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% con fi dence 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 signi fi cantly 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 fl ushing 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). (Fertil Steril (R) 2020;114:155-62. (C) 2020 by American Society for Reproductive Medicine.

Comparing the cumulative live birth rate of cleavage-stage versus blastocyst-stage embryo transfers between IVF cycles:a study protocol for a multicentre randomised controlled superiority trial (the ToF trial)

Introduction In vitro fertilisation (IVF) has evolved as an intervention of choice to help couples with infertility to conceive. In the last decade, a strategy change in the day of embryo transfer has been developed. Many IVF centres choose nowadays to transfer at later stages of embryo development, for example, transferring embryos at blastocyst stage instead of cleavage stage. However, it still is not known which embryo transfer policy in IVF is more efficient in terms of cumulative live birth rate (cLBR), following a fresh and the subsequent frozen-thawed transfers after one oocyte retrieval. Furthermore, studies reporting on obstetric and neonatal outcomes from both transfer policies are limited. Methods and analysis We have set up a multicentre randomised superiority trial in the Netherlands, named the Three or Fivetrial. We plan to include 1200 women with an indication for IVF with at least four embryos available on day 2 after the oocyte retrieval. Women are randomly allocated to either (1) control group: embryo transfer on day 3 and cryopreservation of supernumerary good-quality embryos on day 3 or 4, or (2) intervention group: embryo transfer on day 5 and cryopreservation of supernumerary good-quality embryos on day 5 or 6. The primary outcome is the cLBR per oocyte retrieval. Secondary outcomes include LBR following fresh transfer, multiple pregnancy rate and time until pregnancy leading a live birth. We will also assess the obstetric and neonatal outcomes, costs and patients' treatment burden. Ethics and dissemination The study protocol has been approved by the Central Committee on Research involving Human Subjects in the Netherlands in June 2018 (CCMO NL 64060.000.18). The results of this trial will be submitted for publication in international peer-reviewed and in open access journals. Trial registration number Netherlands Trial Register (NL 6857)

A Natural Female Disadvantage? Maternal Mortality and the Role of Nutrition Related Causes of Death in the Netherlands, 1875-1899

This article addresses the question whether maternal mortality should be excluded from the study of excess female mortality. This phenomenon points to lower survival chances for women in certain age groups as opposed to men in the same age group. The existence of excess female mortality has been established for a number of European countries, primarily for the nineteenth century period, and it has also been observed for the Netherlands between approximately 1850 and 1930. There are strong indications that in this period Dutch women were at a disadvantage compared to men, most notably between the ages of 10 to 19, but also in the adult years after age 20. The survival disadvantage for women between age 20 and 50 may be related to the dangers of pregnancy and childbirth. These maternal mortality risks may seem a natural female disadvantage. However, deficiencies in nutrition may seriously enhance the dangers of pregnancy and childbirth. Hence, if women are less privileged in access to food, causing increased levels of maternal mortality, the risk to die during pregnancy and during or after childbirth should be considered as part of the phenomenon of excess female mortality. The results of our analysis indicate that maternal mortality in this period in the Netherlands is partly the effect of the female nutritional disease environment. In particular, the incidence of nutrition-related deaths among women in fertile ages, such as tuberculosis, increase maternal mortality. We therefore assume that gender disadvantages in the access to foodstuffs of sufficient nutritional quality increased the level of maternal mortality. Consequently, in research on excess female mortality maternal mortality cannot be simply discounted as a natural disadvantage which should be left out of measures of excess female mortality

A Natural Female Disadvantage? Maternal Mortality and the Role of Nutrition Related Causes of Death in the Netherlands, 1875-1899

This article addresses the question whether maternal mortality should be excluded from the study of excess female mortality. This phenomenon points to lower survival chances for women in certain age groups as opposed to men in the same age group. The existence of excess female mortality has been established for a number of European countries, primarily for the nineteenth century period, and it has also been observed for the Netherlands between approximately 1850 and 1930. There are strong indications that in this period Dutch women were at a disadvantage compared to men, most notably between the ages of 10 to 19, but also in the adult years after age 20. The survival disadvantage for women between age 20 and 50 may be related to the dangers of pregnancy and childbirth. These maternal mortality risks may seem a natural female disadvantage. However, deficiencies in nutrition may seriously enhance the dangers of pregnancy and childbirth. Hence, if women are less privileged in access to food, causing increased levels of maternal mortality, the risk to die during pregnancy and during or after childbirth should be considered as part of the phenomenon of excess female mortality. The results of our analysis indicate that maternal mortality in this period in the Netherlands is partly the effect of the female nutritional disease environment. In particular, the incidence of nutrition-related deaths among women in fertile ages, such as tuberculosis, increase maternal mortality. We therefore assume that gender disadvantages in the access to foodstuffs of sufficient nutritional quality increased the level of maternal mortality. Consequently, in research on excess female mortality maternal mortality cannot be simply discounted as a natural disadvantage which should be left out of measures of excess female mortality

