This review summarises the adverse effects associated with Lipiodol hysterosalpingography, particularly on thyroid function. KEY FINDINGS: 331 articles were identified. Of these, 46 met inclusion criteria. 3 further articles were identified from reference lists. Complications typically cited in the literature include pain, intravasation, life-threatening oil embolism, and lipogranuloma formation. Emerging evidence suggests that Lipiodol hysterosalpingography may also impact maternal and neonatal thyroid function. Women may develop hypo- or hyperthyroidism. Thyroid dysfunction is clinically significant as even subclinical hypothyroidism reduces fertility, increases the risk of pregnancy complications including miscarriage, pre-eclampsia and perinatal mortality, and adversely impacts foetal neurodevelopment. One study suggested a possible link with neonatal congenital hypothyroidism. CONCLUSION: There is emerging evidence to suggest that Lipiodol hysterosalpingography can cause hypo- or hyperthyroidism, in addition to known adverse effects of pain, intravasation, oil embolism, and lipogranuloma formation. IMPLICATIONS FOR PRACTICE: Given the significance of these risks, and contention surrounding whether Lipiodol truly increases pregnancy rates compared to aqueous mediums, careful consideration is required in the selection of contrast agent. In particular, Lipiodol hysterosalpingography may not be suitable for women with pre-existing thyroid dysfunction.

Infertility: Evaluation and Management.

Infertility is the inability to achieve a pregnancy after 12 months of regular, unprotected sexual intercourse. Evaluation and treatment are recommended earlier than 12 months when risk factors for infertility exist, if the female partner is 35 years or older, and in the setting of nonheterosexual partnerships. A comprehensive medical history and physical examination emphasizing the thyroid, breast, and pelvic areas should be performed to help direct diagnosis and treatment. Causes of infertility in females include uterine and tubal factors, ovarian reserve, ovulatory dysfunction, obesity, and hormone-related disorders. Common male factor infertility issues include abnormal semen, hormonal disorders, and genetic abnormalities. Semen analysis is recommended for the initial assessment of the male partner. Evaluation of the female should include assessment of the uterus and fallopian tubes with ultrasonography or hysterosalpingography when indicated. Laparoscopy, hysteroscopy, or magnetic resonance imaging may be needed to evaluate for endometriosis, leiomyomas, or evidence of a previous pelvic infection. Treatment with ovulation induction agents, intrauterine insemination, in vitro fertilization, donor sperm or eggs, or surgery may be necessary. Unexplained male and female infertility can be treated with intrauterine insemination or in vitro fertilization. Limiting alcohol intake, avoiding tobacco and illicit drug use, consuming a profertility diet, and losing weight (if obese) may improve pregnancy success rates.

The effectiveness of immediate versus delayed tubal flushing with oil-based contrast in women with unexplained infertility (H2Oil-timing study): study protocol of a randomized controlled trial.

BACKGROUND: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography leads to significantly more live births as compared to tubal flushing with water-based contrast during hysterosalpingography. However, it is unknown whether incorporating tubal flushing with oil-based contrast in the initial fertility work-up results to a reduced time to conception leading to live birth when compared to delayed tubal flushing that is performed six months after the initial fertility work-up. We also aim to evaluate the effectiveness of tubal flushing with oil-based contrast during hysterosalpingography versus no tubal flushing in the first six months of the study. METHODS: This study will be an investigator-initiated, open-label, international, multicenter, randomized controlled trial with a planned economic analysis alongside the study. Infertile women between 18 and 39 years of age, who have an ovulatory cycle, who are at low risk for tubal pathology and have been advised expectant management for at least six months (based on the Hunault prediction score) will be included in this study. Eligible women will be randomly allocated (1:1) to immediate tubal flushing (intervention) versus delayed tubal flushing (control group) by using web-based block randomization stratified per study center. The primary outcome is time to conception leading to live birth with conception within twelve months after randomization. We assess the cumulative conception rate at six and twelve months as two co-primary outcomes. Secondary outcomes include ongoing pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, number of complications, procedural pain score and cost-effectiveness. To demonstrate or refute a shorter time to pregnancy of three months with a power of 90%, a sample size of 554 women is calculated. DISCUSSION: The H2Oil-timing study will provide insight into whether tubal flushing with oil-based contrast during hysterosalpingography should be incorporated in the initial fertility work-up in women with unexplained infertility as a therapeutic procedure. If this multicenter RCT shows that tubal flushing with oil-based contrast incorporated in the initial fertility work-up reduces time to conception and is a cost-effective strategy, the results may lead to adjustments of (inter)national guidelines and change clinical practice. TRIAL REGISTRATION NUMBER: The study was retrospectively registered in International Clinical Trials Registry Platform (Main ID: EUCTR2018-004153-24-NL).

