Embryo Transfer with Controlled Injection Speed to Increase Pregnancy Rates: A Randomized Controlled Trial.

BACKGROUND/AIMS: Catheter injection speed affects depth and placement of the embryo into the uterine cavity and is shown to be highly variable in, and between, subjects in a manually performed embryo transfer. In an effort to standardize the injection speed during embryo transfer, we developed an automated transfer pump: the pump-regulated embryo transfer (PRET) device. In this randomized controlled trial, we aimed to investigate if standardization of the injection speed and pressure with this PRET results in a better controlled positioning of the transferred embryo(s). METHODS: Five hundred ninety-nine in-vitro fertilization/intracytoplasmic sperm injection/frozen-thawed embryo transfer cycles were randomly assigned to the PRET or manual transfer. Positioning of the embryo(s) into the uterine cavity was measured with ultrasound. RESULTS: The PRET device generates a significantly smaller variance of the positioning of the embryo(s) into the uterine cavity. This resulted in an ongoing pregnancy rate of 21% in the PRET versus 17% in the manual (p = 0.22) transfer group; frozen-thawed embryo transfers resulted in 17.5 versus 10.9% (p = 0.097), respectively. CONCLUSION: The PRET results in better controlled positioning of the embryo(s), and it also gives the opportunity to standardize embryo transfer. Whether the PRET may positively influence pregnancy rates, needs to be investigated in a multicenter trial.

Reproductive outcome after early-onset pre-eclampsia.

BACKGROUND: Early-onset pre-eclampsia is an important cause of maternal and neonatal morbidity and mortality and is believed to have a significant impact on future maternal physical and psychological health. However, structured follow-up data of women with a history of early-onset pre-eclampsia are lacking. This study aims to present comprehensive data of a large cohort of women with a history of early-onset pre-eclampsia with respect to future reproductive health, family planning and subsequent pregnancy rates. METHODS: A tertiary referral cohort of 304 women entered the follow-up study at 6-12 months after their first delivery. Detailed data on maternal and neonatal outcomes, family planning and subsequent pregnancies were recorded. In addition, data on perspectives, major concerns and decision-making of women who had not achieved a second pregnancy were collected by questionnaire and structured interviews. Data were compared with a population of 268 low-risk primiparous women with an uncomplicated delivery. RESULTS: At a mean of 5.5 years after first delivery, 65.8% of women with a history of early-onset pre-eclampsia had achieved a second pregnancy compared with 77.6% of healthy controls. At follow-up, 19.1% of women with a history of early-onset pre-eclampsia had an active wish to become pregnant, whereas 15.1% of women did not wish to achieve a future pregnancy. In the latter group, decision-making was most commonly influenced by fear of recurrent disease (33%) and fear of delivering another premature child (33%) among others reasons, e.g. post-partum counseling and concerns of the partner. CONCLUSIONS: The majority of women with a history of early-onset pre-eclampsia achieve or wish to achieve a second pregnancy within a few years of their delivery. Nonetheless, first pregnancy early-onset pre-eclampsia appears to have a significant impact on future reproductive health and decision-making, emphasizing the importance of careful post-partum counseling.

Blood-borne angiogenic factors and sustained multiple implantation: a comparison of singleton and twin pregnancies.

This study aimed to compare longitudinal serum concentrations of angiogenic implantation factors between ongoing singleton and twin pregnancies after double-embryo transfer and to investigate whether these are involved in sustained double implantation. Sixteen patients with an ongoing singleton and nine patients with an ongoing twin pregnancy after double-embryo transfer were included in this prospective observational study. Main outcome measures were concentrations of vascular endothelial growth factor-A (VEGF-A), inhibin A, glycodelin A, insulin-like growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II), insulin-like growth factor binding protein-1 (IGFBP-1) and insulin-like growth factor binding protein-3 (IGFBP-3) at baseline, during the IVF treatment and in early pregnancy. It appeared that VEGF-A concentrations prior to any treatment and at early implantation as well as body mass index (BMI) were higher in women who conceived a twin pregnancy (P = 0.04). Soon after implantation, inhibin A concentrations were higher in twin pregnancies (P=0.02). Secretion profiles of glycodelin A and members of the IGF family did not differ between singleton and twin pregnancies. VEGF-A appears to play a role in sustained double implantation. Furthermore a high BMI is associated with ongoing double implantation. Future studies should investigate the predictive value of VEGF-A for having an ongoing singleton or twin pregnancy.

