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).

Intrauterine insemination: simultaneous with or 36 h after HCG? A randomized clinical trial.

RESEARCH QUESTION: Does intrauterine insemination (IUI) carried out simultaneously with HCG triggering ('simultaneous IUI') increase the ongoing pregnancy rate compared with IUI 32-36 h after HCG triggering ('regular IUI')? STUDY DESIGN: An open-label randomized clinical trial was conducted in seven Dutch fertility clinics. One hundred and sixty-six couples were randomized to receive simultaneous IUI and 208 couples to receive regular IUI. Treatment was allocated using a computer-based randomization algorithm using sealed opaque envelopes. Data were analysed according to the intention-to-treat principle. Couples with unexplained or mild-to-moderate male factor subfertility were eligible. Exclusion criteria were female age 42 years or older, female body mass index 35 kg/m2 or over, double-sided tubal pathology or severe male factor subfertility. Mild ovarian stimulation was carried out by subcutaneous FSH self-administration. 'Simultaneous IUI' was carried out at the point of HCG triggering for ovulation. 'Regular IUI' was carried out 32-36 h after HCG triggering. RESULTS: The cumulative ongoing pregnancy rate after a maximum of four cycles was 26.2% for simultaneous IUI (43 ongoing pregnancies) and 33.7% for regular IUI (70 ongoing pregnancies) (RR 0.78 95% CI 0.57 to 1.07). Ongoing pregnancy rates per cycle in the simultaneous IUI group were 6.8%, 10.5%, 9.5% and 7.4% for the first, second, third and fourth IUI cycle. In the regular IUI group, ongoing pregnancy rates were 8.3%, 16.4%, 13.5% and 9.0% for the first, second, third and fourth IUI cycle. CONCLUSIONS: This multicentre randomized controlled trial did not demonstrate that IUI carried out at the point of HCG triggering increases pregnancy rates compared with IUI carried out around the time of ovulation.

[Leg pain during menstrual period]. / Een pijnlijk been tijdens de menstruatie.

A 31-year-old woman presented at the fertility department with primary subfertility since one year. Last year she had had progressive dysmenorrhea and pain in her right leg and groin during her menstrual period. MRI showed extensive pelvic endometriosis with a lesion in the right round ligament in the inguinal canal.

Gonadotrophins versus clomifene citrate with or without intrauterine insemination in women with normogonadotropic anovulation and clomifene failure (M-OVIN): a randomised, two-by-two factorial trial.

BACKGROUND: In many countries, clomifene citrate is the treatment of first choice in women with normogonadotropic anovulation (ie, absent or irregular ovulation). If these women ovulate but do not conceive after several cycles with clomifene citrate, medication is usually switched to gonadotrophins, with or without intrauterine insemination. We aimed to assess whether switching to gonadotrophins is more effective than continuing clomifene citrate, and whether intrauterine insemination is more effective than intercourse. METHODS: In this two-by-two factorial multicentre randomised clinical trial, we recruited women aged 18 years and older with normogonadotropic anovulation not pregnant after six ovulatory cycles of clomifene citrate (maximum of 150 mg daily for 5 days) from 48 Dutch hospitals. Women were randomly assigned using a central password-protected internet-based randomisation programme to receive six cycles with gonadotrophins plus intrauterine insemination, six cycles with gonadotrophins plus intercourse, six cycles with clomifene citrate plus intrauterine insemination, or six cycles with clomifene citrate plus intercourse. Clomifene citrate dosages varied from 50 to 150 mg daily orally and gonadotrophin starting dose was 50 or 75 IU daily subcutaneously. The primary outcome was conception leading to livebirth within 8 months after randomisation defined as any baby born alive after a gestational age beyond 24 weeks. Primary analysis was by intention to treat. We made two comparisons, one in which gonadotrophins were compared with clomifene citrate and one in which intrauterine insemination was compared with intercourse. This completed study is registered with the Netherlands Trial Register, number NTR1449. FINDINGS: Between Dec 8, 2008, and Dec 16, 2015, we randomly assigned 666 women to gonadotrophins and intrauterine insemination (n=166), gonadotrophins and intercourse (n=165), clomifene citrate and intrauterine insemination (n=163), or clomifene citrate and intercourse (n=172). Women allocated to gonadotrophins had more livebirths than those allocated to clomifene citrate (167 [52%] of 327 women vs 138 [41%] of 334 women, relative risk [RR] 1·24 [95% CI 1·05-1·46]; p=0·0124). Addition of intrauterine insemination did not increase livebirths compared with intercourse (161 [49%] vs 144 [43%], RR 1·14 [95% CI 0·97-1·35]; p=0·1152). Multiple pregnancy rates for the two comparisons were low and not different. There were three adverse events: one child with congenital abnormalities and one stillbirth in two women treated with clomifene citrate, and one immature delivery due to cervical insufficiency in a woman treated with gonadotrophins. INTERPRETATION: In women with normogonadotropic anovulation and clomifene citrate failure, a switch of treatment to gonadotrophins increased the chance of livebirth over treatment with clomifene citrate; there was no evidence that addition of intrauterine insemination does so. FUNDING: The Netherlands Organization for Health Research and Development.