Intravasation complicating hysterosalpingo-foam sonography (HyFoSy) using ExEm® Foam.

BACKGROUND: Transvaginal hysterosalpingo-foam sonography (HyFoSy) assesses tubal patency in an outpatient setting and without ionising radiation, unlike traditional hysterosalpingography (HSG) under fluoroscopy. Like HSG, HyFoSy may be complicated by uterine intramural contrast leak, leading to venous intravasation. Intravasation of particulate contrast agents risks pulmonary or cerebral emboli. AIMS: We aimed to assess the intravasation rate of HyFoSy using ExEm® Foam and association with endometrial thickness, ExEm® Foam volume, uterine length, adenomyosis severity, uterine morphology or pain score. METHODS: An ethics-approved retrospective study on all HyFoSy examinations between 23 January 2018 and 27 October 2021 on sub-fertile patients, trying to conceive. Initial transvaginal sonography confirmed anatomy, uterine morphology, adenomyosis severity and endometrial thickness. Subspecialist radiologists performed HyFoSy with sonographer assistance. Intravasation was identified in real time but also checked for afterwards. Patients were asked to rate instillation pain/discomfort from one to ten immediately afterward. RESULTS: Four hundred and thirty-six (n = 436) patients met inclusion criteria. Thirty (6.9%) experienced intravasation. Endometrial thickness and pain score were associated with intravasation. For every millimetre increase in endometrial thickness, the odds of intravasation decreased by 26% (P = 0.010). For every point increase on the pain scale, the odds of intravasation increased by 22% (P = 0.032). There was no evidence of an association between instilled ExEm® Foam volume or the other previously published parameters with intravasation. CONCLUSION: A 6.9% rate of intravasation was observed. Both endometrial thickness and pain score were significantly associated with intravasation. There was no evidence of an association between ExEm® Foam volume and intravasation.

Diagnostic accuracy of pelvis multiparametric MRI against CT virtual hysterosalpingography: a prospective study of tubal patency through female infertility assessment.

OBJECTIVE: To evaluate the diagnostic accuracy of MRI-hysterosalpingogram (HSG) with semiquantitative dynamic contrast-enhanced perfusion, against the virtual multislice CT hysterosalpingogram (VHSG) as a reference standard. METHODS AND MATERIALS: In this prospective study, 26 women (age >18 years) searching for infertility causes and with VHSG physician request. Thereafter, the assessment performance of both techniques was determined by two reader analyses. k statistics were used for the assessment of tubal patency. Receiver operating characteristic (ROC) analysis was used to compare the capability for tubal patency assessment between both exams on a per-patient and per-tube basis. The McNemar test was used to compare the diagnostic accuracy measures. RESULTS: Tubal patency, uterine morphological, ovarian, and extrauterine abnormalities were evaluated through both exams in all 26 women. There was no significant difference between diagnostic performance measurements between the methods. The ROC curve of VHSG was 0.852 for both per-patient and per-tube analyses, and one and 0.938 for MRI-HSG. Sensitivity and specificity for per-patient and per-tube for VHSG were 95.2 and 97.7, 80 and 87.5%, and for MRI-HSG 100% for both analyses and 100 and 87.5%, respectively. CONCLUSION: This study demonstrates the feasibility of diagnosing tubal patency through MRI, using a semi-quantitative dynamic contrast-enhanced perfusion sequence, and the satisfactory diagnosing of the uterine morphology, ovarian abnormalities, and ovarian and deep endometriosis. ADVANCES IN KNOWLEDGE: Multiparametric MRI with a perfusion real-time sequence as a HSG method can be used in the evaluation not only for uterine and ovarian abnormilities but also tubal patency.

Fluoroscopically-Guided Hysteroscopic Tubal Cannulation: A Procedure for Proximal Tubal Obstruction.

