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.

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.

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.

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.

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 ).

The Impact of Preconceptional Hysterosalpingography with Oil-based Contrast on Maternal and Neonatal Iodine Status.

The objective of this study is to investigate the impact of preconceptional exposure to oil-based iodinated contrast in the hysterosalpingography (HSG) on pregnant women and their offspring's iodine status, thyroid function, and the outcomes of pregnancy. A cross-sectional evaluation of iodine status was performed on pregnant women with the preconceptional experience of ethiodized-oil HSG. For those found to have iodine excess (with serum iodine concentration (SIC) > 92 µg/L), a prospective follow-up was conducted until termination of the pregnancy or 1 week postpartum. Among 70 of 425 pregnant women with preconceptional ethiodized-oil HSG, iodine excess was initially confirmed in 38 (54.3%), with an elevated SIC (294.00 µg/L [142.00, 123.20]) and urinary iodine-to-creatinine ratio (UI/Cr) (830.00 µg/g Cr [437.50, 255.30]), both higher than the normative data (P = 0.000, P = 0.000). Subsequent follow-up in pregnancy showed a downward trend in both SIC and UI/Cr. Thirty-four women delivered healthy neonates at full term, though the other 4 cases of premature birth, abnormal fetal karyotype, spontaneous abortion, and neonatal cardiac defect were reported. After delivery, the iodine concentration in maternal breast milk and neonatal urine was 584.50 µg/L [328.50, 1507.50] and 424.00 µg/L [277.00, 657.50], respectively, both higher than normative data (P = 0.001, P = 0.015). For thyroid evaluation, 25 cases (65.79%) of clinical or subclinical hypothyroidism and 2 cases (5.26%) of thyrotoxicosis were confirmed in women with iodine excess. Neither goiter nor thyroid dysfunction was detected in any offspring. Preconceptional exposure to oil-based contrast in HSG might exert a far-reaching impact on maternal and offspring iodine status, and tend to result in increased risk of maternal thyroid dysfunction.

Tubal flushing with oil-based or water-based contrast at hysterosalpingography for infertility: long-term reproductive outcomes of a randomized trial.

OBJECTIVE: To determine the impact of oil-based versus water-based contrast on pregnancy and live birth rates ≤5 years after hysterosalpingography (HSG) in infertile women. DESIGN: A 5-year follow-up study of a multicenter randomized trial. SETTING: Hospitals. PATIENT(S): Infertile women with an ovulatory cycle, 18-39 years of age, and having a low risk of tubal pathology. INTERVENTION(S): Use of oil-based versus water-based contrast during HSG. MAIN OUTCOME MEASURE(S): Ongoing pregnancy, live births, time to ongoing pregnancy, second ongoing pregnancy. RESULT(S): A total of 1,119 women were randomly assigned to HSG with oil-based contrast (n = 557) or water-based contrast (n = 562). After 5 years, 444 of 555 women in the oil group (80.0%) and 419 of 559 women in the water group (75.0%) had an ongoing pregnancy (relative risk [RR] 1.07; 95% confidence interval [CI] 1.00-1.14), and 415 of 555 women in the oil group (74.8%) and 376 of 559 women in the water group (67.3%) had live births (RR 1.11; 95% CI 1.03-1.20). In the oil group, 228 pregnancies (41.1%) were conceived naturally versus 194 (34.7%) pregnancies in the water group (RR 1.18; 95% CI 1.02-1.38). The time to ongoing pregnancy was significantly shorter in the oil group versus the water group (10.0 vs. 13.7 months; hazard ratio, 1.25; 95% CI 1.09-1.43). No difference was found in the occurrence of a second ongoing pregnancy. CONCLUSION(S): During a 5-year time frame, ongoing pregnancy and live birth rates are higher after tubal flushing with oil-based contrast during HSG compared with water-based contrast. More pregnancies are naturally conceived and time to ongoing pregnancy is shorter after HSG with oil-based contrast. CLINICAL TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NTR) 3270 and NTR6577(www.trialregister.nl).

Treatment effect of oil-based contrast is related to experienced pain at HSG: a post-hoc analysis of the randomised H2Oil study.