Oil-Based or Water-Based Contrast for Hysterosalpingography in Infertile Women.

BACKGROUND: Pregnancy rates among infertile women have been reported to increase after hysterosalpingography, but it is unclear whether the type of contrast medium used (oil-based or water-soluble contrast) influences this potential therapeutic effect. METHODS: We performed a multicenter, randomized trial in 27 hospitals in the Netherlands in which infertile women who were undergoing hysterosalpingography were randomly assigned to undergo this procedure with the use of oil-based or water-based contrast. Subsequently, couples received expectant management or the women underwent intrauterine insemination. The primary outcome was ongoing pregnancy within 6 months after randomization. Outcomes were analyzed according to the intention-to-treat principle. RESULTS: A total of 1119 women were randomly assigned to hysterosalpingography with oil contrast (557 women) or water contrast (562 women). A total of 220 of 554 women in the oil group (39.7%) and 161 of 554 women in the water group (29.1%) had an ongoing pregnancy (rate ratio, 1.37; 95% confidence interval [CI], 1.16 to 1.61; P<0.001), and 214 of 552 women in the oil group (38.8%) and 155 of 552 women in the water group (28.1%) had live births (rate ratio, 1.38; 95% CI, 1.17 to 1.64; P<0.001). Rates of adverse events were low and similar in the two groups. CONCLUSIONS: Rates of ongoing pregnancy and live births were higher among women who underwent hysterosalpingography with oil contrast than among women who underwent this procedure with water contrast. (Netherlands Trial Register number, NTR3270 .).

Prognostic value of the postcoital test for spontaneous pregnancy.

OBJECTIVE: To evaluate the capacity of the postcoital test (PCT) to predict spontaneous pregnancy in a large cohort study of subfertile couples. DESIGN: Prospective study. SETTING: Department of reproductive medicine of 38 hospitals in the Netherlands. PATIENT(S): Between January 2002 and February 2004, we prospectively included consecutive subfertile couples who had not been evaluated previously for subfertility. INTERVENTION(S): We estimated the contribution of the PCT result to the existing prediction model for spontaneous pregnancy by calculating the adjusted hazard ratio (HR) of an abnormal PCT result. We constructed a second prediction model (PCT model) based on the reference model including the PCT. MAIN OUTCOME MEASURE(S): Primary endpoint in this study was ongoing pregnancy. We evaluated the performance of the PCT model in comparison with the reference model by calculating goodness of fit, discrimination, calibration, and the "net reclassification improvement". RESULT(S): We included 3,021 couples of whom 537 (18%) had a spontaneous pregnancy and 55 (1.8%) a nonsuccessful pregnancy; 1,316 (44%) started treatment within 12 months, 824 (27%) neither started treatment nor became pregnant, and 289 (10%) became lost to follow-up within 12 months. The adjusted HR for an abnormal PCT was 0.76 (95% confidence interval [CI]: 0.62 to 0.94). The adjusted HR for an abnormal PCT was 0.63 (95% CI: 0.47 to 0.84) in case of no spermatozoa, 0.81 (95% CI: 0.57 to 1.2) in case of nonmotile spermatozoa, and 1.2 (95% CI: 0.8 to 1.8) in case of motile, nonprogressive spermatozoa. Adding the PCT result to the reference model did not improve goodness of fit. Discrimination was equally poor for the PCT model and the reference model. The calibration plots of both models showed comparably good calibration. The net reclassification improvement of the predictions of the PCT model compared with the reference model was -1.1%. CONCLUSION(S): This study demonstrated that the PCT has prognostic value but does not add substantially to a prognostic model for spontaneous pregnancy.