Objectives: To evaluate the cannulation success rate, cumulative pregnancy, and time to intrauterine pregnancy rate following fluoroscopically-guided hysteroscopic tubal cannulation (FHTC) for infertile subjects with proximal tubal obstruction. Methods: This retrospective study evaluated subjects with unilateral or bilateral proximal tubal obstruction on hysterosalpingography, who failed concomitant selective salpingography and subsequently underwent FHTC at the time of a hysteroscopy performed for findings seen on sonohysterography. FHTC employed a Novy Catheter (CooperSurgical, Inc, Trumbull, CT.) with or without the 3 French inner catheter and guidewire, to cannulate the occluded fallopian tube(s), followed by the injection of HypaqueTM (Amersham Health, Inc, Princeton, NJ.) contrast under C-arm imaging. Technical success rates, complications, post-procedure pregnancies, and average time from surgery to pregnancy were evaluated. Results: Thirty-two women between January 1, 2017 and December 31, 2019 met the entry criteria and underwent FHTC. Of those women with bilateral obstruction, 6/6 (100%) of subjects achieved at least unilateral patency, while patency was achieved in 23/26 (88.5%) subjects with unilateral obstruction. Twenty-nine of 32 (90.6%) subjects had at least one tube successfully cannulated with 34/38 (89.5%) of proximally obstructed tubes opened. Asymptomatic tubal perforation occurred in 1/38 tubes (2.6%). Ten subjects (34.5%) achieved intrauterine pregnancies without in vitro fertilization in an average of 64.9 days from the procedure. There were no multiple pregnancies and one ectopic pregnancy. Conclusions: FHTC is a safe, effective, incision free procedure that results in 90% of tubes successfully cannulated, and an observed short time to intrauterine pregnancy.

Comparison between X-ray-hysterosalpingography and 3 Tesla magnetic resonance-hysterosalpingography in the assessment of the tubal patency in the cause of female infertility.

OBJECTIVES: XR-hysterosalpingography currently represents the gold standard for tubal pathology evaluation. Magnetic resonance-HSG is an innovative technique. With our study, we aim to comprehend if and how MR-HSG, compared to traditional XR-HSG, could give us this additional information in the diagnostic/therapeutic process. MATERIALS AND METHODS: This study included 19 patients between 30 and 42 years old (average age 37.7) affected by infertility. Patients underwent contextually both XR-HSG and MR-HSG, using a single catheterization. The dynamic MR-HSG exam consisted a MR sequence during contrast administration through the cervical catheter. RESULTS: Both XR-HSG and MR-HSG documented that 15 of the 19 patients had bilateral tubal patency, while four patients had monolateral tubal patency. However, MR-HSG allowed us to diagnose additional findings: Two active endometriosis foci in adnexal localization and a condition of adenomyosis A unicornuate uterus malformation A submucous uterine myoma near the tubal ostium A decrease of the ovarian reserve in a patient So MR-HSG could potentially detect in 10/19 (52%) women the cause of their infertility, compared to 4/19 (21%) detected with XR-HSG and about 30% of women would have resulted as false negatives if we only used XR-HSG. Finally, with a questionnaire, we demonstrated that MR-HSG is less painful than XR-HSG. CONCLUSIONS: These data thus confirm that XR-HSG and MR-HSG present the same diagnostic of assessing tubal patency. We also demonstrated that MR-HSG is able to detect further collateral findings that could likewise be a possible therapeutic target and it could possibly become the new gold standard in female infertility diagnostics.

The SELFI Study: Iodine Excess and Thyroid Dysfunction in Women Undergoing Oil-Soluble Contrast Hysterosalpingography.

CONTEXT: Hysterosalpingography (HSG) with oil-soluble contrast medium (OSCM) improves pregnancy rates. However, OSCM has high iodine content and long half-life, leading to potential iodine excess. OBJECTIVE: This work aimed to determine the pattern of iodine excess after OSCM HSG and the effect on thyroid function. METHODS: A prospective cohort study was conducted of 196 consecutive consenting eligible women without overt hypothyroidism or hyperthyroidism. All completed the study with compliance greater than 95%. Participants underwent OSCM HSG (Auckland, 2019-2021) with serial monitoring of thyrotropin (TSH), free thyroxine (FT4), and urine iodine concentration (UIC) for 24 weeks. The main outcome measure was the development of subclinical hypothyroidism (SCH), defined as a nonpregnant TSH greater than 4 mIU/L with normal FT4 (11-22 pmol/L) in those with normal baseline thyroid function. RESULTS: Iodine excess (UIC ≥ 300 µg/L) was almost universal (98%) with UIC peaking usually by 4 weeks. There was marked iodine excess, with 90% and 17% of participants having UIC greater than or equal to 1000 µg/L and greater than 10 000 µg/L, respectively. Iodine excess was prolonged with 67% having a UIC greater than or equal to 1000 µg/L for at least 3 months. SCH developed in 38%; the majority (96%) were mild (TSH 4-10 mIU/L) and most developed SCH by week 4 (75%). Three participants met the current treatment guidelines (TSH > 10 mIU/L). Thyroxine treatment of mild SCH tended to improve pregnancy success (P = .063). Hyperthyroidism (TSH < 0.3 mIU/L) occurred in 9 participants (5%). CONCLUSION: OSCM HSG resulted in marked and prolonged iodine excess. SCH occurred frequently with late-onset hyperthyroidism occasionally. Regular thyroid function tests are required for 6 months following this procedure.