A Natural Female Disadvantage? Maternal Mortality and the Role of Nutrition Related Causes of Death in the Netherlands, 1875-1899

This article addresses the question whether maternal mortality should be excluded from the study of excess female mortality. This phenomenon points to lower survival chances for women in certain age groups as opposed to men in the same age group. The existence of excess female mortality has been established for a number of European countries, primarily for the nineteenth century period, and it has also been observed for the Netherlands between approximately 1850 and 1930. There are strong indications that in this period Dutch women were at a disadvantage compared to men, most notably between the ages of 10 to 19, but also in the adult years after age 20. The survival disadvantage for women between age 20 and 50 may be related to the dangers of pregnancy and childbirth. These maternal mortality risks may seem a natural female disadvantage. However, deficiencies in nutrition may seriously enhance the dangers of pregnancy and childbirth. Hence, if women are less privileged in access to food, causing increased levels of maternal mortality, the risk to die during pregnancy and during or after childbirth should be considered as part of the phenomenon of excess female mortality. The results of our analysis indicate that maternal mortality in this period in the Netherlands is partly the effect of the female nutritional disease environment. In particular, the incidence of nutrition-related deaths among women in fertile ages, such as tuberculosis, increase maternal mortality. We therefore assume that gender disadvantages in the access to foodstuffs of sufficient nutritional quality increased the level of maternal mortality. Consequently, in research on excess female mortality maternal mortality cannot be simply discounted as a natural disadvantage which should be left out of measures of excess female mortality

Reasons for dropping out from a waiting list for in vitro fertilization

Objective: To determine the incidence of couples dropping out of the in vitro fertilization (IVF) waiting list and to describe the couples' reasons. Design: Prospective cohort study. Setting: Fertility center in an academic hospital. Patient(s): 674 women placed consecutively on the IVF waiting list between June 2000 and July 2003. Intervention(s): None. Main Outcome Measure(s): Number of dropouts and reasons for dropping out. Result(s): Follow-up information was collected in 2005 and 2008. Of the 674 couples on the waiting list, 87% started IVF, and 13% dropped out before starting their first IVF cycle. Follow-up data were obtained for 85 of 86 patients (98.8%): 37% dropped out because of spontaneous pregnancy, 36% for personal reasons (passive censoring), and 27% for medical reasons (active censoring). Most of the pregnancies occurred within 3 months after the patient had been placed on the waiting list (30 of 32, 94%). Of the 54 censored couples, four became pregnant. Conclusion(s): On a 6-month waiting list for IVF, 13% of the couples dropped out before starting treatment. The single most important reason for dropout was (spontaneous) pregnancy. Most of these pregnancies occurred within 3 months, which suggests that psychological factors such as stress relief after being placed on the waiting list might be operative. (Fertil Steril (R) 2010; 94:1713-6. (C) 2010 by American Society for Reproductive Medicine.

First Successful Conception Induced by a Male Cystinosis Patient

Cystinosis is a rare autosomal recessive lysosomal storage disease characterized by multi-organ cystine accumulation, leading to renal failure and extra-renal organ dysfunction. Azoospermia of unknown origin is the main cause of infertility in all male cystinosis patients. Although spermatogenesis has shown to be intact at the testicular level in some patients, no male cystinosis patient has been reported yet to have successfully induced conception.We present the first successful conception ever reported, induced by a 27-year-old male renal transplant infantile nephropathic cystinosis patient through percutaneous epididymal sperm aspiration (PESA) followed by intracytoplasmatic sperm injection (ICSI). After 36 weeks and 6 days of an uncomplicated pregnancy, a dichorial diamniotic (DCDA) twin was born with an appropriate weight for gestational age and in an apparently healthy status. Moreover, we demonstrate that the sperm of epididymal origin in selected male cystinosis patients can be viable for inducing successful conception.Our observation opens a new perspective in life for many male cystinosis patients whom nowadays have become adults, by showing that despite azoospermia fathering a child can be realized. In addition, our findings raise questions about the possibility of sperm cryopreservation at a young age in these patients.status: publishe

Comparing the cumulative live birth rate of cleavage-stage versus blastocyst-stage embryo transfers between IVF cycles: a study protocol for a multicentre randomised controlled superiority trial (the ToF trial)

Contains fulltext : 230639.pdf (publisher's version ) (Open Access

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)

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline