The AID study: protocol for a randomised controlled trial of intrauterine insemination in the natural cycle compared with intracervical insemination in the natural cycle.

INTRODUCTION: At present, studies comparing intrauterine insemination in the natural cycle versus intracervical insemination in the natural cycle in women undergoing artificial insemination with donor sperm are scarce. METHODS AND ANALYSIS: We perform a randomised controlled non-inferiority trial among five secondary and tertiary fertility clinics in the Netherlands and one tertiary fertility clinic in Belgium. Women eligible for artificial insemination with donor sperm are included. We perform six cycles of artificial insemination with donor sperm within a time horizon of 8 months comparing intrauterine insemination in the natural cycle with intracervical insemination in the natural cycle. The primary outcome is ongoing pregnancy leading to live birth conceived within eight months after randomisation. Secondary outcomes are clinical pregnancy rate, miscarriage rate, multiple pregnancy rate, pregnancy complications (preterm birth, birth weight <2500 g, pregnancy induced hypertension, (pre-) eclampsia, Hemolysis Elevated Liver enzymes Low Platelets (HELLP)), time to ongoing pregnancy, direct and indirect costs. To demonstrate the non-inferiority of intracervical insemination with a margin of 12%, we need 208 women per arm. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethical Committee of the Academic Medical Centre and from the Dutch Central Committee on research involving human subjects (47330-018-13). The boards of the participating hospitals approved the study. Results will be disseminated through peer-reviewed publications and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NTR4462.

Is routine karyotyping required in prenatal samples with a molecular or metabolic referral?

As a routine, karyotyping of invasive prenatal samples is performed as an adjunct to referrals for DNA mutation detection and metabolic testing. We performed a retrospective study on 500 samples to assess the diagnostic value of this procedure. These samples included 454 (90.8%) chorionic villus (CV) and 46 (9.2%) amniocenteses specimens. For CV samples karyotyping was based on analyses of both short-term culture (STC) and long-term culture (LTC) cells. Overall, 19 (3.8%) abnormal karyotypes were denoted: four with a common aneuploidy (trisomy 21, 18 and 13), two with a sex chromosomal aneuploidy (Klinefelter syndrome), one with a sex chromosome mosaicism and twelve with various autosome mosaicisms. In four cases a second invasive test was performed because of an abnormal finding in the STC. Taken together, we conclude that STC and LTC karyotyping has resulted in a diagnostic yield of 19 (3.8%) abnormal cases, including 12 cases (2.4%) with an uncertain significance. From a diagnostic point of view, it is desirable to limit uncertain test results as secondary test findings. Therefore, we recommend a more targeted assay, such as e.g. QF-PCR, as a replacement of the STC and to provide parents the autonomy to choose between karyotyping and QF-PCR.

Why do parents prefer to know the fetal sex as part of invasive prenatal testing?

Objectives. The aim of this study was to determine whether prospective parents, primarily referred for prenatal diagnosis to exclude Down syndrome, prefer to know the fetal sex as part of invasive testing. Methods. In this prospective study 400 pregnant women undergoing amniocentesis were invited to answer a questionnaire, including information about demographic factors, current pregnancy, and previous children. In two open-ended questions they were asked why they wanted to know the fetal sex after amniocentesis or ultrasound investigation. Scores were given for reasons that could have played a role in the wish whether or not to know the sex of their unborn child. Results. A total of 210 (52.5%) questionnaires were completed. Overall, 69.0% was interested to know the fetal sex as part of the diagnostic test result. The most important reasons were curiosity (77.8%), "just want to know" (68.0%), and "because it is possible" (66.8%). The overall knowledge of sex chromosomal disorders appeared low and did not seem to affect the parent's wish to know the fetal sex. Almost all women (96.6%) planned to have a 20-week ultrasound scan and 96.2% thought the scan to be reliable in detecting the fetal sex. A minority (28%) was willing to learn the fetal sex by ultrasound examination, whereas 65% preferred to learn the fetal sex only after the amniocentesis. Conclusion. Personal values affect the parental desire to know or not to know the fetal sex. This does not appear to be affected by invasive prenatal testing and/or genetic knowledge of sex chromosomal disorders.

Parent's attitudes towards full-scale prenatal testing for genetic disorders.

OBJECTIVES: Innovations in the field of prenatal diagnostic testing have led to the development of molecular tests that allow the rapid detection of specific genetic defects, such as Down syndrome. In addition, full-scale tests have been developed allowing the detection of many genetic disorders in a single test. Here we examined the attitudes of pregnant women in low risk pregnancies towards full-scale genetic testing and explored relationships between demographic characteristics and the level of interest. METHODS: A prospective study was performed on 115 consecutive pregnant women. They completed the same structured questionnaire at two different time points, before counselling (T1) and after 4 weeks (T2), to assess a possible change of attitude. RESULTS: At T1, 33% of the respondents were in favour of full-scale testing of their unborn child, whereas at T2, this percentage had dropped to 18%. Except for educational level, no significant relationships were noted between the demographic variables and the wish to opt for full-scale testing. A low educational level was significantly related to the interest in full-scale testing. CONCLUSIONS: Low risk pregnant women expressed little interest in full-scale genetic testing. Educational level appeared to affect their views.

Limited uterine artery embolization for leiomyomas with tris-acryl gelatin microspheres: 1-year follow-up.

PURPOSE: To assess the safety and efficacy of uterine artery embolization (UAE) using large calibrated tris-acryl gelatin microspheres. MATERIALS AND METHODS: One hundred fifty-eight women with symptomatic uterine fibroids underwent UAE. Embosphere was used in 105 women and Embogold microspheres in 53 women. Major and minor complications were assessed. At 12 months, relief of symptoms and patient satisfaction were assessed and volume reductions of the uterus and dominant fibroid were calculated. RESULTS: Median age of the subjects was 43 years (mean, 42.3 y; range, 23-53 y). Preprocedural symptoms were heavy menstrual bleeding in 89%, pain in 64%, and bulk related symptoms in 57%. At 12 months follow-up, the proportion of women with heavy menstrual bleeding, pain, and bulk-related symptoms had decreased to 9%, 8%, and 8%, respectively. Patient satisfaction was grouped as follows: very satisfied 57%, satisfied 36%, and not satisfied 7%. Mean uterine and dominant fibroid volumes before UAE were 532 cm(3) and 201 cm(3), respectively. At 12-month follow-up MR imaging, mean uterine volume decreased to 260 cm(3) and mean dominant fibroid volume to 78 cm(3). These differences were statistically significant (P < .0001). There were no procedure-related deaths. No emergency hysterectomy was needed. Permanent amenorrhea occurred in 11% of women. Transient amenorrhea occurred in 13% of women, and fibroid expulsion occurred in 10% of women. Twelve women (7.6%) had additional therapy: nine underwent additional embolization and three had hysterectomy. CONCLUSION: Targeted UAE using large calibrated microspheres is safe and effective in the relief of symptoms in the majority of patients. At 12 months, a marked fibroid and uterine volume reduction is obtained.