Lipiodol flushing under ultrasound guidance at time of hystero-salpingo contrast sonography (HyCoSy): A retrospective observational study.

BACKGROUND: Up to 30% of female infertility can be attributed to tubal abnormalities. Assessment of fallopian tube patency forms a component of the basic assessment of infertility. Tubal patency can be checked through hysterosalpingogram (HSG) under radiologic guidance with oil- or water-based contrast medium (OBCM or WBCM), or hystero-salpingo contrast sonography (HyCoSy) under ultrasound guidance with WBCM. Tubal flushing with OBCM has been shown to improve fertility rates. OBJECTIVES: To study the feasibility and tolerability of performing Lipiodol (ethiodised oil) flush concurrently with HyCoSy. To examine the in vivo sonographic visibility of Lipiodol vs normal saline. MATERIALS AND METHODS: Retrospective observational study of patients with subfertility referred for Lipiodol flushing under ultrasound guidance between August 2017-September 2020 at six private ultrasound practices in Sydney, Australia. RESULTS: There were 412 patients who were referred for Lipiodol flushing. Of these, 86 patients did not have concurrent Lipiodol flush at HyCoSy performed due to strict exclusion criteria. Of the 326 patients who proceeded with Lipiodol flushing at HyCoSy, all cases were successful, with no cases of extravasation. There were no major complications. In vivo sonographic visualisation of Lipiodol was similar to that of the commonly used agitated 0.9% saline (n = 20; mean visibility score 4.3 ± 0.9 vs 4.0 ± 1.2). CONCLUSION: Our study has shown that Lipiodol flushing at time of HyCoSy as a single procedure is feasible and tolerable to patients. Flushing with Lipioidol during HyCoSy is likely as sonographically visible as 0.9% saline.

Evaluation of the safety and effectiveness of tubal inflammatory drugs in patients with incomplete tubal obstruction after four-dimensional hysterosalpingo-contrast-sonography examination.

BACKGROUND: To investigate the safety and effectiveness of tubal inflammatory drugs in patients with incomplete tubal obstruction of at least one side after four-dimensional hysterosalpingo-contrast-sonography (4D-HyCoSy) examination. METHODS: Two hundred fifteen cases of tubal incomplete obstruction were diagnosed by ultrasonography from February 2019 to November 2020.According to retrospective analysis,the patients in this study were divided into experimental and control groups; the experimental group combined with salpingitis drugs, and the control group received blank control. Basic information, degree of pain, postoperative complications, and pregnancy rate were then compared between the two groups. RESULTS: Compared with the control group, there was no significant difference in the basic information; in preoperative, intraoperative, or postoperative pain; or in postoperative complications (P > 0.05). The cumulative pregnancy rate of the experimental group (26.8%) was statistically different from that of the control group (14.4%) (P < 0.05). CONCLUSIONS: We observed that for infertile patients with incomplete obstruction of at least one fallopian tube as diagnosed by contrast-enhanced ultrasonography, salpingitis-treatment drugs effectively improved the pregnancy rate postoperatively, with high effectiveness and safety. This regimen is thus worthy of further investigation and promotion in the future.

What is the fertility-enhancing effect of tubal flushing? A hypothesis article.

Hysterosalpingographies (HSGs) have formed an essential part of the fertility workup for more than a century. More recently, tubal flushing, especially with oil-based contrast, has been shown to significantly improve the natural conception rates. Critically, the mechanism of this fertility-enhancing effect during tubal flushing is still unclear. This article postulates hypotheses, based on published and own research, on the potential mechanisms and root cause of tubal flushing fertility enhancement. Possible explanations for the increased fertility rates, especially with oil-based contrast, are divided into the biochemical and interfacial effects derived from the contrast properties. The biochemical effects may include the immunological response of the endometrium or peritoneum, the impact on the endometrial opioid receptors or the iodine content. The interfacial effects may include improvement of interfacial factors due to the lubricant effect or dislodgement of mucus debris within the Fallopian tubes. Impact StatementWhat is already known on this subject? Tubal flushing during hysterosalpingographies (HSGs) increases natural conception rates, and using oil-based over water-based contrast increases that effect even further. However, the underlying mechanism of the observed fertility-enhancing effect is still poorly understood.What do the results of this study add? This article postulates different hypotheses on the potential mechanisms and root cause of the fertility enhancement from tubal flushing.What are the implications of these findings for clinical practice and/or further research? We suggest additional research on the different hypotheses, intending to determine which subfertile women will benefit most from tubal flushing using oil-based contrast and at which stage of their subfertility. Furthermore, we suggest research on administering tubal flushing with oil-based contrast, besides in HSG.

Oil-based versus water-based contrast media for hysterosalpingography in infertile women of advanced age, with ovulation disorders or a high risk for tubal pathology: study protocol of a randomized controlled trial (H2Oil2 study).

BACKGROUND: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography (HSG) increases ongoing pregnancy and subsequent live birth rates when compared to tubal flushing with water-based contrast. It is currently unclear whether an HSG with oil-based contrast also results in more ongoing pregnancies and live births in women of advanced age, women with ovulation disorders, and women with potential tubal pathology when compared to an HSG with water-based contrast. METHODS: We plan an international, multicentre, open-label, randomized controlled trial (RCT) studying three groups of infertile women who have an indication for tubal patency testing according to their treating physician and additionally; (1) are 39 years of age or older, (2) have an ovulation disorder or (3) have a high risk for tubal pathology based on their medical history. Women with an allergy for iodinated contrast medium are excluded, as are women with diabetes, hyperprolactinemia or untreated hyper- or hypothyroidism, and women with a partner with severe male infertility. After informed consent, women will be randomly allocated to the intervention, tubal flushing with the use of oil-based contrast during HSG or the control group, tubal flushing with the use of water-based contrast during HSG in a 1:1 ratio by the web-based system Castor. The primary endpoint will be ongoing pregnancy leading to live birth with conception within six months after randomization. Secondary outcomes are other pregnancy outcomes, used fertility treatments, adverse events and cost-effectiveness. Based on the expected ongoing pregnancy rate of 17% in the control group and 27% in the intervention group, the sample size will be 930 women (465 per group). Study inclusion is expected to be complete in four years. DISCUSSION: This multicentre RCT will establish whether, for women of advanced age, women with ovulatory disease, and women who have a high risk for tubal pathology, there is a fertility enhancing effect of tubal flushing with oil-based contrast during HSG and whether the use of this contrast medium is cost-effective. Trial Registration The study was prospectively registered in the Netherlands Trial Register on August 1st 2019 as 'H2Oil2' (reference number NL7925, https://www.trialregister.nl/trial/7925 ).

Can hysterosalpingo-foam sonography replace hysterosalpingography as first-choice tubal patency test? A randomized non-inferiority trial.