STUDY QUESTION: Does pain or volume of used contrast medium impact the effectiveness of oil-based contrast during hysterosalpingography (HSG)? SUMMARY ANSWER: In women who report moderate to severe pain during HSG, the use of oil-based contrast resulted in more ongoing pregnancies compared to the use of water-based contrast, whereas in women who reported mild or no pain, no difference in ongoing pregnancies was found. WHAT IS KNOWN ALREADY: We recently showed that in infertile women undergoing HSG, the use of oil-based contrast results in more ongoing pregnancies within 6 months as compared to the use of water-based contrast. However, the underlying mechanism of this fertility-enhancing effect remains unclear. STUDY DESIGN, SIZE, DURATION: We performed a post-hoc analysis of the H2Oil study, a multicentre randomised controlled trial (RCT) evaluating the therapeutic effect of oil- and water-based contrast at HSG. Here, we evaluated the impact of pain experienced at HSG and volume of used contrast media during HSG on ongoing pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: In a subset of 400 participating women, pain during HSG by means of the Visual Analogue Scale (VAS) (range: 0.0-10.0 cm) was reported, while in 512 women, we registered the volume of used contrast (in millilitres). We used logistic regression analyses to assess whether pain and volume of used contrast media modified the effect of oil-based contrast on ongoing pregnancy rates. Data were analysed according to intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: In 400 women in whom pain scores were reported, the overall median pain score was 5.0 (Interquartile range (IQR) 3.0-6.8) (oil group (n = 199) 4.8 (IQR 3.0-6.4); water group (n = 201) 5.0 (IQR 3.0-6.7); P-value 0.28). There was a significant interaction between pain (VAS ≤5 versus VAS ≥6) and the primary outcome ongoing pregnancy (P-value 0.047). In women experiencing pain (VAS ≥6), HSG with oil-based contrast resulted in better 6-month ongoing pregnancy rates compared to HSG with water-based contrast (49.4% versus 29.6%; RR 1.7; 95% CI, 1.1-2.5), while in women with a pain score ≤5, 6-month ongoing pregnancy rates were not significantly different between the use of oil- (28.8%) versus water-based contrast (29.2%) (RR 0.99; 95% CI, 0.66-1.5). In the 512 women in whom we recorded contrast, median volume was 9.0 ml (IQR 5.7-15.0) in the oil group versus 8.0 ml (IQR 5.9-13.0) in the water group, respectively (P-value 0.72). Volume of used contrast was not found to modify the effect of oil-based contrast on ongoing pregnancy (P-value for interaction 0.23). LIMITATIONS, REASONS FOR CAUTION: This was a post-hoc analysis that should be considered as hypothesis generating. The RCT was restricted to infertile ovulatory women, younger than 39 years of age and with a low risk for tubal pathology. Therefore, our results should not be generalised to infertile women who do not share these features. WIDER IMPLICATIONS OF THE FINDINGS: The underlying mechanism of the fertility-enhancing effect induced by HSG with the use of oil-based contrast remains unclear. However, these findings suggest a possible mechanistic pathway, that is increasing intrauterine pressure occurring prior to dislodging pregnancy hindering debris or mucus plugs from the proximal part of otherwise normal fallopian tubes. This information might help in the search of the underlying fertility-enhancing mechanism found by using oil-based contrast during HSG. STUDY FUNDING/COMPETING INTEREST(S): The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (AMC and VUmc) of the Amsterdam UMC. The funders had no role in study design, collection, analysis and interpretation of the data. K.D. reports consultancy for Guerbet. H.V. reports consultancy fees from Ferring. C.B.L. reports speakers' fees from Ferring and research grants from Ferring, Merck and Guerbet. V.M. reports receiving travel and speakers fees as well as research grants from Guerbet. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research grants from Merck KGaA and Guerbet. The other authors do not report conflict of interests. TRIAL REGISTRATION NUMBER: The H2Oil study was registered at the Netherlands Trial Registry (NTR 3270). TRIAL REGISTRATION DATE: 1 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 3 February 2012.

Combined Real-Time Three-Dimensional Hysterosalpingo-Contrast Sonography with B Mode Hysterosalpingo-Contrast Sonography in the Evaluation of Fallopian Tube Patency in Patients Undergoing Infertility Investigations.

OBJECTIVE: This prospective study aimed to investigate the use of real-time three-dimensional hysterosalpingo-contrast sonography (4D-HyCoSy), using contrast agent SonoVue, with B mode hysterosalpingo-contrast sonography (B mode-HyCoSy), to evaluate tubal patency and the wall of the Fallopian tubes in infertility patients. METHOD: In total, we recruited 739 women with fertility requirements from the First Affiliated Hospital of Shantou Medical College between January 2017 and July 2018. All cases received 4D-HyCoSy using contrast agent SonoVue, immediately followed by the B mode-HyCoSy. Of these patients, 145 showed pathological findings in the Fallopian tubes during HyCoSy; 34 of these (62 Fallopian tubes) were verified by laparoscopy and the dye test against routine reference standards. Sonographic findings, along with laparoscopic findings and dye test results, were used to compare the two techniques using the Cohen kappa coefficient. We also investigated the duration of examination and pain score. RESULTS: Compared with laparoscopy and the dye test, the tubal occlusion diagnostic accordance rates for 4D-HyCoSy were 88.7% (32+23)/62, with a kappa coefficient of 0.769 and a 76.9% agreement rate. Distal occlusion diagnostic accordance rates for 4D-HyCoSy were 100% (8/8) with a k coefficient of 1.000 and a 100% agreement rate. CONCLUSIONS: The use of 4D-HyCoSy, with B mode-HyCoSy, for the diagnosis of tubal patency is safe, feasible, noninvasive, and highly accurate. B mode-HyCoSy allowed us to observe tubal walls in an intuitive manner.

Oil-based versus water-based contrast for hysterosalpingography in infertile women: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To determine the effect of the using oil-soluble contrast material (OSCM) vs. water-soluble contrast material (WSCM) for hysterosalpingography on pregnancy rates in infertile women. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women. INTERVENTION(S): We included randomized controlled trials comparing pregnancy outcomes in women with infertility undergoing hysterosalpingography using OSCM and WSCM. Paired reviewers independently screened citations, assessed risk of bias of included studies, and extracted data. A random-effects model was used to report all outcomes. The Grading of Recommendations Assessment, Development, Evaluation（GRADE） system was used to quantify absolute effects and quality of evidence. MAIN OUTCOME MEASURE(S): The primary outcome was ongoing pregnancy per randomized women. RESULT(S): Six trials with a total of 2,562 patients were selected. Our meta-analysis showed OSCM was associated with significantly higher rates of ongoing pregnancy compared with WSCM (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.12-1.93; I2 = 44%, moderate-quality evidence). Three trials reported live birth, but they were not pooled owing to extreme statistical heterogeneity (I2 = 86%). There was no difference in incidence of miscarriage (OR 0.83, 95% CI 0.56-1.24) or ectopic pregnancy (OR 0.65, 95% CI 0.18-2.36) between OSCM and WSCM groups. Three trials were rated as low risk of bias, whereas three were considered unclear. CONCLUSION(S): Women who previously underwent hysterosalpingography using oil contrast had higher rates of ongoing pregnancy compared with women who underwent this procedure using water contrast. There is not enough evidence to either support or oppose the difference between groups concerning miscarriage and ectopic pregnancy.

Examination of the antioxidant effects of pre-HSG melatonin use on ovarian surface epithelium in rats: An experimental study.

BACKGROUND: There is no study of whether the dysplastic changes in the ovarian surface epithelium of X-ray-exposed rats during hysterosalpingography (HSG) decrease or not with the use of Lipiodol and melatonin given both intraperitoneally (i.p.) and into the suspensorium ovarii. OBJECTIVES: We investigated the restorative effects of melatonin and Lipiodol administration during the HSG procedure on the dysplastic changes in the ovarian surface epithelium of X-ray-exposed rats. MATERIAL AND METHODS: A total of 50 Wistar rats with regular estrous cycles were randomly divided into 5 groups. Group 1 was the control group. In other groups, X-ray was applied (group 2), 0.1 mL Lipiodol was applied to each uterine horn (group 3), 20 mg/kg intraperitoneal melatonin application was followed by 0.1 mL Lipiodol administration to each uterine horn after 15 min (group 4), and 20 mg/kg melatonin was administered to the ligamentum suspensorium ovarii, followed by 0.1 mL Lipiodol application to each uterine horn after 15 min (group 5). The rats in groups 2-5 were exposed to whole body radiation 3 times. After 3 h, the abdomens of all rats were reopened and left oophorectomy was performed. RESULTS: The presence of nucleoli and mitosis values were found similar among the groups. All other parameters were significantly higher in group 2 compared to other groups, except for the presence of nucleoli and mitosis values (p < 0.05). The presence of hyperchromasia and the total score were found to be the highest in group 2, followed by group 3, when compared to other groups (p < 0.05). It was detected that the detrimental effects of X-ray exposure diminished with Lipiodol use, and were further reduced by the use of melatonin in combination. CONCLUSIONS: We suggest that the use of melatonin and Lipiodol during HSG may prevent the carcinogenic changes exerted by radiation on the ovarian surface epithelium.