Lower incidence of hypertensive complications during pregnancy in patients treated with low-dose aspirin during in vitro fertilization and early pregnancy.

BACKGROUND: The use of aspirin during in vitro fertilization (IVF) has been investigated for its effect on pregnancy rates after IVF. In most of these studies, aspirin administration was then prolonged throughout the first trimester of pregnancy. By inhibiting vasoconstriction, the use of low-dose aspirin in the first trimester could influence placentation and therefore prevent or delay development of hypertensive pregnancy complications, such as pregnancy-induced hypertension (PIH) and pre-eclampsia (PE). METHODS: This study involved the follow-up by questionnaires and hospital records of patients with an ongoing pregnancy in a prospective, randomized, double-blind, placebo-controlled trial on the effect of low-dose aspirin during IVF. Aspirin treatment was continued throughout the first trimester of pregnancy. The primary end-point of this follow-up study was the incidence of pregnancy complications. The original trial is registered with the Dutch Trial Register and as an International Standard Randomized Clinical Trial, No. ISRNCTM97507474. RESULTS: There were 54 patients who had ongoing pregnancies in the original trial; 90.7% returned the questionnaire and all Dutch hospital records were retrieved. A significant difference was found in the incidence of hypertensive pregnancy complications: 3.6% in the aspirin group and 26.9% in the placebo group (P < 0.05), resulting in numbers-needed-to-treat (NNT) of 10.3 to prevent hypertensive complications in one pregnancy after IVF treatment. CONCLUSIONS: The incidence of hypertensive complications was significantly lower in the group of women treated with low-dose aspirin throughout IVF treatment and first trimester of pregnancy. These results suggest a potential benefit of low-dose aspirin during IVF and first trimester to prevent hypertensive pregnancy complications. The findings justify further investigation in placebo-controlled randomized trials.

Effectiveness of highly purified human menopausal gonadotropin in intra-uterine insemination.

OBJECTIVE: In assisted reproductive techniques it is important to find a balance between high pregnancy and acceptable multiple pregnancy rates. In IVF treatment, stimulation with highly purified human menopausal gonadotropin (hMG) results in comparable or even higher pregnancy rates at lower oocyte yields compared to recombinant FSH. Since highly purified hMG contains LH activity, a number of the advantages of highly purified hMG may be attributed to this LH activity. In IUI treatment the effectiveness of highly purified hMG has been barely investigated. The aim of this study was to examine the effectiveness of highly purified hMG in IUI patients treated with a mild stimulation protocol. STUDY DESIGN: In this retrospective study 378 patients were included, receiving 1400 IUI cycles between January 2006 and December 2007. Patients were first treated with three subsequent natural cycles without controlled ovarian hyperstimulation, followed by three subsequent cycles stimulated with highly purified hMG. Primary outcomes were ongoing pregnancy rate and multifollicular growth. Secondary outcomes were multiple pregnancy and miscarriage rates. Primary and secondary outcomes were expressed in percentages with associated 95% confidence intervals (95%CI). Differences in the outcomes between natural and stimulated cycles were calculated using χ(2) tests. Statistical differences were determined at P < 0.05. RESULTS: Ongoing pregnancy rates increased from 6% (95%CI 4.7-7.7) per natural cycle to 7.4% (95%CI 5.2-10.3) per highly purified hMG stimulated cycle (p = 0.34). The highest ongoing pregnancy rate was observed in the fifth treatment cycle (10.8% (95%CI 6.6-17)), which is significantly higher than the ongoing pregnancy rate in the unstimulated group (p = 0.03). In the highly purified hMG group three (9.7% (95%CI 3.3-24.9)) of the ongoing pregnancies were twin pregnancies, in the unstimulated group there was one (1.7% (95%CI 0.3-9.0)) twin pregnancy (p = 0.08). CONCLUSION: Our results indicate that mild stimulation with highly purified hMG in IUI treatment results in an acceptable balance between ongoing and multiple pregnancy rates. Future prospective trials should compare mild stimulation protocols to protocols directly starting with controlled ovarian hyperstimulation. Furthermore, these trials should compare other types and dosages of gonadotropins.