External validation of a prediction model for an ongoing pregnancy after intrauterine insemination.

OBJECTIVE: To assess the accuracy of our recently developed prediction model in a prospective validation study to predict the outcome of intrauterine insemination (IUI). DESIGN: Descriptive prospective validation study. SETTING: Seven fertility centers in the Netherlands. PATIENT(S): Couples treated with IUI of whom the female partner had a regular cycle. INTERVENTION(S): Intrauterine insemination with or without controlled ovarian hyperstimulation. MAIN OUTCOME MEASURE(S): Ongoing pregnancy after intrauterine insemination. Performance of the prediction model was assessed with calibration and discriminative capacity. Calibration was assessed by comparing the predicted ongoing pregnancy rate with the observed ongoing pregnancy rate. Discriminative capacity was assessed with receiver operation characteristic (ROC) analysis. For daily practice, a score worksheet of the validated model was developed to estimate the chance of an ongoing pregnancy after IUI per treatment cycle. RESULT(S): We included 1,079 subfertile couples who underwent 4,244 cycles of IUI. There were 278 ongoing pregnancies, that is, an ongoing pregnancy rate of 6.6% per cycle. External validation of the model showed good calibration. The predicted probability never differed by more than 1.5% of the mean observed probability. The area under the ROC curve was 0.56 (95% confidence interval, 0.53-0.59) at external validation. CONCLUSION(S): The prediction model was able to make a good distinction between couples with a good pregnancy chance and those with a poor pregnancy chance after IUI. This model can help in deciding which couples will benefit from IUI and which couples will not.

Bipolar radio frequency endometrial ablation compared with balloon endometrial ablation in dysfunctional uterine bleeding: impact on patients' health-related quality of life.

OBJECTIVE: To compare health-related quality of life (HRQoL) after bipolar radio frequency ablation and thermal balloon ablation in women with dysfunctional uterine bleeding. DESIGN: Randomized clinical trial. SETTING: Teaching hospital. PATIENT(S): Women suffering from dysfunctional uterine bleeding. INTERVENTION(S): Bipolar radio frequency ablation and thermal balloon ablation. MAIN OUTCOME MEASURE(S): Patients were asked to complete HRQoL questionnaires at baseline, and at 2 days, 2 weeks, 3 months, 6 months, and 12 months after surgery. The questionnaires contained the medical outcomes study Short-Form 36 (SF-36), the Self-rating Depression Scale, the Rotterdam Symptom Checklist, State-Trait Anxiety Inventory, and a structured clinical history questionnaire. RESULT(S): Data on HRQoL were available on at least two different time points in 115 of 126 randomized patients. HRQoL improved significantly over time in both groups, except for the domain of general health in the SF-36. None of the dimensions showed a significant difference between both groups, neither was there a significant interaction between time and treatment effect. CONCLUSION(S): Both methods significantly improved HRQoL in women with dysfunctional uterine bleeding. However, despite better amenorrhea and satisfaction rates after bipolar radio frequency ablation, there was no difference in HRQoL between the two groups.

Randomised controlled trial of bipolar radio-frequency endometrial ablation and balloon endometrial ablation.