The FOAM study: is Hysterosalpingo foam sonography (HyFoSy) a cost-effective alternative for hysterosalpingography (HSG) in assessing tubal patency in subfertile women? Study protocol for a randomized controlled trial.

BACKGROUND: Tubal pathology is a causative factor in 20% of subfertile couples. Traditionally, tubal testing during fertility work-up is performed by hysterosalpingography (HSG). Hysterosalpingo-foam sonography (HyFoSy) is a new technique that is thought to have comparable accuracy as HSG, while it is less expensive and more patient friendly. HyFoSy would be an acceptable alternative for HSG, provided it has similar effectiveness in terms of patient outcomes. METHODS/DESIGN: We aim to compare the effectiveness and costs of management guided by HyFoSy or by HSG. Consenting women will undergo tubal testing by both HyFoSy and HSG in a randomized order during fertility work-up. The study group will consist of 1163 subfertile women between 18 and 41 years old who are scheduled for tubal patency testing during their fertility work-up. Women with anovulatory cycles not responding to ovulation induction, endometriosis, severe male subfertility or a known contrast (iodine) allergy will be excluded. We anticipate that 7 % (N = 82) of the participants will have discordant test results for HyFoSy and HSG. These participants will be randomly allocated to either a management strategy based on HyFoSy or a management strategy based on HSG, resulting in either a diagnostic laparoscopy with chromopertubation or a strategy that assumes tubal patency (intrauterine insemination or expectant management). The primary outcome is ongoing pregnancy leading to live birth within 12 months after randomization. Secondary outcomes are patient pain scores, time to pregnancy, clinical pregnancy, miscarriage rate, multiple pregnancy rate, preterm birth rate and number of additional treatments. Costs will be estimated by counting resource use and calculating unit prices. DISCUSSION: This trial will compare the effectiveness and costs of HyFoSy versus HSG in assessing tubal patency in subfertile women. TRIAL REGISTRATION: Dutch Trial Register (NTR 4746, http://www.trialregister.nl ). Date of registration: 19 August 2014.

The effect of oil and water-soluble contrast medium in hysterosalpingography on thyroid function.

Hysterosalpingography (HSG) using iodinated contrast medium is X-ray diagnostic test that examines the inside of the uterus and fallopian tubes in infertile women. In this study, we compared thyroid function (thyroid stimulating hormone: TSH and free-T4: FT4 levels) after HSG with an oil-soluble contrast medium (OSCM) and a water-soluble contrast medium (WSCM). One hundred and sixty-four and 94 patients with normal thyroid function received HSG with OSCM and WSCM, respectively. Approximately 25% of the women in the OSCM group developed subclinical hypothyroidism (SCH), whereas only less than 10% of the patients in the WSCM group developed SCH. Our data clearly indicate that WSCM is safe for thyroid function in women who plan to get pregnant.

Retained Products of Conception Associated with Intravasation of Hysterosalpingogram Contrast and Hysteroscopic Distention Media: A Case Report.

BACKGROUND: Hysteroscopic resection of retained products of conception has not been previously described to increase the risk for volume overload at the time of hysteroscopy. CASE: A 35-year-old woman with a history of recurrent pregnancy loss was evaluated by a hysterosalpingogram that identified retained products of conception with adjacent contrast intravasation. She underwent a hysteroscopic resection of the uterine septum and products of conception. During the 15 minute operating time she developed a fluid deficit of 2,300 cc of 3% sorbitol with resulting hyponatremia despite normal pressure and flow settings on the fluid management equipment. CONCLUSION: When a hysterosalpingogram demonstrates likely retained products of conception with an accompanying intravasation of contrast media, the provider should consider this finding a potential risk factor for excess intravasation of hysteroscopic distention media and take additional precautions to avoid volume overload.