STUDY QUESTION: Does hysterosalpingo-foam sonography (HyFoSy) lead to similar pregnancy outcomes, compared with hysterosalpingography (HSG), as first-choice tubal patency test in infertile couples? SUMMARY ANSWER: HyFoSy and HSG produce similar findings in a majority of patients and clinical management based on the results of either HyFoSy or HSG, leads to comparable pregnancy outcomes. HyFoSy is experienced as significantly less painful. WHAT IS KNOWN ALREADY: Traditionally, tubal patency testing during fertility work-up is performed by HSG. HyFoSy is an alternative imaging technique lacking ionizing radiation and iodinated contrast medium exposure which is less expensive than HSG. Globally, there is a shift towards the use of office-based diagnostic methods, such as HyFoSy. STUDY DESIGN, SIZE, DURATION: This multicentre, prospective, comparative study with a randomized design was conducted in 26 hospitals in The Netherlands. Participating women underwent both HyFoSy and HSG in randomized order. In case of discordant results, women were randomly allocated to either a management strategy based on HyFoSy or one based on HSG. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included infertile women between 18 and 41 years old who were scheduled for tubal patency testing during their fertility work-up. Women with anovulatory cycles not responding to ovulation induction, endometriosis, severe male infertility or a known iodine contrast allergy were excluded. The primary outcome for the comparison of the HyFoSy- and HSG-based strategies was ongoing pregnancy leading to live birth within 12 months after inclusion in an intention-to-treat analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, 1026 women underwent HyFoSy and HSG. HyFoSy was inconclusive in 97 of them (9.5%), HSG was inconclusive in 30 (2.9%) and both were inconclusive in 9 (0.9%). In 747 women (73%) conclusive tests results were concordant. Of the 143/1026 (14%) with discordant results, 105 were randomized to clinical management based on the results of either HyFoSy or HSG. In this group, 22 of the 54 women (41%) allocated to management based on HyFoSy and 25 of 51 women (49%) allocated to management based on HSG had an ongoing pregnancy leading to live birth (Difference -8%; 95% CI: -27% to 10%). In total, clinical management based on the results of HyFoSy was estimated to lead to a live birth in 474 of 1026 women (46%) versus 486 of 1026 (47%) for management based on HSG (Difference -1.2%; 95% CI: -3.4% to 1.5%). Given the pre-defined margin of -2%, statistically significant non-inferiority of HyFoSy relative to HSG could not be demonstrated (P = 0.27). The mean pain score for HyFoSy on the 1-10 Visual Analogue Scale (VAS) was 3.1 (SD 2.2) and the mean VAS pain score for HSG was 5.4 (SD 2.5; P for difference < 0.001). LIMITATIONS, REASONS FOR CAUTION: Since all women underwent both tubal patency tests, no conclusions on a direct therapeutic effect of tubal flushing could be drawn. WIDER IMPLICATIONS OF THE FINDINGS: HyFoSy or HSG produce similar tubal pathology findings in a majority of infertile couples and, where they differ, a difference in findings does not lead to substantial difference in pregnancy outcome, while HyFoSy is associated with significantly less pain. STUDY FUNDING/COMPETING INTEREST(S): The FOAM study was an investigator-initiated study funded by ZonMw, The Netherlands organization for Health Research and Development (project number 837001504). ZonMw funded the whole project. IQ Medical Ventures provided the ExEm-foam® kits free of charge. The funders had no role in study design, collection, analysis and interpretation of the data. K.D. reports travel and speaker fees from Guerbet. F.J.M.B. reports personal fees as a member of the external advisory board for Merck Serono, The Netherlands, and a research support grant from Merck Serono, outside the submitted work. C.B.L. reports speakers' fee from Ferring in the past, and his department receives research grants from Ferring, Merck and Guerbet. J.S. reports a research agreement with Takeda on MR of motility outside the submitted work. M.V.W. reports leading The Netherlands Satellite of the Cochrane Gynaecology and Fertility Group. B.W.J.M. is supported by an NHMRC Investigator grant (GNT1176437). B.W.J.M. reports consultancy for Guerbet and research funding from Merck and Guerbet. V.M. reports non-financial support from IQ medicals ventures, during the conduct of the study; grants and personal fees from Guerbet, outside the submitted work. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: NTR4746/NL4587 (https://www.trialregister.nl). TRIAL REGISTRATION DATE: 19 August 2014. DATE OF FIRST PATIENT'S ENROLMENT: 7 May 2015.

The effect of hyoscine-N-butylbromide on pain perception during and after hysterosalpingography in infertile women: a systematic review and meta-analysis of randomised controlled trials.

This paper reports a systematic review and meta-analysis of the effectiveness of hyoscine-N-butylbromide (HBB) administration in hysterosalpingography (HSG). Four electronic databases were searched for randomised controlled trials (RCTs) that compared HBB versus placebo or no intervention in infertile women undergoing HSG. Pain during and after HSG and different adverse events including nausea, vomiting, and dizziness were evaluated. Three RCTs with 335 patients were included. The analysis showed HBB was significantly effective in reducing pain during and after HSG (MD = -0.76 mm, 95% CI [-1.35, -0.17], p = 0.01) and (MD = -0.81 mm, 95% CI [-1.07, -0.56], p < 0.001), respectively. There were no significant differences in adverse events between HBB and control groups. The methodological evidence quality was high as evaluated by GRADEpro. In conclusion, this review provides good evidence that prior administration of HBB is effective in reducing induced pain during and after HSG with tolerable side effects.