OBJECTIVE: To compare the effectiveness of two second-generation ablation techniques, bipolar radio-frequency impedance-controlled endometrial ablation (NovaSure) and balloon ablation (ThermaChoice), in the treatment of menorrhagia. DESIGN: Double-blind, randomised, controlled trial. SETTING: A large teaching hospital with 500 beds in The Netherlands. POPULATION: Women suffering from menorrhagia referred by their general practitioner. METHODS: Women suffering from menorrhagia, without intracavitary abnormalities, were randomly allocated to bipolar radio-frequency ablation (bipolar group) and balloon ablation (balloon group) in a 2:1 ratio. At follow up, both women and observers were unaware of the type of treatment that had been performed. MAIN OUTCOME MEASURES: The main outcome measure was amenorrhea at 3, 6 and 12 months after randomisation. RESULTS: One hundred and twenty-six women were included in the study, of which 83 were allocated to the bipolar group, and 43 to the balloon group. No complications occurred in either of the treatment groups. At the one-year follow up stage, amenorrhea rates were 43% (34/83) in the bipolar group and 8% (3/43) in the balloon group (treatment effect in time P < 0.001). At this stage, 90% of the patients in the bipolar group were satisfied with the result of the treatment against 79% in the balloon group (treatment effect in time P= 0.003). CONCLUSION: The bipolar radio-frequency impedance-controlled endometrial ablation system is more effective than balloon ablation in the treatment of menorrhagia.

Treatment of dysfunctional uterine bleeding: patient preferences for endometrial ablation, a levonorgestrel-releasing intrauterine device, or hysterectomy.

OBJECTIVE: To investigate patient preferences for endometrial ablation and a levonorgestrel-releasing intrauterine device (IUD) as alternatives to hysterectomy in the treatment of dysfunctional uterine bleeding. DESIGN: Comparative study based on structured interviews. SETTING: A large teaching hospital with 500 beds in the Netherlands. PATIENT(S): Ninety-six patients who were scheduled for endometrial ablation, 25 patients who were scheduled for hysterectomy, and 23 patients who were scheduled for a levonorgestrel-releasing IUD were interviewed. All of the women had dysfunctional uterine bleeding. INTERVENTION(S): Patients were asked to state their most significant complaints and their reasons for choosing a particular treatment. Subsequently, the preference for endometrial ablation and a levonorgestrel-releasing IUD as alternatives to hysterectomy was assessed during a structured interview. Women were informed about the advantages and disadvantages of all three treatment options. Patients rated their preferences according to different hypothetical success rates. The success rates after endometrial ablation and levonorgestrel-releasing IUD were varied until patients found an acceptable treatment outcome. MAIN OUTCOME MEASURE(S): Patient preference of endometrial ablation and the levonorgestrel-releasing IUD over hysterectomy. RESULT(S): The main reason for the treatment of choice differed between the three groups. Most of the patients in the hysterectomy group wanted a definite solution to their problems, whereas patients in the levonorgestrel-releasing IUD group and in the ablation group put greater emphasis on a minimally invasive intervention with or without a short hospital stay. In women undergoing ablation, 70% of the patients preferred this treatment and the levonorgestrel-releasing IUD to hysterectomy in cases in which the success rate of noninvasive treatment was presumed to be 50%. In women having a levonorgestrel-releasing IUD inserted, 95% of the patients preferred this approach over hysterectomy in cases in which the success rate of this device was presumed to be 50%, whereas 35% of patients preferred ablation over hysterectomy in cases in which the success rate of ablation was presumed to be 50%. In women undergoing hysterectomy, 30% would have opted for ablation and 45% would have opted for a levonorgestrel-releasing IUD in cases in which success rates were 50%. Of patients who opted for hysterectomy, however, 60% stated that they would have preferred a noninvasive treatment if the success rate of this type of treatment were >80%. CONCLUSION(S): A majority of the patients who had dysfunctional uterine bleeding and who were scheduled for an endometrial ablation or a levonorgestrel-releasing IUD were inclined to take a risk of 50% likelihood of treatment failure to avoid a hysterectomy. As a consequence, research of treatment for dysfunctional uterine bleeding should focus on this 50% success level.