4D-HyCoSy performed in a reproductive center: retrospective analysis of pain perception, complications and spontaneous pregnancy rate after the technique.

OBJECTIVE: Nowadays 4D hysterosalpingocontrast sonography (4D-HyCoSy) represents a primary technique in the evaluation of tubal impairment, with a low rate of pain referred and complications related, but its role in increasing the chance of spontaneous clinical pregnancy in women in childbearing age is still debated. PATIENTS AND METHODS: Retrospective study of 359 women performed 4D-HyCoSy at Reproductive Physiopathology and Andrology Unit, Sandro Pertini Hospital, Rome, during the period 2018-2020. INCLUSION CRITERIA: women attending our IVF (in vitro fertilization) center with at least 1 year of infertility. EXCLUSION CRITERIA: female age over 43 years, previously known severe tubal infertility, suspected anovulation, and semen abnormalities. PRIMARY OUTCOME: evaluation of tubal patency, complications related to technique, and pain perception evaluated thanks to a 10-cm visual analogue scale (VAS) Scale. SECONDARY OUTCOMES: clinical pregnancy rate (PR) after the technique confronted between the group of women with bilateral tubal patency (group A) with the group of monolateral tubal patency (group B) within 30 days and between 30-180 days, and 180 days-1 year from the exam. Time to pregnancy (TTP) and other obstetrical outcomes were evaluated too. RESULTS: The average age of the study's population was 33.3 years. Mean duration of infertility was 2.1 years. Complication rate was 6.4%, and in any case the use of ephedrine was required. 182 (50.6%) women reported absence of pain during the exam (VAS scale value 0) and 131 (36.5%), reported mild pain experience (VAS scale value between 1-4). Spontaneous pregnancy rate was of 29.3% in group A and 30.3% in group B; time to pregnancy was 32 ± 14.7 days in group A and 35 ± 13.1 days in group B. The insurgence of a spontaneous pregnancy was significantly lower for both 4D-HyCosy sub-groups after 30 days following technique respect to 30-180 days and 180 days-1 year following the technique (both p-value < 0.001). CONCLUSIONS: We confirm that 4D-HyCoSy is a safe and user-friendly technique, used as first line assessment of tubal patency of women afferent to a reproductive center. We also reported a positive impact on spontaneous pregnancy rate in women performing 4D-HyCoSy, emphasized within the first following month. This mandatory technique for tubal investigation, has not only a function in the diagnostic assessment of female infertility, but also has a therapeutic role, in young women who desire a pregnancy, avoiding, in some cases, the need of IVF treatments and clinical risks linked, while saving medical and monetary resources.

Effect of X-ray exposure during hysterosalpingography on capabilities of female germ cells.

PURPOSE: To elucidate the effect of X-ray exposure during hysterosalpingography (HSG) on subsequent laboratory outcomes in in vitro fertilization (IVF). METHODS: A total of 1458 oocytes, consisting of 990 oocytes retrieved from 70 women (89 cycles) who underwent HSG prior to IVF and 468 oocytes from 45 women (57 cycles) who underwent IVF without HSG, were evaluated for their retrieval number, maturity, fertilization, and development post fertilization. X-ray exposure during HSG was recorded as reference air kerma (RAK) (mGy). Subjects were stratified according to the amount of RAK (Nil: IVF without HSG, L-RAK: RAK < 16.23, mH-RAK: RAK ≥ 16.23). The number of oocytes retrieved, oocyte maturation, fertilization, and embryo development was compared among 3 groups. Further, multivariate analyses were performed to investigate the effect of X-ray exposure on laboratory outcomes in IVF. RESULTS: There was a statistically significant difference in the fertilization rate among 3 groups (Nil: 71.6%, L-RAK: 80.5%, mH-RAK: 78.3%). The good-quality blastocyst rate in mH-RAK (46.2%) was significantly higher than L-RAK (35.3%) and Nil (32.4%). Multivariate analyses revealed that X-ray exposure was associated with higher fertilization, higher blastocyst development, and higher good-quality blastocyst development rates with adjustment for patient age, BMI, ovarian stimulation types, and fertilization methods. Association between X-ray exposure and the number of oocytes retrieved, and oocyte maturation was not confirmed. CONCLUSIONS: The present study suggests that X-ray exposure of the female reproductive organs during HSG could enhance the potential of oocytes rather than adversely.

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.